Postmortem findings and possible causes of unexpected death in patients treated with intraventricular pacing.
The study comprises 10 consecutive medicolegal autopsies of patients treated with intraventricular cardiac pacing who died unexpectedly outside of a hospital. The treatment was indicated by AV-block grade I-III in eight cases, by bradyarrhythmia in one case, and sick sinus syndrome in the last case. Four patients died during a sudden epileptiform seizure, three were found dead, and three died in their sleep. Recent hemorrhages close to the AV-node and His bundle were seen in five cases. The local findings in the vicinity of the pacemaker leads were numerous and multiple consisting of thrombosis of the superior vena cava, tortuous and corroded leads, leads attached to the atrial endocardium, constricted orifice of the coronary sinus, and acute ulcerations, endocarditis, shrinking, and ruptures of the cusps of the tricuspid valve. The right atrium of the pacemaker patients was significantly dilated. The mean value of the ratios between right atrial and ventricular length (AV ratio) of the 10 pacemaker patients was 1.2 in contrast to the mean value of the same ratio of 30 controls, which was 0.6. The AV ratio was particularly increased in patients with lesions of the tricuspid valve and with a long history of cardiac pacing. In 3 of the 10 patients the immediate cause of death was related to anatomical and technical complications of long-term intraventricular pacing. Such complications were clinically unrecognized thrombosis of the superior vena cava, rupture of the chordae tendinae, and cable breakage.


[Hyperbaric oxygen therapy].
Oxygen inhalation in a chamber at the pressure exceeded 0.2 MPa produces some positive effects, that are explored for therapeutic purposes at about 30 years. Oxygen increases bactericidal capacity of leukocytes, reduces tissue edema, protects intracellular ATP, maintain tissue oxygenation even in the absence of hemoglobin. Stimulates fibroblast replication, increases collagen production, stimulates arborisation of capillaries into ischemic tissue, protects from lipid peroxidation. These properties of oxygen are exploit in acute, life threatened conditions and in various chronic ischemias. Hyperbaric oxygen therapy as an adjuvant together with conservative and invasive therapy methods helps to decrease morbidity, work incapability, invalidisation and mortality in oclusive and inflammatory arteriities, diabetic gangrene and other forms of clinical leg ischemia. The use of hyperbaric oxygenation will become increasingly common as more hyperbaric facilities are established.


Regulation of the mitochondrial adenine nucleotide pool size in liver: mechanism and metabolic role.
The ATP-Mg/Pi carrier in liver mitochondria can catalyze the exchange of ATP-Mg on one side of the inner membrane for Pi on the other. This mechanism allows for net uptake or release of ATP-Mg from mitochondria and thus regulates the matrix ATP + ADP + AMP pool size. In isolated mitochondria, carrier activity is stimulated by submicromolar concentrations of calcium, suggesting that calcium may regulate transport rates in vivo. Whenever the carrier is active, the direction of any net changes in the matrix adenine nucleotide pool size is determined mainly by the extent to which the prevailing ATP-Mg concentration gradient deviates from an equilibrium related to delta pH through the phosphate concentration gradient. Thus it seems that in the cell, energy status (reflected by ATP:ADP ratios in the cytoplasm and matrix) determines whether calcium-mediated hormone activation of the carrier will produce an increase or a decrease in the matrix adenine nucleotide content. Consequent variations in the absolute concentrations of ATP, ADP, and AMP in the matrix may contribute to the selective regulation of those metabolic activities in the cell that have adenine nucleotide dependent steps localized to the mitochondrial compartment (gluconeogenesis, urea synthesis, mitochondrial biogenesis, and even oxidative phosphorylation).


Neuroendocrine insights into neurosteroid therapy for postpartum depression.
Postpartum depression (PPD) is associated with a decline in progesterone-derived anxiolytic-antidepressant neurosteroids after delivery. Neurosteroid replacement therapy (NRT) with GABA-A receptor-modulating allopregnanolone (brexanolone) shows promise as the first drug treatment for PPD. Here we describe the molecular insights of the neurosteroid approach for rapid relief of PPD symptoms compared with traditional antidepressants.


Arterial Switch Operation in Single Coronary Ostium With Intramural Course: Subclavian Artery Patch Angioplasty.
This report describes a neonatal arterial switch operation in a transposition of the great arteries with single ostium and intramural course coronary pattern. The technique proposed is based on the creation of two coronary neoostia by incising the left coronary intramural course and splitting the common button followed by a patch enlargement of left coronary button using the left subclavian artery.


Antioxidant and cytotoxic isoprenylated coumarins from Mammea americana.
Antioxidant-guided fractionation of Mammea americana L. seeds resulted in the identification of three new isoprenylated coumarins, mammea B/BA hydroxycyclo F (1), mammea E/BC (2), and mammea E/BD (3). In addition, twelve known isoprenylated coumarins, mammea A/AA (4), mammea A/AA cyclo D (5), mammea A/AA cyclo F (6), mammea A/AC cyclo D (7), mammea A/AD cyclo D (8), mammea B/BA (9), mammea B/BA cyclo F (10), mammea B/BB (11), mammea B/BC (12), mammea B/BD (13), mammea E/BA (14), and mammea E/BB (15), as well as two known flavanols, (+)-catechin (16) and (-)-epicatechin (17) were identified. The fifteen isoprenylated coumarins were screened for their cytotoxicity in the SW-480, HT-29, and HCT-116 human colon cancer cell lines and antioxidant capacities in the DPPH (1,1-diphenyl-2-picrylhydrazyl) free-radical assay. Compounds 1 - 15 exhibited significant cytotoxic activities in the SW-480, HT-29, and HCT-116 human colon cancer cell lines (IC50 ranges 13.9 - 88.1, 11.2 - 85.3, and 10.7 - 76.7 microM, in the three cell lines, respectively) at concentrations comparable to 5-fluorouracil (IC50 = 53.0, 46.1, and 45.1 microM), a drug frequently used for human colon cancer treatment. Compounds 2 - 4, 9, and 11 - 15 displayed high antioxidant activity in the DPPH assay (IC50 range 86 - 135 microM), compounds 1, 5 - 8, and 10, however, had no antioxidant activity (IC50 > 200 microg/mL) in the DPPH assay. The results of these assays were used to study the structure-activity relationships for this class of compounds. In the SW-480 cell line, the three new coumarins, 1 - 3, also exhibited dose-dependent increases in sub-diploid cells by flow cytometry, indicating that they induce apoptosis.


Molecular and biological characterization of pyocyanin from clinical and environmental Pseudomonas aeruginosa.
Pyocyanin is a secondary metabolite secreted by P. aeruginosa. It is a redox-active blue/green phenazine pigment that has various beneficial applications. The present study aims at screening the production of pyocyanin among clinical and environmental P. aeruginosa isolates in Dakahlya governorate, Egypt. Thereafter, large-scale production, purification, structure elucidation, and assessment of the biological activity of the highest pyocyanin producers were targeted. Pyocyanin from the highest clinical (PsC05) and environmental (PsE02) producers were subjected to large-scale production, followed by purification using silica gel column. Pyocyanin was characterized using TLC, UV-Vis, 1 H NMR, and FTIR spectroscopy to confirm its structure and purity. Purified pyocyanin showed remarkable antimicrobial efficacy against all tested food-borne pathogens, MDR/XDR clinically isolated bacteria and C. albicans. Furthermore, it showed a substantial effect on biofilm inhibition and eradication of pre-formed biofilm against strong biofilm producing bacterial pathogens. However, it had limited antibiofilm activity against C. albicans. Pyocyanin from PsC05 had higher antioxidant and radicals scavenging activity than that from PsE02 as determined by FRAP, DPPH, and ABTS assays. Likewise, pyocyanin from PsC05 was more active against tested cancer cell lines, especially human Breast Cancer (MCF-7) and Colorectal Carcinoma (HCT-116), than that from PsE02. More importantly, it showed minimal cytotoxicity to normal cells. P. aeruginosa clinical and environmental isolates produce pyocyanin pigment in varying amounts. Pyocyanin exhibits substantial anti-bacterial, and anti-fungal activity; thus, enhancing its medical applicability. It could be used to inhibit and/or eradicate biofilm from the surfaces of medical devices which is a chief source of nosocomial infections. Its antioxidant along with cytotoxic activity against cancer cell lines, make it a promising contender for use as a substitute for synthetic agents in cancer treatment.


Accelerating hyperpolarized metabolic imaging of the heart by exploiting spatiotemporal correlations.
Hyperpolarized (13)C-labeled pyruvate is a promising tool to investigate cardiac metabolism. It has been shown that changes in substrate metabolism occur following the induction of ischemia. To investigate the metabolic changes that are confined to spatial regions, high spatiotemporal resolution is required. The present work exploits both spatial and temporal correlations using k-t principal component analysis (PCA) to undersample the spatiotemporal domain, thereby speeding up data acquisition. A numerical model was implemented to investigate optimal acquisition and reconstruction parameters for pyruvate, lactate and bicarbonate maps of the heart. Subsequently, prospectively undersampled in vivo data on rat hearts were acquired using a combination of spectral-spatial signal excitation and a variable-density single-shot echo planar readout. Using five-fold k-t PCA, a spatial resolution of 1 × 1 mm(2) at a temporal resolution of 3 s was achieved.


Midterm Outcomes for Polytetrafluoroethylene Valved Conduits.
Various conduits for right ventricular outflow tract reconstruction have been reported, but most of them are not available in China. The study investigators developed a simple handsewn valved conduit using expanded polytetrafluoroethylene (ePTFE). This study evaluated the midterm outcomes for this conduit. This retrospective study included a total of 72 patients who underwent right ventricular outflow tract reconstruction with ePTFE valved conduits between January 2014 and June 2020. During follow-up, echocardiograms were performed for all patients, and magnetic resonance imaging was performed for patients with repaired tetralogy of Fallot. Patients had a median age of 69 months (interquartile range, 28-127 months) and a median follow-up period of 33 months (interquartile range, 9-51 months). There was no early death, but 2 late deaths (2.78%) occurred. The median conduit size was 18 mm (interquartile range, 18-20 mm) and the z score was +1.3 (interquartile range, +0.6-+2). Peak velocity across the ePTFE valve was 2.38 m/s (95% CI, 2.11-2.63 m/s). Pulmonary valve regurgitation was none or trivial in 27 (38.5%) patients, mild in 42 (60.0%) patients, and moderate in 1 (1.4%) patient. Conduit dysfunction occurred in 5 patients: 4 had moderate conduit stenosis, and 1 had moderate regurgitation. The right ventricular end-diastolic volume index in repaired tetralogy of Fallot was significantly decreased after surgery (171 mL/m2 vs 130 mL/m2; P < .001). No reintervention or conduit replacement was needed. This handsewn ePTFE valved conduit was associated with appreciable hemodynamic outcomes during the midterm follow-up period. Long-term follow-up studies are needed to corroborate these findings.


