Predicting Difficulty in Laparoscopic Cholecystectomies: An Evaluation of the Labbad-Vivas Score and Its Correlation With the Parkland Grading Scale.

Background Difficult laparoscopic cholecystectomy (DLC) denotes the surgical extraction of the gallbladder under circumstances where associated conditions within the same organ, adjacent structures, or patient-specific conditions impede a smooth, expeditious, and comfortable dissection. It is imperative to utilize tools that aid in anticipating this challenging surgical scenario, enabling the implementation of appropriate measures. Objective This study aimed to assess the effectiveness of the Labbad-Vivas score (LVS) in predicting DLC and its correlation with the Parkland Grading Scale (PGS). Methodology A prospective study was conducted, including patients diagnosed with gallstone disease undergoing LC (laparoscopic cholecystectomy) at the "Dr. Luis Razetti" University Hospital in Barcelona, Venezuela, between September and December 2023. Results Forty patients were studied, with 80% (n=32) being female and 95% (n=38) under the age of 65; surgeries were elective in 72.5% (n=29) of cases; 35% (n=14) had an LVS ≥16 (difficult cholecystectomy); and 62.5% (n=25) of patients presented Grades 1 and 2 on the PGS. Total cholecystectomy was performed in 95% (n=38) of the patients. The LVS showed a sensitivity of 80%, specificity of 92%, positive predictive value of 85.7%, and negative predictive value of 88.5% to predict DLC, with an area under the receiver operating characteristic curve of 0.897 (95% confidence interval (CI) = 0.792-1.003). A Pearson correlation coefficient of 0.805 (95% CI = 0.656 - 0.904) was obtained between both scores. Conclusion The use of the LVS score in the preoperative setting is feasible as a predictor of DLC, given its effectiveness and high correlation with the PGS.

Clinical inertia in newly diagnosed type 2 diabetes mellitus among patients attending selected healthcare institutions in Colombia.

BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.

Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts.

Epigenetic changes through altered DNA methylation have been implicated in critical aspects of tumor progression, and have been extensively studied in a variety of cancer types. In contrast, our current knowledge of the aberrant genomic DNA methylation in tumor-associated fibroblasts (TAFs) or other stromal cells that act as critical coconspirators of tumor progression is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from non-small cell lung cancer patients using the HumanMethylation450 microarray. We found widespread DNA hypomethylation concomitant with focal gain of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-ß pathway. The latter included promoter hypermethylation-associated SMAD3 silencing, which was associated with hyperresponsiveness to exogenous TGF-ß1 in terms of contractility and extracellular matrix deposition. In turn, activation of CFs with exogenous TGF-ß1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-ß1 may be necessary but not sufficient to elicit such alterations. Moreover, integrated pathway-enrichment analyses of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in non-small cell lung cancer patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance.

Matrix stiffening and ß1 integrin drive subtype-specific fibroblast accumulation in lung cancer.

UNLABELLED: The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal- or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by ß1 integrin mechano-sensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in ß1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), ß1 expression, and ERK1/2 (pT202/Y204) than ADC-TAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (>50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or ß1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs. IMPLICATIONS: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.

Magnetic resonance image enhancement by reducing receptors' effective size and enabling multiple channel acquisition.

Magnetic resonance imaging is empowered by parallel reading, which reduces acquisition time dramatically. The time saved by parallelization can be used to increase image quality or to enable specialized scanning protocols in clinical and research environments. In small animals, the sizing constraints render the use of multi-channeled approaches even more necessary, as they help to improve the typically low spatial resolution and lesser signal-to-noise ratio; however, the use of multiple channels also generates mutual induction (MI) effects that impairs imaging creation. Here, we created coils and used the shared capacitor technique to diminish first degree MI effects and pre-amplifiers to deal with higher order MI-related image deterioration. The constructed devices are tested by imaging phantoms that contain identical solutions; thus, creating the conditions for several statistical comparisons. We confirm that the shared capacitor strategy can recover the receptor capacity in compounded coils when working at the dimensions imposed by small animal imaging. Additionally, we demonstrate that the use of pre-amplifiers does not significantly reduce the quality of the images. Moreover, in light of our results, the two MI-avoiding techniques can be used together, therefore establishing the practical feasibility of flexible array coils populated with multiple loops for small animal imaging.

Enhanced thermal resistance of Salmonella in marinated whole muscle compared with ground pork.

The internal muscle environment may enhance thermal resistance of bacterial pathogens. Based on the migration of pathogens into whole muscle products during marination, the validity of current thermal inactivation models for whole muscle versus ground products has been questioned. Consequently, the objective of this work was to compare thermal resistance of Salmonella in whole muscle versus ground pork. Irradiated samples of whole and ground pork loin (5.5 to 7.5 g) were exposed to a Salmonella-inoculated (10(8) CFU/ml) marinade (eight serovar cocktail) for 20 min, placed in sterile brass tubes (12.7 mm diameter), sealed, and heated isothermally at 55, 58, 60, 62, or 63 degrees C, and surviving salmonellae were enumerated on Petrifilm aerobic count plates. The thermal lag times and initial bacterial counts were similar for both whole muscle and ground samples (P > 0.05), with all samples having equivalent compositions, inocula, and thermal histories. Heating temperature and physical state of the meat (whole versus ground muscle) affected Salmonella inactivation, with greater thermal resistance observed in whole than in ground muscle (P < 0.05). Assuming log-linear inactivation kinetics, Salmonella was 0.64 to 2.96 times more heat resistant in whole muscle than in ground pork. Therefore, thermal process validations for pork products should also account for the physical state of the product to ensure microbial safety.

