Novel Bioactive Magnesium-Hopeite composite by friction stir processing for orthopedic implant applications.

Magnesium (Mg) shows excellent potential for orthopedic implant applications owing to its equivalent mechanical properties compared to cortical bone and its biocompatibility. However, the rapid degradation rate of magnesium and its alloys in the physiological environment results in losing their mechanical integrity before complete bone healing. In light of this, friction stir processing (FSP), a solid-state process, is used to fabricate Hopeite (Zn(PO4)2.4H2O) reinforced novel magnesium composite. As a result of the novel composite fabricated by FSP, grain refinement of the matrix phase occurs significantly. The samples were immersed in simulated body fluid (SBF) for in-vitro bioactivity and biodegradability tests. The corrosion behavior of pure Mg, FSP Mg, and FSP Mg-Hopeite composite samples was compared using electrochemical and immersion tests in SBF. It found that Mg-Hopeite composite has better corrosion resistance than FSP Mg and pure Mg. Because of grain refinement and the presence of secondary phase Hopeite in the composite, the mechanical properties and corrosion resistance improved. The bioactivity test was performed in the SBF environment, and a rapid apatite layer was formed on the surface of Mg-Hopeite composite samples during the test. Osteoblast-like MG63 cells were exposed to samples, and the MTT assay confirmed the non-toxicity of the FSP Mg-Hopeite composite. The wettability of the Mg-Hopeite composite was improved than pure Mg. The present research findings showed that the novel Mg-Hopeite composite fabricated by FSP is a promising candidate for orthopedic implant applications, unreported in the literature.

Prevalence of familial hypercholesterolemia in patients with confirmed premature coronary artery disease in Ranchi, Jharkhand.

BACKGROUND: Familial hypercholesterolemia (FH) is an under-diagnosed autosomal co-dominant genetic disorder characterized by very high plasma levels of low-density lipoprotein cholesterol (LDL-C), premature coronary artery disease (CAD) with arcus cornealis, and xanthomas. Among patients with CAD, the frequency of FH is significantly higher than that of the general population, but little data are available in India in this regard. This study aimed to assess the prevalence of FH in patients with premature coronary artery disease for the first time in the Jharkhand population. RESULTS: The study was conducted on 200 premature CAD patients at RIMS hospital, Ranchi, from January 2020 to June 2021 with CAG-confirmed acute coronary syndrome. The study, without taking the aid of genetic profiling of the patients and using the Dutch Lipid Clinic Network Criteria, revealed quite a high (23.5%) prevalence of potential FH in patients with premature CAD apart from the conventional risk factors. Mean LDL-C levels among patients with definite, probable, possible, and no FH were recorded as 250.39, 184.32, 136.11, and 108.09 mg/dl, respectively. Arcus cornealis was seen in 55.31% of patients with potential FH, 90% in definite FH, and 44.40% with probable FH. Patients with potential FH were more likely to be younger (age < 40 years) males, having a history of CAD and a family history of premature CAD as compared to patients without FH. CONCLUSIONS: There was no previous report of large studies on FH or its epidemiology and its natural history from India. The present study is the first one to show a high prevalence of potential FH in premature CAD (about 23.5%). This preliminary study revealed that the prevalence of FH in patients with premature CAD who came to the tertiary care hospital of Ranchi, Jharkhand, was high, apart from the conventional risk factors.

Solid papillary carcinoma of the breast.

Solid Papillary Carcinoma (SPC) of the breast is a rare tumor with an incidence of less than 1%, mainly affecting elderly females. It is morphologically characterized by well-defined nodules with low-grade nuclear features associated with fibrovascular cores and shows neuroendocrine differentiation. SPC can be in-situ or invasive but has a favorable prognosis. It is a morphological mimicker of some pre-malignant conditions leading to its frequent misdiagnosis. An appropriate immunohistochemical (IHC) panel workup helps in distinguishing this tumor from its various morphological mimics. In this report, we present one such case of SPC with a small focus of invasion, reviewing the literature.

Impact of enhanced personal protective equipment on the physical and mental well-being of healthcare workers during COVID-19.

