Chikungunya virus antagonizes cGAS-STING mediated type-I interferon responses by degrading cGAS.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-ß transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.

The electronic nose as a rule-out test for tuberculosis in an indigenous population.

INTRODUCTION: To end the tuberculosis (TB) epidemic, efficient diagnostic tools are needed. In a previous calibration study, a portable 'point of care' electronic nose device (AeonoseTM ) proved to be a promising tool in a hospital setting. We evaluated this technology to detect TB in an indigenous population in Paraguay. METHODS: A total of 131 participants were enrolled. eNose results were compared with anamnesis, physical examinations, chest radiography and mycobacterial cultures in individuals with signs and symptoms compatible with TB. The eNose analysis was performed in two stages: first, the training with a combination of a previous study population plus 47 participants from the new cohort (total n = 153), and second, the 'blind prediction' of 84 participants. RESULTS: 21% of all participants (n = 131) showed symptoms and/or chest radiography abnormalities suspicious of TB. No sputum samples resulted culture positive for Mycobacterium tuberculosis complex. Only one patient had a positive smell print analysis. In the training model, the specificity was 92% (95% confidence interval (CI): 85%-96%) and the negative predictive value (NPV) was 95%. In the blind prediction model, the specificity and the NPV were 99% (95% CI: 93%-99%) and 100%, respectively. Although the sensitivity and positive predictive value of the eNose could not be assessed in this cohort due to the small sample size, no active TB cases were found during a one year of follow-up period. CONCLUSION: The eNose showed promising specificity and negative predictive value and might therefore be developed as a rule-out test for TB in vulnerable populations.

Experimental characterization of a biosensor based on a tapered optical fiber for kisspeptin detection.

This paper presents the development of a biosensor based on optical fiber, using a polyclonal antibody kisspeptin receptor as a biological recognition element that is connected to puberty onset and may also help to suppress metastasis in melanoma breast cancer. The fiber surface was chemically prepared to immobilize the antibody. The structural homogeneity of the biosensor, at each stage of the self-assembly, was characterized by Fourier transform infrared spectroscopy and by measurements of the transmission at the output of the biosensor. The morphological homogeneity analysis was performed by optical microscopy and scanning electron microscopy. The biosensor developed was checked to detect kisspeptin in brain tissues by spectral transmission using a superluminescent diode. The data were analyzed using principal component analysis. The interaction of the kisspeptin with its counterpart by means of the evolution of the transmission spectrum as a function of time was observed.

[Emergencies in oncological gynaecology]. / Urgencias en ginecología oncológica.

This article describes the signs for suspecting neoplasia that lead the patient to come to the Accident and Emergency Service, concentrating on genital bleeding, pelvic mass and vulvar pruritus. Patients can also come due to processes resulting from complications of the disease, such as urethral obstruction, carcinomatosis, ascites, thromboembolic processes, haemorrhages, constipation, nausea and vomiting, intestinal obstruction and pain. Finally, we describe complications that are secondary to the treatment, such as abdominal and inguinal lymphocele and post-radiotherapy enteritis and proctitis.

Giant mesenteric cyst from the small bowel mesentery in a young adult patient.

Mesenteric cysts are rare tumors, they can emerge from any part of the mesentery of the bowel from the duodenum to the rectum. Their symptomatology can mimic almost any abdominal disease making diagnosis troublesome. In some circumstances, these cysts can grow to considerable sizes making resection almost impossible since its size can compromise different structures. Surgery is the treatment of choice as complete resection is the only curative treatment. We present a case of a female patient, she suffered from recurrent episodes of abdominal pain mistaken as gastritis. After a profound evaluation, a giant mass in her abdomen was identified and successfully treated. Giant primary mesenteric cyst was the final diagnosis.

Percepción del comportamiento alimentario en los hogares de Cali para el primer trimestre de la cuarentena por COVID-19 en 2020 / Perception of feeding behavior in Cali homes during the first trimester of quarantine due to COVID-19 in 2020

Resumen Introducción: En 2020, la Organización Mundial de la Salud (OMS) declaró la emergencia de salud pública por SARS-CoV-21; el 11 de marzo de 2020 se notificó la pandemia global por COVID-19 y el gobierno colombiano decretó para todas las ciudades el aislamiento preventivo obligatorio2. Para el mes de mayo, Cali reportó 1635 casos de COVID confirmados y 85 fallecidos por un virus con un 4,95% de letalidad3. Lo anterior influenció de forma importante las rutinas alimentarias de las familias durante el primer trimestre del periodo de confinamiento. Considerando que esta situación era atípica en el país, era necesario describir la percepción del comportamiento alimentario durante este primer trimestre de aislamiento preventivo obligatorio en la ciudad de Cali, considerando las normas de bioseguridad establecidas para el periodo mencionado. Objetivo: Describir el comportamiento alimentario de 1814 familias en Cali durante el primer trimestre de aislamiento preventivo obligatorio. Metodología: Estudio cuantitativo, descriptivo transversal, con técnica de encuesta. Se aplicó un instrumento virtual compuesto por 28 ítems, que indagó el comportamiento alimentario de las familias. Discusión: Se encontró que el 95,1% de los hogares percibió escasez y aumento de precios en alimentos que componen la canasta alimentaria familiar, y el 67,2% de las familias estuvieron preocupadas por la alimentación. Hubo un aumento en el consumo de alimentos y se modificó el número de tiempos de comida/día. Los hábitos alimentarios, ingesta de refrescos y consumo de alcohol también se modificaron durante confinamiento. Conclusiones: Se puede afirmar que durante el primer trimestre de cuarentena por COVID-19 en Cali se modificó el comportamiento alimentario de las familias encuestadas, una de las razones estuvo relacionada con un cambio en los ingresos económicos, que afectó la cantidad de dinero disponible para alimentos. Durante este periodo se modificaron también los tiempos de comida y la variedad en la ingesta de alimentos. En general, se describieron aspectos que afectaron la seguridad alimentaria de las familias.

Abstract Introduction: In 2020, the World Health Organization (WHO) declared a public health emergency due to SARS-CoV-21. On March 11, 2020, the global pandemic due to COVID-19 was declared, with which the Colombian government decreed mandatory preventive isolation in the country2. In May, Cali reported 1,635 confirmed COVID cases and 85 deaths from a virus with a 4.95 % case fatality rate3. This situation affected families eating routines during this period. Considering that this situation was atypical in the country, it was necessary to describe the perception of feeding behavior during this first trimester of mandatory preventive isolation in the city of Cali, considering the biosafety standards established by the national government. Objetive: To describe the feeding behavior of 1,814 families in Cali during the first trimester of mandatory preventive isolation. Methodology: Cross-sectional, descriptive and quantitative study. A virtual instrument composed of 28 items was applied, which investigated the feeding behavior of the families. Convenience sampling. Results: The results show that the economic income of families, as well as the distribution of expenses within the home, were affected in the evaluated period. In addition, it was found that 95.1 % of households perceived shortages and price increases in foods that make up the family food basket; 67.2% of families were concerned about food. There was an increase in food consumption and the number of perhaps consider, meals per day was modified. Eating habits, soft drink intake and alcohol consumption also changed during confinement in the evaluated time. Conclusions: It can be affirmed families modified their feeding behaviors during the first quarter of quarantine due to COVID-19. Because the economic income of families was affected, the money available for food purchases was affected as well. During this time, perhaps consider: meal frequencies and, in general, the variety in food intake was also modified. Finally, the results suggest perhaps consider: a negative effect in the food security of families.

[Severe intoxication with verapamil]. / Intoxicación grave con verapamilo.

Calcium channel blockers are currently widely used to treat many cardiological alterations; however, overdose and poisoning have been associated with morbidity and mortality mainly in those patients with suicidal attempts. We report a case and review the pathophysiology of overdose, treatment, and prognosis.

Reactions of amino alcohols in superacid: the direct observation of dicationic intermediates and their application in synthesis.

[reaction: see text]. The chemistry of amino alcohols has been studied in superacidic media, and these compounds have been found to ionize cleanly to the dication intermediates. Several dicationic species have been directly observed by low-temperature 13C NMR, including those from epinephrine (adrenaline) and synephrine. Amino alcohols react (70-99% yields) with C6H6 in triflic acid (CF3SO3H) by electrophilic aromatic substitution.

