Post-COVID-19 syndrome, inflammation and insulin resistance: a retrospective cohort study.

BACKGROUND: COVID-19-induced diabetes is a novel and enigmatic disease. Our aim was to evaluate a possible relationship between post-COVID-19 syndrome (PCS) and increased insulin resistance (IR) in non-diabetic outpatients after mild COVID-19. METHODS: Repeated measures design. Three evaluations [1E (pre-COVID, baseline), 2E (3 months post-COVID) and 3E (21 months post-COVID)] were performed, directed to PCS+ and PCS- subjects. Triglyceride-glucose (TyG) index ≥8.74 was considered IR, and albumin-to-globulin ratio (AGR) <1.50, inflammation. RESULTS: We analyzed 112 individuals (median [IQR] age=44 [20] years, 58% women, 36 PCS+, 76 PCS-). PCS+ with very low basal IR (TyG <7.78, lowest quartile) showed a reduced inflammatory burden (basal AGR=1.81 [0.4] vs. 1.68 [0.2] in 2E; P=0.23), and increased TyG across evaluations (from basal 7.62 [0.2] to 8.29 [0.5]; P=0.018]. Conversely, PCS+ subjects with high basal TyG (TyG ≥8.65, highest quartile) did not show significant variations in TyG, but a greater inflammatory load (basal AGR=1.69 [0.3] vs. 1.44 [0.3] in 2E; P=0.10). In multivariable models addressing groups with reduced basal IR (TyG <8.01), PCS has been a consistent predictor for TyG, after adjusting for confounders. Partial correlation and multivariable analyses showed similarities involving acute polysymptomatic COVID-19 and PCS regarding IR. CONCLUSIONS: PCS was associated with increased IR, being more evident when the baseline degree of IR was very low. PCS and increased IR were separately associated with inflammation. Acute polysymptomatic COVID-19 and PCS could be clinical expressions of underlying inflammatory state, which in turn may also trigger IR.

Blood group O is associated with post-COVID-19 syndrome in outpatients with a low comorbidity index.

BACKGROUND: ABO blood group system modulates the inflammatory response and has been implicated in COVID-19. Group O protects against SARS-CoV-2 infection, but there are no data regarding post-COVID-19 syndrome (PCS). Our aim was to assess this possible association. METHODS: Case-control study in a community setting, with subjects who had experienced mild COVID-19. Cases were PCS+, controls were PCS-, and the exposure variable, group O. We collected age, sex, BMI, smoking, comorbidities, inflammatory markers, anti-SARS-CoV-2 IgG antibodies, blood type and clinical data. Five composite inflammatory indices were developed. Multivariate analyses were performed. RESULTS: We analysed 121 subjects (56.2% women), mean age 45.7 ± 16 years. Blood group frequencies were 41.5%, 7.9%, 5.9%, and 44.5% for A, B, AB and O, respectively. Thirty-six patients were PCS+, without significant differences between cases and controls. Compared to non-O, a higher prevalence of PCS (p = .036), and number of symptoms of PCS (p = .017) were noted in group O. Concerning biomarkers, PCS + and PCS- showed no differences in A, B, and AB groups. In contrast, group O PCS + patients had significantly lower albumin-to-globulin ratio and higher lymphocyte count, fibrinogen, CRP levels, and higher percentages of 3 composite indices, than PCS- subjects. Group O showed a 6-fold increased risk of PCS, compared to non-O (adjusted OR = 6.25 [95%CI, 1.6-23]; p = .007). CONCLUSIONS: Group O has shown a consistent relationship with PCS, characterised by a more intense inflammatory burden than the other blood groups. Blood group O could be part of the immunological link between acute COVID-19 and PCS.

Intestinal parasitosis in children from a rural Caribbean area in Colombia / Parasitosis intestinal en niños de una zona rural del Caribe de Colombia

Abstract In Colombia, the prevalence of intestinal parasitosis varies throughout its regions, social classes, and living conditions. We performed a cohort study (2017-2018) on children from 1-10 years old in El Cedro, Ayapel, Colombia. We tested a convenience sampling of those who accepted and signed the consent form. The National Intestinal Parasite Survey was applied; feces and water source sampling were tested for coprological and microbiology analysis, respectively. Education and pharmacologic treatment to the minor and co-inhabitants were performed. After the recruiting, we followed up at 7 and 12 months. Statistical analysis was performed using IBM® SPSS22. Participants 47, 61,7% male, average age 5,7 years. The caretakers had a low educational background. The monthly income of 72,3% of households was < USD 87. The coprological test showed 61,7% with at least one type of parasite; 32,2% with two or more. Trichuris trichiura was the most frequent. Water sources were positive for Escherichia coli. The population tested showed a high frequency of parasitic infection. We did not find a reduction of intestinal parasitosis with educa tion and pharmacologic treatment at the end of the follow-up. It must be necessary to impact social determinants of public health to achieve intestinal parasitosis control.

