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Objectives Recent meta-analyses suggest a physical activity health paradox: high levels of occupational physical activity (OPA) increase cardiovascular disease (CVD) risk, while leisure-time physical activity (LTPA) decreases risk. However, studies of women and cerebrovascular disease are limited. This report examines physical activity effects on stroke and transient ischemic attack (TIA) among working women in the United States. Methods OPA history, health status, and lifestyle were assessed by baseline interviews of 31 270 employed Sister Study participants aged 35-74 years. OPA was assessed at six intensity levels (lowest: \"mostly sitting\"); the highest three were combined as \"high intensity work.\" Independent OPA and LTPA effects on 6-year cerebrovascular disease incidence were estimated in adjusted Cox proportional hazard models. Results Stroke (N=441) and TIA (N=274) risk increased with more standing and higher intensity work at current and longest held job. Compared with mostly sitting, high intensity work at the current job increased TIA risk by 57% [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.04-2.38]. High intensity OPA at the longest held job increased risk for stroke by 44% (HR 1.44; 95% CI 1.08-1.93). Among women with CVD, sitting and standing equally, especially at the current job, increased risks up to two-fold (TIA HR 1.98, 95% CI 1.10-3.55) compared with mostly sitting at work. LTPA showed inverse associations. Conclusions Higher intensity levels of OPA increased stroke and TIA risks, while LTPA decreased risks; results corroborate the physical activity health paradox for women and cerebrovascular disease. More standing at work increased cerebrovascular disease risks, especially for women with CVD.

Cell penetrating peptides (CPPs) offer great potential to deliver therapeutic molecules to previously inaccessible intracellular targets. However, many CPPs are inefficient and often leave their attached cargo stranded in the cell’s endosome. We report a versatile platform for the isolation of peptides delivering a wide range of cargos into the cytoplasm of cells. We used this screening platform to identify multiple “Phylomer” CPPs, derived from bacterial and viral genomes. These peptides are amenable to conventional sequence optimization and engineering approaches for cell targeting and half-life extension. We demonstrate potent, functional delivery of protein, peptide, and nucleic acid analog cargos into cells using Phylomer CPPs. We validate in vivo activity in the cytoplasm, through successful transport of an oligonucleotide therapeutic fused to a Phylomer CPP in a disease model for Duchenne’s muscular dystrophy. This report thus establishes a discovery platform for identifying novel, functional CPPs to expand the delivery landscape of druggable intracellular targets for biological therapeutics.

This study tested the hypothesis that bioelectrical impedance vectors, group and individual, are valid indicators of total body water (TBW) and hydration status in women experiencing fluid gain and loss during and after pregnancy. We measured TBW, assessed with D 2O dilution, and resistance (R) and reactance (Xc), determined with 800 μA at 50 kHz and standardized for height (H) and plotted on a bivariate (R-Xc) graph, in 15 women, 21–37 y of age, longitudinally before and during pregnancy and postpartum (PP). Body weight (61.9 ± 2.3 to 75.5 ± 2.3 kg) and TBW (31.4 ± 1.1 to 38.2 ± 1.1 L) increased ( P < 0.05) from before pregnancy to the third trimester of pregnancy and decreased PP (67.0 ± 2.3 kg and 32.7 ± 1.1 L, P < 0.05). R/H and Xc/H decreased during pregnancy ( P < 0.05, 361 ± 10 to 318 ± 10 and 44 ± 1 to 36 ± 1 ω/m, respectively) and increased PP ( P < 0.05, 355 ± 10 and 41 ± 1 Ω/m). Vector length decreased ( P < 0.05, 363 ± 10 to 320 ± 10 Ω) during pregnancy and increased PP ( P < 0.05, 357 ± 10 Ω). Changes in vector length and TBW during pregnancy and PP were correlated ( r = −0.599, P < 0.001). Women with vectors exceeding a 75% tolerance interval had greater TBW gain (10–12 versus 5–6 L) during pregnancy compared with other women with vectors within this tolerance level. These findings indicate that impedance vectors provide quantitative evidence of hydration status during pregnancy and that the impedance vector method is useful in monitoring hydration status in pregnancy.

