Comparison of weight-based and pinna size method for ProSeal laryngeal mask airway size selection in children receiving general anesthesia: A randomized clinical study.

Background and Aims: Several methods are in use for LMA ProSeal™ size selection in pediatric patients. Weight-based method is most commonly used. Pinna size-based method is a promising new technique for accurate size selection. Material and Methods: A total of 146 children aged between 6 months and 12 years undergoing surgery under general surgery were included. They were randomized into either pinna-based group (group X) or weight-based group (group Y). Both groups were compared for accurate placement of ProSeal™ laryngeal mask airway (PLMA), ease of insertion, number of attempts needed, and peak airway pressures. Results: A Comparable number of patients had a Brimacombe score of 3 and above, indicating correct placement in both groups (P = 0.407). PLMA was easily inserted in 79.5% and 87.7% of patients of groups X and Y, respectively (P = 0.180). Insertion was found to be difficult in 20.5% of patients in group X, whereas it was difficult in only 12.3% of patients of group Y (P = 0.180). The two groups were comparable as per the number of attempts needed for insertion (P = 0.161). Mean peak airway pressures too were comparable between both groups. Ease of insertion too, was statistically insignificant between both groups. Conclusions: Pinna size-based estimation of LMA size is an effective alternative method to weight-based selection.

Computational Analysis of Mechanical Properties in Polymeric Sandwich Composite Materials.

This article focuses on the computational analysis of sandwich composite materials based on polypropylene, polyester, glass, and cotton fibers. In the automotive components prepared from these fiber materials, the various components are used in different proportions. Through the manufacturing process, isotropic materials become somewhat anisotropic. Part of this article is aimed at obtaining input values of material characteristics for calculations using finite element analysis (FEM) and the comparison of experimental results with FEM-based material models created using the Digimat 2023.1 software. This article analyzes the modeling of two-phase as well as multiphase composite materials. This work focuses on calculations using FEM according to the test defined in the PR375 standard for loading the finished product in the luggage compartment of a car. The defined methodology enables the application of the FEM-based calculation directly to the product design in the initial phase of research. The construction and production of expensive prototypes and the subsequent production of automotive parts is replaced by computer-based simulation. This procedure makes it possible to simulate several optimization cycles over a relatively shorter time. From the results of computational simulations, it is clear that materials based on PP/PET/glass fibers show a much higher modulus of elasticity than materials created using cotton, i.e., materials of the PP/PET/cotton type. In order to achieve a high strength and stiffness, it is, therefore, appropriate to use glass fibers in the composite materials used for such applications.

Elastomer-Based Sealing O-Rings and Their Compatibility with Methanol, Ethanol, and Hydrotreated Vegetable Oil for Fueling Internal Combustion Engines.

Green methanol, ethanol, and diesel-based hydrotreated vegetable oils are some of the renewable liquid fuels that show satisfactory performance in diesel engines. A notable advantage of these fuels is that they are renewable and do not require significant modifications in the existing engines for successful operation. Suitable fuel systems, especially their material compatibility, remain unresolved, and therefore, it is a weak link in their large-scale adaptation. Elastomer-based sealing O-rings lose their mechanical properties after a short exposure time to these fuels, adversely impacting their functionality. This research study evaluated the long-term material compatibility of different elastomer-based sealing materials by immersing the O-rings in these test fuels (hydrotreated vegetable oil, methanol, ethanol, and diesel) for different time intervals (i.e., up to 15 months). The material compatibility was assessed mainly by investigating these changes in various mechanical properties of these O-rings, namely tensile strength (ΔTs), elongation at break (ΔEb), Shore A hardness (ΔH), and mass (ΔM). The degradation of mechanical properties was studied and analyzed during the immersion interval from 0.9 to 15.2 months and compared with O-rings kept in a normal atmosphere. It was noted that individual fuels affect various mechanical properties significantly. In a short interval of 0.9 months (28 days), significant changes in the mechanical properties of the sealing O-rings were observed.

JNJ-10450232 (NTM-006), A novel non-opioid with structural similarities to acetaminophen, produces relatively long-lasting analgesia after a single dose in patients undergoing 3rd molar extraction.

