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Prostate cancer (PC) depicts a major health challenge all over the globe due to its complexities in the treatment and diverse clinical trajectories. Even in the advances in the modern treatment strategies, the spectrum of resistance to the therapies continues to be a significant challenge. This review comprehensively examines the underlying mechanisms of the therapy resistance occurred in PC, focusing on both the tumor microenvironment and the signaling pathways implicated in the resistance. Tumor microenvironment comprises of stromal and epithelial cells, which influences tumor growth, response to therapy and progression. Mechanisms such as microenvironmental epithelial-mesenchymal transition (EMT), anoikis suppression and stimulation of angiogenesis results in therapy resistance. Moreover, dysregulation of signaling pathways including androgen receptor (AR), mammalian target of rapamycin/phosphoinositide 3 kinase/AKT (mTOR/PI3K/AKT), DNA damage repair and Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways drive therapy resistance by promoting tumor survival and proliferation. Understanding these molecular pathways is important for developing targeted therapeutic interventions which overcomes resistance. In conclusion, a complete grasp of mechanisms and pathways underlying medication resistance in PC is important for the development of individualized treatment plans and enhancements of clinical outcomes. By studying and understanding the complex mechanisms of signaling pathways and microenvironmental factors contributing to therapy resistance, this study focuses and aims to guide the development of innovative therapeutic approaches to effectively overcome the PC progression and improve the survival rate of patients.

Introduction: Chronic Ankle Instability (CAI) is an injury that presents persistent instability and “giving way” symptoms. The higher rate of reinjury following an initial Lateral Ankle Sprain (LAS) is associated with the development of CAI, which affects athletic and functional performance. Impairment of musculotendinous receptors following an initial ankle sprain may result in recurrent ankle instability. Some studies have suggested an association between CAI and issues with static and dynamic balance. Comparisons of static balance between recreational badminton and volleyball players and dynamic balance between recreational badminton and volleyball players with CAI are required to provide athletes with the proper balance training exercises. Aim: To analyse the static balance of badminton and volleyball recreational players with CAI using the Balance Error Scoring System (BESS) and a Plantar Pressure Analysis System (PPAS), as well as the dynamic balance of those players using the Y Balance Test (YBT). Materials and Methods: A cross-sectional study was conducted where recreational players with CAI who play badminton and volleyball were screened using the Cumberland Ankle Instability Tool (CAIT), and 46 participants were selected based on inclusion and exclusion criteria. The study was conducted in the indoor and outdoor stadiums of NITTE (Deemed to be University), Mangaluru, Karnataka, India. The study duration was from March 2023 to March 2024. Ethical clearance was obtained from the same university for the study. Following this, static and dynamic balance of each group was assessed using BESS (number of errors), PPAS (sway velocity), and YBT (distance reached by the limb). The static balance between the groups and dynamic balance between the groups were analysed in Jamovi software using independent sample t-test. Results: Following the analysis, static balance between badminton and volleyball recreational players using BESS showed a non significant difference with a p-value of 0.282, while PPAS showed non significant differences with p-values of 0.174 for double leg stance and 0.063 for single leg stance. Similarly, dynamic balance between badminton and volleyball recreational players using YBT showed non significant differences with p-values of 0.467, 0.768, and 0.299 for anterior, posteromedial, and posterolateral directions, respectively. Conclusion: The study concluded that there was no significant difference in static as well as dynamic balance between badminton and volleyball recreational players with CAI. However, it is important to evaluate the static and dynamic balance of recreational players to enhance performance and prevent injuries.

Background: Standard treatment workflows (STWs) indeed play a crucial role in enhancing healthcare delivery by providing structured guidelines for managing prevalent diseases. These guidelines are particularly beneficial in primary and secondary healthcare settings, where they help standardize treatment protocols, streamline referrals, and ultimately improve healthcare efficiency. Methods: Indian Council of Medical Research, in collaboration with the National Health Authority and the World Health Organisation India country office developed the STWs. The broad medical specialities were identified and speciality expert groups each of 5–12 experienced members led by an eminent chairperson were constituted. Priority disease conditions were identified and the speciality experts deliberated on the evidence available for various recommendations and developed the content for the STW. These were then converted to a one-pager infographic. The draft STWs were reviewed by relevant experts for internal and external validation of content. Results: 125 STWs in 23 specialties have been developed. Conclusion: STWs are one-page summaries of clinical guidelines designed to improve healthcare delivery in India. Training healthcare profesionals and collaboration with medical bodies are crucial for successful implementation. This can ensure standardized, evidence-based care throughout India's healthcare system.

