KRAS(G12D) drives lepidic adenocarcinoma through stem-cell reprogramming.

Many cancers originate from stem or progenitor cells hijacked by somatic mutations that drive replication, exemplified by adenomatous transformation of pulmonary alveolar epithelial type II (AT2) cells1. Here we demonstrate a different scenario: expression of KRAS(G12D) in differentiated AT1 cells reprograms them slowly and asynchronously back into AT2 stem cells that go on to generate indolent tumours. Like human lepidic adenocarcinoma, the tumour cells slowly spread along alveolar walls in a non-destructive manner and have low ERK activity. We find that AT1 and AT2 cells act as distinct cells of origin and manifest divergent responses to concomitant WNT activation and KRAS(G12D) induction, which accelerates AT2-derived but inhibits AT1-derived adenoma proliferation. Augmentation of ERK activity in KRAS(G12D)-induced AT1 cells increases transformation efficiency, proliferation and progression from lepidic to mixed tumour histology. Overall, we have identified a new cell of origin for lung adenocarcinoma, the AT1 cell, which recapitulates features of human lepidic cancer. In so doing, we also uncover a capacity for oncogenic KRAS to reprogram a differentiated and quiescent cell back into its parent stem cell en route to adenomatous transformation. Our work further reveals that irrespective of a given cancer's current molecular profile and driver oncogene, the cell of origin exerts a pervasive and perduring influence on its subsequent behaviour.

Sensitization to textile dyes in Spain: Epidemiological situation (2019-2022).

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.

The state of transience, and its influence on the wish to die of advanced disease patients: insights from a qualitative phenomenological study.

BACKGROUND: The experience of Wish to Die is common in patients living with Advanced Disease. It has been studied worldwide and qualitative studies have contributed to the understanding of the complexity of the phenomenon of the WTD but a deeper understanding on the individual's views is still needed. The objective of this study was to identify common characteristics of the experience of wish to die in advanced disease. METHODS: A phenomenological study was carried out with multicenter participation of patients with advanced disease who had expressed their wish to die to health professionals. Semi-structured interviews were employed to obtain an in-depth perspective of each patient's lived experience. A phenomenological analysis of the data collected was performed to describe and explore the characteristic aspects of the phenomenon under study. RESULTS: Fourteen patients with advanced disease were interviewed. Most of them had cancer. In the analysis of the patients' accounts of their experiences, three common characteristics were identified: a) experiencing a state of transience; b) the attempt to reconnect with oneself; and c) additional disease-related aspects that influence the wish to die. Patients expressed the need for a safe space to address the wish to die and the importance of receiving care that considers both 'being' and 'doing'. CONCLUSIONS: Patients with advanced disease and wish to die experience a state of transience where the patient lives and ephemeral state of existence. Interventions focused on reinforcing the intrinsic value of the individual emerge as essential components of a compassionate accompaniment of those facing the wish to die.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Measured GFR in murine animal models: review on methods, techniques, and procedures.

Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with increasing rates of morbidity and mortality. Thus, early detection is essential to prevent severe adverse events and the progression of kidney disease to an end stage. Glomerular filtration rate (GFR) is the most appropriate index to evaluate renal function in both clinical practice and basic medical research. Several animal models have been developed to understand renal disease induction and progression. Specifically, murine models are useful to study the pathogenesis of renal damage, so a reliable determination of GFR is essential to evaluate the progression of CKD. However, as in clinical practise, the estimation of GFR in murine by levels of serum/urine creatinine or cystatin-C could not be accurate and needed other more reliable methods. As an alternative, the measurement of GFR by the clearance of exogenous markers like inulin, sinistrin, 51Cr-EDTA, 99mTc-DTPA, 125I-iothalamate, or iohexol could be performed. Nevertheless, both approaches-estimation or measurement of GFR-have their limitations and a standard method for the GFR determination has not been defined. Altogether, in this review, we aim to give an overview of the current methods for GFR assessment in murine models, describing each methodology and focusing on their advantages and limitations.

