Identification of Determinants that Allow Maintenance of High-Level Fluoroquinolone Resistance in Acinetobacter baumannii.

Acinetobacter baumannii is associated with multidrug resistant (MDR) infections in healthcare settings, with fluoroquinolones such as ciprofloxacin being currently ineffective. Clinical isolates largely harbor mutations in the GyrA and TopoIV fluoroquinolone targets, as well as mutations that increase expression of drug resistance-nodulation-division (RND) efflux pumps. Factors critical for maintaining fitness levels of pump overproducers are uncharacterized despite their prevalence in clinical isolates. We here identify proteins that contribute to the fitness of FQR strains overexpressing three known RND systems using high-density insertion mutagenesis. Overproduction of the AdeFGH efflux pump caused hypersensitization to defects in outer membrane homeostatic regulation, including lesions that reduced LOS biosynthesis and blocked production of the major A. baumannii porin. In contrast, AdeAB pump overproduction, which does not affect the outer membrane pump component, was relatively tolerant to loss of these functions, consistent with outer membrane protein overproduction being the primary disruptive component. Surprisingly, overproduction of proton-transporting efflux pumps had little impact on cytosolic pH, consistent with a compensatory response to pump activity. The most striking transcriptional changes were associated with AdeFGH pump overproduction, resulting in activation of the phenylacetate (PAA) degradation regulon. Disruption of the PAA pathway resulted in cytosolic acidification and defective expression of genes involved in protection from peroxide stress. These results indicate that the RND outer membrane protein overproduction is compensated by cytoplasmic buffering and maintenance of outer membrane integrity in A. baumannii to facilitate fitness of FQR isolates.

Antibiotic Over-Prescription by Dentists in the Treatment of Apical Periodontitis: A Systematic Review and Meta-Analysis.

After pulp infection and necrosis, the passage of microbial antigens into the periapical space causes apical periodontitis (AP). Most of the clinical forms of AP can be managed without prescribing antibiotics, only with root canal treatment and abscess drainage or, where appropriate, tooth extraction. However, the scientific literature provides evidence of inappropriate antibiotic prescriptions by dentists in the management of apical disease. OBJECTIVES: The aim of this systematic review and meta-analysis was to analyze the global pattern of antibiotic prescription in the treatment of apical disease. METHODS: PRISMA Guidelines were followed to carry out this systematic review. The research question was as follows: What is the pattern of antibiotic prescription by dentists in the treatment of the different clinical forms of apical periodontitis? A systematic search was conducted on MEDLINE/PubMed, Wiley Online Database, Web of Science and Scopus. All studies reporting data about the pattern of antibiotic prescription by dentists in the treatment of apical disease were included. The meta-analyses were calculated using the Open Meta Analyst version 10.10 software. Random-effects meta-analyses were performed. The risk of bias was assessed using the Newcastle-Ottawa Scale. The certainty of evidence was assessed using GRADE. RESULTS: The search strategy identified 96 articles and thirty-nine cross-sectional studies fulfilled the inclusion criteria. The overall percentage of antibiotic prescriptions by dentists in cases of symptomatic AP was 25.8%, and 31.5% in cases of asymptomatic AP with sinus tract present. The percentage of dentists prescribing antibiotics in cases of acute apical abscess with no/mild symptoms was 47.7%, whereas, in cases of acute apical abscess with moderate/severe symptoms, 88.8% of dentists would prescribe antibiotics. Endodontists prescribe antibiotics at a lower rate than general practitioners. The total risk of bias was considered moderate, and the final rating for the certainty of the evidence was low. CONCLUSIONS: Dentists worldwide are over-prescribing antibiotics in the management of apical disease. It is necessary to improve antibiotic prescribing habits in the treatment of endodontic infections, as well as educational initiatives to encourage the rational and appropriate prescription of antibiotics in periapical diseases.

Detection of a Human Adenovirus Outbreak, Including Some Critical Infections, Using Multipathogen Testing at a Large University, September 2022-January 2023.