Hirayama Disease (HD) is a type of localised amyotrophy that mostly affects motor neurons. It is benign, self-limiting, and does not progress. It is not the same as distal limb juvenile muscular atrophy, which is a symptom of motor neuron disease. Together with other immunological and physical variables, cervical cord compression, particularly during cervical flexion, is one cause of HD. Over three to five years, the illness usually worsens progressively, resulting in wasting and distal weakness in one or both upper extremities. In addition, patients may experience cold paralysis, coarse finger tremors, and non specific sensory loss. Hereby, the authors present a case report of a 22-year-old male who had been steadily developing right upper extremity weakness for three years was evaluated in the Outpatient Department. The physical examination revealed atrophy of the right forearm muscle, reduced range of motion in right wrist flexion and extension, weak wrist extensors, finger extensors, supinator muscles of the forearm, and shoulder flexors. As HD does not have a well-defined physiotherapy protocol, tailor-made treatment was given for four weeks aimed at improving upper extremity muscle strength and overall hand function. The present case report will aid the physiotherapists understand the assessment and treatment of HD.

Millions of patients’ lives have been improved by orthopaedic implants. Joint replacement surgery has helped to relieve pain and improve function, while fracture fixation implants promote faster bone healing, resulting in a quicker return to daily activities. The use of more wear-resistant bearing surfaces has increased the longevity of artificial joints. As with any implant, special attention must be paid to the material and design used to create the implants; otherwise, bone fractures or defects may occur, and bone healing may not occur at all. This review highlights the parameters of implant design, the different biomaterials used in implants, and the types of implants, along with their biomechanics. The review provides a brief explanation of the factors involved in designing an implant, the materials used to manufacture it, and the biomechanical principles behind the most common types of implants.

Introduction: Sacroiliac Joint Dysfunction (SIJD) refers to a condition that causes pain and discomfort, commonly due to dysfunction of the Sacroiliac Joint (SIJ). It is a plausible source of Low Back Pain (LBP). Static palpation tests, motion palpation, and pain provocation tests are mostly employed to check for SIJD. Aim: To determine the commonly used tests in the assessment of SIJD by physiotherapists. Materials and Methods: A cross-sectional Questionnaire-based study was conducted among physiotherapists in India from November 2022 to April 2023 at the Nitte Institute of Physiotherapy, NITTE (deemed to be University), Mangalore, Karnataka, India. The study included physiotherapists specialising in orthopaedics and obstetrics and gynaecology. The practitioners’ years of experience were considered. An online survey was conducted using a questionnaire developed to determine the frequently used bony landmark for checking SIJ asymmetry, commonly affected structures, and commonly used motion palpation and pain provocation tests for examining SIJD. Questionnaires were sent to at least 100 physiotherapists, and 72 responses were included in the study. Data was collected and analysed using descriptive statistics: frequency and percentage. Data analysis was performed using Statistical Package for Social Sciences (SPSS) software version 26.0. Results: Seventy-two practitioners responded to the online survey. The commonly assessed bony landmark was the Posterior Superior Iliac Spines (PSIS) with 52 responses (28%). The most frequently preferred motion palpation examination test was the compression test with 36 responses (17.2%). Tenderness or tissue texture change was mainly checked at the PSIS with 54 responses (37.8%), and the commonly used pain provocation tests were the thigh thrust test and supine SIJ springing test with 46 responses (26.6%). Conclusion: According to this study, many physiotherapists employed diagnostic techniques congruent with Mitchell’s model, but they also frequently added additional motion tests, measured tenderness, and used pain provocation techniques. Most preferred the ASIS compression and thigh thrust tests to assess SIJD.

