Interferon-tau suppresses prostaglandin F2alpha secretion independently of the mitogen-activated protein kinase and nuclear factor kappa B pathways.
Pregnancy is established in ruminants through inhibitory actions of interferon (IFN)-tau on the release of prostaglandin F2alpha (PGF), which allows the corpus luteum to survive and continue to produce progesterone. Experiments were designed to 1) delineate the signal transduction pathway coordinating the synthesis of PGF, 2) determine how rapidly recombinant bovine (rb) IFN-tau attenuated phorbol ester (PDBu)-induced secretion of PGF, and 3) establish the site at which rbIFN-tau attenuates the secretion of PGF in cultured bovine endometrial (BEND) cells. BEND cells were untreated (control) or treated for 5, 10, 60, 180, or 300 min with PDBu (100 ng/ml), rbIFN-tau (50 or 500 ng/ml), PDBu + rbIFN-tau, or PDBu + PD98059 (MEK-1 inhibitor; 50 microM). Secretion of PGF was induced (P < 0.0001) by PDBu within 180 min, but induction was inhibited 74% by the addition of rbIFN-tau (P < 0.0001) and was ablated completely by PD98059. Parallel results were obtained for cyclooxygenase (COX)-2 protein expression. PDBu induced (P < 0.05) activation of the Raf-1/MEK-1/ERK-1/2 pathway, which was obligatory for the expression of COX-2 and secretion of PGF but was not altered by cotreatment with rbIFN-tau. PDBu induced (P < 0.05) transcription of c-jun and c-fos mRNAs within 30 min; induction was inhibited (P < 0.05) by cotreatment with PD98059 but not by cotreatment with rbIFN-tau. Treatment of BEND cells with rbIFN-tau also did not attenuate PDBu-induced degradation of IkappaBalpha, suggesting that the IkappaBalpha/NFkappaB pathway is not a site of IFN-tau inhibition of PGF. However, rbIFN-tau did block transcription of the COX-2 gene induced by PDBu within 30 min. In conclusion, COX-2 expression and PGF secretion induced by PDBu is mediated through the Raf-1/MEK-1/ERK-1/2 pathway, but this pathway is not disrupted by rbIFN-tau. Because rbIFN-tau inhibits COX-2 mRNA within 30 min, we hypothesized that transcription factors activated by rbIFN-tau rapidly and directly attenuate COX-2 gene expression, thereby suppressing secretion of PGF.


CXCL17 Is a Specific Diagnostic Biomarker for Severe Pandemic Influenza A(H1N1) That Predicts Poor Clinical Outcome.
The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.


Intraoperative tissue classification methods in orthopedic and neurological surgeries: A systematic review.
Accurate tissue differentiation during orthopedic and neurological surgeries is critical, given that such surgeries involve operations on or in the vicinity of vital neurovascular structures and erroneous surgical maneuvers can lead to surgical complications. By now, the number of emerging technologies tackling the problem of intraoperative tissue classification methods is increasing. Therefore, this systematic review paper intends to give a general overview of existing technologies. The review was done based on the PRISMA principle and two databases: PubMed and IEEE Xplore. The screening process resulted in 60 full-text papers. The general characteristics of the methodology from extracted papers included data processing pipeline, machine learning methods if applicable, types of tissues that can be identified with them, phantom used to conduct the experiment, and evaluation results. This paper can be useful in identifying the problems in the current status of the state-of-the-art intraoperative tissue classification methods and designing new enhanced techniques.


Expression of the co-stimulatory molecule BB-1, the ligands CTLA-4 and CD28 and their mRNAs in chronic inflammatory demyelinating polyneuropathy.
To examine whether the Schwann cells in patients with autoimmune neuropathies have the potential to behave as professional antigen-presenting cells, we investigated the expression of the co-stimulatory molecules BB-1, B7-1 (CD80) B7-2 (CD86) and their counter-receptors CD28 or CTLA-4 (CD152) at the protein and mRNA levels in sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP associated with human immunodeficiency virus infection (HIV-CIDP), IgM paraproteinaemic neuropathy and normal or non-immune axonal neuropathy. In single- and double-labelling experiments, we used the S-100 antigen as a pan-Schwann cell marker, myelin-associated glycoprotein as a marker for myelinating Schwann cells and the fibrillary acidic protein as a marker for unmyelinating Schwann cells. The expression of the B7 family of molecules was limited to BB-1 and was observed only on the Schwann cells. There was constitutive expression of BB-1 on unmyelinating Schwann cells in all nerves studied. However, in CIDP and HIV-CIDP, but not the other diseases, there was prominent upregulation of BB-1 on the myelinating Schwann cells. The endoneurial T cells in the proximity of BB-1-positive Schwann cells expressed the CD28 or CTLA-4 counter-receptors. Reverse transcription-polymerase chain reaction confirmed that these ligands were upregulated only in CIDP. Because the myelinating BB-1-positive Schwann cells expressed HLA-DR antigen, the findings indicate that, in CIDP, Schwann cells possess the necessary markers to function as antigen-presenting cells.


Using of WHO guidelines for the management of severe malnutrition to cases of marasmus and kwashiorkor in a Colombia children's hospital.
In 2007, the Hospital Infantil Los Ángeles (HILA) in Colombia implemented a slightly-modified version of the WHO guidelines for the diagnosis and management of malnutrition during childhood. To evaluate the efficacy of the WHO-HILA protocol in children hospitalized with severe, chronic marasmus and kwashiorkor malnutrition (MS-KWK) in 2007 and 2008. In this descriptive retrospective study the records of 100 children hospitalized with MSKWK were initially evaluated. Of these, 30 fulfilled the inclusion criteria: children of both sexes with a primary diagnosis of MS-KWK. Patients with any chronic disease liable to cause malnutrition were excluded. Anthropometric parameters, clinical signs and biochemical indicators of malnutrition were assessed upon admission and again at discharge following application of the WHO guidelines. Univariate analysis was performed for each study variable; serum hemoglobin and albumin levels on admission and at discharge were compared, and data were subjected to bivariate analysis. Marasmus was diagnosed in 23.3% of children, kwashiorkor in 73.3% and marasmic kwashiorkor in 3.3%. The major clinical findings were: edema (70%), emaciation (40%), "flag sign" hair (42.86%), low serum albumin (93%) and anemia (80%). Thirteen children following the WHO-HILA protocol showed a significant nutritional status improvement (p<0.05), whereas no improvement was noted in the 17 children not treated according to the protocol. Application of the WHO-HILA protocol was associated with reduced morbimortality in children with marasmus-kwashiorkor malnutrition. Implementation of this protocol should therefore be considered in all children´s hospitals in countries where this disease is prevalent.


Myocardial biochemical, contractile, and electrical performance after imposition of hypertension in young and old rats.
The effects of renovascular hypertension on the biochemical, contractile, and electrical performance of myocardial tissue from rats of various ages has been examined. Male Fischer rats, 2, 7, 12, and 17 months old, were made hypertensive by constriction of the left renal artery. Ten weeks after the onset of hypertension, left ventricular papillary muscles were isolated from those four groups when 5, 10, 15, and 20 months old, respectively. Mechanical performance and transmembrane electrical events were recorded simultaneously. Contractile protein enzyme activity was determined in the same hearts from which papillary muscles were used for acquisition of mechanical and electrical information. There was a slight increase in blood pressure in control groups as a function of age while blood pressure maintained a range of approximately 179-188 mm Hg for all hypertensive groups. Heart weight of control animals increased significantly from 5 months to 20 months of age from 539 +/- 26 to 1088 +/- 56 mg, representing an increase of 101%. In hypertensive animals, heart weight increased 50% in 5-month-, 15% in 10-month-, 50% in 15-month-, and 11.7% in 20-month-old animals. Although control groups revealed alterations in mechanical, electrical, and biochemical parameters that increased as a function of age, the magnitude of the biochemical, contractile, and electrical response to hypertension varied monotonically with the extent of myocardial hypertrophy, rather than age per se. Adaptation to the stress of hypertension was observed in each age group, and was revealed as prolongation of mechanical and electrical timing parameters, depression of the load-velocity relation, and contractile protein enzyme activity. Thus, the stress of hypertension, which was tolerated by the 10- and 20-month-old animals with lesser relative hypertrophy and lesser changes in measured parameters, may represent a differential adaptation to the stress of hypertension.


Race and Ethnic Disparities in Stroke Incidence in the Northern Manhattan Study.
Background and Purpose- An excess incidence of strokes among blacks versus whites has been shown, but data on disparities related to Hispanic ethnicity remain limited. This study examines race/ethnic differences in stroke incidence in the multiethnic, largely Caribbean Hispanic, NOMAS (Northern Manhattan Study), and whether disparities vary by age. Methods- The study population included participants in the prospective population-based NOMAS, followed for a mean of 14±7 years. Multivariable-adjusted Cox proportional hazards models were constructed to estimate the association between race/ethnicity and incident stroke of any subtype and ischemic stroke, stratified by age. Results- Among 3298 participants (mean baseline age 69±10 years, 37% men, 24% black, 21% white, 52% Hispanic), 460 incident strokes accrued (400 ischemic, 43 intracerebral hemorrhage, 9 subarachnoid hemorrhage). The most common ischemic subtype was cardioembolic, followed by lacunar infarcts, then cryptogenic. The greatest incidence rate was observed in blacks (13/1000 person-years), followed by Hispanics (10/1000 person-years), and lowest in whites (9/1000 person-years), and this order was observed for crude incidence rates until age 75. By age 85, the greatest incidence rate was in Hispanics. Blacks had an increased risk of stroke versus whites overall in multivariable models that included sociodemographics (hazard ratio, 1.51 [95% CI, 1.13-2.02]), and stratified analyses showed that this disparity was driven by women of age ≥70. The increased rate of stroke among Hispanics (age/sex-adjusted hazard ratio, 1.48 [95% CI, 1.13-1.93]) was largely explained by education and insurance status (a proxy for socieoeconomic status; hazard ratio after further adjusting for these variables, 1.17 [95% CI, 0.85-1.62]) but remained significant for women age ≥70. Conclusions- This study provides novel data regarding the increased stroke risk among Caribbean Hispanics in this elderly population. Results highlight the need to create culturally tailored campaigns to reach black and Hispanic populations to reduce race/ethnic stroke disparities and support the important role of low socioeconomic status in driving an elevated risk among Caribbean Hispanics.


