Search

Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.

Camelia Alkhzouz,1,2 Georgiana Cabau,2 Cecilia Lazea,2,3 Carmen Asavoaie,3 Simona Bucerzan,1,2 Andreea Manuela Mirea,2 Marius Farcas,2 Maria Miclaus Jnr,2 Radu Popp,2 Diana Miclea1,2 1Department of Medical Genetics, Clinical Emergency Hospital for Children, Cluj-Napoca, Romania; 2“Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania; 3First Pediatric Clinic, Clinical Emergency Hospital for Children, Cluj-Napoca, RomaniaCorrespondence: Diana MicleaDepartment of Medical Genetics, Clinical Emergency Hospital for Children, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, RomaniaEmail diana.miclea@umfcluj.roIntroduction: Articular and bone damage, which is so disabling in Mucopolysaccharidosis (MPS), requires attention as to the explanatory bias of the pathogenetic mechanisms identified to date. The vitamin D receptor (VDR) has been investigated in many studies in correlation with bone metabolism, osteoporosis, and the impaired bone mineral density associated with certain polymorphisms of the VDR gene.Aim: This study aims to observe whether there is an association between clinical features, phospho-calcium metabolism parameters and the VDR gene polymorphisms in patients with MPS.Patients and Method: We evaluated six patients with MPS type I, 20 patients with MPS type II, two patients with MPS types IIIA and IIIB and three patients with MPS type IVB. In these patients, phospho-calcium metabolism, markers of bone formation, bone radiographs and bone densitometry were evaluated, as were four polymorphisms of the VDR gene (ApaI, BsmI, FokI and TaqI).Results: There was a deficiency in 25 hydroxy vitamin D in MPS type I patients at the final evaluation and in MPS type II patients, both at ERT initiation and at the last evaluation. The analysed polymorphisms were not associated with modified calcium-phosphor levels, but some differences were observed regarding the level of 25 OH vitamin D. Thus, in the case of AA polymorphism, all patients have a 25 OH vitamin D deficiency, and one patient with the AA genotype and three with Aa have a 25 OH vitamin D deficiency and secondary hyperparathyroidism due to this deficiency (four patients), all of them having the Bb phenotype.Conclusion: In MPS patients, vitamin D deficiency is observed, as it is in some patients with secondary hyperparathyroidism, which indicates vitamin D supplementation to protect bone metabolism. There are no obvious correlations between VDR polymorphism and bone metabolism in MPS patients.Keywords: mucopolysaccharidosis, vitamin D receptor, ApaI, BsmI, FokI, TaqI

Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și este produsă de mutații în gena CFTR, ce codifică un canal anionic pentru clor și bicarbonat cu rol în reglarea metabolismului bicar-bonatului și sării.În momentul de față, aproximativ jumătate din totalul pacienților cu fibroză chistică pot beneficia de terapie perso-nalizată cu ajutorul modulatorilor, substanțe care restaurează sau îmbunătățesc funcționalitatea și stabilitatea CFTR. Mai mult, la ora actuală se află în stadiul de studiu clinic și alte tipuri de terapii, ca de exemplu terapia geni-că utilizând sistemul CRISP/CAS-9, oligonucleotide antisens modificate sau inserția genei sălbatice utilizând parti-cule nanolipidice sau vectori virali. Acest articol își propune să treacă în revistă principalele tipuri de terapii aproba-te sau aflate în stadiul de studiu clinic pentru tratamentul fibrozei chistice.

1q44 microdeletion syndrome (1q44 monosomy) is a newly described genetic syndrome characterized by the haploinsufficiency of a 6 Mb locus on the long arm of chromosome 1. The main features are global developmental delay, seizures, hypotonia and craniofacial dysmorphism. With a prevalence below one in a million cases, this syndrome is very rare and, hence, often passes undiagnosed. We present the case of a one year old girl admitted to our hospital with global developmental delay and several congenital abnormalities suggesting a plurimalformative syndrome. Microarray analysis detected a 967 kb deletion in the 1q44 region as well as a a 530 kb microduplication in the 14q31.1q31.2 region, the latter having unknown clinical significance as it contains no currently known OMIM genes. The patient’s phenotype was in accordance to 1q44 microdeletion syndrome. Furthermore, after studying the 1q44 microdeletion syndrome cases reported so far in the literature, we have noticed that our patient presented previously undescribed features of this syndrome, namely prenatal hydronephrosis, bifid hallux and grey matter heterotopy. Based on the cerebral, renal and skeletal involvement in 1q44 microdeletion syndrome, we suspect these might be additional, previously unreported features of 1q44 microdeletion syndrome.

