The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors.

Dim light exposure of the mother during pregnancy has been proposed as one of the environmental factors that affect the fetal brain development in schizophrenia. Melatonin circulating levels are regulated by the environmental light/dark cycle. This hormone stimulates neuronal differentiation in the adult brain. However, little is known about its role in the fetal human brain development. Olfactory neuronal precursors (ONPs) are useful for studying the physiopathology of neuropsychiatric diseases because they mimic all the stages of neurodevelopment in culture. Here, we first characterized whether melatonin stimulates neuronal differentiation in cloned ONPs obtained from a healthy control subject (HCS). Then, melatonin effects were evaluated in primary cultures of ONPs derived from a patient diagnosed with schizophrenia (SZ) and an age- and gender-matched HCS. Axonal formation was evidenced morphologically by tau immunostaining and by GSK3ß phosphorylated state. Potassium-evoked secretion was assessed as a functional feature of differentiated neurons. As well, we report the expression of MT1/2 receptors in human ONPs for the first time. Melatonin stimulated axonal formation and ramification in cloned ONPs through a receptor-mediated mechanism and enhanced the amount and velocity of axonal and somatic secretion. SZ ONPs displayed reduced axogenesis associated with lower levels of pGSK3ß and less expression of melatonergic receptors regarding the HCS ONPs. Melatonin counteracted this reduction in SZ cells. Altogether, our results show that melatonin signaling is crucial for functional differentiation of human ONPs, strongly suggesting that a deficit of this indoleamine may lead to an impaired neurodevelopment which has been associated with the etiology of schizophrenia.

[Hematological indices associated with mortality in critically ill patients with COVID-19]. / Índices hematológicos asociados con mortalidad en pacientes críticos con COVID-19.

Background: The COVID-19 disease has represented one of the most important threats to health. The most severe form is acute respiratory distress syndrome (ARDS). The inflammatory response can cause hematologic changes. Objective: To determine the association between the Neutrophil/lymphocyte ratio (NLR) and the mean platelet volume (MPV) associated with mortality in critically ill patients with COVID-19 and ARDS. Material and methods: A retrospective study was carried out in an intensive care unit (ICU) in a public hospital, with patients in critical condition due to COVID-19 and on mechanical ventilation. The clinical characteristics of admission and severity of the disease were recorded. The end point was the ICU discharge condition. Results: 162 subjects were gathered, 103 were men, with a mean age of 54.54 ± 13.53 years. 66.7% died in the ICU. The NLR had an area under the curve (aROC) of 0.62, with a cut-off point for mortality of > 7.04, sensitivity of 94.4%, specificity of 29.63%. The VPM had an aROC of 0.65 with a cut-off point > 9.5, sensitivity of 30.84%, and specificity of 92.59%; finally, the APACHE II had an aROC of 0.67 with a cut-off point > 14, sensitivity of 51.4% and specificity of 80%. The NLR presented an odds ratio (OR) of 5.02, the VPM 2.06 and the APACHE II score 1.16. Conclusions: NLR, MPV, and APACHE II at ICU admission are associated with mortality for critically ill patients with COVID-19.

Introducción: la enfermedad por COVID-19 ha representado una de las amenazas más importantes para la salud. La forma más grave es el síndrome de insuficiencia respiratoria aguda (SIRA). La respuesta inflamatoria puede ocasionar cambios hematológicos. Objetivo: determinar la asociación entre el Índice neutrófilo/linfocito (INL) y el volumen plaquetario medio (VPM) asociado con la mortalidad en pacientes críticos con COVID-19 y SIRA. Material y métodos: se hizo un estudio de corte retrospectivo en una unidad de cuidados intensivos (UCI) de un hospital público, con pacientes en estado crítico por COVID y en ventilación mecánica. Se registraron las características clínicas de ingreso y severidad de la enfermedad. El punto final fue la condición de egreso de la UCI. Resultados: se reunieron 162 sujetos, 103 fueron hombres, con edad promedio de 54.54 ± 13.53 años. El 66.7% murieron en la UCI. El INL tuvo un área bajo la curva (aROC) de 0.62, con un punto de corte para mortalidad > 7.04, sensibilidad del 94.4% y especificidad del 29.63%. El VPM tuvo una aROC de 0.65 con un punto de corte > 9.5, sensibilidad de 30.84% y especificidad de 92.59%; finalmente, el APACHE II tuvo una ROC de 0.67, con un punto de corte > 14, sensibilidad de 51.4% y especificidad de 80%. El INL presentó una razón de momios (RM) de 5.02, el VPM una de 2.06 y el puntaje APACHE II una de 1.16. Conclusiones: el INL, el VPM y el APACHE II al ingreso a la UCI están asociados con la mortalidad para los pacientes críticos con COVID-19.

