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Detection of ERG11 gene in fluconazole resistant urinary candida isolates

Egypt J Immunol. 2022 Oct;29(4):134-147.

ABSTRACT

Candida species resistant to fluconazole and voriconazole were screened for the presence of ERG11gene by polymerase chain reaction (PCR). Also, the association of this gene with the demonstration of Candida virulence factors; biofilm formation, phospholipase and proteinases activities were studied. A total of 61 Candida isolates were collected from urine specimens. Candida species were identified by API 20 C Aux test. Extracellular phospholipase, secretory aspartyl proteinase and biofilm formation were determined. ERG11 gene was detected by PCR. C. albicans was identified in 34.5%, C. glabrata in 29.5% and C. tropicalis and C. krusei in 18% each. Candida species was resistant to fluconazole and voriconazole in 55.7% and 27.9%, respectively. Seventeen (50%) of fluconazole resistant Candida isolates were sensitive to voriconazole. The most frequently Candida species revealed fluconazole resistance were C. glabrata (47.1%), C. krusei (29.4%), and C. tropicalis and C. albicans (11.8% each). Biofilm formation, phospholipase and proteinase activity were determined in 41.2%, 67.6% and 35.3% of fluconazole resistant Candida isolates, respectively. Erg 11 gene was determined in 82.4% of fluconazole resistant Candida isolates and prominent in C. glabrata (93.75%), followed by C. krusei (90%), C. tropicalis (75%) and C. albicans (25%). Erg 11 gene was detected in 64.7% (11/17) of fluconazole resistant-voriconazole sensitive Candida isolates. Regarding, correlation of Erg11 gene positivity and virulence factors among fluconazole resistant Candida isolates, 34.5% exhibited biofilm formation and 62.1% and 31% showed phospholipase and proteinase activities, respectively. There were statistically significant difference concerning the association of proteinase activities and Erg 11 gene expression among fluconazole resistance Candida isolates (P=0.04). The study emphasizes the high prevalence of Erg11 gene among fluconazole resistant Candida species. There was association between the proteinase activity, fluconazole resistance and the presence of Erg11 among Candida species. Voriconazole maintains better activity towards Candida species and represent an alternative therapy.

PMID:36208042

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Statistical evidence for high-penetrance MODY-causing genes in a large population-based cohort

Endocrinol Diabetes Metab. 2022 Oct 8:e372. doi: 10.1002/edm2.372. Online ahead of print.

ABSTRACT

AIMS: Numerous genes have been proposed as causal for maturity-onset diabetes of the young (MODY). Scoring systems to annotate mutation pathogenicity have been widely used; however, statistical evidence for being a highly penetrant MODY gene has not been well-established.

METHODS: Participants were from the UK Biobank with whole-exome sequencing data, including 14,622 with and 185,509 without diagnosis of diabetes. Pathogenic/likely pathogenic (P/LP) mutations in 14 reported and 3 possible MODY genes were annotated using American College of Medical Genetics criteria. Evidence for being a high-penetrant MODY gene used two statistical criteria: frequency of aggregate P/LP mutations in each gene are (1) significantly more common in participants with a diagnosis of diabetes than without using the SKAT-O (p < .05) and (2) lower than the maximum credible frequency in the general population.

RESULTS: Among the 17 genes, 6 (GCK, HNF1A, HNF4A, NEUROD1, KCNJ11 and HNF1B) met both criteria, 7 (ABCC8, KLF11, RFX6, PCBD1, WFS1, INS and PDX1) met only one criterion, and the remaining 4 (CEL, BLK, APPL1 and PAX4) failed both criteria, and were classified as ‘consistent’, ‘inconclusive’ and ‘inconsistent’ for being highly penetrant diabetes genes, respectively. Diabetes participants with mutations in the ‘consistent’ genes had clinical presentations that were most consistent with MODY. In contrast, the ‘inconclusive’ and ‘inconsistent’ genes did not differ clinically from non-carriers in diabetes-related characteristics.

