Refinement of an Organizational Skills Intervention for Adolescents with ADHD for Implementation by School Mental Health Providers.
The purpose of the study was to modify, test, and refine the Homework, Organization, and Planning Skills (HOPS) intervention for adolescents with ADHD for use by school mental health (SMH) providers. Ten SMH providers from three school districts implemented the HOPS intervention with 11 middle school students with ADHD. Parent and teacher ratings of materials organization and homework management were collected pre- and post-intervention and treatment fidelity was assessed. SMH providers and teachers participated in focus groups and provided feedback on ways to improve the feasibility and usability of the HOPS intervention. Students made large improvements in organization skills (d = 1.8) and homework problems (d = 1.6) according to parent ratings however, no improvements were observed on teacher ratings. Qualitative data generated from coding the focus groups and audio-recorded HOPS sessions were combined with the quantitative results to systematically refine the HOPS intervention for further evaluation of intervention effectiveness and disseminability.


A review on the possible molecular mechanism of action of N-acetylcysteine against insulin resistance and type-2 diabetes development.
N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against insulin resistance. The possible mechanisms of action were reviewed using the major findings of more than 100 papers relating to the antioxidant, anti-inflammatory and anti-apoptotic properties of NAC. The anti-oxidative activity of NAC has been attributed to its fast reactions with free radicals as well as the restitution of reduced glutathione. Further, NAC has anti-inflammatory and anti-apoptotic properties which can have positive effects during the inflammatory process in insulin resistance. Moreover, NAC can modulate certain signaling pathways in both insulin target cells and β cells. The diverse biological effects of NAC may make it a potential adjuvant or therapeutic target in the treatment of type-2 diabetes. So, further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity.


Treatment and the process of care in musculoskeletal conditions. A multidisciplinary perspective and integration.
Chronic musculoskeletal pain for which there is not an obvious underlying physical cause is one of the most common reasons for long-term disability. There is a need to develop better ways of managing these problems. Improving the understanding of the basis for decision making, the processes of care, and the beliefs and expectations of patients and health care professionals seems as fundamental as basic laboratory science is to understanding inflammatory arthopathies. Little is known about the beliefs and expectations of patients and health care professionals, nor the multitude of factors such as traditions within professional groups, education, and language that professionals use in decision making. When better understanding of these factors and the mismatch between professionals and patients is achieved, then theoretical frameworks, treatment approaches, and the education of professionals in appropriate management will be improved.


Uniformity and Efficacy of Dry Powders Delivered to the Lungs of a Mycobacterial-Surrogate Rat Model of Tuberculosis.
Pulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than systemic medication. However, in the pre-clinical study phase, there is a lack of devices for effective delivery of dry powders to the lungs of small rodents. In this study, an administration device which utilizes Venturi effect to deliver dry powders to the lungs homogeneously was developed. A Venturi-effect administration device which synchronizes with breathes by use of a ventilator and aerosolizes the dry powders was created. Pulmonary distribution of inhalable dry powders prepared by spray-drying poly(lactic-co-glycolic) acid and an antituberculosis agent rifampicin and anti-tuberculosis effect of the powders on mycobacteria infected rats by administration with the Venturi-effect administration device and a conventional insufflation device were evaluated. Homogeneous distribution of the dry powders in the lung was achieved by the Venturi-effect administration device due to efficient and recurring aerosolization of loaded dry powders while synchronizing with breathes. Amount of rifampicin delivered to the lungs by the Venturi-effect administration device was three times higher than that by a conventional insufflation device, demonstrating three times greater antimycobacterial activity. The Venturi-effect administration device aerosolized inhalable antituberculosis dry powders efficiently, achieved uniform pulmonary distribution, and aided the dry powders to exert antituberculosis activity on lung-residing mycobacteria.


Long-term outcomes of pericardiectomy for constrictive pericarditis.
Constrictive pericarditis is a rare and disabling disease that can result in chronic fibrous thickening of the pericardium. The purpose of this study was to evaluate the long-term outcomes following treatment of constrictive pericarditis by pericardiectomy. Between September 1992 and May 2014, 47 patients who underwent pericardiectomy for constrictive pericarditis were retrospectively examined. Demographic, pre-, intra- and postoperative data and long-term outcomes were analyzed. Thirty of the patients were male, the mean age was 45.8 ± 16.7. Aetiology of constrictive pericarditis was tuberculosis in 22 (46.8 %) patients, idiopathic in 15 (31.9 %), malignancy in 3 (6.4 %), prior cardiac surgery in 2 (4.3 %), non-tuberculosis bacterial infections in 2 (4.3 %), radiotherapy in 1 (2.1 %), uraemia in 1 (2.1 %) and post-traumatic in 1 (2.1 %). The surgical approach was achieved via a median sternotomy in all patients except only 1 patient. The mean operative time was 156.4 ± 45.7 min. Improvement in functional status in 80 % of patients' at least one New York Heart Association (NYHA) functional class was observed. In-hospital mortality rate was 2.1 % (1 of 47 patients). The cause of death was pneumonia leading to progressive respiratory failure. The late mortality rate was 23.4 % (11 of 47 patients). The mean follow-up time was 61.2 ± 66 months. The actuarial survival rates were 91 %, 85 % and 81 % at 1, 5 and 10 years, respectively. Recurrence requiring a repeat pericardiectomy was developed in no patient during follow-up. Pericardiectomy is associated with high morbidity and mortality rates. Cases with neoplastic diseases, diminished cardiac output, cases in need of reoperation are expected to have high mortality rates and less chance of functional recovery.


Evaluation of cellular immunity in diabetic uraemics by cutaneous response to recall antigens and 2:4 dinitrochlorobenzene and T-cell rosette formation.
Twenty diabetic uraemics and twenty two healthy matched controls comprised the material for this study. Cell mediated immunity was assessed by estimation of T-cell rosette percentage and cutaneous response to recall antigens--purified protein derivative, candida antigen and 2:4 dinitrochlorobenzene. Results analysis revealed depressed cell mediated immunity in diabetic uraemics in the form of impaired cutaneous response to recall antigens and reduction in T cell rosette percentage, in comparison to controls.


Predictors of adverse effects to antiseizure drugs in adult patients with epilepsy from Colombia: A case-control study.
Adverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures. The aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia. This case-control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons. Three hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment. In adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.


Cyclic di-AMP: Small molecule with big roles in bacteria.
Cyclic dinucleotides are second messengers that are present in all the three domains of life, bacteria, archaea, and eukaryotes. These dinucleotides have important physiological and pathophysiological roles in bacteria. Cyclic di-AMP (cdA) is one of the recently discovered cyclic dinucleotides present predominantly in gram-positive bacteria. cdA is synthesized through diadenylate cyclase (DAC) activity from ATP in a two-step process and hydrolyzed to linear dinucleotide pApA (and to 5' AMP in certain cases) by specific phosphodiesterases. cdA regulates various physiological processes like K+ transport and osmotic balance, DNA repair, cell wall homeostasis, drug resistance, central metabolism either by binding directly to the target protein or regulating its expression. It also participates in host-pathogen interaction by binding to host immune receptors ERAdP, RECON, and STING.


The Sequence Basis for Selectivity of Ephrin-B2 Ligand for Eph Receptors and Pathogenic Henipavirus G Glycoproteins: Selective Ephrin-B2 Decoys for Nipah and Hendra Virus.
Ephrin-B2 (EFNB2) is a ligand for six Eph receptors in humans and functions as a cell entry receptor for several henipaviruses including Nipah virus (NiV), a pathogenic zoonotic virus with pandemic potential. To understand the sequence basis of promiscuity for EFNB2 binding to the attachment glycoprotein of NiV (NiV-G) and Eph receptors, we performed deep mutagenesis on EFNB2 to identify mutations that enhance binding to NiV-G over EphB2, one of the highest affinity Eph receptors. The mutations highlight how different EFNB2 conformations are selected by NiV-G versus EphB2. Specificity mutations are enriched at the base of the G-H binding loop of EFNB2, especially surrounding a phenylalanine hinge upon which the G-H loop pivots, and at a phenylalanine hook that rotates away from the EFNB2 core to engage Eph receptors. One EFNB2 mutant, D62Q, possesses pan-specificity to the attachment glycoproteins of closely related henipaviruses and has markedly diminished binding to the six Eph receptors. However, EFNB2-D62Q has high residual binding to EphB3 and EphB4. A second deep mutational scan of EFNB2 identified combinatorial mutations to further enhance specificity to NiV-G. A triple mutant of soluble EFNB2, D62Q-Q130L-V167L, has minimal binding to Eph receptors but maintains binding, albeit reduced, to NiV-G. Soluble EFNB2 decoy receptors carrying the specificity mutations were potent neutralizers of chimeric henipaviruses. These findings demonstrate how specific residue changes at the shared binding interface of a promiscuous ligand (EFNB2) can influence selectivity for multiple receptors, and may also offer insight towards the development of henipavirus therapeutics and diagnostics.


Advancing Cardiac Critical Care: A Call for Training, Collaboration, and Family Engagement.
The evolution and development of pediatric cardiac critical care as a distinct subspecialty have occurred rapidly over the past 20 years. As the field has grown, models for education, training, and care delivery have changed as well. This review will highlight the current state of education, training, and parental involvement in care delivery for pediatric cardiac critical care as initially.


2-(7-Methyl-1H-indol-3-yl)acetonitrile.
In the title compound, C(11)H(10)N(2), the carbonitrile group is twisted away from the indole plane [C(cy)-C(me)-C(ar)-C(ar) = 66.6 (2)°; cy = cyanide, me = methyl-ene and ar = aromatic]. In the crystal, N-H⋯N hydrogen bonds link the mol-ecules into C(7) chains propagating in the [001] direction.


