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Testosterone Supplements Won't Help Most Men, Doctors' Group Says

Title: Testosterone Supplements Won't Help Most Men, Doctors' Group Says
Category: Health News
Created: 1/6/2020 12:00:00 AM
Last Editorial Review: 1/7/2020 12:00:00 AM




doc

What Is a Choledochojejunostomy?

Title: What Is a Choledochojejunostomy?
Category: Procedures and Tests
Created: 5/6/2020 12:00:00 AM
Last Editorial Review: 5/6/2020 12:00:00 AM




doc

The Doctor Gap: In Areas of Greatest Need, Primary Care Is a Team Effort

Title: The Doctor Gap: In Areas of Greatest Need, Primary Care Is a Team Effort
Category: Health News
Created: 3/19/2020 12:00:00 AM
Last Editorial Review: 3/20/2020 12:00:00 AM




doc

Could AI Help Doctors Map Out Treatments for Brain Cancers?

Title: Could AI Help Doctors Map Out Treatments for Brain Cancers?
Category: Health News
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/27/2020 12:00:00 AM




doc

Examining the Case for Dental Hygienists Teaching Predoctoral Dental Students: A Two-Part Study

Dental students in North American dental schools are exposed to faculty members with various professional backgrounds. These faculty members may include dentists, dental hygienists, and scientists without clinical dental credentials. The practice of dental hygienists’ educating predoctoral dental students has not been well documented. The aims of this two-part study were to investigate the parameters of didactic, preclinical, and clinical instruction of dental students by dental hygienist faculty members in North American dental schools and to explore dental students’ perceptions of this form of teaching. In part one, a survey was sent electronically to the clinical or academic affairs deans of all 76 American Dental Education Association (ADEA) member dental schools in 2017. Twenty-nine responded, for a 38.2% response rate. In 76% of the responding schools, dental hygienists were teaching dental students. Most respondents reported that, in their schools, the minimum degree required to teach didactically was a master’s, while a bachelor’s degree was required for preclinical and clinical courses. There was no significant association between dental hygienists’ instructing dental students and having a dental hygiene educational program at the institution. In part two of the study, a questionnaire was completed by 102 graduating dental students (85% response rate) at one U.S. university to evaluate the impact of dental hygienist educators. Among the respondents, 87% reported feeling that dental hygienists were very effective educators. There were no significant differences in responses between traditional and advanced standing international dental students. This study found that dental hygienists were educating dental students in many North American dental schools and were doing so in curricular content beyond periodontics and that their educational contributions at a sample school were valued by the dental students there.




doc

CDC: Vaccine for recent flu season cut visits to doctors by nearly half

This season’s flu vaccine was 45% effective overall and 55% effective among children and teens, the Centers for Disease Control and Prevention reported in February.




doc

ARHGEF7 ({beta}-PIX) Is Required for the Maintenance of Podocyte Architecture and Glomerular Function

Background

Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown.

Methods

We used a proximity-based ligation assay, BioID, to identify guanine nucleotide exchange factors that activate Cdc42 in immortalized human podocytes. We generated podocyte-specific ARHGEF7 (commonly known as β-PIX) knockout mice by crossing β-PIX floxed mice with Podocin-Cre mice. Using shRNA, we established cultured mouse podocytes with β-PIX knockdown and their controls.

Results

We identified β-PIX as a predominant guanine nucleotide exchange factor that interacts with Cdc42 in human podocytes. Podocyte-specific β-PIX knockout mice developed progressive proteinuria and kidney failure with global or segmental glomerulosclerosis in adulthood. Glomerular podocyte density gradually decreased in podocyte-specific β-PIX knockout mice, indicating podocyte loss. Compared with controls, glomeruli from podocyte-specific β-PIX knockout mice and cultured mouse podocytes with β-PIX knockdown exhibited significant reduction in Cdc42 activity. Loss of β-PIX promoted podocyte apoptosis, which was mediated by the reduced activity of the prosurvival transcriptional regulator Yes-associated protein.

