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.

Exploring relationship of poor sleeping habits with prenatal stress among pregnant women in Pakistan: a cross-sectional study.

OBJECTIVE: Pregnancy is a complex phenomenon accompanied by biological, physiological and psychosocial changes for a mother. It is also regarded as a stressful life event where a woman's role, identity and interpersonal relationships are restructured. The present study from Pakistan explores the association of sleep quality and poor sleeping habits with prenatal stress using Pittsburgh Sleep quality Index. RESULTS: There were a total of 516 women (mean age = 29.82 years), with more than half reporting poor sleep quality. Ethnically, a majority (395, 76.6%) were natives of the Punjab province while rest were non-natives. A high percentage of respondents reported poor subjective sleep quality (22.1%), sleep latency (44.1%), habitual sleep efficiency (27.5%), sleep disturbance (30.1%), use of medications (7.1%) and daytime dysfunction (29.5%). According to logistic regression analysis, respondents with poor sleep quality were 2.24 (95% CI = 1.55-3.22, P < 0.001) times more likely to have high stress levels (P < 0.001).

Economic costs of perinatal depression and anxiety in a lower middle income country: Pakistan.

BACKGROUND: Women's mental health during the perinatal period is a major public health problem in Pakistan. Many challenges and competing priorities prevent progress to address the large treatment gap. Aim To quantify the long-term impacts of untreated perinatal depression and anxiety in economic terms, thus highlighting its overall burden based on country-specific evidence. METHODS: Cost estimates were generated for a hypothetical cohort of women giving birth in 2017, and their children. Women and children experiencing adverse events linked to perinatal mental health problems were modelled over 40 years. Costs assigned to adverse events included were those linked to losses in quantity and quality-of-life, productivity, and healthcare-related expenditure. Present values were derived using a discount rate of 3 %. Data were taken from published cohort studies, as well as from sources of population, economic and health indicators. RESULTS: The total costs were $16.5 billion for the cohort and $2680 per woman giving birth. The by far largest proportion referred to quality-of-life losses ($15.8 billion). Productivity losses and out-of-pocket expenditure made up only a small proportion of the costs, due to low wages and market prices. When the costs of maternal suicide were included, total costs increased to $16.6 billion. LIMITATIONS: Important evidence gaps prevented the inclusion of all cost consequences linked to perinatal mental health problems. CONCLUSIONS: Total national costs are much higher compared with those in other, higher middle-income countries, reflecting the excessive disease burden. This study is an important first step to inform resource allocations.

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.

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.

A REML method for the evidence-splitting model in network meta-analysis.

Checking for possible inconsistency between direct and indirect evidence is an important task in network meta-analysis. Recently, an evidence-splitting (ES) model has been proposed, that allows separating direct and indirect evidence in a network and hence assessing inconsistency. A salient feature of this model is that the variance for heterogeneity appears in both the mean and the variance structure. Thus, full maximum likelihood (ML) has been proposed for estimating the parameters of this model. Maximum likelihood is known to yield biased variance component estimates in linear mixed models, and this problem is expected to also affect the ES model. The purpose of the present paper, therefore, is to propose a method based on residual (or restricted) maximum likelihood (REML). Our simulation shows that this new method is quite competitive to methods based on full ML in terms of bias and mean squared error. In addition, some limitations of the ES model are discussed. While this model splits direct and indirect evidence, it is not a plausible model for the cause of inconsistency.

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.

Optimizing cognitive and behavioral approaches for perinatal depression: A systematic review and meta-regression analysis.

Cognitive behavioral therapies (CBT) have been demonstrated efficacious in treating perinatal depression (PND). This has been demonstrated in several meta-analyses of randomized controlled trials and quasi-experimental studies. However, there is a need for up-to-date meta-analytical evidence providing reliable estimates for CBT's effectiveness in treating and preventing PND. Furthermore, with the world moving toward precision medicine, approaches require a critical synthesis of psychotherapies, especially to unpack their mechanisms of action and to understand what approaches work best for whom. Therefore, the present systematic review and meta-regression analyses aim to answer these research questions. We searched six academic databases through February 2022 and identified 56 studies for an in-depth review. Using pretested data extraction sheets, we extracted patient-level and intervention-level characteristics and effect size data from each study. Random-effects meta-analyses and mixed-effect subgroup analyses were run to delineate the effectiveness and moderators of CBT interventions for PND, respectively. CBT-based interventions yielded a strong effect size (SMD = -0.74, 95% confidence interval [CI]: -0.91 to -0.56, n = 9,722) in alleviating depressive symptoms. These interventions were effective across different delivery formats (individual, group, and electronic) and could be delivered effectively by specialists and nonspecialists. Longer duration CBT interventions may not necessarily be more effective than shorter ones. Moreover, CBT-based interventions should consider including various behavioral ingredients to maximize intervention benefits.