[The use of vitaprost in the treatment of patients with prostate diseases].
Inflammatory diseases of the prostate are common among men. These diseases are frequently characterized by long-term course and relapses. Prostatitis-associated symptoms significantly reduce the quality of life of patients. Due to the lack of generally accepted criteria for the diagnosis of prostatitis, the frequency of inflammatory diseases of the prostate is difficult to establish. Inflammatory diseases of the prostate should be differentiated from chronic pelvic pain syndrome. The mainstay of treatment of infectious and inflammatory processes in the prostate are antibacterial drugs (generations III and IV fluoroquinolones). The recommended course of treatment includes 4-6 weeks. Prostate peptides from bovine (cytomedines) have proven efficacy in the treatment of patients with prostatitis; cytomedines influence the differentiation and proliferation of prostate cells, have anti-inflammatory and immunomodulatory properties. In clinical trials, high efficiency of cytomedines in prostatitis and prostate adenoma, as well as long-term remission of the diseases is demonstrated.


The law of relocation of children.
The trend in the law of relocation of children following divorce or determination of paternity is to decide cases based on their own facts rather by strong presumptions for or against relocation. Another common approach is to divide the burden between parents. Statutes of many states require the custodial parent to give notice, between 30 and 90 days, of the intent to relocate with the child. Courts consider a variety of factors in relocation cases but differ on the degree to which a benefit to the custodial parent will be presumed to be a benefit to the child. Three national organizations have developed standards for deciding disputes regarding the relocation of children, but none of the standards have been widely adopted. When courts focus on the facts of each case and make careful finding of fact, the best interests of the child are served.


Sources and fate of microplastics in marine and beach sediments of the Southern Baltic Sea-a preliminary study.
Microplastics' (particles size ≤5 mm) sources and fate in marine bottom and beach sediments of the brackish are strongly polluted Baltic Sea have been investigated. Microplastics were extracted using sodium chloride (1.2 g cm-3). Their qualitative identification was conducted using micro-Fourier-transform infrared spectroscopy (μFT-IR). Concentration of microplastics varied from 25 particles kg-1 d.w. at the open sea beach to 53 particles kg-1 d.w. at beaches of strongly urbanized bay. In bottom sediments, microplastics concentration was visibly lower compared to beach sediments (0-27 particles kg-1 d.w.) and decreased from the shore to the open, deep-sea regions. The most frequent microplastics dimensions ranged from 0.1 to 2.0 mm, and transparent fibers were predominant. Polyester, which is a popular fabrics component, was the most common type of microplastic in both marine bottom (50%) and beach sediments (27%). Additionally, poly(vinyl acetate) used in shipbuilding as well as poly(ethylene-propylene) used for packaging were numerous in marine bottom (25% of all polymers) and beach sediments (18% of all polymers). Polymer density seems to be an important factor influencing microplastics circulation. Low density plastic debris probably recirculates between beach sediments and seawater in a greater extent than higher density debris. Therefore, their deposition is potentially limited and physical degradation is favored. Consequently, low density microplastics concentration may be underestimated using current methods due to too small size of the debris. This influences also the findings of qualitative research of microplastics which provide the basis for conclusions about the sources of microplastics in the marine environment.


Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease.
Depression is associated with more severe cognitive deficits in many neurological disorders, though the investigation of this relationship in Huntington disease (HD) has been limited. This study examined the relationship between depressive symptom severity and measures of executive functioning, learning/memory, and attention in prodromal HD. Participants (814 prodromal HD, 230 gene-negative) completed a neuropsychological test battery and the Beck Depression Inventory-II (BDI-II). Based on the BDI-II, there were 637 participants with minimal depression, 89 with mild depression, 61 with moderate depression, and 27 with severe depression in the prodromal HD group. ANCOVA (controlling for age, sex, and education) revealed that performance on SDMT, Trails B, Hopkins Verbal Learning Test--Revised (HVLT-R) Immediate Recall, and Stroop interference was significantly different between the BDI-II severity groups, with the moderate and severe groups performing worse than the minimal and mild groups. There were no significant differences between the BDI-II severity groups for Trails A or HVLT-R Delayed Recall. Linear regression revealed that both gene status and depression severity were significant predictors of performance on all cognitive tests examined, with contributions of BDI-II and gene status comparable for Trails A, SDMT, and Stroop interference. Gene status had a higher contribution for HVLT-R Immediate and Delayed Recall and Trails B. Our results suggest that depressive symptom severity is related to poorer cognitive performance in individuals with prodromal HD. Though there are currently no approved therapies for cognitive impairment in HD, our findings suggest that depression may be a treatable contributor to cognitive impairment in this population.


Antimicrobial efficacy of Acacia nilotica, Murraya koenigii (L.) Sprengel, Eucalyptus hybrid, Psidium guajava extracts and their combination on Streptococcus mutans and Lactobacillus acidophilus.
The aim of this in vitro study was to assess antimicrobial efficacy of Acacia nilotica, Murraya koenigii (L.) Sprengel, Eucalyptus hybrid, Psidium guajava extracts, and their combination on Streptococcus mutans and Lactobacillus acidophilus. The branches of four plants were collected, identified, and authenticated by a taxonomist. The plants were rinsed in water, healthy leaves were separated and shade dried over a period of 3-4 weeks. Soxhlet apparatus using ethanol was employed for extraction procedure. The combinations of plant extracts were prepared by mixing equal quantities of 10% solutions of each of these extracts. 0.2% chlorhexidine and dimethyl sulfoxide were used as positive and negative controls, respectively. The antimicrobial efficacy testing was done using agar well-diffusion method under anaerobic conditions. The mean diameter of inhibition zone was computed and compared between different categories using one-way analysis of variance and Tukey's post-hoc test. A qualitative assay was carried out to identify the various phytochemical constituents in the plants. The data was assessed by SPSS version 20. The statistical significance was fixed at 0.05. All the plants extracts and their combinations inhibited S. mutans and L. acidophilus. However, the quadruple combination of A. nilotica + M. koenigii (L.) Sprengel + Eucalyptus hybrid + P. guajava produced the maximum inhibition zone (23.5 ± 2.2 mm) against S. mutans. Although, 0.2% chlorhexidine produced the highest inhibition zone against L. acidophilus (18.8 ± 1.2 mm), A. nilotica extract produced maximum inhibition among the various plant extracts and their combinations (14.1 ± 1.8 mm). All the individual plant extracts and their combinations were effective against S. mutans and L. acidophilus. These could be tried as herbal alternates to chlorhexidine. However, these in vitro results have to be further evaluated for any toxicity of the polyherbal combinations in animal models and effectiveness has to be assessed using in vivo studies on humans.


[Relationship between epidural analgesia and type of delivery].
To study the relationship which exists between the administration of an epidural analgesic during labor and an instrument-aided, either with forceps or a suction cup, childbirth in the Teresa Herrera Maternity-Infant Care Hospital in A Coruña for the clinical cases studied during 1999. 380 cases were selected by lot by going through clinical files; of these 190 had received epidural analgesia while the other 190 had not. Regarding isolated association between epidural analgesic usage and instrument-aided childbirth, we found that the risk of an instrument-aided childbirth is high (OR 2.7) when an epidural analgesic is administered. However, when we analyze our results weighing various factors which may cause confusion, we discover that if it is a woman's first birth, if the newborn's weight is greater than or equal to 3500 g and if an epidural analgesic is administered have an independent effect, in this order, on the presence of an instrument-aided childbirth. At the same time, this study showed a similar occurrence of cases of intra-labor fetal suffering for both groups (5.8% among childbirths in which epidural analgesia was administered and 5.3% among childbirths in which epidural analgesia was not administered); a statistically insignificant relationship (since is less than 0.05%). The increase of an instrument-aided childbirth when an epidural analgesic is administered is due more to factors related to the aforementioned analgesia (such as first child birth, fetal weight greater than or equal to 3500 g or a tendency to shorten labor without fetal suffering,...) than to the analgesic itself. The impact of this on the latest developments in childbirth could be affected by a change in obstetrics practices.


An influenza HA stalk reactive polymeric IgA antibody exhibits anti-viral function regulated by binary interaction between HA and the antibody.
IgA antibodies, which are secreted onto the mucosal surface as secretory IgA antibodies (SIgAs), play an important role in preventing influenza virus infection. A recent study reported that anti-hemagglutinin (HA) head-targeting antibodies increase anti-viral functions such as hemagglutination inhibition (HI) and virus neutralization (NT), in addition to HA binding activity (reactivity) via IgA polymerization. However, the functional properties of anti-viral IgA antibodies with mechanisms of action distinct from those of anti-HA head-targeting antibodies remain elusive. Here, we characterized the functional properties of IgG, monomeric IgA, and polymeric IgA anti-HA stalk-binding clones F11 and FI6, and B12 (a low affinity anti-HA stalk clone), as well as Fab-deficient (ΔFab) IgA antibodies. We found that IgA polymerization impacts the functional properties of anti-HA stalk antibodies. Unlike anti-HA head antibodies, the anti-viral functions of anti-HA stalk antibodies were not simply enhanced by IgA polymerization. The data suggest that two modes of binding (Fab paratope-mediated binding to the HA stalk, and IgA Fc glycan-mediated binding to the HA receptor binding site (RBS)) occur during interaction between anti-stalk HA IgA antibodies and HA. In situations where Fab paratope-mediated binding to the HA stalk exceeded IgA Fc glycan-mediated binding to HA RBS, IgA polymerization increased anti-viral functions. By contrast, when IgA Fc glycan-mediated binding to the HA RBS was dominant, anti-viral activity will fall upon IgA polymerization. In summary, the results suggest that coordination between these two independent binding modules determines whether IgA polymerization has a negative or positive effect on the anti-viral functions of anti-HA stalk IgA antibodies.


Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol.
Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT. DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0-2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0-2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment. The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal. NCT03969511.


Signal-to-Noise-Ratio-Aware Dynamic Range Compression in Hearing Aids.
Fast-acting dynamic range compression is a level-dependent amplification scheme which aims to restore audibility for hearing-impaired listeners. However, when being applied to noisy speech at positive signal-to-noise ratios (SNRs), the gain function typically changes rapidly over time as it is driven by the short-term fluctuations of the speech signal. This leads to an amplification of the noise components in the speech gaps, which reduces the output SNR and distorts the acoustic properties of the background noise. An adaptive compression scheme is proposed here which utilizes information about the SNR in different frequency channels to adaptively change the characteristics of the compressor. Specifically, fast-acting compression is applied to speech-dominated time-frequency (T-F) units where the SNR is high, while slow-acting compression is used to effectively linearize the processing for noise-dominated T-F units where the SNR is low. A systematic evaluation of this SNR-aware compression scheme showed that the effective compression of speech components embedded in noise was similar to that of a conventional fast-acting system, whereas natural fluctuations in the background noise were preserved in a similar way as when a slow-acting compressor was applied.


Is ebullition or diffusion more important as methane emission pathway in a shallow subsaline lake?
Methane (CH4) emissions via ebullition contribute significantly to greenhouse gas emissions from freshwater bodies. According to the literature, the ebullition pathway may even be the most important pathway in some cases, particularly in shallow lakes. Ebullition rates are not often estimated because of the high uncertainty associated with episodic releases, leading to difficulties in their determination. This study provides an estimate of such emissions in a large, shallow, subsaline lake in eastern Austria, Lake Neusiedl, and compares them to the diffusion pathway. Ebullition gas sampling was conducted every 5-10 days over a period of 107 days from late March to mid-July 2021, using ebullition traps placed in three distinct locations: Reed belt, Channel and Open water/Lake. The aim was to study the temporal and spatial heterogeneity of ebullition and its contribution to total emissions. At the same time, several water quality and other environmental parameters were measured and then tested against the CH4 ebullition rates to explore them as potential drivers for this pathway. The carbon isotope fractionation factor (αC) of the measured CH4 ebullition gas, ranging from 1.03 to 1.06, indicates a dominance of the acetoclastic methanogenesis in the sediments of Lake Neusiedl, regardless of the location. The Reed belt location showed the highest mean CH4 ebullition rate (17 ± 28 mg CH4 m-2 d-1), which is >340-fold higher than the mean of the other two locations, and demonstrated also a strong temperature dependency. In all locations at Lake Neusiedl, the median CH4 fluxes via diffusion are significantly higher than via ebullition. Our analyses do not confirm the dominance of the ebullition pathway in any of the studied locations. Whereas at the Reed belt, ebullition accounts for 48 % of the CH4 emissions, in the other two locations, is responsible only for about 1 %.


[Structure of chromatin from the pigeon brain. I. Composition, electrophoretic motility and circular dichroism spectra of nucleosome particles].
Composition and structural properties of pigeon brain hemisphere neuron chromatin have been studied. In these cells nucleosomal DNA repeat length is about 165 nucleotide pairs. The content of H1 and H2A histones was found to decrease by 18 and 30% respectively in comparison with the chromatin possessing the normal quantity of those histones. At the same time the content of protein uH2A (A-24), being the conjugate of H2A histone and ubiquitine, is increased. Mononucleosomes isolated from neuron chromatin was found to have relatively low electrophoretic mobility in polyacrylamide gel taking into account the size of their DNA fragment. Circular dichroism spectra of nucleosome particles show that the neuron mononucleosomes are more unfolded than the rat thymus ones. Data obtained allow to suggest that the short DNA repeat and accumulation of protein uH2A in neurons are the factors influencing the compactization of neuron chromatin.


Self-explanation in learning clinical reasoning: the added value of examples and prompts.
Recent studies suggest that self-explanation (SE) while diagnosing cases fosters the development of clinical reasoning in medical students; however, the conditions that optimise the impact of SE remain unknown. The example-based learning framework justifies an exploration of students' use of their own SEs combined with the study of examples. This study aimed to assess the impact on medical students' diagnostic performance of: (i) combining students' SEs with their listening to examples of residents' SEs, and (ii) the addition of prompts (specific questions) while working with examples. This study consisted of a training phase and an assessment phase conducted 1 week later. In the training phase, 54 Year 3 medical students were randomly assigned to one of three groups. In all groups, students first solved four clinical cases using SE. Subsequently, Group 1 listened to examples of residents' SEs with prompts; Group 2 listened to examples of residents' SEs without prompts, and the control group solved word puzzles. Then, all students again solved the same four cases. One week later, all students solved four similar and four different cases. Students' diagnostic performance and diagnostic accuracy scores were assessed for each case at each time-point. Although all groups' diagnostic accuracy scores on similar cases improved significantly between the training and the assessment phase, Group 1 showed a significantly higher diagnostic performance score after 1 week than the control group (p = 0.037). On different cases, Group 1 obtained significantly higher diagnostic accuracy (p = 0.011) and diagnostic performance (p < 0.001) scores than the control group and a significantly higher diagnostic performance score than Group 2 (p = 0.018). Self-explanation seems to be an effective technique to help medical students learn clinical reasoning. Its impact is increased significantly by combining it with examples of residents' SEs and prompts. Although students' exposure to examples of clinical reasoning is important, their 'active processing' of these examples appears to be critical to their learning from them.


IL-12, IFN-gamma, and TNF-alpha released from mononuclear cells inhibit the spread of varicella-zoster virus at an early stage of varicella.
The activity of mononuclear cells to inhibit plaque formation of varicella-zoster virus (VZV) was investigated by an in vitro infectious center assay. Peripheral blood mononuclear cells (PBMC) inhibited VZV plaque formation by co-cultivation with VZV-infected fibroblasts. As compared to mononuclear cells from normal individuals, mononuclear cells from umbilical cord blood and from patients receiving corticosteroids showed a significant decrease in the ability to inhibit viral replication. This ability was significantly increased for mononuclear cells collected during the acute phase of varicella. PBMC obtained from patients in the acute phase of varicella produced significantly higher amounts of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-12 in the supernatant compared with those of healthy individuals. These data suggest that the cytokines have an important role in the inhibition of the spread of VZV at an early stage of varicella. Th1 type adaptive immunity might play a major role in VZV infection.


Radiotherapy Combination: Insight from Tumor Immune Microenvironment (TIME).
The view of Radiotherapy (RT) as a simple inducer of DNA damage resulting in tumor cell death has dramatically changed in recent years, and it is now widely accepted that RT can trigger an immune response which provides a sound basis for combining RT with immunotherapy. Given that, radiation can be delivered with different regimens, its effect on immune responses and Tumor Immune Microenvironment (TIME) may vary with dose and fractionation schedule. This fractional dose dependency may need to be more considered because of recent developments in RT delivery techniques making it possible to deliver precisely higher dosages per fraction (hypofractionation) while reducing exposure to normal tissues. Although combining radiotherapy with immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy, the selection of the best-matched combination of immunotherapy with each radiotherapy scheme remains to be addressed. Thus, for designing better therapeutic combinations, it is necessary to understand the immunological effects of RT. Here, we review the impact of conventional and different hypofractionation radiation schedules on the TIME. Subsequently, we highlight how knowing about these interactions may have implications for choosing a rational combination with targeted therapies.


Ovarian epithelial cell lineage-specific gene expression using the promoter of a retrovirus-like element.
We have isolated 462 bp of sequence termed ovarian-specific promoter 1 (OSP-1) that is part of a retrovirus-like element specifically expressed in the rat ovary. We have evaluated the ability of OSP-1 to activate gene expression in normal and neoplastic cell lines derived from the ovaries of rats and women. We have found that there was marked specificity in the ability of OSP-1 to drive reporter gene expression in an ovarian epithelial cell lineage manner. The expression of herpes simplex virus thymidine kinase (HSV-TK) under OSP-1 control was sufficiently ovarian cancer cell line specific to render ganciclovir approximately 50-fold more toxic in the A2780 human ovarian cancer cell line compared with clones of the HCT-116 and HT-29 colon cancer cell lines. Furthermore, ganciclovir had marked antitumor efficacy in vivo in severe combined immunodeficient mice bearing A2780OSP-1-HSV-TK as a s.c. xenograft. We suggest that these data support the use of OSP-1 as a tool to provide specificity to the gene therapy of ovarian cancer and to drive ovarian-specific oncogene expression for the creation of transgenic mouse models of ovarian cancer.


