Standardized Quantification of Mast Cells in the Gastrointestinal Tract in Adults.

BACKGROUND: Current data on the normal quantity of mast cells throughout the adult gastrointestinal tract are limited in several domains. These include microanatomic localization of mast cells, standardization of staining and counting methods, and reporting of microscope field of view. OBJECTIVE: To address this lack of reliable reference ranges to facilitate the study of and diagnosis of emerging mast cell-mediated diseases. METHODS: We examined biopsies obtained from the esophagus, stomach, duodenum, and colon from an unselected cohort. Mean and peak mast cell density were determined on slides stained for tryptase and CD117, and were expressed per high power field (hpf) and surface area (mm2), thus deriving reference ranges (average ± 2 SDs). RESULTS: For the most common hpf surface area (0.238 mm2), upper limits of the derived reference ranges for average/peak mast cells were 0.15/3.67 (esophagus, tryptase), 0.70/5.98 (esophagus, CD117), 22.56/35.30 (stomach, tryptase), 31.32/53.10 (stomach, CD117), 30.28/49.77 (duodenal crypts, tryptase), 41.96/65.26 (duodenal crypts, CD117), 4.98/11.56 (duodenal villi, tryptase), 8.38/14.17 (duodenal villi, CD117), 26.58/41.08 (colon, tryptase), and 35.57/57.92 (colon, CD117). Interobserver variability was moderate to good. There was significant correlation between average and peak mast cell counts. CONCLUSIONS: These data help standardize mast cell reference ranges throughout the gastrointestinal tract in adults, which can be used to determine whether abnormal levels of mast cells are present in patients with suspected mast cell-mediated disease. Our data show that the commonly used cutoff of 20 mast cells per hpf irrespective of the gastrointestinal tract segment is an underestimate of an appropriate cutoff in stomach, duodenum (crypt area), and colon.

Clinicopathological profile of post-COVID-19 mucormycosis cases: A report from a tertiary care center.

Introduction: Mucormycosis is a fatal fungal infection, which is rare but commonly affects immunocompromised patients. Coronavirus disease 2019 (COVID-19) patients who were immunocompromised, due to comorbid conditions, such as hematological malignancy and diabetes mellitus (DM), and patients on immunosuppressive therapy such as steroid therapy were the important host for mucormycosis infection. Aim: This study aimed to study the clinicopathological correlation of mucormycosis in post-COVID-19 patients. Material and Methods: The study was a retrospective study conducted in the Department of Pathology, Sarojini Naidu Medical College, Agra, Uttar Pradesh, India, over four months from April 2021 to July 2021, and clinically diagnosed mucormycosis cases were included in this study. Clinical details, histology slides, and blocks were reviewed, and the data were analyzed. Three- to four-micrometer sections were taken from the blocks and stained with hematoxylin and eosin, and two more slides were made for each case for periodic acid-Schiff (PAS) and Grocott methenamine silver (GMS) staining. Result: In this study, the maximum cases were above the fifth decade of life. Males were more commonly affected than females with a male-to-female ratio of 2.09:1. Of the total of 65 cases, 46 (70.77%) cases were positive for mucormycosis and 19 (29.23%) cases were negative on histopathological examination and special stain PAS and GMS. A significant correlation was found between mucormycosis-positive cases on steroid therapy and oxygen supply during the treatment for COVID-19 with P- values of 0.001 and 0.027, respectively. Conclusion: For COVID-19 patients with altered glycemic control, receiving steroid therapy and oxygen supply poses a significant threat to the development of mucormycosis.

A Study of Comparison and Evaluation of Various Intralesional Therapies in Cutaneous Warts.

Background: The study compares the efficacy of four immunotherapeutic agents, measles mumps and rubella (MMR), purified protein derivative (PPD), Candida extract, and vitamin D3, in the treatment of multiple cutaneous warts. Aim and Objectives: To observe the clinical responses and safety of different intralesional immunotherapeutic agents and compare their efficacy. Materials and Methods: Hundred patients with multiple (>5) cutaneous warts were enrolled in the study and randomized into four groups: Group A: MMR, Group B: PPD, Group C: Candida extract, and Group D: Vitamin D. Target wart was selected, and the intralesional injections were given at three weekly intervals for a maximum of three doses. Response was observed in target and distant warts three months after the last injection. Results: Intralesional vitamin D3 had the highest efficacy, while MMR had the lowest efficacy in clearance of target wart. Intralesional Candida extract had the highest efficacy, while vitamin D3 had the lowest efficacy in clearance of distant warts. Intralesional Candida extract was the most effective treatment for both local and distant warts. Side effects were minimal and transitory in nature. Conclusion: Intralesional immunotherapy is a safe, affordable, and efficacious treatment for warts.

