Towards an evolutionary perspective of bipolar disorders: Is there a genetic link between bipolar disorders and non-pathological (adaptive) hyperactivity?

The new-developed Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA), represents an innovative approach to hyperthymic features by embracing a broader concept of spectrum, which conceptualizes as a continuum the potential transition between pathological and adaptive aspects. The two basic components of the hyperthymic temperament that stand out are hyperactivity and goal achievement. This kind of temperament can be classified as abnormal only in the presence of chronic hypomanic symptoms or advanced mood disorders. In general, temperaments have been verified to belong to the domain of normality rather than the sphere of pathology, in accordance with their putative adaptive role. Commonly, achieving success, experiencing excitement and joy, and moving towards core life goals are moments of great importance in life. In this approach, goal and drive achievement demonstrates an adaptive and beneficial side of hyperthymia. It indicates the willingness to set high goals and spend energy pursuing them, which could help clarify the high rates of creative efforts among people with a hyperthymic temperament. However, the pathological scenery appears linked to variability in the adaptiveness with which people follow life goals and accomplishments. In the later stages of the study, this tool was very helpful in identifying older adults (60 years of age and older) with features of well-defined hyperactivity and novelty-seeking. The Questionnaire for Adaptive Hyperactivity and Goal Achievement (AHGA) measures the adaptive characteristics of hyperactivity and goal pursuit in contrast to the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) tool, which measures its pathological characteristics. According to the results regarding the investigated genetic variant (RS1006737) of the CACNA1C gene, an association was found with the characteristics of hyperactivity rather than just BD. Also, this genetic variant, recognized in the literature as associated with bipolar disorders, was found in well-adapted older adults without bipolar disorders and high hyperactivity traits with a similar frequency as in older adults with a diagnosis of bipolar disorders but higher than in older adults without bipolar disorders and without hyperactivity. This could led to the new interpretation and a new approach to supporting drug therapy in which the rediscovery of the adaptive potential resources would be central to the recovery of the individual who has suffered a bipolar disorder onset. Furthermore, the interpretation of the disorder not as the simple consequence of a genetic weakness could be an element against stigma and self-stigma. When comparing the biological material, although saliva and blood differ in composition and biological properties, sample type has no effect on the detection of a mutation in the genetic variant of interest. Blood and saliva can both be used as biological materials in later stages of this research. The combination of the new questionnaire tool (Questionnaire for Adaptive Hyperactivity and Goal Achievement) with the genetic analysis appears to be an innovative, practicable, and original approach. The following development of this study will include more genetic variables with higher susceptibility for bipolar disorders (ANK3, NCAN, ODZ4, SYNE1, and TRANK1 genes) and obviously more numerous target and control samples

Underlying cause of neonatal macrosomia

Background: High blood sugar levels (BSL) in pregnant could be a reason for macrosomia. The aim of our study was to present some indicators in LGA babies related to maternal diabetes. Methods: This was a cohort prospective study conducted in the first six months in 2020 at the University Clinic for Gynecology and Obstetrics in Skopje, North Macedonia. The identification of the LGA newborns was according to WHO growth standards for both sexes. Results: 108 LGA newborns, divided into three groups: A-36 LGA babies (33,3%) whose mothers had no history of Diabetes; B-14 LGA babies (12,9%) of mothers with pre-gestational Diabetes; C-56 LGA babies (51,6%) of mothers with Gestational diabetes were examined. Glycaemia was taken according to the National Guidelines (30 minutes after the second feed). The results showed significantly lower BSL in group C, mean 1,6±0,2 mmol/L (OR 2.19, 95% CI, 1.25–3.82, P=0.01). Both groups of newborns (A and B) had no significant difference in the mean value of BSL. The ratio of male/female was significantly higher in group A (1,4) compared to the other two groups, suggesting that associated factors other than diabetes are responsible for the macrosomia. The results showed that LGA babies have a much higher risk if their mothers have gestational diabetes compared to pre-existing diabetes, or with those whose mothers had no history or parameters of diabetes. Conclusion: The impact of gestational diabetes during pregnancy depends on early identification and good management

