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Abstract Neuromorphic computing has emphasized the need for memristors with non-volatile, multiple conductance levels. This paper demonstrates the potential of hexagonal boron nitride (hBN)/graphene heterostructures to act as memristors with multiple resistance states that can be optically tuned using visible light. The number of resistance levels in graphene can be controlled by modulating doping levels, achieved by varying the electric field strength or adjusting the duration of optical illumination. Our measurements show that this photodoping of graphene results from the optical excitation of charge carriers from the nitrogen-vacancy levels of hBN to its conduction band, with these carriers then being transferred to graphene by the gate-induced electric field. We develop a qualitative model to describe our observations. Additionally, utilizing our device architecture, we propose a memristive crossbar array for vector-matrix multiplications.

Abstract Spatially resolved molecular assays provide high dimensional genetic, transcriptomic, proteomic, and epigenetic information in situ and at various resolutions. Pairing these data across modalities with histological features enables powerful studies of tissue pathology in the context of an intact microenvironment and tissue structure. Increasing dimensions across molecular analytes and samples require new data science approaches to functionally annotate spatially resolved molecular data. A specific challenge is data-driven cross-sample domain detection that allows for analysis within and between consensus tissue compartments across high volumes of multiplex datasets stemming from tissue atlasing efforts. Here, we present MILWRM (multiplex image labeling with regional morphology)—a Python package for rapid, multi-scale tissue domain detection and annotation at the image- or spot-level. We demonstrate MILWRM’s utility in identifying histologically distinct compartments in human colonic polyps, lymph nodes, mouse kidney, and mouse brain slices through spatially-informed clustering in two different spatial data modalities from different platforms. We used tissue domains detected in human colonic polyps to elucidate the molecular distinction between polyp subtypes, and explored the ability of MILWRM to identify anatomical regions of the brain tissue and their respective distinct molecular profiles.

Introduction: There is much debate over the best choice of restorative material and the placement method for the most successful treatment. Many teeth that have undergone endodontic treatment may not have enough structure to support a restoration or crown. To improve retention for the restorative material, ferrule may be used. Adhesive techniques have transformed the way we restore teeth after root canal treatment, starting with the shift from using cast post-and-core to using fibre post. The use of fibre-reinforced posts has been found to prevent irreparable root fractures thereby improving the longevity of the treatment. Aim: To compare two different types of aesthetic fibre posts for 12 months. Materials and Methods: A prospective interventional study was carried out in the Department of Prosthodontics, Manav Rachna Dental College (Faridabad) for a period of 12 months from Nov 2022- Oct 2023. Forty participants with single rooted, endodontically treated, maxillary anterior teeth in the age bracket of 15-55 years, both males and females of the north Indian population were included in the study. Teeth were selected where a post-retained crown was indicated and post space was prepared using a piezo reamer drill at 5000 rpm. At least 4 mm of obturation is left in the canal to maintain the apical seal. Furthermore, Zircon-enriched silicon fibre and glass fibre-reinforced posts were cemented into the prepared post space. Metal-ceramic crowns were cemented and baseline periapical radiographs were obtained. At the interval of one month, three months, six months and one year, the patients were evaluated.The Fischer’s exact test was utilised to establish the association between categorical variables and the level of significance (p-value

The objective is to minimize the inaccuracies in two-step impressions by homogenizing the polymerization shrinkage of elastomeric impression material in fixed prosthesis fabrication. The objective is accomplished by the technique of spacer adaptation and custom tray fabrication for two-step impressions. The technique makes the use of two vacuum-adapted spacers, selected based on the viscosity of elastomeric impression, and a vacuum-adapted custom tray. The procedure of using the specially fabricated custom tray for impression making is also presented. Consistent thickness of the two different viscosities of impression material is maintained due to vacuum adaptation of the spacers. This homogenizes the polymerization shrinkage of the elastomeric material in different regions of impression, as uniform space is occupied by the material in the space created by the spacer. The procedure of vacuum adaption of the tray material also limits the dimensional change of the tray. The technique minimizes the inaccuracies of impression by homogenizing the polymerization shrinkage of the elastomeric impression, thus promising a well-fitting prosthesis.

Abstract Crohn’s disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify a distinct epithelial cell type in both terminal ileum and ascending colon (hereon as ‘LND’) with high expression of LCN2, NOS2, and DUOX2 and genes related to antimicrobial response and immunoregulation. LND cells, confirmed by in-situ RNA and protein imaging, are rare in non-IBD controls but expand in active CD, and actively interact with immune cells and specifically express IBD/CD susceptibility genes, suggesting a possible function in CD immunopathogenesis. Furthermore, we discover early and late LND subpopulations with different origins and developmental potential. A higher ratio of late-to-early LND cells correlates with better response to anti-TNF treatment. Our findings thus suggest a potential pathogenic role for LND cells in both Crohn’s ileitis and colitis.

Introduction: Providing complete denture therapy to patients with atrophic residual alveolar ridges is challenging, because these patients suffer ongoing resorption of the denture foundation; regardless of contemporary treatment options, physiologically optimal denture contours and appropriate denture tooth arrangement should be achieved to maximize prosthesis stability, comfort and function for patients. One of the methods used to achieve the stability is the neutral zone technique. Aim: It is in this zone that the natural dentitions lie and this is where the artificial teeth should be positioned. This article describes a preview of faciolingual positioning of denture teeth along with a novel approach of recording the neutral zone. Conclusion: The neutral zone is the area where the displacing forces of the lips, cheeks and tongue are in balance. Physiologic recording of the neutral zone aids in stability to the prosthesis.

Abstract Basal cell carcinoma (BCC) is the most common skin cancer. Skin cancers may present either as a non-invasive tumor or an invasive malignancy. The terminology of carcinoma in situ is used when the tumor is either just limited to epidermis or not present as single cells or nests in the dermis. However, currently the terminology superficial BCC is inappropriately used instead of BCC in situ when the skin cancer is limited to epidermis. In this study we compare the pathologic changes of superficial, nodular, and infiltrative BCCs using electron microscopy to identify the ultrastructural characteristics and validate the previously proposed terminology. Three cases of BCC (superficial BCC, nodular BCC, and infiltrative BCC) diagnosed by dermatopathologists at our institute were selected for review. Paraffin block tissues from these cases were sent for electron microscopy studies which demonstrated disruption of basal lamina in both nodular and infiltrative type of BCC, while it remains intact in BCC superficial type after extensive examination. Therefore, similar to other in situ skin cancers, there is no invasion of the neoplasm in superficial BCC into the dermis. Hence, the older term superficial BCC should be appropriately replaced with the newer terminology BCC in situ.

