Daily Archives: April 19, 2021

Blood Clots, Birth Control, and the Johnson & Johnson Vaccine: What We Mean by Medical Risk – The New Republic

Posted: April 19, 2021 at 7:16 am

The greatest risk inequitably enforced in this country is the most essential: general well-being. It is allowable, under our present systems, for trans people, for women, for Black women in particular, for poor people, for fat people, for the mentally ill, for the chronically ill and disabled, all to have worse health outcomesthese things are accepted and narrated to us by powerful institutions as an unfortunate but inescapable fact of medicine. And in doing so, they reiterate that these people are of lesser value, and are in fact inconvenient. These people are a burden, and so they should be grateful for what they get.

There was a hope among some at the very early start of the pandemic that, as horrific as it was going to be, it might force people with privilege to see how inextricably all of our lives are intertwined, how the health of one person isnt just their health but yours, too. We had to learn to wear masks not to protect ourselves but to protect others. Those with money suffered inconvenience at the very least from the fact that the people who serve and enable their lifestyles had no access to health care, to childcare, to workplace protections, to a real, functioning social safety netto any of the things that would allow them to stay home when sick, instead of risking a widespread infection to pack boxes for Amazon.

It would be impossible, as well as wholly undesirable, to avoid risk entirely in medical enterprise. Medicine is science, and science is experimentation, and experimentation can only happen if we take risks. And theres just no such thing as a risk-free existence. Aversion to risk in some contexts contributed to the inequities were dealing with today: In the 1970s, the FDA decided women of childbearing age shouldnt participate in clinical trials, out of concern not for the participants themselves but for possible future fetuses. As a result, it became the norm for new medicine to be developed exclusively on men; eight of the 10 prescription drugs withdrawn from the market between 1997 and 2000 posed greater health risks for women than for men.

The problem arises when a constitutionally unequal system assumes that the calculus by which we accept risk is neutral, rather than critically analyzing not just how research and regulatory decisions are made but how services are both distributed and received. A medical establishment predicated on the acceptance of profit-driven health care will inevitably favor the wealthy and the powerful, at the expense of everyone else.

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[Full text] Binding of the SARS-CoV-2 Spike Protein | HMER – Dove Medical Press

Posted: at 7:16 am

Introduction

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic and its damaging effects on both health and economics worldwide. Transmission and pathology of the virus appears to be mediated through the respiratory system via interaction of the viral spike protein with the ACE-2 receptor13 differentially presented on various cells within the respiratory system.4,5 Expression of ACE-2 has been reported on lung alveolar epithelial cells, enterocytes of the small intestine, circulatory endothelial cells, arterial smooth muscle cells,6 adipose tissue, bone marrow, duodenum, endometrium, heart, kidney, testis, and thyroid7 suggesting a potential direct effect of COVID-19 on those tissues. Additionally, infection with COVID-19 has been associated with significant liver injuries and altered liver function tests.8

Alterations in liver function have been attributed to secondary effects of cytokine cascade, hypoxia, underlying liver disease,911 or infection of ACE-2 positive cholangiocytes.12 There have also been reports of coronavirus particles in hepatocytes without a defined mechanism for infection.13

In a recent report studying the receptome of spike binding, ACE-2 was confirmed as the primary receptor for the spike protein via the binding domain (RBD) on the spike 1 portion of the molecule and the N-terminal-domain as the sites critical for virushost interaction.14 Additionally, the report described binding of the spike protein with ectopically expressed ASGR1 and KREMEN1 in transfected non-liver cells. The results strongly suggested the existence of additional entry points into cells for the SARS-CoV-2 virus via the spike protein. Differences in primary infection sites and clinical manifestations of SARS-CoV and SARS-CoV-2, both utilizing ACE-2 as the primary site of cellular infection, suggested that other cellular receptors may be involved in SARS-CoV-2 host interactions.14

E12 TERT-immortalized multi-lineage progenitor cells (MLPC) derived from human umbilical cord blood have been differentiated into immortalized AT2-like cells (AT2) (manuscript submitted) and fused directly with primary human hepatocytes to create immortalized hepatocyte-like cells (HLC).15 The resultant E12 AT2-like cells expressed the characteristics of small airway epithelial cells associated with alveolar type 2 cells and not alveolar type 1 cells. The E12/PHH fusion cells (HLC) expressed the characteristics of fully mature and highly differentiated hepatocytes.15

This report studied the interactions of the SARS-CoV-2 spike protein with potential receptors on human cord blood-derived MLPC differentiated AT2, HLC and primary human hepatocytes (PHH) by confocal analysis. The characteristics of spike protein binding were examined using biotinylated spike proteins and blockade of binding by un-labeled spike proteins, spike protein-directed neutralizing antibodies and an antibody directed against the hepatocyte surface membrane asialoglycoprotein receptor 1 (ASGr1). The results suggested that binding and inhibition analyses can be used to assess the potential mechanisms of viral host cell interactions with a myriad of different target cells in the body, but also to assess therapeutics designed to inhibit that binding.

Immortalized AT2 and HLC could provide accurate and reproducible tools to study the differential virushost interactions between these targets of COVID-19 infection and aid in the development of therapeutics designed to inhibit binding and infection by the SARS-CoV-2 virus. In addition, the potential binding of spike protein to the ASGr1 on hepatocytes suggested a mechanism of viral entry via the clathrin-coated pit receptor-mediated pathway and direct injury to the liver.16,17

MLPC are multi-potent non-hematopoietic stem cells isolated from human umbilical cord blood.15 Umbilical cord blood was collected as part of an FDA submission to market PrepaCyte-CB, a product to de-bulk cord blood for cryo-banking and transplantation. IRB approval of the studies was conducted by the University of Minnesota, the Saint Louis Cord Blood Bank and by Quorum Review Protocol #800, March 3, 2005. The cord blood samples were collected by the American Red Cross Cord Blood Program (Saint Paul, Minnesota) and Ridgeview Medical Center (Waconia, MN). Donations were collected with donor consent for research use only.

Briefly, isolated leukocytes were incubated overnight in MSCGM (PT-4105, Lonza, Walkerville, MD) after which non-adherent cells were removed. Cells were cultured in MSCGM until 8090% of cells had a fibroblastic morphology. These cells were transfected with the gene for TERT, as previously described15 and were cloned by limited dilution. The E12 clone was selected for both immortality and differentiating potential. The E12 MLPC, expanded and cryopreserved for over 14 years, were used as undifferentiated control cells and as the source of cells for the development of the AT2-like cells and the fusion partner in the development of MLPC/hepatocyte hybrid cells.15 For confocal analysis, E12 cells (106/mL in MSCGM, 200 L per well) were plated in non-coated 16 well chamber slides (Nalge, Nunc International, Rochester, NY) and allowed to attach overnight before use in the analysis.

AT2-like cells were developed from the differentiation of E12 MLPC. Briefly, E12 cells (3 x 105 cells/mL) in MSCGM were added to non-coated tissue culture vessels and allowed to attach overnight. Medium was then exchanged with SAGM (SAGM, Lonza, Walkerville, MD, cat # 3118) and allowed to culture for 814 days with 3 medium changes per week. Upon achieving 70% confluence, cells were harvested by treatment with Tryp-LE (12605028, Life Technologies, Grand Island, NY) allowed to dissociate from the culture vessel and used for confocal analysis, as a positive control for binding spike proteins and ACE-2 expression. Cells (106/mL in SAGM, 200 L per well) were plated in non-coated 16 well chamber slides and allowed to adhere overnight prior to confocal analysis.

Hepatocyte-like fusion cells were created by the fusion of E12 MLPC with primary human hepatocytes, as previously described.15 Equal numbers of E12 MLPC and primary hepatocytes were fused using 50% polyethylene glycol in RMPI + 0.01% EDTA. Resultant cells were plated into collagen-coated 75 cm2 tissue culture flasks and were cultured for 7 days in RPMI + 20% FBS. After 7 days, non-fused PHH were no longer viable and did not contribute to the HLC cell lines. HLC were examined for hepatocyte-specific markers including albumin and urea production. HLC were demonstrated to express markers and production consistent with fully mature and well-differentiated hepatocytes. HLC (106/mL in hepatocyte expansion medium, 200 L per well) were plated in collagen-coated 16 well chamber slides and were allowed to adhere overnight prior to confocal analysis. Hepatocyte expansion medium consisted of Williams Medium E supplemented with 2% fatty acid-free BSA (Sigma, A7030), 1% ITS solution (Lonza, 17838Z), 5mM hydrocortisone 21-hemisuccinate (Sigma, H2270) and glutamax (35050, Gibco) supplemented with FGF basic (20 ng/mL) (233-FB), FGF-4 (20 ng/mL) (7460-F4), HFG (40 ng/mL) (294-HG), SCF (40 ng/mL) (255-SC), Oncostatin M (20 ng/mL) (295-OM), BMP-4 (20 ng/mL) (314-BP), EGF (40 ng/mL) (236-EG) and IL-1 (20 ng/mL)(201-LB) all from R&D Systems (Minneapolis, MN).

