Clinical and persistent remission in anti-HMGCR immune-mediated necrotizing myopathy to a single cycle of rituximab - a case-based review.

Anti-HMGCR myopathy is an increasingly recognized immune-mediated necrotizing myopathy. However, there are currently no evidence-based treatments available, so case reports and clinical experience are used to guide current management. We report a case of a 49-year-old man, treated with atorvastatin, who presented to the emergency department with progressive proximal muscle weakness. Anti-HMGCR antibodies were detected, and muscle biopsy revealed necrotizing myopathy. Initially, therapy with high-dose glucocorticoids and methotrexate was started, but 12 weeks later, the patient developed clinical deterioration with dysphagia. Then, he was successfully treated with one cycle of rituximab along with physical therapy. The use of rituximab in immune-mediated necrotizing myopathy has been heterogeneously described in the literature but mostly in case reports. The European Neuromuscular Centre working group recommends the use of rituximab in refractory cases. However, some studies highlight the importance of early and aggressive treatment for this disease. Clinical prospective studies are necessary to make proper evidence-based recommendations.

Brain MRI in patients with V30M hereditary transthyretin amyloidosis.

BACKGROUND: Central nervous system dysfunction is common in longstanding hereditary transthyretin amyloidosis (ATTRv) caused by the V30M (p.V50M) mutation. Neuropathology studies show leptomeningeal amyloid deposition and cerebral amyloid angiopathy (CAA). Brain MRI is widely used in the assessment of Aß associated CAA but there are no systematic studies with brain MRI in ATTRv amyloidosis. METHODS: we performed 3 T brain MRIs in 16 patients with longstanding (>14 years) ATTRV30M. We additionally retrospectively reviewed 48 brain MRIs from patients followed at our clinic. CNS symptoms and signs were systematically accessed, and MRIs were blindly reviewed for ischaemic and haemorrhagic lesions. RESULTS: in the prospective cohort, we found white matter hyperintensities in 8/16 patients (50%, Fazekas score> =1). There were no relevant microbleeds, large ischaemic or haemorrhagic lesions or superficial siderosis. In the retrospective cohort, microbleeds were found in 5/48 patients (10,4%), two of which with > =20 microbleeds. White matter hyperintensities were found in 20/48 cases (41.7%). White matter lesions, microbleeds and cortical atrophy were not associated with disease duration. CONCLUSIONS: white matter hyperintensities are common in ATTRV30M, irrespective of disease duration. Haemorrhagic lesions are rare, even in patients with longstanding disease, suggesting the existence of other risk factors.

Rescuing a Troubled Tolcapone with PEGylated PLGA Nanoparticles: Design, Characterization, and Hepatotoxicity Evaluation.

Tolcapone is an orally active catechol-O-methyltransferase (COMT) inhibitor used as adjuvant therapy in Parkinson's disease. However, it has a highly hepatotoxic profile, as recognized by the U.S. Food and Drug Administration. As a possible solution, nanoscience brought us several tools in the development of new functional nanomaterials with tunable physicochemical properties, which can be part of a solution to solve several drawbacks, including drug's short half-life and toxicity. This work aims to use PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a stable carrier with lower hydrodynamic size and polydispersity to encapsulate tolcapone in order to overcome its therapeutic drawbacks. Using the nanoprecipitation method, tolcapone-loaded nanoparticles with a DLC% of 5.7% were obtained (EE% of 47.0%) and subjected to a lyophilization optimization process to obtain a final shelf-stable formulation. Six different cryoprotectants in concentrations up to 10% (w/v) were tested. A formulation of PLGA nanoparticles with 3% hydroxypropyl-ß-cyclodextrin (HPßCD) as a cryoprotectant (PLGA-HP@Tolc), presenting sub-200 nm sizes and low polydispersity (PdI < 0.200) was selected. Cytotoxicity assays, namely, MTT and SRB, were used to study the metabolic activity and cell density of tolcapone and PLGA-HP@Tolc-treated cells. In both assays, a hepatocarcinoma cell line (HepG2) growing in glucose or glucose-free media (galactose-supplemented medium) was used. The results demonstrated that the treatment with the PLGA-HP@Tolc formulation led to a decrease in cytotoxicity in comparison to free tolcapone-treated cells in both media tested. Moreover, the elected formulation also counteracted ATP-depletion and excessive ROS production induced by tolcapone. The results suggest that HPßCD might have a dual function in the formulation: cryoprotectant and anticytotoxic agent, protecting cells from tolcapone-induced damage. Using an in vitro COMT inhibition assay, the PLGA-HP@Tolc formulation demonstrated to inhibit COMT as efficiently as free tolcapone. Overall, the results suggest that tolcapone-loaded PLGA NPs could be an interesting alternative to free tolcapone, demonstrating the same in vitro efficacy in inhibiting COMT but with a safer cytotoxic profile.

