Genetic variability profiling of the p53 signaling pathway in chronic lymphocytic leukemia. Individual and combined analysis of TP53, MDM2 and NQO1 gene variants.

TP53 gene disruption, including 17p13 deletion [del(17p)] and/or TP53 mutations, is a negative prognostic biomarker in chronic lymphocytic leukemia (CLL) associated with disease progression, treatment failure and shorter survival. Germline variants in p53 signaling pathway genes could also lead to p53 dysfunction, but their involvement in CLL has not been thoroughly evaluated. The aim of this study was to determine the association of TP53, MDM2 and NQO1 gene variability with clinical and genetic data of CLL patients. Individual genotype and haplotype data of CLL patients were compared with clinical prognostic factors, cytogenetic and molecular cytogenetic findings as well as IGHV and TP53 mutational status. The study included 116 CLL patients and 161 healthy blood donors. TP53 (rs1042522, rs59758982, rs1625895), NQO1 (rs1800566) and MDM2 (rs2279744, rs150550023) variants were genotyped using different PCR approaches. Analysis of genotype frequencies revealed no association with the risk of CLL. TP53 rs1042522, rs1625895 and MDM2 rs2279744 variants were significantly associated with abnormal karyotype and the presence of del(17p). Similarly, these two TP53 variants were associated with TP53 disruption. Moreover, TP53 C-A-nondel and G-A-del haplotypes (rs1042522-rs1625895-rs59758982) were associated with an increased likelihood of carrying del(17p) and TP53 disruptions. MDM2 T-nondel haplotype (rs2279744-rs150550023) was found to be a low risk factor for del(17p) (OR = 0.32; CI: 0.12-0.82; p = 0.02) and TP53 disruptions (OR = 0.41; CI: 0.18-0.95; p = 0.04). Our findings suggest that TP53 and MDM2 variants may modulate the risk to have chromosome alterations and TP53 disruptions, particularly del(17p). To our knowledge this is the first study of several germline variants in p53 pathway genes in Argentine patients with CLL.

Gram-negative ESKAPE bacteria bloodstream infections in patients during the COVID-19 pandemic.

Bloodstream infections due to bacteria are a highly consequential nosocomial occurrences and the organisms responsible for them are usually multidrug-resistant. The aims of this study were to describe the incidence of bacteremia caused by Gram-negative ESKAPE bacilli during the COVID-19 pandemic and characterize the clinical and microbiological findings including antimicrobial resistance. A total of 115 Gram-negative ESKAPE isolates were collected from patients with nosocomial bacteremia (18% of the total bacteremias) in a tertiary care center in Mexico City from February 2020 to January 2021. These isolates were more frequently derived from the Respiratory Diseases Ward (27), followed by the Neurosurgery (12), Intensive Care Unit (11), Internal Medicine (11), and Infectious Diseases Unit (7). The most frequently isolated bacteria were Acinetobacter baumannii (34%), followed by Klebsiella pneumoniae (28%), Pseudomonas aeruginosa (23%) and Enterobacter spp (16%). A. baumannii showed the highest levels of multidrug-resistance (100%), followed by K. pneumoniae (87%), Enterobacter spp (34%) and P. aeruginosa (20%). The bla CTX-M-15 and bla TEM-1 genes were identified in all beta-lactam-resistant K. pneumoniae (27), while bla TEM-1 was found in 84.6% (33/39) of A. baumannii isolates. The carbapenemase gene bla OXA-398 was predominant among carbapenem-resistant A. baumannii (74%, 29/39) and bla OXA-24was detected in four isolates. One P. aeruginosa isolate was bla VIM-2 gene carrier, while two K. pneumoniae and one Enterobacter spp were bla NDM gene carriers. Among colistin-resistant isolates mcr-1 gene was not detected. Clonal diversity was observed in K. pneumoniae, P. aeruginosa and Enterobacter spp. Two outbreaks caused by A. baumannii ST208 and ST369 were detected, both belonging to the clonal complex CC92 and IC2. A. baumannii was associated with a death rate of 72% (28/32), most of them (86%, 24/28) extensively drug-resistant or pandrug-resistant isolates, mainly in patients with COVID-19 (86%, 24/28) in the Respiratory Diseases Ward. A. baumannii isolates had a higher mortality rate (72%), which was higher in patients with COVID-19. There was no statistically significant association between the multidrug-resistant profile in Gram-negative ESKAPE bacilli and COVID-19 disease. The results point to the important role of multidrug-resistant Gram-negative ESKAPE bacteria causing bacteremia in nosocomial settings before and during the COVID-19 epidemic. Additionally, we were unable to identify a local impact of the COVID-19 pandemic on antimicrobial resistance rates, at least in the short term.

Recovery and Resilience in the Canal Community: Economic Impacts and Solutions During the COVID-19 Pandemic.

BACKGROUND: Public health pandemics, such as COVID-19, not only impact the physical health and wellbeing of communities but also often have far-reaching effects on their social, psychological, environmental, and economic welfare. The coronavirus pandemic has highlighted the significant inequities experienced among those who are Black, Indigenous, and People of Color (BIPOC), especially in the areas of housing instability, unemployment, and debt accrual. This study investigates the socioeconomic impacts of COVID-19 on residents of the Canal neighborhood ("The Canal"), a low-income Latinx community in Marin County, California. This study also uplifts mitigation strategies already underway to facilitate post-pandemic recovery efforts. METHODS: This study utilized a mixed-methods, community participatory approach in which community leaders from a local nonprofit, Canal Alliance, administered a survey assessing the impact of COVID-19 on Canal residents. Additionally, community stakeholders including nonprofits, small businesses, and public officials were interviewed, and their field notes were analyzed through exploratory open coding. RESULTS: On a macro level, the data showed that Canal residents were severely impacted by COVID-19 in the form of massive job loss (61.2% of respondents were unemployed or underemployed) as well as financial stress related to eviction, housing instability, and debt accrual (78.8% of respondents struggled to cover rent and often had to borrow money from friends and family). CONCLUSIONS: In spite of the severe socioeconomic impacts of COVID-19 on The Canal, there is a significant opportunity for recovery and growth because of an overwhelming investment by residents, community-based organizations, and public officials to support those who have been financially impacted by the pandemic. Some key areas of policy focus include expansion of affordable housing, pandemic-resistant workforce development, and restructuring of social services to increase accessibility. This report will explore recommendations related to strategic funding of community-based programs as well as short-term and long-term solutions for economic recovery.

