Nevin Manimala

AMB Express. 2021 Aug 30;11(1):122. doi: 10.1186/s13568-021-01282-w.

ABSTRACT

Klebsiella pneumoniae is a multidrug-resistant (MDR) opportunistic pathogen that causes nosocomial infections. Virulence analysis and molecular typing as powerful approaches can provide relevant information on K. pneumoniae infection. In the current study, antibiotic resistance, virulence-associated genes analysis, as well as molecular typing of K. pneumoniae strains were investigated. Out of 505 clinical samples collected from hospitalized patients, 100 K. pneumoniae strains were isolated by standard microbiological methods and subjected to the phenotypic and genotyping analysis. The highest prevalence of resistance was observed against ciprofloxacin (75%), trimethoprim-sulfamethoxazole (73%) and nitrofurantoin (68%). Virulence associated genes including entB, traT, ybts, magA, iucC, htrA and rmpA were found in 80%, 62%, 75%, 5%, 30%, 72% and 48%, of the isolates, respectively. The prevalence of biofilm-associated genes including mrkA, fimH, and mrkD were equally 88% for all tested isolates. Moreover, the efflux pump genes including AcrAB, TolC and mdtK were observed in 41 (41%), 33 (33%) and 26 (26%) of the strains respectively. A significant statistical association was observed between MDR strains and high expression of efflux pump and biofilm genes. The K. pneumoniae strains were differentiated into 11 different genetic patterns using the repetitive element sequence-based PCR (rep-PCR) technique. High prevalence of resistance, presence of various virulence factors, high level of efflux pump, and biofilm gene expression in diverse clones of K. pneumoniae strains pose an important health issue in clinical settings.

PMID:34460016 | DOI:10.1186/s13568-021-01282-w

Bull Math Biol. 2021 Aug 30;83(10):102. doi: 10.1007/s11538-021-00931-2.

NO ABSTRACT

PMID:34460011 | DOI:10.1007/s11538-021-00931-2

J Anesth. 2021 Aug 28. doi: 10.1007/s00540-021-02993-x. Online ahead of print.

ABSTRACT

PURPOSE: Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation.

METHODS: The effects of midazolam, diazepam and propofol (1, 10, 50 µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P < 0.05 was considered statistically significant.

RESULTS: Fifty µM of midazolam significantly impaired endothelial cell proliferation, migration, and in vitro capillary tube formation. Propofol, diazepam or lower dose midazolam did not show any enhancing or suppressive effects on in vitro angiogenesis. Fifty µM of midazolam remarkably activated ERK, but not p38 MAPK in HUVEC.

CONCLUSION: Propofol and benzodiazepines except high-dose midazolam did not affect in vitro angiogenesis. High-dose midazolam may impair in vitro capillary tube formation due to by suppressing proliferation and migration of endothelial cells via activation of ERK.

PMID:34460008 | DOI:10.1007/s00540-021-02993-x

Clin Oral Investig. 2021 Aug 30. doi: 10.1007/s00784-021-04152-8. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the in vitro effect of enamel matrix derivative (EMD) and hyaluronic acid (HA) and their synergistic combination on lipopolysaccharides (LPS)-induced inflammation in human keratinocytes and osteoblasts.

MATERIAL AND METHODS: Cells were challenged with LPS (1 μg/ml) and cultured in the following treatment groups with EMD (30 mg/ml) and HA (30 mg/ml): LPS, EMD, HA, EMD + HA, EMD + LPS, HA + LPS, and EMD + HA + LPS. Cell viability, inflammatory cytokine expression, and cell migration were determined using colorimetric assay, quantitative real-time polymerase chain reaction (qPCR), and scratch wound healing assay, respectively.

RESULTS: Cell viability was decreased when exposed to LPS compared to the controls. Overall, LPS treatment expressed upregulation on inflammatory cytokine tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6). EMD and HA reduced up to 3.0-fold the cytokine expression caused by LPS (p < 0.05). EMD and HA statistically induced higher migration in osteoblasts and keratinocytes, respectively. Migration was impaired by LPS, whereas it significantly increased after addition of EMD and HA.

