Effects of Crotalus durissus collilineatus venom in the isolated rat kidney.

Ophidian accidents caused by the subspecies Crotalus durissus are responsible for high morbity and mortality rates. Acute renal failure is a common complication observed in these accidents. The aim of the present study was to investigate the renal effects promoted by the venom of C. d. collilineatus and its fractions, crotoxin and phospholipase A2. C. d. collilineatus (Cdc; 30 microg mL(-1)), crotoxin (CTX; 10 microg mL(-1)) and phospholipase A2 (PLA2; 10 microg mL(-1)) were tested in isolated rat kidney. The first 30 min of each experiment were used as an internal control and Cdc or its fractions, CTX and PLA2 were added to the system after this period. All experiments lasted 120 min. The venom of Cdc decreased perfusion pressure (PP; control120 = 110.3 +/- 3.69 mmHg; Cdc120 = 96.7+/-8.1 mmHg), renal vascular resistance (RVR; control120 = 6.42+/-0.78 mmHg mL g(-1) min(-1); Cdc120 = 4.8+/-0.56 mmHg/mL g(-1) min(-1)), urinary flow (UF; control120 = 0.19+/-0.03 mL g(-1) min(-1); Cdc120 = 0.12 +/- 0.01 mL g(-1) min(-1)), and glomerular filtration rate (GFR; control120 = 0.79 +/- 0.07 mL g(-1) min(-1); Cdc120 = 0.53 +/- 0.09 mL g(-1) min(-1)), but had no effect on the percent of sodium tubular transport (%TNa+), percent of chloride tubular transport (%TK+) and percent of potassium tubular transport (%TCl-). CTX and PLA2 reduced the GFR, while UF, PP and RVR remained stable during the full 120 min of perfusion. Crotoxin administration also diminished the %TK+ (control120 = 69.94 +/- 6.49; CTX120 = 33.28 +/- 4.78) and %TCl- (control120 = 79.53 +/- 2.67; CTX120 = 64.62 +/- 6.93). PLA2 reduced the %TK+, but exerted no effect on the %TNa+ or on that of TCl-. In conclusion, the C. d. collilineatus venom altered the renal functional parameters evaluated. We suggest that crotoxin and phospholipase A2 were involved in this process, since the renal effects observed would be due to the synergistic action of the components of the venom.     

Genetic variations and haplotype structures of the ABC transporter gene ABCC1 in a Japanese population

Multidrug resistance-related protein 1 (MRP1), an ATP-binding cassette transporter encoded by the ABCC1 gene, is expressed in many tissues, and functions as an efflux transporter for glutathione-, glucuronate- and sulfate-conjugates as well as unconjugated substrates. In this study, the 31 exons and their flanking introns of ABCC1 were comprehensively screened for genetic variations in 153 Japanese subjects to elucidate the linkage disequilibrium (LD) profiles and haplotype structures of ABCC1 that is necessary for pharmacogenetic studies of the substrate drugs. Eighty-six genetic variations including 31 novel ones were found: 1 in the 5'-flanking region, 1 in the 5'-untranslated region (UTR), 20 in the coding exons (9 synonymous and 11 nonsynonymous variations), 4 in the 3'-UTR, and 60 in the introns. Of these, eight novel nonsynonymous variations, 726G>T (Trp242Cys), 1199T>C (Ile400Thr), 1967G>C (Ser656Thr), 2530G>A (Gly844Ser), 3490G>A (Val1164Ile), 3550G>A (Glu1184Lys), 3901C>T (Arg1301Cys), and 4502A>G (Asp1501Gly), were detected with an allele frequency of 0.003. Based on the LD profiles, the analyzed regions of the gene were divided into five LD blocks (Blocks -1 and 1 to 4). The multiallelic repeat polymorphism in the 5'-UTR was defined as Block -1. For Blocks 1, 2, 3 and 4, 32, 23, 23 and 13 haplotypes were inferred, and 9, 7, 7 and 6 haplotypes commonly found on > or = 10 chromosomes accounted for > or = 91% of the inferred haplotypes in each block. Haplotype-tagging single nucleotide polymorphisms for each block were identified to capture the common haplotypes. This study would provide fundamental and useful information for the pharmacogenetic studies of MRP1-dependently effluxed drugs in Japanese.     

The relationship between frailty and motor function among living in the community elderly females

[Purpose] This study aimed to investigate the prevalence of frailty among community-dwelling elderly females, and to examine its relation to motor function and the main risk factors of frailty. [Participants and Methods] The participants were 67 community-dwelling elderly females, aged 76.2 ± 7.7 years. We performed measurements of physical parameters, motor functions (such as grip strength), timed up and go test (TUG), walking speed, and frailty (measured using the Kihon Checklist [KCL]). [Results] KCL scores were 31.3%, 31.3%, and 37.3% in the frailty, pre-frailty, and robust groups, respectively. The frailty group was older than the pre-frailty and robust groups. Additionally, the different groups showed significant differences in grip strength, TUG, and walking speed. The highest median KCL score was for depression, followed by physical function. As a results, frailty was evident even among health-conscious elderly people. [Conclusion] It is essential to identify frailty at an early stage and identify its preventive factors, in order to extend the healthy life expectancy of the local population.     