Carpal Tunnel Syndrome (CTS) is one of the preeminent types of peripheral neuropathies of the upper limb, where the median nerve is injured in the carpal tunnel, leading to a cascade of symptoms. CTS can cause pain, substantial motor function and sensory impairment, and a weakened ability to perform skilled work. Utilising the Neurodynamic Technique (NDT), a hands-on manual therapy approach can effectively address CTS. This technique focuses on manipulating neural tissues and the adjacent non-neural structures related to the nervous system, to alter pain physiology. The current narrative review aimed to ascertain the effectiveness of NDT in the management of CTS so that it can guide the practitioners in effectively managing and understanding CTS and also help in adding the literature to the existing evidence. The review evaluated outcome measures such as pain intensity, motor issues, physical function, and nerve conduction investigations. The review was done to demonstrate that NDT can offer significant therapeutic advantages and can serve as a practical approach to managing CTS.

Introduction: Knee Osteoarthritis (OA) is a common degenerative joint disease that affects millions of people worldwide. It is characterised by progressive loss of joint cartilage, resulting in pain, stiffness, and significant disability, leading to a reduced quality of life. Fear of pain is a significant psychosocial factor that affects individuals with knee OA, leading to decreased physical activity. However, the relationship between Toe Grip Strength (TGS) and fear of pain in individuals with knee OA is poorly understood, even though fear of pain has been known to impact strength in both the upper and lower limbs. Aim: To examine the correlation between fear and TGS among individuals with knee OA, both with and without fear of pain. Materials and Methods: This cross-sectional study was conducted at the Department of Physiotherapy, Nitte Institute of Physiotherapy, affiliated with the University of Mangalore, Karnataka, India, from April 2022 to March 2023. The study included 60 individuals, with 30 in each group, diagnosed with knee OA using the Kellgren and Lawrence (KL) grading system (grade 2 and above). The participants, both men and women aged between 45 and 80 years, were informed about the study’s purpose. The Fear Avoidance Belief Questionnaire (FABQ) form was completed by the screened patients, who were then divided into fear and non fear groups. Body Mass Index (BMI) was determined by measuring height with a wall-mounted device and weight using a traditional analog scale. TGS was evaluated in both groups using a pinch grip dynamometer. The Pearson correlation coefficient was used for data analysis, with a p-value 0.05) with TGS (both right and left-side) (r: -0.296 (right) and -0.302 (left)), and a positive correlation (p-value

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC.

Summary: This study investigates the role of integrin β4 (ITGB4) and stemness-associated factor SOX2 in platinum resistance in lung squamous cell carcinoma (LUSC). The expression of SOX2 and ITGB4 is found to be high in all LUSC subtypes, but the impact of ITGB4 expression on overall patient survival varies by subtype. Cancer stem cells (CSCs) isolated from LUSC patients were found to be resistant to cisplatin, but knocking down ITGB4 or SOX2 sensitized them to cisplatin. Carfilzomib (CFZ) synergized with cisplatin and suppressed CSC growth by inhibiting ITGB4 and SOX2 expression. Additionally, CFZ was found to inhibit SOX2 expression epigenetically by inhibiting histone acetylation at the SOX2 promoter site. CFZ also suppressed the growth of SOX2-dependent small cell lung cancer cells in vitro and in vivo. The study highlights the unique function of CFZ as a transcriptional suppressor of SOX2, independent of its proteasome inhibitory function.