Resumen En Colombia, la prevalencia de parasitosis intestinal varía por regiones, clases sociales, condiciones de vida. Realizamos estudio de cohorte (2017-2018) en niños de 1-10 años en El Cedro, Ayapel, Colombia. Muestra por conveniencia, se incluyeron aquellos que aceptaron y firmaron el consentimiento. Se aplicó la Encuesta Nacional de Parásitos Intestinales; se analizaron muestras de heces y fuentes de agua para análisis coprológico y microbiológico, respectivamente. Se realizó educación y tratamiento farmacológico al menor y cohabitantes. Después del reclutamiento, seguimiento a los 7 y 12 meses. El análisis estadístico se realizó con IBM® SPSS22. Participantes 47, 61,7% hombres, promedio de edad 5,7 años. Cuidadores con bajo nivel educativo, ingreso mensual del 72,3% de los hogares fue <USD 87. La población analizada mostró una alta frecuencia de infección parasitaria, un 61,7% con al menos un tipo de parásito; 32,2% con dos o más. Trichuris trichiura fue el más frecuente. Las fuentes de agua fueron positivas para Escherichia coli. Al final del seguimiento, no se redujo la frecuencia de la parasitosis intestinal a pesar de educación y tratamiento farmacológico. Se requiere incidir en los determinantes sociales y de salud pública para lograr el control de las parasitosis intestinales.

Disclosing azole resistance mechanisms in resistant Candida glabrata strains encoding wild-type or gain-of-function CgPDR1 alleles through comparative genomics and transcriptomics.

The pathogenic yeast Candida glabrata is intrinsically resilient to azoles and rapidly acquires resistance to these antifungals, in vitro and in vivo. In most cases azole-resistant C. glabrata clinical strains encode hyperactive CgPdr1 variants, however, resistant strains encoding wild-type CgPDR1 alleles have also been isolated, although remaining to be disclosed the underlying resistance mechanism. In this study, we scrutinized the mechanisms underlying resistance to azoles of 8 resistant clinical C. glabrata strains, identified along the course of epidemiological surveys undertaken in Portugal. Seven of the strains were found to encode CgPdr1 gain-of-function variants (I392M, E555K, G558C, and I803T) with the substitutions I392M and I803T being herein characterized as hyper-activating mutations for the first time. While cells expressing the wild-type CgPDR1 allele required the mediator subunit Gal11A to enhance tolerance to fluconazole, this was dispensable for cells expressing the I803T variant indicating that the CgPdr1 interactome is shaped by different gain-of-function substitutions. Genomic and transcriptomic profiling of the sole azole-resistant C. glabrata isolate encoding a wild-type CgPDR1 allele (ISTB218) revealed that under fluconazole stress this strain over-expresses various genes described to provide protection against this antifungal, while also showing reduced expression of genes described to increase sensitivity to these drugs. The overall role in driving the azole-resistance phenotype of the ISTB218 C. glabrata isolate played by these changes in the transcriptome and genome of the ISTB218 isolate are discussed shedding light into mechanisms of resistance that go beyond the CgPdr1-signalling pathway and that may alone, or in combination, pave the way for the acquisition of resistance to azoles in vivo.

Post-COVID-19 syndrome, low-grade inflammation and inflammatory markers: a cross-sectional study.

