Mortality reduction of cardiac resynchronization and implantable cardioverter-defibrillator therapy in heart failure: an updated meta-analysis. Does recent evidence change the standard of care?
The recent publication of the MADIT-CRT and RAFT trials has more than doubled the number of patients in which a direct comparison of the combination of cardiac resynchronization therapy (CRT) and implantable cardioverter-defibrillator (ICD) versus ICD alone was carried out. The present meta-analysis aims to assess the impact of combined CRT and ICD therapy on survival of heart failure (HF) patients. Medline, Embase, and the Cochrane Library databases were searched, and all randomized controlled trials of CRT alone or combined with ICDs in HF resulting from left ventricular systolic dysfunction were included. Main outcome was all-cause mortality. Summary relative risk (RR) and 95% confidence interval (CI) were calculated employing random-effects models. Twelve studies were included, with a total of 8,284 randomized patients. For the comparison of CRT alone versus medical therapy, pooled analysis of 5 available trials demonstrated a significant reduction in all-cause mortality with CRT (RR 0.76, 95% CI: 0.64-0.9). Pooled analysis of 6 trials that compared the combination of CRT and ICD therapy to ICD alone also showed a statistically significant reduction in all-cause mortality (RR 0.83, 95% CI: 0.72-0.96). Stratified analysis showed significant mortality reductions in all New York Heart Association class subgroups, with greater effect in classes III-IV (RR 0.70; 95% CI: 0.57-0.88). Pooled estimates of implant-related risks were 0.6% for death and 8% for implant failure. Combined CRT and ICD therapy reduces overall mortality in HF patients when compared with ICD alone.


Hemispheric differences in frequency dependent dipole orientation of the human auditory evoked field component N100m.
Auditory evoked fields (AEF) of 19 healthy male subjects were recorded bilaterally with a Philips 31 -channel biomagnetometer, using two conditions of stimulation (1000 vs. 5000 Hz tones). The N100m latency was characterized by a single moving dipole for each condition and hemisphere using a boundary element model (BEM) as volume conductor. While the right hemispheric dipole orientations and locations did not change with respect to condition, the left hemispheric dipoles differed significantly between the 1000 and 5000 Hz tones, especially in dipole orientation. The left hemispheric dipoles were orientated on average 10.8 degrees more vertically for the 5000 Hz condition. This result points to interhemispheric differences on the level of sensory processing.


A Genomic Perspective on the Near-term Impact of Doxycycline Post-exposure Prophylaxis on Neisseria gonorrhoeae Antimicrobial Resistance.
Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits the effectiveness of post-exposure prophylaxis (PEP) with doxycycline against gonorrhea, and selection for tetracycline resistance may influence prevalence of multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from N. gonorrhoeae, we assessed the near-term impact of doxycycline PEP on N. gonorrhoeae resistance.


Lower prostate specific antigen outcome than expected following radical prostatectomy in patients with high grade prostate and a prostatic specific antigen level of 4 ng/ml. Or less.
We report the estimates of 10-year prostate specific antigen (PSA) outcome following radical prostatectomy in patients with or without grade 4 or 5 disease in the needle biopsy or prostatectomy specimen stratified by the presenting PSA level. From 1989 to 2001, 2,254 patients treated with radical prostatectomy for clinically localized prostate cancer comprised the study cohort. PSA outcome was estimated using the actuarial method of Kaplan and Meier, and was stratified by the presenting PSA level and needle biopsy and prostatectomy Gleason score. The 10-year estimates of PSA outcome declined significantly (p </=0.002) for patients with biopsy or prostatectomy Gleason score 6 or less as the presenting PSA level increased. This trend was observed for biopsy and prostatectomy Gleason score 7 or higher except for the PSA 4 or less group which did significantly worse (46% versus 62%, p = 0.03) compared to the PSA greater than 4 to 10 ng./ml. group. This finding may be explained by a low serum free testosterone level and the presence of a significantly higher proportion of prostatectomy Gleason score 8 to 10 disease (25% versus 16%, p = 0.03) in the PSA 4 or less versus greater than 4 to 10 ng./ml. group. Patients with Gleason grade 4 or 5 disease in the radical prostatectomy specimen and a presenting PSA of 4 ng./ml. or less may be androgen deficient and have a significantly lower estimate of 10-year PSA outcome then expected based on the presenting PSA level.


Echocardiographic assessment of anomalous origin of the left coronary artery from the pulmonary artery.
Transthoracic echocardiography of a 4-month-old boy with heart failure revealed poor left ventricular contractility with severe mitral regurgitation. Deformation analysis revealed significantly decreased circumferential strain in the anterior and anteroseptal segments. Furthermore, post-systolic shortening was evident in the anterior and lateral segments. The pulmonary arterial short-axis view showed that the left coronary artery originated from the pulmonary artery and color Doppler flow mapping showed retrograde flow in the left coronary artery. These findings were quite helpful for concluding the anomalous origin of the left coronary artery from the pulmonary artery.


A simple and efficient genetic transformation system for soybean (Glycine max (L.) Merrill) targeting apical meristem of modified half-seed explant.
The present study is an attempt to establish a fast, highly reproducible transformation with a simplified regeneration system in soybean targeting the apical meristem. The modified half-seed explants from soybean cultivar (cv.) JS335 were subjected to different time intervals of sonication (0, 1, 10, 20, and 30 min) and vacuum infiltration (0, 1, 10, 20, and 30 min) in the presence of Agrobacterium tumefaciens strain EHA105 harbouring pCAMBIA1301. The explants were then co-cultivated and subjected to a modified plant regeneration process that involves only two steps (1) primary shoot regeneration, and (2) in vitro rooting of primary shoot. The rooted plantlets were hardened and maintained in the greenhouse until maturity. Sonication treatment of 10 min, followed by plant regeneration using a modified method, recorded the highest transformation efficiency of 26.3% compared to other time duration tested. Furthermore, 10 min of vacuum infiltration alone resulted in even higher transformation efficiency after regeneration, reaching 28.0%. Interestingly, coupling sonication and vacuum infiltration for 10 min respectively produced the highest transformation efficiency after regeneration of 38.0%. The putative transformants showed gus expression in mature leaves, trifoliate leaves, flowers, and pods. The presence of hpt II was also confirmed in putative transformants, with an amplicon size of 500 bp. Quantitative real-time PCR confirmed the existence of hpt II as one to two copies in the soybean genome of T0 plants. Furthermore, the segregation pattern was observed in the T1 generation soybean plants which were confirmed using PCR for hpt II. The optimized protocol when tested with other Indian soybean cultivars showed an enhanced transformation efficiency ranging from 19.3% (cv. MAUS47) to 36.5% (cv. CO1). This optimized protocol could provide a reliable platform to overcome the challenges that are associated with the genetic engineering of soybean. The online version contains supplementary material available at 10.1007/s13205-023-03715-8.


Prevention of carcinomatosis and bloody malignant ascites in the rat by an inhibitor of angiogenesis.
It has previously been shown that protamine sulfate is an angiogenesis inhibitor. Regional infusion of protamine into the peritoneal cavity is now reported to prevent the growth of intraperitoneal vascularized tumor masses in rats. Walker 256 carcinoma was implanted directly into the liver or into the peritoneal cavity of rats. Hepatic implants grew in the liver with metastases to the wound and mesentery. Injected tumor cells grew as solid tumor masses in the mesentery. Bloody ascites developed after 7 days. Animals received an intraperitoneal infusion of protamine or saline. Protamine significantly inhibited growth of solid tumors in the mesentery (P less than 0.001). Histology showed tumor cells growing only in monolayer but without vascularization. Ascites was not bloody. In saline-treated animals large vascularized tumors grew in the peritoneal cavity and ascites became bloody.


Sustainable Conversion of Microplastics to Methane with Ultrahigh Selectivity by a Biotic-Abiotic Hybrid Photocatalytic System.
Efficient conversion of microplastics into fuels provides a promising strategy to alleviate environmental pollution and the energy crisis. However, the conventional processes are challenged by low product selectivity and potential secondary pollution. Herein, a biotic-abiotic photocatalytic system is designed by assembling Methanosarcina barkeri (M. b) and carbon dot-functionalized polymeric carbon nitrides (CDPCN), by which biodegradable microplastics-poly(lactic acid) after heat pretreatment can be converted into CH4 for five successive 24-day cycles with nearly 100 % CH4 selectivity by the assistance of additional CO2 . Mechanistic analyses showed that both photooxidation and photoreduction methanogenesis worked simultaneously via the fully utilizing photogenerated holes and electrons without chemical sacrificial quenchers. Further research validated the real-world applicability of M. b-CDPCN for non-biodegradable microplastic-to-CH4 conversion, offering a new avenue for engineering the plastic reuse.


Morphological change and mobility enhancement in PEDOT:PSS by adding co-solvents.
Adding ethylene glycol (EG) to a poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) solution improves the crystallinity of the PEDOT and the ordering of the PEDOT nanocrystals in solid films. The carrier-mobility enhancement is confirmed by using ion-gel transistors combined with in situ UV-vis-NIR spectroscopy.


Single-walled carbon nanotubes induce cell death and transcription of TNF-α in macrophages without affecting nitric oxide production.
Single-walled carbon nanotubes (SWCNTs) are potent nanomaterials that have diverse shapes and features. The utilization of these molecules for drug delivery is being investigated; thus, it is important to determine whether they alter immune responses against pathogens. In this study, we show that macrophages treated with a mixture of lipopolysaccharide and SWCNTs produced normal levels of nitric oxide and inducible nitric oxide synthase mRNA. However, these treatments induced cell death, presumably via necrosis. In addition, treating cells with SWCNTs induced the expression of tumor necrosis factor-α mRNA, a potent pro-inflammatory cytokine. These results suggest that SWCNTs may influence immune responses, which could result in unexpected effects following their administration for the purpose of drug delivery.