Genomic analysis of high copy-number sequences for the targeted detection of Listeria species using a flow-through surveillance system.

The bacterial foodborne pathogen Listeria monocytogenes has been implicated in fresh produce outbreaks with a significant economic impact. Given that L. monocytogenes is widespread in the environment, food production facilities constantly monitor for the presence of Listeria species. To develop a surveillance platform for food processing facilities, this study conducted a comparative genomic analysis for the identification of conserved high copy sequences in the ribosomal RNA of Listeria species. Simulated folding was performed to assess RNA accessibility in the identified genomic regions targeted for detection, and the developed singleplex assay accurately detected cell amounts lower than 5 cells, while no signals were detected for non-targeted bacteria. The singleplex assay was subsequently tested with a flow-through system, consisting of a DNA aptamer-capture step, followed by sample concentration and mechanical lysis for the detection of Listeria species. Validation experiments indicated the continuous flow-through system accurately detected Listeria species at low cell concentrations.

The Neutrophil-to-Monocyte Ratio and Lymphocyte-to-Neutrophil Ratio at Admission Predict In-Hospital Mortality in Mexican Patients with Severe SARS-CoV-2 Infection (Covid-19).

There is a deep need for mortality predictors that allow clinicians to quickly triage patients with severe coronavirus disease 2019 (Covid-19) into intensive care units at the time of hospital admission. Thus, we examined the efficacy of the lymphocyte-to-neutrophil ratio (LNR) and neutrophil-to-monocyte ratio (NMR) as predictors of in-hospital death at admission in patients with severe Covid-19. A total of 54 Mexican adult patients with Covid-19 that met hospitalization criteria were retrospectively enrolled, followed-up daily until hospital discharge or death, and then assigned to survival or non-survival groups. Clinical, demographic, and laboratory parameters were recorded at admission. A total of 20 patients with severe Covid-19 died, and 75% of them were men older than 62.90 ± 14.18 years on average. Type 2 diabetes, hypertension, and coronary heart disease were more prevalent in non-survivors. As compared to survivors, LNR was significantly fourfold decreased while NMR was twofold increased. LNR ≤ 0.088 predicted in-hospital mortality with a sensitivity of 85.00% and a specificity of 74.19%. NMR ≥ 17.75 was a better independent risk factor for mortality with a sensitivity of 89.47% and a specificity of 80.00%. This study demonstrates for the first time that NMR and LNR are accurate predictors of in-hospital mortality at admission in patients with severe Covid-19.

Simulation-Based Structured Education Supports Focused Neonatal Cranial Ultrasound Training.

OBJECTIVES: Brain injury in preterm neonates may cause clinical deterioration and requires timeous bedside diagnosis. Teaching cranial ultrasound (US) skills using fragile preterm neonates is challenging. The purpose of this study was to test the effectiveness and feasibility of using task-trainer computer-based simulators and US-suitable cranial phantoms in combination with teaching sessions in teaching novices to perform focused cranial US evaluations for identifying substantial intraventricular hemorrhage. METHODS: This was a prospective interventional educational study targeting participants with no prior skills in neonatal cranial US. Participants attended a 2-day training workshop, with didactic and hands-on interactive sessions using computer-based and 3-dimensional printed phantom simulators. Participants then performed a cranial US scan on a healthy neonate to assess the diagnostic quality of the images acquired. Individual precourse and postcourse knowledge tests were compared. To test recall, participants also submitted US images acquired on neonates within 3 and 6 months of attending the course. RESULTS: Forty-five participants completed the training modules. Mean knowledge scores increased significantly (in brain anatomy, brain physiology, intracranial disorders, and US physics domains). Thirty-eight cranial US scans were acquired during the course, 22 within 3 months after completion, and 34 within 6 months after completion. Thirty-two (84%) of the initial 38 case images, 17 (77%) of 22 images submitted within 3 months, and 32 (94%) of 34 images submitted within 6 months after course completion were of diagnostic quality. CONCLUSIONS: A structured training module with didactic and hand-on training sessions using simulators and phantoms is feasible and supports training of clinicians to perform focused cranial US examinations.

Latino immigration: Preparing school psychologists to meet students' needs.

As the population of immigrant Latino students continues to rise, school psychologists serving Latino children and families must develop the knowledge and skills necessary to provide high-quality psychological services to culturally and linguistically diverse students from immigrant families. Following a review of the relevant literature on the educational, social, and emotional needs of immigrant Latino children, we describe Project SUPERB (Scholars Using Psychology and Education to Reach Bilinguals), a grant-funded initiative to address the shortage of bilingual (Spanish-English) school psychologists. We discuss important issues regarding training and preparation to develop the competencies necessary for effective assessment, intervention, and collaboration in the context of school settings to help immigrant children achieve success. Finally, we identify ways in which school psychologists may adopt a leadership role in working with schools and families to promote positive outcomes. (PsycINFO Database Record