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.

Technology-assisted cognitive-behavior therapy delivered by peers versus standard cognitive behavior therapy delivered by community health workers for perinatal depression: study protocol of a cluster randomized controlled non-inferiority trial.

BACKGROUND: The lack of trained mental health professionals is a key barrier to scale-up of evidence-based psychological interventions in low and middle-income countries. We have developed an app that allows a peer with no prior experience of health-care delivery to deliver the cognitive therapy-based intervention for perinatal depression, the Thinking Healthy Programme (THP). This trial aims to assess the effectiveness and cost-effectiveness of this Technology-assisted peer-delivered THP versus standard face-to-face Thinking Healthy Programme delivered by trained health workers. METHODS: We will employ a non-inferiority stratified cluster randomized controlled trial design comparing the two formats of intervention delivery. A total of 980 women in the second or third trimester of pregnancy with a diagnosis of Major Depressive Episode, evaluated with the Structured Clinical Interview for DSM-V Disorders (SCID), will be recruited into the trial. The unit of randomization will be 70 village clusters randomly allocated in a 1:1 ratio to the intervention and control arms. The primary outcome is defined as remission from major depressive episode at 3 months postnatal measured with the SCID. Data will also be collected on symptoms of anxiety, disability, quality of life, service use and costs, and infant-related outcomes such as exclusive breastfeeding and immunization rates. Data will be collected on the primary outcome and selected secondary outcomes (depression and anxiety scores, exclusive breastfeeding) at 6 months postnatal to evaluate if the improvements are sustained in the longer-term. We are especially interested in sustained improvement (recovery) from major depressive episode. DISCUSSION: This trial will evaluate the effectiveness and cost-effectiveness of a technology-assisted peer-delivered cognitive behavioral therapy-based intervention in rural Pakistan. If shown to be effective, the novel delivery format could play a role in reducing the treatment gap for perinatal depression and other common mental disorders in LMIC. TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (NCT05353491) on 29 April 2022.

Effect of Leflunomide-Metal Complexes on ROS, TNF, and Brain Indolamines in Comparison with Anti-Depressants as Adjunct Therapy in Rheumatoid Arthritic Model.

Leflunomide is an isoxazole immunomodulating drug used to treat rheumatoid arthritis (RA). It is adopted as a metal-containing molecule to proceed with saturated salts of essential and detected metals; it amends the pharmacokinetic and pharmacodynamics activity of leflunomide to provide [M(Lef)4]X2-type complexes. Earlier it has been reported that after forming complexes with metals, leflunomide anti-arthritic activity was significantly altered in an acute arthritic model. In the present study, we evaluated the possible modification in anti-arthritic activities of leflunomide-metal complexes (Mg+2, Ca+2, Fe+2, Zn+2) with and without an anti-depressant drug, i.e., fluoxetine (10 mg/kg) in a chronic AIA model. Rats (n = 5) were administered with 0.1 mL of CFA into the right hind paw while treated groups received leflunomide and its metal complexes orally (3.2 mg/kg) for 24 days. On the final day of experiment, rats were sacrificed; a specific rat immunoassay ELISA kit was used to assess TNF-α in serum samples and read at 450 nm; a tissue sample of a paw was homogenized in a phosphate buffer using DCFH-DA dye for binding to assess ROS. A rat's brain sample was homogenized and evaluated for tryptophan, serotonin (5-HT), and HIAA by RP-HPLC with EC detector. The overall TNF production was altered in treated rats. In addition, a decreased ROS was observed in all categories, except lef+Mg+2 group. Moreover, depletion in the brain indolamine levels were found in treated groups; an upraised level of these indolamines was observed when fluoxetine was added. It is concluded that metals affect leflunomide activity on complexation and simultaneous administration of fluoxetine cope up with the depression in arthritic-induced rats.