Structural modelling and thermostability of a serine protease inhibitor belonging to the Kunitz-BPTI family from the Rhipicephalus microplus tick.
rBmTI-A is a recombinant serine protease inhibitor that belongs to the Kunitz-BPTI family and that was cloned from Rhipicephalus microplus tick. rBmTI-A has inhibitory activities on bovine trypsin, human plasma kallikrein, human neutrophil elastase and plasmin with dissociation constants in nM range. It is characterized by two inhibitory domains and each domain presents six cysteines that form three disulfide bonds, which contribute to the high stability of its structure. Previous studies suggest that serine protease inhibitor rBmTI-A has a protective potential against pulmonary emphysema in mice and anti-inflammatory potential. Besides that, rBmTI-A presented a potent inhibitory activity against in vitro vessel formation. In this study, the tertiary structure of rBmTI-A was modeled. The structure stabilization was evaluated by molecular dynamics analysis. Circular dichroism spectroscopy data corroborated the secondary structure found by the homology modelling. Also, in circular dichroism data it was shown a thermostability of rBmTI-A until approximately 70 °C, corroborated by inhibitory assays toward trypsin.


Genetic mapping and prediction for novel lesion mimic in maize demonstrates quantitative effects from genetic background, environment and epistasis.
A novel locus was discovered on chromosome 7 associated with a lesion mimic in maize; this lesion mimic had a quantitative and heritable phenotype and was predicted better via subset genomic markers than whole genome markers across diverse environments. Lesion mimics are a phenotype of leaf micro-spotting in maize (Zea mays L.), which can be early signs of biotic or abiotic stresses. Dissecting its inheritance is helpful to understand how these loci behave across different genetic backgrounds. Here, 538 maize recombinant inbred lines (RILs) segregating for a novel lesion mimic were quantitatively phenotyped in Georgia, Texas, and Wisconsin. These RILs were derived from three bi-parental crosses using a tropical pollinator (Tx773) as the common parent crossed with three inbreds (LH195, LH82, and PB80). While this lesion mimic was heritable across three environments based on phenotypic ([Formula: see text] = 0.68) and genomic ([Formula: see text] = 0.91) data, transgressive segregation was observed. A genome-wide association study identified a single novel locus on chromosome 7 (at 70.6 Mb) also covered by a quantitative trait locus interval (69.3-71.0 Mb), explaining 11-15% of the variation, depending on the environment. One candidate gene identified in this region, Zm00001eb308070, is related to the abscisic acid pathway involving in cell death. Genomic predictions were applied to genome-wide markers (39,611 markers) contrasted with a marker subset (51 markers). Population structure explained more variation than environment in genomic prediction, but other substantial genetic background effects were additionally detected. Subset markers explained substantially less genetic variation (24.9%) for the lesion mimic than whole genome markers (55.4%) in the model, yet predicted the lesion mimic better (0.56-0.66 vs. 0.26-0.29). These results indicate this lesion mimic phenotype was less affected by environment than by epistasis and genetic background effects, which explain its transgressive segregation.


Communication in a disaster: success of text messages.
Text messages on cell phones got through when other communication was out--as it has in other disasters. Governments, companies, and individuals should build on this success for future emergencies.


Negative impact of severity of pain on mood, social life and general activity in Parkinson's disease.
Pain is an important non-motor symptom of Parkinson's disease (PD); however, it remains understudied. The purpose of previous studies on the relationship between PD and pain, has been to explore the cause, origin and types of pain. This case control study is designed for clinicians and rehabilitation specialists to effectively identify pain from the patient's point of view. Pain present in PD patients correlates with significant disruption to their daily lives, which was seen by analysing characteristics, frequency, severity and interference of pain. A total of 100 PD patients and 100 control healthy individuals, consisting of 66 males and 34 females were evaluated during routine clinical assessment followed by a neurological exam. The Brief Pain Inventory (BPI) was used to measure chronic pain in terms of pain severity, pain interference and pain frequency between the two groups. It was determined that PD patients had significantly higher pain severity scores compared to controls (p < 0.05). PD patients with depressive symptoms had significantly higher pain severity and pain interference scores than controls without depressive symptoms. PD patients reported greater scores on Global BPI pain interference and all components of the pain interference subscale. PD and depression seem to be correlated with higher perceived pain, severity and interference. These findings have not been reported by other case control studies, and warrant further causal research into pain, depression and PD.


Discharge clinical characteristics and 60-day readmission in patients hospitalized with heart failure.
Heart failure is a clinical syndrome that incurs a high prevalence, mortality, morbidity, and economic burden in our society. Patients with heart failure may experience hospitalization because of an acute exacerbation of their condition. Recurrent hospitalizations soon after discharge are an unfortunate occurrence in this patient population. The purpose of this study was to explore the clinical and diagnostic characteristics of individuals hospitalized with a primary diagnosis of heart failure at the time of discharge and to compare the association of these indicators in individuals who did and did not experience a heart failure hospitalization within 60 days of the index stay. The study is a descriptive, correlational, quantitative study using a retrospective review of 134 individuals discharged with a primary diagnosis of heart failure. Records were reviewed for sociodemographic characteristics, health histories, clinical assessment findings, and diagnostic information. Significant predictors of 60-day heart failure readmissions were dyspnea (β = 0.579), crackles (β = 1.688), and assistance with activities of daily living (β = 2.328), independent of age, gender, and multiple other factors. By using hierarchical logistical regression, a model was derived that demonstrated the ability to correctly classify 77.4% of the cohort, 78.2% of those who did have a readmission (sensitivity of the prediction), and 76.7% of the subjects in whom the predicted event, readmission, did not occur (specificity of the prediction). Hospitalizations for heart failure are markers of clinical instability. Future events after hospitalization are common in this patient population, and this study provides a novel understanding of clinical characteristics at the time of discharge that are associated with future outcomes, specifically 60-day heart failure readmissions. A consideration of these characteristics provides an additional perspective to guide clinical decision making and the evaluation of discharge readiness.


Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model.
Experimental fluid-percussion models produce brain injury by rapidly injecting saline into the closed cranium. In the present study we characterize the physiological, histopathological and neurological responses to mechanical brain injury in the rat produced by lateral fluid-percussion injury of graded severity. Physiological experiments (n = 105) demonstrated that all levels of injury produced an acute and transient systemic hypertension and bradycardia. Acute hypertension followed by significant hypotension occurred at higher magnitudes of injury. Post-injury suppression of electroencephalographic amplitude was related to the severity of injury. An increase in slow wave (delta/theta) electroencephalographic activity with a concomitant decrease in alpha/beta electroencephalographic activity were observed only at moderate and high magnitude of injury and were correlated with a worsened neurological outcome (r = 0.84; P less than 0.05) and increased mortality (r = 0.66; P less than 0.05). Alterations in brainstem auditory-evoked potentials were also observed only at the higher levels of injury. Histopathological analysis revealed that the extent of post-injury hemorrhage, cavitation and vascular disruption (as measured by extravasation of Evans Blue dye) was greater at the higher magnitudes of injury. Neurological scoring performed over a 4-week post-injury period demonstrated that lateral fluid-percussion brain injury produces a chronic neurological deficit that is directly related to the severity of injury. Survival was also significantly reduced at the higher magnitudes of injury. These data demonstrate that the lateral model of fluid-percussion injury in the rat reproduces many of the features of head injury observed in other models and species and may therefore be a useful experimental model for the study of the pathophysiology of traumatic brain injury.


How does green credit affect carbon emissions in China? A theoretical analysis framework and empirical study.
As an important part of China's green finance, green credit is regarded as an important tool to promote China's transformation to a low-carbon economy. In order to clarify the mechanism of green credit on carbon emissions, this paper puts forward a theoretical analysis framework including "functional attributes - micro subject response - key influencing factors" from the macro and micro perspectives. We select the panel data of 30 provinces in China from 2005 to 2019 for an empirical test and identify the action paths of green credit on carbon emission based on the mediating effect model. Further, we consider the special mechanism of "signal formation" and test it based on the dynamic panel threshold model. The results show that: (1) China's green credit mainly inhibits carbon emissions through three paths: industrial structure, energy structure and energy intensity. (2) There is a signal formation mechanism for the impact of green credit on carbon emissions, which mainly acts on the two action paths of industrial structure and energy intensity. (3) The signal formation mechanism is heterogeneous in each province. According to the empirical results, we divide the provinces into three echelons and propose corresponding suggestions.


Non-Surgical Rhinoplasty: The Ascending Technique and a 14-Year Retrospective Study of 2130 Cases.
Non-surgical rhinoplasty or liquid/filler rhinoplasty is one of the fastest-growing cosmetic procedures worldwide. While several papers have been published on this topic, there has been no standardization of the technique. Most techniques advise injection in a top-down manner, similar to a traditional rhinoplasty. We present our ascending technique performed in 2130 cases. This constitutes one of the largest series published on this subject. Patient records were retrospectively analysed from 2006 to 2019. All patients were injected with hyaluronic acid fillers. We employed an ascending approach which consisted of four sites: nasal tip, columellar base, dorsum (including supratip) and radix. The tip was first set at the appropriate projection and rotation and then the dorsum adjusted to meet it. Since 2006, 2130 patients underwent non-surgical rhinoplasty; 2023 patients were female (95%), and 107 were male (5%). The proportions by site injected were tip 95%, columella 58%, dorsum 83%, radix 62%. Sixty-two percent (1321) repeated the procedure after 1 year. Two percent of patients had persistent tip redness which recovered. There was no skin necrosis or ocular complications. In non-surgical rhinoplasty, all modifications are being done by pure addition, unlike surgical rhinoplasty. In this scenario, the risk of over-projecting the tip is higher. Hence, we believe it is important to set the tip at the desired projection and size and then raise the dorsum accordingly to match. Our high satisfaction rate over 2130 patients validates the efficacy of this ascending technique. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors - www.springer.com/00266 .


[Stability of bituminous-salt mass-washing sarin, soman, and Russian VX destruction products in the aquatic environment and their effects of the sanitary conditions of water supplies].
The water environmental stability of O-isopropylmethyl phosphonate, O-pinacolylmethyl phosphonate, and O-isobutylmethyl phosphonate was studied. The very high hydrolytic stability of these products was established. The threshold and non-effective concentrations of O-isopropylmethyl phosphonate, O-pinacolylmethyl phosphonate, and O-isobutylmethyl phosphonate were determined, which affected the sanitary conditions of water bodies.


