2-Cys peroxiredoxins contribute to thylakoid lipid unsaturation by affecting ω-3 fatty acid desaturase 8.

Fatty acid unsaturation levels affect chloroplast function and plant acclimation to environmental cues. However, the regulatory mechanism(s) controlling fatty acid unsaturation in thylakoid lipids is poorly understood. Here, we have investigated the connection between chloroplast redox homeostasis and lipid metabolism by focusing on 2-Cys peroxiredoxins (Prxs), which play a central role in balancing the redox state within the organelle. The chloroplast redox network relies on NADPH-dependent thioredoxin reductase C (NTRC), which controls the redox balance of 2-Cys Prxs to maintain the reductive activity of redox-regulated enzymes. Our results show that Arabidopsis (Arabidopsis thaliana) mutants deficient in 2-Cys Prxs contain decreased levels of trienoic fatty acids, mainly in chloroplast lipids, indicating that these enzymes contribute to thylakoid membrane lipids unsaturation. This function of 2-Cys Prxs is independent of NTRC, the main reductant of these enzymes, hence 2-Cys Prxs operates beyond the classic chloroplast regulatory redox system. Moreover, the effect of 2-Cys Prxs on lipid metabolism is primarily exerted through the prokaryotic pathway of glycerolipid biosynthesis and fatty acid desaturase 8 (FAD8). While 2-Cys Prxs and FAD8 interact in leaf membranes as components of a large protein complex, the levels of FAD8 were markedly decreased when FAD8 is overexpressed in 2-Cys Prxs-deficient mutant backgrounds. These findings reveal a function for 2-Cys Prxs, possibly acting as a scaffold protein, affecting the unsaturation degree of chloroplast membranes.

High Rate of Union of Scaphoid Pseudoarthrosis Treated With Arthroscopic Olecranon Bone Graft Using Antegrade Percutaneous Headless Compression Screw.

PURPOSE: To assess the healing rate of scaphoid pseudoarthrosis treated with wrist arthroscopy, olecranon bone graft, and anterograde screw fixation, as well as evaluate complications and clinical and radiologic outcomes. METHODS: All patients with scaphoid nonunion were selected between January 2017 and December 2022. Inclusion criteria were patients between 18 and 60 years of age, a diagnosis of scaphoid pseudoarthrosis, complete clinical patient-reported outcomes, radiographic measurements, and at least a 1-year follow-up. Scaphoid pseudoarthrosis was treated arthroscopically with olecranon bone graft and anterograde screw fixation. Clinical assessment was performed through visual analog scale (VAS) for pain, QuickDASH (Disabilities of the Arm, Shoulder, and Hand) questionnaire, wrist range of motion using a standard goniometer, and grip strength in kilograms with a Jamar hydraulic hand dynamometer. Clinical relevance was measured with the minimal clinically important difference (MCID) for VAS and QuickDASH. Scapholunate angle was measured. Union was assessed on a computed tomography scan. RESULTS: Seventeen patients were included with a mean follow-up of 17.2 months. The mean age was 30.1 years, and the average time from injury to arthroscopic surgery was 11.1 months. At latest follow-up, there was an improvement in VAS pain score and QuickDASH score. Range of motion and grip strength increased at last follow-up. MCID threshold for the VAS and QuickDASH score was reached by 100% and 94.1%, respectively. Union was achieved in 16 patients (94.1%) after a median of 16 weeks (interquartile range, 16-20). CONCLUSIONS: Arthroscopic treatment of scaphoid pseudoarthrosis with olecranon bone graft and antegrade percutaneous headless compression screw allows a high grade of union and improves pain and function at short-term follow-up. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

A chloroplast redox relay adapts plastid metabolism to light and affects cytosolic protein quality control.

