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Protein crystallization plays a central role in structural biology. Despite this, the process of crystallization remains poorly understood and highly empirical, with crystal contacts, lattice packing arrangements and space group preferences being largely unpredictable. Programming protein crystallization through precisely engineered side-chain-side-chain interactions across protein-protein interfaces is an outstanding challenge. Here we develop a general computational approach for designing three-dimensional protein crystals with prespecified lattice architectures at atomic accuracy that hierarchically constrains the overall number of degrees of freedom of the system. We design three pairs of oligomers that can be individually purified, and upon mixing, spontaneously self-assemble into >100 µm three-dimensional crystals. The structures of these crystals are nearly identical to the computational design models, closely corresponding in both overall architecture and the specific protein-protein interactions. The dimensions of the crystal unit cell can be systematically redesigned while retaining the space group symmetry and overall architecture, and the crystals are extremely porous and highly stable. Our approach enables the computational design of protein crystals with high accuracy, and the designed protein crystals, which have both structural and assembly information encoded in their primary sequences, provide a powerful platform for biological materials engineering.

ObjectiveMarijuana, tobacco and alcohol use are prevalent among people with HIV and may adversely affect kidney function in this population. We determined the association of use of these substances with estimated glomerular filtration rate (eGFR) among women with HIV (WWH) and women without HIV.DesignWe undertook a repeated measures study of 1043 WWH and 469 women without HIV within the United States Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-seropositive and HIV-seronegative women.MethodsWe quantified substance exposures using semi-annual questionnaires. Using pooled eGFR data from 2009 to 2019, we used linear regression models with multivariable generalized estimating equations to ascertain associations between current and cumulative substance use exposures with eGFR, adjusting for sociodemographics, chronic kidney disease risk factors and HIV-related factors.ResultsMarijuana use of 1-14 days/month versus 0 days/month was associated with 3.34 ml/min per 1.73 m 2 [95% confidence interval (CI) -6.63, -0.06] lower eGFR and marijuana use of >0.02-1.6 marijuana-years versus 0-0.2 marijuana-years was associated with 3.61 ml/min per 1.73 m 2 (95% CI -5.97, -1.24) lower eGFR. Tobacco use was not independently associated with eGFR. Alcohol use of seven or more drinks/week versus no drinks/week was associated with 5.41 ml/min per 1.73 m 2 (95% CI 2.34, 8.48) higher eGFR and alcohol use of >0.7-4.27 drink-years and >4.27 drink-years versus 0-0.7 drink-years were associated with 2.85 ml/min per 1.73 m 2 (95% CI 0.55, 5.15) and 2.26 ml/min per 1.73 m 2 (95% CI 0.33, 4.20) higher eGFR, respectively.ConclusionAmong a large cohort of WWH and women without HIV, marijuana use was associated with a lower eGFR while alcohol use was associated with a higher eGFR.

Introduction: Undocumented immigrants are excluded from benefits that help compensate for scheduled outpatient hemodialysis (HD), compelling them to use emergency departments (ED) for HD. Consequently, these patients can receive “emergency-only” HD after presenting to the ED with critical illness due to untimely dialysis. Our objective was to describe the impact of emergency-only HD on hospital cost and resource utilization in a large academic health system that includes public and private hospitals.  Methods: This retrospective observational study of health and accounting records took place at five teaching hospitals (one public, four private) over 24 consecutive months from January 2019 to December 2020. All patients had emergency and/or observation visits, renal failure codes (International Classification of Diseases, 10th Rev, Clinical Modification), emergency HD procedure codes, and an insurance status of “self-pay.” Primary outcomes included frequency of visits, total cost, and length of stay (LOS) in the observation unit. Secondary objectives included evaluating the variation in resource use between persons and comparing these metrics between the private and public hospitals. Results: A total of 15,682 emergency-only HD visits were made by 214 unique persons, for an average of 36.6 visits per person per year. The average cost per visit was $1,363, for an annual total cost of $10.7 million. The average LOS was 11.4 hours. This resulted in 89,027 observation-hours annually, or 3,709 observation-days. The public hospital dialyzed more patients compared to the private hospitals, especially due to repeat visits by the same persons. Conclusion: Health policies that limit hemodialysis of uninsured patients to the ED are associated with high healthcare costs and a misuse of limited ED and hospital resources.