miR-99b-3p/Mmp13 axis regulates NLRP3 inflammasome-dependent microglial pyroptosis and alleviates neuropathic pain via the promotion of autophagy.
Neuropathic pain significantly impairs quality of life, and effective interventions are limited. NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated microglial pyroptosis and the subsequent proinflammatory cytokine production are critical in exacerbating pain. Considering microglial pyroptosis as a potential target for developing specific analgesic interventions for neuropathic pain, our study investigated the pathogenesis and therapeutic targets in this condition. In vitro experiments involved the co-culture of the immortalized BV-2 microglia cell line with lipopolysaccharide (LPS) to induce microglial pyroptosis. Differentially expressed microRNAs (miRNAs) were identified using high-throughput sequencing analysis. The downstream target genes of these miRNAs were determined through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and the downstream target genes, combined with miRNAs, were predicted and verified through dual luciferase reporter gene assays. In vivo experiments were conducted to construct a chronic constriction injury (CCI) neuropathic pain model in rats and evaluate the analgesic effects of intrathecal injection of an adeno-associated virus vector (AAV) carrying miR-99b-3p. Gene expression was modulated through mimic or siRNA transfection. Western blot analysis assessed the expression of microglial pyroptosis and autophagy-related proteins, whereas RT-qPCR measured changes in proinflammatory cytokines expression. LPS-stimulated up-regulation of proinflammatory cytokines in microglia, accompanied by NLRP3-dependent pyroptosis, including increased NLRP3, GSDMD-N, Caspase1-p20, and mature-IL-1β expression. High-throughput sequencing analysis revealed 16 upregulated and 10 downregulated miRNAs in LPS-stimulated microglia, with miR-99b-3p being the most downregulated. KEGG analysis revealed that the target genes of these miRNAs are primarily enriched in calcium, FoxO, and mitogen-activated protein kinase (MAPK) signal pathways. Furthermore, overexpression of miR-99b-3p through mimic transfection significantly inhibited the inflammatory response and NLRP3-mediated pyroptosis by promoting autophagy levels in activated microglia. In addition, we predicted that the 3' untranslated region (UTR) of matrix metalloproteinase-13 (Mmp13) could bind to miR-99b-3p, and knockdown of Mmp13 expression through siRNA transfection similarly ameliorated enhanced proinflammatory cytokines expression and microglial pyroptosis by enhancing autophagy. In vivo, Mmp13 was co-localized with spinal dorsal horn microglia and was suppressed by intrathecal injection of the AAV-miR-99b-3p vector. Moreover, overpressed miR-99b-3p alleviated CCI-induced mechanical allodynia and neuroinflammation while suppressing pyroptosis by enhancing autophagy in the spinal cord of CCI rats. miR-99b-3p exerts analgesic effects on neuropathic pain by targeting Mmp13. These antinociceptive effects are, at least in part, attributed to the promotion of autophagy, thereby inhibiting neuroinflammation and NLRP3-mediated pyroptosis in activated microglia.


Hydrogen Embrittlement and Improved Resistance of Al Addition in Twinning-Induced Plasticity Steel: First-Principles Study.
Understanding the mechanism of hydrogen embrittlement (HE) of austenitic steels and developing an effective strategy to improve resistance to HE are of great concern but challenging. In this work, first-principles studies were performed to investigate the HE mechanism and the improved resistance of Al-containing austenite to HE. Our results demonstrate that interstitial hydrogen atoms have different site preferences in Al-free and Al-containing austenites. The calculated binding energies and diffusion barriers of interstitial hydrogen atoms in Al-containing austenite are remarkably higher than those in Al-free austenite, indicating that the presence of Al is more favorable for reducing hydrogen mobility. In Al-free austenite, interstitial hydrogen atoms caused a remarkable increase in lattice compressive stress and a distinct decrease in bulk, shear, and Young's moduli. Whereas in Al-containing austenite, the lattice compressive stress and the mechanical deterioration induced by interstitial hydrogen atoms were effectively suppressed.


Coping, mastery, stress appraisals, mental preparation, and unit cohesion predicting distress and performance: a longitudinal study of soldiers undertaking evacuation tasks.
The study aimed to assess the associations of psychological and military variables with distress and performance evaluation among 168 Israeli soldiers who took part in evacuating fellow Israeli civilians in the summer of 2005 during the disengagement from Gaza. Coping, mastery, stress appraisals, mental preparation, unit cohesion, and psychological distress were assessed at T1, one to two weeks before the disengagement. A sub-sample of 68 of the 168 soldiers completed the distress measure again at T2, eight to nine weeks after T1, together with performance evaluation of the disengagement task. The main findings indicated positive associations of T1 distress with high T1 emotion-focused coping, and negative associations with education and T1 mastery. Emotion-focused coping at T1 predicted low performance evaluation at T2, while mental preparation at T1 predicted high performance evaluation at T2. Stress appraisals at T1 were found to be an important mediator of the associations of T1 coping, mastery, unit cohesion, and mental preparation with T1 distress. Similar mediator results were found for T2 performance evaluation.


Biased monitoring of fresh water-salt water mixing zone in coastal aquifers.
In coastal aquifers, significant vertical hydraulic gradients are formed where fresh water and underlying salt water discharge together upward to the seafloor. Monitoring boreholes may act as "short circuits" along these vertical gradients, connecting between the higher and the lower hydraulic head zones. When a sea tide is introduced, the fluctuations of both the water table and the depth of the mixing zone are also biased due to this effect. This problem is intensified in places of long-screen monitoring boreholes, which are common in many places in the world. For example, all approximately 500 boreholes of the fresh water-salt water mixing zone in the coastal aquifer of Israel are installed with 10 to 50 m long screens. We present field measurements of these fluctuations, along with a three-dimensional numerical model. We find that the in-well fluctuation magnitude of the mixing zone is an order of magnitude larger than that in the porous media of the actual aquifer. The primary parameters that affect the magnitude of this bias are the anisotropy of the aquifer conductivity and the borehole hydraulic parameters. With no sea tide, borehole interference is higher for the anisotropic case because the vertical hydraulic gradients are high. When tides are introduced, the amplitude of the mixing zone fluctuation is higher for the isotropic case because the overall effective hydraulic conductivity is greater than the conductivity in the anisotropic case. In the aquifer, the fresh water-salt water mixing zone fluctuations are dampened, and tens of meters inland from the shoreline, the fluctuations are on the order of few centimeters.


Use and self-perceived effects of social media before and after the COVID-19 outbreak: a cross-national study.
To (i) examine the use of social media before and after the COVID-19 outbreak; (ii) examine the self-perceived impact of social media before and after the outbreak; and (iii) examine whether the self-perceived impacts of social media after the outbreak varied by levels of mental health. A cross-national online survey was conducted in Norway, UK, USA and Australia. Participants (n = 3810) reported which social media they used, how frequently they used them before and after the COVID-19 outbreak, and the degree to which they felt social media contributed to a range of outcomes. The participants also completed the 12-item General Health Questionnaire. The data were analyzed by chi-square tests and multiple linear regression analysis. Social media were used more frequently after the pandemic outbreak than compared to before the outbreak. Self-perceived effects from using social media increased after the COVID-19 outbreak, and in particular stress and concern for own and others' health. Emotional distress was associated with being more affected from using social media, in particular in terms of stress and concern for own or others' health. The use of social media has increased during the coronavirus outbreak, as well as its impacts on people. In particular, the participants reported more stress and health concerns attributed to social media use after the COVID-19 outbreak. People with poor mental health appear to be particularly vulnerable to experiencing more stress and concern related to their use of social media.


Reading accuracy and speed of vowelized and unvowelized scripts among dyslexic readers of Hebrew: the road not taken.
The present study examined the effects of orthographic transparency on reading ability of children with dyslexia in two Hebrew scripts. The study explored the reading accuracy and speed of vowelized and unvowelized Hebrew words of fourth-grade children with dyslexia. A comparison was made to typically developing readers of two age groups: a group matched by chronological age and a group of children who are 2 years younger, presumably at the end of the reading acquisition process. An additional purpose was to investigate the role of vowelization in the reading ability of unvowelized script among readers with dyslexia in an attempt to assess whether vowelization plays a mediating role for reading speed of unvowelized scripts. The present study found no significant differences in reading accuracy and speed between vowelized and unvowelized scripts among fourth-grade readers with dyslexia. The reading speed of fourth-graders with dyslexia was similar to typically developing second-graders for both the vowelized and unvowelized words. However, fourth-grade children with dyslexia performed lower than the typically developing second-graders in the reading accuracy of vowelized script. Furthermore, for readers with dyslexia, accuracy in reading both vowelized and unvowelized words mediated the reading speed of unvowelized scripts. These results may be a sign that Hebrew-speaking children with dyslexia have severe difficulties that prevent them from developing strategies for more efficient reading.


MYH7 variants cause complex congenital heart disease.
MYH7, encoding the myosin heavy chain sarcomeric β-myosin heavy chain, is a common cause of both hypertrophic and dilated cardiomyopathy. Additionally, families with left ventricular noncompaction cardiomyopathy (LVNC) and congenital heart disease (CHD), typically septal defects or Ebstein anomaly, have been identified to have heterozygous pathogenic variants in MHY7. One previous case of single ventricle CHD with heart failure due to a MYH7 variant has been identified. Herein, we present a single center's experience of complex CHD due to MYH7 variants. Three probands with a history of CHD, LVNC, and/or arrhythmias were identified to have MYH7 variants through multigene panel testing or exome sequencing. These three patients collectively had 12 affected family members, four with a history of Ebstein anomaly and seven with a history of LVNC. These findings suggest a wider phenotypic spectrum in MYH7-related CHD than previously understood. Further investigation into the possible role of MYH7 in CHD and mechanism of disease is necessary to fully delineate the phenotypic spectrum of MYH7-related cardiac disease. MYH7 should be considered for families with multiple individuals with complex CHD in the setting of a family history of LVNC or arrhythmias.


