Assessment of Nutrition Status and Its Effect on Outcomes in Patients With Limb Injuries Using the Subjective Global Assessment as a Screening Tool.

Background Malnutrition in hospitalized patients is a significant problem. This study aimed to assess the utility of the Subjective Global Assessment (SGA) in predicting the association between serum biomarkers and malnutrition in patients with limb injuries as well as the impact of malnutrition on clinical and radiological bone healing. Methodology This prospective study included 93 patients with limb injuries. Basic demographic details, serum biomarker levels, nutritional status assessed using the SGA, and the correlation of the Radiological Union Shaft Tibia (RUST) score with nutrition status were assessed along with the secondary outcomes. Results According to the SGA, patients were classified into Group A (well-nourished), Group B (moderately malnourished), and Group C (severely malnourished). Serum biomarkers (albumin, hemoglobin, platelets, and total leucocyte count) were significantly higher in Group A than in Group B + C (p < 0.0001). The nutritional status of patients from admission up to six months in Group A was significantly higher (p < 0.0001) compared to Group B + C. The radiological healing according to the RUST score had a negative correlation with C-reactive protein and a positive correlation with various parameters at six months. Conclusions The serum biomarker levels and the clinical and radiological bone healing, as measured by the RUST scoring system, showed a positive correlation with the nutritional status of the patients. Malnutrition significantly increases the chance of developing complications such as wound infection, decubitus, and infected implants.

Comparing maternal substance use and perinatal outcomes before and during the COVID-19 pandemic.

OBJECTIVE: To examine the effect of the COVID-19 pandemic on maternal substance abuse and neonatal outcomes. STUDY DESIGN: Cross-sectional observational study of neonates admitted to the NICU and born to mothers with evidence of substance abuse pre-pandemic compared to during the COVID-19 pandemic. RESULT: We noted a significant increase in fentanyl (12% vs. 0.6%, p < 0.001) and tobacco use (64% vs. 33%, p < 0.001) during the pandemic compared to pre-pandemic, including an increase in fentanyl use among mothers enrolled in opioid maintenance therapy (OMT) during the pandemic (32.3% vs. 1.5%, p < 0.001). There was a significant increase in preterm births (58% vs. 48%, p = 0.022) and lower birth weight (2315 ± 815 vs. 2455 ± 861 g, p = 0.049) during pandemic. CONCLUSION: There was a significant increase in maternal fentanyl use during the pandemic, even with OMT enrollment, with an increase in preterm births and lower birth weights among infants born to mothers with substance use.

Assessing Neonatal Opioid Withdrawal Syndrome Severity as a Function of Maternal Buprenorphine Dose and Umbilical Cord Tissue Concentrations.

BACKGROUND: Infants born to mothers with opioid use disorder (OUD) and prenatally treated with buprenorphine have a significantly lower incidence of neonatal opioid withdrawal syndrome (NOWS), its treatment duration, and hospital length of stay compared with methadone. However, risk of NOWS remains and clinicians continue to lack an objective methodology to predict NOWS severity among these infants. OBJECTIVE: The purpose of this study was to assess the relationship between buprenorphine exposure, umbilical cord tissue (UCT) concentrations, and NOWS development and severity. METHODS: A single-center retrospective observational cohort study from March 2018 through June 2020 of newborns exposed to buprenorphine in utero. Associations between quantified buprenorphine exposure, neonatal UCT concentrations, NOWS diagnosis, and severity were made using regression analyses. RESULTS: A total of 24 mothers and 25 neonates were included. Length of maternal buprenorphine therapy (months) positively correlated to norbuprenorphine (r2 = 0.234, P = 0.019) and buprenorphine + norbuprenorphine UCT concentrations (r2 = 0.203, P = 0.031). A positive relationship was seen between active metabolite concentrations and cumulative morphine dose (mg/kg) for treatment of severe NOWS (r2 = 0.471, P = 0.007). A 0.36 ng/g buprenorphine + norbuprenorphine UCT (CI = 0.002-0.72, P = 0.049) equated in a 1-point increase in modified peak Finnegan score. CONCLUSION AND RELEVANCE: Buprenorphine and norbuprenorphine UCT concentrations can allow for quantification of in utero fetal exposure and demonstrate an association with a longer duration of exposure with the severity and treatment of NOWS in exposed infants.