Robust expression of the TRPC1 channel associated with photoreceptor loss in the rat retina.

Baseline intracellular calcium levels are significantly higher in neuronal and glial cells of rat retinas with retinitis pigmentosa (RP). Although this situation could initiate multiple detrimental pathways that lead to cell death, we considered the possibility of TRPC1 being involved in maintaining calcium homeostasis in the retina by acting as a component of store-operated calcium (SOC) channels with special relevance during photoreceptor degeneration. In this study, we examined by Western blot the expression of TRPC1 in healthy control rat retinas (Sprague-Dawley, SD) and retinas with RP (P23H-1 rats). We also analyzed its specific cellular distribution by immunofluorescence to recognize changes during neurodegeneration and to determine whether its presence is consistent with high basal calcium levels and cellular survival in degenerating retinas. We found that TRPC1 immunostaining was widely distributed across the retina in both rat strains, SD and P23H, and its expression levels significantly increased in the retinas with advanced degeneration compared to the age-control SD rats. In the outer retina, TRPC1 immunoreactivity was distributed in pigment epithelium cells, the photoreceptor inner segments of older animals, and the outer plexiform layer. In the inner retina, TRPC1 labeling was detected in horizontal cells, specific somata of bipolar and amacrine cells, and cellular processes in all the strata of the inner plexiform layer. Somata and processes were also highly immunoreactive in the ganglion cell layer and astrocytes in the nerve fiber layer in all animals. In the P23H rat retinas, the TRPC1 distribution pattern changed according to advancing photoreceptor degeneration and the gliosis reaction, with TRPC1 immunoreactive Müller cells mainly in advanced stages of disease. The cellular TRPC1 immunoreactivity found in this work suggests different mechanisms of activation of these channels depending on the cell type. Furthermore, the results support the idea that photoreceptor loss due to RP is associated with robust TRPC1 protein expression in the rat inner retina and raise the possibility of TRPC1 channels contributing to maintain high basal calcium levels during neurodegeneration and/or maintenance processes of the inner retina.

Monkeypox: a review of epidemiological modelling studies and how modelling has led to mechanistic insight.

Human monkeypox (mpox) virus is a viral zoonosis that belongs to the Orthopoxvirus genus of the Poxviridae family, which presents with similar symptoms as those seen in human smallpox patients. Mpox is an increasing concern globally, with over 80,000 cases in non-endemic countries as of December 2022. In this review, we provide a brief history and ecology of mpox, its basic virology, and the key differences in mpox viral fitness traits before and after 2022. We summarize and critique current knowledge from epidemiological mathematical models, within-host models, and between-host transmission models using the One Health approach, where we distinguish between models that focus on immunity from vaccination, geography, climatic variables, as well as animal models. We report various epidemiological parameters, such as the reproduction number, R0, in a condensed format to facilitate comparison between studies. We focus on how mathematical modelling studies have led to novel mechanistic insight into mpox transmission and pathogenesis. As mpox is predicted to lead to further infection peaks in many historically non-endemic countries, mathematical modelling studies of mpox can provide rapid actionable insights into viral dynamics to guide public health measures and mitigation strategies.

Sensitization to isothiazolinones in the Spanish Contact Dermatitis Registry (REIDAC): 2019-2021 epidemiological situation.

BACKGROUND: Current frequency and risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), benzisothiazolinone (BIT) and octylisothiazolinone (OIT) in Spain are not well known. OBJECTIVES: To study the frequency of sensitization, risk factors and simultaneous sensitization between the four isothiazolinones. MATERIALS AND METHODS: We analysed all 2019-2021 consecutive patients patch-tested with MI (0.2% aq.), MCI/MI (0.02% aq.), BIT (0.1% pet.) and OIT (0.1% pet) within the Spanish Contact Dermatitis Registry (REIDAC). RESULTS: A total of 2511 patients were analysed. Frequencies of sensitization were: any isothiazolinone 15.7%, MI 6.8%, MCI/MI 4.8%, BIT 3.5% and OIT 0.5%. MI and MCI/MI sensitization was associated with being occupationally active, hand dermatitis, detergents and age over 40. BIT sensitization was associated with leg dermatitis and age over 40. About one in nine MI-positive patients were positive to BIT, whereas one in five BIT-positive patients were positive to MI. CONCLUSIONS: Sensitization to MI, MCI/MI and BIT is still common in Spain, while sensitization to OIT is rare. Currently, sensitization to MI and MCI/MI seems to be occupationally related. Although its origin is unknown, sensitization to BIT is more frequent in patients aged over 40 years. Simultaneous sensitization between MI and BIT is uncommon.