CONCLUSIONS: EMD and HA are advantageous biomaterials that individually generate strong directional migratory keratinocyte and osteoblast response. Their combination also enhances cell viability, and anti-inflammatory and migratory abilities to promote healing specially under LPS inflammatory stimulus. Future in vivo and animal research is necessary to further characterize the effect of EMD and HA on periodontal regeneration.

CLINICAL RELEVANCE: The use of EMD in conjunction with HA resulted in a reduction of inflammation and improvement of tissue healing at wound sites. Both biomaterials combined may potentially improve the effectiveness of bone regeneration in periodontal bone defects, pointing to the potential clinical relevance of both materials in regenerative periodontal surgery.

PMID:34460002 | DOI:10.1007/s00784-021-04152-8

Bull Math Biol. 2021 Aug 30;83(10):103. doi: 10.1007/s11538-021-00935-y.

ABSTRACT

We combine a systems pharmacology approach with an agent-based modelling approach to simulate LoVo cells subjected to AZD6738, an ATR (ataxia-telangiectasia-mutated and rad3-related kinase) inhibiting anti-cancer drug that can hinder tumour proliferation by targeting cellular DNA damage responses. The agent-based model used in this study is governed by a set of empirically observable rules. By adjusting only the rules when moving between monolayer and multi-cellular tumour spheroid simulations, whilst keeping the fundamental mathematical model and parameters intact, the agent-based model is first parameterised by monolayer in vitro data and is thereafter used to simulate treatment responses in in vitro tumour spheroids subjected to dynamic drug delivery. Spheroid simulations are subsequently compared to in vivo data from xenografts in mice. The spheroid simulations are able to capture the dynamics of in vivo tumour growth and regression for approximately 8 days post-tumour injection. Translating quantitative information between in vitro and in vivo research remains a scientifically and financially challenging step in preclinical drug development processes. However, well-developed in silico tools can be used to facilitate this in vitro to in vivo translation, and in this article, we exemplify how data-driven, agent-based models can be used to bridge the gap between in vitro and in vivo research. We further highlight how agent-based models, that are currently underutilised in pharmaceutical contexts, can be used in preclinical drug development.

PMID:34459993 | DOI:10.1007/s11538-021-00935-y

Surg Endosc. 2021 Aug 30. doi: 10.1007/s00464-021-08697-3. Online ahead of print.

ABSTRACT

BACKGROUND: Gender disparities in surgical leadership have come under increased scrutiny, and in order to better understand why these disparities exist, it is important to study the disparities across surgical fellowship programs.

METHODS: Data derived from the Fellowship Council (FC) database for fellows completing training from academic years 2015-2019 were analyzed. Available information included institution, fellowship type, program director (PD), associate program director (APD), faculty, and fellow names for all FC Fellowships. Faculty and fellow gender were determined from personal knowledge or publicly available online biographical information.

RESULTS: A total of 1023 fellows and 221 programs were analyzed. The advanced gastrointestinal (GI)/minimally invasive surgery (MIS) fellowship programs included 321 fellows, with a small increase in the percentage of female fellows from 28 to 31% over 5 years. Advanced GI/MIS/bariatric fellowship programs had a total of 262 fellows, also with a small increase in the percent of female fellows, from 29 to 38% in the study period. The gender of program directors, assistant program directors, and faculty for the fellowship programs studied were analyzed as well. Of the 221 programs in the Fellowship Council data, 13.6% of program directors, 18.3% of associate program directors, and 19.9% of faculty were female. Advanced GI/MIS fellowship programs had the lowest percentage of female PDs, with only 9.3% of the program directors being female. Colorectal surgery fellowships had the highest percentage of female PDs, with 33% being female.

CONCLUSIONS: In conclusion, women are underrepresented in gastrointestinal surgery fellowships among both trainees and educators. It is likely that a significant contributing factor to this underrepresentation of female fellows is the underrepresentation of female program directors and faculty; although neither our study nor any previously published study has proven that statistically.

PMID:34459975 | DOI:10.1007/s00464-021-08697-3

Eur J Pediatr. 2021 Aug 30. doi: 10.1007/s00431-021-04215-8. Online ahead of print.

