Two-dimensional LC-MS/MS and three-dimensional LC analysis of chiral amino acids and related compounds in real-world matrices.
Amino acids normally have a chiral carbon and d/l-enantiomers are present. Due to the homochirality features on the present Earth, l-enantiomers are predominant in the living beings and the d-enantiomers are rare. Along with the progress and development of cutting edge analytical methods, several d-amino acids were found even in the higher animals including humans, and their biological functions and diagnostic values have also been reported. However, the amounts of these d-amino acids are much lower than the l-forms, and development/utilization of highly sensitive and selective methods are practically essential to avoid the disturbance from uncountable intrinsic substances. In the present review, multi-dimensional HPLC methods for the determination of chiral amino acids, especially two-dimensional LC-MS/MS and three-dimensional LC methods, and their applications to a variety of real-world matrices are summarized.


Shear stress-induced collagen XII expression is associated with atherogenesis.
Fluid shear stress has been shown to modulate various endothelial functions. We selected a shear stress-specific clone, identified as collagen XII, from a bovine aortic endothelial cell (BAEC) cDNA library. We confirmed that shear stress induces collagen XII expression at both the mRNA and protein levels in cultured BAECs and human umbilical vein ECs (HUVECs) by stimulating transcription. When HUVECs were exposed to shear stress, they secreted collagen XII protein and it was deposited underneath them. Strong expression of collagen XII was found in the intima of human aortic wall lacking atherosclerotic lesions, whereas weak expression was seen in the intima of atherosclerotic plagues. Furthermore, the downstream portion of atherosclerotic plaques showed apparently weak collagen XII expression compared with the upstream portion. These results suggest that collagen XII expression induced by fluid shear stress may play a role in stabilizing the vascular structure and preventing the formation of atherosclerotic lesions.


Reduction sensitive hyaluronan-SS-poly(ε-caprolactone) block copolymers as theranostic nanocarriers for tumor diagnosis and treatment.
Tumor-targeted multifunctional nanocarriers play an important role in tumor diagnosis and treatment. Herein, disulfide bonds linked amphiphilic hyaluronan-SS-poly(ε-caprolactone) diblock copolymers (HA-SS-PCL) were synthesized and studied as theranostic nanocarriers for tumor diagnosis and treatment. The chemical structure of HA-SS-PCL was confirmed by Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR). The self-assembling behavior of the HA-SS-PCL into GSH-responsive micelles and their degradation were characterized by fluorescence spectroscopy, dynamic light scattering (DLS) and transmission electron microscopy (TEM). Theranostic nanocarriers encapsulating doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) were formed via a dialysis. In vitro drug release results suggested that the HA-SS-PCL micelles possessed reductant-triggered doxorubicin release ability, which was confirmed by 100% of DOX release from HA-SS-PCL micelles within 12 h under 10 mM of glutathione (GSH), whereas about 40% of DOX was released under non-reductive condition within 24 h. Both flow cytometry and confocal laser scanning microscopy (CLSM) analysis revealed that the HA-SS-PCL micelles loaded with DOX were internalized in HepG2 cell via a receptor mediated mechanism between hyaluronan and the CD44 receptor. Furthermore, the MTT assay and cell apoptosis analysis revealed that the DOX-loaded HA-SS-PCL micelles exhibited pronounced antitumor ability towards HepG2 cells compared with that of the reduction-insensitive HA-PCL micelles at the same DOX dosage. The r2 relaxivity value of the DOX/SPIO loaded HA-SS-PCL micelles was up to 221.2 mM-1 s-1 (Fe). Thus, the obtained HA-SS-PCL block copolymers demonstrate promising potential as tumor targeting theranostic nanocarriers in the field of tumor diagnosis and treatment.


A novel voltammetric sensor for citalopram based on multiwall carbon nanotube/(poly(p-aminobenzene sulfonic acid)/β-cyclodextrin).
Multi-walled carbon nanotube (MWCNTS) coated with poly p-aminobenzene sulfonic acid/β-cyclodextrin (p-ABSA/β-CD) film was used as an effective strategy for modification of the surface of glassy carbon electrode (GCE). Electrochemical study and determination of citalopram (CT) were investigated at the p (p-ABSA)/β-CD/MWCNT/GC using cyclic and differential pulse anodic stripping voltammetric techniques. The results indicate that the p (p-ABSA)/β-CD/MWCNT/GC significantly enhanced the oxidation peak current of CT. The modified electrode was characterized by electrochemical impedance spectroscopy (EIS), scanning electron microscopy(SEM) and cyclic voltammetry (CV).The fabricated electrochemical sensor exhibits a fast and reversible linear response toward CT within the concentration ranges of 90 nM-1 μM, 1-11 μM and 11-100 μM with correlation coefficients greater than 0.99 and detection limit of 44 nM. The resulting functionalized polymer film features interesting electrochemical properties such good recovery, reproducibility and selectivity toward CT. The applicability of the proposed sensor was tested by determination of CT in pharmaceutical combinations and human body fluids.


Early Readmissions After Hospitalization for Posterior Reversible Encephalopathy Syndrome.
To evaluate the frequency, etiologies, and risk factors for 90-day readmissions following hospitalization for PRES. Data were obtained from the Nationwide Readmissions Database 2016-2018. Patients with primary diagnosis of PRES, survival to discharge, and known discharge disposition were included. Primary outcome was non-elective readmission within 90 days of discharge. Survival analysis was performed, and independent predictors of readmission were analyzed using multivariable Cox proportional hazards regression. Based on the study inclusion criteria, 6,155 eligible patients were included (mean±SD age: 55.9±17.3 years, female: 71.0%). Non-elective readmission within 90 days of discharge occurred for 1,922 (31.2%) patients. Of these, 617 readmissions were due to PRES-related or neurological etiologies and the remaining 1305 readmissions were due to non-neurological conditions. In multivariable analysis, age was inversely associated with risk of readmission [hazards ratio (HR): 0.92 for every 10 years increase in age, 95% confidence interval (CI): 0.88-0.97]. Patients with diabetes (HR: 1.21, 95% CI: 1.04-1.42), systemic lupus erythematosus (HR: 1.42, 95% CI: 1.03-1.96), acute kidney injury (HR: 1.28, 95% CI: 1.11-1.47) and higher Charlson comorbidity index score (HR: 1.09, 95% CI: 1.06-1.13) were more likely to be readmitted. Further, patients admitted at large bed size hospitals (HR: 1.19, 95% CI: 1.03-1.39), those with longer length of stay (HR: 1.01, 95% CI: 1.00-1.02) and those not discharged to home (HR: 1.33, 95% CI: 1.14-1.55) during the index hospitalization were also at a higher risk for readmission. Nearly one-third of patients hospitalized due to PRES are readmitted within 90 days of discharge and about one-third of these readmissions are due to PRES-related or neurological etiologies. Younger age, a higher comorbidity burden, longer length of hospital stay, and discharge disposition other than to home are independently associated with the risk of readmission.


In situ carbon coated flower-like VPO4 as an anode material for potassium-ion batteries.
Here we design a novel carbon coating method for phosphate-based VPO4 with three different morphologies, via the intercalation of isobutanol to layered VOPO4·2H2O combined with thermal reduction. The well-constructed flower-like VPO4 delivers a high reversible capacity of 400 mA h g-1 with a long cycle-life of more than 500 cycles, proving that the special structure is suitable to accommodate the large volume expansion during the electrochemical charge-discharge process.


Hyperhomocysteinemia and venous thrombosis: a meta-analysis.
Hyperhomocysteinemia is an established risk factor for atherosclerosis and vascular disease. Until the early nineties the relationship with venous thrombosis was controversial. At this moment ten case-control studies on venous thrombosis are published. We performed a metaanalysis of these reports. We performed a MEDLINE-search from 1984 through June 1997 on the keywords "homocysteine" or "hyperhomocysteinemia" and "venous thrombosis", which yielded ten eligible case-control studies. We found a pooled estimate of the odds ratio of 2.5 (95% CI 1.8-3.5) for a fasting plasma homocysteine concentration above the 95th percentile or mean plus two standard deviations calculated from the distribution of the respective control groups. For the post-methionine increase in homocysteine concentration we found a pooled estimate of 2.6 (95% CI 1.6-4.4). These data from case-control studies support hyperhomocysteinemia as a risk factor for venous thrombosis. Further research should focus on the pathophysiology of this relationship and on the clinical effects of reducing homocysteine levels by vitamin supplementation.


Failure of SCH 23390 to function as a discriminative stimulus in rats.
Four rats were studied in a two-lever, food-reinforced drug discrimination paradigm using the Dl dopamine antagonist SCH 23390 (0.03 mg/kg, IP, 30 minutes prior to the session) and saline as the training stimuli. After at least 100 training sessions there was no evidence of stimulus control over responding by SCH 23390 in 3 of the 4 rats, and only briefly in the fourth. On the other hand, food delivery exerted control over behavior indicating that SCH 23390 did not disrupt control of behavior by the reinforcing stimulus. An increase in training dose to 0.06 mg/kg for an additional 12 sessions did not improve discriminative accuracy although this dose reduced rate of responding to an extent that made further training using 0.06 mg/kg untenable. The results provide no evidence of stimulus control of behavior by SCH 23390 and suggest that SCH 23390 does not function as a discriminative stimulus in rats.


Heme oxygenase-1 induction mediates chemoresistance of breast cancer cells to pharmorubicin by promoting autophagy via PI3K/Akt pathway.
Concerns about breast cancer had become the most dangerous cancer to women over the world, more and more anti-cancer agents are developed to treat this malignancy. Pharmorubicin is a cytotoxic drug, widely used in the treatment of breast cancer, but its role is limited because of chemoresistance produced by cells. This study focused on exploring the influence of autophagy on the resistance of pharmorubicin in breast cancer cells. The cell survival of breast cancer cells was detected by MTT. The mRNA expression of heme oxygenase-1 (HO-1) was tested by qRT-PCR. The protein expression of HO-1, autophagic proteins (LC3-I,LC3-II and Beclin-1), PI3K and Akt was detected by Western blot. Cell autophagy was examined by Cyto-ID Autophagy Detection Kit. After being treated with pharmorubicin, the expression of HO-1 and autophagy related proteins was significantly enhanced, but the cell survival ratio in the two cell lines decreased. After autophagy was inhibited, HO-1 expression in two cells was down-regulated. When pharmorubicin-resistant cells were transfected with si-HO-1, the cell survival decreased and the protein expression of HO-1, autophagic proteins (LC3-II/LC3-I and Beclin-1) as well as autophagy were all down-regulated, while in pharmorubicin-resistant cells transfected with pcDNA3.1-HO-1, the results were reverse. When the PI3K or Akt was inhibited, PI3K, p-Akt, HO-1, autophagic proteins and autophagy were decreased remarkably. It was proved that HO-1 induction mediated chemoresistance of pharmorubicin in breast cancer cells by promoting autophagy via PI3K/Akt pathway.


