Temperature variation in caves and its significance for subterranean ecosystems.

Climate change affects all ecosystems, but subterranean ecosystems are repeatedly neglected from political and public agendas. Cave habitats are home to unknown and endangered species, with low trait variability and intrinsic vulnerability to recover from human-induced disturbances. We studied the annual variability and cyclicity of temperatures in caves vis-à-vis surface in different climatic areas. We hypothesize that cave temperatures follow the average temperature pattern at the surface for each location with a slight delay in the signal, but we found three different thermal patterns occurring in caves: (1) high positive correlation and a similar thermal pattern to the surface, (2) low correlation and a slight thermal delay of the signal from the surface, and (3) high negative correlation with an extreme delay from the surface. We found daily thermal cycles in some caves, which may potentially control the circadian rhythms of cave organisms. Our results show that caves had lower thermal amplitude than the surface, and that thermal averages within caves approximately correspond to the to the annual average of surface temperature. Caves buffer external temperature and act as refugia for biota in extreme climatic events. Likewise, temperature increases at surface will lead to increment in caves, threatening subterranean biota and ecosystem services.

Exploring the genetic background of the botulism neurotoxin BoNT/B2 in Spain.

To determine whether the neurotoxin BoNT/B2 causing botulism in Spain is clonal, the genetic diversity and phylogenetic relationships of Clostridium botulinum from food-borne episodes and infant cases of the condition were explored. The botulinum toxin gene (bont) subtype, the variable region of the flagellin gene (flaVR), and a seven-gene multi-locus sequence type were examined by sequencing 37 BoNT-positive cultures obtained over the period 2010 to 2022. Out of 37 botulism events, 16 food-borne episodes and 16 infant cases were associated with bont/b2. Eight bont/b2 alleles were detected [nucleotide distance range 0.0259-0.415%, Hunter and Gaston discrimination index (HGDI) 0.71]. The most common bont/b2 allele corresponded to that of strain Prevot 25 NCASE and its single and double locus variations (87.5%). Four known flaVR types were identified (HGDI 0.79), along with one previously unknown (flaVR-15). Sixteen sequence types (STs) (HGDI 0.89) were recorded including seven new STs (ST164-ST170; 10 new alleles) and five new STs (ST171-ST175; with new allele combinations) were also noted. Correlations among some STs and flaVR types were seen. Overall, the present results show that the combined analysis of bont/b2-flaVR-ST at the nucleotide level could be used to track botulism events in Spain. The neurotoxin BoNT/B2 has largely been responsible for human botulism in Spain. The polymorphism analysis of bont/b2, flaVR typing, and sequence type determinations, revealed a wide variety of clones to be responsible for human botulism, ruling out a common source of acquisition. IMPORTANCE Botulism, a potentially fatal disease, is classically characterized by a symmetrical descending flaccid paralysis, which if left untreated can lead to respiratory failure and death. Botulinum neurotoxin (BoNT), produced by certain species of Clostridium, is the most potent biological toxin known, and the direct cause of botulism. This study characterizes the acquisition in Spain of two forms of botulism, i.e., food-borne and infant botulism, which are largely caused by the main neurotoxin BoNT/B2. Polymorphism analysis of the bont/b2 gene, typing of the flagellin variable region sequence (flaVR), and multilocus sequence typing, were used to explore the genetic background of Clostridium botulinum group I. To our knowledge, this is the first phylogenetic and typing study of botulism undertaken in Spain.

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb-V and dialysis in Spanish clinical practice - Vie-KinD study.

