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Infection with human immunodeficiency virus (HIV) is the most powerful risk factor known to predispose to Mycobacterium tuberculosis infection and further progression to active disease, which increases the risk of latent TB reactivation. TB is one of the most common opportunistic infections worldwide.

Compared to other respiratory viruses, the proportion of hospitalizations due to SARS-CoV-2 among children is relatively low. While severe illness is not common among children and young individuals, a particular type of severe condition called multisystem inflammatory syndrome in children (MIS-C) has been reported. The aim of this prospective cohort study, which followed a group of individuals under the age of 19, was to examine the characteristics of patients who had contracted SARS-CoV-2, including their coexisting medical conditions, clinical symptoms, laboratory findings, and outcomes. The study also aimed to investigate the features of children who met the WHO case definition of MIS-C, as well as those who required intensive care. A total of 270 patients were included between March 2020 and December 2021. The eligible criteria were individuals between 0-18 with a confirmed SARS-CoV-2 infection at the Infectious Disease Hospital “Prof. Ivan Kirov” in Sofia, Bulgaria. Nearly 76% of the patients were ≤ 12 years old. In our study, at least one comorbidity was reported in 28.1% of the cases, with obesity being the most common one (8.9%). Less than 5% of children were transferred to an intensive care unit. We observed a statistically significant difference in the age groups, with children between 5 and 12 years old having a higher likelihood of requiring intensive care compared to other age groups. The median values of PaO2 and SatO2 were higher among patients admitted to the standard ward, while the values of granulocytes and C-reactive protein were higher among those transferred to the intensive care unit. Additionally, we identified 26 children who met the WHO case definition for MIS-C. Our study data supports the evidence of milder COVID-19 in children and young individuals as compared to adults. Older age groups were associated with higher incidence of both MIS-C and ICU admissions.

Introduction: Humanity has benefited from the presence of antibiotics to treat bacterial infections for decades. However, due to the overuse of antibiotics bacteria develop resistance against these drugs, leading to the emergence of untreatable superbugs. Antibiotic resistance is one of the biggest threats to global health. It is rising to dangerously high levels with hundreds of thousands of deaths reported worldwide every year. Dealing with the ongoing antibiotic crisis requires the discovery of compounds with novel mechanisms of action that are capable to treat drug-resistant infections. A newly found antibiotic from a glycopeptides family with "a unique approach" to attacking and killing bacteria was announced in 2020. The purpose of our work is to provide information about Corbomycin. Materials and methods: a review of scientific literature and studies that provide information on Corbomycin. Conclusion: In recent years, researchers have been increasingly searching for new approaches to treat life-threatening bacterial infections. Corbomycin - an antibiotic that kills bacteria by blocking the function of their cell wall is a promising clinical candidate in the fight against antimicrobial resistance. [ABSTRACT FROM AUTHOR]

The putative physiological roles of nitrogen oxide (NO) in young maize plants and its potential ability to enhance plant tolerance to environmental constrains, like heavy metal toxicity were studied. Cadmium (Cd) stress decreased the shoot and root length and chlorophyll content, reduced the photosynthetic rate, transpiration and stomatal conductance. The exogenous simultaneous application of sodium nitroprusside, the NO donor, to Cd-treated plants recovered to high extent the rate of photosynthesis, transpiration and chlorophyll content. NO mitigated the cadmium damage to photosystem II reaction center by increasing the maximum quantum yield and markedly enhancing the effective quantum yield. The membrane permeability was restored. The data suggest that nitric oxide may protect cells by exerting ameliorating effect on Cd toxicity and partially restore photosynthesis. [ABSTRACT FROM AUTHOR]

The article focuses on the aspects of intuition as a method used for social cognition. The author discusses and compares the outlooks of two modern philosophers namely Rene Descartes and Henri Bergson, and their perception of social cognition. The author mentions that Bergson's philosophy applies a research method not based on building outlooks, but following lines of facts. The author notes that Descartes philosophy is a privileged form based on the intuition as a method.