Role of complement in thrombogenesis. I. Complement-dependent coagulation in a model system.
Chondroitin sulphate was used to isolate from plasma a system that clotted with Russell's viper venom, brain extract and activated contact factors. Clotting appeared to depend on concomitant change in C4, C3 and C1s in the system. Brain extract additionally reacted with C9. Reconstitution of specifically defective plasmas suggested a specific role for each of these complement components in clotting.


Lipid modification in mouse peritoneal macrophages after chronic cadmium exposure.
The effect of cadmium (Cd) exposure through drinking water on lipid status in mouse peritoneal macrophages (pM) was studied. After 2 months, adult male Balb/c mice that had drunk water with 15 ppm of Cd, showed tissue damage mediated by oxidative stress, as assessed by serum measuring of tissue damage and lipoperoxidation indicators. Resident pM obtained from Cd-exposed mice showed diminution in total lipids, total cholesterol, free cholesterol/esterified cholesterol ratio (FC/EC) and phospholipids in relation to control pM. On a percentage basis, the phospholipid composition showed that phosphatidylcholine (PC) and phosphatidylglycerol decreased, phosphatidylethanolamine (PE) increased, while phosphatidylinositol, sphingomyeline and phosphatidylserine did not change. The incorporation in vitro of [14C]-methyl-choline and [14C]-phosphorylcholine, as well as the activity of regulatory enzyme CTP-phosphocholine cytidylyltransferase, decreased in PC after 60 min. The incorporation of [14C]-linoleic acid increased after 1 h and the incorporation of [14C]-ethanolamine increased after 90 min in PC. The incorporation in vitro of [3H]-cholesterol in total lipids decreased after 120 min of incubation. Besides, the stearic acid and arachidonic acid content increased, while the contents of palmitoleic acid and linoleic acid decreased. Chronic Cd exposure alters the lipid composition in resident pM of Balb/c mice.


Lipid transport through the plasma: the metabolic basis of hyperlipidaemia.
Plasma lipid abnormalities derive their importance from their association with coronary artery disease. Elevated cholesterol levels accentuate risk, and clinical trials have shown that reductions lead to a decline in coronary events. The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes by interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin:cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognizable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal.


Ultrastructural localisation of spectrin in sensory and supporting cells of guinea-pig organ of Corti.
Spectrin is a cytoskeletal protein found in the cortex of many cell types. It is known to occur in cochlear outer hair cells (OHCs) with previous immunoelectron microscopical studies showing that it is located in the cuticular plate and the cortical lattice. The latter is a network of filaments associated with the lateral plasma membrane that is thought to play a role in OHC motility. Spectrin has also been found in inner hair cells (IHCs) and supporting cells using immunofluorescent techniques, but its ultrastructural distribution in these cells has not yet been described. This has, therefore, been investigated using a monoclonal antibody to alpha-spectrin in conjunction with pre- and post-embedding immunogold labelling for transmission electron microscopy. Labelling was found in a meshwork of filaments beneath the plasma membranes of both IHCs and supporting cells and, in pillar cells, close to microtubule/microfilament arrays. It was also found in association with the stereocilia of OHCs and IHCs and, as expected, in the cortical lattice and cuticular plate of OHCs. Thus, spectrin is a general component of cytoskeletal structures involved in maintaining the specialised cell shapes in the organ of Corti and may contribute to the mechanical properties of all the cell types examined.


Four new steroidal glycosides from Solanum torvum and their cytotoxic activities.
Two novel C-22 steroidal lactone saponins, namely solanolactosides A, B (1, 2) and two new spirostanol glycosides, namely torvosides M, N (3, 4) were isolated from ethanol extract of aerial parts of Solanum torvum. Their structures were characterized as solanolide 6-O-[alpha-l-rhamnopyranosyl-(1-->3)-O-beta-d-quinovopyranoside] (1), solanolide 6-O-[beta-d-xylopyranosyl-(1-->3)-O-beta-d-quinovopyranoside] (2), yamogenin 3-O-[beta-d-glucopyranosyl-(1-->6)-O-beta-d-glucopyranoside] (3) and neochlorogenin 3-O-[beta-d-glucopyranosyl-(1-->6)-O-beta-d-glucopyranoside] (4) on the basis of spectroscopic analysis. The cytotoxicities of the saponins (1-4) were evaluated in vitro against a panel of human cancer cell lines. Compounds 3 and 4 showed significant cytotoxic activity with the cell lines.


Immunochemical identification and differential phosphorylation of alternatively spliced forms of the alpha 1A subunit of brain calcium channels.
Biochemical properties of the alpha 1 subunits of class A brain calcium channels (alpha 1A) were examined in adult rat brain membrane fractions using a site-directed anti-peptide antibody (anti-CNA3) specific for alpha 1A. Anti-CNA3 specifically immunoprecipitated high affinity receptor sites for omega-conotoxin MVIIC (Kd approximately 100 pM), but not receptor sites for the dihydropyridine isradipine or for omega-conotoxin GVIA. In immunoblotting and immunoprecipitation experiments, anti-CNA3 recognized at least two distinct immunoreactive alpha 1A polypeptides, a major form with an apparent molecular mass of 190 kDa and a minor, full-length form with an apparent molecular mass of 220 kDa. The 220- and 190-kDa alpha 1A polypeptides were also specifically recognized by both anti-BI-Nt and anti-BI-1-Ct antibodies, which are directed against the NH2- and COOH-terminal ends of alpha 1A predicted from cDNA sequence, respectively. These data indicate that the predicted NH2 and COOH termini are present in both size forms and therefore that these isoforms of alpha 1A are created by alternative RNA splicing rather than post-translational proteolytic processing of the NH2 or COOH termini. The 220-kDa form was phosphorylated preferentially by cAMP-dependent protein kinase, whereas protein kinase C and cGMP-dependent protein kinase preferentially phosphorylated the 190-kDa form. Our results identify at least two distinct alpha 1A subunits with different molecular mass, demonstrate that they may result from alternative mRNA splicing, and suggest that they may be differentially regulated by protein phosphorylation.


Metropolitan wastewater analysis for COVID-19 epidemiological surveillance.
The COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly emerging pandemic which has enforced extreme containment measures worldwide. In the absence of a vaccine or efficient treatment, cost-effective epidemiological surveillance strategies are urgently needed. Here, we have used RT-qPCR for SARS-CoV-2 detection in a series of longitudinal metropolitan wastewaters samples collected from February to April 2020, during the earliest stages of the epidemic in the Region of Valencia, Spain. We were able to consistently detect SARS-CoV-2 RNA in samples taken in late February, when communicated cases in that region were only incipient. We also find that the wastewater viral RNA context increased rapidly and anticipated the subsequent ascent in the number of declared cases. Our results strongly suggest that the virus was undergoing community transmission earlier than previously believed, and suggest that wastewater analysis could be sensitive and cost-effective strategy for COVID-19 epidemiological surveillance. Routine implementation of this surveillance tool would significantly improve our preparedness against new or re-occurring viral outbreaks.


Infantile McCune-Albright syndrome.
McCune-Albright syndrome is a rare disorder caused by an activating mutation of the alpha subunit of the Gs protein and is characterized by multiple hormonal abnormalities, fibrous dysplasia of bone, and cutaneous pigmentation. We report a 10-week-old infant with McCune-Albright syndrome. He presented with failure to thrive, cardiorespiratory distress, and pigmented macules on his face, trunk, and limbs. Following the clinical diagnosis of McCune-Albright syndrome, he was subsequently shown to have hypercortisolism and hyperthyroidism.


Assessing the functional properties of tenogenic primed mesenchymal stem cells in ex vivo equine tendon and ligament explants: A preliminary study.
Injuries to equine tendons and ligaments are career-compromising, causing reduced performance and premature retirement. Promising treatment alternatives have been investigated in the field of mesenchymal stem cells (MSCs). In this study, the tissue adherence and protein expression of tenogenic primed mesenchymal stem cells (tpMSCs) after administration to ex vivo tendon and ligament explants is investigated. First, collagen type I (COL I) and smooth muscle actin (SMA) expression was assessed in cytospins prepared from native MSCs and tpMSCs. Second, equine superficial digital flexor tendon and suspensory ligament explants were cultivated, and a lesion was treated with both cell types. Subsequently, cell adhesion to the explants and the amount of COL I and SMA positive cells was evaluated. The cytospins revealed a significantly higher COL I and lower SMA expression in tpMSCs compared to native MSCs. In the explants, tpMSCs showed a significantly higher tendon and ligament adherence. Furthermore, a significantly higher percentage of COL I positive and a lower percentage of SMA positive cells were observed in the lesions treated with tpMSCs. The results of these explant co-cultures may demonstrate at least a part of the mechanism of action and functional properties of tpMSCs in restoring function to tendons and ligaments.


