Search

Abstract Objectives The aim of the ITI Consensus Workshop on zygomatic implants was to provide Consensus Statements and Clinical Recommendations for the use of zygomatic implants. Materials and methods Three systematic reviews and one narrative review were written to address focused questions on (1) the indications for the use of zygomatic implants; (2) the survival rates and complications associated with surgery in zygomatic implant placement; (3) long-term survival rates of zygomatic implants and (4) the biomechanical principles involved when zygoma implants are placed under functional loads. Based on the reviews, three working groups then developed Consensus Statements and Clinical Recommendations. These were discussed in a plenary and finalized in Delphi rounds. Results A total of 21 Consensus Statements were developed from the systematic reviews. Additionally, the group developed 17 Clinical Recommendations based on the Consensus Statements and the combined expertise of the participants. Conclusions Zygomatic implants are mainly indicated in cases with maxillary bone atrophy or deficiency. Long-term mean zygomatic implant survival was 96.2% [95% CI 93.8; 97.7] over a mean follow-up of 75.4 months (6.3 years) with a follow-up range of 36–141.6 months (3–11.8 years). Immediate loading showed a statistically significant increase in survival over delayed loading. Sinusitis presented with a total prevalence of 14.2% [95% CI 8.8; 22.0] over a mean 65.4 months follow-up, representing the most common complication which may lead to zygomatic implant loss. The international experts suggested clinical recommendations regarding planning, surgery, restoration, outcomes, and the patient’s perspective.

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.

Background: Currently, more than 150 surgical techniques have been described for the treatment of hallux valgus. The abundance of techniques indicates that there is no technique that has been designated as a gold standard. In recent years, a particular interest in the use of minimally invasive techniques has grown. The aim of this study was to prospectively compare clinical, radiologic, and postoperative outcomes between the MICA technique and open chevron technique over a 1-year follow-up period. Methods: Between January 2016 and August 2020, data were prospectively collected from consecutive patients preoperatively and at 6 weeks, 3 months, and 12 months following minimally invasive chevron and Akin (MICA) or open chevron osteotomies. Radiographic outcomes were measured using weightbearing radiographs preoperatively and at 3 and 12 months postoperatively. Clinical outcomes were measured using the American Orthopaedic Foot & Ankle Society (AOFAS), Manchester-Oxford Foot Questionnaire (MOXFQ), VAS (visual analog scale), Foot Function Index (FFI), Foot and Ankle Outcome Score (FAOS), and Euro-QoL-5D (EQ5D) questionnaires. Results: Of the 68 patients, 42 patients (62%) underwent a MICA surgery and 26 patients (38%) underwent open chevron osteotomy. Both groups showed significant improvement in HVA, IMA, and DMAA at the 1-year follow-up. Our findings show that both clinical and radiologic outcomes of the MICA technique are comparable to the conventional open technique. No significant differences were found in clinical outcomes (VAS, AOFAS, MOXFQ, FFI, and FAOS), complication rate, and operative times. Conclusion: These results show that MICA is a safe alternative for chevron osteotomy. The clinical and radiologic outcomes of these 2 techniques by 12 months are comparable. Level of Evidence: Level II, prospective cohort study.

Rising carbon emissions are worsening global climatic conditions, posing a grave threat to the environment. Analysing and reducing carbon footprints are vital for combating climate change. A carbon footprint analysis categorises emissions into three scopes, aiming to identify re- duction areas and promote sustainable practices, such as energy efficiency, renewable energy use, and eco-friendly choices in consumption. The current study’s purpose is to track and analyse the carbon emissions in the inbound and outbound logistics of a process industry belonging to Micro Small and Medium Enterprises using life cycle analysis. Ultimately, this study recommends mitigation strategies to bring down the carbon footprint.

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder. Plexiform neurofibromas (PNFs) are benign tumors commonly formed in patients with NF1. PNFs have a high incidence of developing into malignant peripheral nerve sheath tumors (MPNSTs) with a 5-year survival rate of only 30%. Therefore, the accurate diagnosis and differentiation of MPNSTs from benign PNFs are critical to patient management. We studied a fluorine-18 labeled tryptophan positron emission tomography (PET) radiotracer, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp), to detect NF1-associated tumors in an animal model. An ex vivo biodistribution study of L-[18F]FETrp showed a similar tracer distribution and kinetics between the wild-type and triple mutant mice with the highest uptake in the pancreas. Bone uptake was stable. Brain uptake was low during the 90-min uptake period. Static PET imaging at 60 min post-injection showed L-[18F]FETrp had a comparable tumor uptake with [1⁸F]fluorodeoxyglucose (FDG). However, L-[18F]FETrp showed a significantly higher tumor-to-brain ratio than FDG (n = 4, p < 0.05). Sixty-minute-long dynamic PET scans using the two radiotracers showed similar kidney, liver, and lung kinetics. A dysregulated tryptophan metabolism in NF1 mice was further confirmed using immunohistostaining. L-[18F]FETrp is warranted to further investigate differentiating malignant NF1 tumors from benign PNFs. The study may reveal the tryptophan–kynurenine pathway as a therapeutic target for treating NF1.

