Toxicity, inflammation, and anti-human immunodeficiency virus type 1 activity following exposure to chemical moieties of C31G.

C31G, which has potent activity against the human immunodeficiency virus type 1 (HIV-1) and an established record of safety in animal studies and human trials, is a microbicidal agent comprised of a buffered equimolar mixture of two amphoteric, surface-active agents: an alkyl amine oxide (C14AO) and an alkyl betaine (C16B). Studies of long-term in vitro exposure to C31G and its constituents have suggested that the components of C31G may contribute differentially to its toxicity and efficacy. In the present studies, in vitro assays of cytotoxicity and anti-HIV-1 activity demonstrated that C16B was slightly less cytotoxic compared to either C31G or C14AO, whereas the anti-HIV-1 activities of C31G and its individual constituents were similar. In the murine model of cervicovaginal microbicide toxicity, in vivo exposure to C14AO resulted in severe cervical inflammation followed by a delayed disruption of the columnar epithelium. In contrast, exposure to C16B caused severe cervical epithelial disruption and a secondary, less intense inflammatory response. These results demonstrate that (i) there are both mechanistic and temporal differences in toxicity associated with the components of C31G not necessarily predicted by in vitro assessments of cytotoxicity and (ii) contributions of each component to the anti-HIV-1 activity of C31G appear to be equal. In addition, these findings indicate that direct and indirect mechanisms of in vivo toxicity can be observed as separate but interrelated events. These results provide further insight into the activity of C31G, as well as mechanisms potentially associated with microbicide toxicity.     

Coexistence of salivary gland cysticercosis with squamous cell carcinoma of the mandible.

Cysticercosis is a parasitic infestation caused by the pork tapeworm larval stage, Cysticercus cellulosae. The majority of the cases present in ocular, cerebral, and subcutaneous locations. We report the presence of cysticercosis inside the submandibular gland in association with squamous cell carcinoma of the inferior alveolar ramus of the mandible. To the best of our knowledge, this is the first case report documenting cysticercosis inside a salivary gland. A 65-year-old male presented with complaints of an ulcerative lesion on the inferior alveolar ramus present for 2 months. Histological examination revealed a keratinizing well-differentiated squamous cell carcinoma involving the alveolar margin and mandible. The histopathological examination of the submandibular gland revealed cysticercosis. This case emphasizes the importance of adequate sampling of all the tissues obtained for associated infectious disorders, more so in immunosuppressed patients, which will help the clinician to manage the case appropriately.     

Experimental neurotoxicity of the anorectic fenfluramine

Summary Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic reactive microglia were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.Paper presented at the Erwin Riesch symposium on Lysosomal Disorders of the Nervous System, Berlin (Convenor, Prof. Cervos-Navarro); and as poster-talk at the 9th International Congress of Neuropathology, Vienna, September 1982     

Food Program Participation Influences Nutrition Practices in Early Care and Education Settings

ObjectiveTo determine differences by Child and Adult Care Food Program (CACFP) participation on nutrition requirements and best practices and barriers to implementing both in early care and education programs (ECEs) stratified by context (centers vs home-based ECEs).DesignCross-sectional survey.SettingThree-thousand and fourteen licensed Nebraska ECEs in 2017.ParticipantsOne-thousand three hundred forty-five ECEs.Main Outcome Measure(s)Director-reported nutrition practices in classrooms serving children aged 2-5 years (8 requirements for foods served, 5 best practices for foods served, and 14 best practices for mealtime behaviors).AnalysisChi-square analysis adjusted for multiple comparisons.ResultsOf the sample, 86.8% participated in CACFP, 21.7% were center-based, and 78.3% were home-based. Overall, CACFP participation was related to the higher implementation of CACFP requirements for foods served (P < 0.004 for all) and receiving professional development on nutrition (P < 0.012). In home-based ECEs only, CACFP participation was related to a higher prevalence of serving meals family-style (P = 0.002); however, these practices had low implementation overall.Conclusion and ImplicationsFindings suggest strengthening of requirements to include staff mealtime behaviors beyond service of healthful foods. Improving CACFP enrollment and including CACFP standards in state licensing requirements may be key strategies for improving nutrition practices in ECEs.     

Variation in acute fluid resuscitation among pediatric burn centers

BackgroundAccurate resuscitation of pediatric patients with large thermal injury is critical to achieving optimal outcomes. The goal of this project was to describe the degree of variability in resuscitation guidelines among pediatric burn centers and the impact on fluid estimates.MethodsFive pediatric burn centers in the Pediatric Injury Quality Improvement Collaborative (PIQIC) contributed data from patients with ≥15% total body surface area (TBSA) burns treated from 2014 to 2018. Each center's resuscitation guidelines and guidelines from the American Burn Association were used to calculate estimated 24-h fluid requirements and compare these values to the actual fluid received.ResultsDifferences in the TBSA burn at which fluid resuscitation was initiated, coefficients related to the Parkland formula, criteria to initiate dextrose containing fluids, and urine output goals were observed. Three of the five centers’ resuscitation guidelines produced statistically significant lower mean fluid estimates when compared with the actual mean fluid received for all patients across centers (4.53 versus 6.35 ml/kg/% TBSA, p < 0.001), (4.90 versus 6.35 ml/kg/TBSA, p = 0.002) and (3.38 versus 6.35 ml/kg/TBSA, p < 0.0001).ConclusionsThis variation in practice patterns led to statistically significant differences in fluid estimates. One center chose to modify its resuscitation guidelines at the conclusion of this study.     

