Sleep Health among Community-Recruited Opioid-Using People Who Inject Drugs in Los Angeles, CA and Denver, CO.

Chronic insufficient and poor-quality sleep are linked to hypertension, diabetes, depression, heart attack, and stroke. While studies on substance use and sleep typically focus on people in or entering treatment, there is a lack of research on sleep health among community-recruited people who inject drugs (PWID). To address this literature gap, we examined factors associated with insufficient and poor-quality sleep among community-recruited PWID. We recruited and interviewed 472 active opioid-using PWID (injected within the last 30 days) in Los Angeles, CA and Denver, CO between 2021 and 2022. Participants completed computer-assisted interviews covering demographics, subsistence measures, drug use patterns, injection-related behaviors, health risks, and sleep duration and quality in the last 3 months. Descriptive statistics were used to analyze all variables for subjects with complete responses to sleep items (n = 464). Bivariate analyses determined factors associated with sleep measures using chi-square and t-tests. Collinear variables were removed, and binomial linear multivariable regression calculated risk ratios (RR) for insufficient and poor-quality sleep in the last 3 months. Participants exhibited low sleep duration (mean = 4.99, standard deviation (SD) = 2.70), with 76% reporting insufficient sleep and 62% poor-quality sleep. Bivariate analyses associated both sleep measures with drug use, high subsistence scores, violent victimization, and poor health outcomes. Multivariable analyses showed a high subsistence score predicting insufficient (RR = 1.31) and poor-quality sleep (RR = 1.69) compared to low subsistence. Poor sleep health is common among structurally vulnerable community-recruited PWID, as measured by subsistence index associated with adverse sleep outcomes. Further research on structural interventions to address sleep and subsequent health outcomes among PWID is imperative.

Associations of hair cortisol levels with violence, poor mental health, and harmful alcohol and other substance use among female sex workers in Nairobi, Kenya.

Violence, poor mental health, and harmful substance use are commonly experienced by female sex workers (FSWs) in sub-Saharan Africa, all of which are associated with increased HIV susceptibility. We aimed to investigate the associations between violence, poor mental health and harmful alcohol/substance use with hair cortisol concentration (HCC) levels as a potential biological pathway linking the experiences of these stressors and HIV vulnerability. We used the baseline data of the Maisha Fiti study of FSWs in Nairobi, Kenya. Participants reported recent violence, poor mental health, and harmful alcohol/substance use. Hair samples proximal to the scalp were collected to measure cortisol levels determined by ELISA. We analysed the data of 425 HIV-negative respondents who provided at least 2 cm of hair sample. The prevalence of recent violence was 89.3% (physical 54.6%; sexual 49.4%; emotional 77.0% and financial 66.5%), and 29.1% had been arrested due to sex work. 23.7% of participants reported moderate/severe depression, 11.6% moderate/severe anxiety, 13.5% PTSD and 10.8% recent suicidal thoughts and/or attempts. About half of the participants (48.8%) reported recent harmful alcohol and/or other substance use. In multivariable linear regression analyses, both physical and/or sexual violence (adjusted geometric mean ratio (aGMR) = 1.28; 95% CI 1.01-1.62) and harmful alcohol and/or other substance use (aGMR = 1.31; 95% CI 1.03-1.65) were positively and independently associated with increased HCC levels. Findings suggest a role of violence and substance use in elevated HCC levels, which could increase HIV risk due to cortisol-related T cell activation. However, longitudinal and mechanistic studies are needed to confirm this hypothesis.

IL-2-armored peptide-major histocompatibility class I bispecific antibodies redirect antiviral effector memory CD8+ T cells to induce potent anti-cancer cytotoxic activity with limited cytokine release.