In chloroplasts, thiol-dependent redox regulation is linked to light since the disulfide reductase activity of thioredoxins (Trxs) relies on photo-reduced ferredoxin (Fdx). Furthermore, chloroplasts harbor an NADPH-dependent Trx reductase (NTR) with a joint Trx domain, termed NTRC. The activity of these two redox systems is integrated by the redox balance of 2-Cys peroxiredoxin (Prx), which is controlled by NTRC. However, NTRC was proposed to participate in redox regulation of additional targets, prompting inquiry into whether the function of NTRC depends on its capacity to maintain the redox balance of 2-Cys Prxs or by direct redox interaction with chloroplast enzymes. To answer this, we studied the functional relationship of NTRC and 2-Cys Prxs by a comparative analysis of the triple Arabidopsis (Arabidopsis thaliana) mutant, ntrc-2cpab, which lacks NTRC and 2-Cys Prxs, and the double mutant 2cpab, which lacks 2-Cys Prxs. These mutants exhibit almost indistinguishable phenotypes: in growth rate, photosynthesis performance, and redox regulation of chloroplast enzymes in response to light and darkness. These results suggest that the most relevant function of NTRC is in controlling the redox balance of 2-Cys Prxs. A comparative transcriptomics analysis confirmed the phenotypic similarity of the two mutants and suggested that the NTRC-2-Cys Prxs system participates in cytosolic protein quality control. We propose that NTRC and 2-Cys Prxs constitute a redox relay, exclusive to photosynthetic organisms that fine-tunes the redox state of chloroplast enzymes in response to light and affects transduction pathways towards the cytosol.

The impact of neighborhood socioeconomic status on retention in care and viral suppression among people living with HIV.

Our study combined publicly available neighborhood socioeconomic status (nSES) data from the U.S. Census and clinical data to investigate the relationships between nSES, retention in care (RIC) and viral suppression (VS). Data from 2275 patients were extracted from 2009 to 2015 from a midwestern infectious diseases clinic. RIC was defined as patients who kept ≥ 3 visits and VS as an average viral load <200 copies/mL during their index year of study. Logistic regression models provided estimates for neighborhood-level and patient-level variables. In multivariable models, patients living in zip codes with low disability rates (1.50, 1.30-1.70), who wereolder (1.02, 1.01-1.03), and receiving antiretroviral therapy (ART; 3.81, 3.56-4.05) were more likely to have RIC, while those who were unemployed (0.72, 0.45-0.98) and self-reported as BIPOC (0.79, 0.64-0.97) were less likely to have RIC. None of the nSES variables were significantly associated with VS in multivariable models, yet older age (1.05, 1.04-1.05) and self-reported as BIPOC (1.68, 1.36-2.09) were modestly associated with VS, and receiving ART (6.14, 5.86-6.42) was a strong predictor of VS. In multivariable models, nSES variables were independently predictive more than of patient-level variables, for RIC but not VS.

Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcome?

INTRODUCTION: Metabolic syndrome (MS) and cardiovascular risk factors are common in liver transplant (LT) candidates and recipients. Cardiovascular events and de novo tumors are increasingly common causes of mortality in liver transplant recipients. The aim of this study were (i) assess the prevalence of MS in LT recipients and its growth over the years and (ii) determine if the presence of MS pre-LT is associated with a higher risk of post-LT cardiovascular events (CVE), de novo tumors or early and late survival. PATIENTS AND METHODS: A retrospective study was performed that included LT recipients from January 2012 to December 2017. Baseline features (MS before LT and at 1year post-LT) and outcomes (CVE, de novo tumors and survival) were recorded. RESULTS: 483 recipients were included, MS was present in 20% of pre-LT with an increasing prevalence over time, from 16% in 2012 to 34% in 2017 (p=0.025). One-year post-LT, an additional 12% had developed de novo MS. At a median of 56-months follow-up, 13% developed a CVE and 9% a de novo tumor. One and 5-yr survival rates were 91% and 83% in those with pre-LT MS and 93% and 85% in those without (p=0.94).The presence of MS before LT was independently associated with a higher risk of post-LT CVE (HR: 2.66 IC (95%): 1.6-4.4 p< 0.001), but not with de novo tumors (p=0.94) nor early and late survival (p=0.58 and p=0.87). CONCLUSION: Pre-LT MS is increasing among LT candidates and is associated with a higher risk of post-LT morbidity CVE yet without affecting mortality. .

Association between delivering live-born twins and acute psychiatric illness within 1 year of delivery.