Cryo-preserved primary human hepatocytes and media were obtained from Zenotech (Kansas City, KS). Cells were thawed with OptiThaw medium and enumerated with OptiCount medium in a standard hemacytometer. Hepatocytes were diluted to a final concentration of 106 cells/mL of OptiPlate medium and were plated in collagen-coated 16 well chamber slides at 200 L per well. After 4 hours of plating, the medium was changed to OptiCulture medium to allow overnight attachment and spread of cells prior to confocal analysis.

Cells were prepared for staining with antibodies and binding of spike proteins by fixing the cells in 1% formaldehyde for 1 hour. Cells were then washed x 2 with PermaCyte permeabilization medium (WBP-1000, CMDG, St. Paul, MN). All staining took place in the presence of PermaCyte. Cells were incubated with an unlabeled primary antibody (100 ng) for 30 minutes at room temperature. ACE-2 (labeled with alexa 594, FAB9332T), albumin (MAB1456) and asialoglycoprotein receptor 1 (MAB4394) antibodies were obtained from R&D Systems (Minneapolis, MN). Unbound antibody was removed by washing with PermaCyte and the cells were counterstained with a secondary antibody specific for mouse (A-11005) antibody labelled with Alexa 594 dye (Life Technologies, (Eugene, OR)). Marker expression was confirmed by positive staining when compared to cells stained with antibody isotype controls (QTC1000, CMDG, St. Paul, MN). The nuclei of the cells were visualized by staining with DAPI.

The binding of SARS-CoV-2 spike and spike 1 proteins was analyzed by confocal microscopy using biotinylated spike proteins. Cells were prepared as described above. Cells were labelled with 250 ng of either biotinylated spike (RBD) (SPD-C8E9, ACROBiosystems, Newark, DE) or biotinylated spike 1 protein (SIN-C82E8, ACROBiosystems) for 30 minutes. Unbound spike proteins were removed by washing cells twice with PermaCyte medium. Bound spike proteins were visualized by secondary staining with streptavidin-alexa 594 (S11227 Life Technologies). Cells were counterstained with DAPI to visualize the nuclei.

Specificity of biotinylated spike proteins binding to the cells was confirmed by blockade of binding by a 5 molar excess of unlabeled spike protein. Cells were prepared as per the confocal analysis of antibody binding. Cells were incubated with 1.25 g of unlabeled spike protein (ACROBiosystems, SPD-S52H6) or spike 1 protein (ACROBiosystems, S1N-C52H3) for 1 hour. Without washing the unbound unlabeled spike protein, biotinylated spike and spike 1 proteins were added to the cells and incubated for 30 minutes. Cells were washed twice with PermaCyte medium to remove any unbound proteins. Bound biotinylated spike proteins were observed by secondary labeling with streptavidin-alexa 594. Cells were counterstained with DAPI to visualize the nucleus.

The effects of antibodies on the binding of the spike proteins to the cells were examined using two commercially available neutralizing antibodies obtained from ACROBiosystems (SAD-S35) and Novatein Biosystems (PR-nCOV-mABS1, Boston, MA) and the ASGr1-specific antibody (R&D Systems). One g of either neutralizing antibody was preincubated with the spike protein for one hour prior to the addition of the mixture to the cells prepared as described for binding of the spike proteins. The ASGr1 antibody (300 ng) was preincubated with cells prior to the addition of the spike protein. Visualization of the binding of biotinylated spike protein was accomplished by secondary staining with streptavidin-alexa 594. The nuclei of the cells were visualized with DAPI.

Cells were analyzed on the Olympus Fluoview 1000 confocal microscope. The confocal images in Figures 14 are representative of at least 3 studies done on different days.

Figure 1 Biotinylated spike and spike 1 protein binding to E12 differentiated AT2-like cells and inhibition by unlabeled spike protein and neutralizing antibodies. Bound biotinylated spike proteins were visualized by sequential labeling with streptavidin-alexa 594. Cells positive for binding are shown by red fluorescence. Blue nuclei were visualized by counterstaining with DAPI. (A) Binding of biotinylated spike protein (containing RBD). (B) Inhibition of biotinylated spike protein binding by co-incubation with a 5 molar excess of unlabeled spike protein (RBD). (C) Binding of spike 1 protein. (D) Inhibition of biotinylated spike protein binding by preincubation with a neutralizing antibody from ACROBiosystems. (E) Lack of binding inhibition by neutralizing antibody from Novatein Bio. (F) Inhibition of biotinylated spike 1 binding by unlabeled spike (RBD) protein.

Abbreviation: RBD, receptor-binding domain.

Figure 2 Expression of ACE-2, ASGr1 and serum albumin. Undifferentiated E12 MLPC data are shown in (AD). E12 HLC fusion cell results are presented in (EH). Primary human hepatocytes (PHH) are shown in (IL). Cells were incubated with unlabeled primary antibody and sequentially stained with secondary antibody labeled with alexa-594. Positive binding is shown by red fluorescence. Blue nuclei were visualized by DAPI counterstaining. Figures (A, E and I) were stained with isotype control antibodies. Figures (B, F and J) were stained with antibody specific for ACE-2. Figures (C, G and K) were stained with antibody specific for the asialoglycoprotein receptor 1 (ASGr1). Figures (D, H and L) were stained with antibody specific for serum albumin.

Figure 3 Undifferentiated E12 MLPC confocal microscopy is shown in (AD). E12 HLC fusion cell data are presented in (E-H). Primary human hepatocytes (PHH) are shown in (IL). Positive binding is indicated by red fluorescence. Blue nuclei were visualized with DAPI counterstaining. Figures (A, E and I) were labeled with Sav-594. Figures (B, F and J) were labeled with biotinylated spike protein followed by sequential staining with streptavidin-alexa 594. Figures (C, G and K) were labeled with biotinylated spike 1 protein followed by sequential staining with streptavidin-alexa 594. Figures (D, H and L) biotinylated spike protein binding was blocked by a 5 molar excess of unlabeled spike protein (RBD) followed by sequential staining with streptavidin-alexa 594.

Figure 4 Inhibition of biotinylated spike binding by neutralizing antibodies to spike 1, spike and ASGr1. E12 HLC fusion cell data are shown in (AD). Primary human hepatocytes (PHH) are shown in (EH). Positive binding of biotinylated spike proteins is shown by red fluorescence. Blue nuclei are visualized by counterstaining with DAPI. Figures (A and E) confocals show the inability of a 5 molar excess of unlabeled spike 1 protein to block the binding of biotinylated spike protein. Figures (B and F) show inhibition of binding of biotinylated spike protein by neutralizing antibody from ACROBiosystems. Figures (C and G) show binding inhibition of biotinylated spike protein by neutralizing antibody from Novatein Bio. Figures (D and H) demonstrate inhibition of any detectable binding of biotinylated spike protein by antibody specific for the hepatocyte membrane ASGr1.

In a parallel study that surveyed the differentiation of E12 MLPC to AT2-like cells, it was demonstrated that AT2-like cells were positive for markers associated with AT2 cells (surfactant protein C, ACE2, TM4SF1, HT2-280), negative for markers associated with AT1 cells (AGER, caveolin 1 and aquaporin) and positive for markers not unique to AT2 cells but known to be expressed on AT2 cells (CK19, CD26 and EpCAM). These results were identical to primary small airway epithelial cells. Both cell types were also shown to bind spike and spike 1 proteins. Biotinylated spike proteins could be blocked by unlabeled spike protein (RBD). Pre-incubation with neutralizing antibodies prevented the binding of biotinylated spike protein by the ACROBiosystems neutralizing antibody, but not the Novatein antibody. Expressions of ACE-2, spike protein binding and inhibition were repeated for this study to confirm the involvement of the ACE-2 receptor (Figure 1).

The expressions of ACE-2, ASGr1 and albumin in control E12 MLPC, HLC and PHH were studied by antibody staining. E12 MLPC were shown to be negative for ACE-2, ASGr1 and albumin expression. In contrast, ASGr1 and albumin were shown to be strongly expressed by both HLC and PHH. ACE-2 was not detectible in either cell type (Figure 2).