Benign lymphoepithelial lesion associated with squamous cell carcinoma of the skin: an immunohistochemical and molecular genetic study.
Benign lymphoepithelial lesions (BLEL) are usually found in salivary glands in autoimmune disorders. Some LEL are recognized to already be, or may progress to become, lymphomas. Skin lesions similar to LEL have been described in lymphomas, and are caused by neoplastic lymphocytes which infiltrate adnexal structures. To date, BLEL have not widely been recognized in the skin. We describe skin lesions similar to BLELs, at the periphery of squamous cell carcinomas (SCC) in 8 healthy patients, in one of whom the lesion recurred. Immunocharacterization of both epithelial and lymphocytic components and molecular genetic investigation was performed. Polymerase chain reaction (PCR) analysis was done to detect IgH chain gene, and T-cell receptor beta and gamma gene rearrangements. Association with Epstein-Barr virus (EBV) was also tested by in situ hybridization (ISH) for EBV-encoded RNAs (EBERs). Epithelial cells showed the immunophenotype of eccrine sweat gland ducts. Infiltrating lymphocytes expressed overwhelming B antigens and CD5. Neither clonal B and/or T proliferations nor EBERs signals were demonstrable. We observed skin lesions similar to BLELs, showing modifications of sweat gland duct and CD5+, B lymphocytic expansion. In our cases there were no associated autoimmune disorders; the local immunoresponse to SCC might have caused BLEL.


1H-MRS can monitor metabolites changes of lateral intraventricular BDNF infusion into a mouse model of Alzheimer's disease in vivo.
Proton magnetic resonance spectroscopy (1H-MRS) can provide noninvasive detection of brain metabolite changes in vivo in Alzheimer's disease (AD). AD is a prevalent neurodegenerative disorder characterized by deposition of β-amyloid peptides (Aβ) in multiple brain regions. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose level has been shown to be decreased in AD. BDNF supplementation can offer improvement in AD. However, the means of evaluation are still relatively limited. In the present study, 1H-MRS was applied to evaluate the therapeutic effects of bilateral intraventricular BDNF infusion into APP+PS1 (amyloid precursor protein+presenilin 1) transgenic mice. For comparison to the 1H-MRS changes in the prefrontal cortex, Morris water maze (MWM) test, Fluoro-Jade B staining and immunofluorescence for Aβ, glial fibrillary acidic protein and tropomyosin-related kinase B (TrkB) were also performed. Our results showed that N-acetylaspartate (NAA) levels increased and myo-inositol levels decreased in Tg-BDNF mice compared with Tg-PBS mice. But NAA level in Tg-BDNF mice was still lower than that in wild-type mice at 6weeks after infusion. These changes correlated with increased immunoreactivity of TrkB, reduced compact Aβ peptide and FJB+ neurons in Tg-BDNF mice compared to Tg-PBS mice. However, Tg-BDNF mice did not present obvious changes in behavior in the MWM. Taken together, we suggest that 1H-MRS may be a sensitive means of evaluating metabolic changes in response to therapeutic strategies in AD. Moreover, BDNF, may be a viable means of offering trophic support during disease.


Triac regulation of transcription is T(3) receptor isoform- and response element-specific.
3,5,3'-triiodothyroacetic acid (Triac) is a naturally occurring triiodothyronine (T(3)) analog, which has been used on an empirical basis to treat the syndrome of resistance to thyroid hormone (RTH). The aim of our studies was to compare the effects of Triac and T(3) on negative and positive thyroid hormone response elements (TREs). We used transient transfections with luciferase reporter genes to show that on palindromic, inverted palindrome and human TRH reporters, Triac is more potent than T(3) for transcriptional regulation by TRbeta1 and TRbeta2 isoforms, while regulation by TRalpha1 is equivalent for both ligands. Other TREs (direct repeat, hTSHalpha and hTSHbeta) are not regulated differently by Triac and T(3). Dose-response curves show that the difference between Triac and T(3) is maximal in the 1-10 nM range. Receptor-binding studies reveal a greater affinity of Triac than T(3) for TRbeta1 and TRbeta2 isoforms, which could explain its isoform-specific effects. These data suggest that the TRE- and TR isoform-specific effects of Triac favor its use in RTH.


Time from symptoms onset to remdesivir is associated with the risk of ICU admission: a multicentric analyses.
Shorter duration of symptoms before remdesivir has been associated with better outcomes. Our goal was to evaluate variables associated with the need of ICU admission in a cohort of hospitalized patients for COVID-19 under remdesivir including the period from symptoms onset to remdesivir. We conducted a retrospective multicentric study analysing all patients admitted with COVID-19 in 9 Spanish hospitals who received treatment with remdesivir in October 2020. The main outcome was the need of ICU admission after 24 h of the first dose of remdesivir. In our cohort of 497 patients, the median of days from symptom onset to remdesivir was 5 days, and 70 of them (14.1%) were later admitted into ICU. The clinical outcomes associated with ICU admission were days from symptoms onset (5 vs. 6; p = 0.023), clinical signs of severe disease (respiratory rate, neutrophil count, ferritin levels and very-high mortality rate in SEIMC-Score) and the use of corticosteroids and anti-inflammatory drugs before ICU. The only variable significatively associated with risk reduction in the Cox-regression analyses was ≤ 5 days from symptoms onset to RDV (HR: 0.54, CI95%: 0.31-0.92; p = 0.024). For patients admitted to the hospital with COVID-19, the prescription of remdesivir within 5 days from symptoms onset diminishes the need of ICU admission.


The role of constructed meaning in adaptation to the onset of life-threatening illness.
Do the meanings inherent within a traumatic life event increase our understanding of differential mental health outcomes? In light of this question two central issues are addressed in this article: (1) what variables influence the meaning that is constructed in response to a crisis, and (2) how does this meaning affect the self and ultimately the adaptation/mental health outcome as indicated by the level of emotional distress? A theoretical model is evaluated via a comparative analysis that incorporates the data of 76 persons with cancer and 130 persons with HIV/AIDS. Three primary findings support this model and the significance of the role of meaning in response to a crisis: (1) the meaning constructed in response to a crisis can be operationalized and its role evaluated as a dimension of the adaptation process, (2) evidence indicates constructed meaning affects self-perception, which subsequently affects adaptation, and (3) the pattern of effects does not differ by illness type since analyses indicate meaning is central to individuals' responses regardless of differences in characteristics of the event.


The microvascular endothelial glycocalyx: An additional piece of the puzzle in veterinary medicine.
The endothelial glycocalyx (eGlx) is a critically important structure lining the luminal surface of endothelial cells. There is increasing evidence, in human patients and animal models, for its crucial role in the maintenance of health. Moreover, its damage is associated with the pathogenesis of multiple disease states. This review provides readers with an overview of the eGlx; summarising its structure, essential functions, and evidence for its role in disease. We highlight the lack of studies regarding the eGlx in cats and dogs, particularly in naturally occurring diseases. Importantly, we discuss techniques to aid its study, which can be applied to veterinary species. Finally, we present targeted therapies aimed at preserving, and in some cases, restoring damaged eGlx.


Evaluation of right atrial function using right atrial speckle tracking analysis in patients with pulmonary artery hypertension.
In patients with pulmonary artery hypertension (PAH), right ventricular pressure overload eventually causes right heart failure (RHF), leading to a poor prognosis. Right atrial (RA) overload and RA dysfunction occur in patients with PAH-complicated RHF. We evaluated RA function using right atrial longitudinal strain (RALS) by two-dimensional speckle tracking echocardiography (2D-STE) and investigated the association between RALS and the severity of RHF in patients with pulmonary artery hypertension (PAH) noninvasively. We performed 2D-STE in 56 PAH patients and 20 normal control subjects. The peak global RALS and peak global RA longitudinal strain rate (RALSR) were analyzed by 2D-STE. Simultaneous right heart catheterization was performed to determine the right atrial pressure (RAP) and cardiac index (CI). Peak global RALS (34.6 ± 14.1 vs. 58.3 ± 9.9%, p < 0.0001) and peak global RALSR (2.5 ± 1.3 vs. 3.1 ± 1.2 s(-1), p < 0.0001) were significantly lower in PAH patients compared with normal controls. There was a significant negative correlation between peak global RALS and RAP (r = -0.8037, p < 0.0001). There was a significant positive correlation between peak global RALS and CI (r = 0.8179, p < 0.0001). Peak global RALSR was also correlated with RAP (r = -0.7308, p < 0.0001) and CI (r = 0.7596, p < 0.0001). RALS and RALSR by 2D-STE were useful for noninvasive evaluation of RA dysfunction and the severity of RHF in patients with PAH.


Spontaneous and rapid reexpression of functional CXCR4 by human steady-state peripheral blood CD34+ cells.
Although only 5% of steady-state peripheral blood (PB) CD34+ cells were found to express chemokine receptor CXCR4, 45% of the cells became CXCR4+ after incubation at 37 degrees C for 4 hours. In contrast, there were no remarkable differences between PB CD34+ cells before and after the 37 degrees C incubation in their expression of selectin ligand, VLA-4, and VLA-5 or in their affinity for VCAM-1 or fibronectin. This increase in CXCR4 expression level was inhibited by the addition of brefeldin A, actinomycin D, or cycloheximide. When PB CD34+ cells with CXCR4 expression levels enhanced by a 4-hour preincubation at 37 degrees C or bone marrow (BM) CD34+ cells were exposed overnight to stromal cell-derived factor 1 (SDF-1), the expression levels of CXCR4 were greatly reduced, and when SDF-1 was removed, CXCR4 levels were thereafter up-regulated. The reexpressed CXCR4 was able to elicit integrin-dependent migration of hematopoietic progenitor cells. There was no difference in the severe combined immunodeficient mouse repopulating cell activity between PB CD34+ cells with and cells without a 37 degrees C preincubation.


Virtual landscape-scale restoration of altered channels helps us understand the extent of impacts to guide future ecosystem management.
Human modification of hydrological connectivity of landscapes has had significant consequences on ecosystem functioning. Artificial drainage practices have fundamentally altered northern landscapes, yet these man made channels are rarely considered in ecosystem management. To better understand the effects of drainage ditches, we conducted a landscape-scale analysis across eleven selected study regions in Sweden. We implemented a unique approach by backfilling ditches in the current digital elevation model to recreate the prehistoric landscape, thus quantifying and characterizing the channel networks of prehistoric (natural) and current (drained) landscapes. Our analysis detected that 58% of the prehistoric natural channels had been converted to ditches. Even more striking was that the average channel density increased from 1.33 km km-2 in the prehistoric landscape to 4.66 km km-2 in the current landscape, indicating the extent of ditching activities in the northern regions. These results highlight that man-made ditches should be accurately mapped across northern landscapes to enable more informed decisions in ecosystem management.