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

T-cell numbers and antigen-specific T-cell function follow different circadian rhythms.

PURPOSE: Circadian rhythms play an important role in modulating cellular immune responses. The present study was performed to characterise circadian variations in lymphocyte numbers and antigen-specific T-cell functionality in healthy individuals under physiological conditions. METHODS: Blood leukocyte populations of six healthy volunteers were quantified over 24 h. In addition, antigen-specific T-cell functionality was analysed directly ex vivo from whole blood using flow cytometry based on intracellular cytokine induction after a 6-hour stimulation with adenovirus antigen and Staphylococcus aureus enterotoxin B (SEB), respectively. RESULTS: T-cell numbers and reactivity were stable during daytime, whereas a significant increase was observed during late evening and early morning hours. The percentage of T cells reacting towards adenovirus antigen and SEB showed a 1.76 ± 0.55-fold (p = 0.0002) and a 1.42 ± 0.33-fold (p = 0.0002) increase, respectively. Dynamics in T-cell reactivity were independent of the mode of antigen stimulation and inversely correlated with plasma levels of endogenous cortisol. Interestingly, peak frequencies of reactive T cells occurred late in the evening and did not directly coincide with peak numbers of bulk T cells that were observed in the early morning hours. CONCLUSIONS: Taken together, our data reveal a circadian regulation of T-cell immune responses in the peripheral blood of humans under physiological conditions. This knowledge may be of practical consequence for the timing of blood sampling for functional T-cell assays as well as for immunosuppressive drug intake after organ transplantation, where T-cell function may be influenced not only by drug-mediated inhibition but also by circadian fluctuations in T-cell reactivity.

[Ketamine as a treatment of bronchospasm due to an anaphylaxis. A case report]. / Ketamina como tratamiento de broncoespasmo asociado a anafilaxia. Reporte de un caso.

Background: Ketamine is used in intravenous anesthesia for the maintenance in the general anesthesia. It has characteristics to prevent the difficult of breathing due to bronchospasm, as well as the delivery of histamine associated with asthmatic attack. These effects come from the direct action in the bronchial muscle, as well as from the potentiation of its catecholamines, which is why its use is very controversial, given that there are not enough trials to back it up. Moreover, the effect of ketamine on bronchospasm due to anaphylactic reaction has not been studied. The election treatment is epinephrine and there are factors associated with its use. The objective was to present the case of a patient with a history of allergic reaction to midazolam, who presented bronchospasm due to the administration of this drug, and who received unconventional treatment with positive outcomes. Clinical case: We present the case of a young female with a history of allergies to medicines, specifically to benzodiazepines, who presented bronchospasm and oxygen saturation drop after receiving a dose of midazolam into her eye while she was working. The use of ketamine was proposed after adrenaline, a beta-agonist, inhaled anticholinergics, a steroid and antihistamine drugs were used. Conclusion: Trials are needed in order to demonstrate the efficacy of ketamine in this particular context; however, the outcome in this case was positive.

Introducción: la ketamina es utilizada en anestesia intravenosa en el mantenimiento en la anestesia general. Su efecto cuenta con propiedades para prevenir la dificultad respiratoria asociada a broncoconstricción y la secreción de histamina asociada a crisis asmática. Estos efectos derivan de la acción directa en el músculo bronquial, así como de la potencialización de las catecolaminas, por lo que su uso muy controversial, ya que hasta el día de hoy no hay suficientes estudios que lo sustenten. Además, el efecto de la ketamina en el broncoespasmo debido a anafilaxia no está estudiado. El tratamiento de elección es la epinefrina y hay factores que están asociados en el éxito de esta. El objetivo fue presentar el caso de una paciente con antecedente de alergia a midazolam, que presentó broncoespasmo al estar en contacto con este y a la que se le administró tratamiento no convencional con resultados favorables. Caso clínico: presentamos el caso de una mujer joven con antecedentes de alergias a medicamentos, específicamente a benzodiacepinas, la cual presentó broncoespasmo y caída de la saturación posteriores al contacto con midazolam intraocular mientras laboraba. Se propuso la utilización de ketamina posterior a adrenalina, betaagonista y anticolinérgicos inhalados, esteroide y antihistamínico. Conclusión: es necesario hacer estudios que demuestren la eficacia de la ketamina en este contexto en particular; en este caso, los resultados fueron positivos.

A Case of Fatal Rhino-Orbital Mucormycosis Associated With New Onset Diabetic Ketoacidosis and COVID-19.