Isolates from fecal samples of patients with diarrhea syndrome from "Prof. Dr. Stoyan Kirkovich" AD (University) - Strara Zagora Hospital were included in our study for 2013. We examinated 2292 fecal samples and identified 93 strains. The most common strains were from genus Shigella and genus Salmonella, followed by diarrhea-causing E. coli, Y. enterocolitica and P. aeruginosa. Each of the isolates had been tested to antimicrobials. [ABSTRACT FROM AUTHOR]

Background: Mixed infections can worsen disease symptoms. This study investigated the impact of mixed infections with viral and bacterial pathogens in patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: Using the in-house multiplex PCR method, we tested 337 SARS-CoV-2 positive samples for co-infections with three bacterial and 14 other viral pathogens., Results: Between August 2021 and May 2022, 8% of 337 SARS-CoV-2-positive patients had bacterial co-infections, 5.6% had viral co-infections, and 1.4% had triple mixed infections. The most common causes of mixed infections were Haemophilus influenzae (5.93%) and respiratory syncytial virus (RSV) (1.18%). Children < 5 years old had more frequent co-infections than adults < 65 years old (20.8% vs. 16.4%), while adults showed a more severe clinical picture with a higher C-reactive protein (CRP) level (78.1 vs.16.2 mg/L; p = 0.033), a lower oxygen saturation (SpO2) (89.5 vs. 93.2%), and a longer hospital stay (8.1 vs. 3.1 days; p = 0.025) (mean levels). The risk of a fatal outcome was 41% in unvaccinated patients ( p = 0.713), which increased by 2.66% with co-infection with two pathogens ( p = 0.342) and by 26% with three pathogens ( p = 0.005). Additionally, 50% of intensive care unit (ICU) patients had a triple infection, compared with only 1.3% in the inpatient unit ( p = 0.0029). The risk of death and/or ICU admission was 12 times higher ( p = 0.042) with an additional pathogen and increased by 95% ( p = 0.003) with a third concomitant pathogen., Conclusions: Regular multiplex testing is important for prompt treatment and targeted antibiotic use.

The increased life expectancy of PLHIV (People Living with HIV) and the successful highly combined antiretroviral therapy (cART) poses new clinical challenges regarding aging and its co-morbid condition. It is commonly believed that HIV infection "accelerates" aging. Human immunodeficiency virus type 1 (HIV-1) infection is characterized by inflammation and immune activation that persists despite cART, and that may contribute to the development of co-morbid conditions. In this regard, we aimed to compare current cART regimens in light of premature aging to evaluate differences in their ability to reduce immune activation and inflammation in virologically suppressed patients. We studied a panel of biomarkers (IFN-γ, IL-1β, IL-12p70, IL-2, IL-4, IL-5, IL-6, IL-13, IL-18, GM-CSF, TNF-α, C-reactive protein, D-dimer, soluble CD14), which could provide a non-invasive and affordable approach to monitor HIV-related chronic inflammation. The results of the current study do not provide hard evidence favoring a particular cART regimen, although they show a less favorable regimen profile containing a protease inhibitor. Our data suggest an incomplete reduction of inflammation and immune activation in terms of the effective cART. It is likely that the interest in various biomarkers related to immune activation and inflammation as predictors of clinical outcomes among PLHIV will increase in the future.

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders., Competing Interests: Declaration of interests B.S. is a shareholder in EpiSign Inc, involved in commercial uses of EpiSign(TM) technology D.A.C. and K.G.M. are employees of GeneDx, LLC., (Copyright © 2024. Published by Elsevier Inc.)