Ego development and sex attitudes in heterosexual and homosexual men and women.
A comparison was made of heterosexual and homosexual men and women utilizing Loevinger's concept of ego development and focusing on the relationships among ego levels and attitudes toward homosexuality and on personal sex guilt and other sociosexual variables. Previous comparative studies were critically analyzed with respect to the adequacy of definition and description of sampling procedures, and the appropriateness of research question. A pilot study reported here concerns the development of a measure of "attitudes toward homosexuality." The major study utilized 200 subjects who completed an anonymous and lengthy questionnaire. This sample was relatively young, well-educated, white, and Protestant. Self-ratings on the two Kinsey-type scales clearly differentiated the self-identified primarily heterosexual and homosexual groups. In this study there were no significant differences in ego levels between the heterosexual and the homosexual groups, suggesting that ego development and sexual orientation development are independent phenomena. Among both homosexual and heterosexual subjects there were low but significant correlations between higher levels of ego development and more positive attitudes toward homosexuality. More negative attitudes toward homosexuality were correlated with higher levels of personal sex guilt for heterosexual and homosexual men and for heterosexual women. Our measure of sex guilt proved to be related to ego level only for heterosexual males, although the measure of this construct requires additional research and refinement. Other correlates of these variables are also reported.


Case management of the anemic patient: epoetin alfa--focus on iron supplementation.
Epoetin alfa stimulates erythropoiesis, thus creating an increased need for iron, and virtually all patients with end-stage renal disease who receive this therapy will eventually require iron supplementation. This article describes the appropriate use of oral and intravenous iron supplementation, including patient assessment, education, and management.


Advances in coupling droplet microfluidics to mass spectrometry.
Droplet microfluidics enables development of workflows with low sample consumption and high throughput. Fluorescence-based assays are most used with droplet microfluidics; however, the requirement of a fluorescent reporter restricts applicability of this approach. The coupling of droplets to mass spectrometry (MS) has enabled selective assays on complex mixtures to broaden the analyte scope. Droplet microfluidics has been interfaced to MS via electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI). The works reviewed herein outline the development of this nascent field as well as initial exploration of its application in biotechnology and bioanalysis, including synthetic biology, reaction development, and in vivo sensing.


Effect of hydrophobization of basic pancreatic proteinase inhibitor on the inhibition of bovine trypsin and human leukocyte elastase.
The effect of modification of basic pancreatic trypsin inhibitor (BPTI) by derivatives of fatty acids (oleic, stearic) on the inhibition of bovine trypsin and human leukocyte elastase (HLE) was studied. Kinetic constants of interaction with trypsin and inhibition constants of both enzymes were determined. Hydrophobization of BPTI had virtually no effect on its high affinity for trypsin. The coupling of cis-unsaturated oleoyl radicals to the inhibitor molecule significantly increased the efficiency of HLE inhibition, whereas the coupling of saturated stearoyl radicals completely canceled the anti-elastase activity and in some cases promoted the substrate hydrolysis.


The influence of waste from electronic cigarettes, conventional cigarettes and heat-not-burn tobacco products on microorganisms.
Tobacco smoking, especially conventional cigarettes, is widespread throughout the world. Simultaneously, there is a growing interest in new alternative products that allow delivering nicotine to the users' organisms, including electronic cigarettes and heat-not-burn tobacco products. However, there are few scientific reports regarding the effect of waste generated from the above-mentioned products on microorganisms. The aim of the manuscript was to investigate the influence of substances leached from conventional cigarette butts, butts from heat-not-burn tobacco products, cartridges and e-liquids for electronic cigarettes on microorganisms. The commercial multispecies MARA (microbial assay for risk assessment) test and non-selected microorganisms from the Brynica River (Poland), as well as an effluent from the wastewater treatment plant (Sosnowiec-Zagórze, Poland), were used in the ecotoxicity assessment of the investigated waste. The results of the experiments revealed that the waste from electronic cigarettes, i.e. cartridges and e-liquids, does not pose a considerable threat to the microbiocenosis. On the other hand, a particularly strong ecotoxic effect on the investigated microorganisms has been reported for leachate from smoked cigarette butts and butts from heat-not-burn tobacco products. Their high ecotoxicity combined with a high supply is worrying and it can require interventions to protect the aquatic environment. The retention of the waste can have an adverse effect on microorganisms in reservoirs surface waters or a sludge activity in wastewater treatment plants.


[The achievement of surgery in the overall therapy plan in Crohn disease].
The analysis of 205 prospectively investigated patients with Crohn's disease under conservative (112) and operative (93) treatment with essentially comparable distribution of age and duration of the disease resulted in a significantly better outcome of the operated patients judging by the time free of recurrencies and the frequency of recurrencies for the localisation of ileocolitis and colitis. In ileitis, however, the results are nearly equal for both groups. The results warrant a more liberal indication for operation especially in those patients with involved colon.


Mutational analysis of the ABCC6 gene and the proximal ABCC6 gene promoter in German patients with pseudoxanthoma elasticum (PXE).
Pseudoxanthoma elasticum (PXE) is a genetic disorder characterized by calcification of elastic fibers in dermal, ocular, and cardiovascular tissues. Recently, ABCC6 mutations were identified as causing PXE. In this follow-up study we report the investigation of 61 German PXE patients from 53 families, hitherto the largest cohort of German PXE patients screened for the complete ABCC6 gene. In addition, we characterized the proximal ABCC6 promoter of PXE patients according to mutation. In this study we identified 32 disease-causing ABCC6 variants, which had been described previously by us and others, and 10 novel mutations (eight missense mutations and two splice site alterations). The mutation detection rate among index patients was 87.7%. Frequent alterations were the PXE-mutations p.R1141X, Ex23,_Ex29del, and c.2787+1G > T. In the ABCC6 promoter we found the polymorphisms c.-127C > T, c.-132C > T, and c.-219A > C. The difference in the c.-219A > C frequencies between PXE patients and controls were determined as statistically significant. Interestingly, c.-219A > C is located in a transcriptional activator sequence of the ABCC6 promoter and occurred in a binding site for a transcriptional repressor, predominantly found in genes that participate in lipid metabolism. Obtaining these genetic data signifies our contribution to elucidating the pathogenetics of PXE.


High-Columbic-Efficiency Lithium Battery Based on Silicon Particle Materials.
Micro-sized polycrystalline silicon particles were used as anode materials of lithium-ion battery. The columbic efficiency of the first cycle reached a relatively high value of 91.8 % after prelithiation and increased to 99 % in the second cycle. Furthermore, columbic efficiency remained above 99 % for up to 280+ cycles. The excellent performances of the batteries were the results of the use of a proper binder to protect the electrode from cracking and the application of a suitable conductive agent to provide an efficient conductive channel. The good performance was also significantly attributed to the electrolyte in the packaging process.


Visual versus auditory (musical) stimulus preferences in autistic children: a pilot study.
This study investigated perceptual preferences of autistic children comparing responses to auditory musical and visual stimuli. The results indicated a weak preference of autistic children for the auditory musical stimulus, however, without the data approaching statistical significance. The autistic children spent significantly more time with the musical stimulus than the two control groups of normal children, equated by chronological and developmental age, respectively. Implications of these findings for a music therapy treatment concept are discussed.


Extensive analysis of the 13q14 region in human prostate tumors: DNA analysis and quantitative expression of genes lying in the interval of deletion.
Loss of heterozygosity (LOH) on chromosome arm 13q14 is one of the most consistent genetic alterations in sporadic prostate cancer. This alteration may be involved in prostate oncogenesis through inactivation of one or more tumor suppressor genes (TSGs). Candidate gene expression is an approach to focus the search for TSGs in this region. We tested 41 human sporadic prostate tumors for 13q14 LOH by using seven polymorphic markers overlapping the critical region and used a real-time quantitative RT-PCR assay to study the same tumors for expression of the 31 genes located in this genomic region (localized by the Human Genome Project Working Draft). Allelic loss on at least one locus was found in 18 (41%) of the 41 tumor DNAs. Only four genes (ITM2B, CHC1L, KIAA0970, and LOC51131), located in the region most frequently deleted in prostate carcinoma, showed a significant difference in expression between normal and neoplastic prostate tissues. Given their location in the LOH hotspot, as indicated by our genomic analysis, ITM2B, CHC1L, KIAA0970, and LOC51131 are candidate tumor suppressor genes in this region. ITM2B that showed a significant association (P < 0.005) between expression and LOH at the corresponding locus could, furthermore, be the main target of the observed LOH at 13q in prostate tumors.


Which vertebral level should be used to calculate sarcopenia in covid-19 patients? A systematic review and meta-analysis.
Evidence shows that CT-derived sarcopenia can predict adverse outcomes in COVID-19 patients. However, discrepancies exist as to which vertebral level can be used to calculate sarcopenia which can effectively serve as a prognostic tool. Thus, we aim to investigate the difference in sarcopenia calculated at the Thoracic and Lumbar vertebral levels. An online literature search was conducted on Electronic databases such as PubMed, Cochrane CENTRAL, and Google scholar. Meta-analysis was performed by using Revman 5.3 software. A total of 14 articles were selected for meta-analysis. The prevalence of sarcopenia calculated at the Thoracic level was 31% (95%CI 24%-37%; p < 0.00001; I2 = 86%), while sarcopenia calculated at the Lumbar vertebral level was 63% (95%CI 51%-75%; p < 0.00001; I2 = 88%). Meanwhile, sarcopenia calculated at the Upper thoracic level was a significant predictor of mortality OR 3.47 (95%CI 1.74-6.91; p = 0.0004; I2 = 56%)as compared to sarcopenia calculated at the lower thoracic OR 1.74 (95%Cl 0.91-3.33; p = 0.10; I2 = 60%)or lumbar level OR 2.49 (95%CI 0.45-13.72; p = 0.30; I2 = 57%). In addition to this sarcopenia calculated at the Upper thoracic level was also a significant predictor of severe illness OR 3.92 (95%CI 2.33-6.58; p < 0.00001; I2 = 0%) as compared to lower thoracic OR 1.40 (95%CI 0.78-2.53; p = 0.26; I2 = 67%) or lumbar level OR 1.64 (95%CI 0.26-10.50; p = 0.60; I2 = 81%) CONCLUSIONS: Sarcopenia calculated at the thoracic vertebrae and lumber level has different prognostic values. Sarcopenia is prevalent at the lumbar level. Sarcopenia at the thoracic level has a higher mortality and severity rate.


