A case study to engage students in the research design and ethics of high-throughput metagenomics.

Case studies present students with an opportunity to learn and apply course content through problem solving and critical thinking. Supported by the High-throughput Discovery Science & Inquiry-based Case Studies for Today's Students (HITS) Research Coordination Network, our interdisciplinary team designed, implemented, and assessed two case study modules entitled "You Are What You Eat." Collectively, the case study modules present students with an opportunity to engage in experimental research design and the ethical considerations regarding microbiome research and society. In this manuscript, we provide instructors with tools for adopting or adapting the research design and/or the ethics modules. To date, the case has been implemented using two modalities (remote and in-person) in three courses (Microbiology, Physiology, and Neuroscience), engaging over 200 undergraduate students. Our assessment data demonstrate gains in content knowledge and students' perception of learning following case study implementation. Furthermore, when reflecting on our experiences and student feedback, we identified ways in which the case study could be modified for different settings. In this way, we hope that the "You Are What You Eat" case study modules can be implemented widely by instructors to promote problem solving and critical thinking in the traditional classroom or laboratory setting when discussing next-generation sequencing and/or metagenomics research.

Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

Lethal metabolism of Candida albicans respiratory mutants.

The destructive impact of fungi in agriculture and animal and human health, coincident with increases in antifungal resistance, underscores the need for new and alternative drug targets to counteract these trends. Cellular metabolism relies on many intermediates with intrinsic toxicity and promiscuous enzymatic activity generates others. Fuller knowledge of these toxic entities and their generation may offer opportunities of antifungal development. From this perspective our observation of media-conditional lethal metabolism in respiratory mutants of the opportunistic fungal pathogen Candida albicans was of interest. C. albicans mutants defective in NADH:ubiquinone oxidoreductase (Complex I of the electron transport chain) exhibit normal growth in synthetic complete medium. In YPD medium, however, the mutants grow normally until early stationary phase whereupon a dramatic loss of viability occurs. Upwards of 90% of cells die over the subsequent four to six hours with a loss of membrane integrity. The extent of cell death was proportional to the amount of BactoPeptone, and to a lesser extent, the amount of yeast extract. YPD medium conditioned by growth of the mutant was toxic to wild-type cells indicating mutant metabolism established a toxic milieu in the media. Conditioned media contained a volatile component that contributed to toxicity, but only in the presence of a component of BactoPeptone. Fractionation experiments revealed purine nucleosides or bases as the synergistic component. GC-mass spectrometry analysis revealed acetal (1,1-diethoxyethane) as the active volatile. This previously unreported and lethal synergistic interaction of acetal and purines suggests a hitherto unrecognized toxic metabolism potentially exploitable in the search for antifungal targets.

New approaches for understanding the potential role of microbes in Alzheimer's disease.

Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the "germ hypothesis" of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: "New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease." Discussion centered around the antimicrobial protection hypothesis of amyloid accumulation, and other mechanisms by which microbes could influence AD pathology including immune cell activation, changes in blood-brain barrier, or direct neurotoxicity. This summary of proceedings reviews the content presented in the symposium and provides a summary of major topics and key questions discussed in the workshop.

Usefulness of ultrasound in clinical decision-making in rheumatology clinical practice: A single-center longitudinal study.

OBJECTIVE: The purpose of the present study is to identify the extent to which it affects clinical decisions in a single-centre observational retrospective study. METHOD: The results of 801 requests and 1174 consecutive individual ultrasound examinations performed over 10 months were analysed. RESULTS: The most frequent indication was diagnostic assistance (39%) followed by assessment of inflammatory activity (34%). By topography, the hand was the most frequently studied region (51%), followed by the foot (18.1%). Of all requests, 67% had an impact on decision-making. The impact on clinical decision-making was associated with a shorter waiting time for the evaluation of the results, being the greatest in those ultrasound scans performed on demand on the same day of the request. In 73% of bilateral ultrasound studies, findings in one of the joints exemplified the overall result reported. CONCLUSIONS: Rheumatological musculoskeletal ultrasound has proven to be a useful decision-making technique, the greater the impact of which is seen the shorter the waiting time before it is performed.

