Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display.

TNF superfamily death ligands are expressed on the surface of immune cells and can trigger apoptosis in susceptible cancer cells by engaging cognate death receptors. A recombinant soluble protein comprising the ectodomain of Apo2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has shown remarkable preclinical anticancer activity but lacked broad efficacy in patients, possibly owing to insufficient exposure or potency. We observed that antibody cross-linking substantially enhanced cytotoxicity of soluble Apo2L/TRAIL against diverse cancer cell lines. Presentation of the ligand on glass-supported lipid bilayers enhanced its ability to drive receptor microclustering and apoptotic signaling. Furthermore, covalent surface attachment of Apo2L/TRAIL onto liposomes--synthetic lipid-bilayer nanospheres--similarly augmented activity. In vivo, liposome-displayed Apo2L/TRAIL achieved markedly better exposure and antitumor activity. Thus, covalent synthetic-membrane attachment of a cell-surface ligand enhances efficacy, increasing therapeutic potential. These findings have translational implications for liposomal approaches as well as for Apo2L/TRAIL and other clinically relevant TNF ligands.

Randomized controlled trial investigating the role of yoga at workplace in improving fatigue, burnout, pain, strength, and quality of life among blue-collar workers.

BACKGROUND: Due to the physical demands of work, blue-collar workers (BCW) frequently experience fatigue, musculoskeletal pain, and burnout. The purpose of this study was to determine the feasibility and utility of introducing yoga-based loosening exercises (YLE) at the workplace for improving fatigue, musculoskeletal pain, and burnout among BCW. MATERIALS AND METHODS: One hundred and twenty-eight BCW were randomized into a yoga group that received 40 minutes of supervised YLE daily, 5 days a week, for 1 month, followed by 1 month of unsupervised practice at home or a waitlisted control group. The Chalder Fatigue Scale (CFS), Visual Analog Scale for pain, Oldenburg Burnout Inventory (OLBI), sit-and-reach test (SRT), handgrip strength dynamometer, and the Short Form-8 (SF-8) questionnaire were measured at baseline, at the end of the first month, and at follow-up after the first month. RESULTS: All the participants adhered well to the YLE (≈86% at the workplace, ≈70% at home). Compared to the controls, the yoga group reported significant reductions in fatigue, pain, and burnout and significant improvements in flexibility, strength, and quality of life (P < 0.001) at all the time points. CONCLUSION: Our findings demonstrate that workplace yoga programs for BCW are feasible and can considerably reduce fatigue, pain, and burnout and improve their quality of life.

Lifestyle medicine approach in managing pemphigus vulgaris: A case report.

A 58-year-old female presented to a lifestyle medicine clinic in 2019 with a one-year history of pemphigus vulgaris (PV) and having itching, burning sensations, and bulla formation all over her body. She further had a recent diagnosis of type 2 diabetes mellitus and also complained of malaise, indigestion, and anxiety due to her skin condition. She was on methyl prednisolone, metformin, and other herbal supplements for 1 year to control her PV and diabetes. Laboratory investigations revealed the presence of autoantibodies Desmoglein 1 and 3 with titers of 3.26 and 3.5, respectively.The patient underwent a yoga & naturopathy-based lifestyle modification program for a period of 53 days in 2019, followed by 10 days in 2020 and 15 days in 2021, and subsequent follow-up measures. This included hydrotherapy, yoga, a vegetarian diet, herbal preparations, massage, etc. By the end of 2020, the patient was tapered from all medications, and there was complete remission from PV. Given the multidimensional impact of PV, a holistic, patient-centered lifestyle approach as described in this case may be beneficial in managing PV. Further research is warranted in this area.

Impact of COVID-19 vaccines on the health status of young female adults from India: A cross-sectional study.

