Long noncoding RNA MALAT1 in dermatologic disorders: a comprehensive review.

Dermatologic disorders, affecting the integumentary system, involve diverse molecular mechanisms such as cell proliferation, apoptosis, inflammation and immune responses. Long noncoding RNAs, particularly Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1), are crucial regulators of gene expression. MALAT1 influences inflammatory responses, immune cell function and signaling pathways, impacting various physiological and pathological processes, including dermatologic disorders. Dysregulation of MALAT1 is observed in skin conditions like psoriasis, atopic dermatitis and systemic lupus erythematosus. However, its precise role remains unclear. This review consolidates knowledge on MALAT1's impact on skin biology and pathology, emphasizing its potential diagnostic and therapeutic implications in dermatologic conditions.

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Modulator Effect of AT1 Receptor Knockdown on THP-1 Macrophage Proinflammatory Activity.

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.

Effect of mycobacterial proteins that target mitochondria on the alveolar macrophages activation during Mycobacterium tuberculosis infection.

Purpose of the study: During the early and progressive (late) stages of murine experimental pulmonary tuberculosis, the differential activation of macrophages contributes to disease development by controlling bacterial growth and immune regulation. Mycobacterial proteins P27 and PE_PGRS33 can target the mitochondria of macrophages. This study aims to evaluate the effect of both proteins on macrophage activation during mycobacterial infection. Materials and methods: We assess both proteins for mitochondrial oxygen consumption, and morphological changes, as well as bactericide activity, production of metabolites, cytokines, and activation markers in infected MQs. The cell line MH-S was used for all the experiments. Results: We show that P27 and PE_PGRS33 proteins modified mitochondrial dynamics, oxygen consumption, bacilli growth, cytokine production, and some genes that contribute to macrophage alternative activation and mycobacterial intracellular survival. Conclusions: Our findings showed that these bacterial proteins partially contribute to promoting M2 differentiation by altering mitochondrial metabolic activity.

La Medicina Natural y Tradicional en el tratamiento de la hipertensión arterial / Natural and Traditional Medicine in the treatment of high blood pressure

La Hipertensión Arterial es la enfermedad que se produce cuando las cifras de tensión arterial, medidas como promedio en tres tomas realizadas en condiciones apropiadas, con intervalos de tres a siete días entre cada toma, se encuentran por encima de 140mmHg de tensión arterial sistólica y 90mmHg de tensión arterial diastólica. Tratar la Hipertensión Arterial mediante las diferentes técnicas de la Medicina Natural y Tradicional tiene una gran importancia ya que se evitan de cierto modo los efectos adversos de los fármacos en los pacientes. La presente revisión bibliográfica tuvo como objetivo describir la aplicación de las diferentes técnicas de la Medicina Natural y Tradicional en el tratamiento de la Hipertensión Arterial como enfermedad crónica no trasmisible. Se realizó una exhaustiva revisión documental (bases de datos PubMed, SciELO Regional, Cochrane e infomed), de las cuales se escogieron 11 referencias bibliográficas. Se concluyó que El uso adecuado de estos métodos y técnicas terapéuticas amplía significativamente las posibilidades de los profesionales de la salud cubanos en el tratamiento de los pacientes, a la vez que recurrir a tales recursos contribuye a disminuir el uso de fármacos sintéticos y otros procedimientos más invasivos

The Cholinergic System Contributes to the Immunopathological Progression of Experimental Pulmonary Tuberculosis.