Leader-following consensus of nonlinear discrete-time multi-agent systems with limited bandwidth and switching topologies.
This paper considers the leader-following consensus problem of discrete-time nonlinear multi-agent systems over switching topologies with limited bandwidth. Through the encoding-decoding data, we design a distributed feedback control protocol which is closely associated with the connectivity of relevant channel at each time step. An adaptive communication mechanism is presented to ensure fewer bits of information transmission at each time step under the premise that the quantizer for encoding and decoding is not saturated. Although the nonlinear model over switching topologies introduces a cumulative error with respect to consensus error at previous time steps, the convergence rate of the system can be characterized. Through a rigorous convergence analysis, we illustrate that if the jointly connected condition of communication networks is satisfied, consensus issues will be resolved. A numerical simulation example shows that based on the designed distributed control law, all states of the follower agents are ultimately the same as the leader's state.


Gene order on the short arm of human chromosome 11: regional assignment of the LDH A gene distal to catalase in two translocations.
Leukemic cells with reciprocal translocations involving 11p13 and 14q13 were obtained from two patients with T-cell acute lymphoblastic leukemia and fused with mouse Ltk- cells. DNA from independent hybrid clones was screened by Southern blot and hybridization to molecular probes for the human catalase and Ha-ras-1 genes. Several clones showed segregation of these two genes, indicating the presence of either the der11 or der14 human chromosomes. When DNA from these hybrid clones was examined for the presence of the human genes for calcitonin and gamma-globin, both genes were found to segregate with the Ha-ras-1 gene and the der14 chromosome indicating that they lie distal to catalase. When the hybrid clones were examined for the presence of human lactate dehydrogenase A (LDH A) activity, only those clones containing the der14 chromosome expressed activity indicating that the LDH A gene is also distal to catalase on the short arm of chromosome 11.


Correlation of the cell surface antigens with stage and grade in cancer of the bladder.
We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.


Evaluation of portable blood glucose meters for measurement of blood glucose concentration in ferrets (Mustela putorius furo).
To evaluate agreement of 3 models of portable blood glucose meters (PBGMs; 2 designed for use with human samples and 1 designed for veterinary use) with a laboratory analyzer for measurement of blood glucose concentrations in ferrets (Mustela putorius furo). Evaluation study. 52 ferrets. Samples were analyzed with 4 PBGMs (whole blood) and a laboratory analyzer (plasma). Two PBGMs of the model designed for veterinary use were tested; each was set to a code corresponding to canine or feline sample analysis throughout the study. Agreement and bias between measurements obtained with the PBGMs and the laboratory analyzer were assessed with Bland-Altman plots. Linear regression analysis was performed to evaluate associations with venipuncture site by comparison of central (jugular) and peripheral (lateral saphenous or cephalic) venous blood samples. Plasma glucose concentrations measured with the laboratory analyzer ranged from 41 to 160 mg/dL. Results from the PBGM for veterinary use coded to test a canine blood sample had the greatest agreement with the laboratory analyzer (mean bias, 1.9 mg/dL); all other PBGMs significantly underestimated blood glucose concentrations. A PBGM designed for use with human samples had the least agreement with the laboratory analyzer (mean bias, -34.0 mg/dL). Blood glucose concentration was not significantly different between central and peripheral venous blood samples for any analyzer used. Significant underestimation of blood glucose concentrations as detected for 3 of the 4 PBGMs used in the study could have a substantial impact on clinical decision making. Verification of blood glucose concentrations in ferrets with a laboratory analyzer is highly recommended.


A Doppler waveform index to characterize hepatic vein velocity pattern and evaluate hepatic fibrosis.
To describe a Doppler waveform index representing the hepatic vein flow velocity pattern and to examine its relationship to the degree of hepatic fibrosis. Doppler waveforms were obtained in 66 patients scheduled for percutaneous liver needle biopsy and categorized as normal (with a retrograde flow phase) or abnormal (without retrograde flow). Waveforms were also characterized using a hepatic vein waveform index (HVWI): (maximum - minimum velocity)/(maximum velocity). Biopsy specimens were graded for fibrosis. There was a highly significant decrease in HVWI with increasing fibrosis score in the biopsy (p < 0.001, Jonckheere trend test). The biopsy showed cirrhosis in 14 of 29 patients (48%) with absent retrograde flow and 5 of 37 patients (14%) with a normal flow pattern. Using HVWI as the criterion, cirrhosis was present in 13 of 21 (62%) patients with HVWI < 0.75, in 6 of 31 (19%) patients with 0.75 < HVWI < 1.50, and in none of 14 (0%) patients with HVWI > 1.50. HVWI is inversely correlated to the degree of liver fibrosis and may be more efficient than the presence or absence of retrograde flow in diagnosing and grading hepatic fibrosis.


Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.
To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. Across the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.


[Amputation and exarticulation of the lesser toes].
Amputations and exarticulations of the toes may be necessary due to several reasons. The goal is to remove necrosis or infection prior to its spread to the midfoot region. From a functional or cosmetic point of view, amputation/exarticulation of a single toe plays no major role. However, this can be different with exarticulation of several toes. Necrosis, trauma, infection, tumor, deformity. Conditions where amputation/exarticulation of a toe is insufficient, e. g., in progressing peripheral arterial disease. The toe can either be amputated through the distal phalanx or exarticulated in the metatarsophalangeal joint. Orthopedic shoes or orthotic devices are rarely necessary when a single toe is amputated/exarticulated. However, concomitant deformities of the foot have to be thoroughly addressed. If more than one toe is amputated, silicone spacers may be necessary to prevent the remaining toes from deviating. Amputations and exarticulations of the toes are frequent and the procedure is technically simple. However, the complication rate is high due to typical indications making amputation necessary.


Factors controlling cardiac myosin-isoform shift during hypertrophy and heart failure.
Myosin is a molecular motor, which interacts with actin to convert the energy from ATP hydrolysis into mechanical work. In cardiac myocytes, two myosin isoforms are expressed and their relative distribution changes in different developmental and pathophysiologic conditions of the heart. It has been realized for a long time that a shift in myosin isoforms plays a major role in regulating myocardial contractile activity. With the recent evidence implicating that alteration in myosin isoform ratio may be eventually beneficial for the treatment of a stressed heart, a new interest has developed to find out ways of controlling the myosin isoform shift. This article reviews the published data describing the role of myosin isoforms in the heart and highlighting the importance of various factors shown to influence myosin isofrom shift during physiology and disease states of the heart.


Zinc-induced changes in ionic currents of cardiomyocytes.
The whole-cell voltage-clamp technique was applied to isolated ventricular myocytes to investigate the effects of extracellular and intracellular zinc application on L-type Ca2+ channel currents (ICa). Extracellular zinc exposure at micromolar concentration induced a reversible (with washout of ZnCl2) reduction (30%) of ICa with no change in current-voltage relationship. On the other hand, an increase of intracellular free-zinc concentration, [Zn2+]i, from normal (less than 1 nM) to approx 7 nM with 10 microM Zn-pyrithione exposure caused an inhibition of 33+/-6% in the peak of the ICa and altered the voltage dependency of L-type Ca2+ channels with a 10-mV left shift and a hump at around -40 mV in its current-voltage relation. In contrast, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly inhibited the ICa (42+/-2%), with only a small but detectable outward shift of the holding current measured at the end of the pulses. Zn-pyrithione and TPEN caused a reproducible decrease of the ICa. Interestingly, TPEN application, without Zn-pyrithione pretreatment, inhibited the ICa (35+/-2%) with no change in voltage dependency. Taken together, the results suggest that both extracellular and intracellular zinc increases under pathological conditions in cardiomyocytes can alter the ICa, but their effects are not in the same order and same manner. One should consider these possible side effects when it is suggested to be vital to cardiovascular cell integrity and functions.


'Doing the best we can': Registered Nurses' experiences and perceptions of patient safety in intensive care during COVID-19.
To explore registered nurses' experiences of patient safety in intensive care during COVID-19. A qualitative interview study informed by constructivism. Semi-structured interviews were conducted and audio-recorded with 19 registered nurses who worked in intensive care during COVID-19 between May and July 2021. Interviews were transcribed verbatim and thematically analysed utilizing framework. Two key themes were identified. 'On a war footing'-an unprecedented situation which describes the situation nurses faced, and the actions are taken to prepare for the safe delivery of care. 'Doing the best we can'-Safe Delivery of Care which describes the ramifications of the actions taken on short- and long-term patient safety including organization of care, missed and suboptimal care and communication. Both themes were embedded in the landscape of Staff Well-being and Peer Support. Nurses reported an increase in patient safety risks which they attributed to the dilution of skill mix and fragmentation of care. Nurses demonstrated an understanding of the holistic and long-term impacts on patient safety and recovery from critical illness. This study explored the perceived impact of COVID-19 on patient safety in intensive care from a nursing perspective. Dilution of skill mix, where specialist critical care registered nurses were diluted with registered nurses with no critical care experience, and the fragmentation of care was perceived to lead to reduced quality of care and increased adverse events and risk of harm which were not consistently formally reported. Furthermore, nurses demonstrated a holistic and long-term appreciation of patient safety. These findings should be considered as part of future nursing workforce modelling and patient safety strategies by intensive care leaders and managers. No public or patient contribution to this study. The study aims and objectives were developed in collaboration with health care professionals.


Functioning of the Antioxidant Defense System in Rotenone-Induced Parkinson's Disease.
A comprehensive study of the functioning of antioxidant system in rats with rotenone-induced parkinsonism was conducted. The development of pathology led to inhibition of the majority of the studied antioxidant enzymes in the brain and blood serum of animals, which can be associated with decompensation of oxidative stress under conditions of prolonged mitochondrial dysfunction. These changes apparently make an important contribution into neuronal degeneration in the cerebral cortex and striatum and motor disorders in experimental animals.