Purpose: Reports suggest that females experience more adverse events post-coronavirus disease 2019 (COVID-19) vaccination compared to males. However, no gender-specific data on the impact of vaccines on the Indian population are available. The present study was intended to understand the impact of COVID-19 vaccines on the health status of young Indian female adults and to identify the factors associated with experiencing adverse events post-vaccination. Methods: A web-based survey was conducted among 433 young female adults who have taken at least one dose of the COVID-19 vaccine. The prevalence and duration of systemic and generalized symptoms were analyzed using descriptive statistics. The factors associated with symptoms post-vaccination were analyzed using binary logistic regression. Adjusted odds ratios and 95% confidence intervals were computed. A P value of ≤ 0.05 was considered to be statistically significant. Results: Of the 404 surveys returned (93.3%), 371 respondents have received both vaccine doses. COVISHIELD™ was the vaccine of choice among 73% of respondents and nearly 91% of the respondents reported a re-infection post-vaccination. At least one form of the symptom as a side effect of vaccination was experienced by 88.4% (n = 357) of the participants. This included generalized symptoms (77.5%) followed by musculoskeletal (53.2%), localized (38.9%), psychological (35.1%), gastrointestinal (25.5%), gynecological (24%), and endocrine symptoms (22.5%). Presence of chronic ailments was significantly associated with experiencing localized symptoms (OR 2.21, 95% CI 1.25-3.91), psychological symptoms (OR 2.41, 95% CI 1.34-4.34), neurological symptoms (OR 2.98, 95% CI 1.38-6.46), gastrointestinal symptoms (OR 4.76, 95% CI 2.59-8.75), respiratory symptoms (OR 2.45, 95% CI 1.29-4.67), endocrine symptoms (OR 2.92, 95% CI 1.58-5.38), and gynecological symptoms (OR 4.05, 95% CI 2.21-7.44). Older than 21 years was significantly associated with the experience of gynecologic symptoms (OR 2.12, 95% CI 1.24-3.64). Not being re-infected post-vaccination has lower odds of experiencing psychological, gastrointestinal, and respiratory symptoms. Conclusion: Our result suggests serious planning and counseling are warranted while disseminating COVID-19 vaccination among young female adults especially those with comorbidities to foster trust and coverage.

Characteristics of patients who use yoga for pain management in Indian yoga and naturopathy settings: a retrospective review of electronic medical records.

Objectives: The aim of this study is to identify the characteristics of patients who underwent yoga therapy for pain in yoga and naturopathy clinical settings in India. Methods: Electronic medical records of patients who received yoga therapy for pain in three inpatient yoga and naturopathy hospitals were reviewed retrospectively from January 2021 to September 2022. Demographic characteristics and details on pain condition, socioeconomic status, comorbidities, ancillary therapies received, and insurance status were collected. In addition, we prospectively collected data on adherence to yoga practice through a telephonic interview. Results: A total of 984 patients were identified from a pool of 3,164 patients who received yoga therapy for pain for an average of 9.48 (1.13) days. Patients aged between 8 and 80 underwent therapy for varying pain conditions and diseases that include pain in the extremities, pain due to infection, trauma, degenerative diseases, autoimmune diseases, and spine and neurological diseases. The majority of the patients were females (66.3%), from middle class families (74.8%), and who did not have any insurance coverage (93.8%). Most of the patients were under naturopathy treatment (99.8%), followed by ayurveda (56%), and physiotherapy (49.3%), along with yoga therapy. All patients reported a significant reduction in pain post-integrated yoga therapy (p < 0.001). Adherence to yoga was significantly associated with underlying pain conditions, the presence of comorbidities, the types of therapies used, and socioeconomic status (p < 0.001). Conclusion: This study highlights the real-time application of yoga in pain management in Indian yoga and naturopathy settings, as well as implications for future research.

Effect of health education-based yoga & naturopathy lifestyle interventions on personality of patients with non-communicable diseases: A randomized controlled trial.

BACKGROUND: Personality traits play a role in the progression and management of chronic diseases. However, a change in personality is seldom considered an outcome in the management of chronic diseases. The present study explored if a health education-based yoga & naturopathy lifestyle intervention group (HYNLG) can induce change in the personality traits, vitality, quality of life (QoL), and satisfaction in patients with non-communicable diseases compared to a therapy-centric yoga & naturopathy lifestyle intervention (TYNLG). METHODS: This randomized control trial included 56 participants who were equally randomized into the HYNLG and TYNLG groups. Both groups received a 10-day inpatient regimen that included hydrotherapy, mud therapy, diet therapy, supervised fasting, sunbathing, acupressure, and massage therapy. Additionally, HYNLG received a 10-day orientation (1 h/d) on concepts centered around belief systems, lifestyle changes, and their impact on health. Vedic Personality Inventory, SF-12 QoL questionnaire, visual analog scale, Hamilton Anxiety Inventory, and Visit-Specific Patient Satisfaction Questionnaire were used as outcome measures. The changes between the time points were analyzed using parametric and non-parametric tests, and Pearson correlation was used to investigate the association between the variables. RESULTS: The Sattva (balance and stability) personality trait has significantly increased in HYNLG, while the Rajas (activity and imbalance) and Tamas (inertia and dullness) personalities have decreased. HYNLG also demonstrated a significant improvement in mental QoL, vitality, anxiety reduction, and patient satisfaction when compared to TYNLG. CONCLUSION: These findings may have serious clinical and public health implications as they provide insights on the usefulness of introducing a health education component into lifestyle modification programs.

