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Introduction. Green nail syndrome is a condition caused by the Pseudomonas aeruginosa infection. It is most often reported in patients with predisposing conditions that favour the growth of this pathogen such as constant exposure of the hands to water, soaps and detergents, especially in elderly persons. Objective. The aim of this study is to present a case of the green nail syndrome in an elderly patient and bring attention to the greenish colour of the nails as a warning sign of the Pseudomonas aeruginosa infection. Case report. An 88-year-old woman with asymptomatic green-yellowish changes on fingernail plates accompanied by onycholysis. The examination for fungal infection was negative, whereas the bacteriological culture of the nail was positive for Pseudomonas aeruginosa. Conclusions. Green coloration of the nails should be a warning sign of the Pseudomonas aeruginosa infection. Treatment with oral ciprofloxacin, especially in elderly patients could be a valuable option for treating the green nail syndrome. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic dermatosis, manifesting with erythema, papular or pustular eruptions located in the facial area. The authors present a case of an 84-year-old woman with a long-term history of rosacea who had a mycotic infection of the facial skin imitating aggravation of the underlying disease. The case presented by us can be regarded as a variant of "tinea incognito", i.e., undiagnosed mycosis, misdiagnosed as another dermatosis, which is often aggravated by the patient by using local glucocorticosteroids or other local immunomodulators, which hinders proper diagnosis. It may be diagnostically relevant to consider other comorbidities in elderly patients with rosacea. [ABSTRACT FROM AUTHOR]

Over the past 150 years, a certain mythology has arisen around the mechanistic pathways of the oxygenation of organometallics with non‐redox‐active metal centers as well as the character of products formed. Notably, there is a widespread perception that the formation of commonly encountered metal alkoxide species results from the auto‐oxidation reaction, in which a parent metal alkyl compound is oxidized by the metal alkylperoxide via oxygen transfer reaction. Now, harnessing a well‐defined zinc ethylperoxide incorporating a β‐diketiminate ligand, the investigated alkylperoxide compounds do not react with the parent metal alkyl complex as well as Et2Zn to form a zinc alkoxide. Upon treatment of the zinc ethylperoxide with Et2Zn, a previously unobserved ligand exchange process is favored. Isolation of a zinc hydroxide carboxylate as a product of decomposition of the parent zinc ethylperoxide demonstrates the susceptibility of the latter to O−O bond homolysis. [ABSTRACT FROM AUTHOR]

Dermatophytes infection due to Trichophyton verrucosum are not frequent in Europe. A deep inflammatory infiltration is reported of the inframandibular part of the face of 25-year-old male stock farmer due to a zoophilic strain of Trichophyton verrucosum. The fungus was probably acquired from the bull of the patient. The patient developed a severe phlegmoneous inflammation of the bearded part of the face. During hospitalization id reactions like erythema nodosum, tarsal arthritis, and abdominal pain was observed. Ketoconazole in dose of 100 mg was introduced, subsequently fluconazole intravenously, leading to no significant clinical improvement. Afterwards the treatment with fluconazole was discontinued and terbinafine 250 mg once daily was employed. Furthermore was administred systemic antibiotics and external drugs. [ABSTRACT FROM AUTHOR]

The battle against emerging viral infections has been uneven, as there is currently no broad-spectrum drug available to contain the spread of novel pathogens throughout the population. Consequently, the pandemic outbreak that occurred in early 2020 laid bare the almost empty state of the pandemic box. Therefore, the development of novel treatments with broad specificity has become a paramount concern in this post-pandemic era.Here, we propose copolymers of poly (sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and poly (sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS75-b-PAaUn) and random (P(AMPSm-co-AaUn)) that show efficacy against a broad range of alpha and betacoronaviruses.Owing to their intricate architecture, these polymers exhibit a highly distinctive mode of action, modulating nano-mechanical properties of cells and thereby influencing viral replication. Through the employment of confocal and atomic force microscopy techniques, we discerned perturbations in actin and vimentin filaments, which correlated with modification of cellular elasticity and reduction of glycocalyx layer. Intriguingly, this process was reversible upon polymer removal from the cells. To ascertain the applicability of our findings, we assessed the efficacy and underlying mechanism of the inhibitors using fully differentiated human airway epithelial cultures, wherein near-complete abrogation of viral replication was documented.Given their mode of action, these polymers can be classified as biologically active nanomaterials that exploit a highly conserved molecular target—cellular plasticity—proffering the potential for truly broad-spectrum activity while concurrently for drug resistance development is minimal.