CONCLUSIONS: Data from a large population-based study provided novel statistical evidence to identify 6 MODY genes as consistent with being highly penetrant. These results have potential implications for interpreting genetic testing results and clinical diagnosis of MODY.

PMID:36208030 | DOI:10.1002/edm2.372

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Inbreeding effects on telomeres in hatchling sand lizards (Lacerta agilis): an optimal family affair?

Mol Ecol. 2022 Oct 8. doi: 10.1111/mec.16723. Online ahead of print.

ABSTRACT

Telomeres are nucleotide-protein caps, predominantly at the ends of Metazoan linear chromosomes, showing complex dynamics with regards to their lengthening and shortening through life. Their complexity has entertained the idea that net telomere length and attrition could be valuable biomarkers of phenotypic and genetic quality of their bearer. Intuitively, those individuals could be more heterozygous and, hence, less inbred. However, some inbred taxa have longer, not shorter, telomeres. To understand the role of inbreeding in this complex scenario we need large samples across a range of genotypes with known maternity and paternity in telomere-screened organisms under natural conditions. We assess the effects of parental and hatchling inbreeding on telomere length in >1,300 offspring from >500 sires and dams in a population of sand lizards (Lacerta agilis). Maternal and paternal ID and their interactions predict hatchling telomere length at substantial effect sizes (R2 > 0.50). Deviation from mean maternal heterozygosity statistically predicts shorter offspring telomeres but this only when sibship is controlled for by paternal ID, and then is still limited (R2 = 0.06). Raw maternal heterozygosity scores, ignoring absolute deviation from the mean, explained 0.07% of the variance in hatchling telomere length. In conclusion, inbreeding is not a driver of telomere dynamics in the sand lizard (Lacerta agilis) study system.

PMID:36208022 | DOI:10.1111/mec.16723

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Learning from COVID-19: Cross-sectional e-survey of critical care nurses’ satisfaction and experiences of their role in the pandemic response across the United Kingdom

Nurs Crit Care. 2022 Oct 7. doi: 10.1111/nicc.12850. Online ahead of print.

ABSTRACT

BACKGROUND: Since the start of the global COVID-19 pandemic in 2019, critical care nurses across the world have been working under extreme levels of pressure.

AIM: To understand critical care nurses’ experiences of and satisfaction with their role in the pandemic response across the United Kingdom (UK).

STUDY DESIGN: A cross-sectional electronic survey of critical care nurses (n = 339) registered as members of the British Association of Critical Care Nurses. Anonymous quantitative and open-ended question data were collected in March and April 2021 during the height of the second surge of COVID-19 in the UK via an online questionnaire. Quantitative data were analysed using descriptive statistics and free text responses were collated and analysed thematically.

RESULTS: There was a response rate of 17.5%. Critical care nurses derived great satisfaction from making a difference during this global crisis and greatly valued teamwork and support from senior nurses. However, nurses consistently expressed concern over the quality of safe patient care, which they perceived to be suboptimal due to staff shortages and a dilution of the specialist skill mix. Together with the high volume of patient deaths, critical care nurses reported that these stressors influenced their personalwell-being.

CONCLUSIONS: This study provides insights into the key lessons health care leaders must consider when managing the response to the demands and challenges of the ongoing COVID-19 pandemic. COVID-19 is unpredictable in its course, and what future variants might mean in terms of transmissibility, severity and resultant pressures to critical care remains unknown.

RELEVANCE TO CLINICAL PRACTICE: Future responses to the challenges that critical care faces must consider nurses’ experiences and create an environment that engenders supportive teamwork, facilitates excellent nursing practice and effective safe patient care where critical care nursing may thrive.

PMID:36208010 | DOI:10.1111/nicc.12850

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QUALITY OF LIFE IN CHILDREN WITH DISEASES CAUSING CENTRAL AIRWAY OBSTRUCTION: RELIABILITY AND VALIDITY OF THE TAPQOL QUESTIONNAIRE

Pediatr Pulmonol. 2022 Oct 7. doi: 10.1002/ppul.26198. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to analyse the psychometric performance (reliability and validity) of the TAPQOL questionnaire in measuring the global quality of life in children with central airway obstruction (CAO), which encompasses pathologies with a low prevalence that have a common anatomical or functional affectation.