Abstract Liver abscess is a potentially life-threatening medical emergency. Prompt empirical antimicrobial with or without percutaneous aspiration or drainage is therapeutic. The rational for using empirical intravenous broad-spectrum antimicrobials upfront instead of oral Fluoroquinolone or Cephalosporin is contentious. In this double blind randomized control clinical trial 69 participants received Ciprofloxacin (500 mg q 12 hourly) and 71 participants received Cefixime (200 mg q 12 hourly) orally for 2 weeks. Both the group received oral Metronidazole (800 mg q 8 hourly) for 2 weeks and percutaneous drainage or aspiration of the abscess was done as per indication and followed-up for 8 weeks. Out of 140 participants, 89.3% (N = 125) achieved clinical cure, 59 (85.5%) in Ciprofloxacin group and 66 (93%) in Cefixime group (p = 0.154). Mean duration of antimicrobial therapy was 16.2 ± 4.3 days, 15.1 ± 4.5 days in Ciprofloxacin group and 16.0 ± 4.2 days in Cefixime group (p = 0.223). Total 15 (10.7%) participants had treatment failure, 10 (14.5%) in Ciprofloxacin group and 5 (7.0%) in Cefixime group (p = 0.154). The most common reason for treatment failure was need of prolong (> 4 weeks) antimicrobial therapy due to persistent hepatic collection requiring drainage, which was significantly (p = 0.036) higher in Ciprofloxacin (14.5%, N = 10) group, compared to the Cefixime (4.2%, N = 3) group. In conclusion, both, the Ciprofloxacin or Cefixime plus Metronidazole for duration of 2–3 weeks were efficacious as empirical oral antimicrobial regimen along with prompt percutaneous drainage or aspiration for the treatment of uncomplicated liver abscess with similar efficacy. Oral Cefixime was better than Ciprofloxacin in term of lesser chance of treatment failure due to persistent collection which is required to be investigated further in larger clinical trial. Trial registration: clinicaltrials.gov PRS ID: NCT03969758, 31/05/2019.

Multidrug-resistant yeast Candida auris is a serious threat to public health with documented survival in various hospital niches. The dynamics of this survival benefit and its trade off with drug resistance are still unknown for this pathogen. In this study we investigate the oxidative stress response (OSR) in fluconazole-resistant C. auris and compare its relative fitness with fluconazole-susceptible strains. A total of 351 C. auris clinical isolates (61 fluconazole-susceptible and 290 fluconazole-resistant) were screened for stress tolerance by spot assay and 95.08 % fluconazole-susceptible isolates were hyper-resistant to oxidative stress while majority (94.5 %) fluconazole-resistant isolates had lower oxidative tolerance. Expression of Hog1 and Cta1 gene transcript levels and cellular catalase levels were significantly higher in fluconazole-susceptible isolates and a corresponding higher intracellular reactive oxygen species level (iROS) was accumulated in the fluconazole-resistant isolates. Biofilm formation and cell viability under oxidative stress revealed higher biofilm formation and better viability in fluconazole-susceptible isolates. Fluconazole-resistant isolates had higher basal cell wall chitin. On comparison of virulence, the % cytotoxicity in A549 cell line was higher in fluconazole-susceptible isolates and the median survival of the infected larvae in G. mellonella infection model was higher in fluconazole-resistant (5; IQR:4.5–5 days) vs. fluconazole-susceptible C. auris (2; IQR:1.5–2.5 days). All organisms evolve with changes in their environmental conditions, to ensure an optimal balance between proliferation and survival. Development of tolerance to a certain kind of stress example antifungal exposure in yeast can leads to a compensatory decrease in tolerance for other stresses. This study provides useful insights into the comparative fitness and antifungal susceptibility trade off in C. auris. We report a negative association between H2O2 tolerance and fluconazole susceptibility. Using in-vitro cell cytotoxicity and in-vivo survival assays we also demonstrate the higher virulence potential of fluconazole-susceptible C. auris isolates corroborating the negative correlation between susceptibility and pathogen survival or virulence. These findings could also be translated to clinical practice by investigating the possibility of using molecules targeting stress response and fitness regulating pathways for management of this serious infection.

Background: Mucormycosis is a fungal infection that can affect multiple organs. The role of fine-needle aspiration cytology (FNAC) in its diagnosis is not well documented. Aim: The objective of this study was to describe the detailed cytomorphologic features of mucormycosis on FNAC samples. Materials and Methods: A retrospective analysis of all cases diagnosed as mucormycosis on FNAC between January 2014 and July 2021 was performed for detailed cytomorphological evaluation and correlation to clinical data and microbiological studies wherever available. FNA was computed tomography-guided (n = 38), ultrasonography-guided (n = 31) or palpation-guided (n = 12), and slides were reviewed in two cases. Results: A total of 83 cases of mucormycosis were evaluated. An immunocompromised setting was observed in 48 cases. The most common site of FNA was the lung (n = 57) followed by liver, soft tissue, palate, mediastinum, orbital/ocular region, and lymph node. Isolated renal involvement, a unique feature, was seen in seven cases. The aspirates were necrotic to pus-like or blood-mixed particulate. Broad, nonseptate, foldable, ribbon-like fungal hyphae showing right-angled branching were seen. The tissue reaction was predominantly necro-inflammatory (n = 36), bland necrotic (n = 22), mixed inflammatory (n = 16), suppurative (n = 5), necrotizing granulomatous (n = 3), and granulomatous (n = 1). Immunocompromised patients showed mixed inflammatory responses more frequently. Fungal culture was positive for Rhizopus species in 2/13 cases and molecular testing in two additional cases corresponding to Rhizopus and Syncephalastrum spp. Conclusion: FNA provides quick and conclusive diagnosis of mucormycosis from varied anatomic sites enabling prompt institution of therapy. The tissue response is variable and to some extent dependent on the immune status of the patient.

Background: Inflammation plays a major role in the pathophysiology of acute cerebrovascular accidents and nowadays, a newer and more sensitive method to test for lower circulating levels of C-reactive protein (CRP), highly sensitive CRP (hsCRP), is being used in apparently healthy individuals for risk assessment. Previous studies show that CRP strongly correlates with stroke severity and independently predicts mortality and recurrence in patients with acute ischemic stroke. The aim of this study was to evaluate the relationship between inflammatory marker-hsCRP and stroke severity by means of volumetric measurement of infarct size. Methods: In this cross-sectional study, 60 patients with acute ischemic stroke were included who were diagnosed using the National Institute of Health Stroke Scale (NIHSS) and magnetic resonance imaging (MRI) scans. Serum levels of hsCRP were measured. Lesion volumes (in ml) were calculated by multiplying slice thickness (4–5 mm) by the total lesion area and divided into quartiles. The relationship between hsCRP levels and diffusion-weighted imaging infarct volume quartiles was examined. Results: Ischemic stroke was predominantly seen in the male population (n = 36, 60%) and the sixth decade of life. The mean NIHSS score of the study population was 10.68 ± 1.068. The mean (± standard deviation [SD]) level of serum hsCRP was 6.69 ± 7.072 mg/L. The mean (± SD) stroke volume was 8.64 ± 14.21 ml. The correlation between hsCRP and the size of infarct on three-dimensional MRI brain scan was statistically highly significant (P < 0.001, r = 0.667). Conclusions: Higher hsCRP levels were associated with larger infarct volumes in acute ischemic stroke suggesting that elevated hsCRP levels, may serve as a helpful serologic marker in the evaluation of the severity of acute ischemic stroke.

