Affect-Logic, Embodiment, Synergetics, and the Free Energy Principle: New Approaches to the Understanding and Treatment of Schizophrenia

This theoretical paper explores the affect-logic approach to schizophrenia in light of the general complexity theories of cognition: embodied cognition, Haken’s synergetics, and Friston’s free energy principle. According to affect-logic, the mental apparatus is an embodied system open to its environment, driven by bioenergetic inputs of emotions. Emotions are rooted in goal-directed embodied states selected by evolutionary pressure for coping with specific situations such as fight, flight, attachment, and others. According to synergetics, nonlinear bifurcations and the emergence of new global patterns occur in open systems when control parameters reach a critical level. Applied to the emergence of psychotic states, synergetics and the proposed energetic understanding of emotions lead to the hypothesis that critical levels of emotional tension may be responsible for the transition from normal to psychotic modes of functioning in vulnerable individuals. In addition, the free energy principle through learning suggests that psychotic symptoms correspond to alternative modes of minimizing free energy, which then entails distorted perceptions of the body, self, and reality. This synthetic formulation has implications for novel therapeutic and preventive strategies in the treatment of psychoses, among these are milieu-therapeutic approaches of the Soteria type that focus on a sustained reduction of emotional tension and phenomenologically oriented methods for improving the perception of body, self, and reality.

Rhinitis sicca anterior in children: epidemiology and treatment with sesame seed oil nasal spray

Excessive dryness in the nose is very common among the population. The diagnosis of rhinitis sicca anterior is established quite often. Therefore, such patients need multicomponent treatment, taking into account all possible factors. The objective of this study was to investigate the effectiveness of sesame seed oil nasal spray (Sezorin manufactured by JSC “Farmak”) in rhinitis sicca anterior among children. As a result of using this drug, we achieved a fairly rapid and sustained reduction in clinical symptoms in our patients, and it is important to note that the effect of treatment with Sezorin spray was long-lasting.

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.

Analyzing human knockouts to validate GPR151 as a therapeutic target for reduction of body mass index

Novel drug targets for sustained reduction in body mass index (BMI) are needed to curb the epidemic of obesity, which affects 650 million individuals worldwide and is a causal driver of cardiovascular and metabolic disease and mortality. Previous studies reported that the Arg95Ter nonsense variant of GPR151, an orphan G protein-coupled receptor, is associated with reduced BMI and reduced risk of Type 2 Diabetes (T2D). Here, we follow up on GPR151 with the Pakistan Genome Resource (PGR), which is one of the largest exome biobanks of human homozygous loss-of-function carriers (knockouts) in the world. Among PGR participants, we identify 3 GPR151 putative loss-of-function (plof) variants (Arg95Ter, Tyr99Ter, and Phe175LeufsTer7) with a cumulative allele frequency of 2.2% and present at homozygosity. We confirm these alleles in vitro as loss-of-function. We test if GPR151 plof is associated with BMI, T2D, or other metabolic traits. GPR151 deficiency is not associated with a significant difference in BMI. Moreover, loss of GPR151 confers a nominally significant increase in risk of T2D (odds ratio = 1.2, p value = 0.03). Relative to wild-type mice, Gpr151-/- animals exhibit no difference in body weight on normal chow, and higher body weight on a high-fat diet, consistent with the findings in humans. Together, our findings indicate that GPR151 antagonism is not a compelling therapeutic approach for obesity.

Breath of Life: Heart Disease Link to Developmental Hypoxia

Heart disease remains one of the greatest killers. In addition to genetics and traditional lifestyle risk factors, we now understand that adverse conditions during pregnancy can also increase susceptibility to cardiovascular disease in the offspring. Therefore, the mechanisms by which this occurs and possible preventative therapies are of significant contemporary interest to the cardiovascular community. A common suboptimal pregnancy condition is a sustained reduction in fetal oxygenation. Chronic fetal hypoxia results from any pregnancy with increased placental vascular resistance, such as in preeclampsia, placental infection, or maternal obesity. Chronic fetal hypoxia may also arise during pregnancy at high altitude or because of maternal respiratory disease. This article reviews the short- and long-term effects of hypoxia on the fetal cardiovascular system, and the importance of chronic fetal hypoxia in triggering a developmental origin of future heart disease in the adult progeny. The work summarizes evidence derived from human studies as well as from rodent, avian, and ovine models. There is a focus on the discovery of the molecular link between prenatal hypoxia, oxidative stress, and increased cardiovascular risk in adult offspring. Discussion of mitochondria-targeted antioxidant therapy offers potential targets for clinical intervention in human pregnancy complicated by chronic fetal hypoxia.