Implementation of Oxygen Enhanced Magnetic Resonance Imaging (OE-MRI) and a Pilot Genomic Study of Hypoxia in Bladder Cancer Xenografts.

BACKGROUND/AIM: Patients with hypoxic bladder cancer benefit from hypoxia modification added to radiotherapy, but no biomarkers exist to identify patients with hypoxic tumours. We, herein, aimed to implement oxygen-enhanced MRI (OE-MRI) in xenografts derived from muscle-invasive bladder cancer (MIBC) for future hypoxia biomarker discovery work; and generate gene expression data for future biomarker discovery. MATERIALS AND METHODS: The flanks of female CD-1 nude mice inoculated with HT1376 MIBC cells. Mice with small (300 mm3) or large (700 mm3) tumours were imaged, breathing air then 100% O2, 1 h post injection with pimonidazole in an Agilant 7T 16cm bore magnet interfaced to a Bruker Avance III console with a T2-TurboRARE sequence using a dynamic MPRAGE acquisition. Dynamic Spoiled Gradient Recalled Echo images were acquired for 5 min, with 0.1mmol/kg Gd-DOTA (Dotarem, Guerbet, UK) injected after 60 s (1 ml/min). Voxel size and field of view of dynamic contrast enhanced (DCE)-MRI and OE-MRI scans were matched. The voxels considered as perfused with significant post-contrast enhancement (p<0.05) in DCE-MRI scans and tissue were further split into pOxyE (normoxic) and pOxyR (hypoxic) regions. Tumours harvested in liquid N2, sectioned, RNA was extracted and transcriptomes analysed using Clariom S microarrays. RESULTS: Imaged hypoxic regions were greater in the larger versus smaller tumour. Expression of known hypoxia-inducible genes and a 24 gene bladder cancer hypoxia score were higher in pimonidazole-high versus -low regions: CA9 (p=0.012) and SLC2A1 (p=0.012) demonstrating expected transcriptomic behaviour. CONCLUSION: OE-MRI was successfully implemented in MIBC-derived xenografts. Transcriptomic data derived from hypoxic and non-hypoxic xenograft regions will be useful for future studies.

Efficacy of massage versus massage with post isometric relaxation in temporomandibular disorders: a randomized controlled trial.

BACKGROUND: Temporomandibular joint disorder (TMD) is a common condition affecting the masticatory muscles and joint mobility. OBJECTIVES: The primary objective was to compare the effects of massage therapy alone and massage therapy combined with post-isometric relaxation exercises in patients with TMD for pain and maximal mouth opening. DESIGN: Assessor-blinded randomized controlled trial. SETTING: Sir Ganga Ram Hospital, Chaudhry Muhammad Akram Dental Hospital, Lahore Medical and Dental Hospital. SUBJECTS: Temporomandibular joint disorder patients. INTERVENTION: Group A (n = 23) received conventional treatment including massage and therapeutic exercises consecutively for 2 weeks. Group B (n = 23) received post-isometric relaxation technique along with conventional treatment for consecutive 2 weeks. MAIN MEASURES: The main outcome measures were pain and maximal mouth opening. Pain was measured using the Visual Analogue Scale (VAS) and maximal mouth opening (MMO) was measured using the TheraBite Scale. RESULTS: Both groups demonstrated significant improvements in pain and MMO scores post-treatment. However, Group B (massage with post-isometric relaxation exercises) showed significantly better outcomes compared to Group A (massage alone). There was a statistically significant difference in post-treatment pain scores (P = 0.000) and MMO scores (P = 0.000) between the two groups. CONCLUSION: The results suggest that massage therapy combined with post-isometric relaxation is more effective than massage therapy alone in managing pain and improving mouth opening in TMD patients. The study provides evidence supporting the use of these therapies in TMD management. TRIAL REGISTRY NUMBER: NCT05810831. Date of registration/First submission: 15 March 2023.

Boosting-based ensemble machine learning models for predicting unconfined compressive strength of geopolymer stabilized clayey soil.