Genetic diversification of acanthocephalans of the genus Floridosentis Ward 1953 (Acanthocephala: Neoechinorhynchidae), parasites of mullets from the Americas.
Adult worms of the genus Floridosentis are endoparasites of marine fishes of the genus Mugil and are broadly distributed in the Americas. Currently, Floridosentis includes two species, F. mugilis, distributed in the Gulf of Mexico and along the Atlantic Ocean coast, and F. pacifica, restricted to the Pacific Ocean coast. The aim of this study was to explore the species limit of both species of the genus Floridosentis, collected in 37 localities in eight countries: Mexico, Guatemala, El Salvador, Honduras, Nicaragua, Costa Rica, Ecuador and Venezuela. We sequenced 253 specimens to build a comprehensive dataset for three genes: the cytochrome c oxidase subunit I (cox 1) from mitochondrial DNA, the internal transcribed spacers ITS1 and ITS2 including the 5.8S gene (ITS region), and the D2 + D3 domains of the large subunit (LSU) of nuclear DNA. Maximum likelihood and Bayesian analyses with the cox 1 and concatenated (cox 1 + ITS+LSU) datasets were conducted. Two species delimitation methods were implemented, the Automatic Barcode Gap Discovery (ABGD), and Bayesian species delimitation (BPP), plus a haplotype network inferred with 253 specimens, allowing us to validate two nominal species of Floridosentis., F. mugilis, plus one linage distributed in the Gulf of Mexico and along the Atlantic Ocean coast, and F. pacifica, plus two additional lineages distributed along the Pacific Ocean coast. All these lineages are shared by both species of mullet (Mugil curema and M. cephalus). The currents in the Atlantic Ocean, Pacific Ocean and Gulf of Mexico, in combination with the biology of the definitive hosts, have played a key role in the distribution of the two nominal species and of the three lineages of Floridosentis across the Americas.


Impact of Genetic Counseling in Women with a Family History of Breast Cancer in Italy.
As the impact of breast cancer (BC) risk assessment in asymptomatic women with a family history of BC had never been explored in Italy, we performed a study on a retrospective series of women who had undergone BC risk assessment. To this aim, a semi-structured telephone interview was administered to 82 women. Most participants considered the information received as clear (96.2 %) and helpful (76.8 %). Thirty-eight (46.3 %) stated that their perceived risk of BC had changed after the counseling: for 40.2 % it had decreased, for 6.1 % increased; however, women highly overestimating their risk at the baseline (≥ 4-fold) failed to show improvements in risk perception accuracy. Sixty-six women (80.5 %) stated they had followed the recommended surveillance, while 19.5 % had not, mainly due to difficulties in arranging examinations. Most women (89.0 %) had shared the information with their relatives, with 57.3 % reporting other family members had undertaken the recommended surveillance. BC risk assessment was associated with high rates of satisfaction and had a favorable impact on risk perception in a subgroup of women. The impact on surveillance adhesion extended to relatives. Organized programs for identification and surveillance may help identify a larger fraction of at-risk women and overcome the reported difficulties in arranging surveillance.


Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues.
Functional nucleic acids can be evolved in vitro using cycles of selection and amplification, starting from diverse-sequence libraries, which are typically restricted to natural or partially-modified polymer chemistries. Here, we describe the efficient DNA-templated synthesis and reverse transcription of libraries entirely composed of serum nuclease resistant alternative nucleic acid chemistries validated in nucleic acid therapeutics; locked nucleic acid (LNA), 2'-O-methyl-RNA (2'OMe-RNA), or mixtures of the two. We evaluate yield and diversity of synthesised libraries and measure the aggregate error rate of a selection cycle. We find that in addition to pure 2'-O-methyl-RNA and LNA, several 2'OMe-RNA/LNA blends seem suitable and promising for discovery of biostable functional nucleic acids for biomedical applications.


Prediction of lymph node metastasis in pancreatic neuroendocrine tumors by contrast enhancement characteristics.
Iso- or hypo-attenuating areas in the arterial phase on contrast-enhanced computed tomography (CE-CT) have been reported to be negative prognostic features in pancreatic neuroendocrine tumors (PNETs). Given that the optimal indication for lymph node dissection in patients with PNET remains unclear, we sought to utilize enhancement characteristics on CE-CT as a preoperative predictor of regional lymph node metastasis in PNETs. The medical records of patients with well-differentiated PNETs who underwent pancreatectomy along with lymphadenectomy were retrospectively analyzed. We divided PNETs into two groups based on the extent of attenuation in the late arterial phase on CE-CT imaging. PNETs that showed hyper-attenuation over the entire area compared to the adjacent normal pancreas were categorized as hyper-PNETs. PNETs that contained both hyper and iso- or hypo-attenuation regions as well as those that showed only iso- or hypo-attenuation over the entire area were categorized as hetero/hypo-PNETs. Forty-one patients with a median age of 64 years were enrolled, including 11 with hyper-PNETs and 30 with hetero/hypo-PNETs. Hetero/hypo-PNETs were significantly larger than hyper-PNETs (P = 0.022), and the former group more frequently comprised G2 tumors, according to the World Health Organization 2010 classification (P < 0.001). On univariate and multivariate analyses, hetero/hypo-PNETs were independently associated with regional lymph node metastasis. The presence of iso- or hypo-attenuating regions appears to be associated with regional lymph node metastasis in PNETs. Tumor enhancement characteristics should be assessed in patients with PNET so as not to miss those at high risk of lymph node metastasis.


The Protective Effect of UBE2G2 Knockdown Against Atherosclerosis in Apolipoprotein E-Deficient Mice and Its Association with miR-204-5p.
Atherosclerosis (AS) is a chronic and progressive inflammatory disease. Ubiquitin-conjugating enzyme E2G 2 (UBE2G2) has been reported to be differentially expressed in subjects with abnormal coronary endothelial function. We intended to further explore the effect of UBE2G2 in AS using apolipoprotein E-deficient (ApoE-/-) mice. Relative UBE2G2 expression in aortic sinus tissues was examined by Real-time reverse transcriptase-polymerase chain reaction and immunohistochemical staining. Atherosclerotic plaque formation was observed through hematoxylin-eosin staining. The protein levels of adhesion biomarkers and inflammatory cytokines was analyzed by western blotting. The direct interaction between UBE2G2 and miR-204-5p was predicted by bioinformatic analysis, and the correlation was analyzed by Pearson's correlation test, and verified by luciferase reporter assay. Human vascular smooth muscle cells (VSMCs) development was detected by 5-ethynyl-2'-deoxyuridine labeling assay and wound healing assays. UBE2G2 was highly expressed in the aortic sinus tissues of high-fat diet-fed ApoE-/- mice. The atherosclerotic plaque formation was increased in ApoE-/- mice, while UBE2G2 knockdown reduced it. Silencing of UBE2G2 also inhibited the expression and protein levels of adhesion biomarkers and inflammatory cytokines in ApoE-/- mice. MiR-204-5p was the upstream effector of UBE2G2 and miR-204-5p overexpression was found to inhibit the proliferation and migration of human VSMCs through regulating UBE2G2 expression. UBE2G2 inhibition attenuated AS in ApoE-/- mice and UBE2G2 expression was negatively regulated by miR-204-5p in human VSMCs.


Simultaneous inhibition of MarR by salicylate and efflux pumps by curcumin sensitizes colistin resistant clinical isolates of Enterobacteriaceae.
Carbapenem resistant Enterobacteriaceae (CRE) infection has been widely treated with last resort antibiotics like colistin. Resistance to colistin has further jeopardized the situation. We have previously reported a combination of MarR inhibitor - salicylate (Sal) and an efflux pump inhibitor (BC1) that successfully restored colistin (Col) sensitivity in multidrug and colistin resistant clinical isolate of E. coli U3790. Since synthetic compounds usually fail during drug development initiatives, we attempted to replace synthetic efflux pump inhibitor (BC1) with plant metabolite as efflux pump inhibitor to restore colistin sensitivity in CRE. Screening 13 plant metabolites, we narrowed on curcumin (CUR) to effectively inhibit efflux in both colistin resistant E. coli U3790 and K. pneumoniae BC936. Combination of Col + CUR showed a remarkable reversal in colistin MIC by 128 fold and 32 fold in E. coli U3790 and K. pneumoniae BC936 respectively. Studies with knock out mutant strains of AcrAB-TolC pump components show that curcumin's efflux inhibition is partly mediated by acrB. Thus, curcumin reduced colistin MIC well below the CLSI breakpoint (<2 μg/ml). Curcumin also exhibited synergy with colistin against most of the clinical isolates of Enterobacteriaceae tested. Efficiency of Col + Sal + CUR was evident in time kill curve analysis, which displayed a 6 log and a 4 log decline in CFU/ml by 24 h in U3790 and BC936 strains respectively. In vivo intramuscular fish infection studies showed that the triad combination reduced the bacterial bioburden of E. coli U3790 by 2.6 log and that of K. pneumoniae BC936 by 1.6 log. Hence, our study shows the efficacy of inhibiting MarR by salicylate and inhibiting efflux pump with curcumin restores colistin sensitivity in colistin resistant Enterobacteriaceae in vitro and in vivo.


Nanoparticles: structure, properties, preparation and behaviour in environmental media.
There is increasing interest and need to develop a deeper understanding of the nature, fate and behaviour of nanoparticles in the environment. This is driven by the increased use of engineered nanoparticles and the increased pressure to commercialise this growing technology. In this review we discuss the key properties of nanoparticles and their preparation and then discuss how these factors can play a role in determining their fate and behaviour in the natural environment. Key focus of the discussion will relate to the surface chemistry of the nanoparticle, which may interact with a range of molecules naturally present in surface waters and sediments. Understanding these factors is a core goal required for understanding the final fate of nanomaterials and predicting which organisms are likely to be exposed to these materials.