Background: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a neurodegenerative disease with neurodevelopmental delay, motor, and speech regression, pronounced extrapyramidal syndrome, and sensory deficits due to TUBB4A mutation. In 2017, a severe variant was described in 16 Roma infants due to mutation in UFM1., Objective: The objective of this study is to expand the clinical manifestations of H-ABC due to UFM1 mutation and suggest clues for clinical diagnosis., Methodology: Retrospective analysis of all 9 cases with H-ABC due to c.-273&#95;-271delTCA mutation in UFM1 treated during 2013-2020 in a Neuropediatric Ward in Plovdiv, Bulgaria., Results: Presentation is no later than 2 months with inspiratory stridor, impaired sucking, swallowing, vision and hearing, and reduced active movements. By the age of 10 months, a monomorphic disease was observed: microcephaly (6/9), malnutrition (5/9), muscle hypertonia (9/9) and axial hypotonia (4/9), progressing to opisthotonus (6/9), dystonic posturing (5/9), nystagmoid ocular movements (6/9), epileptic seizures (4/9), non-epileptic spells (3/9). Dysphagia (7/9), inspiratory stridor (9/9), dyspnea (5/9), bradypnea (5/9), apnea (2/9) were major signs. Vision and hearing were never achieved or lost by 4-8 mo. Neurodevelopment was absent or minimal with subsequent regression after 2-5 mo. Brain imaging revealed cortical atrophy (7/9), atrophic ventricular dilatation (4/9), macrocisterna magna (5/9), reduced myelination (6/6), corpus callosum atrophy (3/6) and abnormal putamen and caput nuclei caudati. The age at death was between 8 and 18 mo., Conclusion: Roma patients with severe encephalopathy in early infancy with stridor, opisthotonus, bradypnea, severe hearing and visual impairment should be tested for the Roma founder mutation of H-ABC in UFM1., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: NGF is a molecule with a pleiotropic role, affecting neuro-immune functions, energy homeostasis, and synaptic plasticity. The mechanisms of NGF-induced neuronal differentiation are well established, but its effect on mitochondria in autism spectrum disorder (ASD) is still unclear. We hypothesize that NGF-induced neuronal development requires large amounts of energy, and mitochondria in ASD are overloaded to meet the new functional requirements., Method: The study includes primary diagnosed ASD children. Peripheral blood mononuclear cells (PBMCs) and plasma were obtained from both patients and typically developing children (TDC). PBMCs were analyzed with Seahorse XFp, and plasma NGF protein levels were measured., Results: We detected nearly 50% higher NGF levels and approximately 40% elevation in spare respiratory capacity in ASD compared to TDC. These findings are consistent with the observed difference in maximal respiration, which was also significantly higher in the patient group. Both mitochondrial respiration and NGF plasma levels exhibit a strong potential to discriminate children with ASD from TDC., Conclusions: This study is the first to link elevated NGF with mitochondrial respiration and altered energy homeostasis in ASD. High NGF correlates with basic bioenergetic signatures that may be used as a screening tool to improve early diagnosis and clinical follow-up in ASD.