X-Linked Myotubular Myopathy: A Novel Mutation Expanding the Genotypic Spectrum of a Phenotypically Heterogeneous Myopathy.

X-linked myotubular myopathy (XLMTM), a centronuclear congenital myopathy secondary to pathogenic variants in the MTM1 gene encoding myotubularin, is typically recognized for its classic and severe phenotype which includes neonatal hypotonia, severe muscle weakness, long-term ventilator dependence, markedly delayed gross motor milestones with inability to independently ambulate, and a high neonatal and childhood mortality. However, milder congenital forms of the condition and other phenotypes are recognized. We describe a 6-year-old boy with a mild XLMTM phenotype with independent gait and no respiratory insufficiency even in the neonatal period. The child has a hemizygous novel splice site variant in the MTM1 gene (c.232-25A > T) whose pathogenicity was confirmed by cDNA studies (exon 5 skipping) and muscle biopsy findings. We also compared the phenotype of our patient with the few reported cases that presented a mild XLMTM phenotype and no respiratory distress at birth, and discussed the potential mechanisms underlying this phenotype such as the presence of residual expression of the normal myotubularin transcript.

Looking at the Molecular Target of NS5A Inhibitors throughout a Population Highly Affected with Hepatitis C Virus.

Hepatitis C virus (HCV) is associated with liver damage and an increased progression rate to cirrhosis and hepatocellular carcinoma. In Portugal, it is prevalent in vulnerable populations such as injection drug users (IDU). HCV is characterized by a high intra-host variability, and the selecting driving forces could select variants containing resistance-associated substitutions (RAS) that reduce treatment effectiveness. The main goal of this study was to analyze the sequence variation of NS5A in treatment-naïve IDU. The epidemiological and clinical status of hepatitis C were analyzed, and samples were sequenced by Sanger and Next-Generation sequencing (NGS) to assess RAS and confirm HCV subtypes. Phylogenetic classification was concordant: 1a, 52.4%; 1b, 10.7%; 3a, 20.2%; 4a, 8.3%; 4d, 7.1%; and one 2k/1b recombinant. A 1a/3a mixed infection was detected by NGS. RAS were found in 34.5% (29/84) of samples using Sanger sequencing, while in 42.9% (36/84) using NGS. In sequences from subtypes 1a and 1b, RAS K24R, M28V, Q30H/R, H58D/P/Q/R, and RAS L31M and P58S were detected, respectively. In subtype 3a, RAS A30S/T, Y93H and polymorphisms in position 62 were identified. Additionally, RAS P58L was detected in genotype 4. The strategy used for the molecular survey of baseline HCV resistance is of particular importance to achieve treatment effectiveness and contribute to the elimination of hepatitis C.

Neuropathology of central nervous system involvement in TTR amyloidosis.

Hereditary transthyretin amyloidosis (ATTRv) is a systemic disease caused by the accumulation of misfolded transthyretin (TTR). It usually presents with an adult-onset progressive axonal peripheral neuropathy and cardiomyopathy. In the central nervous system (CNS), variant TTR is produced by the choroid plexus and accumulates in the leptomeninges. CNS symptoms have been increasingly recognized in this population, including transient focal neurological episodes and stroke, particularly in patients with the V30M mutation and longstanding disease. The prevalence, pathophysiology, and progression of CNS involvement remain to be clarified. The present work explores if there is a recognizable sequence of CNS TTR deposition in ATTRv. We studied the topographical and severity distribution of TTR deposition in 16 patients with ATTRv, aged 27-69 years and with a mean disease duration of 10.9 years (range: 3-29). Our results suggest that CNS pathological involvement in V30M ATTRv occurs early in the disease course, probably starting in pre-symptomatic phases, and follows a distinct sequence. Leptomeninges and subarachnoid meningeal vessels are affected earlier, then followed by perforating cortical vessels and subpial deposition, and finally by deposition in the subependymal and basal ganglia vessels near the ependymal lining. Brainstem and spinal cord show early and severe involvement, with amyloid subpial deposition already seen in initial stages. Despite massive superficial amyloid deposition, no parenchymal deposition outside subpial or subependymal regions was found. Additionally, vascular lesions or superficial cortical siderosis were not frequent. Future studies with more patients from different populations and TTR mutations will be important to confirm these findings. Defining stages of TTR pathology in the CNS may be useful to better understand pathogenic mechanisms leading to symptoms and to interpret neuroimaging biomarkers.