JNJ-10450232 (NTM-006) is a non-opioid, non-NSAID analgesic and antipyretic compound with structural similarity to acetaminophen. Preclinical models show comparable analgesia relative to acetaminophen and no evidence of hepatotoxicity associated with overdose. Moreover, it was safe and generally well tolerated in a First-in-Human Study. This single-dose, single-center, inpatient, randomized, double-blind study in moderate-to-severe acute pain following third molar extraction compared efficacy and safety of 250 mg and 1000 mg JNJ-10450232 (NTM-006), 1000 mg acetaminophen, and placebo during the 24 h following administration. While onset of action of 1000 mg JNJ-10450232 (NTM-006) was relatively slower compared with acetaminophen, its duration of action was sustained up to 24 h being superior beginning 7 h after administration. No clinically important differences among treatment groups in nature or severity of adverse events were observed and no serious adverse events were reported. Increased bilirubin, potentially due to UGT1A1 inhibition and ingestion of blood from oral surgery, was the most commonly reported adverse event and the only event reported by ≥ 5% of subjects across treatment groups. These data support further evaluation of JNJ-10450232 (NTM-006) for the treatment of moderate-to-severe pain. CLINICALTRIALS.GOV ID: NCT02209181.

Mechanical and Thermo-Mechanical Performance of Natural Fiber-Based Single-Ply and 2-Ply Woven Prepregs.

This paper presents a study conducted on prepregs manufactured by a novel method for the impregnation of a thermoplastic matrix. Different composite prepregs based on polypropylene and reinforced with natural fibers (e.g., basalt and jute fibers) were developed. The mechanical and dynamic mechanical properties were investigated. DMA tests were conducted at 1 Hz frequency and properties such as storage modulus and damping (tan δ) were evaluated. The overall mechanical properties of the basalt fiber composites were found to be superior to that of the jute fiber-based samples. Thermo-gravimetric analysis (TG/DTG) of the composite samples showed that the thermal degradation temperatures of the basalt-based composites shifted to higher temperature regions compared to the PP or jute fiber composites. The addition of basalt fiber considerably improved the thermal stability of the composite samples. Microscopic images of the tensile fractured composite samples illustrated better fiber-matrix interfacial interaction due to the novel technology of prepregs. Single-ply and 2-ply prepregs showed significantly superior mechanical, thermal, and thermo-dynamical performance compared to the control sample (pure PP). 2-Ply composites demonstrated higher modulus, tensile strength, and storage modulus due to the higher fiber volume fraction. Basalt-based samples showed a minimum weight loss of about 57% up to 700 °C in contrast to 96.05% weight loss in the jute-based samples and 98.4% in the case of pure PP. The heat resistance index (THRI) is more than twice for basalt compared to jute and PP. Furthermore, the superior thermal stability of basalt is reflected in its DSC curves, showing the highest endothermic peak. The technique of using the resin in the form of thermoplastic yarns offers cost effective and efficient alternatives for composite manufacturing.

A systematic review on traditional, ayurvedic, and herbal approaches to treat solar erythema.

Solar erythema is a kind of radiation burn that strikes living tissue, such as skin, that arises from overexposure to UV radiation often from the sun. Ordinary symptoms of solar erythema include reddish skin, specifically warm to touch, overall tiredness, hurting, and mild whirl. Sunscreen contains SPF value, which measures how much ultraviolet radiation is needed to cause sunburn on sunscreen-applied skin, which is proportional to the quantity of solar energy needed to cause sunburn on unprotected skin. Between 30 and 50 SPF value is sufficient to protect from sunburn, especially for the people who are more sensitive to sunburn. Sunscreen also protects from sun damage including dark spots and discoloration and helps to keep skin smooth, spotless, and more even. Chemical-based sunscreen is widely used because it effectively protects the skin from sun damage, but it clogs pores and can be problematic for sensitive skin as it can cause itching or stinging of the skin and pus in the hair follicles. On the other hand, herbal sunscreen absorbs light preferentially over the range of 280-320 mm without causing any harm to the skin and eyes. Ayurveda rejuvenates dull skin by regaining the skin's natural glow and radiance. This review concludes the damaging and harmful effects of UV rays, along with various traditional, ayurvedic, and herbal approaches to treat solar erythema naturally.

Development of Lightweight Cricket Pads Using Knitted Flexible Thermoplastic Composites with Improved Impact Protection.