BACKGROUND: Having twins is associated with more depressive symptoms than having singletons. However, the association between having twins and psychiatric morbidity requiring emergency department visit or inpatient hospitalization is less well known. OBJECTIVE: This study aimed to determine whether women have higher risk of having a psychiatric diagnosis at an emergency department visit or inpatient admission in the year after having twins vs singletons. STUDY DESIGN: This retrospective cohort study used International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and procedure codes within the Florida State Inpatient Database and State Emergency Department Database, which have an encrypted identifier allowing nearly all inpatient and emergency department encounters statewide to be linked to the medical record. The first delivery of Florida residents at the age of 13 to 55 years from 2005 to 2014 was included, regardless of parity; women with International Classification of Diseases, Ninth Revision, Clinical Modification coding for psychiatric illness or substance misuse during pregnancy or for stillbirth or higher-order gestations were excluded. The exposure was an International Classification of Diseases, Ninth Revision, Clinical Modification code during delivery hospitalization of live-born twins. The primary outcome was an International Classification of Diseases, Ninth Revision, Clinical Modification code during an emergency department encounter or inpatient admission within 1 year of delivery for a psychiatric morbidity composite (suicide attempt, depression, anxiety, posttraumatic stress disorder, psychosis, acute stress reaction, or adjustment disorder). The secondary outcome was drug or alcohol use or dependence within 1 year of delivery. We compared outcomes after delivery of live-born twins with singletons using multivariable logistic regression adjusting for sociodemographic and medical factors. We tested for interactions between independent variables in the primary model and conducted sensitivity analyses stratifying women by insurance type and presence of severe intrapartum morbidity or medical comorbidities. RESULTS: A total of 17,365 women who had live-born twins and 1,058,880 who had singletons were included. Within 1 year of birth, 1.6% of women delivering twins (n=270) and 1.6% of women delivering singletons (n=17,236) had an emergency department encounter or inpatient admission coded for psychiatric morbidity (adjusted odds ratio, 1.00; 95% confidence interval, 0.88-1.14). Coding for drug or alcohol use or dependence in an emergency department encounter or inpatient admission in the year after twin vs singleton delivery was also similar (n=96 [0.6%] vs n=6222 [0.6%]; adjusted odds ratio, 1.11; 95% confidence interval, 0.91-1.36). However, women with public health insurance were more likely to be coded for drug or alcohol use or dependence after twin than singleton delivery (n=75 [1.2%] vs n=4858 [1.0%]; adjusted odds ratio, 1.27; 95% confidence interval, 1.01-1.60). Women with ≥1 medical comorbidity, severe maternal morbidity, or low income also had an increased risk of psychiatric morbidity after twin delivery (comorbidities, n=7438 [42.8%]; adjusted odds ratio, 1.30; 95% confidence interval, 1.25-1.34; severe maternal morbidity, n=940 [5.4%]; adjusted odds ratio, 1.65; 95% confidence interval, 1.49-1.81; lowest income quartile, n=4409 [26.8%]; adjusted odds ratio, 1.31; 95% confidence interval, 1.23-1.40; second-lowest income quartile, n=4770 [29.0%]; adjusted odds ratio, 1.34; 95% confidence interval, 1.26-1.43). CONCLUSION: Overall, diagnostic codes for psychiatric illness or substance misuse in emergency department visits or hospital admissions in the year after twin vs singleton delivery are similar. However, women with who are low income or have public health insurance, comorbidities, or severe maternal morbidity are at an increased risk of postpartum psychiatric morbidity after twin vs singleton delivery.

Disparities in health behaviors and outcomes at the intersection of race and sexual identity among women: Results from the 2011-2016 National Health and Nutrition Examination Survey.

The purpose of this study was to explore potential differences in health behaviors and outcomes of sexual minority women (SMW) of color compared to White SMW, heterosexual women of color, and White heterosexual women. Data from 4878 women were extracted from the 2011 to 2016 National Health and Nutritional Examination Survey. The four-category independent variable (SMW of color, White SMW, heterosexual women of color, and White heterosexual women) was included in binary and multinomial logistic regression models predicting fair/poor self-reported health status, depression, cigarette smoking, alcohol, cannabis, and illicit drug use. Compared to White heterosexual women, SMW of color and heterosexual women of color had significantly higher odds of fair/poor self-reported health and lower odds of being a current or former smoker, binge drinking or using alcohol in the past year, being a former cannabis user, and ever using illicit drugs. In contrast, White SMW had significantly greater odds of depression, current smoking and cannabis and illicit drug use. Results of post-hoc tests indicated that the adjusted ORs for SMW of color differed significantly from those of White SMW for all outcomes, and did not differ significantly from those for heterosexual women of color for any outcome other than no binge drinking (OR = 0.34 vs. 0.67, p < 0.01) and current cannabis use (OR = 0.93 vs. 0.44, p < 0.01). SMW of color are more similar to heterosexual women of color than to White SMW in terms of depression, substance use, and self-reported health.

Fluctuation analysis to select for Samarium bio-uptaking microalgae clones the repurposing of a classical evolution experiment.