Brain drug delivery and neurodegenerative diseases: Polymeric PLGA-based nanoparticles as a forefront platform.

The discovery of effective drugs for the treatment of neurodegenerative disorders (NDs) is a deadlock. Due to their complex etiology and high heterogeneity, progresses in the development of novel NDs therapies have been slow, raising social/economic and medical concerns. Nanotechnology and nanomedicine evolved exponentially in recent years and presented a panoply of tools projected to improve diagnosis and treatment. Drug-loaded nanosystems, particularly nanoparticles (NPs), were successfully used to address numerous drug glitches, such as efficacy, bioavailability and safety. Polymeric nanoparticles (PNPs), mainly based on polylactic-co-glycolic acid (PLGA), have been already validated and approved for the treatment of cancer, neurologic dysfunctions and hormonal-related diseases. Despite promising no PNPs-based therapy for neurodegenerative disorders is available up to date. To stimulate the research in the area the studies performed so far with polylactic-co-glycolic acid (PLGA) nanoparticles as well as the techniques aimed to improve PNPs BBB permeability and drug targeting were revised. Bearing in mind NDs pharmacological therapy landscape huge efforts must be done in finding new therapeutic solutions along with the translation of the most promising results to the clinic, which hopefully will converge in the development of effective drugs in a foreseeable future.

The [4Fe4S] Cluster of Yeast DNA Polymerase ε Is Redox Active and Can Undergo DNA-Mediated Signaling.

Many DNA replication and DNA repair enzymes have been found to carry [4Fe4S] clusters. The major leading strand polymerase, DNA polymerase ε (Pol ε) from Saccharomyces cerevisiae, was recently reported to have a [4Fe4S] cluster located within the catalytic domain of the largest subunit, Pol2. Here the redox characteristics of the [4Fe4S] cluster in the context of that domain, Pol2CORE, are explored using DNA electrochemistry, and the effects of oxidation and rereduction on polymerase activity are examined. The exonuclease deficient variant D290A/E292A, Pol2COREexo-, was used to limit DNA degradation. While no redox signal is apparent for Pol2COREexo- on DNA-modified electrodes, a large cathodic signal centered at -140 mV vs NHE is observed after bulk oxidation. A double cysteine to serine mutant (C665S/C668S) of Pol2COREexo-, which lacks the [4Fe4S] cluster, shows no similar redox signal upon oxidation. Significantly, protein oxidation yields a sharp decrease in polymerization, while rereduction restores activity almost to the level of untreated enzyme. Moreover, the addition of reduced EndoIII, a bacterial DNA repair enzyme containing [4Fe4S]2+, to oxidized Pol2COREexo- bound to its DNA substrate also significantly restores polymerase activity. In contrast, parallel experiments with EndoIIIY82A, a variant of EndoIII, defective in DNA charge transport (CT), does not show restoration of activity of Pol2COREexo-. We propose a model in which EndoIII bound to the DNA duplex may shuttle electrons through DNA to the DNA-bound oxidized Pol2COREexo- via DNA CT and that this DNA CT signaling offers a means to modulate the redox state and replication by Pol ε.

Coordination Compounds As Multi-Delivery Systems for Osteoporosis.