OBJECTIVE: Post-COVID syndrome (PCS) is a poorly known entity. An underlying chronic, low-grade inflammation (LGI) has been theorized as a pathophysiological mechanism. Available data on biomarkers in PCS show conflicting results. Our aim was to know whether subjects with PCS present higher levels of inflammatory markers, after a mild COVID-19. METHODS: Analytical cross-sectional study. Cases of mild COVID-19 in a community setting were included. We collected epidemiological data (age, sex, BMI, smoking, comorbidities), variables of the acute COVID-19 (duration, symptoms), and data at 3 months after the acute phase (symptoms and laboratory test). Serum C-reactive protein (CRP), neutrophil and lymphocyte counts, neutrophil/lymphocyte ratio (NLR), lactate dehydrogenase, ferritin, fibrinogen, and D-dimer levels were analysed. LGI was defined as CRP >0.3 and <1.0 mg/dL. A subject was classified as PCS + if presented signs and symptoms >12 weeks after an infection consistent with COVID-19. Five composite indices (C1-C5) were developed, combining the upper ranges of biomarkers distributions. Multivariate analyses were performed. RESULTS: We analysed 121 mild COVID-19 cases (mean age = 45.7 years, 56.2% women). Among the acute symptoms, women presented a higher frequency of fatigue (54.4% vs 30.2%; p = .008). PCS affected 35.8% of women and 20.8% of men (p = .07), and the most reported symptoms were fatigue (42.8%), anosmia (40%), ageusia (22.8%), dyspnea (17.1%) and myalgia (11.4%). Neutrophil count, NLR, CRP and fibrinogen showed the best correlations with PCS and were selected to develop the indices. In women PCS+, C1, C3 and C4 indices were more frequently met, while in men PCS+, C2, C5 and CRP were in the range of LGI. Anosmia, ageusia and fatigue were related to higher neutrophil counts, with sex differences. Fibrinogen levels were higher in persistent myalgia (510 ± 82 mg/dL vs 394 ± 87; p = .013). In multivariable analysis, a woman with a neutrophil count above the median, or with fibrinogen level or NLR in the highest tertile, had a 4-5-fold increased risk of prevalent PCS. A man with CRP in the range of LGI, or fibrinogen level or a neutrophil count in the highest tertile, had a 10-17-fold increased risk of prevalent PCS. CONCLUSIONS: The data obtained in the present cross-sectional study seems to demonstrate a consistent association between PCS and upper ranges of the neutrophil count, NLR, fibrinogen, and CRP in the LGI range. Furthermore, composite indices appear useful in detecting relationships between slight elevations of biomarkers and PCS, and our study identifies relevant sex differences in symptoms and markers regarding the PCS.

Effect of Chitosan and Naringin on Enteric Methane Emissions in Crossbred Heifers Fed Tropical Grass.

In order to meet consumer needs, the livestock industry is increasingly seeking natural feed additives with the ability to improve the efficiency of nutrient utilization, alternatives to antibiotics, and mitigate methane emissions in ruminants. Chitosan (CHI) is a polysaccharide with antimicrobial capability against protozoa and Gram-positive and -negative bacteria, fungi, and yeasts while naringin (NA) is a flavonoid with antimicrobial and antioxidant properties. First, an in vitro gas production experiment was performed adding 0, 1.5, 3.0 g/kg of CHI and NA under a completely randomized design. The substrate containing forage and concentrate in a 70:30 ratio on a dry matter (DM) basis. Compounds increased the concentration of propionic acid, and a significant reduction in methane production was observed with the inclusion of CHI at 1.5 g/kg in in vitro experiments (p < 0.001). In a dry matter rumen degradability study for 96 h, there were no differences in potential and effective degradability. In the in vivo study, six crossbred heifers fitted with rumen cannulas were assigned to a 6 × 6 Latin square design according to the following treatments: control (CTL), no additive; chitosan (CHI1, 1.5 g/kg DMI); (CHI2, 3.0 g/kg DMI); naringin (NA1, 1.5 g/kg DMI); (NA2, 3.0 g/kg DMI) and a mixture of CHI and NA (1.5 + 1.5 g/kg DMI) given directly through the rumen cannula. Additives did not affect rumen fermentation (p > 0.05), DM intake and digestibility of (p > 0.05), and enteric methane emissions (p > 0.05). CHI at a concentration of 1.5 g/kg DM in in vitro experiments had a positive effect on fermentation pattern increasing propionate and reduced methane production. In contrast, in the in vivo studies, there was not a positive effect on rumen fermentation, nor in enteric methane production in crossbred heifers fed a basal ration of tropical grass.

VIPoma: a rare cause of diarrhea. A case report / VIPoma: una causa poco frecuente de diarrea. Case report