Genetic relatedness of Gram-negative bacteria colonizing gut and skin of neonates and mother's own milk.
We described colonization of mother's own milk with Gram-negative bacteria and its relationship with neonatal colonization. Gram-negative bacteria isolated from weekly collected stool, skin and mother's own milk of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped. Colonization-related factors were determined by logistic regression. Gram-negative bacteria were isolated from mother's own milk of 22.4% (n = 11) and 15% (n = 3) of mothers of preterm and term neonates, respectively. According to pulsed-field gel electrophoresis genetically similar strains were present in mother's own milk and gut of 8.2% (n = 4) of mother-preterm neonate, but none of mother-term neonate pairs. In three of four late-onset sepsis caused by Gram-negative bacteria, colonization of gut, but not mother's own milk, with invasive species preceded late-onset sepsis. Colonization of mother's own milk with Gram-negative bacteria is uncommon and transmission to neonatal gut may occur in less than one-tenth of neonate-mother pairs.


Interactive and multi-sensory analysis of complex mixtures by an automated gas chromatography system.
Methods are presented for increased human-computer interactions in the analysis of metabolic profiles of urinary organic acids. Complex mixtures of trimethylsilylated derivatives are separated by capillary gas-liquid chromatography on a 25-m bonded-phase, fused-silica column. Retention times and areas, determined by a printing integrator, are transferred to a personal computer along with the digitized output of the flame-ionization detector. Post-run computer analysis gives enhanced visual graphic displays with software-driven zooming, scrolling, peak identification and quantitation. In addition, auditory (musical) forms can be produced that increase the scope of human interaction. This novel approach catalyzes simultaneous use of computer calculations and human intuition, optimizing their combined cognitive powers for accurate qualitative and quantitative analyses of these complex mixtures.


Type IVB piliated Salmonella typhi enhance IL-6 and NF-kappaB production in human monocytic THP-1 cells through activation of protein kinase C.
Salmonella typhi is an important human pathogen responsible for typhoid fever. Type IVB pili, encoded by the S. typhi pil operon located in the major pathogenicity island, are used to facilitate bacterial entry into human intestinal cells in vitro and may be important in the mediation of enteric fever in humans. However, possible involvement of the type IVB pili of S. typhi in signal transduction in infected immune cells has not been examined previously. In this study, we have compared the effect of piliated and nonpiliated S. typhi on the activities of protein kinase C (PKC), the production of interleukin-6 (IL-6) and nuclear transcription factor NF-kappaB in human monocytic THP-1 cells. We find that piliated S. typhi can stimulate significantly higher activities of PKC, the production of IL-6 and NF-kappaB than a nonpiliated strain based on substrate phosphorolysis kinase assay, Western blot, RT-PCR, and luciferase reporter gene assay. In time course experiments, PKC activity increased in a time-dependent fashion after stimulation by the piliated bacteria. The PKC inhibitor Dequalinium chloride (DECA) remarkably reduced the production of IL-6, NF-kappaB and the activity of PKC induced by the piliated S. typhi. These results suggest that the induction of IL-6 and NF-kappaB depend on the PKC signal pathway. Our report demonstrates that the type IVB pili of S. typhi play important roles in the production of NF-kappaB and the proinflammatory cytokine IL-6, and in the stimulation of PKC activity and therefore, may have effects on the development of fever and other inflammatory responses.


[Experimental study of Bailian Caogen granule on pharmacodynamics].
To study the analgesic, antipyretic and anti-inflammatory effect of Bailian Caogen granule. The antipyretic effects of Bailian Caogen granule was evaluated in rabbit fever model induced by peptone. The analgesic effect of the drug was studied with pain model of mice induced by acetic acid and hot plate, The severity of oedema in inflamed animal was observed to study the anti-inflammatory effects of Bailian Caogen granule. Bailian Caogen granule could obviously inhibit the fever of rabbits. The number of writhing induced by acetic acid was reduced and the pain threshold of mice was increased by Bailian Caogen granule. Bailian Caogen granule also had anti-inflammatory activity against xylene-induced mouse ear swelling and carrageenin-induced rat paw edema. Bailian Caogen granule has significant analgesic, antipyretic and anti-inflammatory activities.


A randomized controlled trial of the effect of participatory ergonomic low back pain training on workplace improvement.
This study aimed to determine the effects of participatory workplace improvement (PWI) -based provision of ergonomic training and ergonomic action checklists (ACLs) to on-site managers on workplace improvement activities for low back pain (LBP). A randomized controlled trial (RCT) was conducted at a manufacturing company in Japan. Teams entered in the study were randomly assigned to a control and an intervention group. A total of three interventional training sessions on methods of ergonomics were provided to on-site managers in the intervention group, with 1-month intervals between sessions. Ergonomic ACLs were provided at the same time. After completion of the training sessions, each team then provided a report of improvements each month for the next 10 months. Two people in charge of safety and health chose two major objectives of the implemented activities from the five categories. The reported number of improvements was analyzed using a Poisson regression model. In the intervention group, although the incident rate ratio (IRR) of PWIs in countermeasures for the LBP category was significantly elevated after the training sessions, the IRR of improvements decreased over time during the 10-month follow-up period. No significant difference was observed in the IRR of total PWIs in either the control or intervention group. PWI-based provision of ergonomic training sessions and ergonomics ACLs to on-site managers was shown to be effective for workplace improvement activities targeted at LBP. However, because the effects decrease over time, efforts should be made to maintain the effects through regular interventions.


Prediction of drug release from HPMC matrices: effect of physicochemical properties of drug and polymer concentration.
A working equation to predict drug release from hydroxypropyl methylcellulose (HPMC) matrices was derived using a training set of HPMC matrices having different HPMC concentration (w/w, 16.5-55%) and different drugs (solubilities of 1.126-125.5 g/100 ml in water and molecular volumes of 0.1569-0.4996 nm(3)). The equation was log(M(t)/M( infinity ))=-0.6747+1.027 log t -0.1759 (log C(s)) log t +0.4027 (log V) log t -1.041C(H) +0.3213 (log C(s)) C(H) -0.4101 (log V) C(H) -0.3521 (log V) log C(s) (n=263, r=0.9831), where M(t) is the amount of drug released at time t, M( infinity ) the amount of drug released over a very long time, which corresponds in principle to the initial loading, t the release time (h), C(s) the drug solubility in water (g/100 ml), V the volume of drug molecule (nm(3)), and C(H) is HPMC concentration (w/w). The benefit of the novel model is to predict M(t)/M( infinity ) values of a drug from formulation and its physicochemical properties, so applicable to the HPMC matrices of different polymer levels and different drugs including soluble drugs and slightly soluble drugs.


Dopaminergic inhibition of prolactin synthesis and prolactin messenger RNA accumulation in cultured pituitary cells.
Prolactin synthesis was investigated in monolayer cultures of dispersed pituitary cells maintained in defined medium. Electrophoresis of cell extracts from cultures labeled with [35S]methionine demonstrated that treatment with the dopaminergic drug, ergocryptine, specifically inhibited prolactin synthesis. Analysis of the time course of ergocryptine effects demonstrated that prolactin synthesis decreased sharply after 1 to 2 days of treatment and appeared to reach a new level of 26 to 28% of control values after 4 to 6 days of treatment. The concentration of ergocryptine which produced half-maximal inhibition of prolactin synthesis was about 0.3 nM. The inhibition of prolactin synthesis produced by ergoctryptine treatment was reversed by removal of the ergocryptine. Dopamine, ergocryptine, and bromoergocryptine (also a dopamine agonist) all inhibited prolactin synthesis while epinephrine and norepinephrine had little effect. The concentration of prolactin mRNA in cultured cells was assayed by hybridization of total cell RNA to prolactin cDNA. Analysis of cultures treated either for varying times or with varying doses of ergocryptine demonstrated that there was a close correspondence between the inhibition of prolactin synthesis and the inhibition of prolactin mRNA levels. These studies demonstrate the ability of dopaminergic stimulation to specifically inhibit prolactin synthesis and to decrease prolactin mRNA levels in primary cultures of pituitary cells maintained in defined medium.


Correction: Cardiometabolic outcomes of women exposed to hyperglycaemia first detected in pregnancy at 3-6 years post-partum in an urban South African setting.
[This corrects the article DOI: 10.1371/journal.pone.0263529.].


Improved Indicator Algorithms for Tracking a Hydrated Proton as A Local Structural Defect in Grotthuss Diffusion in Aqueous Solutions.
Keeping track of a hydrated proton in dynamics simulations is important and nontrivial. Here, we report two revised algorithms for the proton indicator, a pseudo-atom whose position approximates the location of an excess proton diffusing via the Grotthuss mechanism in aqueous solution. The new methods describe the delocalized proton as a structural defect. Encouragingly, in test simulations of a hydrated proton in bulk water, the new algorithms substantially outperform the original scheme by significantly reducing large displacements in the indicator positions upon donor switch, yielding smoother trajectories that effectively track the movement of the solvated proton.


Chromium (IV) transfer to Amusium pleuronectes by LDPE microplastics: An experimental study.
An experiment was carried out to investigate the potential of virgin LDPE microplastics to transfer heavy metals. Desired shapes (fibres, fragments, and films) and sizes (< 5 mm) of virgin LDPE microplastics were immersed in a known concentration (30 µg/l) of chromium (IV). These Cr-coated microplastics were introduced into a culture tank containing edible scallops (Amusium pleuronectes). After the completion of the experiment (5 days), the sediments in the culture tank and edible tissues of A. pleuronectes were tested for the presence of Cr. In the sediments, a maximum concentration of 1.934 µg/g of Cr was accumulated at a rate of R2 = 0.979, while in the tissues, the maximum accumulation concentration was 0.733 µg/g of Cr at a rate of R2 = 0.807. Energy Dispersive X-ray Spectroscopy analysis also confirmed the presence of Cr (2.61 ± 0.44 mass % and 1.80 ± 0.30 atom%) in the tissues of A. pleuronectes, which was absent in the control tissues. The study showed that when exposed to contaminants such as heavy metals, LDPE microplastics can adhere and transfer them to biotic tissues. LDPE showed the potential to transfer adhered contaminants; however, the effects caused by these transferred contaminants on biota must be studied further. Risk assessment study showed that potential ecological risk of Cr is < 40 indicating low risk however, the combined effect of Cr and LDPE can compound its toxicity which needs to be studied further.