Cricket is one of the most popular global sports, and cricket pads are important personal protective gear used for shock absorption and peak deceleration of the impact forces of the cricket ball for both batsmen and wicket keepers. The materials selection of the padding should be considered according to requirements. In the present study, flexible composites were manufactured using knitted unidirectional thermoplastic composite prepregs. Prepregs were fabricated using thermoplastic yarns, e.g., High Density Polyethylene (HDPE), Polypropylene (PP), and Low Melting Polyester (LMPE). Para-aramid (Kevlar) and Flax yarns were used as inlay. The structures were stacked in three and five layers, and hot compression was used to convert thermoplastic yarn into matrix. A total of twelve samples were prepared, and their mechanical properties were evaluated. Tensile and flexural properties, short beam strength, and impact properties were optimized using the multi-criteria decision-making (MCDM) technique for order performance by similarity to ideal solution (TOPSIS). This approach was used to select the best material for use in cricket pads. The candidate samples were ranked using statistical techniques. The optimum sample was found to be FP5, i.e., Flax with polypropylene using five layers, which exhibited the maximum impact strength. The results showed that the mechanical properties were improved in general by increasing the number of layers. The significance and percentage contribution of each factor was obtained by ANOVA (α = 0.10) and pie chart, which showed Factors A and C (inlay yarn and number of layers) to be the main contributors. The optimal samples showed superior impact-related performance compared to a market sample cricket pad.

Modeling and Simulation of Mechanical Performance in Textile Structural Concrete Composites Reinforced with Basalt Fibers.

This investigation deals with the prediction of mechanical behavior in basalt-fiber-reinforced concrete using the finite element method (FEM). The use of fibers as reinforcement in concrete is a relatively new concept which results in several advantages over steel-reinforced concrete with respect to mechanical performance. Glass and polypropylene (PP) fibers have been extensively used for reinforcing concrete for decades, but basalt fibers have gained popularity in recent years due to their superior mechanical properties and compatibility with concrete. In this study, the mechanical properties of basalt-fiber-reinforced concrete are predicted using FEM analysis, and the model results are validated by conducting experiments. The effect of fiber-volume fraction on the selected mechanical performance of concrete is evaluated in detail. Significant improvement is observed when the loading is increased. There are superior mechanical properties, e.g., load bearing and strain energy in basalt-fiber-reinforced concrete as compared to conventional concrete slabs reinforced with gravel or stones. The results of the simulations are correlated with experimental samples and show a very high similarity. Basalt-fiber-reinforced concrete (BFRC) offers a lightweight construction material as compared to steel-fiber-reinforced concrete (SFRC). Further, the problem of corrosion is overcome by using this novel fiber material in concrete composites.

Indian Society of Critical Care Medicine Consensus Statement for Prevention of Venous Thromboembolism in the Critical Care Unit.

Deep vein thrombosis (DVT) is a preventable complication of critical illness, and this guideline aims to convey a pragmatic approach to the problem. Guidelines have multiplied over the last decade, and their utility has become increasingly conflicted as the reader interprets all suggestions or recommendations as something that must be followed. The nuances of grade of recommendation vs level of evidence are often ignored, and the difference between a "we suggest" vs a "we recommend" is overlooked. There is a general unease among clinicians that failure to follow the guidelines translates to poor medical practice and legal culpability. We attempt to overcome these limitations by highlighting ambiguity when it occurs and refraining from dogmatic recommendations in the absence of robust evidence. Readers and practitioners may find the lack of specific recommendations unsatisfactory, but we believe that true ambiguity is better than inaccurate certainty. We have attempted to comply with the guidelines on how to create guidelines.1 And to overcome the poor compliance with these guidelines.2 Some observers have expressed concern that DVT prophylaxis guidelines may cause more harm than good.3 We have placed greater emphasis on large randomized controlled trials (RCTs) with clinical end point and de-emphasized RCTs with surrogate end points and also de-emphasized hypothesis generating studies (observational studies, small RCTs, and meta-analysis of these studies). We have de-emphasized RCTs in non-intensive care unit populations like postoperative patients or those with cancer and stroke. We have also considered resource limitation settings and have avoided recommending costly and poorly proven therapeutic options. How to cite this article: Jagiasi BG, Chhallani AA, Dixit SB, Kumar R, Pandit RA, Govil D, et al. Indian Society of Critical Care Medicine Consensus Statement for Prevention of Venous Thromboembolism in the Critical Care Unit. Indian J Crit Care Med 2022;26(S2):S51-S65.

Effect of Waterjet Machining Parameters on the Cut Quality of PP and PVC-U Materials Coated with Polyurethane and Acrylate Coatings.

The article focuses on the machining of polymeric materials polypropylene (PP) and un-plasticized poly vinyl chloride (PVC-U) after surface treatment with polyurethane and acrylate coatings using waterjet technology. Two types of waterjet technologies, abrasive waterjet (AWJ) and waterjet without abrasive (WJ), were used. The kerf width and its taper angle, at the inlet and outlet of the waterjet from the workpiece, were evaluated. Significant differences between AWJ and WJ technology were found. WJ technology proved to be less effective due to the creation of a nonuniform cutting gap and significant burrs. AWJ technology was shown to be more efficient, i.e., more uniform cuts were achieved compared to WJ technology, especially at a cutting head traverse speed of 50 mm·min-1. The most uniform kerf width or taper angle was achieved for PP + MOBIHEL (0.09°). The materials (PP and PVC-U) with the POLURAN coating had higher values of the taper angle of the cutting gap than the material with the MOBIHEL coating at all cutting head traverse speeds. The SEM results showed that the inappropriate cutting head traverse speed and the associated WJ technology resulted in significant destruction of the material to be cut on the underside of the cut. Delamination of the POLURAN and MOBIHEL coatings from the base material PP and PVC-U was not demonstrated by SEM analysis over the range of cutting head traverse speeds, i.e., 50 to 1000 mm·min-1.

Nicking and fragmentation are responsible for α-lactalbumin amyloid fibril formation at acidic pH and elevated temperature.

Amyloid fibrils are ordered aggregates that may be formed from disordered, partially unfolded, and fragments of proteins and peptides. There are several diseases, which are due to the formation and deposition of insoluble ß-sheet protein aggregates in various tissue, collectively known as amyloidosis. Here, we have used bovine α-lactalbumin as a model protein to understand the mechanism of amyloid fibril formation at pH 1.6 and 65°C under non-reducing conditions. Amyloid fibril formation is confirmed by Thioflavin T fluorescence and atomic force microscopy (AFM). Our finding demonstrates that hydrolysis of peptide bonds occurs under these conditions, which results in nicking and fragmentation. The nicking and fragmentation have been confirmed on non-reducing and reducing gel. We have identified the fragments by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The fragmentation may initiate nucleation as it coincides with AFM images. Conformational changes associated with monomer resulting in fibrillation are shown by circular dichroism and Raman spectroscopy. The current study highlights the importance of nicking and fragmentation in amyloid fibril formation, which may help understand the role of acidic pH and proteolysis under in vivo conditions in the initiation of amyloid fibril formation.

Comparison of 3D vs 2D laparoscopic-assisted anorectal pull-through (LAARP) for high anorectal malformations in children.

INTRODUCTION: The limitation of two-dimensional (2D) laparoscopic techniques includes lack of stereoscopic vision and depth perception which can affect surgical performance, physical and mental comfort of the operating surgeon. 3D laparoscopic surgery is popular in adults; however, its application and experience in the pediatric age group have been limited. We did a comparison of 2D and 3D laparoscopic-assisted anorectal pull-through (LAARP) in male high anorectal malformations (ARM). MATERIAL AND METHOD: This prospective cohort study included male children diagnosed with high anorectal malformation (recto-prostatic urethral fistula) who underwent LAARP in infancy after a neonatal colostomy between November 2019 to March 2020. The patients were randomized into a 2D group or 3D group at a 1:1 ratio. Patient demographics and operative/postoperative parameters were recorded. The effect of 3D laparoscopy was assessed in terms of laparoscopy visual parameters (image quality, depth perception, hand-eye coordination, and precision), physical discomfort (5-point Likert scale), and mental strain (State-Trait Anxiety Inventory scale). The statistical tests were performed on SPSS version 16. RESULTS: The demographics of both groups, 20 (patients in each), were similar. There was a significant reduction of laparoscopy execution time, physical discomfort (for eye, hand and wrist strain), and overall mental strain in the 3D group. There were similar complications, blood loss, and hospital stay, and no open conversion in two groups. CONCLUSION: 3D LAARP is feasible and safe in the surgical treatment of ARM in children. Further studies with assessment by more than one observer are needed to investigate the wider application of 3D in pediatric surgery.

A novel quality prediction model for component based software system using ACO-NM optimized extreme learning machine.

Component-based software engineering is currently a development strategy used to improve complex embedded systems. The engineers have to deal with a large number of quality requirements (e.g. safety, security, availability, reliability, maintainability, portability, performance, and temporal correctness requirements), hence the development of complex embedded systems is becoming a challenging task. Enhancement of the quality prediction in component-based software engineering systems using soft computing techniques is the foremost intention of the research. Therefore, this paper proposes an extreme learning machine (ELM) classifier with the ant colony optimization algorithm and Nelder-Mead (ACO-NM) soft computing approach for component quality prediction. To promote efficient software systems and the ability of the software to work under several computer configurations maintainability, independence, and portability are taken as three core software components metrics for measuring the quality prediction. The ELM uses AC-NM for updating its weight to transform the quality constraints into objective functions for providing a global optimum quality prediction. The experimental results have shown that the proposed work gives an improved performance in terms of Sensitivity, Precision, Specificity, Accuracy, Mathews correlation coefficient, false positive rate, negative predictive value, false discovery rate, and rate of convergence.

ISCCM Guidelines for the Use of Non-invasive Ventilation in Acute Respiratory Failure in Adult ICUs.

A. ACUTE HYPERCAPNIC RESPIRATORY FAILURE A1. Acute Exacerbation of COPD: Recommendations: NIV should be used in management of acute exacerbation of COPD in patients with acute or acute-on-chronic respiratory acidosis (pH = 7.25-7.35). (1A) NIV should be attempted in patients with acute exacerbation of COPD (pH <7.25 & PaCO2 ≥ 45) before initiating invasive mechanical ventilation (IMV) except in patients requiring immediate intubation. (2A). Lower the pH higher the chance of failure of NIV. (2B) NIV should not to be used routinely in normo- or mildly hyper-capneic patients with acute exacerbation of COPD, without acidosis (pH > 7.35). (2B) A2. NIV in ARF due to Chest wall deformities/Neuromuscular diseases: Recommendations: NIV may be used in patients of ARF due to chest wall deformity/Neuromuscular diseases. (PaCO2 ≥ 45) (UPP) A3. NIV in ARF due to Obesity hypoventilation syndrome (OHS): Recommendations: NIV may be used in AHRF in OHS patients when they present with acute hypercapnic or acute on chronic respiratory failure (pH 45). (3B) NIV/CPAP may be used in obese, hypercapnic patients with OHS and/or right heart failure in the absence of acidosis. (UPP) B. NIV IN ACUTE HYPOXEMIC RESPIRATORY FAILURE: B1. NIV in Acute Cardiogenic Pulmonary Oedema: Recommendations: NIV is recommended in hospital patients with ARF, due to Cardiogenic pulmonary edema. (1A). NIV should be used in patients with acute heart failure/ cardiogenic pulmonary edema, right from emergency department itself. (1B) Both CPAP and BiPAP modes are safe and effective in patients with cardiogenic pulmonary edema. (1A). However, BPAP (NIV-PS) should be preferred in cardiogenic pulmonary edema with hypercapnia. (3A) B2. NIV in acute hypoxemic respiratory failure: Recommendations: NIV may be used over conventional oxygen therapy in mild early acute hypoxemic respiratory failure (P/F ratio <300 and >200 mmHg), under close supervision. (2B) We strongly recommend against a trial of NIV in patients with acute hypoxemic failure with P/F ratio <150. (2A) B3. NIV in ARF due to Chest Trauma: Recommendations: NIV may be used in traumatic flail chest along with adequate pain relief. (3B) B4. NIV in Immunocompromised Host: Recommendations: In Immunocompromised patients with early ARF, we may consider NIV over conventional oxygen. (2B). B5. NIV in Palliative Care: Recommendations: We strongly recommend use of NIV for reducing dyspnea in palliative care setting. (2A) B6. NIV in post-operative cases: Recommendations: NIV should be used in patients with post-operative acute respiratory failure. (2A) B6a. NIV in abdominal surgery: Recommendations: NIV may be used in patients with ARF following abdominal surgeries. (2A) B6b. NIV in bariatric surgery: Recommendations: NIV may be used in post-bariatric surgery patients with pre-existent OSA or OHS. (3A) B6c. NIV in Thoracic surgery: Recommendations: In cardiothoracic surgeries, use of NIV is recommended post operatively for acute respiratory failure to improve oxygenation and reduce chance of reintubation. (2A) NIV should not be used in patients undergoing esophageal surgery. (UPP) B6d. NIV in post lung transplant: Recommendations: NIV may be used for shortening weaning time and to avoid re-intubation following lung transplantation. (2B) B7. NIV during Procedures (ETI/Bronchoscopy/TEE/Endoscopy): Recommendations: NIV may be used for pre-oxygenation before intubation. (2B) NIV with appropriate interface may be used in patients of ARF during Bronchoscopy/Endoscopy to improve oxygenation. (3B) B8. NIV in Viral Pneumonitis ARDS: Recommendations: NIV cannot be considered as a treatment of choice for patients with acute respiratory failure with H1N1 pneumonia. However, it may be reasonable to use NIV in selected patients with single organ involvement, in a strictly controlled environment with close monitoring. (2B) B9. NIV and Acute exacerbation of Pulmonary Tuberculosis: Recommendations: Careful use of NIV in patients with acute Tuberculosis may be considered, with effective infection control precautions to prevent air-borne transmission. (3B) B10. NIV after planned extubation in high risk patients: Recommendation: We recommend that NIV may be used to wean high risk patients from invasive mechanical ventilation as it reduces re-intubation rate. (2B) B11. NIV for respiratory distress post extubation: Recommendations: We recommend that NIV therapy should not be used to manage respiratory distress post-extubation in high risk patients. (2B) C. APPLICATION OF NIV: Recommendation: Choice of mode should be mainly decided by factors like disease etiology and severity, the breathing effort by the patient and the operator familiarity and experience. (UPP) We suggest using flow trigger over pressure triggering in assisted modes, as it provides better patient ventilator synchrony. Especially in COPD patients, flow triggering has been found to benefit auto PEEP. (3B) D. MANAGEMENT OF PATIENT ON NIV: D1. Sedation: Recommendations: A non-pharmacological approach to calm the patient (Reassuring the patient, proper environment) should always be tried before administrating sedatives. (UPP) In patients on NIV, sedation may be used with extremely close monitoring and only in an ICU setting with lookout for signs of NIV failure. (UPP) E. EQUIPMENT: Recommendations: We recommend that portable bilevel ventilators or specifically designed ICU ventilators with non-invasive mode should be used for delivering Non-invasive ventilation in critically ill patients. (UPP) Both critical care ventilators with leak compensation and bi-level ventilators have been equally effective in decreasing the WOB, RR, and PaCO2. (3B) Currently, Oronasal mask is the most preferred interface for non-invasive ventilation for acute respiratory failure. (3B) F. WEANING: Recommendations: We recommend that weaning from NIV may be done by a standardized protocol driven approach of the unit. (2B) How to cite this article: Chawla R, Dixit SB, Zirpe KG, Chaudhry D, Khilnani GC, Mehta Y, et al. ISCCM Guidelines for the Use of Non-invasive Ventilation in Acute Respiratory Failure in Adult ICUs. Indian J Crit Care Med 2020;24(Suppl 1):S61-S81.

