Loop Diuretics: An Overview of Its History and Evolution.

The loop of Henle plays a key role in kidney function, especially in retaining solutes and concentrating urine. Diuretic agents, crucial for managing fluid overload and related conditions like hypertension and heart failure (HF), enhance water and electrolyte excretion. The history of diuretics dates back to 1775 with the discovery of Digitalis, evolving significantly with the introduction of chlorothiazide in 1957, which revolutionized diuretic therapy. Loop diuretics, developed in the 1950s and including drugs like torsemide, furosemide, and ethacrynic acid, are potent agents acting on the loop of Henle. They are vital for treating severe fluid overload conditions and require careful monitoring to manage potential side effects.

Effectiveness of TENS and Acetaminophen for Pain Control During Orthodontic Treatment: A Comparative Study.

Background: Orthodontic treatment often induces pain, especially post appliance placement. This study compares transcutaneous electrical nerve stimulation (TENS) and acetaminophen for orthodontic pain management. Materials and Methods: A randomized trial included 120 fixed orthodontic patients divided into three groups (n = 40): Group A received TENS, group B received acetaminophen, and group C was the control. Data were expressed as mean ± SD. Repeated ANOVA analysis compared mean values, followed by post-hoc Tukey analysis. Pain levels were assessed using a visual analog scale before any intervention and at 30 minutes, 6 hours, and 24 hours post activation. Results: TENS and acetaminophen significantly reduced pain compared to the control. Group A (TENS) showed significant pain reduction post activation. Group B (acetaminophen) exhibited comparable pain relief, with no significant difference between groups. Conclusion: Both TENS and acetaminophen effectively manage orthodontic appliance activation pain.

Barriers to Implementation of Advanced Endoscopic Procedures.

Advanced endoscopy has been shown to be useful in the diagnosis and treatment of both benign and low-grade malignant colorectal lesions. In fact, advanced endoscopic procedures are being adopted as standard approaches to these lesions in many places around the world; however, their implementation in the United States has not been as widespread. We ascribe the difficulty in implementation to two reasons: (1) lack of advanced endoscopic training and (2) failure in reimbursement models as they relate to endoscopy. In this article, we hope to describe these barriers and inspire colorectal surgeons to try and overcome them. As surgical specialists with a mastery of endoscopic techniques, colorectal surgeons would be able to maximize benefit for their patients and minimize health care costs in the long run.

Combined Endoscopy-Laparoscopy Surgery: When and How to Utilize This Tool.

Combined endoscopic and laparoscopic surgery (CELS) has been used to resect colon polyps since the 1990s. These colon-sparing techniques, however, have not yet been widely adopted. With the evolution of technology in both diagnosing and treating colon cancer, colorectal surgeons should strive for a diverse and complete armamentarium through which they can best serve their patients. In this article, we hope to provide clarity on CELS by discussing three topics: (1) the history and fruition of CELS; (2) the techniques involved in CELS; and (3) the utility of CELS within different clinical scenarios. Our goal is to educate readers and stimulate consideration of CELS in select patients who might benefit greatly from these techniques.

Patient Compliance With Bowel Preparation for Elective Colorectal Surgery.

INTRODUCTION: Studies show that mechanical bowel preparation (MBP) plus oral antibiotics (OAs) is associated with decreased rates of postoperative complications after elective colorectal surgery. However, there is a lack of literature regarding patient compliance with bowel preparation (BP). MATERIALS AND METHODS: Patients undergoing elective colorectal surgeryfrom April 2020 to March 2022 at a tertiary care academic hospital (TCAH) and safety net hospital (SNH) were administered a BP compliance survey. Patients were compared on the basis of hospital setting and completeness of BP using student's t-tests and Fisher's exact tests, as appropriate. RESULTS: 105 patients were included as follows: 55 from the TCAH and 50 from the SNH. The median age was 59. 45.7% were female. TCAH had a higher proportion of White patients (36.4% versus 0%), while the SNH had a higher proportion of Hispanic patients (78% versus 10.9%). Most patients at the TCAH reported English as their primary language (80% versus 28%), while most patients at the SNH spoke primarily Spanish (60% versus 7.3%). In total, 88.6% (n = 93) of patients completed the MBP- 87.3% at the TCAH and 90% at the SNH (P = 0.764). 86.7% took all three doses of OA. Compared to the SNH patients, a smaller percentage of TCAH patients took all doses of OA (78.2% versus 96%, P = 0.009). Overall, 45.7% of patients reported adverse symptoms with BP. The only patient factor associated with a complete bowel preparation was SNH setting (P = 0.024). CONCLUSIONS: Overall, almost 90% of patients were compliant with both MBP and OA. Compliance with OA among patients at the TCAH was significantly lower compared to patients at the SNH. An SNH setting was associated with completing a BP. Individual compliance is likely impacted by both institutional practices and patient factors.