BACKGROUND AND AIMS: Limited data are available on the effectiveness and tolerability of direct-acting antivirals (DAAs) therapies in the real world for HCV-infected patients with comorbidities. This study aimed to describe the effectiveness of OBV/PTV/r ± DSV (3D/2D regimen) with or without ribavirin (RBV) in HCV or HCV/HIV co-infected patients with GT1/GT4 and CKD (IIIb-V stages), including those under hemodialysis and peritoneal dialysis in routine clinical practice in Spain in 2015. MATERIAL AND METHODS: Non-interventional, retrospective, multicenter data collection study in 31 Spanish sites. Socio-demographic, clinical variables, study treatment characteristics, effectiveness and tolerability data were collected from medical records. RESULTS: Data from 135 patients with a mean age (SD) of 58.3 (11.4) years were analyzed: 92.6% GT1 (81.6% GT1b and 17.6% GT1a) and 7.4% GT4, 14 (10.4%) HIV/HCV co-infected, 19.0% with fibrosis F3 and 28.1% F4 by FibroScan®, 52.6% were previously treated with pegIFN and RBV. 11.1%, 14.8% and 74.1% of patients had CKD stage IIIb, IV and V respectively. 68.9% of patients were on hemodialysis; 8.9% on peritoneal dialysis and 38.5% had history of renal transplant. A total of 125 (96.2%) of 135 patients were treated with 3D, 10 (7.4%) with 2D and 30.4% received RBV. The overall intention-to-treat (ITT) sustained virologic response at week 12 (SVR12) was 92.6% (125/135) and the overall modified-ITT (mITT) SVR12 was 99.2% (125/126). The SVR12 rates (ITT) per sub-groups were: HCV mono-infected (91.7%), HCV/HIV co-infected (100%), GT1 (92.0%), GT4 (100%), CKD stage IIIb (86.7%), stage IV (95%) and stage V (93%). Among the 10 non-SVR there was only 1 virologic failure (0.7%); 4 patients had missing data due lost to follow up (3.0%) and 5 patients discontinued 3D/2D regimen (3.7%): 4 due to severe adverse events (including 3 deaths) and 1 patient´s decision. CONCLUSIONS: These results have shown that 3D/2D regimens are effective and tolerable in patients with advanced CKD including those in dialysis with GT 1 or 4 chronic HCV mono-infection and HIV/HCV coinfection in a real-life cohort. The overall SVR12 rates were 92.6% (ITT) and 99.2% (mITT) without clinically relevant changes in eGFR until 12 weeks post-treatment. These results are consistent with those reported in clinical trials.

Factores de riesgo de evolución desfavorable en niños con plástica de la válvula mitral / Risk Factors of Unfavorable Outcome in Children with Mitral Valve Repair

RESUMEN Objetivo: Analizar los factores de riesgo de evolución desfavorable (ED) en niños con insuficiencia mitral (IM) sometidos a plástica mitral (PM). Métodos: Se analizaron pacientes con IM sometidos a PM entre los años 2004 y 2014. Se definió ED como la reoperación o la IM significativa (3+, moderada a grave, o 4+, grave) durante el seguimiento. Las variables se expresaron como mediana. Se realizó el análisis univariado y el de regresión logística multivariado de los factores predictores de ED. Resultados: Se sometieron a PM 65 pacientes con IM 3+ e IM 4+. La etiología incluyó displasia (44,6%), endocarditis infecciosa (13,8%), fiebre reumática (18,4%), anomalía coronaria (7,7%) y otras (13,8%). La mediana del tiempo de seguimiento fue 26,5 meses (52 pacientes se encuentran aún en seguimiento). El 44,6% presentó disfunción ventricular y el 46,1% hipertensión pulmonar. La cantidad de pacientes con ED fue de 15: 9 fueron reoperados (7 reemplazos valvulares y 2 replástica). El análisis univariado demostró asociación significativa entre ED y las siguientes condiciones: fiebre reumática (p = 0,005), anillo mitral preoperatorio ≥+5 DS (p = 0,002), diámetro sistólico del ventrículo izquierdo (DSVI) ≥ +4 DS (p = 0,022), hipertensión pulmonar (p = 0,024) e IM residual posoperatoria inmediata ≥ moderada (p = 0,021). El análisis multivariado demostró como variables independientes de ED el diámetro del anillo mitral (p = 0,012), la fiebre reumática (p = 0,026) y la IM residual temprana (p = 0,042). No se produjo mortalidad. Conclusiones: La plástica mitral en niños con IM grave demostró resultados favorables a mediano plazo. La fiebre reumática, el diámetro del anillo mitral ≥ +5 DS y la IM residual ≥ 2+ fueron factores predictores de ED. No se hallaron diferencias estadísticamente significativas durante el seguimiento en relación con la edad ni con la presencia de disfunción ventricular.

ABSTRACT Objective: The aim of this study was to analyze risk factors of unfavorable outcome (UO) in patients with mitral regurgitation (MR) undergoing mitral valve repair (MVR). Methods: Patients with MR who had undergone MVR from 2004 to 2014 were retrospectively analyzed. Unfavorable outcome was defined as reoperation or significant MR [moderate to severe (3+) or severe MR (4+)] during follow-up. Variables were expressed as median. Univariate and multivariate logistic regression analyses were performed to identify predictive factors of UO. Results: Sixty five patients with MR3+ and MR4+ underwent MVR. Etiology was dysplasia in 44.6% of cases, infective endocarditis in 13.8%, rheumatic fever in 18.4%, abnormal coronary origin in 7.7% and other disorders in 13.8%. Median follow-up time was 26.5 months (52 patients are still being followed-up).Ventricular dysfunction was documented in 44.6% of cases and 46.1% had pulmonary hypertension. Fifteen patients presented UO and 9 were reoperated (7 valve replacements and 2 re-repairs). Univariate analysis demonstrated a significant association between UO and the following conditions: rheumatic fever (p=0.005), preoperative mitral annulus ≥+5 SD (p=0.002), left ventricular end-systolic diameter ≥+4 SD (p=0.022), pulmonary hypertension (p=0.024) and immediate postoperative residual MR ≥ moderate (p=0.021). Multivariate analysis demonstrated mitral annulus diameter (p=0.012), rheumatic fever (p=0.026) and early residual MR (p=0.042) as independent variables of UO. No deaths occurred in this series. Conclusions: Mitral valve repair in children with severe MR demonstrated mid-term favourable results. Rheumatic fever, mitral annulus diameter ≥+5 SD and immediate postoperative residual MR ≥2+ were predictive factors of UO. Neither age at surgery nor ventricular dysfunction showed statistically significant differences during follow-up.