Assessing opioid administration in pediatric burn patients with nonsurgical management

BackgroundDespite the vast literature studying the opioid crisis, sparse data describe this in the pediatric burn population. This study sought to assess patient-level characteristics and their potential effects on opioid administration in nonsurgical pediatric burn inpatients.MethodsAdmitted burn patients from 2013 to 2018 with nonsurgical management at an American Burn Association (ABA) verified pediatric burn center were retrospectively identified. Morphine milligram equivalents by weight (MME/kg) per admission were evaluated through a multiple loglinear regression with race, sex, age, total body surface area burned (TBSA), and burn depth as predictors. Simple linear regression was used to evaluate the temporal trend of median opioid utilization.ResultsA total of 806 patients (55% White, 35% Black, 5% Hispanic, 5% Other) were included. In an adjusted analysis, no differences in opioid administration were seen by sex, burn degree, or for Blacks and Hispanics when compared with Whites. Increased MME/kg was associated with older age (10–18 years; p < 0.0001) and larger burns (>5% TBSA burned; p < 0.0001). From 2013 to 2018, median MME/kg per admission declined significantly (2013:0.21, 2018:0.09; p = 0.0103).ConclusionsNonsurgical burn patients who were older and presented with larger TBSA experienced marked increases in opioid utilization. Overall, opioid administration decreased over time.     

Measurement of albumin and low molecular weight proteins in the urine of newborn infants using a cotton wool ball collection method

Objective : The aim of this study was to investigate the inter-relationship between urinary excretion of alpha-1-microglobulin (AIM), retinol-binding protein (RBP) and albumin in term and premature neonates, with urine collected into cotton wool balls and extracted by a novel method. Subjects and methods : Sixty-four infants were studied on the first day of life; 26 had been born at term (37–42 weeks gestation) and 38 prematurely (24–28 weeks n = 16, 29–36 weeks n = 22). Urine collected into cotton wool balls was analysed following a new detergent extraction method, which resulted in a recovery rate of 94–107% for albumin, AIM, RBP and creatinine. Results : Urinary protein excretion, expressed as a ratio to urinary creatinine, decreased significantly with increasing gestational age (24–28 weeks, 29–36 weeks, 37–42 weeks: albuminxreatinine ratio mg/mmol mean 96.9, 31.7, 19.3; AIM: creatinine ratio mg/mmol mean 99.3, 37.0, 7.8; RBP: creatinine ratio mg/mmol mean 16.2, 3.8, and <0.01, below the limit of detection, respectively). When results were corrected for birthweight, this gestation-associated effect was still present for A1M and RBP, but not for albumin. In premature infants there was a significant positive correlation between AIM: creatinine ratio and RBP: creatinine ratio ( r = 0.85), and also between albumin and both AIM and RBP ( r = 0.82 and 0.77). Conclusion : Increased excretion of AIM, RBP and albumin at earlier gestational ages is probably due to proximal tubular immaturity, although tubular damage and also glomerular dysfunction cannot be excluded as possible explanations.     

Custom Ocular Prosthesis: A Palliative Approach

The goal of palliative care is the achievement of the best quality of life for patients and their families. Eyes are generally the first features of the face to be noticed. Loss of an eye is a traumatic event which has a crippling effect on the psychology of the patient. Several ocular and orbital disorders require surgical intervention that may result in ocular defects. An ocular prosthesis is fabricated to restore the structure, function, and cosmetics of the defects created by such conditions. Although an implant eye prosthesis has a superior outcome, due to economic factors it may not be a feasible option for all patients. Therefore, a custom-made ocular prosthesis is a good alternative. This case report presents a palliative treatment for a patient with an enucleated eye by fabricating a custom ocular prosthesis which improved his psychological, physical, social, functional, emotional and spiritual needs.     

Newborn Screening for Hemoglobinopathies and Red Cell Enzymopathies in Tripura State: A Malaria-Endemic State in Northeast India

Hemoglobinopathies are a group of inherited single gene disorders. There are reports on hemoglobin (Hb) variants identified in the tribal and non-tribal populations of Tripura State in northeastern India. This study aimed to determine the spectrum of hemoglobinopathies and enzymopathies by newborn screening in Tripura State and assess the extent of neonatal jaundice. A total of 2400?cord blood samples were collected and analyzed by high performance liquid chromatography (HPLC). Further confirmation of any abnormal HPLC was done by DNA analysis. The samples were also screened for deficiency of enzymopathies, glucose-6-phosphate dehydrogenase (G6PD) deficiency and pyruvate kinase. Of 2400?cord blood samples screened, 225 (9.3%) were Hb E (HBB: c.79G>A) heterozygotes, 80 (3.3%) were Hb E homozygotes and one carried Hb E-β-thalassemia (β-thal). Other Hb abnormalities were also detected including 15 Hb S (HBB: c.20A>T) heterozygotes, two Hb D-Punjab (HBB: c.364G>C) heterozygotes and two compound heterozygotes for Hb D-Punjab and Hb E. Of the 80 homozygous Hb E babies, four were non-tribal and 76 babies were tribal, and 225 patients carried Hb E trait, 141 were tribal, while 84 were non-tribal. Of 40 G6PD deficient babies identified, 13 had coinherited Hb E and two babies had pyruvate kinase deficiency. α Genotyping was performed in 162 affected babies, 50 of them carried α gene deletions. Newborn screening programs for Hb E, other hemoglobinopathies and G6PD deficiency must be encouraged in the malaria-endemic northeastern region of India. Drug-induced hemolysis can also be avoided by screening for G6PD deficiency at birth.