Surgical management of severe pancreatic fistula after pancreatoduodenectomy: a comparison of early versus late rescue pancreatectomy.
Rescue pancreatectomy for postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD) is associated with high mortality. However, in-depth literature is scarce and hard to interpret. This study aimed to evaluate the indications, timing and perioperative outcomes of rescue pancreatectomy for severe POPF after PD. Retrospective single-centre study from all consecutive patients (2008-2020) with POPF-C after PD (ISGPS 2016 definition). Major morbidity and mortality during hospitalization or within 90 days after index surgery were evaluated. Time from index surgery to rescue pancreatectomy was dichotomized in early and late (≤ 11 versus > 11 days). From 1076 PDs performed, POPF-B/C occurred in 190 patients (17.7%) of whom 53 patients (4.9%) with POPF-C were included. Mortality after early rescue pancreatectomy did not differ significantly compared to late rescue pancreatectomy (13.6% versus 35.3%; p = 0.142). Timing of a rescue pancreatectomy did not change significantly during the study period: 11 (IQR, 8-14) (2008-2012) versus 14 (IQR, 7-33) (2013-2016) versus 8 days (IQR, 6-11) (2017-2020) (p = 0.140). Over time, the mortality in patients with POPF grade C decreased from 43.5% in 2008-2012 to 31.6% in 2013-2016 up to 0% in 2017-2020 (p = 0.014). However, mortality rates after rescue pancreatectomy did not differ significantly: 31.3% (2008-2012) versus 28.6% (2013-2016) versus 0% (2017-2020) (p = 0.104). Rescue pancreatectomy for severe POPF is associated with high mortality, but an earlier timing might favourably influence the mortality. Hypothetically, this could be of value for pre-existent vulnerable patients. These findings must be carefully interpreted considering the sample sizes and differences among subgroups by patient selection.


Synthesis and antimicrobial activity of 2,3-bis(bromomethyl)quinoxaline derivatives.
We synthesized 12 derivatives of 2,3-bis(bromomethyl)quinoxaline with substituents at the 6- and/or 7-positions, and evaluated their activities against bacteria and fungi. Of the 12 compounds, nine (1a-h, 1j, and 1k) showed antibacterial activity. The derivative 1g, which bears a trifluoromethyl group at the 6-position, showed the highest activity against Gram-positive bacteria, while 1c, which has a fluoro-group at the 6-position, showed the widest antifungal activity spectrum. However, only the derivative with an ethyl ester substitution, 1k showed activity against Gram-negative bacteria.


Gender Identity, Sexual Orientation, and Eating-Related Pathology in a National Sample of College Students.
This study examined associations of gender identity and sexual orientation with self-reported eating disorder (SR-ED) diagnosis and compensatory behaviors in transgender and cisgender college students. Data came from 289,024 students from 223 U.S. universities participating in the American College Health Association-National College Health Assessment II (median age, 20 years). Rates of past-year SR-ED diagnosis and past-month use of diet pills and vomiting or laxatives were compared among transgender students (n = 479) and cisgender sexual minority (SM) male (n = 5,977) and female (n = 9,445), unsure male (n = 1,662) and female (n = 3,395), and heterosexual male (n = 91,599) and female (n = 176,467) students using chi-square tests. Logistic regression models were used to estimate the odds of eating-related pathology outcomes after adjusting for covariates. Rates of past-year SR-ED diagnosis and past-month use of diet pills and vomiting or laxatives were highest among transgender students and lowest among cisgender heterosexual men. Compared to cisgender heterosexual women, transgender students had greater odds of past-year SR-ED diagnosis (odds ratio [OR], 4.62; 95% confidence interval [CI], 3.41-6.26) and past-month use of diet pills (OR, 2.05; 95% CI, 1.48-2.83) and vomiting or laxatives (OR, 2.46; 95% CI, 1.83-3.30). Although cisgender SM men and unsure men and women also had elevated rates of SR-ED diagnosis than heterosexual women, the magnitudes of these associations were lower than those for transgender individuals (ORs; 1.40-1.54). Transgender and cisgender SM young adults have elevated rates of compensatory behavior and SR-ED diagnosis. Appropriate interventions for these populations are urgently needed.


The effect of an individualized fall prevention program on fall risk and falls in older people: a randomized, controlled trial.
To determine whether an individualized falls prevention program comprising exercise, visual, and counseling interventions can reduce physiological falls risk and falls in older people. Randomized, controlled trial of 12 months' duration. Falls Clinic, Royal North Shore Hospital, Sydney, Australia. Six hundred twenty people aged 75 and older recruited from a health insurance company membership database. Participants in the extensive intervention group (EIG) received individualized interventions comprising exercise and strategies for maximizing vision and sensation; the minimal intervention group (MIG) received brief advice; and the control group (CG) received no intervention. Accidental falls, vision, postural sway, coordinated stability, reaction time, lower limb muscle strength, sit-to-stand performance, and physiological profile assessment (PPA) falls risk scores. At the 6-month follow-up, PPA falls risk scores were significantly lower in the EIG than in the CG. EIG subjects assigned to the extensive exercise intervention group showed significant improvements in tests of knee flexion strength and sit-to-stand times but no improvements in balance. EIG subjects assigned to the extensive visual intervention group showed significant improvements in tests of visual acuity and contrast sensitivity. The rate of falls and injurious falls within the trial period were similar in the three groups. The individualized intervention program reduced some falls risk factors but did not prevent falls. The lack of an effect on falls may reflect insufficient targeting of the intervention to an at-risk group.


Ordered weighted average based grouping of nanomaterials with Arsinh and dose response similarity models.
In the context of the EU GRACIOUS project, we propose a novel procedure for similarity assessment and grouping of nanomaterials. This methodology is based on the (1) Arsinh transformation function for scalar properties, (2) full curve shape comparison by application of a modified Kolmogorov-Smirnov metric for bivariate properties, (3) Ordered Weighted Average (OWA) aggregation-based grouping distance, and (4) hierarchical clustering. The approach allows for grouping of nanomaterials that is not affected by the dataset, so that group membership will not change when new candidates are included in the set of assessed materials. To facilitate the application of the proposed methodology, a software script was developed by using the R programming language which is currently under migration to a web tool. The presented approach was tested against a dataset, derived from literature review, related to immobilization of Daphnia magna and reporting information on several nanomaterials and properties.


American ginseng modulates pancreatic beta cell activities.
The mechanism of the beneficial effects of Panax quinquefolius (Xiyangshen, American ginseng) on diabetes is yet to be elucidated. Recent studies show that Panax quinquefolius increases insulin production and reduces the death of pancreatic beta cells. Mechanism studies indicate that Panax quinquefolius improves cell's immuno-reactivity and mitochondrial function through various factors. Clinical studies show that Panax quinquefolius improves postprandial glycemia in type 2 diabetic patients. Further studies to identify the component(s) of Panax quinquefolius linked with pancreatic islets/beta cells in vitro and in vivo are warranted for better understanding of the full effects of Panax quinquefolius.


Radiochemical quality control of 99mTc-labeled radiopharmaceuticals. Some daily practice guideliens.
Recognizing the fact that each nuclear medicine facility should be able to perform simple radiochemical quality tests on currently used radiopharmaceuticals, this study was undertaken to evaluate a number of radiochromatographic methods. No single ideal method exists to assess the radiochemical composition of 99mTc-labeled antimony sulphur colloid, sulphur colloid, iron ascorbate, citrate, human serum albumin, EHDP, macroaggregates, and microspheres. It is advisable to include thin layer chromatography with both NaCl and methylethylethylketone for the determination of free pertechnetate in each day's program. More detailed radiochemical analysis can be performed by combining these methods with paper chromatography, paper electrophoresis, and gel filtration. It seems reasonable to regard a constant radiochromatographic pattern as a measure for constant radiochemical quality. The four chromatographic tests lead to consistent results regarding the percentage of free pertechnetate in the radiopharmaceutical preparations. Quantitative analysis shows that the radiochemical purity for each radiopharmaceutical is unique for the chromatographic method used and needs to be defined when stated.


Comparative studies of suidatrestin, a specific inhibitor of trehalases.
Suidatrestin, isolated from a Streptomyces strain, was characterized as a new trehalase inhibitor. Its inhibitory potential was 7 to 50-fold higher than that of validamycin when tested against insect, fungal and mammalian trehalases. The kinetic properties of suidatrestin were studied in vitro with trehalases from flight muscle mitochondria of the fly, Protophormia terraenovae, from larval midgut of the moth, Spodoptera littoralis, and from porcine kidney, as well as with maltase from yeast. Suidatrestin was inactive on maltase but inhibited all trehalases with IC50 values of 0.08-0.1 microM; Ki values ranged from 0.02 to 0.05 microM. The very low Ki/K(m) ratios (3.9 x 10(-6) -4.9 x 10(-6)) indicated excellent in vitro inhibitory action of suidatrestin. When injected into larvae of S. littoralis, suidatrestin required high and repetitive doses which lead to reversible inhibition of larval growth only. Consecutive omission of the inhibitor even stimulated weight increase above that of controls. Significant mortality was achieved at a rather high dose only. Injection of a growth-inhibiting dose of suidatrestin did not change hemolymph osmolality as a measure of sugar concentration. The discrepancy between in vitro and in vivo potency of suidatrestin may be understood once its chemical structure is fully known.