Excellent liver transplantation survival and prevention of hepatitis B recurrence using hepatitis B immunoglobulin and nucleoside or nucleotide analogue along with treating physician adherence to treatment protocol.
The introduction of hepatitis B immunoglobulin (HBIG) in the early 1990s dramatically reduced recurrence of hepatitis B after orthotopic liver transplantation (OLT) and thus improved survival. Today a combination of HBIG and a nucleoside or nucleotide analogue (NUC) is recommended as prophylaxis. The optimal protocol is yet to be commonly agreed upon. The aim of this study was to review our results over 25 years. All 56 patients (45 males and 11 females) who underwent OLT due to hepatitis B infection between 1985-2009 were included in the review. Median age at transplantation was 51 years (range, 18-66). Seventeen patients (30%) had hepatocellular carcinoma (HCC) at transplantation. The 1- and 5-year overall survival rates were 89% and 77%, respectively. The 23 patients who underwent transplantation before 2000 showed 1- and 5-year survival rates of 82% and 61%, respectively; the 33 who underwent transplantation between 2000 and 2009, the rates were 94% and 90%, respectively (P < .01). There was no difference in the 5-year survival rate between patients who had or did not have been HCC (75% vs 78%, respectively). Recurrence of hepatitis B, defined as seroconversion to HBsAg positivity, was observed in 9 patients. Three transplantation cases before 1992 consequently did not receive HBIG. The remaining 6, who all underwent OLT between 1993 and 2001, were administered HBIG. In all 6 cases periods of low anti-HBs titers were registered prior to recurrence; treating physician noncompliance with the protocol may have contributed to the low anti-HBs titers. No recurrence was registered after 2001. With a combination of HBIG and NUC, excellent OLT results can be achieved for hepatitis B. It is, however, still important to maintain sufficient anti-HBs titers to prevent recurrence.


[Influence of industrial pollutants on bronchial permeability].
The authors studied influence of chemical hazards with various characteristics on bronchial permeability. Workers exposed to organic chemicals demonstrated respiratory complaints and spirometric signs of bronchial obstruction 1.3-1.8 times more frequently. Longer length of service in hazardous conditions is associated with higher occurrence of bronchial obstruction and more intensive changes of lipid peroxidation.


Immunoglobulin prophylaxis in pediatric hematopoietic stem cell transplant.
After allogeneic hematopoietic stem cell transplantation (HSCT), patients have an increased susceptibility to infections, thought to be due in part to hypogammaglobulinemia. Thus, prophylactic administration of intravenous immunoglobulins (IVIG) has been administered to patients after HSCT as standard of care. This study compares the viral infection rate between dosing IVIG by IgG levels versus by routine monthly administration in pediatric patients after HSCT. In this retrospective chart review, we abstracted from electronic medical records data on pediatric patients undergoing HSCT from 2010 to 2012 for 6 months post-HSCT. We compared rates of infection between patients treated with routine IVIG prophylaxis and patients given IVIG prophylaxis based on IgG tough levels (IgG levels were checked every 2 weeks). Data were available and reviewed for 50 patients dosed with IVIG every 28 days (Group 1) and 100 patients dosed with IVIG based on IgG level > 400 mg/dl (Group 2). There was no significant difference in age (P = 0.98) or sex (P = 0.42), reason for HSCT, alemtuzumab use (P = 0.602), or reduced intensity conditioning (P = 1.00). Significantly more haploidentical donors were in Group 1 (P = 0.04), otherwise there was no significant difference in donor type between groups. Significantly less acute graft versus host disease occurred (P = <0.001) in Group 2 (P = <0.001). PCR documented viral infections were not significantly different (P = 0.412) (Table 1). Group 2 patients received significantly less IVIG (P < 0.001). Dosing IVIG to maintain an IgG level > 400 mg/dl is a cost-effective and safe way to prevent viral infections in pediatric patients undergoing HSCT.


Fatal meningitis with group JK Corynebacterium in a leukopenic patient.
A case of fatal meningitis and septicemia with group JK Corynebacterium species in a leukopenic patient is reported. The strain was susceptible to rifampicin and vancomycin only. The finding of diphtheroids in bacteriological samples from immunocompromised patients should not be ignored. The literature regarding meningitis caused by diphtheroid bacilli is reviewed.


[Results of the surgical treatment of distal femoral fractures].
In a follow-up of 97 operated distal femoral fractures good and satisfactory results were found in 64% of the cases. 22% unsatisfactory and 14% poor findings attribute mainly to the comminuted supracondylar fracture types. More than half of the patients were multiple injured. In 83% of the cases the internal fixation was obtained by the use of the condyle buttress plate.


Liver stiffness as surrogate parameter in emergency assessment for inpatient health care utilization.
Transient elastography (TE) allows non-invasive quantification of liver stiffness (LSM) and steatosis (controlled attenuation parameter, CAP). Here we test the feasibility and utility of TE in the emergency department (ED) and investigate whether LSM predicts longer hospitalization and reimbursement for non-elective patients. LSM and CAP were determined in prospectively recruited consecutive adult patients admitted to the ED of a tertiary referral center. Patients were stratified according to the 9.1 kPa and 13.0 kPa LSM cut-offs. Elastography measurements were correlated with clinical and outcome parameters, including duration of hospital stay and hospitalization costs. In 200 ED patients (133 men, age 18 - 97 years), median LSM was 5.5 kPa (2.4 - 69.1 kPa), and median CAP was 252 dB/m (100 - 400 dB/m). In total, 39 patients (19.5%) presented with LSM ≥ 9.1 kPa, and 24 patients (12.0%) presented with LSM ≥ 13.0 kPa. Heart failure (n = 19) was associated with higher LSM (p = 0.045). Patients with LSM ≥ 9.1 kPa were significantly (p < 0.01) more likely to require longer hospitalization than those with lower LSM. Patients with LSM ≥ 13.0 kPa generated significantly (p = 0.001) higher costs as compared to patients with low LSM. Transient elastography represents an easily accessible screening tool in ED that might help identify patients in need of increased health care resources.


Method of investigation of deviations from the normal duration of the cardiac cycle.
An electronic systems for determining the frequency of deviations from the normal duration of the cardiac cycle is described.


Adherence of group B streptococci to human buccal epithelial cells, its dependence on the biological state of the culture.
The adherence activity of Streptococcus agalactiae (group B) strains is directly dependent on the biological state of cultures. The aim of the present paper was to consider the effect of repeated transfers of cultures alternately on solid and liquid media and the effect of the growth phase. The strains, adhering weakly, strongly and variably to epithelial cells were employed in studies on the effect of repeated transfer. The percentage of adherent epithelial cells differed significantly after the first or the second transfer. On storage of the strains after the 3rd transfer at 4 degrees C for 4 d, the adherence activity decreased to the level of non-transferred strains. Ultrastructural analysis revealed in all strains the presence of capsular material, its character being similar both in strongly and in weakly adhering cultures. In weakly adherent strains, the structure of the capsular layer has not changed during transfer whereas the adherence of the strain increased considerably. The effect of the growth phase was studied during 3-48 h of incubation. The growth phase did not influence the adherence activity in strains that had been allowed to multiply for 3-24 h. After a long-term multiplication beyond 24 h, the adherence activity gradually decreased.


Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system.
One of the most important developmental modifications of the nervous system is Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin segments to provide protection to the axon as well as increase the conduction of action potentials. In vitro neuronal systems provide a unique modality to study a variety of factors influencing myelination as well as diseases associated with myelin sheath degradation. This work details the development of a patterned in vitro myelinating dorsal root ganglion culture. This defined system utilized a serum-free medium in combination with a patterned substrate, utilizing the cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional outgrowth of the neurites and subsequent myelination was controlled by surface modifications, and conformity to the pattern was measured over the duration of the experiments. The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This tissue-engineered system provides a highly controlled, reproducible model for studying Schwann cell interactions with sensory neurons, as well as the myelination process, and its effect on neuronal plasticity and peripheral nerve regeneration. It is also compatible for use in bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the media combination used is the same that we have used previously for motoneurons, muscle, and for neuromuscular junction (NMJ) formation. This work could have application for the study of demyelinating diseases such as diabetes induced peripheral neuropathy and could rapidly translate to a role in the discovery of drugs promoting enhanced peripheral nervous system (PNS) remyelination.


Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines.
The molecular basis for downregulation of the KAI1 metastasis suppressor gene in invasive and metastatic human cancers is unknown. We have used bisulphite methylation analysis of DNA from paraffin-embedded invasive bladder tumour samples and from bladder cancer cell lines to determine if hypermethylation of a CpG island within the KAI1 promoter is responsible for this effect. Representative invasive tumour cell lines were also exposed to 5-aza-2-deoxycytidine. We found no evidence for hypermethylation of the CpG island and suggest that mechanisms other than promoter hypermethylation are responsible for reduced KAI1 expression in invasive bladder tumours and tumour cell lines.


Oral direct factor Xa inhibitors for stroke prevention in atrial fibrillation.
Safe and effective stroke prevention in atrial fibrillation (AF) is crucial as the number of patients with this condition continues to increase. Several novel oral anticoagulants are being developed as replacements for warfarin for this indication. Direct factor Xa inhibitors comprise the largest class of oral anticoagulants in development; the inhibition of factor Xa is recognized to be a promising target for therapeutic anticoagulation, partly because of its location in the coagulation cascade. Apixaban, betrixaban, edoxaban, and rivaroxaban are small-molecule, selective inhibitors that directly and reversibly bind to the active site of factor Xa. Their pharmacokinetic and pharmacodynamic profiles vary, which might allow patient-specific therapy. Several of these agents have been tested in clinical trials for various indications, including AF, with favorable results. In particular, apixaban and rivaroxaban have shown superiority and noninferiority, respectively, to warfarin in phase III clinical trials for stroke prevention in AF. These agents have also been shown to be safe in terms of bleeding risk. Despite these advantages, factor Xa inhibitors have several characteristics, such as potential interactions with other drugs (inhibitors of cytochrome P450 and P-glycoprotein) and the inability to reverse their anticoagulant effects, as well as concerns about poor patient compliance, which must be considered when initiating patients on a novel factor Xa inhibitor.


Thoraco-omphalopagus twins: different perinatal circumstances, different outcome.
Two pairs of omphalopagus twins were encountered at the Polish Mother's Health Institution in Lodz, Poland during the past 15 years. In the first set the prenatal diagnosis was not established and the delivery of the twins in a regional hospital was a complete surprise. Both babies died. In the second case the conjoined twins were diagnosed prenatally, surgical separation was successful, and both twins survived. The prenatal identification of conjoined twins is of cardinal importance for the planning of delivery and possible separation.


A mathematical model for an expanding foam.
A theoretical and numerical model is presented for the shape evolution of the thin liquid films separating the gas bubbles in a foam. The motion is due to capillary action, surface tension gradients, and the overall expansion of the foam. The expansion is the result of the increase in gas content with time. Process modeling is accomplished via the solution of three coupled partial differential equations. Two time scales are included in the model: a process time and a drying or curing time. It is demonstrated that the amount of surfactant is the dominant control mechanism for the final film thickness. If sufficient surfactant is present, the films will be shown to dilate uniformly in space. A number of known features of expanding foams are reproduced by the model.