Blizzard phenomena is a complex atmospheric event, in which the snow that falls or has fallen is blown away by the wind, so that the visibility decrease significant enough and the assessment of the simultaneous snow fall is impossible (Țîșlea, D. et al. 1965). The region of Oltenia is featured by a climate with Mediterranean influences, with the dominance of northwest and east winds (Roșu, Al. Et al. 1971). The contact between the cold and the warm air masses leads to the increase of the horizontal baric gradient, which causes strong wind intensification. Due to the geographical position of the Carpathian chain, the penetration of colder and denser air is directed towards the east and the south of Romania, thereby has an impact on the study area (***Climate of Romania 2008). Out of all the natural phenomena during the cold season, blizzard is by far the most versatile, with a heavily impact on society and environment (Teodoreanu 2004). The purpose of this paper is to emphasize the hydrometeorological outcome of the 2018 blizzard episode from February 24#$ to March 2%&. In order to achieve this, we will identify the spatial and temporal variability of the hazard in the region of Oltenia, the atmospheric mechanism of this late blizzard occurrence, its climatic characteristics and the consequences on the rivers runoff regime. We will analyze the synoptic conditions under which the blizzard appeared, the recorded meteorological data and a series of hydrological data from the stations located on the main rivers (Jiu, Olt and Danube) in order to determine the synoptic weather pattern, the successive number of days with blizzard, the dominant direction and the average and maximum wind speed, the average and maximum amount of precipitation, as well as for the thickness of snow layer and the daily liquid levels and flows.

Romanian Carpathians are considered a biodiversity hotspot in Europe, with large forested areas, including old-growth forests. Past forestry practices, such as selective logging resulting in forest high grading and removal of ancient or decaying trees, reduced the heterogeneity of forest structure and composition. These practices led to forest habitats with few veteran trees and a small amount of deadwood, which protected saproxylic beetles rely on for completing their complex life cycles. Moreover, saproxylic species are considered pest species under traditional forestry practices, as they reduce the value of timber. As such, Romanian forestry practices have actively sought to reduce the amount of deadwood in an effort to decrease the presence of saproxylic species, thus effectively isolating stands with a high diversity of saproxylic beetles.The European Commission will finance the project LIFE19 NAT/RO/000023 Conservation of saproxylic beetles in the Carpathians LIFE ROsalia. The project aims to stop and reverse the loss of protected saproxylic beetles (Rosalia longicorn Rosalia alpina, the hermit beetle Osmoderma eremita, great capricorn beetle Cerambyx cerdo, grey beetle Morimus funereus, and stag beetle Lucanus cervus) in the Carpathians by demonstrating conservation actions for increasing the connectivity of favorable habitats in the ROSCI0208 Putna-Vrancea (Eastern Carpathians, Romania), and transferring and replicating best management practices in other Romanian Natura 2000 sites.LIFE ROsalia will be implemented between 2020 and 2025 by the Environmental Protection Agency Vrancea, the Center for Environmental Research at the University of Bucharest, the Putna-Vrancea Natural Park Administration, and the Association for Biodiversity Conservation.

Testosterone exerts an important regulation of cardiovascular function through genomic and nongenomic pathways. It produces several changes in cardiomyocytes, the main actor of cardiomyopathies, which are characterized by pathological remodeling, eventually leading to heart failure. Testosterone is involved in contractility, in the energy metabolism of myocardial cells, apoptosis, and the remodeling process. In myocarditis, testosterone directly promotes the type of inflammation that leads to fibrosis, and influences viremia with virus localization. At the same time, testosterone exerts cardioprotective effects that have been observed in different studies. There is increasing evidence that low endogenous levels of testosterone have a negative impact in some cardiomyopathies and a protective impact in others. This review focuses on the interrelationships between testosterone and cardiomyopathies and heart failure.

Abstract The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score ≥5) aged 18–45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86–0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86–0.91) and 0.90 (0.87–0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57–0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD.