Rare Earth Elements (REE) increasing demand prompts the research of biotechnological approaches to exploit secondary resources. We made use of the adapted Fluctuation analyses experiment to obtain Chlamydomonas reinhardtii ChlA strains resistant to Samarium (Sm) as the reference REE. The starting hypothesis was that adaptation to metal-containing media leads to an enhanced metal uptake. ChlA was able to adapt to 1.33·10-4 Sm M and pH~3 by pre-existing genetic variability, allowing the evolutionary rescue of 13 of the 99 populations studied. The rescuing resistant genotypes presented a mutation rate of 8.65·10-7 resistant cells per division. The resulting resistant population contradicted the expected fitness cost associated with the adaptation to Sm, selection resulted in larger and faster-growing resistant cells. Among the three isolated strains studied for Sm uptake, only one presented uplifted performance compared to the control population (46.64 µg Sm g-¹ of wet biomass and 3.26·10-7 ng Sm per cell, mainly bioaccumulated within the cells). The selection of microalgae strains with improved tolerance to REEs by this methodology could be a promising solution for REES sequestration. However, increased tolerance can be independent or have negative effects on uptake performance and cellular features studied are not directly correlated with the metal uptake. SUMMARY SENTENCE: Repurposing a classic laboratory evolution experiment to select for microalgae Samarium adapted strains for metals recovery and biotechnology approaches. DATA AVAILABILITY STATEMENT: All data generated or analyzed during this study are included in this published article (and its raw files).

Mild Neonatal Acidemia is Associated with Neonatal Morbidity at Term.

OBJECTIVE: The aim of this study is to determine the association between mild acidemia (umbilical artery [UA] pH: 7.11-7.19) and neonatal morbidity in neonates at term. STUDY DESIGN: This is a secondary analysis of a prospective cohort of women admitted for labor at ≥37 weeks of gestation within a single institution from 2010 to 2015. Universal umbilical cord blood gas assessment was performed and validated. A composite neonatal morbidity index was created including respiratory distress, mechanical ventilation, meconium aspiration syndrome, suspected or confirmed sepsis, hypoxic-ischemic encephalopathy, need for therapeutic hypothermia, seizures and death. The cohort was stratified by UA pH into normal (≥7.20), mild acidemia (7.11-7.19), acidemia (7.00-7.10), and severe acidemia (≤7.00). A subanalysis was also performed where neonates with UA pH between 7.11 and 7.19 were further stratified into two groups (7.11-7.14 and 7.15-7.19) to determine if mildly acidotic infants at the lower end of the pH range were at increased risk of morbidity. Multivariable logistic regression was used to estimate the association between UA pH and neonatal morbidity. RESULTS: Among 6,341 participants, 614 (9.7%) had mild acidemia. These infants were more likely to experience morbidity compared with those with normal UA pH (adjusted odds ratio [aOR]: 2.14; [1.68-2.73]). Among neonates with mild acidemia, UA pH 7.11 to 7.14 was associated with increased risk of composite neonatal morbidity (aOR: 3.02; [1.89-4.82]), as well as respiratory distress and suspected or confirmed sepsis when compared with UA pH 7.15 to 7.19. CONCLUSION: These data demonstrate that term neonates with mild acidemia at birth are at higher odds for short-term morbidity compared with neonates with normal UA pH. Furthermore, among neonates with mild acidemia, those with lower UA pH had worse neonatal outcomes than those with higher UA pH. This suggests that closer evaluation of neonates with UA pH higher than traditionally used could allow for earlier detection of morbidity and possible intervention. KEY POINTS: · Neonates with mild acidemia (umbilical artery [UA] pH: 7.11-7.19) demonstrated an increased risk of composite morbidity compared with those with normal UA pH (≥7.20).. · Among neonates with mild acidemia, those with lower UA pH (7.11-7.14) had a greater risk of morbidity compared with those with higher UA pH (7.15-7.19), suggesting a progression of risk of morbidity as UA pH decreases.. · The majority of prior research has focused on severe acidemia (UA pH ≤ 7.00) using outcomes of severe neurologic morbidity and mortality. These data suggest that an increased risk of morbidity exists at higher pH values when more proximal and less severe outcomes are included, such as respiratory distress and neonatal sepsis..

Physical frailty in liver transplantation.

