Mentorship as an overlooked dimension of research capacity strengthening: how to embed value-driven practices in global health.

Mentorship in global health remains an overlooked dimension of research partnerships. Commitment to effective mentorship models requires value-driven approaches. This includes having an understanding of (1) what mentorship means across different cultural and hierarchical boundaries in the health research environment, and (2) addressing entrenched power asymmetries across different aspects including funding, leadership, data and outputs, and capacity strengthening. Existing guidance towards equity and sustainability fails to inform how to navigate complex relationships which hinder effective mentorship models. We focus this perspective piece on human capacity strengthening in research partnerships through mentorship. Using a case study of a research partnership, we describe the lessons learnt and the challenges faced in the mentor mentee relationship while maintaining an effective and sustainable partnership. Human capacity strengthening must research projects and collaborations, and recognise local leadership and ownership. To be transformative and effective, practices need to be driven by common values across research teams.

Markers of Oxidative Stress and Tyrosinase Activity in Melasma Patients: A Biochemical Investigation.

BACKGROUND: Melasma is a skin hyperpigmentary disorder that develops over time. Genetic factors, oxidative stress, female sex hormones, and UV light may all play a role in the disorder's progression. AIMS: To compare the levels of oxidative stress and tyrosinase activity in melasma patients with healthy volunteers. METHODS: After written consent, 130 patients were enrolled in a case-control study. 65 cases were of melasma disorder, and 65 were served as control. Homogenized skin tissues were taken and used to estimate superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx) (antioxidants), malondialdehyde (MDA) and tyrosine hydroxylase (TH). RESULTS: Melasma patients had lower basal levels of systemic antioxidants than healthy subjects. Tyrosinase activity was shown to be greater in lesional skin than in non-lesional skin. In controls, there was a good positive relationship between TH and MDA and an excellent negative relationship between GPx and GSH. In melasma patients, there were significant associations between CAT, GPx, SOD and MDA. CONCLUSIONS: Increased oxidative stress may affect tyrosinase activity and eumelanin synthesis via the anabolic pathway of melanin synthesis, according to our findings. In conclusion, we discovered a negative relationship between antioxidants and tyrosinase activity.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

Uncemented Total Hip Arthroplasty in an Adult without Osteotomy for Neglected Developmental Dysplasia of Hip.

Introduction: Developmental dysplasia of hip (DDH) is an abnormal development of hip joint which when neglected in early age group can lead to joint pain and secondary osteoarthritic changes. Crowe types III and IV neglected DDH joint is widely managed with total hip arthroplasty with subtrochanteric shortening. Case Report: A 52-year-old female presented with neglected DDH joint which was managed in two stages with femoral lowering followed by uncemented total hip arthroplasty without osteotomy. Conclusion: With the two-stage procedure, subtrochanteric shortening which is widely accepted management for neglected DDH and the related complications were avoidable with a satisfactory Harris hip score.

Subthreshold Doses of Inflammatory Mediators potentiate one another to Elicit Reflex Cardiorespiratory Responses in Anesthetized Rats.

BACKGROUND: Reflex cardio-vascular and respiratory (CVR) alterations evoked by intra-arterial instillation of nociceptive agents are termed vasosensory reflexes. Such responses elicited by optimal doses of inflammatory mediators have been described in our earlier work. OBJECTIVE: The present study was designed to evaluate the interactions between subthreshold doses of inflammatory mediators on perivascular nociceptive afferents in urethane anesthetized rats. METHODS: Healthy male adult rats (Charles-Foster strain) were anesthetized with an intraperitoneal injection of urethane. After anesthesia, the right femoral artery was cannulated. Respiratory movements, blood pressure, and electrocardiogram were recorded. The interactions between subthreshold doses of algogens in the elicitation of vasosensory reflex responses were studied by instillation of bradykinin (1 nM) and histamine (100 µM) into the femoral artery one after the other, in either temporal combination in separate groups of rats. The CVR responses obtained in these groups were then compared with the responses produced by 100 µM histamine and 1 nM bradykinin in saline-pretreated groups, which served as control. RESULTS: Subthreshold doses of histamine elicited transient tachypnoeic, hyperventilatory, hypotensive, and bradycardiac responses, in rats pretreated with subthreshold doses of bradykinin [P <0.01, two-sided Dunnett's test] but not in saline pretreated groups [P >0.05, two-sided Dunnett's test]. Similar responses were elicited by bradykinin after histamine pretreatment compared to the saline-pretreated group. Furthermore, CVR responses produced by histamine in the bradykinin-pretreated group were greater in magnitude as compared to bradykinin-induced responses in the histamine-pretreated group [P <0.05, two-sided Dunnett's test]. CONCLUSION: The present study demonstrates that both bradykinin and histamine potentiate one another in the elicitation of vasosensory reflex responses, and bradykinin is a better potentiator than histamine at the level of perivascular nociceptive afferents in producing reflex CVR changes.