Dieldrin elicits a widespread DNA repair and antioxidative response in mouse brain.

Dieldrin is an organochlorine pesticide that is toxic for monoaminergic neurons. This study was designed to test the hypothesis that a weak DNA repair response to dieldrin by nigrostriatal dopaminergic (DA) neurons results in depletion of striatal DA. The activity of the mammalian base excision repair enzyme oxyguanosine glycosylase was utilized as the index of DNA repair. Other measures of oxidative stress were also studied, including the regional distribution of lipid peroxidation and superoxide dismutase (SOD) activity. The effects of acute and slow infusion of dieldrin on striatal DA levels were biphasic with a transient initial depression followed by increases beyond normal steady-:state levels. Dieldrin administration caused a global oxidative stress evidenced by increased levels of lipid peroxidation in all brain regions, an effect consistent with its capacity to affect mitochondrial bioenergetics. Dieldrin also elicited strong antioxidative and DNA repair responses across the entire mouse brain. Although mitochondrial SOD was not as increased in midbrain as it was in other regions following a cumulative dose of 24 mg/kg, this response, along with the robust DNA repair response, appeared to be sufficient to protect potentially vulnerable DA neurons from cytotoxicity. However, the long-:term consequences of chronic low-:dose dieldrin exposure remain to be studied, especially in light of the concept of "slow excitotoxicity,'' which postulates that even a mild bioenergetic compromise can over time result in the demise of neurons.

Adult hippocampal neural stem/progenitor cells in vitro are vulnerable to the mycotoxin ochratoxin-A.

The common mycotoxin ochratoxin-A (OTA) accumulates in brain, causes oxidative stress, and elicits a DNA repair response that varies across brain regions and neuronal populations. Neural stem/progenitor cells (NSCs) prepared from hippocampus of adult mouse brain were tested for their vulnerability to the toxin in vitro. The following measurements were made in NSC cell cultures in both proliferation and differentiation media: (1) viability (trypan blue exclusion), (2) proliferative activity ([(3)H]-thymidine uptake), (3) the DNA repair response (oxyguanosine glycosylase activity), and (4) antioxidative response (superoxide dismutase). Cells that had proliferated to 90-100% confluency in the presence of epidermal growth factor and basic fibroblast growth factor were induced to differentiate by removal of the growth factors. OTA, added to the cultures in concentrations of 0.01-100 microg/ml, caused a dose- and time-dependent (6-72 h) decrease in viability of both proliferating and differentiating NSC. Proliferating NSC exhibited a greater vulnerability to the toxin than differentiated neurons despite robust DNA repair and antioxidative responses. Preconditioning of NSC with a 12-h incubation with the pro-oxidant diethyl maleate increased DNA repair activity and, subsequently, provided a moderate degree of neuroprotection. Overall, these results lead to speculation that OTA exposure may contribute to impaired hippocampal neurogenesis in vivo, resulting in depression and memory deficits, conditions reported to be linked to mycotoxin exposure in humans.

Ansiedad y depresión en primigestas adolescentes y añosas según la edad gestacional / Anxiety and depression in adolescents and old age womans primigravidas the gestational

El objetivo del presente estudio fué determinar si existe relación entre la edad cronológica de las primigestas (adolescentes y añosas) y sus niveles de ansiedad y drepresión, según la edad gestacional. Se realizó un trabajo de campo de tipo exploratorio. La muestra estuvo conformada por sesenta (60) pacientes primigestas (adolescentes, añosas y en edades intermedias) con edad promedio de 25.1 años, con una edad gestacional promedio de 28.6 semanas, el grado de instruccion predominante fué de secundaria incompleta (47) y un 40 mantenían relación de pareja de tipo concubinaria. El inicio del control del embarazo, un 33 reportó haber planificado el embarazo. Así mismo la edad promedio del inicio de la vida sexual fué de 18.6 años. Un 63 reportó utilizar métodos anticonceptivos. Se concluyó que en las primigestas adolescentes existen mayores niveles de depresión, en las primigestas añosas existen mayores niveles de ansiedad y además que estos niveles de ansiedad y depresión no muestran diferencias estadísticamente significativas según los trimestres del embarazo evaluado.

Hematuria y hemoglobinuria como elementos predictivos de falla renal aguda renal en recién nacidos a término con alteración hipóxico-isquémica / Hematuria and hemoglobinuria as predictive elements of acute renal failure in newborn

Una de las más importantes causas de muerte neonatal es la Encefalopatía Hipóxica Isquémica, frecuentemente asociada al daño renal. Existen pruebas como la fracción excretora de Na que nos ayudan a detectar dicho compromiso renal, con este trabajo intentamos determinar si los valores de hamaturia y hemoglobinuria son útiles como elementos predictivos de dicha alteración. Se realizó una investigación descriptiva transversal: tomando muestras por un período de 4 meses (Octubre 90 - Marzo 91) en la U.R.N. del HRSB (Bogotá); tomando 18 RN de sexo masculino, a término con Apgar menor de 3/10 al minuto y menor de 7/10 a los 5 minutos, a los cuales se les analizó hematuria, hemoglobinuria y FeNa entre las primeras 24 horas y entre las 48-72 horas postparto, obteniendo resultados que indican alta relación (directamente proporcional) entre los datos analizados (Hematuria, Hemoglobinuria y FeNa), y la existencia de falla renal aguda