BJOG. 2021 Mar 5. doi: 10.1111/1471-0528.16674. Online ahead of print.
ABSTRACT
As Georgieva et al point out in this issue of BJOG, the relationship between fetal blood pH and intrapartum brain injury is poor. In contrast, fetal cardiovascular decompensation (CVD) leads via dropping fetal systemic arterial blood pressure (ABP) to a precipitous fall in cerebral perfusion pressure (CPP), resulting in cerebral ischaemia and injury.
PMID:33666319 | DOI:10.1111/1471-0528.16674
Pediatr Pulmonol. 2021 Mar 5. doi: 10.1002/ppul.25359. Online ahead of print.
ABSTRACT
OBJECTIVES: To assess if intrauterine growth retardation (IUGR) was associated with reduced lung function at 16 to 19 years WORKING HYPOTHESIS: Very prematurely born young people who had IUGR would have reduced lung function post-puberty.
STUDY DESIGN: Prospective follow-up study.
PATIENT-SUBJECT SELECTION: One hundred and fifty-nine 16-19 year olds born prior to 29 weeks of gestation; 37 had IUGR.
METHODOLOGY: Lung function tests were performed: spirometry was used to assess forced expiratory volume in one second (FEV1 ), forced expiratory flow at 75%, 50% and 25% of expired vital capacity (FEF75 , FEF50 and FEF25 ), peak expiratory flow (PEF) and forced vital capacity (FVC). Functional residual capacity (FRCpleth ) total lung capacity (TLCpleth ) and residual volume (RVpleth ) were measured. Alveolar function was assessed by diffusion capacity within the lungs of carbon monoxide (DL CO). Impulse oscillometry was used to assess respiratory resistance and lung clearance index to assess ventilation homogeneity. Exercise capacity was assessed using a shuttle sprint test.
RESULTS: After adjustment for BMI, the mean FEV1 /FVC, FEF75 , FEF25-75 , FRCpleth and RVpleth were poorer in those who had had IUGR, with differences between 0.56 and 0.75 z-scores. After further adjustment for BPD and postnatal corticosteroid use, only the difference in RVpleth z-scores remained statistically significant, adjusted difference (95% CI): 0.66 (0.18,1.13). Exercise capacity was lower in those with IUGR and this was more pronounced in males (p=0.04).
CONCLUSIONS: At 16 to 19 years of age, those who had IUGR had poorer lung function and exercise capacity compared with those with adequate intrauterine growth. This article is protected by copyright. All rights reserved.
PMID:33666356 | DOI:10.1002/ppul.25359
Indian J Pharmacol. 2020 Nov-Dec;52(6):476-481. doi: 10.4103/ijp.IJP_174_20.
ABSTRACT
INTRODUCTION: Vernal conjunctivitis comprises 0.5% of allergic eye diseases. The study is intended to collate the effectiveness of drugs by observing the reduction in signs and symptoms.
OBJECTIVES: The objective of the study is to evaluate the effectiveness and safety of olopatadine 0.1% ophthalmic drops with bepotastine besilate 1.5% ophthalmic drops in patients with vernal keratoconjunctivitis (VKC).
MATERIALS AND METHODS: A randomized, open-label, comparative study conducted in Sarojini Devi Eye Hospital, Telangana. The study included 50 patients diagnosed with VKC, of which Group A and Group B were given olopatadine 0.1% ophthalmic drops and bepotastine besilate 1.5% ophthalmic drops, respectively, twice a day for 8 weeks. The reduction in signs and symptoms in both groups was compared. The observations and results were tabulated accordingly, and data were analyzed using the SPSS. The unpaired t-test is used as the test of significance in between two groups. P value is statistically significant when it is less than 0.05.
RESULTS: Overall, 50 cases were included in the study, 72% of total patients were in the age group of 5-10 years, and 28% were in the age group of 11-15 years. There were 39 males and 11 females. After 8 weeks of follow-up, the mean reduction in the scoring of symptoms and signs provided better and quicker relief of watering, ocular discomfort, and conjunctival hyperemia with bepotastine 1.5% eye drops. Olopatadine 0.1% eye drops provided faster improvement in papillary hypertrophy. Both drugs were equally effective in reducing itching. Laboratory findings of absolute eosinophil count had no statistical significance in between the two groups.
CONCLUSIONS: In this study, based on the evaluation of therapeutic performance, bepotastine eye drops proved quicker relief of symptoms and signs compared to olopatadine eye drops but was not statistically significant which would prove beneficial for the patients.
PMID:33666188 | DOI:10.4103/ijp.IJP_174_20
Indian J Pharmacol. 2020 Nov-Dec;52(6):482-487. doi: 10.4103/ijp.IJP_244_19.