Ashtanga Yoga Ethics-Based Yoga Versus General Yoga on Anthropometric Indices, Trigunas, and Quality of Life in Abdominal Obesity: A Randomized Control Trial.

Introduction: The philosophical tenets of yoga such as Ashtanga yoga (AY) and Trigunas are seldom considered while designing yoga programs for chronic diseases. This randomized control trial explored the impact of AY principle-based yoga on the anthropometric indices, personality traits, and quality of life (QoL) in abdominal obesity (AO). Materials and Methods: Sixty-two participants with AO were randomized (n = 31 in each arm) into an AY arm or general yoga (GY) arm. For 12 weeks, both the AY and the GY received the same yoga protocol; however, the AY received an additional AY-based orientation session fortnightly. Changes in waist circumference, hip circumference (HC), height, weight, body mass index (BMI), waist-hip ratio, Vedic Personality Inventory for gunas, and World Health Organization QoL-BREF were measured at baseline and at the end of 12 weeks. Results: By the end of 12 weeks, the AY arm significantly differed from the GY arm in HC (P = 0.05) and BMI scores (P = 0.03). The AY arm has shown a significant increase in the sattva guna (P < 0.001) and reduction in the rajas (P < 0.001) and tamas gunas (P = 0.03). There was a significant improvement in the physical and social QoL domain, whereas the other variables examined remained insignificant. The increase in sattva guna was negatively correlated with waist circumference (P = -0.489) and BMI (r = -0.553). Conclusion: Exposing participants to progressive AY philosophy can change the personality traits which are further associated with melioration in the determiners of AO. Future yoga programs for chronic disorders may consider including AY philosophy for substantive outcomes.

Medical Education, Practice, and Regulation of Acupuncture in India.

Acupuncture is one of the most-utilized forms of integrative medicine therapy across the globe, owing to this modality's wide range of therapeutic benefits. The history of acupuncture use in India is 3000 years old; however, the first documented use of acupuncture in India emerged in 1959. Presently, acupuncture is included as an independent therapy in the yoga and naturopathy (Y&N) category, an indigenous system of medicine under the purview of the Ministry of Ayurveda, Y&N, Unani (Perso-Arabic Medicine), Sidha (Indian Medicine), and homeopathy (AYUSH), and Sowa-Rigpa (Tibetan Medicine), of the government of India. Acupuncture has been taught to Y&N medical graduates through state-run medical universities at both undergraduate and postgraduate levels since 1989 and 2014, respectively. In addition, there are many short-term courses on acupuncture offered by nonmedical universities and academies. Y&N physicians are licensed to practice acupuncture in many states of India; however it is practiced by physicians of other medical systems as well as by nonlicensed practitioners. This is largely due to the nonuniform and flawed regulatory framework of acupuncture practice in India. The government of India, through a task force, is exploring the possibility of recognizing acupuncture as an independent system of medicine and regulating its practice. While the status of acupuncture and its use among integrative medicine physicians has definitely grown in the past 5 decades, the challenges-rooting out quackery, ensuring rigorous training, empowering existing practitioners, maintaining global standards, defining the scope of practice, etc.-warrant an unbiased and firm approach to safeguard acupuncture's scientific and academic rigor.

Role of Acupuncture and Fire Cupping in Reducing the Thyroxine Dose and Improving the Thyroid Function in Hypothyroidism Patients: A Case Series.

Hypothyroidism is one of the most common endocrine disorders linked to various systemic diseases ranging from obesity to cancers. The present line of management is insufficient as reports suggest that there is persistence of symptoms and poor adherence that makes the management of said disease challenging. Acupuncture and other Traditional Chinese Medicine (TCM) therapies are proven to alleviate endocrine dysfunctions. However, reports on acupuncture and cupping therapy on hypothyroidism are very scarce. Here, we report 5 cases of hypothyroid patients aged between 38-44 yrs who were treated with acupuncture and fire cupping for a period of three months. At the baseline, the patients presented with either a weak, wiry or vacuum pulse which represents spleen Qi deficiency. Further, they presented with elevated levels of Thyroid Stimulating Hormone (TSH), and higher Body Mass Index (BMI). Acupuncture treatment at ST36, LI4, SP6, and BL20 was given bilaterally whilst CV4, LR3, LR4, SP9, ST40, SP10, GV4, KI3, ST12, and SI17 were punctured unilaterally. At the end of the time period of three months, patients progressed to normal levels of TSH, reduction in BMI and had succeeded in tapering their medication doses. Supplementing this, the patients reported marked improvement in other symptoms like fatigue, hair loss, and cold feet post-treatment. The effects were consistent even during the three month follow-up period post-interventions. The results encourage the utilization of acupuncture and fire cupping in the management of hypothyroidism. However, large scale studies are warranted to strengthen this recommendation.