COVID-19 from a Perspective of Neuromuscular Diseases: Meeting the Challenges

Dear Editor, The new SARS-CoV-2 epidemic is imposing immense strain on the health systems in several countries. The growth of the epidemic has led the WHO to declare the 2019-nCoV disease as a global pandemic (1). COVID-19 pandemic has the potential to affect patients with neuromuscular diseases. The evaluation of the overall risk of COVID-19 in patients with neuromuscular diseases depends on several factors: the specificity of the neuromuscular disease, the general condition, the presence of other comorbidities, age, and the type of immunosuppressive treatment they receive. It is important to emphasize the fact that most patients with neuromuscular disease are not expected to suffer from severe complications due to coronavirus infection. Corona infections can affect certain myopathies. In a recent study published in China, related to COVID-19 is shown that hospitalized patients experienced fatigue and myalgia (44-70%), and increased creatine kinase (33%) in the serum (2). Apart from this, a third of hospitalized patients infected with the coronavirus had rhabdomyolysis (3). All of this points to the fact that coronavirus infection may be responsible for viral myositis. In addition, is the finding that some of the critical cases have developed polyneuropathy or myopathy (4). On the other hand, it is well known that infection is a trigger for exacerbation of certain neuromuscular diseases. There is no data that measured the risk of exacerbation as a result of coronaviruses infection for neuromuscular disorders. However, in one retrospective study, COVID-19 infection was a leading reason for the exacerbation of myasthenia gravis (5). As a result of this, an increased incidence of exacerbations of certain neuromuscular diseases should be expected, as well as the appearance of new clinical presentations during this pandemic. It is important to note that there are still no neuromuscular diseases-specific recommendations for patients who are infected with the coronavirus. Observation is recommended in patients at high and medium risk, especially in those patients where there is a possibility of a decrease in respiratory function. Last but not least, we would like to emphasize the need for reorganization of clinical care for these patients (6). The goal is to reduce exposure of patients to areas where the coronavirus could be found. Moreover, non-urgent or outpatient care is remarkably reduced. In conclusion, we must learn to apply our clinical practices in order to reduce the complications that may occur in patients with neuromuscular disease due to COVID-19. The primary goal is to develop evidence-based medical practices in order to reduce morbidity and mortality. Collaboration among institutions worldwide will be able to give us the data needed for planning management for neuromuscular disorders with COVID-19 and maintain clinical research against strong challenges

The impact of social determinants on growth and health in preschool children

Introduction: It is worldwide known that social, cultural, political, and economic environment has a direct impact on the preschool children's health and growth. Although, there is a significant rate of preschool child morbidity and mortality in Macedonia, and there is not precise data about the impact of social determinants on health and growth of preschool children yet. Aim of the study: The purpose of this thesis is to gain insight into the causal link between the common social determinants and the health and growth of preschool children, on the other hand. The results should serve to improve prevention and develop local programs to promote a sustainable system for improving children's health, with the help of reliable data. Material and methods of work: As a material, it was used health documentation from the parent pediatric institutions from Public Health Center – Zeleznicar (Skopje), and from outpatient clinic in municipality of Butel (Skopje). Statistically, there were processed 50 health documents randomly selected from both institutions, a total of 100, in the period of 2013 - 2017. Results: With the help of this paper, it will be possible to identify the link between social determinants and health with growth in children under five years of age. Of the group of mothers with primary education, 71% had a newborn with low birth weight, of the mothers with secondary education 18% had a newborn with low birth weight and a group of mothers with a university education, 2% had a newborn with low birth weight. In the study, one congenital anomaly was observed in a mother of age 36. That was congenital non – neoplastic nevus. In families where there are no employees 100% of the pre-school children had chronic infections, in families with 1 employee 87% of pre-school children had chronic infections and in families with 2 employees 77% of pre-school children had chronic infections. In children who only had healthy drinking water, there was no episode of diarrhea coming from contaminated drinking water, while pre-school children who came in contact with, in 100% there was diarrhea caused by contaminated drinking water. In the group of pre-school children living in homes with sanitary conditions, 100% are absent digestive disorders caused by unsecured sanitation in the home. In the group of pre-school children living in homes where no sanitary conditions are provided, 100% of them were digestive diseases where unsecured sanitation appeared as an aetiological moment. Conclusion: Determining levels of inequality is essential for improving the health and nutrition of the poor. This does not mean only a set of solutions that involve multiple institutions, but also their effective dealing with all levels of determination. The social determinants of health are not vacuumed. Their quality and accessibility to the population are usually the result of public policy decisions made by the authorities. Keywords: social determinants, preschool children, health, growth

Can an Investigation of a Single Gene be Effective in Differentiating Certain Features of the Bipolar Disorder Profile?

Bipolar disorder (BD) is amongst the most common heritable mental disorders, but the clarification of its genetic roots has proven to be very challenging. Many single nucleotide polymorphisms (SNPs) have been identified to be associated with BD. SNPs in the CACNA1C gene have emerged as the most significantly associated with the disease. The aim of the present study is to provide a concise description of SNP 1006737 variants identified by Real Time PCR and confirm sequencing analysis with the Sanger method in order to estimate the association with BD. The molecular method was tested on 47 Sardinian subjects of whom 23 were found to not be mutated, 1 was found to be a carrier of the homozygous A allele and 23 were found to be carriers of the heterozygous G allele. Moreover, the positive results of the preliminary application suggest that the development of the screener could be extended to the other 5 genetic variables identified as associated with BD