Background: Human adenoviruses (HAdVs) can cause outbreaks of flu-like illness in university settings. Most infections in healthy young adults are mild; severe illnesses rarely occur. In Fall 2022, an adenovirus outbreak was identified in university students. Methods: HAdV cases were defined as university students 17-26 years old who presented to the University Health Service or nearby emergency department with flu-like symptoms (eg, fever, cough, headache, myalgia, nausea) and had confirmed adenovirus infections by polymerase chain reaction (PCR). Demographic and clinical characteristics were abstracted from electronic medical records; clinical severity was categorized as mild, moderate, severe, or critical. We performed contact investigations among critical cases. A subset of specimens was sequenced to confirm the HAdV type. Results: From 28 September 2022 to 30 January 2023, 90 PCR-confirmed cases were identified (51% female; mean age, 19.6 years). Most cases (88.9%) had mild illness. Seven cases required hospitalization, including 2 critical cases that required intensive care. Contact investigation identified 44 close contacts; 6 (14%) were confirmed HAdV cases and 8 (18%) reported symptoms but never sought care. All typed HAdV-positive specimens (n = 36) were type 4. Conclusions: While most students with confirmed HAdV had mild illness, 7 otherwise healthy students had severe or critical illness. Between the relatively high number of hospitalizations and proportion of close contacts with symptoms who did not seek care, the true number of HAdV cases was likely higher. Our findings illustrate the need to consider a wide range of pathogens, even when other viruses are known to be circulating.

Efficacy of physical activity shared between parents and children to improve sports initiation in the M.A.M.I.deporte® program.

Objective: To determine if the active methodology for improving sports initiation (M.A.M.I.deporte®) shared between children and parents successfully promotes children in sports activities, maintains their activity and improves long-term adherence. Participants: The study involved 118 participants aged between 2 and 11 years (6.3 ± 2.3). In the first season, 34 participated (16 girls; 18 boys); in the second season, 46 participated (22 girls; 24 boys) and in the third season, 38 participated (19 girls; 19 boys). Methodology: It was carried out from October to June over three academic years for two hours a week. Every 4 sessions a different sporting activity was carried out, planned so that parents and children could practise them, simultaneously. Analysis: At the beginning and end of each period, a survey was carried out on the sports activities in which the participants had started. If participants remained in the activity, the survey was face-to-face and if participants no longer attended the activity, they were contacted by telephone. Descriptive values were obtained for the variables in absolute and percentage form and a repeated measures anova was performed. Results: Vigorous physical activity performed was 3.82 ± 1.16 h/week in the first year, 3.38 ± 1.59 in the second year and 2.99 ± 1.46 in the third year with no significant differences between any of the years. 32.20% joined other sporting activities and only 6.78% gave up vigorous physical activity. Conclusion: Joint activity of parents and children contributed to maintaining vigorous physical activity at the recommended levels in the child population with only 6.78% (n = 8) of the participants dropping out.

Genotype-phenotype correlation in CLCN4-related developmental and epileptic encephalopathy.

CLCN4-related disorder is a rare X-linked neurodevelopmental condition with a pathogenic mechanism yet to be elucidated. CLCN4 encodes the vesicular 2Cl-/H+ exchanger ClC-4, and CLCN4 pathogenic variants frequently result in altered ClC-4 transport activity. The precise cellular and molecular function of ClC-4 remains unknown; however, together with ClC-3, ClC-4 is thought to have a role in the ion homeostasis of endosomes and intracellular trafficking. We reviewed our research database for patients with CLCN4 variants and epilepsy, and performed thorough phenotyping. We examined the functional properties of the variants in mammalian cells using patch-clamp electrophysiology, protein biochemistry, and confocal fluorescence microscopy. Three male patients with developmental and epileptic encephalopathy were identified, with differing phenotypes. Patients #1 and #2 had normal growth parameters and normal-appearing brains on MRI, while patient #3 had microcephaly, microsomia, complete agenesis of the corpus callosum and cerebellar and brainstem hypoplasia. The p.(Gly342Arg) variant of patient #1 significantly impaired ClC-4's heterodimerization capability with ClC-3 and suppressed anion currents. The p.(Ile549Leu) variant of patient #2 and p.(Asp89Asn) variant of patient #3 both shift the voltage dependency of transport activation by 20 mV to more hyperpolarizing potentials, relative to the wild-type, with p.(Asp89Asn) favouring higher transport activity. We concluded that p.(Gly342Arg) carried by patient #1 and the p.(Ile549Leu) expressed by patient #2 impair ClC-4 transport function, while the p.(Asp89Asn) variant results in a gain-of-transport function; all three variants result in epilepsy and global developmental impairment, but with differences in epilepsy presentation, growth parameters, and presence or absence of brain malformations.