Transperineal Intracath Meconiolysis and Evacuation Technique of "Distended" Bowel Evacuation for One-Stage Laparoscopic Anorectoplasty for High Anorectal Malformations in Males.

Introduction: One-stage anorectoplasty provides maximum potential for "normal" defecation reflexes right at birth and avoids complications and problems of colostomy. One-stage laparoscopic anorectoplasty (OSLARP) for rectourinary fistula (RUF) is restricted by distended bowel obscuring the working space for laparoscopy. This study describes transperineal intracath meconiolysis and evacuation (TIME) technique for OSLARP in the treatment of RUF in neonates. Materials and Technique: High male anorectal malformation (ARM) admitted from January 2016 to March 2019 were included in the study. Diagnosis of level of ARM was made on the basis of invertogram. Patient presenting with lethal comorbidities were excluded who underwent colostomy. The technique involved placement of a 16G intracath in the perineum through the site of future neo-anus, which was identified using muscle stimulator. Meconiolysis and evacuation was done using warm saline and 2% N-acetyl. The creation of enough abdominal space was achieved after evacuation and two working instruments were placed in paraumbilical positions. The laparoscopic dissection and division of fistula was done as followed in standard laparoscopic anorectoplasty. Results: Seventeen patients were selected for TIME technique but on laparoscopy 2 patients had severe necrotizing enterocolitis hence they underwent laparoscopy-assisted high sigmoid colostomy. Fifteen patients underwent OSLARP successfully. Mean weight was 2.5 ± 0.4 kg, mean gestational age was 36 ± 5 weeks, and mean age of presentation was 3.5 ± 1 days after birth. The TIME technique was successful decompressing bowel in all the patients. Out of 15 patients of OSLARP, 14 had rectoprostatic urethral fistula and 1 had rectovesical fistula. Mean total operative duration of OSLARP was 46 ± 15 minutes. Patients who could be followed for 3 years had good results in terms of continence and bowel movements. Discussion: TIME technique is a very simple and effective way to overcome the problem of associated colonic distention in neonatal one-stage laparoscopic anoplasty.