Photoelectrocatalytic activity of highly ordered TiO2 nanotube arrays modified with polyaniline for tetrabromobisphenol A degradation in water.
Polyaniline (PANI) is a useful conductive polymer material, and has good adsorption property, which makes it a good modification material. In this work, for the sake of highly enhancing the utilization of visible region in sunlight and accelerating photocatalytic degradation of tetrabromobisphenol A (TBBPA), a typical polybrominated flame retardant, titanium dioxide nanotube arrays (TiO2 NTAs) were modified with PANI by chemical and electrochemical polymerization. The coated amount of PANI was controlled via adjusting the polymerization time and the amount of aniline in the electrochemical method. The results demonstrate that the EC-PANI/TiO2 NTAs (synthesized electrochemically) exhibit higher catalytic activity than bare TiO2 NTAs and C-PANI/TiO2 NTAs (synthesized chemically) in photoelectrocatalytic degradation of TBBPA under visible light, and the degradation efficiency for TBBPA could reach 94.37% within 120 min. The improved performance was contributed to the synergetic effect of PANI modification which integrated the broad absorption of PANI in visible light region and high catalytic property of TiO2 NTAs. Interestingly, it was also found that the degradation efficiency of TBBPA by EC-PANI/TiO2 was further enhanced by up to 95.74% when the ethanol was present in the reaction system as the hole scavenger. Furthermore, the EC-PANI/TiO2 exhibited excellent stability after 10 cycling experiments. All the results indicated that this new modified material presented strong potential as a photoelectrocatalyst and had great practical applications in the future.


Prospective validation of a brief questionnaire for predicting the severity of pediatric obstructive sleep apnea.
Pediatric obstructive sleep apnea (OSA) is diagnosed and stratified by polysomnography. However, due to cost and inaccessibility, up to 90% of children undergo tonsillectomy and adenoidectomy (T&A) solely based on clinical criteria. We previously developed a data-driven brief screening questionnaire ('Selected Features,' SF) that predicted OSA severity than alternatives. The SF asks the parent whether a child: (i) has had breath-holding spells at night over the past 4 weeks, (ii) is a mouth-breather during the day, (iii) has stopped growing at a normal rate any time since birth, and (iv) is overweight. This study sought prospectively validate the SF questionnaire. We conducted a prospective assessment of the predictive accuracy of SF compared to the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorder (PSQ-SRBD) scale in otherwise healthy children with sleep disordered breathing referred for T&A. We compared the model fits of PSQ-SRDB and SF for (i) a linear regression model for the prediction of OSA, and (ii) a logistic regression model for severe OSA, defined as apnea hypopnea index (AHI) > 10. P < 0.05 was significant. A total of 124 patients were included. The average age was 7.3 years (95% confidence interval, 6.6-8.0) and 66 (54%) were male. The racial composition was 54 (44%) black, 41 (33%) white, and 28 (23%) other. The median AHI was 4.8 (interquartile range 12) and 43 (35%) of patients had severe OSA. In linear and logistic regression models, SF outperformed the PSQ-SRBD and null models as measured by Akaike Information Criteria. The overall accuracy in predicting AHI >10 for PSQ-SRBD was 0.65 (0.56-0.73, P = 0.54) compared to 0.73 (0.64-0.80, P = 0.04) for SF. By eliminating redundancy, we have developed a questionnaire with improved prediction of OSA and its severity, in children with high pre-test probability of the condition. While multi-site validation is necessary, SF demonstrates value in screening children prior to T&A in resource-limited environments.


LAIR-1 overexpression inhibits epithelial-mesenchymal transition in osteosarcoma via GLUT1-related energy metabolism.
Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor belonging to the immunoglobulin superfamily. Although previous studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying the functions of LAIR-1 as a regulator of tumor biological functions remain unclear. LAIR-1 expression was evaluated by immunohistochemical analysis using an osteosarcoma (OS) tissue microarray. Wound healing and transwell migration assays were performed to evaluate tumor cell migration. Quantitative real-time polymerase chain reaction (qPCR) and western blotting were conducted to detect the expression of epithelial-mesenchymal transition (EMT)-related molecules. RNA-sequencing (RNA-seq) was conducted to evaluate the mRNA expression profiles after overexpressing LAIR-1 in OS cells. Glucose transporter (Glut)1 expression in OS cells was evaluated by western blotting. LAIR-1 expression was significantly different between the T1 and T2 stages of OS tumors, and it inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of Twist1, an EMT-associated transcription factor, via the Forkhead box O1 signal transduction pathway. Furthermore, RNA-seq and qPCR demonstrated that the expression of EMT energy metabolism-related molecules was significantly reduced after LAIR-1 overexpression. LAIR-1 overexpression decreased the expression of Glut1 and inhibited the expression of EMT-related molecules in OS cells. These findings provide new insights into the molecular mechanism underlying OS progression.


[Post-traumatic astrocytoma].
A 25 year old woman developed a mixed pilocytic and fibrillary astrocytoma in scar tissue 20 years after the brain contusion. The case fulfilled the criteria of traumatic etiology of this brain tumor.


Advanced Materials for Electrochemical Energy Conversion and Storage Devices.
Electrochemical energy conversion and storage is attracting particular attention due to the drawbacks and limitations of existing fossil fuel-based technologies [...].


[Relevance of lower oesophageal sphincter manometry in prae- and postoperative evaluation of gastrooesophageal reflux disease (author's transl)].
In 27 patients with refluxoesophagitis the resting LES-pressure was approximatly 80% lower than in 12 patients with asymptomatic hiatal hernia and 15 controls. All patients in the first group were operated on and 21 fundoplications (Nissen) and 6 anterior plications (Dor) were performed. The postiperativ LES-pressures were 70% higher than praeoperative and almost identical for both methods. The effective restitution of a functional sphincter with these operations could be demonstrated in this way.


A simple flow cytometric assay for routine paroxysmal nocturnal hemoglobinuria testing based on immature reticulocytes and granulocytes.
The aim of this study was to test an easy-to-perform flow cytometric (FCM) assay for the routine investigation for diagnosis of paroxysmal nocturnal hemoglobinuria (PNH), through the simultaneous detection of PNH clones on immature reticulocytes (i-RET) and granulocytes. During the last 5 years, eight patients were diagnosed with PNH in our laboratory, among 90 patients prospectively studied for PNH. The determination of glycosylphosphatidylinositol (GPI) deficient cells on the erythroid lineage was made with a two-color FCM assay of CD71 and CD59, evaluating the PNH clone on i-RET. Three color combinations based on CD66b/CD16/CD45 and CD59/CD24/CD45 were used for the determination of GPI-deficient granulocytes. In all the patients with PNH, the PNH clones determined with CD71(+)CD59(-) red blood cells (RBC) were nearly identical to the respective clones determined with CD16(dim/-)/CD66b(-) and CD59(-)/CD24(-) granulocytes, in contrast to the clones determined with CD59-deficient erythrocytes only, which were significantly lower. Our results indicate that the simultaneous assessment of the PNH clone on CD71(+)/CD59(-)i-RET and CD16(dim/-)/CD66b(-) granulocytes, could offer a reliable method of two series PNH screening, at low cost and with ease of application.


Occurrence of virulence factors among human intestinal enterococcal isolates.
The aim of this study was to investigate the frequency of enterococcal virulence factors among human intestinal Enterococcus faecalis strains and to find out whether the pattern differs from that seen in published reports on food and clinical isolates. The E. faecalis isolates were cultured from human faecal samples obtained from five ulcerative colitis patients in remission phase. The species identification was based on API120 strips and species-specific PCR primers. The isolates were further characterized using the pulsed-field gel electrophoresis. The presence of seven different known enterococcal virulence factors among the confirmed E. faecalis isolates were screened using PCR techniques and published primers. Among the 35 isolates representing nine different pulsotypes the most frequent virulence factors were cpd (33 isolates), agg (25 isolates), gelE (22 isolates) and esp (15 isolates). No complete sets of genes associated for the production of functional cytolysin were encountered indicating that intestinal enterococci may differ in this respect from clinical strains. According to the results, the commensal enterococcal strains appear to differ from clinical isolates in their complement of presumed virulence factors.


Fatty acid beta-oxidation in peroxisomes and mitochondria: the first, unequivocal evidence for the involvement of carnitine in shuttling propionyl-CoA from peroxisomes to mitochondria.
We have investigated how [1-14C]propionyl-CoA, which is the first product of the peroxisomal beta-oxidation of [1-14C] pristanic acid, is transported to mitochondria for further oxidation in human skin fibroblasts from patients with a defect in the mitochondrial carnitine/acylcarnitine translocase and carnitine-palmitoyltransferase II (CPT II) (EC 22.214.171.124), respectively. Oxidation of pristanic acid was found to be partially deficient in both types of mutant cells. More important, 14CO2 production was completely deficient in the carnitine/acylcarnitine translocase deficient cells but not in the carnitine-palmitoyltransferase II deficient cells. These results strongly suggest that formation of 14CO2 in the Krebs cycle from [1-14C]propionyl-CoA as generated in peroxisomes requires the active participation of the mitochondrial carnitine/acylcarnitine translocase. The results described in this paper provide the first evidence suggesting that propionyl-CoA leaves the peroxisome as a carnitine ester and strongly suggest that the commonly accepted concept that peroxisomal beta-oxidation is not dependent on carnitine is incorrect.


The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls.
Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls. Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus. The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness. Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning.


An interview with Jayaraj Rajagopal.
Jayaraj (Jay) Rajagopal is a Principal Investigator at the Center for Regenerative Medicine at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. A Howard Hughes Medical Institute Faculty Scholar, his lab works on the development and regeneration of the lung. He uses stem cell and animal models to develop novel insights that hopefully will provide inspiration for therapies to help treat human lung disease. He was awarded the Dr Susan Lim Award for Outstanding Young Investigator at the 2017 International Society for Stem Cell Research (ISSCR) meeting in Boston (MA,USA), where we met him to talk about how a fish tank started a life-long fascination with the lung, the transition to running his own lab, and his optimism for the future of both basic stem cell research and its clinical translation.