Background: The burden experienced by spouses of patients with Alzheimer's disease (AD) may have negative consequences for their physical health. We describe here a method for analyzing United States Medicare records to determine the changes in health service use and costs experienced by spouses after their marital partner receives an AD diagnosis.Methods: We initially identified all beneficiaries in the 2001-2005 Medicare 5% sample who had multiple claims listing the ICD-9 diagnostic code for AD, 331.0. The 5% sample includes spouses who share a Medicare account with their marital partners because they lack a sufficient work history for full eligibility on their own. A matched cohort study assessed incremental health costs in the spouses of AD patients versus a control group of spouses of non-AD patients. Longitudinal and cross-sectional analyses tracked the impact of a patient's AD diagnosis on his or her spouse's healthcare costs.Results: Our method located 54,593 AD patients of whom 11.5% had spouses identifiable via a shared Medicare account. AD diagnosis in one member of a couple was associated with significantly higher monthly Medicare payments for the other member's healthcare. The spouses' elevated costs commenced 2 to 3 months before their partners' AD diagnosis and persisted over the follow-up period. After 31 months, the cumulative additional Medicare reimbursements totaled a mean $4,600 in the spouses of AD patients. This excess was significant even after accounting for differences in baseline health status between the cohorts.Conclusion: The study methodology provides a framework for comprehensively evaluating medical costs of both chronically ill patients and their spouses. This method also provides monthly data, which makes possible a longitudinal evaluation of the cost effects of specific health events. The observed correlations provide a coherent demonstration of the interdependence between AD patients' and spouses' health. Future research should examine caregiving burden and other possible factors contributing to the AD spouses' health outcomes. It should also extend the method presented here to evaluations of other chronic diseases of the elderly. [ABSTRACT FROM AUTHOR]

Recenzja książki: Andrzej Piwowar, Język Grecki Nowego Testamentu. I. Gramatyka – indeksy. II. Klucz do ćwiczeń – słownik – paradygmaty (Materiały Pomocnicze do Wykładów z Biblistyki 15; Lublin: Wydawnictwo KUL 2022). Pp. 681 + 391 (key). ISBN 978-83-8288-058-8 (vol. 1). ISBN 978-83-8288-057-1 (vol. 2).

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered.

Aims Endothelial dysfunction (ED) and red blood cell distribution width (RDW) are both prognostic factors in heart failure (HF), but the relationship between them is not clear. In this study, we used a unique mouse model of chronic HF driven by cardiomyocyte-specific overexpression of activated Gαq protein (Tgαq*44 mice) to characterize the relationship between the development of peripheral ED and the occurrence of structural nanomechanical and biochemical changes in red blood cells (RBCs). Methods and results Systemic ED was detected in vivo in 8-month-old Tgαq*44 mice, as evidenced by impaired acetylcholine-induced vasodilation in the aorta and increased endothelial permeability in the brachiocephalic artery. ED in the aorta was associated with impaired nitric oxide (NO) production in the aorta and diminished systemic NO bioavailability. ED in the aorta was also characterized by increased superoxide and eicosanoid production. In 4- to 6-month-old Tgαq*44 mice, RBC size and membrane composition displayed alterations that did not result in significant changes in their nanomechanical and functional properties. However, 8-month-old Tgαq*44 mice presented greatly accentuated structural and size changes and increased RBC stiffness. In 12-month-old Tgαq*44 mice, the erythropathy was featured by severely altered RBC shape and elasticity, increased RDW, impaired RBC deformability, and increased oxidative stress (gluthatione (GSH)/glutathione disulfide (GSSG) ratio). Moreover, RBCs taken from 12-month-old Tgαq*44 mice, but not from 12-month-old FVB mice, coincubated with aortic rings from FVB mice, induced impaired endothelium-dependent vasodilation and this effect was partially reversed by an arginase inhibitor [2(S)-amino-6-boronohexanoic acid]. Conclusion In the Tgαq*44 murine model of HF, systemic ED accelerates erythropathy and, conversely, erythropathy may contribute to ED. These results suggest that erythropathy may be regarded as a marker and a mediator of systemic ED in HF. RBC arginase and possibly other RBC-mediated mechanisms may represent novel therapeutic targets for systemic ED in HF. [ABSTRACT FROM AUTHOR]

