Investigation of the molecular structure of CHBP, biological activities and SARS-CoV-2 protein binding interaction by molecular and biomolecular spectroscopy approaches.

The objective of this investigation is to learn more about the structural, electrical, spectroscopic, and physiochemical characteristics of biologically active cyano-4'-hydroxybiphenyl (CHBP). The title molecule's optimized conformational analysis was computed using the DFT/B3LYP/6-311++G (d, p) level of theory. The observed wavenumbers were compared with theoretical FT-IR and FT-Raman spectra. 1H and 13C NMR experimental spectra in CDCl3 solution (solvent phase) were recorded and the chemical shift was calculated. NBO analysis was used to examine the transfer of charge as well as the intermolecular and intramolecular bonding of orbitals. The TD-DFT (time-dependent DFT) approach was used to estimate theoretical values for both the gas and solvent (ethanol) in the corresponding transitional research, which was conducted using UV-Vis's spectra. Energy gap (Eg = 0.26764 eV) implies that the strong potential for charge transfer, and the stability of the CHBP compound. CHBP compound's has bioactive nature, its drug-likeness and biological properties were evaluated. The predicted topological polar surface area of 44.02 \AA2 for the molecule falls within the permissible range of < 140 \AA2. Based on the docking results, the most stable docking score value is -6.84 kcal/mol. In that interaction, MET 165 affects both phenyl rings in a pi-sulphur fashion and a single bond hydrogen with protein moieties GLN 192. This suggests that the pi-alkyl in PRO 168 is a hydroxyl substitutional ring. Our findings demonstrate the CHBP compound is a good inhibitor against the SAR COVID-19 viral protein.

Legal and Ethical Issues Associated With Challenges in the Implementation of the Electronic Medical Record System and Its Current Laws in India.

Electronic health records (EHR) have revolutionized healthcare by providing efficient access to patient information, but their implementation poses various challenges. This paper examines the ethical and legal issues surrounding EHR adoption, particularly focusing on the healthcare landscape in India. Ethical considerations, including patient autonomy, confidentiality, beneficence, and justice, must guide EHR implementation to protect patient rights and privacy. Legal issues such as medical errors, malpractice, data breaches, and billing inaccuracies underscore the importance of robust policies and security measures. Threats to EHRs, such as phishing attacks, malware, encryption vulnerabilities, and insider threats, emphasize the need for comprehensive cybersecurity strategies. Overcoming challenges in EHR implementation requires meticulous planning, financial investment, staff training, and stakeholder support. Despite the complexities involved, the benefits of EHR adoption in improving patient care and operational efficiency justify the efforts required to address legal, ethical, and technical concerns. Embracing EHRs while mitigating associated risks is essential for delivering high-quality healthcare in the digital age.

Electro-Amputation of Lower Limbs Due to a High-Voltage Shock: Report of an Unusual Case.

Electrical injuries due to high voltage are not frequent but can cause a high mortality rate. The body of a 45-year-old security guard was found at an apartment with an alleged history of being electrocuted while working when he came into contact with a high-voltage transformer. The police brought the body for a post-mortem examination. The autopsy revealed superficial to deep-degree burns with bilateral lower limb amputation. The cause of death was shock due to 80%-85% of the total body surface area being burned due to high-voltage electrocution. This article suggests a new mechanism, i.e., electrocution-induced amputation, called electro-amputation, which is unusual and not reported in the literature to the best of our knowledge. The authors also recommend a forensic surgeon should consider detailed circumstantial findings, a scene of crime visit, and a meticulous post-mortem examination before concluding the exact cause of death as high-voltage electrocution.

EUFOREA summit in Brussels 2023: inspiring the future of allergy & respiratory care.

In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.

Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of TH 1 T-cells.

BACKGROUND: Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. METHODS: BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. RESULTS: Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. CONCLUSIONS: BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.

Solitary Vulvar Syringoma With Deep Extension; Potential for Misdiagnosis as the Microcystic Adnexal Carcinoma (MAC).

