Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications

PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications

Probability of Major Depression Classification Based on the SCID, CIDI and MINI Diagnostic Interviews : A Synthesis of Three Individual Participant Data Meta-Analyses

Three previous individual participant data meta-analyses (IPDMAs) reported that, compared to the Structured Clinical Interview for the DSM (SCID), alternative reference standards, primarily the Composite International Diagnostic Interview (CIDI) and the Mini International Neuropsychiatric Interview (MINI), tended to misclassify major depression status, when controlling for depression symptom severity. However, there was an important lack of precision in the results.To compare the odds of the major depression classification based on the SCID, CIDI, and MINI.We included and standardized data from 3 IPDMA databases. For each IPDMA, separately, we fitted binomial generalized linear mixed models to compare the adjusted odds ratios (aORs) of major depression classification, controlling for symptom severity and characteristics of participants, and the interaction between interview and symptom severity. Next, we synthesized results using a DerSimonian-Laird random-effects meta-analysis.In total, 69,405 participants (7,574 [11%] with major depression) from 212 studies were included. Controlling for symptom severity and participant characteristics, the MINI (74 studies; 25,749 participants) classified major depression more often than the SCID (108 studies; 21,953 participants; aOR 1.46; 95% confidence interval [CI] 1.11-1.92]). Classification odds for the CIDI (30 studies; 21,703 participants) and the SCID did not differ overall (aOR 1.19; 95% CI 0.79-1.75); however, as screening scores increased, the aOR increased less for the CIDI than the SCID (interaction aOR 0.64; 95% CI 0.52-0.80).Compared to the SCID, the MINI classified major depression more often. The odds of the depression classification with the CIDI increased less as symptom levels increased. Interpretation of research that uses diagnostic interviews to classify depression should consider the interview characteristics

Problem-based learning: medical students’ perception toward their educational environment at Al-Imam Mohammad Ibn Saud Islamic University

Abdulaziz Abdulrahman Aldayel, Abdulrahman Omar Alali, Ahmed Abdullah Altuwaim, Hamad Abdulaziz Alhussain, Khalid Ahmed Aljasser, Khalid A Bin Abdulrahman, Majed Obaid Alamri, Talal Ayidh Almutairi College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia Background: Problem-based learning (PBL) is a student-centered innovating instructional approach in which students define their learning objectives by using triggers from the problem case or scenario.Objectives: To assess undergraduate medical students’ perception toward PBL sessions and to compare their perceptions among different sex and grade point average (GPA) in the college of medicine, Al-Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.Materials and methods: We conducted a cross-sectional study based on a self-administered anonymous online questionnaire during the first semester of the 2017–2018 academic year in IMSIU. The data were collected from male and female students of the second and third year, as well as male students of the fourth year.Results: Out of 259 students, 152 (58.7%) completed the questionnaire. The students’ perception toward PBL was more positive than negative. Most of the students reported that PBL sessions increased their knowledge of basic sciences (P=0.03). Furthermore, most students agreed that PBL provided a better integration between basic and clinical sciences which differed significantly between the different GPA groups (P=0.02). Nevertheless, only 28.3% of the students agreed that the teaching staff is well prepared to run the sessions with significant statistical difference among different GPA groups (P=0.02). Moreover, only 26.3% of the students reported that there was proper student training before starting the PBL sessions with no significant difference. Additionally, only 34.2% and 28.9% of the students felt that they learn better and gain more knowledge thorough PBL than lectures respectively, with no significant difference.Conclusion: This study showed that tutors should be trained to guide the process of PBL effectively to achieve its goals. Moreover, students should be securely introduced to PBL and experience the development of their clinical reasoning through PBL. Further improvements are needed to provide students with an effective favorable learning environment and to take the students recommendations into consideration. Keywords: medical students, problem-based learning, education, perception, curriculum &nbsp