Book Review - Promoting Law Student and Lawyer Well-Being in Australia and Beyond

Promoting Law Student and Lawyer Well-Being in Australia and Beyond is a book on how to alleviate pathological levels of psychological distress (‘distress’) in people who choose to study law for legal practice (‘legal profession’). The book showcases the Australian Wellness For Law Network’s normative orthodoxy, that the entire legal academic community must be, or become, responsible for law students’ mental health

Development of a protocol for maintaining viability while shipping organoid-derived retinal tissue.

Retinal organoid technology enables generation of an inexhaustible supply of three-dimensional retinal tissue from human pluripotent stem cells (hPSCs) for regenerative medicine applications. The high similarity of organoid-derived retinal tissue and transplantable human fetal retina provides an opportunity for evaluating and modeling retinal tissue replacement strategies in relevant animal models in the effort to develop a functional retinal patch to restore vision in patients with profound blindness caused by retinal degeneration. Because of the complexity of this very promising approach requiring specialized stem cell and grafting techniques, the tasks of retinal tissue derivation and transplantation are frequently split between geographically distant teams. Delivery of delicate and perishable neural tissue such as retina to the surgical sites requires a reliable shipping protocol and also controlled temperature conditions with damage-reporting mechanisms in place to prevent transplantation of tissue damaged in transit into expensive animal models. We have developed a robust overnight tissue shipping protocol providing reliable temperature control, live monitoring of the shipment conditions and physical location of the package, and damage reporting at the time of delivery. This allows for shipping of viable (transplantation-competent) hPSC-derived retinal tissue over large distances, thus enabling stem cell and surgical teams from different parts of the country to work together and maximize successful engraftment of organoid-derived retinal tissue. Although this protocol was developed for preclinical in vivo studies in animal models, it is potentially translatable for clinical transplantation in the future and will contribute to developing clinical protocols for restoring vision in patients with retinal degeneration

Prevalence of Hepatitis C Virus Antibody in Patients With Sexually Transmitted Diseases Attending a Harrisburg, PA, STD Clinic

Objective: The prevalence of hepatitis B and hepatitis C in a sexually transmitted disease (STD) clinic population was studied, along with the prevalence of various STD agents, in an attempt to identify possible STD markers for the hepatitis C virus and help delineate the role of hepatitis C as an STD. The hepatitis C antibody rates found in the STD clinic were also compared with those found among patients attending a local OB/GYN clinic and those enrolled in a blood donor program, all from the same geographical area

Neural Correlates of Speech Processing in Prelingually Deafened Children and Adolescents with Cochlear Implants

Prelingually deafened children with cochlear implants stand a good chance of developing satisfactory speech performance. Nevertheless, their eventual language performance is highly variable and not fully explainable by the duration of deafness and hearing experience. In this study, two groups of cochlear implant users (CI groups) with very good basic hearing abilities but non-overlapping speech performance (very good or very bad speech performance) were matched according to hearing age and age at implantation. We assessed whether these CI groups differed with regard to their phoneme discrimination ability and auditory sensory memory capacity, as suggested by earlier studies. These functions were measured behaviorally and with the Mismatch Negativity (MMN). Phoneme discrimination ability was comparable in the CI group of good performers and matched healthy controls, which were both better than the bad performers. Source analyses revealed larger MMN activity (155–225 ms) in good than in bad performers, which was generated in the frontal cortex and positively correlated with measures of working memory. For the bad performers, this was followed by an increased activation of left temporal regions from 225 to 250 ms with a focus on the auditory cortex. These results indicate that the two CI groups developed different auditory speech processing strategies and stress the role of phonological functions of auditory sensory memory and the prefrontal cortex in positively developing speech perception and production

Global, Regional, and National Sex-Specific Burden and Control of the HIV Epidemic, 1990-2019, for 204 Countries and Territories: The Global Burden of Diseases Study 2019

Background The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. Methods To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold \u3e75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold \u3c0.03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold \u3c1.0). Findings In 2019, there were 36.8 million (95% uncertainty interval [UI] 35.1-38.9) people living with HIV worldwide. There were 0.84 males (95% UI 0.78-0.91) per female living with HIV in 2019, 0.99 male infections (0.91-1.10) for every female infection, and 1.02 male deaths (0.95-1.10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28.52% decrease in incident cases, 95% UI 19.58-35.43, and a 39.66% decrease in deaths, 36.49-42.36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0.05 (95% UI 0.05-0.06) and the global incidence-to-mortality ratio was 1.94 (1.76-2.12). No regions met suggested thresholds for progress. Interpretation Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics

Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging

SummaryEver since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible

Crystal structure of a copper-mefenamate complex solvated with diglyme and water

In the copper-mefenamate complex, the asymmetric unit comprises a Cu(II) cation coordinated to two mefenamate ligands solvated with a water molecule and diglyme molecule. The complex adopts a paddlewheel motif and is compared to structural analogues crystallised with dimethylformamide and dimethyl sulfoxide

Attitudes towards terminal sedation: an empirical survey among experts in the field of medical ethics

BACKGROUND: "Terminal sedation" regarded as the use of sedation in (pre-)terminal patients with treatment-refractory symptoms is controversially discussed not only within palliative medicine. While supporters consider terminal sedation as an indispensable palliative medical treatment option, opponents disapprove of it as "slow euthanasia". Against this background, we interviewed medical ethics experts by questionnaire on the term and the moral acceptance of terminal sedation in order to find out how they think about this topic. We were especially interested in whether experts with a professional medical and nursing background think differently about the topic than experts without this background. METHODS: The survey was carried out by questionnaire; beside the provided answering options free text comments were possible. As test persons we chose the 477 members of the German Academy for Ethics in Medicine, an interdisciplinary society for medical ethics. RESULTS: 281 completed questionnaires were returned (response rate = 59%). The majority of persons without medical background regarded "terminal sedation" as an intentional elimination of consciousness until the patient's death occurs; persons with a medical background generally had a broader understanding of the term, including light or intermittent forms of sedation. 98% of the respondents regarded terminal sedation in dying patients with treatment-refractory physical symptoms as acceptable. Situations in which the dying process has not yet started, in which untreatable mental symptoms are the indication for terminal sedation or in which life-sustaining measures are withdrawn during sedation were evaluated as morally difficult. CONCLUSION: The survey reveals a great need for research and discussion on the medical indication as well as on the moral evaluation of terminal sedation. Prerequisite for this is a more precise terminology which describes the circumstances of the sedation

Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant

Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants