Analytical validation of HER2DX genomic test for early-stage HER2-positive breast cancer.

BACKGROUND: HER2DX, a multianalyte genomic test, has been clinically validated to predict breast cancer recurrence risk (relapse risk score), the probability of achieving pathological complete response post-neoadjuvant therapy (pCR likelihood score), and individual ERBB2 messenger RNA (mRNA) expression levels in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This study delves into the comprehensive analysis of HER2DX's analytical performance. MATERIALS AND METHODS: Precision and reproducibility of HER2DX risk, pCR, and ERBB2 mRNA scores were assessed within and between laboratories using formalin-fixed paraffin-embedded (FFPE) tumor tissues and purified RNA. Robustness was appraised by analyzing the impact of tumor cell content and protocol variations including different instruments, reagent lots, and different RNA extraction kits. Variability was evaluated across intratumor biopsies and genomic platforms [RNA sequencing (RNAseq) versus nCounter], and according to protocol variations. RESULTS: Precision analysis of 10 FFPE tumor samples yielded a maximal standard error of 0.94 across HER2DX scores (1-99 scale). High reproducibility of HER2DX scores across 29 FFPE tumors and 20 RNAs between laboratories was evident (correlation coefficients >0.98). The probability of identifying score differences >5 units was ≤5.2%. No significant variability emerged based on platform instruments, reagent lots, RNA extraction kits, or TagSet thaw/freeze cycles. Moreover, HER2DX displayed robustness at low tumor cell content (10%). Intratumor variability across 212 biopsies (106 tumors) was <4.0%. Concordance between HER2DX scores from 30 RNAs on RNAseq and nCounter platforms exceeded 90.0% (Cohen's κ coefficients >0.80). CONCLUSIONS: The HER2DX assay is highly reproducible and robust for the quantification of recurrence risk, pCR likelihood, and ERBB2 mRNA expression in early-stage HER2-positive breast cancer.

Horizontal transfer of miR-383 sensitise cells to cisplatin by targeting VEGFA-Akt signalling loop.

BACKGROUND: Cellular resistance to cisplatin has been one of the major obstacles in the success of combination therapy for many types of cancers. Emerging evidences suggest that exosomes released by drug resistant tumour cells play significant role in conferring resistance to drug sensitive cells by means of horizontal transfer of genetic materials such as miRNAs. Though exosomal miRNAs have been reported to confer drug resistance, the exact underlying mechanisms are still unclear. METHODS AND RESULTS: In the present study, mature miRNAs secreted differentially by cisplatin resistant and cisplatin sensitive HepG2 cells were profiled and the effect of most significantly lowered miRNA in conferring cisplatin resistance when horizontally transferred, was analysed. we report miR-383 to be present at the lowest levels among the differentially abundant miRNAs expressed in exosomes secreted by cisplatin resistant cells compared to that that of cisplatin sensitive cells. We therefore, checked the effect of ectopic expression of miR-383 in altering cisplatin sensitivity of Hela cells. Drug sensitivity assay and apoptotic assays revealed that miR-383 could sensitise cells to cisplatin by targeting VEGF and its downstream Akt mediated pathway. CONCLUSION: Results presented here provide evidence for the important role of miR-383 in regulating cisplatin sensitivity by modulating VEGF signalling loop upon horizontal transfer across different cell types.

Assessment of the prevalence of types of head and neck cancer in a tertiary cancer center at Madurai, Tamil Nadu: A cross-sectional study.

AIM: The aim of the study was to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu. OBJECTIVES: The objectives of the study were to assess the prevalence of types of head and neck cancer in Madurai, Tamil Nadu using a questionnaire. MATERIALS AND METHODS: A descriptive cross-sectional study was carried out for two months among 300 head and neck cancer patients at a tertiary cancer center in Madurai. A convenience sampling technique was used. The data were collected using a pretested, self-structured questionnaire. The data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 20.0 software. RESULTS: Of 300 head and neck cancer patients, the mean age of the patients was about 51.04 ± 16.49 years. The majority of the patients were male (80%), employed (85%), and literate (65%). Among the head and neck cancer patients, 65% were tobacco users and 42.4% were alcohol consumers. Squamous cell carcinoma was the most common type of head and neck cancer, and 79.7% were diagnosed at an advanced stage of said cancer, such as stages III and IV. CONCLUSION: Lack of knowledge and awareness is a major cause of increasing prevalence of head and neck cancer in our country. It is most important to increase the knowledge and awareness of early symptom recognition and its seriousness among the general population.

Carcinoma buccal mucosa treated with definitive hypofractionated accelerated radiotherapy: a retrospective analysis of treatment outcomes.

Introduction: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. Methods: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. Results: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Conclusion: Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

An unusual case of eosinophilia, myalgia and skin contractures: Shulman's disease revisited.

Shulman's disease (eosinophilic fasciitis) is a very rare autoimmune disorder with an unknown etiopathogenesis. During the initial period of disease, it usually causes limb and trunk edema followed by collagenous thickening of the subcutaneous fascia. Eosinophilia is a predominant laboratory finding during the initial phase of the disease and less prominent in the later phases. Patients may also present with arthritis, myositis, peripheral neuropathy, and rarely pleuropericarditis. Here, we are reporting a case of eosinophilic fasciitis presenting with vague constitutional symptoms, fever, and peripheral blood eosinophilia followed by rapidly evolving skin tightening with joint contractures and muscle stiffness, which misled the treating team toward Scleroderma and its overlap syndromes. The diagnosis was finally clinched by a full-thickness skin biopsy along with underlying fascia and muscle tissue from an effected area, with a gratifying treatment response to standard immune suppression.

Spectrum of Surgically Resected Lesions of the Cavernous Sinus: A Neuropathologic Audit.

Background The cavernous sinus is a complex space composed of extradural venous plexus within dural folds. Several important structures like the carotid artery, cranial nerves, and sympathetic nerve fibers traverse through this space. Radiological diagnosis may not be definitive and in the context of discordance between clinical and neuroimaging diagnosis, histopathological evaluation becomes essential for diagnosis and management. Literature on the pathological spectrum of lesions is scarce as, with a shift in the treatment paradigm, most small lesions of cavernous sinus are treated with radiosurgery. However, surgical management still plays a role for larger lesions and in radiologically ambiguous cases for planning the definitive management. Materials and Methods We retrospectively reviewed all surgically resected lesions of the cavernous sinus over the last two decades (1998-2019). The clinical presentation, neuroimaging features, and histopathological findings were reviewed. Lesions extending from sella and other adjacent areas were excluded. Results Thirty-eight cases of isolated cavernous sinus mass lesions were diagnosed over the last two decades (1998-2019). Cavernous hemangiomas (19 cases, 50%) constituted the most frequent pathology, followed by aspergilloma, meningioma, schwannoma, metastatic adenocarcinoma, chondrosarcoma, and chordoma. Overall, 29.4% (10/34) could not be accurately diagnosed on neuroimaging. Of these, four cases of cavernous hemangiomas were mistaken for either meningioma (three cases) or schwannoma (one case). Neither chordoma nor chondrosarcoma was suspected. Conclusion This is the first study in literature, enumerating the pathological and imaging spectrum of surgically resected cavernous sinus lesions. Cavernous hemangiomas, metastases and chordomas, and chondrosarcoma posed the greatest difficulty in diagnosis on neuroimaging and the reasons for the same are analyzed. In the context of clinical and neuroimaging discordance in diagnosis, pathological characterization becomes essential for appropriate and timely management.

Fibrous Dysplasia With Aneurysmal Bone Cyst Presenting as Sinonasal Mass.

Craniofacial involvement in fibrous dysplasia is a rare occurrence and complications of it are even rarer. Involvement of the sinonasal region can pose a challenge in both diagnosis and management. We hereby present a case of craniofacial fibrous dysplasia complicated with secondary aneurysmal bone cyst formation in a 15-year-old male patient.

An Unusual Perianal Presentation of a Tailgut Cyst.

Tailgut cysts or retrorectal cystic hamartomas are rare, congenital, development lesions arising from the remnants of the hindgut during embryogenesis. It is most often misdiagnosed due to its rarity, variable clinical presentation, and malignant potential. The following report describes an unusual case of a tailgut cyst in a 60-year-old male with a history of a perianal mass for 12 years. Surgical resection was done, and histopathological examination revealed a multiloculated cyst filled with brownish fluid, grossly, and a cyst lined by various epithelia such as stratified squamous epithelium, pseudostratified columnar epithelium, and flattened to cuboidal and mucin-secreting columnar epithelium along with cyst wall made up of bundles of smooth muscles, microscopically. Several lesions mimic a tailgut cyst and need to be excluded from the differentials. Although no malignancy was documented in this case, these cysts have been known to undergo malignant transformation into adenocarcinoma and neuroendocrine carcinoma, to name a few. This warrants a thorough and accurate histopathological assessment and mandatory follow-up.

Ex vivo-expanded human CD19+TIM-1+ regulatory B cells suppress immune responses in vivo and are dependent upon the TIM-1/STAT3 axis.

