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In the publication [...].
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Head and neck cancer is a significant public health concern in India and globally, with substantial social and economic consequences for affected individuals and their families. The study aimed to assess the socioeconomic impact of head and neck cancer. This paper presents the results of a questionnaire-based study involving 178 head and neck cancer patients who were evaluated at least two years post-completion of their treatment. The questionnaire data collected data on various factors, including site of cancer, treatment modality, speech and diet impairment, changes in earning capacity, occupation, and salary. This was collected from all patients visiting our tertiary cancer care center outpatient department in Ahmedabad, India, between January 2023 and August 2023. The findings highlight the diverse and profound socioeconomic consequences of head and neck cancer. The findings emphasize the need for comprehensive support systems for affected individuals and their families.
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The N-benzyl piperidine (N-BP) structural motif is commonly employed in drug discovery due to its structural flexibility and three-dimensional nature. Medicinal chemists frequently utilize the N-BP motif as a versatile tool to fine-tune both efficacy and physicochemical properties in drug development. It provides crucial cation-π interactions with the target protein and also serves as a platform for optimizing stereochemical aspects of potency and toxicity. This motif is found in numerous approved drugs and clinical/preclinical candidates. This review focuses on the applications of the N-BP motif in drug discovery campaigns, emphasizing its role in imparting medicinally relevant properties. The review also provides an overview of approved drugs, the clinical and preclinical pipeline, and discusses its utility for specific therapeutic targets and indications, along with potential challenges.
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PURPOSE: Femur shaft fractures commonly occur due to high velocity trauma and most of them are fixed with nailing. Malrotation is common after fixation. A rotational malalignment more than 30° is a deformity which requires correction. Various techniques described for rotational deformities are: the 'cable techniques' for the determination of varus-valgus malalignment; the 'hyperextension test', 'radiographic recurvatum sign', 'tibial plateau sign', and 'meterstick technique' for length analysis; and the 'hip rotation test', 'lesser trochanter shape sign', 'cortical step sign', and 'diameter difference sign' for rotational analysis. We describe integration sign at the medial or lateral aspect of notch of femur in fixed internal or external rotation due to condensation of trabeculae. METHODS: This is a prospective observational study. Informed consent was taken, and this study was approved by institutional review board. C arm imaging study of 50 knees was done at our institution in which rotational profile of distal femur was analyzed In 3 different views -AP , Internal and external rotation views. The rotation views were taken sequentially and each observer was asked to identify the sign at its appearance and at rotation when it was best seen. All the observers were asked to draw the sign on linear line diagram of distal femur. The data was analysed statistically. RESULTS: Sign of integral (∫) for rotational deformity was seen at Mean external rotation of 22±1.71 with a range of 19 degree to 25 degree and Mean internal rotation of 15.78±1.21 with a range of 14 degree to 18 degree. CONCLUSION: The integration sign can be used as intraoperative C arm sign to understand the rotational deformity of distal fragment of femur. This helps the surgeon to understand the alignment and revise if needed intraoperatively. If combined with position of lesser trochanter, this will give alignment for both proximal as well as distal fragment of femur.
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Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-µm-thick, mechanically flexible micro-electrocorticography (µECoG) BCI, integrating 256×256 electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording and 16,384 stimulation channels, from which we can simultaneously record up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.