The ability of E12 MLPC, HLC and PHH to bind spike and spike 1 proteins was studied using biotinylated spike proteins. E12 MLPC were unable to bind either spike or spike 1 proteins. HLC and PHH were able to bind spike protein but not spike 1 protein. The binding of biotinylated spike protein could be blocked by pre-incubation with unlabeled spike protein (Figure 3). The binding of biotinylated spike protein could not be blocked by spike 1, but could be blocked by ACROBiosystems and Novatein neutralizing antibodies and also an antibody directed against the ASGr1 (Figure 4).

It is critical to elucidate the mechanisms of virus/host interactions of the SARS-CoV-2 for the development of therapeutics designed to inhibit the binding and internalization of the virus to a myriad of cell types. The overarching strategy for the development of vaccines or therapeutics has involved the interaction between the S1 portion of the viral spike protein and the ACE-2 cellular receptor found in the respiratory tract and in various other tissues.47 Differences in transmission, pathology and organ involvement between SARS-CoV and SARS-CoV-2 (both dependent upon ACE-2 binding) suggested that additional receptors may contribute to the attachment and internalization of the SARS-CoV-2 virus14 in both the respiratory lungs and other organ systems.

The potential infection of tissues that are ACE-2 negative has spurred the search for additional receptor interactions of the spike protein. Some of these potential spike protein receptor targets include neuropilin-1,18 ASGR1 and KREMEN1.14 The observation of SARS-CoV-2 particles in hepatocytes8 and the robust expression of ASGr1 receptors and neuropilin-1 on hepatocytes suggested that altered liver function associated with COVID-19 infection may be directly caused by infection with the virus and mediated by binding to one or both receptors.

We investigated the potential virus: receptor interactions via the spike protein using fluorescent confocal microscopy and biotinylated spike (RBD) and spike 1 proteins. In a parallel study, E12 MLPC were differentiated to AT2-like cells (manuscript submitted). These cells expressed markers associated with AT2 cells (surfactant protein C, ACE2, TM4SF1, HT2-280), negative for markers associated with AT1 cells (AGER, caveolin 1 and aquaporin) and positive for markers not unique to AT2 cells but known to be expressed on AT2 cells (CK19, CD26 and EpCAM). These results were identical to primary small airway epithelial cells. The binding of biotinylated spike proteins and specific blocking by unlabeled protein and neutralizing antibodies confirmed that the primary interaction of spike protein with AT2-like cells and primary small airway epithelial cells was via the S1 portion of the protein with the ACE-2 receptor. We repeated those studies in support of our findings with the HLC and PHH. The differential inhibition of spike protein binding with two different antibodies suggested that viral neutralization could result from mechanisms other than direct inhibition of S1 (RBD) binding to ACE-2.

The characteristics of SARS-CoV-2 interactions with hepatocytes were studied by observing the binding of biotinylated spike (RBD) and spike 1 proteins to HLC and PHH using the undifferentiated E12 as a known negative control. It was observed that HLC and PHH were both negative for ACE-2, precluding that as a potential site of viral binding. This was confirmed by the inability of the cells to bind S1 protein. The binding of biotinylated spike protein and blockade by unlabeled spike protein on HLC and PHH suggested that the binding was specific, and via a mechanism distinct from ACE-2. The complete inhibition of spike binding by an antibody directed against the ASGr1 is strongly suggestive that ASGr1 is a binding site for the spike protein on hepatocytes. Interestingly, blockade of spike binding by both neutralizing antibodies on HLC and PHH was distinct from AT2 cells where inhibition occurred solely with the antibody that was directed against the RBD. This is suggestive of neutralizing activity that can occur outside the RBD.

Utilization of multiple cell types to study the interactions of spike protein binding will help identify additional receptor pathways for infection with COVID-19. They could also provide a powerful tool to aid in the development of therapeutics against multiple sites on the spike protein or receptors of the host cells. With the existent emergence of new variants and mutations of the SARS-CoV-2 exhibiting enhanced transmissibility, it is especially important to expand our repertoire of cellular models to investigate the effects of the mutations on the binding characteristics of the virus to host cells. The availability of immortalized cells with the stable characteristics of human alveolar type 2 cells and mature well-differentiated hepatocytes could provide an accurate and reproducible tool to effectively study the various virushost interactions via spike proteins by providing potential viral receptors that are segregated according to cell type. We believe that AT2 and HLC provide such a tool.

Dr Daniel P Collins reports personal fees from BioE, LLC, during the conduct of the study. In addition, Dr Daniel P Collins has a patent Composition for an in vitro culture medium to maintain and expand stem cell-derived hepatocyte-like cells pending, as well as,a patent Methods to develop immortalized hybrid hepatocyte-like cells, also pending. The authors report no other conflicts of interest in this work.

1. Shang J, Wan Y, Luo C, et al. Cell entry mechanisms of SARS-CoV-2. Proc Natl Acad Sci USA. 2020;117(21):1172711734. doi:10.1073/pnas.2003138117

2. Lan J, Ge J, Yu J, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215220. doi:10.1038/s41586-020-2180-5

3. Premkumar L, Segovia-Chumbez B, Jadi R, et al. The receptor-binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48):eabc8413. doi:10.1126/sciimmunol.abc8413

4. Hikmet F, Mar L, Edvinsson , et al. The protein expression profile of ACE2 in human tissues. Mol Sys Biol. 2020;16(7):e9610. doi:10.15252/msb.20209610

5. Sungnak W, Huang N, Bcavin C, et al. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med. 2020;26(5):681687. doi:10.1038/s41591-020-0868-6

6. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS corona virus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631637. doi:10.1002/path.1570

7. Wang D, Eraslan B, Weiland T, et al. A deep proteome and transcriptome abundance atlas of 29 healthy human tissues. Mol Syst Biol. 2019;15(2):e8503. doi:10.15252/msb.20188503

8. Wang Y, Liu S, Liu H, et al. SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19. J Hepatol. 2020;73(4):807816. doi:10.1016/jhep.2020.05.002

9. Desai N, Neyaz A, Szabolcs A, et al. Temporal and spatial heterogeneity of host response to SARS-CoV pulmonary infection. Nat Comm. 2020;11(1):6319. doi:10.1038/s41467-020-20139-7

10. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):10331034. doi:10.1016/S0140-6736(20)30628-0

11. Chu H, Chan JF, Wang Y, et al. Comparative replication and immune activation profiles of SARS-CoV-2 and SARS-CoV in human lungs: an ex vivo study with implications for the pathogenesis of COVID-19. Clin Infect Dis. 2020;71(6):14001409. doi:10.1093/cid/ciaa410

12. Chai X, Hu L, Zhang Y, et al. Specific ACE2 expression in cholangiocytes may cause liver damage after 2019-nCoV infection. bioRxiv. 2020. doi:10.1107/2020.02.03.931/766

13. Lozano-Sepulveda SA, Galan-Huerta K, Martnez-Acua N, Arellanos-Soto D, Rivas-Estilla AM. SARS-CoV-2 another kind of liver aggressor, how does it do that? Ann Hepatol. 2020;19(6):592596. doi:10.1016/j.aohep.2020.08.062

14. Gu Y, Cao J, Zhang X, et al. Interaction network of SARS-CoV-2 with host receptome through spike protein. bioRxiv. 2020. doi:10.1101/2020.09.09.28/508

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[Full text] Binding of the SARS-CoV-2 Spike Protein | HMER - Dove Medical Press

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In Canada, psychedelics re-emerge in treatment of depression – The Japan Times

Posted: at 7:15 am

Toronto To manage her stress and fears, Andrea Bird who is suffering from terminal cancer uses psychedelics, which are seeing a sudden re-emergence in Canada as a possible treatment for mental health conditions such as anxiety and depression.

The 60-year-old Canadian was diagnosed with breast cancer in 2012. Despite aggressive treatment, the disease returned five years later, spreading to her lungs, bones and brain.

As she tries to cope with her incurable ailment, Bird uses psilocybin, the psychoactive substance of hallucinogenic mushrooms that was banned in the 1970s.

I found it to be the most helpful thing that I did in coming to terms with the fact that my life is ending much sooner than I thought it would, Bird said.

Im still dying, she said matter-of-factly, but added that psilocybin makes me feel like I can stand up.

I really love my life, and I really dont want to die, but I have to find a way to surrender to what is actually happening.

Bird, who lives in Ontario, is among about 30 Canadians, most of them struggling to face the end of their lives, who have received federal dispensation since August 2020 to use psilocybin for therapeutic purposes.

TheraPsil, a nonprofit organization based in British Columbia, has helped most of them get exemptions to Canadas controlled substances and drug act for compassionate treatment.

The group also has connected patients to doctors and therapists who oversee their use of the drug.

