A Stitch in Time Saves Nine: Planning for Artesunate Supply with Malaria on the Rise.

Background: Malaria is extremely rare in the United States. Physicians should not only be familiar with signs and symptoms, but also be aware of the available resources at their respective institutions to be able to effectively treat it. Presentation: 52-year-old female presented with worsening generalized fatigue. Vitals were stable. Labs were significant for anemia and thrombocytopenia. Peripheral smear showed ring formed parasitic trophozoites consistent with Plasmodium falciparum. Due to unavailability of antimalarial agents at our hospital, the patient was transferred to a tertiary care center. Patient was started on IV artesunate therapy. Repeat smear after 3 days showed <1% parasitemia after 3 days and the patient was discharged with artemether/lumefantrine for 3 additional days, resulting in full recovery. Conclusion: This case gives a unique insight into the challenges that hospitals in non-endemic regions may have to face, in terms of diagnosing malaria and having access to antimalarial agents.

Cefepime extended infusion versus intermittent infusion: Clinical and cost evaluation.

Background: Extended infusion cefepime (1 gram every 6 hours administered over 3 hours) achieves pharmacodynamic efficacy against bacteria with a MIC of ≤8 mg/L in Monte Carlo simulations. This regimen has not been evaluated in clinical practice. Objective: Compare clinical and economic outcomes for cefepime by intermittent infusion and by extended infusion in the acute-care setting. Design: Single-center, retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Hospitalized adults who received cefepime between August 2016 and July 2018 with a diagnosis of sepsis or pneumonia. Methods: Clinical and economic outcomes were compared for patients who received empiric cefepime via intermittent infusion (30-minute infusion of 2 g every 8 hours) or extended infusion (3-hour infusion of 1 g every 6 hours). Clinical outcomes analyses were carried out using appropriate statistical methods. Results: Overall, 111 patients received intermittent infusion and 93 patients received extended infusion. Approximately half of the included patients had a positive culture for a bacterial pathogen (intermittent infusion 45.9% vs extended infusion 47.3%). Median hospital length of stay (intermittent infusion 6 days vs extended infusion 6 days; P = .67) and 90-day readmission rates (intermittent infusion 61.3% vs extended infusion 67.7%; P = .34) did not differ between the groups. Mortality was infrequent in both groups (intermittent infusion 2.9% vs extended infusion 1.5%; P = .45). Cefepime cost per patient was lower with cefepime by extended infusion: average total daily cost $86.06 for intermittent infusion versus $43.39 for extended infusion. Conclusions: Cefepime via extended infusion (4 grams/day) did not differ in clinical outcomes compared to intermittent infusion (6 grams/day) but reduced drug expenditure. Prospective, multicenter, high-quality studies should be conducted to evaluate a mortality difference between these regimens.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene abnormalities in Indian males with congenital bilateral absence of vas deferens & renal anomalies.

BACKGROUND & OBJECTIVES: The role of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in congenital bilateral absence of vas deferens and unilateral renal agenesis (CBAVD-URA) has been controversial. Here, we report the cases of five Indian males with CBAVD-URA. The objective was to evaluate the presence or absence of CFTR gene mutations and variants in CBAVD-URA. The female partners of these males were also screened for cystic fibrosis (CF) carrier status. METHODS: Direct DNA sequencing of CFTR gene was carried out in five Indian infertile males having CBAVD-URA. Female partners (n=5) and healthy controls (n=32) were also screened. RESULTS: Three potential regulatory CFTR gene variants (c.1540A>G, c.2694T>G and c.4521G>A) were detected along with IVS8-5T mutation in three infertile males with CBAVD-URA. Five novel CFTR gene variants (c.621+91A>G, c.2752+106A>T, c.2751+85_88delTA, c.3120+529InsC and c.4375-69C>T), four potential regulatory CFTR gene variants (M470V, T854T, P1290P, Q1463Q) and seven previously reported CFTR gene variants (c.196+12T>C, c.875+40A>G, c.3041-71G>C, c.3271+42A>T, c.3272-93T>C, c.3500-140A>C and c.3601-65C>A) were detected in infertile men having CBAVD and renal anomalies Interpretation & conclusions: Based on our findings, we speculate that CBAVD-URA may also be attributed to CFTR gene mutations and can be considered as CFTR-related disorder (CFTR-RD). The CFTR gene mutation screening may be offered to CBAVD-URA men and their female partners undergoing ICSI. Further studies need to be done in a large sample to confirm the findings.

SAS1B protein [ovastacin] shows temporal and spatial restriction to oocytes in several eutherian orders and initiates translation at the primary to secondary follicle transition.

BACKGROUND: Sperm Acrosomal SLLP1 Binding (SAS1B) protein (ovastacin) is an oolemmal binding partner for the intra-acrosomal sperm protein SLLP1. RESULTS: Immunohistochemical localization revealed that SAS1B translation is restricted among adult tissues to the ovary and oocytes, SAS1B appearing first in follicles at the primary-secondary transition. Quiescent oocytes within primordial follicles and primary follicles did not stain for SAS1B. Examination of neonatal rat ovaries revealed SAS1B expression first as faint signals in postnatal day 3 oocytes, with SAS1B protein staining intensifying with oocyte growth. Irrespective of animal age or estrus stage, SAS1B was seen only in oocytes of follicles that initiated a second granulosa cell layer. The precise temporal and spatial onset of SAS1B expression was conserved in adult ovaries in seven eutherian species, including nonhuman primates. Immunoelectron micrographs localized SAS1B within cortical granules in MII oocytes. A population of SAS1B localized on the oolemma predominantly in the microvillar region anti-podal to the nucleus in ovulated MII rat oocytes and on the oolemma in macaque GV oocytes. CONCLUSIONS: The restricted expression of SAS1B protein in growing oocytes, absence in the ovarian reserve, and localization on the oolemma suggest this zinc metalloprotease deserves consideration as a candidate target for reversible female contraceptive strategies.