Introduction: This study aimed to determine the prevalence, viral profile, and clinical features of coinfections with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and other respiratory viruses., Methods: Nasopharyngeal samples and clinical data of 221 hospitalized patients and 21 outpatients were collected and analyzed. Real-time reverse transcription-polymerase chain reaction was used to detect SARS-CoV-2, influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV) 1,2,3, rhinovirus (RV), adenovirus (AdV), bocaviruses (BoV), and seasonal coronaviruses (OC43, 229E, NL63, and HKU1). Viral load was determined by capillary electrophoresis., Results: From November 2020 to mid-March 2022, 242 SARS-CoV-2 positive patients were tested for seasonal respiratory viruses, and 24 (9.9%) cases of coinfections were detected. The distribution of viruses involved in cases of coinfections were as follows: HMPV ( n = 6; 25%), RSV ( n = 4;16.7%), AdV ( n = 4; 16.7%), BoV ( n = 4; 16.7%), PIV3 ( n = 2; 8.3%), influenza A (H3N2; n = 2; 8.3%), RV ( n = 1; 4.62%), and RV+BoV ( n = 1; 4.62%). The proportion of detected coinfections with SARS-CoV-2 was highest in children aged 0-5 years (59%), followed by those >65 years (33%). In specimens with detected coinfection, the viral load of influenza was higher than that of SARS-CoV-2, and the mean viral load of SARS-CoV-2 was higher than that of the other respiratory viruses. C-reactive protein (CRP) and lymphocytes count in co-infected patients >65 years of age were on average higher than in children <16 years of age (mean CRP of 161.8 ± 133.1 mg/L; 19.7 ± 3.09% vs. mean 6.9 ± 8.9 mg/L, 0.9 ± 3.1%; p < 0.01). Patients >65 years of age co-infected with SARS-CoV-2 and other respiratory viruses had longer hospital stays than those <16 years of age (mean 9 ± 3.96 days vs. 5.44 ± 1.89 days; p = 0.025). The combination of AdV and SARS-CoV-2 is fatal for patients aged >65 years., Conclusion: In patients aged >65 years, coinfection with SARS CoV-2 and other respiratory viruses, together with concomitant diseases, causes worsening of the clinical picture and complications, and can be fatal. Screening of patients with SARS CoV-2 for other respiratory viruses is needed to select appropriate treatments and prevent a fatal outcome of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Trifonova, Christova, Madzharova, Angelova, Voleva, Yordanova, Tcherveniakova, Krumova and Korsun.)

Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.

The steady elaboration of the Metagenomic and Metadesign of Subways and Urban Biomes (MetaSUB) international consortium project raises important new questions about the origin, variation, and antimicrobial resistance of the collected samples. CAMDA (Critical Assessment of Massive Data Analysis, http://camda.info/) forum organizes annual challenges where different bioinformatics and statistical approaches are tested on samples collected around the world for bacterial classification and prediction of geographical origin. This work proposes a method which not only predicts the locations of unknown samples, but also estimates the relative risk of antimicrobial resistance through spatial modeling. We introduce a new component in the standard analysis as we apply a Bayesian spatial convolution model which accounts for spatial structure of the data as defined by the longitude and latitude of the samples and assess the relative risk of antimicrobial resistance taxa across regions which is relevant to public health. We can then use the estimated relative risk as a new measure for antimicrobial resistance. We also compare the performance of several machine learning methods, such as Gradient Boosting Machine, Random Forest, and Neural Network to predict the geographical origin of the mystery samples. All three methods show consistent results with some superiority of Random Forest classifier. In our future work we can consider a broader class of spatial models and incorporate covariates related to the environment and climate profiles of the samples to achieve more reliable estimation of the relative risk related to antimicrobial resistance., Competing Interests: SK was employed by company Bristol-Myers Squibb, NJ. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past collaboration with the authors DD and DV., (Copyright © 2021 Zhelyazkova, Yordanova, Mihaylov, Kirov, Tsonev, Danko, Mason and Vassilev.)

Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities., Introduction: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using Peripheral Blood Mononuclear Cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease., Methods: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children is selected. Bioenergetic and metabolic studies of isolated PBMCs are performed with a Seahorse XFp analyzer., Results: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment., Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Andermann syndrome (AS) is caused by mutation of SLC12A6 gene. It comprises severe progressive sensory and motor neuropathy with early onset, varying degree of agenesis of corpus callosum (ACC) and mental retardation. AS occurs occasionally among population outside the northeastern Quebec-Saguenay-Lac- St-Jean and Charlevoix regions, inhabited by French Canadians. None of the described patients were of Roma ethnic origin. We present an 8-month-old infant of Roma ethnic origin with AS, caused by a novel frame shift mutation c.2604delT,p.(Asp868GlufsTer11) in exon 20 of SLC12A6 gene. Our case presented with several atypical findings: clinical presentation resembling "spinal muscular atrophy plus" syndrome; tongue fasciculations, which are not reported in the literature; early contractures of the wrists; normal motor action potentials and preserved sensory action potentials. Our patient is the first of Roma origin from nonconsanguineous parents, which suggests that this mutation might be widespread in the Roma population, although screening for this mutation in 140 alleles from Roma individuals originating from the same geographic region did not reveal further carriers, implying the mutation is rare. We recommend that Roma patients presenting with the clinical phenotype of AS should be tested for this mutation primarily., (© 2019 Wiley Periodicals, Inc.)