As professional phagocytes, macrophages represent the first line of defence against invading microbial pathogens. Various cellular processes such as programmed cell death, autophagy and RNA interference (RNAi) of macrophages are involved directly in elimination or assist in elimination of invading pathogens. However, parasites, such as Leishmania, have evolved diverse strategies to interfere with macrophage cell functions, favouring their survival, growth and replication inside hostile and restrictive environments of macrophages. Therefore, identification and detailed characterization of macrophage-pathogen interactions is the key to understanding how pathogens subvert macrophage functions to support their infection and disease process. In recent years, great progress has been achieved in understanding how Leishmania affects with critical host macrophage functions. Based on latest progress and accumulating knowledge, this review exclusively focuses on macrophage-Leishmania interaction, providing an overview of macrophage cellular processes such as programmed cell death, autophagy and RNAi during Leishmania infection. Despite extensive progress, many questions remain and require further investigation.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02–0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03–16], itraconazole [0.03–16], posaconazole [0.03–8], and isavuconazole [0.03–16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

The intracellular protozoan parasite Leishmania causes leishmaniasis in humans, leading to serious illness and death in tropical and subtropical areas worldwide. Unfortunately, due to the unavailability of approved vaccines for humans and the limited efficacy of available drugs, leishmaniasis is on the rise. A comprehensive understanding of host-pathogen interactions at the molecular level could pave the way to counter leishmaniasis. There is growing evidence that several intracellular pathogens target RNA interference (RNAi) pathways in host cells to facilitate their persistence. The core elements of the RNAi system are complexes of Argonaute (Ago) proteins with small non-coding RNAs, also known as RNA-induced silencing complexes (RISCs). Recently, we have shown that Leishmania modulates Ago1 protein of host macrophages for its survival. In this study, we biochemically characterize the Ago proteins' interactome in Leishmania-infected macrophages compared to non-infected cells. For this, a quantitative proteomic approach using stable isotope labelling by amino acids in cell culture (SILAC) was employed, followed by purification of host Ago-complexes using a short TNRC6 protein-derived peptide fused to glutathione S-transferase beads as an affinity matrix. Proteomic-based detailed biochemical analysis revealed Leishmania modulated host macrophage RISC composition during infection. This analysis identified 51 Ago-interacting proteins with a broad range of biological activities. Strikingly, Leishmania proteins were detected as part of host Ago-containing complexes in infected cells. Our results present the first report of comprehensive quantitative proteomics of Ago-containing complexes isolated from Leishmania-infected macrophages and suggest targeting the effector complex of host RNAi machinery. Additionally, these results expand knowledge of RISC in the context of host-pathogen interactions in parasitology in general.

Academic interest in comprehending flood resilience concepts and their evaluation is growing with the increasing frequency and severity of disasters due to climate change (CC). This paper conducts a comprehensive and systematic literature review on urban flood resilience assessment (UFRA) to address the inadequacy of urban preparedness, response and lengthy recovery process. The review covers the UFRA process considering urban elements, methods, tools and techniques, and challenges in achieving resilience and provides guidance for constructing advance resilience assessment frameworks. Scopus and Web of Science databases were accessed by employing pertinent keywords. The review of UFRA literature reveals a prevalence of frameworks analysing isolated or clustered urban elements rather than a comprehensive framework for assessing flood resilience. Various methods, tools and techniques, such as multi-criteria decision-making methods (MCDM), hydrological modelling, household surveys, and geographic information system (GIS) techniques, are commonly employed in the flood resilience assessment of single or clustered elements. However, to achieve overall resilience in an urban area, there is a need for an integrated and comprehensive approach that accounts for the evolving risk landscape. Creating a comprehensive framework poses challenges due to the intricate nature of the urban system, which requires collaboration across multiple disciplines and integration of modern tools and techniques, including computational modelling such as agent-based modelling (ABM) and system dynamics approaches, artificial intelligence techniques, and cognitive fuzzy modelling. The outcome of this research serves as a valuable resource for researchers, academicians, and policymakers. It aids in understanding the urban flood resilience process, focusing on urban elements and their inter-relationships, assessment methods and approaches, dimensions and indicators necessary for achieving flood resilience scenarios comprehensively.

Scedosporium aurianticum infection developed in 2 recipients of kidney transplants in India, acquired from the same deceased near-drowning donor. Given the substantial risk for death associated with Scedosporium infection among solid-organ transplant recipients, safety protocols for organ transplantation from nearly drowned donors should be thoroughly revaluated and refined.

Granuloma annulare (GA) is a benign, self-limiting granulomatous inflammatory disease that exhibits different histologic patterns. Infrequently, granuloma annulare can be associated with malignancy, the so-called malignancy-associated granuloma annulare (MGA). In this study, we aimed to compare the clinical and histopathological differences between GA and MGA. We retrospectively reviewed patient charts and identified 35 patients diagnosed with GA and concurrent hematological or solid organ malignancies as a case group. Additionally, we identified 33 patients without any known solid organ or hematological malignancy as a control group. MGA is commonly seen in the seventh decade of life, while GA affects the younger population. MGA is most commonly presented in the extremities of the body. The most common malignancy associated with MGA was chronic lymphocytic leukemia. Prostate cancer was the most common type of solid organ malignancy that was associated with MGA. The most common histopathological pattern seen in MGA was interstitial, comprising half of the cases. Multinucleated giant cells were present in half of the MGA cases and in most of the control group. In the literature, there are no established features that distinguish MGA from GA. Although MGA and GA have overlapping features, in our series, we found that the interstitial pattern was more common in MGA, while the necrobiotic pattern was more common in GA.

Breast cancer is the most common cancer among women. Currently, it poses a significant threat to the healthcare system due to the emerging resistance and toxicity of available drug candidates in clinical practice, thus generating an urgent need for the development of new potent and safer anti-breast cancer drug candidates. Coumarin (chromone-2-one) is an elite ring system widely distributed among natural products and possesses a broad range of pharmacological properties. The unique distribution and pharmacological efficacy of coumarins attract natural product hunters, resulting in the identification of numerous natural coumarins from different natural sources in the last three decades, especially those with anti-breast cancer properties. Inspired by this, numerous synthetic derivatives based on coumarins have been developed by medicinal chemists all around the globe, showing promising anti-breast cancer efficacy. This review is primarily focused on the development of coumarin-inspired anti-breast cancer agents in the last three decades, especially highlighting design strategies, mechanistic insights, and their structure–activity relationship. Natural coumarins having anti-breast cancer efficacy are also briefly highlighted. This review will act as a guideline for researchers and medicinal chemists in designing optimum coumarin-based potent and safer anti-breast cancer agents.

Introduction CT perfusion (CTP) has been utilized to appropriately select patients with large vessel occlusion (LVO) for endovascular thrombectomy (EVT). Elderly patients and patients with fast‐growing ischemic cores have been shown to have worse outcomes after EVT. There is limited data on elderly patients aged ≥90 years old and ischemic core growth related to outcomes. We aimed to examine age, ischemic core growth, and outcomes in patients with LVO treated with EVT [1]. Methods This is a retrospective study using prospectively collected data from a large academic medical center. Patients with LVO and treated with EVT between December 2017 and December 2022 were included in this study. Patients without CTP completed prior to EVT, patients with missing baseline or 90‐day modified Rankin Scale scores (mRS), and patients in which CTP was completed but failed were excluded from this study. Early infarct growth rate (relative cerebral blood flow < 30% / last known well to CTP) was used to determine if ischemic core growth was fast (≥10ml/h) or slow ( 0.38. Conclusion Excellent reperfusion rates were not affected by age or ischemic core growth rate. Despite this, elderly patients with fast ischemic core growth were more likely to experience worse 90 day functional outcomes compared to younger patients and patients with slower core growth prior to EVT.