Subclinical synovitis impact on the progression of lupus joint disease: A 10-year longitudinal multicenter study.

OBJECTIVE: To determine the effect of subclinical synovitis on the progression of joint disease in a cohort of patients with systemic lupus erythematosus over a mean follow-up of 10 years. METHODS: A longitudinal follow-up of 96 patients diagnosed with lupus was performed. All patients were considered clinically free of joint disease or with minimal joint impairment at baseline and were studied through ultrasound study of their dominant hand to assess the prevalence of subclinical synovitis. Now, over 10 years after we contacted them and reviewed their evolution to determine the impact of had or had not been diagnosed with subclinical synovitis in their current joint condition. RESULTS: Thirty-one of the 91 reached patients developed clinical progression in their joint manifestations (at least one ordinal degree of worsening). Of these, 23 (74,9%) had demonstrated subclinical synovitis at baseline. In the group of patients who did not progress clinically, 46 (76,6%) did not have this finding at the start of follow-up (p < .01, OR 9,44 95%CI 3,46-25,74). The patients in whom clinical progression was demonstrated had worse combined ultrasound scores than the rest of the patients: 6,41 SD 1,45 vs. 1,15 SD 0,97 (p < .01). CONCLUSIONS: The finding of subclinical synovitis in patients with systemic lupus erythematosus is associated with the development of joint disease progression both clinically and ultrasonographically.

Utilidad de la ecografía reumatológica en la toma de decisiones en la práctica clínica: Estudio unicéntrico longitudinal / Usefulness of ultrasound in clinical decision-making in rheumatology clinical practice: A single-center longitudinal study

Objetivo: El propósito del presente estudio es identificar en qué medida la ecografía reumatológica afecta a las decisiones clínicas mediante un estudio unicéntrico observacional retrospectivo. Método: Se analizaron los resultados de 801 solicitudes y 1174 ecografías individuales consecutivas realizadas a lo largo de 10 meses. Resultados: La indicación más frecuente fue la asistencia diagnóstica (39%) seguida de la evaluación de actividad inflamatoria (34%). Por topografía, la mano fue la región más estudiada (51%), seguida del pie (18,1%). De todas las solicitudes, en el 67% se constató un impacto en la toma de decisiones. El impacto en la decisión clínica se asoció a un menor tiempo de espera hasta la evaluación de los resultados, siendo el mayor en aquellas ecografías realizadas a demanda el mismo día de su petición. En el 73% de los estudios ecográficos bilaterales, los hallazgos en una de las articulaciones ejemplificaban el resultado global emitido. Conclusiones: La ecografía reumatológica demuestra ser una técnica útil en la toma de decisiones, cuyo mayor impacto se constata cuanto menor es el tiempo de espera hasta la evaluación de los resultados.(AU)

Objective: The purpose of the present study is to identify the extent to which rheumatological musculoskeletal ultrasound affects clinical decisions in a single-centre observational retrospective study. Method: The results of 801 requests and 1174 consecutive individual ultrasound examinations performed over 10 months were analysed. Results: The most frequent indication was diagnostic assistance (39%) followed by assessment of inflammatory activity (34%). By topography, the hand was the most frequently studied region (51%), followed by the foot (18.1%). Of all requests, 67% had an impact on decision-making. The impact on clinical decision-making was associated with a shorter waiting time for the evaluation of the results, being the greatest in those ultrasound scans performed on demand on the same day of the request. In 73% of bilateral ultrasound studies, findings in one of the joints exemplified the overall result reported. Conclusions: Rheumatological musculoskeletal ultrasound has proven to be a useful decision-making technique, the greater the impact of which is seen the shorter the waiting time before it is performed.(AU)

Basal characteristics of patients who responded to Ovarian Fragmentation for Follicular Activation (OFFA) or In Vitro Activation (IVA): a systematic review and meta-analysis.