Abstract Introduction: Vasoactive intestinal peptide-secreting tumor (VIPoma) is a rare functional pancreatic neuroendocrine tumor (F-PNET) characterized by secretory diarrhea, hypokalemia, and hypochlorhydria. Its low incidence and high risk of malignancy pose a clinical challenge that requires a high degree of clinical suspicion. Case presentation: A 61-year-old woman visited the emergency department of a tertiary care hospital in Medellín, Colombia, due to chronic diarrhea (7 months) that led to dehydration, renal failure, metabolic acidosis, and hypokalemia. As a result, a treatment based on loperamide, intravenous fluids and broad-spectrum antibiotics was started. In addition, chromogranin A levels of 477 ug/L (<100) were reported, while an abdominal MRI showed a 33x30mm mass in the head and uncinate process of the pancreas, so outpatient surgical management was decided. However, three days after discharge, and due to the persistence of clinical signs, the patient was admitted to another hospital (also a tertiary care hospital), where, given the high suspicion of VIPoma, and once the diarrhea was solved, the mass was removed (Whipple procedure) without any complication. Finally, the diagnosis was confirmed based on serum vasoactive intestinal peptide levels (930 pg/mL (RV<75)) and the pathology report (PNET tumor grade 2). Two years after the surgery, the patient was asymptomatic, and no residual lesions or metastases were evident in a control MRI. Conclusion: Late diagnosis of VIPoma is associated with worsened quality of life, severe complications, and high prevalence of metastasis. Therefore, it should be suspected in patients with chronic secretory diarrhea that is not caused by an infection, since early diagnosis and timely treatment can contribute to achieving better survival rates in these patients.

Resumen Introducción. El tumor secretor de péptido intestinal vasoactivo o VIPoma es un tumor funcional neuroendocrino pancreático (F-PNET) raro caracterizado por diarrea secretora, hipokalemia e hipoclorhidria. Su baja incidencia y alto riesgo de malignidad representan un reto clínico que requiere un alto grado de sospecha clínica. Presentación del caso. Mujer de 61 años quien consultó al servicio de urgencias de un hospital de tercer nivel en Medellín, Colombia, por diarrea crónica (7 meses) que llevó a des-hidratación, falla renal, acidosis metabólica e hipokalemia, por lo que se inició manejo con loperamida, líquidos endovenosos y antibióticos de amplio espectro. Además, se reportaron niveles de cromogranina A de 477 ug/L (<100) y, mediante resonancia magnética (RM) abdominal, se identificó masa de 33x30mm en cabeza y proceso uncinado de páncreas, por lo que se decidió manejo quirúrgico ambulatorio. Sin embargo, tres días después del alta, la paciente ingresó, por persistencia de los signos, a un segundo hospital (también de tercer nivel), donde ante la alta sospecha de VIPoma, y una vez superada la diarrea, se extirpó la masa (procedimiento de Whipple). Finalmente, con base en los niveles séricos de péptido intestinal vasoactivo (930 pg/ml (VR<75)) y el informe de patología (tumor PNET grado 2), se confirmó el diagnóstico. Dos años después del procedimiento, la paciente se encontraba asintomática y sin evidencia de lesiones residuales ni metástasis en RM de control. Conclusión. El diagnóstico tardío de VIPoma se asocia con detrimento de la calidad de vida, complicaciones graves y alta prevalencia de metástasis, por lo que debe sospecharse en pacientes con diarrea crónica secretora no causada por infecciones, pues de diagnosticarse a tiempo e iniciarse el tratamiento oportuno se pueden lograr mejores tasas de supervivencia en estos pacientes.

Unexplained Anemia in the Elderly.

Anemia is frequently diagnosed in elderly patients, and it is a key indicator of many reactive and clonal conditions. Furthermore, the older age is the most common presenting age for myelodysplastic syndromes (MDS). Anemia in older age may be attributed to an inflammatory state due to senescence, comorbidities, nutritional deficiencies, or primary bone marrow conditions. As diagnostic possibilities and life expectancy increase, the prevalence of anemia of the elderly increases as well. The etiology has a direct impact on the treatment and quality of life of these patients, in whom is a usual clinical challenge as it may be due to a multifactorial origin. In a minority group, when no etiology is identified, it is classified as unexplained anemia (UA) or clonal cytopenia of unknown significance (CCUS). The underlying cause of anemia remains unexplained in 30% of cases, and a great part of unexplained cytopenia may account for myeloid neoplasms. Anemia in the elderly is associated with worse cognitive and functional outcomes and increased mortality.

Role of Secondary Plant Metabolites on Enteric Methane Mitigation in Ruminants.