T cell engagers (TCEs) are becoming an integral class of biological therapeutic owing to their highly potent ability to eradicate cancer cells. Nevertheless, the widespread utility of classical CD3-targeted TCEs has been limited by narrow therapeutic index (TI) linked to systemic CD4+ T cell activation and aberrant cytokine release. One attractive approach to circumvent the systemic activation of pan CD3+ T cells and reduce the risk of cytokine release syndrome is to redirect specific subsets of T cells. A promising strategy is the use of peptide-major histocompatibility class I bispecific antibodies (pMHC-IgGs), which have emerged as an intriguing modality of TCE, based on their ability to selectively redirect highly reactive viral-specific effector memory cytotoxic CD8+ T cells to eliminate cancer cells. However, the relatively low frequency of these effector memory cells in human peripheral blood mononuclear cells (PBMCs) may hamper their redirection as effector cells for clinical applications. To mitigate this potential limitation, we report here the generation of a pMHC-IgG derivative known as guided-pMHC-staging (GPS) carrying a covalent fusion of a monovalent interleukin-2 (IL-2) mutein (H16A, F42A). Using an anti-epidermal growth factor receptor (EGFR) arm as a proof-of-concept, tumor-associated antigen paired with a single-chain HLA-A *02:01/CMVpp65 pMHC fusion moiety, we demonstrate in vitro that the IL-2-armored GPS modality robustly expands CMVpp65-specific CD8+ effector memory T cells and induces potent cytotoxic activity against target cancer cells. Similar to GPS, IL-2-armored GPS molecules induce modulated T cell activation and reduced cytokine release profile compared to an analogous CD3-targeted TCE. In vivo we show that IL-2-armored GPS, but not the corresponding GPS, effectively expands grafted CMVpp65 CD8+ T cells from unstimulated human PBMCs in an NSG mouse model. Lastly, we demonstrate that the IL-2-armored GPS modality exhibits a favorable developability profile and monoclonal antibody-like pharmacokinetic properties in human neonatal Fc receptor transgenic mice. Overall, IL-2-armored GPS represents an attractive approach for treating cancer with the potential for inducing vaccine-like antiviral T cell expansion, immune cell redirection as a TCE, and significantly widened TI due to reduced cytokine release.

Factors Associated with Usage of Oral-PrEP among Female Sex Workers in Nairobi, Kenya, Assessed by Self-Report and a Point-of-Care Urine Tenofovir Immunoassay.

Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

Alcohol withdrawal and amphetamine co-use in an animal model for attention deficit hyperactivity disorder.

Background: Non-medical use of amphetamine and other stimulants prescribed for treatment of attention deficit/hyperactivity disorder (ADHD) is of special concern when combined with alcohol consumption. In a previous study, we modeled chronic ethanol-amphetamine co-use in adolescent Long-Evans (LE) rats and provided evidence that amphetamine attenuates alcohol withdrawal symptoms.Objectives: This project modeled co-use of amphetamine with alcohol in adolescents with ADHD-like symptoms by examining ethanol-amphetamine administration in adolescent Spontaneously Hypertensive Rats (SHR), an experimental model for the study of ADHD. Withdrawal symptoms were compared among SHR and two control rat strains, LE and Wistar Kyoto (WKY).Methods: At postnatal day 32, parallel groups of 12-24 male SHR, WKY and LE rats were administered a liquid diet containing ethanol (3.6%) and/or amphetamine (20 mg/L). Following administration periods up to 26 days, rats were withdrawn from their treatment and tested for overall severity of alcohol withdrawal symptoms, general locomotor activity, and anxiety-like behavior.Results: Overall withdrawal severity was lower for SHR than for LE (p < .001) or WKY (p = .027). Co-consumption of amphetamine decreased withdrawal severity for LE (p = .033) and WKY (p = .011) but not SHR (p = .600). Only WKY showed increased anxiety-like behavior during withdrawal (p = .031), but not after amphetamine co-administration (p = .832).Conclusion: Alcohol withdrawal severity may be attenuated when co-used with amphetamine. However, as a model for ADHD, SHR adolescents appeared resistant to developing significant signs of alcohol withdrawal following alcohol consumption. Whether alcohol withdrawal symptoms are attenuated or absent, potential consequences could include a decreased awareness of an emerging problem with alcohol use.

Methodology and Characterization of a 3D Bone Organoid Model Derived from Murine Cells.

Here, we report on the development of a cost-effective, well-characterized three-dimensional (3D) model of bone homeostasis derived from commonly available stocks of immortalized murine cell lines and laboratory reagents. This 3D murine-cell-derived bone organoid model (3D-mcBOM) is adaptable to a range of contexts and can be used in conjunction with surrogates of osteoblast and osteoclast function to study cellular and molecular mechanisms that affect bone homeostasis in vitro or to augment in vivo models of physiology or disease. The 3D-mcBOM was established using a pre-osteoblast murine cell line, which was seeded into a hydrogel extracellular matrix (ECM) and differentiated into functional osteoblasts (OBs). The OBs mineralized the hydrogel ECM, leading to the deposition and consolidation of hydroxyapatite into bone-like organoids. Fourier-transform infrared (FTIR) spectroscopy confirmed that the mineralized matrix formed in the 3D-mcBOM was bone. The histological staining of 3D-mcBOM samples indicated a consistent rate of ECM mineralization. Type I collagen C-telopeptide (CTX1) analysis was used to evaluate the dynamics of OC differentiation and activity. Reliable 3D models of bone formation and homeostasis align with current ethical trends to reduce the use of animal models. This functional model of bone homeostasis provides a cost-effective model system using immortalized cell lines and easily procured supplemental compounds, which can be assessed by measuring surrogates of OB and OC function to study the effects of various stimuli in future experimental evaluations of bone homeostasis.