A systematic review and meta-analysis were performed to identify if there is a subset of patients with POI who are more likely to show follicular growth after ovarian fragmentation for follicular activation (OFFA) or in vitro activation (IVA). Five studies met inclusion criteria for meta-analysis with a total of 164 patients. Forty-three patients showed follicle development (26.21%). Of those, the pregnancy rate was 35.58% (11/43) and the live birth rate was 20.93% (9/43). Our meta-analysis showed that age was not associated with follicle growth. However, lower baseline FSH, lower duration of amenorrhea/diagnosis, and presence of follicles remaining in biopsy were statistically significant for follicle development. Patients with basal characteristics mentioned before may have more chances to show follicle growth after OFFA or IVA. Taking into account that approximately 20% of patients with follicle growth had live birth, these results are very promising. Given the overall certainty of evidence, future studies are needed to confirm said results.

ANCA-associated vasculitis presenting with isolated neurological manifestations in a patient with cocaine abuse: a case report and literature review.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of rare conditions predominantly affecting small vessels of skin, musculoskeletal, pulmonary, renal, and rarely central and peripheral nervous systems. Isolated neurological manifestations of AAV are uncommon and challenging to diagnose. Cocaine has been reported as a potential trigger for the development of AAV. There are only a few case reports of isolated neurological involvement in cocaine-induced AAV with poorly characterized histopathological features. We present a unique case of AAV with isolated neurological manifestations presenting with multiple cranial neuropathies, leptomeningeal enhancement on imaging and histopathologic evidence of small-vessel vasculitis in the leptomeninges and brain and extensive dural fibrosis in a patient with cocaine abuse. The patient's progressive neurological deficits were controlled after starting immunosuppression with rituximab and prednisone. We also reviewed the literature to provide the diagnostic overview of AAV and evaluate intervention options. To our knowledge, this is the first case of AAV with isolated neurological manifestations and histopathologic evidence of small-vessel vasculitis in a patient with cocaine abuse. Patients with multiple cranial neuropathies and meningeal involvement should be screened for AAV, especially if they have a history of cocaine abuse.

Quality of life of patients with rheumatic diseases / Calidad de vida de los pacientes con enfermedades reumáticas

Objective: Health-related quality of life (HRQoL) is an important indicator of population health and can measure the impact of medical actions. The main objective of this study was to determine the HRQoL of patients with rheumatic diseases (RD) and compare it with that of the general population. Methods: Observational, cross-sectional, single-center study, with consecutive inclusion of outpatients over 18 years of age seen at a Rheumatology hospital-based outpatient clinic in Madrid. Sociodemographic, clinical variables and HRQoL were recorded. HRQoL was measured with the 5-dimension, 5-level EuroQoL (EQ-5D-5L), which includes the EQ-Index (0–1 scale) and a visual analog scale (VAS, 0–100 scale). A descriptive analysis and a comparison with the HRQoL of the Spanish general population were performed. Results: 1144 patients were included, 820 (71.68%) women, with a mean age of 56.1 years (range 18–95), of whom 241 (25.44%) were new patients. In patients with RD, the HRQoL measured with the EQ-Index and with the VAS, was 0.186 and 12 points lower, respectively, than in the general population. The decrease in HRQoL affected the 5 health dimensions, especially “pain/discomfort”, followed by “daily activities” and “mobility”. This reduction in HRQoL was observed in both men and women, and in all age ranges, although it was greater between 18 and 65 years of age. The reduction in HRQoL affected all RD subtypes, especially the “peripheral and axial mechanical pathology” and the “soft tissue pathology” group. Conclusions: Patients with rheumatic diseases report worse HRQoL when compared to the general population in all dimensions of HRQoL.(AU)