The present research employs new boosting-based ensemble machine learning models i.e., gradient boosting (GB) and adaptive boosting (AdaBoost) to predict the unconfined compressive strength (UCS) of geopolymer stabilized clayey soil. The GB and AdaBoost models were developed and validated using 270 clayey soil samples stabilized with geopolymer, with ground-granulated blast-furnace slag and fly ash as source materials and sodium hydroxide solution as alkali activator. The database was randomly divided into training (80%) and testing (20%) sets for model development and validation. Several performance metrics, including coefficient of determination (R2), mean absolute error (MAE), root mean square error (RMSE), and mean squared error (MSE), were utilized to assess the accuracy and reliability of the developed models. The statistical results of this research showed that the GB and AdaBoost are reliable models based on the obtained values of R2 (= 0.980, 0.975), MAE (= 0.585, 0.655), RMSE (= 0.969, 1.088), and MSE (= 0.940, 1.185) for the testing dataset, respectively compared to the widely used artificial neural network, random forest, extreme gradient boosting, multivariable regression, and multi-gen genetic programming based models. Furthermore, the sensitivity analysis result shows that ground-granulated blast-furnace slag content was the key parameter affecting the UCS.

Fall risk screening and balance rehabilitation in elderly: a missing healthcare intervention in Pakistani healthcare system.

Elderly are one of the fastest-growing population globally and require significant healthcare services due to age-related deterioration in physiological systems. Poor postural control due to aging results in impaired balance leading to increase in frequency of falls, poor quality of life, and rise in disability and mortality rates. In Pakistan, due to lack of awareness, and resources, fall prevention and screening programmes for the elderly are lacking. Regular fall risk screening utilizing balance assessment tools, integration of fall prevention programmes and balance rehabilitation approach as part of elderly healthcare services can serve as tools to lower the incidence of falls in the elderly population of Pakistan. Moreover, integration of latest technology as part of balance rehabilitation can also be considered. The review aims to highlight appropriate strategies for fall risk screening and balance rehabilitation in an effort to promote an important healthcare intervention for elderly in Pakistan.

Hearing impairment and its impact on children and parents in Pakistan.

Background: Hearing impairment and its consequences in children are often worsened by late identification in Pakistan. Deep-rooted cultural beliefs make some parents reluctant to seek clinical treatment, making adaptable solutions that traverse levels of socio-ecological model necessary. Aims: To determine the impact of hearing impairment on children's participation in social activities, and the financial burden on their parents. Methods: This cross-sectional study included 377 parents of children with hearing impairment. The sample was recruited from special education schools and hospitals in Islamabad and Lahore, Pakistan, from November 2015 to April 2016. A 15-item structured questionnaire was used for data collection. SPSS version 21 was used for statistical analysis. Results: Among children with hearing impairment, 47.5% faced moderate challenges in joining social activities, and 26.0% faced severe challenges. There was a significant positive correlation between the severity of hearing impairment, the person who suspected hearing impairment, age of detection of hearing impairment, and time of referral. Children with hearing impairment caused moderate financial strain on 39.0% of parents and mild strain on 26.8%. Conclusion: Hearing impairment can significantly impact children's participation in social activities and cause financial burdens on their parents.

Body composition profiling and obesity analysis of healthy adults: A cross-sectional study.

Obesity as depicted by changes in the body composition is considered a global epidemic of the 21st century, predisposing to cardiometabolic diseases. This analytical cross-sectional study evaluated body composition parameters in both genders and conducted an obesity analysis of healthy adult Pakistani population. Using non-probability purposive sampling technique, data was collected from 205 healthy adults (aged 18-45 years), who had not been participating in any structured exercise or dietary regime over the last six months. Body composition was assessed using bioelectrical impedance analyser. For data analysis, descriptive statistics, Mann-Whitney U-test and one-sample T-test were applied. The mean body mass index was 24.3±4.93 kg/m2. Body composition components which were significantly higher in males included soft lean mass, fat-free mass index, skeletal muscle mass index and bone mineral content, whereas females had significantly higher percentage of body fat (PBF), visceral fat area and fat mass index (p<0.05). For obesity analysis, the mean PBF (34.61±9.68%) of our sample was higher than White, Hispanics and European adults. Majority of healthy adults had greater body fat mass and lower skeletal muscle mass. The primary obesity index was significantly higher in Pakistani population compared to other ethnicities, with females exhibiting a higher trend towards obesity.