Safety and efficacy of ozone therapy in mild to moderate COVID-19 patients: A phase 1/11 randomized control trial (SEOT study).

INTRODUCTION: The Corona virus disease 19 (COVID-19) has accounted for multiple deaths and economic woes.While the entire medical fraternity and scientists are putting their best feet forward to find a solution to contain this deadly pandemic, there is a growing interest in integrating other known alternative therapies in to standard care. This study is aimed at evaluating the safety and efficacy of ozone therapy (OT), as an adjuvant to the standard of care (SOC). METHODS: In the current randomized control trial, 60 patients with mild to moderate score NEWS score were included in two parallel groups (n = 30/group). The interventional group (OZ) received ozonized rectal insufflation and minor auto haemotherapy, daily along with SOC, while the control group (ST) received SOC alone. The main outcome measures included changes in clinical features, oxygenation index (SpO2), NEWS score, Reverse transcription polymerase chain reaction(RT-PCR), inflammatory markers, requirement of advanced care, and metabolic profiles. RESULTS: The OZ group has shown clinically significant improvement in the mean values of all the parameters tested compared to ST Group. However, statistical significance were only observed in RT-PCR negative reaction (P = 0.01), changes in clinical symptoms (P < 0.05) and requirement for Intensive care (P < 0.05). No adverse events were reported in OZ group, as against 2 deaths reported in ST group. CONCLUSION: OT when integrated with SOC can improve the clinical status and rapidly reduce the viral load compared to SOC alone, which facilitate early recovery and check the need for advanced care and mortality as demonstrated in this study.

Raising burden of non-communicable diseases: importance of integrating Yoga and Naturopathy at primary care level.

Primary health care is a vital component in health care delivery. Non-communicable diseases (NCD's) are rising like a major threat to human survival, which is expected to account for 75% of the total mortality by 2030. Lifestyle and behavioural changes are reckoned as the way ahead. Yoga and Naturopathy, a drugless system of medicine has intersecting paradigms which addresses all planes of health effectively. Yoga and Naturopathy through its holistic approach educate and make the people responsible for their own health. It has shown its efficacy in alleviating and preventing various NCD's. A systematic approach should be initiated, which can channelize the integration of Yoga and Naturopathy at the primary care level considering its cost-effectiveness and efficacy over NCD's.

Naturopathy and Yoga as an Adjuvant for People Living With HIV/AIDS - A Case Series Report.

Human Immunodeficiency Virus (HIV) is an infection that poses a great threat to both developed and developing countries. Health facilities offering complementary care, along with standard care, have been considered as a useful strategy to overcome the burden of HIV and promote quality and wellbeing among people living with HIV/AIDS (PLWHA). In this report, we make reference to seven participants diagnosed with HIV, who underwent naturopathy and yoga based lifestyle intervention (NYLI), for varying durations, at a sanatorium for PLWHA. The cases suggest that NYLI functions as an adjuvant therapy that complements standard care, improves adherence and promotes health-related outcomes in HIV affiliated clinical markers, such as haemoglobin, weight and CD4+ counts. However, further controlled trials are required to establish warranting evidence.

Alternate hot and cold application in the management of heel pain: A pilot study.