Association between ELP4 rs986527 polymorphism and the occurrence and development of intracranial arachnoid cyst.
The association between ELP4 rs986527 polymorphism and the occurrence and development of intracranial arachnoid cyst was studied in this paper. Eighty-five patients diagnosed with intracranial arachnoid cysts by cerebral computed tomography scan were selected. Sixty-three healthy volunteers for medical examination in hospitals served as controls. The cognition, depressive symptoms, and the likelihood of headache, dizziness, head trauma history, dementia, depression, and epilepsy were assessed. ELP4 genotypes and its allele frequency were determined by PCR, endonuclease restriction analysis, and gel electrophoresis. ELP4 rs986527 had three genotypes: TT, TC, and CC. The intracranial arachnoid cyst group showed no statistically significant difference in genotype frequencies compared with healthy controls. There was no significant correlation between ELP4 rs986527 polymorphism and location of intracranial arachnoid cyst. TC and C genotype frequencies were associated with a higher incidence of clinical symptoms than TT genotype frequencies, and C allele frequencies were associated with a significantly higher incidence of clinical symptoms compared with T allele frequencies. There was no significant difference in TNF-α and IL-1β levels between TT/TC/CC genotypes before treatment. After treatment, the levels of TNF-α and IL-1β were significantly decreased in different genotypes, and the decrease in CC was the greatest. The frequency of TT and TC genotypes was higher than that of CC genotypes. ELP4 rs986527 polymorphism affected the incidence of clinical symptoms and the levels of TNF-α and IL-1β in patients with intracranial arachnoid cysts.


Collision metastasis: Renal cell carcinoma and prostatic adenocarcinoma to a retroperitoneal lymph node.
Prostatic adenocarcinoma and renal cell carcinoma (RCC) can coexist. However, the incidence of collision metastasis of both prostatic adenocarcinoma and RCC is a rare phenomenon. A 50-year-old non-smoker male with end stage renal disease and a history of prostate adenocarcinoma was noted to have a left renal mass in the upper pole during CT surveillance. With the use of immunohistochemical stains the collision of two distinct malignancies from two different topographical regions was elucidated in a retroperitoneal lymph node. We report the second known case of collision metastasis of RCC and prostatic adenocarcinoma to a retroperitoneal lymph node.


Detection and quantification of proteins using self-excited PZT-glass millimeter-sized cantilever.
A composite self-excited PZT-glass cantilever (4mm in length and 2mm wide) was fabricated and used to measure the binding and unbinding of model proteins. A key feature of the cantilever is that its resonant frequency is dependent on its mass. The fabricated cantilever has mass change sensitivity in liquid of 7.2 x 10(-11)g/Hz. Resonant frequency change was measured as protein reacted or bound with the sensing glass cantilever surface. Protein concentrations, 0.1 and 1.0mg/mL, which resulted in nanogram mass change were successfully detected. The mass change sensitivity gave a total mass change of 54+/-0.45 ng for the binding of anti-rabbit IgG (biotin conjugated) to rabbit IgG immobilized cantilever and the subsequent binding of captavidin. The unbinding of anti-rabbit IgG and captavidin gave a total mass change of 54+/-1.70 ng. Fluorescence based assays showed the combined mass of both proteins in the released samples was 54+/-2.24 ng. The binding kinetics of the model proteins is modeled as first order. The initial binding rate constant of anti-rabbit IgG to rabbit IgG was 1.36+/-0.02(min(mg/mL))(-1). The initial binding rate constant of captavidin to biotinylated anti-rabbit IgG was (2.57 x 10(-1))+/-0.003(min(mg/mL))(-1). The significance of the results we report here is that millimeter-sized PZT-actuated glass cantilevers have the sensitivity to measure in real-time protein-protein binding, and the binding rate constant.


Environmental factors and incidence of thyroid cancer in the world (1990-2019): an ecological study.
Thyroid cancer (TC) is the most common endocrine malignancy. Environmental risk factors such as presence of pollutants in air as well as the combustion of fossil fuels or carbon as a cooking habit in closed environments inside houses affect thyroid hormonal homeostasis and diseases. This study aimed to estimate the association between environmental risk factors and the incidence of thyroid cancer worldwide from 1990 to 2019 including particulate pollutants coming from fossil fuels employed in closed environments. Data on the incidence of thyroid cancer and some environmental risk factors were extracted from the Global Cancer Observatory (GLOBOCAN) for 204 countries and territories from 1990 to 2019. Pearson's correlation coefficient was used to determine the correlation between the thyroid cancer incidence and environmental risk factors. Finally, a generalized additive model was fitted for modeling. R 3.5.0 was used for analysis of the data. The most relevant results showed that the age-standardized incidence rate (ASIR) of thyroid cancer has a positive and significant correlation with environmental air pollution by O3 (r=0.63, P value<0.001), by particulate matter pollution (r=0.23, P value<0.001), and by household PM2.5 air pollution (r=0.52, P value≤0.001). In contrast, the correlation between ASIR and high temperature (T>25.6°C) (r=-0.27, P value<0.001) is negative and significant. The modeling results showed that particulate matter pollution and O3 pollution and household PM2.5 air pollution which originated from solid fuels are risk factors for thyroid cancer. Therefore, more research in this field is necessary in areas with high levels of air pollution at the national and international levels.


Sleep Deprivation and Circadian Disruption Stress, Allostasis, and Allostatic Load.
Getting a good night's sleep seems a panacea for improving mood and cognition. These subjective impressions are supported by countless studies exploring the impacts of sleep (and sleep loss) on mental health, metabolism, and immune function. Similarly, being "out of phase" with local time, commonly experienced by shift workers of jet-lagged air travelers, demonstrates that there are both neural and physiologic effects of internal circadian (daily) time being misaligned with external environmental time. This article reviews these areas contextualized using the model of allostasis and allostatic load emphasizing the impact of this "wear and tear" on the brain and body.


Molybdenum disulfide loading on a Z-scheme graphitic carbon nitride and lanthanum nickelate heterojunction for enhanced photocatalysis: Interfacial charge transfer and mechanistic insights.
Interfacial design and the co-catalyst effect are considered to be effective to achieve separation and transport of photogenerated carriers in composite photocatalysts. In this study, a Z-scheme heterojunction was successfully combined with a co-catalyst to achieve a highly efficient LaNiO3/g-C3N4/MoS2 photocatalyst. MoS2 flakes were loaded on a hybrid material surface, which was formed by LaNiO3 nanocubes embedded on layered g-C3N4, and a good heterostructure with multiple attachment sites was obtained. Experimental studies confirmed that the Z-scheme heterojunction completely preserves the strong redox ability of the photogenerated electrons and holes. As a cocatalyst, MoS2 further promoted interfacial charge separation and transport. The synergistic effect of the Z-scheme heterojunction and co-catalyst effectively realized the transfer of photogenerated carriers from "slow transfer" to "high transfer" and promoted water decomposition and pollutant degradation. Results revealed that under simulated sunlight irradiation, LaNiO3/g-C3N4/MoS2 composites exhibit superior hydrogen evolution of 45.1 μmol h-1, which is 19.1 times that of g-C3N4 and 4.9 times that of LaNiO3/g-C3N4, respectively. Moreover, the LaNiO3/g-C3N4/MoS2 Z-scheme photocatalyst exhibited excellent photocatalytic performance for antibiotic degradation and heavy-metal ion reduction under visible light. This study might provide some insights into the development of photocatalysts for solar energy conversion and environmental remediation.


Comparing the efficacy of Cartiva synthetic cartilage implant hemiarthroplasty vs osteotomy for the treatment of conditions affecting the second metatarsal head.
Cartiva synthetic cartilage implants (SCI) have been designed for treatment of conditions affecting the second metatarsal head. Osteotomies are regularly performed for the treatment of conditions affecting the second metatarsal head such as Freiburg's disease. A comparative study between these two procedures has not yet been performed. Patients at a single centre with symptomatic conditions affecting the second metatarsal head who received Cartiva SCI or a primary Osteotomy were identified, and patient-reported outcomes were evaluated using MOXFQ and the FAAM questionnaires. Six Cartiva SCI and 7 Osteotomy patients were identified and included in this study. All patients were female and were followed up for an average of 19 months (SD +/- 5.6) and 27 months (SD +/- 10.9) respectively. Cartiva SCI MOXFQ Index scores improved by 13 points from 57 to 44 (33%). Walking/and Pain domain scores improved, however, Social interaction deteriorated. Mean FAAM scores improved by 10% from 65% to 75%, and subjective FAAM scores improved by 7% from 48% to 55%. Four of the six Cartiva patients (3 Freiberg's disease and 1 Osteochondral defect) had revisions to Weil osteotomies at a mean of 15 months post-operatively. The Osteotomy group had improved MOXFQ Index and 3 Domain scores. FAAM scores improved by 26% from 66% to 92% and subjective FAAM scores improved by 28% from 60% to 88%. Second metatarsal head osteotomies result in high functional outcomes and should be the mainstay of treatment, especially when there is avascular necrosis of the metatarsal head.


The Human Immunopeptidome Project: A Roadmap to Predict and Treat Immune Diseases.
The science that investigates the ensembles of all peptides associated to human leukocyte antigen (HLA) molecules is termed "immunopeptidomics" and is typically driven by mass spectrometry (MS) technologies. Recent advances in MS technologies, neoantigen discovery and cancer immunotherapy have catalyzed the launch of the Human Immunopeptidome Project (HIPP) with the goal of providing a complete map of the human immunopeptidome and making the technology so robust that it will be available in every clinic. Here, we provide a long-term perspective of the field and we use this framework to explore how we think the completion of the HIPP will truly impact the society in the future. In this context, we introduce the concept of immunopeptidome-wide association studies (IWAS). We highlight the importance of large cohort studies for the future and how applying quantitative immunopeptidomics at population scale may provide a new look at individual predisposition to common immune diseases as well as responsiveness to vaccines and immunotherapies. Through this vision, we aim to provide a fresh view of the field to stimulate new discussions within the community, and present what we see as the key challenges for the future for unlocking the full potential of immunopeptidomics in this era of precision medicine.


A computational analysis of the binding affinities of FKBP12 inhibitors using the MM-PB/SA method.
The FK506-binding proteins have been targets of pharmaceutical interests over years. We have studied the binding of a set of 12 nonimmunosuppressive small-molecule inhibitors to FKBP12 through molecular dynamics simulations. Each complex was subjected to 1-ns MD simulation conducted in an explicit solvent environment under constant temperature and pressure. The binding free energy of each complex was then computed by the MM-PB/SA method in the AMBER program. Our MM-PB/SA computation produced a good correlation between the experimentally determined and the computed binding free energies with a correlation coefficient (R(2)) of 0.93 and a standard deviation as low as 0.30 kcal/mol. The vibrational entropy term given by the normal mode analysis was found to be helpful for achieving this correlation. Moreover, an adjustment to one weight factor in the PB/SA model was essential to correct the absolute values of the final binding free energies to a reasonable range. A head-to-head comparison of our MM-PB/SA model with a previously reported Linear Response Approximation (LRA) model suggested that the MM-PB/SA method is more robust in binding affinity prediction for this class of compounds.