ABSTRACT: A 43-year-old woman presented with a palpable, pruritic, minimally painful right vulvar lesion. Physical examination revealed approximately 2.0-cm tender nodule at 70' clock in the right labia majora. Histological sections of the excision specimen showed an unremarkable epidermis with large, well-circumscribed dermal proliferation with extension to the reticular dermis. Within this proliferation are small solid and ductal structures relatively evenly distributed in the sclerotic stroma. The epithelial elements consisted of monomorphous cuboidal cells and assumed round, oval, curvilinear, or have other peculiar geometric shapes, including "comma-like" or "tadpole"-like configurations. The tumor cells were positive for CEA, EMA, and estrogen receptor and negative for progesterone receptor. The clinical presentation and the deep extension of the tumor were similar to the microcystic adnexal carcinoma. Although a syringoma generally presents with multiple lesions and usually involves the superficial dermis, a syringoma with deep extension was favored based on the lack of follicular differentiation, atypia, mitoses, and perineural invasion. Microcystic adnexal carcinoma and syringoma have a morphologic overlap and are misdiagnosed in 30% of the cases. Thus, it is exceptionally important for pathologists to be aware of and be able to distinguish these entities. To the best of our knowledge, this is the first case of a solitary, painful vulvar syringoma with deep extension.

Primary Cutaneous Ewing Sarcoma of the Scalp With Metastasis to the Lung: An Unusual Manifestation During Pregnancy.

ABSTRACT: A 32-year-old G2P1L1 (5 months pregnant) woman presented with a 3-month history of a slow-growing cystic lesion on her scalp vertex. Similar lesions in the exact location were excised twice in the past with a diagnosis of trichilemmal carcinoma (TC). A biopsy of the scalp lesion showed morphology and immunoprofile consistent with previously diagnosed TC. Staging PET/CT demonstrated a 4.7 cm right upper lobe lung, and a subsequent lung biopsy showed a small, round blue-cell tumor with necrosis, morphologically identical to the prior biopsies from the scalp. Considering the unusual clinical course of TC, a lung biopsy was sent for next-generation sequencing that showed EWSR1-FLI1 (type1) fusion. Additionally, CD99 immunostaining revealed uniform cytoplasmic and membranous staining in the tumor cells. The previous scalp excision specimen was also sent for mutation analysis, which showed EWSR1-FLI1 fusion. In conjunction with clinical history and histological and molecular findings, a definitive diagnosis of primary cutaneous Ewing sarcoma (PCES) with local recurrence and metastasis to the lung was made. We present a case of PCES, which was previously misdiagnosed and treated as TC. This case emphasizes the importance of CD99 in the initial screening of cutaneous small round blue-cell tumors to avoid misdiagnosis from other morphological overlaps. Also, despite its rarity, PCES should be included in the differential diagnosis of small, round, blue cell tumors at cutaneous sites. Our case also exemplifies common biases in medical decision-making, including premature closure and anchoring bias which can result in misdiagnosis or diagnostic delay and associated delay in appropriate management.

Nuclear medicine in the management of superficial skin abnormalities and institutional experience.

Keloid, hypertrophic scars and basal cell carcinoma (BCC) falls under the category of non-melanoma skin cancer. Intralesional steroids, external beam radiation therapy, 5-Fluorouracil, cryotherapy, laser, etc are the available treatment options. However, recurrence has been reported with each type of treatment mode. In the present article, various treatment modes have been discussed and institutional experience of Rhenium-188 skin patches for the treatment of keloids and BCC has been discussed.

A Case of Primary Myelofibrosis With Transformation to Leukemia Cutis.