Household Transmission of SARS-CoV-2 in the Third Wave of the Pandemic with Special Reference to Clinico-epidemiological Characteristics.

Background: Coronavirus disease 2019 (COVID-19) pandemic began in India in 2020. Despite successful vaccination, cases again started increasing from mid-December 2021. Therefore, this study was undertaken to find out the clinico-epidemiological characteristics and effectiveness of vaccination in the household transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in and around Pune. Material and Methods: All samples received from December 15, 2021, till February 15, 2022, were included in the study. Samples received in viral transport medium (VTM) were extracted by the MagMAX RNA Extraction Kit, and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed by the CoviPath Kit as per kit guidelines. Values of nucleocapsid (N) gene and open reading frame (ORF) less than 37 were considered positive. Clinico-epidemiological data were analyzed from the sample referral form (SRF). Results: A total of 712 of 1032 household contacts of 271 families were positive. When geographical areas were compared, it was found that rural areas were affected more (63.76%) as compared to urban areas (36.24%). Males were more affected than females. The most commonly affected age group was 41-50 years (26.54%). Small families were found to have more household transmission. Mild symptoms were present in 97.89%. Among 271 infected individuals, seven were admitted to hospital, of which one patient died due to pneumonia. Two doses of vaccination were completed in 93.95%, and 3.79% had taken booster dose. Conclusions: Data from this study showed that a high rate of transmission was observed in household contact despite two doses of vaccination. However, these vaccinated individuals had mild symptoms, maybe due to the effect of vaccination and infecting variant omicron.

Stem cells in regenerative dentistry: Current understanding and future directions.

BACKGROUND: Regenerative dentistry aims to enhance the structure and function of oral tissues and organs. Modern tissue engineering harnesses cell and gene-based therapies to advance traditional treatment approaches. Studies have demonstrated the potential of mesenchymal stem cells (MSCs) in regenerative dentistry, with some progressing to clinical trials. This review comprehensively examines animal studies that have utilized MSCs for various therapeutic applications. Additionally, it seeks to bridge the gap between related findings and the practical implementation of MSC therapies, offering insights into the challenges and translational aspects involved in transitioning from preclinical research to clinical applications. HIGHLIGHTS: To achieve this objective, we have focused on the protocols and achievements related to pulp-dentin, alveolar bone, and periodontal regeneration using dental-derived MSCs in both animal and clinical studies. Various types of MSCs, including dental-derived cells, bone-marrow stem cells, and umbilical cord stem cells, have been employed in root canals, periodontal defects, socket preservation, and sinus lift procedures. Results of such include significant hard tissue reconstruction, functional pulp regeneration, root elongation, periodontal ligament formation, and cementum deposition. However, cell-based treatments for tooth and periodontium regeneration are still in early stages. The increasing demand for stem cell therapies in personalized medicine underscores the need for scientists and responsible organizations to develop standardized treatment protocols that adhere to good manufacturing practices, ensuring high reproducibility, safety, and cost-efficiency. CONCLUSION: Cell therapy in regenerative dentistry represents a growing industry with substantial benefits and unique challenges as it strives to establish sustainable, long-term, and effective oral tissue regeneration solutions.

Primary Sjogren's Syndrome with Bicytopenia: A Case Report.

Sjogren's syndrome is a chronic multisystem autoimmune disease presenting a wide variety of clinical manifestations ranging from mild sicca symptoms to severe systemic symptoms involving pulmonary, renal, musculoskeletal, cutaneous, and haematological diseases. These symptomatic diversities can delay the correct diagnosis of Sjogren's Syndrome for a long time. Here, we report the case of a 59-year-old woman with fatigue and weakness in whom bicytopenia was documented. A thorough bicytopenia workup brought us to the final diagnosis of Sjogren's syndrome. Hydroxychloroquine was started which normalized the patient's blood parameters and clinical symptoms. The haematological alterations in Sjogren's syndrome are not pathognomonic. However, only bicytopenia can be the initial presentation of Sjogren's syndrome as in our patient. Therefore, inexplicable bicytopenia in a middle-aged female may alert the clinician about the possibility of Sjogren's syndrome. Keywords: autoimmune diseases; case reports; cytopenia; sjogren's syndrome.

