ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity.

ATP9A, a lipid flippase of the class II P4-ATPases, is involved in cellular vesicle trafficking. Its homozygous variants are linked to neurodevelopmental disorders in humans. However, its physiological function, the underlying mechanism as well as its pathophysiological relevance in humans and animals are still largely unknown. Here, we report two independent families in which the nonsense mutations c.433C>T/c.658C>T/c.983G>A (p. Arg145*/p. Arg220*/p. Trp328*) in ATP9A (NM_006045.3) cause autosomal recessive hypotonia, intellectual disability (ID) and attention deficit hyperactivity disorder (ADHD). Atp9a null mice show decreased muscle strength, memory deficits and hyperkinetic movement disorder, recapitulating the symptoms observed in patients. Abnormal neurite morphology and impaired synaptic transmission are found in the primary motor cortex and hippocampus of the Atp9a null mice. ATP9A is also required for maintaining neuronal neurite morphology and the viability of neural cells in vitro. It mainly localizes to endosomes and plays a pivotal role in endosomal recycling pathway by modulating small GTPase RAB5 and RAB11 activation. However, ATP9A pathogenic mutants have aberrant subcellular localization and cause abnormal endosomal recycling. These findings provide strong evidence that ATP9A deficiency leads to neurodevelopmental disorders and synaptic dysfunctions in both humans and mice, and establishes novel regulatory roles for ATP9A in RAB5 and RAB11 activity-dependent endosomal recycling pathway and neurological diseases.

Relationship of neutrophil lymphocyte ratio, monocyte lymphocyte ratio and neutrophil monocyte ratio with treatment response in pulmonary tuberculosis patients during intensive phase treatment.

OBJECTIVE: To determine the relationship of Neutrophil Lymphocyte Ratio (NLR), Monocyte Lymphocyte Ratio (MLR), and Neutrophil Monocyte Ratio (NMR) with treatment response in Pulmonary Tuberculosis (PTB) patients during intensive phase treatment (IPT). METHODS: This analytical cross-sectional study was conducted at Ojha Institute of Chest Diseases (OICD), Dow University of Health Sciences, from February to December 2021. 100 patients were enrolled using purposive sampling technique. Both male and female of age 18 and above, rifampicin sensitive newly diagnosed cases of PTB by Acid Fast Bacilli (AFB) microscopy and Gene Xpert MTB/RIF were included. SPSS version 26 was used to analyze data. Numerical data was expressed in median and interquartile range and categorical data was expressed in frequencies and percentages. RESULTS: Out of total 100 patients, 81% (n = 81) showed treatment response with negative AFB Sputum Smear Microscopy (SSM) after 2nd month. Out of 81% (n = 81) of the patients who achieved treatment response, 83.9% (n = 68) also had decreased NLR, 85.2% (n = 69) had decreased MLR and 83.9% (n = 68) had decreased NMR from baseline. However 19% (n = 19) did not achieved treatment response with positive AFB SSM after 2nd month of ATT (Anti tuberculosis treatment), among them 10.52% (n = 2) were INH resistant with no decrease in all the ratios after 2nd month. CONCLUSION: Leukocyte ratios decreased significantly from baseline as PTB was treated in patients who achieved treatment response with negative AFB SSM after two months of ATT and hence these ratios could be used as markers to monitor the treatment response.

Gain-of-function p.F28S variant in RAC3 disrupts neuronal differentiation, migration and axonogenesis during cortical development, leading to neurodevelopmental disorder.

BACKGROUND: RAC3 encodes a Rho family small GTPase that regulates the behaviour and organisation of actin cytoskeleton and intracellular signal transduction. Variants in RAC3 can cause a phenotypically heterogeneous neurodevelopmental disorder with structural brain anomalies and dysmorphic facies. The pathomechanism of this recently discovered genetic disorder remains unclear. METHODS: We investigated an early adolescent female with intellectual disability, drug-responsive epilepsy and white matter abnormalities. Through exome sequencing, we identified the novel de novo variant (NM_005052.3): c.83T>C (p.Phe28Ser) in RAC3. We then examined the pathophysiological significance of the p.F28S variant in comparison with the recently reported disease-causing p.Q61L variant, which results in a constitutively activated version of RAC3. RESULTS: In vitro analyses revealed that the p.F28S variant was spontaneously activated by substantially increased intrinsic GTP/GDP-exchange activity and bound to downstream effectors tested, such as PAK1 and MLK2. The variant suppressed the differentiation of primary cultured hippocampal neurons and caused cell rounding with lamellipodia. In vivo analyses using in utero electroporation showed that acute expression of the p.F28S variant caused migration defects of excitatory neurons and axon growth delay during corticogenesis. Notably, defective migration was rescued by a dominant negative version of PAK1 but not MLK2. CONCLUSION: Our results indicate that RAC3 is critical for brain development and the p.F28S variant causes morphological and functional defects in cortical neurons, likely due to the hyperactivation of PAK1.

Association of demographics, lumbar active range of motion and disability in chronic low back: a baseline data analysis of a randomized controlled trial from Pakistan.

BACKGROUND: The disability and significant economic costs accredited to Low back pain (LBP) are likely to rise which is an essential problem in low and middle-income countries like Pakistan. The associated factors of LBP are age, sex, and race including physical activity, high spinal load, lifting, bending, and twisting occupations. The literature highlighted there is substantial differences in associated factors of LBP within available studies in developing countries. The objective is to investigate the association of demographic factors and lumbar range of motion with disability in patients with chronic low back. METHODS: A baseline data analysis was performed as an analytical cross-sectional study among 150 patients with chronic low back in a randomized controlled trial with a duration from March 2020 and January 2021. After recording demographics, Modified-Modified Schober's test was used to measure lumbar flexion and extension and Oswestry disability index for disability. After the descriptive analysis the continuous variables, age and pain were analyzed with Spearman's correlation. Variables that were significant in bivariate analysis were then fitted in a multivariable linear regression. The Kruskal-Wallis test was used to analyze variations of disability in gender, marital status, work status, education level, and duration of pain. The p-value of 0.05 was significant. RESULTS: The results showed a significant correlation between age and pain in sitting (rh=-0.189, p = 0.021 and rh = 0.788, p < 0.001) with the disability but no significant effects of age and pain in sitting (B=-0.124, p = 0.212 and B = 1.128, p = 0.082) on disability were found. The decrease in lumbar flexion and extension was found to increase disability (B=-6.018 and - 4.032 respectively with p < 0.001). Female gender (x2(1) = 15.477, p = < 0.001) and unmarried marital status (x2(1) = 4.539, p = 0.033) had more disability than male gender and married marital status, respectively. There was a significance between groups of the duration of pain regarding disability (x2 (2) = 70.905, p < 0.001). Age, education level, and work status showed no significance (p > 0.05). CONCLUSIONS: The female gender and unmarried marital status are associated with functional disability. Decreased lumbar range of motion accompanies more disability, while age, education level, and work status do not effect on disability.

Comparison of two composite resin materials for splinting of dental luxation injuries: A double blind randomized controlled trial.

BACKGROUND/AIM: Luxation is a common traumatic dental injury treated with a wire composite (WC) splint. However, bulk-fill flowable composite and conventional packable composite have not been compared for retaining these splints. Therefore, the objectives of this randomized controlled trial were (1) to compare retention of WC splints, and (2) to compare adhesive point dimension, application and removal time, and effect on tooth mobility between the two WC splints. MATERIALS AND METHODS: In this parallel group, non-inferiority double blind randomized controlled trial, a total of 90 patients, aged 16-50 years participated. They were randomly allocated into two groups, the packable composite group (PC) n = 45 and the bulk-fill flowable composite group (BF-FC) n = 45 by lottery method. Following measurements were taken at the splint application appointment. Horizontal tooth mobility measured via Periotest, splint application time, and frontal images of splinted teeth to measure the percentage composite adhesive point area. After 2 weeks, splints were visually inspected for retention, whereas mobility and removal times were also recorded. Statistically, comparisons were made using independent samples sample T-test, Fisher's exact test, and Mann-Whitney U at p ≤ .05. RESULTS: A total of 88 patients with 156 luxated teeth completed the trial, as two patients were lost to follow-up. Two patients in the PC group reported with completely de-bonded splints while none de-bonded in the BF-FC group. Both groups were similar in terms of splint retention (p = .352), reduction of mobility (p = .426), and splint removal times (p = .372). The BF-FC group performed significantly better in adhesive point dimension percentages (p < .001) and splint application time (p < .001). CONCLUSION: Both groups were comparable in most parameters of the study. However, for BF-FC group application time and adhesive point dimension were significantly less.