These trial cases come amid mounting interest from researchers and investors, as well as a public push to reconsider bans on psilocybin, LSD, DMT, mescaline and other mind-altering substances such as MDMA, commonly known as ecstasy.

In the U.S., Oregon legalized psilocybin for therapeutic use last November.

Psychedelics have been used by indigenous peoples for millennia, but Western researchers only started delving into their properties and potential uses in earnest in the middle of last century.

But that work came grinding to a halt when the substances quickly became symbols of the anti-establishment counter-culture movement of the 1960s and were banned.

Over the past 20 years, however, the persistence of some researchers, a mental health crisis and a shift in public opinion toward greater tolerance of drugs such as cannabis which Canada legalized for recreational use in 2018 paved the way for a psychedelics renaissance.

Now there are more people who are willing to just look at the facts rather than the political weight they may carry, explains Rotem Petranker, associate director of the University of Torontos Psychedelic Studies Research Program, which looks at the effects of micro-dosing on mood and creativity.

Researchers are studying the potential benefits of these substances for treating depression, anxiety, post-traumatic stress disorder (PTSD), substance addictions and anorexia.

The most advanced clinical trials are focused on using psilocybin for severe or treatment-resistant depression and MDMA for PTSD.

Ecstasy powder after a seizure of drugs in Nice, France. | AFP-JIJI

Some of the studies have yielded promising results.

A recent clinical trial from Marylands Johns Hopkins University which has just opened a research center dedicated to psychedelics showed that two doses of psilocybin, accompanied by psychotherapy, produced large, rapid and sustained effects in patients suffering from serious depression.

Of the 24 participants, 71% showed a reduction of more than 50% of their symptoms after four weeks and half went into remission, the study revealed.

Another small-scale study involving 59 participants, conducted by Imperial College Londons Center for Psychedelic Research, showed psilocybin was at least as effective as conventional antidepressants, the research team said this week, though adding that larger trials were needed.

Were experiencing a revolution in psychiatry, said Alexandre Lehmann, a cognitive neuroscientist who teaches at McGill University in Montreal.

There are new approaches to alleviating and curing serious and disabling mental health problems, which affect a large number of people, and for which there are currently no good solutions.

Since their discovery in the 1950s, drug treatments for depression have hardly changed at all.

Conventional antidepressants which notably target serotonin, a key hormone that regulates mood have been criticized for being slow to act and for their side effects, including dulling emotions and reducing creativity.

They also dont always work, explains Nisha Ravindran, psychiatrist and professor at the University of Toronto.

We know that standard antidepressants dont help a significant proportion of the population. In fact, more than 30 to 40% simply dont respond and require alternatives, he said.

For some patients, psychedelics could come to the rescue through a new model of therapy involving a limited number of doses providing a transformative experience that might address their core issues.

Psychedelics can cause a profound alteration of perceptions and consciousness. The experience is unpredictable. For some, it can seem otherworldly.

Although much is still not known about how the drugs work, researchers believe they act on the brains default mode network, associated with introspective thoughts and ruminations, by temporarily lulling the ego, explains Lehmann.

Animal studies suggest they enhance brain plasticity, helping to re-organize neural connections, he says.

Psychedelics have low toxicity and are generally not addictive, but they can cause paranoia and anxiety attacks, especially in high doses. Researchers are still unsure about the addictive nature of MDMA, a derivative of amphetamines.

For therapy uses, doses are prepared in labs and the experience is supervised, so the risks are limited, Lehmann says.

The substances make patients more sensitive to their emotions and allow them to examine their thoughts from a new perspective.

Psychedelics are catalysts for psychotherapy, Lehmann says.

Before receiving government dispensation to use the drugs, Bird had twice tried psychedelics on her own, ingesting them at her home in the company of a guide.

She brewed and drank a hallucinogenic mushroom tea that led to several hours of vivid waking dreams. It took months of analysis to make sense of them, she says.

Death showed up a couple of times but it was not at all scary it was just waiting for me, she said of her first experience in late 2018.

It was the idea that this happens to everyone, that life is a gift that we get to have for a little while and then we have to give it back. And that became very clear to me.

Since the cancer spread to her brain, Bird has on the advice of her doctors reduced her intake of the drug and now takes micro-doses.

Hallucinogenic mushrooms for sale at a shop in Amsterdam. | AFP-JIJI

The potential medical benefits of psychedelics have piqued the interest of a growing number of investors in recent years.

Some startups are developing treatments based on these substances, while others are opening psychedelic therapy clinics.

Several are listed on stock exchanges, notably in Toronto and New York, which already trade shares in numerous cannabis companies.

The British firm Compass Pathways, one of the heavyweights in the sector, is currently valued at more than $1.4 billion on the Nasdaq.

Field Trip Health is one of those companies betting on psychedelics.

Founded in Toronto in 2019, it has already opened five clinics in Canada and the United States and plans to build a network of 75 clinics in North America by 2024.

Psychedelics are happening, says Ronan Levy, one of the founders.

The company offers psychotherapy enhanced by low doses of ketamine, a dissociative anesthetic that is legal for medical use, which can induce a trance-like state or a sense of disconnect between body and mind.

Ketamine has been used in surgeries since the 1960s and also became a fixture on the club scene. Some studies have suggested it may allow rapid relief of depressive symptoms for people with treatment-resistant depression.

With moss-covered walls, essential oil diffusers and comfy armchairs, the Field Trip Health clinic in Toronto located in a trendy neighborhood, in a loft with exposed pipes and with a view of the iconic CN Tower has the feel of a spa.

The clinic is accessible to those whose depression or other mental disorder is clinically resistant to treatment, meaning patients must have already tried at least two types of conventional treatments.

A typical course of treatment costing 4,700 Canadian dollars (about 409,000) includes six doses of ketamine and about ten sessions of psychotherapy.

Lying on a zero gravity chair with a mask over their eyes and music in their ears, patients let a ketamine lozenge melt under their tongues and are transported on a trip of about an hour.

A therapist stays in the room throughout the treatment, and then talks to the patients.

Mathieu, a 35-year-old who underwent treatment in June 2020 and asked only to be identified by his first name, called the experience really powerful.

I had the impression of breaking into a thousand pieces and being everywhere at the same time, he said.

When I was going back down, there was an hour window where my emotions felt pure what I had in mind came out without worry, I had no more filters.

Putting aside the hype and promising early results, the use of ketamine in mental health care is not universally backed.

The length of its effects appear to be limited, and critics point to risks of dependence and other possible complications. There is also no consensus on the value of combining its use with psychotherapy.

In the United States, many are worried about the boom in private clinics offering intravenous ketamine, without systematic psychiatric follow-up.

For Jeffrey Lieberman, chief psychiatrist at Columbia University Medical Center, it is a worrying sign that the practice has leapt ahead of the research.

More generally, others note that there is still a lack of solid evidence on the benefits of psychedelics. They say more and larger clinical trials are needed.

LSD blotter tabs on top of a U.S. coin. | AFP-JIJI

Some researchers are also concerned that the current commercial craze and enthusiasm among top proponents are giving rise to a sense that psychedelics are a miracle pill, leading some to try it alone or with low-quality substances.

In Canada, reports have surfaced of people turning to unlicensed therapists and bootleg psychedelics for personal growth or to ease pandemic fatigue, leading to a blossoming black market.

Proponents of ketamine therapy say it helps lay the groundwork for the future use of classic psychedelics such as psilocybin, with the most enthusiastic projections suggesting the first new treatments will be approved in the coming years.

The U.S. Food and Drug Administration has already indicated that it is receptive to the idea: Since 2017, it has granted a breakthrough therapy designation for trials on psilocybin and MDMA.

In Canada, a pioneer of the cannabis industry, legalization of psychedelics is not yet on the table, but Health Minister Patty Hajdu has said she is open to supporting research, saying it would help move forward this conversation.

In addition to exemptions for patients, the government has just authorized 19 health professionals to test psilocybin themselves in an effort to understand its effects and train themselves on how to use it in a therapeutic context.

The country has also announced its intention to restore access to restricted drugs including psychedelics through its Special Access Program, which allows doctors to request the use of substances not yet approved for clinical use in dire situations. A public consultation ended in mid-February.

If the proposal is approved, requests will be handled on a case-by-case basis, meaning access to these therapies for certain patients could be facilitated.

Bird says she hesitated before speaking publicly about her use of psychedelics, but she says she felt it was important to do so to help remove the stigma and try to illuminate this option for other people.

Im not that adventurous, drug-wise, she said. But it has been really helpful to me So, why hide that?

In a time of both misinformation and too much information, quality journalism is more crucial than ever.By subscribing, you can help us get the story right.