Family Attitudes regarding Newborn Screening for Krabbe Disease: Results from a Survey of Leukodystrophy Registries.
Newborn screening (NBS) for Krabbe disease (KD) is currently underway in eight states in the USA, and there is continued discussion of whether to implement KD NBS in additional states. Workgroup members sought to survey a large number of families affected by KD. Families in KD and leukodystrophy family registries were contacted to seek their participation in The Krabbe Newborn Screening-Family Perspective Survey. The 170 respondents are comprised of the following: 138 family members with a KD individual diagnosed after development of symptoms, 20 notified about KD via NBS, and 12 with a KD individual diagnosed through family history of KD. The key results are that all NBS families with an early-infantile KD family member elected to pursue hematopoietic stem cell transplantation therapy. Of the 170 responders, 165 supported the implementation of KD NBS in all states in the USA.


Demography and life history characteristics of two honey bee races (Apis mellifera).
Intra-colony demography and life history characteristics of neotropical Africanized and temperate European honey bearaces were compared under simulated feral conditions. Major differences in colony demography were found which nevertheless resulted in some similar reproductive characteristics. European colonies were larger than Africanized colonies, had more rapid initral growth rates of worker populations, showed better survivorship of brood and adult workers, and differed in patterns of worker age distribution. However, both races were similar in the brood and adult populations when colonies swarmed, the frequency and timing of swarming, and the number of workers in prime swarms. The factors most important in determining these colony growth and reproductive patterns were likely worker mortality rates, climate, and resource availability.


Attitudes of primary care physicians toward prescribing buprenorphine: a narrative review.
The opioid epidemic is a major public health issue associated with significant overdose deaths. Effective treatments exist, such as the medication buprenorphine, but are not widely available. This narrative review examines the attitudes of primary care providers (PCPs) toward prescribing buprenorphine. Narrative review of 20 articles published after the year 2000, using the Consolidated Framework for Implementation Research (CFIR) to organize the findings. Three of the five CFIR domains ("Intervention Characteristics," "Outer Setting," "Inner Setting") were strongly represented in our analysis. Providers were concerned about the clientele associated with buprenorphine, diversion, and their self-efficacy in prescribing the medication. Some believed that buprenorphine does not belong in the discipline of primary care. Other barriers included philosophical objections and stigma toward substance use disorders. Notably, two studies reported a shift in attitudes once physicians prescribed buprenorphine to actual patients. Negative attitudes toward buprenorphine encompassed multi-layered concerns, ranging from skepticism about the medication itself, the behaviors of patients with opioid use disorders, and beliefs regarding substance use disorders more generally. We speculate, however, that negative attitudes may be improved by tailoring support strategies that address providers' self-efficacy and level of knowledge.


Nonexcisional therapy for benign skin lesions.
Benign skin lesions are commonly seen and treated in the physician's office using standard equipment. These simple techniques may be easily learned and can and should be effectively employed by plastic surgeons.


Topography of inferior olivary neurons that encode canal and otolith inputs.
Vestibular information arising from rotational head movement and that from translational head movement are detected respectively by the semicircular canal and otolith organ in the inner ear. Spatiotemporal cues are in turn processed by the vestibulo-olivo-cerebellar pathway for sensorimotor coordination, but the role of the inferior olive (IO) in this pathway remains unclear. To address whether rotational and translational movements are differentially represented in the IO, we studied the distribution pattern of IO neurons recruited into the circuitry following selective activation of receptor hair cells of the horizontal semicircular canal or the utricle in adult rats. Neurons in the beta nucleus of IO (IOβ) and dorso-medial cell column of IO were responsive to horizontal translation, but not rotation. Notably, otolith-related neurons were observable largely in the rostral IOβ. In contrast, the subnucleus A of IO (IOA), subnucleus C of IO (IOC), and dorsal cap of Kooy (IOK) were responsive to horizontal rotation, but not translation. In the IOA, these canal-related neurons were clustered in the medial portion of the subnucleus. In the IOC, canal-related neurons were skewed towards the rostral half. In the IOK, canal-related neurons were found throughout the subnucleus. These indicate that the distributions of canal- and otolith-related neurons encoding horizontal motions are clearly segregated in the IO. These discrete IO subnuclei therefore provide a topographic map for temporal and adaptive operations of sensorimotor coordination and spatial reference.


Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma.
Since the carcinomas of the cardia and the adenocarcinomas of the esophagus show many similarities in their histological and morphological descriptions, a detailed comparative study was attempted on the basis of 66 esophageal carcinomas in adenoid differentiation, 359 carcinomas of the cardia, 1288 gastric carcinomas in infracardial localisation, and 492 squamous carcinomas of the esophagus. The evaluation yielded no significant differences between the adenocarcinomas of the esophagus and the cardia neither in age and sex distribution nor with regard to the classifications of Borrmann, WHO, Ming, and Laurén, but a significant discrimination was possible between esophageal and cardial adenocarcinoma together, on the one hand, and infracardial gastric carcinoma on the other. Furthermore, esophageal adenocarcinomas were localized preferentially in the lower third, unlike squamous carcinomas of the same organ. These results suggest that esophageal adenocarcinoma and carcinoma of the cardia must be considered as one separate entity, probably originating from a common stem cell. They further suggest that the cardia belongs to the esophagus rather than to the stomach.


Effect of liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) instillations on dynamics and function of continent cecal urinary reservoirs.
We assessed the impact of twice daily instillations of 10 ml. liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) on the dynamics and function of continent urinary reservoirs constructed from intact cecum and ascending colon. Six patients were treated for 1 to 3 weeks at 3 to 8 months postoperatively. The treatments reduced the frequency of spontaneous reservoir contractions, as well as the basal and contraction pressures of the reservoirs. The reservoir capacities were increased modestly. These alterations in reservoir dynamics were accompanied by a decrease in the cramping characteristically associated with reservoir distension and increased intervals between reservoir catheterization. Two patients who had incontinence after initially successful operations regained continence during treatment. No systemic side effects were observed, although dilution of the drug may be required to prevent reservoir irritability. Diphenoxylate hydrochloride and atropine sulfate instillations may prevent acute and possibly long-term pressure-related complications of continent urinary reservoirs constructed from intact cecum and ascending colon.


Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes.
Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB-t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.


Dysproteinuria induced in rats by O,O,S-trimethyl phosphorothioate.
Administration of a single oral dose of 60 mg/kg O,O,S-trimethyl phosphorothioate (OOS-Me), a malathion impurity, resulted in a substantial increase in the amounts of amino acids along with a change in the nature of proteins excreted in the urine of treated rats. In contrast to control rats, a small increase in albumin and a small decrease in alpha 1-globulin were observed. However, alpha2-, beta- and gamma 1-globulin, which were not detected in the urine of control rats, were found in substantial amounts in the urine of OOS-Me-treated rats. These findings, coupled with observed increases in urinary glucose levels and consistent specific gravity readings of 1.01 even though treated rats were experiencing oliguria, provide evidence for OOS-Me-induced kidney tubule damage.


The coronavirus recombination pathway.
Recombination is thought to be a mechanism that facilitates cross-species transmission in coronaviruses, thus acting as a driver of coronavirus spillover and emergence. Despite its significance, the mechanism of recombination is poorly understood, limiting our potential to estimate the risk of novel recombinant coronaviruses emerging in the future. As a tool for understanding recombination, here, we outline a framework of the recombination pathway for coronaviruses. We review existing literature on coronavirus recombination, including comparisons of naturally observed recombinant genomes as well as in vitro experiments, and place the findings into the recombination pathway framework. We highlight gaps in our understanding of coronavirus recombination illustrated by the framework and outline how further experimental research is critical for disentangling the molecular mechanism of recombination from external environmental pressures. Finally, we describe how an increased understanding of the mechanism of recombination can inform pandemic predictive intelligence, with a retrospective emphasis on SARS-CoV-2.


Use of aminopeptidase M as a hypotensive agent in spontaneously hypertensive rats.
The present investigation determined that a commercially available aminopeptidase M (AmM, Sigma Chemical) can be utilized to lower blood pressure in normotensive and hypertensive rats. In vitro analyses indicated that the predominant peptidase present in this preparation was AmM; however, it also contained some aminopeptidase A (AmA) and less DAP IV. Although no DAP IV-mediated metabolism of angiotensin II (AII) or angiotensin III (AIII) was measured, both AmM and AmA metabolized AII and AIII. Upon further examination, it appeared that AII could be converted to AIII by either AmM or AmA; however, Arg was cleaved from the N-Terminal of AIII predominantly by AmM. The aminopeptidase inhibitors actinonin (AC), amastatin (AM), and bestatin (BE) effectively blocked the AmM-induced hydrolysis of the Asp-Arg bond of AII, and the Arg-Val bond of AIII. The activity of AmA was inhibited by AM but was relatively resistant to inhibition by AC and BE. Next, exogenous aminopeptidase replacement was employed in the anesthetized spontaneously hypertensive rat (SHR) in an attempt to temporarily correct a hypothesized brain deficiency of receptor-associated peptidases and lower blood pressure. Third-ventricle infusion of AmM produced significant drops in blood pressure and heart rate in both SHRs and Wistar-Kyoto normotensive controls. Pretreatment with AC or BE was particularly effective at interfering with the subsequent AmM-induced hypotensive effect, while AM was less effective. The central mechanisms underlying these effects are in need of further investigation; however, they are at least partially dependent upon the brain angiotensin system.