ABSTRACT: We report an extraordinary case of primary myelofibrosis with transformation to leukemia cutis. A 64-year-old Caucasian man with a history of JAK2-positive primary myelofibrosis presented with erythematous papulonodules on his right lower extremity. A punch biopsy revealed a normal epidermis with an underlying diffuse dermal infiltrate composed of medium-to-large-sized myeloid cells and leukocytes. Neoplastic cells were immunoreactive for LCA, CD34, CD61, CD117, and CD68 and negative for lysozyme, CD20, CD3, myeloperoxidase, and TdT. These findings were consistent with a diagnosis of leukemia cutis. A concurrent bone marrow biopsy demonstrated a markedly fibrotic, hypercellular marrow without a significant increase in blasts. With no morphologic evidence of bone marrow involvement by acute myeloid leukemia, our case suggests that the patient's primary myelofibrosis transformed to leukemia cutis. Our patient died 2 months after the onset of his skin nodules. Our case demonstrates that leukemia cutis should be included in the differential diagnosis for cutaneous nodular lesions in patients with a history of an advanced-stage hematological malignancy.

Fatal necrotizing fasciitis in illegal abortion and the negligence tort.

The present paper is a case-based review on rare complications of illegal abortion, i.e., necrotizing fasciitis missed early by the treating gynecologists which landed up into a negligence tort against the physicians. The common complications of the abortion like incomplete abortion, haemorrhage, sepsis, etc. are usually handled successfully by the gynecologists; however, early detection often missed when a rare complication like necrotising fasciitis occurs. Eventually leading to litigations in case of death of the patient. The newer techniques have reduced the complications in medically terminated pregnancies (MTP); however, the deaths due to illegal abortions carried out by the clandestine abortion practitioners (CAP) poses a challenge, especially in rural areas. A 30-year-old woman went for an illegal abortion from a CAP to avoid social stigma. She developed sepsis & necrotising fasciitis (NF) of right lower limb due to intra-vaginal use of abortifacient herbs prescribed by the CAP. She was succumbed to the complications of necrotising fasciitis allegedly due to delayed diagnosis by the gynecologists. This led to a negligence tort filed by her family members against the treating gynecologists. The prudent medicolegal and medical steps are discussed here, that could have prevented such sequel.

Prospective impact of Corona virus disease (COVID-19) related lockdown on shrimp aquaculture sector in India - a sectoral assessment.

The lockdown on account of the Coronavirus disease 2019 (COVID-19) adversely impacted the food production sector including aquaculture, globally. Unfortunately, it coincided with the major shrimp farming season in India which contributes 60% of the national annual shrimp production hence the impact was substantial. An on-line survey was carried out among the stakeholders of the shrimp farming sector to evaluate the prospective impact of COVID-19 related lockdown across the shrimp supply chain. The study estimated an economic loss of 1.50 billion USD to the shrimp aquaculture sector during the current year. It is expected that shrimp production and its export performance may be declining by 40% in the current season. The Garret ranking and Rank Based Quotient analyses projected severe constraints in shrimp seed production and supply, disruptions in the supply chain, logistics, farming, processing, marketing and loss of employment and income for the workers due to the pandemic. To mitigate the impact, the Government of India declared fisheries and aquaculture as an essential activity, facilitated the movement of inputs and services. Further, a major Fisheries Development Scheme(PMMSY) with a financial outlay of 267 million USD has been announced to usher in a blue revolution by strengthening the value chain, doubling the fisher/farmer income, employment generation, economic and social security for fishers/fish farmers adhering to the sustainability principles. Short and medium-term technical and policy measures are suggested to tide over the impact of COVID-19 related lockdown and related restrictions.

Psychological disturbances in patients with pigmentary disorders: a cross-sectional study.