Capturing the holistic value of biosimilars in Europe - part 1: a historical perspective.

INTRODUCTION: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics. METHODS: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets. Key insights were also sought from an expert panel of European stakeholders. RESULTS: Survey respondents were clinicians, pharmacists, and payers from Europe (N = 103). Perceived benefits of biosimilars included increased access to innovative medicines (73% of respondents) or biologic treatments (66%). Biosimilar competition was thought to expand access to biologics (~50% of respondents) or drug combinations (~36%) and reduce biologic access time (34%). Key drivers of biologic access after biosimilar competition included increased biologic awareness (51%) and changes to prescribing guidelines (37%) and/or treatment paradigms (28%). The expert panel developed a market maturity framework of biosimilar adoption/opportunities comprising three stages: 'Invest,' 'Expand,' and 'Harvest.' Findings were supported by published literature. CONCLUSIONS: In Europe, the perceptions of well-informed survey/interview respondents are that biosimilars have improved patient outcomes via increased access to biologics and innovative biologic products, contributing to earlier and longer treatment of a broader population.

Leveraging the holistic benefits of biosimilars in Europe - part 2: how payers can safeguard the future of a healthy biosimilar market environment.

INTRODUCTION: Biosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets. AREAS COVERED: An expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1). Directional recommendations are provided for payers. EXPERT OPINION: The panel's market maturity framework for biosimilars has three stages: 'Invest,' 'Expand' and 'Harvest.' Across market stages, re-thinking the benefits of biosimilars beyond cost-savings, considering earlier or expanded access/new indications, product innovations, and re-investment of biosimilar-generated cost-savings should be communicated to stakeholders to promote further engagement. During 'Expand' and 'Harvest' stages, development of efficient, forward-looking procurement systems and mechanisms that drive uptake and stabilize competition between manufacturers are key. Future biosimilars will target various therapy areas beyond those targeted by existing biosimilars. To ensure a healthy, accessible future market, stakeholders must align their objectives, communicate, collaborate, and coordinate via education, incentivization, and procurement, to maximize the totality of benefits.

Growth hormone therapy is associated with improved uterine dimensions in girls with Turner syndrome prior to oestrogen replacement.

BACKGROUND: Adult women with Turner syndrome (TS) have high rates of miscarriage, presumably due to the abnormal size and shape of the uterus. There is a paucity of data regarding the determinants of uterine volume (UtVol) in young girls with TS before the initiation of oestrogen replacement therapy (ERT). METHODS: We performed a cross-sectional study on premenarchal girls with TS, aged 5-15 years, pubertal stage B1-B3, not having received ERT (n = 73) and 50 age-matched healthy controls. Anthropometric parameters and a history of growth hormone (GH) therapy (≥1 year) were noted. Uterine length (UtL), UtVol, and mean-ovarian-volume (MOV) standard-deviation scores (SDS) were determined from transabdominal ultrasonography data. RESULTS: Girls with TS had lower median UtVol-SDS (-1.07 vs. 0.86; p < .001), UtL-SDS (-3.72 vs. -0.41; p < .001) and MOV-SDS (-5.53 vs. 1.96; p < .001) compared to age-matched controls. Among TS girls, recipients of GH (n = 38) had higher UtVol-SDS (-0.63 vs. -1.39; p = .0001), UtL-SDS (-1.73 vs. -6.49; p < .0001) but similar MOV-SDS compared to nonrecipients (n = 35). Those with normal uterine volume for age (NUVA, n = 29) had earlier initiation (7.8 vs. 9.3 years; p = .03) and a longer duration of GH (3.71 vs. 2.14 years; p = .002) than those with low UtVol for age (n = 44). UtVol-SDS correlated with duration of GH (ρ = 0.411, p = .01) and negatively with age at GH initiation (ρ = -0.479, p = .003). In a model adjusted for pubertal status, karyotype and height-SDS, GH use could independently predict having NUVA (odds ratio: 5.09, confidence interval: 1.63-15.94, p = .005). CONCLUSION: GH therapy has a stimulatory effect on uterine dimensions in pre-and peripubertal girls with TS. Earlier initiation and longer duration of GH is important in TS girls before ERT.