Conclusions

These findings indicate that β-PIX is required for the maintenance of podocyte architecture and glomerular function via Cdc42 and its downstream Yes-associated protein activities. This appears to be the first evidence that a Rho–guanine nucleotide exchange factor plays a critical role in podocytes.




doc

Roles of the DOCK-D family proteins in a mouse model of neuroinflammation [Neurobiology]

The DOCK-D (dedicator of cytokinesis D) family proteins are atypical guanine nucleotide exchange factors that regulate Rho GTPase activity. The family consists of Zizimin1 (DOCK9), Zizimin2 (DOCK11), and Zizimin3 (DOCK10). Functions of the DOCK-D family proteins are presently not well-explored, and the role of the DOCK-D family in neuroinflammation is unknown. In this study, we generated three mouse lines in which DOCK9 (DOCK9−/−), DOCK10 (DOCK10−/−), or DOCK11 (DOCK11−/−) had been deleted and examined the phenotypic effects of these gene deletions in MOG35–55 peptide-induced experimental autoimmune encephalomyelitis, an animal model of the neuroinflammatory disorder multiple sclerosis. We found that all the gene knockout lines were healthy and viable. The only phenotype observed under normal conditions was a slightly smaller proportion of B cells in splenocytes in DOCK10−/− mice than in the other mouse lines. We also found that the migration ability of macrophages is impaired in DOCK10−/− and DOCK11−/− mice and that the severity of experimental autoimmune encephalomyelitis was ameliorated only in DOCK10−/− mice. No apparent phenotype was observed for DOCK9−/− mice. Further investigations indicated that lipopolysaccharide stimulation up-regulates DOCK10 expression in microglia and that microglial migration is decreased in DOCK10−/− mice. Up-regulation of C–C motif chemokine ligand 2 (CCL2) expression induced by activation of Toll-like receptor 4 or 9 signaling was reduced in DOCK10−/− astrocytes compared with WT astrocytes. Taken together, our findings suggest that DOCK10 plays a role in innate immunity and neuroinflammation and might represent a potential therapeutic target for managing multiple sclerosis.




doc

The Endocannabinoid System Alleviates Pain in a Murine Model of Cancer-Induced Bone Pain [Drug Discovery and Translational Medicine]

Metastatic breast cancer is prevalent worldwide, and one of the most common sites of metastasis is long bones. Of patients with disease, the major symptom is pain, yet current medications fail to adequately result in analgesic efficacy and present major undesirable adverse effects. In our study, we investigate the potential of a novel monoacylglycerol lipase (MAGL) inhibitor, MJN110, in a murine model of cancer-induced bone pain. Literature has previously demonstrated that MAGL inhibitors function to increase the endogenous concentrations of 2-arachydonylglycerol, which then activates CB1 and CB2 receptors to inhibit inflammation and pain. We demonstrate that administration of MJN110 significantly and dose dependently alleviates spontaneous pain behavior during acute administration compared with vehicle control. In addition, MJN110 maintains its efficacy in a chronic-dosing paradigm over the course of 7 days without signs of receptor sensitization. In vitro analysis of MJN110 demonstrated a dose-dependent and significant decrease in cell viability and proliferation of 66.1 breast adenocarcinoma cells to a greater extent than KML29, an alternate MAGL inhibitor, or the CB2 agonist JWH015. Chronic administration of the compound did not appear to affect tumor burden, as evidenced by radiograph or histologic analysis. Together, these data support the application for MJN110 as a novel therapeutic for cancer-induced bone pain.

SIGNIFICANCE STATEMENT

Current standard of care for metastatic breast cancer pain is opioid-based therapies with adjunctive chemotherapy, which have highly addictive and other deleterious side effects. The need for effective, non–opioid-based therapies is essential, and harnessing the endogenous cannabinoid system is proving to be a new target to treat various types of pain conditions. We present a novel drug targeting the endogenous cannabinoid system that is effective at reducing pain in a mouse model of metastatic breast cancer to bone.




doc

Lidocaine Binding Enhances Inhibition of Nav1.7 Channels by the Sulfonamide PF-05089771 [Articles]