Improved MAIT cell functions following fecal microbiota transplantation for metastatic renal cell carcinoma.
Strategies to modify the gut microbiome in cancer patients using fecal microbiota transplantation (FMT) have gained momentum as a therapeutic intervention. However, how FMT impacts innate-like, antimicrobial T lymphocytes is unclear. In this study, we assessed peripheral blood (PB) mucosa-associated invariant T (MAIT) cell frequencies and functions in patients with metastatic renal cell carcinoma (mRCC) before and seven days after they received FMT as part of a clinical trial. We found comparable MAIT cell frequencies in healthy controls and mRCC patients. In contrast, γδ T cells exhibited a numerical decline in mRCC, which was partially reversed by FMT. We also found a significant increase in the PB CD4+ MAIT cell compartment of mRCC patients with or without FMT. Paired sample analyses revealed CD69 upregulation on MAIT cells accompanied by decreased PD-1 levels post-FMT. These changes were unique to MAIT cells as non-MAIT T lymphocytes showed either no trend or a trend in the opposite direction. Importantly, FMT did not render MAIT cells exhausted as also judged by their stable expression of TIM-3, LAG-3, BTLA, CTLA-4, TIGIT and VISTA. These findings were corroborated in functional assays in which MAIT cells were stimulated with MR1 ligands or with a combination of IL-12 and IL-18 to produce inflammatory cytokines and granzyme B. Indeed, when stimulated ex vivo with IL-12 and IL-18, MAIT cells mounted a more rigorous TNF-α response post-FMT. In conclusion, FMT improves MAIT cell functions, which should serve patients well in subsequent microbial challenges in the face of cancer-elicited immunosuppression. Trial Registration: https://clinicaltrials.gov/ Identifier: NCT04163289 (registration date: November 14, 2019).


Factors related to health-promoting behaviors among Thai middle-aged men.
To study factors related to health promoting behaviors of Thai middle-aged men. Descriptive research. Nine hundred and five Thai males, aged between 40-59 years, living in six provinces of Thailand, were selected by multi-stage random sampling. Data were collected using interview, physical examination, and laboratory test. Thai middle-aged men mostly perceived their health status as fair (85.6%). Health screening showed that 7.2% had hormone deficiency, 65.7% had slight prostatic hypertrophy, and 27.3% had erectile dysfunction symptoms. Overall health promoting behaviors were at moderate level (50.7%). Marital status, having annual health examination, social support, receiving health information, and health belief were significantly related to health promoting behaviors (p < 0.05). Providing health information through materials, media, and family members would also increase accessibility to health services and promote effective health-promoting behavior of Thai middle-aged men.


Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous flow in patients with cirrhosis.
The aim of the study was to evaluate the usefulness of color Doppler sonography in the detection of spontaneous portosystemic shunts and abnormal blood flow direction in the portal vein in patients with cirrhosis. Patients were 67 men and 42 women (mean age, 53 +/- 14 years) with cirrhosis confirmed by liver biopsy. All patients underwent abdominal gray-scale and color Doppler sonographic evaluations to detect the presence of spontaneous portosystemic shunts and to analyze portal vein blood flow direction. Spontaneous portosystemic shunts were found in 41 patients (38%), most often as splenorenal shunts (21%) and patent umbilical veins (14%). Less frequent were gastric collaterals, gallbladder varices, collaterals to thrombotic portal veins, mesoiliac shunts, and portorenal shunts to the right kidney. The presence of shunts was associated with that of esophageal varices (p < 0.01), ascites (p < 0.01), and inversion of portal flow (p < 0. 001) but not with splenomegaly. The direction of portal venous flow was normal (hepatopetal) in 80 patients (73%), hepatofugal in 10 (9%), and bidirectional in 7 (6%); 12 patients (11%) had partial portal vein thrombosis. Portosystemic shunts and the direction of portal venous flow are important features in the sonographic diagnosis of portal hypertension.


Construction, expression and functional analysis of anti-B7-H4- scFv-CH3 recombinant antibody.
The B7-H4 molecule, a unique negative regulator of T lymphocytes which is overexpressed on the surface of various tumor cells, is a particularly important target candidate for tumor therapy because it can be blocked with anti-B7-H4 antibodies to inhibit the B7-H4 signaling pathway. Our previous work established an anti-B7-H4 single-chain variable fragment (scFv) library, so we have now amplified the genes encoding anti-B7-H4-scFv and human IgG1 CH3 and ligated them by overlap extension PCR to obtain a recombinant gene. After sequencing, the gene was cloned into the expression vector pET43.1a and expression was induced in E. coli BL21 (DE3) by isopropyl-β-D-1-thiogalactopyranoside (IPTG). The protein was purified on a nickel-nitrilotriacetic acid (Ni-NTA) resin column and its antigen specificity and affinity were examined by ELISA and western blotting. We also established a Lewis lung cancer model in C57BL/6 mice to further identify the biological function of the scFv protein in vivo. The results showed that tumor volume, body weight and necrotic tissues in the control group were significantly greater than in the experimental group, indicating that selected scFvs had good biological activity and could inhibit tumor growth in tumor-bearing mice. Our work thus offers a new approach for the development of cancer-targeted therapy.


The plasma level of complement component 4A decreases with aripiprazole treatment in patients with early psychosis.
The complement component 4 (C4) gene has been reported to be significantly associated with schizophrenia, and C4A RNA expression was found to increase in postmortem brains of schizophrenia patients. This study aimed to examine the plasma levels of C4A and C4B proteins in patients with early psychosis and their changes following aripiprazole treatment. We recruited 45 patients, including 17 patients with ultra-high-risk and 28 patients with first-episode psychosis, and 45 age-matched and sex-matched controls. All patients received aripiprazole treatment for 4 weeks. Each patient received symptom evaluation before and after the treatment period. We measured the plasma levels of C4A and C4B in the pretreatment and posttreatment stages of patients and controls using an enzyme-linked immunosorbent assay. We found no significant differences in C4A and C4B levels between patients and controls, but the C4A level decreased significantly with aripiprazole treatment. Multivariate analysis showed that the decrease rate of C4A was significantly associated with the treatment response of the positive symptom dimension. In summary, we found that the plasma level of C4A decreased with aripiprazole treatment, and the decrease rate was associated with the treatment response of the positive dimension in patients with early psychosis. This mechanism deserves further clarification.


Hydration and lateral organization in phospholipid bilayers containing sphingomyelin: a 2H-NMR study.
Interfacial properties of lipid bilayers were studied by (2)H nuclear magnetic resonance spectroscopy, with emphasis on a comparison between phosphatidylcholine and sphingomyelin. Spectral resolution and sensitivity was improved by macroscopic membrane alignment. The motionally averaged quadrupolar interaction of interlamellar deuterium oxide was employed to probe the interfacial polarity of the membranes. The D(2)O quadrupolar splittings indicated that the sphingomyelin lipid-water interface is less polar above the phase transition temperature T(m) than below T(m). The opposite behavior was found in phosphatidylcholine bilayers. Macroscopically aligned sphingomyelin bilayers also furnished (2)H-signals from the amide residue and from the hydroxyl group of the sphingosine moiety. The rate of water-hydroxyl deuteron exchange could be measured, whereas the exchange of the amide deuteron was too slow for the inversion-transfer technique employed, suggesting that the amide residue is involved in intermolecular hydrogen bonding. Order parameter profiles in mixtures of sphingomyelin and chain-perdeuterated phosphatidylcholine revealed an ordering effect as a result of the highly saturated chains of the sphingolipids. The temperature dependence of the (2)H quadrupolar splittings was indicative of lateral phase separation in the mixed systems. The results are discussed with regard to interfacial structure and lateral organization in sphingomyelin-containing biomembranes.


[Significance of crown-down root canal preparation technique in endodontic therapy by using the hydroxylapatite sealer].
To evaluate the crown-down preparation technique, and the use of hydroxylapatite based material for the definitive root canal obturation. The investigation included 20 single-canal roots with chronic periapical inflammatory lesion. Biomechanical medicamentous canal preparation was done using the double-flared technique with balanced force, and the obturation was performed with hydroxylapatite sealer (unicone technique). Clinical and radiographic check-up performed 12 months after the treatment, used the following parameters: pain, swelling, percussion and palpation sensitivity, and the presence of fistula. The obtained results showed a successful treatment in 18 cases, while in the 2 cases the treatment failed. These findings suggested that the crown-down preparation technique efficiently cleaned and shaped the root canal, and that the hydroxylapatite-based material created the homogenous and hermetic root canal obturation, so this methodology could be recommended for the endodontic therapy.


Linezolid treatment of ventriculoperitoneal shunt infection without implant removal.
Ventriculoperitoneal shunt infection is a serious clinical problem for which implant removal is considered the treatment of choice. However, surgery is sometimes associated with considerable risks that may outweigh the benefits. Presented here is a case of ventriculoperitoneal shunt infection treated successfully with linezolid without implant removal. This case shows linezolid could be a therapeutic alternative when surgery is contraindicated.


Step-cut distal ulnar-shortening osteotomy.
Several techniques for ulnar-shortening osteotomies have been described in recent years, reflecting the difficulties that sometimes are encountered in what seems to be a relatively simple procedure. We describe the use of a simple step-cut ulnar-shortening osteotomy stabilized with a lag screw and a palmarly placed 3.5-mm neutralization plate. Twenty-nine patients had the surgery. The indication was ulnar-impaction syndrome in 23 patients and symptomatic ulnar-plus variance secondary to trauma in 6 patients (4 with previous distal radius fractures, 2 with Essex-Lopresti injuries). The preoperative ulnar variance ranged from +1 mm to +6 mm. The mean follow-up period was 34 months. All osteotomies healed uneventfully. The mean postoperative ulnar variance was +0.2 mm (range, -1 mm to +1.5 mm). Three patients had hardware removal. The step-cut osteotomy resulted in solid union in all patients. It provides ample bone-to-bone contact and easier control of rotation, and no special instrumentation is necessary. Stable fixation permitted early mobilization of the wrist and palmar placement of the plate minimized the need for plate removal. This is a simple and effective technique for ulnar shortening.