Discordance of estrogen and progesterone receptors after neoadjuvant chemotherapy in locally advanced breast cancer.

Aims and Objective: This study aimed to compare hormone receptor (HR) status before and after neoadjuvant chemotherapy that is discordance in locally advanced breast cancer patients, which are amenable for surgery. The secondary objective was to study the correlation between tumor response and HR expression. Materials and Methods: The duration of the study was from August 2018 to December 2020. A total of 23 patients were selected as per certain inclusion criteria. American Society of Clinical Oncologys methodology was used to analyze estrogen receptor (ER) and progesterone receptor (PR) status of histopathology specimen. For study purposes, patients were classified into four groups after core biopsy of breast lump and after definitive surgery (post-NACT (neoadjuvant chemotherapy)) - Group A (ER+, PR+), Group B (ER+, PR-), Group C (ER-, PR+), and Group D (ER-, PR-). Results: ER discordance was found to be (2/23) 8.69% (P value 0.76). PR discordance was (4/23) 17.39%. PR discordance was found to be higher than ER discordance. Changes in staining patterns in ERs were seen in 14 patients (93.33%). Changes in staining percentage in PRs were seen in eight patients (80%). It was found that both receptor-positive and negative diseases had an equal proportion of stable disease. Conclusion: From the study, it is noted that performing ER PR study twice (before and after chemotherapy) is necessary as discordance is noted and this may impact the further treatment strategy.

Herlyn-Werner-Wunderlich Syndrome: A Case Report.

Herlyn-Werner-Wunderlich syndrome is a rare Mullerian and mesonephric ductal anomaly characterized by a triad of didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis complex. This entity is also known as obstructed hemivagina and ipsilateral renal anomaly. We present a case of a 24-year-old nulliparous female with Herlyn-Werner-Wunderlich who presented with dysmenorrhea and intermenstrual bleeding. The diagnosis was initially made through ultrasound and confirmed on magnetic resonance imaging. The nonspecific nature of symptoms and variability in presentation depending on the classification and type of Herlyn-Werner-Wunderlich syndrome often leads to misdiagnosis or a delay in diagnosis. Therefore, a high index of suspicion is required. Keywords: case reports; mesonephric ducts; mullerian ducts.

Monolayer Graphene-MoSSe van der Waals Heterostructure for Highly Responsive Gate-Tunable Near-Infrared-Sensitive Broadband Fast Photodetector.

Transition metal dichalcogenides (TMDCs) are potential two-dimentional materials as natural partners of graphene for highly responsive van der Waals (vdW) heterostructure photodetectors. However, the spectral detection range of the detectors is limited by the optical bandgap of the TMDC, which acts as a light-absorbing medium. Bandgap engineering by making alloy TMDC has evolved as a suitable approach for the development of wide-band photodetectors. Here, broadband (visible to near-infrared) photodetection with high sensitivity in the near-infrared region is demonstrated in a MoSSe/graphene heterostructure. In the ambient environment, the photodetector exhibits high responsivity of 0.6 × 102 A/W and detectivity of 7.9 × 1011 Jones at 800 nm excitation with a power density of 17 fW/µm2 and 10 mV source-drain bias. The photodetector shows appreciable responsivity in self-bias mode due to nonuniform distribution of MoSSe flakes on the graphene layer between the source and drain end and the asymmetry between the two electrodes. Time-dependent photocurrent measurements show fast rise/decay times of ∼38 ms/∼48 ms. A significant gate tunability on the efficiency of the detector has been demonstrated. The device is capable of low power detection and exhibits high operational frequency, gain, and bandwidth. Thus, the MoSSe/graphene heterostructure can be a promising candidate as a high-speed and highly sensitive near-infrared photodetector capable of operating at ambient conditions with low energy consumption.

Developing synergistic drug combinations to restore antibiotic sensitivity in drug-resistant Mycobacterium tuberculosis.