The rumen microbiome plays a fundamental role in all ruminant species, it is involved in health, nutrient utilization, detoxification, and methane emissions. Methane is a greenhouse gas which is eructated in large volumes by ruminants grazing extensive grasslands in the tropical regions of the world. Enteric methane is the largest contributor to the emissions of greenhouse gases originating from animal agriculture. A large variety of plants containing secondary metabolites [essential oils (terpenoids), tannins, saponins, and flavonoids] have been evaluated as cattle feedstuffs and changes in volatile fatty acid proportions and methane synthesis in the rumen have been assessed. Alterations to the rumen microbiome may lead to changes in diversity, composition, and structure of the methanogen community. Legumes containing condensed tannins such as Leucaena leucocephala have shown a good methane mitigating effect when fed at levels of up to 30-35% of ration dry matter in cattle as a result of the effect of condensed tannins on rumen bacteria and methanogens. It has been shown that saponins disrupt the membrane of rumen protozoa, thus decreasing the numbers of both protozoa and methanogenic archaea. Trials carried out with cattle housed in respiration chambers have demonstrated the enteric methane mitigation effect in cattle and sheep of tropical legumes such as Enterolobium cyclocarpum and Samanea saman which contain saponins. Essential oils are volatile constituents of terpenoid or non-terpenoid origin which impair energy metabolism of archaea and have shown reductions of up to 26% in enteric methane emissions in ruminants. There is emerging evidence showing the potential of flavonoids as methane mitigating compounds, but more work is required in vivo to confirm preliminary findings. From the information hereby presented, it is clear that plant secondary metabolites can be a rational approach to modulate the rumen microbiome and modify its function, some species of rumen microbes improve protein and fiber degradation and reduce feed energy loss as methane in ruminants fed tropical plant species.

Reincorporación laboral de mujeres con cáncer de mama: experiencia de un centro oncológico en la ciudad de Medellín / Return to work after breast cancer: experience of an oncological referral centre in Medellín, Colombia

INTRODUCCIÓN: los avances en el diagnóstico y tratamiento del cáncer de mama han mejorado el pronóstico para estas pacientes, por lo tanto, se espera que un mayor número de supervivientes se enfrenten con el proceso de retornar al trabajo. El objetivo del presente estudio es analizar la frecuencia, la mediana del tiempo, así como los factores relacionados con el retorno al trabajo de pacientes con cáncer de mama, posterior al diagnóstico en un centro de referencia oncológico de la ciudad de Medellín, Colombia. MÉTODOS: estudio de cohorte retrospectiva realizado con los registros de pacientes con cáncer de mama (n = 141) atendidas un centro oncológico de referencia. Se midieron variables sociodemográficas, laborales, relacionadas con el tratamiento y de retorno al trabajo. RESULTADOS: la edad promedio al diagnóstico fue de 45.8 ± 9 años, La mayoría de las mujeres estaban en la premenopausia, el 45% realizaban trabajo manual. Los indicadores de mayor severidad de la enfermedad, así como el trabajo manual, la presencia de linfedema y un mayor número y días de incapacidad se relacionaron negativamente con el retorno al trabajo de estas pacientes. El 93% de las pacientes retornaron al trabajo. CONCLUSIONES: el retorno al trabajo después de un cáncer de mama difiere según la severidad de la enfermedad, factores relacionados con el tratamiento y tipo de trabajo

INTRODUCTION: Advances in the diagnosis and treatment of breast cancer have improved the prognosis for these patients. Consequently, a greater number of survivors are facing the process of returning to work. The objective of the present study was to analyze the frequency, median time and factors related to the return to work of patients with breast cancer, after diagnosis and completion of treatment at a cancer referral center in the city of Medellín, Colombia. METHODS: a retrospective cohort study was carried out with registries of patients with breast cancer (n = 141) from a reference cancer center. Sociodemographic, occupational, treatment variables and prevalence of return to work were measured. RESULTS: The average age at diagnosis was 45.8 ± 9 years, Most of the women were premenopausal, and 45% performed manual labour. Advanced disease stage, manual labour, the presence of lymphedema and a greater number of episodes and days of disability were negatively related to return to work. A total of 93% of patients returned to work. CONCLUSIONS: This study shows that return to work differs according to disease stage, treatment-related factors and type of work

[Return to work after breast cancer: experience of an oncological referral centre in Medellín, Colombia]. / Reincorporación laboral de mujeres con cáncer de mama: experiencia de un centro oncológico en la ciudad de Medellín.

INTRODUCTION: Advances in the diagnosis and treatment of breast cancer have improved the prognosis for these patients. Consequently, a greater number of survivors are facing the process of returning to work. The objective of the present study was to analyze the frequency, median time and factors related to the return to work of patients with breast cancer, after diagnosis and completion of treatment at a cancer referral center in the city of Medellín, Colombia METHODS: a retrospective cohort study was carried out with registries of patients with breast cancer (n = 141) from a reference cancer center. Sociodemographic, occupational, treatment variables and prevalence of return to work were measured. RESULTS: The average age at diagnosis was 45.8 ± 9 years, Most of the women were premenopausal,and 45% performed manual labour. Advanced disease stage, manual labour, the presence of lymphedema and a greater number of episodes and days of disability werenegatively related to return to work. A total of 93% of patients returned to work. CONCLUSIONS: This study shows that return to work differs according to disease stage, treatment-related factors and type of work.