PF-05089771 is an aryl sulfonamide Nav1.7 channel blocker that binds to the inactivated state of Nav1.7 channels with high affinity but binds only weakly to channels in the resting state. Such aryl sulfonamide Nav1.7 channel blockers bind to the extracellular surface of the S1-S4 voltage-sensor segment of homologous Domain 4, whose movement is associated with inactivation. This binding site is different from that of classic sodium channel inhibitors like lidocaine, which also bind with higher affinity to the inactivated state than the resting state but bind at a site within the pore of the channel. The common dependence on gating state with distinct binding sites raises the possibility that inhibition by aryl sulfonamides and by classic local anesthetics might show an interaction mediated by their mutual state dependence. We tested this possibility by examining the state-dependent inhibition by PF-05089771 and lidocaine of human Nav1.7 channels expressed in human embryonic kidney 293 cells. At –80 mV, where a small fraction of channels are in an inactivated state under drug-free conditions, inhibition by PF-05089771 was both enhanced and speeded in the presence of lidocaine. The results suggest that lidocaine binding to the channel enhances PF-05089771 inhibition by altering the equilibrium between resting states (with D4S4 in the inner position) and inactivated states (with D4S4 in the outer position). The gating state–mediated interaction between the compounds illustrates a principle applicable to many state-dependent agents.

SIGNIFICANCE STATEMENT

The results show that lidocaine enhances the degree and rate of inhibition of Nav1.7 channels by the aryl sulfonamide compound PF-05089771, consistent with state-dependent binding by lidocaine increasing the fraction of channels presenting a high-affinity binding site for PF-05089771 and suggesting that combinations of agents targeted to the pore-region binding site of lidocaine and the external binding site of aryl sulfonamides may have synergistic actions.




doc

Impact of a Multidisciplinary, Endocrinologist-Led Shared Medical Appointment Model on Diabetes-Related Outcomes in an Underserved Population

A multidisciplinary endocrinologist-led shared medical appointment (SMA) model showed statistically significant reductions in A1C from baseline over 3 years that were not significantly different from appointments with endocrinologists or primary care providers alone within a resource-poor population. Similarly, the SMA model achieved clinical outcomes on par with endocrinologist-only visits with the added benefit of improving endocrine provider productivity and specialty access for patients. Greater patient engagement with the SMA model was associated with significantly lower A1C.




doc

Are You Still a Postdoc? How My Scientific Identity Intersects with My Immigrant Status

ABSTRACT

Academics in non-tenure-track positions encounter a unique set of challenges on the road toward tenure. Institutionalized policies and lack of mentors are additional burdens for foreign scientists, resulting in representation differences. Becoming a scientist has been a personal and moving journey in which my multiple selves intersect and clash every now and again. My identity as a scientist is a life project and has intersected with my other identities: a young Latina immigrant in Western Europe. This crossroad has molded, and at times, challenged my participation in science.




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Evolutionary insights in Amazonian turtles (Testudines, Podocnemididae): co-location of 5S rDNA and U2 snRNA and wide distribution of Tc1/Mariner [RESEARCH ARTICLE]

Manoella Gemaque Cavalcante, Cleusa Yoshiko Nagamachi, Julio Cesar Pieczarka, and Renata Coelho Rodrigues Noronha

Eukaryotic genomes exhibit substantial accumulation of repetitive DNA sequences. These sequences can participate in chromosomal reorganization events and undergo molecular cooption to interfere with the function and evolution of genomes. In turtles, repetitive DNA sequences appear to be accumulated at probable break points and may participate in events such as non-homologous recombination and chromosomal rearrangements. In this study, repeated sequences of 5S rDNA, U2 snRNA and Tc1/Mariner transposons were amplified from the genomes of the turtles, Podocnemis expansa and Podocnemis unifilis, and mapped by fluorescence in situ hybridization. Our data confirm the 2n=28 chromosomes for these species (the second lowest 2n in the order Testudines). We observe high conservation of the co-located 5S rDNA and U2 snRNA genes on a small chromosome pair (pair 13), and surmise that this represents the ancestral condition. Our analysis reveals a wide distribution of the Tc1/Mariner transposons and we discuss how the mobility of these transposons can act on karyotypic reorganization events (contributing to the 2n decrease of those species). Our data add new information for the order Testudines and provide important insights into the dynamics and organization of these sequences in the chelonian genomes.