Mucormycosis is an invasive fungal infection, often acute and extremely severe, occurring in patients with an underlying condition. Coinfection in patients with coronavirus disease 2019 (COVID-19) has been reported, often bacterial. A 24-year-old female is presented with acute fatal rhino-orbital mucormycosis and COVID-19. We report one of the first cases of rhino-orbital mucormycosis and COVID-19. With this case, we highlight the importance of considering mycotic coinfection in COVID-19 patients with diabetes.

Síndrome de Wünderlich asociado a hemodiálisis / Wünderlich syndrome associated with hemodialysis

INTRODUCCIÓN. El Síndrome de Wunderlich es un hallazgo infrecuente en la práctica urológica, se caracteriza por dolor lumboabdominal intenso, inestabilidad hemodinámica y masa palpable en flanco ipsilateral (Triada de Lenk). En la mayoría de casos, la etiología es de origen tumoral (Angiomiolipoma); así como discrasias sanguíneas y enfermedad renal quística adquirida, considerada como factor de riesgo para que ocurra hemorragia espontánea en pacientes con hemodiálisis a largo plazo. La tomografía computarizada es el examen de imagen estándar para el diagnóstico; el tratamiento va desde el manejo conservador hasta nefrectomía de emergencia. CASO CLÍNICO. Paciente masculino de 29 años con antecedentes de Hidrocefalia y Enfermedad Renal Crónica estadio IV, en tratamiento con Hemodiálisis. Acudió por dolor abdominal y descenso de valores de he-moglobina. RESULTADOS. En Urotomografía simple/contrastada se reportó hematoma retroperitoneal, por lo que se realizó una nefrectomía simple, se encontró un hematoma más trauma renal grado V. El paciente falleció en el posquirúrgico. DISCUSIÓN. Se han reportado algunos casos de Síndrome de Wunderlich relacionados a hemodiálisis que se acompañaron de dolor abdominal intenso, y se sospechó de esta patología. CONCLU-SIÓN. El diagnóstico temprano y tratamiento oportuno en el Síndrome de Wünderlich fue crucial para el manejo médico del paciente.

INTRODUCTION. Wunderlich Syndrome is an infrequent finding in urological practi-ce, it ́s characterized by intense lumbo-abdominal pain, hemodynamic instability and palpable mass in the ipsilateral flank (Lenk's Triad). In most cases, the etiology is of tumor origin (Angiomyolipoma); as well as blood dyscrasias and acquired cystic kidney disease, considered a risk factor for spontaneous bleeding in patients with long-term hemodialysis. Computed tomography is the standard imaging test for diag-nosis; Treatment ranges from conservative management to emergency nephrectomy. CLINICAL CASE. 29-year-old male patient with a history of Stage IV Hydrocephalus and Chronic Kidney Disease, undergoing treatment with hemodialysis. He came for abdominal pain and decreased hemoglobin values. RESULTS. A simple / contrasted urotomography revealed retroperitoneal hematoma, for which a simple nephrectomy was performed, a hematoma plus grade V renal trauma was found. The patient died postoperatively. DISCUSSION. Some cases of Wunderlich Syndrome related to he-modialysis that were accompanied by severe abdominal pain have been reported, and this pathology was suspected. CONCLUSION. Early diagnosis and timely treat-ment in Wünderlich Syndrome was crucial for the medical management of the patient.

La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias / Melatonin as a neuronal differentiation factor: therapeutic implications for dementia

Dementias are progressive and neurodegenerative neuropsychiatry disorders, with a high worldwide prevalence. These disorders affect memory and behavior, causing impairment in the performance of daily activities and general disability in the elders. Cognitive impairment in these patients is related to anatomical and structural alterations at cellular and sub-cellular levels in the Central Nervous System. In particular, amyloid plaques and neurofibrillar tangles have been defined as histopathological hallmarks of Alzheimer's disease. Likewise, oxidative stress and neuroinflammation are implicated in the etiology and progression of the disease. Neuronal precursors from human olfactory neuroepithelium have been recently characterized as an experimental model to identify neuropsychiatric disease biomarkers. Moreover, this model not only allows the study of neuropsychiatric physiopathology, but also the process of neurodevelopment at cellular, molecular and pharmacological levels. This review gathers the evidence to support the potential therapeutic use of melatonin for dementias, based on its antioxidant properties, its anti-inflammatory effect in the brain, and its ability to inhibit both tau hyper-phosphorylation and amyloid plaque formation. Furthermore, since melatonin stimulates neurogenesis, and promotes neuronal differentiation by inducing the early stages of neuritogenesis and dendrite formation, it has been suggested that melatonin could be useful to counteract the cognitive impairment in dementia patients.