Rational Primer and Probe Construction in PCR-Based Assays for the Efficient Diagnosis of Drifting Variants of SARS-CoV-2.

The genome sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving via genomic drifts resulting in "emerging/drifting variants" circulating worldwide. The construction of polymerase chain reaction (PCR) assays for the reliable, efficient, and specific diagnosis of the drifting variants of SARS-CoV-2 is specifically governed by the selection and construction of primers and probes. The efficiency of molecular diagnosis is impacted by the identity/homology of the genome sequence of SARS-CoV-2 with other coronaviruses, drifting variants or variants of concern (VOCs) circulating in communities, inherent capacity of mutation(s) of various target genes of SARS-CoV-2, and concentration of genes of interest in host cells. The precise amplicon selection and construction of primers and probes for PCR-based assays can efficiently discriminate specific SARS-CoV-2 drifting variants. The construction of single nucleotide polymorphism (SNP)-specific primers and probes for PCR assays is pivotal to specifically distinguish SARS-CoV-2 variants present in the communities and contributes to better diagnosis and prevention of the ongoing COVID-19 pandemic. In this study, we have utilized in silico-based bioinformatic tools where the alignment for genes, the positions and types of SNPs/mutations of VOCs, and the relative number of SNPs per nucleotide in different genomic regions were investigated. Optimal and specific genome region (amplicon) selection with comparatively lower mutability in the SARS-CoV-2 genome should be prioritized to design/construct PCR assays for reliable and consistent diagnosis in various regions of the world for a longer duration of time. Further, the rational selection of target genes that is at an optimal detectable concentration in biological samples can bolster PCR assays of high analytical sensitivity. Hence, the construction of primers and probes with the rational selection of targeting specific E gene, genomic regions with highly conserved sequences, multiple target genes with relatively lower mutability and detectable level of concentration, SNP-specific binding regions of spike (S gene) protein, and shorter amplicon size (100-150 bp) are vital for the PCR assays to achieve optimal efficiency in the point-of-care laboratory diagnosis of circulating drifting variants of SARS-CoV-2 with optimal accuracy.

Psychological Predictors of Adherence to Self-Care Behaviour amongst Patients with Type 2 Diabetes Mellitus (T2DM) Visiting Public Hospital, North India.

Background and Aims: Patients with type 2 diabetes mellitus (T2DM) need a high degree of self-care behavior, treatment adherence, and good psychological health. Psychological health play a vital role in adherence to treatment regimen and self-management of diabetes. This study aims to identify the psychological predictors of self-care behaviors among patients with T2DM. Methods: A descriptive cross-sectional survey was conducted at a diabetic clinic at a tertiary care hospital in North India. Structured pre-tested personal and clinical profile and self-efficacy, diabetes distress, depression and anxiety, and complications and fear of developing hypoglycaemia due to diabetes mellitus in the future are measured through standardized questionnaires. Results: The mean age of the participants was 53.5 (±3.68) years, and 41.4% were in the overweight (BMI: 25.0-29.9) and obese (16.7%, BMI > 30) category. Self-care behaviours found significant association with self-efficacy (r = 0.34, P < 0.001), anxiety (r = -0.28, P < 0.001), depression (r = -0.28, P < 0.001) and diabetes-related distress (r = -0.30, P < 0.001). Further, self-efficacy (P = 0.001), diabetes distress (P < 0.001) and fear of developing hypoglycaemia (P < 0.001) were reported independent predictors of self-care behaviour in patients with T2DM. Conclusions: The current study suggests that self-efficacy, fear of hypoglycaemia and emotional state played an important role in adherence to self-care behaviour in T2DM management. Patients with diabetes mellitus should be routinely screened for psychological factors at diabetes clinics. Thus, developing tailored interventions to raise belief and self-efficacy might be a useful way to increase the involvement of patients in treatment.

Effect of prenatal marijuana exposure on sleep wake cycles and amplitude-integrated electroencephalogram (aEEG).