Effects of glucosamine and chondroitin sulfate supplementation in addition to resistance exercise training and manual therapy in patients with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: To determine the added benefits of short-term glucosamine and chondroitin sulfate supplementation in combination with manual therapy and resistance exercise training in the management of knee osteoarthritis. METHODS: A parallel-design, double-blind randomised controlled trial was conducted from January to September 2020 at the Foundation University Institute of Rehabilitation Sciences and Fauji Foundation Hospital, Rawalpindi, Pakistan, and comprised of knee osteoarthritis patients of either gender having radiological evidence of grade III or less on Kellgren classification. The subjects were randomly allocated to active comparator group A and experimental group B. Both the groups received manual therapy and resistance exercise training, while group B additionally received glucosamine and chondroitin sulfate supplementation for 4 weeks. Study outcomes included pain, function, quality of life, range of motion, strength, fall risk, skeletal muscle mass, visceral fat area, body fat, intracellular water ratio, and segmental lean and fat mass. Data was analysed using SPSS 21. RESULTS: Of the 24 subjects, there were 12(50%) in each of the two groups. Each groups had 9(75%) males and 3(25%) females. In terms knee osteoarthritis grade, there was no significant difference between the groups (p=1.00). No significant differences were observed in any of the outcome measures neither at 2 weeks, nor at 4 weeks post-intervention between the groups (p>0.05) except for percentage change in segmental lean mass of the right leg at 2nd week and of the left leg at 4th week (p<0.05). CONCLUSIONS: Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis, however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits. Clinical Trial Number: NCT04654871. https://www.clinicaltrials.gov/ct2/show/NCT04654871.

Comparative effectiveness of proprioceptive neuromuscular facilitation and passive vertebral mobilization for neck disability in patients with mechanical neck pain: A randomized controlled trial.

OBJECTIVE: To compare the effectiveness of Proprioceptive Neuromuscular Facilitation (PNF) and Passive Vertebral Mobilization (PVM), both when given in adjunct to routine physical therapy (RPT), on neck disability in patients with mechanical neck pain (MNP). METHODS: A single-blinded randomized controlled trial was conducted on 90 patients with MNP at the National Institute of Rehabilitation Medicine, Islamabad, Pakistan, from September 2015 to March 2018. The participants aged between 18 and 65 years were recruited through a simple random sampling technique and randomly divided into three groups i.e. PNF + RPT, PVM + RPT, and RPT. Each participant was evaluated pre and post-intervention (after four weeks) through neck disability index (NDI). The data were analyzed by using SPSS version 21. RESULTS: The MANOVA was run on the pre-post mean differences of the variables to determine the changes within the groups which showed that the participants improved significantly in all the groups in terms of the NDI components and overall NDI score (p < 0.05). Univariate analysis with the post-hoc comparison and Tuckey HSD correction was used to determine the differences between the groups which showed that there was a significant difference between the interventional groups in the overall pain intensity, as well as pain experienced while performing personal care activities, reading, doing work, driving, sleeping, recreation and in the total NDI score (p < 0.05). CONCLUSION: PVM (in adjunct to RPT) was more effective than PNF (in adjunct to RPT) for the patients with MNP to manage themselves in daily activities. CLINICAL TRIAL REGISTRATION: NCT03813680 (at clinicaltrials.gov) (https://clinicaltrials.gov/ct2/show/NCT03813680).

Habitat Imaging of Tumors Enables High Confidence Sub-Regional Assessment of Response to Therapy.

Imaging biomarkers are used in therapy development to identify and quantify therapeutic response. In oncology, use of MRI, PET and other imaging methods can be complicated by spatially complex and heterogeneous tumor micro-environments, non-Gaussian data and small sample sizes. Linear Poisson Modelling (LPM) enables analysis of complex data that is quantitative and can operate in small data domains. We performed experiments in 5 mouse models to evaluate the ability of LPM to identify responding tumor habitats across a range of radiation and targeted drug therapies. We tested if LPM could identify differential biological response rates. We calculated the theoretical sample size constraints for applying LPM to new data. We then performed a co-clinical trial using small data to test if LPM could detect multiple therapeutics with both improved power and reduced animal numbers compared to conventional t-test approaches. Our data showed that LPM greatly increased the amount of information extracted from diffusion-weighted imaging, compared to cohort t-tests. LPM distinguished biological response rates between Calu6 tumors treated with 3 different therapies and between Calu6 tumors and 4 other xenograft models treated with radiotherapy. A simulated co-clinical trial using real data detected high precision per-tumor treatment effects in as few as 3 mice per cohort, with p-values as low as 1 in 10,000. These findings provide a route to simultaneously improve the information derived from preclinical imaging while reducing and refining the use of animals in cancer research.

