Genomic signatures of selection,local adaptation and production type characterisation of East Adriatic sheep breeds

Background The importance of sheep breeding in the Mediterranean part of the eastern Adriatic has a long tradition since its arrival during the Neolithic migrations.Sheep production system is extensive and generally carried out in traditional systems without intensive systematic breeding programmes for high uniform trait production(carcass,wool and milk yield).Therefore,eight indigenous Croatian sheep breeds from eastern Adriatic treated here as metapopulation(EAS),are generally considered as multipurpose breeds(milk,meat and wool),not specialised for a particular type of production,but known for their robustness and resistance to certain environmental conditions.Our objective was to identify genomic regions and genes that exhibit patterns of positive selection signatures,decipher their biological and productive functionality,and provide a"genomic"characterization of EAS adaptation and determine its production type.Results We identified positive selection signatures in EAS using several methods based on reduced local variation,linkage disequilibrium and site frequency spectrum(eROHi,iHS,nSL and CLR).Our analyses identified numerous genomic regions and genes(e.g.,desmosomal cadherin and desmoglein gene families)associated with environmental adaptation and economically important traits.Most candidate genes were related to meat/production and health/immune response traits,while some of the candidate genes discovered were important for domestication and evolutionary processes(e.g.,HOXa gene family and FSIP2).These results were also confirmed by GO and QTL enrichment analysis.Conclusions Our results contribute to a better understanding of the unique adaptive genetic architecture of EAS and define its productive type,ultimately providing a new opportunity for future breeding programmes.At the same time,the numerous genes identified will improve our understanding of ruminant(sheep)robustness and resistance in the harsh and specific Mediterranean environment.

Can Physical Activities Suppress Negative Impact of Stress on the Mental Health of Adolescents?

Early adolescence is a crucial developmental phase marked by significant physical,cognitive,and socioemotional changes.While stress is widely recognized as a notable risk factor during this period,not all individuals experiencing stress concurrently manifest compromised mental health.The association between stress and mental health outcomes is influenced by individual differences in characteristics and coping strategies.This study’s purpose was to assess the negative impact of stress on mental health,specifically focusing on symptoms of anxiety,depression,and psychological distress.Additionally,the research investigates whether different levels of physical activity can suppress the negative effects of stress.A total of 212 upper elementary school students(52.8%girls and 47.2%boys)from rural and urban areas voluntarily participated in the research.Participants online self-assessed on several measures:The Young Person’s CORE,Children’s Anxiety Scale,Children’s Depression Inventory,School Stress Intensity Scale for Students,and Physical Activity Questionnaire for Older Children.The results revealed a significant increase in adolescents experiencing impaired mental health.More than two-thirds(67.5%)of students self-assessed significant symptoms of depression,additionally,57.5%of them had significant symptoms of psychological distress,and 27.8%had significant symptoms of anxiety.Stress demonstrated a significant direct negative effect,leading to increased symptoms of anxiety(t=5.35,p=0.00)and psychological distress(t=4.29,p=0.00);however,there was no significant influence on depression(t=1.33,p=0.18)).Regarding regular physical activity,a significant moderating effect was identified,effectively suppressing the negative impact of stress on anxiety(F=3.88(2,206);p=0.02).In contrast,no significant moderation effect of physical activity was found for symptoms of depression(F=1.45(2,206);p=0.24)and psychological distress(F=1.14(2,206);p=0.32),highlighting a complex and intricate association between physical activity and various mental health outcomes.In conclusion,the practical implications of this study emphasize the importance of creating environments that reduce stressors for adolescents and promote regular physical activity as a means of fostering positive mental health outcomes.

Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of insulin.Diabetic foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic patients.The aim of this study is to provide an evidence-based overview of diabetic foot complications.Due to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin lesions.In patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and amputations.Hyperglycemia compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound healing.In addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial resistance.As a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be overlooked.Issues associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed annually.Although antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.