Electrodiagnosis of diabetic peripheral polyneuropathy. A multivariate analytic approach.
Traditional univariate comparisons of nerve conduction data against standard norms may produce conflicting estimates of the presence or absence of a diabetic neuropathy, depending upon the data obtained and the specific nerves sampled. Alternatively, a multivariate analytic approach, using discriminant functions, provides a useful single measure of the degree of neuropathy determined as a weighted combination of the available data. The weights are derived from the linear discriminant function, which maximizes statistical separation of diabetic and nondiabetic subject groups. In this study, 12 electrophysiologic attributes are used to generate a single discriminant function that clearly separates diabetic from nondiabetic subjects and is interpretable as a neuropathic index. Each individual's index of diabetic neuropathy (I) can be quantified as follows: (Formula: see text) where Ai is the original electrophysiologic attribute (i = 12), ai is the coefficient for each attribute that defines the discriminant function and C is a constant specific for that function. For the first time, the degree of diabetic neuropathy can thus be quantified for purposes of comparison and correlation with other quantifiable clinical/somatic measures of diabetes. The index allows for a higher percentage of type II diabetic patients to be classified as neuropathic than previously described and enables determination of degree of neuropathy is affected individuals by an interpolative method.


Conduction study in human muscle fibers in situ--a useful technique for diagnosing myopathies.
Direct muscle conduction studies were carried out using monopolar needle electrodes in the distal portion of the brachial biceps muscles in 13 normal and 10 myopathic subjects. Two monopolar Teflon-coated needles with exposed tips were placed as stimulation electrodes in the distal end of the biceps muscle. A pick-up monopolar electrode was then placed 4 cm proximal to the stimulation electrodes along the same muscle with a surface reference electrode in the vicinity of the active electrode. After the maximal evoked response was detected, the shape, amplitude and duration were recorded. The results revealed that the muscle conduction velocity was slower in polymyositis patients compared with normal subjects but was not significantly different in patients with progressive muscular dystrophy. However, the shape, amplitude and duration of the muscle-evoked potential were characteristic in the myopathies. It is concluded that this muscle conduction study technique is simple and of clinical use in making electrodiagnosis.


Evolutionary analyses of gap junction protein families.
Gap junctions are intercellular channels that link the cytoplasm of neighboring cells in animals, enabling straight passage of ions and small molecules. Two different protein families, pannexins and connexins, form these channels. Pannexins are present in all eumetazoans but echinoderms (and are termed innexins in non-chordates) whereas connexins are exclusive of chordates. Despite little sequence similarity, both types of proteins assemble into a common secondary structure with four hydrophobic transmembrane domains linked by one cytoplasmic and two extracellular loops. Although all pannexins and connexins are packed into hexamers forming single channels, only non-chordate pannexins (innexins) and connexins form gap junctions. Here, we revisit and review evolutionary features of pannexin and connexin protein families. For that, we retrieved members of both families from several complete genome projects, and searched for conserved positions in the independent alignments of pannexin and connexin protein families. In addition, the degree of evolutionary conservation was mapped onto the 3D structure of a connexon (i.e. the assembly of six connexins). Finally, we reconstructed independent phylogenies of pannexins and connexins using probabilistic methods of inference. Non-chordate (Drosophila and Caenorhabditis) pannexins (i.e. innexins) were recovered as sister group of chordate pannexins, which included Ciona paralogs and vertebrate pannexins (pannexin-1 and pannexin-3 were recovered as sister groups to the exclusion of pannexin-2). In the reconstructed phylogeny of connexins, subfamilies α and β were recovered as sister groups to the exclusion of subfamily γ, whereas δ and (the newly identified) ζ subfamilies were recovered at the base of the tree. A sixth highly divergent subfamily (ε) was not included in the phylogenetic analyses. Several groups of paralogy were identified within each subfamily. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.


Separation of some enantiomeric di- and tripeptides on chiral stationary phases.
The chromatographic behavior of the N-3,5-dinitrobenzoyl derivatives of twelve dipeptide esters and two tripeptide esters was investigated on three different chiral stationary phases (CSPs). It is observed that the stereoisomers present in each sample may be cleanly separated on each chiral phase. A degree of regularity is noted in the elution order of the enantiomers and often of the diastereomers. Elution order of the enantiomers is related to a chiral recognition model for each CSP.


Cavity hydration dynamics in cytochrome c oxidase and functional implications.
Cytochrome c oxidase (CcO) is a transmembrane protein that uses the free energy of O2 reduction to generate the proton concentration gradient across the membrane. The regulation of competitive proton transfer pathways has been established to be essential to the vectorial transport efficiency of CcO, yet the underlying mechanism at the molecular level remains lacking. Recent studies have highlighted the potential importance of hydration-level change in an internal cavity that connects the proton entrance channel, the site of O2 reduction, and the putative proton exit route. In this work, we use atomistic molecular dynamics simulations to investigate the energetics and timescales associated with the volume fluctuation and hydration-level change in this central cavity. Extensive unrestrained molecular dynamics simulations (accumulatively [Formula: see text]4 [Formula: see text]s) and free energy computations for different chemical states of CcO support a model in which the volume and hydration level of the cavity are regulated by the protonation state of a propionate group of heme a3 and, to a lesser degree, the redox state of heme a and protonation state of Glu286. Markov-state model analysis of [Formula: see text]2-[Formula: see text]s trajectories suggests that hydration-level change occurs on the timescale of 100-200 ns before the proton-loading site is protonated. The computed energetic and kinetic features for the cavity wetting transition suggest that reversible hydration-level change of the cavity can indeed be a key factor that regulates the branching of proton transfer events and therefore contributes to the vectorial efficiency of proton transport.


Peripheral blood mononuclear cells from women with recurrent abortion exhibit an aberrant reaction to release cytokines upon the direct contact of human leukocyte antigen-G-expressing cells.
In search for pathogenesis of recurrent abortion, we examined whether lymphocytes/macrophages from women with recurrent abortion exhibited an aberrant ability to release cytokines upon the direct contact of human leukocyte antigen (HLA)-G. The amounts of cytokines released from peripheral blood mononuclear cells (PBMCs) from women with recurrent abortion were compared with those from normal multiparous women or normal nulligravidous women when cocultured with or without HLA-G-expressing target cells. When cocultured with HLA-G-expressing target cells, the amount of interleukin-1 beta released from PBMCs was increased in recurrent aborters whereas it decreased in both normal multiparous and nulligravidous women. The amount of interleukin-3 released from PBMCs did not differ with or without HLA-G-expressing cells in recurrent aborters, whereas it increased in the presence of HLA-G-expressing cells in normal controls. The amount of tumor necrosis factor-alpha released from PBMCs was decreased in the presence of HLA-G-expressing cells in both recurrent aborters and normal controls. The aberrant reaction of maternal lymphocytes/macrophages in releasing cytokines upon the contact of HLA-G expressed on trophoblasts may impact negatively on trophoblastic growth, which may be pathogenic in recurrent abortion.


Genetic dissection of maize plant architecture with an ultra-high density bin map based on recombinant inbred lines.
Plant architecture attributes, such as plant height, ear height, and internode number, have played an important role in the historical increases in grain yield, lodging resistance, and biomass in maize (Zea mays L.). Analyzing the genetic basis of variation in plant architecture using high density QTL mapping will be of benefit for the breeding of maize for many traits. However, the low density of molecular markers in existing genetic maps has limited the efficiency and accuracy of QTL mapping. Genotyping by sequencing (GBS) is an improved strategy for addressing a complex genome via next-generation sequencing technology. GBS has been a powerful tool for SNP discovery and high-density genetic map construction. The creation of ultra-high density genetic maps using large populations of advanced recombinant inbred lines (RILs) is an efficient way to identify QTL for complex agronomic traits. A set of 314 RILs derived from inbreds Ye478 and Qi319 were generated and subjected to GBS. A total of 137,699,000 reads with an average of 357,376 reads per individual RIL were generated, which is equivalent to approximately 0.07-fold coverage of the maize B73 RefGen_V3 genome for each individual RIL. A high-density genetic map was constructed using 4183 bin markers (100-Kb intervals with no recombination events). The total genetic distance covered by the linkage map was 1545.65 cM and the average distance between adjacent markers was 0.37 cM with a physical distance of about 0.51 Mb. Our results demonstrated a relatively high degree of collinearity between the genetic map and the B73 reference genome. The quality and accuracy of the bin map for QTL detection was verified by the mapping of a known gene, pericarp color 1 (P1), which controls the color of the cob, with a high LOD value of 80.78 on chromosome 1. Using this high-density bin map, 35 QTL affecting plant architecture, including 14 for plant height, 14 for ear height, and seven for internode number were detected across three environments. Interestingly, pQTL10, which influences all three of these traits, was stably detected in three environments on chromosome 10 within an interval of 14.6 Mb. Two MYB transcription factor genes, GRMZM2G325907 and GRMZM2G108892, which might regulate plant cell wall metabolism are the candidate genes for qPH10. Here, an ultra-high density accurate linkage map for a set of maize RILs was constructed using a GBS strategy. This map will facilitate identification of genes and exploration of QTL for plant architecture in maize. It will also be helpful for further research into the mechanisms that control plant architecture while also providing a basis for marker-assisted selection.


The Application of Machine Learning ICA-VMD in an Intelligent Diagnosis System in a Low SNR Environment.
This paper proposes a new method called independent component analysis-variational mode decomposition (ICA-VMD), which combines ICA and VMD. The purpose is to study the application of ICA-VMD in low signal-to-noise ratio (SNR) signal processing and data analysis. ICA is a very important method in the field of machine learning. It is an unsupervised learning algorithm that can dig out the independent factors hidden in the observation signal. The VMD method estimates each signal component by solving the frequency domain variational optimization problem, and it is very suitable for mechanical fault diagnosis. The advantage of ICA-VMD is that it requires two sensory cues to distinguish the original source from the unwanted noise. In the three cases studied here, the original source was first contaminated by white Gaussian noise. The three cases in this study are under different SNR conditions. The SNR in the first case is -6.46 dB, the SNR in the second case is -21.3728, and the SNR in the third case is -46.8177. The simulation results show that the ICA-VMD method can effectively recover the original source from the contaminated data. It is hoped that, in the future, there will be new discoveries and advances in science and technology to solve the noise interference problem through this method.