The Obesity Epidemic: Call for Physical Activity and Exercise.

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Neurorehabilitation in time of COVID 19: A perspective from Pakistan.

A global public health emergency, the coronovirus disease-2019 pandemic has impacted every way of life, including neuro-rehabilitation, worldwide. Issues related to increased service demand in primary care, exhausted or insufficient healthcare facilities were significantly high in low and middle-income countries, like Pakistan, with already a struggling health infrastructure. This required major change in health service delivery and impacted rehabilitation care of vulnerable patients with neurological conditions and impairments. For the current review, relevant key words and their combinations were used for literature search, including 'COVID 19', 'SARS-CoV-2', 'Corona Virus', 'rehabilitation', 'physical rehabilitation', 'pandemic', 'NCOC', 'lockdown', 'health services', 'physical therapy', 'disability', 'access', 'tele-rehabilitation', 'research', 'human resource', 'healthcare', etc. The platforms searched were Google search, Google Scholar and PubMed. The idea was to highlight how the pandemic impacted neuro-rehabilitation care in countries like Pakistan throughout the pandemic duration and during the lockdowns.

Effects of high-intensity multi-modal exercise training (HIT-MMEX) on bone mineral density and muscle performance in postmenopausal women. A Pilot randomized controlled trial.

Objectives: To determine the effects of high-intensity multimodal exercise training on bone mineral density and muscle performance in postmenopausal women. METHODS: The two-armed, parallel, pilot randomised controlled trial was conducted from November 2020 to July 2021 at Riphah Rehabilitation Centre, Rawalpindi, Pakistan, and comprised women aged 45-70 having been in the post-menopause phase for at least 3 years, with body mass index <30, community ambulant and willing to have exercise therapy. The subjects were randomised into two equal groups. The experimental group A received supervised high-intensity resistance, weight-bearing, balance and mobility training twice weekly for 8 months. The control group B received low-to-moderate intensity exercises. Femoral neck and lumbar spine bone mineral density (g/cm2) were taken through a dual-energy X-ray absorptiometry scan. Muscle performance was measured using 1 repetition maximum for leg and trunk extensors, and 30 sec sit to stand test. Data was analysed using SPSS 21. RESULTS: Of the 101 women screened, 28(27.7%) were enrolled; 14(50%) in group A having mean age 53.36±6.28 years, and 14(50%) in group B having mean age 51.71±4.82 years (p>0.05). Group A showed significantly more improvement than group B both with respect to lumbar spine bone mineral density and muscle performance (p<0.05). CONCLUSIONS: Supervised high-intensity multimodal exercise training protocol had a positive effect on lumbar spine bone mineral density and muscle performance in postmenopausal women. Clinical Trial Number: NCT04653350, Link https://clinicaltrials.gov/ct2/show/NCT04653350.

Aphasia-Diagnostic Challenges and Trends: Speech-Language Pathologist's Perspective.

OBJECTIVES: To explore current aphasia assessment practices and barriers among Pakistani speech language pathologists. METHODS: Descriptive study design with qualitative parameters was used. Participants were identified using purposive sampling over a period of eight months from 1st December 2018 to 31st July 2019. Sample comprised of ten speech-language pathologists with least five years' experience of working with aphasic clients from four major cities of Pakistan including Islamabad, Karachi, Lahore and Peshawar. Study included in depth interviews using a self-structured interview guide with probe questions. Data recorded was transcribed and thematic analyses were drawn manually. RESULTS: Thematic analysis revealed that most Speech language pathologists rely heavily on informal assessment techniques. With no aphasia assessment tool available in Urdu language, no consensus as to the optimal evaluation strategy or tool for aphasia assessment was noted. However, need for such tool was highlighted by all participants. Hence, non-availability of standardized and culturally appropriate assessment tool in "Urdu" language turned out to be the major barrier in adopting formal assessment for aphasic clients, while time consumed in formal testing remained second most reported issue. CONCLUSION: There is a dire need of quick aphasia assessment tool in Urdu language with established psychometric properties and culturally appropriate norms.