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Introduction: Minimal Access Surgery (MAS) has shown better peri-operative outcomes with equivalent oncological outcomes in gastrointestinal and thoracic oncology. Open CRS (O-CRS) procedure accompanies inevitable and significant surgical morbidity in patients. The aim of the review article is to compare outcomes of M-CRS and HIPEC/EPIC with open procedure in peritoneal surface malignancies. Content: Comprehensive search of databases was done and total 2,807 articles were found (2793-PubMed and 14-Cochrane review). PRISMA flow chart was prepared and 14 articles were selected. Meta-analysis was performed according to PRISMA guidelines using random-effects model (DerSimonian Laird) and fixed effect model. Publication bias was tested with Funnel plot and Egger's regression test. Quality of studies was assessed by Newcastle-Ottawa scale. Summary and Outlook: Patients in both groups [total (732), M-CRS(319), O-CRS(413)] were similar in demographic characteristics. Peri-operative outcomes were significantly better in M-CRS group in terms of blood loss SMD=-2.379, p<0.001 (95â¯% CI -2.952 to -1.805), blood transfusion RR=0.598, p=0.011 (95â¯% CI 0.402 to 0.889), bowel recovery SMD=-0.843, p=0.01 (95â¯% CI -1.487 to -0.2), hospital stay SMD=-2.348, p<0.001 (95â¯% CI -3.178 to -1.519) and total morbidity RR=0.538, p<0.001 (95â¯% CI 0.395 to 0.731). Duration of surgery SMD=-0.0643 (95â¯% CI -0.993 to 0.865, p=0.892) and CC0 score RR=1.064 (95â¯% CI 0.992 to 1.140, p=0.083) had no significant difference. Limited studies which evaluated survival showed similar outcomes. This meta-analysis shows that M-CRS and HIPEC/EPIC is feasible and has better peri-operative outcomes compared to open procedure in patients with limited peritoneal carcinoma index (PCI) peritoneal surface malignancies. Survival outcomes were not calculated. Further studies are warranted in this regard.
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Introduction: Giant Cell Tumours (GCT) are benign tumours with aggressive potential that disrupt the local bony architecture, which can be especially problematic in peri-articular locations. Our aim was to assess the outcomes of patients with GCT of the distal ulna who were treated by resection without reconstruction. Methods: The study included 21 patients with distal ulna GCT that were treated with resection without reconstruction. There were 12 males and 9 females, with a mean age of 30.4years (range 14-45 years). The patients mean follow-up period was 4.4 years, with a two-year minimum follow-up. Results: Painful swelling was the presenting symtom in all cases. Nineteen patients had Campanacci grade 3 and two had Campanacci grade 2. The mean resected length of the distal ulna was 6.8 cm (range 4-10) cm. The Musculoskeletal Tumor Society score (MSTS) was 26.1. (range 22-28). Grip strength of the affected hand was reduced by 10.5% on average. (range 0%-16%). Two patients were having multi-centric disease on presentation and none of the cases had pathological fracture on presentation. One case had a local recurrence which was treated with surgery. Conclusion: Based on current study, GCT of the distal ulna, en bloc resection without reconstruction can be recommended as a valuable treatment option for Campanacci grades 2 and 3 tumours. Resection of the distal end of the ulna without reconstruction results in excellent functional outcomes, with forearm rotational movement and hand function preserved. According to review of literature this is the largest series of GCT Ulna and we recommend a multicentre and comparitive studies on this topic.
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Differentiated Thyroid carcinoma (DTC) with distant skeletal metastases is associated with a very poor prognosis and are unfortunately resistant to radioiodine therapy (RIT). Surgical removal of the metastases in such selected cases is a beneficial adjunct to RIT. We report two cases of DTC with sternal metastases whom we successfully managed with surgical resection of the sternal lesion with reconstruction of the chest wall defect using titanium mesh implant and myocutaneous flap.
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Head and neck osteosarcoma is an uncommon yet aggressive tumor which presents therapeutic challenges to get favourable results. Surgery remained the most effective treatment modality in this entity eventhough chemoradiotherapy have been tried in various studies for better outcome but still not yet becomes the standard in the management of these cases unlike in extremity osteosarcoma. We present our experience in the management of this uncommon yet lethal malignant tumor, i.e. head and neck osteosarcoma. To study the clinicopathological and prognostic features of Osteosarcoma in head and neck subsite. Retrospective study of patients diagnosed with head and neck osteosarcoma between 2003 and 2019. Total of 25 patients were included in our study. Mean age of our population is 27.5 years with slight male predominant. Mandible is the most commonly involved site. Multimodal treatment applied with surgical resection forms the main part in the management. Median DFS and OS were 16 and 36 months respectively with 5 year overall survival of 42%. Out of the various factors studied, absence of surgery, margin positivity are the principle features affecting the prognosis. Head and neck osteosarcoma is generally a jaw bone tumor commonly occurs in young adults with poor outcome. Since there is no universal guidelines to address this uncommon tumor, multiple studies have shown various results in the management. Till date, surgery remained the curative modality with mixed response on the role of chemotherapy and radiotherapy.