BACKGROUND: The COVID-19 pandemic has necessitated the use of enhanced personal protective equipment (PPE) in healthcare workers in patient-facing roles. We describe the impact on the physical and mental well-being of healthcare professionals who use enhanced PPE consistently. METHODS: We conducted a single-centre, cross-sectional study among healthcare professionals who use enhanced PPE. A web-based questionnaire was disseminated to evaluate the effects on individuals' physical and mental well-being. Physical and mental impact was assessed through a visual analogue scale. RESULTS: Prospective analysis of the views of 72 respondents is reported. 63.9% were women and 36.1% were men. Physical impact included exhaustion, headache, skin changes, breathlessness and a negative impact on vision. Communication difficulties, somnolence, negative impact on overall performance and difficulties in using surgical instrumentation were reported. CONCLUSION: Our study demonstrates the undeniable negative impact on the front-line healthcare workers using enhanced PPE and lays the ground for larger multicentric assessments given for it to potentially be the norm for the foreseeable future.

Solid papillary carcinoma of the breast

Solid Papillary Carcinoma (SPC) of the breast is a rare tumor with an incidence of less than 1%, mainly affecting elderly females. It is morphologically characterized by well-defined nodules with low-grade nuclear features associated with fibrovascular cores and shows neuroendocrine differentiation. SPC can be in-situ or invasive but has a favorable prognosis. It is a morphological mimicker of some pre-malignant conditions leading to its frequent misdiagnosis. An appropriate immunohistochemical (IHC) panel workup helps in distinguishing this tumor from its various morphological mimics. In this report, we present one such case of SPC with a small focus of invasion, reviewing the literature.

Correlates of depression, anxiety, self-esteem, and suicidal ideas in COVID-associated mucormycosis patients and the effects of treatment.

AIM: The aim was to study the correlates of depression, anxiety, self-esteem, and suicidal ideas in patients of COVID-associated mucormycosis (CAM) and effects of treatment. MATERIALS AND METHODS: A cross-sectional, analytical study was performed in a tertiary care center in Western Maharashtra. By purposive sampling, 34 patients of CAM were included in the study with their informed consent and after obtaining ethical clearance. A self-made questionnaire to include demographic and clinical details was filled. Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-Esteem Scale (RSES), and Suicidal Ideation Attributes Scale (SIDAS) were applied after initial diagnosis. The HADS, RSES, and SIDAS were reapplied after their operative treatment. RESULTS: A significant reduction in anxiety and depression scores postoperatively was seen. No significant difference was found in self-esteem or suicidal ideas postoperatively in the study population. However, patients who underwent orbital exenteration showed a significant reduction in level of self-esteem with anxiety and depression postoperatively. No specific correlation was found between the computed tomography score, family history, intensive care unit admission, or orbital exenteration with anxiety, depression, self-esteem, and suicidal ideas. CONCLUSION: Levels of anxiety and depression in patients of CAM reduced significantly after treatment, but self-esteem worsened in males more than females owing to disfigurement. There is a need of psychological counseling in patients of mucormycosis undergoing a debilitating surgery both pre- and postoperatively for a better outcome and recovery.

Biosynthesis of Hyaluronic acid polymer: Dissecting the role of sub structural elements of hyaluronan synthase.

Hyaluronic acid (HA) based biomaterials have several biomedical applications. HA biosynthesis is catalysed by hyaluronan synthase (HAS). The unavailability of 3-D structure of HAS and gaps in molecular understanding of HA biosynthesis process pose challenges in rational engineering of HAS to control HA molecular weight and titer. Using in-silico approaches integrated with mutation studies, we define a dictionary of sub-structural elements (SSE) of the Class I Streptococcal HAS (SeHAS) to guide rational engineering. Our study identifies 9 SSE in HAS and elucidates their role in substrate and polymer binding and polymer biosynthesis. Molecular modelling and docking assessment indicate a single binding site for two UDP-substrates implying conformationally-driven alternating substrate specificities for this class of enzymes. This is the first report hypothesizing the involvement of sites from SSE5 in polymer binding. Mutation at these sites influence HA production, indicating a tight coupling of polymer binding and synthase functions. Mutation studies show dispensable role of Lys-139 in substrate binding and a key role of Gln-248 and Thr-283 in HA biosynthesis. Based on the functional architecture in SeHAS, we propose a plausible three-step polymer extension model from its reducing end. Together, these results open new avenues for rational engineering of Class I HAS to study and regulate its functional properties and enhanced understanding of glycosyltransferases and processive enzymes.

Invasive and Non-Invasive Fungal Rhinosinusitis-A Review and Update of the Evidence.