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy. [ABSTRACT FROM AUTHOR]

Using ethylene carbonate as a sample solvent, we investigated two molecular parameters used to estimate the reduction potential of the solvent: electron affinity, and the energy of the lowest unoccupied molecular orbital (LUMO). The results showed that the values of these parameters are inconsistent for a single ethylene carbonate molecule in vacuum calculations and in the continuous effective solvent. We performed a series of calculations employing explicit or hybrid (explicit/continuous) solvent models for aggregates of solvent molecules or solvated salt ions. In the hybrid solvent model, values of the two estimates extrapolated to an infinite system size converged to one common value, whereas the difference of 1 eV was calculated in the purely explicit solvent. The values of the gap between the highest occupied molecular orbital (HOMO) and the LUMO obtained in the hybrid model were significantly larger than those resulting from the explicit solvent calculations. We related these differences to the differences in frontier orbitals and changes of electron density obtained in the two solvent models. In the hybrid solvent model, the location of the additional electron in the reduced system usually corresponds to the LUMO orbital of the oxidized system. The presence of salt ions in the solvent affects the extrapolated values of the electron affinity and LUMO energy.

Hypomyelinating leukodystrophies (HLDs) are a rare group of heterogeneously genetic disorders characterized by persistent deficit of myelin observed on magnetic resonance imaging (MRI). To identify a new disease-associated gene of HLD, trio-based whole exome sequencing was performed for unexplained patients with HLD. Functional studies were performed to confirm the phenotypic effect of candidate protein variants. Two de novo heterozygous variants, c.227T>G p.(L76R) or c.227T>C p.(L76P) in TMEM163 were identified in two unrelated HLD patients. TMEM163 protein is a zinc efflux transporter localized within the plasma membrane, lysosomes, early endosomes, and other vesicular compartments. It has not been associated with hypomyelination. Functional zinc flux assays in HeLa cells stably-expressing TMEM163 protein variants, L76R and L76P, revealed distinct attenuation or enhancement of zinc efflux, respectively. Experiments using a zebrafish model with knockdown of tmem163a and tmem163b (morphants) showed that loss of tmem163 causes dysplasia of the larvae, locomotor disability and myelin deficit. Expression of human wild type TMEM163 mRNAs in morphants rescues the phenotype, while the TMEM163 L76P and L76R mutants aggravated the condition. Moreover, poor proliferation, elevated apoptosis of oligodendrocytes, and reduced oligodendrocytes and neurons were also observed in zebrafish morphants. Our findings suggest an unappreciated role for TMEM163 protein in myelin development and add TMEM163 to a growing list of genes associated with hypomyelination leukodystrophy.

Introduction: Despite mounting evidence that increased frequency and duration of hemodialysis (HD) improves outcomes, less than 1% of HD patients worldwide receive nocturnal hemodialysis (NHD). Many perceived barriers exist to providing NHD and increasing its provision. Methods: A retrospective analysis of nocturnal therapy using a low‐flow dialysate system in 4 European centers for a minimum of 12 months, with data collected on patient demographics, training times, safety features, medications, and biochemical parameters at baseline and at 6 and 12 months. Findings: Data were collected on 21 patients, with 12‐month analysis available for 20 patients. Mean dialysis duration was 28 hours per week, with most dialysis on an alternate night regimen using 50–60 L of dialysate per session. All vascular access types were represented, and low molecular weight heparin was used as a bolus. All biochemical parameters met European standards, with a trend for improvement in standardized Kt/V, phosphate, hemoglobin, and albumin. There was a significant reduction in phosphate binder usage and a reduction in blood pressure medication. Training time was 9.6 sessions for independence at home, with 2 additional sessions to transition to NHD. Additional safety features included an alarmed drip tray under the cycler and moisture sensors under the venous needle (all patients used dual‐cannulation technique). No patient safety events were reported. Discussion: These data support the use of a low‐flow dialysate system for provision of NHD at home. Biochemical parameters were good, medication burden was reduced at 12 months, and all patients received more than double the duration of HD provided in standard in‐center units. While patient numbers were small, low‐flow dialysis in this cohort was both effective and safe. Use of this alternative HD system could reduce some of the barriers to NHD, increasing the uptake of therapy in Europe, and improving long‐term patient outcomes. [ABSTRACT FROM AUTHOR]