Effect of Atorvastatin, Curcumin, and Quercetin on miR-21 and miR-122 and their correlation with TGFβ1 expression in experimental liver fibrosis.
Liver fibrosis is an inflammatory and fibrogenic process that occurs following chronic liver damage. TGFβ1 is the key inducer of fibrosis. MiR-21 and miR-122 are two miRNAs that their expression changes during fibrosis. In the present study, we investigate the effects of curcumin, quercetin, and atorvastatin on the expression levels of miR-21 and miR-122 and evaluated their correlation with TGFβ1 expression in bile duct ligation (BDL)-induced fibrotic rats. Thirty two adult male Wistar rats were divided into 8 groups (n = 8 for each): Sham, Sham + curcumin (100 mg/kg/day), Sham + quercetin (30 mg/kg/day), Sham + atorvastatin (15 mg/kg/day), BDL, BDL + curcumin, BDL + quercetin, BDL + atorvastatin and treated for four weeks via oral gavage. The expression of miR-21, miR-122, and TGFβ1 was evaluated via RT-qPCR. The expression levels of TGFβ1 and miR-21 were significantly increased in the BDL group compared to the Sham group (P < 0.05), but the expression of miR-122 was significantly decreased in the BDL group compared to the Sham group (P < 0.05). Curcumin, quercetin, and atorvastatin treatment lead to down-regulation of miR-21 and TGFβ1 and up-regulation of miR-122 in the BDL groups. There was no significant difference between these drugs in altering gene expression and all had the same effects. Moreover, a direct significant correlation was observed between mir-21 and TGFβ1 and an inverse significant correlation between mir-122 and TGFβ1 expression. In summary, targeting these molecular pathways may partially prevent the progression of liver fibrosis.


Retention of skills 2 years after completion of a postpartum hemorrhage simulation training program in rural Rwanda.
To evaluate the long-term retention of skills gained by rural physicians who completed a postpartum hemorrhage simulation-training program. A quasi-experimental pre-post intervention study enrolled a convenience sample of generalist physicians in rural Rwanda. Participants underwent initial simulation training including pre- and post-training testing in February 2012. Simulation drills to assess skill retention were conducted in March 2014. Participants were scored based on their communication, evaluation, and management skills. Median scores and inter-quartile ranges were calculated and the Wilcoxon signed-rank sum test was used to compare the pre-training, post-training, and retention scores. Physician confidence was assessed using a survey. In total, 11 physicians were enrolled; eight were available for the 2-year skill-retention evaluation. Significant improvements were observed when comparing participants' pre-training and post-training communication (P=0.03), evaluation (P=0.05), and management (P=0.02) scores, and there were no changes between participants' post-training and 2-year communication (P>0.99), evaluation (P=0.16), and management (P=0.46) scores. There were no differences in the self-reported confidence measures across the duration of the study. Simulation training is an effective method for teaching postpartum hemorrhage-management skills to generalist physicians in rural areas and skills are retained for at least 2 years. Further studies could determine the optimal time intervals for refresher training.


Unusual substructure conformations observed in crystal structures of a dicistrovirus RNA-dependent RNA polymerase suggest contribution of the N-terminal extension in proper folding.
The Dicistroviridae is a virus family that includes many insect pathogens. These viruses contain a positive-sense RNA genome that is replicated by the virally encoded RNA-dependent RNA polymerase (RdRP) also named 3Dpol. Compared with the Picornaviridae RdRPs such as poliovirus (PV) 3Dpol, the Dicistroviridae representative Israeli acute paralysis virus (IAPV) 3Dpol has an additional N-terminal extension (NE) region that is about 40-residue in length. To date, both the structure and catalytic mechanism of the Dicistroviridae RdRP have remain elusive. Here we reported crystal structures of two truncated forms of IAPV 3Dpol, namely Δ85 and Δ40, both missing the NE region, and the 3Dpol protein in these structures exhibited three conformational states. The palm and thumb domains of these IAPV 3Dpol structures are largely consistent with those of the PV 3Dpol structures. However, in all structures, the RdRP fingers domain is partially disordered, while different conformations of RdRP substructures and interactions between them are also present. In particular, a large-scale conformational change occurred in the motif B-middle finger region in one protein chain of the Δ40 structure, while a previously documented alternative conformation of motif A was observed in all IAPV structures. These experimental data on one hand show intrinsic conformational variances of RdRP substructures, and on the other hand suggest possible contribution of the NE region in proper RdRP folding in IAPV.


Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases.
Although invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. We retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. We present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. Our experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.


Loss-of-function mutations of OsbHLH044 transcription factor lead to salinity sensitivity and a greater chalkiness in rice (Oryza sativa L.).
The most hazardous abiotic stress, salinity, restricted the world crop production, and grain chalkiness affected the grain quality to limit consumers' acceptance. The basic helix-loop-helix (bHLH) proteins modulate massive biological processes in plants. Here the CRISPR/Cas9 gene editing mutants were obtained to detect the function of OsbHLH044. The loss-of-function of OsbHLH044 mutants showed numerous altered plant phenotypes. Notably, the osbhlh044 mutants resulted in prominently reduced morphological and physiological parameters under salt stress. Lower antioxidant activities and higher lipid peroxidation and hydrogen peroxide (H2O2) accumulation in the osbhlh044 mutants caused salinity sensitivity due to elevated reactive oxygen species (ROS). Under salt stress, both shoots and roots of the osbhlh044 mutants acquired higher Na+. Moreover, the expression of ion homeostasis-related genes (OsHKTs, OsHAK, OsSOSs, and OsNHX) and ABA-responsive gene (OsLEA3) was significantly altered in the osbhlh044 mutants after salt stress. The expression levels of genes coding for starch (OsAGPL1, OsSSIIa, OsWx, and OsFLO2) and seed storage proteins (GluA1 and Globulin 1) were significantly decreased, indicating that they synthesize less store starch and proteins, resulting in grain chalkiness in the osbhlh044 mutants. Yeast one Hybrid (Y1H) showed that OsbHLH044 could activate salt- (OsHKT1;3, OsHAK7, OsSOS1, OsSOS2, OsNHX2, and OsLEA3 but not OsHKT2;1), and starch-related genes (OsSSIIa, OsWx, and OsFLO2) by binding to the G-boxes of their promoters. Therefore, the OsbHLH044 gene editing mutants revealed multiple functions, specifically a positive regulator of salt stress and grain quality, which might bring new insights into the breeding of rice varieties.


Induction of Multichotomous Branching by CLAVATA Peptide in Marchantia polymorpha.
A key innovation in land plants was the evolution of meristems with stem cells possessing multiple cutting faces (division planes) from which three-dimensional growth is derived in both haploid (gametophyte) and diploid (sporophyte) generations [1-3]. Within each meristem exists a pool of stem cells that must be maintained at a relatively constant size for development to occur appropriately [4-6]. In flowering plants, stem cells of the diploid generation are maintained by CLAVATA3/EMBRYO SURROUNDING REGION-related (CLE) peptide signaling [7, 8]. In the liverwort Marchantia polymorpha, the haploid body undergoes dichotomous branching, an ancestral characteristic of growth derived from the meristem, in which two equivalent body axes are developed via stem cell division, regulated by unknown molecular mechanisms. We show here that in M. polymorpha, treatment with MpCLE2/CLAVATA3 (CLV3) peptide resulted in the accumulation of undifferentiated cells, marked by MpYUC2 expression, in the apical meristem. Removal of MpCLE2 peptide resulted in multichotomous branching from the accumulated cells. Genetic analysis demonstrated that the CLAVATA1 (MpCLV1) receptor, but not the WUSCHEL-related HOMEOBOX (MpWOX) transcription factor, is responsible for MpCLE2 peptide signaling. In the apical meristem, MpCLV1 was expressed broadly in the central region, including the MpYUC2-positive area, whereas MpCLE2 was expressed in a largely complementary manner compared to MpYUC2, suggesting MpCLE2 mediates local cell-to-cell communication. CLV3/CLE peptide, a negative regulator of diploid stem cells in flowering plants, acts as a haploid stem cell-promoting signal in M. polymorpha, implicating a critical role for this pathway in the evolution of body plan in land plants.


Effects of electrical stimulation of low-threshold muscle afferents on visual reaction time.
Human subjects performed plantar flexions of the foot in visual reaction time (RT) situations. In the simple RT task, the same foot had to be moved during the whole session, in the choice RT task, the right or left foot was moved in a random sequence. Low-threshold muscle afferents which evoked a monosynaptic H reflex were electrically activated on both sides at various intervals after the onset of the light stimulus. In both RT situations. RT was shortened equally by the electrical stimulation. The intersensory facilitation in the choice RT task provided support for the preparation enhancement model, since the subjects could not react to the electrical stimulus alone.


Reducing the Threshold of Primary Prevention of Cardiovascular Disease to 10% Over 10 Years: The Implications of Altered Intensity "Statin" Therapy Guidance.
Cardiovascular disease (CVD) is a significant noncommunicable disease associated with high long-term mortality. In addition to more effective secondary therapies, the primary prevention of CVD has developed markedly in the past several years. This study aims to investigate the evidence and impact of reducing the threshold for primary CVD risk management to 10% over 10 years with "statin" therapy. To conduct research a systematic review utilizing 5 electronic database searches was completed for studies, analyzing the clinical effect of reducing the threshold of CVD risk to 10% over 10 years for primary prevention with statin therapy. The study included six (6) trials. Statin therapy was allocated to 31,018 participants. The mean age was 61 years and the mean follow-up was 4.6 years. The mean relative reduction in total cholesterol was 19% (from an average of), low-density lipoprotein cholesterol was 28.3% (from mmol/L to mmol/L) and triglycerides were 14.8% (from mmol/L to mmol/L). High-density lipoprotein cholesterol was observed to increase by a mean of 3.3% (from mmol/L to mmol/L). When examining all-cause mortality, statin therapy was associated with a 12% relative risk reduction compared with control, where overall rates were reduced from 1.4% to 1. % There is a 30% risk reduction in general major coronary events (from to %). There is a 19% risk reduction in general major cerebrovascular events with the statin group. While there is undoubtedly statistical evidence that supports the observation of the effectiveness of statin therapy for primary prevention, there is a risk that many hundreds of patients need to be treated to avoid a single adverse clinical outcome.