Sustaining rice productivity through weather-resilient agricultural practices.

BACKGROUND: Enhancing productivity and profitability and reducing climatic risk are the major challenges for sustaining rice production. Extreme weather can have significant and varied effects on crops, influencing agricultural productivity, crop yields and food security. RESULTS: In this study, a comparative evaluation of two crop management systems was performed involving farmers adopting a weather forecast-based advisory service (WFBAS) and usual farmers' practice (FP). WFBAS crop management followed the generated weather forecast-based advice whereas the control farmers (FP) did not receive any weather forecast-based advice, rather following their usual rice cultivation practices. The results of the experiments revealed that WFBAS farmers had a significant yield advantage over FP farmers. With the WFBAS technology, the farmers used inputs judiciously, utilized the benefit of favorable weather and minimized the risk resulting from extreme weather events. As a result, besides the yield enhancement, WFBAS provided a scope to protect the environment with the minimum residual effect of fertilizer and pesticides. It also reduced the pressure on groundwater by ensuring efficient water management. Finally, the farmers benefited from higher income through yield enhancement, reduction of the costs of production and reduction of risk. CONCLUSION: A successful and extensive implementation of WFBAS in the rice production system would assist Bangladesh in achieving Sustainable Development Goal 2.4, which focuses on rice productivity and profitability of farmers as well as long-term food security of the country. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The outcomes of nutritional therapy in patients with non-alcoholic fatty liver disease (NAFLD): Pitfalls in getting fit from fat.

Objective: To evaluate the outcomes of nutritional intervention on non-alcoholic fatty liver disease parameters, and to determine the reasons for non-compliance with nutritional therapy. METHODS: The interventional study was conducted from May 2020 to October 2022 at the National Institute of Liver and Gastrointestinal diseases, Dow University Hospital, Ojha Campus, Karachi, and comprised patients of either gender aged 18-65 years who had been diagnosed with non-alcoholic fatty liver disease based on abdominal ultrasound. Anthropometrics, physical activity level, and biochemical markers were evaluated at baseline and 6 months after the intervention that involved nutritional assessment, counselling and guidance related to dietary modification and optimisation of physical activity level. The effect of the intervention was evaluated by improvement in liver enzymes, biochemical parameters, anthropometric indices and any change in the level of physical activity. The reasons for noncompliance were also recorded. Data was analysed using SPSS 22. RESULTS: Out of 118 subjects enrolled, 61(51.69%) completed the study. Most patients were females 81(68.6%), married 25(21.2%) and housewives 64(54.2%). There were 16(26.2%) subjects who had 3-10kg weight reduction. The reduction in serum cholesterol and triglyceride levels was not significant (p>0.05). Also, no significant change was observed in the level of physical activity compared to the baseline (p>0.05). Overall, 27(44.3%) patients showed compliance with treatment. The main reasons for noncompliance were lack of time 21(34.4) and knee joint pain 5(8.2%). Conclusion: Lifestyle modification can be beneficial for weight-loss in the management of non-alcoholic fatty liver disease. However, awareness of its importance and willingness in initiating real-life practical steps with subsequent adherence to dietary therapy was found lacking in the sample studied.

The effects of lumbar stabilization exercises with and without jaw movements in non-specific low back pain (A randomized controlled trial).

Objective: This study aimed to investigate the added effect of jaw clenching on the efficacy of lumbar stabilization exercises to manage chronic non-specific low back pain. Methods: This randomized controlled trial was conducted at the Sindh Institute of Physical Medicine and Rehabilitation (SIPM&R) Karachi from April 2021 to April 2023. Eighty patients with chronic non-specific low back pain participated in this study. Forty patients each were randomly allocated to the lumbar stability exercise (LSE) group' and the lumbar stability exercise with teeth clenching (LSETC) group. Patients in both groups performed respective exercises twice weekly for 12 weeks. The Numeric Pain Rating Scale (NPRS), Roland Morris Disability Questionnaire (RMDQ), and Pressure Biofeedback Unit (PBU) were used to assess pain, disability, and muscle endurance respectively. Data were collected at the baseline, after six weeks and 12 weeks of intervention. A p-value of <0.05 was considered statistically significant. Results: Both groups showed statistically significant improvements in pain, disability, and muscle endurance. Upon further stratification, participants aged 20-30 years in the LSETC group showed significantly higher scores than the LSE group for NPRS, RMDQ, and PBU after 12 weeks. Overall, the LSETC group showed relatively higher improvement in mean scores for NPRS, RMDQ, and PBU than the LSE group. Conclusion: Lumbar stabilization exercises with and without jaw movement are effective for the treatment of chronic non-specific low back pain. The addition of teeth clenching enhanced the effectiveness of lumbar stability exercises, especially in young adults. Trial Registration: Clinicaltrials.gov (NCT04801212), Prospectively registered on March 16, 2021.