Ab initio molecular dynamics simulations modeling low-energy collisions of a sodium atom with a cluster with more than 30 water molecules are presented. We follow the dynamics of the atom-cluster interaction and the delocalization of the valence electron of sodium together with the changes in the electron binding energy. This electron tends to be shared by the nascent sodium cation and the water cluster. IR spectra of the sodium-water cluster are both computationally and experimentally obtained, with a good agreement between the two approaches. [ABSTRACT FROM AUTHOR]

Mechanically activated (MA) ion channels convert physical forces into electrical signals. Despite the importance of this function, the involvement of mechanosensitive ion channels in human disease is poorly understood. Here we report heterozygous missense mutations in the gene encoding the MA ion channel TMEM63A that result in an infantile disorder resembling a hypomyelinating leukodystrophy. Four unrelated individuals presented with congenital nystagmus, motor delay, and deficient myelination on serial scans in infancy, prompting the diagnosis of Pelizaeus-Merzbacher (like) disease. Genomic sequencing revealed that all four individuals carry heterozygous missense variants in the pore-forming domain of TMEM63A. These variants were confirmed to have arisen de novo in three of the four individuals. While the physiological role of TMEM63A is incompletely understood, it is highly expressed in oligodendrocytes and it has recently been shown to be a MA ion channel. Using patch clamp electrophysiology, we demonstrated that each of the modeled variants result in strongly attenuated stretch-activated currents when expressed in naive cells. Unexpectedly, the clinical evolution of all four individuals has been surprisingly favorable, with substantial improvements in neurological signs and developmental progression. In the three individuals with follow-up scans after 4 years of age, the myelin deficit had almost completely resolved. Our results suggest a previously unappreciated role for mechanosensitive ion channels in myelin development. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the effect of home‐based primary care (HBPC) for frail older adults, operating under Independence at Home (IAH) incentive alignment on long‐term institutionalization (LTI). DESIGN: Case‐cohort study using HBPC site, Medicare administrative data, and National Health and Aging Trends Study (NHATS) benchmarks. SETTING: Three IAH‐participating HBPC sites in Philadelphia, PA, Richmond, VA, and Washington, DC. PARTICIPANTS: HBPC integrated with long‐term services and supports (LTSS) cases (n = 721) and concurrent comparison groups (HBPC not integrated with LTSS: n = 82; no HBPC: n = 573). Cases were eligible if enrolled at one of the three HBPC sites from 2012 to 2015. Independence at Home‐qualified (IAH‐Q) concurrent comparison groups were selected from Philadelphia, PA; Richmond, VA; and Washington, DC. INTERVENTION: HBPC integrated with LTSS under IAH demonstration incentives. MEASUREMENTS: Measurements include LTI rate and mortality rates, community survival, and LTSS costs. RESULTS: The LTI rate in the three HBPC programs (8%) was less than that of both concurrent comparison groups (IAH‐Q beneficiaries not receiving HBPC, 16%; patients receiving HBPC but not in the IAH demonstration practices, 18%). LTI for patients at each HBPC site declined over the three study years (9.9%, 9.4%, and 4.9%, respectively). Costs of home‐ and community‐based services (HCBS) were nonsignificantly lower among integrated care patients ($2151/mo; observed‐to‐expected ratio =.88 [.68‐1.09]). LTI‐free survival in the IAH HBPC group was 85% at 36 months, extending average community residence by 12.8 months compared with IAH‐q participants in NHATS. CONCLUSION: HBPC integrated with long‐term support services delays LTI in frail, medically complex Medicare beneficiaries without increasing HCBS costs. See related editorial by Leff et al. [ABSTRACT FROM AUTHOR]