Osteoporosis therapies leveraging bisphosphonates and mineral components (e.g., magnesium, calcium, and strontium) have been raising attention because of their potential for managing this ever-growing disease. The administration of multicomponent therapeutics (combined therapy) in elderly patients is complex and suffers from low patient adherence. Herein, we report an all-in-one combination of four antiosteoporotic components into a new family of coordination complexes: [M2(H4alen)4(H2O)2]·1.5H2O [where M2+ = Mg2+ (1), (Mg0.535Ca0.465)2+ (2) and (Mg0.505Ca0.450Sr0.045)2+ (3)]. These solid-state complexes were prepared, for the first time, through microwave-assisted synthesis. It is demonstrated that the compounds are capable of releasing their antiosteoporotic components, both in conditions that mimic the path along the gastrointestinal tract and in long periods under physiological conditions (pH ∼7.4). More importantly, when administered in low concentrations, the compounds did not elicit a cytotoxic effect toward liver, kidney, and osteoblast-like cell lines. Besides, it is important to highlight the unique coordination complex with four bone therapeutic components, [(Mg0.505Ca0.450Sr0.045)2(H4alen)4(H2O)2]·1.5H2O (3), which significantly promoted osteoblast metabolic activity up to ca. 1.4-fold versus the control group. These findings bring this type of compounds one-step closer to be considered as an all-in-one and more effective treatment for managing chronic bone diseases, prompting further research on their therapeutic properties.

Unconventional Surgical Intervention for Left Ventricular Pseudoaneurysm Associated With Staphylococcus aureus in a Pediatric Patient.

Ventricular pseudoaneurysms are very unusual in children. A six-year-old child developed left ventricular pseudoaneurysm associated with methicillin-sensitive Staphylococcus aureus. The patient responded favorably to antibiotic therapy and ventriculoplasty through an unconventional surgery due to the constrictive pericarditis.

Posterior reversible encephalopathy syndrome associated with the use of chemotherapeutic agents: a rare complication after treatment with vinorelbine.

The posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome characterised by a combination of headache, encephalopathy, seizures and visual disturbances, associated with high-intensity abnormalities on T2-weighted images affecting subcortical white and grey matter of the occipital and parietal lobes. Among other causes, PRES has been associated with the use of several medications including chemotherapeutic agents. Here we report a case of a 65-year-old patient with squamous cell carcinoma of the lung treated with cisplatin/vinorelbine. Following the second administration of vinorelbine, she was admitted to the hospital for a generalised seizure. Blood pressure was just slightly elevated and, except for drowsiness, she had a near-normal neurological examination. MRI corroborated the diagnosis. Vinorelbine-induced PRES has been reported only once in the literature, also in association with cisplatin. Our case underlines the role of vinorelbine and suggests that its association with cisplatin in this setting may enhance the risk of PRES.

Salud mental en estudiantes de pregrado de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos / Mental health in undergraduate students from Universidad Nacional Mayor de San Marcos School of Medicine

Introducción. Estudios previos evidencian problemas de salud mental en estudiantes de pre-grado de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos (UNMSM). Objetivo. Evaluar si existen diferencias entre la frecuencia de problemas de salud mental entre los estudiantes de primer año, y el resto de años de estudio, en alumnos de las cinco escuelas profesionales de la Facultad de Medicina de la UNMSM. Métodos. Estudio transversal. Se utilizaron instrumentos validados para evaluar problemas de salud mental: intento suicida, pensamiento homicida, conducta disocial, problemas con el alcohol, depresión y angustia. Adicionalmente, se midieron niveles de resiliencia. Se incluyeron estudiantes de todas las escuelas profesionales de la Facultad de Medicina, en dos grupos de análisis: estudiantes de primer año y estudiantes de los otros años. Resultados. Se evidenció que en alumnos de primer año se encontró un 7,5% de intento suicida, 18,9% de conducta disocial y 21,9% de pensamiento homicida de prevalencia de vida. Asimismo, se encontró un 4,8% de problemas con el alcohol, 8,5% de depresión y 3,2% de angustia de prevalencia periódica. La frecuencia de problemas de salud mental fue mayor según transcurrieron los años de estudio, aunque con diferencias estadísticamente significativas sólo en depresión, angustia y problemas con el alcohol. El 29,3% de encuestados tuvo bajo nivel de resiliencia. Conclusión. Se encontraron frecuencias preocupantes de problemas de salud mental en los estudiantes de pregrado de la Facultad de Medicina de la UNMSM, aunque un porcentaje de alumnos ya ingresa a la universidad afectado por ellos. El entorno universitario sería factor agravante en depresión, ansiedad y problemas con el alcohol.