Impact of N-glycosylation site variants during human PrP aggregation and fibril nucleation.

Misfolding and aggregation of the human prion protein (PrP) cause neurodegenerative transmissible spongiform encephalopathies such as Creutzfeldt-Jakob disease. Mature native PrP is composed of 209 residues and is folded into a C-terminal globular domain (residues 125-209) comprising a small two-stranded ß-sheet and three α-helices. The N-terminal domain (residues 23-124) is intrinsically disordered. Expression of truncated PrP (residues 90-231) is sufficient to cause prion disease and residues 90/100-231 is comprising the amyloid-like fibril core of misfolded infectious PrP. During PrP fibril formation under native conditions in vitro, the disordered N-terminal domain slows down fibril formation likely due to a mechanism of initial aggregation forming morphologically disordered aggregates. The morphological disordered aggregate is a transient phase. Nucleation of fibrils occurs from this initial aggregate. The aggregate phase is largely circumvented by seeding with preformed PrP fibrils. In vivo PrP is N-glycosylated at positions Asn181 and Asn197. Little is known about the importance of these positions and their glycans for PrP stability, aggregation and fibril formation. We have in this study taken a step towards that goal by mutating residues 181 and 197 for cysteines to study the positional impact on these processes. We have further by organic synthetic chemistry and chemical modification generated synthetic glycosylations in these positions. Our data shows that residue 181 when mutated to a cysteine is a key residue for self-chaperoning, rendering a trap in the initial aggregate preventing conformational changes towards amyloid fibril formation. Position 197 is less involved in the aggregate trapping and is more geared towards ß-sheet structure conversion within amyloid fibrils. As expected, synthetic glycosylated 197 is less affected towards fibril formation compared to glycosylated 181. Our data are rather compatible with the parallel in-register intermolecular ß-sheet model structure of the PrP90-231 fibril and sheds light on the misfolding transitions of PrP in vitro. We hypothesize that glycosylation of position 181 is a key site for prion strain differentiation in vivo.

Laparoscopic 'steering wheel' derotation technique for midgut volvulus in children with intestinal malrotation.

INTRODUCTION: Since the first description by William Ladd, the Ladd's procedure has been the surgery of choice for the correction of malrotation. The laparoscopic Ladd's procedure is becoming popular with the advent of minimal access surgery and is described in the literature. Various techniques of the Ladd's procedure have been described but none of them describes the stepwise technique for derotation of volvulus which is the most difficult and confusing part of the surgery. We describe 'steering wheel' technique for easy derotation of volvulus associated with malrotation. METHOD: A total of 62 patients were diagnosed to have an intestinal malrotation between 2010 and 2017. All cases which had complete non-rotation with a midgut volvulus were reviewed. Out of these, 48 patients were operated with open technique and 14 patients were subjected to the laparoscopic correction. TECHNIQUE: Using three-port technique, stepwise derotation of volvulus is done which simulates the rotation of steering of car at an acute turn and has been described in four simple steps. This technique also stresses the importance of the release of Ladd's band before derotation. RESULTS: Of 62 patients diagnosed with malrotation, 14 (22.6%) patients underwent the laparoscopic Ladd's procedure. The mean age was 26 + 8 months, mean weight was 10 + 2 kg and included eight males (57%) and six females (43%). There was only one (7.14%) conversion to open technique, due to a huge dilatation of duodenum causing difficulty in dissection in a patient with malrotation without volvulus. The laparoscopic Ladd's procedure took an average time of 70 ± 15 min. CONCLUSION: The laparoscopic 'steering wheel' derotation technique is easy and provides a stepwise description of the laparoscopic derotation of volvulus associated with malrotation in children.

Cobalt and nickel impair DNA metabolism by the oxidative stress independent pathway.