INTRODUCCIÓN: los avances en el diagnóstico y tratamiento del cáncer de mama han mejorado el pronóstico para estas pacientes, por lo tanto, se espera que un mayor número de supervivientes se enfrenten con el proceso de retornar al trabajo. El objetivo del presente estudio es analizar la frecuencia, la mediana del tiempo, así como los factores relacionados con el retorno al trabajo de pacientes con cáncer de mama, posterior al diagnóstico en un centro de referencia oncológico de la ciudad de Medellín, Colombia. MÉTODOS: estudio de cohorte retrospectiva realizado con los registros de pacientes con cáncer de mama (n=141) atendidas un centro oncológico de referencia. Se midieron variables sociodemográficas, laborales, relacionadas con el tratamiento y de retorno al trabajo. RESULTADOS: la edad promedio al diagnóstico fue de 45.8 ±9 años. La mayoría de las mujeres estaban en la premenopausia, el 45% realizaban trabajo manual. Los indicadores de mayor severidad de la enfermedad, así como el trabajo manual, la presencia de linfedema y un mayor número y días de incapacidad se relacionaron negativamente con el retorno al trabajo de estas pacientes. El 93% de las pacientes retornaron al trabajo. CONCLUSIONES: el retorno al trabajo después de un cáncer de mama difiere según la severidad de la enfermedad, factores relacionados con el tratamiento y tipo de trabajo.

An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains.

Fungal infections and, in particular, those caused by species of the Candida genus, are growing at an alarming rate and have high associated rates of mortality and morbidity. These infections, generally referred as candidiasis, range from common superficial rushes caused by an overgrowth of the yeasts in mucosal surfaces to life-threatening disseminated mycoses. The success of currently used antifungal drugs to treat candidiasis is being endangered by the continuous emergence of resistant strains, specially among non-albicans Candida species. In this review article, the mechanisms of action of currently used antifungals, with emphasis on the mechanisms of resistance reported in clinical isolates, are reviewed. Novel approaches being taken to successfully inhibit growth of pathogenic Candida species, in particular those based on the exploration of natural or synthetic chemicals or on the activity of live probiotics, are also reviewed. It is expected that these novel approaches, either used alone or in combination with traditional antifungals, may contribute to foster the identification of novel anti-Candida therapies.

The Role of Chitosan as a Possible Agent for Enteric Methane Mitigation in Ruminants.

Livestock production is a main source of anthropogenic greenhouse gases (GHG). The main gases are CH4 with a global warming potential (GWP) 25 times and nitrous oxide (N2O) with a GWP 298 times, that of carbon dioxide (CO2) arising from enteric fermentation or from manure management, respectively. In fact, CH4 is the second most important GHG emitted globally. This current scenario has increased the concerns about global warming and encouraged the development of intensive research on different natural compounds to be used as feed additives in ruminant rations and modify the rumen ecosystem, fermentation pattern, and mitigate enteric CH4. The compounds most studied are the secondary metabolites of plants, which include a vast array of chemical substances like polyphenols and saponins that are present in plant tissues of different species, but the results are not consistent, and the extraction cost has constrained their utilization in practical animal feeding. Other new compounds of interest include polysaccharide biopolymers such as chitosan, mainly obtained as a marine co-product. As with other compounds, the effect of chitosan on the rumen microbial population depends on the source, purity, dose, process of extraction, and storage. In addition, it is important to identify compounds without adverse effects on rumen fermentation. The present review is aimed at providing information about chitosan for dietary manipulation to be considered for future studies to mitigate enteric methane and reduce the environmental impact of GHGs arising from livestock production systems. Chitosan is a promising agent with methane mitigating effects, but further research is required with in vivo models to establish effective daily doses without any detrimental effect to the animal and consider its addition in practical rations as well as the economic cost of methane mitigation.

Anti-Inflammatory Effect of Atorvastatin on the Kidney Graft of Living Donor Transplants.