METHOD: The study population consisted of 109 patients with CAO attended in a national reference airway unitafter signing informed consent. The TAPQOL questionnaire was used to measure the global quality of life and its psychometric characteristics were analysed. The reliability was determined using Cronbach’s alpha statistic and the validity was determined by means of a principal component analysis.

RESULTS: The mean age was 4.8 years and there was no predominant sex. The most frequent diagnosis was laryngomalacia (24.5%), followed bysubglotticstenosis (20.2%). The lowest score in the TAPQOLquestionnaire was obtained for the scales of anxiety (66.2±23.7), respiratory (67.9±29.6) and conduct 68.2±21.4). The Cronbach’salpha was above 0.7 in the majority of the scales and the validity study by principal component analysis with a total variance of 76.7% fits the original 12-component model.

CONCLUSIONS: TAPQOL is a valid tool to measure the health-related quality of life in patients with CAO. Measuring it in these patients indicates which fields are most affected, highlighting therapeutic needs that have not been resolved but which can be approached in normal clinical practice. This article is protected by copyright. All rights reserved.

PMID:36207999 | DOI:10.1002/ppul.26198

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Non-surgical treatment of mild to moderate peri-implantitis using an oscillating chitosan brush or a titanium curette – a randomized multicentre controlled clinical trial

Clin Oral Implants Res. 2022 Oct 7. doi: 10.1111/clr.14007. Online ahead of print.

ABSTRACT

OBJECTIVES: This prospective, parallel-group, examiner-blinded, multicentre, randomized, controlled clinical trial aimed to assess the efficacy of an oscillating chitosan brush (OCB) versus titanium curettes (TC) on clinical parameters in the non-surgical treatment of peri-implantitis.

MATERIAL AND METHODS: In five dental specialist clinics, 39 patients with one implant with mild to moderate peri-implantitis, defined as 2-4 mm radiographic reduced bone level, bleeding index (BI)≥2, and probing pocket depth (PPD)≥4 mm were randomly allocated to test and control groups, receiving OCB or TC debridement, respectively. Treatment was performed at baseline and three months. PPD, BI, and Plaque index (PI) were measured at six sites per implant and recorded by five blinded examiners at baseline, one, three, and six month(s). Pus was recorded as present/not present. Changes in PPD and BI were compared between groups and analysed using multilevel partial ordinal and linear regression.

RESULTS: Thirty-eight patients completed the study. Both groups showed significant reductions in PPD and BI at six months compared to baseline (p<0.05). There was no statistically significant difference in PPD and BI changes between the groups. Eradication of peri-implant disease as defined was observed in 9.5 % of cases in the OCB group and 5.9 % in the TC group.

CONCLUSIONS: Within the limitations of this six-month multicentre clinical trial, non-surgical treatment of peri-implantitis with OCB and TC showed no difference between the interventions. Eradication of disease was not predictable for any of the groups.

PMID:36207993 | DOI:10.1111/clr.14007

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Clinical outcomes of Hereditary Angioedema on multiparous women

J Cosmet Dermatol. 2022 Oct 7. doi: 10.1111/jocd.15438. Online ahead of print.

ABSTRACT

OBJECTIVE: Significant concerns for patients with hereditary angioedema (HAE) include hormonal fluctuations and drug safety during pregnancy. The impact of the disease on childbearing in multiparous women remains to be elucidated. We aimed to investigate the clinical course and impacts of multiparity on HAE patients.

STUDY DESIGN: This observational study included 15 multiparous women with HAE; a total of 88 pregnancies were assessed using a questionnaire and the patient’s medical records.