Pathologic Outcomes of Short-Course and Long-Course Radiotherapy for Locally Advanced Rectal Cancers Treated With Total Neoadjuvant Therapy.

INTRODUCTION: Total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer (LARC) is now the standard of care. Randomized trials suggest the use of short-course radiotherapy (SCRT) and long-course radiotherapy (LCRT) are oncologically equivalent. OBJECTIVE: To describe pathologic outcomes after surgical resections of patients receiving SCRT versus LCRT as part of TNT for LARC. PARTICIPANTS: All patients with LARC treated at a single tertiary hospital who underwent proctectomy after completing TNT were included. Patients were excluded if adequate details of TNT were not available in the electronic medical record. RESULTS: A total of 53 patients with LARC were included. Thirty-nine patients (73.5%) received LCRT and 14 (26.4%) received SCRT. Forty-nine patients (92.5%) were clinical stage III (cN1-2) prior to treatment. The average lymph node yield after proctectomy was 20.9 for SCRT and 17.0 for LCRT (P = .075). Of the 49 patients with clinically positive nodes before treatment, 76.9% of those who received SCRT and 72.2% of those who received LCRT achieved pN0 disease after TNT. Additionally, there were no significant differences in rates of pathologic complete response between patients who received SCRT and LCRT, 7.1% and 12.8%, respectively (P = .565). CONCLUSION: Pathologic outcomes of patients with LARC treated with SCRT or LCRT, as part of TNT, may be similar. Further prospective trials are needed to assess long-term clinical outcomes and to determine best treatment protocols.

Cadaveric Study of Colon-Lengthening Maneuvers After Sigmoidectomy.

BACKGROUND: Creation of a tension-free colorectal anastomosis after left colon resection or low anterior resection is a key requirement for technical success. The relative contribution of each of a series of known lengthening maneuvers remains incompletely characterized. OBJECTIVE: The aim of this study was to compare technical procedures for lengthening of the left colon before rectal anastomosis. DESIGN: A series of lengthening maneuvers was performed on 15 fresh cadavers. Mean distance gained was measured for each successive maneuver, including 1) high inferior mesenteric artery ligation, 2) splenic flexure takedown, and 3) high inferior mesenteric vein ligation by the ligament of Treitz. SETTING: Cadaveric study. MAIN OUTCOME MEASURES: The premobilization and postmobilization position of the proximal colonic end was measured relative to the inferior edge of the sacral promontory. Measurements of the colonic length relative to the sacral promontory were taken after each mobilization maneuver. The inferior mesenteric artery, sigmoid colon, and rectum specimen lengths were measured. The distance from the inferior border of the sacral promontory to the pelvic floor was measured along the sacral curvature. RESULTS: Mean sigmoid colon resection length was 34.7 ± 11.1 cm. Before any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained. LIMITATIONS: The study was limited by nature of being a cadaver study. CONCLUSIONS: Stepwise lengthening maneuvers allow significant additional reach to allow a tension-free left colon to rectal anastomosis. See Video Abstract . ESTUDIO CADAVRICO DE MANIOBRAS DE ALARGAMIENTO COLNICO TRAS UNA SIGMOIDECTOMA: ANTECEDENTES:La creación de una anastomosis colorrectal libre de tensión tras una resección de colon izquierdo o tras una resección anterior baja es un requisito clave para el éxito relacionado con la técnica quirúrgica. La relativa contribución de las diversas maniobras de alargamiento permanece caracterizada de manera incompleta.OBJETIVO:El propósito de este estudio fue la de comparar procedimientos técnicos de alargamiento del colon izquierdo previo a la anastomosis rectal.DISEÑO:Una serie de maniobras de alargamiento fueron realizados en 15 cadáveres frescos. La distancia promedio ganada fue medida para cada maniobra sucesiva, incluyendo (1) ligadura alta de la arteria mesentérica inferior, (2) descenso del ángulo esplénico, (3) ligadura alta de la vena mesentérica interior mediante el ligamento de Treitz.AJUSTES:Estudio cadavérico.PRINCIPALES MEDIDAS DE RESULTADO:La posición premobilizacion y postmobilizacion del extremo proximal del colon fue medido tomando en cuenta el borde inferior del promontorio sacro. Las mediciones de la longitud colónica en relación al sacro fueron tomadas luego de cada maniobra de movilización. Fueron tomadas así mismo las longitudes de la arteria mesentérica inferior, el colon sigmoides y recto. Las distancias desde el borde inferior del promontorio sacro al suelo pelvico fueron medidas a lo largo de la curvatura sacra.RESULTADOS:Average sigmoid colon resection length was 34.7 ± 11.1 cm. Prior to any lengthening, baseline reach was -1.3 ± 4.2 cm from the sacral promontory. Inferior mesenteric artery ligation yielded an additional 11.5 ± 4.7 cm. Subsequent splenic flexure takedown added an additional 12.8 ± 9.6 cm. Finally, inferior mesenteric vein ligation added an additional 11.33 ± 6.9 cm, bringing the total colonic length to 35.7 ± 14.7 cm. BMI and weight negatively correlated with length gained.LIMITACIONES:Este estudio tuvo como limitación la naturaleza de haber sido un estudio cadavérico.CONCLUSIONES:Maniobras de alargamiento permiten un alcance adicional significativo permitiendo de esta manera una anastomosis de colon izquierdo a recto libre de anastomosis. (Traducción-Dr Osvaldo Gauto ).