In the last decade of the twentieth century, the phenomenon of volunteering began to take shape in Romania. Therefore, it is necessary to study its evolution, the necessary resources, the implications and benefits it brings to society at the collective level but also at the individual level. The purpose of the paper is to determine the degree of involvement of young people in volunteer activities. About volunteering it can be said that it can contribute to the development of young people on several levels: social, psychological, human and why not even economic. In the first part of the present study are presented some theoretical aspects regarding the volunteer activity, and in the second part are presented the research methodology and the results of the data analysis obtained through the questionnaire.

Introduction. Ehlers Danlos syndrome is a group of hereditary diseases of the connective tissue with a combined prevalence of 1 in 5,000 cases which have in common articular hyperlaxity and skin abnormalities. In some types, rapid diagnosis can mean saving the life of the patient. Case presentation. We will present the case of a two year old girl which was brought for genetic consult with the suspicion of Ehlers Danlos syndrome. The patient had joint and skin hyperextensibility, velvety skin with a tendency of bruising, congenital hip luxation with a failed surgical intervention, talus varus and severe motor development retardation. Genetic testing revealed the substitution c.1780C>T, p.(Arg594*) in the COL5A1 gene which leads to the apparition of a premature stop codon, the mutation being class 2 (potentially pathogenic). Conclusions. Up until now, this variant has been reported in the literature in only two patients, ours being the third. All three cases correspond to the classic type Ehlers Danlos syndrome.

The paper presents a small circular mirror frame found in the rural settlement at Acic Suat. The mirror is made out of lead and decorated with radial lines on the frame, missing the reflective surface. Even though, such finds are numerous in the Danubian and Black Sea provinces, their functionality is still questionable, ranging from cosmetic to votive. Discussing the find from Acic Suat, together with the analogies and their potential functions, allows us to integrate the item in a wider context. Two sets of analyses were performed on the mirror, ED-XRF and PIXE, revealing its composition and highlighting the presence of bismuth and silver which can be indicators for the provenance of the lead core.

Nowadays, schizophrenia is treated with atypical antipsychotics that can determine neuroleptic malignant syndrome or rhabdomyolysis appearance. In addition to trauma and muscular hypoxia, there are some drugs and toxins associated with rhabdomyolysis development, among which olanzapine. A case of severe rhabdomyolysis syndrome, with extremely high levels of serum creatine kinase (CK), followed by acute kidney failure, secondary to olanzapine overdose and prolonged immobilization is outlined. Continuous renal replacement therapy was performed, with a slow clearance of serum CK levels. Under supportive therapy, systemic alkalinisation with volume resuscitation and corticotherapy, patient’s general condition was improved, as well as his lower limb paresis. He followed frequent psychiatric evaluations and psychotherapies, before and after being transferred to a medical service. Rhabdomyolysis diagnosis is difficult in mild cases due to non-specific signs and symptoms, but it also has some typical manifestation, generically called “the rhabdomyolysis syndrome triad”. The treatment is usually supportive; renal replacement therapy is required in the presence of acute kidney injury unresponsive to aggressive volume resuscitation. The systemic myoglobin release is responsible for renal injury. Olanzapine muscle toxicity can lead to severe rhabdomyolysis syndrome complicated with acute kidney injury and multiple organ dysfunction syndrome. Rapid identification and aggressive therapeutic management are essential for improving patients’ outcome and prevent the occurrence of irreversible injuries.

Medical schools in Romania enroll a high number of students and invest in them serious amounts of money to prepare them afterwards in the residency. Once these residents become specialists, they are left to seek out jobs for themselves. However, the job offer is scarce in the public sector, even though there is a real national deficit of doctors, especially in the rural areas. For this reason, young doctors are forced to seek jobs in private practice or to go abroad. The following survey aims to see the perspectives of the students and young doctors regarding the future jobs they will have and possible solutions to correct the paradox between having too many unemployed doctors in contrast to having a poor national coverage with medical personnel.