[Injuries of the brachial plexus and neighboring peripheral nerves in vertebral fractures and other trauma of the cervical spine].
On the one hand, out of 115 patients admitted to hospital with 162 various fractures of the cervical spine without injury to the spinal cord, only 3 (2.6%) had an associated lesion to the brachial plexus or nerves in the vicinity. On the other hand, among 500 consecutive patients with injuries to the brachial plexus, 55 (11%) presented fractures of the cervical spine (including T1 and the 1st rib), whiplash injuries, severe distortions and dislocations, and contusions of that vertebral segment. Five (1% resp. 9%) had spinal cord injuries, including four patients with partial Brown-Sequard's syndrome, which was caused by multilevel root avulsions of the brachial plexus. In rather severe trauma to the lower cervical spine and concomitant brachial plexus lesion, root avulsions must be expected in 83% of cases, and in almost half of these patients three or more roots are avulsed from the spinal cord. Fractures around the shoulder-girdle as well as arterial ruptures are also significant for this severe nerve injury. Of these patients 39 (71%), were victims of motorcycle accidents.


The role of epigenetic modification in postoperative cognitive dysfunction.
With the ageing of the population, the health problems of elderly individuals have become particularly important. Through a large number of clinical studies and trials, it has been confirmed that elderly patients can experience postoperative cognitive dysfunction after general anesthesia/surgery. However, the mechanism of postoperative cognitive dysfunction is still unknown. In recent years, the role of epigenetics in postoperative cognitive dysfunction has been widely studied and reported. Epigenetics includes the genetic structure and biochemical changes of chromatin not involving changes in the DNA sequence. This article summarizes the epigenetic mechanism of cognitive impairment after general anesthesia/surgery and analyses the broad prospects of epigenetics as a therapeutic target for postoperative cognitive dysfunction.


Psychosomatic aspects of the effect of conjugated estrogens in patients with postoperative ovarian deficiency syndrome.
Fifty-three uterine cancer patients who complained of the syndrome dur to vasomotor manifestations or psychosomatic response after ovariectomy were given Premarin tablets, 1.25 mg per day or placebo for 3 weeks and improvement in their complaints was compared from the psychosomatic aspects by the double-blind method. Premarin was significantly more effective than placebo (P less than 0.001) in the psychologically normal patients. On the other hand, no difference in the effectiveness of these drugs were found in the psychologically abnormal patients (P = 0.119). According to the self evaluation by the patients, Premarin was significantly more effective than placebo (P less than 0.05) in the psychologically normal patients. However, there was no difference in the effects of these agents in the psychologically abnormal patients.


High performance liquid chromatographic determination of dothiepin and northiaden in human plasma and serum.
A method has been developed for the separation and measurement of dothiepin and the N-demethyl metabolites, northiaden, in human plasma or serum by high performance liquid chromatography. The method uses a structurally-related drug, amitriptyline, as an internal standard and provides a limit of detection of about 10 ng/ml for each component. At a concentration of 20 ng/ml, northiaden and dothiepin could be measured with +/-11% and +/- 6% of the mean respectively and at 200 ng/ml within +/-3% and 1% of the mean. The method has been applied to the analysis of serum from patients undergoing dothiepin therapy.


Interaction of Rhodococcus equi with phagocytic cells from R. equi-exposed and non-exposed foals.
The interaction of Rhodococcus equi with alveolar macrophages from adult horses, foals experimentally exposed to R. equi (sensitized foals) and non-exposed foals was studied using in vitro bactericidal assays, cytochemical staining and transmission electron microscopy. It was demonstrated that R. equi is a facultative intracellular parasite, able to survive and multiply within the alveolar macrophages of the host by interfering with phagosome-lysosome fusion. Opsonization of R. equi with antibody against capsular components was associated with increased phagosome-lysosome fusion and significantly enhanced (P less than 0.05) killing of the organism by alveolar macrophages from non-exposed foals. Macrophages from non-exposed foals were able to ingest the non-opsonized organism, but unable to kill greater than 65% of the infective dose by 6 h post-exposure. Alveolar macrophages from sensitized foals behaved as adult macrophages, able to kill greater than 95% of the infective dose by 6 h. Lymphocyte factors, derived by in vitro incubation of sensitized peripheral blood lymphocytes with R. equi surface antigens, enhanced macrophage bactericidal activity. Macrophages from non-exposed foals incubated in the presence of the lymphocyte factors had a 50% increase in killing of R. equi, while sensitized macrophages incubated with lymphocyte factors had a greater than 100% increase in killing capacity.


Complications after cardiac transplantation. The role of immunosuppression.
Increased numbers of cardiac transplantations are being performed as a therapeutic option for end-stage cardiac disease. Immunosuppressive therapy combining multiple drugs to prevent rejection is essential to the success of this procedure. Although the patient's primary problem of heart failure is alleviated by a successful transplant, the secondary effect of immunosuppression causes many potential problems for this patient population. Infection from common pathogens or opportunistic microorganisms is the primary complication causing death in the post-transplant patient. Bacterial, viral, fungal, or parasitic infection may ensue during the postoperative period. Life-long immunosuppressive therapy places the patient at continuous risk for the development of infection. Nurses play an important role in the management of the cardiac transplant patient. A thorough knowledge of normal immune system function and the specific actions of each immunosuppressive drug on the immune system function is a prerequisite for providing care for these patients. Continuous monitoring of the patient to detect the signs and symptoms of infection or other side effects of the drugs is part of the nurse's role in caring for these patients. Maintenance of the patient's nonspecific host defenses is supported by specific nursing actions. In preparation for the life-long effects of the drugs, education of the patient and family regarding the implications of therapy with immunosuppressive agents is a crucial nursing function for the successful management of the cardiac transplant patient.


Connections associated with a healthy spirituality: are these unrecognized intermediary determinants that shape health inequities in Canadian young people?
The health of adolescents is determined by structural and intermediary factors. Such factors operate through pathways that foster different opportunities to achieve health and wellbeing, contributing to inequities. Past analyses of cross-national adolescent health data show that measures of child spirituality, conceptualized as the strength of the connections in our lives, may operate as intermediary determinants in some Western countries. Inspired by this idea, the current analysis provides an in-depth exploration of such pathways among Canadian adolescents. Our objectives were to confirm the existence of relationships between economic position and seven indicators of adolescent health status, then explore whether any observed inequities could be explained by the strength of connections afforded by a healthy spirituality. Cycle 8 of the Canadian Health Behaviour in School-aged Children (HBSC) study was conducted in 2017-18. A school-based sample (n = 18,962) of adolescents was obtained from across Canada following a standard cross-national protocol. Eligible participants completed a general survey about their health, health behaviours and their determinants. Survey data were used to model the potential effect of perceived levels of relative affluence on each of seven health indicators. Comparison of crude and adjusted relative risks estimates from weighted log-binomial regression models provided evidence of indirect mediating effects attributable to each of four domains of spirituality. As perceived levels of family affluence increased, the percentages of young people who reported each (7/7) of the negative health outcomes decreased. The spiritual health domain "connections to self" (i.e., the importance of meaning, purpose, joy and happiness in life) mediated the strength of relationships between relative affluence and each (7/7) of the outcomes in boys and girls. "Connections to others" (the importance of kindness, respect and forgiveness) mediated the strength of relationships between relative affluence and each (7/7) of the outcomes among girls. Inconsistent evidence of possible mediation was identified for connections to others in boys, as well as the other two domains of spirituality (connections to nature, then connections to the transcendent) in boys and girls. Specific connections afforded by a healthy spirituality could be intermediary determinants of health in Canadian adolescent populations.


Soluble and particulate forms of rat catechol-O-methyltransferase distinguished by gel electrophoresis and immune fixation.
Catechol-O-methyltransferase (COMT) was visualized in homogenates and subcellular fractions of rat tissues, including liver and brain, by gel electrophoresis, electrophoretic transfer of proteins to nitrocellulose (Western blotting), and immune fixation with antiserum to highly purified soluble rat liver COMT. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of all tissue homogenates examined revealed three major immune-specific proteins with apparent molecular weights 23,000, 26,000, and 66,000 (23K, 26K and 66K). Centrifugation of homogenates at 100,000 X g for 60 min resulted in the enrichment of the 26K species protein in the pellet whereas the 23K and 66K proteins were the predominant forms in the supernatant. The 66K protein appeared in variable amounts depending on the tissue being examined and the length of transfer of protein and is assumed to be an "aggregate" of the smaller form(s). The 26K protein was essentially the only immunoreactive species seen in a purified preparation of rat liver outer mitochondrial membrane. Isoelectric focusing (IEF) under denaturing conditions and two-dimensional gel electrophoresis of brain and liver fractions showed that the 23K protein was resolved into three bands of pI 5.1, 5.2, and 5.3, whereas the 26K protein had a pI of 6.2. Analysis of COMT activity in slices from nondenaturing IEF gels indicated that the pI 5.1-5.3 species are biologically active; the pI 6.2 species could not be detected under these conditions. COMT activity was demonstrated, however, in outer mitochondrial membranes from rat liver, which contain predominantly the 26K, pI 6.2 immunoreactive species. The major form of COMT in all rat tissues examined is "soluble" with an apparent Mr of 23K and a pI of 5.2. The nature of the modifications giving rise to pI 5.1 and 5.3 forms of this enzyme are not clear, nor is the relationship between the 23K and 26K forms. Further studies are needed to elucidate the relationship of immunoreactive forms of COMT to each other, their intracellular location, and their functional significance.