Widefield fluorescence lifetime imaging of protoporphyrin IX for fluorescence-guided neurosurgery: An ex vivo feasibility study.

Achieving a maximal safe extent of resection during brain tumor surgery is the goal for improved patient prognosis. Fluorescence-guided neurosurgery using 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX has thereby become a valuable tool enabling a high frequency of complete resections and a prolonged progression-free survival in glioblastoma patients. We present a widefield fluorescence lifetime imaging device with 250 mm working distance, working under similar conditions such as surgical microscopes based on a time-of-flight dual tap CMOS camera. In contrast to intensity-based fluorescence imaging, our method is invariant to light scattering and absorption while being sensitive to the molecular composition of the tissue. We evaluate the feasibility of lifetime imaging of protoporphyrin IX using our system to analyze brain tumor phantoms and fresh 5-ALA-labeled human tissue samples. The results demonstrate the potential of our lifetime sensing device to go beyond the limitation of current intensity-based fluorescence-guided neurosurgery.

The relation of fibrosis stage with nutritional deficiencies and bioelectrical impedance analysis of body composition in patients with chronic hepatitis C.

UNLABELLED:  Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage. MATERIAL AND METHODS: Body multifrequency bioimpedance analysis (BIA) and a wide and simultaneous analytical profile were prospectively performed in 74 CHC patients (36 male) with known METAVIR fibrosis stage established with liver biopsy or transient elastography. Results were analyzed to identify deviations from the normal range and variations according to the fibrosis stage. RESULTS: Body fat compartment was greater in women. Body composition did not change among the 4 stages of liver fibrosis. Low levels (< 30 µg/L) of vitamin D were detected in 74.3% of patients irrespective of the fibrosis stage. Most analytical results remained into the normal range with the exceptions of thrombocytopenia and vitamin A deficiency, that were limited to the stage 4 of fibrosis, and low Zn and LDL-cholesterol values, that were frequently found in patients with advanced (F3 and F4) fibrosis stage. CONCLUSION: Body composition and most biochemical parameters, including cyanocobalamin, folic acid and vitamin E, are well preserved in compensated patients with CHC, with the exception of generalized vitamin D insufficiency and of deficiencies of vitamin A and zinc that are restricted to the more advanced, although still compensated, stages of the disease.

GC Gene Polymorphism and Unbound Serum Retinol-Binding Protein 4 Are Related to the Risk of Insulin Resistance in Patients With Chronic Hepatitis C: A Prospective Cross-Sectional Study.

Insulin resistance (IR) is found in chronic hepatitis C (CHC) more frequently than in other chronic liver diseases.Prospective cross-sectional study to evaluate a wide multitest panel to identify factors related with IR in CHC and their possible interactions.In 76 patients with CHC we performed a series of routine laboratory analysis as well as specifically designed serum biochemical tests [retinol, retinol-binding protein 4 (RBP4), 25-OH vitamin D, Vitamin E, lipopolysaccharide-binding protein (LBP), interleukin-6 (IL-6), and cystatin C]. The single nucleotide polymorphisms rs7041 and rs4588 GC-DBP (group-specific component-Vitamin D-binding protein), rs738409 PNPLA3 (patatin-like phospholipase domain containing 3), and rs12979860 IL28B (interleukin-28 B) genes were determined. Insulin sensitivity was established with the HOMA-IR and IR was diagnosed when HOMA-IR > 3. Fibrosis staging was assessed with liver biopsy or transient elastography.After backward logistic regression analysis, independent variables associated with IR were Gc1s/Gc1s DBP phenotype, that results from the homozygous carriage of the rs7041G/rs4588C haplotype (P = 0.033); low retinol/RBP4 ratio, reflecting a greater rate of unbound RBP4 (P = 0.005); older age (P = 0.01); high serum tryglicerides (P = 0.026); and advanced (F3-F4) fibrosis stage. The AUROC provided by the multivariate model was 0.950 (95% CI = 0.906-0.993).In addition to previously known ones, the Gc1s/Gc1s phenotype variant of DBP and the unbound fraction of plasma RBP4 may be considered as factors related with the incidence, and possibly the risk, of IR in CHC patients.