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-13C]glucose intravenously over 80+ h while maintaining euglycemia. 13C-glycogen levels in the occipital lobe were measured by 13C magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior 13C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established. [ABSTRACT FROM AUTHOR]

Reaction of the nitrogen-rich triazole–tetrazole hybrid ligand 5-(4H-1,2,4-triazol-yl)-2H-tetrazole (trz–tetH) with Li+, Na+, K+ and Ba2+ in water leads to the coordination polymers [Li(trz–tet)H2O]n, [Na(trz–tet)(H2O)2]n, [K(trz–tetH)(trz–tet)(H2O)2]n and [Ba2(trz–tet)4(H2O)9]n, exhibiting different topologies and coordination modes. Salt-like structures with anionic triazole–tetrazole building blocks [Mg(H2O)6](trz–tet)2 and [Ca(H2O)8](trz–tet)2 were also obtained. All structures were simplified by topological analysis, which showed that the structures of [Mg(H2O)6](trz–tet)2 and [Ca(H2O)8](trz–tet)2 can be considered as underlying networks, constructed from the hydrogen bonded [Mg(H2O)6]2+ or [Ca(H2O)8]2+ cations and trz–tet ligands, with the rare binodal 5,10-connected topology alb-5,10,P21/c-1 and a unique binodal 5,12-connected topology, respectively. According to TGA/DTA analysis, all compounds show endothermic mass losses below 200 °C due to dehydration processes. The dehydrated residues are stable up to 300 °C. It was also established that the anionic form of the coordinated ligand trz–tet decomposes with an abrupt mass loss accompanied by a sharp and intense exothermic effect, while the non-coordinated trz–tet, as in the structures of the Mg- and Ca-based compounds, decomposes with a more gradual mass loss and significantly broad exothermic effect. Static DFT, ab initio molecular dynamics simulations as well as charge and energy decomposition (ETS-NOCV) based studies are performed in order to shed light on the stability of the newly obtained crystals. [ABSTRACT FROM AUTHOR]

In the present research, we developed and conducted a field test of the computerized adaptive rating scale (CARS) for assessing military officer performance. Participants completed the CARS and a behaviorally anchored rating scale (BARS) which were both designed to assess five leadership competencies (action orientation/initiative, communication, developing self and others, behavioral flexibility, and teamwork). We obtained data from 116 supervisors and 207 peers who provided ratings on 126 officer ratees. Although interrater reliability estimates were lower for CARS ratings on some competencies, there was a 20-25% improvement in standard error of measurement, the measurement precision in CARS ratings compared to the BARS. Results support findings from a previous lab study. [ABSTRACT FROM AUTHOR]

Nitrones are important building blocks for natural and biologically active compounds, used as spin-trap reagents and therapeutic agents. All this makes nitrones intriguing and valuable compounds for fundamental studies and as useful chemicals in various synthetic strategies. Therefore, nitrones are still of great interest and in the limelight of researches. With our initial goal to solve synthetic problems toward 5-phenyl-2,2′-bipyridine (Phbpy), we found that this reaction can proceed through the formation of 6-phenyl-3-(pyridin-2-yl)-1,2,4-triazin-4(3H)-ol (4-OH), which rapidly isomerizes to a 3,4-dihydro-1,2,4-triazine-based nitrone, namely 6-phenyl-3-pyridin-2-yl-2,3-dihydro-1,2,4-triazin-4-oxide (4′), This encouraged us to study condensation of hydrazonophenylacetaldehyde oxime (2), obtained from 2-isonitrosoacetophenone (1), with other aldehydes. The reaction with both salicylaldehyde and p-tolualdehyde leads to the open-chain isomers, namely (2-hydroxybenzylidene)hydrazono-2-phenylacetaldehyde oxime (5) and (4-methylbenzylidene)hydrazono-2-phenylacetaldehyde oxime (6), respectively. The latter product exists in solution in equilibrium with its cyclic isomer 6-phenyl-3-(4-methylphenyl)-2,3-dihydro-1,2,4-triazin-4-oxide (6′), while the former one exists in solution exclusively in the open-chain form. It was also found that 2 reacts with acetone with the formation of 3,3-dimethyl-6-phenyl-2,3-dihydro-1,2,4-triazin-4-oxide (7′), which also exists in solution in equilibrium with its open-chain isomer 2-phenyl-2-(propan-2-ylidenehydrazono)acetaldehyde oxime (7). The static DFT as well as ab initio molecular dynamics simulations have corroborated the experimental findings. [ABSTRACT FROM AUTHOR]