For countries to rapidly decarbonize, they need strong leadership, according to both academic studies and popular accounts. But leadership is difficult to measure, and its importance is unclear. We use original data to investigate the role of presidents, prime ministers, and monarchs in 155 countries from 1990 to 2015 in changing their countries' gasoline taxes and subsidies. Our findings suggest that the impact of leaders on fossil fuel taxes and subsidies is surprisingly limited and often ephemeral. This holds true regardless of the leader's age, gender, education, or political ideology. Rulers who govern during an economic crisis perform no better or worse than other rulers. Even presidents and prime ministers who were recognized by the United Nations for environmental leadership had no more success than other leaders in reducing subsidies or raising fuel taxes. Where leaders appear to play an important role-primarily in countries with large subsidies-their reforms often failed, with subsidies returning to prereform levels within the first 12 mo 62% of the time, and within 5 y 87% of the time. Our findings suggest that leaders of all types find it exceptionally hard to raise the cost of fossil fuels for consumers. To promote deep decarbonization, leaders are likely to have more success with other types of policies, such as reducing the costs and increasing the availability of renewable energy.

Although steady progress has been achieved toward upcycling waste CO2 through diverse catalytic strategies, each approach has distinct limitations, hampering the generation of complex products like sugars. Here, we provide a roadmap that evaluates the feasibility associated with state-of-the-art electrochemical processes eligible for converting CO2 into glycolaldehydes and formaldehydes, both essential components for sugar generation through the formose reaction. We establish that even in low concentrations, glycolaldehyde plays a crucial role as an autocatalytic initiator during sugar formation and identify formaldehyde production as a bottleneck. Our study demonstrates the chemical resilience of the formose reaction successfully carried out in the chemically complex CO2 electrolysis product stream. This work reveals that CO2-initiated sugars constitute an adequate feedstock for fast-growing and genetically modifiable Escherichia coli. Altogether, we introduce a roadmap, supported by experimental evidence, that pushes the boundaries of product complexity achievable from CO2 electroconversion while integrating CO2 into life-sustaining sugars.

ObjectiveTo assess differences in rates of postpartum hospitalisations among homeless women compared with non-homeless women.DesignCross-sectional secondary analysis of readmissions and emergency department (ED) utilisation among postpartum women using hierarchical regression models adjusted for age, race/ethnicity, insurance type during delivery, delivery length of stay, maternal comorbidity index score, other pregnancy complications, neonatal complications, caesarean delivery, year fixed effect and a birth hospital random effect.SettingNew York statewide inpatient and emergency department databases (2009-2014).Participants82 820 and 1 026 965 postpartum homeless and non-homeless women, respectively.Main outcome measuresPostpartum readmissions (primary outcome) and postpartum ED visits (secondary outcome) within 6 weeks after discharge date from delivery hospitalisation.ResultsHomeless women had lower rates of both postpartum readmissions (risk-adjusted rates: 1.4% vs 1.6%; adjusted OR (aOR) 0.87, 95% CI 0.75 to 1.00, p=0.048) and ED visits than non-homeless women (risk-adjusted rates: 8.1% vs 9.5%; aOR 0.83, 95% CI 0.77 to 0.90, p

BackgroundSexual health is generally considered an integral part of medical and allied healthcare professional training. However, many medical schools do not offer this as a mandatory curriculum, or minimize it. Sexual health as an academic area was introduced in the 1970s, but there have been few cohort evaluations of its impact. This was limited by the availability of few psychometric scales for evaluation. We evaluated the full, mandatory, sexual health course in year 1 medicine at a large state university in the Midwest US, including the course with lectures; panels and tutorials; a video app to give students feedback on their sexual history taking skills; and a 3-station sexual history OSCE at the end of the course.ResultsSeventy-four medical students (43% of the course cohort) volunteered, for an incentive, to complete evaluation materials pre- and post-course. We used the Sexual Health Education for Professionals Scale (SHEPS), designed and with appropriate psychometric standardization for such evaluation. The SHEPS data covers 7-point Likert scale ratings of 37 patient situations, asking first how well the student could communicate with such a patient, and on the second part how much knowledge they have to care for such a patient. The third subscale examines personal sexual attitudes and beliefs. Data indicated that the matched pretest-posttest ratings for skills and knowledge were all statistically significant and with very large effect sizes. Few of the attitude subscale items were significant and if so, had small effect sizes. Sexual attitudes and beliefs may be well-formed before entry into medical school, and sexual health teaching and learning has minimal effect on sexual attitudes in this US sample. However, using the 3 sexuality OSCE cases scores as outcomes, two of the 26 attitude-belief items predicted > 24% of the variance.ConclusionsThe sexual health course produced major changes in Communications with patients sexual health skills and Knowledge of sexual health, but little change in personal Attitudes about sexuality. These data suggest that personal attitude change is not essential for teaching US medical students to learn about sexual health and sexual function and dysfunction, and comfortably take a comprehensive sexual history.