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Symptomatic overlap of depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) is a major diagnostic and therapeutic problem. Mania in medical history remains the only reliable distinguishing marker which is problematic given that episodes of depression compared to episodes of mania are more frequent and predominantly present at the beginning of BD. Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, task-free, and well-tolerated method that may provide diagnostic markers acquired from spontaneous neural activity. Previous rs-fMRI studies focused on differentiating BD from MDD depression were inconsistent in their findings due to low sample power, heterogeneity of compared samples, and diversity of analytical methods. This meta-analysis investigated resting-state activity differences in BD and MDD depression using activation likelihood estimation. PubMed, Web of Science, Scopus and Google Scholar databases were searched for whole-brain rs-fMRI studies which compared MDD and BD currently depressed patients between Jan 2000 and August 2020. Ten studies were included, representing 234 BD and 296 MDD patients. The meta-analysis found increased activity in the left insula and adjacent area in MDD compared to BD. The finding suggests that the insula is involved in neural activity patterns during resting-state that can be potentially used as a biomarker differentiating both disorders.

Primary hyperoxaluria type 1 is caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. This trial tested whether an oligonucleotide drug can reduce the production of hepatic oxalate.

5‐(5‐Formylthiophen‐2‐yl)cytosine, 7‐(5‐formylthiophen‐2‐yl)‐7‐deazaadenosine 2′‐deoxyribonucleosides, and their 5′‐O‐triphosphates (dNTPs) were converted into the 2,4‐dinitrophenylhydrazone or nitrobenzofurazanyl. The hydrazone‐modified dNTPs were enzymatically incorporated into DNA by polymerase catalyzed primer extension (PEX). This direct incorporation of hydrazone‐linked dNTPs was compared to previously reported incorporation of aldehyde‐modified dNTPs followed by postsynthetic hydrazone formation on DNA to show that the direct incorporation can be used for incorporation of more hydrazone units, however, cleaner PEX products are formed by incorporation of aldehydes and subsequent reaction with hydrazines. Extensive study of electrochemical behavior of the nitroarylhydrazone‐linked nucleosides and DNA was performed confirming the potential utility of the hydrazone, nitroaryl, and benzofurazane groups for redox labeling of DNA. Redox labeling of DNA through nitroarylhydrazone modification has been achieved either by polymerase incorporation of hydrazone‐modified dNTPs or by incorporation of aldehydes and subsequent hydrazone formation (see figure). Electrochemical studies revealed the potential utility of different redox‐active groups for DNA labeling for bioanalysis.

In line with the concept of sustainable development, the paper deals with the issue of environmental education and training to increase the awareness of tourism participants of their own responsibility for the practical implementation of sustainable tourism. The aim is to map the behavior of tourism participants and to propose some sustainable behavior principles in the form of a miniguide. The motto of the miniguide is not to simply see travel as just fun, or passive source of information, but as an incentive to learn about nature, culture and customs of local people, to promote and deepen language and other skills, including active protection of the environment. The miniguide might also be an incentive to sustainable tourism development. An important aspect of putting the principles of sustainability into practice is to publish and disseminate these principles so that they become freely available to the general public. That may be through information materials, educational signs, social networks, etc. Spreading awareness of the need to protect nature and the countryside will help to make people aware of their own responsibility for our common future.

The paper applies a genological approach to assessing the Czech and Slovak variants of the Japanese art of haiku. The main focus is on haiku as a genre that is modified under the influence of time and the style of individual creators. The genre categories of the Japanese invariant are analyzed using the example of the Czech and Slovak haiku of Katka Soustružníková and Peter Kovalik. These authors represent the classical haiku, defined by rules stemming from the origins of Japanese aesthetics. The individual principles of this minimalist poetry are revealed not only with regard to the poetics of haiku, but also the authors’ individual styles. The paper thus implicitly points to the artistically com pelling realization of a genre invariant, which ultimately enriches domestic literature.