Structure function relationships of ENaC and its role in sodium handling.
The epithelial sodium channel (ENaC) in the apical membrane of polarized epithelial cells is the rate-limiting step for Na entry into the cell; in series with the basolateral Na pump, it allows the vectorial transepithelial transport of Na ions. ENaC is expressed in different epithelia like the distal nephron or colon, and the airways epithelium. In the lung ENaC controls the composition and the amount of pulmonary fluid, whereas in the distal nephron ENaC under the control of aldosterone and vasopressin, is essential to adapt the amount of Na+ reabsorbed with the daily sodium intake. Activating mutations of ENaC cause severe disturbances of Na+ homeostasis leading to hypertension in human and in mouse models. Functional expression of ENaC in different cell systems allowed the identification of structural domains of the protein that are essential for channel function and/or modulation of channel activity. Site-directed mutations in specific domains of the channel protein lead to channel hyperactivity or channel loss of function. Knowledge about ENaC structure-function relationships opens new opportunities for development of pharmacological tools for controlling ENaC activity, such as channel activators of potential benefit in the treatment of pulmonary edema, or highly potent ENaC blockers with natriuretic effects.


The 188Re(III)-EDTA complex--a multipurpose starting material for the preparation of relevant 188Re complexes under mild conditions.
An easy and gentle method for the preparation of 188Re(V) complexes with bidentate and tetradentate ligands is described starting from the precursor complex 188Re(III)-EDTA. That complex is prepared at room temperature in acidic solution and reacts by a combined re-oxidation/ligand exchange reaction with appropriate ligands like DMSA or ECD (DMSA = dimercapto succinic acid, ECD = L,L-ethylene dicysteine diethyl ester) or en, tau, and cyclam (en = ethylene diamine, tau = 1,4,8,11-tetraazaundecane, cyclam = 1,4,8,11-tetraazacyclo-tetradecane) to the 188Re(V)-oxo- and dioxocomplexes, respectively. The chelates were unambiguously identified by chromatographic comparison with spectroscopically characterised samples or known 99mTc-kit reconstitutions. The reaction succeeds under mild conditions (room temperature, short time, neutral or weak basic solutions) with high yields and has potential for labelling of sensitive biomolecules with 188Re.


Changes in and correlates of Australian public attitudes toward illicit drug use.
The present study explores Australian public support for more lenient treatment of persons found in possession of small amounts of illegal drugs for personal use. Data for the study are drawn from the 2013, 2016 and 2019 National Drug Strategy Household Surveys. Bivariate associations were tested using χ2 tests corrected for survey design. Multivariate analyses of public support for legalisation and imprisonment involved logistic regression. Multivariate analyses of public preferences for various responses to those found in possession of illicit drugs involved the use of multinomial regression. Support for legalising personal use of three drugs (cannabis, ecstasy and cocaine) has risen significantly since 2013 but remained stable (and low) for two (heroin and methamphetamine). Support for no action, a caution or a warning has grown for those found in possession of cannabis, ecstasy and heroin for personal use but not for those found in possession of methamphetamine. There is, however, more support for responding to this group with treatment, education or a small fine than there is for imprisonment. There is strong support for legalising use of cannabis. There is little support for legalising use of ecstasy and cocaine but growing public support for a less punitive approach to those who use these drugs. There is little public support for a change in the current approach to heroin and methamphetamine.


Imidacloprid induced histomorphological changes and expression of TLR-4 and TNFα in lung.
The imidacloprid is used worldwide as a pesticide and has been linked with endocrine disturbances and reduced pulmonary function. However, effects of imidacloprid alone or in combination with microbial molecules on lungs are not fully understood. Because the pulmonary effects of interactions of endotoxins with imidacloprid are unknown, we designed a study to investigate that in a mouse model. Mice (N=14) were given imidacloprid orally @ 1/20(th) of LD50 dissolved in corn oil for 30days. After the treatments, six animals from each group were challenged with E. coli lipopolysaccharide (LPS) @ 80μg/animal via intranasal route and remaining animals were challenged with normal saline solution @ 80μl/animal via same route. Imidacloprid in combination with LPS led to significant increase in total cell and neutrophil counts in BAL and peripheral blood. Semi-quantitative histopathology revealed lung injury in imidacloprid treatment group and injury was more marked in animal receiving both imidacloprid and LPS. There was no change (p<0.05) in the expression of TLR-4 and TNF-α both at mRNA and protein levels following exposure to imidacloprid alone or in combination with LPS. The data show that imidacloprid alone or in combination with LPS resulted changes in lung morphology without altering the expression of TLR-4 and TNF-α. Furthermore, pre-treatment with imidacloprid didn't affect response to LPS.


Evolutionary game theory in an agent-based brain tumor model: exploring the 'Genotype-Phenotype' link.
To investigate the genotype-phenotype link in a polyclonal cancer cell population, here we introduce evolutionary game theory into our previously developed agent-based brain tumor model. We model the heterogeneous cell population as a mixture of two distinct genotypes: the more proliferative Type A and the more migratory Type B. Our agent-based simulations reveal a phase transition in the tumor's velocity of spatial expansion linking the tumor fitness to genotypic composition. Specifically, velocity initially falls as rising payoffs reward the interactions among the more stationary Type A cells, but unexpectedly accelerates again when these A-A payoffs increase even further. At this latter accelerating stage, fewer migratory Type B cells appear to confer a competitive advantage in terms of the tumor's spatial aggression over the overall numerically dominating Type A cells, which in turn leads to an acceleration of the overall tumor dynamics while its surface roughness declines. We discuss potential implications of our findings for cancer research.


HSV-1-based vectors for gene therapy of neurological diseases and brain tumors: part II. Vector systems and applications.
Many properties of HSV-1 are especially suitable for using this virus as a vector to treat diseases affecting the central nervous system (CNS), such as Parkinson's disease or malignant gliomas. These advantageous properties include natural neurotropism, high transduction efficiency, large transgene capacity, and the ability of entering a latent state in neurons. Selective oncolysis in combination with modulation of the immune response mediated by replication-conditional HSV-1 vectors appears to be a highly promising approach in the battle against malignant glioma. Helper virus-free HSV/AAV hybrid amplicon vectors have great promise in mediating long-term gene expression in the PNS and CNS for the treatment of various neurodegenerative disorders or chronic pain. Current research focuses on the design of HSV-1-derived vectors which are targeted to certain cell types and support transcriptionally regulatable transgene expression. Here, we review the recent developments on HSV-1-based vector systems and their applications in experimental and clinical gene therapy protocols.


Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice.
Prenatal exposure to excess glucocorticoids associates with low birthweight in rodents, primates and humans and its involvement in programming glucose homeostasis is suspected. Our aim was to further dissect the role of glucocorticoids on beta cell development and function in mice. Using the model of maternal general food restriction during the last week of pregnancy, we thoroughly studied in the CD1 mouse-mothers and fetal and adult offspring--the pancreatic, metabolic and molecular consequences of maternal undernutrition associated with excess glucocorticoids. The specific involvement of the glucocorticoid receptor (GR) was studied in mutant fetuses lacking GR in pancreatic precursors or mature beta cells. Maternal general food restriction in the mouse is associated with decreased maternal glucose and increased corticosterone levels. Fetuses from underfed dams had increased corticosterone levels, decreased pancreatic endocrine gene expression but increased exocrine gene expression and a lower beta cell mass. The offspring of these dams had a low birthweight, permanent postnatal growth retardation and, as adults, impaired glucose tolerance, decreased beta cell mass (-50%) and massively reduced islet expression (-80%) of most of the genes involved in beta cell function (e.g. Pdx1, Sur1 [also known as Abcc8], insulin). Moreover, using mutant fetuses lacking GR in pancreatic precursors or beta cells we show that the deleterious effect of undernutrition on fetal beta cell development requires the presence of the GR in pancreatic precursor cells. These results demonstrate the crucial role of excess fetal glucocorticoids and the importance of GR signalling in progenitor cells to programme beta cell mass and dysfunction.


Excitation-dependent ratiometric fluorescence response to mercury ion based on single hexagonal boron nitride quantum dots.
Since a vast majority of mercury ion (Hg2+)-responsive fluorescence probes suffer from significant false positive interference in practical applications originating from their fluorescence quenching mechanism, it is still a challenge to develop a fluorescence enhancement sensor for its assay. In this work, single hexagonal boron nitride quantum dots (BNQDs)-based probe was presented for Hg2+ assay in a fluorescence enhancement-based ratiometric manner. When Hg2+ was present, the BNQDs exhibited a new fluorescence emission peak located at 560 nm under 280 nm excitation, while the original blue fluorescence of the probe at 461 nm was quenched, realizing a ratiometric fluorescence response to Hg2+. Furthermore, it is found that fluorescence enhancement at 560 nm was dramatically suppressed under 365 nm excitation, the mechanism behind this phenomenon has been explored by experiments and relevant theories. In addition to high selectivity and detection sensitivity with LOD of 0.7 nM, the prepared probe successfully demonstrated its accuracy in Hg2+ detection in environmental water samples. Moreover, the probe could be adopted for paper sensor design, and an accurate and reliable cell phone-based portable platform was demonstrated for Hg2+ assay with LOD of 1.9 nM, suggesting its potential in point-of-care detection application.


Psychological sequelae after head traumas in adults.
Head trauma can generate various psychopathological sequelae either in intellectual functions or personality. The post-traumatic sequelae that are focused on in this work are memory disturbances, dementia and personality problems. It partially sums up fifteen years of psychological studies on head injuries conducted in the department of neurosurgery of Prof. Jean Brihaye.


Rotating consensus for double-integrator multi-agent systems with communication delay.
In this paper, the rotating consensus problem for the multi-agent systems of double-integrator dynamic is mainly considered with and without communication delay. A fully distributed control strategy is given on the more general complex plane. For the case without communication delay, we design a distributed control protocol with the help of local relative information and obtain the sufficient and necessary condition with the lower bounded control parameter for the directed communication topology. Furthermore, with taking communication delay into consideration, the sufficient and necessary condition with the upper bounded communication delay is obtained with the help of frequency domain analysis method. Compared with some existing results, the communication topology considered is a more general directed graph. Finally, some simulation examples are presented to clarify the correctness of our results.