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In Canada, psychedelics re-emerge in treatment of depression - The Japan Times

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Psychedelics re-emerge in treatment of depression in Canada – Deccan Herald

Posted: at 7:15 am

To manage her stress and fears, Andrea Bird who is suffering from terminal cancer uses psychedelics, which are seeing a sudden re-emergence in Canada as a possible treatment for mental health conditions such as anxiety and depression.

The 60-year-old Canadian was diagnosed with breast cancer in 2012. Despite aggressive treatment, the disease returned five years later, spreading to her lungs, bones and brain.

As she tries to cope with her incurable ailment, Bird uses psilocybin, the psychoactive substance of hallucinogenic mushrooms that was banned in the 1970s.

"I found it to be the most helpful thing that I did in coming to terms with the fact that my life is ending much sooner than I thought it would," Bird told AFP.

"I'm still dying," she said matter-of-factly, but added that psilocybin "makes me feel like I can stand up."

"I really love my life, and I really don't want to die, but I have to find a way to surrender to what is actually happening."

Bird, who lives in Ontario province, is among about 30 Canadians, most of them struggling to face the end of their lives, who have received federal dispensation since August 2020 to use psilocybin for therapeutic purposes.

Read |Canada Post's psychedelic trucks bring cheer amid pandemic gloom

TheraPsil, a non-profit organization based in British Columbia, has helped most of them get exemptions to Canada's controlled substances and drug act for "compassionate treatment."

The group also has connected patients to doctors and therapists who oversee their use of the drug.

The US state of Oregon legalized psilocybin for therapeutic use last November.

Psychedelics have been used by indigenous peoples for millennia, but Western researchers only started delving into their properties and potential uses in earnest in the middle of last century.

But that work came grinding to a halt when the substances quickly became symbols of the anti-establishment counter-culture movement of the 1960s and were banned.

Over the past 20 years, however, the persistence of some researchers, a mental health crisis and a shift in public opinion towards greater tolerance of drugs such as cannabis -- which Canada legalized for recreational use in 2018 paved the way for a psychedelics renaissance.

"Now there are more people who are willing to just look at the facts rather than the political weight they may carry," explains Rotem Petranker, associate director of the University of Toronto's Psychedelic Studies Research Program, which looks at the effects of micro-dosing on mood and creativity.

Researchers are studying the potential benefits of these substances for treating depression, anxiety, post-traumatic stress disorder (PTSD), substance addictions and anorexia.

The most advanced clinical trials are focused on using psilocybin for severe or treatment-resistant depression, and MDMA for PTSD.

Some of the studies have yielded promising results.

A recent clinical trial from Baltimore's Johns Hopkins University which has just opened a research centre dedicated to psychedelics -- showed that two doses of psilocybin, accompanied by psychotherapy, produced "large, rapid and sustained" effects in patients suffering from serious depression.

Of the 24 participants, 71 per cent showed a reduction of more than 50 per cent of their symptoms after four weeks and half went into remission, the study revealed.

Another small-scale study involving 59 participants, conducted by Imperial College London's Centre for Psychedelic Research, showed psilocybin was "at least as effective" as conventional antidepressants, the research team said this week, though adding that larger trials were needed.

"We're experiencing a revolution in psychiatry," Alexandre Lehmann, a cognitive neuroscientist who teaches at McGill University in Montreal, told AFP.

"There are new approaches to alleviating and curing serious and disabling mental health problems, which affect a large number of people, and for which there are currently no good solutions."

Since their discovery in the 1950s, drug treatments for depression have hardly changed at all.

Conventional antidepressants -- which notably target serotonin, a key hormone that regulates mood -- have been criticized for being slow to act and for their side effects, including dulling emotions and reducing creativity.

They also don't always work, explains Nisha Ravindran, psychiatrist and professor at the University of Toronto.

"We know that standard antidepressants don't help a significant proportion of the population. In fact, more than 30 to 40 per cent simply don't respond and require alternatives," he said.

For some patients, psychedelics could come to the rescue through a new model of therapy involving a limited number of doses providing a "transformative experience" that might address their core issues.

Psychedelics can cause a profound alteration of perceptions and consciousness. The experience is unpredictable. For some, it can seem otherworldly.

Although much is still not known about how the drugs work, researchers believe they act on the brain's default mode network, associated with introspective thoughts and ruminations, by "temporarily lulling the ego," explains Lehmann.

Animal studies suggest they enhance brain plasticity, helping to re-organize neural connections, he says.

For therapy uses, doses are prepared in labs and the experience is supervised, so the "risks are limited," says Lehmann.

The substances make patients more sensitive to their emotions and allow them to examine their thoughts from a new perspective.

"Psychedelics are catalysts for psychotherapy," says Lehmann.

Before receiving government dispensation to use the drugs, Bird had twice tried psychedelics on the sly, ingesting them at her home in the company of a "guide."

She brewed and drank a hallucinogenic mushroom tea that led to several hours of "vivid" waking dreams. It took months of analysis to make sense of them, she says.

"Death showed up a couple of times but it was not at all scary... it was just waiting for me," she said of her first experience in late 2018.

"It was the idea that this happens to everyone, that life is a gift that we get to have for a little while and then we have to give it back. And that became very clear to me."

Since the cancer spread to her brain, Bird has -- on the advice of her doctors -- reduced her intake of the drug and now takes micro-doses.

The potential medical benefits of psychedelics have piqued the interest of a growing number of investors in recent years.

Some startups are developing treatments based on these substances, while others are opening psychedelic therapy clinics.

Several are listed on stock exchanges, notably in Toronto and New York, which already trade shares in numerous cannabis companies.

The British firm Compass Pathways, one of the heavyweights in the sector, is currently valued at more than Can$1.8 billion (US$1.4 billion) on the Nasdaq.

Field Trip Health is one of those companies betting on psychedelics.

Founded in Toronto in 2019, it has already opened five clinics in Canada and the United States and plans to build a network of 75 clinics in North America by 2024.

"Psychedelics are happening," Ronan Levy, one of the founders, told AFP.

The company offers psychotherapy enhanced by low doses of ketamine, a dissociative anaesthetic that is legal for medical use, which can induce a trance-like state or a sense of disconnect between body and mind.

Ketamine has been used in surgeries since the 1960s, and also became a fixture on the club scene. Some studies have suggested it may allow rapid relief of depressive symptoms for people with treatment-resistant depression.

With moss-covered walls, essential oil diffusers and comfy armchairs, the Field Trip Health clinic in Toronto located in a trendy neighbourhood, in a loft with exposed pipes and with a view of the iconic CN Tower has the feel of a spa.

A typical course of treatment costing Can$4,700 (US$3,700) includes six doses of ketamine and about ten sessions of psychotherapy.

Lying on a zero gravity chair with a mask over their eyes and music in their ears, patients let a ketamine lozenge melt under their tongues and are transported on a "trip" of about an hour.

A therapist stays in the room throughout the treatment, and then talks to the patients.

Mathieu, a 35-year-old Canadian who underwent treatment in June 2020 and asked only to be identified by his first name, called the experience "really powerful."

"I had the impression of breaking into a thousand pieces and being everywhere at the same time," he told AFP.

"When I was going back down, there was an hour window where my emotions felt pure -- what I had in mind came out without worry, I had no more filters."

Putting aside the hype and promising early results, the use of ketamine in mental health care is not universally backed.

In the United States, many are worried about the boom in private clinics offering intravenous ketamine, without systematic psychiatric follow-up.

For Jeffrey Lieberman, chief psychiatrist at Columbia University Medical Center, it is a worrying sign that "the practice has leapt ahead of the research."

More generally, others note that there is still a lack of solid evidence on the benefits of psychedelics. They say more and larger clinical trials are needed.

Some researchers are also concerned that the current commercial craze and enthusiasm among top proponents are giving rise to a sense that psychedelics are a "miracle pill," leading some to try it alone or with low-quality substances.

In Canada, reports have surfaced of people turning to unlicensed therapists and bootleg psychedelics for personal growth or to ease pandemic fatigue, leading to a blossoming black market.

The US Food and Drug Administration (FDA) has already indicated that it is receptive to the idea: since 2017, it has granted a "breakthrough therapy" designation for trials on psilocybin and MDMA.

If the proposal is approved, requests will be handled on a case-by-case basis, meaning access to these therapies for certain patients could be facilitated.

Bird says she hesitated before speaking publicly about her use of psychedelics, but she says she felt it was important to do so to help "remove the stigma" and "try to illuminate this option for other people."

"I'm not that adventurous, drug-wise," she said. "But it has been really helpful to me... So, why hide that?"