Eventos de vida estresantes y su efecto en la conducta suicida en mujeres durante la pandemia por Covid-19 en México.

OBJETIVO: Analizar la estructura factorial, la validez convergente y divergente de la Escala Columbia de Severidad Suicida (CSSRS) y el Cuestionario de Eventos de Vida Estresantes (EVE) y medir la asociación entre EVE y conducta suicida (CS) en mujeres mexicanas durante la pandemia por Covid-19. Material y métodos. Se usaron datos de 2 398 mujeres que participaron en un estudio multicéntrico, realizado en México entre mayo y octubre de 2021. La información se recolectó mediante un cuestionario en línea que incluyó la CSSRS y el EVE. Se hizo un análisis factorial confirmatorio para valorar el ajuste de los modelos. RESULTADOS: El modelo final mostró asociación entre los EVE y la CS, y tuvo a la violencia como variable central. Dicho modelo presentó un ajuste adecuado (CFI = 0.950, IFI = 0.950, MFI = 0.975, RMSEA = 0.031, CI RMSEA = 0.026-0.036). CONCLUSIONES: La pandemia por Covid-19 evidenció la necesidad de crear e implementar estrategias que promuevan el cuidado de la salud mental, reduzcan la exposición a la violencia y faciliten los procesos de duelo para prevenir la CS en mujeres mexicanas.

Corrigendum: Enteric Budesonide in Transplant and Native IgA Nephropathy: Real-World Clinical Practice.

[This corrects the article DOI: 10.3389/ti.2022.10693.].

Long-term outcomes of transobturator suburethral tapes for female stress urinary incontinence.

AIMS: The aim is to evaluate long-term effectiveness and safety of transobturator midurethral slings (TO-MUS) for treating female stress urinary incontinence (SUI). Possible risk factors for failure and complications are also evaluated. METHODS: A descriptive retrospective study was performed among women with SUI treated at a tertiary urogynecology unit between January 2004 and December 2006. Women with stress-predominant mixed urinary incontinence or with associated pelvic organ prolapse were also included. Postoperative follow-up was performed at 1, 6, and 12 months and yearly thereafter. Outcomes were classified as cured, improved or failed. RESULTS: Of 896 women operated on over the study period, 565 were suitable for the analysis. Of them, 327 women completed the 5-year, 225 the 7-year, and 172 the 10-year follow-up periods. Success rates were 77.6%, 73.8%, and 73.2% at 5, 7, and 10 years, respectively. On multivariate Cox regression models age, body mass index, and previous incontinence surgery were related to failure. Complications of any type were described in 24.9% of patients, although most of them were mild. Only concomitant prolapse surgery was related to intraoperative and peroperative complications and the inside-out route to an increased odds of groin pain (odds ratio = 4.0). CONCLUSIONS: This study showed that TO-MUS is an effective and safe procedure in the long-term. The expected outcomes and possible side effects profile should be discussed in detail during the counseling process before opting for a treatment option.

Neoadjuvant Gene-Mediated Cytotoxic Immunotherapy for Non-Small-Cell Lung Cancer: Safety and Immunologic Activity.