Objetivo: La calidad de vida relacionada con la salud (CVRS) se considera un indicador importante para valorar el estado de salud poblacional y medir el impacto de las actuaciones médicas. El principal objetivo de este estudio es conocer la CVRS de los pacientes con enfermedades reumáticas (RD, por sus siglas en inglés) y compararla con la población general. Métodos: Estudio observacional, transversal, unicéntrico, con inclusión consecutiva de pacientes ambulatorios mayores de 18 años atendidos en la consulta hospitalaria de reumatología. Se recogieron variables sociodemográficas, clínicas y CVRS medida con el EuroQoL de 5 dimensiones y 5 niveles (EQ-5D-5L) que incluye el EQ-Índex (escala 0-1) y una escala visual analógica (EVA, escala 0-100). Se realizó un análisis descriptico y una comparación con la población española según la Encuesta Nacional de Salud. Resultados: Se han incluido 1.144 pacientes, 820 (71,68%) mujeres, con edad media de 56,1 años (rango 18-95), de los que 241 (25,44%) eran pacientes nuevos. En los pacientes con RD, la CVRS medida con el EQ-Index y con la EVA, fue de 0,186 y 12 puntos menor, respectivamente, que en la población general. La CVRS afectó a las 5 dimensiones de salud, especialmente a «dolor/malestar», seguida de «actividades cotidianas» y «movilidad». Esta reducción de la CVRS se mantuvo tanto en varones y mujeres, y en todos los segmentos de edad, aunque fue mayor entre los 18 y 65 años. La reducción de CVRS afectó a todos los subtipos de RD, especialmente a la «Enfermedad mecánica periférica y axial» y al grupo de «Enfermedad de tejidos blandos». Conclusiones: Los pacientes con enfermedades reumáticas declaran peor CVRS en comparación a la población general en todas las dimensiones de la CVRS.(AU)

Nutrient structure dynamics and microbial communities at the water-sediment interface in an extremely acidic lake in northern Patagonia.

Lake Caviahue (37° 50 'S and 71° 06' W; Patagonia, Argentina) is an extreme case of a glacial, naturally acidic, aquatic environment (pH ~ 3). Knowledge of the bacterial communities in the water column of this lake, is incipient, with a basal quantification of the bacterioplankton abundance distribution in the North and South Basins of Lake Caviahue, and the described the presence of sulfur and iron oxidizing bacteria in the lake sediments. The role that bacterioplankton plays in nutrient utilization and recycling in this environment, especially in the phosphorus cycle, has not been studied. In this work, we explore this aspect in further depth by assessing the diversity of pelagic, littoral and sediment bacteria, using state of the art molecular methods and identifying the differences and commonalties in the composition of the cognate communities. Also, we investigate the interactions between the sediments of Lake Caviahue and the microbial communities present in both sediments, pore water and the water column, to comprehend the ecological relationships driving nutrient structure and fluxes, with a special focus on carbon, nitrogen, and phosphorus. Two major environmental patterns were observed: (a) one distinguishing the surface water samples due to temperature, Fe2+, and electrical conductivity, and (b) another distinguishing winter and summer samples due to the high pH and increasing concentrations of N-NH4+, DOC and SO42-, from autumn and spring samples with high soluble reactive phosphorus (SRP) and iron concentrations. The largest bacterial abundance was found in autumn, alongside higher levels of dissolved phosphorus, iron forms, and increased conductivity. The highest values of bacterial biomass were found in the bottom strata of the lake, which is also where the greatest diversity in microbial communities was found. The experiments using continuous flow column microcosms showed that microbial growth over time, in both the test and control columns, was accompanied by a decrease in the concentration of dissolved nutrients (SRP and N-NH4+), providing proof that sediment microorganisms are active and contribute significantly to nutrient utilization/mobilization.

Quality of life of patients with rheumatic diseases.

OBJECTIVE: Health-related quality of life (HRQoL) is an important indicator of population health and can measure the impact of medical actions. The main objective of this study was to determine the HRQoL of patients with rheumatic diseases (RD) and compare it with that of the general population. METHODS: Observational, cross-sectional, single-center study, with consecutive inclusion of outpatients over 18 years of age seen at a Rheumatology hospital-based outpatient clinic in Madrid. Sociodemographic, clinical variables and HRQoL were recorded. HRQoL was measured with the 5-dimension, 5-level EuroQoL (EQ-5D-5L), which includes the EQ-Index (0-1 scale) and a visual analog scale (VAS, 0-100 scale). A descriptive analysis and a comparison with the HRQoL of the Spanish general population were performed. RESULTS: 1144 patients were included, 820 (71.68%) women, with a mean age of 56.1 years (range 18-95), of whom 241 (25.44%) were new patients. In patients with RD, the HRQoL measured with the EQ-Index and with the VAS, was 0.186 and 12 points lower, respectively, than in the general population. The decrease in HRQoL affected the 5 health dimensions, especially "pain/discomfort", followed by "daily activities" and "mobility". This reduction in HRQoL was observed in both men and women, and in all age ranges, although it was greater between 18 and 65 years of age. The reduction in HRQoL affected all RD subtypes, especially the "peripheral and axial mechanical pathology" and the "soft tissue pathology" group. CONCLUSIONS: Patients with rheumatic diseases report worse HRQoL when compared to the general population in all dimensions of HRQoL.