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Psilocybins complicated relationship with creativity revealed in new placebo-controlled neuroimaging study – PsyPost

Posted: at 7:15 am

People under the influence of psilocybin the active component of magic mushrooms report having more profound and original thoughts, but tend to score lower on cognitive tests of creative ability, according to new research published in Translational Psychiatry. But the findings indicate that the psychedelic substance can still boost creative ability in the long-term.

The study also collected functional magnetic resonance imaging and proton magnetic resonance spectroscopy data, providing some new insights into the underlying neurobiological mechanisms associated with creative ability.

Creativity is an essential cognitive ability linked to all areas of our everyday life, allowing us to adapt to an ever-changing environment and come up with ways to solve problems, said lead researcher Natasha Mason (@NL_Mason), a PhD candidate at Maastricht University.

Importantly, as well as being an essential process for everyday functioning, the (in)ability to think outside of the box has also been associated with psychological disorders, such as depression and anxiety. These individuals can get stuck in maladaptive thought patterns, which can facilitate habitual (negative) behaviors. Thus, finding a way to enhance creativity is of broad interest.

Scientists had found some preliminary evidence in the 1960s that the psychedelic drug LSD could enhance creative problem-solving. There was also some evidence that the psychedelic state induced by LSD could harm creative ability. But the issue has received little scientific attention since then.

Over the years, a number of anecdotal reports have accumulated suggesting that the consumption of psychedelic drugs, like LSD and psilocybin, can enhance creativity, Mason said. Famous examples of psychedelic-affiliated creative breakthroughs include Kary Mullis discovery of the polymerase chain reaction, the 1960s California-based computer industry, and the literary works of authors, such as Aldous Huxley and Ken Kesey. That said, although there are a large number of claims that psychedelics do this, no one has investigated this in a placebo-controlled experimental trial.

In their study, the researchers examined two types of deliberate creativity convergent thinking and divergent thinking. The former represents the ability to generate a single optimal solution to a problem, while the latter represents the ability to generate many solutions to a problem with several possible answers.

The study included 60 healthy participants, who had previous experience with a psychedelic drug but not within the past 3 months.

Mason and her colleagues found that both types of creativity appeared to be impaired during the psychedelic state. But psilocybin appeared to produce lasting improvements in divergent thinking, when not under the influence of the substance. A week after receiving psilocybin, participants tended to generate more novel ideas for uses of everyday objects compared to those who received placebo.

We found that when under the influence, psychedelics do not enhance creativity per se. Instead, it seems a bit more complicated, Mason told PsyPost. We used classic measures of creativity, for example the alternate uses test, in which people have to come up with as many uses as possible for a brick. Here, we found that under the influence of a psychedelic, individuals performed worse than placebo (they came up with fewer uses for a brick, and the uses they did come up with were not any more original than during placebo).

However, individuals reported that they felt more creative throughout the day, in that they said they had more experiences of insight and were able to figure out solutions to their own, personal problems, Mason explained. This could mean one of two things either under the influence of psychedelics, peoples idea generation and evaluation (creativity) is impaired, but their feelings of the quality of ideas is enhanced. Or we are seeing a difference in types of creativity maybe psychedelics reduce individuals deliberate creativity (taskbased, with an end goal), but increases spontaneous creativity (insight).

We also asked participants to come back 7 days later and repeat the tasks, Mason said. Here we see that after psilocybin, individuals performed better on one part of the task. Namely, they were able to come up with more novel responses. Thus we see that maybe psychedelics do increase aspects of deliberate creativity in the long-term.

The researchers also found that psilocybin-induced changes in creativity were associated with connectivity patterns within the default mode network, a large-scale brain network involved with daydreaming, imagination, and spontaneous thinking, among other things. We found changes in the brain that predicted both the acute and long-term changes in creative performance after psilocybin, so we can start to get an idea of how these drugs are working to enhance or impair creative thinking, Mason said.

In particular, decreased integrity of the default mode network was associated with greater subjective feelings of insightfulness, as well as long-term increases in divergent thinking.

The findings are in line with previous research conducted by Mason and her colleagues, which took place at a psychedelic retreat. Unlike the current study, however, the past research was limited by its lack of a placebo condition.

But, despite the improved methodology, there is still a need for additional research. We dont know if under the influence of psychedelics, individuals just feel more creative or if these drugs are actually increasing the spontaneous side of creativity, so this needs to be further tested, Mason explained.

These distinctions are of particular importance, as psychedelics are currently being investigated to treat a number of mental health disorders, characterized by rigid, inflexible thought patterns (like anxiety and depression). Thus, it could be suggested that the ability of psilocybin to acutely alter different aspects of creative thinking could aid in the therapeutic process by opening up a window of opportunity where therapeutic interventions could prove more effective.

Namely, while under the influence of a psychedelic, rigid thought content could be decreased, while unguided, spontaneous thoughts may give rise to new insights and perspectives of previous events and current problems, Mason added. Subacutely, patients may then be able to integrate these insights with a therapist, and come up with new, more effective strategies that facilitate adaptive interpretation and coping abilities. Thus, future studies should be employed in clinical populations in order to assess this proposal, as well as the underlying neurobiological mechanisms.

The study, Spontaneous and deliberate creative cognition during and after psilocybin exposure, was published April 8, 2021.

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Psyched Wellness: Partly psychedelics and partly consumer wellness – Proactive Investors USA & Canada

Posted: at 7:15 am

Proactive Research analyst Ed Stacey takes a closer look atLtd (CSE: PSYC) (OTCQB: PSYCF), a health supplements company developing a unique range of products which harness the properties of a specific type of mushroom.

The functional mushrooms market is a large and growing segment in consumer health, currently running at around US$30bn per year globally.

Within the sector, many companies are looking at ways to work with psychedelic mushrooms, which are believed to offer physical and mental health benefits when consumed at low doses.

Click here to read Proactive analyst Ed Stacey's initiation report on 'Psyched Wellness - The drink of the gods'

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Psyched Wellness: Partly psychedelics and partly consumer wellness - Proactive Investors USA & Canada

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J. Prince Appears to Have Bought His Own Private Island: ‘They Said It Couldn’t Be Done’ – Complex

Posted: at 7:14 am

Welcome to Prince Island No. 1.

J. Princetook to Instagram to show off what appears to be his own private island. They said itcouldnt be done,he can be overheard saying as he seems to be riding a jet ski in avideo he posted to Instagram. They told me I was dreaming too big. They told me I was crazy. They said it was impossible. I done made the impossible possible. Prince Island No. 1.Loyalty for life.

Prince doesnt give away much about the island regarding the location, how much it cost,or even how it looks up close, but we can gather from name itself is that he seems to have his sights set on getting more private islands in the future.

The Rap-A-Lot Records founderjoins a handful of celebrities who have reportedly bought an island. The Sun reports JAY-Z spent nearly $4 million in 2016 on an island in the Bahamas so that he andBeyonc can do the little things, like go to the beach with Blue Ivy. Back in 2009, Tyler Perry bought an island for his 40thbirthday. Im a loner by nature, so when Im out there on these islands, I just feel like the only person in the world, Perry explained.

Check out J. Princes video up top.

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J. Prince Appears to Have Bought His Own Private Island: 'They Said It Couldn't Be Done' - Complex

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You can rent an entire private island in Ireland with your mates for 40pppn including a bar, sauna and h… – The Sun

Posted: at 7:14 am

YOU can rent an entire private island in Ireland with 21 of your mates for just 40 each a night.

Collanmore Island, just 10 minutes from the town of Westport, can welcome groups of friends or families across the four bedrooms.

It takes just two minutes to get to the island, with a return fare from Rosmoney Pier just 10 each.

On the island is a private beach with water activities such as kayaking and paddle boarding available.

Also on the island is a private bar which you can stock with your own drinks, and an outdoor seating area and BBQ area with amazing views of the sea.

A hot tub and steam room is also open to guests and the lodge includes WiFi and air conditioning.

If the weather drops, then there are amazing views from inside too with floor-to-ceiling windows in the living area.

Previous guests have praised the "stunning views" on the island with views of Clew Bay.

One person wrote: "The views are stunning and the activities are endless. We were heartbroken when our stay was up."

Another person added "Definitely be interested in returning next summer when the weather is a bit better and do some of the water sport activities!"

Nights start from 880, but if you can split it between 22 of you then you only have to pay 40 per night each.

Sadly its fully booked for summer but you can find available dates for October.

If you can book for a week, you get a 50 per cent discount - meaning it would set you back just 20 each per night.

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We've rounded up some of the best private islands you can rent in Europe including France, Spain and Croatia without splashing the cash.

Or, you can buy a a number of private islands from just 51,000 - less than the cost of a UK flat.