In patients with cirrhosis, frailty represents a status of global physical dysfunction associated with a multiplicity of factors, including muscle wasting, undernutrition and malnutrition, and functional impairment. This condition is particularly prevalent among those with advanced cirrhosis, such as liver transplant (LT) candidates. Studies in this vulnerable population have demonstrated that its presence is independently predictive of adverse outcomes both pre- and post-transplantation, and thus that its incorporation into clinical practice could result in improved clinical decision-making, particularly regarding the identification of candidates for physical and nutritional interventions. There are, however, some limitations to its immediate incorporation into organ allocation prioritization models, including the wide heterogeneity of instruments used for measuring frailty, and particularly the lack of a single one suitable in all LT clinical scenarios (inpatient vs outpatient; pre- vs post-transplant). Finally, the data on the potential effects of frailty improvement on the diverse range of outcome measures are still preliminary.

The effect of intrapartum oxygen supplementation on category II fetal monitoring.

BACKGROUND: Maternal oxygen administration is a widely used intrauterine resuscitation technique for fetuses with category II electronic fetal monitoring patterns, despite a paucity of evidence on its ability to improve electronic fetal monitoring patterns. OBJECTIVE: This study investigated the effect of intrapartum oxygen administration on Category II electronic fetal monitoring patterns. STUDY DESIGN: This is a secondary analysis of a randomized trial conducted in 2016-2017, in which patients with fetuses at ≥37 weeks' gestation in active labor with category II electronic fetal monitoring patterns were assigned to 10 L/min of oxygen by face mask or room air until delivery. Trained obstetrical research nurses blinded to allocation extracted electronic fetal monitoring data. The primary outcome was a composite of high-risk category II features including recurrent variable decelerations, recurrent late decelerations, prolonged decelerations, tachycardia, or minimal variability 60 minutes after randomization to room air or oxygen. Secondary outcomes included individual components of the composite high-risk category II features, resolution of recurrent decelerations within 60 minutes of randomization, and total deceleration area. The outcomes between the room air and oxygen groups were compared using univariable statistics. Time-to-event analysis was used to compare time to resolution of recurrent decelerations between the groups. Paired analysis was used to compare the pre- and postrandomization outcomes within each group. RESULTS: All 114 randomized patients (57 room air and 57 oxygen) were included in this analysis. There was no difference in resolution of recurrent decelerations within 60 minutes between the oxygen and room air groups (75.4% vs 86.0%; P=.15). The room air and oxygen groups had similar rates of composite high-risk category II features including recurrent variable decelerations, recurrent late decelerations, prolonged decelerations, tachycardia, and minimal variability 60 minutes after randomization. Time to resolution of recurrent decelerations and total deceleration area were similar between the room air and oxygen groups. Among patients who received oxygen, there was no difference in the electronic fetal monitoring patterns pre- and postrandomization. Similar findings were observed in the electronic fetal monitoring patterns pre- and postrandomization in room air patients. CONCLUSION: Intrapartum maternal oxygen administration for category II electronic fetal monitoring patterns did not resolve high-risk category II features or hasten the resolution of recurrent decelerations. These results suggest that oxygen administration has no impact on improving category II electronic fetal monitoring patterns.

The Impact of Clinic Policy Attendance and the Ryan White HIV/AIDS Medical Case Management Program on HIV Clinical Outcomes: A Retrospective Longitudinal Study.

Clinic appointment attendance is a significant determinant of improved HIV health outcomes. A retrospective longitudinal analysis from 2009 to 2015 examined the relationship of clinic policy attendance with and without medical case management (MCM) on HIV clinical outcomes. Clinical parameters were abstracted across the study years and latent growth models measured HIV clinical outcomes as a function of time. A total of 2773 patients were included in this study. More than the majority of individuals had 75% clinic policy attendance during each of the study years and the median number of MCM contact visits with the case manager was 4.0 visits per year (p < 0.01). While the overall trend identified improved HIV clinical outcomes across the clinic population over the study period, it also revealed individuals receiving MCM and with 75% clinic policy attendance had significantly faster improvement in HIV clinical outcomes compared to the individuals who did not receive MCM nor had 75% clinic policy attendance. This study identified how MCM, in combination with clinic policy attendance efforts, are useful in quickly improving HIV viral load and CD4 T-cell count. These findings support the continued need for funding of the Ryan White Care Act as it assists with the support of MCM and appointment attendance through the guidance of wrap-around services.

Acidemia Can Occur Despite Category I Tracing.