Establishing Stability in Organic Semiconductor Photocathodes for Solar Hydrogen Production.
As organic semiconductors attract increasing attention to application in the fields of bioelectronics and artificial photosynthesis, understanding the factors that determine their robust operation in direct contact with aqueous electrolytes becomes a critical task. Herein we uncover critical factors that influence the operational stability of donor:acceptor bulk heterojunction photocathodes for solar hydrogen production and significantly advance their performance under operational conditions. First, using the direct photoelectrochemical reduction of aqueous Eu3+ and impedance spectroscopy, we determine that replacing the commonly used fullerene-based electron acceptor with a perylene diimide-based polymer drastically increases operational stability and identify that limiting the photogenerated electron accumulation at the organic/water interface to values of ca. 100 nC cm-2 is required for stable operation (>12 h). These insights are extended to solar-driven hydrogen production using MoS3, MoP, or RuO2 water reduction catalyst overlayers where it is found that the catalyst morphology strongly affects performance due to differences in charge extraction. Optimized performance of bulk heterojunction photocathodes coated with a MoS3:MoP composite gave 1 Sun photocurrent density up to 8.7 mA cm-2 at 0 V vs RHE (pH 1). However, increased stability was gained with RuO2 where initial photocurrent density (>8 mA cm-2) deceased only 15% or 33% during continuous operation for 8 or 20 h, respectively, thus demonstrating unprecedented robustness without a protection layer. This performance represents a new benchmark for organic semiconductor photocathodes for solar fuel production and advances the understanding of stability criteria for organic semiconductor/water-junction-based devices.


Brain structure volumes in the mole rat, Spalax ehrenbergi (Spalacidae, Rodentia) in comparison to the rat and subterrestrial insectivores.
Natural blindness and a subterranean, digging mode of life demand peculiar adaptations of the central nervous system in the mole rat Spalax ehrenbergi, which are the focus of this quantitative investigation. Volumes of 25 brain structures in Spalax were evaluated allometrically, using the least encephalized mammalian species, the Madagassian hedgehog-like tenrecs (Tenrecinae) as a reference base, and their sizes compared with those of the rat (as a more generalized representative of rodents) and of some subterranean Insectivora. The allometric approach reveals that Spalax has a larger brain than tenrecs and the rat. Within the brain, the neocortex and diencephalon are well developed, an observation also made in other mammalian species with a relatively high encephalization. An unique feature in Spalax is the enlargement of motor structures of the brain, such as the cerebellum (and cerebellar nuclei), and the striatum. Most conspicuous is the large size of the nucleus motorius nervi trigemini, reflecting the importance of masticatory muscles for the special digging technique, which demand an intense use of the teeth for loosening the soil.


Anterior cingulate proton spectroscopy glutamate levels differ as a function of smoking cessation outcome.
Cigarette smoking is the leading preventable cause of death. Unfortunately, the majority of smokers who attempt to quit smoking relapse within weeks. Abnormal dorsal anterior cingulate cortex (dACC) function may contribute to tobacco smoking relapse vulnerability. Growing evidence suggests that glutamate neurotransmission is involved in mediating nicotine dependence. We hypothesized that prior to a cessation attempt, dACC glutamate levels would be lower in relapse vulnerable smokers. Proton magnetic resonance spectra (MRS) were obtained from dACC and a control region, the parieto-occipital cortex (POC), using two-dimensional J-resolved MRS at 4T and analyzed using LCModel. Nine nicotine-dependent women were scanned prior to making a quit attempt. Subjects then were divided into two groups; those able to maintain subsequent abstinence aided by nicotine replacement therapy (NRT) and those who slipped while on NRT (smoked any part of a cigarette after attaining at least 24h of abstinence). Slip subjects exhibited significantly reduced dACC MRS glutamate (Glu/Cr) levels (p<0.03) compared to abstinent subjects. This effect was not observed in the POC control region. Our preliminary findings suggest that dACC Glu levels as measured with MRS may help identify and/or be a biomarker for relapse vulnerable smokers. Future research following up on these findings may help clarify the role of dACC Glu in smoking dependence that may lead to new treatment strategies.


Risk of subarachnoid haemorrhage reduces with blood pressure values below hypertensive thresholds.
Hypertension is a known risk factor for subarachnoid haemorrhage (SAH). The aim of this study was to describe the relationship between blood pressure and SAH using a large cohort study and perform a meta-analysis of the published literature. Participants in the UK Biobank were followed up via electronic records until 31 March 2017. Cox proportional hazards models were used to analyse the association between baseline blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and MABP [mean arterial blood pressure]) and subsequent aneurysmal SAH. Linearity was assessed by comparing models including and excluding cubic splines. Electronic databases were searched from inception until 11 February 2022 for studies reporting on blood pressure and SAH. A total of 500,598 individuals were included with 539 (0.001%) suffering from aneurysmal SAH. Nonlinear models including cubic splines visually appeared linear between SBP of 110 and 180 mmHg and there was minimal difference in fit between linear and nonlinear models. When values were stratified, those with SBP 120-130 mmHg were at higher risk compared to those with SBP <120 mmHg (hazard ratio [HR] 1.41 [1.02, 1.95]). The meta-analysis demonstrated a similar increased risk of SAH in individuals with SBP 120-130 mmHg relative to those with <120 mmHg (HR 1.41 [1.17, 1.72]). A stepwise increase in risk was also seen at each subsequent threshold (130-140 mmHg: HR 1.85 [1.53, 2.24], 140-160 mmHg: HR 2.16 [1.57, 2.98], 160-180 mmHg: HR 2.81 [1.85, 4.29], >180 mmHg: HR 5.84 [1.94, 17.54]). The rate of SAH increases linearly with higher SBP in the general population and specifically appears lower in those with SBP <120 mmHg.


Chicken TLR21 is an innate CpG DNA receptor distinct from mammalian TLR9.
TLRs comprise a family of evolutionary conserved sensory receptors that respond to distinct classes of ligands. For one major evolutionary branch of TLRs, the ligands are still largely unknown. Here we report the cloning and function of one member of this group, chicken TLR21 (chTLR21). This TLR is absent in the human species but has homologs in fish and frog and displays similarity with mouse TLR13. Expression of chTLR21 in HEK293 cells resulted in activation of NF-kappaB in response to unmethylated CpG DNA, typically recognized by mammalian TLR9. Silencing of chTLR21 (but not chTLR4) in chicken macrophages inhibited the response to CpG-DNA (but not to LPS), indicating similar functionality of the endogenous receptor. ChTLR21 responded to human- and murine-specific TLR9 ligands, as well as to bacterial genomic DNA isolated from Salmonella enterica serovar Enteritidis. Confocal microscopy located chTLR21 in the same intracellular compartments as human TLR9. Inhibition of the chTLR21 response by the endosomal maturation inhibitor chloroquine suggested that the receptor is functional in endolysosomes, as known for TLR9. The analogous localization and function of the phylogenetically only distantly related chTLR21 and mammalian TLR9 suggest that during evolution different classes of TLRs have emerged that recognize the same type of ligands.


Case of yellow fever vaccine--associated viscerotropic disease with prolonged viremia, robust adaptive immune responses, and polymorphisms in CCR5 and RANTES genes.
The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines. Despite its excellent safety record, some cases of viscerotropic adverse events develop, which are sometimes fatal. The mechanisms underlying such events remain a mystery. Here, we present an analysis of the immunologic and genetic factors driving disease in a 64-year-old male who developed viscerotropic symptoms. We obtained clinical, serologic, virologic, immunologic and genetic data on this case patient. Viral RNA was detected in the blood 33 days after vaccination, in contrast to the expected clearance of virus by day 7 after vaccination in healthy vaccinees. Vaccination induced robust antigen-specific T and B cell responses, which suggested that persistent virus was not due to adaptive immunity of suboptimal magnitude. The genes encoding OAS1, OAS2, TLR3, and DC-SIGN, which mediate antiviral innate immunity, were wild type. However, there were heterozygous genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES, which influence the migration of effector T cells and CD14+CD16bright monocytes to tissues. Consistent with this, there was a 200-fold increase in the number of CD14+CD16bright monocytes in the blood during viremia and even several months after virus clearance. In this patient, viscerotropic disease was not due to the impaired magnitude of adaptive immunity but instead to anomalies in the innate immune system and a possible disruption of the CCR5-RANTES axis.


Efficacy of ceftiofur for treatment of experimental salmonellosis in neonatal calves.
To evaluate therapeutic efficacy of a high extralabel dose of ceftiofur for treatment of experimental salmonellosis in neonatal calves. Forty-two 1- to 4-day-old Holstein bull calves. 36 calves were orally challenged with Salmonella enteritica serovar Typhimurium (6.5 x 10(8) colony-forming units). Six additional calves were retained as nonmedicated nonchallenged control calves. Four days following Salmonella challenge, surviving calves were randomly allocated to ceftiofur-treated (5 mg/kg, IM, q 24 h) or nonmedicated control groups. Calves assigned to the treated group were medicated daily for 5 days starting on day 4 after challenge. Calves were monitored for 18 days following Salmonella challenge. Outcome assessments included clinical parameters (attitude, appetite, fecal characteristics, and rectal temperature), mortality rate, and quantitative Salmonella culture of fecal samples, mesenteric lymph nodes, and cecal contents. Ceftiofur treatment was associated with a significant decrease in rectal temperature and diarrhea. Three of 15 medicated calves and 4 of 14 non-medicated calves died or were euthanatized between days 4 and 18. A significant decrease in fecal shedding of Salmonella organisms was observed in treated calves, compared with nonmedicated calves. Salmonella organisms were isolated from all 10 non-medicated calves at necropsy, whereas no Salmonella organisms were isolated from 5 of 12 medicated calves. Treatment of salmonellosis in neonatal calves with a high extralabel dose of ceftiofur (5 mg/kg, IM, q 24 h) promotes animal welfare, reduces fecal shedding of Salmonella organisms, and may promote clearance of Salmonella infections when plasma ceftiofur concentrations are maintained above minimal inhibitory concentrations.