The cholinergic system is present in both bacteria and mammals and regulates inflammation during bacterial respiratory infections through neuronal and non-neuronal production of acetylcholine (ACh) and its receptors. However, the presence of this system during the immunopathogenesis of pulmonary tuberculosis (TB) in vivo and in its causative agent Mycobacterium tuberculosis (Mtb) has not been studied. Therefore, we used an experimental model of progressive pulmonary TB in BALB/c mice to quantify pulmonary ACh using high-performance liquid chromatography during the course of the disease. In addition, we performed immunohistochemistry in lung tissue to determine the cellular expression of cholinergic system components, and then administered nicotinic receptor (nAChR) antagonists to validate their effect on lung bacterial burden, inflammation, and pro-inflammatory cytokines. Finally, we subjected Mtb cultures to colorimetric analysis to reveal the production of ACh and the effect of ACh and nAChR antagonists on Mtb growth. Our results show high concentrations of ACh and expression of its synthesizing enzyme choline acetyltransferase (ChAT) during early infection in lung epithelial cells and macrophages. During late progressive TB, lung ACh upregulation was even higher and coincided with ChAT and α7 nAChR subunit expression in immune cells. Moreover, the administration of nAChR antagonists increased pro-inflammatory cytokines, reduced bacillary loads and synergized with antibiotic therapy in multidrug resistant TB. Finally, in vitro studies revealed that the bacteria is capable of producing nanomolar concentrations of ACh in liquid culture. In addition, the administration of ACh and nicotinic antagonists to Mtb cultures induced or inhibited bacterial proliferation, respectively. These results suggest that Mtb possesses a cholinergic system and upregulates the lung non-neuronal cholinergic system, particularly during late progressive TB. The upregulation of the cholinergic system during infection could aid both bacterial growth and immunomodulation within the lung to favor disease progression. Furthermore, the therapeutic efficacy of modulating this system suggests that it could be a target for treating the disease.

Decreased Quality of Life in Individuals with Type 2 Diabetes Mellitus Is Associated with Emotional Distress.

Background: individuals with type 2 diabetes show emotional distress as they learn how to cope with the disease. The emotional distress increases the possibility of complications in these patients. The aims of the present study were to evaluate the impact of the emotional distress in the quality of life of individuals with diabetes, and to investigate the demographic and clinical characteristics associated with the emotional distress of living with diabetes in a Mexican population. Methods: a total of 422 Mexican individuals with type 2 diabetes were recruited from the outpatient Diabetes Clinic of the Hospital Regional de Alta Especialidad Dr. Gustavo A. Rovirosa of Villahermosa, Tabasco. Demographic and clinical characteristics along with quality of life (SF-36) were assessed in these individuals. The emotional distress of living with diabetes was measured using the 5-item Problem Areas in Diabetes. Patients were divided according to the presence of high or low distress. Results: we identified that 31.8% (n = 134) of patients presented high diabetes-related emotional distress. We observed that hepatic diseases as comorbidities (p = 0.008) and diagnosis of major depression (p = 0.04) are factors associated with the emotional distress of living with diabetes. These patients showed a reduced quality of life in all dimensions (p < 0.001); the most affected dimensions were physical role (d = 0.37) and general health (d = 0.89) showing lower scores in comparison with patients with low emotional distress. Conclusions: our results suggest that Mexican individuals with type 2 diabetes mellitus show high emotional distress living with the disease and have a decreased quality of life. Therefore, it is necessary to decrease factors associated with the high emotional distress of living with diabetes in patients with type 2 diabetes.

Vortioxetine versus sertraline in metabolic control, distress and depression in Mexican patients with type 2 diabetes.

BACKGROUND: Depression in patients with type 2 diabetes (T2D) is often undiagnosed and remains untreated, leading to poor therapy adherence and ill health-related outcomes. We evaluated the effect of vortioxetine versus sertraline in the treatment of depression, distress and metabolic control in subjects with T2D and depression. METHODS: Participants were selected from the Clinic for Diabetes, diagnosed with depression when the score was ≥14 in the Hamilton Depression Rating Scale, and verified by a psychiatrist in agreement with the DSM-5 instrument (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). The criteria for recruitment also included glycosylated hemoglobin ≥7.5%, 18 to 60 years of age, and written informed consent. Pharmacological treatment for depression was assigned randomly: vortioxetine (10 mg/day) or sertraline (75 mg/day) for 8 weeks. Biochemical parameters, anthropometric measures and depression symptoms were evaluated after antidepressant treatment. This was a randomized singled-blind study. RESULTS: Subjects that met the inclusion criteria were 50, of which only 21 patients with T2D and depression finished the treatment. Vortioxetine and sertraline showed partial remission of depression. Vortioxetine showed a major effect size in glycosylated hemoglobin and a moderate effect size on weight loss, fasting plasma glucose (FPG), cholesterol and triacylglycerol levels. On the other hand, patients treated with sertraline presented a slight increase in body weight, body mass index (BMI), and in all biochemical markers. CONCLUSIONS: Vortioxetine may ameliorate depressive symptoms and metabolic control in patients with T2D and depression. Trial registration number: NCT03978286.