When compared to conventional forceps biopsy, the use of a flexible cryoprobe allows for the sampling of endobronchial lesions, yielding well-preserved, circumferential, and substantial specimens, resulting in a higher diagnostic yield, as demonstrated in multiple studies. We evaluated the utility of cryobiopsy in the diagnosis of endobronchial lesions as well as its safety profile in this study. This retrospective study included 200 patients who underwent cryobiopsy for bronchoscopically visible endobronchial lesions between March 2016 and July 2022. Cryobiopsy was performed under conscious sedation using a flexible cryoprobe. Data on baseline patient characteristics, post-biopsy bleeding, and final histopathological diagnosis were collected. We evaluated the procedure's diagnostic yield and safety. The majority of the patients were male (84.5%) and the mean age of the patients was 56.96±13.64 years. In our study, the average size of cryobiopsy specimen was 6.8±1.2 mm. In 93% of cases, a definitive diagnosis was established; the most common diagnosis was squamous cell carcinoma of the lung (42.5%), followed by adenocarcinoma (18.5%) and small cell carcinoma (13.5%). Tuberculosis and sarcoidosis were reported in 2.5% and 1% of cases, respectively. In this study, 1% of patients had severe bleeding that required intubation and ICU admission, while 26% had moderate bleeding that was treated with cold saline and local epinephrine instillation. No mortality was reported in the study. Endobronchial cryobiopsy with a flexible bronchoscope is a safe procedure with a high diagnostic yield. This approach, which has a favorable safety profile, holds the promise of improving diagnostic and treatment outcomes in lung cancer and other benign lung diseases.

Objectives: Tracheoesophageal fistula (TEF) is a congenital disorder that presents as a surgical emergency in neonates. In regions where neonatal intensive care unit facilities and resources are inadequate and skilled personnel are scarce, not extubating neonates on table, contributes to mortality. Our aim was to assess and compare the on-table extubation rate, extubation time, and postoperative pain scores between opioid and opioid-free anesthesia techniques in neonates undergoing surgical repair of TEF. Methods: We conducted a prospective, single-blind, randomized trial over 18 months between January 2021 and June 2022 in Safdarjung Hospital, New Delhi on 60 full-term neonates scheduled for TEF surgeries randomly allocated to two groups according to the mode of analgesia administered. Group O were given fentanyl injection 1 µg/kg intravenous (IV) loading dose with IV injection. acetaminophen at 7.5 mg/kg and top-up of 0.25 µg/kg fentanyl IV si opus sit. Group NO were given pre-surgical local infiltration and intercostal block with 0.25% and 0.5% bupivacaine, respectively, with IV acetaminophen at 7.5 mg/kg. Results: Mean age in days, gender distribution, and weight in both groups were statistically comparable. The difference in the number of neonates extubated on table was statistically significant (p =0.002) in group NO compared to group O. Lower mean extubation time was seen in group NO (9.0 min 40.0 secs±3.0 min 3.0 secs) compared to group O (16.0 min 45.0 secs±8.0 min 5.0 secs) (p < 0.001). There was a statistically significant (p =0.010) lower Neonatal Infant Pain Scale score in group NO with mean and SD as 1.8±0.8 compared with group O, 2.5±1.1 at 90 min. Conclusions: In neonates undergoing TEF repair, opioid-free anesthesia is a safe and effective method, providing a better extubation rate, faster time to extubation, and better postoperative pain control.

Abstract Well-defined fluid flows are the hallmark feature of microfluidic culture systems and enable precise control over biophysical and biochemical cues at the cellular scale. Microfluidic flow control is generally achieved using displacement-based (e.g., syringe or peristaltic pumps) or pressure-controlled techniques that provide numerous perfusion options, including constant, ramped, and pulsed flows. However, it can be challenging to integrate these large form-factor devices and accompanying peripherals into incubators or other confined environments. In addition, microfluidic culture studies are primarily carried out under constant perfusion conditions and more complex flow capabilities are often unused. Thus, there is a need for a simplified flow control platform that provides standard perfusion capabilities and can be easily integrated into incubated environments. To this end, we introduce a tunable, 3D printed micro pressure regulator (µPR) and show that it can provide robust flow control capabilities when combined with a battery-powered miniature air pump to support microfluidic applications. We detail the design and fabrication of the µPR and: (i) demonstrate a tunable outlet pressure range relevant for microfluidic applications (1–10 kPa), (ii) highlight dynamic control capabilities in a microfluidic network, (iii) and maintain human umbilical vein endothelial cells (HUVECs) in a multi-compartment culture device under continuous perfusion conditions. We anticipate that our 3D printed fabrication approach and open-access designs will enable customized µPRs that can support a broad range of microfluidic applications.

Background & Aims: Recently, novel inborn errors of metabolism were identified because of mutations in V-ATPase assembly factors TMEM199 and CCDC115. Patients are characterized by generalized protein glycosylation defects, hypercholesterolemia, and fatty liver disease. Here, we set out to characterize the lipid and fatty liver phenotype in human plasma, cell models, and a mouse model. Methods and Results: Patients with TMEM199 and CCDC115 mutations displayed hyperlipidemia, characterized by increased levels of lipoproteins in the very low density lipoprotein range. HepG2 hepatoma cells, in which the expression of TMEM199 and CCDC115 was silenced, and induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells from patients with TMEM199 mutations showed markedly increased secretion of apolipoprotein B (apoB) compared with controls. A mouse model for TMEM199 deficiency with a CRISPR/Cas9-mediated knock-in of the human A7E mutation had marked hepatic steatosis on chow diet. Plasma N-glycans were hypogalactosylated, consistent with the patient phenotype, but no clear plasma lipid abnormalities were observed in the mouse model. In the siTMEM199 and siCCDC115 HepG2 hepatocyte models, increased numbers and size of lipid droplets were observed, including abnormally large lipid droplets, which colocalized with lysosomes. Excessive de novo lipogenesis, failing oxidative capacity, and elevated lipid uptake were not observed. Further investigation of lysosomal function revealed impaired acidification combined with impaired autophagic capacity. Conclusions: Our data suggest that the hypercholesterolemia in TMEM199 and CCDC115 deficiency is due to increased secretion of apoB-containing particles. This may in turn be secondary to the hepatic steatosis observed in these patients as well as in the mouse model. Mechanistically, we observed impaired lysosomal function characterized by reduced acidification, autophagy, and increased lysosomal lipid accumulation. These findings could explain the hepatic steatosis seen in patients and highlight the importance of lipophagy in fatty liver disease. Because this pathway remains understudied and its regulation is largely untargeted, further exploration of this pathway may offer novel strategies for therapeutic interventions to reduce lipotoxicity in fatty liver disease.

