Cadaveric Study of Colon Lengthening Maneuvers Following 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 prior to rectal anastomosis. DESIGN: A series of lengthening maneuvers was performed on 15 fresh cadavers. Average 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 pre-mobilization and post-mobilization 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 following 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: 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. 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.

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.

Effect of different impression techniques on marginal fit of restoration - An In Vitro study.

Introduction: Impression making is one such important clinical step, which is critical in the accurate fitting of resulting prostheses. Impression making itself depends on the type of material and the impression technique used to record the details. Various combinations of material and the technique have been described in the literature. Aim: To evaluate the effect of three different impression techniques on the marginal fit of computer-aided designed/computer-aided manufactured (CAD/CAM) single unit composite fixed dental prostheses (FDP), different consistencies of addition silicone impression material and different tray design were utilized. Method: Impression of prepared tooth on typodont was made using Matrix impression system, two-step putty wash technique, and individual tooth tray technique. Prosthesis was fabricated using CAD/CAM technology and marginal accuracy was evaluated using scanning electron microscopy (SEM). Result: In the present study, the matrix impression system resulted in less microgap in both mid-buccal and mid-mesial region, whereas putty wash technique showed very high standard deviation in the interproximal region. Conclusion: Matrix impression system had the best results at both mid-buccal and mid-mesial position with least marginal discrepancy. Clinical Implication: The findings of this study could be used by clinicians to help them choose the viscosity of polyvinylsiloxane material and impression techniques for FDP that will result in high-accuracy impressions and well-fitting prostheses.

Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection.

Background: Considering the potential clinical and therapeutic implications, there is a need to determine whether or not COVID infection induces or unmasks new-onset/newly diagnosed hypertension/diabetes during the acute phase and post-COVID-19. Aim: In the current article, we discuss the current data at the intersection of COVID, hypertension, and COVID and diabetes, from prevalence, risk factors, and underlying mechanisms during an acute and post-COVID phase; focusing on new-onset hypertension and new onset type 2 diabetes. Method: We have performed a literature search via online databases such as PubMed/MEDLINE and Google Scholar from December 2019-August 2022. The data from various studies and review articles have been included. Results: Current evidence suggests the occurrence of new-onset hypertension and new onset type 2 diabetes in patients infected with the SARS-CoV-2 virus. Data also indicate a higher risk of negative outcomes in these patients. Conclusions: It is evident that the tenacity of these new-onset diseases post-COVID-19 is likely to have huge implications in terms of unexpected morbidity. Therefore, screening and follow-up of these patients seems reasonable. Clinicians shall have to deal with this evolving challenge and adequately equip themselves to address this facet of COVID-19 as well. Further data from various follow-up studies and registries like the CoviDIAB Project is required to be better equipped to propose exact recommendations for patients with NOD. On the contrary, more evidence is required for incidence and long-term sequelae for patients with new-onset hypertension. How to cite this article: Gupta A, Duggal R. Incidence of New-onset Hypertension and New-onset Type 2 Diabetes during or after SARS-CoV-2 Infection. J Assoc Physicians India 2023;71(10):78-82.

Computer-Vision-Based Vibration Tracking Using a Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method.

Computer-vision-based target tracking is a technology applied to a wide range of research areas, including structural vibration monitoring. However, current target tracking methods suffer from noise in digital image processing. In this paper, a new target tracking method based on the sparse optical flow technique is introduced for improving the accuracy in tracking the target, especially when the target has a large displacement. The proposed method utilizes the Oriented FAST and Rotated BRIEF (ORB) technique which is based on FAST (Features from Accelerated Segment Test), a feature detector, and BRIEF (Binary Robust Independent Elementary Features), a binary descriptor. ORB maintains a variety of keypoints and combines the multi-level strategy with an optical flow algorithm to search the keypoints with a large motion vector for tracking. Then, an outlier removal method based on Hamming distance and interquartile range (IQR) score is introduced to minimize the error. The proposed target tracking method is verified through a lab experiment-a three-story shear building structure subjected to various harmonic excitations. It is compared with existing sparse-optical-flow-based target tracking methods and target tracking methods based on three other types of techniques, i.e., feature matching, dense optical flow, and template matching. The results show that the performance of target tracking is greatly improved through the use of a multi-level strategy and the proposed outlier removal method. The proposed sparse-optical-flow-based target tracking method achieves the best accuracy compared to other existing target tracking methods.