Daily symptom burden in end-stage chronic organ failure: a systematic review.
Chronic diseases are nowadays the major cause of morbidity and mortality worldwide. Patients with end-stage chronic organ failure may suffer daily from distressful physical and psychological symptoms. The objective of the present study is to systematically review studies that examined daily symptom prevalence in patients with end-stage chronic organ failure, with attention to those that included patients with either congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) or chronic renal failure (CRF). Thirty-nine articles (8 CHF, 7 COPD, 2 CHF and COPD, 22 CRF) have been included. The included studies used various study designs. There was a wide range of daily symptom prevalence that may be due to the heterogeneity in methodology used. Nevertheless, findings suggest significant symptom burden in these patients. This review highlights the need for further prospective and longitudinal research on symptom prevalence in patients with end-stage CHF, COPD and CRF to facilitate the development of patient-centred palliative care programs.


Trends in Hospitalization for Opioid Overdose among Rural Compared to Urban Residents of the United States, 2007-2014.
Hospitalizations and deaths due to opioid overdose have increased over the last decades. We used data from the National Inpatient Sample and the American Community Survey to describe trends in hospitalization rates for opioid overdose among rural residents compared with urban residents in the United States from 2007 to 2014. Hospitalization rates for heroin overdose increased in all years and were higher in urban residents compared with rural residents (5.5 per 100,000 in large urban populations vs 2.1 per 100,000 in rural populations in 2014). In contrast, hospitalization rates for prescription opioid overdose were 20% to 30% higher in rural populations compared with large urban populations between 2007 and 2012, before declining in rural populations in 2013 and 2014. The proportion of rural patients admitted for overdose who are cared for in urban hospitals increased from 23.1% in 2007 to 41.2% in 2014. These trends are clinically relevant as rural patients and urban patients may have different discharge needs.


Chronic hypoxia induces prolonged angiogenesis in skeletal muscles of rat.
Skeletal muscle capillarity and fibre cross-sectional area were investigated within and between diaphragm (Diaph), extensor digitorum longus (EDL), soleus (SOL) and tibialis anterior (TA) muscles of control and chronic hypoxic (12 % O(2) for 6 weeks) adult male Wistar rats (final body mass approximately 355 g). Cryostat sections were stained for alkaline phosphatase activity to depict all capillaries, and for succinic dehydrogenase to demonstrate regional differences in oxidative capacity within the muscles. Hypoxia-induced angiogenesis occurred in all muscles (P < 0.01), with capillary-to-fibre ratio (C:F) being higher in the more active and oxidative muscles, Diaph (27 %) and SOL (26 %), than phasically active and glycolytic muscles, TA (21 %) and EDL (15 %). Diaph, SOL and EDL maintained fibre size, and hence showed an increased capillary density (CD) and reduced intramuscular diffusion distance (DD), whereas TA showed fibre hypertrophy and maintained CD and DD compared to control muscles. The extent of angiogenesis among different regions of muscle varied so as to suggest that muscle fibre size has an additional influence on capillary growth during chronic systemic hypoxia, which is progressive over an extended period of systemic hypoxia.


Vitamin D intake and its food sources in Taiwanese.
In the early 20th Century, vitamin D was discovered and its Recommended Daily Allowance developed. However, average daily dietary intakes have not been reported until recently in the US. There are no food composi-tion and no intake data for vitamin D available in Taiwan. We have taken advantage of several population representative Nutrition and Health Surveys in Taiwan (NAHSIT) conducted from 1993 onwards of various age groups to examine this possibility systematically. Firstly, we collected and compiled the vitamin D content of foods from various sources to supplement the Taiwanese Food Composition Tables. Though these vitamin D data may not be fully representative of local food items, they serve as a reference point. Secondly, we have used the three NAHSITs databases, which all used the 24-hr recall method to collect dietary intake date and five food frequency questionnaire type questions to collect supplement data, to estimate most gender- and age-specific (in-clude: school children, adults and elderly) vitamin D intake from food source and supplements. Thirdly, we have defined the sources of vitamin D intake in Taiwanese (gender- and age-specific). Vitamin D intakes of Taiwanese were adequate except girls of high school and indigenous people. Fish and its products, milk, mushroom were the major vitamin D food sources. Supplement source vitamin D also varied greatly between age and gen-der groups. Elderly women consumed almost 20% of vitamin D from supplements; 16-18 years old boys consumed 2.47% vitamin D from supplements only.


Hyperparathyroidism in Paget's disease of bone.
The association between Paget's disease and hyperparathyroidism was explored in 12 patients by means of a calcium loading test. Parathyroid adenomata were discovered at surgery in 2 and parathyroid hyperfunction was found in varying degrees in 4 others. Differing responses to the calcium loading test were interpreted as reflecting different stages in the bone formation-resorption disequilibrium found in Pagetic bone. A prolonged imbalance in favour of formation is suggested as constituting a stress on the homeostasis of extracellular fluid calcium levels that leads to parathyroid hyperfunction.


Commensal bacteria regulate thymic Aire expression.
Commensal bacteria in gastrointestinal tracts are reported to function as an environmental factor to regulate intestinal inflammation and immune responses. However, it remains largely unknown whether such bacterial function exerts any effect on other immune organs distant from the intestine. In this study, the influence of commensal bacteria in the thymus, where T cell lineages develop into mature type to form proper repertoires, was investigated using germ-free (GF) mice and Nod1-deficient mice lacking an intracellular recognition receptor for certain bacterial components, in which a commensal bacterial effect is predicted to be less. In both mice, there was no significant difference in the numbers and subset ratios of thymocytes. Interestingly, however, autoimmune regulator (Aire) expression in thymic epithelial cells (TECs), main components of the thymic microenvironment, was decreased in comparison to specific pathogen-free (SPF) mice and Nod1 wild-type (WT) mice, respectively. In vitro analysis using a fetal thymus organ culture (FTOC) system showed that Aire expression in TECs was increased in the presence of a bacterial component or a bacterial product. These results suggest that through their products, commensal bacteria have the potential to have some effect on epithelial cells of the thymus in tissues distant from the intestine where they are originally harbored.


Spatial coherence measurement of polychromatic light with modified Young's interferometer.
Partial spatial coherence is a fundamental concept in optical systems. Theoretically, the normalized mutual coherence function gives a quantitative measure for partial spatial coherence regardless of the spectral nature of the radiation. For narrowband light the degree of spatial coherence can be measured in terms of the fringe modulation in the classic Young's two-pinhole interferometer. Though not commonly appreciated, with polychromatic radiation this is not the case owing to the wavelength dependence of diffraction. In this work we show that with a modified two-beam interferometer containing an achromatic Fresnel transformer the degree of spatial coherence is again related to the visibility of intensity fringes in Young's experiment for any polychromatic light. This result, which is demonstrated both theoretically and experimentally, thus restores the usefulness of the two-pinhole interferometer in the measurement of the spatial coherence of light beams of arbitrary spectral widths.


Fibroblast growth factor-1 stimulation of quiescent NIH 3T3 cells increases G/T mismatch-binding protein expression.
Polypeptide growth factors promote cell-cycle progression in part by the transcriptional activation of a diverse group of specific genes. We have used an mRNA differential-display approach to identify several fibroblast growth factor (FGF)-1 (acidic FGF)-inducible genes in NIH 3T3 cells. Here we report that one of these genes, called FGF-regulated (FR)-3, is predicted to encode G/T mismatch-binding protein (GTBP), a component of the mammalian DNA mismatch correction system. The murine GTBP gene is transiently expressed after FGF-1 or calf serum treatment, with maximal mRNA levels detected at 12 and 18 h post-stimulation. FGF-1-stimulated NIH 3T3 cells also express an increased amount of GTBP as determined by immunoblot analysis. These results indicate that elevated levels of GTBP may be required during the DNA synthesis phase of the cell cycle for efficient G/T mismatch recognition and repair.


The Effect of Adipocyte-Secreted Factors in Activating Focal Adhesion Kinase-Mediated Cell Signaling Pathway towards Metastasis in Breast Cancer Cells.
Obesity-associated perturbations in the normal secretion of adipocytokines from white adipocytes can drive the metastatic progression of cancer. However, the association between obesity-induced changes in secretory factors of white adipocytes and subsequent transactivation of the downstream effector proteins impacting metastasis in breast cancer cells remains unclear. Focal adhesion kinase, a cytoplasmic signal transducer, regulates the biological phenomenon of metastasis by activating downstream targets such as beta-catenin and MMP9. Thus, the possible role of phosphorylated FAK in potentiating cancer cell migration was investigated. To elucidate this potential relationship, MCF7 (ER+), MDA-MB-231 (Triple Negative) breast cancer cells, and MCF-10A non-tumorigenic breast cells were exposed to in vitro murine adipocyte-conditioned medium derived from 3T3-L1 MBX cells differentiated to obesity with fatty acid supplementation. Our results show that the conditioned medium derived from these obese adipocytes enhanced motility and invasiveness of breast cancer cells. Importantly, no such changes were observed in the non-tumorigenic breast cells. Our results also show that increased FAK autophosphorylation was followed by increased expression of beta-catenin and MMP9 in the breast cancer cells when exposed to obese adipocyte-conditioned medium, but not in the MCF10A cells. These results indicate that adipocyte-derived secretory factors induced FAK activation through phosphorylation. This in turn increased breast cancer cell migration and invasion by activating its downstream effector proteins beta-catenin and MMP9.