The comorbidity of autistic spectrum disorder (ASD) and epilepsy has been widely discussed but many questions still remain unanswered. The aim of this study was to establish the occurrence of epilepsy among children with ASD to define the type of epileptic seizures and syndromes, the age of onset of epilepsy, EEG abnormalities, the used antiepileptic drugs and the therapeutic responses for seizures and autistic behavior, as well as to find some correlations between epilepsy and gender, etiology and intellectual disability (ID). A retrospective study of medical files of 59 patients (aged 1⁻18 years) with ASD during a 5-year period was performed. ASD diagnosis was based on the DSM-5 diagnostic criteria. The patients were examined with a detailed medical history, physical and neurological examination, as well as some additional functional, imaging, laboratory and genetic investigations ASD etiology was syndromic in 9, probable syndromic in 9, and idiopathic in 41 children. ID was established in 90% of ASD children, and epilepsy in 44.4%. The onset of epilepsy prevailed before 7 years of age. The most common seizure types were focal with or without secondary generalization (53.4%). Focal epileptiform EEG abnormalities prevailed. Therapeutic response to seizures was good: 58% were seizure-free, while 27% had >50% seizure reduction but no improvement in autistic behavior. There was no correlation between epilepsy and either occurrence or degree of ID. There was a correlation between the frequency of epileptic seizures and the degree of ID. There was no significant difference among epilepsy rates in different etiologic, gender, and ID groups, probably because of the high percentage of ID and because this was a hospital-based study. Our study showed a significant percentage of epilepsy in ASD population and more than 1/4 were of symptomatic etiology. Those could be managed with specific treatments based on the pathophysiology of the gene defect.

Rationale, Aims, and Objectives: Developmental testing is essential for early recognition of the various developmental impairments. The tools used should be composed of items that are age specific, adapted, and standardized for the population they are applied to. The achievements of neurosciences, medicine, psychology, pedagogy, etc. are applied in the elaboration of a comprehensive examination tool that should screen all major areas of development. The key age of 5 years permits identification of almost all major developmental disabilities leaving time for therapeutic intervention before school entrance. The aim of the research is to evaluate the developmental performance of 5-year-old Bulgarian children using the approach of translation neuroscience., Method: A comprehensive test program was developed composed of 89 items grouped in the following domains: fine and gross motor development, coordination and balance, central motor neuron disturbances, language development and articulation, perception, attention and behavior, visual acuity, and strabismus. The overall sample comprises 434 children of mean age 63.5 months (SD-3.7). Male to female ratio is 1:1.02. From this group, 390 children are between 60 and 71 months of age. The children are examined in 51 kindergartens in 21 villages and 18 cities randomly chosen in southern Bulgaria. Eight children were excluded from the final analysis because they fulfilled less than 50% of the test items (7 children did not cooperate and 1 child was with autistic spectrum disorder)., Results: The items with abnormal response in less than 5% of the children are 43. The items with abnormal response in 6% to 35% of the children are 37. The items with high abnormal response (more than 35%) rate are only 9., Conclusions: The test is an example of a translational approach in neuroscience. On one hand, it is based on the results of several sciences studying growth and development from different perspective. On the other hand, the results from the present research may be implemented in other fields of child development-education, psychology, speech and language therapy, and intervention programs., (© 2018 John Wiley & Sons, Ltd.)