Age-stratified Assessment of Brain Volumetric Segmentation on the Indian Population Using Quantitative Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: Automated methods for quantifying brain tissue volumes have gained clinical interest for their objective assessment of neurological diseases. This study aimed to establish reference curves for brain volumes and fractions in the Indian population using Synthetic MRI (SyMRI), a quantitative imaging technique providing multiple contrast-weighted images through fast postprocessing. METHODS: The study included a cohort of 314 healthy individuals aged 15-65 years from multiple hospitals/centers across India. The SyMRI-quantified brain volumes and fractions, including brain parenchymal fraction (BPF), gray matter fraction (GMF), white matter fraction (WMF), and myelin. RESULTS: Normative age-stratified quantification curves were created based on the obtained data. The results showed significant differences in brain volumes between the sexes, but not after normalization by intracranial volume. CONCLUSION: The findings provide normative data for the Indian population and can be used for comparative analysis of brain structure values. Furthermore, our data indicate that the use of fractions rather than absolute volumes in normative curves, such as BPF, GMF, and WMF, can mitigate sex and population differences as they account for individual differences in head size or brain volume.

Impact of Chest Wall Perforator Flaps on Rates of Total Mastectomy in Breast Cancer.

Breast-conserving surgery (BCS) outcomes are comparable to mastectomy in breast cancer treatment. However, patients with large tumours were offered mastectomy due to the resulting poor cosmetic sequelae after standard BCS. With the introduction of chest wall perforator flaps (CWPF), BCS is an option in patients with large tumour:breast ratio. The objective of our study was to evaluate the surgical outcomes of CWPFs and their impact on mastectomy rates. In order to assess the impact of CWPF on mastectomy rates, patients who underwent breast cancer surgery from January 2016 to December 2019 were included in a cohort named group A. In group A, the type of surgery performed was collected for each year from January 2016 to December 2019. Patients who underwent BCS and CWPF from July 2016 to June 2021 were included in another cohort named group B. In group B, patient-related and disease-specific details including post-operative complications were collected and analysed. In group A, following the introduction of CWPF, the mastectomy rates dropped by 10.69% and the mastectomy with reconstruction rates dropped by 23.29%. In group B, a total of 152 patients underwent CWPF reconstructions. The median tumour size was 20 mm (range = 0-80). A majority of patients were discharged within 24-h hospital stay (98.2%). Seventeen patients (11.11%) had a re-operation for margin positivity. Sixteen patients (10.46%) developed early complications and 19 patients (12.42%) developed delayed complications. CWPFs expand indications for BCS thus reducing mastectomy rates. It also has less morbidity when compared to reported mastectomy and reconstruction rates, thus making it a safe option for suitable patients.

An Audit on Oncological Safety with Magseed Localised Breast Conserving Surgery.

Wire-localised wide local excision (W-WLE) has been standard of care for impalpable breast lesions. Logistics and risks of wire localisation can be challenging. Magseed-localised wide local excision (M-WLE) is an alternative to W-WLE. We compare safety parameters and length of hospital stay (LOS) in patients undergoing M-WLE to W-WLE. All M-WLEs performed at single institution over an 8-month period were included and compared to historic matched cohort of W-WLEs who would have been suitable for Magseed localisation. Data including patient demographics, successful placements, re-excision rates, tumour size, and length of stay (LOS) was analysed. Two hundred thirty-eight patients were included in the study. Cancers were safely excised in all cases. A significant difference in re-excisions rates favouring M-WLE group was seen (2.9% vs 10.4%). Median waiting time to surgery was significantly shorter in M-WLE group (4 h 15 min vs 7 h 3 min). No significant difference in median LOS between the two groups was seen. M-WLE has been shown to be oncologically safe and non-inferior to W-WLE with significantly lower re-excision rate. Reduced pre-operative waiting time in the M-WLE group will have a positive effect on patient journey. Further research should focus on potential impact on day-bed utilisation and theatre efficiency.

Chitosan augments bioactive properties and drought resilience in drought-induced red kidney beans.

Application of 0.25% chitosan during seed priming or its foliage spray on Phaseolus vulgaris L. grown under restricted irrigations was assessed for its role in the enhancement of bioactive properties like antioxidant potential of dry seed. Seven hydroxycinnamic acid and eleven hydroxybenzoic acid derivatives were identified and quantified in seeds collected from treated plants using LC-MS/MS. The major phenolics in all the treatments were in the order; ferulic acid > p-coumaric acid > o-coumaric acid > gallic acid and salicylic acid. However, the concentrations of each differed significantly at p < 0.01, with ferulic acid (324.304 µg/g) in red kidney bean seed grown under 30% irrigation with primed seed as the most predominant phenolic. Phenolics reported are representative of the phenylpropanoid pathway having a defined role in combating abiotic stress. The DPPH free radical scavenging activity, metal chelation, and reducing power antioxidant activities of the crude extract of seeds were investigated and found to elevate with increase in imposing more drought stress. Total soluble phenol content was found to have a strong correlation with the antioxidant activities with DPPH radical scavenging activity (-0.88), reducing power activity (0.87) and chelating power activity (-0.85). Principal components PC1 and PC2 accounted for almost 64.40% as the principal contributors in augmenting the bioactive properties and drought resilience. Overall, our findings indicate that 0.25% chitosan as seed and foliar spray augments bioactive properties and drought resilience in drought induced red kidney beans.

