The role of M1 (CD11c) and M2 (CD163) interplay in the pathogenesis of oral submucous fibrosis and its malignant transformation: An immunohistochemical analysis.

OBJECTIVES: The M1/M2 macrophage framework is crucial in organ fibrosis and its progression to malignancy. This study investigated the possible role of M1/M2 macrophage interplay in the pathogenesis of oral submucous fibrosis (OSF) and its malignant transformation by analysing immunohistochemical expression of CD11c (M1) and CD163 (M2) markers. METHODS: Immunohistochemistry was performed using primary antibodies against CD11c and CD163 on ten formalin-fixed paraffin-embedded tissue blocks for each group: (i) Stage 1 OSF, (ii) Stage 2 OSF, (iii) Stage 3 OSF, (iv) Stage 4 OSF, (v) well-differentiated squamous cell carcinoma (WDSCC) with OSF, and (vi) WDSCC without OSF. Ten cases of healthy buccal mucosa (NOM) served as controls. RESULTS: Epithelial quick scores of M1 (CD11c) in NOM, Stages 1-4 OSF, and WDSCC with and without OSF were 0, 1.8, 2.9, 0.4, 0, 0, and 0, while connective tissue scores were 0, 3.2, 4.3, 2.7, 0.5, 1.2, and 2.4, respectively. Epithelial scores for M2 (CD163) were 0, 0.8, 0.8, 2.1, 0.6, 0.8, and 0.2, and connective tissue scores were 0, 1.8, 2.6, 3.9, 2.2, 5, and 4.4, respectively. Stages 3 and 4 OSF, WDSCC with and without OSF exhibited higher M2/M1 ratios compared to NOM and Stages 1-2 OSF. CONCLUSION: The interaction between M1 (CD11c) and M2 (CD163) macrophages, leading to M2 polarisation, plays a crucial role in the pathogenesis of OSF and its potential malignant transformation.

Plasma proteins and persistent postsurgical pelvic pain among adolescents and young adults with endometriosis.

BACKGROUND: Noninvasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biologic pathways underlying endometriosis-associated pain and symptom progression. OBJECTIVE: To use plasma proteins in relation to the persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform. STUDY DESIGN: We conducted a prospective analysis including 142 participants with laparoscopically-confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1305 plasma protein levels, including markers for immunity, angiogenesis, and inflammation, using SomaScan. Worsening or persistent postsurgical pelvic pain was defined as having newly developed, persistent (ie, stable), or worsening severity, frequency, or persistent life interference of dysmenorrhea or acyclic pelvic pain at 1-year postsurgery compared with presurgery. We calculated odds ratios and 95% confidence intervals using logistic regression adjusted for age, body mass index, fasting status, and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions. RESULTS: The median age at blood draw was 17 years (interquartile range, 15-19 years), and most participants were White (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year postsurgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, whereas pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain 1-year postsurgery (nominal P<.05). Compared with those with improved pelvic pain 1-year postsurgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (odds ratio, 2.98 [95% confidence interval, 1.44-6.19]) and CD47 (odds ratio, 2.68 [95% confidence interval, 1.28-5.61]), but lower levels of Sonic Hedgehog protein (odds ratio, 0.55 [95% confidence interval, 0.36-0.84]) in presurgical blood. Pathways related to cell migration were up-regulated, and pathways related to angiogenesis were down-regulated in those with worsening or persistent postsurgical pelvic pain compared with those with improved pain. When we examined the change in protein levels from presurgery to postsurgery and its subsequent risk of worsening or persistent postsurgical pain at 1-year follow-up, we observed increasing levels of Sonic Hedgehog protein from presurgery to postsurgery was associated with a 4-fold increase in the risk of postsurgical pain (odds ratio [quartile 4 vs 1], 3.86 [1.04-14.33]). CONCLUSION: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain postsurgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Impact of urbanization on the abundance and distribution of Anophelines population in Ghaziabad district, Uttar Pradesh, India.