Systematic review of involuntary hospitalisation and long-term compliance

Introduction Involuntary hospitalisation denies autonomy and freedom of decision-making and is frequent in psychiatric clinical practice. However, there is still a lack of knowledge of long-term compliance after Involuntary commitment. Methods We conducted a systematic review of published studies reporting people compliance after involuntary hospitalisation and people compliance after voluntary admission. Two investigators independently searched PubMed, PsycINFO, EMBASE and CINAHL up to December 17th, 2021 to identify eligible studies. The study is registered with PROSPERO number CRD42022299437. Results Ten independent studies analysing the main indicators of compliance, engagement with services and medication adherence, were included. Three studies show that compliance is worse in people that have been involuntary hospitalised and in the others no association is found. Just two of the ten studies show an association with improved compliance. Outcomes are assessed from the first follow-up appointment after discharge up to 96 months. Conclusions Although evidences carried out so far are weak, the data do not show a trend of improvements and do not seem to exclude the possibility of worse compliance after compulsory hospitalisation. More appropriate methodologies and reliable assessment are needed in future research to provide scientific evidence on involuntary admission health effects

Erythrodermiaichtyosisformis congenital – A case report

Non-bullous congenital ichthyosi-form erythroderma is an autosomal recessive congenital keratinization disorder. We present the only one registered case of congenital non-bullous ichthyosiformerythroderma in North Macedonia. Our patient now is a 29-year old man from Gostivar. He was born with low birth weight and a low Apgar score (5/7). After birth, the skin was so cracked, that there were bleeding in certain places. Furthermore, the entire body, especially the head, was covered with yellow-green scales of varying size, which were firmly attached to the substrate. There was no history of similar or same illness in the family. Little is known about the oral manifestations of this disorder. The prognosis is variable. The disease has a strong impact on the quality of life due to altered physical appearance, problematic symptoms and treatment restrictions

Antenatal Thymosin β4: a New Tool for Accelerating Fetal Development in Preterms? Thymosin Beta-4: a Breakthrough in the "Physiological" Regenerative Medicine in Preterm Newborns

To prevent the health risks related to prematurity, multiple drugs have been introduced in clinical practice in recent years. This paper focuses on a new "physiological" regenerative approach to be started in the perinatal period, particularly on very low birth weight preterm infants. This new preventive approach underlined the necessity to start regenerative medicine very early after birth, a period in which kidney, brain, pancreas, and lung stem cells maintain their proliferative and differentiating abilities. Among the multiple factors proposed in the literature as potential growth promoters for preterm neonates, thymosin beta-4 (Tβ4) has been indicated as one of the most important candidates for regenerative medicine

Is a Genetic Variant associated with Bipolar Disorder Frequent in People without Bipolar Disorder but with Characteristics of Hyperactivity and Novelty Seeking?

Objective: The objective is to verify whether a genetic condition associated with bipolar disorder (BD) is frequent in old adults adapted to their environment, without BD, but with aptitudes for hyperactivity and novelty seeking (H/NS). Methods: In this cross-sectional study, the study sample included healthy elderly people (40 participants, aged 60 or older) living in an urban area and recruited from a previous study on physical exercise and active aging, who were compared with 21 old adults with BD from the same area. The genetic methodology consisted of blood sampling, DNA extraction, real-time PCR jointly with FRET probes, and the SANGER sequencing method. The genetic variant RS1006737 of CACNA1C, found to be associated with bipolar disorder diagnosis, was investigated. Results: The frequency of the RS1006737 genetic variant in the study group (H/NS) is not higher than in the BD group and is statistically significantly higher than in all the control groups found in the literature. However, the familiarity for BD is higher in old adults with BD than in the H/NS sample without BD. The risk of BD in the family (also considering those without BD but with family members with BD) is not associated with the presence of the genetic variant examined. Conclusion: The study suggests that the gene examined is associated with characteristics of hyperactivity rather than just BD. Nevertheless, choosing to participate in an exercise program is an excessively general way to identify H/NS. The next step would be to identify the old adults with welldefined H/NS features with an adequate tool

The Impact of Social Determinants on Perinatal Outcome

The health of the pregnant woman has high impact over the health of her offspring. The social determinants of health are the circumstances in which people are born, grow, live, work and age.  Aim: to evaluate the impact of few pre-pregnancy and social determinants on overall conceptual model of perinatal health. Material and methods: prospective cohort study evaluating preterm, SGA and LBW newborns in relation to social determinants in pregnant women at University Clinic for Gynecology and Obstetrics-Skopje. Results: the Relative Risk (RR) for delivering preterm baby (35-37 g.w. in unemployed mother is 2,96 with significant Confidence Interval, (1,86-4,71). If four more mothers are employed, there is a chance to get one preterm baby less, which means that this intervention could be beneficial for both. The Relative risk of delivering SGA baby in unemployed mothers is 1,98. The Relative risk to get preterm baby if BMI < 18 is 3,08 and is much higher than getting SGA baby (RR=1,85). The RR for delivering preterm baby and SGA baby at mothers with BMI >25 is 2,96 and 1,44 respectively. On the other hand, the RR for the both outcomes has no statistical significance independently whether the mother is living in rural or urban areas. Discussion and Conclusion: there is different impact of the social determinants on the perinatal outcome, and varying extent, depending on the country, social security, economic development. Many complementary actions should be undertaken by the Government, because the social determinants tackle every cell of the society