Role of MRI in predicting response to neo-adjuvant systemic therapy (NAST) in breast cancer.

BACKGROUND AND OBJECTIVES: MRI is generally performed to assess response to Neo-adjuvant systemic therapy (NAST) in breast cancer. OBJECTIVE: To assess role of MRI in determining the probability of having residual disease in patients undergoing NAST. We also evaluated synchronous cancers diagnosed following MRI. METHODS: This is a retrospective study which included all patients who had pre-and post-NAST MRI between June 2014 and December 2019. Data on demographics, tumour characteristics and pathology were collected and analysed. Pre- and post-MRI probability were calculated and depicted on nomograms. RESULTS: The study included 205 patients. Overall pre-MRI probability of having residual disease was 55% (OR:1.2). The post-MRI probability was 78% (95% CI 72-83%; OR:3.5) if MRI showed residual disease and 23% (95% CI 16-31%, OR:0.3) if imaging showed complete response. The absolute benefit was higher in TNBC and HR-HER2. Additional cancers were identified in 8.78% of patients. CONCLUSION: MRI is beneficial in evaluating response to NAST specifically in TNBC and HR-HER2 cancers. Pre- and post-MRI probabilities of residual disease depicted on nomograms are a useful tool for clinicians. MRI can potentially impact the treatment decisions by identification of synchronous cancers.

Detection of Leishmania tarentolae in lizards, sand flies and dogs in southern Italy, where Leishmania infantum is endemic: hindrances and opportunities.

BACKGROUND: Leishmania tarentolae is a protozoan isolated from geckoes (Tarentola annularis, Tarentola mauritanica), which is considered non-pathogenic and is transmitted by herpetophilic Sergentomyia spp. sand flies. This species occurs in sympatry with Leishmania infantum in areas where canine leishmaniasis is endemic. In the present study, we investigated the circulation of L. tarentolae and L. infantum in sand flies, dogs and lizards in a dog shelter in southern Italy, where canine leishmaniasis by L. infantum is endemic. METHODS: Sheltered dogs (n = 100) negative for Leishmania spp. (March 2020) were screened by immunofluorescence antibody test (IFAT) using promastigotes of both species at two time points (June 2020 and March 2021). Whole blood from dogs, tissues of Podarcis siculus lizards (n = 28) and sand flies (n = 2306) were also sampled and tested by a duplex real-time PCR (dqPCR). Host blood meal was assessed in sand flies by PCR. RESULTS: Overall, 16 dogs became positive for L. infantum and/or L. tarentolae by IFAT at one or both sampling periods. One canine blood sample was positive for L. infantum, whilst two for L. tarentolae by dqPCR. At the cytology of lizard blood, Leishmania spp. amastigote-like forms were detected in erythrocytes. Twenty-two tissue samples, mostly lung (21.4%), scored molecularly positive for L. tarentolae, corresponding to 10 lizards (i.e., 35.7%). Of the female Sergentomyia minuta sampled (n = 1252), 158 scored positive for L. tarentolae, four for L. infantum, and one co-infected. Two Phlebotomus perniciosus (out of 29 females) were positive for L. tarentolae. Engorged S. minuta (n = 10) fed on humans, and one P. perniciosus, positive for L. tarentolae, on lagomorphs. CONCLUSIONS: Dogs and lacertid lizards (Podarcis siculus) were herein found for the first time infected by L. tarentolae. The detection of both L. tarentolae and L. infantum in S. minuta and P. perniciosus suggests their sympatric circulation, with a potential overlap in vertebrate hosts. The interactions between L. tarentolae and L. infantum should be further investigated in both vectors and vertebrate hosts to understand the potential implications for the diagnosis and control of canine leishmaniasis in endemic areas.

Beneficial effects of specific natural substances on oral health.