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Neoadjuvant chemoradiation followed by surgery has been the standard of care for locally advanced carcinoma esophagus. We present our experience and inference of various factors associated with the same treatment and the prognostic influence of the same. A retrospective analysis of a cohort of 132 squamous cell carcinoma esophagus patients post neoadjuvant chemoradiation operated with curative intent was carried out. The 2-year overall survival rate was 64.5%. A pathological complete response was achieved in 32.5% of patients and was the only factor that significantly determined overall survival (p = 0.048). Neoadjuvant chemoradiation before surgery for locally advanced squamous cell cancer of the esophagus remains the standard of care with a pathological complete response being a significant factor in predicting overall survival. More prospective randomized studies are necessary to analyze factors affecting and predicting a pathological complete response which would help organ preservation in patients with a complete response.
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Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.
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Bifidobacterium bifidum , Mesalamine , Polymethacrylic Acids , Hydrogels/pharmacology , Colon , Anti-Inflammatory Agents/pharmacologyABSTRACT
BACKGROUND: Oral submucous fibrosis (OSF) is a pathological condition characterized by excessive tissue healing resulting from physical, chemical, or mechanical trauma. Notably, areca nut consumption significantly contributes to the development of oral fibrosis. The current definition of OSF, recognizing its potential for malignant transformation, necessitates a more comprehensive understanding of its pathophysiology and etiology. HIGHLIGHTS: Areca nut induces fibrotic pathways by upregulating inflammatory cytokines such as TGF-ß and expressing additional cytokines. Moreover, it triggers the conversion of fibroblasts to myofibroblasts, characterized by α-SMA and γSMA expression, resulting in accelerated collagen production. Arecoline, a component of areca nut, has been shown to elevate levels of reactive oxygen species, upregulate the expression of various cytokines, and activate specific signaling pathways (MEK, COX2, PI3K), all contributing to fibrosis. Therefore, we propose redefining OSF as "Areca nut-induced oral fibrosis" (AIOF) to align with current epistemology, emphasizing its distinctive association with areca nut consumption. The refined definition enhances our ability to develop targeted interventions, thus contributing to more effective prevention and treatment strategies for oral submucous fibrosis worldwide. CONCLUSION: Arecoline plays a crucial role as a mediator in fibrosis development, contributing to extracellular matrix accumulation in OSF. The re-evaluation of OSF as AIOF offers a more accurate representation of the condition. This nuanced perspective is essential for distinguishing AIOF from other forms of oral fibrosis and advancing our understanding of the disease's pathophysiology.
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Areca , Arecoline , Oral Submucous Fibrosis , Oral Submucous Fibrosis/pathology , Oral Submucous Fibrosis/etiology , Oral Submucous Fibrosis/metabolism , Humans , Areca/adverse effects , Arecoline/adverse effects , Cytokines/metabolism , Signal Transduction , Nuts/adverse effectsABSTRACT
Coronary artery disease (CAD) and peripheral vascular disease (PVD) often coexist and are prevalent due to population ageing, smoking, diabetes, unhealthy lifestyles, and the epidemic of obesity. In high-risk patients, it is critical to minimize the overall burden of surgery to avoid poor outcomes and morbidity. Here, we present a case of successful coronary artery bypass grafting (CABG) with thoraco-bifemoral bypass surgery for PVD via a left thoracotomy approach. Traditionally, median sternotomy is done for these kinds of surgeries. However, we preferred thoracotomy over sternotomy to avoid morbidity in old age. Our case suggests that combined CABG with thoraco-bifemoral bypass via thoracotomy approach is a reliable surgical option depending on the anatomy of the lesion.