Introduction. Previous studies pointed out mental health problems in undergraduate health students of school of medicine from Universidad Nacional Mayor de San Marcos (UNMSM). Objective. To assess if there are differences between the frequency of mental health problems between first-year students and other years’ students from five professional schools of the UNMSM school of medicine. Methods. A cross-sectional study. Validated instruments were used to assess mental health problems: suicidal intent, homicidal thinking, disocial behavior, alcoholism, depression and anguish. In addition, levels of resilience were evaluated. Students from all professional schools of the Faculty of Medicine were included in two analysis groups: first-year students and other years’ students. Results. 7,5% of suicide attempts, 18,9% of disocial behavior and 21,9% of homicidal thinking lifetime prevalence were found in first-year students. Similarly, 4,8% of alcoholism, 8,5% of depression and 3,2% of anxiety point prevalence were found on same group of study. The frequency of mental health problems was higher according to the years of study, with statistically significant differences only in depression, anxiety and alcoholism. 29,3% of respondents have a low level of resilience Conclusion. Concerning frequencies of mental health problems were found in undergraduate students of UNMSM School of Medicine, although a percentage of students were admitted in university with mental health problems. The university environment would be an aggravating factor in depression, anxiety and alcohol problems.

Therapeutic Potential of Two Visible Light Responsive Luminescent photoCORMs: Enhanced Cellular Internalization Driven by Lipophilicity.

Herein we report the synthesis, characterization, and cellular internalization properties of two visible-light active luminescent Mn-based photoCORMs. The enhanced membrane permeability of the photoactive Mn carbonyl complex (photoCORM) derived from a designed lipophilic ligand namely, [Mn(CO)3(Imdansyl)(L1)](CF3SO3) (1) (where L1 = a diazabutadiene-based ligand containing two highly lipophilic adamantyl motifs, Imdansyl = dansylimidazole) promoted rapid internalization within human colorectal adenocarcinoma (HT-29) cells compared to [Mn(CO)3(Imdansyl)(L2)](CF3SO3) (2) (where L2 = a diazabutadiene ligand bearing two hydrophilic 1,3,5-triazaadamantyl group). Colocalization experiments using membrane stain indicate different extents of localization of the two CO complexes within the cellular matrix. Visible-light triggered CO release from the lipophilic photoCORM induced caspase-3/7 activation on HT-29 cells, which was detected using confocal microscopy. The rapid accumulation of the lipophilic photoCORM 1 in the cellular membrane resulted in more efficient CO-induced cell death compared to the hydrophilic analogue 2.

Human papillomavirus is not associated to non-small cell lung cancer: data from a prospective cross-sectional study.

BACKGROUND: The pathogenesis of lung cancer is triggered by a combination of genetic and environmental factors, being the tobacco smoke the most important risk factor. Nevertheless, the incidence of lung cancer in non-smokers is gradually increasing, which demands the search for different other etiological factors such as occupational exposure, previous lung disease, diet among others. In the early 80's a theory linked specific types of human papillomavirus (HPV) to lung cancer due to morphological similarities of a subset of bronchial squamous cell carcinomas with other HPV-induced cancers. Since then, several studies revealed variable rates of HPV DNA detection. The current study aimed to provide accurate information on the prevalence of HPV DNA in lung cancer. METHODS: Biopsies were collected from 77 newly diagnosed non-small cell lung cancer (NSCLC) patients treated at the Thoracic Oncology Department at Barretos Cancer Hospital. The samples were formalin fixed and paraffin embedded (FFPE), histologic analysis was performed by an experienced pathologist. DNA was extracted from FFPE material using a commercial extraction kit and HPV DNA detection was evaluated by multiplex PCR and HPV16 specific real-time PCR. RESULTS: HPV was not identified in any of the samples analysed (69). CONCLUSIONS: Our data demonstrated a lack of HPV DNA in a series of NSCL cancers.

Flower isoforms promote competitive growth in cancer.