doc

The human encounter, attention, and equality: the value of doctor-patient contact




doc

Mothers in medicine: in praise of the home doctor




doc

What I Wish My Doctor Really Knew: The Voices of Patients With Obesity [Reflections]

Few health care professionals receive comprehensive training in how to effectively help their patients with obesity. Yet patients are often wanting, needing, and looking for help when they go to the doctor. We, as a group of patients with obesity, share our common experiences and needs when going to the doctor from a place of honesty and hope, with the assumption that clinicians want to know what their patients really think and feel. Our "wish list" for a treatment plan may represent an ideal, but our hope is that our language will speak to clinicians about how they can help their patients manage their obesity.




doc

Multifunctional Acidocin 4356 Combats Pseudomonas aeruginosa through Membrane Perturbation and Virulence Attenuation: Experimental Results Confirm Molecular Dynamics Simulation [Biotechnology]

A longstanding awareness in generating resistance to common antimicrobial therapies by Gram-negative bacteria has made them a major threat to global health. The application of antimicrobial peptides as a therapeutic agent would be a great opportunity to combat bacterial diseases. Here, we introduce a new antimicrobial peptide (~8.3 kDa) from probiotic strain Lactobacillus acidophilus ATCC 4356, designated acidocin 4356 (ACD). This multifunctional peptide exerts its anti-infective ability against Pseudomonas aeruginosa through an inhibitory action on virulence factors, bacterial killing, and biofilm degradation. Reliable performance over tough physiological conditions and low hemolytic activity confirmed a new hope for the therapeutic setting. Antibacterial kinetic studies using flow cytometry technique showed that the ACD activity is related to the change in permeability of the membrane. The results obtained from molecular dynamic (MD) simulation were perfectly suited to the experimental data of ACD behavior. The structure-function relationship of this natural compound, along with the results of transmission electron microscopy analysis and MD simulation, confirmed the ability of the ACD aimed at enhancing bacterial membrane perturbation. The peptide was effective in the treatment of P. aeruginosa infection in mouse model. The results support the therapeutic potential of ACD for the treatment of Pseudomonas infections.

IMPORTANCE Multidrug-resistant bacteria are a major threat to global health, and the Pseudomonas bacterium with the ability to form biofilms is considered one of the main causative agents of nosocomial infections. Traditional antibiotics have failed because of increased resistance. Thus, finding new biocompatible antibacterial drugs is essential. Antimicrobial peptides are produced by various organisms as a natural defense mechanism against pathogens, inspiring the possible design of the next generation of antibiotics. In this study, a new antimicrobial peptide was isolated from Lactobacillus acidophilus ATCC 4356, counteracting both biofilm and planktonic cells of Pseudomonas aeruginosa. A detailed investigation was then conducted concerning the functional mechanism of this peptide by using fluorescence techniques, electron microscopy, and in silico methods. The antibacterial and antibiofilm properties of this peptide may be important in the treatment of Pseudomonas infections.




doc

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study

Purpose:

KEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).

Patients and Methods:

Pembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary).

Results:

A total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29–80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1–positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6–33.4). ORR was 3.7% (95% CI, 1.0–9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1–negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5–5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8–32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3–5 AEs.

Conclusions:

Pembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.




doc

Novel Endochin-Like Quinolones Exhibit Potent In Vitro Activity against Plasmodium knowlesi but Do Not Synergize with Proguanil [Susceptibility]

Quinolones, such as the antimalarial atovaquone, are inhibitors of the malarial mitochondrial cytochrome bc1 complex, a target critical to the survival of both liver- and blood-stage parasites, making these drugs useful as both prophylaxis and treatment. Recently, several derivatives of endochin have been optimized to produce novel quinolones that are active in vitro and in animal models. While these quinolones exhibit potent ex vivo activity against Plasmodium falciparum and Plasmodium vivax, their activity against the zoonotic agent Plasmodium knowlesi is unknown. We screened several of these novel endochin-like quinolones (ELQs) for their activity against P. knowlesi in vitro and compared this with their activity against P. falciparum tested under identical conditions. We demonstrated that ELQs are potent against P. knowlesi (50% effective concentration, <117 nM) and equally effective against P. falciparum. We then screened selected quinolones and partner drugs using a longer exposure (2.5 life cycles) and found that proguanil is 10-fold less potent against P. knowlesi than P. falciparum, while the quinolones demonstrate similar potency. Finally, we used isobologram analysis to compare combinations of the ELQs with either proguanil or atovaquone. We show that all quinolone combinations with proguanil are synergistic against P. falciparum. However, against P. knowlesi, no evidence of synergy between proguanil and the quinolones was found. Importantly, the combination of the novel quinolone ELQ-300 with atovaquone was synergistic against both species. Our data identify potentially important species differences in proguanil susceptibility and in the interaction of proguanil with quinolones and support the ongoing development of novel quinolones as potent antimalarials that target multiple species.