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Background: Oral submucous fibrosis (OSF) is a persistent oral mucosal condition that carries an elevated risk of undergoing malignant transformation. Our objective was to elucidate the involvement of epithelial-to-mesenchymal transition (EMT) in OSF and its progression to malignancy by studying a panel of EMT markers, thereby understanding the molecular mechanisms. Methods: An immunohistochemical analysis was done to detect the presence of E-cadherin, N-cadherin, pan-cytokeratin (PanCK), vimentin, α-SMA (alpha-smooth muscle actin), and CD44 in a total of 100 tissue samples. These samples comprised 40 cases of OSF, 20 cases of oral squamous cell carcinoma associated with OSF (OSFSCC), and 40 cases of oral squamous cell carcinoma (OSCC). A whole transcriptomic analysis was performed on a group of seven matched samples encompassing NOM, OSF, OSFSCC, and OSCC. Results: We observed significantly decreased expression of E-cadherin and PanCK, while N-cadherin, vimentin, α-SMA, and CD44 showed significantly higher expression in OSFSCC and OSCC as compared to OSF, both at protein and RNA levels. CD44 expression was noticeably higher in OSFSCC (p < 0.001) than in OSCC. Conclusion: Downregulation of epithelial markers with concomitant upregulation of mesenchymal and stem cell markers suggests the potential role of EMT and stemness in accelerating the pathogenesis and malignant transformation of OSF. The high levels of CD44 expression seen in OSFSCC indicate a high propensity for aggressiveness and acquisition of stem-like characteristics by the cells undergoing EMT.
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Contact lenses (CLs) have become an essential tool in ocular drug delivery, providing effective treatment options for specific eye conditions. In recent advancements, Therapeutic CLs (TCLs) have emerged as a promising approach for maintaining therapeutic drug concentrations on the eye surface. TCLs offer unique attributes, including prolonged wear and a remarkable ability to enhance the bioavailability of loaded medications by more than 50%, thus gaining widespread usage. They have proven beneficial in pain management, medication administration, corneal healing, and protection. To achieve sustained drug delivery from TCLs, researchers are exploring diverse systems, such as polymeric nanoparticulate systems, lipidic systems, and the incorporation of agents like vitamin E or rate-limiting polymers. However, despite breakthrough successes, certain challenges persist, including ensuring drug stability during processing and manufacturing, controlling release kinetics, and biomaterial interaction, reducing protein adhesion, and addressing drug release during packaging and storage etc. While TCLs have shown overall success in treating corneal and ocular surface disorders, careful consideration of potential issues and contraindications is vital. This review offers an insightful perspective on the critical aspects that need to be addressed regarding TCLs, with a specific emphasis on their advantages and limitations.
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The goal of this investigation is to evaluate the accuracy of handheld ultrasound score in assessing right atrial (RA) pressure in patients with obesity with heart failure. We prospectively studied 123 patients with heart failure referred for right-sided cardiac catheterization. Handheld ultrasound was performed before catheterization to evaluate volume status by estimating RA pressure using end-expiratory inferior vena cava (IVC) dimension, IVC respiratory collapsibility, and right internal jugular (RIJ) vein respiratory collapsibility. A 3-point simple score was created using multiple logistic regression. The patients were divided into 2 groups based on body mass index. The performance of this score was assessed using the receiver operating characteristics curve in each subgroup and was compared with the performance of the 2-point score (expiratory IVC dimension, IVC respiratory collapsibility). Median age was 58 years (interquartile range 48 to 65), and 37% were women. The 3-point score including RIJ performed better than did the 2-point score in patients with obesity (area under the curve 0.84 [0.74 to 0.95] vs 0.69 [0.58 to 0.81], p = 0.001). The performance of the scores did not differ in patients without obesity (area under the curve 0.85 [0.74 to 0.95] vs 0.82 [0.71 to 0.93], p = 0.49). In patients with obesity, the 3-point score had a specificity of 100% and sensitivity of 21% (11% to 31%) for elevated RA pressure ≥10 mm Hg. In conclusion, a 3-point score including both RIJ and IVC assessment performed better in patients with obesity with heart failure and highlights the importance of comprehensive evaluation in patients with obesity to achieve an accurate, noninvasive assessment of volume status.