Inking outside the box: systematic review on the utility of tattooing lesions in rectal cancer.

PURPOSE: Endoscopic tattooing in rectal cancer is infrequently utilized for fear of tattoo ink obscuring anatomical planes, increasing the difficulty of surgical excision. Colon cancer tattooing has demonstrated increased lymph node yields and increased accuracy in establishing adequate margins. Rectal cancer tattooing may be especially helpful after neoadjuvant chemoradiation, where complete clinical responses could limit lesion identification and lymph node yields are typically less robust. We seek to review and identify the effects of tattooing in rectal cancer. METHODS: A systematic literature search was performed in PubMed, Embase, and SCOPUS. Studies on endoscopic tattooing with cohorts consisting of at least ≥ 25% of rectal cancer patients were selected. Studies focusing solely on rectal cancer were also reviewed separately. RESULTS: Of 416 studies identified, 10 studies encompassing 2460 patients were evaluated. Seven studies evaluated lymph node yields; five reported beneficial effects of endoscopic tattooing, while two reported no significant difference. Among four studies reporting lesion localization, successful localization rates were between 63 and 100%. Rates of intraoperative endoscopy performed to reevaluate lesion location ranged from 5.7 to 20%. The distal margin was evaluated in two studies, which reported more accurate placement of the distal resection margin after tattooing. When complications of tattooing were documented (7 studies with 889 patients), only five direct complications of endoscopic tattooing were observed (0.6%). CONCLUSIONS: Although the data is heterogenous, it suggests that endoscopic tattooing in rectal cancer may improve lymph node yields and assist in determining accurate distal margins without high rates of complication. Further research must be completed before practice management guidelines can change. TRIAL REGISTRATION: No. CRD42021271784.

Amyloids on Membrane Interfaces: Implications for Neurodegeneration.

Membrane interfaces are vital for various cellular processes, and their involvement in neurodegenerative disorders such as Alzheimer's and Parkinson's disease has taken precedence in recent years. The amyloidogenic proteins associated with neurodegenerative diseases interact with the neuronal membrane through various means, which has implications for both the onset and progression of the disease. The parameters that regulate the interaction between the membrane and the amyloids remain poorly understood. The review focuses on the various aspects of membrane interactions of amyloids, particularly amyloid-ß (Aß) peptides and Tau involved in Alzheimer's and α-synuclein involved in Parkinson's disease. The genetic, cell biological, biochemical, and biophysical studies that form the basis for our current understanding of the membrane interactions of Aß peptides, Tau, and α-synuclein are discussed.

Exploration of high dimensional free energy landscapes by a combination of temperature-accelerated sliced sampling and parallel biasing.

Temperature-accelerated sliced sampling (TASS) is an enhanced sampling method for achieving accelerated and controlled exploration of high-dimensional free energy landscapes in molecular dynamics simulations. With the aid of umbrella bias potentials, the TASS method realizes a controlled exploration and divide-and-conquer strategy for computing high-dimensional free energy surfaces. In TASS, diffusion of the system in the collective variable (CV) space is enhanced with the help of metadynamics bias and elevated-temperature of the auxiliary degrees of freedom (DOF) that are coupled to the CVs. Usually, a low-dimensional metadynamics bias is applied in TASS. In order to further improve the performance of TASS, we propose here to use a highdimensional metadynamics bias, in the same form as in a parallel bias metadynamics scheme. Here, a modified reweighting scheme, in combination with artificial neural network is used for computing unbiased probability distribution of CVs and projections of high-dimensional free energy surfaces. We first validate the accuracy and efficiency of our method in computing the four-dimensional free energy landscape for alanine tripeptide in vacuo. Subsequently, we employ the approach to calculate the eight-dimensional free energy landscape of alanine pentapeptide in vacuo. Finally, the method is applied to a more realistic problem wherein we compute the broad four-dimensional free energy surface corresponding to the deacylation of a drug molecule which is covalently complexed with a ß-lactamase enzyme. We demonstrate that using parallel bias in TASS improves the efficiency of exploration of high-dimensional free energy landscapes.