Serum Zinc Levels in Hidradenitis Suppurativa: A Case-Control Study.

BACKGROUND: Serum zinc levels in patients with hidradenitis suppurativa (HS) have not been previously studied. OBJECTIVE: The aim was to investigate the association between HS and serum zinc levels. METHODS: A multicenter, prospective clinical and analytical case-control study was designed to assess the possible association between HS and serum zinc levels. Consecutive patients with moderate or severe HS (Hurley II or III exclusively) were enrolled. A control population was recruited from primary care clinics. Fasting blood samples were extracted from each patient and serum zinc levels determined. Candidate predictors for low serum zinc levels were determined using logistic regression models. RESULTS: In total, 122 patients with HS and 122 control subjects were studied. Of the 122 HS patients, 79 (64.8%) were Hurley II and 43 (35.2%) were Hurley III. Low serum zinc levels (≤ 83.3 µg/dL) were more prevalent in HS (adjusted odds ratio [ORa] 6.7, P < 0.001). After logistic regression analysis, low serum zinc levels were associated with Hurley III (ORa 4.4, P < 0.001), Dermatology Life Quality Index ≥ 9 (ORa 3.1, P = 0.005), number of affected sites ≥ 3 (ORa 2.4, P = 0.042), genital location (ORa 2.9, P = 0.009), and perineal location (ORa 2.5, P = 0.025). CONCLUSION: Low serum zinc levels are more prevalent in HS than in a healthy population, an indicator that may also be associated with disease severity.

Cutaneous Metastases From Malignant Mesothelioma of the Tunica Vaginalis Testis.

Mesotheliomas are uncommon tumors arising from mesothelial cells lining the serous membranes of the pleura, pericardium, peritoneum, and tunica vaginalis testis. Less than 100 cases arising from the tunica vaginalis testis have been published and, to our knowledge, only 5 cases of cutaneous involvement from these tumors have been reported. We report an additional case with fatal outcome. A 93-year-old man presented with multiple polypoid nodules on the left scrotum. Ulceration was also present, and a firm 5-cm palpable testicular mass was also found. The patient had been exposed to asbestos for 40 years. Histologic examination of a skin biopsy from one of the nodules showed diffuse dermal infiltration of markedly atypical cuboidal cells, with polymorphous and hyperchromatic nuclei. Mitotic figures were common. These cuboidal cells lined clefts, forming a tubular and micropapillary pattern throughout papillary and reticular dermis. Immunohistochemical study showed strong nuclear and cytoplasmic positivity for calretinin, epithelial membrane antigen (cytoplasmic), and cytokeratin-7 (cytoplasmic) and nuclear positivity for Wilms tumor-1. These findings were consistent with cutaneous infiltration from malignant mesothelioma of the tunica vaginalis testis. Treatment of this rare tumor remains challenging because there are currently no recommended guidelines, but radical inguinal orchiectomy is an optimal choice.

Tafazzin splice variants and mutations in Barth syndrome.

Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28. The human tafazzin gene produces four major mRNA splice variants; two of which have been shown to be functional (TAZ lacking exon 5 and full-length) in complementation studies with yeast and Drosophila. This study characterizes the multiple alternative splice variants of TAZ mRNA and their proportions in blood samples from a cohort of individuals with Barth syndrome (BTHS). Because it has been reported that collection and processing methods can affect the expression of various genes, we tested and chose a stabilizing medium for collecting, shipping and processing of the blood samples of these individuals. In both healthy controls and in BTHS individuals, we found a greater variety of alternatively spliced forms than previously described, with a sizeable proportion of minor splice variants besides the four dominant isoforms. Individuals with certain exonic and intronic splice mutations produce additional mutant mRNAs that could be translated into two or more proteins with different amino acid substitutions in a single individual. A fraction of the minor splice variants is predicted to be non-productive.