Introduction: Continuous texting is associated with more stress on the thumb, which may cause the onset of a variety of wrist and thumb conditions. Today’s youth spend the majority of their time on smartphones, which might cause texting thumb symptoms to occur. As there is a lack of a questionnaire that can evaluate their awareness and views, this was the first study that develops as well as evaluates the validity and reliability of a self-designed questionnaire. Aim: To assess the validity and reliability of a self-designed questionnaire that measured knowledge and perception of Short Message Service (SMS) Thumb. Materials and Methods: This cross-sectional pilot survey was conducted in Mangalore, Karnataka, India from June 2022 to July 2022. Validity and reliability were performed in two sections. A panel of four experts reviewed the questionnaire’s content validity to determine its Content Validity Index (CVI), while reliability was performed by using test-retest reliability method which was carried out through an online survey among 31 young individuals with the inclusion criteria of non medical students aged between 18 to 25 years. CVI was used to analyse the questionnaire’s validity. Test-retest statistical analysis was performed by Statistical Package for the Social Sciences (SPSS Inc; Chicago, IL), Version 26.0 and internal consistency were used to assess the reliability. Pearson correlation was used to perform the reliability. Results: The item Content Validity Index (i-CVI) of the questionnaire was 1.00 for 20 of the 25 questions, while the average scale CVI of the questionnaire was 0.95. Test-retest reliability and internal consistency were both evaluated using Cronbach’s alpha coefficient and Pearson’s correlation ratio, respectively. The questionnaire was significantly reliable with a p-value

Introduction: The ability of the visual system to coordinate the information acquired from the eyes to control, and guide the hands in completing a task is known as hand-eye coordination. The typical hand-eye coordination involves the synergistic function of numerous sensorimotor systems, including the visual system, vestibular system, and proprioception, as well as the head, eye, and arm control systems. Aim: To investigate which gender is superior and efficient in learning hand-eye coordination using the mirror drawing task. Materials and Methods: A cross-sectional study was conducted at a tertiary care hospital, Mangalore, Karnataka, India from April 2020 to April 2021 involving a total of 90 young adults divided into two groups of 45 males (group A) and 45 females (group B). A mirror drawing task was given to each student with four trials and two minutes rest in between the trials. Subjects were expected to trace a shape, most typically a polygon while only seeing the upturned reflection of their hand in a mirror and staying within the confines of a double boundary using a mirror drawing test. The number of errors, time taken to complete the task, and efficiency index of each student was calculated manually using the efficiency index formula and compared between the two groups. Results: Total 90 participants were included with a mean age of 21.2 and 21.8 years for group A and group B, respectively. Group A (males) showed a greater efficiency index (5.52±2.29) when compared to group B (females) (4.61±1.77) (p-value-0.039). The Spearman’s ratio of mean error and mean time was 0.575 in males and 0.483 in females. Conclusion: The males outperformed in efficiency index when compared to females in hand-eye coordination with repeated practice. The study concluded that males were having greater efficiency index and less number of errors and less time taken compared to females.

Introduction: Reduced Toe Grip Strength (TGS) is associated with an increased risk of knee pain. In India, toe grip is rarely examined and examination of TGS lacks quantifiable values. The pinch gauge dynamometer is an instrument/tool which is apposite in the assessment of grip strength. The present study is a first of its kind to establish the reliability of pinch gauge dynamometer in assessing TGS. Aim: To evaluate intrarater and inter-rater reliability of pinch gauge dynamometer in measuring TGS. Materials and Methods: This cross-sectional study was conducted at the Department of Physiotherapy, Deemed to be the University of Mangalore, Karnataka, India during the 1st week of August 2022. Out of 30 individuals, 15 were males and 15 were females. TGS was assessed using a pinch gauge dynamometer. For data analysis, the mean of the three trials was used and the reliability test was calculated using the Intraclass Correlation Coefficient (ICC). The level of significance was set at 5%. Results: Intrarater reliability showed ICC scores of 0.991 and 0.985 for both right and left feet, and inter-rater reliability showed scores of 0.985 and 0.977, respectively. In the female group inter-rater agreement on right side pinch strength was 0.923 and left side was 0.924. Among males inter-rater agreement, right side ICC score was 0.983 and left side was 0.967 between the raters. Conclusion: The pinch gauge dynamometer is reliable for measuring TGS with excellent intra and inter-rater reliability values.