A novel biallelic variant further delineates PRDX3-related autosomal recessive cerebellar ataxia.

Cerebellar ataxias (CAs) comprise a rare group of neurological disorders characterized by extensive phenotypic and genetic heterogeneity. In the last several years, our understanding of the CA etiology has increased significantly and resulted in the discoveries of numerous ataxia-associated genes. Herein, we describe a single affected individual from a consanguineous family segregating a recessive neurodevelopmental disorder. The proband showed features such as global developmental delay, cerebellar atrophy, hypotonia, speech issues, dystonia, and profound hearing impairment. Whole-exome sequencing and Sanger sequencing revealed a biallelic nonsense variant (c.496A > T; p.Lys166*) in the exon 5 of the PRDX3 gene that segregated perfectly within the family. This is the third report that associates the PRDX3 gene variant with cerebellar ataxia. In addition, associated hearing impairment further delineates the PRDX3 associated gene phenotypes.

50 years of rice breeding in Bangladesh: genetic yield trends.

To assess the efficiency of genetic improvement programs, it is essential to assess the genetic trend in long-term data. The present study estimates the genetic trends for grain yield of rice varieties released between 1970 and 2020 by the Bangladesh Rice Research Institute. The yield of the varieties was assessed from 2001-2002 to 2020-2021 in multi-locations trials. In such a series of trials, yield may increase over time due to (i) genetic improvement (genetic trend) and (ii) improved management or favorable climate change (agronomic/non-genetic trend). In both the winter and monsoon seasons, we observed positive genetic and non-genetic trends. The annual genetic trend for grain yield in both winter and monsoon rice varieties was 0.01 t ha-1, while the non-genetic trend for both seasons was 0.02 t ha-1, corresponding to yearly genetic gains of 0.28% and 0.18% in winter and monsoon seasons, respectively. The overall percentage yield change from 1970 until 2020 for winter rice was 40.96%, of which 13.91% was genetic trend and 27.05% was non-genetic. For the monsoon season, the overall percentage change from 1973 until 2020 was 38.39%, of which genetic and non-genetic increases were 8.36% and 30.03%, respectively. Overall, the contribution of non-genetic trend is larger than genetic trend both for winter and monsoon seasons. These results suggest that limited progress has been made in improving yield in Bangladeshi rice breeding programs over the last 50 years. Breeding programs need to be modernized to deliver sufficient genetic gains in the future to sustain Bangladeshi food security.

Exploring Heterogeneity in perinatal depression: a comprehensive review.

Perinatal depression (PND) is a significant contributor to maternal morbidity globally. Recognized as a major cause of poor infant development, epidemiological and interventional research on it has increased over the last decade. Recently, studies have pointed out that PND is a heterogeneous condition, with variability in its phenotypes, rather than a homogenous latent entity and a concrete diagnosis, as previously conceptualized in psychometric literature and diagnostic systems. Therefore, it is pertinent that researchers recognize this to progress in elucidating its aetiology and developing efficacious interventions.This systematic review is conducted in accordance with the Meta-analysis of observational studies in epidemiology (MOOSE). It aims to provide an updated and comprehensive account of research on heterogeneity in phenotypes of PND and its implications in research, public health, and clinical practice. It provides a synthesis and quality assessment of studies reporting heterogeneity in PND using cutting-edge statistical techniques and machine learning algorithms. After reporting the phenotypes of PND, based on heterogeneous trajectories and symptom profiles, it also elucidates the risk factors associated with severe forms of PND, followed by robust evidence for adverse child outcomes. Furthermore, recommendations are made to improve public health and clinical practice in screening, diagnosis, and treatment of PND.