OBJECTIVE: Electronic fetal monitoring (EFM) is intended to assess fetal well-being during labor. Our objective was to test the hypothesis that findings of a category I tracing at any time in the 60 minutes prior to delivery would rule out neonatal acidemia. STUDY DESIGN: This was a planned secondary analysis of a single-center prospective cohort study of 8,580 singleton pregnancies undergoing labor with nonanomalous infants at term. Monitoring was reviewed by obstetric research nurses at 10-minute intervals in the 60 minutes prior to delivery. The primary outcome was acidemia, defined as an umbilical cord arterial pH of 7.10 or less. RESULTS: Of the 4,274 patients included, 42 (0.98%) infants had acidemia at birth. Of the 42 infants with acidemia, 13 (31%) had category I tracings in the 30 minutes prior to delivery. Three (7%) infants had neonatal acidemia despite category I tracing for >40 minutes in the 60 minutes prior to delivery. CONCLUSION: Even in the presence of category I tracing in the 60 minutes prior to delivery, neonatal acidemia can still occur. Periods of category I should be interpreted within the clinical context of a priori risk for acidemia, knowing that it does not completely rule out acidemia.

Patient and obstetric provider communication regarding weight gain management among socioeconomically disadvantaged African American women who are overweight/obese.

To examine the communication between obstetric providers and their socioeconomically disadvantaged, African American patients who are overweight and obese during pregnancy, and whether this communication relates to outcomes. Pregnant patients and their obstetric providers were surveyed between October 2012 and March 2016 at Washington University School of Medicine in St. Louis, MO. Percent agreement between patients' and obstetric providers' survey responses was analyzed and measured (κ coefficient). Descriptive and multilevel logistic regression analyses aimed at identifying the relation of perceived communication between providers and patients to gestational weight gain, diet, and exercise during pregnancy. A total of 99 pregnant women and 18 obstetric providers participated in the study. Significant lack of agreement was observed between patients and obstetric providers regarding communication about weight gain recommendations, risk factors associated with excessive weight gain, what constitutes adequate exercise per week, exercise recommendations, dietary recommendations, and risk factors associated with a poor diet. Our findings suggest patients were not receiving intended messages from their obstetric providers. Thus, more effective patient-obstetric provider communication is needed regarding gestational weight gain, exercise and dietary recommendations among overweight/obese, socioeconomically disadvantaged, African American women.

Efficacy and Safety of Nitazoxanide in Addition to Standard of Care for the Treatment of Severe Acute Respiratory Illness.

BACKGROUND: Effective therapeutics for respiratory viruses are needed. Early data suggest that nitazoxanide (NTZ) may be beneficial for treating acute respiratory viral illness. METHODS: From March 2014 through March 2017, a double-blind, placebo-controlled trial was conducted in 260 participants ≥1 year old hospitalized with influenza-like illness at 6 hospitals in Mexico. Participants were randomized 1:1 to NTZ (age ≥12 years, 600 mg twice daily; age 4-11 years and 1-3 years, 200 or 100 mg twice daily, respectively) or placebo for 5 days in addition to standard of care. The primary endpoint was time from first dose to hospital discharge. Influenza reverse-transcription polymerase chain reaction and Respifinder 22 multiplex test were used for virus detection. RESULTS: Of 260 participants enrolled, 257 were randomized and took at least 1 dose of study treatment (intention-to-treat population): 130 in the NTZ group and 127 in the placebo group. The Kaplan-Meier estimate of the median duration of hospitalization was 6.5 (interquartile range [IQR], 4.0-9.0) days in the NTZ group vs 7.0 (IQR, 4.0-9.0) days in the placebo group (P = .56). Duration of hospitalization between the 2 treatments was similar in children (P = .29) and adults (P = .62), influenza A and B (P = .32), and other respiratory viruses. Seven (5.4%) and 6 (4.7%) participants in the NTZ and placebo groups, respectively, reported serious adverse events. CONCLUSIONS: Treatment with NTZ did not reduce the duration of hospital stay in severe influenza-like illness. Further analyses based on age and evaluations by virus did not reveal any subgroups that appeared to benefit from NTZ. CLINICAL TRIALS REGISTRATION: NCT02057757.

Association between stillbirth ≥23 weeks gestation and acute psychiatric illness within 1 year of delivery.