Prevalence of posttraumatic stress disorder following acute coronary syndrome and clinical characteristics of patients referred to cardiac rehabilitation

BACKGROUND Studies have demonstrated that patients who have experienced acute coronary syndrome(ACS)have an increased risk of developing posttraumatic stress disorder(PTSD)and experiencing worse survival outcomes than those who do not develop PTSD.Nevertheless,the prevalence rates of PTSD following ACS vary widely across studies,and it is noteworthy that in most cases,the diagnosis of PTSD was based on self-report symptom questionnaires,rather than being established by psychiatrists.Additionally,the individual characteristics of patients who develop PTSD after ACS can differ widely,making it difficult to identify any consistent patterns or predictors of the disorder.AIM To investigate the prevalence of PTSD among a large sample of patients undergoing cardiac rehabilitation(CR)after ACS,as well as their characteristics in comparison to a control group.METHODS The participants of this study are patients who have experienced ACS with or without undergoing percutaneous coronary intervention and are enrolled in a 3-wk CR program at the largest CR center in Croatia,the Special Hospital for Medical Rehabilitation Krapinske Toplice.Patient recruitment for the study took place over the course of one year,from January 1,2022,to December 31,2022,with a total of 504 participants.The expected average follow-up period for patients included in the study is about 18 mo,and currently ongoing.Using self-assessment questionnaire for PTSD criteria and clinical psychiatric interview,a group of patients with a PTSD diagnosis was identified.From the participants who do not have a PTSD diagnosis,patients who would match those with a PTSD diagnosis in terms of relevant clinical and medical stratification variables and during the same rehabilitation period were selected to enable comparability of the two groups.RESULTS A total of 507 patients who were enrolled in the CR program were approached to participate in the study.Three patients declined to participate in the study.The screening PTSD Checklist-Civilian Version questionnaire was completed by 504 patients.Out of the total sample of 504 patients,74.2%were men(n=374)and 25.8%were women(n=130).The mean age of all participants was 56.7 years(55.8 for men and 59.1 for women).Among the 504 participants who completed the screening questionnaire,80 met the cutoff criteria for the PTSD and qualified for further evaluation(15.9%).All 80 patients agreed to a psychiatric interview.Among them,51 patients(10.1%)were diagnosed with clinical PTSD by a psychiatrist according to Diagnostic and Statistical Manual of Mental Disorders criteria.Among the variables analyzed,there was a noticeable difference in the percentage of theoretical maximum achieved on exercise testing between the PTSD and non-PTSD groups.Non-PTSD group achieved a significantly higher percentage of their maximum compared to the PTSD group(P=0.035).CONCLUSION The preliminary results of the study indicate that a significant proportion of patients with PTSD induced by ACS are not receiving adequate treatment.Furthermore,the data suggest that these patients may exhibit reduced physical activity levels,which could be one of the possible underlying mechanisms in observed poor cardiovascular outcomes in this population.Identifying cardiac biomarkers is crucial for identifying patients at risk of developing PTSD and may derive benefits from personalized interventions based on the principles of precision medicine in multidisciplinary CR programs.

Quo vadis cardiac rehabilitation;the role of comprehensive cardiac rehabilitation in modern cardiology

In accordance with the guidelines established by prominent European and global cardiology associations,comprehensive cardiac rehabilitation(CR)stands as an officially endorsed and highly recommended therapeutic approach(class I recommendations;level of evidence A)for a diverse spectrum of cardiac patients.Nevertheless,it is a cause for concern to observe that fewer than 50%of eligible patients are being effectively referred for CR,whether in an outpatient or in-patient setting.Concurrently,studies reveal that a substantial proportion of individuals with atherosclerotic cardiovascular disease maintain unhealthy lifestyles and exhibit suboptimal management of modifiable cardiovascular risk factors,including hypertension,lipid levels,and diabetes.Beyond the conven-tional patient profile encompassing those recovering from acute coronary syndrome with or without percutaneous coronary intervention,as well as patients who have undergone coronary or valvular surgery,contemporary CR now emphasizes specialized subgroups of patients.These include frail elderly patients,the female population with its unique considerations,individuals burdened by multiple cardiovascular comorbidities,those who have developed psychological consequences due to a cardiac illness and particularly those grappling with chronic heart failure.This editorial seeks to offer a state-of-the-art assessment of the significance and role of comprehensive CR within modern cardiology.