BACKGROUND: Despite a long-standing tradition of naturopathic physical therapy and hydrotherapy use in the treatment of musculoskeletal conditions, neither naturopathy, nor specific aspects of hydrotherapy have been tested for efficacy in the treatment of heel pain. METHODS: Patients (n=20) were assigned to standard naturopathic physiotherapy care (NPC) with two adjuvant therapy groups: a control group (therapeutic ultrasound, n=10), or alternating compresses (n=10). Pain scores were measured before and after treatment using Visual Analog Scale (VAS) and foot functionality was measured using the Foot Function Index (FFI). RESULTS: FFI reduced from 46.97 to 31.98 (p=0.005) among normal protocol patients and from 49.72 to 21.35 (p=<0.001) among patients receiving the alternating compress protocol. Average VAS pain intensity in the seven days of treatment decreased from 3.53 to 2.53cm (p=<0.001) among patients receiving NPC and from 4.09 to 2.61cm (p=<0.001) amongst those receiving NPC plus alternating compresses. There was no significant difference in pain score reduction between the two groups (p=0.206), but patients with alternating compresses as part of their treatment had significant improvements in foot functionality (p=0.007). DISCUSSION: Naturopathic physical therapy significantly improves foot functionality and pain scores in heel pain. Additionally, alternating compresses improve foot functionality scores.

Role of therapeutic fasting in women's health: An overview.

Fasting is a therapeutic tool practiced since millennia by different cultures and medical systems heterogeneously. PubMed and Google Scholar search engines were searched using the keywords "fasting," "intermittent fasting," "calorie restriction," "women's health," "women's disorders," "fasting and aging," and "fasting and health." All the animal and human studies which address women's health and disorders were included in the review. Fasting has shown to improve the reproductive and mental health. It also prevents as well as ameliorates cancers and musculoskeletal disorders which are common in middle-aged and elderly women. The present studies available have limitations such as majority of the studies are preclinical studies and human studies are with lesser sample size. Future studies should address this gap by designing medically supervised fasting techniques to extract better evidence. Nevertheless, fasting can be prescribed as a safe medical intervention as well as a lifestyle regimen which can improve women's health in many folds.

Membrane display and functional analysis of juxtacrine ligand-receptor signaling.

We developed a strategy for identifying modulators of juxtacrine signaling, triggered by a cell-surface ligand displayed on synthetic lipid bilayers, via cognate receptors on apposed cells. Using readouts for receptor lateral transport and intracellular signaling, we screened a small interfering RNA (siRNA) library and identified specific receptor tyrosine kinases (RTKs) that directly or indirectly modulate apoptosis signaling by a model death ligand through its cognate death receptors. This approach may be broadly useful for studying juxtacrine cell-cell signaling systems.

Effect of electroacupuncture on function and quality of life in Parkinson's disease: a case report.

A 56-year-old man diagnosed in 2003 as having Hoehn & Yahr stage III Parkinson's disease (PD) came to our clinic in 2012 with slurred speech, right-sided bradykinesia, erectile dysfunction, rigidity, emotional instability and depression. His PD showed progressive signs with postural instability, moderate bilateral signs, and he rated 80% on the Schwab & England Activities of Daily Living Scale. A modified protocol of electroacupuncture was administered for a period of 5 weeks, six times per week, with each session lasting for 30 min. Assessments were based on the Berg Balance Scale (BBS) and Parkinson's Disease Questionnaire-39 (PDQ-39) items, a disease-specific measure of subjective health status. He showed improvement on the BBS, suggesting improved functional status. His quality of life showed improvement particularly on the 'activities of daily living', 'cognition' and 'communication' dimensions of the PDQ-39. Acupuncture treatments in animal experiments have generated valuable mechanistic insights that could be relevant to PD, for example, demonstrating its neuroprotective potential from stimulation of various neuroprotective agents. The literature also suggests acupuncture may play a role in the improvement of motor function and quality of life in PD. Acupuncture is tolerated well by individuals with PD and should be considered as an integrative approach for their symptomatic management.

Using patterned supported lipid membranes to investigate the role of receptor organization in intercellular signaling.

Physical inputs, both internal and external to a cell, can directly alter the spatial organization of cell surface receptors and their associated functions. Here we describe a protocol that combines solid-state nanolithography and supported lipid membrane techniques to trigger and manipulate specific receptors on the surface of living cells and to develop an understanding of the interplay between spatial organization and receptor function. While existing protein-patterning techniques are capable of presenting cells with well-defined clusters of protein, this protocol uniquely allows for the control of the spatial organization of laterally fluid receptor-ligand complex at an intermembrane junction. A combination of immunofluorescence and single-cell microscopy methods and complementary biochemical analyses are used to characterize receptor signaling pathways and cell functions. The protocol requires 2-5 d to complete depending on the parameters to be studied. In principle, this protocol is widely applicable to eukaryotic cells and herein is specifically developed to study the role of physical organization and translocation of the EphA2 receptor tyrosine kinase across a library of model breast cancer cell lines.