A Hospital based study on sudden sensorineural Hearing Loss: It's audiological characteristics and prevalence.

OBJECTIVES: To analyze the prevalence & characteristics of sudden sensorineural hearing loss. METHODS: This cross sectional study including n=377 cases of sensorineural hearing impairment, using non-probability convenience sampling, who fulfilled the selection criteria was conducted from 1st July 2019 to 31st October 2019. Study was conducted at Audiology section of ENT department, Lahore General Hospital, Pakistan. Sample included both genders, aged 17-70 years. Cases suffering from inflammatory or obstructive conditions of the external or middle ear and those who could not undergo pure tone audiometry were excluded from the study. Following consent for inclusion in study, data was collected using basic demographic and medical history sheet followed by Audiometric evaluation. Statistical Software for Social Sciences Version 20.0 was used for data analysis. RESULTS: The prevalence rate of sudden sensorineural hearing loss of 14(3.7%) being significantly more common in males 11(78%) than females 3(22%) (p=0.05) & age group 15-35 years (p=0.001). It is commonly of severe or profound degree with downward sloping audiogram (p<0.05), however it is not associated with vertigo (p=0.32), tinnitus (p=0.08) with no side predilection (p=0.27). CONCLUSION: We conclude that the prevalence of SSNHL is 3.7% being significantly more prevalent in males and those aged15-25 years. It is mostly characterized by severe to profound degree of hearing loss with downward sloping audiogram with no associated vertigo, tinnitus and side predilection.

Prevalence and associated risk factors among patients with overactive bladder syndrome in Pakistan.

OBJECTIVES: To determine the Prevalence and associated risk factors among patients with overactive bladder syndrome in Pakistan. METHODS: This was a community-based, face to face, cross sectional survey to calculate the prevalence and its associated risk factors. A sample of 1058 patients, women and men aged between 35 to 60 years having symptoms of overactive bladder was selected through convenience sampling from different cities of Pakistan during September to December 2020. Data was collected by using an Overactive Bladder Scoring System (OABSS) tool for prevalence and a developed questionnaire to rule out the risk factors. RESULTS: The prevalence was 27.4% (n=289) and it increased with age. The average ages for women and men were 44.60±7.88 and 46.14±7.69 years respectively. The OAB prevalence was the lowest among the participants aged 35-43 years 15.2% (n=55) while it was highest among those who were aged 53-60 years 49.6%, (n=127). The age, body mass index, diabetes mellitus, income, family history, parity and urinary tract infection were found to be significant associated risk factors for overactive bladder with p value <0.05. CONCLUSION: The overall prevalence of overactive bladder was 27.4% and it does not differ by gender, hypertension, pelvic surgery, smoking, constipation and sleep while it has significant association with age, body mass index, diabetes mellitus, income, parity and urinary tract infections.

Effects of structured exercise regime on lipid profile and renal function tests in gestational diabetes mellitus patients:A pilot study.