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.

Assessment of the perceived stress and burden of family caregivers of the head-and-neck cancer patients at a tertiary care cancer center: A cross-sectional study.

INTRODUCTION: Cancer is a major life-threatening disease and has an impact on both patients and their family members. Caring for cancer patients may lead to several levels of stress which may affect their own health as well as their quality of life. AIM: To assess the perceived stress and burden of family caregivers of head and neck cancer patients (HNC) attending cancer care centre at a tertiary care centre, Tamil Nadu. OBJECTIVES: To assess the perceived stress and the burden among caregivers of patients with head and neck cancer using the Perceived Stress Scale (PSS) and Caregiver Strain Index (CSI) respectively. MATERIALS AND METHOD: A Cross-sectional study was carried out for a period of three months among the caregivers of head and neck cancer patients at a cancer care centre, Madurai. A total of 200 caregivers were selected by Convenience sampling method. Data was collected using a pretested, self-structured, closed-ended questionnaire by face to face interview method. RESULTS: The study population consisted of Caregivers aged 21-60 years, mostly females (80%), spouses (54%), employed (57%) and uneducated (66%). Most of the caregivers were from lower socioeconomic status (66%) and those who are providing care for 1 to 6 months were more in number. In this study, 82% of caregivers reported high caregiver burden (CSI ≥7) and 67% of caregivers reported high stress (PSS ≥ 26 - 40). CONCLUSION: Caregivers are experiencing significant burden, particularly with respect to their physical and psychological well-being, economic circumstances, social and personal relationships.

Outcomes of MPFL reconstruction with tibial tubercle transfer for recurrent patellar instability with high grade trochlear dysplasia in Indian population.

BACKGROUND: Patellar instability is a painful condition which affects the quality of life and mobility of young individuals. The aim of this study is to observe the results of medial patello-femoral ligament reconstruction with hamstring autograft along with a modified Fulkerson osteotomy, for recurrent instability of patella with high-grade trochlear dysplasia in Indian population. MATERIALS & METHODS: We conducted a prospective observational study of 26 knees (21 patients) who attended our outpatient department from June 2014 to February 2019, with recurrent instability of the patella and high-grade trochlear dysplasia. All knees were treated with MPFL reconstruction with hamstring autograft and modified Fulkerson osteotomy. RESULTS: The mean follow-up period was 30 months (range: 24-50). The mean Lysholm scores improved from 49.9 (range: 30-63) preoperatively to 82.5 (range: 51-100) (p < 0.05), Kujala scores from 55.5 (36-67) to 85.9 (55-100) and International Knee Documentation Committee (IKDC) scores from 50.2 (31.6-62.3) to 82.9 (54.7-98.3) (p < 0.05) at 2 years follow-up. TT-TG distance decreased from 21.2 mm (18-25) to 11.6 mm (10-13) (p < 0.05) and patellar tilt angle decreased from 24.2° (18°-35°) to 7.2° (5°-10°) (p < 0.05). One knee had superficial skin infection in immediate post-operative period. Three knees had postoperative stiffness, which improved on manipulation under anesthesia. Six knees had implant irritation from the osteotomy screws which were removed after bony union was achieved. Functional scores were low in two knees due to patello-femoral pain, but they did not have recurrent instability. CONCLUSION: MPFL reconstruction with tibial tubercle transfer gives good functional outcomes in 92.3% patients with recurrent patellar instability, associated with high-grade trochlear dysplasia in Indian population.

Is Perls Prussian Blue Stain for Hemosiderin a Useful Adjunct in the Diagnosis of Vasculitic Neuropathies?

BACKGROUND: Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored. OBJECTIVE: We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)]. RESULTS: Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P < 0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%. CONCLUSION: These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity.

Role of bronchoscopy and imaging in long-standing foreign body bronchus presenting as recurrent or non-resolving lower respiratory tract infection.

INTRODUCTION: A long-standing retained foreign body in the bronchus is unusual. In majority of cases, an adequate history is not obtained, the clinical picture is usually clouded by superadded pathological changes. CASE SERIES: We report three cases of long-standing foreign body in the airway who presented with recurrent lower respiratory tract infection. Examination of respiratory system revealed no significant abnormality. Chest radiograph was normal. CT scan of the chest was useful to indicate endobronchial opacity in the airway suggestive of a foreign body. The patients underwent rigid bronchoscopy under general anesthesia for successful removal of the foreign body. CONCLUSION: So the patients with non-resolving or recurrent lower respiratory symptoms in spite of medical treatment and without any obstructive findings must undergo diagnostic bronchoscopy evaluation and imaging.