Efficacy of Triglyceride Glucose Index-Neck Circumference and Triglyceride Glucose Index-Neck-to-Height Ratio in the Diagnosis of Cardiovascular Diseases and Metabolic Syndrome.

BACKGROUND: A group of characteristics known as metabolic syndrome raises the chance of developing diabetes and cardiovascular disease. Insulin resistance (IR) and obesity are regarded as critical metabolic syndrome pathophysiology. OBJECTIVES: The diagnostic accuracy of IR indicators, triglyceride (TG) glucose index-neck circumference (TyG-NC), and TG glucose index-neck-to-height ratio (TyG-NHtR) to be evaluated for the detection of cardiovascular diseases and metabolic syndrome in nondiabetic individuals. MATERIALS AND METHODS: A cross-sectional study was conducted and passed by the Ethics Committee of the institute. The age should be 18 years or older, and subjects should not have diabetes. Each patient's clinical information was gathered, and lab tests were run. The study was done for a period of 1 year. RESULTS: The study has 100 participants. Around 74% of the group was women. Only 26.5% of the group had an obesity diagnosis. Poor fasting plasma glucose levels were found in 19.4% of the research team. Receiver operating characteristic (ROC)-area under the curve (AUC) testing revealed that all examined IR indices can differentiate individuals with metabolic syndrome from those who are healthy. Our analysis laid out the soaring high area under the ROC curve for TyG index and the low stunted area under the ROC curve for TyG-NC. For obesity, all indices showed appreciable diagnostic efficacy, indicating the maximum achieved area under the ROC curve for TyG index and the minimum recorded metabolic score for IR. The AUC in the case of the metabolic score for IR (METS-IR) male sample population was found to be not statistically compelling. CONCLUSION: The exploration of indirect indices, the proposed ones, namely TyG-NC and TyG-NHtR, emphasized an intricate link between cardiovascular diseases and metabolic syndrome.

Development of a novel CT-based index for predicting the number of extracorporeal shockwave lithotripsy (ESWL) sessions required for successful fragmentation of obstructing pancreatic duct stones.

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Complete mesocolic excision and extended lymphadenectomy: Where should we stand?

Debate regarding the risks and merits of complete mesocolic excision and extended lymphadenectomy is ongoing, particularly for right-sided colon cancers. In this article, we hope to provide a succinct yet encompassing review of the relevant literature. We posit that complete mesocolic excision with D3 dissection is indicated in select patients with colon cancers, particularly those distal to the cecum.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Erratum to 'successful epidural fibrin glue patch to treat intracranial hypotension in a patient with bacteraemia and malignancy' [BJAOpen 4 (2022) 100091].

[This corrects the article DOI: 10.1016/j.bjao.2022.100091.].