The effect of tequila in the synaptonemal complex structure of mouse spermatocytes.

The effect of tequila in the synaptonemal complex (SC) of mouse spermatocytes was determined. We tested 3 dosages (2.1, 4.2 and 8.4 g/kg) administered in a single intraperitoneal inoculation. The frequency of SC alterations was established in pachytenic nuclei 5 days after the administration using a silver impregnation technique. Three types of alterations were observed (desynapses, breaks and multiaxials) and the rate of each alteration was compared with that obtained with appropriate controls, including cyclophosphamide (CP) (150 mg/kg). The results showed a significant increase induced by tequila only in the frequency of desynapses. This damage began at the second highest dose (4.2 g/kg). The other SC alterations were in the control range. CP, however, induced a significant increase in all 3 types of SC alterations.

[Immunoreactive urinary thromboxane B2 in experimental mesenteric thrombosis in dogs]. / Tromboxano B2 urinario inmunorreactivo en trombosis mesentérica experimental en perros.

Thromboxane B2 (TxB2) the stable metabolite of thromboxane A2 may be released as a response to ischemia. With the aim of investigating its role as an early diagnostic test in mesenteric thrombosis, immunoreactive TxB2 was measured in urine aliquotes in six sham operated dogs, nine dogs subjected to superior mesenteric artery ligation, and twelve dogs with superior mesenteric vein ligation. One hour urine volumes were collected before surgery and during the eight hours after the experimental procedures, and urinary osmolarities were also determined in each sample. Basal TxB2 levels were comparable in all groups. Although all groups showed a significant and rapid (one hour) increase in TxB2 as a response to surgery, in the controls it returned to normal after six hours, whereas in the rest a continuously increased production persisted throughout the study period. There was no difference in t-test comparisons depending on the sort of thrombosis. In spite of the urinary dilution induced during the study, a persistent increase in TxB2 excretion was found. We conclude that urinary TxB2 levels could prove useful in the early diagnosis of mesenteric ischemia.

[Effect of trace metals on cell morphology, enzyme activation, and production of citric acid in a strain of Aspergillus wentii]. / Efecto de metales traza sobre la morfología celular, actividad enzimática y producción de ácido cítrico en una cepa de Aspergillus wentii.

Data concerning the effect of very low concentrations of metals on citric acid production by microorganisms, as well as on the activity of enzymes presumptively involved in the process, are confuse. The bulk of information was obtained mainly studying selected strains of Aspergillus niger. Information concerning other citric acid producer filamentous fungi, such as A. wentii, is scanty. In the present article we report the effect of different cations on the growth pattern of A. wentii P1 as well as on the related citric acid production and the activity of several enzymes. It was found that without any addition to the culture medium the fungus developed a pelleted form of growth, pellets being about 1.5 mm in diameter. The citric acid yield was about 90%. The addition of Cu2+ impaired the sugar uptake, as well as the production of citric acid and biomass. The uptake of sugar increased in the presence of Zn2+, and there was a marked increase of the biomass production, which could account for the low citric acid production. The addition of Fe2+ impaired the citric acid production and, as sulfate, the sugar uptake. The presence of Fe3+ markedly impaired the citric acid production and increased the sugar uptake. There is no agreement about the enzymes involved in the accumulation of citric acid by microorganisms. In spite of this, aconitase (Ac), isocitrate lyase (IL), isocitrate dehydrogenase NAD(+)-dependent (ICDH- NAD+) and isocitrate dehydrogenase NADP(+)-dependent (ICDH-NADP+) are often postulated as key enzymes. In our case, these enzymes were active during the standard fermentation, although with variations, particularly concerning Ac and IL. The behavior of enzymes might be different when tested in vivo or in vitro, mainly from the quantitative point of view. Nevertheless, the activity determined in vitro might give some indication concerning the effect on fermentation of substances present in the medium. It was found that all the enzymes tested increased their activity in the presence of Fe2+ and Fe3+. The addition of Cu2+ improved the activity of Ac, IL and ICDH-NADP+, while that of ICDH-NAD+ was impaired. The presence of Zn2+ decreased the activity of the enzymes excepting that of ICDH-NADP+ which increased. It must be pointed out that according to these results there are differences concerning the behavior of ICDH-NAD+ and ICDH-NADP+ in the presence of Cu2+ or Zn2+.