Gene-mediated cytotoxic immunotherapy (GMCI) is an immuno-oncology approach involving local delivery of a replication-deficient adenovirus expressing herpes simplex thymidine kinase (AdV-tk) followed by anti-herpetic prodrug activation that promotes immunogenic tumor cell death, antigen-presenting cell activation, and T cell stimulation. This phase I dose-escalation pilot trial assessed bronchoscopic delivery of AdV-tk in patients with suspected lung cancer who were candidates for surgery. A single intra-tumoral AdV-tk injection in three dose cohorts (maximum 1012 viral particles) was performed during diagnostic staging, followed by a 14-day course of the prodrug valacyclovir, and subsequent surgery 1 week later. Twelve patients participated after appropriate informed consent. Vector-related adverse events were minimal. Immune biomarkers were evaluated in tumor and blood before and after GMCI. Significantly increased infiltration of CD8+ T cells was found in resected tumors. Expression of activation, inhibitory, and proliferation markers, such as human leukocyte antigen (HLA)-DR, CD38, Ki67, PD-1, CD39, and CTLA-4, were significantly increased in both the tumor and peripheral CD8+ T cells. Thus, intratumoral AdV-tk injection into non-small-cell lung cancer (NSCLC) proved safe and feasible, and it effectively induced CD8+ T cell activation. These data provide a foundation for additional clinical trials of GMCI for lung cancer patients with potential benefit if combined with other immune therapies.

Factores asociados con el consumo excesivo de alcohol: Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19.

Objetivo. Conocer la magnitud del consumo excesivo de alcohol (CEA) y su asociación con los factores individuales, familiares y sociales entre agosto y noviembre de 2020 en México. Material y métodos. Con base en los datos de la Encuesta Nacional de Salud y Nutrición 2020 sobre Covid-19, se analizaron 8 595 adultos mayores de 20 años. Se estimaron modelos de regresión logística estratificados por sexo y se obtuvieron razones de momios (RM) con intervalos de confianza al 95% (IC95%). Resultados. El CEA fue de 40.43%; hombres 56.49% y mujeres 25.70%. Los principales factores asociados fueron ser hombre (RM=3.66; IC95%: 3.22,4.12), edad de 20 a 29 años (RM=3.65; IC95%: 2.89,4.63), salir a trabajar durante la pandemia (RM=1.56; IC95%: 1.33,1.81) y tener dos o más escolares en el hogar (RM=1.20; IC95%: 1.03,1.39). Conclusiones. En México, el patrón de CEA es prevalente; por su naturaleza de riesgo y su amplia distribución poblacional, es prioritario implementar intervenciones preventivas individuales y de salud pública.

Encodat 2016: Violencia de pareja y uso de tabaco, alcohol y drogas. Nuevos retos para la salud mental.

Objetivo. Estimar la prevalencia de violencia de pareja por sexo y su asociación con el uso de tabaco, alcohol y drogas en México. Material y métodos. Estudio transversal de la Encuesta Nacional de Consumo de Drogas, Alcohol y Tabaco 2016, que incluyó a 34 861 personas de 12 a 65 años. Se esti-maron modelos de regresión logística para obtener razones de momios (RM) e intervalos de confianza al 95% (IC95%). Resultados. La prevalencia de violencia de pareja fue de 15.14%; 18.16% en mujeres y 11.89% en hombres. Factores asociados: consumo excesivo de alcohol (RM: 1.64; IC95% 1.38-1.96), consumo de tabaco (RM:1.71;IC95% 1.42-2.07), consumo de medicamentos psicotrópicos sin receta (RM: 3.72; IC95% 1.76-7.88) y consumo de marihuana (RM: 3.06; IC95%: 1.58-5.91). Conclusiones. Los resultados apoyan la necesidad de implementar intervenciones multisectoriales, fortalecer competencias psicosociales para lograr la mejora de la calidad y acceso a los servicios de salud mental y adic-ciones en México.

Inpatient dermatology: Where are we headed? A nationwide population-based study of Spain from 2006 to 2016.

