Exposed Online: Why the New Federal Health Privacy Regulation Doesn't Offer Much Protection to Internet Users

Provides an analysis of how the HIPAA regulation may or may not cover consumer-oriented health Web sites and Internet based health care. Comments on what new standards will be required for those sites covered by the regulation

Total synthesis of the azolemycins

The first total syntheses of newly isolated polyazole natural products azolemycins A–D, along with the synthesis of the tetra-oxazole non-natural analogue, are described

A bioinformatic approach to identify new potential resistance relevant amino acid substitutions (AAS) in HIV-1 protease (H1P)

Background: Predicting potential drug resistance mutations are important when evaluating protein-drug interactions of potential new antiviral drugs. Here we used evolutionary data from the Retroviral Aspartyl Protease (RVP) family (PF00077, 54135 sequences) to estimate plausible PI resistant-associated AAS within the H1P. Methods: Using a Hidden Markov Model (HMM) of the RVP family probabilities were extracted for each possible AAS limited to the 38 positions reported in the IAS drug resistance listing for H1P (December 2008 version). The HMM is a dynamic Bayesian network, modeling sequences of amino acids. The HMM is based on curated and representative sequences from the RVP family. Results: Theoretically 760 AAS (20 × 38) are possible for the 38 evaluated positions within the H1P. Of these, the RVP-HMM detected a total of 229 AAS (30.1%) with a probability above 1/20 (0.05). Of the 229 AAS, 51 (70%) were among the 73 AAS included in the IAS listing as PI-resistant mutations, leaving 178 AAS with P > 0.05 as evolutionary plausible. Conclusion: Based on exploration of the RVP family by HMM, 70% of the established PI-resistant associated AAS could be predicted to occur. Additional 178 AAS was identified as evolutionary plausible and potentially could allow for drug-resistance. In conclusion, we provide a probability landscape of plausible/unfavorable AAS based on inherited structure through evolution and genetic distance, which could prove useful for future drug design

NMR-based assignment of isoleucine vs allo-isoleucine stereochemistry

A simple 1H and 13C NMR spectrometric analysis is demonstrated that permits differentiation of isoleucine and allo-isoleucine residues by inspection of the chemical shift and coupling constants of the signals associated with the proton and carbon at the α-stereocentre. This is applied to the estimation of epimerisation during metal-free N-arylation and peptide coupling reactions

Unique post-translational oxime formation in the biosynthesis of the azolemycin complex of novel ribosomal peptides from Streptomyces sp. FXJ1.264

Streptomycetes are a rich source of bioactive specialized metabolites, including several examples of the rapidly growing class of ribosomally-biosynthesized and post-translationally-modified peptide (RiPP) natural products. Here we report the discovery from Streptomyces sp. FXJ1.264 of azolemycins A–D, a complex of novel linear azole-containing peptides incorporating a unique oxime functional group. Bioinformatics analysis of the Streptomyces sp. FXJ1.264 draft genome sequence identified a cluster of genes that was hypothesized to be responsible for elaboration of the azolemycins from a ribosomally-biosynthesized precursor. Inactivation of genes within this cluster abolished azolemycin production, consistent with this hypothesis. Moreover, mutants lacking the azmE and azmF genes accumulated azolemycin derivatives lacking the O-methyl groups and an amino group in place of the N-terminal oxime (as well as proteolysed derivatives), respectively. Thus AzmE, a putative S-adenosyl methionine-dependent methyl transferase, is responsible for late-stage O-methylation reactions in azolemycin biosynthesis and AzmF, a putative flavin-dependent monooxygenase, catalyzes oxidation of the N-terminal amino group in an azolemycin precursor to the corresponding oxime. To the best of our knowledge, oxime formation is a hitherto unknown posttranslational modification in RiPP biosynthesis