Characteristics and Presentations of Hospitalized Children Due to 3 Predominate COVID-19 Variants Within a Health Care Network.

Objective of this article is to describe differences in the demographic and clinical characteristics, severity of illness, and outcomes in pediatric patients with different SARS-CoV-2 variants. We conducted a retrospective study of pediatric patients admitted with COVID-19 during the 3 large waves of infection within a health network in New Jersey. We included demographic characteristics, clinical features, and outcomes and compared the data with respect to the different variants. Of 351 total patients included in this study, 74 were admitted during wave 1, 94 during wave 2, and 181 during wave 3. The median age of patients decreased from wave 1 (11.5 years) to wave 3 (3 years) (P = .0034). 87.7% of the patients were unvaccinated. The overall incidence of admissions due to pneumonia related to COVID-19 decreased in wave 3. COVID-19 bronchiolitis or croup admissions occurred mostly in wave 3. There was no significant difference in the number of patients requiring intensive care in any particular wave. Length of stay decreased across the waves (P < .0001). Treatments required did not vary between the waves except for a decrease in antibiotic use with each subsequent wave (P < .0001). The impact of COVID-19 on the pediatric population differs from the adult population, and the overall number of hospitalized children has mirrored the peak in cases observed during each infection wave. Our study illustrates the changes in clinical presentation and severity observed with the different coronavirus variants.

Surviving pandemic control measures: The experiences of female sex workers during COVID-19 in Nairobi, Kenya.

At the beginning of the COVID-19 pandemic, the Kenya Ministry of Health instituted movement cessation measures and limits on face-to-face meetings. We explore the ways in which female sex workers (FSWs) in Nairobi were affected by the COVID-19 control measures and the ways they coped with the hardships. Forty-seven women were randomly sampled from the Maisha Fiti study, a longitudinal study of 1003 FSWs accessing sexual reproductive health services in Nairobi for an in-depth qualitative interview 4-5 months into the pandemic. We sought to understand the effects of COVID-19 on their lives. Data were transcribed, translated, and coded inductively. The COVID-19 measures disenfranchised FSWs reducing access to healthcare, decreasing income and increasing sexual, physical, and financial abuse by clients and law enforcement. Due to the customer-facing nature of their work, sex workers were hit hard by the COVID-19 restrictions. FSWs experienced poor mental health and strained interpersonal relationships. To cope they skipped meals, reduced alcohol use and smoking, started small businesses to supplement sex work or relocated to their rural homes. Interventions that ensure continuity of access to health services, prevent exploitation, and ensure the social and economic protection of FSWs during times of economic strain are required.

Childhood and adolescent factors shaping vulnerability to underage entry into sex work: a quantitative hierarchical analysis of female sex workers in Nairobi, Kenya.

OBJECTIVE: To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya. BACKGROUND: Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation. DESIGN: Building on previous qualitative research with this cohort, analysis of behavioural-biological cross-sectional data using hierarchical logistic regression. PARTICIPANTS AND MEASURES: FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural-biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling. RESULTS: Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (<18 years). In the multivariable analysis, factors associated with entering sex work while underage included incomplete secondary school education (aOR=2.82; 95% CI=1.69 to 4.73), experiencing homelessness as a child (aOR=2.20; 95% CI=1.39 to 3.48), experiencing childhood physical or sexual violence (aOR=1.85; 95% CI=1.09 to 3.15), young age of sexual debut (≤15 years) (aOR=5.03; 95% CI=1.83 to 13.79) and being childless at time of sex work initiation (aOR=9.80; 95% CI=3.60 to 26.66). CONCLUSIONS: Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences.

Performance of HDP-Gestosis Score and Ophthalmic Artery Doppler in Prediction of Pre-eclampsia.