Spontaneous gastric hematoma as a rare cause of acute abdomen:A case report

BACKGROUND Spontaneous gastric hematoma is an exceedingly rare condition characterized by the accumulation of blood within the gastric wall without any apparent iatrogenic or traumatic cause.Coagulopathies are the most frequent cause of gastric he-matomas.However,other causes include amyloidosis,pancreatitis,visceral vas-cular aneurysms,endoscopy complications and others.The pathophysiology of spontaneous gastric hematoma is not completely understood.However,it is postulated that it is caused by disruption of submucosal vessels that leads to dissection of the muscularis layer and formation of false lumen.The rarity of this condition increases the challenge of diagnosis,and there is no standard treatment protocol.CASE SUMMARY We present the case of a spontaneous gastric hematoma in a 22-year-old male.He presented to our emergency department complaining of pain in the left flank area lasting for 2 wk.There was no history of trauma,antico-agulant medications or endoscopy procedures.His hemoglobin and hematocrit levels were slightly lower than normal.Multi-slice computed tomography,ultrasound and endoscopy confirmed a gastric intramural hematoma.We recommended conservative treatment because there was no hemodynamic instability nor significant bleeding.The patient responded well,and there were no unexpected events.At the 3-mo follow-up,the ultrasound exa-mination revealed complete regression of the hematoma.CONCLUSION After reviewing the literature and our experience,we recommend that more of these cases should be treated conservatively.The tendency to treat these cases with potentially burdensome procedures such as total or subtotal gastrectomy should be significantly reduced.

Hypoxia-inducible factor-1αin myocardial infarction

Hypoxia-inducible factor 1(HIF1)has a crucial function in the regulation of oxygen levels in mammalian cells,especially under hypoxic conditions.Its importance in cardiovascular diseases,particularly in cardiac ischemia,is because of its ability to alleviate cardiac dysfunction.The oxygen-responsive subunit,HIF1α,plays a crucial role in this process,as it has been shown to have cardioprotective effects in myocardial infarction through regulating the expression of genes affecting cellular survival,angiogenesis,and metabolism.Furthermore,HIF1αexpression induced reperfusion in the ischemic skeletal muscle,and hypoxic skin wounds in diabetic animal models showed reduced HIF1αexpression.Increased expression of HIF1αhas been shown to reduce apoptosis and oxidative stress in cardiomyocytes during acute myocardial infarction.Genetic variations in HIF1αhave also been found to correlate with altered responses to ischemic cardiovascular disease.In addition,a link has been established between the circadian rhythm and hypoxic molecular signaling pathways,with HIF1αfunctioning as an oxygen sensor and circadian genes such as period circadian regulator 2 responding to changes in light.This editorial analyzes the relationship between HIF1αand the circadian rhythm and highlights its significance in myocardial adaptation to hypoxia.Understanding the changes in molecular signaling pathways associated with diseases,specifically cardiovascular diseases,provides the opportunity for innovative therapeutic interventions,especially in low-oxygen environments such as myocardial infarction.

How to treat an extensive form of primary intestinal lymphangiectasia?

We report a case of a 42-year-old man with a rare disorder known as primary intestinal lymphangiectasia,which is characterized by dilated intestinal lymphatics that lead to the development of protein-losing enteropathy. The patient presented with a grand mal seizure caused by malabsorption-derived electrolytes and a protein disorder. Signs of the disease, including chronic diarrhea and peripheral edema, manifested10 years ago, but a diagnosis was never made. The diagnosis was suspected because of the clinical manifestations, laboratory tests, imaging and endoscopic findings. Hyperemic and edematous mucosa of the small intestine corresponded to scattered white spots with dilated intestinal lymphatics and whitish villi in the histological specimen of the biopsied jejunal mucosa.Although numerous therapeutic strategies are available,only octreotide therapy proved to be an effective means of therapeutic resolution in this patient. Although the patient had a partial remission following the use of a slow release formula of octreotide, his prognosis, clinical course, and future treatment challenges are yet to be determined.

Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157,L-NAME,L-arginine(alone/combined),saline] was bath at the blood deprived colon segment. During reperfusion,medication was BPC 157 or saline. We recorded(USB microscope camera) vessel presentation through next 15 min of ischemic colitis(ICrats) or reperfusion(removed ligations)(IC + RL-rats);oxidative stress as MDA(increased(IC-and IC + RLrats)) and NO levels(decreased(IC-rats);increased(IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction(OB)] for 3 d(IC + OBrats),then received BPC 157 bath. RESULTS Commonly,in colon segment(25 mm,2 ligations on left colic artery and vein,3 arcade vessels within ligated segment),in IC-,IC + RL-,IC + OB-rats,BPC 157(10 μg/kg) bath(1 m L/rat) increased vessel presentation,inside/outside arcade interconnections quickly reappeared,mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME(5 mg) and L-arginine(100 mg). MDA-and NO-levels were normal in BPC 157 treated IC-rats and IC + RLrats. In addition,on day 10,BPC 157-treated IC + OBrats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects;the treated colon segment was of normal diameter,and only small adhesions were present.CONCLUSION BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

Epidemiology of hepatitis C in Croatia in the European context

We analyzed prevalence, risk factors and hepatitis C virus(HCV) genotype distribution in different population groups in Croatia in the context of HCV epidemiology in Europe, with the aim to gather all existing information on HCV infection in Croatia which will be used to advise upon preventive measures. It is estimated that 35000-45000 of the Croatian population is chronically infected with HCV. Like in other European countries, there have been changes in the HCV epidemiology in Croatia over the past few decades. In some risk groups(polytransfused and hemodialysis patients), a significant decrease in the HCV prevalence was observed after the introduction of routine HCV screening of blood/blood products in 1992. Injecting drug users(IDUs) still represent a group with the highest risk for HCV infection with prevalence ranging from 29% to 65%. Compared to the prevalence in theCroatian general population(0.9%), higher prevalence rates were found in prison populations(8.3%-44%), human immunodeficiency virus-infected patients(15%), persons with high-risk sexual behavior(4.6%) and alcohol abusers(2.4%). Low/very low prevalence was reported in children and adolescents(0.3%) as well as in blood donors(0%-0.009%). In addition, distribution of HCV genotypes has changed due to different routes of transmission. In the general population, genotypes 1 and 3 are most widely distributed(60.4%-79.8% and 12.9%-47.9%, respectively). The similar genotype distribution is found in groups with high-risk sexual behavior. Genotype 3 is predominant in Croatian IDUs(60.5%-83.9%) while in the prison population genotypes 3 and 1 are equally distributed(52.4% and 47.6%). Data on HCV prevalence and risk factors for transmission are useful for implementation of preventive measures and HCV screening.

Hepatitis B and circadian rhythm of the liver

The circadian rhythm in humans is determined by the central clock located in the hypothalamus’s suprachiasmatic nucleus,and it synchronizes the peripheral clocks in other tissues.Circadian clock genes and clock-controlled genes exist in almost all cell types.They have an essential role in many physiological processes,including lipid metabolism in the liver,regulation of the immune system,and the severity of infections.In addition,circadian rhythm genes can stimulate the immune response of host cells to virus infection.Hepatitis B virus(HBV)infection is the leading cause of liver disease and liver cancer globally.HBV infection depends on the host cell,and hepatocyte circadian rhythm genes are associated with HBV replication,survival,and spread.The core circadian rhythm proteins,REV-ERB and brain and muscle ARNTL-like protein 1,have a crucial role in HBV replication in hepatocytes.In addition to influencing the virus’s life cycle,the circadian rhythm also affects the pharmacokinetics and efficacy of antiviral vaccines.Therefore,it is vital to apply antiviral therapy at the appropriate time of day to reduce toxicity and improve the effectiveness of antiviral treatment.For these reasons,understanding the role of the circadian rhythm in the regulation of HBV infection and host responses to the virus provides us with a new perspective of the interplay of the circadian rhythm and anti-HBV therapy.Therefore,this review emphasizes the importance of the circadian rhythm in HBV infection and the optimization of antiviral treatment based on the circadian rhythm-dependent immune response.