BACKGROUND OBJECTIVES: In urban areas, upsurge in population has resulted in more breeding sites for malaria vectors, and hence this scenario potentially undermine malaria elimination and control programs. The change in land use due to urbanization may result in the presence and distribution of malaria vectors. Understanding potential malaria vectors is essential for current and future malaria transmission control strategies. This study investigated the effects of rapid urbanization on malaria vectors An. culicifacies s.l. and An. stephensi L. in Ghaziabad district. METHODS: Ghaziabad district which presents several levels of urbanization was selected for this study. Entomological investigations were conducted seasonally from 2014-2016 in the rural, urban, and peri-urban regions. Vector incrimination study was done using ELISA (confirmation by PCR) on suspected Anopheles vectors viz. An. culicifacies, An. stephensi, An. annularis and An. subpictus. RESULTS: An. culicifacies showed alteration in distribution influenced by rural and agricultural land whereas An. stephensi was found to be influenced by artificial habitats and population growth. INTERPRETATION CONCLUSION: The study also confirms the association between the abundance of malaria vectors and land use change.

Influence of climatic factors on the life stages of Aedes mosquitoes and vectorial transmission: A review.

BACKGROUND OBJECTIVES: Aedes aegypti and Aedes albopictus are two sympatric mosquito species that compete with each other for resources when their breeding habitats overlap. This study examines what happens when sympatric Aedes aegypti and Aedes albopictus mosquitoes' mate with each other and other species by looking at insemination rates, fecundity, and hatchability rate. METHODS: We performed controlled mating experiments in laboratory setting, assessing both conspecific and interspecific crosses. We measured insemination rates, egg numbers, and hatching success to examine the reproductive interference dynamics between these two distinct mosquito species. RESULTS: In the context of conspecific mating, it was observed that both female Ae. aegypti and Ae. albopictus exhibited high insemination rates, with percentages of 98% and 94%, respectively. However, interspecific mating exhibited interesting asymmetries: Ae. albopictus males achieved a notable insemination success rate of 28% when mating with Ae. aegypti females, while Ae. aegypti males achieved only 8% insemination success with Ae. albopictus females. Additionally, females that mated with interspecific males had reduced production of viable eggs compared to conspecific mating. Most notably, interspecific mating resulted in the production of infertile eggs, while conspecific mating led to successful hatching. INTERPRETATION CONCLUSION: The study reveals that, Ae. aegypti and Ae. albopictus can asymmetrically interfere with each other's reproduction, causing a 'satyr' effect. This understanding of interspecific competition and reproductive interference in these mosquito species could impact their coexistence in shared breeding habitats.

Susceptibility status of Aedes aegypti (Diptera: Culicidae) against insecticides of public health use in Delhi and NCR region, India.

BACKGROUND & OBJECTIVES: Aedes (Stegomyia) aegypti is a primary vector responsible for the transmission of various arboviral diseases in India. Without an effective drug or vaccine against these diseases, chemical insecticide-based vector control supplemented with source reduction remains the best option for their effective management. The development of insecticide resistance due to the continuous use of insecticides might affect the control operations. METHODS: Adults and larvae of Aedes aegypti were collected from different localities in Delhi. Larvae were exposed to discriminating (0.02mg/l) and application (1mg/l) doses of temephos. WHO tube assay was conducted for F1 adults using impregnated insecticide papers of dichlorodiphenyltrichloroethane (DDT), malathion, deltamethrin, permethrin, cyfluthrin, and lambda-cyhalothrin. RESULTS: Larvae of Ae. aegypti were found resistant (76.0%) to the discriminating dose of temephos, whereas suscep-tible (100.0%) to the application dose of the temephos. Adult Aedes (Fl) mosquitoes were resistant to DDT (23.7%), malathion (90.5%), deltamethrin (76.0%), permethrin (96.2 %) cyfluthrin (85.5%), and lambda-cyhalothrin (94.0%). INTERPRETATION & CONCLUSION: Indoor residual spray is not used in Delhi for vector control. Resistance in Aedes might be due to pesticide usage for agricultural activities in peripheral regions of Delhi. There is a need to investigate more on the insecticide resistance mechanisms for indirect resistance development. Understanding the insecticide susceptibility status of urban vectors is critical for planning effective control strategies.

