Molecular confirmation of the causes of inherited visual impairment in Northern Pakistan

Families with inherited visual impairment were identified and examined from January 2000 to December 2005 and given a clinical diagnosis. Known genes and loci were screened for mutations or linkage at Institute of Ophthalmology and Neurosciences, University of Leeds, in order to provide molecular confirmation. Inherited retinal disease was the most common cause of inherited visual impairment in 38 of 57 families (66.6%) with Leber\u27s congenital amaurosis, rod-cone dystrophy and cone-rod dystrophy being the most common diagnoses in 22, 8 and 3 families respectively. Anterior segment dysgenesis was diagnosed in 8 families (14%). Mutations in known genes or linkage to known loci were identified in 23 of 57 families (40%). All families had molecular confirmation of autosomal recessive inheritance or a pedigree consistent with this mode of inheritance, with evidence of first-cousin marriage. Knowledge of carrier status and genetic counseling may allow families to make an informed decision regarding marriage, and thus begin to plan a way of reducing the incidence of inherited visual impairment

The effect of the COVID-19 pandemic in intestinal rehabilitation and transplant patients, initial results of an international survey

Introduction: On January 30, 2020 the World Health Organization (WHO) declared the 2019-CoV outbreak in China as a global public health emergency and subsequently, a pandemic on March 11th. It was considered that intestinal failure and intestinal transplant patients might have a higher risk of severe complications from the COVID-19 disease, multidisciplinary intestinal failure teams had to adapt their clinical approaches in order to keep this vulnerable group of patients as safe as possible during the pandemic; but data was lacking. Therefore, in order to improve our knowledge, we designed a voluntary, international survey aiming to address the impact of the COVID-19 disease in intestinal failure and transplant patients worldwide. Patient and Methods: A retrospective, observational, multicenter survey was sent to all centers registered at the Intestinal Rehabilitation and Transplant Association (IRTA). The survey contained three modules: the 1st one consisted of 14 questions about the hospital\u27s activity during the COVID-19 pandemic. The 2nd one, contained 43 questions, was about intestinal failure patient management and outcome and the 3rd one (52 questions) focused on intestinal transplant patients. We used the Google Form platform. We aim to present the preliminary results of the first module. Statistical analysis was performed with the IBM SPSS Statistic version 25.0® program. Results: 13/42 (41%) centers responded; including centers from France, Netherlands, Italy, United States, UK, Sweden, Germany and Argentina. Only 2 centers reported moratorium on intestinal (IT) or multivisceral transplant (MVT), with a mean of 3 months (±4) [Table 1]. Since the pandemic started, 2 institutions reported 4 patients with intestinal rehabilitation or on TPN diagnosed with COVID-19 while 7 centers hospitals claimed to have had 9 patients post-IT/MTV affected by the disease. While 7 centers had their routine follow up and \u27protocol biopsies\u27 in the post-IT/MTV affected, none reported higher rates of rejection or complications. At the same time, 8 centers (77%) were affected by a mean of 15% decrease in referrals for new evaluations of intestinal failure or transplantation (compared to 2019) [Figure 1]. All centers adapted to utilizing telemedicine to follow up on IT/MVT patients. Conclusions: Many aspects of healthcare have been impacted by the COVID-19 pandemic. The survey showed that the number of affected patients has been lower than expected, the reduced number of centers required transient moratorium of their activity, but a secondary observation was that despite the availability of telemedicine, and probably related to the lockdown, there has been a significant reduction in the referrals for evaluation of intestinal failure and transplant patients, that may have the deleterious effect of the delay of treatment in health care system

A Group Parenting Intervention for Depressed Fathers (LTP + Dads): A Feasibility Study from Pakistan

Introduction: In this study, we feasibility tested Learning Through Play Plus Dads (LTP+ Dads), a group parenting psychoeducation program adapted for depressed Pakistani fathers of children under three years of age. Methods: A total of 18 fathers with depression were recruited in Karachi, Pakistan for a pre-post feasibility study. Ten sessions of group LTP+ Dads were offered over three months. Clinical assessments were administered at baseline, 3 and 6 months and included the Edinburgh Postnatal Depression Scale, 17-item Hamilton Depression Rating Scale, Brief Disability Questionnaire, Multidimensional Scale of Perceived Social Support, Euro-Qol-5 Dimensions, Rosenberg Self-esteem Scale, Parenting Stress Index, and Knowledge, Attitude and Practices questionnaire. Results: The intervention was feasible to implement and acceptable based on a recruitment rate of 100% of eligible participants and a 100% attendance rate for 5 of the 10 sessions. Within this preliminary sample, fathers showed, on average, a reduction in depressive symptoms, an increase in most areas of fathers’ knowledge and positive attitudes about child development. Perceived social support, self-esteem and functioning scores also increased. Limitations: The small sample size and lack of control group are limitations of this study. Conclusions: In this first study of paternal depression in Pakistan, a low cost culturally adapted group intervention was found to be feasible and acceptable. Changes in depression, parenting-related and other outcomes are promising and inform a future larger trial. Keywords: Paternal depression, Cultural Adaptation, CBT, Parenting, Low and middle income countr