Gestationally dependent immune organization at the maternal-fetal interface.
The immune system and placenta have a dynamic relationship across gestation to accommodate fetal growth and development. High-resolution characterization of this maternal-fetal interface is necessary to better understand the immunology of pregnancy and its complications. We developed a single-cell framework to simultaneously immuno-phenotype circulating, endovascular, and tissue-resident cells at the maternal-fetal interface throughout gestation, discriminating maternal and fetal contributions. Our data reveal distinct immune profiles across the endovascular and tissue compartments with tractable dynamics throughout gestation that respond to a systemic immune challenge in a gestationally dependent manner. We uncover a significant role for the innate immune system where phagocytes and neutrophils drive temporal organization of the placenta through remarkably diverse populations, including PD-L1+ subsets having compartmental and early gestational bias. Our approach and accompanying datasets provide a resource for additional investigations into gestational immunology and evoke a more significant role for the innate immune system in establishing the microenvironment of early pregnancy.


Phenox HPC and Phenox flow modulation devices for the endovascular treatment of intracranial aneurysms: a systematic review and meta-analysis.
Surface-modified flow diverters are increasingly used in clinical settings. However, their safety profiles and additional benefits over non-coated devices still need to be explored. In this meta-analysis, we aimed to investigate and compare the clinical outcomes of the uncoated Phenox and coated Phenox HPC flow diverters. A systematic literature review was performed using PubMed, Scopus, Embase, and Web of Science databases. Collected data were pooled and corresponding 95% confidence intervals (CI) were calculated. Outcomes of interest included aneurysm occlusion (>6 months) and complication rates. Additionally, the safety outcomes of prophylactic single (SAPT) and dual antiplatelet treatment (DAPT) approaches were compared for patients treated with coated Phenox HPC flow diverters. We included 17 studies with 1238 patients. The overall complete occlusion rates were 80% (95% CI 74.01% to 86.56%) for Phenox HPC and 71.3% (95% CI 59.71% to 85.20%) for non-coated Phenox flow diverters (p=0.24). Ischemic complication rates were 7.3% (95% CI 4.6% to 11.39%) with the Phenox HPC and 5.3% (95% CI 4.07% to 6.91%) with the Phenox (p=0.24). For patients treated with Phenox HPC, the SAPT (5.5%; 95% CI 2.83% to 10.85%) and DAPT (7.1%; 95% CI 1.23% to 41.45%) approaches resulted in comparable ischemic complication rates (p=0.79). The DAPT group (4.8%; 95% CI 1.46% to 16.24%) had higher hemorrhagic complication rates than the SAPT group (1.7%; 95% CI 0.52% to 6.09%), but the difference was not statistically significant for patients treated with Phenox HPC (p=0.25). Our findings indicate that Phenox HPC is equally as safe and effective as non-coated Phenox devices. Additionally, our results suggest that prasugrel monotherapy might effectively prevent ischemic complications in patients treated with Phenox HPC flow diverters.


Intraocular calcidiol: Uncovering a role for vitamin D in the eye.
Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease. 25-Hydroxyvitamin D3 (25(OH)D3) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D3-generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease. 25(OH)D3 was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D3 concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D3 did not correlate with serum levels of 25(OH)D3. There was no difference between the level of 25(OH)D3 measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001). Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis.


Development of electrophoretically mediated microanalysis method for the kinetics study of flavin-containing monooxygenase in a partially filled capillary.
An electrophoretically mediated microanalysis method with a partial filling technique was developed for flavin-containing monooxygenase, form 3 (FMO3). The in-line enzymatic reaction was performed in 100 mM phosphate reaction buffer (pH 7.4) whereas 150 mM phosphate buffer (pH 3.3) was used as a background electrolyte. A long plug of cofactor NADPH dissolved in reaction buffer was hydrodynamically injected into a fused-silica capillary, followed by enzyme and substrate solution. The reaction was initiated at 37 degrees C in the thermostated part of the cartridge by the application of 9 kV for 0.9 min. The voltage was turned off to increase the product amount (zero-potential amplification) and again turned on at a constant voltage of 10 kV to elute all the components. Direct detection was performed at 191 nm. The developed electrophoretically mediated microanalysis method was applied for the kinetics study of FMO3 using clozapine as a substrate probe. A Michaelis-Menten constant (K(m)) of 410.3 microM was estimated from the corrected peak area of the product, clozapine N-oxide. The calculated value of the maximum reaction velocity (V(max)) was found to be 1.86 nmol/nmol enzyme/min. The acquired FMO3 kinetic parameters are in accordance with the published literature data.


Tuberculosis combined with Burkitt lymphoma in a kidney transplant recipient: A case report and literature review.
Tuberculosis (TB) and post-transplant lymphoproliferative disorder are serious complications affecting the long-term survival of kidney transplant recipients (KTRs). Both of complications have overlapping clinical symptoms, signs, and high similar imaging presentation, which make early clinical diagnosis challenging. In this paper, we reported a rare case of post-transplant pulmonary TB combined with Burkitt lymphoma (BL) in KTR. A 20-year-old female KTR presented to our hospital with abdominal pain and multiple nodules throughout the body. TB is diagnosed based on the lung histopathology showed fibrous connective tissue hyperplasia with number of chronic inflammatory changes, localized necrosis, granuloma formation and multinucleated giant cells were seen in the lung tissue. Moreover, lung histopathology specimen tested positive for TB gene. TB The culture for tuberculosis was positive. BL was diagnosed as metastatic after completion of liver and bone marrow biopsy. After an early diagnosis of TB, the patient received intensification of anti-tubercular therapy. Because the patient was diagnosed with BL, rituximab, cardioprotection, hepatoprotection and alkalinization of urine were added. After an early diagnosis of TB, the patient received anti-tubercular therapy and her clinical symptoms and imaging manifestations improved. After the diagnosis of BL was made, the patient's condition progressed rapidly, followed by multi-organ damage and died 3 months later. Therefore, in organ transplant patients, who present with multiple nodules and normal tumor markers, they should be alerted to the possibility of concurrent TB and post-transplant lymphoproliferative disorder, and perfect tests such as Epstein-Barr virus, β2-microglobulin, lactate dehydrogenase, γ-interferon release test and Xpert Mycobacterium TB/rifampicin test and perform early lesion site biopsy to clarify the diagnosis with a view to improving the prognosis.


TSH Normalization in Bariatric Surgery Patients After the Switch from L-Thyroxine in Tablet to an Oral Liquid Formulation.
Drug malabsorption is one of the potential troubles after bariatric surgery. Evidence for diminished levothyroxine (L-T4) absorption has been reported in patients after bariatric surgery. This study reports 17 cases of hypothyroid patients [who were well replaced with thyroxine tablets (for >1 year) to euthyroid thyrotropin (TSH) levels before surgery (13 Roux-en-Y gastric bypasses (RYGB); 4 biliary pancreatic diversions (BPD))]. From 3 to 8 months after surgery, these patients had elevated TSH levels. Patients were then switched from oral tablets to a liquid L-T4 formulation (with the same dosage, 30 min before breakfast). Two-three months after the switch, TSH was significantly reduced both in patients treated with RYGB, as in those treated with BPD, while FT4 and FT3 levels were not significantly changed (RYGB group, TSH μIU/mL: 7.58 ± 3.07 vs 3.808 ± 1.83, P < 0.001; BPD group, TSH μIU/mL: 8.82 ± 2.76 vs 3.12 ± 1.33, P < 0.01). These results first show that liquid L-T4 could prevent the problem of malabsorption in patients with BPD and confirm those of previous studies in patients submitted to RYGB, suggesting that the L-T4 oral liquid formulation could circumvent malabsorption after bariatric surgery.


Functional connectivity of the world's protected areas.
Global policies call for connecting protected areas (PAs) to conserve the flow of animals and genes across changing landscapes, yet whether global PA networks currently support animal movement-and where connectivity conservation is most critical-remain largely unknown. In this study, we map the functional connectivity of the world's terrestrial PAs and quantify national PA connectivity through the lens of moving mammals. We find that mitigating the human footprint may improve connectivity more than adding new PAs, although both strategies together maximize benefits. The most globally important areas of concentrated mammal movement remain unprotected, with 71% of these overlapping with global biodiversity priority areas and 6% occurring on land with moderate to high human modification. Conservation and restoration of critical connectivity areas could safeguard PA connectivity while supporting other global conservation priorities.


Pexid-induced rat retinal pathology.
Three morphologically distinct kinds of cytoplasmic inclusion (lamellar, reticular and crystalloid) developed in the retinal cells of suckling rats treated with Pexid (300 mg/kg/day). Lamellar inclusions were most abundant and they were seen in all types of retinal cells. This variety of inclusion was especially numerous in the ganglion cells. Reticular inclusions were encountered less commonly than the lamellar type and their distribution did not show any particular cellular predilection. Crystalloid inclusions were observed only in the pigment epithelial cells. The mechanism of formation of the three types of inclusion is not known, nor is the reason why certain types of inclusion occur most commonly in a particular kind of cell. One can speculate, however, that the dissimilarity of form may reflect differences in the metabolism and physiochemical properties of the various retinal cells.


Head tilt in rats during exposure to a high magnetic field.
During exposure to high strength static magnetic fields, humans report vestibular symptoms such as vertigo, apparent motion, and nausea. Rodents also show signs of vestibular perturbation after magnetic field exposure at 7 tesla (T) and above, such as locomotor circling, activation of vestibular nuclei, and acquisition of conditioned taste aversions. We hypothesized that the acute effects of the magnetic field might be seen as changes in head position during exposure within the magnet. Using a yoked restraint tube that allowed movement of the head and neck, we found that rats showed an immediate and persistent deviation of the head during exposure to a static 14.1 T magnetic field. The direction of the head tilt was dependent on the orientation of the rat in the magnetic field (B), such that rats oriented head-up (snout towards B+) showed a rightward tilt of the head, while rats oriented head-down (snout towards B-) showed a leftward tilt of the head. The tilt of the head during magnet exposure was opposite to the direction of locomotor circling immediately after exposure observed previously. Rats exposed in the yoked restraint tube showed significantly more locomotor circling compared to rats exposed with the head restrained. There was little difference in CTA magnitude or extinction rate, however. The deviation of the head was seen when the rats were motionless within the homogenous static field; movement through the field or exposure to the steep gradients of the field was not necessary to elicit the apparent vestibulo-collic reflex.