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.

Undiagnosed Rare Genetic Disorders: Importance of Functional Characterization of Variants.

Rare Genetic Disorders (RGDs) are defined as disorders that affect less than 1 in 2000 people, and collectively affect more than 300 million people worldwide [...].

Community centred co-design methodology for designing and implementing socio-behavioural interventions to counter COVID-19 related misinformation among marginalized population living in the squatter settlements of Karachi, Pakistan: a methodology paper.

BACKGROUND: Misinformation regarding COVID-19 pandemic and vaccination is damaging COVID-19 vaccine trust and acceptance in Low- and Middle-Income Countries (LMIC). Identification of misinformation and designing locally acceptable solutions are needed to improve COVID-19 vaccine acceptance. This study aimed to utilize community-led co-design methodology to evaluate misinformation regarding COVID-19 and develop contextual interventions to address misinformation in a marginalized peri urban slum communities of Landhi town Karachi, Pakistan. METHODS: This study was conducted between January and December 2021, in marginalized peri-urban slum dwellers of Muslimabad Colony, Landhi Town Karachi, Pakistan. We used a community-centred co-design methodology embedded within mixed study design to identify misinformation, co-design, test and implement locally acceptable solutions. The co-design methodology involved five stages of the design thinking model: (1) Empathize, (2) Define, (3) Ideate, (4) Prototype, and (5) Test. The project involved active engagement and participation of wide range of stakeholders and community beneficiaries (end users) including local EPI vaccinators, informal healthcare workers, religious leaders (male and female), schoolteachers (male and female), local government representatives, community leaders, housewives, youth, and general population. To develop a trusting relationship, and understand local culture, values, practices, and traditions, we allowed one month of observation period (observe, engage, watch, and listen) in the beginning, followed by door-to-door survey along with focus group discussions (FGD) and in-depth interviews (IDI) at baseline. Co-design workshops (separate for male and female) were conducted at each stage of co-design methodology to design and test locally acceptable solutions. CONCLUSION: Community-centred co-design methodology was not only successful in designing, testing, and evaluating locally acceptable solutions but it also actively engaged and empowered the marginalized population living in peri urban slum communities of Karachi, Pakistan.

Weed infestation and productivity of wheat crop sown in various cropping systems under conventional and conservation tillage.

Introduction: Climate change, pest infestation, and soil degradation are significantly reducing wheat (Triticum aestivum L.) yield. Wheat is cultivated in rice-wheat and cotton-wheat cropping systems and escalating global population is exerting substantial pressure on the efficiency of these systems. Conservation tillage and crop rotation could help in lowering soil degradation and pest infestation, and improving wheat yield. Methods: This three-year study evaluated soil properties, weed infestation and wheat yield under various tillage and cropping systems. Six different cropping systems, i.e., cotton-wheat, sorghum-wheat, mungbean-wheat, rice-wheat, sunflower-wheat, and fallow-wheat (control) and three tillage systems, i.e., conventional tillage (CT), zero-tillage (ZT) and minimum tillage (MT) were included in the study. Results: The individual and interactive effects of tillage and cropping systems significantly affected soil properties, weed infestation and yield of wheat crop. Overall, CT resulted in lower soil bulk density and higher porosity, while ZT behaved oppositely at all locations in this regard. Similarly, mungbean-wheat cropping system resulted in lower bulk density and higher porosity and nitrogen (N) contents, while fallow-wheat cropping system resulted in higher bulk density, and lower soil porosity and N contents. Similarly, ZT and CT resulted in higher and lower weed infestation, respectively. Likewise, lower and higher weed density and biomass were recorded in wheat-sorghum and wheat-fallow cropping systems, respectively at all locations. In the same way higher number of productive tillers, number of grains per spike, 1000-grain weight, grain yield, and economic returns of wheat crop were recorded for CT, whereas ZT resulted in lower values of these traits. Regarding interactions, wheat-mungbean cropping system with CT resulted in lower bulk density and higher porosity and N contents, whereas wheat-fallow system with ZT behaved oppositely at all locations in this regard. Similarly, higher and lower values for yield-related traits and economic returns of wheat crop were noted for mungbean-wheat cropping system under CT and fallow-wheat and sorghum-wheat cropping systems under ZT, respectively. It is concluded that the mungbean-wheat cropping system improved wheat productivity and soil health and sorghum-wheat cropping system could lower weed infestation. Therefore, these cropping systems can be practiced to lower weed infestation and improve wheat yield and economic returns.