BACKGROUND: Stillbirth has been associated with emotional and psychologic symptoms. The association between stillbirth and diagnosed postpartum psychiatric illness is less well-known. OBJECTIVE: The purpose of this study was to determine whether women have a higher risk of experiencing clinician-diagnosed psychiatric morbidity in the year after stillbirth vs livebirth. STUDY DESIGN: This retrospective cohort study used International Classification of Diseases, 9th Revision, Clinical Modification diagnosis and procedure codes to identify participants, exposures, and outcomes within the Florida State Inpatient and State Emergency Department databases. The first delivery of female Florida residents aged 13-54 years old from 2005-2014 was included; women with International Classification of Diseases, 9th Revision, Clinical Modification coding for psychiatric illness or substance use during pregnancy were excluded. The exposure was an International Classification of Diseases, 9th Revision, Clinical Modification diagnosis code during delivery hospitalization of a stillbirth at ≥23 weeks gestation. The primary outcome was a primary or secondary International Classification of Diseases, 9th Revision, Clinical Modification diagnosis code during an Emergency Department encounter or inpatient admission within 1 year of delivery for a composite of psychiatric morbidity: suicide attempt, depression, anxiety, posttraumatic stress disorder, psychosis, acute stress reaction, or adjustment disorder. The secondary outcome was a substance use composite of drug or alcohol use or dependence. We compared outcomes after delivery of stillbirth vs livebirth using multivariable logistic regression, adjusting for maternal sociodemographic factors, medical comorbidities, and severe intrapartum morbidity. We also used Cox proportional hazard models and tested for violation of the proportional hazard assumption to identify the highest risk time within the year after stillbirth delivery for the primary outcome, adjusting for the same factors and morbidities as in the logistic regression model. RESULTS: A total of 8292 women with stillborn singletons and 1,194,758 with liveborn singletons were included. Within 1 year of hospital discharge after stillbirth, 4.0% of the women (n=331) had an Emergency Department encounter or inpatient admission that was coded for psychiatric morbidity; the risk was nearly 2.5 times higher compared with livebirth (1.6%; n=19,746); adjusted odds ratio, 2.47; 95% confidence interval, 2.20- 2.77). Women also had higher risk of having an Emergency Department encounter or inpatient admission coded for drug or alcohol use or dependence in the year after delivery of stillbirth vs livebirth (124 [1.5%] vs 7033 [0.6%]; adjusted odds ratio, 2.41; 95% confidence interval, 1.99-2.90). Cox proportional hazard modeling suggested that the highest risk interval for postpartum psychiatric illness was within 4 months of stillbirth delivery (adjusted hazard ratio, 3.26; 95% confidence interval, 2.63-4.04), although the risk remained high during the 4-12 months after delivery (adjusted hazard ratio, 2.42; 95% confidence interval, 2.13-2.76). CONCLUSION: Coding for psychiatric illness or substance misuse in Emergency Department visits or hospital admissions in the year after delivery of livebirths was not uncommon, corresponding to nearly 2 per 100 women. However, having a stillbirth was associated with increased risk of both psychiatric morbidity (corresponding to 1 per 25 women) and substance misuse (corresponding to 3 in 100 women), with the highest risk of postpartum psychiatric morbidity occurring from delivery until 4 months after delivery.

A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer.

Paclitaxel (PTX), a chemotherapy agent widely used to treat lung cancer, is characterised by high toxicity, low bioavailability and the need to use of excipients with serious side effects that limit its use. Paclitaxel encapsulation into nanoparticles (NPs) generates drug pharmacokinetic and pharmacodynamic advantages compared to free PTX. In this context, a NP carrier formed from a copolymer of lactic acid and glycolic acid (PLGA) has demonstrated high biocompatibility and low toxicity and therefore being approved by FDA to be used in humans. We synthesised a new PLGA NP and loaded it with PTX to improve drug efficacy and reduce side effects. This nanoformulation showed biocompatibility and no toxicity to human immune system. These NPs favor the intracellular uptake of PTX and enhance its antitumor effect in human and murine lung cancer cells, with up to 3.6-fold reductions in the PTX's IC50. Although PLGA NPs did not show any inhibitory capacity against P-glycoprotein, they increased the antitumor activity of PTX in cancer stem cells. Treatment with PLGA-PTX NPs increased apoptosis and significantly reduced the volume of the tumorspheres derived from A549 and LL2 cells by up to 36% and 46.5%, respectively. Biodistribution studies with PLGA-PTX NPs revealed an increase in drug circulation time, as well as a greater accumulation in lung and brain tissues compared to free PTX. Low levels of PTX were detected in the dorsal root ganglion with PLGA-PTX NPs, which could exert a protective effect against peripheral neuropathy. In vivo treatment with PLGA-PTX NPs showed a greater decrease in tumor volume (44.6%) in immunocompetent mice compared to free PTX (24.4%) and without increasing the toxicity of the drug. These promising results suggest that developed nanosystem provide a potential strategy for improving the chemotherapeutic effect and reducing the side effects of PTX.