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Heart Failure , Humans , Female , Middle Aged , Male , Ultrasonography/methods , Heart Failure/complications , Heart Failure/diagnostic imaging , ROC Curve , Logistic Models , Vena Cava, Inferior/diagnostic imaging , Obesity/complicationsABSTRACT
Purpose: Lung cancer is one of the most common cancers in India. However, less than half receive treatment with a curative intent and very few undergo surgery amongst them. We present our surgical experience with non-small cell lung cancer. Methods: A retrospective analysis of a cohort of 92 non-small cell lung cancer patients operated with curative intent. Results: Less than 2% patients of lung cancer were operated on at our centre. Adenocarcinoma was the most common histological subtype. Right upper lobectomy was the most common surgery performed. Two- and 3-year overall survival was 74.3% and 70.6% respectively. Two- and 3- year disease-free survival was 65.4% and 60.8% respectively. Conclusion: The fraction of patients who are operated for lung cancer is very less. There is a definite missed window of opportunity. We have comparable survival to international data.
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Background: To compare the efficacy of McLaughlin Bennett Trevisi (MBT) appliance and Clear Aligner Therapy (CAT) among nonextraction Class I crowding cases. Methods: The study sample (60 patients) was allotted into two equal groups (30 patients each) using block randomization wherein Group 1: treated with 0.018" MBT appliance and Group 2: treated with CAT for correction of malocclusion. At the end of treatment (T1), treatment duration, chairside time, laboratory time, number, and type of appointments were noted from treatment record cards. For comparing the acceptability among patients treated with both modalities at T1, the patients were interviewed regarding the comfort and ease of using an appliance with a questionnaire-based survey. Results: The median number of nonscheduled/emergency and finishing stage appointments was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The median duration of treatment at the scheduled, finishing, and overall appointments, was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The median chairside time of all appointments was significantly higher in Group 1 compared to Group 2 (P-value <0.001). The experience with treatment and overall acceptability was significantly higher in Group 2 compared to Group 1 (P-value <0.001). However, mean laboratory time per aligner fabrication in Group 2 was 30.26 ± 3.45 min against no laboratory time consumed in Group 1. Conclusions: CAT significantly reduces treatment duration, chairside time, number of nonscheduled/emergency, and finishing stage appointments in nonextraction Class I crowding cases. Prospective studies with 3D aligner systems are recommended to add further evidence in this regard. Clinical Trials Registry-India Registration No: CTRI/2018/04/013301.
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BACKGROUND: Drought is one of the important abiotic stresses that can significantly reduce crop yields. In India, about 24% of Brassica juncea (Indian mustard) cultivation is taken up under rainfed conditions, leading to low yields due to moisture deficit stress. Hence, there is an urgent need to improve the productivity of mustard under drought conditions. In the present study, a set of 87 B. carinata-derived B. juncea introgression lines (ILs) was developed with the goal of creating drought-tolerant genotypes. METHOD: The experiment followed the augmented randomized complete block design with four blocks and three checks. ILs were evaluated for seed yield and its contributing traits under both rainfed and irrigated conditions in three different environments created by manipulating locations and years. To identify novel genes and alleles imparting drought tolerance, Quantitative Trait Loci (QTL) analysis was carried out. Genotyping-by-Sequencing (GBS) approach was used to construct the linkage map. RESULTS: The linkage map consisted of 5,165 SNP markers distributed across 18 chromosomes and spanning a distance of 1,671.87 cM. On average, there was a 3.09 cM gap between adjoining markers. A total of 29 additive QTLs were identified for drought tolerance; among these, 17 (58.6% of total QTLs detected) were contributed by B. carinata (BC 4), suggesting a greater contribution of B. carinata towards improving drought tolerance in the ILs. Out of 17 QTLs, 11 (64.7%) were located on the B genome, indicating more introgression segments on the B genome of B. juncea. Eight QTL hotspots, containing two or more QTLs, governing seed yield contributing traits, water use efficiency, and drought tolerance under moisture deficit stress conditions were identified. Seventeen candidate genes related to biotic and abiotic stresses, viz., SOS2, SOS2 like, NPR1, FAE1-KCS, HOT5, DNAJA1, NIA1, BRI1, RF21, ycf2, WRKY33, PAL, SAMS2, orf147, MAPK3, WRR1 and SUS, were reported in the genomic regions of identified QTLs. CONCLUSIONS: The significance of B. carinata in improving drought tolerance and WUE by introducing genomic segments in Indian mustard is well demonstrated. The findings also provide valuable insights into the genetic basis of drought tolerance in mustard and pave the way for the development of drought-tolerant varieties.