Fungal infections are a subset of infectious processes that an otolaryngologist is required to be familiar with. They can be encountered in otology, rhinology and head and neck surgery. The presence of fungal rhinosinusitis is well recognised by otolaryngologists, but the classifications and appropriate management are not so well understood. The prevalence of fungal sinus disease is thought to be have been increasing in recent decades There is speculation that this may be due to increased awareness, antibiotic overuse and increased use of immunosuppressant medications. Added to this, there has been a large amount published on the role of fungi as a causative organism in chronic rhinosinusitis. Given the importance of fungal rhinosinusitis in clinical practice, we aim to review the classification and current management strategies based on up-to-date literature.

Prevalence of familial hypercholesterolemia in premature coronary artery disease patients admitted to a tertiary care hospital in North India.

AIMS: The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. METHODS: A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. RESULTS: Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). CONCLUSION: FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used.

Systematic review of patient-reported outcomes after revision endoscopic sinus surgery.

BACKGROUND: Revision endoscopic sinus surgery (RESS) may be required for partially controlled or uncontrolled chronic rhinosinusitis. Studies that reported technical success, e.g., sinus ostia patency after RESS, do not address whether the patient's symptoms and quality of life (QOL) improve after surgery. However, patient-reported outcome measures (PROM) are useful to assess the impact of sinus surgery on a patient's symptoms and QOL. OBJECTIVE: This systematic review was undertaken to evaluate the impact of RESS on PROMs. METHODS: Medical literature databases were searched for studies in English. References from retrieved articles and relevant reviews were examined for additional studies. Those studies that reported QOL outcome tools in patients who underwent RESS and with a minimum follow-up of 6 months were included. RESULTS: A search of the sources yielded 1856 citations. There were 72 articles after abstract review and exclusion, identified for full-text review, with 12 studies (which contained data from 1308 patients) that met the inclusion criteria for this systematic review. There were four "good" and eight "fair" studies. Three studies used the Rhinosinusitis Disability Index and Chronic Sinusitis Survey in tandem; two each used the 20-item Sino-Nasal Outcome Test and the 22-item Sino-Nasal Outcome Test; the remaining studies used either the Adelaide Disease Severity Score, Patient Response Score (PRS), Rhinosinusitis Symptom Inventory, Rhinosinusitis Outcome Measure 31, or the Chinese version of the University of Pennsylvania Smell Identification Test. All studies used validated PROMs apart from the study that used PRS. Studies consistently reported improvement in the five key symptoms of nasal obstruction, rhinorrhea, postnasal drip, facial pain, and anosmia, although improvement in halitosis, fever, dental pain, and cough were modest. CONCLUSION: Several PROMs demonstrated that RESS improves patient's QOL symptoms. Future studies that examine QOL should use a consistent PROM to allow a meta-analysis.

Sialendoscopy: what is it and what is its awareness?

In expanding the scope of sialendoscopy across the globe and assessing the impact of training activities at the European Sialendoscopy Training Centre, this study was conducted to find out the knowledge and attitude among respondents as well as identify potential obstacles to the initiation of the procedure. Delegates attending the 2011 International Federation of Otorhinolaryngological Societies meeting received a set of five questions. There were a total of 257 responses from 57 countries. Nearly all (238/257) were practising in the academic setting. A significant number of respondents had heard about sialendoscopy (231/257). An equal number found it interesting and were keen to learn more about the procedure (233/257). More than 85 % (219/257) respondents expressed their desire to start sialendoscopy. Hurdles to overcome included financial limitations (110) and "not enough knowledge" (100). Awareness about the existence of the procedure was rather high although the knowledge was limited. Several of the responders seemed keen on starting it, but had not done so due to financial limitations. However, there was a high rate of bias owing to the limited number of responders per country precluding a country-wise inference of awareness. Moreover, meetings of this nature tend to be attended by academics who in general seem to be more aware of new developments than their non-academic peers. Future surveys can address these issues as part of ensuring the universal adoption of sialendoscopy.

Determinants of survival in adult HIV patients on antiretroviral therapy in Eastern Uttar Pradesh: a prospective study.