Effects of Alt-RAMEC protocol with facemask therapy in cleft lip palate patients in a sample of Pakistani population.

OBJECTIVE: The objective of the study is to evaluate the skeletal, dentoalveolar and soft tissue changes before and after treatment with Alt-RAMEC protocol and protraction headgear in comparison to the controls. MATERIAL AND METHODS: A quasi experimental study was conducted in the orthodontic department on 60 patients of cleft lip and palate. These patients were divided into two groups. Group I was the Alt-RAMEC group that underwent Alt-RAMEC protocol followed by facemask therapy while group II was the control group that underwent RME and facemask therapy. Total treatment time in both the groups was approximately 6 to 7 months. Mean and standard deviation was calculated for all the quantitative variables. Pre and post treatment changes between treatment and control groups were made using paired t-test. Intergroup comparison between treatment and control group was analyzed using independent t-test. Significance for all tests was predetermined at a P-value of ≤ 0.05. RESULTS: The Alt-RAMEC group showed significant forward movement of maxilla and improvement in the maxillary base. A remarkable improvement in SNA was seen. The overall outcome was better maxillo-mandibular relationship as shown by positive ANB values and angle of convexity. More effect on maxilla and least effect on mandible was notified with Alt-RAMEC protocol and facemask therapy. Improvement in transverse relationship was also evident in the Alt-RAMEC group. CONCLUSION: Alt-RAMEC protocol in combination with protraction headgear is a better alternative to treat cleft lip and palate patients in comparison to the conventional protocol.

Inter observer reliability for peritoneal carcinomatosis at computed tomography.

OBJECTIVE: To determine whether there is inter-observer reliability between radiologists for reporting peritoneal carcinomatosis and computed tomography peritoneal carcinomatosis index estimation. METHODS: The retrospective, cross-sectional study was conducted at Dow Institute of Radiology, Dow University of Health Sciences (DUHS), Ojha campus and comprised computed tomography scans done between December 1, 2019, to May 31, 2020, that were extracted from the institutional database searched using key words 'peritoneal carcinomatosis' and/or 'serosal deposits'. The first readers had 1-4 years of post-fellowship experience, while the 2nd readers were senior radiologists. Inter-observer reliability was assessed quantitatively and qualitatively for 15 peritoneal sites using, among other tolls, the Sugarbaker computed tomography peritoneal carcinomatosis index. Data was analysed using SPSS 21. RESULTS: Out of 236 subjects with mean age 53.6±13.6 years, there were 173(73.3%) females and 63(26.7%) males. The most common primary cancer was ovarian 145(61.4%), followed by colon 26(11%). The size of peritoneal deposit was not reported in 75(31.8%) cases. Of the 15 sites analysed, good agreement was not found in 7(46.7%). There was an excellent intra-class correlation for measuring computed tomography peritoneal carcinomatosis index scores among the radiologists irrespective of the grade of the faculty (>0.90). CONCLUSIONS: The inter-observer reliability was low, but good agreement for computed tomography peritoneal carcinomatosis index would encourage radiologists to use it in peritoneal cancer reporting.

Benign and malignant breast diseases during pregnancy and lactation: a diagnostic challenge.

OBJECTIVE: To determine the frequency of breast cancer associated with pregnancy and lactation, and to evaluate the lesions on ultrasound. Methods: The descriptive, observational study was conducted at the Dow Institute of Radiology, DUHS, Karachi from December 2020 to August 2021, and comprised of pregnant and lactating women with clinically palpable breast lumps and/or painful breast. The margins, orientation, echo pattern and associated features of the lesions were studied on ultrasound and were assigned a Breast Imaging Reporting and Data System grade. All the lumps were followed and ultrasound-guided core needle biopsy for histopathology was done of grades IV and V cases. Incidence and Accuracy of ultrasound for diagnosis of pregnancy-associated breast cancer was estimated. Data was analysed using SPSS 26. RESULTS: Of the 237 women, 19(8%) were pregnant and 218(92%) were lactating. The overall mean age was 28.4±5.5 years. Ultrasound findings for lactating and pregnant women were significantly different (p=0.05). Significant association of Breast Imaging Reporting and Data System grades III, IV and V lesions with heterogeneous echo texture of mass was seen (p<0.001). Biopsy was performed in 20(8.4%) cases, and 12(60%) of them had benign results on histopathology. CONCLUSIONS: A variety of benign and malignant breast diseases were found in women during pregnancy and lactation phases.