ABSTRACT

A retrospective study that compared children younger than 6 months versus older children of a Spanish cohort of patients diagnosed with Kawasaki disease between 2011 and 2016 (Kawa-Race study). From the 598 patients recruited, 42 patients were younger than 6 months (7%) and presented more frequently with an incomplete diagnosis of Kawasaki disease (52.4 vs 27.9%, p = 0.001). Cardiac abnormalities detected by echocardiography were more common in younger patients (52.4 vs 30%, p = 0.002). These younger patients presented with a higher proportion of coronary aneurysms as well (19 vs 8.6%, p < 0.001). Shock at diagnosis (9.5 vs 1.9%, p = 0.016) and admission to intensive care units (17.7 vs 4.1%, p = 0.003) were more frequent in patients younger than 6 months. There were no statistically significant differences in relation to infections, non-response to IVIG, or mid- or long-term outcomes.Conclusion: Data of the Spanish cohort are consistent with other American and Asian studies, although Spanish children younger than 6 months had a lower rate of non-response to IVIG and better clinical outcomes. A high index of suspicion should be considered for this population due to a higher risk of coronary abnormalities, presentation of shock, and admission to the intensive care unit. What is Known: •Children below 6 months of age with Kawasaki disease (KD) have different features compared to older. •Younger patients usually have an incomplete form of KD and coronary artery abnormalities. What is New: •Younger than 6 months with KD presented with shock and required admission to PICU more frequently compared to older. •Infections play a similar role in KD despite the age of the patients.

PMID:34459958 | DOI:10.1007/s00431-021-04215-8

Arch Orthop Trauma Surg. 2021 Aug 30. doi: 10.1007/s00402-021-04135-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The guidelines regarding rehabilitation after pediatric anterior cruciate ligament reconstruction (ACLR) are sparse. The aim of the study was to retrospectively describe the long-term outcome regarding further surgery and with special emphasis on the revision rate after two different postoperative rehabilitation programs following pediatric ACLR.

MATERIAL AND METHODS: 193 consecutive patients < 15 years of age who had undergone ACLR at two centers, A (n = 116) and B (n = 77), in 2006-2010 were identified. Postoperative rehabilitation protocol at A: a brace locked in 30° of flexion with partial weight bearing for 3 weeks followed by another 3 weeks in the brace with limited range of motion 10°-90° and full weight bearing; return to sports after a minimum of 9 months. B: immediate free range of motion and weight bearing as tolerated; return to sports after a minimum of 6 months. The mean follow-up time was 6.9 (range 5-9) years. The mean age at ACLR was 13.2 years (range 7-14) years. The primary outcome measurement in the statistical analysis was the occurrence of revision. Multivariable logistic regression analysis was performed to investigate five potential risk factors: surgical center, sex, age at ACLR, time from injury to ACLR and graft diameter.

RESULTS: Thirty-three percent had further surgery in the operated knee including a revision rate of 12%. Twelve percent underwent ACLR in the contralateral knee. The only significant variable in the statistical analysis according to the multivariable logistic regression analysis was surgical center (p = 0.019). Eight percent of the patients at center A and 19% of the patients at B underwent ACL revision.

CONCLUSIONS: Further surgery in the operated knee could be expected in one third of the cases including a revision rate of 12%. The study also disclosed a similar rate of contralateral ACLR at 12%. The revision rate following pediatric ACLR was lower in a center which applied a more restrictive rehabilitation protocol.

LEVEL OF EVIDENCE: Case-control study, Level III.

PMID:34459955 | DOI:10.1007/s00402-021-04135-0

JAMA Netw Open. 2021 Aug 2;4(8):e2129041. doi: 10.1001/jamanetworkopen.2021.29041.

ABSTRACT

IMPORTANCE: Housing insecurity induced by evictions may increase the risk of contracting COVID-19.

OBJECTIVE: To estimate the association of lifting state-level eviction moratoria, which increased housing insecurity during the COVID-19 pandemic, with the risk of being diagnosed with COVID-19.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included individuals with commercial insurance or Medicare Advantage who lived in a state that issued an eviction moratorium and were diagnosed with COVID-19 as well as a control group comprising an equal number of randomly selected individuals in these states who were not diagnosed with COVID-19. Data were collected from OptumLabs Data Warehouse, a database of deidentified administrative claims. The study used a difference-in-differences analysis among states that implemented an eviction moratorium between March 13, 2020, and September 4, 2020.