doc

Tedizolid as Step-Down Therapy following Daptomycin versus Continuation of Daptomycin against Enterococci and Methicillin- and Vancomycin-Resistant Staphylococcus aureus in a Rat Endocarditis Model [Experimental Therapeutics]

Tedizolid (TZD) and daptomycin (DAP) were assessed in a rat endocarditis model against Enterococcus faecalis, Enterococcus faecium (resistant to vancomycin and ampicillin), and Staphylococcus aureus. As a monotherapy, TZD for 5 days was not effective in a comparison with no-treatment controls, while DAP for 5 days was significantly effective against these bacteria. Step-down therapy (DAP for 3 days followed by TZD for 2 days) was as effective as DAP for 5 days and was comparable to 3 days of DAP plus ceftriaxone against all bacteria and to 3 days of DAP plus gentamicin against E. faecalis OG1RF.




doc

Comparative single-cell RNA sequencing (scRNA-seq) reveals liver metastasis-specific targets in a patient with small intestinal neuroendocrine cancer [RESEARCH REPORT]

Genomic analysis of a patient's tumor is the cornerstone of precision oncology, but it does not address whether metastases should be treated differently. Here we tested whether comparative single-cell RNA sequencing (scRNA-seq) of a primary small intestinal neuroendocrine tumor to a matched liver metastasis could guide the treatment of a patient's metastatic disease. Following surgery, the patient was put on maintenance treatment with a somatostatin analog. However, the scRNA-seq analysis revealed that the neuroendocrine epithelial cells in the liver metastasis were less differentiated and expressed relatively little SSTR2, the predominant somatostatin receptor. There were also differences in the tumor microenvironments. RNA expression of vascular endothelial growth factors was higher in the primary tumor cells, reflected by an increased number of endothelial cells. Interestingly, vascular expression of the major VEGF receptors was considerably higher in the liver metastasis, indicating that the metastatic vasculature may be primed for expansion and susceptible to treatment with angiogenesis inhibitors. The patient eventually progressed on Sandostatin, and although consideration was given to adding an angiogenesis inhibitor to her regimen, her disease progression involved non-liver metastases that had not been characterized. Although in this specific case comparative scRNA-seq did not alter treatment, its potential to help guide therapy of metastatic disease was clearly demonstrated.




doc

Race May Not Impact Endocrine Therapy-Related Changes in Breast Density

Background:

Reduction in breast density may be a biomarker of endocrine therapy (ET) efficacy. Our objective was to assess the impact of race on ET-related changes in volumetric breast density (VBD).

Methods:

This retrospective cohort study assessed longitudinal changes in VBD measures in women with estrogen receptor–positive invasive breast cancer treated with ET. VBD, the ratio of fibroglandular volume (FGV) to breast volume (BV), was measured using Volpara software. Changes in measurements were evaluated using a multivariable linear mixed effects model.

Results:

Compared with white women (n = 191), black women (n = 107) had higher rates of obesity [mean ± SD body mass index (BMI) 34.5 ± 9.1 kg/m2 vs. 30.6 ± 7.0 kg/m2, P < 0.001] and premenopausal status (32.7% vs. 16.7%, P = 0.002). Age- and BMI-adjusted baseline FGV, BV, and VBD were similar between groups. Modeled longitudinal changes were also similar: During a follow-up of 30.7 ± 15.0 months (mean ± SD), FGV decreased over time in premenopausal women (slope = –0.323 cm3; SE = 0.093; P = 0.001), BV increased overall (slope = 2.475 cm3; SE = 0.483; P < 0.0001), and VBD decreased (premenopausal slope = –0.063%, SE = 0.011; postmenopausal slope = –0.016%, SE = 0.004; P < 0.0001). Race was not significantly associated with these longitudinal changes, nor did race modify the effect of time on these changes. Higher BMI was associated with lower baseline VBD (P < 0.0001). Among premenopausal women, VBD declined more steeply for women with lower BMI (time x BMI, P = 0.0098).