A Novel Exonic Splicing Mutation in the TAZ (G4.5) Gene in a Case with Atypical Barth Syndrome.

OBJECTIVE: Barth syndrome is an X-linked recessive disorder characterized by dilated cardiomyopathy, neutropenia, 3-methylglutaconic aciduria, abnormal mitochondria, variably expressed skeletal myopathy, and growth delay. The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28. We report a novel exonic splicing mutation in the TAZ gene in a patient with atypical Barth syndrome. PATIENT & METHODS: The 4-month-old proband presented with respiratory distress, neutropenia, and dilated cardiomyopathy with reduced ejection fraction of 10%. No 3-methylglutaconic aciduria was detected on repeated urine organic acid analyses. Family history indicated that his maternal uncle died of endocardial fibroelastosis and dilated cardiomyopathy at 26 months. TAZ DNA sequencing, mRNA analysis, and cardiolipin analysis were performed. RESULTS: A novel nucleotide substitution c.553A>G in exon 7 of the TAZ gene was identified in the proband, predicting an amino acid substitution p.Met185Val. However, this mutation created a new splice donor signal within exon 7 causing mis-splicing of the message, producing two messages that only differ in the presence/absence of exon 5; these retain intron 6 and have only 11 bases of exon 7. Cardiolipin analysis confirmed the loss of tafazzin activity. The proband's mother, maternal aunt, and grandmother carry the same mutation. CONCLUSIONS: The identification of a TAZ gene mutation, mRNA analysis, and monolysocardiolipin/cardiolipin ratio determination were important for the diagnosis and genetic counseling in this family with atypical Barth syndrome that was not found to be associated with 3-methylglutaconic aciduria.

Barth syndrome.

First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.

A homozygous double mutation in SMN1: a complicated genetic diagnosis of SMA.

Spinal muscular atrophy (SMA), the most common autosomal recessive cause of infant death, is typically diagnosed by determination of SMN1 copy number. Approximately 3-5% of patients with SMA retain at least one copy of the SMN1 gene carrying pathogenic insertions, deletions, or point mutations. We report a patient with SMA who is homozygous for two mutations carried in cis: an 8 bp duplication (c.48_55dupGGATTCCG; p.Val19fs*24) and a point mutation (c.662C>T; p.Pro221Leu). The consanguineous parents carry the same two mutations within one SMN1 gene copy. We demonstrate that a more accurate diagnosis of the disease is obtained through a novel diagnostic assay and development of a capillary electrophoresis method to determine the copy number of their mutant alleles. This illustrates the complexity of SMN mutations and suggests additional testing (gene sequencing) may be appropriate when based on family lines.

Bioinformatic identification of Mycobacterium tuberculosis proteins likely to target host cell mitochondria: virulence factors?