Colistin (Polymyxin E) Use in Abdominal Solid Organ Transplant Recipients.

Background: Patients undergoing solid organ transplantation are at a higher risk of multi-drug resistant (MDR) bacterial infections especially during the immediate post operative period. Objective: To audit the usage, dosage appropriateness and safety of colistin use in abdominal solid organ transplant recipients to treat immediate post-transplant bacterial infections. Methods: After completion of 1000 abdominal solid organ transplants at our institute, data of the transplant recipients who received colistin between October 2010 and December 2019 was extracted from the hospital health information system. Data of all microbiological culture isolates, the minimum inhibitory concentration (MIC) of colistin, appropriateness of colistin dosing and nephrotoxicity associated with colistin use was assessed. Results: Of the 1170 (732 liver and 438 renal) solid organ transplant recipients, 82 (66 liver and 16 renal) received colistin to treat posttransplant MDR bacterial infections. Nearly 60% received colistin as definitive therapy and 87.81% received colistin as combination. Mean duration of colistin therapy was found to be higher in renal than liver transplant recipients. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Colistin in combination with meropenem (36.4%) was the most commonly used dual therapy. Out of the total 89 bacterial isolates, there were 2 colistin resistant Klebsiella strains. Overall in-hospital mortality of patients who received colistin was 43.9%. Renal impairment occurred in 28.8% of liver transplant recipients. Conclusion: Infection necessitating colistin use increases mortality by three folds in liver transplant recipients and by five percentage points in renal transplant recipients.

A self-reported survey on the implementation of infection prevention and control elements in Indian hospitals, part of a HAI surveillance network: Results from 23 hospitals conducting a standardized IPC assessment.

BACKGROUND: Healthcare-associated infections (HAIs) are one of the most common adverse events in patient care that account for substantial morbidity and mortality. We evaluate the existing Infection Prevention and Control (IPC) practices in hospitals participating in the nationally representative HAI Surveillance network. METHODS: This cross-sectional survey was conducted in 23 hospitals across 22 states of India from October-2015 to September-2018 in the HAI surveillance network. The World Health Organization (WHO) IPC core components assessment tool for health-care facility level (IPCAT-H) was adapted from IPC assessment tool developed by US Centers for Disease Control and Prevention (US CDC) under the Epidemiology and Laboratory Capacity (ELC) Infection Control Assessment and Response (ICAR) Program. Mann-Whitney U test was used to calculate the significant difference between scores (P < .05). RESULTS: Amongst the participating hospitals, 7 were private sectors and 16 were public health care facilities. Infection IPCAT-H average score per multimodal strategy was less than 50% for programmed IPC activities (45.7); implementation of health care workers (HCWs) immunization programme (43.5%); monitoring and evaluation component (38.30%). CONCLUSIONS: There is potential for improvement in Human Resources, Surveillance of HAIs as well as Monitoring and Evaluation components.

GPIIb/IIIa Receptor Targeted Rutin Loaded Liposomes for Site-Specific Antithrombotic Effect.