Intrarater Reliability Of Cervical Range Of Motion Device Among Adults With And Without Chronic Non-Specific Neck Pain.

Objective: To evaluate the intrarater reliability of the cervical range of motion device among adults with and without chronic non-specific neck pain. METHODS: The analytical, cross-sectional study was conducted from January to March 2019 at the Sindh Institute of Physical Medicine and Rehabilitation, Karachi, and comprised healthy adults with no neck pain in the preceding 6 months in Group A, and adults of either gender with chronic non-specific neck pain for >3 months in Group B. The two groups were further divided into age groups 21-30 years, 31-40 years and 41-50 years. A cervical range of motion device was used to measure the range of flexion, extension, right and left lateral flexion and right and left rotation of all the subjects. The measurements were taken by a single tester on day-1 and day-3 to assess the intrarater reliability. Data was analysed using SPSS 26. RESULTS: Of the 60 subjects, there were 30(50%) in each of the two groups. Within the groups, there were 10(33.3%) subjects in each of the 3 age subgroups. Overall, there were 27(45%) males and 33(55%) females. In Group A, the intraclass correlation coefficient values for all cervical ranges were between 0.81 and 0.99, whereas in Group B, the values ranged from 0.64 to 0.88. The intraclass correlation coefficient values yielded good to excellent agreement in both groups (>0.75) except for left lateral flexion in Group B (p=0.64), and all the values were statistically significant (p<0.05). Conclusion: There was good to excellent intrarater reliability of cervical range of motion device in adults with and without chronic non-specific neck pain.

Assessing the between-country genetic correlation in maize yield using German and Polish official variety trials.

KEY MESSAGE: We assess the genetic gain and genetic correlation in maize yield using German and Polish official variety trials. The random coefficient models were fitted to assess the genetic correlation. Official variety testing is performed in many countries by statutory agencies in order to identify the best candidates and make decisions on the addition to the national list. Neighbouring countries can have similarities in agroecological conditions, so it is worthwhile to consider a joint analysis of data from national list trials to assess the similarity in performance of those varieties tested in both countries. Here, maize yield data from official German and Poland variety trials for cultivation and use (VCU) were analysed for the period from 1987 to 2017. Several statistical models that incorporate environmental covariates were fitted. The best fitting model was used to compute estimates of genotype main effects for each country. It is demonstrated that a model with random genotype-by-country effects can be used to borrow strength across countries. The genetic correlation between cultivars from the two countries equalled 0.89. The analysis based on agroecological zones showed high correlation between zones in the two countries. The results also showed that 22 agroecological zones in Germany can be merged into five zones, whereas the six zones in Poland had very high correlation and can be considered as a single zone for maize. The 43 common varieties which were tested in both countries performed equally in both countries. The mean performances of these common varieties in both countries were highly correlated.

Screening programs for common maternal mental health disorders among perinatal women: report of the systematic review of evidence.

Postpartum depression and anxiety are highly prevalent worldwide. Fisher et al., estimated the prevalence of depression and anxiety at 15.6% during the antenatal and 19.8% during the postpartum period. Their impact on maternal and child health is well-recognized among the public health community, accounting for high societal costs. The public health impact of these conditions has highlighted the need to focus on the development and provision of effective prevention and treatment strategies.In recent decades, some advances have been made in the development of effective universal and targeted screening programmes for perinatal depression and anxiety disorders. Recent research has shown potential benefits of universal and targeted screening for perinatal depression, to identify and treat undiagnosed cases, and help thwart its deleterious consequences. Ethical implications, however, for these screening programmes, without the provision of treatment have often been emphasized.The present mixed-methods systematic review and meta-analysis was conducted to collate evidence for screening programmes for perinatal depression and anxiety. It aims to answer the following questions, in a global context: For women in the perinatal period, do screening programmes for perinatal depression and anxiety compared with no screening improve maternal mental health and infant outcomes?A series of meta-analyses reveal a reduction in perinatal depression and anxiety among perinatal women undergoing screening programmes. For the outcome of depressive disorder, meta-analysis indicates a positive impact in favour of the intervention group (OR = 0.55, 95% CI: 0.45 to 0.66, n = 9009), with moderate quality of evidence. A significant improvement (high quality) was also observed in symptoms of anxiety among perinatal women (SMD = - 0.18, 95% CI: - 0.25 to - 0.12, n = 3654).