OBJECTIVE: To assess whether prenatal exposure to marijuana (THC) results in abnormal amplitude integrated encephalograms (aEEG). DESIGN: This was a (2018-2020) prospective cohort study of prenatally THC-exposed newborns. Maternal and Infant demographics, urine (UDS) and umbilical cord drug screening (UCDS) were recorded. A limited channel continuous aEEG was obtained within 48 h of birth. Statistical analysis included univariate, multivariate, and logistical regression. RESULTS: A total of 30 mother/infant dyads were enrolled. 60% (18/30) of neonates had abnormal aEEGs with sleep wake cycle (SWC) disturbances (p < 0.001). UCDS Carboxy-THC pg/g levels were similar in infants with abnormal [1758 (296,2838)] and normal aEEG [1589 (332,2794)], p = 0.82. CONCLUSIONS: Absence of SWCs on aEEG is associated with prenatal THC exposure. While THC UCDS levels did not correlate to aEEG results future longitudinal studies are necessary to obtain detailed history of THC use and to evaluate its association with abnormal aEEG and the neurodevelopmental outcomes.

Racial differences in opioid withdrawal syndrome among neonates with intrauterine opioid exposure.

BACKGROUND: The aim of this study was to investigate the association between race and severe neonatal opioid withdrawal syndrome (NOWS) in infants exposed to intrauterine opioids. METHODS: This is a prospective observational study on intrauterine opioid-exposed term infants. Exposure to opioids was based on maternal disclosure, urine, or umbilical cord drug screening. Severe NOWS was defined based on modified Finnegan scoring and the need for pharmacological intervention. RESULTS: One hundred and fifty mother-infant pairs, 60 Black and 90 White with history of opioid exposure during pregnancy, were included. More White than Black infants developed NOWS that required pharmacological treatment, 70 vs. 40%: RR = 1.75 (1.25-2.45). In adjusted analysis, there was no significant association between race and the development of severe NOWS in mothers who attended opioid maintenance treatment program (OMTP). However, in mothers who did not attend OMTP, White race remained a significant factor associated with the development of severe NAS, RR = 1.69 (1.06, 2.69). CONCLUSIONS: Severe NOWS that required pharmacological intervention was significantly higher in White than in Black infants born to mothers who did not attend OMTP. Larger studies are needed to evaluate the association between social as well as genetic factors and the development of NOWS. IMPACT: There is a significant association between race and development of severe NOWS.

Sequence mismatch in PCR probes may mask the COVID-19 detection in Nepal.

•Most of the COVID-19 cases in Nepal are in the Southern districts of Nepal bordering India with travel histories to India.•Very few positive cases of COVID-19 are detected in Nepal which could either be due to early national lockdown.•Low PCR positivity rates could also be due to inefficiency of the PCR methods.•Whole genomes of 93 clinical samples from COVID-19 patients were analyzed to find the primer and probe binding sites.•Mutations in probe binding sites were found which could impact PCR efficiency resulting in false negative results.

Protein Tyrosine Phosphatase (PTP1B): A promising Drug Target Against Life-threatening Ailments.

BACKGROUND: Protein tyrosine phosphatases are enzymes which help in the signal transduction in diabetes, obesity, cancer, liver diseases and neurodegenerative diseases. PTP1B is the main member of this enzyme from the protein extract of human placenta. In phosphate inhibitors development, significant progress has been made over the last 10 years. In early-stage clinical trials, few compounds have reached whereas in the later stage trials or registration, yet none have progressed. Many researchers investigate different ways to improve the pharmacological properties of PTP1B inhibitors. OBJECTIVE: In the present review, authors have summarized various aspects related to the involvement of PTP1B in various types of signal transduction mechanisms and its prominent role in various diseases like cancer, liver diseases and diabetes mellitus. CONCLUSION: There are still certain challenges for the selection of PTP1B as a drug target. Therefore, continuous future efforts are required to explore this target for the development of PTP inhibitors to treat the prevailing diseases associated with it.

Charting the challenges behind the testing of COVID-19 in developing countries: Nepal as a case study.

The infrastructure needed to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (COVID-19) that complies completely with WHO guidelines is lacking across many parts of the globe, especially in developing countries, including Nepal. We outline the problems faced by such countries and suggest that the national and international community should collaborate in the development and adoption of novel protocols for the rapid detection of COVID-19 according to locally available infrastructure, in order to fight against the outbreak.