DNA methylation study of Huntington's disease and motor progression in patients and in animal models.
Although Huntington's disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly (p < 10-7) associated with 33 CpG sites, including the HTT gene (p = 6.5 × 10-26). These Htt/HTT associations were replicated in the Q175 Htt knock-in mouse model (p = 6.0 × 10-8) and in the transgenic sheep model (p = 2.4 × 10-88). We define a measure of HD motor score progression among manifest HD cases based on multiple clinical assessments. EWAS of motor progression in manifest HD cases exhibits significant (p < 10-7) associations with methylation levels at three loci: near PEX14 (p = 9.3 × 10-9), GRIK4 (p = 3.0 × 10-8), and COX4I2 (p = 6.5 × 10-8). We conclude that HD is accompanied by profound changes of DNA methylation levels in three mammalian species.


Reproductive cycle, thyroxine and corticosterone in females of the giant swamp frog Dicroglossus occipitalis at the equator.
Females of the giant swamp frog Dicroglossus occipitalis were captured in the tributaries of the Zaïre River near Kisangani, a town situated close to the equator (00 degree 31' N) with virtually constant conditions as to photoperiod, temperature, precipitation, and relative humidity. An annual variation in the reproductive capacity of this species could be demonstrated. A reproductive quiescence with a low gonadal somatic index (GSI), undeveloped eggs, and minimal plasma concentrations of estradiol-17 beta (E2) and progesterone (P4) was found from October to January. E2 and P4 and thyroxine (T4) contents of the thyroids were positively correlated with GSI and egg size. Plasma T4 concentrations, however, were negatively correlated with GSI, whereas variations in corticosterone correlated only with E2. No correlation between plasma concentrations of glucose and GSI or all other hormonal parameters could be found. It is concluded that during egg maturation, increased amounts of E2 and P4 are produced. The observed variations in thyroidal and plasma T4 may be the result of an activation of thyroid function by the peripheral conversion of T4 into triiodothyronine.


Dentinogenesis imperfecta: endodontic implications. Case report.
Dentinogenesis imperfecta is a hereditary disorder resulting in defective dentin in both the primary and secondary dentitions. The complications of dentinogenesis imperfecta are difficult to manage and provide a challenge to the dentist. This case report concerns treating an African American patient with dentinogenesis imperfecta who appeared for treatment with endodontic pathosis. It illustrates the need for appropriate and timely restorative treatment to prevent pulpal pathosis. Also demonstrated is the difficulty of endodontically treating dentinogenesis imperfecta teeth because of pulpal obliteration and abnormal dentin mineralization. Early and correct diagnosis of dentinogenesis imperfecta is imperative to enable appropriate preventive interventions and optimal dental treatment. Although pulpal pathosis is rarely reported with dentinogenesis imperfecta, endodontic treatment is occasionally necessary and has a guarded prognosis if initiated after pulp canal obliteration has occurred.


Catheter Ablation of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy is an inherited desmosomal myopathy characterized by progressive fibrofatty replacement of the myocardium, right ventricular enlargement, and malignant ventricular arrhythmias. Ventricular tachycardias is one of the most common initial presentation of ARVC. This manuscript addresses invasive VT ablation options for the managmenet of VT in patients with ARVC.


Piperazine neurotoxicity: worm wobble revisited.
Piperazine has been used to treat pinworm and roundworm infections for over 40 years. Piperazine-induced cerebellar ataxia, causing the dropping of objects, clumsiness, and gait abnormalities, has been infrequently reported, usually in the setting of overdose or renal insufficiency. The unusual case of an otherwise well child who developed ataxia following seven days of piperazine citrate therapy is reported.


Alleviating effect of Mallotus roxburghianus in heat-induced testicular dysfunction in Wistar rats.
Hyperthermia causes detrimental effects on the testes leading to fertility problems. Mallotus roxbhurghianus Muell. Arg. (Euphorbiaceae) is used in traditional medicine and possesses antioxidant property. However, the mechanisms remain unknown in the context of alleviative action of M. roxburghianus against heat stress. The objective of this study was to demonstrate the alleviating activity of M. roxburghianus and its mechanism in scrotal hyperthermia. Scrotal hyperthermia experiments were performed in three groups (n = 7 per group) consisting of (i) the control group (C) maintained at 22 °C for 30 min, (ii) the heat stress-induced group (HS), and (iii) the heat stress-induced M. roxburghianus-treated group (HSM - 400 mg/kg each) in a thermostatically controlled water bath at 43 °C for 30 min. Subsequent to the heat treatment HS group, rats were treated with saline p.o and methanol extract of M. roxburghianus was administered to the rats of HSM group along with their standard food for 14 d. Scrotal hyperthermic effects were evaluated. Scrotal hyperthermia significantly (p < 0.0001) elevated malondialdehyde levels while decreasing the body and testes weights, serum testosterone, and antioxidant enzyme levels due to oxidative stress. Disorganisation of seminiferous tubules and arrest of spermatogenesis were observed in the HS group. The administration of methanol extract of M. roxburghianus (400 mg/kg) for 14 d after heat treatment significantly suppressed the lipid peroxidation, restored the antioxidant enzyme and testosterone levels, revived the spermatogenesis, and increased the cell proliferation activity in the HSM group. The methanol extract of M. roxburghianus accelerates testicular recovery from the damaging influence of hyperthermia.


Does the transition temperature of Cu-NiTi archwires affect the amount of tooth movement during alignment?
To examine whether the transition temperature of Cu-NiTi archwires has an effect on the tooth movement during the alignment phase of orthodontic treatment. 'Split mouth' design in randomly selected patients. The Department of Orthodontics, School of Dentistry, University of Aarhus. Fifteen randomly selected patients with identical level of irregularity in the alignment phase of their treatment. Experiment Variable - Specially manufactured Cu-NiTi archwires for the upper arch were inserted. These consisted of two separate halves, each with its own transition temperature, respectively 27 degrees and 40 degrees C, and clamped together in the middle. The tooth movement, expressed as two translations and a rotation, in the occlusal plane was measured from the patients' intraoral photographs taken upon insertion of the archwires and again after 1 month. Tooth movements tended to be larger on the 40 degrees C-side, however only in case of the total translation of the premolars was this difference significant. In general, patients had not noticed any difference between the two sides of the archwire, although one patient stated the 27 degrees C-side to be more comfortable as the 40 degrees C-side had bothered her when drinking hot beverages. The transition temperature of Cu-NiTi archwires has indeed an effect on the amount of tooth movement during alignment. However, the differences are so small though that it is the question whether they can be noticed clinically. The study corroborates the trend towards the use of lower forces within orthodontics.


Lipid nanoparticle-encapsulated, chemically modified anti-adenoviral siRNAs inhibit hepatic adenovirus infection in immunosuppressed Syrian hamsters.
RNA interference has demonstrated its potential as an antiviral therapy for treatment of human adenovirus (hAd) infections. The only existing viral vector-based system for delivery of anti-adenoviral artificial microRNAs available for in vivo use, however, has proven to be inefficient in therapeutic applications. In this study, we investigated the potential of stabilized small interfering RNA (siRNA) encapsulated in lipid nanoparticles (LNPs) for treatment of hepatic hAd serotype 5 (hAd5) infection in an hAd infection model using immunosuppressed Syrian hamsters. The siRNA sipTPmod directed against the adenoviral pre-terminal protein (pTP) and containing 2'-O-methyl modifications as well as phosphorothioate linkages effectively inhibited hAd5 infection in vitro. In light of this success, sipTPmod was encapsulated in LNPs containing the cationic lipid XL-10, which enables hepatocyte-specific siRNA transfer, and injected intravenously into hAd5-infected immunosuppressed Syrian hamsters. This resulted in a significant reduction of liver hAd5 titers, a trend toward reduced liver injury and inflammation, and reduction of viral titers in the blood and spleen compared with hAd5-infected animals that received a non-silencing siRNA. These effects were demonstrated in animals infected with low and moderate doses of hAd5. These data demonstrate that hepatic hAd5 infection can be successfully treated with anti-adenoviral sipTPmod encapsulated in LNPs.


Trafficking of amyloid β-precursor protein products C83 and C99 on the endocytic pathway.
Amyloid β-precursor protein (APP) proteolytic products C83 and C99 are substrates for γ-secretase as well as products, respectively, of α- or β-secretase. In contrast to APP, C83 and C99 were derivatized by a water soluble biotinylation reagent to a much greater extent at 18°C than at 0°C in CHO cells expressing the Swedish mutant form of APP750. Intracellular C99 and C83 cycle to the cell surface when maintained in buffered saline at 18°C thus identifying proteins derivatized at 18°C as residing in recycling compartments. More than 80% of C99 and C83 biotinylated at 18°C is associated with detergent resistant membrane (DRM). There thus appears to be no differential distribution of α- or β-secretase products into the DRM fraction that would be expected if localization to DRM determines alternative secretase pathways. γ-Secretase inhibitors increased the fraction of C99 but not C83 in the 18°C pool by >50% and doubled the half-life of C99 in that compartment, showing that a substantial amount of C99 is proteolyzed by γ-secretase in a compartment rich in recycling proteins. The temporal appearance of APP on the cell surface preceded that of C99 in the recycling compartment, further supporting the cleavage of APP in recycling endosomes.


DeepSAT: Learning Molecular Structures from Nuclear Magnetic Resonance Data.
The identification of molecular structure is essential for understanding chemical diversity and for developing drug leads from small molecules. Nevertheless, the structure elucidation of small molecules by Nuclear Magnetic Resonance (NMR) experiments is often a long and non-trivial process that relies on years of training. To achieve this process efficiently, several spectral databases have been established to retrieve reference NMR spectra. However, the number of reference NMR spectra available is limited and has mostly facilitated annotation of commercially available derivatives. Here, we introduce DeepSAT, a neural network-based structure annotation and scaffold prediction system that directly extracts the chemical features associated with molecular structures from their NMR spectra. Using only the 1H-13C HSQC spectrum, DeepSAT identifies related known compounds and thus efficiently assists in the identification of molecular structures. DeepSAT is expected to accelerate chemical and biomedical research by accelerating the identification of molecular structures.