Background Inguinal hernia recurrence after surgical repair is a major concern. The authors report their experience with open and laparoscopic repair of recurrent inguinal hernias. Methods After institutional review board approval, a retrospective review was performed with the charts of 197 patients who had undergone surgical repair of recurrent inguinal hernias from January 2000 through August 2009, and the data for 172 patients who met the inclusion criteria were analyzed. Surgical variables and clinical outcomes were compared using Student’s t test, the Mann–Whitney U test, chi-square, and Fisher’s exact test as appropriate. Results The review showed that 172 patients had undergone either open mesh repair ( n  = 61) or laparoscopic mesh repair ( n  = 111) for recurrent inguinal hernias. Postoperative complications were experienced by 8 patients in the open group and 17 patients in laparoscopic group ( p  = 0.70). Five patients (8.2%) in the open group and four patients (3.6%) in the laparoscopic group had re-recurrent inguinal hernias ( p  = 0.28). Four patients in the open group (9.5%) and no patients in the laparoscopic group had recurrence during long-term follow-up evaluation ( p  = 0.046). In the laparoscopic group, 76 patients (68.5%) underwent total extraperitoneal (TEP) repair, and 35 patients (31.5%) had transabdominal preperitoneal (TAPP) repair. Postoperative complications were experienced by 13 patients in the TEP group and 4 patients in the TAPP group ( p  = 0.44). Two patients (2.6%) in the TEP group and two patients (5.7%) in the TAPP group had re-recurrent inguinal hernias ( p  = 0.59). Conclusions This retrospective review showed no statistical difference in the re-recurrence rate between the two techniques during short-term follow-up evaluation. However, the laparoscopic technique had a significantly lower re-recurrence rate than the open technique during long-term follow-up evaluation. Both procedures were comparable in terms of intra- and postoperative complications. Among laparoscopic techniques, TEP and TAPP repair are acceptable methods for the repair of recurrent inguinal hernia. A multicenter prospective randomized control trial is needed to confirm the findings of this study.

The ability of cell penetrating peptides (CPPs) to deliver biologically relevant cargos into cells is becoming more important as targets in the intracellular space continue to be explored. We have developed two assays based on CPP-dependent, intracellular delivery of TEM-1 β-lactamase enzyme, a functional biological molecule comparable in size to many protein therapeutics. The first assay focuses on the delivery of full-length β-lactamase to evaluate the internalization potential of a CPP sequence. The second assay uses a split-protein system where one component of β-lactamase is constitutively expressed in the cytoplasm of a stable cell line and the other component is delivered by a CPP. The delivery of a split β-lactamase component evaluates the cytosolic delivery capacity of a CPP. We demonstrate that these assays are rapid, flexible and have potential for use with any cell type and CPP sequence. Both assays are validated using canonical and novel CPPs, with limits of detection from <500 nM to 1 µM. Together, the β-lactamase assays provide compatible tools for functional characterization of CPP activity and the delivery of biological cargos into cells.

The safety of primary series COVID-19 vaccine exposure in pregnancy has been well-studied; however, no research to date has been conducted among United States (US) military service members, a unique population with specific vaccination requirements for active duty service and early COVID-19 vaccine access. This retrospective cohort study leveraged data from the Department of Defense Birth and Infant Health Research program to identify live births among active duty US military service members in calendar year 2021. Administrative military personnel data, immunization files, and medical encounter records were used to develop study variables and determine COVID-19 vaccine receipt in pregnancy. Cox and modified Poisson regression models estimated hazard (HR) and risk ratios (RR), respectively, with 95 % confidence intervals (CI) for vaccine receipt and selected neonatal outcomes; models were adjusted for baseline characteristics using inverse probability of treatment weighting and further adjusted for SARS-CoV-2 infection in pregnancy. There were 7184 singleton live births included for analysis, of which 2867 (39.9 %) were among service members exposed to their first COVID-19 vaccine dose in pregnancy and 4317 (60.1 %) among service members unexposed to any COVID-19 vaccine during or prior to pregnancy. Baseline differences between exposed and unexposed service members (e.g., age, race and ethnicity, marital status, occupation) were fully attenuated after applying weights. COVID-19 vaccine initiation in pregnancy was not associated with preterm birth (<37 weeks' gestation; adjusted HR: 1.02, 95 % CI: 0.83–1.26), small for gestational age (<10th percentile; adjusted HR: 1.01, 95 % CI: 0.78–1.30), low birthweight (<2500 g; adjusted HR: 1.01, 95 % CI: 0.80–1.28), or neonatal intensive care unit admission (adjusted RR: 0.90, 95 % CI: 0.75–1.07). Primary series COVID-19 vaccine exposure in pregnancy was common in this military cohort. Vaccine receipt was not associated with increased risk for any adverse outcome under study, substantiating findings from existing literature. •Nearly 40 % of pregnant military service members received a COVID-19 vaccine.•Vaccine exposure in pregnancy was not associated with adverse neonatal outcomes.•Propensity score weighting controlled for baseline differences by exposure status.•Adjustment sets included laboratory-confirmed SARS-CoV-2 infection in pregnancy.

