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Abstract The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = − 22.07 mg/dl (95% CI − 27.17, − 16.97), HbA1c [MD = − 0.53% (95% CI − 0.67, − 0.38)], HOMA-IR [MD = − 1.26 (95% CI − 2.16, − 0.37)], and fasting insulin [MD = − 19.83 pmol/L (95% CI − 29.54, − 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D. PROSPERO registration no. CRD42023412603.

Developmental disorders (DDs), such as autism spectrum disorder (ASD), incorporate various conditions; once identified, further diagnostics are necessary to specify their type and severity. The aim of this exploratory study was to identify genetic variants that can help differentiate ASD early from other DDs. We selected 36 children (mean age 60.1 months) with DDs using Developmental Behavioral Scales (DBS) through “EDUS-Education for All”, an organization providing services for children with developmental disorders in Bosnia and Herzegovina. We further rated children's autistic traits with the preschool version of the Childhood Autism Rating Scale, second edition (CARS-II). We defined ASD if scores were >25.5 and other DDs if scores were

Lower fine motor performance in childhood has been associated with poorer cognitive development and neurodevelopmental conditions such as autism spectrum disorder, yet, biological underpinnings remain unclear. DNA methylation (DNAm), an essential process for healthy neurodevelopment, is a key molecular system of interest. In this study, we conducted the first epigenome-wide association study of neonatal DNAm with childhood fine motor ability and further examined the replicability of epigenetic markers in an independent cohort. The discovery study was embedded in Generation R, a large population-based prospective cohort, including a subsample of 924 ~ 1026 European-ancestry singletons with available data on DNAm in cord blood and fine motor ability at a mean (SD) age of 9.8 (0.4) years. Fine motor ability was measured using a finger-tapping test (3 subtests including left-, right-hand and bimanual), one of the most frequently used neuropsychological instruments of fine motor function. The replication study comprised 326 children with a mean (SD) age of 6.8 (0.4) years from an independent cohort, the INfancia Medio Ambiente (INMA) study. Four CpG sites at birth were prospectively associated with childhood fine motor ability after genome-wide correction. Of these, one CpG (cg07783800 in GNG4) was replicated in INMA, showing that lower levels of methylation at this site were associated with lower fine motor performance in both cohorts. GNG4 is highly expressed in the brain and has been implicated in cognitive decline. Our findings support a prospective, reproducible association between DNAm at birth and fine motor ability in childhood, pointing to GNG4 methylation at birth as a potential biomarker of fine motor ability.

To develop two ethical checklists to evaluate (i) management of ethical concerns in research projects and (ii) awareness of ethical conduct of healthcare laboratory professionals. Comprehensive discussion among the members of IFCC Task Force on Ethics based on pertinent literature. This Checklist for Clinical Research Projects should be useful to evaluate research proposals from an ethical perspective before submitting it to an IRB or its equivalent, thereby diminishing rejection rates and resulting in more time-effective projects. The checklist designed to evaluate the ethical conduct in laboratory medicine could be useful for self evaluation (internal audits) and for certification/accreditation processes performed by third parties. These checklists are simple but powerful tools useful to guide professionals to adhere to ethical principles in their practice, especially in developing countries where accredited ethics committees may be difficult to find. [ABSTRACT FROM AUTHOR]

Purpose: To analyze outcomes after multiple light redirection (MLR) by photoablation of a small paracentral portion of Bowman's layer in each corneal quadrant using standard myopic laser in situ keratomileusis (LASIK) software with non-customized fenestrated MLR corneal light shields (Excimer-MLR) without postoperative visual training or magnification in pseudophakic eyes with central visual loss from age-related macular degeneration (AMD) with geographic atrophy (GA). Methods: Retrospective analysis of two cases. Results: Outcomes after Excimer-MLR in the worse-seeing eyes of an 86-year-old and a 65-year-old pseudophakic man with AMD and GA revealed corrected distance/near visual acuity gains of 6.0/6.0 and 11.8/10.0 lines within 12 days and 5.0/5.0 and 12.2/9.8 lines at 9 months, respectively, with improved Amsler grids, no distance or near glasses change, no complications, and no adverse events related to Excimer-MLR. Contrast sensitivity and stereopsis, measured in case 2, improved postoperatively. Conclusions: This first report showed that Excimer-MLR safely produced large improvements in visual function up to 9 months postoperatively in two eyes with central visual loss from AMD. [Journal of Refractive Surgery Case Reports. 2024;4(4):e29–e35.] [ABSTRACT FROM AUTHOR]

Introduction Schizophrenia (SCH) and bipolar affective disorder (BP) are complex disorders that overlapping both in their clinical symptoms and certain familiar characteristics. They share some common characteristcs but there are also key differences. The frequency of overlapping symptoms between these diseases could give us more information about the current validity of the diagnosis based on existing diagnostic criteria. Similarities within and between these two disorders in the future, can possibly redefine greater reliability of diagnosis. Objectives The aim of the study was to investigate the frequency of overlapping symptoms between BP and SCH. Methods The sample included 159 patients diagnosed with SCH and 61 with BP who were followed over a two year period. The research was conducted at the UCCS Psychiatric Clinic. Assessment of clinical symptoms and diagnosis were performed using a structured clinical interview (SCID I), a list of operationalized criteria (OPSCRIT), a scale for the assessment of positive and negative symptoms (PANSS), a scale for the assessment of manic symptoms (YMRS). Results The overall PANSS score was significantly higher in patients with SCH compared to patients with BP, but on the general psychopatology there are no significant differences betwen SCH and BP. Symptoms of mania are significantly more pronounced in patients with BP compared to those with SCH. Conclusions Our results of overlapping of individual symptoms between SCH and BP can speak infavor of the theory of disease continuum. And can also help us in understanding symptoms and guide us to develop optimal treatment strategies. Disclosure No significant relationships.

Introduction Clozapine is a drug that can cause several side effects. Among the less commonly described is a drug-induced lung disease. Due to its non-specific clinical presentation, it represents a diagnostic challenge. The diagnosis is made based on: 1. Association of exposure to the agent and development of symptoms, 2. Pulmonary infiltration, 3. Exclusion of other causes, 4. Withdrawal of symptoms when the agent is excluded from therapy. To date, there have been only a few descriptions of this condition. Objectives Case report of rare side effect of clozapine. Methods Case report Results Case report: male patient (37) with schizophrenia, was hospitalized after a brutal suicide attempt. The PCR test for COVID-19 that was routinely performed on admission was negative. After the introduction of clozapine into therapy, the patient became febrile. There was a drop in oxygen saturation, a Lung CT scan showed inflammatory changes („ground-glass opacities“), and COVID-19 pneumonia was suspected. Due to the worsening of the mental state, the dose of clozapine was increased. The physical condition further deteriorated: febrile, sO2 declining. After repeated PCR tests for COVID-19 (all negative), interstitial pneumonia caused by clozapine was suspected, and clozapine was excluded from therapy. The physical condition started to improve. Quetiapine was introduced, and occasional episodes of agitation were relieved with intramuscular diazepam. In the following days, the patient’s mental state improved and he was discharged. Conclusions Despite its superiority over other antipsychotics, clozapine was with good rationale ranked third in treatment guidelines for schizophrenia. Disclosure No significant relationships.

Purpose – This study examined how youth would mitigate non-medical use of prescription medication among their peers. Design/methodology/approach – The National Monitoring of Adolescent Prescription Stimulants Study (N-MAPSS) was conducted as an interview comprising 11,048 youth of 10–18 years of age between 2008 and 2011 from entertainment venues of 10 US urban, suburban, and rural areas. Using a mixed-methods approach, participants completed a survey culminating in open-ended questions asking: (1) How should kids your age be informed about prescription drugs and their effects? (2) If you ran the world, how would you stop kids from taking other people’s prescription medicines? (3) Why do people use prescription stimulants without a prescription? Responses from a random sample of 900 children were analyzed using qualitative thematic analyses. Findings – The random sample of 900 youth (52 percent female, 40 percent white, with a mean age of 15.1 years) believed they should be educated about prescription drugs and their negative effects at schools, at home by parents, through the media, and health professionals. Youth would stop kids from using other people’s prescription drugs through more stringent laws that restricted use, and providing education about negative consequences of use. Peer pressure was the most common reason the youth gave for using other’s pills, though some reported taking them out of curiosity. Originality/value – The importance of considering youth’s opinions on non-medical use of prescription medications is often overlooked. This evidence, from a peer perspective, could end the illicit use of prescription drugs among today’s youth.

The main contribution of this paper lies in applying Adam Smith's moral theory to explain how some actions become jointly recognized as socially appropriate while others do not, and how these jointly recognized rules affect actual behavior. To illustrate the strength of Smith's theory, we apply it to the norm-elicitation method by Krupka and Weber (2013) among a representative sample to explain how different elicited social norms vary across “giving” and “taking” contexts in the dictator game.