Morphological and ecological divergence in two populations of European glass lizard,Pseudopus apodus(Squamata:Anguidae)

The European glass lizard,Pseudopus apodus(Pallas,1775),is a large,legless lizard with wide distribution across south-eastern Europe and eastern and central Asia.To date,morphological diversification among populations on a geographically small scale has not yet been reported in this lizard.Thus,we investigated the morphological variations and corresponding differences in habitat utilization between two populations of P.apodus inhabiting the same biogeographical zone within a relatively close geographic area.We hypothesized that minor differences in habitat could induce a significant level of morphological differentiation,thus indicating morphological plasticity in this species on a small geographical scale.We sampled 164 individuals(92 from the Croatian mainland and 72 from the island of Cres).Results showed that P.apodus indeed exhibited morphological differences between populations in the same biogeographical zone within a relatively close geographic area,with the Cres Island individuals being generally larger than the individuals from the mainland.Some ecological characteristics were similar in both populations(e.g.,soil temperature,distance to hiding place),whereas others were distinct(e.g.,air temperature and humidity).In addition,vegetation cover differed between the two sites,with more vegetation present on the mainland than on the island.Furthermore,the Cres Island population showed clear sexual dimorphism,which was absent in the mainland population.

Growing importance of urogenital candidiasis in individuals with diabetes:A narrative review

Both diabetes and fungal infections contribute significantly to the global disease burden,with increasing trends seen in most developed and developing countries during recent decades.This is reflected in urogenital infections caused by Candida species that are becoming ever more pervasive in diabetic patients,particularly those that present with unsatisfactory glycemic control.In addition,a relatively new group of anti-hyperglycemic drugs,known as sodium glucose cotransporter 2 inhibitors,has been linked with an increased risk for colonization of the urogenital region with Candida spp.,which can subsequently lead to an infectious process.In this review paper,we have highlighted notable virulence factors of Candida species(with an emphasis on Candida albicans)and shown how the interplay of many pathophysiological factors can give rise to vulvovaginal candidiasis,potentially complicated with recurrences and dire pregnancy outcomes.We have also addressed an increased risk of candiduria and urinary tract infections caused by species of Candida in females and males with diabetes,further highlighting possible complications such as emphysematous cystitis as well as the risk for the development of balanitis and balanoposthitis in(primarily uncircumcised)males.With a steadily increasing global burden of diabetes,urogenital mycotic infections will undoubtedly become more prevalent in the future;hence,there is a need for an evidence-based approach from both clinical and public health perspectives.

Prehabilitation of overweight and obese patients with dysglycemia awaiting bariatric surgery: Predicting the success of obesity treatment

Bariatric surgery offers the best health results in overweight and obese patients but is not a risk and/or complication-free treatment.In cases with additional hyperglycemia,the burden of surgery can be even higher and alter both shortterm and long-term outcomes.Although bariatric surgery offers glycemic improvements and in the case of early onset diabetes disease remission,weight loss results are lower than for obese patients without diabetes.Different multimodal programs,usually including interventions related to patients’performance,nutritional and psychological status as well as currently available pharmacotherapy before the surgery itself might considerably improve the immediate and late postoperative course.However,there are still no clear guidelines addressing the prehabilitation of obese patients with dysglycemia undergoing bariatric surgery and therefore no unique protocols to improve patients’health.In this minireview,we summarize the current knowledge on prehabilitation before bariatric surgery procedures in patients with obesity and dysglycemia.

Bicuspid aortic valve with associated aortopathy, significant left ventricular hypertrophy or concomitant hypertrophic cardiomyopathy: A diagnostic and therapeutic challenge

Due to its prevalence of 0.5%to 2%in the general population,with a 75%predominance among men,bicuspid aortic valve is the most common congenital heart defect.It is frequently accompanied by other cardiac congenital anomalies,and clinical presentation can vary significantly,with stenosis being the most common manifestation,often resulting in mild to moderate concentric hypertrophy of the left ventricle.Echocardiography is the primary diagnostic modality utilized for establishing the diagnosis,and it is often the sole diagnostic tool relied upon by clinicians.However,due to the heterogeneous clinical presentation and possible associated anomalies(which are often overlooked in clinical practice),it is necessary to employ various diagnostic methods and persist in finding the accurate diagnosis if multiple inconsistencies exist.By employing this approach,we can effectively manage these patients and provide them with appropriate treatment.Through a clinical case from our practice,we provide an overview of the literature on bicuspid aortic valve with aortophaty and the possible association with hypertrophic cardiomyopathy,diagnostic methods,and treatment options.This review article highlights the critical significance of achieving an accurate diagnosis in patients with bicuspid aortic valve and significant left ventricular hypertrophy.It is crucial to exclude other possible causes of left ventricular outflow tract obstruction,such as sub-or supra-aortic obstructions,and hypertrophic cardiomyopathy.