The Effects of Acute Deep Seawater Supplementation on Muscle Function after Triathlon.

(1) Background: Trainers and athletes have always sought to reduce the failure of muscle function during long endurance events. However, nowadays, it is a topic that is generating much debate in the scientific field. Currently, deep-sea water (DSW) intake seems to be a suitable hydration alternative for this type of endurance event. Therefore, the aim of this study was to determine whether DSW consumption during a triathlon event could preserve muscle function after exercise. (2) Methods: Nineteen trained male triathletes (age = 39.0 ± 4.25 years; BMI = 23.67 ± 1.81 kg/m2) randomly performed three triathlons, one of them consuming DSW (Totum SPORT 30 AB, Laboratories Quinton International, S.L., Spain), the other consuming isotonic placebo and the last with tap water-hydration. A vertical jump test with countermovement and an isometric muscle strength test were conducted before and after the triathlon test. (3) Results: There was a significant difference between treatment × time during the isometric muscle strength test. Based on the Tukey post hoc analysis, the peak net force decreased statistically in the placebo (p = 0.045) and control conditions (p = 0.026), but not in the experimental condition (p = 0.121). In addition, all of the conditions studied obtained similar results in the countermovement vertical jump after exercise. (4) Conclusions: As a result, consumption of DSW seems to delay the failure of muscle function specifically in isometric exercises but does not improve performance in sports. Thus, DSW does not alter muscle capacity in a negative way; therefore, its consumption may be recommended.

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease-EXVEDOCOL.

BACKGROUND: Real-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. METHODS: EXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. RESULTS: Thirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. CONCLUSIONS: High clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

Anesthetic Management for Kidney Transplant in a Young Patient With Mitral Regurgitation: Case Report.

Patients with chronic kidney disease who are candidates for transplant may experience changes in capillary permeability, coagulation, and the endocrine system; alterations in the pulmonary vasculature; and cardiac structural and functional changes. Patients with renal replacement by hemodialysis have a mortality rate 30 times higher than those who do not have uremia. According to the onset, duration, and severity of chronic kidney disease, cardiovascular disease will be reflected in baseline function and response to stress. For this reason, it is important to establish the functional condition so that preoperative management can be started and factors inherent to the patient and the surgical procedure can be modified. Here, we report a 29-year-old male patient with chronic kidney disease secondary to renal hypoplasia, with no family history. The patient had renal replacement therapy with peritoneal dialysis and had progressive deterioration of general status, decreased functional capacity, decreased tolerance to physical activity, presence of fatigue and pulmonary congestion, and retention of liquids, with a diagnosis of moderate to severe mitral regurgitation.

Systematic Comparison of Atomistic Force Fields for the Mechanical Properties of Double-Stranded DNA.

The response of double-stranded DNA to external mechanical stress plays a central role in its interactions with the protein machinery in the cell. Modern atomistic force fields have been shown to provide highly accurate predictions for the fine structural features of the duplex. In contrast, and despite their pivotal function, less attention has been devoted to the accuracy of the prediction of the elastic parameters. Several reports have addressed the flexibility of double-stranded DNA via all-atom molecular dynamics, yet the collected information is insufficient to have a clear understanding of the relative performance of the various force fields. In this work, we fill this gap by performing a systematic study in which several systems, characterized by different sequence contexts, are simulated with the most popular force fields within the AMBER family, bcs1 and OL15, as well as with CHARMM36. Analysis of our results, together with their comparison with previous work focused on bsc0, allows us to unveil the differences in the predicted rigidity between the newest force fields and suggests a roadmap to test their performance against experiments. In the case of the stretch modulus, we reconcile these differences, showing that a single mapping between sequence-dependent conformation and elasticity via the crookedness parameter captures simultaneously the results of all force fields, supporting the key role of crookedness in the mechanical response of double-stranded DNA.

Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron.

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part by Outer Membrane Vesicles (OMVs). Here, we developed a high-throughput screen to identify genes required for OMV biogenesis and its regulation in Bacteroides thetaiotaomicron (Bt). We identified a family of Dual membrane-spanning anti-sigma factors (Dma) that control OMV biogenesis. We conducted molecular and multiomic analyses to demonstrate that deletion of Dma1, the founding member of the Dma family, modulates OMV production by controlling the activity of the ECF21 family sigma factor, Das1, and its downstream regulon. Dma1 has a previously uncharacterized domain organization that enables Dma1 to span both the inner and outer membrane of Bt. Phylogenetic analyses reveal that this common feature of the Dma family is restricted to the phylum Bacteroidota. This study provides mechanistic insights into the regulation of OMV biogenesis in human gut bacteria.