The effects of positive end-expiratory pressure on cardiac function: a comparative echocardiography-conductance catheter study.
Echocardiographic parameters of diastolic function depend on cardiac loading conditions, which are altered by positive pressure ventilation. The direct effects of positive end-expiratory pressure (PEEP) on cardiac diastolic function are unknown. Twenty-five patients without apparent diastolic dysfunction undergoing coronary angiography were ventilated noninvasively at PEEPs of 0, 5, and 10 cmH2O (in randomized order). Echocardiographic diastolic assessment and pressure-volume-loop analysis from conductance catheters were compared. The time constant for pressure decay (τ) was modeled with exponential decay. End-diastolic and end-systolic pressure volume relationships (EDPVRs and ESPVRs, respectively) from temporary caval occlusion were analyzed with generalized linear mixed-effects and linear mixed models. Transmural pressures were calculated using esophageal balloons. τ values for intracavitary cardiac pressure increased with the PEEP (n = 25; no PEEP, 44 ± 5 ms; 5 cmH2O PEEP, 46 ± 6 ms; 10 cmH2O PEEP, 45 ± 6 ms; p < 0.001). This increase disappeared when corrected for transmural pressure and diastole length. The transmural EDPVR was unaffected by PEEP. The ESPVR increased slightly with PEEP. Echocardiographic mitral inflow parameters and tissue Doppler values decreased with PEEP [peak E wave (n = 25): no PEEP, 0.76 ± 0.13 m/s; 5 cmH2O PEEP, 0.74 ± 0.14 m/s; 10 cmH2O PEEP, 0.68 ± 0.13 m/s; p = 0.016; peak A wave (n = 24): no PEEP, 0.74 ± 0.12 m/s; 5 cmH2O PEEP, 0.7 ± 0.11 m/s; 10 cmH2O PEEP, 0.67 ± 0.15 m/s; p = 0.014; E' septal (n = 24): no PEEP, 0.085 ± 0.016 m/s; 5 cmH2O PEEP, 0.08 ± 0.013 m/s; 10 cmH2O PEEP, 0.075 ± 0.012 m/s; p = 0.002]. PEEP does not affect active diastolic relaxation or passive ventricular filling properties. Dynamic echocardiographic filling parameters may reflect changing loading conditions rather than intrinsic diastolic function. PEEP may have slight positive inotropic effects. https://clinicaltrials.gov/ct2/show/NCT02267291 , registered 17. October 2014.


Male Factor Infertility and Clomiphene Citrate: A Meta-Analysis-The Effect of Clomiphene Citrate on Oligospermia.
Clomiphene citrate has long been administered with inconclusive outcomes. It has often been used as empirical treatment for male factor infertility, presumably by increasing the sperm concentration. However, to our knowledge there has been no meta-analysis of the exact impact on semen parameters. We performed a systematic review and meta-analysis of the impact of clomiphene citrate on sperm parameters in men with oligospermia. We systematically reviewed pertinent randomized, controlled, prospective trials using the bibliographic databases MEDLINE® (1966 to 2013), Embase® (1980 to 2013) and the Cochrane Collaboration. References of selected articles were reviewed for additional relevant citations. The net treatment effect of the observed change in sperm concentration was analyzed. Data pooled from 2 randomized, controlled trials and 1 prospective trial in men with infertility and oligospermia included a total of 197 men with a mean age of 32.8 years (range 18 to 65). In the treatment arm 115 men were treated with a minimum dose of 25 mg clomiphene citrate at least every other day for a minimum of 3 months. The placebo or no treatment arm included 82 men. Pooled meta-analysis data revealed a highly significant increase of 7.7 million sperm per ml after administering clomiphene citrate compared to placebo or no treatment. There was no evidence of significant heterogeneity across the groups. Available data suggest that clomiphene citrate is associated with an increased sperm count compared to placebo.


Facilitative effect of repetitive presentation of one stimulus on cortical responses to other stimuli in macaque monkeys--a possible neural mechanism for mismatch negativity.
The event-related potential 'mismatch negativity' (MMN) is an indicator of a perceiver's ability to detect deviations in sensory signal streams. MMN and its homologue in animals, mismatch activity (MMA), are differential neural responses to a repeatedly presented stimulus and a subsequent deviant stimulus (oddball). Because neural mechanisms underlying MMN and MMA remain unclear, there is a controversy as to whether MMN and MMA arise solely from stimulus-specific adaptation (SSA), in which the response to a stimulus cumulatively attenuates with its repetitive presentation. To address this issue, we used electrocorticography and the auditory roving-oddball paradigm in two awake macaque monkeys. We examined the effect of stimulus repetition number on MMA and on responses to repeated stimuli and oddballs across the cerebral cortex in the time-frequency domain. As the repetition number increased, MMA spread across the temporal, frontal and parietal cortices, and each electrode yielded a larger MMA. Surprisingly, this increment in MMA largely depended on response augmentation to the oddball rather than on SSA to the repeated stimulus. Following sufficient repetition, the oddball evoked a spectral power increment in some electrodes on the frontal cortex that had shown no power increase to the stimuli with less or no preceding repetition. We thereby revealed that repetitive presentation of one stimulus not only leads to SSA but also facilitates the cortical response to oddballs involving a wide range of cortical regions. This facilitative effect might underlie the generation of MMN-like scalp potentials in macaques that potentially shares similar neural mechanisms with MMN in humans.


Functional reconstitution of U6 snRNA in nematode cis- and trans-splicing: U6 can serve as both a branch acceptor and a 5' exon.
Maturation of nuclear pre-mRNAs in nematodes requires both cis- and trans-splicing. Both processing pathways involve analogous two-step phosphotransfer reactions and both are dependent upon the integrity of U6 snRNA. We have developed a functional reconstitution assay to assess the U6 snRNA sequence requirements for cis- and trans-splicing. Branch formation between the splicing substrates and U6 snRNA was observed. The frequency of this event was greatly enhanced when a highly conserved sequence in U6 snRNA was altered by mutation. In cis- and trans-splicing reactions reconstituted with this mutant U6 snRNA the liberated exon of U6 proceeded through the second step of splicing using the appropriate splice acceptor sites. These results demonstrate covalent interactions between a U snRNA required for splicing and a splicing substrate, and they provide evidence for an unexpected degree of catalytic flexibility within the spliceosome.


DNA amplifications on chromosomes 7, 9 and 12 in glioblastoma detected by reverse chromosome painting.
Biopsies and cell culture, respectively, of four human glioblastoma multiforme (WHO 4) have been evaluated for gene amplification using reverse chromosome painting. Three of the tumours showed amplified domains within chromosome bands 12q13-15. The exact localisation and extension of the amplified domains, however, varies within this region. Southern blot analysis revealed amplification of the GLI oncogene in two of the glioblastomas which were found to contain amplified domains within 12q13-15. Reverse chromosome painting also identified amplified domains within bands 7q21 and 9p23-24. Amplification within region 9p23-24 has previously not been reported in glioblastoma. The amplified domain encompassing 9p23-24 was detected in the same glioblastoma which contained an amplification unit within bands 12q13-14. These data, together with previous reports, indicate that amplifications are predominantly found on chromosomes 7, 9 and 12 in glioblastoma. In addition, this study provides further evidence that coamplification is not a rare event in glioblastoma.


The cost of intensive and special care of the newborn.
The cost of providing intensive (level-3) and special (level-2) care for newborn infants in a tertiary perinatal service was determined prospectively and was expressed in 1984 Australian dollars. Direct costs that were expressed per occupied bed-day were $690 for level-3, high-dependency care; $421 for level-3, low-dependency care; $544 for over-all level-3 care; $242 for level-2, high-dependency care; $170 for level-2, low-dependency care; and $201 for over-all level-2 care. Each level of care generated additional costs of $42 per occupied bed-day. Taking these additional costs into account, the over-all occupied bed-day cost of level-3 and level-2 neonatal care was $339. The major components of this over-all cost were: nursing staff members, 50%; medical staff members, 11%; consumable and recyclable items, 12%; and diagnostic services, 8%.


The papain-like protease of avian infectious bronchitis virus has deubiquitinating activity.
Coronavirus papain-like proteases (PLPs) can act as proteases that process virus-encoded large replicase polyproteins and also as deubiquitinating (DUB) enzymes. Like the PLPs of other coronaviruses (CoVs), the avian infectious bronchitis virus (IBV) PLP catalyzes proteolysis of Gly-Gly dipeptide bonds to release mature cleavage products. However, the other functions of the IBV PLP are not well understood. In this study, we found that IBV exhibits strong global DUB activity with significant reductions of the levels of ubiquitin (Ub)-, K48-, and K63-conjugated proteins. The DUB activity exhibited a clear time dependence, with stronger DUB activity in the early stage of viral infection. Furthermore, the IBV replicase-encoded PLP, including the downstream transmembrane (TM) domain, is a DUB enzyme and dramatically reduced the level of Ub-conjugated proteins, while processing both K48- and K63-linked polyubiquitin chains. By contrast, PLP did not cause any reduction of haemagglutinin (HA)-Ub-conjugated proteins. In addition, mutations of the catalytic residues of PLP-TM, Cys1274Ser and His1437Lys, reduced DUB activity against Ub-, K48- and K63- conjugated proteins, indicating that the DUB activity of the PLP-TM wild-type protein is not completely dependent on its catalytic activity. Overall, these results demonstrate that the IBV-encoded PLP-TM functions as a DUB enzyme and suggest that IBV may interfere with the activation of host antiviral signaling pathway by degrading polyubiquitin-associated proteins.