Muierilor Cave is one of Romania’s most important show caves, with paleontological and archeological deposits. Recently, a new chamber was discovered in the cave, with unique yellow calcite crystals, fine-grained crusts, and black sediments. The deposits in this chamber were related to a leaking process from the upper level that contains fossil bones and a large pile of guano. Samples were taken from the new chamber and another passage to investigate the relationship between the substrate and microbial community. Chemical, mineralogical, and whole community 16S rRNA gene-based metabarcoding analyses were undertaken, and the base of the guano deposit was radiocarbon dated. Our study indicated bacteria linked to the presence of high phosphate concentration, most likely due to the nature of the substrate (hydroxyapatite). Bacteria involved in Fe, Mn, or N cycles were also found, as these elements are commonly identified in high concentrations in guano. Since no bat colonies or fossil bones were present in the new chamber, a high concentration of these elements could be sourced by organic deposits inside the cave (guano and fossil bones) even after hundreds of years of their deposition and in areas far from both deposits. Metabarcoding of the analyzed samples found that ∼0.7% of the identified bacteria are unknown to science, and ∼47% were not previously reported in caves or guano. Moreover, most of the identified human-related bacteria were not reported in caves or guano before, and some are known for their pathogenic potential. Therefore, continuous monitoring of air and floor microbiology should be considered in show caves with organic deposits containing bacteria that can threaten human health. The high number of unidentified taxa in a small sector of Muierilor Cave indicates the limited knowledge of the bacterial diversity in caves that can have potential applications in human health and biotechnology.

Over the last thousands of years, human impact led to significant changes in the landscape, with impacts on the environment and the functioning of the ecosystems. We assumed that even small human settlements developed around water bodies might have a substantial impact that surpasses the natural cycles of climate change in an area, especially linked to forest cutting. We have chosen a temporary lake in the Romanian Carpathians as temporary lakes are overlooked in paleoclimatic studies, although they have potential as hotspots for paleoenvironmental research studies. Zăton Lake has exposed riverbank sediments dated with radioactive lead and optical stimulated luminescence techniques, analyzed for sediments and paleomagnetism, and sampled for fossil Oribatida mites. The results show that for the last 2,200 years, natural cycles of warm and cold periods changed the oribatid communities around the lake, with warmer cycles of rich fauna alternating with poor fauna during colder periods. However, in the last few centuries, the increased human occupation in the area replaced the ecologically diverse fauna with eurytopic taxa, more similar to the colder periods of the environmental evolution around the lake. Even if the human occupation around the lake was negligible, probably a few hundred to ∼2,500 people as in the present, the impact on the area is drastic, with ecologically nonspecific species becoming dominant. In conclusion, even small and temporary water bodies can contain unique and valuable information on past histories of climate change and human impacts. At regional scales, the combined effects of climate change and long-term human impacts in local areas can have deleterious effects on invertebrate species and communities.

Spinal muscular atrophy is a neuromuscular degenerative disorder characterized by progressive apoptosis of motor neurons, with severe weakness and bulbar dysfunction. The aim of the study was to analyze the correlations between the moment of initiation of treatment (nusinersen) and clinical evolution, and also the change of electrophysiological parameters and motor scales, fol-lowed up for 2 years. This study was carried out between 2018 and 2022 on 60 SMA children (29 girls, 31 boys), (29 type 1 and 31 type 2; 29 with 2 copies of SMN2, 29 with 3 copies, and 2 with 4 copies), aged between 3 weeks and 196 months, divided into 2 groups according type of SMA. For both types of SMA, statistically significant negative correlations were found between the elapsed interval from the onset of the disease to the initiation of treatment and upper motor acquisitions (type 1: p < 0.0001, r = -0.713, type 2: p

Prostate cancer is among the most frequently diagnosed cancers and a leading cause of cancer-related death in men. Currently, the most reliable and widely used imaging test for prostate cancer diagnosis is multiparametric pelvic magnetic resonance imaging (mpMRI). Modern biopsy techniques are based on the computerised merging of ultrasound and MRI images to provide better vision during the biopsy procedure (Fusion Biopsy). However, the method is expensive due to high equipment cost. Cognitive fusion of ultrasound and MRI images has recently emerged as a cheaper and easier alternative to computerised fusion. The aim of this prospective study is to perform an in-patient comparison of the systematic prostate biopsy procedure (SB) vs. cognitive fusion (CF) guided prostate biopsy method in terms of safety, ease of use, cancer detection rate and clinically significant cancer detection. We enrolled 103 patients with suspected prostate cancer that were biopsy naive, with PSA > 4 ng/dL and PIRADS score of 3, 4 or 5. All patients received a transperineal standard 12–18 cores systematic biopsy (SB) and a four-cores targeted cognitive fusion (CF) biopsy. Following the prostate biopsy, 68% of the patients were diagnosed with prostate cancer (70/103 patients). SB diagnosis rate was 62% while CF biopsy was slightly better with a 66% rate. There was a significant 20% increase in clinically significant prostate cancer detection rate for the CF compared to SB (p < 0.05) and a significant prostate cancer risk upgrade from the low to the intermediate risk category (13%, p = 0.041). Transperineal cognitive fusion targeted prostate biopsy is a straightforward biopsy method that is easy to perform and is a safe alternative to standard systematic biopsy with improved significant cancer detection accuracy. A combined targeted and systematic approach should be used for the best diagnostic results.

