Practices in the Management of Incidental Gallbladder Cancer.

Peeyush VarshneyBackground Histopathology of gallbladder removed for stones may reveal incidental gallbladder cancer (iGBC). We conducted this online e-survey to document the knowledge and practices of management of iGBC among surgeons in India. Methods A 38-question online e-survey Results Two-hundred thirty responses were recorded. Ninety-eight out of two-hundred (49%) responses were general surgeons. Two-hundred ten out of two-hundred twenty-one (95%) saw at least one iGBC per year, but only 74/225 (32%) correctly defined true iGBC. One-hundred seventy-eight out of two hundred twenty-two (80%) did computed tomography/magnetic resonance imaging for thick-walled gallbladder (GB) detected on ultrasound, while 25/222 (11%) did laparoscopic cholecystectomy and 14/222 (6%) did open cholecystectomy. For GB mass on laparoscopy, 16/222 (7%) responses went ahead with simple cholecystectomy. Seventy-four out of two-hundred twenty-five (32%) responses routinely used bag while extracting GB. One-hundred ninety-one out of two-hundred twenty-five (86%) mentioned about stone/bile spill, 121/220 (55%) mentioned about use of bag for extraction while 137/220 62% mentioned port used for extraction of GB in operation notes. One-hundred sixty-six out of two-hundred twenty-seven (73%) always cut open GB after cholecystectomy. On encountering a mass/lesion on cut open GB, 111/225 (49%) sent it for frozen section, 89/225 (40%) sent for routine histopathology while 10% (22/225) directly proceeded for extended cholecystectomy. Ten out of two-hundred twenty-seven (4.4%) did not consider it important to send GB for histopathology. T stage on histopathology is most important factor for deciding reoperation by 205/223 (91%). Conclusion There are lacunae in understanding and deficiencies in management of iGBC in India-a high GBC incidence country. The situation is likely to be worse in low GBC incidence areas. There is need for more awareness and knowledge for proper management of iGBC among surgeons.

Pd/C-catalyzed regiodivergent hydrocarboxylation and esterification of alkynes.

An unprecedented and highly reactive Pd/C catalytic system has been introduced for the regiodivergent hydrocarboxylation of terminal alkynes to selectively afford various acrylic and cinnamic acids employing oxalic acid as a CO source as well as a promoter for the formation of the active Pd-H complex. Herein, the formation of cinnamic acid is proposed to follow a unique anti-Markovnikov hydroiodination mechanism and the formation of acrylic acid might follow the traditional hydrocarboxylation pathway. Additionally, internal alkynes undergo hydrocarboxylation and carbonylative esterification with aliphatic alcohols to yield different α,ß-unsaturated acids and esters respectively. The designed strategies were successfully leveraged for a diverse class of α,ß-unsaturated acids and esters with excellent selectivity and yields under mild reaction conditions. Furthermore, the acid functionalization of complicated naturally derived alkynes, utilizing economical and bench-stable oxalic acid and a commercially accessible reusable catalyst with gram-scale applicability are the additional benefits of the established protocol.

In Vivo Imaging Techniques for the Human Scalp: A Systematic Review of the Literature.

OBJECTIVE: Scalp inflammation and alopecia are distressing conditions for which patients regularly present to dermatology. Although some diagnoses can be made clinically, others require biopsy, which carries the risk of pain, infection, bleeding, and scarring. This review examines the existing literature regarding noninvasive in vivo imaging techniques and their evidence and utility in evaluating scalp pathology, with a focus on the diagnostics of hair conditions. METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines without timeframe restrictions. The PubMed and Clarivate (Web of Science) databases were searched using the terms ("imaging" OR "in-vivo imaging" OR "non-invasive imaging" OR "non-invasive in vivo imaging" "imaging," "in-vivo imaging) AND ("human scalp disorders" OR "scalp" OR "hair loss" OR "alopecia"). Peer-reviewed randomized control trials (RCTs), prospective studies, retrospective studies, and case series or reports discussing in vivo imaging of the scalp published before 2022 were selected. RESULTS: Forty-two studies were included and discussed; modalities included laser devices (n = 27), ultrasound (US) (n = 13), infrared thermography (n = 1), skin capacitance imaging (SCI), and ultraviolet light-enhanced visualization (ULEV) (n = 1). The most common laser devices used were reflectance confocal microscopy (RCM), multiphoton microscopy (MPM), and optical coherence tomography (OCT). US techniques included high-frequency US (HFUS) and US biomicroscopy (UBM). CONCLUSION: Quality imaging of the scalp in the setting of alopecic, neoplastic, and inflammatory diseases is highly sought after. Many of these noninvasive imaging techniques show promise, each with individual advantages and disadvantages in imaging-specific conditions. Ultimately, noninvasive imaging techniques may be used to optimize patient management and minimize morbidity associated with scalp biopsies.