Conclusions:

Race does not appear to impact ET-related longitudinal changes in VBD.

Impact:

Racial disparities in estrogen receptor–positive breast cancer recurrence and mortality may not be explained by differential declines in breast density due to ET.




doc

Dốc sạch vốn liếng vào đất rồi ôm nợ vì tư tưởng “1 vốn 4 lời”

Dốc hết vốn liếng vào đất để mong thành đại gia nhưng dịch bệnh khiến thu nhập bị cắt giảm, tiền mặt thiếu hụt trong khi có quá nhiều khoản phải chi nên nhiều nhà đầu tư quay cuồng trong nợ nần.




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TP.HCM: Tín dụng vào bất động sản vẫn tăng nhưng thu ngân sách “tụt dốc”

Tín dụng “rót” vào bất động sản cả nước trong 8 tháng đầu năm 2019 là 1,5 triệu tỷ đồng (tăng gần 14,6% so với cuối năm 2018), vào TP.HCM là 269.000 tỷ đồng (chỉ tăng 3,41% so với cuối năm 2018). Đáng chú ý, trong khi nguồn thu ngân sách từ đất đai của cả nước tăng thì số thu từ tiền sử dụng đất dự án ở TP.HCM lại tiếp tục sụt giảm.




doc

BÁN ĐẤT THỔ CƯ 100%, NGAY RESORT BIỂN DỐC LẾT.XÂY KHÁCH SẠN, NHÀ HÀNG RẤT TỐT.

BÁN ĐẤT THỔ CƯ 100%, NGAY RESORT BIỂN DỐC LẾT. **Dốc Lết là 1 trong những bãi biển ĐẸP nhất hành tinh. -DIỆN TÍCH: 245.3m2 - NGANG 12M - DÀI 22M. -VỊ TRÍ: Mặt tiền đường Mê Linh - Rộng 12 mét. Đường nhựa. ***Giá bán: 7,5 TRIỆU/M2 . Bao sang tên sổ hồng. CAM KẾT GIÁ THẤP HƠN THỊ T...




doc

Skydio's Dock in a Box Enables Long-Term Autonomy for Drone Applications

This cozy little box provides a remote home for Skydio's fully autonomous obstacle-avoiding drone





doc

Circus of Books review – tender doc about family life and gay porn

An affectionate and absorbing documentary from film-maker Rachel Mason about her devout parents, who ran a famous adult bookstore in early-80s LA

Here is a documentary with an absorbing and unexpectedly complicated story to tell, whose paradoxes and sadnesses are not entirely resolved by the end. Artist and film-maker Rachel Mason has created an affectionate portrait of her elderly parents, Karen and Barry, who in many ways are like one of the (fictional) old couples in When Harry Met Sally.

Karen is a former journalist, devoutly Jewish, and Barry is a former special visual effects engineer who worked on Stanley Kubrick’s 2001 and invented a modification for kidney dialysis machines. But they found themselves in a tough financial spot in the early 1980s and took over Circus of Books, a gay porn bookstore in Los Angeles that also sold movies called things like Confessions of a Two Dick Slut and Don’t Drop the Soap, and was one of Larry Flynt’s first distribution points. Under their shrewd management, the store boomed, opened another branch and became a well-known meeting place for LGBT people, while all the time, the Masons were a conventional family who kept their three children well away from the business. Karen movingly – and honestly – recounts how upset she was to discover that one of her sons was gay: the business and family life were that separate.