The risk of death in HIV-TB coinfected individuals is far greater than in HIV-only patients. It is critical to provide timely and appropriate therapy in HIV-TB coinfected patients in order to reduce morbidity and mortality. The purpose of this study was to evaluate the clinical presentation and outcome of TB treatment in HIV-TB co-infected patients receiving daily anti-tubercular therapy (ATT) and concurrent antiretroviral therapy (ART) at a tertiary respiratory care centre in New Delhi, India. The research was cross-sectional, observational, and hospital-based A. From September 2018 to August 2019, a total of 53 patients with HIV-TB coinfection were enrolled at the Institute's ART centre. Patients were evaluated with a structured proforma. Data were evaluated using SPSS version 23.0 and p-value of less than 0.05 was considered statistically significant. Among the patients enrolled, the mean age was 35.98 years. Among the patients enrolled, 56.6% patients had EPTB, 32% had PTB and 11.3% had both PTB and EPTB. The majority of the enrolled patients (n=46, 86.7%) had favourable TB treatment outcomes, while 13.3% (n=7) had unfavourable outcome [including death (n=5) and loss to follow up (n=2)]. During the study and follow-up period, no patients transferred out or relapsed. In univariate analysis, low SES, bedridden functional status, low BMI, anaemia, hypoalbuminemia, and a low CD-4 cell count (

Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is a significant burden on global tuberculosis (TB) prevention and eradication efforts. MDR-TB can be treated, but it is expensive, takes a long time (typically two years), and contains potentially toxic drugs. Under certain conditions, the WHO recommends standard regimens lasting 9 to 11 months rather than individual regimens lasting at least 18-20 months. The current study sought to identify factors associated with treatment outcome in RR/MDR-TB patients receiving an injection-based regimen for 9-11 months. This ambispective (prospective and retrospective) observational study was conducted at a tertiary tuberculosis institute in New Delhi, India. Between February 2021 and March 2022, patients with RR/MDR-pulmonary TB who received an injection-based shorter regimen were enrolled. Factors related to treatment outcome were investigated and compared in patients who had a successful outcome versus those who did not. A total of 55 patients were enrolled, with 50.91% being successful (cured/treatment completed) and 49.09% failing (including failure, lost to follow up, death, and regimen changed). The following factors were significantly associated with the unsuccessful outcome, according to univariate analysis: BMI (18.5 kg/m2), anaemia, previous anti-TB treatment, bilateral chest X-ray involvement, and far advanced disease on chest X-ray BMI (18.5 kg/m2), anaemia, and far advanced disease on chest X-ray were all significantly associated with mortality. Anaemia was associated with an unsuccessful outcome (p=0.049) and mortality (p=0.048) in the multiple logistic regression analysis. Early treatment initiation, improved nutrition and anaemia, and regular monitoring can all improve RR/MDR-TB patients' outcomes and prognoses.

Follicular dendritic cell sarcoma is a rare low grade malignant neoplasm that arises from follicular dendritic cells in lymphoid tissue germinal centres and accounts for 0.4% of all soft tissue sarcomas. It is extremely rare to have pulmonary follicular dendritic cell sarcoma with endobronchial extension and as an anterior mediastinal mass with mediastinal lymph node involvement. We present the case of a 34-year-old male non-smoker who had been experiencing chest pain for three months. A lobulated left peri-hilar mass with endobronchial spread into the left main bronchus and mediastinal lymphadenopathy was identified on a chest CT. The bronchoscope-guided cryobiopsy of the endobronchial mass was inconclusive. After a thorough multidisciplinary discussion, the patient underwent left sided pneumonectomy, mediastinal mass resection, and systematic lymph node dissection. Histologic examination using immunohistochemistry revealed follicular dendritic cell sarcoma.

In India, tuberculosis (TB) notification has been required since 2012. Notwithstanding, notification rates remain low. Non-reporting of tuberculosis cases not only results in an underestimation of cases, but also impedes the country's TB control strategy. Our research aims to assess practitioners' awareness, perception, and practice of tuberculosis case notification, as these factors can help reduce the TB burden. A cross-sectional study of 142 physicians was conducted between August 2018 and December 2019. Doctors were interviewed and given evaluation forms. Seventy-seven percent of the 142 physicians polled worked in medicine-related specialties, while 33% worked in surgery. Public sector physicians (64.7%) knew more about the Nikshay App than private practitioners (40.8%). The vast majority of public-sector doctors were only notified through their hospital's National Tuberculosis Elimination Programme (NTEP) center. However, the majority of private practitioners (47.8%) notified cases directly through the hospital, the local District Tuberculosis Officer (DTO) or NTEP medical officer (24 percent), or the Nikshay portal (28%), whereas the majority of public sector doctors notified only through the hospital NTEP center (85.9%). The primary reasons for non-notification are the high patient load on doctors, a lack of understanding about Nikshay App and its functionality, technological difficulties in using the Nikshay App, and the stigma associated with tuberculosis. The Nikshay App must be popularized as a notification mechanism through the NTEP program. To increase notification rates, practitioners must overcome the challenges they face. In terms of notification, more seminars and training, particularly hands-on training, should be held on a regular basis.