A private island in the Bahamas is up for sale, with six miles of beach, although you will have to drop some serious cash.

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This Country Wants You To Visit So Badly, Itll Give You A Covid Vaccine – Forbes

Posted: at 7:14 am

Weve been hearing a lot about vaccine passports and destinations getting creative with ways to lure travelerslike offering to subsidize your travel costs on a trip to Malta this summer. But a glamorous group of islands in the Indian Ocean just announced an idea we can get onboard with: The Maldives are planning to give travelers a Covid-19 vaccination when they arrive on vacation.

This new initiative, which the countrys tourism minister Abdulla Mausoom announced on CNBC, is just one part of three-pronged attempt to revive the countrys economy. Mausoom calls it a 3V strategyvisit, vaccinate and vacation. The date when it will go into effect hasnt been announced yet.

The idea comes on the heels of another creative concept that the Maldives cooked up in the past year: the worlds first-ever destination loyalty program. Called Maldives Border Miles, its like an airline frequent flier program, with travelers earning points based on the number of visits and the duration of their stay. Visitors can also earn additional points for celebrating special occasions in the Maldives.

Like many other destinations that depend on tourism, the Maldives has been hard hit during the pandemic. Tourism accounts for about 28% of the economy. Typically, upwards of 1.7 million visitors come to the Maldives every year. In 2020, the archipelago saw less than a third of that number, with 555,494 foreigners vacationing in these idyllic islandsthough that was actually considered a success story.

Sea plane flying above the Maldives, which has just announced that it will be offering vaccinations ... [+] to travelers.

Since July 2020, theMaldiveshas allowed travelers from any country to visitand it is trying to make it easier and easier. On April 16, the country announced that it will allow people who are fully vaccinated to enter, restriction-free, two weeks after their second dose. Unvaccinated foreign visitors must have a negative PCR test prior to departure. Visitors also have to download a national contact tracing app and use it during their journey.

TheCDC has the country at a level 4for a very-high level of Covid, though numbers have been decreasing in this island nation, with90new infections reported on average each day. According toReuters, about 28.6% of the countrys 500,000 residents are fully vaccinated, and Mausoom says that 90% of its front-line tourism workers have been vaccinated.

Given the prospect of this exciting new initiative, we think its an ideal time to start dreaming about a trip to these dreamy islands. Check out a few of the most beautiful places in the Maldives.

Six Senses Laamu, Maldives

Six Senses Laamu,Maldives

An idyllic palm-fringed paradise, Six Senses Laamu,Maldives combines luxury and sustainability. An award-winning marine conservation initiative based at the resort focuses on research, guest education and community outreach goals. And for budding conservationists age 6 to 16, theres a unique Junior Marine Biology program.

Anantara Kihavah Villas's underwater SEA restaurant.

Anantara Kihavah Villas

A promise of great adventures awaits at Anantara Kihavah Villas. Go snorkeling with manta rays, stargaze at the only overwater observatory in theMaldives and enjoy fine dining underwater at SEA, the worlds first oceanic restaurant and wine cellar. The resort also has the largest collection of private pool residences in the world.

Soneva Jani

Soneva Jania collection of island sanctuaries and overwater villas set within a lagoon of crystal-clear waterscaters to everyone from kids to honeymooners. With the new Soneva Academy, children aged 12 and up can take a series of educational courses that cover a range of fascinating topics relevant to the Maldives, from Marine Life to the Night Sky to Zero Waste. (The program is also offered at sister property Soneva Fushi.)

Hurawalhi Maldives and its underwater restaurant.

Hurawalhi Maldives

An adults-only paradise, HurawalhiMaldivesis famous for its 5.8 Underwater Restaurant. Its located in theLhaviyaniAtoll, where there are more than 50 dive sites within easy reach.

COMO Maalifushi

For ocean and beach lovers,COMO Maalifushi is well regarded for its diving and surf breaks. One of the newest water excursions is theWhale Shark Night Snorkel. Guests are taken on a boat from the resort to find the largest fish in the sea. The clear Maldivian waters allow for an aquarium-like view of the gentle giants.

Soneva in Aqua yacht.

Soneva in Aqua

Travelers can now set sail from the barefoot luxury resortSoneva Fushi on a new four-day, three-night Goidhoo experience aboardSoneva in Aqua. The yacht offers an ultra-luxurious escape to the island of Goidhoo, which can only be reached by boat and offers a rare untouched paradise full of vibrant marine life and corals.

Niyama Private Islands Maldives

Set on two islands, Niyama Private IslandsMaldives is the only luxury resort in theMaldiveswith its own wave breaking onto the shore. After a day of surfing, guests can hang out at the Surf Shack with its tomato-red food truck, comfy bean bags and seaside swings, relaxing to a reggae soundtrack. The hotels 134 villas, suites and pavilions are dotted along the beaches and extend out over the lagoon

The Ritz-Carlton Maldives, Fari Islands

The Ritz-CarltonMaldives, Fari Islands

The Ritz-CarltonMaldives, Fari Islands aims tobring families together, spark curiosity in young minds and challenge the notion that getting away from it all means sitting still.There are 30 different activities for kids, including several adventures with Jean-Michel Cousteaus Ambassadors of the Environment Programfrom anislandtreasure hunt to a bike safari round the resort.

Velaa Private Island

In 2020,Velaa Private Islandplanted 2,000 new corals and is now seeing a surge in tropical fish and thriving marine life in the transplant areas.This year, Velaa offers eco-conscious guests the chance to shadow the coral biologists by collecting research as they snorkel and plant new corals themselves.

Skydiving at The Nautilus Maldives.

The Nautilus Maldives

The NautilusMaldives has launched a new adrenaline-fueled adventure:skydiving, allowing adrenaline-lovers to jump from heights of 12,000 feet above the Indian Ocean and enjoy a full 360-degree view of the baa atoll.

Kudadoo Maldives Private Island

An exclusive resort with 15 overwater villas, KudadooMaldivesPrivate Island has a fully-inclusive Anything, Anytime, Anywhere approach.All private dining, access to an expansive wine cellar, spa treatments and water experiences are fully included in the price per night.

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$12,000 Houses In Italy: Two Surprisingly Cheap (And Beautiful) Villages Making It Easy To Move There

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How the Lush Caribbean Island of Dominica Became a Superyacht Haven – Robb Report

Posted: at 7:14 am

Sixteen years ago, Hubert Winston was standing on a beach in Dominicas Prince Rupert Bay, watching a string of yachts sail by in the distance. It looked like a flotilla, recalls Winston, who had just moved back to the island from Florida.

They were traveling between Martinique and Guadeloupe, but not one of them ever stopped here. I didnt understand that. We had so much to offer.

With no marinas or international airport, the lush, mountainous island represented a big X on superyacht charts. Captains were reluctant to venture to Dominica in case they had engine problems or couldnt find a decent anchorage. Theyd rather visit its French neighbors, with plenty of marinas, than gamble with the unknown, alluring as the green island looked from the distance.

Secret Bays Zabuco Honeymoon Villa, perched on a clifftop promontory.Photo Courtesy: Secret Bay

Even now Dominica remains a tightly held secret among superyacht owners. It turns out that the crewstypically young, restless and adventurousstarted going to the island for R&R, then informed their owners about what an unspoiled paradise it is. Nicknamed the Nature Island, it offers a natural bounty of mountain terrain, rainforests, dormant volcanoes and coastal reefs that is unparalleled in the Caribbean. The locals provide the same authentic welcomea bit cautious but unmistakableI experienced on other islands 30 years ago, before it evaporated with modern development and stock-market booms. No condo commandos have invaded Dominica, thanks to its relative inaccessibility.

That aura of untouched remoteness has proven to be a siren song for superyachts, which typically gather in Prince Rupert Bay and smaller, more intimate anchorages, where the only other vessels are a few sailboats and the local fishing fleet, with its brightly colored wooden hulls.

Named by Christopher Columbus, who first sighted it on his second voyage to the hemisphere, in 1493, Dominica was colonized by the French and then traded back and forth between France and England across the 18th century. Gallic vestiges endure, though the few fortresses on the water were built by the British to repel French attacks. The country gained full independence from the UK in 1978. Prized for its bananas, grapefruit and oranges, it has otherwise remained a largely unspoiled Eden. Rustic charm, clich as it sounds, describes the island perfectly. Waterfront cafs with names like Keepin it Real and Cocoyea serve seafood caught from nearby bays and just-picked tropical-fruit juices. Scenes from Pirates of the Caribbean were filmed across the island because of its unsullied beauty.