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.

A placebo-controlled randomized clinical trial of antibiotics versus probiotics as an adjuvant to nonsurgical periodontal treatment among smokers with Stage III, Grade C generalized periodontitis.

BACKGROUND: Probiotics are viable microorganisms, which if delivered in appropriate dose can provide health benefits. Lactobacillus reuteri (DM17938+ATCC PTA 5289) has been recommended as a safe choice for probiotics. The objective of this study is to compare the improvement in the periodontal parameters amongst smokers with generalized periodontitis with Stage III, Grade C treated with nonsurgical periodontal treatment (NSPT) to which either an antibiotics or probiotics were given as an adjuvant. METHODS: Sixty smokers with Stage III, Grade C generalized periodontitis were randomized in two groups after taking informed consent. Periodontal parameters including bleeding on probing (BOP), probing depth (PD), attachment loss (AL), gingival index (GI), and plaque index (PI) were recorded. Group 1 received (after NSPT and oral hygiene instructions) amoxicillin and metronidazole for 7 days and a placebo for probiotics for 30 days. Group 2 was provided (after NSPT and oral hygiene instructions) with one tablet of Lactobacillus reuteri probiotics (2 × 108 CFU) twice daily for 30 days and placebo antibiotics for 7 days. The periodontal parameters were recorded again at 1- and 3-month follow-ups as outcome variables. Mean, standard deviation, and confidence interval were reported using SPSS 20.0. RESULTS: A statistically significant clinical improvement in the PD, BOP, PI, and GI were observed in both the groups at 3-month follow-up. However, the AL remained unchanged in both the groups. CONCLUSIONS: Administration of probiotics and antibiotics along with NSPT yield statistically significant differences in PD and BOP from baseline to 3-month follow-up. However, between the group differences were not statistically significant for the periodontal parameters (AL, PD, and BOP).

Biallelic Variants in Seven Different Genes Associated with Clinically Suspected Bardet-Biedl Syndrome.

Bardet-Biedl syndrome (BBS) is a rare clinically and genetically heterogeneous autosomal recessive multi-systemic disorder with 22 known genes. The primary clinical and diagnostic features include six different hallmarks, such as rod-cone dystrophy, learning difficulties, renal abnormalities, male hypogonadism, post-axial polydactyly, and obesity. Here, we report nine consanguineous families and a non-consanguineous family with several affected individuals presenting typical clinical features of BBS. In the present study, 10 BBS Pakistani families were subjected to whole exome sequencing (WES), which revealed novel/recurrent gene variants, including a homozygous nonsense mutation (c.94C>T; p.Gln32Ter) in the IFT27 (NM_006860.5) gene in family A, a homozygous nonsense mutation (c.160A>T; p.Lys54Ter) in the BBIP1 (NM_001195306.1) gene in family B, a homozygous nonsense variant (c.720C>A; p.Cys240Ter) in the WDPCP (NM_015910.7) in family C, a homozygous nonsense variant (c.505A>T; p.Lys169Ter) in the LZTFL1 (NM_020347.4) in family D, pathogenic homozygous 1 bp deletion (c.775delA; p.Thr259Leufs*21) in the MKKS/BBS5 (NM_170784.3) gene in family E, a pathogenic homozygous missense variant (c.1339G>A; p.Ala447Thr) in BBS1 (NM_024649.4) in families F and G, a pathogenic homozygous donor splice site variant (c.951+1G>A; p?) in BBS1 (NM_024649.4) in family H, a pathogenic bi-allelic nonsense variant in MKKS (NM_170784.3) (c.119C>G; p.Ser40*) in family I, and homozygous pathogenic frameshift variants (c.196delA; p.Arg66Glufs*12) in BBS5 (NM_152384.3) in family J. Our findings extend the mutation and phenotypic spectrum of four different types of ciliopathies causing BBS and also support the importance of these genes in the development of multi-systemic human genetic disorders.

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.