Introduction Vertebral artery web has been rarely identified compared to the frequently reported, carotid artery web as etiology of ischemic stroke. Here we present a young patient with symptomatic vertebral artery web. Methods Case Report Results 35‐year‐old male presented with persistent, intermittent, bilateral visual scintillations lasting 30‐60 seconds for one month. Neurological examination positive for bi nasal superior quadrantanopia. Computed tomography (CT) of head showed patchy hypo density in right posterior circulation artery (PCA) territory. Magnetic resonance imaging (MRI) showed restriction diffusion over bilateral PCA territories right greater than left (image A). MR Angiogram head and neck showed abnormal contour within right vertebral artery in V2 segment compatible with dissection (image B). Patient’s hypercoaguable, inflammatory and rheumatological markers were unremarkable. The patient was started on aspirin 81 mg daily and Plavix 75 mg daily for three weeks followed by aspirin monotherapy. Repeat CT angiogram 11 months later still showed right V1/V2 junction irregularity (image C). DSA performed one month later revealed right cervical vertebral artery web with mild stagnation of blood flow (image D). Patient had no recurrence of symptoms and was continued on aspirin. Conclusion Ischemic stroke is rare in young adults. According to recent studies, prevalence of stroke in young adults’ ranges from 10‐15% of entire population stroke burden. Our case describes a young patient with posterior circulation stroke caused by a vertebral artery web which was confirmed with DSA. Vertebral artery web has limited scientific documentation throughout the literature. A literature review performed by B.J.A. Pereira et al. demonstrated that only 7.3% of vessel webs were found in the vertebral artery, compared to 91.66% in the carotid artery (3). Because of this, a review of medical literature showed limited case reports on treatment and surgical options for vertebral webs causing posterior circulation stroke. Lenck et al. first reported 3 patients with vertebral webs diagnosed by DSA and having MRI show ischemic strokes in the vascular territory were treated with endovascular stenting and had no recurrence of an ischemic event (4). A literature review reported by Pereira demonstrated that out of 23 vessel webs, 13 were treated with supportive care (including antiplatelets or anticoagulation), eight were treated with angioplasty and stenting (which included the vertebral artery web case), and two were treated with surgery (3). In other literature, Lizhang et al (2019) diagnosed an incidental vertebral artery web on DSA for anterior circulation TIA and was treated successfully with DAPT therapy and atorvastatin 20 mg (5).

Introduction Here, we describe a patient in whom ischemic stroke was caused by compression of the Internal Carotid Artery (ICA) by a Pseudoaneurysm (PSA) of the External Carotid Artery (ECA) after Gun Shot injury. Eventually, the PSA of the Internal maxillary artery (IMAX) was embolized, resulting in resolution of the patient's symptoms. Methods Case Report Results A 75‐year‐old male with a history of atrial fibrillation on Eliquis presented to the emergency department after sustaining a gunshot wound to the left face. He had extensive injuries through the left masticator and submandibular space with an inferior orbital wall fracture. A Computed Tomography Angiography (CTA) neck showed injuries to the left proximal IMAX with a small PSA. As the PSA was asymptomatic it was managed with observation. On HOD day 13, CTA was done for a brief period of unresponsiveness, which showed high‐grade narrowing of left cervical ICA due to extrinsic compression from PSA which was supplied by a branch of the left ECA with distal re‐constitution (image A). The next day, patient developed right sided plegia and aphasia with NIHSS of 17. A CT head showed no acute intracranial abnormality. The patient underwent emergent Digital Subtraction Angiography (DSA), which demonstrated occlusion of the left cervical ICA from compression from a left IMAX PSA which was treated with n‐butyl‐cyanoacrylate TRUFILL embolization with resolution of flow limitation in the left cervical ICA (Image B1,B2). After embolization, the patient was oriented and able to lift right arm and leg anti‐gravity. Magnetic Resonance Imaging (MRI) was contraindicated due to retained bullet fragments. Repeat CT head did not show stroke. Conclusion A Pseudo aneurysm is characterized by a rupture of the arterial wall and the formation of an aneurysmal sac by the adjacent structures while the sustaining artery remains intact. The most prevalent causes are penetrating or acute blunt neck trauma, hyperextension injury, and injury to the base of the skull (1). Predisposing factors for PSA include carotid endarterectomy or a late complication of carotid artery dissection, infection, radiotherapy, and malignancy (1‐2). Cox et al. reported 124 patients with significant neck and head penetrating injuries. Eleven patients were found to have thirteen head and neck PSA: two in the ICA, one in the vertebral artery, and ten involving branches of the ECA. Two of seven symptomatic PSAs manifested with episodes of massive hemorrhage (3). There have been case reports describing the consequences of an elongated styloid process causing an ischemic stroke due to subsequent dissection and PSA formation (4). According to our knowledge, this case report is one of the first to describe acute ischemic symptoms resulting from ECA PSA‐induced ICA compression, with resolution of symptoms following PSA embolization. The educational value of our case lies not only in the rarity of the condition but also in the uniqueness of its presentation. This case is a fundamental addition to the existing literature on rare neuro‐vascular anomalies leading to potential catastrophic outcomes.

Background: Recently, numerous surveys have been conducted amongst different communities to assess the fear of coronavirus diseases-2019 (COVID-19), using the Fear of COVID-19 Scale (FCV-19) scale. Currently, there is a spot within the literature published regarding fear of COVID-19 amongst dentists, and hence, we conducted a questionnaire-based survey to assess the fear of COVID-19 amongst dentists practicing in India. Aim: Assessment of coronavirus fear amongst Indian dentists practicing in the Delhi NCR region using the modified FCV-19. Materials and Methods: A questionnaire was formulated using FCV-19S, which gathered the demographic data and fear in relation to COVID-19. Except for the seven-item FCV-19S, three questions were formulated for dentists particularly. The responses were recorded on a five-point Likert scale, starting from strongly disagree to strongly agree. Dentists residing in the Delhi NCR region and above 18 years old were included in the study. Results: A total of 202 responses were obtained, which were considered for the survey analysis. The results obtained after the compilation of the information were subjected to one-way analysis of variance test, and post-hoc Tukey Bonferroni tests were used for multiple comparisons. The study population comprised 65.8% of females and 34.2% of males, with approximately 68.3% belonging to the 18–30 years age group. The t-test for total fear and gender shows total fear score was 18.85 with standard deviation = 6.23. Conclusion: The study suggests that the population associated with healthcare showed lower levels of fear and anxiety than the general population. The fear of COVID-19 has reduced over a period of time due to the awareness of the disease and vaccination. Media plays a significant role in the psychological aspect of the person, irrespective of the profession, which leads to certain disturbances like lack of sleep. More than 50% of dentists agree that the use of precautionary protocols in our dental practice can reduce the risk of getting infected.