In humans, the adaptive immune system uses the exchange of information between cells to detect and eliminate foreign or damaged cells; however, the removal of unwanted cells does not always require an adaptive immune system1,2. For example, cell selection in Drosophila uses a cell selection mechanism based on 'fitness fingerprints', which allow it to delay ageing3, prevent developmental malformations3,4 and replace old tissues during regeneration5. At the molecular level, these fitness fingerprints consist of combinations of Flower membrane proteins3,4,6. Proteins that indicate reduced fitness are called Flower-Lose, because they are expressed in cells marked to be eliminated6. However, the presence of Flower-Lose isoforms at a cell's membrane does not always lead to elimination, because if neighbouring cells have similar levels of Lose proteins, the cell will not be killed4,6,7. Humans could benefit from the capability to recognize unfit cells, because accumulation of damaged but viable cells during development and ageing causes organ dysfunction and disease8-17. However, in Drosophila this mechanism is hijacked by premalignant cells to gain a competitive growth advantage18. This would be undesirable for humans because it might make tumours more aggressive19-21. It is unknown whether a similar mechanism of cell-fitness comparison is present in humans. Here we show that two human Flower isoforms (hFWE1 and hFWE3) behave as Flower-Lose proteins, whereas the other two isoforms (hFWE2 and hFWE4) behave as Flower-Win proteins. The latter give cells a competitive advantage over cells expressing Lose isoforms, but Lose-expressing cells are not eliminated if their neighbours express similar levels of Lose isoforms; these proteins therefore act as fitness fingerprints. Moreover, human cancer cells show increased Win isoform expression and proliferate in the presence of Lose-expressing stroma, which confers a competitive growth advantage on the cancer cells. Inhibition of the expression of Flower proteins reduces tumour growth and metastasis, and induces sensitivity to chemotherapy. Our results show that ancient mechanisms of cell recognition and selection are active in humans and affect oncogenic growth.

Prevalencia y factores asociados a conducta suicida en estudiantes de la Universidad Nacional Mayor de San Marcos, Lima-Perú / Prevalence and associated factors of suicidal behavior in students of the Universidad Nacional Mayor de San Marcos, Lima-Peru

Introducción. La Organización Mundial de la Salud ha señalado el incremento de riesgo suicida en personas de 15 a 44 años, grupo etario en el que se ubican los estudiantes universitarios. Objetivo. Determinar prevalencias de conducta suicida y variables asociadas en estudiantes de pregrado de la Universidad Nacional Mayor de San Marcos (UNMSM), Lima-Perú. Métodos. Estudio analítico, transversal. La población objetivo fue de 24 118 estudiantes matriculados en 2015. Se aplicaron los instrumentos de conducta suicida de la Encuesta Nacional de Salud Mental en el Perú 2002 y 2012, las escalas de ansiedad y depresión de Zung y el cuestionario CAGE para problemas de alcohol, a una muestra de 1819 estudiantes obtenida mediante muestreo bietápico. Se estimaron prevalencias y se empleó regresión logística para determinar factores asociados. Resultados. Las prevalencias de vida, último año, últimos seis meses y último mes de los componentes de la conducta suicida fueron: deseos de morir (35%; 13,9%; 11% y 5,6%); ideación suicida (22,4%; 8,2%; 6% y 3,3%); plan suicida (17,7%; 4,4%; 3,5% y 1,6%); e intento suicida (11,1%; 3,7%; 2,8% y 1,4%). Los factores de riesgo en términos de odds ratio (OR) ajustados y sus IC 95% fueron: condición de mujer 1,48 (IC 95%: 1,03-2,12), depresión 2,46 (IC 95%: 1,49-4,06), angustia 2,5 (IC 95%: 1,38-4,6), y vivir en hogar no nuclear 2,51 (IC 95%: 1,70-3,72). De los estudiantes que intentaron suicidarse sólo 16% buscó ayuda profesional y 21% pensó repetir el intento. Conclusiones. Los estudiantes de la UNMSM tienen mayor riesgo de conducta suicida que los de la población en general, tanto por razones científicas como por responsabilidad moral se recomienda implementar estrategias de intervención para revertir esta tendencia y proteger a este valioso recurso humano.