Understanding innate and adaptive responses during radiation combined burn injuries.

The occurrence of incidents involving radiation-combined burn injuries (RCBI) poses a significant risk to public health. Understanding the immunological and physiological responses associated with such injuries is crucial for developing care triage to counter the mortality that occurs due to the synergistic effects of radiation and burn injuries. The core focus of this narrative review lies in unraveling the immune response against RCBI. Langerhans cells, mast cells, keratinocytes, and fibroblasts, which induce innate immunity, have been explored for their response to radiation, burns, and combined injuries. In the case of adaptive immune response, exploring behavioral changes in T regulatory (Treg) cells, T helper cells (Th1, Th2, and Th17), and immunoglobulin results in delayed healing compared to burn and radiation injury. The review also includes the function of complement system components such as neutrophils, acute phase proteins (CRP, C3, and C5), and cytokines for their role in RCBI. Combined insults resulting in a reduction in the cell population of immune cells display variation in response based on radiation doses, burn injury types, and their intrinsic radiosensitivity. The lack of approved countermeasures against RCBI poses a significant challenge. Drug repurposing might help to balance immune cell alteration, resulting in fast recovery and decreasing mortality, which gives it clinical significance for its implication on the site of such incidence. However, the exact immune response in RCBI remains insufficiently explored in pre-clinical and clinical stages, which might be due to the non-availability of in vitro models, standard animal models, or human subjects, warranting further research.

In the realm of public health, RCBI presents significant risks and obstacles. This hazard is quite serious, and it might get worse in the future as evidenced by incidents like nuclear meltdowns and medical mistakes. Diagnosis and treatment become more challenging when serious injuries, particularly burns, are combined with radiation exposure. Features like early shock, poor wound healing, and hematopoietic instability call for advancements in both diagnosis and therapy. Furthermore, the immune system's response to RCBI is complicated and involves changes in cytokine concentrations, immune cell activity, and adaptive immune responses compared to single injuries. Immune cell radiosensitivity varies depending on the type of cell, radiation dose, and length of exposure, so it's important to understand. Repurposing drugs is one of the potential techniques to reduce mortality and speed up healing which are discussed in the manuscript. Still, more research is needed. To effectively tackle RCBI, more investigation into molecular processes, treatment strategy optimization, and information gap closure are essential.

Evaluation of Pericardial Effusions in Alopecia Patients on Low-Dose Oral Minoxidil Therapy.

BACKGROUND: Minoxidil is an anti-hypertensive vasodilator increasingly used off-label for the treatment of alopecia. It is associated with an increased risk of pericardial effusions, with recent reports even in patients on low-dose oral minoxidil (LDOM) therapy. OBJECTIVE: To evaluate whether LDOM is associated with increased prevalence of pericardial effusions in patients with alopecia. METHODS: In this cross-sectional study, point-of-care ultrasound was used to screen alopecia patients at dermatology appointments. Scans were evaluated by two independent cardiologists for the presence and size of effusions. The prevalence of effusions was compared between patients on LDOM therapy and patients not on minoxidil therapy. RESULTS: A total of 100 patients were evaluated for pericardial effusion: 51 LDOM patients and 49 control patients. The two groups were similar in terms of age (53.7 vs 54.1; P=0.91), sex (86% vs 73% female; P=0.14), and race. Small pericardial effusions (<1 cm) were identified in 5.8% of LDOM patients and 6% of control patients (P=1), none of which were symptomatic. LIMITATIONS: This is a small, cross-sectional study with limitations on speculation of causality in confirmed cases. CONCLUSION: We did not find evidence of increased prevalence of pericardial effusions in a small group of alopecia patients on LDOM. J Drugs Dermatol. 2024;23(9):725-728. doi:10.36849/JDD.8029.

Exosomes: A new perspective for radiation combined injury as biomarker and therapeutics.