Substances that are consumed daily or occasionally may influence an individual's oral health. Some substances, such as alcohol, tobacco, and areca nut, adversely affect the oral region. However, some other substances, such as honey and green tea, which have antimicrobial properties, and berries, which have anticarcinogenic potential, exhibit beneficial effects on oral health. The effectiveness of synthetic drugs in maintaining oral health cannot be ignored; however, the benefits of synthetic drugs are associated with adverse effects and high costs. By contrast, the medicinal use of natural substances is associated with safety, affordability, and long-term benefits. In this paper, we review various natural substances that are potentially beneficial to oral health.

Role of MicroRNAs in the development and function of innate immune cells.

MicroRNAs act as crucial post-transcriptional regulators of various biological processes. Their role in regulating the differentiation and development of the various immune cells of the body is of paramount importance. The development of immune cells from the hematopoietic progenitors involves the complex interplay of transcription factors, cell signaling proteins and growth factors. MicroRNAs govern and sometimes work in a common axis alongside these factors to regulate the differentiation of immune cells. MicroRNAs are also involved in regulating the functions of innate immune cells such as phagocytosis, antigen presentation, endotoxin tolerance and natural killer cell cytotoxicity. Several microRNAs have shown to be activated during the inflammatory response and they limit the excessive immune response. The dysregulation of several microRNAs have shown to cause uncontrolled production of inflammatory cytokines resulting in various diseases. Overall, microRNAs are found to be crucial regulators of the development and function of innate immune cells and maintenance of immune homeostasis.

Role of microRNAs in sepsis.

INTRODUCTION: MicroRNAs have been found to be of high significance in the regulation of various genes and processes in the body. Sepsis is a serious clinical problem which arises due to the excessive host inflammatory response to infection. The non-specific clinical features and delayed diagnosis of sepsis has been a matter of concern for long time. FINDINGS: MicroRNAs could enable better diagnosis of sepsis and help in the identification of the various stages of sepsis. Improved diagnosis may enable quicker and more effective treatment measures. The initial acute and transient phase of sepsis involves excessive secretion of pro-inflammatory cytokines which causes severe damage. MicroRNAs negatively regulate the toll-like receptor signaling pathway and regulate the production of inflammatory cytokines during sepsis. Likewise, microRNAs have shown to regulate the vascular barrier and endothelial function in sepsis. They are also involved in the regulation of the apoptosis, immunosuppression, and organ dysfunction in later stages of sepsis. Their importance at various levels of the pathophysiology of sepsis has been discussed along with the challenges and future perspectives. CONCLUSION: MicroRNAs could be key players in the diagnosis and staging of sepsis. Their regulation at various stages of sepsis suggests that they may have an important role in altering the outcome associated with sepsis.

Differential Paradigms in Animal Models of Sepsis.

Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis.

Could stem cells be the future therapy for sepsis?

The severity and threat of sepsis is well known, and despite several decades of research, the mortality continues to be high. Stem cells have great potential to be used in various clinical disorders. The innate ability of stem cells such as pluripotency, self-renewal makes them potential agents for therapeutic intervention. The pathophysiology of sepsis is a plethora of complex mechanisms which include the initial microbial infection, followed by "cytokine storm," endothelial dysfunction, coagulation cascade, and the late phase of apoptosis and immune paralysis which ultimately results in multiple organ dysfunction. Stem cells could potentially alter each step of this complex pathophysiology of sepsis. Multiple organ dysfunction associated with sepsis most often leads to death and stem cells have shown their ability to prevent the organ damage and improve the organ function. The possible mechanisms of therapeutic potential of stem cells in sepsis have been discussed in detail. The route of administration, dose level, and timing also play vital role in the overall effect of stem cells in sepsis.

siRNAs encapsulated in recombinant capsid protein derived from Dengue serotype 2 virus inhibits the four serotypes of the virus and proliferation of cancer cells.

siRNA delivery potential of the Dengue virus capsid protein in cultured cells was recently reported, but target knockdown potential in the context of specific diseases has not been explored. In this study we have evaluated the utility of the protein as an siRNA carrier for anti Dengue viral and anti cancer applications using cell culture systems. We show that target specific siRNAs delivered using the capsid protein inhibit infection by the four serotypes of Dengue virus and proliferation of two cancer cell lines. Our data confirm the potential of the capsid for anti Dengue viral and anti cancer RNAi applications. In addition, we have optimized a fermentation strategy to improve the yield of Escherichia coli expressed D2C protein since the reported yields of E. coli expressed flaviviral capsid proteins are low.

Evaluation of target mRNA cleavage by aurorakinase B specific siRNA in prostate and hepatic cancer cells and its therapeutic potential in mouse models of liver cancer.