BACKGROUND & OBJECTIVES: The National AIDS Control Organization (NACO) of India has been providing free ARV (antiretroviral) drugs since 2004. b0 y 2012, 486,173 patients had received treatment through the antiretroviral therapy (ART) centres. The objective of this observational study was to assess the factors determining survival of patients on ART under routine programme conditions in an ART centre in north India five years after its inception. METHODS: Treatment naive HIV positive patients who were enrolled in the ART centre between May 2009 and May 2010 and started on ART as per the Revised NACO guidelines 2009, were included in the study and outcome was assessed after two years of follow up. RESULTS: A total of 1689 patients were included in the analysis, of whom 272 (16.10%) expired, 205 (12.13%) were lost to follow up (LFU), 526 (31.14%) were transferred out to other facilities and 686 (40.63%) were alive at the end of two years. Majority (92%) of the deaths occurred in the first six months of therapy. Age >30 yr, male gender, poor functional status, haemoglobin level <11 g/dl, body weight <45 kg and CD4 count <100/µl at baseline had significantly higher relative hazard of death. Most LFU also occurred in the first six months and these patients had significantly low CD4 count, weight, haemoglobin level and higher number of patients in Stages III and IV as compared to those who survived. INTERPRETATION & CONCLUSIONS: The study findings revealed poor survival in the first six months of therapy especially in those with severe immunosuppression. This emphasizes the need for early enrolment into the programme. The high LFU occurring early after initiation of therapy suggests the urgent need to build an efficient patient retrieval system in the programme.

Chromosomal integration of hyaluronic acid synthesis (has) genes enhances the molecular weight of hyaluronan produced in Lactococcus lactis.

Microbial production of hyaluronic acid (HA) is an attractive substitute for extraction of this biopolymer from animal tissues. Natural producers such as Streptococcus zooepidemicus are potential pathogens; therefore, production of HA by recombinant bacteria that are generally recognized as safe (GRAS) organisms is a viable alternative that is being extensively explored. However, plasmid-based expression systems for HA production by recombinant bacteria have the inherent disadvantage of reduced productivity because of plasmid instability. To overcome this problem, the HA synthesis genes (hasA-hasB and hasA-hasB-hasC) from has-operon of S. zooepidemicus were integrated into the chromosome of Lactococcus lactis by site-directed, double-homologous recombination developing strains VRJ2AB and VRJ3ABC. The chromosomal integration stabilized the genes and obviated the instability observed in plasmid-expressed recombinant strains. The genome-integrated strains produced higher molecular weight (3.5-4 million Dalton [MDa]) HA compared to the plasmid-expressed strains (2 MDa). High molecular weight HA was produced when the intracellular concentration of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and uridine diphosphate-glucuronic acid (UDP-GlcUA) was almost equal and hasA to hasB ratio was low. This work suggests an optimal approach to obtain high molecular weight HA in recombinant strains.

Initial presentation with dilated cardiomyopathy in a patient of tuberous sclerosis: a rare case report.

A 35-year-old man presented with dilated cardiomyopathy, an unusual association with tuberous sclerosis. Clinical history and examination were consistent with tuberous sclerosis including major features of tuberous sclerosis complex (TSC) like facial angiofibroma, shagreen patch, subependymal nodules, and angiomyolipoma of kidney. The clinical manifestations, pathogenesis and evaluation of tuberous sclerosis are discussed.

Optimization of stability, encapsulation, release, and cross-priming of tumor antigen-containing PLGA nanoparticles.

PURPOSE: In order to investigate Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) as potential vehicles for efficient tumor antigen (TA) delivery to dendritic cells (DC), this study aimed to optimize encapsulation/release kinetics before determining immunogenicity of antigen-containing NP. METHODS: Various techniques were used to liberate TA from cell lines. Single (gp100) and multiple (B16-tumor lysate containing gp100) antigens were encapsulated within differing molecular weight PLGA co-polymers. Differences in morphology, encapsulation/release and biologic potency were studied. Findings were adopted to encapsulate fresh tumor lysate from patients with advanced tumors and compare stimulation of tumor infiltrating lymphocytes (TIL) against that achieved by soluble lysate. RESULTS: Four cycles of freeze-thaw + 15 s sonication resulted in antigen-rich lysates without the need for toxic detergents or protease inhibitors. The 80 KDa polymer resulted in maximal release of payload and favorable production of immunostimulatory IL-2 and IFN-γ. NP-mediated antigen delivery led to increased IFN-γ and decreased immunoinhibitory IL-10 synthesis when compared to soluble lysate. CONCLUSIONS: Four cycles of freeze-thaw followed by 15 s sonication is the ideal technique to obtain complex TA for encapsulation. The 80 KDa polymer has the most promising combination of release kinetics and biologic potency. Encapsulated antigens are immunogenic and evoke favorable TIL-mediated anti-tumor responses.

Transcription analysis of hyaluronan biosynthesis genes in Streptococcus zooepidemicus and metabolically engineered Lactococcus lactis.