Rutin (RUT) is a flavonoid obtained from a natural source and is reported for antithrombotic potential, but its delivery remains challenging because of its poor solubility and bioavailability. In this research, we have fabricated novel rutin loaded liposomes (RUT-LIPO, nontargeted), liposomes conjugated with RGD peptide (RGD-RUT-LIPO, targeted), and abciximab (ABX-RUT-LIPO, targeted) by ethanol injection method. The particle size, ζ potential, and morphology of prepared liposomes were analyzed by using DLS, SEM, and TEM techniques. The conjugation of targeting moiety on the surface of targeted liposomes was confirmed by XPS analysis and Bradford assay. In vitro assessment such as blood clot assay, aPTT assay, PT assay, and platelet aggregation analysis was performed using human blood which showed the superior antithrombotic potential of ABX-RUT-LIPO and RGD-RUT-LIPO liposomes. The clot targeting efficiency was evaluated by in vitro imaging and confocal laser scanning microscopy. A significant (P < 0.05) rise in the affinity of targeted liposomes toward activated platelets was demonstrated that revealed their remarkable potential in inhibiting thrombus formation. Furthermore, an in vivo study executed on Sprague Dawley rats (FeCl3 model) demonstrated improved antithrombotic activity of RGD-RUT-LIPO and ABX-RUT-LIPO compared with pure drug. The pharmacokinetic study performed on rats demonstrates the increase in bioavailability when administered as liposomal formulation as compared to RUT. Moreover, the tail bleeding assay and clotting time study (Swiss Albino mice) indicated a better antithrombotic efficacy of targeted liposomes than control preparations. Additionally, biocompatibility of liposomal formulations was determined by an in vitro hemolysis study and cytotoxicity assay, which showed that they were hemocompatible and safe for human use. A histopathology study on rats suggested no severe toxicity of prepared liposomal formulations. Thus, RUT encapsulated nontargeted and targeted liposomes exhibited superior antithrombotic potential over RUT and could be used as a promising carrier for future use.

Drug repurposing toward the inhibition of RNA-dependent RNA polymerase of various flaviviruses through computational study.

Numerous pathogens affecting human is present in the flavivirus family namely west nile, dengue, yellow fever, and zika which involves in development of global burden and distressing the environment economically. Till date, no approved drugs are available for targeting these viruses. The threat which urged the identification of small molecules for the inhibition of these viruses is the spreading of serious viral diseases. The recent outbreak of zika and dengue infections postured a solemn risk to worldwide public well-being. RNA-dependent RNA polymerase (RdRp) is the supreme adaptable enzymes of all the RNA viruses which is responsible for the replication and transcription of genome among the structural and nonstructural proteins of flaviviruses. It is understood that the RdRp of the flaviviruses are similar stating that the japanese encephalitis and west nile shares 70% identity with zika whereas the dengue serotype 2 and 3 shares the identity of 76% and 81%, respectively. In this study, we investigated the binding site of four flaviviral RdRp and provided insights into various interaction of the molecules using the computational approach. Our study helps in recognizing the potent compounds that could inhibit the viral protein as a common inhibitor. Additionally, with the conformational stability analysis, we proposed the possible mechanism of inhibition of the identified common small molecule toward RdRp of flavivirus. Finally, this study could be an initiative for the identification of common inhibitors and can be explored further for understanding the mechanism of action through in vitro studies for the study on efficacy.

Bimetallic Au-Ag Nanoparticles: Advanced Nanotechnology for Tackling Antimicrobial Resistance.

To date, there are no antimicrobial agents available in the market that have absolute control over the growing threat of bacterial strains. The increase in the production capacity of antibiotics and the growing antibacterial resistance of bacteria have majorly affected a variety of businesses and public health. Bimetallic nanoparticles (NPs) with two separate metals have been found to have stronger antibacterial potential than their monometallic versions. This enhanced antibacterial efficiency of bimetallic nanoparticles is due to the synergistic effect of their participating monometallic counterparts. To distinguish between bacteria and mammals, the existence of diverse metal transport systems and metalloproteins is necessary for the use of bimetallic Au-Ag NPs, just like any other metal NPs. Due to their very low toxicity toward human cells, these bimetallic NPs, particularly gold-silver NPs, might prove to be an effective weapon in the arsenal to beat emerging drug-resistant bacteria. The cellular mechanism of bimetallic nanoparticles for antibacterial activity consists of cell membrane degradation, disturbance in homeostasis, oxidative stress, and the production of reactive oxygen species. The synthesis of bimetallic nanoparticles can be performed by a bottom-up and top-down strategy. The bottom-up technique generally includes sol-gel, chemical vapor deposition, green synthesis, and co-precipitation methods, whereas the top-down technique includes the laser ablation method. This review highlights the key prospects of the cellular mechanism, synthesis process, and antibacterial capabilities against a wide range of bacteria. Additionally, we also discussed the role of Au-Ag NPs in the treatment of multidrug-resistant bacterial infection and wound healing.