Amplitude-integrated EEG in infants with neonatal abstinence syndrome.

BACKGROUND: To describe amplitude-integrated encephalogram (aEEG) characteristics of neonates with neonatal abstinence syndrome (NAS). METHODS: This is a prospective observational study. Newborns exposed to prenatal opioids and their gestational matched controls were included. A single-channel aEEG was obtained using Olympic 6000 CFM monitor. The background activity (continuous/discontinuous), the amplitudes (µV) and the presence of sleep-wake cycle (SWC) were documented. RESULTS: A total of 59 infants, 23 with NAS and 36 controls were enrolled. All aEEG were completed within 48 hours of life prior to initiation of treatment. Birth weight and gestational age were similar in both groups. An aEEG was abnormal (discontinuous pattern and/or absent SWC) in 78 % (18/23) of infants with NAS versus only 25% in control group (9/36), [OR 10.8, CI (2.7-46.5) P < 0.001]. 61% of infants with NAS had discontinuous pattern [OR 7.8, CI (2-32) P = 0.001] and 39% had absence of sleep-wake cycle [OR 7.1, CI (1.4-39.4) P = 0.007]. CONCLUSIONS: A majority of infants with NAS have abnormal aEEG activity.

Is there a Role for Sodium Orthovanadate in the Treatment of Diabetes?

BACKGROUND: Diabetes is a metabolic disorder, whose incidences are increasing day by day. Various classes of anti-diabetic drugs are clinically approved by the Food and Drug Administration (FDA) for the treatment of diabetes mellitus, but unfortunately, none of them is able to treat this condition. Thus, the exploration of novel mechanistic pathways of existing molecules may help to develop more safe and effective anti-diabetic agents. Sodium orthovanadate is a well known common laboratory agent used to preserve the protein tyrosyl phosphorylation state of the protein. METHODS: The data related to sodium orthovanadate and diabetes mellitus has been collected from Pubmed. RESULTS: Various reports have indicated the potential of sodium orthovanadate as Protein Tyrosine Phosphatase (PTP1B) inhibitors which play an important role in the pathogenesis of diabetes. However, safety of Sodium orthovanadate is still questionable. CONCLUSION: The sodium orthovanadate could be developed as an anti-diabetic agent. However, further studies are required to confirm its safety profile in the treatment of diabetes mellitus before starting a clinical trial.

Protective Effect of Alpha-Tocopherol in Deltamethrin Induced Immunotoxicity.

BACKGROUND AND OBJECTIVE: α-Tocopherol is the active form of vitamin E which has various biological functions. However, the exact molecular mechanism of its action is not fully understood. Thus, the main objective of the current study is to determine the contribution of α-tocopherol in counteraction of the apoptogenic signaling pathways induced by deltamethrin in murine thymocytes and splenocytes. METHODS AND RESULTS: Deltamethrin (25 µM) induces apoptosis at 18 h through the activation of reactive oxygen species, caspases and depletion of glutathione in thymocytes and splenocytes. MTT assay results have shown that α-tocopherol (10 and 50 µg/ml) when added along with Deltamethrin (25µM), increases the viability of thymocytes and splenocytes in a concentration-dependent manner. The α-tocopherol treatment reduces the early markers of cell death (ROS and caspase3 activation) significantly. Further, the depleted GSH by deltamethrin has also been restored by α-tocopherol. At 18 h, α-tocopherol (50 µg/ml) significantly reduced the Deltamethrin induced cell death. In additional, phenotyping and cytokines assay have demonstrated that alpha-tocopherol significantly ameliorated the altered immune functions. CONCLUSION: These findings indicate that α-tocopherol shows immunoprotective effects in Deltamethrin induced splenic and thymic apoptosis by inhibiting oxidative stress and caspasedependent apoptogenic pathways.

Endothelial Progenitor Cells as Molecular Targets in Vascular Senescence and Repair.