Aims: The indigenously developed Indian Council of Medical Research (ICMR)-NIV COVID Kavach IgG enzyme linked immunosorbent assay (ELISA) has been recommended for seroprevalence among vulnerable populations in India, which provided essential services throughout the lockdown. The staff working in the High Court was one such group. We compared anti-SARS-CoV-2 IgG seropositivity among the staff of Jodhpur and Jaipur High Courts, Rajasthan, India. Methods: Asymptomatic judiciary staff of Jodhpur and Jaipur benches of High Courts were enrolled after informed written consent. A questionnaire was filled and 3–5 ml venous blood was collected from participants. The ICMR-NIV COVID Kavach IgG ELISA and EUROIMMUN IgG ELISA were used for detection of Anti-SARS-CoV-2 IgG antibodies. Results: A total of 63 samples (41 from Jodhpur and 22 from Jaipur) were collected between 28th July to 4th August 2020. The overall anti-SARS-CoV-2 IgG seroprevalence was found to be 6.35%. Seropositivity was higher among the staff from Jaipur (13.64%) as compared to Jodhpur (2.44%). The Kavach ELISA results were in complete agreement with EUROIMMUN ELISA. The infection control measures were deemed effective. Conclusion: Seroprevalence among the staff of Jodhpur High Court was found to be lower than Jaipur, reflecting higher susceptibility to COVID-19 in the former. Many offices worldwide are closed till mid 2020 but need to come up with pre-emptive policies eventually. This study may help to anticipate the possible challenges when other government/private offices start functioning. The infection control practices of one workplace may help formulate guidelines for other offices.

Development of rapid, reliable, and easy diagnostic tests with high-throughput is the need of the hour for laboratories combating the COVID-19 pandemic. While real-time polymerase chain reaction (RT-PCR) is the gold standard for diagnosing active infections, it is expensive and time-consuming. Serological diagnostic assays with a premise to aid rapid contact tracing, immune status determination, and identification of potential convalescent plasma donors hold great promise. Timely diagnosis, effective treatment, and future prevention are key to management of COVID-19.

Histoplasmosis is a systemic fungal disease caused by dimorphic fungus Histoplasma capsulatum and is more common in immunocompromised patients. We report two cases of disseminated histoplasmosis in immunocompetent individuals from a non-endemic zone in Western India. Rapid diagnostic tests like urinary antigen detection and molecular assays comprise the need of the hour as early initiation of antifungal therapy can be life-saving. Clinicians need to be aware of this entity to prevent misdiagnosis and initiate prompt effective management.

Summary: The tyrosine kinase receptor ephrin receptor A2 (EPHA2) is overexpressed in lung (LSCC) and head and neck (HNSCC) squamous cell carcinomas. Although EPHA2 can inhibit tumorigenesis in a ligand-dependent fashion via phosphorylation of Y588 and Y772, it can promote tumorigenesis in a ligand-independent manner via phosphorylation of S897. Here, we show that EPHA2 and Roundabout Guidance Receptor 1 (ROBO1) interact to form a functional heterodimer. Furthermore, we show that the ROBO1 ligand Slit Guidance Ligand 2 (SLIT2) and ensartinib, an inhibitor of EPHA2, can attenuate growth of HNSCC cells and act synergistically in LSCC cells. Our results suggest that patients with LSCC and HNSCC may be stratified and treated based on their EPHA2 and ROBO1 expression patterns. Although ~73% of patients with LSCC could benefit from SLIT2+ensartinib treatment, ~41% of patients with HNSCC could be treated with either SLIT2 or ensartinib. Thus, EPHA2 and ROBO1 represent potential LSCC and HNSCC theranostics.

Biliary tract shows a large number of anatomic variations and duplication of the gallbladder (GB) is a rare congenital anomaly. Although it is very often detected incidentally, it may present with complications due to gall stone disease. Careful identification of this anomaly on imaging is important to prevent any serious surgical complications. We here report a case of duplicated GB in a 26-year-old male, who presented with right hypochondriac pain and detected to have two GB on magnetic resonance imaging (MRI).

Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. Emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells, when co-cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit a ‘persister-like’ behavior and are attenuated by sensitive cells; they also appear to ‘educate’ sensitive cells to evade chemotherapy. Further, tolerant cells can switch phenotypes to become sensitive, especially at low cisplatin concentrations. Finally, switching treatment from continuous to an intermittent regimen can attenuate the emergence of tolerant cells, suggesting that intermittent chemotherapy may improve outcomes in lung cancer.

We describe the construction and phenotypic analysis of a human embryonic stem cell model of progressive Aβ-dependent neurodegeneration (ND) with potential relevance to Alzheimer’s disease (AD). We modified one allele of the normal APP locus to directly express a secretory form of Aβ40 or Aβ42, enabling expression from this edited allele to bypass the normal amyloidogenic APP processing pathway. Following neuronal differentiation, edited cell lines specifically accumulate intracellular aggregated/oligomeric Aβ, exhibit a synaptic deficit, and have an abnormal accumulation of endolysosomal vesicles. Edited cultures progress to a stage of overt ND. All phenotypes appear at earlier culture times for Aβ42 relative to Aβ40. Whole transcriptome RNA-Seq analysis identified 23 up and 70 down regulated genes (differentially expressed genes) with similar directional fold change but larger absolute values in the Aβ42 samples suggesting common underlying pathogenic mechanisms. Pathway/annotation analysis suggested that down regulation of extracellular matrix and cilia functions is significantly overrepresented. This cellular model could be useful for uncovering mechanisms directly linking Aβ to neuronal death and as a tool to screen for new therapeutic agents that slow or prevent human ND.

Immunocompromised patients are predisposed to a variety of infections due to both common and uncommon pathogens. Achromobacter xylosoxidans, is an opportunistic pathogen most commonly encountered among immunocompromised patients. The authors report two cases of pulmonary infection due to A. xylosoxidans for the first time from this geographical area. First case is a 55-year-old diabetic female with pulmonary tuberculosis and second case is a 67-year-old male with Chronic Obstructive Pulmonary Disease (COPD). Alertness and rapid diagnosis led to favourable outcome in both these cases.

Introduction: Shoulder Impingement Syndrome (SIS) is one of the common cause of shoulder ailment which leads to pain and restriction of the movements. Though Mobilisation with Movement and cryotherapy, both are found to be effective in managing SIS, there is no comparison done between the two treatments. Aim: To compare the effectiveness of Mobilisation With Movement (MWM) and cryotherapy in SIS. Materials and Methods: A randomised clinical trial was conducted on 22 subjects who aged between 18-64 years, and those who had a positive painful arc, three positive tests out of five i.e., Neer’s Impingement, Hawkin’s Kennedy, Jobe’s, Speed and Gerber test. These subjects were randomised using block randomisation method and allocated to one of the two groups receiving treatment of MWM or cryotherapy, along with impairment based exercises for six sessions. Outcome measures included reporting of pain on the Visual Analogue Scale (VAS), Range of Motion (ROM) and Shoulder Pain and Disability Index (SPADI). A blinded assessor inscribed the outcome measures prior to the intervention, immediately after the intervention on the first day (except SPADI) and also on the sixth-day posts the intervention. The data were analysed using Wilcoxon Signedrank test for within the group analysis and Mann-Whitney U test was used to analyse data between the groups. Results: There was a significant reduction in pain and disability scores and improvement in ROM in both the groups after six treatment sessions (p

Introduction: Sacroiliac Joint (SIJ) is a familiar nociceptive source of Low Back Pain (LBP). Patients with SIJ pain commonly present with tenderness around the Posterior Superior Iliac Spine (PSIS) which can be recorded by using pressure pain algometer. Mechanical Diagnosis and Therapy (MDT) is a manual therapy technique which uses repetitive movements to assess and treat the dysfunction. MDT is found to be effective in treating SIJ pain; however, its effect on Pain Pressure Threshold (PPT) is not yet determined. Aim: To determine the effect of Mechanical Diagnosis and Therapy on Pain Pressure Threshold in Sacroiliac Joint pain. Materials and Methods: A total of 25 subjects with unilateral LBP of age group 20-65 years participated in the study. Subjects with the direction of preference, pain around the PSIS, positive on two out of four pain provocation tests were included in the study. These patients were given 30 repetitions of either anterior or posterior rotation of the innominate, for four sessions. PPT and Visual Analogue Scale (VAS) were used to measure the effect of treatment. Data were analysed by using paired t-test. Results: There was a significant improvement seen (p