Background. The present study evaluated the clinical and radiographic outcomes of Biodentine pulpotomy for 24 months in symptomatic vital mature permanent teeth with caries exposure. Methods. Seventy-three patients with a chief complaint of spontaneous pain in permanent teeth were screened. Finally, 47 mature permanent teeth underwent a Biodentine pulpotomy procedure. Clinical evaluation of 47 teeth was carried out at 1, 3, 6, 9, 12, and 24 months and radiographic evaluations were made at 6, 12, and 24 months. The success of Biodentine pulpotomy was evaluated using Pearson’s chi-square test. The significance level was determined at P

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.

Background: In 2018, India decriminalized same-sex relationships, marking a major victory for the LGBTQIA+ community. However, it’s well known that only policy reforms are not enough for revolutionary changes. One starting point is the exploration of the quality of life, health, and wellness of these populations through careful research and examining the threats they are facing today so that early interventions can be initiated to improve the conditions and reduce the pain. Objective: To assess whether a relationship exists between adverse childhood experiences (ACE) and resilience in cis- gender heterosexual and LGBTQIA+ individuals in India and whether a significant difference exists between the two samples in their measures of the same. Method: Online forms were circulated through various social media platforms, the sample consisted of 81 participants (48 cis-gender heterosexual individuals, 33 LGBTQIA+ individuals) within the age range of 18-25 years residing in Urban areas of India. The forms consisted of two questionnaires: The ACEs Questionnaire, and Brief Resilience Scale (BRS). For Data analysis, the Pearson Product moment correlation, and the Non-parametric Kruskal-Wallis H test were carried out. Results & Conclusion: Findings reveal a negative correlation between ACE and resilience amongst cis-gender heterosexuals r(46) = 0.47, p < .01, a negative correlation between ACE and resilience amongst the LGBTQIA+, r(31) = 0.13, p = .47, a significant difference between cis-gender heterosexual individuals and LGBTQIA+ individuals in the ACE scores, H (1) = 16.65, p < .01, a significant difference between cis-gender heterosexuals and LGBTQIA+ in the Resilience scores, H (1) = 5.35, p < .05. The results indicate that the LGBTQIA+ individuals did experience more adverse experiences in their childhood as compared to cis-gender heterosexual counterparts, one of the many reasons could be homonegative and trans negative attitudes towards this population. Limitations of the study are that it was only a quantitative study, with a small sample size, and not all communities were equally represented, that is, more data is required from people who identify as pansexual and transgenders. Future directives for researchers are to become gender and culture-informed and conduct deeper research using narrative analysis approaches.

Gigantic melanocytosis is a rare and peculiar familial disorder of pigmentation. It presents as diffuse hyperpigmentation interspersed by raindrop-like hypopigmented macules predominantly involving the sun-exposed areas and later progressing to involve the photoprotected areas as well. All the cases described in the literature were observed to be commencing in the first year of life and were more common in males. Hereby, we report a 28-year-old female who presented with adult-onset gigantic melanocytosis with no similar familial history.

The synthesis of tailored and highly engineered multifunctional pharmaceutical nanocarriers is an emerging field of study in drug delivery applications. They have a high surface-area-to-volume ratio, aiding the targeted drug’s biodistribution and pharmacokinetic properties. Therefore, the characterization of nanocarriers is critical for understanding their physicochemical properties, which significantly impact their molecular and systemic functioning. To achieve specific goals, particle size, surface characteristics, and drug release properties of nanocarriers must be managed. This mini review provides an overview of the applications of non-destructive testing techniques (NDTT) to reveal the characteristics of nanocarriers, considering their surface charge, porosity, size, morphology, and crystalline organization. The compositional and microstructural characterization of nanocarriers through NDTT, such as dynamic light scattering, X-ray diffraction, confocal laser scanning microscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, atomic force microscopy, and nuclear magnetic resonance spectroscopy, have been comprehensively reviewed. Furthermore, NDTT is only used to characterize physicochemical parameters related to the physiological performance of nanocarriers but does not account for nanocarrier toxicity. Hence, it is highly recommended that in the future, NDTT be developed to assess the toxicity of nanocarriers. In addition, by developing more advanced, effective, and precise techniques, such as machine vision techniques using artificial intelligence, the future of using NDTT for nanocarrier characterization will improve the evaluation of internal quality parameters.

Osteogenesis imperfecta (OI) is a rare congenital condition, marked by fragile bones, skeletal deformities and additional extra-skeletal symptoms. Depending upon the degree of seriousness, affected people can either carry on with a mostly unrestricted, independent life, or their mobility is severely affected, making them dependent on others for support. Despite that, there is no effect on intellectual capacities. The medical and surgical treatments of OI are directed towards improving the patient's quality of life, mobility and functional independence. Because of the close biochemical relationship that exists between collagen and dentine, the teeth are affected in certain patients, leading to dentinogenesis imperfecta (DI) which is described by the appearance of opalescent teeth. To enable preventive intervention and effective dental treatment, it is essential that the correct diagnosis of DI is done at an early stage.

Aim: The aim of this study was to evaluate the intracanal effectiveness of cryotherapy, curcumin irrigant, and normal saline as a final irrigant in reducing postendodontic pain in primary teeth. Materials and Methods: A total of 120 teeth between the ages of 4 and 7 years requiring pulpectomy in primary teeth were included in the study. The teeth were randomly assigned to one of the three treatment groups: intracanal cryotherapy using 2.5°C cold saline, curcumin irrigant, or normal saline. Following completion of chemomechanical preparation, final irrigation with 2.5°C cold saline, curcumin irrigant, and normal saline solution at room temperature were employed in the groups. Participants were asked to rate the severity of their postoperative pain on the Visual Analog Scale before, immediate postoperative after wearing of local anesthetic effect, and 24 h after the procedure. The results were analyzed statistically. Results: The differences in reduction of postendodontic pain between the three irrigating regimens were statistically not significant. Cryotherapy utilizing 2.5°C cold saline or curcumin irrigant can be used instead of normal saline as a final irrigant in pulpectomy of primary teeth. Conclusions: Cryotherapy can be a straightforward, cost-effective, and nontoxic treatment option for the management of postendodontic pain. Curcumin irrigant with its anti-inflammatory properties is also a better alternative as a final irrigant for reducing postoperative pain in primary teeth.