Radiation Combined Injuries (RCI) pose formidable public health risks, particularly in the context of nuclear incidents, necessitating specialized treatments and development of biomarkers. RCI encompasses instances where ionizing radiation exposure coincides with burns, wounds, or trauma. However, the limited understanding of cellular responses hinders progress in developing effective therapies. This article underscores the pivotal role of exosomes, nano-sized particles (30-120 nm) actively secreted by cells, in addressing the intricate challenges posed by RCI. Exosomes serve as vehicles for the transportation of bioactive molecules, including proteins, lipids, and miRNA, thereby facilitating processes critical to radiotherapy, burn injury, and wound healing. Exosomes hold significant promise for the transformation of RCI management by reducing inflammation, promoting wound healing, managing sepsis, altering immunological responses, and modulating signal transduction pathways. Moreover, exosomes are also being explored as biomarker for various diseases and stress conditions including radiation exposure and associated injuries. This comprehensive review highlights the burgeoning potential of exosomes in advancing the management of RCI, thereby enhancing public health preparedness and response.

Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe-S cluster homeostasis in Mycobacterium tuberculosis.

The ability of Mycobacterium tuberculosis (Mtb) to tolerate nitric oxide (•NO) and superoxide (O2•-) produced by phagocytes contributes to its success as a human pathogen. Recombination of •NO and O2•- generates peroxynitrite (ONOO-), a potent oxidant produced inside activated macrophages causing lethality in diverse organisms. While the response of Mtb toward •NO and O2•- is well established, how Mtb responds to ONOO- remains unclear. Filling this knowledge gap is important to understand the persistence mechanisms of Mtb during infection. We synthesized a series of compounds that generate both •NO and O2•-, which should combine to produce ONOO-. From this library, we identified CJ067 that permeates Mtb to reliably enhance intracellular ONOO- levels. CJ067-exposed Mtb strains, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) clinical isolates, exhibited dose-dependent, long-lasting oxidative stress and growth inhibition. In contrast, Mycobacterium smegmatis (Msm), a fast-growing, non-pathogenic mycobacterial species, maintained redox balance and growth in response to intracellular ONOO-. RNA-sequencing with Mtb revealed that CJ067 induces antioxidant machinery, sulphur metabolism, metal homeostasis, and a 4Fe-4S cluster repair pathway (suf operon). CJ067 impaired the activity of the 4Fe-4S cluster-containing TCA cycle enzyme, aconitase, and diminished bioenergetics of Mtb. Work with Mtb strains defective in SUF and IscS involved in Fe-S cluster biogenesis pathways showed that both systems cooperatively protect Mtb from intracellular ONOO- in vitro and inducible nitric oxide synthase (iNOS)-dependent growth inhibition during macrophage infection. Thus, Mtb is uniquely sensitive to intracellular ONOO- and targeting Fe-S cluster homeostasis is expected to promote iNOS-dependent host immunity against tuberculosis (TB).

The Burden of Melasma: Race, Ethnicity, and Comorbidities.

INTRODUCTION: In an effort to define the characteristics of populations affected by melasma, we utilized a large global health research network database from 108 health care organizations (TriNetx) to quantify the associations between race, ethnicity, and comorbidities. METHODS: We identified the cohort of all patients with melasma from the TriNetx database, and subsequently generated a control cohort. ICD-10 codes were used to identify the prevalence of various comorbidities associated with melasma. RESULTS: A total of 41,283 patients with melasma (93% female, mean [SD] age 48.8 [12.6] year) were identified. The most frequently associated risk factors included hypertension (25% of the melasma cohort) and hormonal contraception (24%). Rosacea (OR=5.1), atopic dermatitis (OR=3.3), lupus (OR=2.5), history of skin cancer (OR=2.5), history of internal malignancy (OR=2.1), and hormonal contraception use (OR=2.1) possessed the highest odds ratios for development of melasma (all P< 0.01). A statistically significant association was identified for melasma in Asian or Other/Unknown races (OR=2.0 and OR=1.7, P< 0.01), as well as Hispanic ethnicity (OR=1.3, P< 0.01). White, Black/African American, and Not Hispanic groups all revealed slightly lower odds (all 0.8, P< 0.01). CONCLUSION: This latest global update on the etiopathology of melasma further supports findings from prior epidemiologic study reporting preference in melanized phenotypes (Fitzpatrick skin type III-V), but less so in extreme skin types (I, II, VI). Increased associations with rosacea, atopic dermatitis, and history of cancer may emphasize the importance of treating concurrent inflammatory environments and the consideration of more frequent malignancy surveillance. J Drugs Dermatol. 2024;23(8):691-693.  doi:10.36849/JDD.8233.