The anti proliferative potential of siRNA26, targeted to Aurora kinase B, in prostate cancer cells is known from a previous study from our laboratory. Here we first show that siRNA26 cleaves at the same position of the target mRNA in the prostate cancer and hepatocellular carcinoma cell lines, PC3 and HepG2 respectively. Aurorakinase B specific siRNA, but not a control siRNA, inhibited PC3 and HepG2 cell proliferation and cell migration. These effects correlated to RNA silencing of Aurorakinase B in both the cell lines. Intra-tumoral administration of HiPerfect complexed siRNA26 inhibited the growth of HepG2 xenografts in SCID mice. In an orthotopic setting, intravenous administration of HiPerfect encapsulated siRNA26 appeared to reduce the severity of multifocal lesions.

A prospective study of the Bedside Index for Severity in Acute Pancreatitis (BISAP) score in acute pancreatitis: an Indian perspective.

INTRODUCTION: A simple and easily applicable system for stratifying patients with acute pancreatitis is lacking. The aim of our study was to evaluate the ability of BISAP score to predict mortality in acute pancreatitis patients from our institution and to predict which patients are at risk for development of organ failure, persistent organ failure and pancreatic necrosis. METHODS: All patients with acute pancreatitis were included in the study. BISAP score was calculated within 24 h of admission. A Contrast CT was used to differentiate interstitial from necrotizing pancreatitis within seven days of hospitalization whereas Marshall Scoring System was used to characterize organ failure. RESULTS: Among 246 patients M:F = 153:93, most common aetiology among men was alcoholism and among women was gallstone disease. 207 patients had no organ failure and remaining 39 developed organ failure. 17 patients had persistent organ failure, 16 of those with BISAP score ≥3. 13 patients in our study died, out of which 12 patients had BISAP score ≥3. We also found that a BISAP score of ≥3 had a sensitivity of 92%, specificity of 76%, a positive predictive value of 17%, and a negative predictive value of 99% for mortality. DISCUSSION: The BISAP score is a simple and accurate method for the early identification of patients at increased risk for in hospital mortality and morbidity.

Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation.

AG129 mice are known to be permissive to infection by multiple serotypes of Dengue virus (DENV). There exists a concern that mouse passaged strains of the virus may induce neurological complications rather than increased vascular permeability in these mice, hence the use of human clinical isolates of the virus to develop the AG129 mouse model of Dengue disease with increased vascular permeability. The present study evaluated four mouse brain passaged DENV strains, each belonging to a different serotype and three of them having an original isolation history in India, for their suitability to serve as candidates to induce rapid lethal disease in AG129 mice. While all the viruses were able to establish a productive infection in the spleen, none of them induced paralysis despite their mouse brain passage history. Only the type-2 virus acquired the ability to induce a lethal disease after a single round of spleen to spleen passage, and became highly virulent after five more rounds. This apparently non-neurological lethal disease was characterized by high viral burden, elevated vascular permeability, serum TNF-α surge immediately before moribund stage, transient leukocytosis followed by severe leukopenia, lymphopenia throughout the course of the infection, and transient thrombocytopenia. The disease was also characterized by inflammatory splenic collapse during moribund stage, reminiscent of spontaneous splenic rupture reported in rare cases of severe Dengue in humans.

Gossypiboma: an unusual foreign body of the male urethra.

We present a case of a fifty year old man who presented with multiple incisions in the peno-scrotal skin with extensive gangrenous changes. At debridement, a defect was identified in the bulbar urethra, through which two gauze pieces were removed. The post infective raw area was covered with a gracilis myocutaneous flap.

Inferior alveolar nerve canal position among South Indians: A cone beam computed tomographic pilot study.

PURPOSE: To document a clinically relevant position of the inferior alveolar nerve (IAN) in complete dentate south Indian patients in the age group of 20-29 years using cone beam computerized tomograms. MATERIALS AND METHODS: The investigators used a cross-sectional study design and a study sample of subjects who had a radiographically identifiable IAN canal with complete set of 28 permanent teeth excluding 3(rd) molars. Predictor variables were age, tooth position, and side. Outcome variables were the linear distances between the buccal and lingual aspect of the IAN canal, buccal and lingual cortical thickness, IAN canal diameter, and the superior aspect of the IAN canal from the periapex of first and second mandibular molar. Descriptive statistics and Mann-Whitney U test were performed. P value of ≤ 0.05 was taken as significant. RESULTS: The study sample was composed of 10 male and 10 female patients with a mean age of 24.2 ± 3.00 years. On average, the lingual cortical thickness was 1.68 mm at 1(st) molar and 1.44 at 2(nd) molar level. Gender and side influenced the outcome with varying statistical significance. CONCLUSIONS: The range of linear dimension of mandibular canal, cortical bone thickness, and distance between tooth apex and IAN canal have been presented for the South Indian population in the age group of 20-29 years. The implications of the findings will influence on the course of surgery. Further large-scale studies are needed to validate the findings of this study.