The has operon genes in the hyaluronan (HA) producer, Streptococcus zooepidemicus, encode for some of the critical enzymes in the HA biosynthetic pathway. Heterologous expression of different combinations of multiple has genes has resulted in increasing HA production to varying degrees in different recombinant strains. In this work, a recombinant Lactococcus lactis strain (SJR6) was constructed, with insertion of three has operon genes (hasABD) from S. zooepidemicus. The SJR6 strain was found to be a better HA producer than two previously constructed recombinant L. lactis strains (SJR2 and SJR3), containing hasAB and hasABC genes, respectively, but exhibited lower HA production than the native HA producer S. zooepidemicus. To understand the differences in HA yield between the various strains, transcriptions of the HA biosynthesis genes (has genes and their homologues) were compared at different phases of exponential growth of the L. lactis and S. zooepidemicus cultures. The mRNA levels of all the heterologous has genes were expectedly far higher than their corresponding homologues in the L. lactis strains. The relative mRNA level of the hasB-homologue, viz. ugd (encoding UDP-glucose dehydrogenase), was found to be much lower than that of other homologues, corroborating earlier reports which indicate tight transcriptional regulation of the ugd gene in L. lactis. Interestingly, all the has gene homologues were found to be up-regulated in all the recombinant L. lactis strains, when compared with the corresponding genes in the untransformed strain, L. lactis NZ9000. A transcription analysis of S. zooepidemicus cultures revealed that the has operon was down-regulated in the mid-exponential growth phase in comparison to the early- and late-exponential growth phases. The transcription analyses in this study have provided insights for the design of recombinant strains with higher HA productivity.

Polymer nanoparticles containing tumor lysates as antigen delivery vehicles for dendritic cell-based antitumor immunotherapy.

Encapsulation of tumor-associated antigens in polymer nanoparticles (NP) is a promising approach to enhance efficiency of antigen delivery for anti-tumor vaccines. Head and neck squamous carcinoma (HNSCC) cell lines were initially used to generate tumor-associated antigens (TAA)-containing poly (lactic-co-glycolic acid) (PLGA) NP; encapsulation efficiency and release kinetics were profiled. Findings were adopted to entrap fresh tumor lysate from five patients with advanced HNSCC. To test the hypothesis that NP enhance antigen presentation, dendritic cell (DC) produced from patient blood monocyte precursors were loaded with either the un-encapsulated or NP-encapsulated versions of tumor lysates. These were used to stimulate freshly-isolated autologous CD8+ T cells. In four of five patients, anti-tumor CD8+ T cells showed significantly increased immunostimulatory IFN-γ (p=0.071) or decreased immmunoinhibitory IL-10 production (p=0.0004) associated with NP-mediated antigen delivery. The observations represent an enabling step in the production of clinically-translatable, inexpensive, highly-efficient, and personalized polymer-based immunotherapy for solid organ malignancies. FROM THE CLINICAL EDITOR: Enhancing the antigen presentation may be a viable approach to increase the efficiency of tumor cell directed cytotoxicity via immune mechanisms. This study presents an example for this using head and neck cancer cell lines and nanotechnology-based encapsulated antigen presentation to dendritic cells. The observed CD8+ T-cell response was significantly enhanced. This method may pave the way to a highly efficient cancer cell elimination method with minimal to no toxicity.

Hyaluronic acid production is enhanced by the additional co-expression of UDP-glucose pyrophosphorylase in Lactococcus lactis.

Hyaluronic acid (HA) production was metabolically engineered in Lactococcus lactis by introducing the HA synthetic machinery from the has operon of the pathogenic bacterium Streptococcus zooepidemicus. This study shows that the insertion of uridine diphosphate (UDP)-glucose pyrophosphorylase (hasC) gene in addition to the HA synthase (hasA) and UDP-glucose dehydrogenase (hasB) genes has a significant impact on increasing HA production. The recombinant L. lactis NZ9000 strain transformed with the plasmid pSJR2 (co-expressing hasA and hasB genes only) produced a maximum of 107 mg/l HA in static flask experiments with varying initial glucose concentrations, while the corresponding experiments with the transformant SJR3 (co-expressing hasA, hasB, and hasC genes) gave a maximum yield of 234 mg/l HA. The plasmid cloned with the insertion of the full has operon comprising of five different genes (hasA, hasB, hasC, hasD, and hasE) exhibited structural instability. The HA yield was further enhanced in batch bioreactor experiments with controlled pH and aeration, and a maximum of 1.8 g/l HA was produced by the SJR3 culture.