Left-ventricular hypertrophy (LVH) is a risk factor for cardiovascular morbidity. Antihypertensive treatment with angiotensin-converting enzyme inhibitors (ACEI) is able to induce the regression of LVH in adults. However, there has been no study of the ability of ACEI to induce the regression of LVH in children. Our aim was to investigate the effect of ramipril on left-ventricular mass and blood pressure (BP) in hypertensive children. Twenty-one children (median age, 15 years) with renal (76%) or primary (24%) hypertension were prospectively treated with ramipril monotherapy for 6 months. Blood pressure was evaluated using ambulatory BP monitoring, with hypertension defined as mean BP ≥95th percentile. Left-ventricular hypertrophy was defined either as left-ventricular mass index (LVMI) >38.6 g/m 2.7 (pediatric definition) or as LVMI >51.0 g/m 2.7 (adult definition). Nineteen children completed the study. The median LVMI decreased from 36.8 g/m 2.7 (range, 18.9 to 55.8 g/m 2.7) to 32.6 g/m 2.7 (range, 19.0 to 52.1 g/m 2.7; P < .05) after 6 months. The prevalence of LVH decreased from 42% to 11% using the pediatric definition ( P < .05) and did not change using the adult definition (ie, it remained at 5%). The median ambulatory BP decreased by 11, 7, 8, and 7 mm Hg for daytime systolic, daytime diastolic, nighttime systolic, and nighttime diastolic BP ( P < .05), respectively. A positive correlation was found between LVMI and nighttime systolic BP at the start of the study ( r = 0.46, P < .05). Ramipril is an effective drug in children with hypertension, for its ability to reduce not only BP but also left-ventricular mass and induce regression of LVH.

This paper describes the role of rural tourism in the sustainable development of rural areas and stresses out the importance of strategic approach in the planning of their development. The author identifies core problems, which eliminate their use and disable individual strategies set by some entrepreneurs in rural tourism. Concretely it is the absence of developing projects and focus on the development of individual villages. Then it is the lack of will to cooperate, local resources are not effectively used and the local community is not adequately involved.

Richard Lifton, Véronique Frémeaux-Bacchi and colleagues report that recessive mutations in DGKE cause atypical hemolytic-uremic syndrome with an early age of onset progressing to chronic kidney disease. The authors propose that loss of DGKE results in a prothrombotic state that underlies disease pathogenesis. Pathologic thrombosis is a major cause of mortality. Hemolytic-uremic syndrome (HUS) features episodes of small-vessel thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure 1 . Atypical HUS (aHUS) can result from genetic or autoimmune factors 2 that lead to pathologic complement cascade activation 3 . Using exome sequencing, we identified recessive mutations in DGKE (encoding diacylglycerol kinase ɛ) that co-segregated with aHUS in nine unrelated kindreds, defining a distinctive Mendelian disease. Affected individuals present with aHUS before age 1 year, have persistent hypertension, hematuria and proteinuria (sometimes in the nephrotic range), and develop chronic kidney disease with age. DGKE is found in endothelium, platelets and podocytes. Arachidonic acid–containing diacylglycerols (DAG) activate protein kinase C (PKC), which promotes thrombosis, and DGKE normally inactivates DAG signaling. We infer that loss of DGKE function results in a prothrombotic state. These findings identify a new mechanism of pathologic thrombosis and kidney failure and have immediate implications for treating individuals with aHUS.

BackgroundPeritonitis is an important complication and cause of morbidity in patients undergoing peritoneal dialysis (PD). Corynebacterium species, often considered skin and mucosal contaminants, are a rare cause of PD-associated peritonitis and have been acknowledged in published guidelines for the diagnosis and treatment of PD peritonitis only over the last decade.Case-Diagnosis/TreatmentWe present two children with difficult-to-treat episodes of PD peritonitis due to Corynebacterium amycolatum. Episodes were associated with fever, abdominal pain and cloudy dialysate, high dialysate polymorphonuclear leukocyte counts, and elevated serum C-reactive protein and procalcitonin concentrations. Symptoms persisted beyond 5 days in 4 of 5 peritonitis episodes, and peritonitis relapsed despite in vitro sensitivity of the bacterial isolates to guideline-recommended antibiotics. C. amycolatum was cultured from the PD catheter tip despite 4 weeks of intraperitoneal glycopeptide therapy and clinical peritonitis resolution suggestive of efficient biofilm formation. Our systematic literature search identified three previous (adult) case descriptions of C. amycolatum peritonitis, all with repeat episodes by the same organism. The incidence of C. amycolatum as a cause of PD peritonitis has not yet been established but is likely underreported due to challenges in species differentiation.ConclusionsC. amycolatum is a rarely identified cause of refractory and/or relapsing PD peritonitis. Species differentiation of non-diphtheriae Corynebacterium isolates is critical, and prolonged antibiotic treatment, preferably with a glycopeptide antibiotic, is recommended, with a low threshold for PD catheter change or removal in case of repeat peritonitis.