Last male sperm precedence in a polygamous squid

Differential sperm usage from consecutive matings, or sperm precedence, is vital in determining male reproductive success and the outcome of sperm competition for many organisms. Sperm precedence also has significant consequences for mating system dynamics, including both male and female adaptations for increasing reproductive success and avoiding the costs of mating. Despite sexual selection being a strong driver of reproductive behaviour and morphology in cephalopods, surprisingly few studies have investigated sperm dynamics in this group. To redress this gap, we experimentally quantified sperm precedence patterns in the dumpling squid, Euprymna tasmanica, controlling for recent male mating history (first vs. second mating), mating position, and mating frequency. We found that the last male to mate gains an advantage in this system, with the second mating male siring up to 75% of offspring at the beginning of the laying period. The proportion of offspring attributable to the second mating male decreases to 54% by the end of the laying period, potentially as a result of changes in the velocity or number of sperm released from spermatangia over time. There is also significant variation among females in patterns of sperm precedence. This variation was not associated with whether it was the male's first or second mating, male mass, the duration of copulation or the number of pumps (sperm removal behaviour) by the second male. If widespread in cephalopods, last male sperm precedence could help to explain the evolution of mate guarding (or long copulation duration) and sperm removal behaviour in this group

Factors affecting consistency and accuracy in identifying modern macroperforate planktonic foraminifera

Planktonic foraminifera are widely used in biostratigraphic, palaeoceanographic and evolutionary studies, but the strength of many study conclusions could be weakened if taxonomic identifications are not reproducible by different workers. In this study, to assess the relative importance of a range of possible reasons for among-worker disagreement in identification, 100 specimens of 26 species of macroperforate planktonic foraminifera were selected from a core-top site in the subtropical Pacific Ocean. Twenty-three scientists at different career stages – including some with only a few days experience of planktonic foraminifera – were asked to identify each specimen to species level, and to indicate their confidence in each identification. The participants were provided with a species list and had access to additional reference materials. We use generalised linear mixed-effects models to test the relevance of three sets of factors in identification accuracy: participant-level characteristics (including experience), species-level characteristics (including a participant’s knowledge of the species) and specimen-level characteristics (size, confidence in identification). The 19 less experienced scientists achieve a median accuracy of 57 %, which rises to 75 % for specimens they are confident in. For the 4 most experienced participants, overall accuracy is 79 %, rising to 93 % when they are confident. To obtain maximum comparability and ease of analysis, everyone used a standard microscope with only 35× magnification, and each specimen was studied in isolation. Consequently, these data provide a lower limit for an estimate of consistency. Importantly, participants could largely predict whether their identifications were correct or incorrect: their own assessments of specimen-level confidence and of their previous knowledge of species concepts were the strongest predictors of accuracy

Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review

Objectives To determine the extent and nature of changes in utilisation of healthcare services during COVID-19 pandemic.Design Systematic review.Eligibility Eligible studies compared utilisation of services during COVID-19 pandemic to at least one comparable period in prior years. Services included visits, admissions, diagnostics and therapeutics. Studies were excluded if from single centres or studied only patients with COVID-19.Data sources PubMed, Embase, Cochrane COVID-19 Study Register and preprints were searched, without language restrictions, until 10 August, using detailed searches with key concepts including COVID-19, health services and impact.Data analysis Risk of bias was assessed by adapting the Risk of Bias in Non-randomised Studies of Interventions tool, and a Cochrane Effective Practice and Organization of Care tool. Results were analysed using descriptive statistics, graphical figures and narrative synthesis.Outcome measures Primary outcome was change in service utilisation between prepandemic and pandemic periods. Secondary outcome was the change in proportions of users of healthcare services with milder or more severe illness (eg, triage scores).Results 3097 unique references were identified, and 81 studies across 20 countries included, reporting on >11 million services prepandemic and 6.9 million during pandemic. For the primary outcome, there were 143 estimates of changes, with a median 37% reduction in services overall (IQR −51% to −20%), comprising median reductions for visits of 42% (−53% to −32%), admissions 28% (−40% to −17%), diagnostics 31% (−53% to −24%) and for therapeutics 30% (−57% to −19%). Among 35 studies reporting secondary outcomes, there were 60 estimates, with 27 (45%) reporting larger reductions in utilisation among people with a milder spectrum of illness, and 33 (55%) reporting no difference.Conclusions Healthcare utilisation decreased by about a third during the pandemic, with considerable variation, and with greater reductions among people with less severe illness. While addressing unmet need remains a priority, studies of health impacts of reductions may help health systems reduce unnecessary care in the postpandemic recovery.PROSPERO registration number CRD42020203729