Age distribution of patients with advanced non-melanoma skin cancer in the United States.
The epidemiology of non-melanoma skin cancer (NMSC) is not well understood due to exclusion from most US cancer registries. Patients with at least two claims with a NMSC diagnosis (ICD-9-CM 173.xx) at least 60 days apart, or at least one claim for a NMSC-specific treatment from 1/2010 to 12/2010, were identified from a large US commercial insurance claims database and grouped into one of three cohorts: metastatic (MET), locally advanced (LA), or "all other". MET patients had at least two claims with a metastasis code at least 30 days apart. LA patients had at least two visits to a medical oncologist, one diagnostic imaging service, two radiation therapy services, or one visit to two or more physician specialties. Remaining patients were "all other". Incidence and prevalence of NMSC were calculated from among the total number of persons continuously enrolled in the plan during the study period and standardized to the 2010 US population. From among 6,610,256 patients, there were 47,451 incident cases of NMSC (MET n=16, LA n=387, all other n=47,048). The age-adjusted incidence rate of 693 per 100,000 persons (2010 population) approximates to 2,139,535 total NMSC cases in the US (0.7% of population). 671 prevalent cases had advanced disease (MET n=43, LA n=628); an age-adjusted rate of 0.6 and 10 per 100,000 US persons equivalent to 1,993 and 29,841 MET and LA cases, respectively. Although NMSCs rarely progress, the number of patients with advanced disease is significant. Further studies to determine proportions of advanced NMSC by subtype are needed.


Hypertrophic cardiomyopathy with cardiac rupture and tamponade caused by congenital disorder of glycosylation type Ia.
Hypertrophic cardiomyopathy (HCM) is a rare presenting feature of congenital disorder of glycosylation type Ia (CDG-Ia). We report two female siblings with CDG-Ia and cardiomyopathy. Patient no. 1 died at 12 days of age from cardiac rupture and tamponade, which has not previously been reported in CDG-Ia. The second patient died at 2 months of age from HCM. The severe cardiac manifestations seen in our patients emphasize the importance of early cardiac assessment in all patients with CDG-Ia.


Classification of cat retinal ganglion cells into X- and Y-cells with a contrast reversal stimulus.
A contrast reversal (alternating phase) stimulus was used to study the responses of 150 retinal ganglion cells from 15 adult cats. Because the majority of the cells did not show perfect linear spatial summation, a ratio of the firing rates at two time periods was used to express the degree of nonlinearity. Y-cells showed a high degree of nonlinearity, and their mean null ratio was significantly lower than that of X-cells. With the stimulus at the null position, X-cells had an unmodulated discharge rate which was significantly higher than maintained activity, while the firing rate of Y-cells was lower than maintained activity. With the stimulus placed at an eccentric position in the receptive field, X-cells responded in a sustained manner, while Y-cells respond transiently. Because of these observations, we conclude that X-cells correspond to the sustained cells, while Y-cells correspond to the transient cells.


Wide-open conformation of UDP-MurNc-tripeptide ligase revealed by the substrate-free structure of MurE from Acinetobacter baumannii.
MurE ligase catalyzes the attachment of meso-diaminopimelic acid to the UDP-MurNAc-l -Ala-d -Glu using ATP and producing UDP-MurNAc-l -Ala-d -Glu-meso-A2 pm during bacterial cell wall biosynthesis. Owing to the critical role of this enzyme, MurE is considered an attractive target for antibacterial drugs. Despite extensive studies on MurE ligase, the structural dynamics of its conformational changes are still elusive. In this study, we present the substrate-free structure of MurE from Acinetobacter baumannii, which is an antibiotic-resistant superbacterium that has threatened global public health. The structure revealed that MurE has a wide-open conformation and undergoes wide-open, intermediately closed, and fully closed dynamic conformational transition. Unveiling structural dynamics of MurE will help to understand the working mechanism of this ligase and to design next-generation antibiotics targeting MurE.


Interaction between a synthetic polypeptide, TIGAL, and Fc receptors on non-bursa-derived chicken lymphoid cells.
Autoradiographic studies have shown that radioiodinated TIGAL binds in vitro to a small but varying fraction of lymphoid cells from bursectomized, agammaglobulinemic chickens, whereas no binding of radioiodinated TGAL or a variety of other radioiodinated antigens can be observed. The binding of [125I]TIGAL is inhibited by antigen-antibody complexes. Radioiodinated antigen-antibody complexes are bound to a similar proportion of the lymphoid cells from bursectomized chickens, and this binding is inhibited by preincubation of the cells with unlabeled TIGAL but not with TGAL. These results indicate a cross-reaction at the level of Fc receptors between determinants on TIGAL and on IgG.


Serum relaxin levels in prostaglandin E2 induced abortions.
Relaxin, a peptide hormone produced only by the corpus luteum of pregnancy, can be used as a marker of luteal function in human pregnancy. Serum immunoreactive relaxin levels were measured serially in six women having second trimester abortions induced with intravaginal prostaglandin E2 (PGE2) suppositories. All patients aborted within 17 hours of the first suppository. No significant changes were detectable in serum relaxin levels in any of the patients. It is concluded that PGE2 does not interfere with the corpus luteum's ability to secrete relaxin in the second trimester of human pregnancy.


Roles of SIRT1/FoxO1/SREBP-1 in the development of progestin resistance in endometrial cancer.
The prevalence of endometrial cancer (EC) is increasing worldwide. Progestin therapy is effective for both early stage EC patients who require preserving fertility and advanced or recurrent patients. Progestin resistance resulting from downregulation of progesterone receptor (PR) remains a major problem, and its mechanism is currently unclear. It was demonstrated that Sirtuin 1 (SIRT1), forkhead transcription factor 1 (FoxO1) and sterol regulatory element binding protein-1 (SREBP-1) may act as a pathway and play crucial roles in the development of EC in our previous studies. In the present study, we investigated the effect on the development of progestin resistance and the relationship with PR of SIRT1/FoxO1/SREBP-1. A progestin-resistant Ishikawa cell line was established in the stimulation and selection of medroxyprogesterone acetate (MPA), and the resistance was analyzed by MTT assay, flow cytometry, and Transwell invasion assay. qRT-PCR and western blotting were conducted to detect the expression of SIRT1, FoxO1, SREBP-1 and PR. SIRT1 knockdown progestin-resistant cells were established by lentiviral transduction. The new progestin-resistant cell line presented sufficient resistance to MPA in aspects of proliferation, distribution of cell cycle and apoptosis compared with original Ishikawa cells. Besides, the invasion capability of progestin-resistant cells was observably increased. In both protein and mRNA levels, SIRT1 and SREBP-1 were upregulated in progestin-resistant cells, while PR and FoxO1 were downregulated. SIRT1 was knocked down by lentivirus transfection in progestin-resistant cells, resulting in upregulation of PR, FoxO1 and downregulation of SREBP-1, thereby SIRT1 knockdown cells were more sensitive to MPA compared with progestin-resistant cells. SIRT1/FoxO1/SREBP-1 act as a pathway targeting PR and involve in the development of progestin resistance in Ishikawa cells.


Renewable microbial lipid production from Oleaginous Yeast: some surfactants greatly improved lipid production of Rhodosporidium toruloides.
Microbial oil is drawing increasing interest worldwide as an alternative non-food oil feedstock for biodiesel industry. Nowadays researchers have been increasingly focused on the improvement of microbial oil production process. Oleaginous yeast Rhodosporidium toruloides (R. toruloides) is considered an important candidate due to its excellent capabilities of lipid accumulation, broad adaptabilities to various carbon substrates, and the potential of co-production of some pigments. In present work, the individual effects of non-ionic, cationic, and anionic surfactant on cell growth and lipid accumulation of R. toruloides were investigated for the first time. Interesting results were noticed when some anionic surfactants were supplemented. The most significant effect was observed with addition of 0.2 % (w/v) sodium lignosulfonate, that biomass concentration, lipid concentration, and lipid yield was increased by 25.1, 44.9, and 15.7 %, respectively. The fatty acid compositions of R. toruloides lipids remained unchanged, which is similar to that of vegetable oils, and is considered potential feedstock for biodiesel preparation.


Evaluating the effect of ovarian stimulation and exogenous progesterone on CD31-positive cell density, VEGF protein, and miR-17-5p expression of endometrium immediately before implantation.
MicroRNAs (miRNAs) form a special class of RNAs regulating endometrial functions like cell proliferation, differentiation, angiogenesis, and blastocyst implantation. In addition to providing suitable conditions for embryo development, angiogenesis is a prerequisite to natural pregnancy. The family of vascular endothelial growth factor (VEGF) and its receptors are the main physiological and pathological angiogenesis regulators in the endometrium. In the past, research has demonstrated alteration of angiogenesis and subsequent endometrial receptivity in the stimulated and luteal phase support cycles, when compared with natural cycles. The objective of this study is to investigate the effect of ovarian stimulation and exogenous progesterone on the density of CD31-positive cell (Endothelial cell), VEGF protein, and miR-17-5p expression in the mouse endometrium immediately before implantation. We employed ovarian stimulated and luteal phase support mice models induced by HMG/HCG and progesterone. The endometrial CD31-positive cell density was determined by immunohistochemistry (IHC) staining, the level of VEGF protein by IHC and western blot analysis, and finally the miR-17-5p expression was determined by the real-time PCR method. The density of endothelial cell, VEGF protein, and miR-17-5p expression increased in all of the experimental mice when compared to the control group, with the maximum increase having been seen in the group that had received progesterone after ovarian stimulation. This research indicates that ovarian stimulation and exogenous progesterone lead to an increase in the number of endothelial cells by upregulating the VEGF protein. Moreover, except for miR-17-5p, other microRNAs and molecules are presumably involved in angiogenic pathways, thereby requiring more studies.