A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in†vivo Antidiabetic and Hypolipidemic Effects.

Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.

Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma.

Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID-19). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.

Declining tissue nicotinamide adenine dinucleotide (NAD) levels are linked to ageing and its associated diseases. However, the mechanism for this decline is unclear. Here, we show that pro-inflammatory M1-like macrophages, but not naive or M2 macrophages, accumulate in metabolic tissues, including visceral white adipose tissue and liver, during ageing and acute responses to inflammation. These M1-like macrophages express high levels of the NAD-consuming enzyme CD38 and have enhanced CD38-dependent NADase activity, thereby reducing tissue NAD levels. We also find that senescent cells progressively accumulate in visceral white adipose tissue and liver during ageing and that inflammatory cytokines secreted by senescent cells (the senescence-associated secretory phenotype, SASP) induce macrophages to proliferate and express CD38. These results uncover a new causal link among resident tissue macrophages, cellular senescence and tissue NAD decline during ageing and offer novel therapeutic opportunities to maintain NAD levels during ageing.

COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new pandemic infectious disease that originated in China. COVID-19 is a global public health emergency of international concern. COVID-19 causes mild to severe illness with high morbidity and mortality, especially in preexisting risk groups. Therapeutic options are now limited to COVID-19. The hallmark of COVID-19 pathogenesis is the cytokine storm with elevated levels of interleukin-6 (IL-6), IL-1ß, tumor necrosis factor-alpha (TNF-α), chemokine (C-C-motif) ligand 2 (CCL2), and granulocyte-macrophage colony-stimulating factor (GM-CSF). COVID-19 can cause severe pneumonia, and neurological disorders, including stroke, the damage to the neurovascular unit, blood-brain barrier disruption, high intracranial proinflammatory cytokines, and endothelial cell damage in the brain. Mast cells are innate immune cells and also implicated in adaptive immune response, systemic inflammatory diseases, neuroinflammatory diseases, traumatic brain injury and stroke, and stress disorders. SARS-CoV-2 can activate monocytes/macrophages, dendritic cells, T cells, mast cells, neutrophils, and induce cytokine storm in the lung. COVID-19 can activate mast cells, neurons, glial cells, and endothelial cells. SARS-CoV-2 infection can cause psychological stress and neuroinflammation. In conclusion, COVID-19 can induce mast cell activation, psychological stress, cytokine storm, and neuroinflammation.

Prevalence of work related musculoskeletal disorders among occupational bus drivers of Karnataka, South India.

BACKGROUND: Work-related health problems result in an economic loss of 4-6% in GDP (Gross domestic Product) of the most countries. In the industrialized countries, 1/3rd of the health-related absence to duty are due to musculoskeletal disorders. Professional driving is one such occupation which looks like sedentary occupation, but involves many risk factors that contribute to work-related musculoskeletal disorders (WMSD) due to its nature of working and work environment. This research describes the various risk factors associated with WMSDs and their effects on drivers health. OBJECTIVE: To assess the prevalence of WMSD and its associated risk factors among the bus drivers of Karnataka State Road Transport Corporation (KSRTC), Karnataka. METHODS: Subjects considered in this study are 301 full-time bus drivers from the central division KSRTC which consists of 6 depots in Bengaluru. Information regarding reported WMSD symptoms during immediate past 7 days to 12 months, the intervention of WMSD in their day-to-day life and the overall comfort of the body are determined through Standardized Nordic Questionnaire and also by direct observation. The survey questionnaire is conducted by face to face interview. FINDINGS: From the statistical analysis, it is found that around 55.8% of the study population has experienced WMSD. The prevalence of WMSD is most common in the age group of 29-39 years (53.5%) followed by the age group of >40 years. CONCLUSION: In this study, some of the work-related and lifestyle/health-related factors show significant association with WMSD in bus drivers of Karnataka. Musculoskeletal disorders can be prevented by designing the driver's workspace ergonomically so that the design suits to all sorts of drivers and the drivers should also be trained on basics of vehicle ergonomics (posture, seat adjustments, in-vehicle controls adjustments). INTERPRETATION: KSRTC should educate drivers on the basics of vehicle ergonomics, harmful use of tobacco/alcohol, unhealthy food habits and also to involve in physical exercise at least 75-150 mins weekly. If not, the trend of drivers suffering from WMSD belonging to mid-age will increase exponentially. SCOPE FOR FUTURE WORK: Statistical result and direct observation insist on undertaking further studies on ergonomic interventions at driver's cabin, lifestyle/occupational health factors which mitigate WMSD in different parts of the body during driving.