Effects of high-potassium solutions and caffeine on synaptic vesicle exoendocytosis processes in the frog neuromuscular junction.
Studies on frog skin-pectoris muscle preparations using vital fluorescent microscopy showed that stimulation of transmitter secretion using high-potassium solutions with the endocytosis marker FM 1-43 induced bright spots in all motor nerve terminals, these representing accumulations of vesicles undergoing the exoendocytic cycle in the active zones of nerve endings. Stimulation of transmitter secretion with caffeine evoked bright spots only in some nerve terminals and only in some parts of the terminals. In summer, the number of bright spots on stimulation of transmitter secretion by caffeine increased sharply. Extracellular recording of spontaneous synaptic signals showed that high-potassium solutions, like caffeine, produced dose-dependent increases in the frequency of miniature endplate currents. However, while high-potassium solutions always increased the frequency, this occurred with caffeine in only a proportion of experiments. This leads to the conclusion that exoendocytosis processes can occur both because of the influx of Ca(2+) ions into nerve endings as a result of depolarization (high-potassium solutions) and because of the release of Ca(2+) ions from the endoplasmic reticulum (caffeine). The possible spatial localization of the endoplasmic reticulum in nerve endings is discussed. The endoplasmic reticulum is suggested to have a role in synapse remodeling processes.


The large-conductance Ca2+-activated K+ channel is essential for innate immunity.
Neutrophil leukocytes have a pivotal function in innate immunity. Dogma dictates that the lethal blow is delivered to microbes by reactive oxygen species (ROS) and halogens, products of the NADPH oxidase, whose impairment causes immunodeficiency. However, recent evidence indicates that the microbes might be killed by proteases, activated by the oxidase through the generation of a hypertonic, K+-rich and alkaline environment in the phagocytic vacuole. Here we show that K+ crosses the membrane through large-conductance Ca2+-activated K+ (BK(Ca)) channels. Specific inhibitors of these channels, iberiotoxin and paxilline, blocked oxidase-induced 86Rb+ fluxes and alkalinization of the phagocytic vacuole, whereas NS1619, a BK(Ca) channel opener, enhanced both. Characteristic outwardly rectifying K+ currents, reversibly inhibited by iberiotoxin, were demonstrated in neutrophils and eosinophils and the expression of the alpha-subunit of the BK channel was confirmed by western blotting. The channels were opened by the combination of membrane depolarization and elevated Ca2+ concentration, both consequences of oxidase activity. Remarkably, microbial killing and digestion were abolished when the BK(Ca) channel was blocked, revealing an essential and unexpected function for this K+ channel in the microbicidal process.


The application of health literacy measurement tools (collective or individual domains) in assessing chronic disease management: a systematic review protocol.
The term "health literacy" (HL) was first coined in 1974, and its most common definition is currently defined as a person's ability to access, understand, evaluate, communicate, and use health information to make decisions for one's health. The previous systematic reviews assessing the effect of existing HL measurement tools on health outcomes have simply searched for the term "health literacy" only to identify measures instead of incorporating either one or more of the five domains in their search. Furthermore, as the domain "use" is fairly new, few studies have actually assessed this domain. In this protocol, we propose to identify and assess HL measures that applied the mentioned five domains either collectively or individually in assessing chronic disease management, in particular for asthma and chronic obstructive pulmonary disease (COPD). The ultimate goal is to provide recommendations towards the development and validation of a patient-centric HL measurement tool for the two diseases. A comprehensive, electronic search will be conducted to identify potential studies dating from 1974 to 2016 from databases such as Embase, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, Web of Science, ERIC, PsycINFO, and HAPI. Database searches will be complemented with grey literature. Two independent reviewers will perform tool selection, study selection, data extraction, and quality assessment using pre-designed study forms. Any disagreement will be resolved through discussion or a third reviewer. Only studies that have developed or validated HL measurement tools (including one or more of the five domains mentioned above) among asthma and COPD patients will be included. Information collected from the studies will include instrument details such as versions, purpose, underlying constructs, administration, mapping of items onto the five domains, internal structure, scoring, response processes, standard error of measurement (SEM), correlation with other variables, clinically important difference, and item response theory (IRT)-based analyses. The identified strengths and weaknesses as well as reliability, validity, responsiveness, and interpretability of the tools from the validation studies will also be assessed using the COSMIN checklist. A synthesis will be presented for all tools in relation to asthma and COPD management. This systematic review will be one of several key contributions central to a global evidence-based strategy funded by the Canadian Institutes of Health Research (CIHR) for measuring HL in patients with asthma and COPD, highlighting the gaps and inconsistencies of domains between existing tools. The knowledge generated from this review will provide the team information on (1) the five-domain model and cross domains, (2) underlying constructs, (3) tool length, (4) time for completion, (5) reading level, and (6) format for development of the proposed tool. Other aspects of the published validation studies such as reliability coefficients, SEM, correlations with other variables, clinically important difference, and IRT-based analyses will be important for comparison purposes when testing, interpreting, and validating the developed tool. PROSPERO CRD42016037532.


Adrenal cortical carcinoma with hepatic metastasis: preoperative radiological evaluation.
Preoperative evaluation of a patient with adrenal carcinoma and hepatic metastases was performed by arteriography, computed tomography (CT) and computed tomographic arteriography (CTA). Early and complete demonstration of tumor involvement by these imaging modalities allowed an accurate assessment of tumor extension and subsequent aggressive surgical removal of the primary as well as the metastasis in the liver.


Improving survival in a large French ALS center cohort.
The aim of this work was to determine whether survival changed during 2002-2009 at a French amyotrophic lateral sclerosis (ALS) center. We included all patients with ALS who were seen consecutively at the center from January 2002-May 2009. Participants were followed from date of first visit through death, date of censoring, or December 31, 2009, whichever occurred first. Cox proportional hazard models computed hazard ratios (HR; 95% confidence interval CI) of death, and flexible modeling of continuous predictors (splines) assessed trends in survival. We analyzed a total of 2,037 ALS patients, of whom 1,471 died before the end of follow-up. Median survival was 2.83 years from onset and 1.65 years from first visit. Compared to patients first seen before 2004, the HR of death was 0.97 (95% CI = 0.85-1.11, p = 0.6721) for patients first seen in 2004-2005, 0.96 (95% CI = 0.83-1.10, p = 0.5125) for 2006-2007, and 0.56 (95% CI = 0.46-0.69, p < 0.0001) after 2007, while adjusting for other survival predictors. Spline analysis confirmed that survival remained stable during 2002-2006, then markedly improved. The proportion of patients receiving non-invasive ventilation (NIV) increased from 16 (2004) to 51% (2008). At this large ALS center, survival improved after 2006. Because more aggressive use of NIV was the principal therapeutic adaptation, our data suggest that better survival resulted from improved respiratory care.


Improving Memory and Cognition in Individuals with Down Syndrome.
Down syndrome (DS), often due to trisomy 21, is the most common genetic cause of intellectual disability (ID). In addition, virtually all individuals with DS develop the neuropathology of Alzheimer's disease (AD) by the age of 40 years and almost 60 % will manifest symptoms of AD dementia by the age of 65 years. Currently, there are no pharmacological treatments available for ID in individuals with DS and only limited symptomatic treatments for AD dementia. Advances in our understanding in both the molecular basis of ID and the pathogenesis of AD have created opportunities to study potential therapeutic targets. Recent studies in animal models of DS continue to provide a rational basis for translating specific compounds into human clinical trials. However, target and compound selection are only initial steps in the drug development pathway. Other necessary considerations include appropriate study designs to assess efficacy in the DS population, as well as operational aspects specifically tailored to assess cognition in this population. We discuss recent progress in the development of compounds for both ID and AD in individuals with DS, as well as concepts for the design and conduct of clinical trials with such compounds.


Comparison of the effects of epidural or intravenous methadone on the minimum alveolar concentration of isoflurane in dogs.
The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs (16.5 ± 2.5 kg bodyweight) received three treatments in random order during isoflurane anaesthesia, with a 7 day washout interval between each study. Methadone was injected via a lumbosacral epidural catheter introduced 10 cm cranially into the epidural canal and the electrical stimulation for ISO(MAC) determination was applied either to the thoracic (EP(T) treatment) or to the pelvic limb (EP(P) treatment) during separate study days. In the IV treatment, ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC) decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction lasted longer following epidural methadone in the thoracic limb (decreases from baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV treatments, respectively). Although the isoflurane sparing effect provided by epidural methadone was not significantly greater than IV methadone during the initial stage (2.5h), it was more prolonged than the IV route in specific dermatomes (5h in the thoracic limb) with the epidural technique employed. Methadone may therefore provide a greater isoflurane sparing effect when administered epidurally, compared to IV, when noxious stimulation occurs in specific dermatomes.


Serum alpha-N-acetylglucosaminidase: determination, characterization, and corrective activity in Sanifilippo B fibroblasts.
Assays for the determination of serum alpha-N-acetylglucosaminidase (EC 22.214.171.124) activity are described employing p-nitrophenyl-N-acetyl-alpha-D-glucosaminide, phenyl-N-acetyl-alpha-D-glucosaminide, and UDP-N-acetylglucosamine as substrates. A log normal distribution of the serum enzyme activity was found. The determination of serum alpha-N-acetylglucosaminidase activity proved to be a valuable tool for the recognition of homozygous and heterozygous carriers of the Sanfilippo B gene.


Rapid dynamic CT scanning to distinguish schizophrenic from normal subjects.
Rapid dynamic computerized axial tomography (CT) density-time curves were used to detect abnormal brain regions in groups of controls and DSM-III diagnosed schizophrenics. Density-time curves were designated as plateau curves if, following a bolus injection of contrast material, they exhibited a plateau from the peak value rather than a decrease. Five of the 10 schizophrenics versus none of the 11 controls were found to possess two or more plateau curves. The physiological basis for the plateau curves is not known, but an increase in blood-brain-barrier permeability could be involved.


Correction to: A multimodal imaging features of the brain in adult-onset neuronal intranuclear inclusion disease.
In the original article, Zaiqiang Zhang was affiliated to Department of Neurology, Beijing Hospital, National Center of Gerontology, Beijing, China. The corrected affiliation should be: Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.