Persistent Buccopharyngeal Membrane - A Systematic Review of Case Reports and Case Series.

OBJECTIVE: Persistent buccopharyngeal membrane (PBM) is a rare anomaly associated with failure of ecto-endodermal resorption of the buccopharyngeal membrane on the 26th day of intrauterine life. The current literature has insufficient information about PBM. DESIGN: Systematic Review. PATIENTS, PARTICIPANTS: Online electronic databases such as PubMed-MEDLINE, Embase, and Scopus were searched using appropriate keywords from the earliest available data until 30th August 2022, with no language restriction. Additional sources such as Google Scholar, major journals, gray literature, conference proceedings, and cross-referencing were also explored. MAIN OUTCOME MEASURES: The present systematic review evaluated and analysed the data available on PBM along with its treatment options and clinicopathological findings, prevalence, and prognosis of the patient. RESULTS: Thirty-four publications with 37 reported cases were included in this systematic review. The majority of patients had dyspnea (n = 18), followed by dysphagia (n = 10). Approximately 16 patients suffering from PBM reported orofacial abnormalities. Seventeen patients reported complete PBM, and 18 patients had partial PBM. The treatment modality followed by most patients (n = 15) was surgical excision of the membrane, along with stent placement in four patients. Oropharyngeal reconstruction was performed in four cases. The overall prognosis and survival rate of this rare condition is good. CONCLUSION: This review suggests that PBM is poorly understood, and the diagnosis of partial PBM is confirmed only when the patient complains of difficulty in breathing or eating. In-depth analysis and follow-up of the reported cases should be performed to diagnose the disease early so that clinicians can provide adequate treatment to the patients.

Absence of BRAFV600E immunohistochemical expression in sporadic odontogenic keratocyst, syndromic odontogenic keratocyst and orthokeratinized odontogenic cyst.

BACKGROUND: Odontogenic keratocyst (OKC) is a unique developmental odontogenic cyst that has the potential to behave aggressively and is associated with the nevoid basal cell carcinoma syndrome. Orthokeratinized odontogenic cyst (OOC) is a distinct, uncommon odontogenic cyst. It significantly differs from OKC not only in its epithelial lining but also in proliferating kinetics, clinical, immunohistochemical and biological behaviour. BRAF gene located on chromosome 7q34 encodes a cytoplasmic serine-threonine kinase. Various immunohistochemical studies have been conducted to express the BRAFV600E gene mutation in various odontogenic cyst and tumours with varying results. The present study was conducted to evaluate the possible role of BRAFV600E in the pathogenesis of sporadic OKC, syndromic OKC and OOC by immunohistochemistry. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 15 diagnosed cases each of sporadic OKC, syndromic OKC and OOC were retrieved from the archives of Department of Oral Pathology and subjected to immunohistochemical staining for the detection of BRAFV600E mutation using a novel rabbit monoclonal antibody clone RM8. RESULTS: Immunohistochemical analysis showed complete absence of BRAFV600E mutation in all cases of sporadic OKC, syndromic OKC and OOC. CONCLUSION: The negative immunohistochemical expression of BRAFV600E in sporadic OKC, syndromic OKC and OOC suggests that BRAFV600E plays no role in the pathogenesis of sporadic OKC, syndromic OKC and OOC.

The Influence of the Mandibular Gonial Angle on the Incidence of Mandibular Angle Fracture-A Radiomorphometric Study.