Sub-monthly time scale forecasting of harmful algal blooms intensity in Lake Erie using remote sensing and machine learning.

Harmful algal blooms of cyanobacteria (CyanoHAB) have emerged as a serious environmental concern in large and small water bodies including many inland lakes. The growth dynamics of CyanoHAB can be chaotic at very short timescales but predictable at coarser timescales. In Lake Erie, cyanobacteria blooms occur in the spring-summer months, which, at annual timescale, are controlled by the total spring phosphorus (TP) load into the lake. This study aimed to forecast CyanoHAB cell count at sub-monthly (e.g., 10-day) timescales. Satellite-derived cyanobacterial index (CI) was used as a surrogate measure of CyanoHAB cell count. CI was related to the in-situ measured chlorophyll-a and phycocyanin concentrations and Microcystis biovolume in the lake. Using available data on environmental and lake hydrodynamics as predictor variables, four statistical models including LASSO (Least Absolute Shrinkage and Selection Operator), artificial neural network (ANN), random forest (RF), and an ensemble average of the three models (EA) were developed to forecast CI at 10-, 20- and 30-day lead times. The best predictions were obtained by using the RF and EA algorithms. It was found that CyanoHAB growth dynamics, even at sub-monthly timescales, are determined by coarser timescale variables. Meteorological, hydrological, and water quality variations at sub-monthly timescales exert lesser control over CyanoHAB growth dynamics. Nutrients discharged into the lake from rivers other than the Maumee River were also important in explaining the variations in CI. Surprisingly, to forecast CyanoHAB cell count, average solar radiation at 30 to 60 days lags were found to be more important than the average solar radiation at 0 to 30 days lag. Other important variables were TP discharged into the lake during the previous 10 years, TP and TKN discharged into the lake during the previous 120 days, the average water level at 10-day lag and 60-day lag.

Generalized neural closure models with interpretability.

Improving the predictive capability and computational cost of dynamical models is often at the heart of augmenting computational physics with machine learning (ML). However, most learning results are limited in interpretability and generalization over different computational grid resolutions, initial and boundary conditions, domain geometries, and physical or problem-specific parameters. In the present study, we simultaneously address all these challenges by developing the novel and versatile methodology of unified neural partial delay differential equations. We augment existing/low-fidelity dynamical models directly in their partial differential equation (PDE) forms with both Markovian and non-Markovian neural network (NN) closure parameterizations. The melding of the existing models with NNs in the continuous spatiotemporal space followed by numerical discretization automatically allows for the desired generalizability. The Markovian term is designed to enable extraction of its analytical form and thus provides interpretability. The non-Markovian terms allow accounting for inherently missing time delays needed to represent the real world. Our flexible modeling framework provides full autonomy for the design of the unknown closure terms such as using any linear-, shallow-, or deep-NN architectures, selecting the span of the input function libraries, and using either or both Markovian and non-Markovian closure terms, all in accord with prior knowledge. We obtain adjoint PDEs in the continuous form, thus enabling direct implementation across differentiable and non-differentiable computational physics codes, different ML frameworks, and treatment of nonuniformly-spaced spatiotemporal training data. We demonstrate the new generalized neural closure models (gnCMs) framework using four sets of experiments based on advecting nonlinear waves, shocks, and ocean acidification models. Our learned gnCMs discover missing physics, find leading numerical error terms, discriminate among candidate functional forms in an interpretable fashion, achieve generalization, and compensate for the lack of complexity in simpler models. Finally, we analyze the computational advantages of our new framework.

Probing the general base for DNA polymerization in telomerase: a molecular dynamics investigation.

Telomerase is an RNA-dependent DNA polymerase that plays a role in the maintenance of the 3' end of the eukaryotic chromosome, known as a telomere, by catalyzing the DNA polymerization reaction in cancer and embryonic stem cells. The detailed molecular details of the DNA polymerization by telomerase, especially the general base for deprotonating the terminal 3'-hydroxyl, which triggers the chemical reaction, remain elusive. We conducted a computational investigation using hybrid quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations to probe the detailed mechanism of the reaction. Our simulations started with the telomerase:RNA:DNA:dNTP ternary complex, and by using enhanced sampling QM/MM MD simulations, we probed the general base involved directly in the polymerization. We report the participation of an aspartate (Asp344) coordinated to Mg and an active site water molecule, jointly acting as a base during nucleic acid addition. The Asp344 residue remains transiently protonated during the course of the reaction, and later it deprotonates by transferring its proton to the water at the end of the reaction.