In vitro activity of delafloxacin against anaerobic bacteria compared with other antimicrobials.

The aim of this study was to describe the in vitro activity of delafloxacin against 230 anaerobic isolates and compare it with the activity of other antimicrobials used against infections caused by anaerobic microorganisms. Minimal inhibitory concentrations (MICs) were lower for delafloxacin than for all other antibiotics tested with the exception of piperacillin-tazobactam and meropenem against Gram-positive anaerobic cocci. Only two (0.8 %) isolates of Bacteroides spp. showed a MIC ≥4 µg/mL. With some exceptions, the present results show lower MICs for delafloxacin in comparison to the other antibiotics used against anaerobes.

Dyssynergic Defecation Concerning Proctalgia Fugax: An Observational Study

Introduction: There is no clarity about manometric findings in patients with proctalgia fugax; evidence shows different results. This study aims to evaluate dyssynergic defecation through anorectal manometry in Colombian patients in two gastroenterology centers in Bogotá, Colombia. Materials and methods: A cross-sectional descriptive observational study in adult patients with proctalgia fugax undergoing anorectal manometry and treated in two gastroenterology centers in Bogotá between 2018 and 2020. Results: 316 patients were included, predominantly women (65%), with a median age of 45.2 (range: 18-78; standard deviation [SD]: 28.3). Four percent of patients had hypertonicity, 50% were normotonic, and 46% were hypotonic. Regarding manometric parameters, 50% had normal pressure, and 46% had anal sphincter hypotonia; 76% had a normal voluntary contraction test. Dyssynergic defecation was documented in 5% of patients, and the most frequent was type I, followed by type III. A rectoanal inhibitory reflex was identified in all patients, 42% with altered sensory threshold and 70% with abnormal balloon expulsion. There was an agreement between the results of the anorectal manometry and the subjective report of the digital rectal exam by the head nurse who performed the procedure. Conclusions: The data obtained in the present study suggest that proctalgia is not related to the elevated and sustained basal contracture of the sphincter but neither to the alteration in voluntary contraction since most patients have typical values.

Introducción: Actualmente, no hay claridad acerca de los hallazgos manométricos en pacientes con proctalgia fugaz, y la evidencia muestra diferentes resultados. Se plantea como objetivo en el presente estudio evaluar la presencia de disinergia defecatoria con manometría anorrectal en pacientes colombianos en dos centros de gastroenterología en Bogotá, Colombia. Metodología: Estudio observacional descriptivo de corte transversal en pacientes adultos sometidos a manometría anorrectal con proctalgia fugaz y atendidos en dos centros de gastroenterología de la ciudad de Bogotá entre el 2018 y el 2020. Resultados: Se incluyó a 316 pacientes, predominantemente mujeres (65%), con mediana de edad 45,2 (rango: 18-78; desviación estándar [DE]: 28,3). El 4% de los pacientes presentaban hipertonicidad, el 50% eran normotónicos y el 46%, hipotónicos. En cuanto a parámetros manométricos, el 50% tenía presión normal y el 46%, hipotonía de esfínter anal. El 76% tuvo una prueba de contracción voluntaria normal. En 5% pacientes se documentó disinergia defecatoria, y la más frecuente fue el tipo I, seguido del tipo III. En todos los pacientes se identificó reflejo recto anal inhibitorio, 42% con alteración en umbral sensitivo y 70% con expulsión de balón anormal, y hubo concordancia entre los resultados de la manometría anorrectal y el reporte subjetivo del tacto rectal de la jefe de enfermería que realizó el procedimiento. Conclusiones: Los datos obtenidos en el presente estudio sugieren que la proctalgia no está relacionada con la contractura basal elevada y sostenida del esfínter, pero tampoco con la alteración en la contracción voluntaria, ya que la mayoría de los pacientes presentan valores normales.