Endothelial progenitor cells are circulating blood cells derived from various sources like bone marrow, spleen, umbilical cord, liver, kidney and other sources that play a vital role in the regeneration of the endothelial lining of blood vessels and wound repair. There are two types of EPCs, early EPCs and late EPCs. EPCs are believed to originate from hematopoietic stem cells and mesenchymal stem cells. The mobilization of progenitor cells from bone marrow to the peripheral circulation is highly regulated under both normal physiological conditions and stress. EPCs contribute to neovascularization and tissue repair in the musculoskeletal, neural tissues and the bone which are mobilized and recruited to the injured tissue. Cell-based therapies of endothelial progenitor cells are time-consuming and expensive for performing in-vitro cell expansion procedures. New therapeutic approaches are being developed using animal models based on the specific functions of EPC in in-vitro and in-vivo experiments which have revealed the importance of various signalling pathways. It has been clear that the activation state of EPCs is critical to the vessel repair process and the role has not been completely understood.

Opening a Can of Worms: Leprosy Reactions and Complicit Soil-Transmitted Helminths.

BACKGROUND: >94% of new annual leprosy cases are diagnosed in populations co-endemic for soil-transmitted helminths (STH). STH can profoundly dysregulate host immune responses towards Th2 bias, which can be restored over time after deworming. We hypothesize that STH co-infection is associated with leprosy reaction (denoted as simply "reaction" herein) occurrence within a co-endemic population. METHODS: A cohort study was performed on a cohort of Nepalese leprosy patients across treatment and diagnostic classifications who were screened by routine fecal smear microscopy and multiplex quantitative PCR (qPCR) for Ascaris lumbricoides (Al), Strongyloides stercoralis (Ss), Ancyclostoma duodenale (Ad) and Necator americanus (Na). RESULTS: Among 145 patients, 55% were positive for ≥1 STH (STH+): 34% Al+, 18% Ss+, 17% Ad+and 5% Na+. Significant inverse STH and reaction relationships were evidenced by the bulk of cases: 63% reaction-negative were STH+ of total cases (p=0.030) while 65% reaction-positive were STH- in new cases (96; p=0.023). Strikingly, the majority of STH+ were reaction-negative, even when considering each species: 59% Al+, 60% Ss+, 62% Ad+and 67% Na+of new leprosy cases. CONCLUSIONS: Absence of STH co-infection is associated with leprosy reaction at diagnosis within a co-endemic population. This is likely due to immune reconstitution effects after deworming or interruption of chronic STH-mediated immune dysregulation.

Anatomical Closure of Left-to-Right Shunts in Premature Infants with Bronchopulmonary Dysplasia and Pulmonary Hypertension: A Cautionary Tale.

Closure of a systemic to pulmonary shunt in premature infants with bronchopulmonary dysplasia may be beneficial, but in the presence of pulmonary hypertension is controversial. Here, we discuss two premature infants with pulmonary hypertension who developed acute pulmonary hypertensive crisis after closure of these shunts and hence advise caution.

Staphylococcus aureus, including community-acquired methicillin-resistant S. aureus, in a level III NICU: 2001 to 2008.

OBJECTIVE: To determine epidemiology and clinical characteristics of infants with methicillin-susceptible (MSSA) and -resistant Staphylococcus aureus (MRSA) in a level III neonatal intensive care unit (NICU). STUDY DESIGN: All NICU admissions (2001 to 2008) with any positive S. aureus culture were included as cases. Cases were further characterized as either colonized or infected with invasive disease. RESULTS: Four thousand three hundred four infants were admitted; 273 (6.3%) had at least one culture positive for S. aureus, including 198 with MSSA and 75 with MRSA. Invasive disease occurred in 23.2% of MSSA cases versus 29.3% MRSA (p = 0.298). Between the study periods 2001 to 2005 versus 2006 to 2008, the incidence of all MSSA cultures (colonization and invasive disease) decreased from 53.6 to 38.9/1000 admissions (p = 0.044), and that of MRSA increased from 13.7 to 24.77/1000 admissions (p = 0.010). The incidence of invasive MSSA (p = 0.49) and MRSA (p = 0.38) disease between the two periods remained similar. Infants with invasive MRSA versus MSSA had a longer duration of positive cultures (55 versus 19 days, p = 0.009). None of five available isolates collected prior to 2006 was characterized as USA300, but 11/21 isolates collected subsequently were USA300 (p = 0.053). CONCLUSION: The incidence of MRSA (colonization and infection) nearly doubled during the study period coinciding with emergence of community-acquired MRSA USA300.