Las demencias son enfermedades neuropsiquiátricas, progresivas, neurodegenerativas y con una alta prevalencia a nivel mundial. Ocupan uno de los primeros lugares como enfermedades que causan incapacidad en los adultos mayores. En estos pacientes el Sistema Nervioso Central presenta alteraciones anatómico-estructurales a nivel celular y subcelular que se asocian con deficiencias cognitivas. En particular, en la enfermedad de Alzheimer se han caracterizado marcadores histopatológicos como las placas amiloides y las marañas neurofibrilares. Se sabe que el estrés oxidativo y la neuroinflamación participan en la etiología y el desarrollo de la enfermedad. Recientemente se caracterizó a los precursores neuronales del neuroepitelio olfatorio humano como un modelo experimental adecuado para identificar biomarcadores de rasgo y para estudiar la fisiopatología de diversas enfermedades neuropsiquiátricas, así como el proceso del neurodesarrollo, a nivel celular, molecular y farmacológico. En este trabajo se presenta la evidencia que sustenta que la melatonina puede ser útil en el tratamiento de las demencias, por su capacidad antioxidante, por su efecto anti-inflamatorio, así como por el efecto inhibidor de la hiperfosforilación de la proteina tau y de la formación de placas amiloides. Además, al estimular la formación de nuevas neuronas, la neuritogénesis en sus etapas tempranas y la formación de dendritas, la melatonina podría contribuir a contrarrestar la pérdida de las funciones cognitivas que se observa en estos padecimientos.

Age-related decrease in adenovirus-specific T cell responses.

Infections with persistent viruses, such as cytomegalovirus (CMV) or adenovirus, are not, in general, clinically apparent but may cause serious complications in the immunocompromised host. As has been shown for CMV, the cellular arm of the immune response is essential in controlling viral replication. However, cellular immunity toward adenoviruses has not been well characterized in humans. The aim of the present study was the quantitative and functional analysis of adenovirus-specific T cell responses from 171 healthy individuals and 59 long-term renal transplant recipients by use of flow-cytometric, as well as standard proliferation and enzyme-linked immunosorbant, assays. Adenovirus-specific immunity is dominated by CD4 T cells with memory/effector phenotype. Of interest, the frequency of adenovirus-specific T cells decreases significantly with age. This age-related decline indicates the eventual elimination of adenoviruses within a lifetime that may explain the well-known clinical observation of a predominant incidence of adenoviral complications in children and young adults, compared with older adults, after transplantation.

Sylvatic focus of American Trypanosomiasis in the State of Morelos, Mexico

Wild vectors and reservoir hosts of Trypanosoma cruzi were surveyed from February 1993 to June 1994 in Ticumßn (18 degrees 46'N, 99 degrees 07'W), Mexico (Deciduous Tropical Forest). Direct faeces examination showed that 87 of Triatoma pallidipennis hosted the parasite; T. cruzi forms were present in cultures inoculated with faeces of fifty 67 triatomine bugs and thirty CD-1 strain mice (10 d old) inoculated (peritoneum) with faeces of positive insects T. cruzi amastigotes were found in heart 67, kidneys 47, liver 80, lungs 50, oesophagus 60, skin 23, spleen 73 and stomach 60. T. cruzi was isolated by direct blood examination from seven 21 chiropterans and five 38 rodents and T. cruzi forms were present in cultures inoculated with blood of twenty-three 68 chiropterans and seven 54 rodents and T. cruzi amastigotes were seen in the kidneys of one 3 chiropterans and four 31 rodents and only in one Pteronotus parnellii mexicanus, organisms were seen in skin 2. There was no association between organs and T. cruzi infection (p > 0.05).

Gestión de producción en la planta de elaboración de filtros de la Compañia Industrial de Tabacos S.A.

El objetivo general del estudio es aplicar las técnicas de la ingeniería industrial en el sistema de producción de la Compañia Industrial de Tabacos S.A. para obtener niveles de eficiencia y calidad productiva en la planta de producción de filtros. Los objetivos específicos: Se pretende realizar un estudio de tiempos y movimientos a fin de determinar tiempos estándar de producción para la planta de producción de filtros de C.I.T.S.A. Realizar un análisis de la planta a fin de aplicar el estudio de métodos, determinando así el número de personas requeridas en el proceso de producción de filtros. A través del control estadístico de la calidad, determinar estándares en cada uno de los tipos de filtros, así como métodos de muestreo para un control eficiente. Diseñar un plan de producción con base en un análisis de la demanda para satisfacer los requerimientos del mercado. Establecer los niveles de inventario de materia prima como de producto en proceso para garantizar el abastecimiento de filtros en la producción de cigarrillos.