Tuberculosis (TB) is a leading global cause of mortality owing to an infectious agent, accounting for almost one-third of antimicrobial resistance (AMR) deaths annually. We aimed to identify synergistic anti-TB drug combinations with the capacity to restore therapeutic efficacy against drug-resistant mutants of the causative agent, Mycobacterium tuberculosis We investigated combinations containing the known translational inhibitors, spectinomycin (SPT) and fusidic acid (FA), or the phenothiazine, chlorpromazine (CPZ), which disrupts mycobacterial energy metabolism. Potentiation of whole-cell drug efficacy was observed in SPT-CPZ combinations. This effect was lost against an M. tuberculosis mutant lacking the major facilitator superfamily (MFS) efflux pump, Rv1258c. Notably, the SPT-CPZ combination partially restored SPT efficacy against an SPT-resistant mutant carrying a g1379t point mutation in rrs, encoding the mycobacterial 16S ribosomal RNA. Combinations of SPT with FA, which targets the mycobacterial elongation factor G, exhibited potentiating activity against wild-type M. tuberculosis Moreover, this combination produced a modest potentiating effect against both FA-monoresistant and SPT-monoresistant mutants. Finally, combining SPT with the frontline anti-TB agents, rifampicin (RIF) and isoniazid, resulted in enhanced activity in vitro and ex vivo against both drug-susceptible M. tuberculosis and a RIF-monoresistant rpoB S531L mutant.These results support the utility of novel potentiating drug combinations in restoring antibiotic susceptibility of M. tuberculosis strains carrying genetic resistance to any one of the partner compounds.

Platelet-Rich Plasma in Androgenetic Alopecia: Is It Really Worth the Hype?

Introduction: Androgenetic alopecia (AGA) is defined as progressive, patterned hair loss that occurs as a result of androgen-mediated conversion of terminal hairs to vellus hairs. By the age of 60 years, 45% of men and 35% of women develop AGA. The Hamilton-Norwood scale is used to assess the extent and severity of AGA and classify the stages of male pattern hair loss in men, whereas the Ludwig scale is preferred for women. Currently, U.S. Food and Drug Administration-approved treatments for AGA include oral finasteride and topical minoxidil. Due to the limited number of effective therapies for AGA, platelet-rich plasma (PRP) has become an effective alternative treatment. A number of studies on PRP have shown promising results, leading to increased hair density and thickness with minimal or no side effects. Aims: We aim to study the safety, efficacy, and side effects of PRP therapy in patients of AGA and to study demographic data in the form of age, sex, age of onset of hair loss, and grade of AGA in patients. Materials and Methods: Fifty patients, 38 males and 12 females, with AGA were enrolled in the study. PRP was prepared using a double-spin method. Upon activation, PRP was injected in the involved areas of scalp once every 2 weeks for 6 months. Follow-up photos were taken every 3 months. Results: At 6 months, majority of the patients (45%) were unsatisfied and showed no change in hair growth after PRP therapy and few patients were lost in follow-up. Adverse effects were minimal and no long-term serious adverse effects were noted. Conclusion: We conclude from the results in our study that PRP therapy is not significantly effective in treatment of AGA. There is a need to develop standard protocols with regard to total length of PRP therapy and spacing between the two sessions of PRP for AGA.

Citrus Essential Oils in Aromatherapy: Therapeutic Effects and Mechanisms.

Citrus is one of the main fruit crops cultivated in tropical and subtropical regions worldwide. Approximately half (40-47%) of the fruit mass is inedible and discarded as waste after processing, which causes pollution to the environment. Essential oils (EOs) are aromatic compounds found in significant quantities in oil sacs or oil glands present in the leaves, flowers, and fruit peels (mainly the flavedo part). Citrus EO is a complex mixture of ~400 compounds and has been found to be useful in aromatic infusions for personal health care, perfumes, pharmaceuticals, color enhancers in foods and beverages, and aromatherapy. The citrus EOs possess a pleasant scent, and impart relaxing, calming, mood-uplifting, and cheer-enhancing effects. In aromatherapy, it is applied either in message oils or in diffusion sprays for homes and vehicle sittings. The diffusion creates a fresh feeling and enhances relaxation from stress and anxiety and helps uplifting mood and boosting emotional and physical energy. This review presents a comprehensive outlook on the composition, properties, characterization, and mechanism of action of the citrus EOs in various health-related issues, with a focus on its antioxidant properties.