BACKGROUND AND OBJECTIVES: Information about hospital admissions for skin diseases is restricted to studies describing admissions to single centers, to specific wards, or only for a few diagnoses, and there is no information about the outcomes between different wards. The aim of this research is to describe hospital admissions due to dermatological diseases. PATIENTS AND METHODS: Cross-sectional study of hospital discharges at Spanish hospitals. Discharges were assumed to be the same as admissions. RESULTS: 519,440 discharges (1.1 % of total discharges) were identified. Most admissions (60.1 %) were done from emergency departments. Only 7 % of cases were admitted to dermatology wards. The most prevalent group was cellulitis and acute lymphangitis. Median age was 57 years, and men were more common. The median length of hospital stay was four days; 40,823 (7.9 %) cases required readmission. There were 13,558 (2.6 %) hospital deaths. After adjusted analysis (by age, sex and group of diagnosis), the OR of readmission was 1.49 (95 % CI: 1.42-1.57) times higher and length of stay was 0.22 (95 % CI: 0.15-0.29) days longer in non-dermatology wards (P < 0.0001). From 2006-2016, admissions to dermatology wards decreased 38 %, while in non-dermatology wards they increased 8 %. CONCLUSIONS: A non-negligible number of patients require dermatological inpatient management. This is mainly provided by non-dermatologists. Some of our findings may indicate an improved overall care by dermatologists.

The algorithm used for the interpretation of doravirine transmitted drug resistance strongly influences clinical practice and guideline recommendations.

OBJECTIVES: We report the results of the reverse transcriptase (RT)/protease (PR) transmitted drug resistance (TDR) prevalence study in 2018, focusing on doravirine resistance-associated mutations and the differences observed when Stanford or French National Agency for AIDS Research (ANRS)/Spanish Network of AIDS Research (RIS)/IAS-USA resistance interpretation algorithms are used to describe clinically relevant resistance. METHODS: We used the WHO 2009 list to investigate the prevalence of NNRTI, NRTI and PI TDR, in treatment-naive HIV-1-infected patients, adding mutations E138A/G/K/Q/R, V106I, V108I, V179L, G190Q, H221Y, F227C/L/V, M230IDR, L234I, P236L and Y318F in RT. The prevalence of doravirine resistance-associated mutations, as described by Soulie et al. in 2019, was evaluated. Clinically relevant TDR was investigated using the latest versions of ANRS, RIS, IAS-USA and Stanford algorithms. RESULTS: NNRTI mutations were detected in 82 of 606 (13.5%) patients. We found 18 patients (3.0%) with NRTI mutations and 5 patients (0.8%) with PI mutations. We detected 11 patients harbouring doravirine resistance-associated mutations (prevalence of 1.8%). Furthermore, we observed important differences in clinically relevant resistance to doravirine when ANRS/RIS (0.7%), IAS-USA (0.5%) or Stanford algorithms (5.0%) were used. V106I, which was detected in 3.8% of the patients, was the main mutation driving these differences. V106I detection was not associated with any of the clinical, demographic or virological characteristics of the patients. CONCLUSIONS: The prevalence of NRTI and PI TDR remains constant in Spain. Doravirine TDR is very infrequent by RIS/ANRS/IAS-USA algorithms, in contrast with results using the Stanford algorithm. Further genotype-phenotype studies are necessary to elucidate the role of V106I in doravirine resistance.

The estimation of GFR and the adjustment for BSA in overweight and obesity: a dreadful combination of two errors.