Continue reading...




doc

Wuhan’s covid-19 crisis: Intensive care doctors share their stories

Three doctors reveal what it was like at the heart of Hubei province’s coronavirus crisis, as the epidemic peaked in Wuhan and spread elsewhere





doc

Flynn prosecutor's contested claims impacted judge's pivotal December opinion, FBI docs suggest

Newly released FBI documents suggest a federal judge in Washington was swayed by apparent misrepresentations from a top prosecutor when he issued a memorandum opinion in December 2019 -- a ruling that marked one of the lowest points in former U.S. national security adviser Michael Flynn's effort to withdraw a guilty plea on a charge of lying to investigators.



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doc

Ohio State University will pay $41M to 162 men who were sexually abused by a team doctor

"The process will account for wide variations in abuse and provide a pathway for survivor healing," Richard Schulte, one of the lawyers for the men, said in the university's statement.




doc

Three junior doctors inundated with offers for new home after south London landlord &apos;not happy to let them stay&apos;

Follow our live Covid-19 update HERE Coronavirus: The symptoms




doc

Hackney doctor who warned PM about urgent need for PPE dies after contracting coronavirus

Coronavirus: the symptoms Read our LIVE updates on the coronavirus here




doc

Son of NHS doctor Abdul Mabud Chowdhury &apos;proud&apos; of dad for raising PPE concerns before he died

Read our live updates on coronavirus HERE Coronavirus: The symptoms




doc

Half of A&amp;E staff at one hospital test positive for coronavirus, doctor says

Read our live coronavirus updates HERE




doc

Man jailed after attacking doctor outside A&amp;E during coronavirus pandemic

Follow our live coronavirus updates HERE Coronavirus: the symptoms




doc

Brazil&apos;s Christ the Redeemer illuminated as doctor to commend those fighting coronavirus outbreak

Follow our live coronavirus updates HERE Coronavirus: The symptoms




doc

Facial protection will become the norm in wake of coronavirus, top WHO doctor warns

Dr David Nabarro, the WHO's Covid-19 envoy, said that people would need to become accustomed to a "new reality".




doc

&apos;Our family has been torn apart&apos;: doctor dies weeks from retiring

Hospital consultant and ward housekeeper are among latest NHS victims in London Follow our live coronavirus updates here Coronavirus: the symptoms




doc

David vs Goliath: Haye swaps boxing ring for poker table in new Amazon Prime documentary

When David Haye agreed to swap the boxing gym for a poker table and challenge the world's best, the former heavyweight and cruiserweight world champion admits he did not know what he was letting himself in for.




doc

Britain will be hit by further waves of coronavirus with up to 40k deaths in first wave alone, leading doctor warns

Britain will face "further waves" of Covid-19 and could reach 40,000 deaths in this first wave alone, a leading physician has warned.




doc

Doctors and nurses fear protective kit could run out amid coronavirus outbreak as NHS faces crisis

Some hospitals face running out of personal protection equipment this weekend amid growing concerns over supplies amid the coronavirus outbreak.




doc

Top doctor: Care home shielding &apos;completely failed&apos; during coronavirus pandemic

Shielding of care and nursing homes has "completely failed", a GP and academic said today amid fears that the number of elderly people who have died is far higher than official statistics show.




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Prince Harry warned Meghan&apos;s father Thomas that speaking to press would &apos;backfire&apos;, court documents show




doc

Doctors in China wake from fighting virus on life support to find skin has changed colour

Two doctors in Wuhan who survived coronavirus after long battles on life support found their skin changed colour as a result of their treatment.




doc

Chatham Dockside: Man arrested after &apos;gunshots&apos; fired from flat balcony in Kent

A man in his 30s has been arrested in Chatham following reports of gunshots being fired from the balcony of an apartment block.




doc

Doctors perform emotional rendition of Ave Maria to celebrate nurse&apos;s recovery from coronavirus

Doctors performed an emotional rendition of Ave Maria to celebrate the recovery of a fellow nurse from the coronavirus.




doc

Married doctors bring legal challenge against Government over PPE shortage

A pregnant doctor and her husband are bringing a legal challenge against the Government which questions the lawfulness of current guidance and a failure to source PPE.




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&apos;Superhero&apos; doctor who died from Covid-19 &apos;pleaded for PPE days before contracting disease&apos;

An NHS doctor who died after contracting coronavirus had reportedly pleaded with his hospital to provide protective equipment (PPE) in the days before he caught the disease.