Impaired cellular bioenergetics caused by GBA1 depletion sensitizes neurons to calcium overload.
Heterozygous mutations of the lysosomal enzyme glucocerebrosidase (GBA1) represent the major genetic risk for Parkinson's disease (PD), while homozygous GBA1 mutations cause Gaucher disease, a lysosomal storage disorder, which may involve severe neurodegeneration. We have previously demonstrated impaired autophagy and proteasomal degradation pathways and mitochondrial dysfunction in neurons from GBA1 knockout (gba1-/-) mice. We now show that stimulation with physiological glutamate concentrations causes pathological [Ca2+]c responses and delayed calcium deregulation, collapse of mitochondrial membrane potential and an irreversible fall in the ATP/ADP ratio. Mitochondrial Ca2+ uptake was reduced in gba1-/- cells as was expression of the mitochondrial calcium uniporter. The rate of free radical generation was increased in gba1-/- neurons. Behavior of gba1+/- neurons was similar to gba1-/- in terms of all variables, consistent with a contribution of these mechanisms to the pathogenesis of PD. These data signpost reduced bioenergetic capacity and [Ca2+]c dysregulation as mechanisms driving neurodegeneration.


Regulation of PTEN expression by noncoding RNAs.
Phosphatase and tensin homologue (PTEN) triggers a battery of intracellular signaling pathways, especially PI3K/Akt, playing important roles in the pathogenesis of multiple diseases, such as cancer, neurodevelopmental disorders, cardiovascular dysfunction and so on. Therefore PTEN might be a biomarker for various diseases, and targeting the abnormal expression level of PTEN is anticipated to offer novel therapeutic avenues. Recently, noncoding RNAs (ncRNAs) have been reported to regulate protein expression, and it is definite that PTEN expression is controlled by ncRNAs epigenetically or posttranscriptionally as well. Herein, we provide a review on current understandings of the regulation of PTEN by ncRNAs, which could contribute to the development of novel approaches to the diseases with abnormal expression of PTEN.


Efficient preparation of high-purity cellulose from moso bamboo by p-toluenesulfonic acid pretreatment.
This work proposed a promising biorefinery method for the deconstruction of moso bamboo by using p-toluenesulfonic acid (P-TsOH) pretreatment to product high-purity cellulose (dissolving pulp). The cellulose pulp with high α-cellulose content (82.36 %) was successfully prepared for 60 min at low pretreatment temperature (90 °C) and atmospheric pressure. After the simple bleaching and cold caustic extraction (CCE) processes, the properties of cellulose pulp, such as α-cellulose content, polymerization, ISO brightness, all met the standard of dissolving pulp. In general, the cooking method through P-TsOH pretreatment can shorten the preparation time, which can effectively reduce energy consumption and chemical consumption. Therefore, this work may provide a new perspective for the green preparation of dissolving pulp that can be used to produce lyocell fiber after ash and metal ion treatment.


An unexpected cause of chest pain, dyspnea and palpitations in a young patient during a post-COVID syndrome.
A 31-year-old male presented with sudden onset of chest pain and dyspnea after a COVID-19 infection. Initially labeled as a myopericarditis related to COVID-19, because of the young age and low risk profile, after a multiparametric evaluation was possible to diagnose and treat an unstable lesion on an intermediate branch of left coronary.


Progress in plasmonic engineering of surface-enhanced Raman-scattering substrates toward ultra-trace analysis.
This review describes advances made toward the application of surface-enhanced Raman scattering (SERS) in sensitive analysis and diagnostics. In the early sections of this review we briefly introduce the fundamentals of SERS including a discussion of SERS at the single-molecule level. Applications relevant to trace analysis, environmental monitoring, and homeland security and defense, for example high explosives and contaminant detection, are emphasized. Because the key to wider application of SERS analysis lies in the development of highly enhancing substrates, in the second half of the review we focus our attention on the extensive progress made in designing innovative soluble, supported, and ordered SERS-active nano-architectures to harness the potential of this technique toward solving current and emerging analytical tasks. No attempt or claim is made to review the field exhaustively in its entirety nor to cover all applications, but only to describe several significant milestones and progress made in these important areas and to provide some perspective on where the field is quickly moving.


Towards shortening the Brief Addiction Monitor-Revised (BAM-R).
The Brief Addiction Monitor-Revised (BAM-R) is a widely used, 17-item assessment of substance use, risk, and protective factors associated with recovery from substance use disorders. Despite wide adoption in the U.S. Department of Veterans Affairs (VA) and recommendations for use in measurement-based care (MBC), administration may not be feasible in many MBC settings due to time constraints. The purpose of this study was to derive a shortened version of the BAM-R for use in fast-paced healthcare settings. BAM-R data from 32,002 Veterans were obtained through the VA's Corporate Data Warehouse. We used logistic regression models to identify items for removal based on prediction of two clinical outcomes (90-day substance use disorder (SUD) treatment retention and 12-month mortality) and item-level sensitivity to change during substance use treatment. Although no intake BAM-R items predicted SUD treatment retention or mortality, effect sizes for item-level sensitivity to change during substance use treatment varied from small to large. Seven items were judged as relevant for MBC of SUD. Among all BAM-R items, Heavy Alcohol Use, Self-Help, Drug Use, Craving, and Mood items demonstrated the greatest magnitude of sensitivity to change. Although additional research is recommended before a shortened BAM-R can be implemented in non-specialty MBC settings, we identified 5 BAM-R items with perceived clinical utility and scores that demonstrated evidence of sensitivity to change. Shortening the BAM-R increases feasibility of use, though more work is needed to optimize measurement for SUD MBC.


Interactions between nonionic Triton X surfactants and cholesterol-containing phosphatidylcholine liposomes.
Solubilization kinetics experiments were developed to study the effects of the polyethylene glycol chain length of Triton X surfactants on their interactions with the cholesterol-containing phosphatidylcholine vesicles. An empirical liposome stability ratio was used to describe the vesicle solubilization process. The effectiveness of Triton X surfactants in solubilizing vesicles decreases with increasing polyethylene glycol chain length of surfactants. It was also shown that vesicles containing the intercalated surfactant molecules with the largest number of ethylene glycol units per molecule exhibited the exceedingly retarded solubilization behavior. Independent experiments based on a thermodynamic approach provide supporting evidence for the conclusions obtained from solubilization kinetics experiments.


Multiple forms of amylase in leaf extracts: electrophoretic transfer of the enzyme forms into amylose-containing polyacrylamide gels.
A method for the analysis of multiple forms of glucan-degrading enzymes is described. The procedure consists of the separation of the proteins by electrophoresis or isoelectric focusing in glucan-free polyacrylamide gels followed by the nondenaturing electrophoretic transfer into a second polyacrylamide layer which contains immobilized glucans. The method combines the resolving power of electrophoretic separations in glucan-free media with the sensitivity of amylase activity detection in amylose-containing polyacrylamide gels. The procedure is especially useful when samples containing low amylase activity, but a large number of multiple enzyme forms, are to be analyzed.


Study on EDTA-degrading bacterium Burkholderia cepacia YL-6 for bioaugmentation.
Bioaugmentation production of EDTA-degrading bacterium Burkholderia cepacia YL-6 was carried out in an aerobic fermentor. Three different carbon sources (ferric-ethylenediaminetetraacetate (Fe-EDTA), potassium acetate, and ethylamine) were used. The bacterium cultivated with Fe-EDTA and maintained in the growth phase could reach the maximum cell concentration on the 38th day. Whereas, the bacterium cultivated with potassium acetate and ethylamine reach the maximum cell concentration at the 76th and 100th hour. The viable-cell counts of the augmentation agents made by feeding Fe-EDTA, potassium acetate, and ethylamine were 8.2x10(10), 6.8x10(11), and 4.3x10(11) CFU/g agent, respectively. The EDTA-degradation time required for the afore-mentioned bioaugmentation agents made by feeding various carbon sources lay in the following order: ethylamine<potassium acetate<Fe-EDTA. Especially, the most efficient bioaugmentation agent (made by feeding ethylamine) only required 10 and 13 days for complete degradation of EDTA from the Fe-EDTA and Cu-EDTA complexes, respectively. It shows that ethylamine was the best substrate for augmentation production of EDTA-degrading bacterium B. cepacia YL-6.


The prognostic value of tumor/lymph node standardized uptake value max ratio and correlation with hematologic parameters in stage III nonsmall cell lung cancer.
Stage III non-small cell lung cancer (NSCLC) is a highly heterogeneous subtype of lung cancer. There are still no widely accepted prognostic parameters for stage III NSCLC. In this study, we evaluated the prognostic value of the standardized uptake value (SUV) max ratio of primary tumor to lymph node (T/N SUV max) and its correlation with various hematological parameters.Patient data were reviewed from the hospital database retrospectively. The T/N SUV max ratio was calculated by dividing the SUV max of the primary tumor by the maximal SUV max of the lymph node. The cut-off value for T/N SUV max ratio was determined by receiver operating characteristic analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. P value < .05 was considered statistically significant.A total of 52 patients were included in this study. The optimal cut-off value for T/N SUV max was 1.96 (area under the curve: 0.74; 72.7% sensitivity and 73.7% specificity). Patients with T/N SUV max ≤1.96 were defined as high risk patients and those with >1.96 were defined as low risk patients. The median event (recurrence or progression) free survival was 24.3 months (95% confidence interval: 12.0-36.6) for low risk patients, and 9.2 months (95% confidence interval: 6.1-12.4) for high risk patients (P = .0015). There was an inverse correlation between T/N SUV max and hemoglobin concentration and mean corpuscular volume (rho: -0.349, P = .011; rho: -0.312, P = .025, respectively).Low risk patients had a more favorable prognosis compared to high risk patients. We demonstrated that T/N SUV max can be of prognostic value in stage III NSCLC. T/N SUV max correlated only with hemoglobin and mean corpuscular volume.