BACKGROUND: Obesity is an established risk factor for renal disease and for disease progression. Therefore, an accurate determination of renal function is necessary in this population. Renal function is currently evaluated by estimated glomerular filtration rate (GFR) by formulas, a procedure with a proven high variability. Moreover, the adjustment of GFR by body surface area (BSA) confounds the evaluation of renal function. However, the error of using estimated GFR adjusted by BSA has not been properly evaluated in overweight and obese subjects. METHODS: We evaluated the error of 56 creatinine- and/or cystatin-C-based equations and the adjustment of GFR by BSA in 944 subjects with overweight or obesity with or without chronic kidney disease (CKD). The error between estimated (eGFR) and measured GFR (mGFR) was evaluated with statistics of agreement: the total deviation index (TDI), the concordance correlation coefficient (CCC) and the coverage probability (cp). RESULTS: The error of eGFR by any equation was common and wide: TDI averaged 55%, meaning that 90% of estimations ranged from -55 to 55% of mGFR. CCC and cp averaged 0.8 and 26, respectively. This error was comparable between creatinine and cystatin-C-based formulas both in obese or overweight subjects. The error of eGFR was larger in formulas that included weight or height. The adjustment of mGFR or eGFR led to a relevant underestimation of renal function, reaching at least 10 mL/min in 25% of the cases. CONCLUSIONS: In overweight and obese patients, formulas failed in reflecting real renal function. In addition, the adjustment for BSA led to a relevant underestimation of GFR. Both errors may have important clinical consequences. Thus, whenever possible, the use of a gold standard method to measure renal function is recommended. Moreover, the sense of indexing for BSA should be re-considered and probably abandoned.

[Prevalence and psychological factors associated withsuicidal behavior in adolescents. Ensanut 2018-19]. / Prevalencia y factores psicológicos asociados con conducta suicida en adolescentes. Ensanut 2018-19.

OBJECTIVE: To estimate the prevalence of suicidal behavior and its association with psychological factors in Mexican adolescents. MATERIALS AND METHODS: Cross-sectional study based on the National Survey of Health and Nutrition (Ensanut 2018-19), with a sample of 17 995 adolescents (10-19 years). Adjusted logistic regression models were estimated, obtaining Odds Ratio (OR) and 95% confidence intervals (95%CI). RESULTS: Prevalence of suicidal ideation and suicide attempt in Mexico were 5.1 and 3.9%, respectively; the high-est prevalence was in Guanajuato (ideation: 9.0%, attempt: 7.8%). Associated factors. Suicidal ideation: tobacco (OR= 2.26; 95%CI: 1.62-3.16), alcohol (OR= 2.12; 95%CI: 1.65-2.73), depressive symptoms (OR= 6.04; 95%CI: 4.71-7.73), sexual abuse (OR= 6.57; 95%CI: 4.57-9.45). Suicidal attempt: tobacco (OR= 2.17; 95%CI: 1.49-3.15), alcohol (OR= 2.32; 95%CI:1.77-3.03), depressive symptoms (OR= 6.47; 95% CI: 4.91-8.51), sexual abuse (OR= 6.76; 95%CI: 4.60-9.96). CONCLUSIONS: By increasing suicidal behavior in Mexican adolescents, it is necessary to implement preventive public policies that articulate mental health, addiction and violence programs.

OBJETIVO: Estimar la prevalencia de conducta suicida y su asociación con factores psicológicos en adolescentes mexi-canos. MATERIAL Y MÉTODOS: Estudio transversal prove-niente de la Encuesta Nacional de Salud y Nutrición (Ensanut 2018-19). Se estimaron modelos de regresión logística, con lo que se obtuvieron razones de momios (RM) con intervalos de confianza al 95% (IC95%). RESULTADOS: nacional de ideación e intento de suicidio fue de 5.1 y 3.9%, respectivamente; fue más alta en Guanajuato (ideación: 9.0%, intento: 7.8%). Factores asociados. Ideación suicida: tabaco (RM= 2.26; IC95%: 1.62-3.16), alcohol (RM= 2.12; IC95%: 1.65-2.73), sintomatología depresiva (RM= 6.04; IC95%: 4.71-7.73), abuso sexual (RM= 6.57; IC95%: 4.57-9.45). Intento de suicidio: tabaco (RM= 2.17; IC95%: 1.49-3.15), alcohol (RM= 2.32; IC95%: 1.77-3.03), sintomatología depresiva (RM= 6.47; IC95%: 4.91-8.51), abuso sexual (RM= 6.76; IC95%: 4.60-9.96). CONCLUSIONES: Debido al incremento de la conducta suicida en adolescentes mexicanos, es necesario implementar políticas públicas pre-ventivas que articulen programas de salud mental, adicciones y violencia.