The reaction of the N-thiophosphorylated thiourea (HOCH2)(Me)2CNHC(S)NHP(S)(O iPr)2 (HL), deprotonated by the thiophosphorylamide group, with NiCl2 leads to green needles of the pseudotetrahedral complex [Ni(L-1,5- S, S′)2] ⋅0.5 ( n-C6H14) or pale green blocks of the trans square-planar complex trans-[Ni(L-1,5- S, S′)2]. The former complex is stabilized by homopolar dihydrogen CH⋅⋅⋅HC interactions formed by n-hexane solvent molecules with the [Ni(L-1,5- S, S′)2] unit. Furthermore, the dispersion-dominated CH⋅⋅⋅ HC interactions are, together with other noncovalent interactions (CH⋅⋅⋅N, CH⋅⋅⋅Ni, CH⋅⋅⋅S), responsible for pseudotetrahedral coordination around the NiII center in [Ni( L-1,5- S, S′)2] ⋅0.5 ( n-C6H14). [ABSTRACT FROM AUTHOR]

Aims Impaired awareness of hypoglycemia (IAH) is a limiting factor in the treatment of type 1 diabetes (T1D) and is a challenging condition to reverse. The objective of this study was to test the hypothesis that naltrexone therapy in subjects with T1D and IAH will improve counterregulatory hormone response and recognition of hypoglycemia symptoms during hypoglycemia. Methods We performed a pilot randomized double blind trial of 4 weeks of naltrexone therapy (n = 10) or placebo (n = 12) given orally in subjects with T1D and IAH. Outcome measures included hypoglycemia symptom scores, counterregulatory hormone levels and thalamic activation as measured by cerebral blood flow using MRI during experimental hypoglycemia in all subjects before and after 4 weeks of intervention. Results After 4 weeks of therapy with naltrexone or placebo, no significant differences in response to hypoglycemia were seen in any outcomes of interest within each group. Conclusions In this small study, short-term treatment with naltrexone did not improve recognition of hypoglycemia symptoms or counterregulatory hormone response during experimental hypoglycemia in subjects with T1D and IAH. Whether this lack of effect is related to the small sample size or due to the dose, the advanced stage of study population or the drug itself should be the subject of future investigation. [ABSTRACT FROM AUTHOR]

Several pyrene based fluorescent probes undergo lysine assisted monomer to excimer conversion in a ratiometric manner. Intracellular lysine is detected using fluorescence microscopy. [ABSTRACT FROM AUTHOR]

Objectives To determine the effect of home-based primary care ( HBPC) on Medicare costs and mortality in frail elders. Design Case-control concurrent study using Medicare administrative data. Setting HBPC practice in Washington, District of Columbia. Participants HBPC cases (n = 722) and controls (n = 2,161) matched for sex, age bands, race, Medicare buy-in status (whether Medicaid covers Part B premiums), long-term nursing home status, cognitive impairment, and frailty. Cases were eligible if enrolled in MedStar Washington Hospital Center's HBPC program during 2004 to 2008. Controls were selected from Washington, District of Columbia, and urban counties in Virginia, Maryland, and Pennsylvania. Intervention HBPC clinical service. Measurements Medicare costs, utilization events, mortality. Results Mean age was 83.7 for cases and 82.0 for controls ( P < .001). A majority of both groups was female (77%) and African American (90%). During a mean 2-year follow-up, in univariate analysis, cases had lower Medicare ($44,455 vs $50,977, P = .01), hospital ($17,805 vs $22,096, P = .003), and skilled nursing facility care ($4,821 vs $6,098, P = .001) costs, and higher home health ($6,579 vs $4,169; P < .001) and hospice ($3,144 vs. $1,505; P = .005) costs. Cases had 23% fewer subspecialist visits ( P = .001) and 105% more generalist visits ( P < .001). In a multivariate model, cases had 17% lower Medicare costs, averaging $8,477 less per beneficiary ( P = .003) over 2 years of follow-up. There was no difference between cases and controls in mortality (40% vs 36%, hazard ratio = 1.06, P = .44) or in average time to death (16.2 vs 16.8 months, P = .30). Conclusion HBPC reduces Medicare costs for ill elders, with similar survival outcomes in cases and controls. [ABSTRACT FROM AUTHOR]