On the Nonaggregation of Normal Adult Hemoglobin and the Aggregation of Sickle Cell Hemoglobin.
Sickle cell disease is a genetic disorder associated with a single mutation (Glu-β6 → Val-β6) in the β chains of hemoglobin, causing the polymerization of deoxygenated sickle cell hemoglobin (deoxy-HbS). The deoxy-HbS binding free energy was recently studied through molecular simulations, and a value of -14 ± 1 kcal mol-1 was found. Here, we studied the binding free energy of normal adult hemoglobin (deoxy-HbA), which does not polymerize at normal physiological conditions, with the aim of elucidating the importance of the presence of Val-β6 and of the absence of Glu-β6 on the aggregation of deoxy-HbS. A binding free energy of -4.4 ± 0.5 kcal mol-1 was found from a one-dimensional potential of mean force. Hydrophobic interactions are shown to represent less than 20% of the interactions in the contact interface, and despite similarly strong hydrogen-bonded ion pairs (i.e., salt bridges) and water bridged electrostatic interactions are found for deoxy-HbA and deoxy-HbS, a large repulsive potential energy is associated with Glu-β6, whereas a mild attractive potential energy is connected with Val-β6. Interestingly, Asp-β73 switches from forming a major electrostatic repulsive pair with Glu-β6 in deoxy-HbA, to forming a major attractive residue pair with Val-β6 in deoxy-HbS, consistent with the view that damping of electrostatic repulsions involving Glu-β6, namely, those associated with Asp-β73, could be responsible for the polymerization of deoxy-HbA at high potassium phosphate concentrations. Solvation analysis shows that functional groups forming salt bridges and water bridged interactions preserve a nearly intact first hydration sphere, avoiding a complete dewetting free energy penalty. These results support the view that the absence of Glu-β6 is more important than the presence of Val-β6, and that although hydrophobic effects, associated with the Val-β6 dehydration and interaction with the hydrophobic pocket in the neighbor tetramer, are important, electrostatic interactions are dominant, opposite to a picture where HbS association is driven by hydrophobic interactions.


Comparison of near-infrared and Raman spectroscopy for on-line monitoring of etchant solutions directly through a Teflon tube.
Both near-infrared (NIR) and Raman spectroscopy have been studied for the quantitative measurement of components (H(3)PO(4), HNO(3), and CH(3)COOH) in an etchant solution and the corresponding prediction robustness has been evaluated. Both measurements were accomplished by illuminating radiation directly through a Teflon tube. Raman spectral features of each component were much clearer and more selective than those observed in the NIR spectrum. Especially, NIR spectral variation pertinent to H(3)PO(4) and HNO(3) were mostly based on the displacement and perturbation of water bands rather than due solely to NIR absorption. Therefore, the resulting spectral variations were not highly specific. When the validation set contained minor spectral variations resulting from a slight instrumental change, NIR prediction performance for all three components degraded substantially by showing obvious prediction bias. However, the accuracies of Raman predictions were maintained. Since partial least squares (PLS) models for each component were built using NIR spectra of poor specificity with broadly overlapping features, even minor spectral differences introduced by instrumental variations sensitively influenced the prediction performance of the NIR models. Overall, the selectivity (specificity) of a targeting spectroscopic method should be considered critically to secure prediction robustness for monitoring components in an etchant solution.


Reduced Plasma BDNF Levels in Normal Tension Glaucoma Compared to Open Angle Glaucoma.
The study suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner. To evaluate differences in systemic brain-derived neurotrophic factor (BDNF) levels between primary open angle glaucoma (POAG) patients and normal tension glaucoma (NTG) patients. This study collected blood samples from 260 NTG patients, 220 age-matched POAG patients, and 120 age-matched cataract patients (as controls). BDNF levels were measured with an antibody-conjugated bead assay system (Luminex). We found that plasma BDNF levels in the NTG group were significantly lower than in the POAG and cataract control groups. There was no significant difference between the POAG and cataract groups. This result suggests that a low level of systemic BDNF may contribute to the pathogenesis of glaucoma in an IOP-independent manner.


Attitudes toward harm reduction and low-threshold healthcare during the COVID-19 pandemic: qualitative interviews with people who use drugs in rural southern Illinois.
Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD. Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping. Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization's office and mobile units. COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services. NCT04427202.


[Multiple analysis of lead concentration in the air and renal function of lead exposure workers].
To determine the lead concentration in the air (pbA) at the workplace and the renal function of lead exposure workers. The lead concentration in the air of 11 printing plants, 4 smelteries and 2 lead mines were measured. Screening urinalysis was performed in 1190 long term lead exposed workers with urine sugar, protein and sigements. It one of the three was abnormal, the workers were given examination of renal function. The relationship between pbA and renal function were confirmed by mutiple linear. The concentrations of pbA in the printing plants, smelteries and lead mines were 0.07 mg/m3, 0.26 mg/m3 and 0.66 mg/m3 respectively. Altogether 157 cases had one and more abnormal renal function. The correlation of concentration PbA in the workplace and the renal function of lead exposure workers was shown (R = 0.894, P < 0.001, R2 = 0.799). The correlation coefficient of skewness of showed that PbA and Bpb. Upb. Bun Scr Usug. Ubeta2MG were positively correlated (P < 0.01 approximately 0.001); Ccr was negatively correlated (P =0.05). Upro, UNAG and Ualb were nonsignificant. The lead concentration in the air at the workplace is related to the renal functions of lead exposure workers. It is important to decrease the lead environment and to prevent renal damage.


A broad-spectrum matrix metalloproteinase inhibitor prevents hemorrhagic complications induced by tissue plasminogen activator in mice.
Delayed activation of tissue plasminogen activator (tPA) can lead to the disruption of the blood-brain barrier (BBB), resulting in hemorrhagic complications. In the present study, we focused on tight junction proteins (TJPs), occludin, zona occludens (ZO)-1, and claudin-5, which are important structural components of the BBB, and investigated whether inhibition of matrix metalloproteinases (MMPs) provides a protective effect against hemorrhagic complications induced by tPA. We subjected mice to 6-h filamental middle cerebral artery occlusion (MCAO) with vehicle, delayed tPA alone, or combined tPA (10 mg/kg, i.v.) plus GM6001 (100 mg/kg, i.p.), a broad-spectrum MMP inhibitor. We evaluated brain hemoglobin and the expression of MMP-9 and TJPs by immunoblotting. GM6001 significantly reduced tPA-elevated brain hemoglobin, MMP-9, and inhibited the degradation of occludin and ZO-1 induced by tPA, but not claudin-5. Treatment with GM6001 also significantly prevented the decrease in the survival rate and the reduction in locomotor activity caused by tPA at 7 days after ischemia/reperfusion. Furthermore, GM6001 treatment also significantly prevented cell damage, determined by release of lactase dehydrogenase (LDH) activity, and the decrease in transendothelial electrical resistance (TEER) induced by tPA. These findings indicate that GM6001 prevented the hemorrhagic complications and improved the behavioral abnormalities induced by tPA, partly via protection of TJPs. This suggests that GM6001 may be a useful candidate for combination therapy against the hemorrhagic complications induced by tPA.


Semiochemical responsive olfactory sensory neurons are sexually dimorphic and plastic.
Understanding how genes and experience work in concert to generate phenotypic variability will provide a better understanding of individuality. Here, we considered this in the main olfactory epithelium, a chemosensory structure with over a thousand distinct cell types in mice. We identified a subpopulation of olfactory sensory neurons, defined by receptor expression, whose abundances were sexually dimorphic. This subpopulation of olfactory sensory neurons was over-represented in sex-separated mice and robustly responsive to sex-specific semiochemicals. Sex-combined housing led to an attenuation of the dimorphic representations. Single-cell sequencing analysis revealed an axis of activity-dependent gene expression amongst a subset of the dimorphic OSN populations. Finally, the pro-apoptotic gene Baxwas necessary to generate the dimorphic representations. Altogether, our results suggest a role of experience and activity in influencing homeostatic mechanisms to generate a robust sexually dimorphic phenotype in the main olfactory epithelium.


Study on Pharmacokinetic Interactions Between HS-10234 and Emtricitabine in Healthy Subjects: An Open-Label, Two-Sequence, Self-Controlled Phase I Trial.
HS-10234, a novel prodrug of tenofovir (TFV), functions by inhibiting nucleotide reverse transcriptase against retroviral infections including hepatitis B virus and human immunodeficiency virus (HIV). As it is a possible substitute for TFV co-administration with emtricitabine, determining the drug-drug interactions (DDI) between HS-10234 and emtricitabine therapy will be helpful for researchers to design and conduct future phase II/III studies and merits careful examination in the era of evolving new combination antiretroviral therapy regimens. We conducted an open-label, two-sequence, two-period, self-controlled phase I trial that enrolled 36 healthy volunteers randomized into two groups (group 1 and group 2). Eighteen subjects in group 1 were orally administered HS-10234 at a 25-mg daily dose for 7 days during period 1 (D1-D7) followed by co-administration of emtricitabine at a 200-mg dose once daily (QD) for 7 additional days during period 2 (D8-D14). Participants in group 2 were orally administered emtricitabine 200 mg QD for 7 days during period 1 (D1-D7) and then co-administered HS-10234 25 mg QD for 7 additional days during period 2 (D8-D14). Pharmacokinetics (PK) of HS-10234 and emtricitabine were characterized when administered alone and in combination. The concentrations of HS-10234 and its metabolites TFV and emtricitabine were determined using high performance liquid chromatography-mass spectrometry (HPLC-MS)/MS. Peripheral blood monocyte cells (PBMCs) were isolated for detection of intracellular concentrations of HS-10234's active metabolite, intracellular tenofovir diphosphate (TFV-DP) pre-dose and 2, 4, 8, 12 and 24 h post-dose on D7 and D14 in group 1. WinNonlin software was used to calculate PK parameters. After multiple-dose administration of HS-10234 with emtricitabine, the AUC0-tau of HS-10234 and TFV-DP was 1.327- and 1.403-fold higher than that with HS-10234 administration alone. The Cmax and AUC0-tau were increased 1.120- and 1.077-fold compared to emtricitabine administration alone. Co-administration of HS-10234 with oral emtricitabine was well tolerated. No serious adverse events were observed. Although a slightly increased steady-state PK exposure of HS-10234 and TFV-DP was observed with co-administration of oral HS-10234 with emtricitabine, these changes were not considered clinically relevant. Thus, dose adjustments are not recommended for HS-10234 combination with emtricitabine. NCT04477096, July 20, 2020.