Unconventional localization of PAI-1 in PML bodies: A possible link with cellular growth of endothelial cells.

Plasminogen activator inhibitor-1 (PAI-1/Serpin E1) is classically known for its antifibrinolytic activity via inhibiting uPA and tPA of the fibrinolytic pathway. PAI-1 has a paradoxical role in tumor progression, and its molecular functions are poorly understood. PAI-1 is a widely accepted secretory protease inhibitor, however, a study suggested the localization of PAI-1 in the cytoplasm and the nucleus. Besides the plethora of its biological functions as a secretory protein, intracellular localization, and functions of PAI-1 remain unexplored at the molecular level. In this study, using various in silico approaches, we showed that PAI-1 possesses a nuclear export signal. Using the CRM1-specific inhibitor leptomycin B, we demonstrated that PAI-1 has a functional CRM1-dependent NES, indicating the possibility of its nuclear localization. Further, we confirm that PAI-1 is localized in the nucleus of endothelial cells using fluorescence microscopy and immunoprecipitation. Notably, we identified an unconventional distribution of PAI-1 in the PML bodies of the nucleus of normal endothelial cells, while the protein was restricted in the cytoplasm of slow-growing cells. The data showed that the localization of PAI-1 in PML bodies is highly correlated with the growth potential of endothelial cells. This conditional nucleocytoplasmic shuttling of PAI-1 during the aging of cells could impart a strong link to its age-related functions and tumor progression. Together, this study identifies the novel behavior of PAI-1 that might be linked with cell aging and may be able to unveil the elusive role of PAI-1 in tumor progression.

The projected impact of the inflation reduction act's climate provisions on cardiovascular and respiratory outcomes.

Onjective: Climate change and environmental pollution have known health effects. The recently introduced inflation reduction act (IRA) by the United States government includes funding initiatives to curb climate change, and reduce environmental pollution, in line with the nationally determined contribution (NDC) plan (40-50 % reduction in greenhouse gas [GHG] emissions by 2030, as compared with 2005). The projected cardiovascular health benefits of the IRA driven climate actions to achieve the NDC goals are not known. Methods: We used the Energy Policy Simulator (EPS), a simulation algorithm based on systems dynamics modelling estimating the impact of various energy policies, to model the impact of achieving NDC targets in the United States on health outcomes by 2050. We further investigated race-specific impact on mortality (absolute and relative) by 2050.We estimated the projected reduction in six adverse health outcomes between 2022 and 2050: asthma attacks, non-fatal heart attacks, hospital admissions, respiratory symptoms and bronchitis, lost workdays, and deaths. Results: Achievement of NDC targets by 2050 will result in 987,415 avoided asthma attacks, 41,565 avoided nonfatal heart attacks, 18,993 avoided hospital admissions, 1,493,010 avoided respiratory symptoms and bronchitis, 3,317,250 avoided lost workdays, and 32,659 avoided deaths (22,839 among white individuals, 4993 among Black individuals, 2801 among Asian individuals, and 2026 among other/multirace individuals). By 2050, minority racial groups had higher relative change in avoided deaths (white -0.74 %, Black -1.01 %, Asian -1.24 %, and other/multirace -1.75 %). Similarly, Hispanics/latinos higher relative reductions in deaths (-1.4 %) compared with non-Hispanic/Latinos (-0.7 %) by 2050. Conclusion: The IRA facilitated achievement of NDC GHG reduction goals by 2050 would result in substantial number of avoided adverse health outcomes and death. Racial and ethnic minorities are expected to have the largest relative reductions in deaths by 2050. The current report underscores the importance of continued climate action investment irrespective of political differences. The appreciation of this aspect of the IRA may be more important to overall preservation of health, beyond the reduction in medication costs.

Method validation, residue behaviour and dietary risk assessment of insecticides (cyantraniliprole, acetamiprid, flubendiamide and its metabolite, des-iodo flubendiamide) in or on broccoli using LC-MS/MS.