Removal of damaged organelles via the process of selective autophagy constitutes a major form of cellular quality control. Damaged organelles are recognized by a dedicated surveillance machinery, leading to the assembly of an autophagosome around the damaged organelle, prior to fusion with the degradative lysosomal compartment. Lysosomes themselves are also prone to damage and are degraded through the process of lysophagy. While early steps involve recognition of ruptured lysosomal membranes by glycan-binding galectins and ubiquitylation of transmembrane lysosomal proteins, many steps in the process, and their interrelationships, remain poorly understood, including the role and identity of cargo receptors required for completion of lysophagy. Here, we employ quantitative organelle capture and proximity biotinylation proteomics of autophagy adaptors, cargo receptors, and galectins in response to acute lysosomal damage, thereby revealing the landscape of lysosome-associated proteome remodeling during lysophagy. Among the proteins dynamically recruited to damaged lysosomes were ubiquitin-binding autophagic cargo receptors. Using newly developed lysophagic flux reporters including Lyso-Keima, we demonstrate that TAX1BP1, together with its associated kinase TBK1, are both necessary and sufficient to promote lysophagic flux in both HeLa cells and induced neurons (iNeurons). While the related receptor Optineurin (OPTN) can drive damage-dependent lysophagy when overexpressed, cells lacking either OPTN or CALCOCO2 still maintain significant lysophagic flux in HeLa cells. Mechanistically, TAX1BP1-driven lysophagy requires its N-terminal SKICH domain, which binds both TBK1 and the autophagy regulatory factor RB1CC1, and requires upstream ubiquitylation events for efficient recruitment and lysophagic flux. These results identify TAX1BP1 as a central component in the lysophagy pathway and provide a proteomic resource for future studies of the lysophagy process.

Background: India is home to 2.1 million people living with HIV with an estimated 44% people having an uninfected partner. Living in HIV serodiscordant setting can be stressful, especially for women and can lead to several common mental disorders (CMDs). However, the occurrence of CMD in this population is not studied in India. Objectives: The study aimed to assess the occurrence of CMD in HIV-uninfected women living in HIV serodiscordant setting. A sample of 152 HIV-uninfected women who are wives of HIV-infected men attending an HIV clinic were interviewed by trained interviewers. Methods: The International Classification of Diseases-10 diagnosis of any of the CMDs was done using standard structured diagnostic interview MINI 5.0.0. Current, past, and lifetime occurrence was estimated for various CMDs. Chi-square and point-biserial correlation coefficients were used to understand the relationship between various sociodemographic and HIV-related factors with current CMD. Results: The current, past, and lifetime occurrence of at least one CMD was 35.5%, 49.3%, and 62.5%, respectively. Common diagnoses were mixed anxiety-depressive disorder, major depressive disorder, and posttraumatic stress disorder. Of the women with CMD, 22% had accompanying suicidality. Conclusions: The high rate of occurrence of CMD observed among the study population calls for more attention on the policy and program level to address the mental health needs of this population. Globally, more number of HIV-infected people are now linked to the care. This provides an opportunity to incorporate mental health care into routine HIV care.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD.

This case series reviews four critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [coronavirus disease 2019 (COVID-19)] suffering from pneumatosis intestinalis (PI) during their hospital admission. All patients received the biological agent tocilizumab (TCZ), an interleukin (IL)-6 antagonist, as an experimental treatment for COVID-19 before developing PI. COVID-19 and TCZ have been independently linked to PI risk, yet the cause of this relationship is unknown and under speculation. PI is a rare condition, defined as the presence of gas in the intestinal wall, and although its pathogenesis is poorly understood, intestinal ischemia is one of its causative agents. Based on COVID-19's association with vasculopathic and ischemic insults, and IL-6's protective role in intestinal epithelial ischemia–reperfusion injury, an adverse synergistic association of COVID-19 and TCZ can be proposed in the setting of PI. To our knowledge, this is the first published, single center, case series of pneumatosis intestinalis in COVID-19 patients who received tocilizumab therapy.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive fibrosis and hypovascularization, resulting in significant intratumoral hypoxia (low oxygen) that contributes to its aggressiveness, therapeutic resistance, and high mortality. Despite oxygen being a fundamental requirement for many cellular and metabolic processes, and the severity of hypoxia in PDAC, the impact of oxygen deprivation on PDAC biology is poorly understood. Investigating how PDAC cells survive in the near absence of oxygen, we find that PDAC cell lines grow robustly in oxygen tensions down to 0.1%, maintaining mitochondrial morphology, membrane potential, and the oxidative metabolic activity required for the synthesis of key metabolites for proliferation. Disrupting electron transfer efficiency by targeting mitochondrial respiratory supercomplex assembly specifically affects hypoxic PDAC proliferation, metabolism, and in vivo tumor growth. Collectively, our results identify a mechanism that enables PDAC cells to thrive in severe, oxygen-limited microenvironments.