Caracterización y comparación de la actividad antibacteriana intrínseca del suero de búfalo y del suero de bovino

La actividad antibacteriana de los sueros de bovino y de búfalo fue evaluada in vitro de manera indirecta con dos reacciones de inmunohemólisis: (i) un ensayo de hemólisis-hemoaglutinación sobre eritrocitos no sensibilizados de conejo y (ii) un ensayo de cinética de eritrocitos no sensibilizados de conejo frente a concentraciones crecientes de suero. La actividad bactericida de los sueros fue evaluada in vitro cuantificando la reducción de desarrollo de un inóculo de Escherichia coli en medio de cultivo enriquecido con suero de ambas especies. En el ensayo de hemólisis-hemoaglutinación, la hemólisis máxima se observó hasta la dilución 1:16 del suero de ambas especies. El mayor porcentaje de hemólisis se obtuvo con el suero de búfalo (84,7 ± 9,71%) respecto del suero bovino (71,0 ± 5,05%). Sin embargo no se hallaron diferencias en las diluciones de suero necesarias para obtener el 50% de la hemólisis total, siendo estas de 10,2 ± 2,48 para el suero de bovinos y de 11,8 ± 2,18 para el suero de búfalo. El suero de búfalo redujo el desarrollo bacteriano en un 69,8% respecto del 47,2% obtenido por el suero de bovino. No obstante estos resultados, se necesitarán estudios adicionales para corroborar estos hallazgos in vivo.

The antibacterial activity of serum of bovine and buffaloes was evaluated in vitro indirectly by two immunohemolysis assays: (i) an unsensitized rabbit blood cells hemolysis-hemagglutination assay and (ii) and a hemolytic-kinetic of unsensitized rabbit blood cells in function of increasing serum concentrations. The serum bactericidal activity was evaluated in vitro by quantifying the reduction of the development of an Escherichia coli inoculum in a culture medium enriched with serum of both species. In the hemolysis-hemagglutination assay, the máximum haemolysis was observed until a 1:16 serum dilution for both species. The highest percentage of hemolysis was obtained with buffalo serum (84.7 ± 9.71%) with respect to bovine serum (71.0 ± 5.05%). However, no differences were found in the serum dilutions necessary to obtain 50% of the total hemolysis, being these 10.2 ± 2.48 for the serum of cattle and 11.8 ± 2.18 for the serum of buffalo. Buffalo serum reduced bacterial growth by 69.8% compared to 47.2% obtained by bovine serum. Despite these results, additional studies will be needed to corroborate these findings in vivo.

[Psychological impact of the diagnosis of Alzheimer's disease]. / Impacto psicológico del diagnóstico de la enfermedad de Alzheimer.

INTRODUCTION: The communication of the diagnosis of Alzheimer's disease (AD) may represent important emotional distress for the patient and his/her caregiver. This present work aimed to investigate if the disclosure of the diagnosis generates any emotional or psychological impact on the patient or his/her caregiver. PATIENTS AND METHODS: Thirty-three consecutive AD patients (NINCDS/ADRDA criteria) and their main caregivers were evaluated before and after the diagnosis disclosure. Patients were evaluated with the Neuropsychiatric Inventory Questionnaire (NPI-Q) and the Geriatric Depression Scale (GDS) and caregivers were evaluated with Beck's Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), the stress subscale from the NPI-Q and Zarit's burden interview. RESULTS: A total of 26 patients wanted to receive the diagnosis. AD diagnosis disclosure did not produce any significant clinical or emotional changes in the patient. On the contrary, the caregivers were significantly affected by AD diagnosis disclosure. This was reflected on the BDI scores, that increased from 6.9+/-6.5 to 9.7+/-7.5 (p=0.003). CONCLUSIONS: AD diagnosis may be safely disclosed to the patient. However, the caregivers should be carefully followed-up since depressive symptoms are common after diagnosis disclosure.

Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection.

Major histocompatibility complex (MHC) class I-deficient and MHC class II-deficient mice lack functional CD8 T cells and CD4 T cells, respectively. These mice were evaluated for infection following oral administration of 10(7) Cryptosporidium parvum oocysts. MHC class II-deficient (but not MHC class I-deficient) mice dosed with C. parvum oocysts at 3 to 5 days of age remained infected 8 weeks postexposure. MHC class II-deficient mice exposed to C. parvum oocysts at 5 to 6 weeks of age were significantly more susceptible to infection than control mice (P < 0.0001).

Murine cytomegalovirus CC chemokine homolog MCK-2 (m131-129) is a determinant of dissemination that increases inflammation at initial sites of infection.

The murine cytomegalovirus CC chemokine homolog MCK-2 (m131-129) is an important determinant of dissemination during primary infection. Reduced peak levels of viremia at day 5 were followed by reduced levels of virus in salivary glands starting at day 7 when mck insertion (RM461) and point (RM4511) mutants were compared to mck-expressing viruses. A dramatic MCK-2-enhanced inflammation occurred at the inoculation site over the first few days of infection, preceding viremia. The data further reinforce the role of MCK-2 as a proinflammatory signal that recruits leukocytes to increase the efficiency of viral dissemination in the host.

[Anomalous response of antibodies in rash-causing viral infections]. / Respuesta anómala de anticuerpos de infecciones virales productoras de rash.

20 pairs of sera from the National System of Seroepidemiological Surveillance of the triple viral vaccine received in the laboratory with febrile rash diagnosis were studied. By using the hemagglutination inhibition test, it was observed an abnormal answer of antibodies to both rubella and measles through a falling of the antibody titre in one or both diseases, or in one of them with seroconversion to the other one. With the aim of defining the existence of a possible polyclonal activation already described in literature, it was decided to study the antibody response to family Herpesviridae (HSV, EBV, CMV, VZV). 80% of answer to these viruses were found. The results are submitted and discussed.

IL-4 protects adult C57BL/6 mice from prolonged Cryptosporidium parvum infection: analysis of CD4+alpha beta+IFN-gamma+ and CD4+alpha beta+IL-4+ lymphocytes in gut-associated lymphoid tissue during resolution of infection.

Resistance of adult C57BL/6 mice to severe Cryptosporidium parvum infection is dependent on CD4+alpha beta+ TCR lymphocytes. In this study, we demonstrated that treatment with anti-IFN-gamma mAb extended oocyst excretion 18 days longer, and anti-IL-4 mAb extended oocyst excretion at least 11 days longer than isotype control mAb treatment. Analysis of the specific activity of anti-IFN-gamma mAb present in treated mouse sera suggested that IFN-gamma may have a limited role in the resolution phase of infection. Changes were also documented in numbers of CD4+alpha beta+IFN-gamma+ and CD4+alpha beta+IL-4+ lymphocytes in Peyer's patches and intraepithelium of adult C57BL/6 mice during resolution of C. parvum infection. Resistance to initial severe infection was associated with CD4+alpha beta+IFN-gamma+ lymphocytes, and eventual resolution of infection was associated with CD4+alpha beta+IL-4+ lymphocytes. Analysis of cytokine expression following in vitro stimulation with C. parvum Ags during resolution of infection demonstrated consistent increases in CD4+alpha beta+IL-4+ lymphocytes, but not CD4+alpha beta+IFN-gamma+ lymphocytes. The relevance of CD4+alpha beta+IL-4+ lymphocytes in protection against C. parvum was then evaluated in C57BL/6 IL-4 gene knockout mice (IL-4(-/-)). Adult IL-4(-/-) mice excreted oocysts in feces approximately 23 days longer than IL-4(+/+) mice. Further, anti-IFN-gamma mAb treatment increased the severity and the duration of infection in IL-4(-/-) mice compared with those in IL-4(+/+) mice. Together, the data demonstrated that IFN-gamma was important in the control of severity of infection, and either IFN-gamma or IL-4 accelerated termination of infection. However, neither IL-4 nor IFN-gamma was required for the final clearance of infection from the intestinal tract of adult mice.