BACKGROUND: Data on prevalence and factors influencing psychological burden in pigmentary disorders are scarce. OBJECTIVE: To determine the point prevalence of anxiety disorder, depression and somatoform disorder in patients with melasma, vitiligo and acquired dermal macular hyperpigmentation (ADMH). METHODS: A prospective cross-sectional study involving 100 patients each with melasma, ADMH and vitiligo with lesions on exposed body parts was conducted in the pigmentary clinic of a tertiary care referral hospital from June 2015 to December 2017. Dermatology life quality index, PRIME-MD Patient Health Questionnaire, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7 and Patient Health Questionnaire-15 were used for assessment of quality of life, psychiatric comorbidities, depression, general anxiety disorder and somatoform disorders, respectively, and correlated with age, gender, occupation, marital status, severity and progression of the disease. RESULTS: The prevalence of anxiety disorder in patients with melasma, vitiligo and ADMH was 11.6%, 21% and 18.7%, respectively. Depression was seen in 12.8%, 27% and 24.1% patients with melasma, vitiligo and ADMH, respectively. Somatoform disorder was more common in vitiligo (17.9%) as compared to ADMH (14.3%) and melasma (8.1%). There were positive correlations between the severity of disease and the point prevalence of anxiety and depression in all disorders. CONCLUSION: A high point prevalence of anxiety, depression and somatoform disorders was observed with pigmentary diseases, especially vitiligo and ADMH. The prevalence of anxiety and depression correlated with the disease severity and activity. Future research involving comparison with the general healthy population is required for a more affirmative conclusion.

Contact sensitization to hair colours in acquired dermal macular hyperpigmentation: results from a patch and photo-patch test study of 108 patients.

BACKGROUND: Acquired dermal macular hyperpigmentation (ADMH) is an umbrella term including lichen planus pigmentosus, erythema dyschromicum perstans and pigmented contact/cosmetic dermatitis. OBJECTIVE: To establish contact sensitization to hair colours as an aetiological factor for ADMH. METHODS: Detailed clinical examination, skin biopsies, and patch and photo-patch testing with Indian standard series and patient's own cosmetic products were performed. RESULTS: Thirty-nine (36.1%) patients were found to demonstrate a positive patch/photo-patch test with 35/39 reacting to their own products (all were hair colours) and 16/39 reacting to antigens from commercial series (commonly paraphenylenediamine). Fourteen patients developed delayed hyperpigmentation on positive patch-test sites at 1 month. Higher mean age, symptomatic pigmentation (pruritus, burning and photosensitivity), hair margins involvement (outer surface, helix and lobule of ear; temples and preauricular area), ill-defined lesions, epidermal atrophy and epidermal melanization extending >3 layers were significantly common in patch-test-positive patients. Well-defined lesions, perioral involvement and associated lichen planus were clinical pointers towards patch-test negativity. CONCLUSION: Index study exemplifies that patch-test results have distinct clinical and histopathological correlates in ADMH. Hair dye contact sensitization appears to be an important aetiological factor in about one-third patients presenting with ADMH.

Reliability assessment and validation of the dermal pigmentation area and severity index: a new scoring method for acquired dermal macular hyperpigmentation.

BACKGROUND: Dermal pigmentation area and severity score (DPASI) is a recently proposed scoring system for acquired dermal macular hyperpigmentation (ADMH). OBJECTIVE: To determine the reliability and validity of DPASI. METHODS: After standardized training, three researchers independently rated 55 patients with ADMH on two consecutive days within 1 week, to determine intra-rater and inter-rater reliability. Validation was performed by comparing DPASI with the physician global assessment score. RESULTS: Test-retest reliability of individual raters tested by Pearson's r showed good correlation for all three raters (r = 0.984, P < 0.0001; r = 0.983, P < 0.000 and r = 0.970, P < 0.0001). Inter-rater agreement computed by intra-class correlation coefficient also showed good correlation (ICC = 0.997, P < 0.0001). Internal consistency as measured by Cronbach's alpha was 0.997. The score faired well in face and content validity (I-CVI of 0.87). On usability assessment, the scale had a median score of 4 on a scale from 1 to 5. The meantime taken to score the patients were 307.2 ± 83, 308.9 ± 84.4, 350.15 ± 91.8 s by three observers, respectively. CONCLUSION: The DPASI is a reliable measure of ADMH severity. The use of dermoscopy decreases inter and intra-observer variation resulting in a more objective score.