Particle swarm optimization has been established to be one of the efficient algorithms for finding solutions for continuous optimization problems. The discretized form of particle swarm optimization, known as the discrete particle swarm optimization is an efficient tool for solving combinatorial optimization problems and other problems involving discrete variables. In this paper, a revised version of the discrete particle swarm optimization algorithm is proposed for solving Quadratic Assignment Problems (QAP). Instead of using the general velocity and position update procedures in particle swarm optimization algorithms, four different possible positions are found out for each particle and the best among them is accepted as the updated position. The algorithm is applied to solve some benchmark instances of QAP taken from QAP Library and the results show minute deviations from best-known solutions.

Surgical management of ranula and mucocele in the pediatric age group is challenging. Various procedures from wide excision with scalpel to laser are associated with few complications. Micro-marsupialization is minimally invasive technique for the management of ranula and mucocele, especially in pediatric age group because it is easy to perform, efficacious, can be performed under topical anesthesia also and lower incidence of complications. This case reports describes the modified micro-marsupialization for the successful management of ranula and mucocele in pediatric age group.

Introduction Adenoidectomy with or without tonsillectomy is a common procedure performed by otolaryngologist in children. Most children between the ages 4 to 12 years have a relative hypertrophy of the lymphoid tissue in pharynx, including both tonsil and adenoid. This enlargement can cause obstructive symptoms of varying degree and several aspects of the speech spectrum such as resonance and articulation are reported to be negatively affected. Change in voice after surgery is often a cause of concern among patients and parents, more so among those who use their voices in a professional capacity. The purposes of the study were to assess the pre and post operatively changes in nasal resonance following adenoidectomy in children. Materials & Methods: The children between 4 to 12 years suffering from chronic adenoiditis, who underwent adenoidectomy at Father Muller Medical College Hospital, Mangalore from November 2015 to June 2016 were included in the study. The children were subjected to detailed ear, nose and throat examination, X- ray of nasopharynx, diagnostic nasal endoscopy and nasometry before adenoidectomy surgery and compared with 3 weeks after surgery. Results: A total of 60 patients were enrolled, out of these 21 were male and 39 were female. The maximum patients were seen in the 7 to 9 age group and majority of the patients were noted to have Grade III tonsils (46.60%) at the time of surgery. The mean preoperative nasalance score was 47.30 percent which decreased to 16.85 percent postoperatively, showed significance (p=0.000). Conclusion: Adenoidectomy can alter the acoustic characteristics of the vocal tract and causes alterations in the nasality.Therefore, surgeon can reassure patients, especially voice professionals.

Aim: The aim of this study was to evaluate sexual dimorphism in nasal proportions of Class I and Class II skeletal malocclusions in adults. Materials And Methods: The sample comprised 120 patients (females 18 years and above and males 21 years and above), with no history of previous orthodontic treatment or functional jaw orthopedic treatment. They were divided into different groups based on point A-Nasion-point B (ANB) angle and gender. Groups I and II included 30 males and 30 females with skeletal class I malocclusion (ANB 0–4 degrees). Groups III and IV included 30 males and 30 females with skeletal class II malocclusion, respectively (ANB above 4 degrees). Results: In regards to the comparison between males and females (Class I + Class II), nasal length (P < 0.001), nasal depth 1 (P < 0.001), nasal depth 2 (P < 0.001), nasobasal angle (P < 0.001), soft tissue convexity angle (P < 0.001), and nasal bone length (P < 0.008) were found to be statistically significant. Nasobasal angle was found to be significantly higher in females than in males (Class I) (P < 0.001). Nasolabial angle was prominent in class I males than in class I females (P < 0.001). Soft tissue convexity angle of Class I participants was significantly lower than that of Class II participants (P < 0.001), whereas nasobasal angle and nasomental angle of Class I participants were found to be significantly higher than that of Class II participants (P < 0.001). Conclusion: Sexual dimorphism was found in various nasal parameters. Significant amount of differences was found in the nasal proportions of Class I and Class II (male and female) participants.

A 3-year-old male presents to the emergency department with chief complaints of fever and vomiting. He had a positive rapid streptococcus throat test with cervical lymphadenopathy. The patient was started on antibiotics. On examination, there was diffuse erythematous macular rash on the chest. Laboratory tests revealed elevated white cell count and C-reactive protein. Electrocardiogram was notable for prolonged PR interval indicating 1st degree atrioventricular block. Echocardiogram revealed ectasia of the right coronary artery (RCA). A presumptive diagnosis of Kawasaki disease was made and the patient was started on high-dose aspirin and intravenous immunoglobulins. Cardiac computed tomography angiography (CTA) showed an aneurysm of the proximal RCA measuring up to 7.4 mm. The RCA immediately proximal to the aneurysm measured 3 mm in diameter. The Z score was 13.4. Oblique coronal image from cardiac CTA and volume rendered images demonstrated an aneurysm of the proximal RCA. The patient improved with treatment.