Efficient delivery of abciximab using mesoporous silica nanoparticles: In-vitro assessment for targeted and improved antithrombotic activity.

Abciximab (ABX) is a chimeric monoclonal antibody reported for antithrombotic activity but their delivery remains challenging due to its poor stability in a biological system. The purpose of this research was to deliver ABX on the target efficiently using mesoporous silica nanoparticles (MSN). ABX coated mesoporous silica nanoparticles (MSN-ABX) were formulated and analyzed for particle size, shape, zeta-potential, surface morphology and surface chemistry. XPS analysis confirmed the presence of ABX on the surface of amino functionalized mesoporous silica nanoparticles (MSN-NH2). The degree of ABX attachment was 67.53 ± 5.81 % which was demonstrated by the Bradford assay. Furthermore, the targeting efficiency of the targeted nanoparticles has been evaluated by capturing the fluorescent images in-vitro which showed the significant accumulation of the ABX coated nanoparticles towards activated platelets. The significant (P < 0.05) increase in affinity of DiD dye loaded nanoparticles towards the activated platelets was confirmed by using an in-vitro imaging through photon imager optima. The hemolysis study of the nanoparticle formulations revealed that they were non-hemolytic for healthy human blood. The in-vitro antithrombotic effects of MSN-ABX were observed by blood clot assay which revealed its superior antithrombotic activity over clinical injection of ABX and could be a promising carrier for improved ABX targeted delivery.

Self-reported survey on infection prevention and control structures in healthcare facilities part of a national level healthcare associated infection surveillance network in India, 2019.

BACKGROUND: Healthcare associated infections (HAIs) are prevalent and difficult to treat worldwide. Most HAIs can be prevented by effective implementation of Infection Prevention and Control (IPC) measures. A survey was conducted to assess the existing IPC practices across a network of Indian Hospitals using the World Health Organization designed self-assessment IPC Assessment Framework (IPCAF) tool. METHODS: This was a cross sectional observation study. Thirty-two tertiary care public and private facilities, part of the existing Indian HAI surveillance network was included. Data collected was analyzed by a central team at All India Institute of Medical Sciences, New Delhi, a tertiary care hospital of India. The WHO questionnaire tool was used to understand the capacity and efforts to implement IPC practices across the network. RESULTS: The overall median score of IPCAF across the network was 620. Based on the final IPCAF score of the facilities; 13% hospitals had basic IPC practices, 28% hospitals had intermediate and 59% hospitals had advanced IPC practices. The component multimodal strategies had the broadest range of score while the component IPC guidelines had the narrowest one. CONCLUSIONS: Quality improvement training for IPC nurses and healthcare professionals are needed to be provided to health facilities.

Development of a novel approach to detect damage in concrete structures with millimeter wave radar assessment system.

Nonintrusive damage assessment of concrete structures is evolving using newer technological interventions. Researchers are using different assessment techniques having their intrinsic limitations. A few are partially destructive, whereas others only provide qualitative information about the damages. Therefore, there is a need for a method using high-resolution imaging techniques for the assessment of exact damages and their depth along with intensity. Millimeter wave may be one of the good options for damage assessment. It is an efficient technique used in imaging applications due to its high resolution and effective penetration. Therefore, a novel millimeter wave assessment method is used in this study as a nondestructive post-fire damage test of concrete based civil engineering structures. An active millimeter wave radar system of 55-65 GHz has been used to measure the complex relative permittivity of concrete cube specimens for evaluation of damages caused by fire. In this study, fire damaged and control concrete cube specimens of 150 mm size were used for the measurement. The results were compared with the existing technique of ultrasonic pulse velocity, and it was found to be in good agreement.