Aim: This study aimed to investigate the conditioning effects of phosphoric acid/5.25% sodium hypochlorite (NaOCl) mixture, 2% chlorhexidine (CHX) digluconate, and 10% polyacrylic acid on cavosurface microleakage and bond strength of glass ionomer (GI) restorations. Materials and Methods: Out of 68 extracted premolars, 34 teeth were selected for microleakage and 34 for bond strength evaluation. The samples were divided into the following four groups. Group 1: pretreatment with 50/50 volume% mixture of 5.25% NaOCl solution and 37% phosphoric acid (H3PO4), Group 2:pretreatment with 2% CHX digluconate, Group 3: pretreatment with 10% polyacrylic acid (positive control), and Group 4: no pretreatment (negative control). All the samples were then restored with glass ionomer cement (GIC). Microleakage was evaluated using a stereomicroscope and rhodamine-B dye penetration test. For bond strength, flat dentin surface was exposed and pretreated as mentioned previously and restored with GIC and was evaluated using universal testing machine. Results: Among all the four groups, Group 1 showed least microleakage and highest bond strength when compared with other groups. Whereas the Group 4 samples which were not pretreated with any of the conditioning agent showed the least shear bond strength with greatest cavosurface microleakage when compared to the groups which were pretreated with the conditioning agents. Conclusions: A combination of 50/50 volume % mixture of 37% H3PO4 and 5.25% NaOCl can be a good choice for surface pretreatment of GI restorations.

Purpose: To study the clinical presentation, mycological profile, and risk factors of fungal keratitis (FK) cases presenting at two tertiary-care centers, one each at North (Chandigarh) and Northeast (Assam) India, and to compare the spectrum of fungi recovered from the clinical and environmental samples at both locations. Methods: All patients with suspected FK were enrolled from both the centers between January 2018 and December 2019. Corneal samples were collected and processed as per standard laboratory protocols. Demographic details and clinical and mycological profiles were noted in all patients. Environmental sampling from the soil, air, and the vegetative matter was performed from both locations and neighboring districts. Results: Of the 475 suspected cases, 337 (71%) were diagnosed as FK (median age: 50 years; 77.2% males). The presence of diabetes, hypertension, blurred vision, and corneal discoloration was significantly higher in patients with FK compared to those without FK. Aspergillus sp. (52.1%) and Fusarium sp. (47.61%) were the predominant etiological agents isolated from cases in North and Northeast India, respectively. FK due to melanized fungi was associated with diabetes, trauma with animal tail, and corneal discoloration. A similar spectrum of fungi was seen in environmental and clinical samples in both the regions. Conclusion: The difference in etiological agents of FK and environmental fungal isolates in North and Northeast India highlights the need to identify the ecological niche of potential fungal pathogens. Prospective, multicenter studies, systematic environmental sampling, and the evaluation of the differences in causative agents and clinical presentation of FK from different parts of the country can substantially improve our understanding of its region-specific clinico-epidemiological profile.

IntroductionRecently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients’ residences.MethodsThe residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients’ residence and cultured on Dichloran Rose–Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients’ clinical isolates.ResultsThe median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients’ bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients’ residences. Rhizopus arrhizus was isolated from the environment of all patients’ residences (n = 25); other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients’ bedrooms and respective clinical isolates from patients.DiscussionThe study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients’ convalescence period and environmental decontamination could minimize exposure in those susceptible patients.

Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.

LAMP diagnosis of malaria is simple and cost-effective with acceptable sensitivity and specificity as compared to standard diagnostic modules such as microscopy, RDTs and nested PCR, and thus its deployment for onsite screening of malaria in resource-limited regions is under consideration. However, the requirement of an electricity-operated dry bath and bulky read-out unit is still a major concern. In an effort to simplify this limitation, we have developed a portable LAMP device and fluorescence readout unit which can be used in the rapid point-of-care diagnosis of malaria. We have developed a point-of-care diagnostic LAMP device that is easy to operate by a mobile application, and the results can be quantified with a fluorescent readout unit. The diagnostic performance of the device was evaluated in 90 P. falciparum-infected clinical isolates stored at 4°C for 6-7 years and 10 freshly collected isolates from healthy volunteers. The LOD and quantitative ability of LAMP in estimating parasitemia levels were revealed with laboratory-grown P. falciparum strain (3D7). The LAMP assay performed in our device was exclusive for P. falciparum detection with sensitivity and specificity determined to be 98.89% and 100%, respectively, in clinical isolates. The LOD was documented to be 1 parasite/µl at the cut-off ADC value of 20. Parasite density estimated from ADC values showed concordance with microscopically determined parasite density of the cultured P. falciparum 3D7 strain. The LAMP assay performed in our device provides a possible portable platform for its deployment in the point-of-care diagnosis of malaria. Further validation of the quantitative ability of the assay with freshly collected or properly stored clinical samples of known parasitemia is necessary for field applicability.

Introduction: Adherence to drug regimen is a very important factor for improvement. Dropping out may affect the treatment outcome and also an indication of poor clinical performance. Patient who left the treatment in between can lead to a deterioration in clinical condition, resulting in the need for more intensive therapy that significantly incurs higher social and economic loss. Therefore, improving medication compliance potentially reduces morbidity and suffering of patients and their families, and the cost of rehospitalisation. Aim: To study the pattern of follow-up among patients of various psychiatric disorders and also to study the therapist factors contributing in adherence to treatment and the socio-demographic profile of patients who dropout from study. Materials and Methods: This was a prospective analytical study conducted in the Department of Psychiatry, GGSMCH Faridkot, Punjab, India. Patients were enrolled in for six month from June 2019 to November 2019 and then followed-up in next six month period from December 2019 to May 2020. A total of 500 psychiatric patients were selected by the convenient non probability sampling technique in the age group between 18-45 years who met the inclusion criteria. These patients were evaluated for illness related variables using psychiatric proforma and Charleston Psychiatric Outpatient Satisfaction Scale (CPOSS) was applied. factors affecting the pattern of follow-up, relating to the treatment and its side effects, disease progression as well as therapist-related factors using a semi-structured questionnaire were recorded. The data, thus generated, was subjected to appropriate statistical analysis. Results: In the socio-demographic profile among dropout education status, occupation, and duration of illness, statistically significant difference was found among different disorders (p

The emphasis so far during the COVID-19 pandemic has been on the respiratory manifestations with little attention being paid to cutaneous manifestations. The novel coronavirus has a wide spectrum of cutaneous manifestations which are broadly divided into exanthematous and vasculopathic type of lesions. The effects of this novel virus on the integumentary system cannot be underestimated as it can mimic various types of viral skin lesions. Thus, dermatologists should have knowledge about COVID-19 disease presentations and which differential diagnosis to consider if they encounter skin lesions in a patient who is known or suspected to have COVID-19. Patient evaluation and workup also needs to be modified during the time of this pandemic. Immunosuppressive/immunomodulatory drugs which are rampantly used in dermatological practice, must be used only after weighing their risks and benefits during the COVID-19 era. Personal Protective Equipment has to be worn when coming in contact with a suspected or a proven case of COVID-19. However, its use itself is associated with dermatological side effects which should be known to dermatologist practising during the COVID-19 era. Teledermatology can go a long way in circumventing these issues and it should be made more accessible, especially in remote areas. Another future recommendation could be setting up of a national level organization or group for recording dermatological data related to COVID-19.