Ipsilesional Motor Cortex Plasticity Participates in Spontaneous Hindlimb Recovery after Lateral Hemisection of the Thoracic Spinal Cord in the Rat.

After an incomplete spinal cord injury (SCI) spontaneous motor recovery can occur in mammals, but the underlying neural substrates remain poorly understood. The motor cortex is crucial for skilled motor learning and the voluntary control of movement and is known to reorganize after cortical injury to promote recovery. Motor cortex plasticity has also been shown to parallel the recovery of forelimb function after cervical SCI, but whether cortical plasticity participates in hindlimb recovery after SCI remains unresolved. Using intracortical microstimulation (ICMS) mapping, behavioral and cortical inactivation techniques in the female Long-Evans rat, we evaluated the spontaneous cortical mechanisms of hindlimb motor recovery 1-5 weeks after lateral hemisection of the thoracic (T8) spinal cord that ablated the crossed corticospinal tract (CST) from the contralesional motor cortex while sparing the majority of the CST from the ipsilesional motor cortex. Hemisection initially impaired hindlimb motor function bilaterally but significant recovery occurred during the first 3 weeks. ICMS revealed time-dependent changes in motor cortex organization, characterized by a chronic abolishment of hindlimb motor representation in the contralesional motor cortex and the development of transient bilateral hindlimb representation in the ipsilesional motor cortex 3 weeks after hemisection, when significant behavioral recovery occurred. Consistently, reversible inactivation of the ipsilesional, but not the contralesional motor cortex, during skilled ladder walking 3 weeks after hemisection reinstated deficits in both hindlimbs. These findings indicate that the ipsilesional motor cortex transiently reorganizes after lateral hemisection of the thoracic spinal cord to support recovery of hindlimb motor function.SIGNIFICANCE STATEMENT Partial motor recovery can occur after an incomplete spinal cord injury and is hypothesized to result from the reorganization of spared descending motor pathways. The motor cortex is crucial for the control of voluntary movement and contains topographical movement representations (motor maps) that are highly plastic. We examined the organization of hindlimb motor maps bilaterally after a lateral hemisection of the spinal cord to show that while motor maps are abolished in the deefferented cortex, the spared ipsilesional cortex transiently reorganizes to gain a representation of the affected hindlimb after injury that relates to recovery. This finding demonstrates that plasticity in the ipsilesional motor cortex at early time points after spinal cord hemisection is initially important to support motor recovery.

Feasibility of the peroral endoscopic myotomy (POEM) procedure with a new small-caliber endoscope (thin-POEM) in patients with achalasia.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a recognized technique for patients with achalasia. We aimed to evaluate the feasibility of using a small-caliber endoscope (thin-POEM) to perform POEM in patients with achalasia. METHODS: Naïve or previously treated patients were included between February 2016 and April 2018. A small-caliber (5.9 mm) nasoendoscope was used, with a modified closure method using cyanoacrylate. Strict follow-up was performed. RESULTS: 45 patients were included, aged 45.5 years (interquartile range [IQR] 22 - 69); 53 % (24/45) had type II achalasia. Median total time for thin-POEM was 54 minutes (IQR 37 - 77) and median myotomy length was 13.5 cm (IQR 6 - 20). Results pre-procedure and 3 months post were Eckardt score 10 vs. 1 (P < 0.001), integrated relaxation pressure (IRP) 25.3 vs. 8.5 mmHg (P < 0.001), and timed barium esophagram (TBE) 100 % severely delayed vs. 86 % normal (P < 0.001), respectively. Type III patients had the longest thin-POEM times (median 58 minutes [IQR 52 - 77]). Reflux was confirmed at 3 months clinically in 17 % of patients, endoscopically in 20 %, and on pH monitoring in 53 %. At 6 months and 12 months, 40 % and 33 % of patients remained positive on pH monitoring and were medically managed. CONCLUSIONS: Thin-POEM seems to be a safe, effective, and efficient procedure for POEM in patients with achalasia, with good short-term follow-up results.