RESULTS: The median age was 36 (IQR, 33-39). Of 72 resulted in healthy babies without any congenital abnormalities. In sixteen pregnancies, 12 (13.6%) ended with spontaneous abortion; three resulted in stillbirth and one neonatal death. Two-thirds of the patients (n=10) enounced a worsening in the frequency of angioedema attacks during pregnancy. There was no statistically significant difference compared to the nonpregnant period (p=0.283). One-fifth of the patients (n=3) reported alleviation in attacks. While most deliveries were vaginally (n=57 babies), 19 deliveries in 6 patients were by cesarean section. None of the patients were aware of the diagnosis of HAE prior to their first pregnancies. After the diagnosis was made, eight patients received 263 vials of plasma-derived C1-inhibitor concentrate during a total of 13 pregnancies. No adverse events were reported.

CONCLUSION: We conclude that our results on clinical course and outcomes of HAE in multiparous patients are consistent with the literature. A greater focus on multiparous HAE patients could produce exciting findings.

PMID:36207991 | DOI:10.1111/jocd.15438

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The effect of steatotic donor livers on the prognosis of donors and recipients after pediatric living donor liver transplantation

Zhonghua Wai Ke Za Zhi. 2022 Oct 1;60(10):922-929. doi: 10.3760/cma.j.cn112139-20220412-00159.

ABSTRACT

Objectives: To evaluate the effects of steatotic donor livers on the safety of donors and the prognosis of donors and recipients in pediatric living donor liver transplantation. Methods: A total of 814 pediatric living donor liver transplantations were performed between January 2013 and December 2020 at Department of Pediatric Organ Transplantation,Tianjin First Central Hospital.The clinical data were collected and a retrospective study was conducted.The recipients and the donors were divided into non-steatotic donor liver group(n=733) and steatotic donor liver group(n=81) according to whether the donor graft had steatosis. The recipients and the donors in the steatotic donor liver group were further divided into mild and moderate steatosis groups based on the degree of liver steatosis.Among the donors of non-steatosis donor group,there were 307 males and 426 females,with a median age of 30 years(range:18 to 57 years);the recipients included 351 males and 382 females,with a median age of 7 months(range:4 month to 14 years).Among the donors of steatosis donor group,there were 41 males and 40 females,with a median age of 31 years(range:22 to 51 years);the recipients included 34 males and 47 females,with a median age of 8 months(range:5 months to 11 years).The donors and the recipients were followed up regularly by means of outpatient reexamination and questionnaire survey after operation.Statistical analysis of data between groups was performed using t-test,Wilcoxon rank-sum test,repeated measures ANOVA,χ2 test,or Fisher’s exact test,respectively.The survival curves of recipients and grafts in different groups were created by Kaplan-Meier method,and the survival rates of the steatotic donor liver group and the non-steatotic donor liver group were compared by Log-rank method. Results: There was no significant difference in the gender of donors in both groups (P=0.132).There were significant differences in the age and blood type distribution as well as body weight and body mass index(all P<0.05) between the two groups.No significant difference was seen in the recovery of liver function markers ALT and AST at 1,2,5 days and 1 month after operation (all P>0.05) between the two groups.The steatotic donor liver group showed longer operation time ((294±75) minutes vs. (264±81) minutes; t=3.149,P=0.002),increased incidence of postoperative biliary leakage (3.7%(3/81) vs. 0.5% (4/733); P=0.025) and delayed incision healing (7.4%(6/81) vs. 2.0%(15/733); P=0.013).There were no significant differences in gender,age,blood type distribution,height,weight and pediatric end-stage liver disease score of recipients between the two groups (all P>0.05).As compared to the non-steatotic donor liver group,the steatotic donor liver group showed similar levels of ALT, AST and total bilirubin within 2 weeks after operation(all P>0.05). The cumulative recipient survival rates in both groups were both 96.3%,the cumulative graft survival rates were 96.3% and 95.5%,respectively,without significant difference(both P>0.05). No statistical difference was observed in the incidence of major complications between the two groups (all P>0.05). There was no significant difference in the recovery of liver function markers of donors and recipients between mild and moderate steatosis groups(all P>0.05).The cumulative recipient survival rates were both 95.9% and the cumulative graft survival rates were both 100% in mild and moderate steatosis groups,without significant difference(P=0.592). Conclusions: The application of mild to moderate steatotic donor livers in pediatric living donor liver transplantation may prolong the operation time of donors,increase the incidence of complications such as biliary leakage and delayed incision healing. But there is no significant impact of mild to moderate steatotic donor livers on the overall postoperative recovery of donors and recipients,and the prognosis is ideal.