ABSTRACT
CONTEXT: The acquisition of antibiotic without a prescription by the general population is a typical practice found in community pharmacies across India, which is a notable contributor of antimicrobial resistance. According to the present regulation in India, sale of certain antimicrobials included in schedule H1 without prescription is unlawful. In this contest, a program was organized by the Drug Control Administration, Government of Andhra Pradesh, to educate pharmacists regarding schedule H1.
AIMS: The aim of our study is to assess the impact of the program on the rate of antibiotics dispensed at community pharmacies.
SETTINGS AND DESIGN: A cross-sectional study was designed to investigate the nonprescription sale of antibiotics, from September to December 2018 through 200 community pharmacies located in and around Guntur city located in the state of Andhra Pradesh in India.
SUBJECTS AND METHODS: A simulated client methodology was used in this study. A total of 3 female actors including an author of this present study are prior trained to present a standardized simulation of clinical conditions (sore throat, urinary tract infection, cold, and fever) to the pharmacist at the community pharmacies.
STATISTICAL ANALYSIS USED: Microsoft excel sheet was used for data analysis.
RESULTS: The simulated patients successfully obtained antibiotic from 78% pharmacies with the highest rate of urinary tract infection when compared to other conditions. Pharmacists who objected to dispense antibiotics (22%) are found in developed locations in the city and appeared well qualified.
CONCLUSIONS: The present study revealed that the antibiotics are continued to be sold without prescription even after the education program on schedule H1. The deregulation of the act is definitely the problem to be addressed by the government.
PMID:33666189 | DOI:10.4103/ijp.IJP_244_19
Phys Chem Chem Phys. 2021 Mar 5. doi: 10.1039/d0cp05013j. Online ahead of print.
ABSTRACT
Water + elastin-like polypeptides (ELPs) exhibit a transition temperature below which the chains transform from collapsed to expanded states, reminiscent of the cold denaturation of proteins. This conformational change coincides with liquid-liquid phase separation. A statistical-thermodynamics theory is used to model the fluid-phase behavior of ELPs in aqueous solution and to extrapolate the behavior at ambient conditions over a range of pressures. At low pressures, closed-loop liquid-liquid equilibrium phase behavior is found, which is consistent with that of other hydrogen-bonding solvent + polymer mixtures. At pressures evocative of deep-sea conditions, liquid-liquid immiscibility bounded by two lower critical solution temperatures (LCSTs) is predicted. As pressure is increased further, the system exhibits two separate regions of closed-loop of liquid-liquid equilibrium (LLE). The observation of bimodal LCSTs and two re-entrant LLE regions herald a new type of binary global phase diagram: Type XII. At high-ELP concentrations the predicted phase diagram resembles a protein pressure denaturation diagram; possible “molten-globule”-like states are observed at low concentration.
PMID:33666204 | DOI:10.1039/d0cp05013j
Clin Pharmacol Ther. 2021 Mar 5. doi: 10.1002/cpt.2224. Online ahead of print.
ABSTRACT
Cell and gene therapies have shown enormous promise across a range of diseases in recent years. Numerous adoptive cell therapy modalities as well as systemic and direct-to-target tissue gene transfer administrations are currently in clinical development. The clinical trial design, development, reporting, and analysis of novel cell and gene therapies can differ significantly from established practices for small molecule drugs and biologics. Here we discuss important quantitative considerations and key competencies for drug developers in preclinical requirements, trial design, and lifecycle planning for gene therapies. We argue that the unique development path of gene therapies requires practicing quantitative drug developers-statisticians, pharmacometricians, pharmacokineticists, epidemiologists, and medical and translational science leads-to exercise active collaboration and cross-functional learning across development stages.
PMID:33666225 | DOI:10.1002/cpt.2224
Elife. 2021 Mar 5;10:e64206. doi: 10.7554/eLife.64206. Online ahead of print.
ABSTRACT
Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies has been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes. Using the same framework and making the assumption that seropositivity indicates immune protection, we propagated estimates and uncertainty through dynamical models to assess uncertainty in the epidemiological parameters needed to evaluate public health interventions, and found that sampling schemes informed by demographics and contact networks outperform uniform sampling. The framework can be adapted to optimize serosurvey design given test characteristics and capacity, population demography, sampling strategy, and modeling approach, and can be tailored to support decision-making around introducing or removing interventions.
PMID:33666169 | DOI:10.7554/eLife.64206
Front Vet Sci. 2021 Feb 16;8:591961. doi: 10.3389/fvets.2021.591961. eCollection 2021.