Changes in Homelessness Among US Veterans After Implementation of the Ending Veteran Homelessness Initiative.

Importance: Homelessness is a persistent and growing problem. What role health systems should play and how that role is incorporated into larger strategic efforts are not well-defined. Objective: To compare homelessness among veterans with that in the general population during a 16-year study period before and after implementation of the Ending Veteran Homelessness Initiative, a program to rehouse veterans experiencing homelessness. Design, Setting, and Participants: This national retrospective cohort study using a mixed-methods approach examined annualized administrative (January 1, 2007, to December 31, 2022) and population data prior to (2007-2009) and during (2010-2022) the Ending Veteran Homelessness initiative. Participants included unhoused adults in the US between 2007 and 2022. Exposure: Enrollment in Veterans Health Administration (VHA) Homeless Program Office components providing housing, case management, and wrap-around clinical and supportive services. Main Outcomes and Measures: Point-in-time (PIT) count data for unhoused veterans and nonveterans during the study period, number of Section 8 housing vouchers provided by Housing and Urban Development-Veterans Administration Supportive Housing, number of community grants awarded by Supportive Services for Veterans and Families, and total number of veterans housed each year. Semistructured interviews with VHA leadership were performed to gain insight into the strategy. Results: In 2022, 33 129 veterans were identified in the PIT count. They were predominantly male (88.7%), and 40.9% were unsheltered. During the active years of the Ending Veteran Homelessness initiative, veteran homelessness decreased 55.3% compared with 8.6% for the general population. The proportion of veterans in this cohort also declined from 11.6% to 5.3%. This change occurred during a shift to "housing first" as agency policy to create low-barrier housing availability. It was also coupled with substantial growth in housing vouchers, grants to community partner agencies, and growth in VHA clinical and social programming to provide homeless-tailored wrap-around services and support once participants were housed. Key respondent interviews consistently cited the shift to housing first, the engagement with community partners, and use of real-time data as critical. Conclusions and Relevance: In this cohort study of the federal Ending Veteran Homelessness initiative, after program implementation, there was a substantially greater decrease in homelessness among veterans than in the general population. These findings suggest an important role for health systems in addressing complex social determinants of health. While some conditions unique to the VHA facilitated the change in homelessness, lessons learned here are applicable to other health systems.

Effects of the fungicide azoxystrobin in two habitats representative of mediterranean coastal wetlands: A mesocosm experiment.

This paper investigates the effects of the fungicide azoxystrobin, a compound widely used in rice farming, on aquatic communities representative of two habitats characteristic of Mediterranean wetland ecosystems: water springs and eutrophic lake waters. The long-term effects of azoxystrobin were evaluated on several structural (phytoplankton, zooplankton, macroinvertebrate populations and communities) and functional (microbial decomposition, macrophyte and periphyton growth) parameters making use of freshwater mesocosms. Azoxystrobin was applied in two pulses of 2, 20, 200 µg/L separated by 14 d using the commercial product ORTIVA (23 % azoxystrobin w/w). The results show that these two habitats responded differently to the fungicide application due to their distinct physico-chemical, functional, and structural characteristics. Although overall sensitivity was found to be similar between the two (lowest NOEC < 2 µg/L), the taxa and processes that were affected differed substantially. In general, the most sensitive species to the fungicide were found in the water spring mesocosms, with some species of phytoplankton (Nitzschia sp.) or macrocrustaceans (Echinogammarus sp. and Dugastella valentina) being significantly affected at 2 µg/L. In the eutrophic lake mesocosms, effects were found on phytoplankton taxa (Desmodesmus sp. and Coelastrum sp.), on numerous zooplankton taxa, on chironomids and on the beetle Colymbetes fuscus, although at higher concentrations. The hemipteran Micronecta scholtzi was affected in both treatments. In addition, functional parameters such as organic matter decomposition or macrophyte growth were also affected at relatively low concentrations (NOEC 2 µg/L). Structural Equation Modelling was used to shed light on the indirect effects caused by azoxystrobin on the ecosystem. These results show that azoxystrobin is likely to pose structural and functional effects on Mediterranean wetland ecosystems at environmentally relevant concentrations. Moreover, it highlights the need to consider habitat-specific features when conducting ecotoxicological research at the population and community levels.