We have used two different live-cell fluorescent protein markers to monitor the formation and localization of double-strand breaks (DSBs) in budding yeast. Using GFP derivatives of the Rad51 recombination protein or the Ddc2 checkpoint protein, we find that cells with three site-specific DSBs, on different chromosomes, usually display 2 or 3 foci that may coalesce and dissociate. This motion is independent of Rad52 and microtubules. Rad51-GFP, by itself, is unable to repair DSBs by homologous recombination in mitotic cells, but is able to form foci and allow repair when heterozygous with a wild type Rad51 protein. The kinetics of formation and disappearance of a Rad51-GFP focus parallels the completion of site-specific DSB repair. However, Rad51-GFP is proficient during meiosis when homozygous, similar to rad51 "site II" mutants that can bind single-stranded DNA but not complete strand exchange. Rad52-RFP and Rad51-GFP co-localize to the same DSB, but a significant minority of foci have Rad51-GFP without visible Rad52-RFP. We conclude that co-localization of foci in cells with 3 DSBs does not represent formation of a homologous recombination "repair center," as the same distribution of Ddc2-GFP foci was found in the absence of the Rad52 protein.

Oral cancer is the most common type of cancer among men in India and other countries in South Asia. Late diagnosis contributes significantly to this mortality, highlighting the need for effective and specific point-of-care diagnostic tools. The same regions with high prevalence of oral cancer have seen extensive growth in mobile phone infrastructure, which enables widespread access to telemedicine services. In this work, we describe the evaluation of an automated tablet-based mobile microscope as an adjunct for telemedicine-based oral cancer screening in India. Brush biopsy, a minimally invasive sampling technique was combined with a simplified staining protocol and a tablet-based mobile microscope to facilitate local collection of digital images and remote evaluation of the images by clinicians. The tablet-based mobile microscope (CellScope device) combines an iPad Mini with collection optics, LED illumination and Bluetooth-controlled motors to scan a slide specimen and capture high-resolution images of stained brush biopsy samples. Researchers at the Mazumdar Shaw Medical Foundation (MSMF) in Bangalore, India used the instrument to collect and send randomly selected images of each slide for telepathology review. Evaluation of the concordance between gold standard histology, conventional microscopy cytology, and remote pathologist review of the images was performed as part of a pilot study of mobile microscopy as a screening tool for oral cancer. Results indicated that the instrument successfully collected images of sufficient quality to enable remote diagnoses that show concordance with existing techniques. Further studies will evaluate the effectiveness of oral cancer screening with mobile microscopy by minimally trained technicians in low-resource settings.

Drought is a major constraint for rainfed lowland and upland rice productivity throughout world. A backcross inbred population derived from ‘Swarna’ and ‘WAB450-I-B-P-157-2-1’ (Oryza sativa L. x O. glaberrima) was evaluated under both irrigated and lowland drought stresses for yield and yield related traits across three different seasons. Significant differences were found among all the analyzed traits. Coefficients of variation were recorded relatively high for filled grains per panicle, spikelet fertility, test weight, harvest index and grain yield and low for panicle length under both conditions during the study interval. Broad sense heritability varied from 0.28 (panicle number) to 0.83 (plant height) under stress and 0.31 (test weight) to 0.86 (plant height) under control. However, heritability estimates for grain yield and harvest index were found to be similar under both conditions. Traits such as filled grains per panicle, spikelet fertility, harvest index and grain yield recorded higher values of both heritability, as well as genetic advance under both conditions, indicating the suitability of these traits as selection criteria to derive high yielding genotypes for drought prone regions. Harvest index exhibited maximum positive direct effect on grain yield under both the conditions; in addition, filled grains per panicle, spikelet fertility and biomass had positive direct effect on grain yield under both irrigated and lowland drought stresses state. Hence, for improving the rice yield under lowland drought ecology, a genotype should posses a large number of panicles per plant, filled grains per panicle, high spikelet fertility and maintains higher biomass and harvest index.

Microfluidic platforms use controlled fluid flows to provide physiologically relevant biochemical and biophysical cues to cultured cells in a well-defined and reproducible manner. Undisturbed flows are critical in these systems, and air bubbles entering microfluidic channels can lead to device delamination or cell damage. To prevent bubble entry into microfluidic channels, we report a low-cost, Rapidly Integrated Debubbler (RID) module that is simple to fabricate, inexpensive, and easily combined with existing experimental systems. We demonstrate successful removal of air bubbles spanning three orders of magnitude with a maximum removal rate (dV/dt)max = 1.5 mL min−1, at flow rates required to apply physiological wall shear stress (1−200 dyne cm−2) to mammalian cells cultured in microfluidic channels.

Introduction: Previous studies have enumerated the advantages of an arthroscopic Anterior Cruciate Ligament (ACL) reconstruction with the use of a Bone Patellar Tendon Bone (BPTB) graft. Complications are extremely rare in such surgeries and one such known complication, which is an extra-articular heterotophic ossification at the femoral tunnel site, is rarely seen only in few patients. Aim: To evaluate the incidence of heterotrophic ossifications at the femoral tunnel site and the efficacy of the preventive measures which were undertaken, in patients who had undergone ACL reconstructions with the use of bone patellar tendon bone grafts. Material and Methods: A total of 285 patients who had ACL tears within a duration of six years, were evaluated prospectively for the incidence of heterotrophic ossifications after they underwent arthroscopic reconstructions with the use of bone patellar tendon bone grafts by the double incision technique. The effect of the efficacy of various preventive measures on the incidence of the heterotophic ossifications post surgery was also studied. Results: The observed incidence of the heterotophic ossifications was 2.58% in patients whom preventive measures were not used. In contrast, an incidence of 1.54% of similar complications was recorded, after preventive measures were undertaken. Our results showed that heterotophic ossifications after arthroscopic reconstructions with the use of bone patellar tendon bone grafts were a rare complication and that their incidence could be further reduced if preventive measures were taken. Conclusion: The heterotophic ossification is a rare complication after an ACL reconstruction is done with the use of a bone patellar tendon bone graft by the double incision technique. Its incidence reduces significantly after preventive measures are undertaken.