PURPOSE: The aim of this radiomorphometric study was to analyze the association between the mandibular gonial angle and the risk of mandibular angle fracture. MATERIALS AND METHODS: A retrospective analysis of medical records and radiographs of patients treated for mandibular fractures was performed. The exposure studied was the presence of a high gonial angle and the outcome was fracture of the mandibular angle. The mandibular gonial angle and mandibular height at the angle were measured using Facad software (Ilexis AB, Linköping, Sweden). Data obtained were analyzed using SPSS 16 (IBM Corp, Armonk, NY). RESULTS: The study sample was comprised of 210 mandibular fractures (70 mandibular angle fractures and 140 non-angle fractures). The mean gonial angle in patients with mandibular angle fractures was 126.8 ± 7.9°, which was 4.5° larger than in patients with other mandibular fractures (P = .0001). Patients with a high gonial angle were 11.77 times more likely to sustain an angle fracture than those with normal or low gonial angles (adjusted odds ratio = 11.77; 95% confidence interval, 3.65-37.94; P < .001). There also was a statistically significant decrease in mandibular height at the angle in patients with a high gonial angle (P = .0001). CONCLUSION: This study shows that people with a high gonial angle are at an increased risk for angle fracture and presents the related clinical implications.

A reduced time to surgery within a 'fast track' pathway for periampullary malignancy is associated with an increased rate of pancreatoduodenectomy.

INTRODUCTION: Pancreatoduodenectomy (PD) typically follows preoperative biliary drainage (PBD) despite PBD being potentially harmful. This study evaluated a pathway to avoid PBD within the framework of the UK's NHS. METHOD: A prospective observational study of jaundiced patients undergoing PD for periampullary cancer. A pathway to provide early surgery without PBD was introduced at the start of the study period. RESULTS: Over 12 months 61 and 32 patients underwent surgery with and without PBD respectively; 95% of patients in the PBD group had been stented before referral. The time from CT scan to surgery was shorter in the no PBD group (16 vs 65 days, p < 0.0001). Significantly more patients underwent PD in the no PBD group (31/32 vs 46/61, p = 0.009) and venous resection (10/31 vs 4/46, p = 0.014). The sensitivity of initial CT scan to define borderline resectable disease was worse in the PBD group (91 vs 50%, p = 0.042). CONCLUSIONS: Early surgery to avoid PBD is possible within the NHS. By reducing the time to surgery it appears that more patients undergo potentially curative resection. It is desirable to understand why surgery without PBD is not performed routinely as are the development of strategies to support its more widespread practice.

Functional Mitral Regurgitation: Patient Selection and Optimization.

Functional mitral regurgitation appears commonly among all heart failure phenotypes and can affect symptom burden and degree of maladaptive remodeling. Transcatheter mitral valve edge-to-edge repair therapies recently became an important part of the routine heart failure armamentarium for carefully selected and medically optimized candidates. Patient selection is considering heart failure staging, relevant comorbidities, as well as anatomic criteria. Indications and device platforms are currently expanding.

Predictive Factors for the Development of Gallbladder Necrosis.

Introduction Acute cholecystitis is a common complication of gallstone disease. Likewise, gallbladder necrosis is a complication of cholecystitis associated with higher risks of morbidity and mortality. Identification of risk factors which portend to gallbladder necrosis is key in prioritizing the management of higher-risk patients. This study aimed to identify such factors that predict the development of gallbladder necrosis. Method A retrospective review of all patients undergoing emergency cholecystectomy in a tertiary hospital over a two-year period was performed. Gallbladder necrosis was diagnosed on histopathological examination of operative specimens. Multivariable logistic regression was performed to determine risk factors for gallbladder necrosis. Results A total of 163 patients underwent acute cholecystectomy and 43 (26%) had proven gallbladder necrosis. Multivariable analysis demonstrated that elevated white cell count (WCC) (OR 1.122, 95%CI 1.031-1.221, p=0.007), elevated C-reactive protein (CRP) (OR 1.004, 95%CI 1.001-1.008, p=0.022) and positive smoking status (OR 5.724, 95%CI 1.323-24.754, p=0.020) were independently predictive of gallbladder necrosis. Notably, advancing age, elevated BMI, diabetes mellitus or American Society of Anesthesiologists (ASA) grade were not found to be associated with developing necrosis. Conclusion Patients at risk of gallbladder necrosis include those with higher WCC, CRP, and active smokers. Given the increased potential complications, these risk factors should be identified early in the management of those admitted with gallstone disease to ensure such patients receive aggressive medical therapy alongside timely and guided surgical intervention.