Loss of Muscleblind-like 1 (Mbnl1) is known to alter Clc-1 splicing to result in myotonia. Mbnl1ΔE3/ΔE3/Mbnl3ΔE2 mice, depleted of Mbnl1 and Mbnl3, demonstrate a profound enhancement of myotonia and an increase in the number of muscle fibers with very low Clc-1 currents, where gClmax values approach ~1 mS/cm2, with the absence of a further enhancement in Clc-1 splice errors, alterations in polyA site selection or Clc-1 localization. Significantly, Mbnl1ΔE3/ΔE3/Mbnl3ΔE2 muscles demonstrate an aberrant accumulation of Clc-1 RNA on monosomes and on the first polysomes. Mbnl1 and Mbnl3 bind Clc-1 RNA and both proteins bind Hsp70 and eEF1A, with these associations being reduced in the presence of RNA. Thus binding of Mbnl1 and Mbnl3 to Clc-1 mRNA engaged with ribosomes can facilitate an increase in the local concentration of Hsp70 and eEF1A to assist Clc-1 translation. Dual depletion of Mbnl1 and Mbnl3 therefore initiates both Clc-1 splice errors and translation defects to synergistically enhance myotonia. As the HSALR model for myotonic dystrophy (DM1) shows similar Clc-1 defects, this study demonstrates that both splice errors and translation defects are required for DM1 pathology to manifest. Research in context: Research in context: Myotonic Dystrophy type 1 (DM1) is a dominant disorder resulting from the expression of expanded CUG repeat RNA, which aberrantly sequesters and inactivates the muscleblind-like (MBNL) family of proteins. In mice, inactivation of Mbnl1 is known to alter Clc-1 splicing to result in myotonia. We demonstrate that concurrent depletion of Mbnl1 and Mbnl3 results in a synergistic enhancement of myotonia, with an increase in muscle fibers showing low chloride currents. The observed synergism results from the aberrant accumulation of Clc-1 mRNA on monosomes and the first polysomes. This translation error reflects the ability of Mbnl1 and Mbnl3 to act as adaptors that recruit Hsp70 and eEF1A to the Clc-1 mRNA engaged with ribosomes, to facilitate translation. Thus our study demonstrates that Clc-1 RNA translation defects work coordinately with Clc-1 splice errors to synergistically enhance myotonia in mice lacking Mbnl1 and Mbnl3.

Aims and objective: To develop novel immunodiagnostic test for tuberculosis. Methods: The selected novel proteins named as Rv2145c (SS1), Rv1437 (SS2), Rv1827 (SS3), and Rv2970c (SS4) were cloned, expressed and purified under specific conditions. Additionally, monoclonal antibodies (mAbs) were developed using these recombinant antigens via hybridoma technology. Hybridoma clones were screened and positive clones were selected for further experiment. The mAbs were purified from cell culture supernatant using protein A/G column chromatography. The diagnostic potential of these recombinant antigens and mAbs were investigated using a well characterized cohort of tuberculosis patients (Pulmonary-TB, Extra-pulmonary, MDR-TB) and healthy subjects sera using ELISA. Monoclonal antibodies (mAbs) raised against these antigens were used to detect the mycobacterial antigens. Result The selected recombinant antigens showed superior activity in the developed TB detection test. The observed sensitivity was 98.6% (SS4), 97.9% (SS1), 97.1% (SS3) and 92.7% (SS2), whereas specificity was 100% (SS1), 98.2% (SS4), 93.6% (SS3) and 87.5% (SS2). The purified mAbs also demonstrated good activity in the diagnosis of TB. Conclusion: The novel recombinant antigens and mAbs generated against these antigen showed very good activity for the immunodiagnosis of TB. The combination of these recombinant antigens and mAbs could be used as novel biomarker for detection of active TB directly from patient sera.