Carcinoma of the lung in Ontario gold miners: possible aetiological factors.
A cohort of 54,128 men who worked in Ontario mines was observed for mortality between 1955 and 1986. Most of these men worked in nickel, gold, or uranium mines; a few worked in silver, iron, lead/zinc, or other ore mines. If mortality that occurred after a man had started to mine uranium was excluded, an excess of carcinoma of the lung was found among the 13,603 Ontario gold miners in the study (standardised mortality ratio (SMR) 129, 95% confidence interval (95% CI) 115-145) and in men who began to mine nickel before 1936 (SMR 141, 95% CI 105-184). The excess mortality from lung cancer in the gold miners was confined to men who began gold mining before 1946. No increase in the mortality from carcinoma of the lung was evident in men who began mining gold after the end of 1945, in men who began mining nickel after 1936, or in men who mined ores other than gold, nickel, and uranium. In the gold mines each year of employment before the end of 1945 was associated with a 6.5% increase in mortality from lung cancer 20 or more years after the miner began working the mines (95% CI 1.6-11.4%); each year of employment before the end of 1945 in mines in which the host rock contained 0.1% arsenic was associated with a 3.1% increase in lung cancer 20 years or more after exposure began (95% CI 1.1-5.1%); and each working level month of exposure to radon decay products was associated with a 1.2% increase in mortality from lung cancer five or more years after exposure began (95% CI 0.02-2.4%). A comparison of two models shows that the excess of lung cancer mortality in Ontario gold miners is associated with exposure to high dust concentrations before 1946, with exposure to arsenic before 1946, and with exposure to radon decay products. No association between the increased incidence of carcinoma of the lung in Ontario gold miners and exposure to mineral fibre could be detected. It is concluded that the excess of carcinoma of the lung in Ontario gold miners is probably due to exposure to arsenic and radon decay products.


Population turnover in a Microcystis bloom results in predominantly nontoxigenic variants late in the season.
Surface samples of the 2007 Microcystis bloom occurring in Copco Reservoir on the Klamath River in Northern California were analyzed genetically by sequencing clone libraries made with amplicons at three loci: the internal transcribed spacer of the rRNA operon (ITS), cpcBA, and mcyA. Samples were taken between June and October, during which time two cell count peaks occurred, in mid-July and early September. The ITS and cpcBA loci could be classified into four or five allele groups, which provided a convenient means for describing the Microcystis population and its changes over time. Each group was numerically dominated by a single, highly represented sequence. Other members of each group varied by changes at 1 to 3 nucleotide positions, while groups were separated by up to 30 nucleotide differences. As deduced by a partial sampling of the clone libraries, there were marked population turnovers during the season, indicated by changes in allele composition at both the ITS and cpcBA loci. Different ITS and cpcBA genotypes appeared to be dominant at the two population peaks. Toxicity (amount of microcystin per cell) and toxigenic potential (mcyB copy number) were lower during the second peak, and the mcyB copy number fell further as the bloom declined.


STUDIES ON AN EPITHELIAL (GLAND) CELL JUNCTION. I. MODIFICATIONS OF SURFACE MEMBRANE PERMEABILITY.
Membrane permeability of an epithelial cell junction (Drosophila salivary gland) was examined with intracellular microelectrodes and with fluorescent tracers. In contrast to the non-junctional cell membrane surface, which has a low permeability to ions (10(-4) mho/cm(2)), the junctional membrane surface is highly permeable. In fact, it introduces no substantial restriction to ion flow beyond that in the cytoplasm; the resistance through a chain of cells (150 ohm cm) is only slightly greater than in extruded cytoplasm (100 ohm cm). The diffusion resistance along the intercellular space to the exterior, on the other hand, is very high. Here, there exists an ion barrier of, at least, 10(4) ohm cm(2). As a result, small ions and fluorescein move rather freely from one cell to the next, but do not leak appreciably through the intercellular space to the exterior. The organ here, rather than the single cell, appears to be the unit of ion environment. The possible underlying structural aspects are discussed.


Accuracy of impressions with different impression materials in angulated implants.
To evaluate the dimensional accuracy of the resultant (duplicative) casts made from two different impression materials (polyvinyl siloxane and polyether) in parallel and angulated implants. Three definitive master casts (control groups) were fabricated in dental stone with three implants, placed at equi-distance. In first group (control), all three implants were placed parallel to each other and perpendicular to the plane of the cast. In the second and third group (control), all three implants were placed at 10° and 15 o angulation respectively to the long axis of the cast, tilting towards the centre. Impressions were made with polyvinyl siloxane and polyether impression materials in a special tray, using a open tray impression technique from the master casts. These impressions were poured to obtain test casts. Three reference distances were evaluated on each test cast by using a profile projector and compared with control groups to determine the effect of combined interaction of implant angulation and impression materials on the accuracy of implant resultant cast. Statistical analysis revealed no significant difference in dimensional accuracy of the resultant casts made from two different impression materials (polyvinyl siloxane and polyether) by closed tray impression technique in parallel and angulated implants. On the basis of the results of this study, the use of both the impression materials i.e., polyether and polyvinyl siloxane impression is recommended for impression making in parallel as well as angulated implants.


The development of swimming rhythmicity in post-embryonic Xenopus laevis.
The post-embryonic development of 'fictive' swimming in immobilized Xenopus laevis tadpoles has been examined during the first day of larval life. In Xenopus embryos (stage 37-38; Nieuwkoop & Faber 1956), the rhythmic ventral root activity underlying swimming occurs as single brief (ca. 7 ms) compound impulses on each cycle. However, by stage 42 (about 24 h after hatching), ventral root discharge consists of bursts lasting around 20 ms per cycle. In addition to increased burst duration in each cycle of larval swimming, the range of cycle periods within an episode increases, although mean period values (ca. 70-80 ms) remain similar to those of the younger animal. Consequently, motoneurons at developmental stage 42 are active during swimming for a greater percentage (ca. 25%) of cycle time than at stage 37-38 (ca. 10%). Developmental stage 40 (ca. 12 h post-hatching) is an intermediate stage in rhythm development. Ventral root discharge varies from bursts of 10-20 ms at the start of an episode to embryonic (ca. 7 ms) spikes at the end of an episode. Furthermore, discharge varies from bursts of activity in rostral segments of stage 40 larvae to 7 ms spikes more caudally, as in embryos. The data thus suggest that Xenopus swimming rhythmicity develops relatively rapidly, along a rostrocaudal gradient, and may involve acquisition of multiple spiking in spinal neurons.


PhyloJIVE: Integrating biodiversity data with the Tree of Life.
Rich collections of biodiversity information such as spatial distributions, species descriptions and trait data are now synthesized in publicly available online sources such as GBIF. Also phylogenetic knowledge now provides a sound understanding of the origin of organisms and their place in the tree of life. We demonstrate with PhyloJIVE that any phylogenetic tree can be linked to online biodiversity data in the browser. This evolutionary view of biodiversity data is demonstrated in a case study that suggests that this approach may be useful to scientists and non-experts users.


Sweet's syndrome associated with Mycobacterium chelonae and herpes simplex virus infections: a case report.
We report a case of Sweet's syndrome associated with Mycobacterium chelonae and herpes simplex virus infection. A 56-year-old Chinese woman presented with a granulomatous subglottic mass and right lung nodules, which responded to a 9-month course of anti-tuberculous treatment. Subsequently, she developed genital herpes simplex virus infection, which was followed by a cutaneous eruption with vesicular plaques associated with fever, bilateral cervical lymph nodes and neutrophilia. Mycobacterium chelonae was isolated from lymph node cultures. The cutaneous presentation of Sweet's syndrome was confirmed on skin biopsy. There was no evidence of underlying immunosuppression, malignancy or connective tissue disease. She was treated with rifampicin, clarithromycin and oral prednisolone. There was complete resolution of her cutaneous lesions and cervical lymphadenopathy. The association between Sweet's syndrome and Mycobacterium chelonae as well as herpes simplex virus, though rare, should be considered in all patients presenting with Sweet's syndrome.


Addiction research centres and the nurturing of creativity: the National Institute on Alcohol Abuse and Alcoholism.
The aim of this paper is to present a concise account of the history, mission, structure and some recent achievements of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA). Created by the US Congress 40 years ago, the NIAAA has evolved from an entity charged mainly with building a national system of alcoholism treatment services to one with responsibility for developing, nurturing and supporting the biomedical and behavioral science foundation necessary to reduce the significant domestic and global public health impact of alcohol use disorders. The NIAAA is unique in that it functions both as a funding agency, supporting research at universities and other external, or 'extramural' research institutions, and is also a research institution itself, where alcohol research is carried out in-house, or 'intramurally'. Of a $450.2 million 2009 Congressional Appropriation, approximately 90% was devoted toward the former and approximately 10% towards the latter objective. The current NIAAA Strategic Plan builds on a new organizing principle for long-range research planning, based on a life-span perspective that recognizes that human biology and behavior continue to change throughout life and changes occurring throughout the life-span affect individuals' drinking patterns as well as the decisions they may make to change their drinking habits or to seek help for alcohol use problems. Within this framework, major efforts are currently being devoted to educating practitioners on clinically useful, science-based assessment and treatment methods that exist today, and development of personalized new treatments for tomorrow.


Caring for People With Dementia Under COVID-19 Restrictions: A Pilot Study on Family Caregivers.
The present pilot study examined to what extent the COVID-19 lockdown affected the behavioral and psychological symptoms of dementia (BPSD) in people with dementia and worsened their family caregivers' distress. The associations between changes in the BPSD of relatives with dementia (RwD) and in their caregivers' distress, and sense of social and emotional loneliness, and resilience were also investigated. Thirty-five caregivers of RwD attending formal healthcare services before the COVID-19 lockdown volunteered for the study, and were interviewed by phone during the lockdown. Caregivers completed the NeuroPsychiatric Inventory (NPI) to assess their care recipients' BPSD and their own distress, and two questionnaires assessing their social and emotional loneliness, and their resilience. No clear changes emerged in either the BPSD of the RwD or the caregivers' distress during lockdown compared with before the pandemic. Caregivers reporting more frequent and severe BPSD in their RwD before the lockdown scored higher on emotional loneliness. Those reporting more frequent and severe BPSD under lockdown, especially men and those taking care of RwD with more advanced dementia, scored higher on both social and emotional loneliness. A significant negative correlation also emerged between caregivers' resilience and changes in their level of distress due to the lockdown, with female caregivers reporting greater resilience. Our findings offer preliminary insight on the effects of loneliness and resilience, and on the influence of individual characteristics on the experience and consequences of informal caregiving for RwD in times of restrictions imposed by a pandemic.