Long-term survival is not affected by severity of complications following esophagectomy.

INTRODUCTION: Outcomes following esophagectomy for esophageal cancer have continued to improve over the last 30 years. Post-operative complications impact upon peri-operative and short-term survival but the effect on long-term survival remains debated. This study aims to investigate the effect of post-operative complications on long-term survival following esophagectomy. MATERIALS AND METHODS: All patients who underwent an esophagectomy between January 2010 and January 2019 were included from a single high-volume center. Data was collected contemporaneously. Patients were separated into three groups; those who experienced no, or very minor complications (Clavien-Dindo 0 or 1), minor complications (Clavien-Dindo 2), and major complications (Clavien-Dindo 3-4), at 30 days. To correct for short-term mortality effects, those who died during the index hospital admission were excluded. Overall survival was analyzed using Kaplan-Meier and log rank testing. RESULTS: The study cohort comprised 721 patients. There were 42.4% (306/721), 29.5% (213/721) and 25.7% (185/721) in the Clavien-Dindo 0-1, Clavien-Dindo 2, and Clavien-Dindo 3-4 group respectively. Seventeen patients (2.4%) died during their index hospital admission and were therefore excluded. There was no significant difference between median survival across the 3 groups (50, 57 and 52 months). Across all 3 groups, overall long-term survival rates were equivalent at 1 (87.5%, 84.9%, 83.2%), 3 (59.7%, 59.6%, 54.2%), and 5 years (43.9%, 48.9%, 45.7%) (p = 0.806). The only factors independently associated with survival in this cohort, were male gender, Charlson comorbidity index, and overall pathological stage of disease. CONCLUSION: Long-term survival is not affected by peri-operative complications, irrespective of severity, following esophagectomy. Further study into the long-term quality of life is required.

Outcomes of Adult Patients With COVID-19 Transitioning From Venovenous to Venoarterial or Hybrid Extracorporeal Membrane Oxygenation in the Extracorporeal Life Support Organization Registry.

This retrospective analysis of the Extracorporeal Life Support Organization (ELSO) registry evaluates the outcomes and identifies risk factors associated with conversion from initial venovenous extracorporeal membrane oxygenation (ECMO) support to venoarterial or hybrid ECMO in patients with coronavirus disease 2019 (COVID-19). We collected deidentified data on all adult patients (≥18 years old) diagnosed with COVID who received venovenous extracorporeal membrane oxygenation between March 2020 and November 2022. Patients initially placed on an ECMO configuration other than venovenous (VV) ECMO were excluded from the analysis. Our analysis included data from 12,850 patients, of which 393 (3.1%) transitioned from VV ECMO to an alternative mode. The primary outcome measure was in-hospital mortality, and the conversion group exhibited a higher in-hospital mortality rate. We also examined baseline variables, including demographic information, biochemical labs, and inotrope requirements. Univariate analysis revealed that pre-ECMO arrest, the need for renal replacement therapy, and the use of inotropic agents, particularly milrinone, were strongly associated with the risk of conversion. Notably, even after implementing a 3:1 propensity score matching, the impact of conversion on both mortality and complications remained substantial. Our study underscores an elevated risk of mortality for COVID-19 patients initially treated with VV ECMO who subsequently require conversion to VA-ECMO or hybrid ECMO.

Epidemiologic correlates of malnutrition among under-three children in the rural community of Northern India.