Bat species inhabit subterranean environments (e.g., caves and mines) in small areas with specific microclimatic conditions, during various periods of their life cycle. Bats can be negatively influenced by microclimatic changes within their roosts if optimal habitat patches become unavailable. Therefore, proper management solutions must be applied for the conservation of vulnerable bat populations, especially in show caves. We have pursued an ensemble species distribution modelling approach in subterranean environments to identify sensible patches for bats. Using multi-annual temperature monitoring and bat distribution surveys performed within ten caves and mines, including show caves, we modelled relevant habitat patches for five bat species. The temperature-based variables generated from this approach proved to be effective when processed via species distribution models, which generated optimal validation results, even for bats that were heavily clustered in colonies. Management measures are proposed for each show cave to help in long-time conservation of hibernation and maternity colonies. These measures include creating suitable microclimatic patches within the caves by ecological reconstruction measures, tourist management practices in relation to bats, and show cave fitting recommendations. This approach has never been performed at this scale due to the complex geostatistical challenges involving subterranean environment mapping and can be further used as best practice guidelines for future conservation projects.

Over the past century, advances in biotechnology, biochemistry, and pharmacognosy have spotlighted flavonoids, polyphenolic secondary metabolites that have the ability to modulate many pathways involved in various biological mechanisms, including those involved in neuronal plasticity, learning, and memory. Moreover, flavonoids are known to impact the biological processes involved in developing neurodegenerative diseases, namely oxidative stress, neuroinflammation, and mitochondrial dysfunction. Thus, several flavonoids could be used as adjuvants to prevent and counteract neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Zebrafish is an interesting model organism that can offer new opportunities to study the beneficial effects of flavonoids on neurodegenerative diseases. Indeed, the high genome homology of 70% to humans, the brain organization largely similar to the human brain as well as the similar neuroanatomical and neurochemical processes, and the high neurogenic activity maintained in the adult brain makes zebrafish a valuable model for the study of human neurodegenerative diseases and deciphering the impact of flavonoids on those disorders.

Macrophage activation and cytokine release play a pivotal role in inflammation-mediated metabolic disturbances in obesity. The proinflammatory macrophage secretes human chitotriosidase (CHIT1). The expression of the CHIT1 in visceral adipose tissue is associated with cytokine production. Our study aimed to assess whether the CHIT1 circulating activity, as a macrophage activation indicator, reflects the change of the adiposity level and the insulin resistance (IR) in children with obesity. We longitudinally (median follow-up period of 7 months; IQR [5 to 8.5] and {2 to 13} months) evaluated the CHIT1 circulating activity, the adiposity level (waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WtHR), and body mass index (BMI)-for-age z score), and two surrogate markers of IR (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR and the triglycerides-to-high density lipoprotein cholesterol ratio, TG/HDLc) in 29 pediatric patients (16 girls and 13 boys) with obesity. We found a significant reduction in CHIT1 circulating activity (Wilcoxon test, p = 0.015) and a decrease in TG/HDLc at the follow-up evaluation (Wilcoxon test, p < 0.001). Indicators of adiposity were positively correlated with HOMA-IR at baseline, among which WC was the sole indicator associated with HOMA-IR (Spearman’s rank correlation coefficients, p < 0.05) at follow-up. Human chitotriosidase has the potential to be a valuable measure of the progression of subclinical inflammation in children with obesity. Subclinical inflammation, as expressed by the circulating CHIT1 activity, progresses independently of the abdominal adiposity, as measured by the clinical indicators, and is associated with a change in insulin resistance.