Modulations of cell cycle checkpoints during HCV associated disease

Background Impaired proliferation of hepatocytes has been reported in chronic Hepatitis C virus infection. Considering the fundamental role played by cell cycle proteins in controlling cell proliferation, altered regulation of these proteins could significantly contribute to HCV disease progression and subsequent hepatocellular carcinoma (HCC). This study aimed to identify the alterations in cell cycle genes expression with respect to early and advanced disease of chronic HCV infection. Methods Using freshly frozen liver biopsies, mRNA levels of 84 cell cycle genes in pooled RNA samples from patients with early or advanced fibrosis of chronic HCV infection were studied. To associate mRNA levels with respective protein levels, four genes (p27, p15, KNTC1 and MAD2L1) with significant changes in mRNA levels (\u3e 2-fold, p-value \u3c 0.05) were selected, and their protein expressions were examined in the liver biopsies of 38 chronic hepatitis C patients. Results In the early fibrosis group, increased mRNA levels of cell proliferation genes as well as cell cycle inhibitor genes were observed. In the advanced fibrosis group, DNA damage response genes were up-regulated while those associated with chromosomal stability were down-regulated. Increased expression of CDK inhibitor protein p27 was consistent with its mRNA level detected in early group while the same was found to be negatively associated with liver fibrosis. CDK inhibitor protein p15 was highly expressed in both early and advanced group, but showed no correlation with fibrosis. Among the mitotic checkpoint regulators, expression of KNTC1 was significantly reduced in advanced group while MAD2L1 showed a non-significant decrease. Conclusion Collectively these results are suggestive of a disrupted cell cycle regulation in HCV-infected liver. The information presented here highlights the potential of identified proteins as predictive factors to identify patients with high risk of cell transformation and HCC development

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Monitoring and Management of Proteinuria Is Often Ignored in Patients Receiving mTOR Therapy Following Orthotopic Liver Transplantation

Purpose: Use ofmTOR inhibitors, such as Everolimus(EVL), in liver transplant (LT) patients continues to rise as the side effect profile becomes more evident. Calcineurin inhibitors, suchas Tacrolimus, have an increased incidence of nephrotoxicity whereas EVLremainsaviableoptiontodecreasethelikelihood of renal dysfunction. In renal transplant patients, standardof care involves regular monitoring urine protein levels. however no such consensus exists amongst LT patients. We analyzed renal function by assessing proteinuria in LT patients started on EVL. Methods: All patients receivingaLTbetween2011 and 2014 treated withEVLwere evaluated. Background infonnation included age, gender and race. Assessment of urine protein to creatinine (UP/C) ratios was done prior to starting EVL. Follow up UP/C ratios were analyzed after starting EVL at 3 months and anytime past 6 months. Nephrotic range was defined as spot urine protein to creatinine ratio greater than 1 gram (g). Statistics were calculated using ANOVA, T-test and Chi-squared tests. Results: 75 LT patients composed primarily of males (76%) with an average age of 60.9years were analyzed. There were 58 Caucasians (77%) and 11 African Americans (14.7%). Out of 75 total patients, 84% of patients had a UP/C ratio measured before starting EVL. After starting EVL, 30.7% had a follow up UP/C ratio measured at any given time. 11 patients had a UP/C ratio measured at 3 months and 17 patients at any time after 6 months. Before starting EVL the mean UP/C ratio was 0.17g. At the 3 monthfollow-up, mean UP/C ratio was 1.30g (p=0.112). At any point past 6 months from the time EVL therapy was started, mean UP/C ratio was 1.45g (p=0.504). 56.5% of patients that had their UP/C ratio checked, EVL was discontinued. The meannumber of months was 17.2 at which EVL was stopped from time ofinitiation. Conclusions: EVL appears to lead to a significant increase in proteinuria in LT patients with the progression of time. There is a potential for worsening renal func-tion, however regular follow up is lacking. It remains imperative that substantial proteinuria shouldlead to the discontinuation of EVL to prevent further renal toxicity