BACKGROUND: M. tuberculosis infection either induces or inhibits host cell death, depending on the bacterial strain and the cell microenvironment. There is evidence suggesting a role for mitochondria in these processes.On the other hand, it has been shown that several bacterial proteins are able to target mitochondria, playing a critical role in bacterial pathogenesis and modulation of cell death. However, mycobacteria-derived proteins able to target host cell mitochondria are less studied. RESULTS: A bioinformaic analysis based on available genomic sequences of the common laboratory virulent reference strain Mycobacterium tuberculosis H37Rv, the avirulent strain H37Ra, the clinical isolate CDC1551, and M. bovis BCG Pasteur strain 1173P2, as well as of suitable bioinformatic tools (MitoProt II, PSORT II, and SignalP) for the in silico search for proteins likely to be secreted by mycobacteria that could target host cell mitochondria, showed that at least 19 M. tuberculosis proteins could possibly target host cell mitochondria. We experimentally tested this bioinformatic prediction on four M. tuberculosis recombinant proteins chosen from this list of 19 proteins (p27, PE_PGRS1, PE_PGRS33, and MT_1866). Confocal microscopy analyses showed that p27, and PE_PGRS33 proteins colocalize with mitochondria. CONCLUSIONS: Based on the bioinformatic analysis of whole M. tuberculosis genome sequences, we propose that at least 19 out of 4,246 M. tuberculosis predicted proteins would be able to target host cell mitochondria and, in turn, control mitochondrial physiology. Interestingly, such a list of 19 proteins includes five members of a mycobacteria specific family of proteins (PE/PE_PGRS) thought to be virulence factors, and p27, a well known virulence factor. P27, and PE_PGRS33 proteins experimentally showed to target mitochondria in J774 cells. Our results suggest a link between mitochondrial targeting of M. tuberculosis proteins and virulence.

Nivel de autoestima de adolescentes escolarizados en zona rural de Pereira, Colombia / Self-esteem Level in Scholarized Adolescents of the Rural Area of Pereira, Colombia

Objetivo: Evaluar el nivel de autoestima de adolescentes escolarizados en un colegio rural de un corregimiento de Pereira. Métodos: Se convocó a los estudiantes a participar, 292 aceptaron desarrollar la encuesta, mientras 20 se abstuvieron de hacerlo. Resultados: Previo análisis de confiabilidad del test, se encontró que 47,9% de los estudiantes presentaron una baja y muy baja autoestima. Un modelo multivariado reportó que la autoestima se reducía a medida que aumentaba la edad. Conclusiones: La comunidad académica y la familia deben interactuar a favor de un buen nivel de autoestima en los adolescentes…

Objective: To assess the level of self-esteem of adolescents in a rural school of a district of Pereira. Methods: Students were called upon to participate, 292 agreed to undergo the test, while 20 abstained. Results: After a previous reliability test analysis, we found that 47.9% of students had low and very low self esteem. A multivariate model reported that self-esteem was reduced as age increased. Conclusions: The academic community and the family must work together in order to improve self-esteem among teenagers in general…

[Self-esteem Level in Scholarized Adolescents of the Rural Area of Pereira, Colombia]. / Nivel de autoestima de adolescentes escolarizados en zona rural de Pereira, Colombia.

OBJECTIVE: To assess the level of self-esteem of adolescents in a rural school of a district of Pereira. METHODS: Students were called upon to participate, 292 agreed to undergo the test, while 20 abstained. RESULTS: After a previous reliability test analysis, we found that 47.9% of students had low and very low self esteem. A multivariate model reported that self-esteem was reduced as age increased. CONCLUSIONS: The academic community and the family must work together in order to improve self-esteem among teenagers in general.

Manual de prácticas obstétricas para la atención primaria de salud / Obstetrics practice manual for primary health care

Para reducir los errores en el proceso de atención de las mujeres en edad fértil, y embarazadas, la capacitación tiene que ser permanente. Por ello, este Manual, aunque está lejos de pretender ser un libro acabado de Obstetricia, tiene como objetivo esencial brindar un instrumento de trabajo a los médicos de familia, quienes se encuentran en la primera línea de atención a las mujeres y embarazadas cienfuegueras. Tiene como fundamento la última versión del Consenso de Obstetricia, en circulación este año, y cuenta además con la revisión de varios compañeros especialistas que se desempeñan en diferentes perfiles de la provincia(AU)

In order to reduce errors in the process of care for both women in childbearing age and pregnant women, professionals training needs to be permanent. Therefore, this Manual, though far from pretending to be a finished Obstetrics book, aims to provide an essential working tool for family doctors, who are in the front line of confrontation with the health of women in general and more specifically with pregnant women in Cienfuegos. It is based on the latest version of the Obstetrics Consensus, circulating this year, and includes also a review on the statements of several specialists colleagues who work in different profiles in the province(AU)