The N-phosphorylated thiourea iPrNHC(S)NHP(O)(OPh)2 (HL) has been synthesized by the reaction of iPrNH2 and (PhO)2P(O)NCS. Recrystallization of HL from aqueous acetone leads to [iPrNH3]+[P(O)2(OPh)2]− in a quantitative yield. Reaction of the deprotonated HL with NiCl2 leads to violet [NiL2] crystals with a 1,3-N,S-coordination mode of the ligands. Static DFT and ab initio molecular dynamics studies indicated that [NiL2] is stabilized predominantly by intramolecular N–H…O=P hydrogen bonding and dynamically by secondary CPh–H…S interactions. All compounds have been characterized by IR, diffuse reflectance, UV-vis and NMR spectroscopy, single crystal X-ray diffraction analysis and elemental analysis. Thermal properties investigated in an air atmosphere by means of TGA revealed a residue corresponding to NiPS3. [ABSTRACT FROM AUTHOR]

Reaction of the deprotonated N-thiophosphorylated thioureas RC(S)NHP(S)(O iPr)2 [R = EtNH ( HLI), iPrNH ( HLII), Et2N ( HLIII), 2,5-Me2C6H3NH ( HLIV), 4-Me2NC6H4NH ( HLV)] with NiII leads to complexes of the formula [NiLI-V2]. The molecular structures of the complexes in the solid were elucidated by single-crystal X-ray diffraction analysis. In the complexes, the metal atom is found to be in a square-planar trans- N2 S2 ( [NiLII,IV2]) environment formed by the C=S sulfur atoms and the P-N nitrogen atoms, or in a square-planar trans- S2 S′2 ( [NiLI,III2]) environment formed by the C=S and P=S sulfur atoms of two deprotonated ligands. Reaction of deprotonated N-thiophosphorylated thiourea HLV with NiCl2 leads to violet [Ni(L-1,3- N, S)2] or dark violet [Ni(L-1,5- S, S′)2]·(CH3)2C=O crystals that were isolated by recrystallization from a mixture of CH2Cl2 or acetone, respectively, and n-hexane. DFT calculations confirmed that the [Ni(LI,II,IV,V- N, S)2] conformers are more stable (by 5-7 kcal/mol) than [Ni(LI,II,IV,V- S, S′)2], whereas [Ni(LIII- N, S)2] is less stable (by 7-9 kcal/mol) than [Ni(LIII- S, S′)2]. The main reason for higher stability of the 1,3- N, S versus 1,5- S, S′ isomers is the formation of intramolecular N-H ···S=P hydrogen bonds. The same hydrogen bonds are impossible in complex [NiLIII2]. In solution, complex [NiLIII2] has revealed an exclusively 1,5- S, S′ coordination, whereas compounds [NiLI,II,IV,V2] reveal at least two isomers in the 1H and 31P{1H} NMR spectra. The major species is assigned to the 1,3- N, S-coordinated isomer, and the minor signals are assigned to the 1,5- S, S′ isomer, which was confirmed by UV/Vis spectroscopic results. The electrochemical measurements reveal reversible one-electron reduction and irreversible oxidations both assigned to ligand-centred processes. Ligand-based oxidation processes agree well with TD-DFT results. [ABSTRACT FROM AUTHOR]

Reaction of the deprotonated N-thiophosphorylated thiourea p-Me2NC6H4NHC(S)NHP(S)(OiPr)2(HL) with NiCl2leads to violet [Ni(L-1,3-N,S)2] or dark violet [Ni(L-1,5-S,S′)2]·(CH3)2CO crystals that were isolated by recrystallization from a mixture of CH2Cl2or acetone, respectively, and n-hexane. [ABSTRACT FROM AUTHOR]