Intracellular pathogens manipulate the host cell for their own survival by contributing to modifications of host epigenome, and thus, altering expression of genes involved in the pathogenesis. Both ATP-dependent chromatin remodeling complex and histone modifications has been shown to be involved in the activation of IFNγ responsive genes. Leishmania donovani is an intracellular pathogen that causes visceral leishmaniasis. The strategies employed by Leishmania donovani to modulate the host epigenome in order to overcome the host defense for their persistence has been worked out in this study. We show that L. donovani negatively affects BRG1, a catalytic subunit of mammalian SWI/SNF chromatin remodeling complex, to alter IFNγ induced host responses. We observed that L. donovani infection downregulates BRG1 expression both at transcript and protein levels in cells stimulated with IFNγ. We also observed a significant decrease in IFNγ responsive gene, Class II transactivator (CIITA), as well as its downstream genes, MHC-II (HLA-DR and HLA-DM). Also, the occupancy of BRG1 at CIITA promoters I and IV was disrupted. A reversal in CIITA expression and decreased parasite load was observed with BRG1 overexpression, thus, suggesting BRG1 is a potential negative regulator for the survival of intracellular parasites in an early phase of infection. We also observed a decrease in H3 acetylation at the promoters of CIITA, post parasite infection. Silencing of HDAC1, resulted in increased CIITA expression, and further decreased parasite load. Taken together, we suggest that intracellular parasites in an early phase of infection negatively regulates BRG1 by using host HDAC1 for its survival inside the host.

Abstract Background Heavy metals are natural components of the earth’s crust and are considered as constant environmental pollutants since they cannot be degraded or destroyed easily. Cadmium (Cd) is present primarily in the ores of zinc, copper, or lead; the extraction and processing of which releases large quantities of cadmium into the atmosphere, hydrosphere, and soil thereby contaminating the human environment. The present study aimed to investigate the possible protective and therapeutic effects of garlic and tomato extract on cadmium-induced AChE activity, biochemical parameters along with the pathological changes in the brain tissue of mice. Methods Male Swiss albino mice (n = 40) were divided into several experimental (protective and therapeutic) groups and were given single dose of cadmium (6 mg/kg bw) with supplementation of garlic (100 mg/kg bw) and tomato (50 mg/kg bw) extract for 15 and 30 days under protective and therapeutic study. Results Cadmium-treated mice showed a significant decline in AChE (p < 0.01) level and total proteins (p < 0.0001) but a nonsignificant decrease in glycogen, cholesterol in the brain tissue activity as compared to control group. The histological study also showed degeneration in the form of vacuolation, congestion, hyperemia, lymphocytic infiltration, and edema in the brain (cortex and hippocampus) of Cd-treated mice. But the antioxidant-treated groups showed significant increment in AChE level and other biochemical parameters in the protective study. But there were significant variations in the therapeutic study, and this was also confirmed by the histological analysis of the brain. Both tomato and garlic administration showed more attenuation in the brain AChE activity, and it may be due to the strong antioxidant potential of their constituents. Conclusion We can conclude that cadmium exposure should be avoided as it causes neuropathological effects. But in daily life, it may not be possible, so we should regularly intake natural antioxidants which may neutralize the effects of heavy metals to some extent.

Owing to the rising consumer awareness and demands for quality foods with eco-friendly packaging, researchers have shifted their focus to sustainable advancements in active packaging systems that preserve food quality and sensory characteristics over time. The inclusion of antimicrobial agents into the biopolymer-based edible films has been a significant advancement in active food packaging technology. It is exceptionally efficient in inhibiting or killing the pathogenic/spoilage microbes causing food contamination. It can reduce the potential undesirable flavors produced due to the direct incorporation of active compounds in foods. The efficiency of synergism of antimicrobial bio-based packaging systems has been further enhanced by applying nanotechnological concepts such as bio-nanocomposites and nanoencapsulation systems. This review analyzes the current scenario and applications of antimicrobial biodegradable films in the food packaging industry while highlighting the ongoing research investigations on the implementation of nanotechnology to develop novel bio-based packaging systems.

The objective of the study was to evaluate the synergistic action of edible antimicrobial packaging with MAP to extend the shelf life of composite dairy confection. GRAS-approved- nisin and natamycin incorporated edible films were tried for their efficacy against Bacillus cereus and Aspergillus niger, in comparison with control films (without antibacterial agents) under MAP environment (N2 and CO2; 70:30) followed by refrigeration storage (4±2 °C). Results depicted a statistically significant (p ≤ 0.05) difference in the shelf-life of control and treated samples with reduced microbial proliferation, better sensory scores, and thereby achieving the shelf-life for treated samples of 42 days in contrast to 21 days in control. However, the variation between the two different antimicrobial films remained non-significant (p ≤ 0.05). The treated product remained significantly (p ≤ 0.05) more acceptable in terms of microbiological, physic-chemical, and sensory quality compared to control. Therefore, the developed antimicrobial edible films could be successfully used along with MAP for shelf-life extension of composite dairy foods.

Serum 1,3-β-d-glucan(BDG) is a broad fungal biomarker for invasive fungal disease (IFD). More data is still required to support the Fujifilm Wako assay as a valuable alternative to the widely used Fungitell assay. We included archived serum samples from 157 individuals (97 cases; 33-IA, 64-IC, and 60 controls) for the comparative performance evaluation of the Fungitell assay and the Fujifilm Wako assay for IFD diagnosis. The BDG value was significantly higher in patients with IFD vs. controls (70.79 pg/mL vs. 3.03 pg/mL, p: 0.0002). An area under the curve (AUC) for the IFD, IC, and IA diagnosis was 0.895, 0.910, and 0.866, respectively, for the Fujifilm Wako assay. Based on the highest Youden’s index (0.667), a cutoff of 5 pg/mL was selected as the optimum for the Fujifilm Wako assay with good sensitivity (79.4%), specificity (88.3%) and agreement (84.7%, Cohen’s k:0.691) with the Fungitell assay. The mean run-time of the Fujifilm Wako assay was 70.12 min, and real-time observation allowed earlier time to result in Fujifilm Wako vs. Fungitell assay (37 vs. 120 min, p: < 0.0001). Thus, our findings support the diagnostic value of the Fujifilm Wako assay for the diagnosis of IFD. However, there is still a need to validate diagnostic protocols to optimize their use in multi-centre studies with different patient groups.

Nanotechnology is an avant-garde field of scientific research that revolutionizes technological advancements in the present world. It is a cutting-edge scientific approach that has undoubtedly a plethora of functions in controlling environmental pollutants for the welfare of the ecosystem. However, their unprecedented utilization and hysterical release led to a huge threat to the soil microbiome. Nanoparticles(NPs) hamper physicochemical properties of soil along with microbial metabolic activities within rhizospheric soils.Here in this review shed light on concentric aspects of NP-biosynthesis, types, toxicity mechanisms, accumulation within the ecosystem. However, the accrual of tiny NPs into the soil system has dramatically influenced rhizospheric activities in terms of soil properties and biogeochemical cycles. We have focussed on mechanistic pathways engrossed by microbes to deal with NPs.Also, we have elaborated the fate and behavior of NPs within soils. Besides, a piece of very scarce information on NPs-toxicity towards environment and rhizosphere communities is available. Therefore, the present review highlights ecological perspectives of nanotechnology and solutions to such implications. We have comprehend certain strategies such as avant-garde engineering methods, sustainable procedures for NP synthesis along with vatious regulatory actions to manage NP within environment. Moreover, we have devised risk management sustainable and novel strategies to utilize it in a rationalized and integrated manner. With this background, we can develop a comprehensive plan about NPs with novel insights to understand the resistance and toxicity mechanisms of NPs towards microbes. Henceforth, the orientation towards these issues would enhance the understanding of researchers for proper recommendation and promotion of nanotechnology in an optimized and sustainable manner.