Using High-Resolution Anoscopy to Detect Anal Dysplasia Due to Papillomavirus in Patients with Inflammatory Bowel Disease

Introduction: Anal squamous cell carcinoma is rare, but its incidence and mortality have been increasing globally; 90% of cases are related to human papillomavirus (HPV) infection(1,2). Patients with inflammatory bowel disease (IBD) have a higher risk of infection with this virus; an incidence of 5.5 per 100,000 patients has been identified in the IBD group compared to 1.8 in the non-IBD group(3). Materials and methods: A descriptive case series study was conducted with 21 patients with IBD and no perianal symptoms between January and July 2022 at the Institute of Coloproctology in Medellín. They underwent anal cytology, HPV genotyping, and high-resolution anoscopy after explanation and acceptance of the procedure. If lesions were found, ablative treatment was performed. Results: 23% of this cohort had low-grade squamous lesions, while 14.2% had high-grade lesions with dysplasia changes during anoscopy. Besides, 90.4% had positive HPV genotyping, of which 76.1% were high-grade. Conclusions: Our study suggests that this series of patients with IBD behaves as a high-risk group for developing premalignant lesions in association with HPV. High-resolution anoscopy is a cost-effective, painless, and affordable method that, in expert hands, may impact the diagnosis and management of premalignant lesions and decrease the incidence of anal cancer in patients with IBD.

Introducción: El carcinoma anal de células escamosas es raro, pero su incidencia y mortalidad han ido en aumento globalmente. El 90% de los casos están relacionados con la infección por el virus del papiloma humano (VPH)1,2 y los pacientes con enfermedad inflamatoria intestinal (EII) tienen un mayor riesgo de infección por este virus; se ha identificado una incidencia de 5,5 por 100.000 pacientes en el grupo de EII frente a 1,8 en el grupo sin EII3. Metodología: Se realizó un estudio descriptivo de serie de casos en el que se incluyó a 21 pacientes con EII, sin síntomas perianales, entre enero y julio de 2022 en el Instituto de Coloproctología de Medellín, a quienes se les realizó citología anal, genotipificación del VPH y anoscopia de alta resolución, previa explicación y aceptación del procedimiento. Si se encontraban lesiones, se realizaba tratamiento ablativo. Resultados: El 23% de esta cohorte tenía lesiones escamosas de bajo grado, mientras que el 14,2% presentaba lesiones de alto grado con cambios de displasia al momento de la anoscopia. El 90,4% tenían genotipificación positiva para VPH, de los cuales el 76,1% eran de alto grado. Conclusiones: Nuestro estudio sugiere que esta serie de pacientes con EII se comporta como un grupo de alto riesgo para desarrollar lesiones premalignas en asociación con el VPH. La anoscopia de alta resolución es un método rentable, indoloro y asequible que, en manos expertas, puede impactar el diagnóstico y manejo de lesiones premalignas y disminuir la incidencia de cáncer anal en pacientes con EII.

Parasitism in viviparous vertebrates: an overview.

The reproductive mode of viviparity has independently evolved in various animal taxa. It refers to the condition in which the embryos or young develop inside the female's body during gestation, providing advantages such as protection, nutrition, and improved survival chances. However, parasites and diseases can be an evolutionary force that limit the host's resources, leading to physiological, morphological, and behavioral changes that impose additional costs on both the pregnant female and her offspring. This review integrates the primary literature published between 1980 and 2021 on the parasitism of viviparous hosts. We describe aspects such as reproductive investment in females, offspring sex ratios, lactation investment in mammals, alterations in birth intervals, current reproductive investment, variations between environments, immune system activity in response to immunological challenges, and other factors that can influence the interaction between viviparous females and parasites. Maintaining pregnancy incurs costs in managing the mother's resources and regulating the immune system's responses to the offspring, while simultaneously maintaining an adequate defense against parasites and pathogens. Parasites can significantly influence this reproductive mode: parasitized females adjust their investment in survival and reproduction based on their life history, environmental factors, and the diversity of encountered parasites.

A cross-sectional epidemiological study conducted in Argentina to evaluate the impact of the exposome on skin aging.