Context: Chronic Myeloid Leukemia (CML) constitutes around 3% of leukemia in the children and adolescent age group. Aims: The aim of the study was to evaluate the characteristics at presentation and the treatment outcome of CML in the children and adolescent age group. Settings and Design: Retrospective analysis was carried out at a single center in India. Materials and Methods: Thirteen patients (≤17 years) attending CML outdoor from April 2008 to August 2012 were included in the analysis. Statistical Analysis Used: The mean and median of various parameters were calculated using a Microsoft excel sheet. SPSS 16.0 version software was used to calculate OS and PFS. Results: CML-CP was the most common phase at presentation. Maximum patients belonged to the 14 - 17 year old age group. Disease was common in the male sex. Splenic discomfort and asthenia were the most common symptoms and splenomegaly was the most common sign. Conclusions: The treatment with Imatinib was effective and well-tolerated.

Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disease with protean clinical manifestations. Recent advances in understanding the pathogenic mechanisms have led to development of target-oriented and vasomodulatory drugs which play a pivotal role in treating various dermatological manifestations. An exhaustive literature search was done using Medline, Embase, and Cochrane library to review the recent concepts regarding pathogenesis and evidence-based treatment of salient dermatological manifestations. The concept of shared genetic risk factors for the development of autoimmune diseases is seen in SSc. It is divided into fibroproliferative and inflammatory groups based on genome-wide molecular profiling. Genetic, infectious, and environmental factors play a key role; vascular injury, fibrosis, and immune activation are the chief pathogenic factors. Vitamin D deficiency has been documented in SSc and correlates with the severity of skin involvement. Skin sclerosis, Raynaud′s phenomenon (RP) with digital vasculopathies, pigmentation, calcinosis, and leg ulcers affect the patient′s quality of life. Immunosuppressives, biologicals, and hematopoietic stem cell transplantation are efficacious in skin sclerosis. Endothelin A receptor antagonists, calcium-channel blockers, angiotensin receptor inhibitors, prostacyclin analogs, and phosphodiesterase type 5 (PDE-5) inhibitors are the mainstay in RP and digital vasculopathies. Pigmentation in SSc has been attributed to melanogenic potential of endothelin-1 (ET-1); the role of ET 1 antagonists and vitamin D analogs needs to be investigated. Sexual dysfunction in both male and female patients has been attributed to vasculopathy and fibrosis, wherein PDE-5 inhibitors are found to be useful. The future concepts of treating SSc may be based on the gene expression signature.

Microfluidic barrier tissue models have emerged as advanced in vitro tools to explore interactions with external stimuli such as drug candidates, pathogens, or toxins. However, the procedures required to establish and maintain these systems can be challenging to implement for end users, particularly those without significant in-house engineering expertise. Here we present a module-based approach that provides an easy-to-use workflow to establish, maintain, and analyze microscale tissue constructs. Our approach begins with a removable culture insert that is magnetically coupled, decoupled, and transferred between standalone, prefabricated microfluidic modules for simplified cell seeding, culture, and downstream analysis. The modular approach allows several options for perfusion including standard syringe pumps or integration with a self-contained gravity-fed module for simple cell maintenance. As proof of concept, we establish a culture of primary human microvascular endothelial cells (HMVEC) and report combined surface protein imaging and gene expression after controlled apical stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We also demonstrate the feasibility of incorporating hydrated biomaterial interfaces into the microfluidic architecture by integrating an ultra-thin (< 1 μm), self-assembled hyaluronic acid/peptide amphiphile culture membrane with brain-specific Young's modulus (~ 1kPa). To highlight the importance of including biomimetic interfaces into microscale models we report multi-tiered readouts from primary rat cortical cells cultured on the self-assembled membrane and compare a panel of mRNA targets with primary brain tissue signatures. We anticipate that the modular approach and simplified operational workflows presented here will enable a wide range of research groups to incorporate microfluidic barrier tissue models into their work.

Adenomatoid odontogenic tumor (AOT) is a rare odontogenic tumor which is often misdiagnosed as odontogenic cyst and accounts for about 1% until 9% of all odontogenic tumors. It is predominantly found in young and female patients, located more often in the maxilla in most cases associated with an unerupted permanent tooth. It is a benign (hamartomatous), noninvasive lesion with slow but progressive growth. There are three variants of AOT: follicular, extrafollicular, and peripheral. We report a rare case of follicular-type AOT in the mandible of a 14-year-old male patient who presented with right -sided jaw swelling.

Aims and Objectives: To study the pattern and burden of trauma cases which presented to a tertiary care centre in an upcoming Dakshina Kannada District of Karnataka, India. Methods: This was an epidemiological study. Data was collected by purposive sampling technique. Study period lasted from Jan 2013 to Aug 2013. Collected data was analyzed. Results: The annual incidence of trauma at our centre was 15.96% (1140 cases). Most of the injuries were reported in 21- 30 years age group. The male to female ratio was approximately 2.3:1. Limb injury (66.92%) constituted the commonest form of injury. Among the various injuries, fall was the commonest cause of injury (60.78%), followed by RTA (16.75%) and assault (11.6%). A majority of the cases were admitted during night time (61.24%). Conclusion: There has been an alarming increase in the number of trauma cases in the past decade. The target age group being the most productive one; it affects the economy directly . There is a need of urgent protective measures which are required for the benefit of the community.