Gram-Negative ESKAPE Bacteria Surveillance in COVID-19 Pandemic Exposes High-Risk Sequence Types of Acinetobacter baumannii MDR in a Tertiary Care Hospital.

The interruption of bacteriological surveillance due to the COVID-19 pandemic brought serious consequences, such as the collapse of health systems and the possible increase in antimicrobial resistance. Therefore, it is necessary to know the rate of resistance and its associated mechanisms in bacteria causing hospital infections during the pandemic. The aim of this work was to show the phenotypic and molecular characteristics of antimicrobial resistance in ESKAPE bacteria in a Mexican tertiary care hospital in the second and third years of the pandemic. For this purpose, during 2021 and 2022, two hundred unduplicated strains of the ESKAPE group (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were collected from various clinical sources and categorized by resistance according to the CLSI. An analysis of variance (ANOVA) complemented by the Tukey test was performed to search for changes in antimicrobial susceptibility profiles during the study period. Finally, the mechanisms of resistance involved in carbapenem resistance were analyzed, and the search for efflux pumps and high-risk sequence types in A. baumannii was performed by multilocus analysis (MLST). The results showed no changes in K. pneumoniae resistance during the period analyzed. Decreases in quinolone resistance were identified in E. coli (p = 0.039) and P. aeruginosa (p = 0.03). Interestingly, A. baumannii showed increases in resistance to penicillins (p = 0.004), aminoglycosides (p < 0.001, p = 0.027), carbapenems (p = 0.027), and folate inhibitors (p = 0.001). Several genes involved in carbapenem resistance were identified (blaNDM, blaVIM, blaOXA, blaKPC, blaOXA-40, and blaOXA-48) with a predominance of blaOXA-40 and the adeABCRS efflux pump in A. baumannii. Finally, MLST analysis revealed the presence of globally distributed sequence types (ST369 and ST758) related to hospital outbreaks in other parts of the world. The results presented demonstrate that the ESKAPE group has played an important role during the COVID-19 pandemic as nosocomial antibiotic-resistant pathogens and in particular A. baumannii MDR as a potential reservoir of resistance genes. The implications of the increases in antimicrobial resistance in pathogens of the ESKAPE group and mainly in A. baumannii during the COVID-19 pandemic are analyzed and discussed.

Mental health impact of the COVID-19 pandemic on patients with neurodegenerative diseases and perceived family caregiver burden in Lima, Peru.

BACKGROUND: Neurodegenerative diseases lead to difficulties with functional activities. In Peru, most caregivers are family members. Little is known about the COVID-19 pandemic's effect on caregivers in Peru. METHODS: This was a cross-sectional, prospective study of family caregivers of dependent patients with dementia or Parkinson's Disease in Lima, Peru. A caregiver burden and mental health questionnaire was administered to the caregiver. RESULTS: We enrolled 48 caregivers (65% females, mean ± SD age 49.0 ± 12.3 years); 70% of patients had dementia. Nearly 40% of caregivers reported having full-time jobs, and 82% felt overwhelmed with almost 75% dedicating more time to caregiving during the pandemic. Caregivers perceived patients felt lonelier (52%), had an increase in hallucinations (50%), or forgetfulness (71%) compared to pre-pandemic. CONCLUSIONS: Our study highlights that perceived caregiver burden and patient behavioral symptoms may have been exacerbated during the pandemic. In countries such as Peru, more caregiving resources and interventions are needed.