BACKGROUND: Skin aging is a gradual cumulative process that may be accelerated by various exposome factors. AIMS: To investigate associations between exposome factors and facial skin aging in 11 locations in Argentina. PATIENTS/METHODS: An observational, cross-sectional study with assessments by exposome questionnaire, Glogau photoaging classification from I to IV, AI-based algorithm analysis of 7 skin aging signs, and SCINEXA score. RESULTS: Of 1346 participants, most were women (82%), aged 31-50 years (62%), of skin phototype III (52%), and living in urban areas (94%). The Glogau skin age was higher than the chronological age for 28% of overall participants, 36% of men, and 45% of participants from Ciudad de Buenos Aires versus 12% from Jujuy (p < 0.001). Being male (OR = 1.59; 95% CI 1.18-2.13), exposed to agrochemicals (OR = 1.59: 95% CI 1.01-2.51), of lower socioeconomic levels (OR = 2.06; 95% CI 1.32-3.21) and doing outdoor physical activity (OR = 1.33; 95% CI 1.00-1.76) increased the risk for premature aging. Odds decreased with high daily intake of water (OR = 0.76; 95% CI 0.59-0.97), daily dermocosmetic use (moisturizers [OR = 0.72; 95% CI 0.55-0.94], cleansers [OR = 0.53; CI 95% 0.42-0.67], retinoids [OR = 0.61; 95% CI 0.39-0.95]), and antiaging treatments (OR = 0.74; 95% CI 0.57-0.97). CONCLUSIONS: Some exposome factors increased the risk for premature skin aging (physical outdoor activity, exposure to agrochemicals), while others were protective factors (high water intake, antiaging treatments, use of dermocosmetics). Locations with higher pollution levels had more premature skin aging.

Intracranial progression of the epidermoid cyst to a white epidermoid cyst in a pediatric patient: a case report.

BACKGROUND: Epidermoid cysts are rare benign lesions that originate from remnants of ectodermal epithelial tissue, particularly infrequent in the pediatric population. They exhibit characteristic imaging features, with occasional variations leading to the development of a "white" epidermoid cyst. This transformation results from the presence of protein and lipid material within the cyst, causing intrinsic hyperintensity in T1-weighted images, signal hypointensity in T2-weighted images, and a bright signal in diffusion-weighted imaging. CASE PRESENTATION: We describe the case of a 5-year-old Latina pediatric patient initially diagnosed with a typical epidermoid cyst. After 13 years of follow-up, this typical epidermoid cyst underwent a transformation, becoming a "white" epidermoid cyst. CONCLUSIONS: Epidermoid cysts are rare intracranial lesions. The term "white epidermoid cyst" does not denote a variant; it represents a distinct transformation within an epidermoid cyst due to liquid and protein accumulation. This transformation should be considered in cases with specific imaging characteristics.

[Frequency of diabetic retinopathy and associated factors in Puerto Montt, Chile]. / Estudio de prevalencia de retinopatía diabética en pacientes diabéticos tipo 2 de la comuna de Puerto Montt y sus factores asociados.

BACKGROUND: Diabetic retinopathy (DR) is an important cause of decreased visual acuity, whose prevalence has increased between 1990 and 2020. In Chile the prevalence of diabetic retinopathy was estimated at 24.8%. AIM: To assess the prevalence of DR in a southern Chilean city. MATERIAL AND METHODS: From a database of diabetic patients attending primary health care centers at Puerto Montt, Chile, 196 patients with DR and 392 patients without DR, matched by age and presence of chronic complications, were chosen for this case-control study. RESULTS: The prevalence of DR in the database of diabetic patients was 33.3%. glycated hemoglobin, the frequency insulin use, systolic blood pressure, HDL cholesterol, microalbuminuria, and proteinuria were significantly worse in cases. A multivariate analysis showed that retinopathy is much more likely to occur when the variables insulin use, neuropathy, and microalbuminuria concur. CONCLUSIONS: DR was associated with worse metabolic parameters and the presence of neuropathy in this case control study.

Caracterización clínica y terapéutica de una cohorte multicéntrica de pacientes con enfermedad inflamatoria intestinal en Colombia / Clinical and therapeutic characterisation of a multicentre cohort of patients with inflammatory bowel disease in Colombia