Relationship between perfusion index and central temperature before and after induction of anesthesia in laparoscopic gastrointestinal surgery: A prospective cohort study

The perfusion index (PI) cutoff value before anesthesia induction and the ratio of PI variation after anesthesia induction remain unclear. This study aimed to clarify the relationship between PI and central temperature during anesthesia induction, and the potential of PI in individualized and effective control of redistribution hypothermia. This prospective observational single center study analyzed 100 gastrointestinal surgeries performed under general anesthesia from August 2021 to February 2022. The PI was measured as peripheral perfusion, and the relationship between central and peripheral temperature values was investigated. Receiver operating characteristic curve analysis was performed to identify baseline PI before anesthesia, which predicts a decrease in central temperature 30 minutes after anesthesia induction, and the rate of change in PI that predicts the decrease in central temperature 60 minutes after anesthesia induction. In cases with a central temperature decrease of ≥ 0.6°C after 30 minutes, the area under the curve was 0.744, Youden index was 0.456, and the cutoff value of baseline PI was 2.30. In cases with a central temperature decrease of ≥ 0.6°C after 60 minutes, the area under curve was 0.857, Youden index was 0.693, and the cutoff value of the PI ratio of variation after 30 minutes of anesthesia induction was 1.58. If the baseline PI is ≤ 2.30 and the PI 30 minutes after anesthesia induction is at least 1.58-fold the PI ratio of variation, there is a high probability of a central temperature decrease of at least 0.6°C within 30 minutes after 2 time points.     

Development and Initial Psychometric Validation of the COVID-19 Pandemic Burden Index for Healthcare Workers

BackgroundThe burden of COVID-19 on healthcare workers (HCWs) is reported to be increasing, yet the psychometric scales now in use evaluate only single aspects; few measure the pandemic-specific burden on HCWs comprehensively.ObjectiveTo develop a scale to quantify the physical, mental, and socioeconomic burden of the COVID-19 pandemic on HCWs.DesignScale development and cross-sectional survey.ParticipantsConsenting HCWs aged ≥20.Main MeasuresDevelopment of an item-list based on literature reviews and HCW panel input, evaluation of content validity and item selection using the Delphi method, psychometric testing conducted on HCWs, validity assessment by factor analyses and hypothesis verification, internal consistency evaluation by Cronbach’s alpha, test-retest analysis, and interpretability assessment.Key ResultsThrough the Delphi process, a 29-item pilot scale was generated. In psychometric testing, data from 863 HCWs contributed to the development of the final version of this scale, called Pandemic Burden Index twenty for HCWs (PBI-20), a 20-item scale to measure six domains: fatigue, fear of infection, inadequacy as a medical professional, mental health concerns, prejudice or discrimination, and anxiety about one’s livelihood and daily life. Factor analysis showed each factor corresponded to the six domains of this scale. Hypothesis verification showed the PBI-20 total score to be moderately to highly correlated with the Short Form 36 vitality score and mental health score and with intention of turnover. The PBI-20 had good internal consistency (Cronbach’s alpha 0.92). Test-retest analysis showed the intraclass correlation coefficient to be 0.70 and the minimal important change to be −7.0.ConclusionsThe psychometrically sound questionnaire we developed to measure pandemic-specific burdens for HCWs provides an understanding of comprehensive burdens on HCWs and may serve to evaluate interventions to reduce the burdens.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-023-08028-3.KEY WORDS: COVID-19, pandemic, burden, health personnel, psychometrics     

Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.     

Subpopulation of adenoidal lymphocytes of recurrent infection in the upper respiratory tract

A subpopulation of adenoidal lymphocytes was determined by the E-and EAC-rosetting techniques in order to study an immunological profile of adenoids in 61 children with recurrent otitis media, rhinosinusitis or recurrent tonsillitis.Though there was no significant difference in E- and EAC-rosette forming cells of adenoid tissues from children with recurrent infection in the upper respiratory tract, our results indicated the following. (1) A higher proportion of EAC-rosette forming cells (EAC-RFC) without a change of E-RFC was found in the adenoids of children with recurrent tonsillitis than those without it. (2) The percentage of EAC-RFC appears to increase proportionally to the size of adenoid viewed on the X-ray film. (3) The higher percentage was more remarkable in cases with rhinosinusitis and recurrent otitis media. From the data obtained it is concluded that adenoids may play some part in immunity responses against infection in the upper respiratory tract reflecting adenoidal hypertrophy.