EXPOSURES: Time since state-level eviction moratoria were lifted.

MAIN OUTCOMES AND MEASURES: The primary outcome measure was a binary variable indicating whether an individual was diagnosed with COVID-19 for the first time in a given week with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code U07.1. The study analyzed changes in COVID-19 diagnosis before vs after a state lifted its moratorium compared with changes in states that did not lift it. For sensitivity analyses, models were reestimated on a 2% random sample of all individuals in the claims database during this period in these states.

RESULTS: The cohort consisted of 509 694 individuals (254 847 [50.0%] diagnosed with COVID-19; mean [SD] age, 47.0 [23.6] years; 239 056 [53.3%] men). During the study period, 43 states and the District of Columbia implemented an eviction moratorium and 7 did not. Among the states that implemented a moratorium, 26 (59.1%) lifted their moratorium before the US Centers for Disease Control and Prevention issued their national moratorium, while 18 (40.1%) maintained theirs. In a Cox difference-in-differences regression model, individuals living in a state that lifted its eviction moratorium experienced higher hazards of a COVID-19 diagnosis beginning 5 weeks after the moratorium was lifted (hazard ratio [HR], 1.39; 95% CI, 1.11-1.76; P = .004), reaching an HR of 1.83 (95% CI, 1.36-2.46; P < .001) 12 weeks after. Hazards increased in magnitude among individuals with preexisting comorbidities and those living in nonaffluent and rent-burdened areas. Individuals with a Charlson Comorbidity Index score of 3 or greater had an HR of 2.37 (95% CI, 1.67-3.36; P < .001) at the end of the study period. Those living in nonaffluent areas had an HR of 2.14 (95% CI, 1.51-3.05; P < .001), while those living in areas with a high rent burden had an HR of 2.31 (95% CI, 1.64-3.26; P < .001).

CONCLUSIONS AND RELEVANCE: The findings of this difference-in-differences analysis suggest that eviction-led housing insecurity may have exacerbated the COVID-19 pandemic.

PMID:34459904 | DOI:10.1001/jamanetworkopen.2021.29041

Health Policy Plan. 2021 Aug 30:czab109. doi: 10.1093/heapol/czab109. Online ahead of print.

ABSTRACT

Implementing context-appropriate neonatal and pediatric advanced life support management interventions has increasingly been recommended as one of the approaches to reduce under-five mortality in resource-constrained settings like Rwanda. One such intervention is ETAT+, which stands for Emergency Triage, Assessment and Treatment plus Admission care for severely ill newborns and children. In 2013, ETAT+ was implemented in Rwandan district hospitals. We evaluated the impact of the ETAT+ intervention on newborn and child health outcomes. We used monthly time series data from the DHIS2-enabled Rwanda Health Management Information System from 2012 to 2016 to examine neonatal and pediatric hospital mortality rate. Each hospital contributed data for 12 and 36 months before and after ETAT+ implementation, respectively. Using controlled interrupted time series analysis and segmented regression model, we estimated longitudinal changes in neonatal and pediatric hospital mortality rate in intervention hospitals relative to matched concurrent control hospitals. We also studied changes in case fatality rate specifically for ETAT+ targeted conditions. Our study cohort consisted of seven intervention hospitals and fourteen matched control hospitals contributing 142,424 neonatal and pediatric hospital admissions. After controlling for secular trends and autocorrelation, we found that the ETAT+ implementation had no statistically significant impact on the rate of all-cause neonatal and pediatric hospital mortality in intervention hospitals relative to control hospitals. However, the case fatality rate for ETAT+ targeted neonatal conditions decreased immediately following implementation by 5% (95% CI: -9.25, -0.77) and over time by 0.8% monthly (95% CI: -1.36, -0.25), in intervention hospitals compared with control hospitals. Case fatality rate for ETAT+ targeted pediatric conditions did not decrease following the ETAT+ implementation. While ETAT+ focuses on improving quality of hospital care for both newborns and children, we only found an impact on neonatal hospital mortality for ETAT+ targeted conditions that should be interpreted with caution given the relatively short pre-intervention period and potential regression to the mean.

PMID:34459893 | DOI:10.1093/heapol/czab109