Few investigations have explored temperature and birth outcomes. In a retrospective cohort study, we examined apparent temperature, a combination of temperature and relative humidity, and term low birth weight (LBW) among 43,629 full-term LBW infants and 2,032,601 normal-weight infants in California (1999-2013). The California Department of Public Health provided birth certificate data, while meteorological data came from the California Irrigation Management Information System, US Environmental Protection Agency, and National Centers for Environmental Information. After considering several temperature metrics, we observed the best model fit for term LBW over the full gestation (per 10-degrees-Fahrenheit (°F) increase in apparent temperature, 13.0% change, 95% confidence interval: 4.1, 22.7) above 55°F, and the greatest association was for third-trimester exposure above 60°F (15.8%, 95% confidence interval: 5.0, 27.6). Apparent temperature during the first month of pregnancy exhibited no significant risk, while the first trimester had a significantly negative association, and second trimester, last month, and last 2 weeks had slightly increased risks. Mothers who were black or older, delivered male infants, or gave birth during the warm season had infants at the highest risks. This study provides further evidence for adverse birth outcomes from heat exposure for vulnerable subgroups of pregnant women.

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Secretins are multimeric outer membrane pore-forming proteins found in complex export systems in Gram-negative bacteria. All type III secretion systems (T3SSs) have a secretin, and one of these is the YsaC secretin of the chromosomally encoded Ysa T3SS of Yersinia enterocolitica. In some cases, pilotin proteins, which are outer membrane lipoproteins, are required for their cognate secretins to multimerize and/or localize to the outer membrane. However, if secretin multimers mislocalize to the inner membrane, this can trigger the protective phage shock protein (Psp) stress response. During a screen for mutations that suppress YsaC toxicity to a psp null strain, we isolated several independent mutations predicted to increase expression of the YE3559 gene within the Ysa pathogenicity island. YE3559, which we have named ysaP, is predicted to encode a small outer membrane lipoprotein, and this location was confirmed by membrane fractionation. Elevated ysaP expression increased the steady-state level of YsaC but made it less toxic to a psp null strain, and it also decreased YsaC-dependent induction of psp gene expression. Subsequent experiments showed that YsaP was not required for YsaC multimerization but was required for the multimers to localize to the outer membrane. Consistent with this, a ysaP null mutation compromised protein export by the Ysa T3SS. All these observations suggest that YsaP is the pilotin for the YsaC secretin. This is only the second pilotin to be characterized for Yersinia and one of only a small number of pilotins described for all bacteria. IMPORTANCESecretins are essential for the virulence of many bacterial pathogens and also play roles in surface attachment, motility, and competence. This has generated considerable interest in understanding how secretins function. However, their fundamental differences from typical outer membrane proteins have raised various questions about secretins, including how they are assembled into outer membrane multimers. Pilotin proteins facilitate the assembly of some secretins, but only a small number of pilotins have been identified, slowing efforts to understand common and distinct features of secretin assembly. This study provides an important advance by identifying a novel member of the pilotin family and also demonstrating a method of pilotin discovery that could be broadly applied.

Aim: Summarize the literature assessing biomarkers in predicting efficacy of anti-PD-1 therapy for patients with high-risk unresectable or metastatic melanoma. Materials & methods: Relevant studies were identified via a systematic literature review. Results: About 334 unique biomarkers or biomarker combinations were identified from 121 citations. Neutrophil-to-lymphocyte ratio was the most frequently studied biomarker, followed by C-reactive protein. Fifty-nine biomarkers were significantly associated with overall survival (OS), 51 with progression-free survival (PFS) and 44 with response. Twenty biomarkers were associated with both OS and PFS; two were associated with OS, PFS and response (MHC-II and tumor mutational burden). Conclusion: Numerous biomarkers could potentially predict the efficacy of anti-PD-1-based therapy for melanoma patients. However, confirmatory studies are needed as well as determination of implications for clinical decision-making.