Assessing the Walkability Environments of Churches in a Rural Southeastern County of the United States.
Churches can serve as important health promotion partners, especially in rural areas. However, little is known about the built environment surrounding churches in rural areas, including how these environments may impact opportunities for physical activity (PA) and may differ by neighborhood income levels. This study described walkability around churches in a rural county and examined differences in church walkability between high-, medium-, and low-income neighborhoods. As part of the Faith, Activity, and Nutrition study, trained data collectors conducted a windshield survey of adjacent street segments within a half-mile of churches. Churches (N = 54) in a rural southeastern county in the United States. A summary walkability score (eg, presence of sidewalks, safety features, low traffic volume) was created with a possible range from 0 to 7. Analysis of variance was used to assess differences in walkability of churches by neighborhood income levels. Walkability scores ranged from 0 to 6 (M = 2.31, SD = 1.23). Few churches had sidewalks, shoulders or buffers, or amenities nearby. In contrast, most churches had low traffic volume and no environmental incivilities. While not statistically significant, churches in low-income neighborhoods scored higher for walkability than churches in medium- and high-income neighborhoods. This study used low-cost environmental audits to analyze walkability in a sample of churches in a rural area and examined differences by neighborhood income. While churches may improve reach of people living in underserved and rural communities, a lack of environmental supports may limit effective PA promotion activities. Partnerships focused on improving existing areas or providing alternative PA opportunities for church and community members may be needed, especially in African American communities.


Neural progenitor cell pyroptosis contributes to Zika virus-induced brain atrophy and represents a therapeutic target.
Mounting evidence has associated Zika virus (ZIKV) infection with congenital malformations, including microcephaly, which raises global alarm. Nonetheless, mechanisms by which ZIKV disrupts neurogenesis and causes microcephaly are far from being understood. In this study, we discovered direct effects of ZIKV on neural progenitor cell development by inducing caspase-1- and gasdermin D (GSDMD)-mediated pyroptotic cell death, linking ZIKV infection with the development of microcephaly. Importantly, caspase-1 depletion or its inhibitor VX-765 treatment reduced ZIKV-induced inflammatory responses and pyroptosis, and substantially attenuated neuropathology and brain atrophy in vivo. Collectively, our data identify caspase-1- and GSDMD-mediated pyroptosis in neural progenitor cells as a previously unrecognized mechanism for ZIKV-related pathological effects during neural development, and also provide treatment options for ZIKV-associated diseases.


Histone-like protein in the prokaryote Thermoplasma acidophilum.
The DNA of the prokaryote Thermoplasma acidophilum is associated with a histone-like protein that has the following properties: it has a high content (23%) of basic amino acids, is positively charged at neutral pH, is soluble in acid, and can stabilize DNA against thermal denaturation. In polyacrylamide gel electrophoresis, in the presence of either sodium dodecylsulfate or urea, it migrates at the same rate as histone IV (F2a1) of calf thymus. The amino acid composition, however, it unusually rich in the amides of acidic amino acids (16-20%), and it does not appear to be closely homologous to any of the classes of eukaryotic histones. Escherichia coli DNA, on the other hand, was associated with no detectable acid-soluble proteins, and the nucleoprotein thermally denatured at a lower temperature than pure DNA.


Cell density, alignment, and orientation correlate with C-signal-dependent gene expression during Myxococcus xanthus development.
Starving Myxococcus xanthus bacteria use short-range C-signaling to coordinate their movements and construct multicellular mounds, which mature into fruiting bodies as rods differentiate into spherical spores. Differentiation requires efficient C-signaling to drive the expression of developmental genes, but how the arrangement of cells within nascent fruiting bodies (NFBs) affects C-signaling is not fully understood. Here, we used confocal microscopy and cell segmentation to visualize and quantify the arrangement, morphology, and gene expression of cells near the bottom of NFBs at much higher resolution than previously achieved. We discovered that "transitioning cells" (TCs), intermediate in morphology between rods and spores, comprised 10 to 15% of the total population. Spores appeared midway between the center and the edge of NFBs early in their development and near the center as maturation progressed. The developmental pattern, as well as C-signal-dependent gene expression in TCs and spores, were correlated with cell density, the alignment of neighboring rods, and the tangential orientation of rods early in the development of NFBs. These dynamic radial patterns support a model in which the arrangement of cells within the NFBs affects C-signaling efficiency to regulate precisely the expression of developmental genes and cellular differentiation in space and time. Developmental patterns in other bacterial biofilms may likewise rely on short-range signaling to communicate multiple aspects of cellular arrangement, analogous to juxtacrine and paracrine signaling during animal development.


Dorsal bridging plates for the treatment of high and low energy distal radius fractures.
Distal radius fractures are common and treatment of complex fracture pattens can be challenging. We assessed functional outcomes, radiographic analysis, and complications of 26 distal radius fractures treated with dorsal bridging plate (DBP) at a mean of 14 months post plate removal (6-34 months). Radiographic parameters were measured pre- and post-operatively and patient reported wrist evaluation scores, patient reported wrist range of movement and satisfaction scores. Mean post-operative total PRWE was 26 (range 0-76) and mean wrist mobility 52° flexion (range 10°-85°) and 50° extension (range 10°-85°). Mean post-operative patient satisfaction score was 89% (range 50-100%). Four patients developed complications (one EPL rupture and three developed CRPS). DBP can reliably restore distal radius anatomy and is associated with good functional outcome scores, return of functional range of wrist movement and high levels of patient satisfaction. III.


Mitochondrial gene expression in Cucurbitaceae: conserved and variable features.
We have examined mitochondrial DNA (mtDNA) sequence conservation, transcriptional patterns of mitochondrial genes, and mitochondrial translation products in four species of the plant family Cucurbitaceae, in which there is a seven-fold range in mitochondrial genome size. A set of conserved mtDNA sequences which we term "core" DNA is present in all cucurbit genomes examined. In watermelon, only those mtDNA restriction fragments which contain "core" DNA hybridize with mtRNA. Similar numbers of polypeptides are synthesized by isolated mitochondria from all species examined, but an extra set of mtDNA sequences is transcribed in the largest genome (muskmelon). Taken together, these results suggest that some mtRNA is untranslated in muskmelon. Cloned mitochondrial genes of known function, from maize, identified mitochondrial transcripts that varied in both size and number among cucurbit species.


Pneumococcal vaccination in adult solid organ transplant recipients: A review of current evidence.
This narrative review summarizes the current literature relating to pneumococcal vaccination in adult solid organ transplant (SOT) recipients, who are at risk of invasive pneumococcal disease (IPD) with its attendant high morbidity and mortality. The effect of the pneumococcal polysaccharide vaccine has been examined in several small cohort studies in SOT recipients, most of which were kidney transplant recipients. The outcomes for these studies have been laboratory seroresponses or functional antibody titers. Overall, in most of these studies the transplant recipients were capable of generating measurable serological responses to pneumococcal vaccination but these responses were less than those of healthy controls. A mathematical model estimated the effectiveness of polysaccharide vaccination in SOT recipients to be one third less than those of patients with HIV. The evidence for the efficacy of the pneumococcal conjugate vaccine in SOT is based on a small number of randomized controlled trials in liver and kidney transplant recipients. These trials demonstrated that SOT recipients mounted a serological response following vaccination however there was no benefit to the use of prime boosting (conjugate vaccine followed by polysaccharide vaccine). Currently there are no randomized studies investigating the clinical protection rate against IPD after pneumococcal vaccination by either vaccine type or linked to vaccine titers or other responses against pneumococcus. Concerns that vaccination may increase the risk of adverse alloresponses such as rejection and generation of donor specific antibodies are not supported by studies examining this aspect of vaccine safety. Pneumococcal vaccination is a potentially important strategy to reduce IPD in SOT recipients and is associated with excellent safety. Current international recommendations are based on expert opinion from conflicting data, hence there is a clear need for further high-quality studies in this high-risk population examining optimal vaccination regimens. Such studies should focus on strategies to optimize functional immune responses.


Vibrational studies of flexible solid polymer electrolyte based on PCL-EC incorporated with proton conducting NH4SCN.
A flexible solid polymer electrolyte (SPE) system based on poly(ε-caprolactone) (PCL), a FDA approved non-toxic and biodegradable material in the effort to lower environmental impact was prepared. Ammonium thiocyanate (NH4SCN) and ethylene carbonate (EC) were incorporated as the source of charge carriers and plasticizing agent, respectively. When 50 wt.% of ethylene carbonate (EC) was added to PCL-NH4SCN system, the conductivity increased by two orders from of 3.94 × 10(-7) Scm(-1) to 3.82 × 10(-5) Scm(-1). Molecular vibrational analysis via infrared spectroscopy had been carried out to study the interaction between EC, PCL and NH4SCN. The relative percentage of free ions, ion pairs and ion aggregates was calculated quantitatively by deconvoluting the SCN(-) stretching mode (2030-2090 cm(-1)). This study provides fundamental insight on how EC influences the free ion dissociation rate and ion mobility. The findings are also in good agreement to conductivity, differential scanning calorimetry and X-ray diffraction results. High dielectric constant value (89.8) of EC had made it an effective ion dissociation agent to dissociate both ion pairs and ion aggregates, thus contributing to higher number density of free ions. The incorporation of EC had made the polymer chains more flexible in expanding amorphous domain. This will facilitate the coupling synergy between ionic motion and polymer segmental motion. Possible new pathway through EC-NH4(+) complex sites for ions to migrate with shorter distance has been anticipated. This implies an easier ion migration route from one complex site to another.


[Corneal collagen crosslinking in keratoconus].
Corneal collagen crosslinking (CXL) is, at present, the only treatment that can slow or even stop the progression of keratoconus. It uses riboflavin and ultraviolet A (UVA) to create covalent bonds ("crosslinks") between collagen fibrils thus increasing corneal rigidity. Although to date there has been no direct evidence of intrastromal corneal crosslinking, several studies have reported the safety and efficacy of the conventional CXL protocol. This protocol is indicated for progressive keratoconus with a minimal corneal thickness (without the epithelium) of at least 400 μm. It should be performed as early as possible in patients under 18 years with keratoconus or with post-LASIK ectasia. Because of the epithelial debridement, it may rarely induce complications such as infectious keratitis or stromal scars. A variety of new protocols is under investigation and may reduce the rate of these complications. In addition, combination of CXL with other surgical treatments (intracorneal ring segments or photorefractive keratectomy) may improve visual outcomes in patients with keratoconus. Finally, the antimicrobial and anti-edematous properties of CXL have been shown, suggesting new therapeutic indications of this procedure such as infectious keratitis or stromal edema in the future.