The oxidative stress that evolves under cobalt and nickel exposure is thought to exert toxicity, though the exact routes of such metal poisoning remain ambiguous. We revisited the metal toxicity in Escherichia coli to show that cobalt and nickel exposure at levels as low as 0.5 and 1 mM, respectively, visibly inhibits growth. We also observed that acidic conditions aggravated, while alkaline conditions alleviated the metal toxicity. Besides, 1 mM manganese, which is non-cytotoxic, as judged by the growth of E. coli, synergistically elevated cobalt and nickel stress. However, the metal toxicity did not lead to oxidative stress in E. coli. On the other hand, we show that cobalt and nickel, but not manganese, reduced the rate of DNA replication to 50% within 2 hours. Interestingly, the metal ions promoted DNA double-strand breaks but did not induce SOS repair pathways, indicating that the metal ions could block SOS induction. To test this, we show that cobalt and nickel, but not manganese, suppressed the nalidixic acid-induced SOS response. Finally, using an in vitro assay system, we demonstrated that cobalt and nickel inhibit RecBCD function, which is essential for SOS induction. Therefore, our data indicate that cobalt and nickel affect DNA replication, damage DNA, and inhibit the SOS repair pathway to exert toxicity.

Estimation of Whole Body Radiation Exposure to Nuclear Medicine Personnel During Synthesis of 177Lutetium-labeled Radiopharmaceuticals.

PURPOSE OF THE STUDY: With rapid development in the field of nuclear medicine therapy, radiation safety of the personnel involved in synthesis of radiopharmaceuticals has become imperative. Few studies have been done on estimating the radiation exposure of personnel involved in the radio labeling of 177Lu-compounds in western countries. However, data from the Indian subcontinent are limited. We have estimated whole body radiation exposure to the radiopharmacist involved in the labeling of: 177Lu-DOTATATE, 177Lu-PSMA-617, and 177Lu-EDTMP. MATERIALS AND METHODS: Background radiation was measured by keeping a pocket dosimeter around the workbench when no radioactive work was conducted. The same pocket dosimeter was given to the radiopharmacist performing the labeling of 177Lu-compounds. All radiopharmaceuticals were synthesized by the same radiopharmacist with 3, 1 and 3 year experience, respectively, in radiolabeling the above compounds. RESULTS: One Curie (1 Ci) of 177Lu was received fortnightly by our department. Data were collected for 12 syntheses of 177Lu-DOTATATE, 8 syntheses of 177Lu-PSMA-617, and 3 syntheses of 177Lu-EDTMP. Mean time required to complete the synthesis was 0.81, 0.65, and 0.58 h, respectively. Mean whole body radiation exposure was 0.023 ± 0.01 mSv, 0.01 ± 0.002 mSv, and 0.002 ± 0.0006 mSv, respectively. Overall mean radiation dose for all the three 177Lu-compounds was 0.014 mSv. Highest exposure was obtained during the synthesis of 177Lu-DOTATATE. CONCLUSION: Our data suggest that the manual radiolabeling of 177Lu compounds is safe, and the whole body radiation exposure to the involved personnel is well within prescribed limits.

The effects of nicotine replacement on cognitive brain activity during smoking withdrawal studied with simultaneous fMRI/EEG.

Impaired attention ('difficulty concentrating') is a cognitive symptom of nicotine withdrawal that may be an important contributor to smoking relapse. However, the neurobiological basis of this effect and the potentially beneficial effects of nicotine replacement therapy both remain unclear. We used functional MRI with simultaneous electroencephalogram (EEG) recording to define brain activity correlates of cognitive impairment with short-term smoking cessation in habitual smokers and the effects of nicotine replacement. We found that irrespective of treatment (ie nicotine or placebo) EEG α power was negatively correlated with increased activation during performance of a rapid visual information processing (RVIP) task in dorsolateral prefrontal, dorsal anterior cingulate, parietal, and insular cortices, as well as, caudate, and thalamus. Relative to placebo, nicotine replacement further increased the α-correlated activation across these regions. We also found that EEG α power was negatively correlated with RVIP-induced deactivation in regions comprising the 'default mode' network (ie angular gyrus, cuneus, precuneus, posterior cingulate, and ventromedial prefrontal cortex). These α-correlated deactivations were further reduced by nicotine. These findings confirm that effects of nicotine on cognition during short-term smoking cessation occur with modulation of neuronal sources common to the generation of both the blood oxygen-level-dependent and α EEG signals. Our observations thus demonstrate that nicotine replacement in smokers has direct pharmacological effects on brain neuronal activity modulating cognitive networks.