In vivo topical gene therapy for recessive dystrophic epidermolysis bullosa: a phase 1 and 2 trial.

Recessive dystrophic epidermolysis bullosa (RDEB) is a lifelong genodermatosis associated with blistering, wounding, and scarring caused by mutations in COL7A1, the gene encoding the anchoring fibril component, collagen VII (C7). Here, we evaluated beremagene geperpavec (B-VEC), an engineered, non-replicating COL7A1 containing herpes simplex virus type 1 (HSV-1) vector, to treat RDEB skin. B-VEC restored C7 expression in RDEB keratinocytes, fibroblasts, RDEB mice and human RDEB xenografts. Subsequently, a randomized, placebo-controlled, phase 1 and 2 clinical trial (NCT03536143) evaluated matched wounds from nine RDEB patients receiving topical B-VEC or placebo repeatedly over 12 weeks. No grade 2 or above B-VEC-related adverse events or vector shedding or tissue-bound skin immunoreactants were noted. HSV-1 and C7 antibodies sometimes presented at baseline or increased after B-VEC treatment without an apparent impact on safety or efficacy. Primary and secondary objectives of C7 expression, anchoring fibril assembly, wound surface area reduction, duration of wound closure, and time to wound closure following B-VEC treatment were met. A patient-reported pain-severity secondary outcome was not assessed given the small proportion of wounds treated. A global assessment secondary endpoint was not pursued due to redundancy with regard to other endpoints. These studies show that B-VEC is an easily administered, safely tolerated, topical molecular corrective therapy promoting wound healing in patients with RDEB.

Trends in Axillary Management of Early Breast Cancer: a Questionnaire-Based Pattern of Practice Survey for India.

Surgical management of breast cancer (BC) has evolved from radical surgeries to conservative with better cosmetic and comparable oncological outcomes. For axillary staging, it has evolved from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB). No detailed information exists in terms of the clinical practice pattern of surgical management of axilla for BC patients in India. A questionnaire-based survey was developed. The survey was done at the annual meeting of the Association of Breast Surgeons of India (ABSI) in November 2018. Responses were recorded and analysed by SPSS 23. One hundred twelve out of 400 (28%) responded to the survey. Half of the respondents were surgical oncologist and 36.6% were performing > 150 BC surgeries/year. The primary technique for axillary staging in node-negative BC was SLNB for 68.5% of respondents. Majority of surgeons (47%) reported performing SLNB by methylene blue dye only. Unavailability of radioisotope (46.7%) and lack of frozen section (26.7%) were reported as two major barriers for not performing SLNB. Twenty-three percent did perform SLNB in post-NACT setting. Only 15.8% have omitted completion ALND in Z0011 trial eligible SLN-positive patients. 45.9% skipped completion ALND in SLN positive with micro metastasis only. Many surgeons in India are adopting SLNB as a method of axillary staging into their clinical practice. However, large number of surgeons still believe in conservative approach, most probably due to unavailability of resources and lack of Indian data. Barrier identified in this survey may be useful for future development.

Clinical Features of Mycetoma and the Appropriate Treatment Options.

Mycetoma is a chronic, suppurative and debilitating granulomatous infection seen mainly in tropical and subtropical areas and is now declared as a neglected tropical disease by the World Health Organization. The clinical diagnosis is usually characterized by a classical triad of localized swelling, underlying sinus tracts, and production of grains or granules, but unusual presentations are also seen. It is classified into eumycetoma caused by the fungus, and actinomycetoma caused by the bacteria. The clinical presentation of both is almost similar and a definite diagnosis is essential before starting the treatment as it differs for both. Surgical debulking followed by a prolonged course of medical therapy now forms the mainstay of treatment due to the long course of the disease and suboptimal response. This review focuses on the various usual as well as unusual clinical presentations of mycetoma, established treatment regimens as well as recent changes in the mode of administration of drugs and newer drugs for mycetoma.

Histopathological evaluation of cutaneous reactions to tattoos: Study at a tertiary care center.