Introduction: The increase of fungal infections is widely observed all over the world. Neonates, particularly those with immature immunity and multiple medications, parenteral nutrition and invasive diagnostic procedures are very prone to fungal infection. Aim: Assesment of risk of fungal infections in neonates requiring intensive care. Material and methods: 3544 blood samples and other samples like urine, skin swabs and mucous membrane swabs obtained from neonates were analysed. All neonates were hospitalised in Department of Neonatology at Poznan University of Medical Sciences. Samples were obtained in the second week of life and underwent a standard, mycological diagnostic procedure. Results: Yeast like fungi were grown in 194 cultures. The dominant was Candida albicans - present in 74.1%. Other isolated species were: C. glabrata, C. parapsilosis, C. sake, C. tropicalis and C. lusitaniae. There was no statistically important correlations between sites of isolations of yeast were found. Medium weight of neonates diagnosed with fungal infections was lower than the one of neonates with no infection, but it was not statistically significant. No lipophylic yeast were cultured. Conclusions: Candida-yeast are a real danger in neonatal intensive care units. [ABSTRACT FROM AUTHOR]

In this paper, systematic studies concerning the influence of selected oxysterols on the structure and fluidity of human erythrocyte membrane modeled as Langmuir monolayers have been performed. Three oxidized cholesterol derivatives, namely 7α-hydroxycholesterol (7α-OH) 7β-hydroxycholesterol (7β-OH) and 7-ketocholesterol (7-K) have been incorporated in two different proportions (10 and 50%) into artificial erythrocyte membrane, modeled as two-component (cholesterol:POPC) Langmuir monolayer. All the studied oxysterols were found to alter membrane fluidity and the effect was more pronounced for higher oxysterol content. 7α-OH increased membrane fluidity while opposite effect was observed for 7β-OH and 7-K. Experiments performed on model systems have been verified in biological studies on red blood cells (RBC). Consistent results have been found, i.e. under the influence of 7α-OH, the elasticity of erythrocytes increased, and in the presence of other investigated oxysterols - decreased. The strongest effect was noticed for 7-K. Change of membrane elasticity was associated with the change of erythrocytes shape, being most noticeable under the influence of 7-K. Unlabelled Image • Influence of B-ring-substituted oxysterols on RBC was determined. • Results from Langmuir monolayers are consistent with biological experiments on RBCs. • The investigated oxysterols (7-K, 7α-OH and 7β-OH) alter RBC elasticity. • The strongest influence on RBC has been observed for 7-K. [ABSTRACT FROM AUTHOR]

The battle against emerging viral infections has been uneven, as there is currently no broad-spectrum drug available to contain the spread of novel pathogens throughout the population. Consequently, the pandemic outbreak that occurred in early 2020 laid bare the almost empty state of the pandemic box. Therefore, the development of novel treatments with broad specificity has become a paramount concern in this post-pandemic era. Here, we propose copolymers of poly (sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and poly (sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS 75 -b-PAaU n ) and random (P(AMPS m -co-AaU n )) that show efficacy against a broad range of alpha and betacoronaviruses. Owing to their intricate architecture, these polymers exhibit a highly distinctive mode of action, modulating nano-mechanical properties of cells and thereby influencing viral replication. Through the employment of confocal and atomic force microscopy techniques, we discerned perturbations in actin and vimentin filaments, which correlated with modification of cellular elasticity and reduction of glycocalyx layer. Intriguingly, this process was reversible upon polymer removal from the cells. To ascertain the applicability of our findings, we assessed the efficacy and underlying mechanism of the inhibitors using fully differentiated human airway epithelial cultures, wherein near-complete abrogation of viral replication was documented. Given their mode of action, these polymers can be classified as biologically active nanomaterials that exploit a highly conserved molecular target-cellular plasticity-proffering the potential for truly broad-spectrum activity while concurrently for drug resistance development is minimal., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests Krzysztof Pyrc reports financial support was provided by 10.13039/501100004281National Science Centre Poland. Maria Nowakowska reports financial support was provided by 10.13039/501100004281National Science Centre Poland., (© 2023 The Authors.)

Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.