Rewarding Effects of the Hallucinogen 4-AcO-DMT Administration and Withdrawal in Rats: A Challenge to the Opponent-Process Theory.

According to the opponent-process theory of drug addiction, the intake of an addictive substance initiates two processes: a rapid primary process that results in the drug's rewarding effects, and a slower opponent process that leads to the aversive motivational state of drug aftereffects. This aversive state is integral in the desire, pursuit, and maintenance of drug use, potentially leading to dependence and addiction. However, current observational and experimental evidence suggests that the administration of a 5-hydroxytryptamine receptors-type 2A (5-HT2A) agonist, while capable of inducing a positive mental state in humans, may not generate the behavioral patterns typically associated with drugs of abuse. In this study, we found that administering the 5-HT2A agonist 4-Acetoxy-N,N-dimethyltryptamine fumarate (4-AcO-DMT) did not result in place preference in male rats compared to control saline administration 24 h later, after the drug has been cleared from the organism. However, in a modified place preference test where only the acute motivational effects of the drug were evaluated (excluding withdrawal), 4-AcO-DMT was found to be rewarding. Furthermore, in another modified place preference test where only the motivational effects of drug withdrawal were evaluated (excluding the acute effects of drug administration), the 24-hour aftereffect of 5-HT2A agonist administration also resulted in a robust place preference. Therefore, while 4-AcO-DMT administration was able to induce place preference, its 24-hour aftereffect also produced a strong reward. In the counterbalanced test, this reward from the aftereffect effectively overshadowed its acute rewarding properties, which could potentially create a false impression that 4-AcO-DMT lacks motivational properties. This suggests that 5-HT2A agonist administration follows a different dynamic than that proposed by the opponent-process theory of motivation and implies that the administration of 5-HT2A agonists may lead to behavioral patterns less typical of drugs associated with addiction.

La resistencia antimicrobiana, una amenaza en tres dimensiones.

Entre los principales problemas de Salud Pública podemos identificar a la resistencia antimicrobiana (RAM), definida por la Organización Mundial de la Salud (OMS) como aquella que se produce cuando los microorganismos (bacterias, hongos, virus y parásitos) sufren cambios al verse expuestos a los antimicrobianos, resultando que los medicamentos se vuelvan ineficaces y las infecciones persistan.

Low-cost inertial microfluidic device for microparticle separation: A laser-Ablated PMMA lab-on-a-chip approach without a cleanroom.

Although microparticles are frequently used in chemistry and biology, their effectiveness largely depends on the homogeneity of their particle size distribution. Microfluidic devices to separate and purify particles based on their size have been developed, but many require expensive cleanroom manufacturing processes. A cost-effective, passive microfluidic separator is presented, capable of efficiently sorting and purifying particles spanning the size range of 15 µm to 40 µm. Fabricated from Polymethyl Methacrylate (PMMA) substrates using laser ablation, this device circumvents the need for cleanroom facilities. Prior to fabrication, rigorous optimization of the device's design was carried out through computational simulations conducted in COMSOL Multiphysics. To gauge its performance, chitosan microparticles were employed as a test case. The results were notably promising, achieving a precision of 96.14 %. This quantitative metric underscores the device's precision and effectiveness in size-based particle separation. This low-cost and accessible microfluidic separator offers a pragmatic solution for laboratories and researchers seeking precise control over particle sizes, without the constraints of expensive manufacturing environments. This innovation not only mitigates the limitations tied to traditional cleanroom-based fabrication but also widens the horizons for various applications within the realms of chemistry and biology.

Bladder triplication associated with exstrophy variant.

A one-day old full-term female neonate presented with a duplicate bladder and exstrophy variant including a patch of exstrophic or ectopic mucosa, duplicate vagina, uterus, and two complete bladders. We report on the surgical management performed in this case and functional urinary results based on a synchronous urodynamic study of the duplicate bladders. To our knowledge, the occurrence of duplicate bladder exstrophy variant with complete urinary continence has not been previously reported.