Residue behaviour and dietary risk assessment of cyantraniliprole, flubendiamide and acetamiprid in broccoli were carried out using the QuEChERS (quick, easy, cheap, effective, rugged and safe) technique coupled with LC-MS/MS. The QuEChERS technique was validated on parameters such as linearity, accuracy, precision, robustness, matrix effects, limit of quantification (LOQ), specificity, retention time and ion ratio as per SANTE (Directorate General for Health and Food Safety) guidelines to attest to the specificity, accuracy and precision of the analytical method in estimating insecticide residues in and on broccoli heads and cropped soil. The LOQ of the method for all three insecticides was 0.01 mg/kg. The initial deposits of cyantraniliprole, flubendiamide and acetamiprid reduced to half of its concentration in 1.873-2.354, 1.975-2.484 and 1.371-1.620 days, respectively. No residues were detected in broccoli-cropped soil at harvest time (30 days after last spray). The proposed maximum residue limits (MRLs) of 1.5, 0.5-0.9 and 2.0-3 mg/kg for cyantraniliprole, flubendiamide and acetamiprid were calculated using the Organisation for Economic Co-operation and Development MRL calculator. The acute and chronic dietary risk assessment of the tested insecticides identified no appreciable dietary risk to the Indian population from the consumption of broccoli heads. The findings of no dietary risk highlight the importance of informed pesticide usage in broccoli and the proposed MRL derived from this study offers crucial guidelines for the regulatory authorities, ensuring the safety of broccoli consumption.

Dissipation kinetics and the evaluation of dietary risks associated with deltamethrin, ethion, fenazaquin, and fenpropathrin on bell pepper (Solanum annuum L.).

Bell peppers, a globally significant crop, face infestations from various pests. In a study, bell peppers were treated with deltamethrin, ethion, fenazaquin, and fenpropathrin at recommended and double the doses, repeated twice with a 10-day interval. The QuEChERS method underwent validation for linearity, matrix match, accuracy, and precision in bell pepper matrices for residue analysis. The limit of detection for the tested pesticides on bell peppers was 0.01 mg/L, with a quantification limit of 0.05 mg/L. Recovery studies showed a range of 94.80% to 102.80%. Initial deposits of deltamethrin, ethion, fenazaquin, and fenpropathrin on bell peppers at recommended doses were 0.371, 1.237, 0.617, and 0.640 mg/L, respectively, and at double doses were 0.712, 1.945, 1.221, and 1.189 mg/L, respectively. Safe waiting periods of 10, 11, 10, and 8 days were suggested for deltamethrin, ethion, fenazaquin, and fenpropathrin, respectively. The corresponding half-lives for the pesticides were 1.96, 1.79, 2.06, and 1.69 days, all following first-order dissipation kinetics. Dietary risk assessment indicated Hazard Quotients (HQ) below 1 and Theoretical Maximum Daily Intake (TMDI) below Acceptable Daily Intake (ADI) and Maximum Permissible Intake (MPI) levels. Therefore, at their recommended doses, the pesticides were deemed safe for bell pepper cultivation.

Current Pediatric Endoscopy Training Situation in the Asia-Pacific Region: A Collaborative Survey by the Asian Pan-Pacific Society for Pediatric Gastroenterology, Hepatology and Nutrition Endoscopy Scientific Subcommittee.

Purpose: To date, there is no region-specific guideline for pediatric endoscopy training. This study aimed to illustrate the current status of pediatric endoscopy training in Asia-Pacific region and identify opportunities for improvement. Methods: A cross-sectional survey, using a standardized electronic questionnaire, was conducted among medical schools in the Asia-Pacific region in January 2024. Results: A total of 57 medical centers in 12 countries offering formal Pediatric Gastroenterology training programs participated in this regional survey. More than 75% of the centers had an average case load of <10 cases per week for both diagnostic and therapeutic endoscopies. Only 36% of the study programs employed competency-based outcomes for program development, whereas nearly half (48%) used volume-based curricula. Foreign body retrieval, polypectomy, percutaneous endoscopic gastrostomy, and esophageal variceal hemostasis, that is, sclerotherapy or band ligation (endoscopic variceal sclerotherapy and endoscopic variceal ligation), comprised the top four priorities that the trainees should acquire in the autonomous stage (unconscious) of competence. Regarding the learning environment, only 31.5% provided formal hands-on workshops/simulation training. The direct observation of procedural skills was the most commonly used assessment method. The application of a quality assurance (QA) system in both educational and patient care (Pediatric Endoscopy Quality Improvement Network) aspects was present in only 28% and 17% of the centers, respectively. Conclusion: Compared with Western academic societies, the limited availability of cases remains a major concern. To close this gap, simulation and adult endoscopy training are essential. The implementation of reliable and valid assessment tools and QA systems can lead to significant development in future programs.