PMID:36207981 | DOI:10.3760/cma.j.cn112139-20220412-00159

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Efficacy of in-situ full-left/full-right split liver transplantation for adult recipients using the living donor liver transplantation technique:a single-center report of 25 cases

Zhonghua Wai Ke Za Zhi. 2022 Oct 1;60(10):906-914. doi: 10.3760/cma.j.cn112139-20220218-00069.

ABSTRACT

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ2 test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.

PMID:36207979 | DOI:10.3760/cma.j.cn112139-20220218-00069

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Clinical efficacy of split liver transplantation in the treatment of children with biliary atresia

Zhonghua Wai Ke Za Zhi. 2022 Oct 1;60(10):900-905. doi: 10.3760/cma.j.cn112139-20220712-00309.

ABSTRACT

Objective: To compare the clinical efficacy of split liver transplantation (SLT) and living donor liver transplantation(LDLT) in the treatment of children with biliary atresia. Methods: The clinical data of 64 children with biliary atresia who underwent SLT and 44 children who underwent LDLT from June 2017 to May 2022 at Liver Surgery & Liver Transplantation Center,the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. Among the children who received SLT, there were 40 males and 24 females. The median age at transplantation was 8 months (range:4 to 168 months). Among the patients who received LDLT, there were 24 males and 20 females. The age at transplantation ranged from 4 to 24 months,with a median age of 7 months. Sixty-four children with biliary atresia were divided into two groups according to the SLT operation time: 32 cases in the early SLT group(June 2017 to January 2019) and 32 cases in the technically mature SLT group (February 2019 to May 2022). Rank sum test or t test was used to compare the recovery of liver function between the LDLT group and the SLT group,and between the early SLT group and the technically mature SLT group. The incidence of postoperative complications was compared by χ2 test or Fisher exact probability method. Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cold ischemia time(M (IQR)) (218 (65) minutes), intraoperative blood loss(175 (100) ml) and graft-to-recipient body weight ratio (3.0±0.7) in the LDLT group were lower than those in the SLT group(500 (130) minutes, 200 (250) ml, 3.4±0.8) (Z=-8.064,Z=-2.969, t=-2.048, all P<0.05). The cold ischemia time(457(158)minutes) and total hospital stay ((37.4±22.4)days) in the technically mature SLT group were lower than those in the early SLT group(510(60)minutes, (53.0±39.0)days).The differences were statistically significant (Z=-2.132, t=1.934, both P<0.05).The liver function indexes of LDLT group and SLT group showed unimodal changes within 1 week after operation. The peak values of ALT, AST, prothrombin time, activeated partial thromboplasting time, international normalized ratio, fibrinogen and creatinine all appeared at 1 day after operation, and the peak value of prothrombin activity appeared at 3 days after operation. All indicators returned to normal at 7 days after operation. The 1-,2-,and 3-year overall survival rates were 95.5% in LDLT group and 93.5% in the technically mature SLT group, and the difference was not statistically significant. The 1-,2-,and 3-year overall survival rates were 90.2% in the early SLT group and 93.5% in the technically mature SLT group, and there was no significant difference between the two groups(P>0.05). The main complications of the early SLT group were surgery-related complications(28.1%,9/32), and the main complications of the technically mature SLT group were non-surgery-related complications(21.9%,7/32). There were 5 deaths in the SLT group,including 4 in the early SLT group and 1 in the technically mature SLT group. Conclusion: The survival rate of SLT in the treatment of biliary atresia is comparable to that of LDLT.

PMID:36207978 | DOI:10.3760/cma.j.cn112139-20220712-00309