BACKGROUND Recent studies have demonstrated that statins have anti-inflammatory and immunomodulatory properties, which could be considered beneficial in kidney transplantations. This study assesses the anti-inflammatory effect of atorvastatin on the kidney grafts of living donor transplants. MATERIAL AND METHODS In a randomized clinical trial, kidney donors were divided into 2 groups. The study group constituted 24 donors who received 40 mg atorvastatin, and 24 donors who received a placebo control, 4 weeks prior to transplantation. Serum C-reactive protein (CRP) levels were measured before and after atorvastatin administration. CRP and renal function of kidney recipients were measured at baseline and 1, 6, and 24 hours after transplantation. RESULTS After 4 weeks of treatment, the CRP level was 5.62±3.82 mg/dL in the control group and 3.27±0.62 mg/dL in the study group (P=0.007). Upon reperfusion, CRP levels in recipients at 1 hour were, 5.8±3.9 and 3.8±1.0 mg/dL, respectively (P=0.04). Twenty-four hours after the kidney transplantations, serum creatinine levels were 2.5±1.5 mg/dL in the study group and 3.7±2.4 mg/dL in the control group (P=0.04). CONCLUSIONS Our study suggests that the use of atorvastatin prior to allograft procurement of kidney transplant, reduces the acute kidney inflammatory burden profile, and promotes an improved kidney function recovery following transplantation.

Comparative genomic and transcriptomic analyses unveil novel features of azole resistance and adaptation to the human host in Candida glabrata.

The frequent emergence of azole resistance among Candida glabrata strains contributes to increase the incidence of infections caused by this species. Whole-genome sequencing of a fluconazole and voriconazole-resistant clinical isolate (FFUL887) and subsequent comparison with the genome of the susceptible strain CBS138 revealed prominent differences in several genes documented to promote azole resistance in C. glabrata. Among these was the transcriptional regulator CgPdr1. The CgPdr1 FFUL887 allele included a K274Q modification not documented in other azole-resistant strains. Transcriptomic profiling evidenced the upregulation of 92 documented targets of CgPdr1 in the FFUL887 strain, supporting the idea that the K274Q substitution originates a CgPdr1 gain-of-function mutant. The expression of CgPDR1K274Q in the FFUL887 background sensitised the cells against high concentrations of organic acids at a low pH (4.5), but had no detectable effect in tolerance towards other environmental stressors. Comparison of the genome of FFUL887 and CBS138 also revealed prominent differences in the sequence of adhesin-encoding genes, while comparison of the transcriptome of the two strains showed a significant remodelling of the expression of genes involved in metabolism of carbohydrates, nitrogen and sulphur in the FFUL887 strain; these responses likely reflecting adaptive responses evolved by the clinical strain during colonisation of the host.

Effect of Acetic Acid and Lactic Acid at Low pH in Growth and Azole Resistance of Candida albicans and Candida glabrata.

Successful colonization of the acidic vaginal niche by C. glabrata and C. albicans depends on their ability to cope with the presence of lactic and acetic acids produced by commensal microbiota. As such, the inhibitory effect of these acids at a low pH in growth of C. glabrata and C. albicans was investigated. The effect of the presence of these organic acids in tolerance of the two Candida species to azoles used in treatment of vaginal infections was also investigated including eventual synergistic effects. Under the different experimental conditions tested lactic acid exerted no significant inhibitory effect against C. albicans or C. glabrata, contrasting with the generalized impression that the production of this acid is on the basis of the protective effect exerted by vaginal lactobacilii. Differently, C. glabrata and C. albicans exhibited susceptibility to acetic acid, more prominent at lower pHs and stronger for the latter species. Synergism between acetic acid and azoles was observed both for C. albicans and C. glabrata, while lactic acid-azole synergism was only efficient against C. albicans. Altogether our in vitro results indicate that tolerance to acetic acid at a low pH may play a more relevant role than tolerance to lactic acid in determining competitiveness in the vaginal tract of C. albicans and C. glabrata including under azole stress. Treatment of vaginal candidiasis with azoles may depend on the level of acetic and lactic acids present and improvements could be achieved synergizing the azole with these acids.

Mechanistic Insights Underlying Tolerance to Acetic Acid Stress in Vaginal Candida glabrata Clinical Isolates.