Background To compare cause-specific mortality between an occupational cohort of U.S. service members and veterans and the general civilian adult population. Methods Dates and cause of death of deceased Millennium Cohort Study participants from 2001 to 2018 were extracted from federal and military databases. Standardized mortality ratios (SMRs) were calculated for cause-specific mortality compared with the general population overall and by sex and deployment history. Results Among 201,618 participants, 3,017 (1.5%) had a recorded cause of death by December 31, 2018. Compared with the U.S. general population, deaths due to natural causes (SMR = 0.36; 95% CI: 0.34–0.38), accidents (SMR = 0.47; 95% CI: 0.44–0.51), and homicides (SMR = 0.22; 95% CI: 0.17–0.29) were lower among service members and veterans. When stratified by sex, deaths by suicide overall were higher for military women (SMR = 1.65, 95% CI: 1.31–2.05) compared with women in the U.S. general population but not for men (SMR = 0.96, 95% CI 0.87–1.05). Deaths from suicide by firearms were elevated for both military women (SMR = 2.83, 95% CI: 2.04–3.82) and men (SMR = 1.33, 95% CI: 1.18–1.49) compared to the U.S. general population. Conclusions Service members and veterans had lower overall mortality but higher mortality attributed to suicide by firearms compared with the U.S. general population. Military women specifically had higher mortality rates from suicide overall. These findings warrant increased attention to reducing suicide deaths in military populations.

The Department of Defense encourages service members ≤26 years of age to receive the human papillomavirus (HPV) vaccine. Although this vaccine is not recommended in pregnancy, inadvertent vaccination may occur. The objective of this study was to assess whether active duty US military women who received the quadrivalent HPV vaccine (4vHPV) during pregnancy were at increased risk for adverse maternal or infant outcomes. The study population included active duty US military women aged 17–28 years with at least one pregnancy between 2007 and 2014, and the infants resulting from those pregnancies. Pregnancies, live births, and outcomes were identified using medical codes in administrative medical records. Exposure to 4vHPV during pregnancy was ascertained from personnel immunization records. Multivariable regression models were used to calculate risk estimates and 95% confidence intervals for the maternal outcomes of spontaneous abortion, preeclampsia/eclampsia and preterm labor, and the infant outcomes of preterm birth, birth defects, growth problems in infancy or in utero, and infant sex. Overall, 90,600 pregnancies and 75,670 singleton infants were identified. Approximately 2% of pregnancies and infants were exposed to 4vHPV during pregnancy. After adjustments, no positive associations were detected between inadvertent exposure to 4vHPV during pregnancy and any adverse pregnancy or infant outcomes. Our findings add to an established body of literature demonstrating the safety of 4vHPV when inadvertently administered during pregnancy. Although 4vHPV is no longer administered in the US, its use continues overseas; therefore, safety studies remain important. Furthermore, such studies can provide reassurance to women inadvertently exposed to nonavalent HPV vaccine (9vHPV) in pregnancy, which protects against four of the same antigens as 4vHPV, since safety of 9vHPV has not yet been established in pregnant women.