The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies.

Introduction: FOXE1 is required for thyroid function and its homozygous mutations cause a rare syndromic form of congenital hypothyroidism (CH). FOXE1 has a polymorphic polyalanine tract whose involvement in thyroid pathology is controversial. Starting from genetic studies in a CH family, we explored the functional role and involvement of FOXE1 variations in a large CH population. Methods: We applied NGS screening to a large CH family and a cohort of 1752 individuals and validated these results by in silico modeling and in vitro experiments. Results: A new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The p.L107V variant demonstrated to significantly reduce the FOXE1 transcriptional activity. The 14-Alanine-FOXE1 displayed altered subcellular localization and significantly impaired synergy with other transcription factors, when compared with the more common 16-Alanine-FOXE1. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity. Discussion: We provide new evidence that disentangle the pathophysiological role of FOXE1 polyalanine tract, thereby significantly broadening the perspective on the role of FOXE1 in the complex pathogenesis of CH. FOXE1 should be therefore added to the group of polyalanine disease-associated transcription factors.

Concomitant transcatheter transfemoral double native valve replacement for severe aortic stenosis and severe mitral stenosis with mitral annular calcification.

Concomitant mitral and aortic valve stenosis in a patient with mitral annular calcification and porcelain aorta poses a unique problem to the surgical team. Transcatheter aortic and mitral valve replacements in native valves offer a viable option for such selected group of patients. We present the case of a 54-year-old male who presented with severe aortic stenosis (AS) and severe mitral stenosis (MS) but was deemed high risk for surgery owing to intense calcification of the aorta and mitral annular calcification, and successfully underwent transcatheter double native valve replacement.

Expression unleashed in artificial intelligence.

The problem of generating generally capable agents is an important frontier in artificial intelligence (AI) research. Such agents may demonstrate open-ended, versatile, and diverse modes of expression, similar to humans. We interpret the work of Heintz & Scott-Phillips as a minimal sufficient set of socio-cognitive biases for the emergence of generally expressive AI, separate yet complementary to existing algorithms.

Increased cost burden associated with robot-assisted rectopexy: do patient outcomes justify increased expenditure?

BACKGROUND: Robot-assisted surgical techniques have flourished over the years, with refinement in instrumentation and optics allowing for adaptation and increasing utilization across surgical fields. Transabdominal rectopexy with mesh for rectal prolapse may stand to benefit significantly from the use of a robotic platform. However, increased operative times and immediate associated costs of robotic surgery may provide a counterargument to widespread adoption. METHODS: To determine which approach to the treatment of rectal prolapse, laparoscopic or robotic, is more cost effective and provides better outcomes with fewer complications, a retrospective review was performed at a single tertiary care academic institution from May 2013 to December 2020. Twenty-two patients underwent transabdominal mesh rectopexy through a robot-assisted DaVinci platform (Intuitive Sunnyvale, CA), and thirty through a laparoscopic platform. Main outcome measures included operative, hospital, and total cost as defined by total charges billed. Secondary outcomes included rate of recurrence, intra-operative complications, median operative time, post-operative complications, average hospital length of stay, inpatient pain medication usage, and post-operative functional outcomes. RESULTS: Cost analysis for robot-assisted versus laparoscopic rectopexy demonstrated operating room costs of $46,118 ± $9329 for the robotic group, versus $33,090 ± $15,395 (p = 0.002) for the laparoscopic group. Inpatient hospital costs were $60,723 ± $20,170 vs. $40,798 ± $14,325 (p = 0.001), and total costs were $106,841 ± $25,513 vs. $73,888 ± $28,129 (p ≤ 0.001). When secondary outcomes were compared for the robotic versus laparoscopic groups, there were no differences in any of the aforementioned outcome variables except for operative time, which was 79 min longer in the robotic group (p ≤ 0.001). CONCLUSIONS: Robot-assisted mesh rectopexy demonstrated no clinical benefit over traditional laparoscopic mesh rectopexy, with significantly higher operative and hospital costs. A reduction in the acquisition and maintenance costs for robotic surgery is needed before large-scale adoption and implementation of the robotic platform for this procedure.