Nonlinear blind source separation using kernels.
We derive a new method for solving nonlinear blind source separation (BSS) problems by exploiting second-order statistics in a kernel induced feature space. This paper extends a new and efficient closed-form linear algorithm to the nonlinear domain using the kernel trick originally applied in support vector machines (SVMs). This technique could likewise be applied to other linear covariance-based source separation algorithms. Experiments on realistic nonlinear mixtures of speech signals, gas multisensor data, and visual disparity data illustrate the applicability of our approach.


Ventricular Ejection Fraction and Global Strains in Connection with the Volume Regulation Graph.
Ejection fraction (EF) is traditionally considered useful to infer ventricular function. Newer metrics such as global function index (GFI) and various strains add supplemental diagnostic or prognostic value. All these candidates refer to dimensionless ratios, rather than to the characteristics of the underlying components. Therefore, we introduced the volume regulation graph (VRG), relating end-systolic volume (ESV) to end-diastolic volume (EDV). An individual patient is then uniquely defined by the prevailing working point in the volume domain. Alternatively, the combination of EF=(1-ESV/EDV) and any suitable companion (denoted as C) metric (e.g. the Pythagorean mean) specifies this working point.An expression relates EF to global longitudinal (GLS) and circumferential strain (GCS): ESV/EDV = (GLS+1) (GCS+1)2, resembling the empirical regression equation for the VRG. However, the latter has a non-zero intercept (mL). The discrepancy can be solved by the introduction of one or more pertinent companion metrics.We studied 96 patients by cardiac magnetic resonance imaging and calculated EF, EFC, GFI, GLS and GCS. The GFI is inversely related to GLS (R2=0.26). For regression we found: ESV=0.74 EDV-27.0 with R2=0.81 for N=96. Similar results were obtained for echocardiography data (N=25). Graphs relating EF to GLS and GCS indicate that EFC can distinguish patients with nearly identical values for these 3 metrics.Thus, the VRG offers a unifying framework that visualizes the association between ESV and EDV, while documenting iso-EF and iso-EFC trajectories. Newer metrics including GFI, GLS and GCS require consideration of a companion variable such as EFC to permit a comprehensive analysis.Clinical Relevance- The VRG allows insight into ventricular functioning and illustrates the working point concept. Companion metrics (having a physical dimension) should be considered in conjunction with any traditional ratio-based index.


Transient Ischemic Attack (TIA) presenting with isolated anomic aphasia due to ischemia in the posterior cingulate gyrus in a 11-year-old girl.
Anomic aphasia, characterized by difficulty in word finding, is a subtype without impairments in fluent speech, comprehension, reading, writing, and repetition. Recognizing pure anomic aphasia in this group is crucial for a comprehensive understanding of localization and brain functions. We present the case of an 11-year-old girl with transient ischemic attack and anomic aphasia. Neuroimaging identified abnormalities in the cingulate gyrus and temporo-occipital regions. No focal neurological findings were observed without aphasia. In terms of etiology, an MTHFR mutation was detected, and aside from this, no hematological or systemic cause could be identified. This case marks the first demonstration of posterior cingulate gyrus involvement in pure anomic aphasia.


Acetylenotrophy: a hidden but ubiquitous microbial metabolism?
Acetylene (IUPAC name: ethyne) is a colorless, gaseous hydrocarbon, composed of two triple bonded carbon atoms attached to hydrogens (C2H2). When microbiologists and biogeochemists think of acetylene, they immediately think of its use as an inhibitory compound of certain microbial processes and a tracer for nitrogen fixation. However, what is less widely known is that anaerobic and aerobic microorganisms can degrade acetylene, using it as a sole carbon and energy source and providing the basis of a microbial food web. Here, we review what is known about acetylene degrading organisms and introduce the term 'acetylenotrophs' to refer to the microorganisms that carry out this metabolic pathway. In addition, we review the known environmental sources of acetylene and postulate the presence of an hidden acetylene cycle. The abundance of bacteria capable of using acetylene and other alkynes as an energy and carbon source suggests that there are energy cycles present in the environment that are driven by acetylene and alkyne production and consumption that are isolated from atmospheric exchange. Acetylenotrophs may have developed to leverage the relatively high concentrations of acetylene in the pre-Cambrian atmosphere, evolving later to survive in specialized niches where acetylene and other alkynes were produced.


The first tyrosyl radical intermediate formed in the S2-S3 transition of photosystem II.
The EPR "split signals" represent key intermediates of the S-state cycle where the redox active D1-Tyr161 (YZ) has been oxidized by the reaction center of the photosystem II enzyme to its tyrosyl radical form, but the successive oxidation of the Mn4CaO5 cluster has not yet occurred (SiYZ˙). Here we focus on the S2YZ˙ state, which is formed en route to the final metastable state of the catalyst, the S3 state, the state which immediately precedes O-O bond formation. Quantum chemical calculations demonstrate that both isomeric forms of the S2 state, the open and closed cubane isomers, can form states with an oxidized YZ˙ residue without prior deprotonation of the Mn4CaO5 cluster. The two forms are expected to lie close in energy and retain the electronic structure and magnetic topology of the corresponding S2 state of the inorganic core. As expected, tyrosine oxidation results in a proton shift towards His190. Analysis of the electronic rearrangements that occur upon formation of the tyrosyl radical suggests that a likely next step in the catalytic cycle is the deprotonation of a terminal water ligand (W1) of the Mn4CaO5 cluster. Diamagnetic metal ion substitution is used in our calculations to obtain the molecular g-tensor of YZ˙. It is known that the gx value is a sensitive probe not only of the extent of the proton shift between the tyrosine-histidine pair, but also of the polarization environment of the tyrosine, especially about the phenolic oxygen. It is shown for PSII that this environment is determined by the Ca(2+) ion, which locates two water molecules about the phenoxyl oxygen, indirectly modulating the oxidation potential of YZ.


Centrophenoxine improves chronic cerebral ischemia induced cognitive deficit and neuronal degeneration in rats.
To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1alpha levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1alpha), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage. The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.


Polychlorinated cyclopentenes from a marine derived Periconia sp. (strain G1144).
Studies on an organic extract of a marine fungus, Periconia sp. (strain G1144), led to the isolation of three halogenated cyclopentenes along with the known and recently reported rhytidhyester D; a series of spectrometric and spectroscopic techniques were used to elucidate these structures. Interestingly, two of these compounds represent tri-halogenated cyclopentene derivatives, which have been observed only rarely from Nature. The relative and absolute configurations of the compounds were established via mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, Mosher's esters method, optical rotation and GIAO NMR calculations, including correlation coefficient calculations and the use of both DP4+ and dJ DP4 analyses. Several of the isolated compounds were tested for activity in anti-parasitic, antimicrobial, quorum sensing inhibition, and cytotoxicity assays and were shown to be inactive.


Lessons for Patient Education Around Long-Acting Injectable PrEP: Findings from a Mixed-Method Study of Phase II Trial Participants.
This study aimed to identify patients' physical and psychosocial experiences of an investigational long-acting injectable PrEP product to aid in the development of patient and provider education materials. Twenty-eight participants of a Phase 2 safety, tolerability, and acceptability study of long-acting integrase inhibitor cabotegravir (CAB-LA) were interviewed on their physical and psychosocial experiences of the injections. Five themes emerged through a framework analysis on these interview transcripts: (1) injection-related pain is highly variable across individuals; (2) pain is more impactful after the injections than during; (3) patient anxiety is critical, but does not determine the experience of injections and decreases over time; (4) intimacy and awkwardness of gluteal injections impacts patients' experiences; (5) patient education and care strategies can mitigate the above factors. These findings can inform further sociobehavioral research within Phase 3 efficacy trials of CAB-LA, as well as patient education and provider guidance for future injectable PrEP products.


Changes in vasoactive intestinal peptide and arginine vasopressin expression in the suprachiasmatic nucleus of the rat brain following footshock stress.
The neuropeptides, arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are synthesized by neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus and are important regulators of SCN function. Previous studies have demonstrated that acute exposure to stressors can disrupt circadian activity rhythms, suggesting the possibility of stress-related alterations in the expression of these neuropeptides within SCN neurons. In this study, we examined the effect of intermittent footshock stress on AVP mRNA and heterogeneous nuclear RNA (hnRNA) and VIP mRNA expression in neurons of the SCN. Young adult male Sprague/Dawley rats were subjected to 15 s of scrambled intermittent footshock (0.50 mA pulses, 1 pulse/s, 300 ms duration) every 5 min for 30 min. Animals were sacrificed 75 or 135 min after the onset of stress and brains examined for AVP mRNA and hnRNA, and VIP mRNA using in situ hybridization. Footshock stress increased AVP hnRNA levels at the 75 min time point whereas AVP mRNA was elevated at both the 75 and 135 min time points. In contrast, footshock stress decreased the number of cells expressing VIP mRNA in the SCN without changing hybridization level per cell. These data indicate that the disruptive effect of stress on activity rhythms correlate with alterations in the expression of regulatory peptides within the SCN.


Solid-state photochemistry of molecular photo-switchable species: the role of photocrystallographic techniques.
Over the last 30 years, the single-crystal photocrystallographic technique has been developed to determine the three-dimensional crystal and molecular structures of metastable species which have been generated in the crystal photochemically. Transition-metal complexes that have been investigated using this methodology include complexes that contain nitrosyl, dinitrogen, sulfur dioxide and nitrite ligands, all of which form new linkage isomers in the solid state when photoactivated by light of the appropriate wavelength. Both steric and electronic factors determine the level of the conversion from the ground-state structure to the metastable isomeric structure, and both the `reaction cavity' size and the nature of the intermolecular interactions are shown to be among the key factors that influence the percentage conversion.