Technology-assisted peer therapy: a new way of delivering evidence-based psychological interventions.

In low-income settings, ninety percent of individuals with clinical depression have no access to evidence-based psychological interventions. Reasons include lack of funds for specialist services, scarcity of trained mental health professionals, and the stigma attached to mental illness. In recent years there have been many studies demonstrating effective delivery of psychological interventions through a variety of non-specialists. While these interventions are cost-effective and less stigmatising, efforts to scale-up are hampered by issues of quality-control, and what has been described by implementation scientists as 'voltage-drop' and 'programme-drift.' Using principles of Human Centred Design in a rural setting in Pakistan, we worked with potential users to co-design a Tablet or Smartphone-based App that can assist a lay-person deliver the Thinking Healthy Programme, a World Health Organization-endorsed evidence-based intervention for perinatal depression. The active ingredients of this cognitive-therapy based intervention are delivered by a virtual 'avatar' therapist incorporated into the App which is operated by a 'peer' (a woman from the neighbourhood with no prior experience of healthcare delivery). Using automated cues from the App, the peer reinforces key therapeutic messages, helps with problem-solving and provides the non-specific but essential therapeutic elements of empathy and support. The peer and App therefore act as co-therapists in delivery of the intervention. The peer can deliver the intervention with good fidelity after brief automated in-built training. This approach has the potential to be applied to other areas of mental health and help bridge the treatment gap, especially in resource-poor settings. This paper describes the process of co-development with end-users and key features of the App.

Effect of post-isometric relaxation versus myofascial release therapy on pain, functional disability, rom and qol in the management of non-specific neck pain: a randomized controlled trial.

BACKGROUND: Non-specific neck pain is the most prevailing musculoskeletal disorder which has a large socioeconomic burden worldwide. It is associated with poor posture and neck strain which may lead to pain and restricted mobility. Physical therapists treat such patients through several means. Post isometric relaxation and Myofascial release therapy are used in clinical practice with little evidence to be firmed appropriately. So, this study was conducted to explore the effect of Post-isometric relaxation in comparison to Myofascial release therapy for patients having non-specific neck pain. METHODOLOGY: Sixty patients were randomly allocated to Post isometric group and the Myofascial group. The treatment period was of 2 weeks. All the patients were evaluated using the Visual analogue scale (VAS), Neck disability index (NDI), Universal Goniometer, and WHO BREF Quality of life-100 in the 1st and 6th sessions. Recorded data was entered on SPSS 21. Data were examined using two-way repeated ANOVA to measure the variance of analysis (group x time). RESULTS: Analysis of the baseline characteristics revealed that both groups were homogenous in terms of age and gender i.e. a total of 60 participants were included in this research study 30 in each group. Out of 60 patients, there were 20(33.3%) males and 40(66.7%) females with a mean age of 32.4(5.0) years. Participants in the Post Isometric group demonstrated significant improvements (p < 0.025) in VAS, NDI, Cervical Extension, left side rotation ranges, and QoL (Social Domain) at the 2-week follow-up compared with those in the Myofascial group. In addition, the Myofascial group indicated significantly better improvement in the mean score of CROM (flexion and right and left side bending). CONCLUSION: The study demonstrated patients with nonspecific neck pain can benefit from the post isometric relaxation with significant improvement in pain, disability, cervical ROM, and Quality of life compared with myofascial release therapy. TRIAL REGISTRATION: Clinical Trial registered on clinicaltrial.gov (NCT number) NCT04638062 , 20/11/2020 (prospectively registered).

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A.

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology modeling was performed for the identified variant and advance microscopy imaging approaches were used to reveal the localization of the DACH1 protein at the base of primary cilia. A disease-causing biallelic missense variant (c.563G > A; p.Cys188Tyr; NM_080760.5) was identified in the DACH1 gene segregating perfectly within the family. Structural analysis using homology modeling of the DACH1 protein revealed secondary structure change that might result in loss of function or influence downstream interactions. Moreover, siRNA-mediated depletion of DACH1 showed a key role of DACH1 in ciliogenesis and cilia function. This study provides the first evidence of involvement of the DACH1 gene in digits development in humans and its role in primary cilia. This signifies the importance and yet unexplored role of DACH1.