During colonization of the vaginal tract Candida glabrata cells are challenged with the presence of acetic acid at a low pH, specially when dysbiosis occurs. To avoid exclusion from this niche C. glabrata cells are expected to evolve efficient adaptive responses to cope with this stress; however, these responses remain largely uncharacterized, especially in vaginal strains. In this work a cohort of 18 vaginal strains and 2 laboratory strains (CBS138 and KUE100) were phenotyped for their tolerance against inhibitory concentrations of acetic acid at pH 4. Despite some heterogeneity has been observed among the vaginal strains tested, in general these strains were considerably more tolerant to acetic acid than the laboratory strains. To tackle the mechanistic insights behind this differential level of tolerance observed, a set of vaginal strains differently tolerant to acetic acid (VG281∼VG49 < VG99 < VG216) and the highly susceptible laboratory strain KUE100 were selected for further studies. When suddenly challenged with acetic acid the more tolerant vaginal strains exhibited a higher activity of the plasma membrane proton pump CgPma1 and a reduced internal accumulation of the acid, these being two essential features to maximize tolerance. Based on the higher level of resistance exhibited by the vaginal strains against the action of a ß-1,3-glucanase, it is hypothesized that the reduced internal accumulation of acetic acid inside these strains may originate from them having a different cell wall structure resulting in a reduced porosity to undissociated acetic acid molecules. Both the vaginal and the two laboratory strains were found to consume acetic acid in the presence of glucose indicating that metabolization of the acid is used by C. glabrata species as a detoxification mechanism. The results gathered in this study advance the current knowledge on the mechanisms underlying the increased competitiveness of C. glabrata in the vaginal tract, a knowledge that can be used to guide more suitable strategies to treat infections caused by this pathogenic yeast.

Genome Sequence of the Nonconventional Wine Yeast Hanseniaspora guilliermondii UTAD222.

In this work, we disclose the genome sequence and a corresponding manually curated annotation of the non-Saccharomyces yeast Hanseniaspora guilliermondii UTAD222, a strain shown to have interesting oenological traits for the production of wines with improved aromatic properties.

The CgHaa1-Regulon Mediates Response and Tolerance to Acetic Acid Stress in the Human Pathogen Candida glabrata.

To thrive in the acidic vaginal tract, Candida glabrata has to cope with high concentrations of acetic acid. The mechanisms underlying C. glabrata tolerance to acetic acid at low pH remain largely uncharacterized. In this work, the essential role of the CgHaa1 transcription factor (encoded by ORF CAGL0L09339g) in the response and tolerance of C. glabrata to acetic acid is demonstrated. Transcriptomic analysis showed that CgHaa1 regulates, directly or indirectly, the expression of about 75% of the genes activated under acetic acid stress. CgHaa1-activated targets are involved in multiple physiological functions including membrane transport, metabolism of carbohydrates and amino acids, regulation of the activity of the plasma membrane H+-ATPase, and adhesion. Under acetic acid stress, CgHaa1 increased the activity and the expression of the CgPma1 proton pump and contributed to increased colonization of vaginal epithelial cells by C. glabrata CgHAA1, and two identified CgHaa1-activated targets, CgTPO3 and CgHSP30, are herein demonstrated to be determinants of C. glabrata tolerance to acetic acid. The protective effect of CgTpo3 and of CgHaa1 was linked to a role of these proteins in reducing the accumulation of acetic acid inside C. glabrata cells. In response to acetic acid stress, marked differences were found in the regulons controlled by CgHaa1 and by its S. cerevisiae ScHaa1 ortholog, demonstrating a clear divergent evolution of the two regulatory networks. The results gathered in this study significantly advance the understanding of the molecular mechanisms underlying the success of C. glabrata as a vaginal colonizer.

Necrólisis epidérmica tóxica: presentación de un caso / Toxic epidermal necrolysis: a case report

Se reporta una paciente de 36 años de edad, reclusa, con antecedentes de diabetes mellitus, hipertensión arterial y artritis gotosa para lo cual lleva tratamiento. Se recibe en el cuerpo de guardia del Hospital General Docente Dr Agostinho Neto con fiebre, ardor ocular y oral, así como eritema en piel de cara y miembros superiores. Evoluciona en días a la descamación o exfoliación de las mucosas oral y conjuntival, y de la piel de la cara, cuello, tronco anterior y posterior, región lumboglútea, y miembros superiores e inferiores. Se realiza diagnóstico de necrólisis epidérmica tóxica, pérdida del 80 por ciento de superficie corporal de piel (epidermis y dermis superficial), con pronóstico de crítico extremo, es atendida de forma multidisciplinaria y egresada curada al día 14(AU)

Patient of 36-year-old, prisoner is reported with a history of diabetes mellitus, arterial hypertension and gouty arthritis which one has treatment ,the patient was received by doctors at the General Teaching Hospital Dr AGostinho Net with fever, ocular and oral burning, erythema in skin face and upper limbs. The patient evolve un days to flaking or peeling of the oral and conjunctival mucus, skin of the face, neck, previous and posterior chest, lumbar region, and upper and lower limbs. It was Diagnosed toxic epidermal necrolysis, loss of 80 percent body surface skin (epidermis and superficial dermis), with bad health situation, is assisted by a multidisciplinary doctors staff and cured at day 14