PGF2alpha Inhibits 20alpha-HSD Expression by Suppressing CK1alpha-induced ERK and SP1 Activation in the Corpus Luteum of Pregnant Mice.
Prostaglandin F2α (PGF2α) is a luteolytic hormone that promotes parturition in mammals at the end of pregnancy by reducing progesterone secretion from the corpus luteum (CL). In rodents and primates, PGF2α rapidly converts progesterone to 20α-hydroxyprogesterone (20α-OHP) by promoting 20α-hydroxysteroid dehydrogenase (20α-HSD) expression. However, the specific mechanism of 20α-HSD regulation by PGF2α remains unclear. Casein Kinase 1α (CK1α) is a CK1 family member that regulates a variety of physiological functions, including reproductive development. Here, we investigated the effects of CK1α on pregnancy in female mice. Our experiments showed that CK1α is expressed in mouse CL, and its inhibition enhanced progesterone metabolism, decreased progesterone levels, and affected mouse embryo implantation. Further, CK1α mediated the effect of PGF2α on 20α-HSD in mouse luteal cells in vitro. Our results are the first to show that CK1α affects the 20α-HSD mRNA level by affecting the ERK signalling pathway to regulate the expression of the transcription factor SP1. These findings improve our understanding of PGF2α regulation of 20α-HSD.


Thermoplastic starch/bentonite clay nanocomposite reinforced with vitamin B2: Physicochemical characteristics and release behavior.
This study presents the development and characterization of a nanocomposite material, consisting of thermoplastic starch (TPS) reinforced with bentonite clay (BC) and encapsulated with vitamin B2 (VB). The research is motivated by the potential of TPS as a renewable and biodegradable substitute for petroleum-based materials in the biopolymer industry. The effects of VB on the physicochemical properties of TPS/BC films, including mechanical and thermal properties, water uptake, and weight loss in water, were investigated. In addition, the surface morphology and chemical composition of the TPS samples were analyzed using high-resolution SEM microscopy and EDS, providing insight into the structure-property relationship of the nanocomposites. The results showed that the addition of VB significantly increased the tensile strength and Young's modulus of TPS/BC films, with the highest values observed for nanocomposites containing 5 php of VB and 3 php of BC. Furthermore, the release of VB was controlled by the BC content, with higher BC content leading to lower VB release. These findings demonstrate the potential of TPS/BC/VB nanocomposites as environmentally friendly materials with improved mechanical properties and controlled release of VB, which can have significant applications in the biopolymer industry.


Effect of placing intentionally high restorations: Randomized clinical trial.
The aim of this study was to examine the behavior of posterior teeth restored with single-tooth restorations with intentionally high occlusal contacts. Consent was obtained from 17 patients who were seen a total of 5 times over 3.5 years. The restorations placed were all full occlusal coverage gold restorations. Tooth mobility was recorded using the Periotest device and tooth movement was determined from impressions and 3D imaging. Patients were randomly assigned into two groups, the control group which received restorations with no intentional increase of the occlusal vertical dimension; or the treatment group where they received intentionally high restorations in 0.5mm supraocclusion. Statistical analysis showed no significant difference in mobility between visits for both the control and the treatment groups while a significant dependency and difference in tooth movement was observed between the subjects of the two groups. Most patients from the treatment group reported discomfort but no pain for the first 7-10 days after the restoration was fitted, which subsided over a period of couple of weeks. At review, 3 years later, no mobility or additional movement was observed. Cementation of an intentionally high single-tooth restoration causes no increase in tooth mobility while occlusal adaptation re-establishes and restores the occlusal plane.


Electrophysiological evidence of phonemotopic representations of vowels in the primary and secondary auditory cortex.
How the brain encodes the speech acoustic signal into phonological representations is a fundamental question for the neurobiology of language. Determining whether this process is characterized by tonotopic maps in primary or secondary auditory areas, with bilateral or leftward activity, remains a long-standing challenge. Magnetoencephalographic studies failed to show hierarchical and asymmetric hints for speech processing. We employed high-density electroencephalography to map the Salento Italian vowel system onto cortical sources using the N1 auditory evoked component. We found evidence that the N1 is characterized by hierarchical and asymmetrical indexes in primary and secondary auditory areas structuring vowel representations. Importantly, the N1 was characterized by early and late phases. The early N1 peaked at 125-135 msec and was localized in the primary auditory cortex; the late N1 peaked at 145-155 msec and was localized in the left superior temporal gyrus. We showed that early in the primary auditory cortex, the cortical spatial arrangements-along the lateral-medial and anterior-posterior gradients-are broadly warped by phonemotopic patterns according to the distinctive feature principle. These phonemotopic patterns are carefully refined in the superior temporal gyrus along the inferior-superior and anterior-posterior gradients. The dynamical and hierarchical interface between primary and secondary auditory areas and the interaction effects between Height and Place features generate the categorical representation of the Salento Italian vowels.


Sotalol.
Sotalol is effective for treating atrial fibrillation (AF), ventricular tachycardia, premature ventricular contractions, and supraventricular tachycardia. Racemic (DL) sotalol inhibits the rapid component of the delayed rectifier potassium current. There is a near linear relationship between sotalol dosage and QT interval prolongation. However, in dose ranging trials in patients with AF, low-dose sotalol was not more effective than placebo. Orally administered sotalol has a bioavailability of nearly 100%. The only significant drug interactions are the need to avoid or limit use of concomitant drugs that cause QT prolongation, bradycardia, and/or hypotension.


Seroprevalence and systemic immune biomarkers associated with Toxoplasma gondii infection in blood donors from Southern Brazil.
The high seroprevalence of Toxoplasma gondii infection in Blood Banks could be a potential risk for contamination of blood recipients. The discovery of new biomarkers may help to distinguish between seropositive and seronegative donors. This study determined the seroprevalence and profile of systemic immune biomarkers associated with Toxoplasma gondii infection among blood donors from Southern Brazil. Peripheral blood was collected from 510 blood donors (52.2 % male; mean age: 36.61), 310, and 200 from Erechim, and Chapecó municipalities, respectively. Specific Toxoplasma gondii IgG and IgM antibodies were detected by Eletrochemioluminescence. Nested PCR and qPCR were performed to detectToxoplasma gondii DNA. Twenty-seven inflammatory factors were analyzed using a high-performance Luminex assay. Among 310 blood donors from Erechim, 44.5 % (138/310) were IgM(-)/IgG(+), and 1.3 % (4/310) were IgM(+)/IgG(+), while out of 200 blood donors from Chapeco, 42.5 % (85/200) were IgM(-)/IgG(+), and 2 % (4/200) were IgM(+)/ IgG(+). We did not find Toxoplasma gondii DNA in the samples analyzed by Nested PCR and qPCR.Additionally, IgM(-)/IgG(+) donors presented higher levels ofdistinct systemic mediators, and were indicated to be high producers of several systemic mediators (CCL11, CCL2, CCL3, CCL4, CXCL10, IL-1β, IL-17, IFN-γ, IL-4, IL-9, IL-13, IL-10, IL-1Ra, vascular endothelial growth factor/VEGF, platelet-derived growth factor/PDGF, granulocyte-macrophage colony-stimulating factor/GM-CSF, and IL-7). However, IgM(+)/IgG(+) donors were found as high producers of CXCL8, CXCL10, CCL4, IL-1β, IL-1Ra, IL-9, IL-13, and PDGF, while IgM(-)/IgG(-) donors showed unaltered levels for the most soluble mediators evaluated. These distinct biomarker signatures might help identify potential factors to distinguish between IgM(-) and IgM(+) donors.


Unique metabolite profiles of Indonesian cocoa beans from different origins and their correlation with temperature.
Chocolate flavors vary depending on the origin of the cocoa beans used. Differences in soil, microorganisms, and environmental factors contribute to the formation of flavor precursors in cocoa beans. During cocoa bean fermentation, environmental temperature has been shown to alter metabolite concentrations. However, the correlation between the metabolite profile of cocoa beans and the temperature of their region of origin has not been fully defined. In this study, the metabolite profiles of Indonesian cocoa beans of various origins were evaluated using gas chromatography/mass spectrometry-based analysis, and were found to differ depending on the origin of the bean. Subsequently, the correlation between metabolite profile and environmental temperature of the origin was assessed using orthogonal projection to latent structure regression (OPLS-R) analysis. The analysis revealed that seven metabolites were associated with temperature: γ-aminobutyric acid (GABA), ethanolamine, glycerol, isocitric acid + citric acid, succinic acid, malic acid, and saccharic acid. The findings of this study will be valuable to chocolate industries for the production of single-origin chocolates.


Comparative evaluation of a new formulation of isosorbide dinitrate oral spray and sublingual nitroglycerin tablets.
The magnitude and time course of the hemodynamic effect of a new formulation of an aqueous solution of isosorbide dinitrate (ISDN) spray were compared with those of sublingual nitroglycerin (NTG) tablets in 12 patients with chronic congestive heart failure. The patients received, in a random order, ISDN spray, 2.5 mg, or sublingual NTG, 0.8 mg. Hemodynamic measurements were performed before and at 1, 3, 5, 10, 20, 30 and 60 minutes after each drug. The second drug was given only after return of the hemodynamic parameters to baseline, plus a washout period of 2 hours. The hemodynamic variables measured were comparable at baseline. Both drugs produced hemodynamic improvement including a decrease in pulmonary capillary wedge pressure (PCWP), right atrial pressure and systemic and pulmonary vascular resistances. Only ISDN spray significantly increased cardiac output. The onset of action of ISDN spray was significantly more rapid than that of NTG. This was primarily evident in the decrease in PCWP. With ISDN spray the decrease started at 1 minute after administration, and at 3 minutes a decrease of 8.6 mm Hg was already found. The corresponding value for sublingual NTG was 1.6 mm Hg. The difference was highly significant (p less than 0.02). The peak effect of ISDN spray on PCWP and right atrial pressure was greater than that of NTG. Thus, the onset of the hemodynamic effect of the new formulation of ISDN spray is much more rapid than that of sublingual NTG tablets. At the doses used, the magnitude of the effect of the ISDN spray on some of the hemodynamic variables is greater than that of sublingual NTG.