Introduction: Seroma of pinna have a high predisposition for recurrence. Its surgical management requires excision of cartilage and perichondrium which can cause scarring, deformity of pinna, perichondritis and abscess formation, postoperatively. The aim of the current study is to the access the outcome of a novel approach using cruciate incision for surgical treatment of seroma/ hematoma of pinna. Materials and Methods: Study was conducted at Father Muller Medical College in the Department of Otorhinolaryngology for a period of three months between January 2014 to March 2014 during which period 30 patients with seroma of the pinna were taken up for the study. Procedure was done under local anaesthesia with all aseptic precautions. A cruciate incision was given over the most dependent part of the swelling and flaps were raised. The collection was drained and the under surface of the flap was scraped using Rosen’s knife followed by pressure dressing for three days. Patients were followed up for three months. Results: A total of 30 patients with seroma were studied. Out of the 30 cases 24 were primary cases and 6 were recurrent cases. Majority of the patients were in the age group 41-50 y. Out of 30 patients 18 were males and 12 were females. Out of 30 patients studied, none of them had recurrence. Four patients however developed perichondrial reaction with pain and inflammation which required analgesics and antibiotics. In 6 cases a thickening of the auricle at the site of incision was noticed which resolved over a period of 4 to 5 months. Overall cosmetic deformity was negligible with most of the patients showing a negligible scar after 6 months of follow up. Conclusion: Cruciate incision is a good technique for treatment of seroma and hematoma of pinna as the outcome is good with no recurrence.

The Mre11-Rad50-Xrs2 nuclease complex, together with Sae2, initiates the 5'-to-3' resection of Double-Strand DNA Breaks (DSBs). Extended 3' single stranded DNA filaments can be exposed from a DSB through the redundant activities of the Exo1 nuclease and the Dna2 nuclease with the Sgs1 helicase. In the absence of Sae2, Mre11 binding to a DSB is prolonged, the two DNA ends cannot be kept tethered, and the DSB is not efficiently repaired. Here we show that deletion of the yeast 53BP1-ortholog RAD9 reduces Mre11 binding to a DSB, leading to Rad52 recruitment and efficient DSB end-tethering, through an Sgs1-dependent mechanism. As a consequence, deletion of RAD9 restores DSB repair either in absence of Sae2 or in presence of a nuclease defective MRX complex. We propose that, in cells lacking Sae2, Rad9/53BP1 contributes to keep Mre11 bound to a persistent DSB, protecting it from extensive DNA end resection, which may lead to potentially deleterious DNA deletions and genome rearrangements.

This study is an attempt to develop a technique by which complete hemostasis can be achieved on table by giving traction to the Foley′s catheter thereby compressing the venous plexus and the avulsed prostatic arteries at the bladder neck by the inflated balloon. A total of 170 cases of BPH were operated by Freyer′s Suprapubic Trans-vesicle prostatectomy. In the technique, bladder mucosa is reposited below the balloon and the balloon is inflated to 60 ml of normal saline. The balloon is kept at the bladder neck and traction is applied to the catheter. Traction is maintained by strapping the catheter to the thigh of the patient with sticking plaster for 24-48 h. The average blood loss was 18.9 ml which proves that the Foley′s balloon pressure traction method at the bladder neck is effective in achieving hemostasis in patients undergoing open prostatectomy.

In budding yeast, an HO endonuclease-inducible double-strand break (DSB) is efficiently repaired by several homologous recombination (HR) pathways. In contrast to gene conversion (GC), where both ends of the DSB can recombine with the same template, break-induced replication (BIR) occurs when only the centromere-proximal end of the DSB can locate homologous sequences. Whereas GC results in a small patch of new DNA synthesis, BIR leads to a nonreciprocal translocation. The requirements for completing BIR are significantly different from those of GC, but both processes require 5' to 3' resection of DSB ends to create single-stranded DNA that leads to formation of a Rad51 filament required to initiate HR. Resection proceeds by two pathways dependent on Exo1 or the BLM homolog, Sgs1. We report that Exo1 and Sgs1 each inhibit BIR but have little effect on GC, while overexpression of either protein severely inhibits BIR. In contrast, overexpression of Rad51 markedly increases the efficiency of BIR, again with little effect on GC. In sgs1Delta exo1Delta strains, where there is little 5' to 3' resection, the level of BIR is not different from either single mutant; surprisingly, there is a two-fold increase in cell viability after HO induction whereby 40% of all cells survive by formation of a new telomere within a few kb of the site of DNA cleavage. De novo telomere addition is rare in wild-type, sgs1Delta, or exo1Delta cells. In sgs1Delta exo1Delta, repair by GC is severely inhibited, but cell viability remains high because of new telomere formation. These data suggest that the extensive 5' to 3' resection that occurs before the initiation of new DNA synthesis in BIR may prevent efficient maintenance of a Rad51 filament near the DSB end. The severe constraint on 5' to 3' resection, which also abrogates activation of the Mec1-dependent DNA damage checkpoint, permits an unprecedented level of new telomere addition.

The aesthetic requirement of severely mutilated primary anterior teeth in case of Early Childhood Caries (ECC) has been a challenge to paediatric dentists. ECC involves the upper anterior teeth early in life and by the time the dentist sees the child, most of the coronal structure is lost. This article presents the clinical sequence of rehabilitation of maxillary anterior primary teeth, and the mandibular posterior teeth.