Purpose of Study: To study the predictive accuracy of maternal characteristics, mean arterial pressure, uterine artery doppler and maternal ophthalmic artery doppler in second trimester for subsequent development of pre-eclampsia. Methods: A prospective cohort study of 440 women at 19-24 weeks' gestation. It included recording of maternal demographic characteristics and calculation of HDP Gestosis Score, measurement of MAP and ultrasound evaluation for fetal anatomy, Uterine artery doppler and maternal ophthalmic artery doppler. The mean Peak Systolic Velocity ratio was obtained by taking two sets of reading from both eyes. The statistical analysis was done using independent t-test for quantitative variables and chi-square test, Fisher's exact test for qualitative variables and Area Under Curve was obtained at 10% False Positive Rate. Results: Among 440 pregnant women, 43(10.8%) developed Hypertensive Disorder of Pregnancy (8 early onset PE, 16 late onset PE and 19 GHTN) and 42 were lost to follow up, with an incidence rate of 10.8%. Combination of Gestosis Score + OAD PSV Ratio had highest AUC of 0.73. Whereas combination of Gestosis Score + MAP + UtAPI + OAD-PSV Ratio had highest sensitivity of 97.67%. The OAD PSV ratio improved detection rate of Gestosis Score (from 90 to 100%) for prediction of development of PE, especially Preterm PE at 10% FPR. Conclusion: Maternal Ophthalmic artery doppler study significantly improved prediction of development of PE at 19-24 weeks' gestation, both independently as well as in combination with HDP-Gestosis Score, MAP and uterine artery doppler.

Essential oils: How safe? How effective?

Given the ubiquity of these plant-based oils, your patients might ask about using them. Here's the evidence on safety and efficacy to guide your response.

Metastatic squamous cell carcinoma masquerading as acute retinal necrosis.

Purpose: To describe a case of retinal and optic nerve metastases masquerading as acute retinal necrosis secondary to primary squamous cell carcinoma of the lung. Observations: A 66-year-old male with a history of Stage IV lung cancer, actively on chemotherapy, presented with right eye vision loss, an afferent pupillary defect, and partial visual field deficiencies. Exam revealed vitritis, macula-involving infiltrative retinitis, optic neuritis, and vasculitis of the right eye. The patient was treated empirically for acute viral retinitis with intravitreal foscarnet and ganciclovir injections and oral acyclovir and trimethoprim-sulfamethoxazole. A diagnostic pars plana vitrectomy with vitreous biopsy, intravitreal antivirals and silicone oil fill was performed. The resulting cytology was positive for malignant squamous cell carcinoma. Conclusions and importance: We present a unique case of primary squamous cell carcinoma metastasizing to the retina and optic nerve which masqueraded as an acute viral retinitis. To date, there have not been any reported cases on Pubmed or Google Scholar at publication time of known squamous cell carcinoma metastases to the retina that demonstrated interval growth leading to emergent elevations in intraocular pressure (IOP). This case demonstrates the importance of considering metastasis when encountering an atypical acute retinal necrosis case, as well as bring awareness to the possibility that elevated IOP may be the first sign of interval metastases, despite surgical debulking, in cases involving known tumor metastases to the retina.

Neonatal Serum Gentamicin Concentrations and Outcomes Following Maternal Once-Daily Gentamicin Dosing.

OBJECTIVE: This study evaluated newborn gentamicin serum concentrations after birth and the effects on the newborn after extended interval gentamicin dosing in peripartum mothers. METHODS: This was a single-center, retrospective chart review of neonates born to mothers that received peripartum once-daily gentamicin dosing of approximately 5 mg/kg within 12 hours of delivery. A gentamicin serum concentration was obtained immediately after birth in the newborn. The primary outcome was initial neonatal gentamicin serum concentration after birth. Several secondary outcomes were evaluated including nephrotoxicity and ototoxicity. A subgroup analysis comparing baseline demographics of mother-newborn dyads with birth neonatal serum concentrations of less than 2 mcg/mL versus 2 mcg/mL or greater was performed. RESULTS: A total of 32 mother-newborn dyads were included. Newborns had a median gestational age of 39.4 weeks and median birth weight of 3.4 kg. The mean initial gentamicin serum concentration was elevated at 3.1 ± 1.9 mcg/mL among all newborns. The median maternal dose based on actual body weight in newborns with gentamicin serum concentrations less than 2 mcg/mL was 3.5 (IQR, 3.3-4.8) mg/kg versus 4.8 (IQR, 4.3-5.2) mg/kg in those that had serum concentrations of 2 mcg/mL or greater (p = 0.025). All newborn gentamicin serum concentrations were less than 2 mcg/mL for maternal doses given less than 1 hour prior to delivery (n = 8). There were no significant differences in nephrotoxicity or ototoxicity. CONCLUSIONS: Peripartum once daily dosing of gentamicin administered between 1 to 12 hours of birth may lead to clinically significant serum concentrations in newborns.

Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration.

Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remain several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration, given their high performance in filling irregularly sized bone defects and their ability to encapsulate cells and bioactive molecules and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote the differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts, as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.