Introduction. World Health Organization has pointed out the increasing suicidal risk in the 115 - 44 years of age. University students are inmerse in that age group risk. Objective. To estimate the prevalence of suicidal behavior and associated variables in undergraduate students of Universidad Nacional Mayor de San Marcos (UNMSM). Methodos. Transversal and analytic study. Target population: 24 118 students registered in 2015. The Suicide Behavior Questionnaire of the 2002, 2012 Mental Health National Survey, the Zung self-rated anxiety and depression scales, and the CAGE questionnaire for potential alcohol-related problems were applied to a sample of 1819 students obtained by a bietapic with probabililty proportional to size sampling procedure. Results. Life, last year, last 6 months, and last month prevalences of suicide behavior`s components of were, in that order: (i) death wish (35%; 13,9%; 11%; 5,6%); (ii) suicidal ideation (22,4%; 8,2%; 6%;3,3%); (iii) suicidal planning (17,7%; 4,4%; 3,5%; 1,6%); and (iv) suicidal attempt (11,1%; 3,7%; 2,8%; 1,4%), and higher than the prevalences of metropolitan Lima general population. Risk factors, in terms of OR and 95% CI were: being female 1,48 (1,03-2,12), depression 2,46 (1,49-4,06), anxiety 2,5 (1,38-4,6), and living in a non nuclear home 2,51 (1,70-3,72). Only 16% of the students who attempted suicide sought professional help and 21% considered repeating the attempt. Conclusions. UNMSM undergraduate students show a riskier suicide behavior tan the general population. Both for scientific reasons and moral responsibility it is highly recommended to implement intervention strategies in order to revert this trend and protect this valuable human resource.

Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia.

INTRODUCTION: Mutations in the EXOSC3 gene are responsible for type 1 pontocerebellar hypoplasia, an autosomal recessive congenital disorder characterized by cerebellar atrophy, developmental delay, and anterior horn motor neuron degeneration. Muscle biopsies of these patients often show characteristics resembling classic spinal muscle atrophy, but to date, no distinct features have been identified. METHODS: Clinical data and muscle biopsy findings of 3 unrelated patients with EXOSC3 mutations are described. RESULTS: All patients presented as a severe congenital cognitive and neuromuscular phenotype with short survival, harboring the same point mutation (c.92G>C; p.Gly31Ala). Muscle biopsies consistently showed variable degrees of sarcomeric disorganization with myofibrillar remnants, Z-line thickening, and small nemaline bodies. CONCLUSIONS: In this uniform genetic cohort of patients with EXOSC3 mutations, sarcomeric disruption and rod structures were prominent features of muscle biopsies. In the context of neonatal hypotonia, ultrastructural studies might provide early clues for the diagnosis of EXOSC3-related pontocerebellar hypoplasia. Muscle Nerve 59:137-141, 2019.

Conducta y personalidad disociales en estudiantes de medicina: implicancias para la educación médica peruana / Dyssocial behavior and personality in medical students: implications for Peruvian medical education

Investigaciones previas sobre conducta suicida realizadas en estudiantes de medicina hallaron, como variable asociada, una alta prevalencia de vida (PV) de indicadores de conducta disocial. Tal resultado obliga a sospechar presencia de personalidad de este tipo en dicha población. Con el objetivo de aportar nuevos elementos que complementen los estudios previos, el presente artículo analiza el concepto de personalidad disocial y discute los resultados de un estudio piloto que evaluó su presencia en una muestra de alumnos recién ingresados a la Escuela de Medicina de la Universidad Nacional Mayor de San Marcos. Se encontró que de 175 estudiantes, 33 resultaron positivos a indicadores de conducta disocial (19% de PV) durante una primera evaluación; de este grupo, 30 se presentaron a una segunda evaluación diagnóstica, de los cuales cinco superaron el punto de corte para personalidad disocial, y 11 obtuvieron puntaje de sospecha de tal desarrollo. Sobre estos resultados sugerimos que la universidad debiera aceptar la responsabilidad de continuar investigando esta área, crear intervenciones preventivo-terapéuticas tempranas e innovaciones curriculares para reducir el riesgo de producir profesionales tecnicamente bien entrenados pero con minusvalías morales.

Previous studies on medical students´suicidal behavior found, as an associated variable, a high life-prevalence (LP) of dissocial behavior indicators. Such findings compel to suspect the presence of dissocial personality in that population. On the purpose to add knowledge to this problem, the present paper analyses the concept of dissocial personality and discusses the results of a pilot-study that evaluated its presence in recently admitted students to San Marcos University´s School of Medicine. In the first evaluation, it was found that 33 out of 175 students resulted positive to dissocial behavior indicators (LP: 19%). From this group, 30 showed up for a second diagnostic evaluation; 5 exceeded the cut-off point to dissocial personality and 11 showed scores very close to it, raising suspiciousness of such development. Upon these results we claim the university must accept the responsibility to continue researching this area, create early preventive-therapeutic interventions and curricula innovations to reduce the risk of generating well trained professionals but morally handicapped.