ABSTRACT
RNA is considered as an indicator of the dynamic genetic expression changes in a cell. RNAScope is a commercially available in situ hybridization assay for the detection of RNA in formalin-fixed paraffin-embedded tissue. In this work, we describe the use of RNAScope as a sensitive and specific method for the evaluation of c-KIT messenger RNA (mRNA) in canine mast cell tumor. We investigated the expression of c-KIT mRNA with RNAscope in 60 canine mast cell tumors (MCTs), comparing it with the histological grade and KIT immunohistochemical expression patterns. Our results showed an overall good expression of c-KIT mRNA in neoplastic cells if compared with control probes. We also observed a statistically significant correlation between histological grade and c-KIT mRNA expression. No correlations were found between KIT protein immunohistochemical distribution pattern and c-KIT mRNA expression or histological grade. Our results provide a reference basis to better understand c-KIT mRNA expression in canine MCTs and strongly encourage further studies that may provide useful information about its potential and significant role as a prognostic and predictive biological marker for canine MCTs clinical outcome.
PMID:33665215 | PMC:PMC7921150 | DOI:10.3389/fvets.2021.591961
Gynecol Oncol Rep. 2021 Feb 12;36:100730. doi: 10.1016/j.gore.2021.100730. eCollection 2021 May.
ABSTRACT
Forgoing hysterectomy as part of borderline ovarian tumor (BOT) staging is considered appropriate for fertility preservation. We evaluated whether forgoing hysterectomy may also be acceptable in non-fertility-sparing surgery by evaluating the frequency of uterine involvement and the rate of recurrence involving the uterus. A review of all BOTs at one institution over ten years (2009-2019) was performed. Patients with hysterectomy prior to BOT diagnosis were excluded. Data were abstracted from electronic medical records. Bivariate statistics were used to compare groups. 129 patients with BOT on final pathology were identified. 67 cases included hysterectomy. Reasons for no hysterectomy (n = 62) included fertility preservation (40), benign intraoperative frozen pathology (4), patient preference (3), comorbidities (7), and unknown (8). Four of 67 (6.0%) uterine specimens had non-invasive serosal implants, of which two had grossly visible uterine involvement and all four had grossly visible extrauterine peritoneal disease. 12 of 129 (9.3%) patients had documented recurrence, of which all had uterine preservation at the time of initial surgery. Of the 12 recurrences with uterus in situ, none were documented to involve the uterus, and all were composed of non-invasive implants. In patients with BOT grossly confined to ovaries at the time of surgery, we found no cases of uterine involvement. We found no cases in which microscopic uterine serosal involvement changed stage and no cases of recurrence involving the uterus. Hysterectomy may be able to be safely excluded from non-fertility-sparing surgery for BOTs, particularly when disease is grossly confined to the ovaries.
PMID:33665295 | PMC:PMC7900677 | DOI:10.1016/j.gore.2021.100730
Front Pediatr. 2021 Feb 16;9:632573. doi: 10.3389/fped.2021.632573. eCollection 2021.
ABSTRACT
Objective: There are mutual influences between intestine and lung, that propose a concept of the gut-lung axis, but the mechanism is still unclear. Microbial colonization in early life plays an important role in regulating intestinal and lung function. In order to explore the characteristics of early microbiota on the gut-lung axis, we studied the correlation between intestinal and pharyngeal microbiota on day 1 and day 28 after birth in premature neonates. Methods: Thirteen neonates born at 26-32 weeks gestational age (GA) hospitalized at the neonatal intensive care unit (NICU) of the West China Second Hospital of Sichuan University were enrolled in this study. Stool samples and pharyngeal swabs samples were collected from each neonate on the first day (T1) and the 28th day (T28) after birth. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System based on the V3-V4 hyper-variable regions of the 16S rRNA gene. Based on the sequencing results, the composition of the intestinal and pharyngeal microbiota was compared and analyzed. Results: At T1, the difference in microbial composition between intestine and pharynx was not statistically significant. The intestinal microbiota was mainly composed of Unidentified Enterobacteriaceae, Ralstonia, Streptococcus, Fusobacterium, Ureaplasma, etc. The pharyngeal microbiota was mainly composed of Ureaplasma, Bacteroides, Fusobacterium, etc. Ureaplasma and Fusobacterium were detected in both intestine and pharynx. At T28, there was a significant difference in microbial composition between intestine and pharynx (p < 0.001). The intestinal microbiota was mainly composed of Unidentified Clostridiales, Klebsiella, Unidentified Enterobacteriaceae, Enterobacter, Streptococcus, etc. Pharyngeal microbiota was mainly composed of Streptococcus, Rothia, etc. Streptococcus was detected in both intestine and pharynx. Conclusions: The intestine and pharynx of premature neonates have a unique microbial composition, and share some common microbiota. Whether these microbiotas play a role in the mechanism of gut-lung crosstalk needs further study.
PMID:33665178 | PMC:PMC7920978 | DOI:10.3389/fped.2021.632573