BACKGROUND: Tattooing has been around for many years and is becoming an increasingly common fashion trend. As there are often few regulatory laws regarding the practice, an increase in the incidence of cutaneous reactions to tattoo inks is noted. These include allergic reactions, granulomatous dermatitis, infections, lichenoid dermatoses, and sometimes malignancy. The present study examines the histopathological changes seen in patients with cutaneous reactions to tattoo ink. METHOD: A prospective observational study was conducted over 18 months in the dermatology clinic of a tertiary care center in western India. The study population included 22 patients with cutaneous reactions over the tattoos. Punch biopsy specimens were sent to study the pattern of histopathological response. RESULTS: All 22 patients studied were between the ages of 17 and 35 years. The mean duration of development of reaction was 8.1 months. Most of the reactions were seen in black ink tattoos performed by amateurs. Perivascular and spongiotic dermatitis suggestive of allergic response was the most common feature on histopathology. Granulomatous response and lichenoid response were seen in five and three biopsies, respectively. CONCLUSION: Legalization is needed for this practice to prevent tattoo reactions. Histopathological evaluation is important as tattoo reactions may be associated with skin infections and malignancies.

Preclinical Evaluation of a Modified Herpes Simplex Virus Type 1 Vector Encoding Human TGM1 for the Treatment of Autosomal Recessive Congenital Ichthyosis.

Autosomal recessive congenital ichthyosis (ARCI) is a diverse group of cornification diseases associated with severe clinical complications and decreased quality of life. Germline mutations in the TGM1 gene, which encodes the enzyme TGM1, are the predominant cause of ARCI. These TGM1 mutations trigger the abnormal epidermal differentiation and impaired cutaneous barrier function observed in patients with ARCI. Unfortunately, current ARCI therapies focus solely on symptomatic relief. Thus, there is a significant unmet need for therapeutic strategies aimed at correcting the TGM1 deficiency underlying ARCI. In this study, we investigated the ability of KB105, a gene therapy vector encoding full-length human TGM1, to deliver functional human TGM1 to keratinocytes. In vitro, KB105 efficiently infected TGM1-deficient human keratinocytes, produced TGM1 protein, and rescued transglutaminase enzyme function. In vivo studies demonstrated that both single and repeated topical KB105 administration induced TGM1 protein expression in the target epidermal layer without triggering fibrosis, necrosis, or acute inflammation. Toxicity and biodistribution assessments on repeat dosing indicated that KB105 was well-tolerated and restricted to the dose site. Overall, our results demonstrate that rescuing TGM1 deficiency in patients with ARCI through topical KB105 application represents a promising strategy for safely and noninvasively treating this debilitating disease.

Foam Cell Macrophages in Tuberculosis.

Mycobacterium tuberculosis infects primarily macrophages in the lungs. Infected macrophages are surrounded by other immune cells in well organised structures called granulomata. As part of the response to TB, a type of macrophage loaded with lipid droplets arises which we call Foam cell macrophages. They are macrophages filled with lipid laden droplets, which are synthesised in response to increased uptake of extracellular lipids, metabolic changes and infection itself. They share the appearance with atherosclerosis foam cells, but their lipid contents and roles are different. In fact, lipid droplets are immune and metabolic organelles with emerging roles in Tuberculosis. Here we discuss lipid droplet and foam cell formation, evidence regarding the inflammatory and immune properties of foam cells in TB, and address gaps in our knowledge to guide further research.

Updates on Management of Leprosy in the Context of COVID-19 Pandemic: Recommendations by IADVL SIG Leprosy.

The Special Interest Group (SIG) on leprosy thought it to be prudent to revisit its previous practice recommendations through this update. During this period, the pandemic course shifted to a 'second wave' riding on the 'delta variant'. While the number of cases increased manifold, so did the research on all aspects of the disease. Introduction of vaccination and data from various drug trials have an impact on current best practices on management of diseases including leprosy. The beneficial results of using steroids in management of COVID-19, gives elbow room regarding its usage in conditions like lepra reactions. On the other hand, the increase in cases of Mucormycosis again underlines applying due caution while recommending immunosuppressants to a patient already suffering from COVID-19. This recommendation update from SIG leprosy reflects current understanding about managing leprosy while the dynamic pandemic continues with its ebbs and flows.

Corrigendum: Foam Cells Control Mycobacterium tuberculosis Infection.

[This corrects the article DOI: 10.3389/fmicb.2020.01394.].