Ipsilateral somatic nerves mediate histamine-induced vasosensory reflex responses involving perivascular afferents in rat models.

Reflex cardiorespiratory alterations elicited after instillation of nociceptive agents intra-arterially (i.a) are termed as 'vasosensory reflex responses'. The present study was designed to evaluate such responses produced after i.a. instillation of histamine (1 mM; 10 mM; 100 mM) and to delineate the pathways i.e. the afferents and efferents mediating these responses. Blood pressure, electrocardiogram and respiratory excursions were recorded before and after injecting saline/histamine, in a local segment of femoral artery in urethane anesthetized rats. Paw edema and latencies of responses were also estimated. Separate groups of experiments were conducted to demonstrate the involvement of somatic nerves in mediating histamine-induced responses after ipsilateral femoral and sciatic nerve sectioning (+NX) and lignocaine pre-treatment (+Ligno). In addition, another set of experiments was performed after bilateral vagotomy (+VagX) and the responses after histamine instillation were studied. Histamine produced concentration-dependent hypotensive, bradycardiac, tachypnoeic and hyperventilatory responses of shorter latencies (2-7 s) favouring the neural mechanisms in eliciting the responses. Instillation of saline (time matched control) in a similar fashion produced no response, excluding the possibilities of ischemic/stretch effects. Paw edema was absent in both hind limbs indicating that the histamine did not reach the paws and did not spill out into the systemic circulation. +NX, +VagX, +Ligno attenuated histamine-induced cardiorespiratory responses significantly. These observations conclude that instillation of 10 mM of histamine produces optimal vasosensory reflex responses originating from the local vascular bed; afferents and efferents of which are mostly located in ipsilateral somatic and vagus nerves respectively.

Targeted nanotherapeutics in the prophylaxis and treatment of thrombosis.

Currently available anti-thrombotic therapy for the prophylaxis and treatment of arterial and venous thrombosis includes intravenous administration of anti-thrombotic drugs which lead to severe bleeding risks such as cerebral hemorrhage and stroke. Targeting approaches that utilize nanosystems to reach the thrombus sites are emerging to increase the local effect of anti-thrombotic drugs, as well as to decrease these severe bleeding complications by diminishing the systemic availability of these drugs. This review emphasizes the emerging targeted nanomedicines (liposomes, micelles, polymeric nanoparticles, material bases nanoparticles and other biological vectors) for the prophylaxis and treatment of thrombotic events as well as multifunctional nanomedicines for theranostic applications. Nanomedicine offers a promising platform for a smart, safe, and effective approach for the management of thrombosis.

Intra-arterial Instillation of a Nociceptive Agent Modulates Cardiorespiratory Parameters Involving 5-HT3 and TRPV1 Receptors in Anesthetized Rats.

BACKGROUND: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in the regulation of cardiorespiratory (CVR) system. OBJECTIVE: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. MATERIALS AND METHODS: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. RESULTS: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin- induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. CONCLUSION: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.

Algogen-induced vasosensory reflexes modulate short-term heart rate variability parameters in experimental rat models.

OBJECTIVES: The present work was designed to study the modulatory effects of algogen-induced vasosensory reflex responses on short-term heart rate variability (HRV) parameters in naïve and vagotomized rat models. METHODS: In this study, vasosensory reflex responses were elicited by instilling algogens (bradykinin/histamine), a component of inflammatory mediators into a local segment of medium-sized peripheral blood vessel (femoral artery) while a continuous electrocardiogram (ECG) was recorded. Short-term (5 min) ECG segments obtained from original recordings were examined in detail and relevant data of HRV parameters were pooled. Time domain and frequency domain analyses were performed using dedicated software (LabChart 8, AD Instruments®, Australia) and results were analyzed. RESULTS: Bradykinin-induced vasosensory reflexes caused significant alterations in both time domain and frequency domain HRV parameters as compared to the time-matched saline control group. Instillation of bradykinin caused a transient increase in NN interval, RMSSD, TSP, HF power (HFP) along with a decrease in the standard deviation of all normal NN intervals (SDNN), SDNN/RMSSD, LF power (LFP), LFP/HFP. Histamine produced a similar pattern of responses, but HRV alterations were less pronounced compared to those with bradykinin. Further analysis revealed that algogen-induced vasosensory reflex responses caused an increase in the parasympathetic influence on the heart accompanied by a decrease in sympathetic influence. In addition, HRV modulation by algogen-induced vasosensory reflexes was significantly attenuated in vagotomized rats, illustrating the principal role of vagus in the reflex HRV modulation. CONCLUSIONS: The present study proposes a novel hypothesis regarding the cardio-protective role of inflammatory mediators during acute stress, by potentiating the vagal impact and attenuating the sympathetic impact on the heart.