Introducción: En Latinoamérica y Colombia hay pocos estudios acerca las características clínicas y terapéuticas de pacientes con enfermedad inflamatoria intestinal (EII). Se plantea como objetivo obtener una aproximación a dichos datos a partir de una muestra de pacientes de diferentes centros de referencia en Colombia. Pacientes y métodos: Estudio de corte transversal en pacientes adultos y pediátricos, con EII, atendidos ambulatoriamente en seis instituciones en diferentes ciudades, entre 2017-2020 se recolectó información en fechas distintas, acerca aspectos demográficos, clínicos y terapéuticos. Resultados: Seiscientos cinco sujetos, 565 (93,4%) adultos, edad promedio de 43 años (DE 12,78), 64% con colitis ulcerosa (CU). La edad de diagnóstico de CU fue 41,9 años, mientras en enfermedad de Crohn (EC) fue 47,9 años. En CU, mayor compromiso izquierdo (47,2%), y en EC, 42,8% ileocolónico (L3). Más de 50% en actividad leve o remisión clínica. En CU, el requerimiento de biológico fue de 27,2%. mientras en EC, 78%. Requerimiento global de hospitalización en 39,5%, y necesidad de cirugía, de 37,5% en CU y 62,5% en EC. También, 40 pacientes pediátricos, 90% mujeres, siendo CU más frecuente (80%). En CU, 83,3% presentaron colitis extensa, y en EC, todas con localización ileocolónica (L3). Más de 95% en actividad leve o remisión. Requerimiento de biológico, en 16,6 y 75%, para CU y EC, respectivamente. La frecuencia hospitalizaciones y cirugía fue 2,7%. Conclusiones: Este estudio muestra algunas características únicas de los pacientes con EII en Colombia. Se requiere de un diagnóstico más temprano, con un mejor enfoque terapéutico. (AU)

Introduction: In Latin America and Colombia there are few studies about the clinical and therapeutic characteristics of patients with inflammatory bowel disease (IBD). The objective of this study is to obtain an approximation to these data from a sample of patients from different reference centres in Colombia. Patients and methods: Cross-sectional study in adult and paediatric patients, with IBD, attended ambulatory in 6 institutions in different cities, between 2017 and 2020 information was collected on different dates, about demographic, clinical, and therapeutic aspects. Results: Six hundred and five subjects, 565 (93.4%) adults, mean age 43 years (SD 12.78), 64% with ulcerative colitis (UC). The age at diagnosis of UC was 41.9 years, while in Crohn's disease (CD) it was 47.9 years. In UC, there was greater left involvement (47.2%), and in CD, 42.8% ileocolonic (L3). More than 50% were in mild activity or clinical remission. In UC, the biologic requirement was 27.2%, while in CD, 78%. Overall hospitalisation requirement was 39.5%, and the need for surgery was 37.5% in UC and 62.5% in CD. Also, 40 pediatric patients, 90% female, with UC being more frequent (80%). In UC, 83.3% presented extensive colitis, and in CD, all with ileocolonic localization (L3). More than 95% were in mild activity or remission. Biologic therapy was required in 16.6% and 75% for UC and CD, respectively. The frequency of hospitalisations and surgery was 2.7%. Conclusions: This study shows some unique characteristics of patients with IBD in Colombia. An earlier diagnosis is required, with a better therapeutic approach. (AU)

LptD depletion disrupts morphological homeostasis and upregulates carbohydrate metabolism in Escherichia coli.

In a previous in silico study, we identified an essential outer membrane protein (LptD) as an attractive target for development of novel antibiotics. Here, we characterized the effects of LptD depletion on Escherichia coli physiology and morphology. An E. coli CRISPR interference (CRISPRi) strain was constructed to allow control of lptD expression. Induction of the CRISPRi system led to ∼440-fold reduction of gene expression. Dose-dependent growth inhibition was observed, where strong knockdown effectively inhibited initial growth but partial knockdown exhibited maximum overall killing after 24 h. LptD depletion led to morphological changes where cells exhibited long, filamentous cell shapes and cytoplasmic accumulation of lipopolysaccharide (LPS). Transcriptional profiling by RNA-Seq showed that LptD knockdown led to upregulation of carbohydrate metabolism, especially in the colanic acid biosynthesis pathway. This pathway was further overexpressed in the presence of sublethal concentrations of colistin, an antibiotic targeting LPS, indicating a specific transcriptional response to this synergistic envelope damage. Additionally, exposure to colistin during LptD depletion resulted in downregulation of pathways related to motility and chemotaxis, two important virulence traits. Altogether, these results show that LptD depletion (i) affects E. coli survival, (ii) upregulates carbohydrate metabolism, and (iii) synergizes with the antimicrobial activity of colistin.