NK/T-cell lymphoma (NKTCL) and γδ T-cell non-Hodgkin lymphomas (γδ T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and γδ T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards γδ T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies.

Objectives: The clinical profile, molecular characteristics and antifungal susceptibility patterns of the Mucoraceous mould, Syncephalastrum spp are poorly characterized. The present study provides a comprehensive overview of these aspects of this rare fungus. Methods: We characterized 8 clinical isolates of Syncephalestrum spp by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), 28S rDNA sequencing, Amplified Fragment Length Polymorphism (AFLP, n = 7) and in-vitro antifungal susceptibility testing. Clinical details of these eight cases were reviewed with all cases of Syncephalestrum infections reported in the literature till August 2020. Results: S. racemosum (n = 4) and S. monosporum (n = 4) were identified by MALDI-TOF, sequencing and AFLP also clearly differentiated the two. All isolates were uniformly susceptible to amphotericin B and terbinafine. Analysis of clinical details in our eight patients with 43 more cases reported in the literature revealed that most of the reports were (78.4%) from India and cutaneous mucormycosis was the most common (37.3%) presentation followed by rhino-orbito-cerebral (23.5%) and pulmonary(17.6%) infection. Association of trauma with skin infection (p:0.042); immunosuppression/steroid use (p:0.005) and neutropenia (p:0.000) with pulmonary infection was seen. Conclusion: S. racemosum, S. monosporum give rise to human infections. The improved database of MALDI-TOF could distinguish the two species. Such rare and emerging infections merit careful consideration and clinical attention.

IntroductionExophiala spp. are important opportunist pathogens causing subcutaneous or even fatal disseminated infections in otherwise both immunosuppressed and healthy individuals but there are no systematic studies on the isolates of Exophiala species from India.MethodsTwenty-four isolates of Exophiala species were retrieved from the National Culture Collection of Pathogenic Fungi (NCCPF) and identified phenotypically and by molecular methods (ITS region sequencing) followed by antifungal susceptibility testing (AFST) as per CLSI-M38A3 guidelines. A review of the literature of cases from India was performed up to 1st January 2021 using the Medline and Cochrane database.ResultsE. dermatitidis (n = 8), E. jeanselmei (n = 6), E. spinifera (n = 6), E. mesophila (n = 1), E. oligosperma (n = 1), E. xenobiotica (n = 1) were identified and the sequencing of ITS, β-tubulin and β-actin revealed a novel species, E. arunalokei sp. nov. (n = 1). The ITS sequence phylogram of E. jeanselmei revealed that the majority (83%) formed a separate cluster close to type A while majority (75%) of E. dermatitidis were type B. The MIC50 (mg/L) of amphotericin, itraconazole, voriconazole, micafungin, caspofungin, anidulafungin, and posaconazole, was 1, 0.25, 0.125, 0.12, 0.125, 0.062, and 0.062, respectively. Sixteen more cases were identified on the literature review and a significant association of E. dermatitidis with history of surgical procedures (p = 0.013), invasive disease (p = 0.032) and of E. mesophila with tuberculosis (p = 0.026) was seen.ConclusionThis, to the best of our knowledge is the first study from India elucidating the molecular and clinical characteristics of Exophiala species and the first Indian report of human infection due to E. xenobiotica and E. arunalokei.

Traumatic dental injuries are the most common orofacial injuries sustained during play and sports. Injuries to anterior teeth with subgingival fractures present a clinical challenge for a predictable esthetic outcome. The treatment modalities of subgingival fractures are surgical crown lengthening and orthodontic extrusion. The purpose of this article is to report a case of a 13-year-old male patient with a subgingival fracture of maxillary anterior teeth managed by a multidisciplinary approach, utilizing orthodontic extrusion after endodontic treatment followed by prosthetic rehabilitation.

Fibrinogen, a major constituent of blood plasma, is highly susceptible to reaction with biological oxidants. It has been proposed that fibrinogen plays a role in antioxidant defence, but oxidation of fibrinogen is also known to disrupt normal blood clotting and is implicated in the pathology of atherosclerosis. In the present study, we show that the biological oxidant hypochlorite promotes the formation of soluble high molecular weight fibrinogen assemblies ≥40 × 106 Da, that do not accumulate when fibrinogen is induced to aggregate by other stresses such as heating or hydroxyl-mediated damage in vitro. Hypochlorite-modified fibrinogen is stable at 37 °C as assessed by precipitation assays, and has reduced susceptibility to iron-induced (hydroxyl-mediated) precipitation compared to native fibrinogen. In contrast to hypochlorite-modified albumin, which is known to be immunostimulatory, hypochlorite-modified fibrinogen does not induce RAW 264.7 (macrophage-like) cells or EOC 13.31 (microglia-like) cells to produce reactive oxygen species or induce cell death. Furthermore, depletion of fibrinogen from human blood plasma increases the immunostimulatory property of blood plasma after it is supplemented with hypochlorite in situ. We propose that reaction of hypochlorite with fibrinogen in blood plasma potentially reduces the accumulation of other hypochlorite-modified species such as immunostimulatory hypochlorite-modified albumin. The latter represent a novel role for fibrinogen in blood plasma antioxidant defence.

Leishmania donovani, an intracellular protozoan parasite upon infection, encounters a range of antimicrobial factors within the host cells. Consequently, the parasite has evolved mechanisms to evade this hostile defense system through inhibition of macrophage activation that, in turn, enables parasite replication and survival. There is growing evidence that epigenetic down-regulation of the host genome by intracellular pathogens leads to acute infection. Epigenetic modification is mediated by chromatin remodeling, histone modifications, or DNA methylation. Histone deacetylases (HDACs) removes acetyl groups from lysine residues on histones, thereby leading to chromatin remodeling and gene silencing. Here, using L. donovani infected macrophages differentiated from THP-1 human monocytic cells, we report a link between host chromatin modifications, transcription of defense genes and intracellular infection with L. donovani. Infection with L. donovani led to the silencing of host defense gene expression. Histone deacetylase 1 (HDAC1) transcript levels, protein expression, and enzyme activity showed a significant increase upon infection. HDAC1 occupancy at the promoters of the defense genes significantly increased upon infection, which in turn resulted in decreased histone H3 acetylation in infected cells, resulting in the down-regulation of mRNA expression of host defense genes. Small molecule mediated inhibition and siRNA mediated down-regulation of HDAC1 increased the expression levels of host defense genes. Interestingly, in this study, we demonstrate that the silencing of HDAC1 by both siRNA and pharmacological inhibitors resulted in decreased intracellular parasite survival. The present data not only demonstrate that up-regulation of HDAC1 and epigenetic silencing of host cell defense genes is essential for L. donovani infection but also provides novel therapeutic strategies against leishmaniasis.