Diagnostic Role of Calretinin in Suspicious Cases of Hirschsprung's Disease.

Background Hirschsprung's disease (HD) is a developmental disorder of the intrinsic component of the enteric nervous system. It is characterized by the absence of ganglion cells in the myenteric and submucosal plexus. Histopathological diagnosis becomes difficult many times due to submucosal ganglionic cells are not easily identifiable. Aims and objective The aim of this study was to examine the clinical and histopathological features of HD and to establish the utility of calretinin staining to diagnose the case of suspicious HD. Materials and methods After taking necessary informed consent, we studied 41 cases in which clinical suspicion of HD had been made, in a study duration of three years (July 2017-June 2020). Open biopsies were taken from spastic segment, transition zone and dilated segment. Histopathological diagnosis had been made in three categories: HD, no Hirschsprung's disease (NHD) and suspicion of HD. Post histopathological diagnosis calretinin immunohistochemistry (IHC) was applied to all cases and interpretations were noted. Results On the basis of histopathological findings, 25 cases were diagnosed as HD, nine cases were marked for suspicion for HD and seven cases as NHD. After evaluating calretinin IHC on the suspicious case, total of 30 cases were confirmed as HD while the remaining 11 cases were confirmed as NHD. Twenty-four patients of HD were males while the remaining six cases were females. The age of patients ranged from four days to 10 years. Median age six days while 22 patients were in the neonatal period. Conclusion Calretinin immunostaining is a useful modality in diagnosing suspicious cases of HD. Its results are easy to interpret by less experienced pathologist with accuracy.

A Multi-target Drug Designing for BTK, MMP9, Proteasome and TAK1 for the Clinical Treatment of Mantle Cell Lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is a type of non-Hodgkin lymphoma characterized by the mutation and overexpression of the cyclin D1 protein by the reciprocal chromosomal translocation t(11;14)(q13:q32). AIM: The present study aims to identify potential inhibition of MMP9, Proteasome, BTK, and TAK1 and determine the most suitable and effective protein target for the MCL. METHODOLOGY: Nine known inhibitors for MMP9, 24 for proteasome, 15 for BTK and 14 for TAK1 were screened. SB-3CT (PubChem ID: 9883002), oprozomib (PubChem ID: 25067547), zanubrutinib (PubChem ID: 135565884) and TAK1 inhibitor (PubChem ID: 66760355) were recognized as drugs with high binding capacity with their respective protein receptors. 41, 72, 102 and 3 virtual screened compounds were obtained after the similarity search with compound (PubChem ID:102173753), PubChem compound SCHEMBL15569297 (PubChem ID:72374403), PubChem compound SCHEMBL17075298 (PubChem ID:136970120) and compound CID: 71814473 with best virtual screened compounds. RESULT: MMP9 inhibitors show commendable affinity and good interaction profile of compound holding PubChem ID:102173753 over the most effective established inhibitor SB-3CT. The pharmacophore study of the best virtual screened compound reveals its high efficacy based on various interactions. The virtual screened compound's better affinity with the target MMP9 protein was deduced using toxicity and integration profile studies. CONCLUSION: Based on the ADMET profile, the compound (PubChem ID: 102173753) could be a potent drug for MCL treatment. Similar to the established SB-3CT, the compound was non-toxic with LD50 values for both the compounds lying in the same range.