Dominica is for a certain kind of client who loves to experience nature up close and personal, says Gina Robertson, a charter broker with Fraser Yachts, ticking off adventure experiences that include canyoning, kayaking and hiking nature trails. In Dominicas favor: Its not the same old same old. Nowadays, charterers dont want to do just the milk runs, and many are on extended charters, so will have more time to explore islands in depth.

The open-air Gommier Spa on Secret Bay overlooks Cabrits National Park.Photo Courtesy: Secret Bay

Andrew Cobra OBrien was one of the pioneers who introduced Dominica to the superyacht community. To compete with other islands, which have bustling marinas providing all manner of conveniences, he founded Cobra Tours & Yacht Services, offering fuel, provisions and mechanic services, as well as customs clearance and private tours of the island. Cobra Tours was instrumental in opening up Dominica by demonstrating that, even without a marina, seafarers would be well cared for. We used to go to yacht shows in Monaco and Ft. Lauderdale to spread the word about what a great destination Dominica is, he says. His firm joined professional groups, including the International Superyacht Society, to help bolster the islands reputation among charter brokers. Last season was the best for superyachts wed ever had. We serviced 30 or 40 of them.

Often, he adds, they come after having their fill of shopping and upscale restaurants on Antigua or St. Barts. Now 95 percent of the yachts dont just stumble on Dominica, OBrien says. Its a destination.

Several other firms that supply visiting vessels have emerged, including Winstons Dominica Yacht Services. Winston, who worked in Floridas marine industry, among other things, before returning to his homeland, saw an untapped market. There was a disconnect back then, but we got the word out to the yachting world, he says. We changed the whole notion of getting stuck in Dominica.

The island has since attracted the late Paul Allens 414-foot Octopus, Nat Rothschilds Planet Nine, Andrey Melnichenkos 390-foot Motor Yacht A and the late Steve Jobss Venus, among others. Bill Gates, Robert De Niro and Edward Norton have been spotted on superyacht tenders in Prince Rupert Bay. Five-star resorts, including Secret Bay and Cabrits Resort & Spa, with a pier on Douglas Bay, have welcomed yacht owners to their bars and restaurants.

Dominica is awash in prime diving spots.Photo Courtesy: Jungle Bay Dominica

Pre-Covid, of course. The rules have changed, with a negative PCR test required 24 to 72 hours before arrival; a visitor also takes a rapid test upon arrival, and it must be negative to enter. Then the visitor must quarantine at a government-designated spot and take yet another test on day five. If the results are negative, one is free to go anywhere. For owners or charter guests with time constraints, sitting on the yacht for six days is a non-starter, especially with that stunning but untouchable backdrop. But in Dominica, the notion of quarantine isnt quite so rigid as elsewhere. The authorities have set up the Safe in Nature program, in which visitors may stay at some of the islands most exclusive resorts and see the approved sights (the best on the island) with a private, Covid-certified guide. Not every resort allows guests off-property, but the two where I stayedSecret Bay Resort at the north end and Jungle Bay Resort & Spa at the southdo. I was not only able to move relatively freely around the island but also to transfer between the two resorts over the six days.

Covid or not, Dominica remains largely undiscovered compared to the heavily boated islands. With 260 square miles of hills and mountains, and the majority of its population of 74,000 living on the coast, most of the interior is rural or undeveloped. Everybody has cruised the [British Virgin Islands], says Winston. We have something different, something special. Guests just fall in love with our serenity.

For yachts, the action is concentrated at the northern and southern ends. Bays on the north side of the island offer sublime, light-blue water, wide-open anchorages and easy access to the town of Portsmouth by tender. The bays often live up to their names. With its two beaches and reef colored by tropical fish, Secret Bay really is. Even though its just around the corner from the much busier Prince Rupert Bay, captains tend to avoid it because of exposure to shifting winds, and instead drop anchor on its edge and send in tenders.

North of Prince Rupert Bay, the road follows a string of more baysDouglas, Toucari, Marceau and Connorthat make postcard-perfect anchorages, with inland destinations like Cold Sulphur Springs (a dormant volcano crater that emits caramel-colored, sulphur-infused water) and Chaudiere Pool, a 30-foot-deep pool beneath a waterfall, being among the norths natural wonders. Four-wheeling up narrow mountain roads to Chaudiere, we pass tiny farms with pineapples and coconuts. Around every corner theres another exceptional ocean view.

Zabuco Villas private plunge pool and outdoor shower.Photo Courtesy: Secret Bay

For a relatively small island, Dominica has diverse terrain. The Indian River is like an Amazon tributary, with slow-moving brackish water and thick vegetation on the banks. I spend a few hours with Fire, a fiftysomething Rastafarian, rowing a handmade red, yellow and green wooden boat upstream. Fire recites the English, Creole and French names for virtually every tree and flower we pass. At the top, we stop at a plantation, a sign at the empty caf reading: time stands still at the bush bar. Thats the feeling I have all week.

The number of outsiders visiting Dominica is a sliver of what it would be during a normal season, so I seem to have the riverand almost every- thing elseto myself. At Secret Bay resort, with its focus on privacythere are just 10 villas, all overlooking the oceanI have a private-chef experience with Fbio Fernandes. The resorts executive chef is a Lisbon native who trained at a Michelin-star restaurant in Portugal and worked at award winners in Austria, Africa and the UK. He plans daily menus around me, as I dine alone on the open terrace of the Zing Zing Restaurant. Fernandes uses locally sourced tuna and kingfish, not to mention farm-to-table vegetables, and elevates them many levels, with creative presentations and fusions of unlikely ingredients. His signature Zero Miles Tuna, with sustainable ingredients, blends sushi-grade fish, shado beni emulsion, mango and ginger gels, and pumpkin puree.

The southern part of the island is all about the water, even inland. Trafalgar Falls, Titou Gorge and Boiling Lake practically beg to be photographed and shared, while the southwestern corner is one of the worlds highest-ranked dive and snorkeling sites. The area south of Champagne Beach down to the protected arm of land at Scotts Head is part of the SoufrireScotts Head Marine Reserve, so yachts must anchor north in LAnse Bateau. Visitors also have to hire local guides for diving and snorkeling. The reserve is mostly a haven for reef fish, but pods of dolphins and even sperm whales are occasional visitors.

Batibou Beach, shaded by a canopy of coconut trees, is popular for swimming and snorkeling.Photo Courtesy: Discover Dominica Authority

With good conditions, visibility is 80 feet below the surface, says Weefers Jules, my guide from Jungle Bay resort, who has been a Dominica dive master for 20 years. With a front having just passed through, the usually clear waters of Champagne Reefso named because the volcanic gases venting through fissures form bubblesare muddied, so we kayak to Labym, or the Abyss, below Witchs Point, where the shoreline reef transitions into a vertical wall that drops 1,000 feet. The water is cool, and wind gusts are pushing us offshore a bit, but the fins propel me through the reef. Schools of sergeant majors, doctor fish, angelfish and spotted moray eels swim around us, while a few stingrays flee into the deep. A hundred yards away, a group is free-diving.

With thousands of dives under his belt, Jules says he never tires of the marine life in Soufrire Bay, the islands dividing line between the calm Caribbean Sea and the much fiercer Atlantic. Within a relatively small space, the Soufrire reservean UNESCO World Heritage Siteoffers a half-dozen world-class dives, such as Scotts Head Pinnacle, beginning with a rock formation called Swiss Cheese, and leading to a volcanic crater that drops as far as 2,000 feet at the center. There are hundreds of soldier fish at the entrance, he says. When you turn sideways, there are lobsters and eels in the walls cracks. At the northern edge of the Soufrire crater, five underwater peaks called Danglebens Pinnacles host plenty of reef fish and also offer glimpses of turtles and horse-eye jacks.

Prince Rupert Bay, on the islands northwest coast, is a popular anchorage.Photo Courtesy: Discover Dominica Authority

The Atlantic side of Dominica has yet more dive sites, including the spectacular Mountain Top, and the northern end of the island has nearly a dozen others, including one, called Elephants Ass, so secluded that most locals dont even know about it. There are also opportunities to swim with sperm whales. Because of Covid-related cancellations, the nearly three-year wait for the experience can be closer to a few weeks.

After snorkeling, I return to Jungle Bay, my home on the southern end of the island. Its an eco-resort with private villas built of local wood and stone, two yoga studios, a restaurant overlooking the water and a Zen-like spa. Nature trails, banana plants and stone walls, plus a large Buddha, define the resort. Like Secret Bay, its an ocean sanctuary.

That feeling of sanctuary, with a heightened sense of exclusivity, is ultimately what attracts superyacht owners to Dominica. And why theyre not telling their friends.

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How the Lush Caribbean Island of Dominica Became a Superyacht Haven - Robb Report

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