Testing the Feasibility of Using Ecological Momentary Assessment to Collect Real-Time Behavior and Mood to Predict Technology-Measured HIV Medication Adherence.

Identifying distinct patterns of behavior and mood in natural environments that interrupt medication adherence among individuals with HIV will be useful in informing intervention development. This pilot study assessed the initial efficacy of using ecologic momentary assessment to define patterns of alcohol use, mood, and medication adherence. Participants reported intraday alcohol use and mood using app-enabled smartphones and MEMSCap pill bottles to measure medication adherence. There were 34 enrolled participants, 29 of whom completed the 28-day study. Participants drank a mean of 7.75 days of the study period. The positive and negative affect scores ranged from 10 to 50, with a mean of 25.7 and 11.4 for each, respectively. The average medication adherence for the sample was 94.1%. These findings suggest these types of data collection methods are increasingly acceptable in measuring real-time mood and behavior, which may better inform interventions addressed at increasing HIV adherence practices.

Association between Uterine Tachysystole during the Last Hour of Labor and Cord Blood Lactate in Parturients at Term Gestation.

OBJECTIVE: To assess whether uterine tachysystole (UT) in labor causes an increase in cord blood lactate. STUDY DESIGN: Secondary analysis of a prospective cohort study of all consecutive singleton gestations ≥ 37 weeks admitted for labor to a single tertiary care institution with universal cord gas policy. Patients with UT in the last hour ("always") were compared with those without UT ("never"). Primary outcome of interest was cord blood lactate ≥ 4 mmol/L. Secondary outcomes included pH ≤ 7.10, base deficit ≥ 8 mmol/L, and admission to the neonatal intensive care unit (NICU). Multivariable logistic regression was used to estimate the risk for elevated cord blood lactate after adjusting for maternal age and body mass index. RESULTS: Of the 8,580 patients included in the analysis, 513 experienced UT 1 hour before delivery (5.9%). UT was significantly associated with elevated cord blood lactate in the "always" (33.5%) compared with the "never" group (26%) (adjusted odds ratio 1.47 [1.17, 1.86]; p < 0.01). However, there were no differences in either umbilical arterial pH, base deficit, or NICU admission rates. CONCLUSION: UT in the last hour preceding delivery increases arterial cord blood lactate suggesting that UT proximate to delivery should be considered as a variable when interpreting cord blood gas values.

Infant Feeding Practices and Perceived Optimal Breastfeeding Interventions among Low-Income Women Delivering at a Baby-Friendly Hospital.

OBJECTIVE: To determine infant feeding practices of low-income women at a Baby-Friendly Hospital and to ascertain breastfeeding interventions they believe would increase exclusive breastfeeding. STUDY DESIGN: This cross-sectional study occurred at a tertiary care Baby-Friendly Hospital. Low-income women without breastfeeding contraindications were recruited at scheduled obstetrician/gynecologist appointments within 6 to 9 months of delivering a term, nonanomalous infant. Participants completed a survey. Outcomes included infant feeding patterns and perceived usefulness of proposed breastfeeding interventions. RESULTS: Of 149 participants, 129 (86.6%) initiated breastfeeding; by postpartum day 2 (PPD2), 47 (31.5%) exclusively breastfed, 51 (34.2%) breastfed with formula, and 51 (34.2%) exclusively formula fed. On a scale of 1 ("strongly agree") to 5 ("strongly disagree"), women who supplemented with formula on PPD2 were significantly more likely than those who exclusively formula fed to agree education on neonatal behavior, 1 (interquartile range [IQR] 1, 2) versus 2 (IQR 1, 3); p = 0.026 and on-demand access to breastfeeding videos on latch or positioning, 1 (IQR 1, 2) versus 2 (IQR 1, 3), p = 0.043; 1 (IQR 1, 2) versus 2 (IQR 1, 3), p = 0.021, respectively, would have helped them exclusively breastfeed. CONCLUSION: Though low-income women at a Baby-Friendly Hospital had high breastfeeding initiation rates, the majority used formula by PPD2. To increase breastfeeding rates among low-income women, future interventions should provide appropriate and effective breastfeeding interventions.