Stable-isotope dilution gas chromatography-mass spectrometric measurement of 3-hydroxyglutaric acid, glutaric acid and related metabolites in body fluids of patients with glutaric aciduria type 1 found in newborn screening.
We developed a simple and sensitive stable-isotope dilution method for the quantification of 3-hydroxyglutaric acid (3HGA) and glutaric acid (GA) in body fluids. In our method, tert-butyldimethylsilyl (tBDMS) derivatives of 3HGA and GA were measured with a conventional electron-impact ionization (EI) mode in gas chromatography-mass spectrometry (GC-MS). The control values for 3HGA in nmol/ml were 0.15+/-0.08 (serum; n=10) and 0.07+/-0.03 (CSF; n=10). In addition, glutarylcarnitine and free carnitine were quantified by electrospray tandem mass spectrometry. Using these methods, we monitored 3HGA, GA, and glutarylcarnitine in the body fluids of three patients with glutaric aciduria type 1 found during newborn screening. None of the patients had experienced neurological strokes, which are possibly caused by the accumulation of 3HGA, at 15-24 months of age under a disease-specific treatment, including carnitine supplementation. Our data showed that 3HGA levels were relatively high in some serum samples with lower glutarylcarnitine and carnitine levels, suggesting that carnitine supplementation may play a role in preventing the accumulation of 3HGA in patients with this disease.


EEG effects of a single low dose of ethanol on afternoon sleep in the nonalcohol-dependent adult.
Three polygraphic recordings (PGR) of afternoon sleep (ANS) related to the duration of one sleep cycle, i.e., 90 min, were performed in 14 healthy adult volunteers (7 men and 7 women): two reference PGR, on two consecutive days (before ingestion of alcohol). Only the second being retained: reference PGR = P1; another recording, on day 3, 50 min after the start of single slow oral ingestion of the equivalent of 0.25 g 95% ethyl alcohol (ETOH) per kg body weight. Alcohol was ingested as 40 degrees whiskey, and the volume administered ranged from 34.5 to 66 ml (ETOH polygraphic recording = P2). Analysis of polygraphic traces was carried out according to the criteria of Rechtschaffen and Kales, and results were presented using the parameters adopted by Gross et al. (2). A single low dose of alcohol, leading to a low mean blood alcohol level (below 30 mg/100 ml, range 9 to 29 mg/100 ml), clearly perturbs sleep in the normal nonalcohol-dependent adult. In this context, ETOH does not appear to be a hypnotic since: a) the latencies to onset of sleep and the appearance of stages II, III, and IV of slow-wave sleep (SWS) are not shortened; b) the total duration of sleep, the percentage of delta sleep, and the duration (and percentage) of rapid eye movement sleep (REMS) are decreased; c) the number, duration, and percentages of intrasleep awakenings are increased, as are the number of stage changes. In addition, the study of afternoon sleep has shown itself to be a sensitive and reliable test for the analysis of the effects of a low dose of alcohol on nonalcohol-dependent subjects.


Cryo-electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B.
The canonical nucleosome, which represents the major packaging unit of eukaryotic chromatin, has an octameric core composed of two histone H2A-H2B and H3-H4 dimers with ∼147 base pairs (bp) of DNA wrapped around it. Non-nucleosomal particles with alternative histone stoichiometries and DNA wrapping configurations have been found, and they could profoundly influence genome architecture and function. Using cryo-electron microscopy, we solved the structure of the H3-H4 octasome, a nucleosome-like particle with a di-tetrameric core consisting exclusively of the H3 and H4 histones. The core is wrapped by ∼120 bp of DNA in 1.5 negative superhelical turns, forming two stacked disks that are connected by a H4-H4' four-helix bundle. Three conformations corresponding to alternative interdisk angles were observed, indicating the flexibility of the H3-H4 octasome structure. In vivo crosslinking experiments detected histone-histone interactions consistent with the H3-H4 octasome model, suggesting that H3-H4 octasomes or related structural features exist in cells.


Impact of the COVID-19 pandemic on suicide rates in Japan through December 2021: An interrupted time series analysis.
The COVID-19 pandemic is negatively impacting mental health globally. While increased social cohesion may have initially decreased suicide risk, there are few reports on the long-term impact. We examined the impact of the pandemic on suicide by gender and age through December 2021 in Japan. We analyzed trends in monthly suicide rates by age and gender from January 2016 to December 2021 using provisional mortality data in an interrupted time series analysis. We also considered linear trends in the pre-pandemic period and seasonal variations. Pandemic onset was defined as from April 2020. Estimated excess deaths by suicide that occurred during the pandemic were calculated. Excess number of suicide deaths during the pandemic period was estimated to be 1208 for men and 1825 for women. While there was no statistically significant increase in suicide rates overall for both men and women during the pandemic compared to the pre-pandemic, age-specific analyses showed a statistically significant increase in men 20-29 and 40-49 years, and in women of all age groups, except those under 20, 40-49 and over 80 years. The COVID-19 pandemic has had a negative impact on suicide rates in Japan and the impact is most pronounced in women and younger age groups. Subgroup analyses are needed, with a particular focus on those considered to be vulnerable and at increased suicide risk. A Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Award Number 21K10462).


Developmental Reorganization of the Core and Extended Face Networks Revealed by Global Functional Connectivity.
Prior studies on development of functional specialization in human brain mainly focus on age-related increases in regional activation and connectivity among regions. However, a few recent studies on the face network demonstrate age-related decrease in face-specialized activation in the extended face network (EFN), in addition to increase in activation in the core face network (CFN). Here we used a voxel-based global brain connectivity approach to investigate whether development of the face network exhibited both increase and decrease in network connectivity. We found the voxel-wise resting-state functional connectivity (FC) within the CFN increased with age in bilateral posterior superior temporal sulcus, suggesting the integration of the CFN during development. Interestingly, the FC of the voxels in the EFN to the right fusiform face area and occipital face area decreased with age, suggesting that the CFN segregated from the EFN during development. Moreover, the age-related connectivity in the CFN was related to behavioral performance in face processing. Overall, our study demonstrated developmental reorganization of the face network achieved by both integration within the CFN and segregation of the CFN from the EFN, which may account for the simultaneous increases and decreases in neural activation during the development of the face network.


In the face of disaster: personal reflections.
The setting was South Central Georgia after the floods of July 1994, when the Red Cross called for medical volunteers to help. This article recounts one nurse's first experience in disaster relief.


Patchy basement membrane of rat Leydig cells shown by ultrastructural immunolabeling.
Rat testes were examined by conventional and immunolabeling transmission electron microscopy. Ultrastructurally identifiable continuous basement membranes were found around seminiferous tubules and the interstitial capillaries. Patches of basement membrane were, additionally, found on free surfaces of Leydig cells, between two Leydig cells, and in macrophage-Leydig cell contact sites. The ultrastructural findings were confirmed by immunocytochemical localization of laminin and collagen type IV in the same areas. A close association between the capillary basement membranes and the surfaces of perivascular Leydig cells was also observed. The possible basement membrane-mediated interactions of Leydig cells with other testicular structures, together with the novel bioactive products and regulators of Leydig cells, support the role of these cells as exceptionally complex regulatory centers of testicular functions.


Design, synthesis, and cytotoxicity evaluation of novel indole-acylhydrazone derivatives of 4-pyridinone as potential histone deacetylase-2 inhibitors.
Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors. Seven indole-acylhydrazone-pyridinone derivatives were synthesized via simple, straightforward chemical procedures. The molecular docking studies were accomplished on HDAC2 compared to panobinostat. The cytotoxicity of all derivatives was studied on MCF-7 and MDA-MB-231 breast cancer cell lines by MTT assay. Molecular docking studies supported excellent fitting to the HADC2 active site with binding energies in the range of -10 Kcal/mol for all derivatives. All compounds were tested for their cytotoxicity against MCF-7 and MDA-MB-231 cell lines; derivatives A, B, F, and G were the best candidates. The half-maximal inhibitory concentration (IC50) values on MCF-7 were below 25 mg/mL and much lower than those obtained on the MDA-MB-231 cell line. The derivatives showed selectivity toward the MCF-7 cell line, probably due to the higher HDAC expression in the MCF-7 cell line. In this regard, debenzylated derivatives F and G showed slightly better cytotoxicity, which should be more studied in the future. Derivatives A, B, F, and G were promising for future enzymatic studies.


The effect of excited state population in photosystem II on the photoinhibition-induced changes in chlorophyll fluorescence parameters
The photoinhibition-induced changes in Photosystem II fluorescence parameters of spinach thylakoids were only slightly sensitive to the excited state population in Photosystem II antenna, as modulated by either quinone quenching or energy spillover. The possibility that this may be due to a small fraction of chlorophyll molecules which are poorly coupled to the antenna is discussed.


In vitro generation of T lymphocytes from embryonic stem cells.
Mature hematopoietic cells, like all other terminally differentiated lineages, arise during ontogeny via a series of increasingly restricted intermediates. Hematopoietic progenitors have their origin in the mesoderm, which gives rise to hemangioblasts that can differentiate into endothelial or endocardial precursors or hematopoietic stem cells. These hematopoietic stem cells in turn may either self-renew or differentiate into lineage-restricted progenitors and ultimately mature effector cells. The ability to generate most hematopoietic lineages in a two-dimensional environment in vitro has facilitated our study of this complex process. Until recently, the T-lymphocyte lineage was the exception and appeared to require the specialized three-dimensional microenvironment of the thymus to develop. However, here we describe a protocol for the generation of T lymphocytes from embryonic stem cells in vitro, within a two-dimensional microenvironment, provided by OP9 bone marrow stromal cells. This procedure will facilitate further study of early T lymphopoiesis by providing a simple model system in which the effects of genetic and environmental manipulations of embryonic stem cell-derived progenitors can be examined without requiring other more complex in vivo or in vitro experimental approaches.


Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR.
Recent developments in sequencing techniques have enabled rapid and high-throughput generation of sequence data, democratizing the ability to compile information on large amounts of genetic variations in individual laboratories. However, there is a growing gap between the generation of raw sequencing data and the extraction of meaningful biological information. Here, we describe a protocol to use the ANNOVAR (ANNOtate VARiation) software to facilitate fast and easy variant annotations, including gene-based, region-based and filter-based annotations on a variant call format (VCF) file generated from human genomes. We further describe a protocol for gene-based annotation of a newly sequenced nonhuman species. Finally, we describe how to use a user-friendly and easily accessible web server called wANNOVAR to prioritize candidate genes for a Mendelian disease. The variant annotation protocols take 5-30 min of computer time, depending on the size of the variant file, and 5-10 min of hands-on time. In summary, through the command-line tool and the web server, these protocols provide a convenient means to analyze genetic variants generated in humans and other species.


Staphylococcal protein A-modified hydrogel facilitates in situ immunomodulation by capturing anti-HMGB1 for islet grafts.
Islet transplantation is regarded as the most promising therapy for type 1 diabetes. However, both hypoxia and immune attack impair the grafted islets after transplantation, eventually failing the islet graft. Although many studies showed that biomaterials with nanoscale pores, like hydrogels, could protect islets from immune cells, the pores on biomaterials inhibited vascular endothelial cells (VECs) to creep in, which resulted in poor revascularization. Thus, a hydrogel device that can facilitate in situ immune modulations without the cost of poor revascularization should be put forward. Accordingly, we designed a spA-modified hydrogel capturing anti-HMGB1 mAB (mAB-spA Gel): the Staphylococcus aureus protein A (spA) was conjugated on the network of hydrogel to capture anti-HMGB1mAB which can inactivate immune cells, while the pore sizes of the hydrogel were more than 100μm which allows vascular endothelial cells (VECs) to creep in. In this study, we screened the optimal spA concentration in mAB-spA Gel according to the physical properties and antibody binding capability, then demonstrated that it could facilitate in situ immunomodulation without decreasing the vessel reconstruction in vitro. Further, we transplanted islet graft in vivo and showed that the survival of islets was elongated. In conclusion, mAB-spA Gel provided an alternative islet encapsulation strategy for type 1 diabetes. STATEMENT OF SIGNIFICANCE: Although various studies have shown that the backbone of the hydrogels can isolate islets grafts from immune cells and the survival of the islets can be prolonged by this way, it is also reported that when the pore size of the backbone is too small the revascularization will be adversely affected. According to this point, it is hard to adjust hydrogel's pore size to protect the islets from the immune attack while allowing endothelial vascular cells to creep in. To solve this dilemma, we designed an immunomodulatory hydrogel inhibiting the activation of T cells by immunosuppressive IgGs instead of the backbone network, so the hydrogel can prolong the survival of islets without the sacrifice of revascularization.


Investigation of postmortem functional changes in human cerebral arteries.
This study demonstrated the time-dependent changes in postmortem responses of isolated human middle cerebral artery strips to vasodilators. The relaxation induced by prostaglandin (PG) I2 or nitroglycerin remained stable for 24 h postmortem. In arterial strips precontracted with PGF2 alpha, substance P and bradykinin both elicited relaxation that was almost completely abolished by removal of the endothelium. The endothelium-dependent response to both peptides was significantly degraded in strips obtained > 12 h postmortem. These results indicate a selective functional or anatomical vulnerability of the vascular endothelium compared with that of the vasodilator mechanisms of the smooth muscle in the postmortem period. However, cerebral arteries isolated from human cadavers within 12 h postmortem should be adequate for studies of both smooth muscle and endothelial reactivity to vasodilators.


The predictive value of procalcitonin for early detection of infection in elderly type 2 diabetes mellitus.
Aimed to investigate the predictive value of procalcitonin (PCT) in early detection of infections in elderly patients with type 2 diabetes, and to discover the optimum cut-off points of PCT. A retrospective study was conducted with type 2 diabetic patients (≥65 years) with lung infection (LI), urinary tract infection (UTI) or skin and soft tissue infection (SSTI). The receiver operating characteristic (ROC) curves of the 3 markers (PCT, WBC count, and CRP) were constructed and compared to assess their accuracies in diagnosing. Among the three different groups with LI, UTI or SSTI, the area under the ROC curve (AUC) of PCT was 0.98 (95% confidence interval (CI): 0.96-0.99, p < 0.05) for the LI group, 0.98 (95% CI: 0.96-0.99, p < 0.05) for the UTI group, and 0.97 (95% CI: 0.94-1.00, p < 0.05) for the SSTI group. The optimum cut-off point of PCT level was 0.73 ng/mL (Sn 89.7%, Sp 97.7%) for the LI group, 1.48 ng/mL (Sn 88.9%, Sp 100%) for the UTI group, and 0.73 ng/mL (Sn 85.7%, Sp 97.7%) for the SSTI group. PCT demonstrated the strongest correlation with each of the infection types, indicating significant diagnostic value. Optimum cut-off points of PCT levels in elderly diabetes were higher.


Application of quantum dots in clinical and alimentary fields using multicommutated flow injection analysis.
In recent years, the number of scientific papers regarding the use of quantum dots (QDs) has increased almost exponentially, especially emphasizing their use for new applications and describing new approaches. One of the future trends in the development of new methods of analysis is the use of automated methodologies. Among them, Multicommutated Flow Injection Analysis has been here selected in order to show its potentiality in pharmaceutical and food analysis. Using water-soluble CdTe QDs modified by mercaptopropionic acid, a flow system was developed for the determination of ascorbic acid. The system was based on the quenching effect produced by ascorbic acid on the fluorescence of QDs. Under the optimized conditions, the relationship between the fluorescence intensity of the QDs and ascorbic acid concentration was linear in the range of 12-250 μg mL(-1), obtaining a sample throughput of 68 determinations per hour. The proposed method was applied to the determination of ascorbic acid in pharmaceutical formulations, goji capsules and fruit juices. The results obtained were in good agreement with those showed by a reference method, so indicating the utility of the proposed method in the clinical and alimentary fields.


Evaluating the cost-effectiveness of low-level HBV DNA screening in occult hepatitis B infection donors: A study from Shandong Blood Center, China.
This study aimed to assess the efficacy of individual-donation nucleic acid testing (ID-NAT) in detecting occult hepatitis B virus infection (OBI) among anti-HBc positive blood donors, compared to minipool nucleic acid testing (MP-NAT). The present study analyzed data from the Shandong Blood Center in China during the period from January 2018 to June 2022, where HBsAg-negative blood donors were screened using the 6-sample minipool nucleic acid testing (6-sample MP NAT) method. NAT-positive samples underwent subsequent anti-HBc and anti-HBs testing. Approximately 5000 samples that passed the nucleic acid mixing test were randomly selected for anti-HBc testing, and over 100 anti-HBc positive samples underwent individual donor nucleic acid testing (ID-NAT). Any HBV DNA positive samples detected by ID-NAT were subsequently confirmed using alternative nucleic acid testing methods. Among 220,445 HBsAg-negative blood donors, the positivity rate of HBV DNA detection using the 6-sample minipool nucleic acid testing (MP NAT) method was found to be 0.031% (69/220,445). Of the 67 HBV DNA positive samples, 55 (82.09%) and 25 (37.31%) were found to be positive for anti-HBc and anti-HBs, respectively, using the supplementary chemiluminescent microparticle immunoassay (CMIA). Among the 4797 HBsAg-negative/MP NAT-negative samples, 909 (18.95%) tested positive for anti-HBc. Further NAT testing was performed on 164 arbitrarily selected anti-HBc-positive/MP HBV DNA-negative samples, revealing a HBV DNA positivity rate of 1.22% (2/164). Using individual donation nucleic acid testing can significantly increase the detection rate of occult hepatitis B virus infection in anti-HBc-positive blood donors, resulting in a detection rate of 0.22% (1.22 × 0.1895). This rate is 8.10 times higher than the detection rate achieved by mixed testing methods (0.031%) [calculated as (0.22 + 0.031)/0.031]. Therefore, it is recommended to perform single HBV DNA testing on anti-HBc-positive blood donors, discard plasma with weakly positive or negative anti-HBs but positive anti-HBc, or avoid transfusing anti-HBc-positive plasma to recipients with weakly positive or negative anti-HBs to prevent HBV infection.


Excess iodinuria in infants and its relation to the iodine in maternal milk.
Iodine is an essential micro nutrient, and a deficiency or excessive intake of this mineral is related to changes in thyroid function. In Brazil, both deficiency and excessive intake of iodine are common; however, excessive intakes have recently been observed. Thus, the objective of the present study was to assess the iodine concentration in maternal milk, taking into account the salt iodine concentration of the participating households and in the infants' urine. Urine samples from 33 infants (less than 6 months of age), maternal milk samples and samples of the kitchen salt used by the mothers were collected. The iodine levels in the urine and maternal milk were assessed by ICP-MS; the iodine levels in the salt were assessed by titration. The median iodinuria value in the infants was 293 μg/L; the mean iodine concentration was 206 μg/L in the maternal milk and 39.9 mg I/kg in the salt. There was a positive correlation between the iodine concentration in the maternal milk and the infant iodinuria value. The median infant iodinuria was elevated due to the high iodine concentration present in the maternal milk. High iodine values were caused by high salt iodine levels, which should be reduced.


Autoimmune-Like Hepatitis: A "Hepatitic" Manifestation of Chronic Graft Versus Host Disease in Post-Stem Cell Transplant.
A 59-year-old female received a matched related donor stem cell transplant for chronic myelogenous leukemia. After being successfully treated with prednisone for chronic graft versus host disease that initially started 50 days posttransplant, she developed hepatic dysfunction during the steroid taper on day 531, as evidenced by jaundice, elevated liver enzymes, and increased bilirubin. Liver biopsy showed histology suggestive of autoimmune-like hepatitis, which is a rare manifestation of chronic "hepatitic" graft versus host disease.