NOTE OF CONCERN: Article published in Journal of Pakistan Medical Association J Pak Med Assoc.February 2021, No. 2-A,Volume 72 Pages 505-507. This editorial expression of concern serves to notify readers that the Editorial Board has identified discernible weaknesses in the study design, statistical concerns and conclusion drawn regarding this previously published article, titled: "Effects of structured exercise regime on lipid profile and renal function tests in gestational diabetes mellitus patients-A pilot study" J Pak Med Assoc. Vol. 71, No. 2-A, February 2021pages 505-507. The Editorial Board has determined that : 1. The article did not discuss the feasibility of the pilot study, instead attempted to draw inference from the analytical outcomes, which does not allow readers to interpret the desired implications correctly. 2. The statistical methods applied were not at par and did not use the baseline data. The authors did not make full use of the data to add to the scientific weightage of the study, which could have been reported in the text. 3. The conclusion only points towards the positive impacts on serum markers for diabetes mellitus and renal functions. Considering the very small sample size used, this is an unjustified extrapolation. The authors did not attempt to mention the feasibility of the whole process, including participants' willingness, management, and resources that should have been assessed and reported to benefit the planning of the full-scale RCT. The editorial board of JPMA decided to publish this editorial expression of concern when we were made aware of deficiencies in the published article so that future researchers can plan their work on better scientific footings OBJECTIVE: To determine the effects of structured exercise regime on biochemical markers of patients of gestational diabetes mellitus during the third trimester. METHODS: The two-arm pilot study was conducted at the Fauji Foundation Hospital, Rawalpindi, Pakistan, from March to July 2019, and comprised women aged 20-40 years with gestational age >20 weeks who were diagnosed with gestational diabetes mellitus and who were able to do 6min walk test under severity level on the 0-10 Borg scale. The subjects were randomized into two groups using the sealed envelope method. The intervention group received 5 weeks of structured exercise programme. including aerobics, stabilisation and pelvic floor muscle training, while the control group only received postural education. Data was noted at baseline and after intervention, and was analysed using SPSS 20. RESULTS: Of the 16 subjects, there were 8(50%) in each of the two groups. The mean age was 31.5±4.17 years in the interventional group and it was 35.0±6.30 years in the control group. Serum low-density lipoprotein and serum creatinine showed significant differences between the groups (p<0.05), while the rest of markers were non-significant (p>0.05). CONCLUSIONS: Structured exercise regime was found to have a positive effect in reducing serum low-density lipoprotein and serum creatinine levels in gestational diabetes mellitus during the third trimester.

Interprofessioal collaboration among Speech Language Pathologists and Nurses in Acute Care in Pakistan.

OBJECTIVE: To find out inter-professional collaboration among speech-language pathologists and nurses in acute care in Pakistan. METHODS: This was a cross sectional study which was conducted in all government and private hospitals of Islamabad and Rawalpindi having facility of ICUs after taking consent from authorities. The duration of study was six months from October 2018 to February 2019. A total number of 350 participants (200 nurses, 150 speech language pathologists) working in ICU of different private and government hospitals of Pakistan were included in the study. Standardized questionnaire of ": assessment of inter-professioal collaboration scale": (AITCS) was circulated to nurses and speech language pathologists (SLPS) working in ICU with its subscale's partnership, coordination, cooperation and shared decision making on a 5-point likert scale. Data was analyzed using SPSS version 21.Measure of mean was obtained by independent sample t-test. P- Value less than 0.05 was considered as significant. RESULTS: Statistical analysis showed measures of mean differences obtained by t-test revealed significant differences at p<0.001 level between partnership scores of SLPS and nurses. This reveals good partnership between two disciplines. Measures of mean differences obtained by t-test revealed significant differences at p<0.001 level between partnership scores of SLPS and nurses. Both do not value each other in cooperation. Measures of mean differences obtained by t-test showed significant differences at p<0.001 level amongst coordination scores of SLPS and nurses. Both have good coordination. Measures of mean differences obtained by t-test revealed significant differences at p<0.001 level amongst shared decision-making scores of SLPS and nurses. Both are involved in shared decision making. CONCLUSION: Results show significant difference in partnership, coordination, and shared decision making. There is no significant difference in cooperation.

The UN Incheon strategy Implementation and the Pakistani quagmire; ground realities.

The Economic and Social Commission for Asia and the Pacific is the regional developmental arm of the United Nations. There are over 650 million persons with disabilities living in the region. In 2012, member countries, including Pakistan, launched the new decade of persons with disabilities from 2013 to 2022, adopting the Incheon Strategy to 'Make the Right Real', based on the Put Convention on the rights of Persons with Disabilities" and aimed at accelerating the disability inclusive development with 10 measurable goals and targets. The year 2017 marked the mid-point of that decade at which point member countries were to submit the Government Members Report on the Implementation of Incheon Strategy. The ambiguity in usage of terms, variable definition of disability, and use of impairment screens in population census of Pakistan has resulted in flawed data and underreporting of persons with disabilities. Pakistan provided data on only 13 of the 30 core indicators as part of its midpoint review. There is lack of awareness among ministries regarding the Incheon Strategy implementation.