Context: Worldwide malnutrition is identified as a major health and nutrition problem. Undernutrition contributes to an estimated 45% of child deaths globally. The prevalence of underweight among children in India is among the highest in the world. Our children also bear a tremendous double burden of malnutrition. Aims: To find out the prevalence and determinants of malnutrition among six months to three-year-old children in the rural community of Northern India. Settings and Design: A community-based cross-sectional study conducted among children aged six months to three years in a rural area of Ludhiana district, Methods and Material: A total of 662 children in the age group of six months to three years from a population of 30,000 were identified and included in the study. All the relevant information regarding these children was collected from family folders. Socioeconomic status was assessed using the modified Udai Pareek scale (MUP). Statistical analysis used: The data collected was entered in MS Excel and was analyzed using SPSS version 26 and WHO Anthro Survey Analyzer. Results: Out of 662 children, 16% were underweight. Almost 50% of the children in the two-three years category were underweight. The prevalence of stunting in the study population was 20.7% and that of overweight was 4.8%. The prevalence of underweight was higher in children of low socioeconomic status than in children from upper socioeconomic status (P = 0.000). There was a significant association between birth order and increasing cases of underweight (P = 0.000). Conclusions: The causes of malnutrition in children are complex and involve multiple factors. There is a need for vigorous monitoring for early detection of malnutrition for children aged two-three years. The improvement of maternal education will improve the nutritional status of the child.

Moving population is a challenge for malaria elimination in India: A cross-sectional study to assess malaria parasite infections in walking pilgrims in western Rajasthan, India.

Objectives: India is vigorously pursuing malaria elimination by 2030 and one of the key challenges is how to prevent the malaria risk associated with long-distance migrations of populations from endemic to non-endemic areas. Millions of pilgrims walking to the holy Ramdevra temple stay in temporary shelters along the route in district of Jaisalmer, Rajasthan state in western India. The main pilgrimage period coincides with the post-monsoon period with elevated vector densities. We investigated this situation to assess the potential risk posed by migrant pilgrims along the four highways in the temple district in disseminating malaria infections associated with their annual movements. Methods: A cross-sectional study was conducted for screening malaria in walking pilgrims from neighboring states at selected sites and a follow-up study for screening residents in Rajasthan from 2021 to 2023. The study comprises state entry routes, Ramdevra shrine, and pilgrimage route villages situated in western Rajasthan. Epidemiologic and entomologic surveillance was conducted during the "fair" period (August-September) and in pilgrimage route villages in three different seasons of the year to assess malaria in humans and the vector's infectivity. Results: Of the 5251 individuals tested for malaria, a total of 76 (1.4%) tested positive for malaria, of whom 40.7% were infected with Plasmodium vivax (n = 31), 36.8% with P. falciparum (n = 28), and 22.3% with P. vivax and P. falciparum (n = 17). Anopheles density was highest during the fair season, peaking in August. An. stephensi exhibited a higher human blood index (0.65) than An. culicifacies (0.50). No mosquitoes were found positive for parasites. Conclusions: Up to 1.5% of pilgrims carried malaria parasites, posing a risk of spreading malaria to surrounding communities that otherwise would have low or no malaria burden. Moving populations pose the risk of local malaria transmission and reintroduction to the areas undergoing elimination. Sentinel point surveillance at the border of states will be helpful for states to share information on malaria and subsequently for the prevention of malaria transmission.

Cardiac allograft vasculopathy diagnosed by vasodilator myocardial contrast echocardiography perfusion imaging.

Cardiac allograft vasculopathy (CAV) remains a common long-term complication of cardiac transplantation. While invasive coronary angiography is considered the gold standard, it is also invasive and lacks sensitivity to detect early, distal CAV. Although vasodilator stress myocardial contrast echocardiography perfusion imaging (MCE) is used in the detection of microvascular disease in non-transplant patients, there is little data guiding its use in transplant recipients. Herein is a case series of four heart transplant recipients that had vasodilator stress MCE performed in addition to invasive coronary angiography for CAV surveillance. MCE at rest and after regadenason was performed using a continuous infusion of lipid-shelled microbubbles. We describe a case of normal microvascular function, diffuse microvascular dysfunction, patchy sub-endocardial perfusion defects and a focal sub-endocardial perfusion defect. Cardiac allograft vasculopathy can be heralded by several different perfusion patterns on MCE in patients after orthotopic heart transplant. The varying prognoses and potential interventions for these different patterns require further investigation.