The importance of the Escherichia coli ribosomal protein L16 for the reconstitution of the peptidyl-tRNA hydrolysis activity of peptide chain termination.
The incubation of the 50 S ribosomal subunit of Escherichia coli with 1.5 M LiCl yields 1.5c core particles inactive in the peptidyl-tRNA hydrolysis activity of in vitro termination. The omission of L16 alone from reconstitutions of the proteins into the core results in inactive ribosomes. The single omission of a number of other proteins, in particular L7/L12, L10, L25, L27, and L15, gives ribosomes with intermediate activity. L16 alone is unable to restore significant activity to 1.5c cores, but together L16 and the above "stimulating" proteins produce particles as active as those reconstituted with the full complement of proteins. The ribosomal proteins important for the expression of peptidyl-tRNA hydrolysis and peptidyl transferase activities are very similar. However, ribosomes lacking both L11 and L16, but not L16 alone, surprisingly can catalyze codon- and release factor 2-dependent peptidyl-tRNA hydrolysis. The addition of L16 dramatically increases the activity. L16 is, therefore, important but not essential for the expression of the release factor 2-dependent peptidyl-tRNA hydrolysis.


Rat liver plasma membrane damage in hexachlorobenzene intoxication and its potentiation by ethanol.
Chronic feeding of male Wistar rats with food containing hexachlorobenzene (HCB) at 17.5 mmol/kg induced elevation of serum amino-transferases and bilirubin content, increase of microsomal cytochrome P-450 concentration, and decrease of 5'-nucleotidase, K+,Na+- and Mg2+-adenosine triphosphatase activities in liver plasma membrane preparations. These changes were potentiated by ethanol consumption suggesting a possible role of liver plasma membrane damage in the pathogenesis of HCB intoxication.


The genome sequence of the clouded yellow, Colias crocea (Geoffroy, 1785).
We present a genome assembly from an individual female Colias crocea (also known as Colias croceus; the clouded yellow; Arthropoda; Insecta; Lepidoptera; Pieridae). The genome sequence is 325 megabases in span. The complete assembly is scaffolded into 32 chromosomal pseudomolecules, with the W and Z sex chromosome assembled. Gene annotation of this assembly on Ensembl has identified 13,803 protein coding genes.


Perforation of acalculous cholecystitis associated with localized atherosclerosis: report of a case.
We describe herein the unusual case of a 68-year-old Japanese man who underwent laparotomy for an acute abdomen caused by diffuse peritonitis, which revealed perforation of the gallbladder without any stones. A cholecystectomy was subsequently carried out, and histological examination showed marked atherosclerosis of the gallbladder associated with acute inflammatory changes. It is most likely that circulatory disturbance of the gallbladder wall due to the atherosclerosis played an important role in the events leading to perforation. Acute acalculous cholecystitis is an uncommon condition which is extremely difficult to diagnose preoperatively. The clinicopathological features of this patient are of particular interest and importance in terms of pathogenesis as well as treatment.


Mucor pyelonephritis. Report of a case diagnosed by urine cytology, with diagnostic considerations in the workup of funguria.
Isolated renal mucormycosis is an uncommon kidney infection affecting patients with underlying systemic diseases and intravenous (IV) drug abuse. We report a unique case in the cytologic literature in which urine cytology provided insight into the diagnosis, renal mucormycosis. The patient, a diabetic and IV drug abuser, presented with complaints of left flank pain, fever and dysuria. All urine cultures were negative. A computed tomography (CT) scan showed changes consistent with left acute pyelonephritis, and the patient was treated for a presumed diagnosis of bacterial pyelonephritis. Late in the hospital stay, the cytology laboratory diagnosed Mucor in a single urine specimen, but the patient had already been discharged. The patient was never treated for funguria, only to present again with left flank pain 13 months later. An abdominopelvic CT scan showed progression to left chronic pyelonephritis. The patient, however, left the hospital against medical advice before any further workup could be completed. Renal mucormycosis should be considered part of the differential diagnosis in patients with underlying diseases or IV drug abuse who present with symptoms of acute pyelonephritis. The differential diagnosis of Mucor funguria should also include fungal ball in the renal pelvis or urinary bladder and fungal cystitis.


Considerations of the impacts of COVID-19 on domestic violence in the United States.
"Stay home, save lives" has been shown to reduce the impacts of COVID-19; however, it is crucial to recognize that efforts not to stress healthcare systems may have unintended social consequences for domestic violence. This commentary addresses domestic violence as an important social and public health implication of COVID-19. As a pandemic with a high contagion level, necessary social distancing measures have been put in place across the world to slow transmission and protect medical services. We first present literature that shows that among the effects of social distancing are social and functional isolation and economic stress, which are known to increase domestic violence. We then present preliminary observations from a content analysis conducted on over 300 news articles from the first six weeks of COVID-19 "lockdown" in the United States: articles predict an increase in domestic violence, report an increase in domestic violence, and inform victims on how to access services. Assessing the intersection of the early news media messaging on the effect of COVID-19 on DV and the literature on social isolation and crisis situations, we conclude the commentary with implications for current policy related to (1) increased media attention, (2) increased attention in healthcare systems, (3) promoting social and economic security, and (4) long-term efforts to fund prevention and response, as well as research implications to consider. The research is presented as ongoing, but the policy and procedure recommendations are presented with urgency.


Surgical strategies for intracranial meningioma in the molecular era.
Surgical resection has long been the treatment of choice for meningiomas and is considered curative in many cases. Indeed, the extent of resection (EOR) remains a significant factor in determining disease recurrence and outcome optimization for patients undergoing surgery. Although the Simpson Grading Scale continues to be widely accepted as the measure of EOR and is used to predict symptomatic recurrence, its utility is under increasing scrutiny. The influence of surgery in the definitive management of meningioma is being re-appraised considering the rapid evolution of our understanding of the biology of meningioma. Although historically considered "benign" lesions, meningioma natural history can vary greatly, behaving with unexpectedly high recurrence rates and growth which do not always behave in accordance with their WHO grade. Histologically confirmed WHO grade 1 tumors may demonstrate unexpected recurrence, malignant transformation, and aggressive behavior, underscoring the molecular complexity and heterogeneity. As our understanding of the clinical predictive power of genomic and epigenomic factors matures, we here discuss the importance of surgical decision-making paradigms in the context of our rapidly evolving understanding of these molecular features.


General or regional anaesthesia for postpartum haemorrhage-A national population-based cohort study.
Anaesthesia is required to assist the treatment of postpartum haemorrhage (PPH) when manual removal of the placenta or emptying of the uterine cavity is required. The choice between general or regional anaesthesia may depend upon factors such as existing epidural, airway, hypovolaemia, and tradition. Data from a randomized controlled trial of PPH (FIB-PPH) was used to reveal differences between delivery centres. In addition, national data of 5,601 PPH procedures requiring anaesthesia during 2010-2015 was collected from the Danish Medical Birth Registry, the National Danish Patient Registry, and the Danish Anaesthesia Database. The aim is to describe the variation in choice of anaesthesia for treatment of PPH. Data from the randomized trial showed large differences in practice between centres not explained by physiological factors. Using national Danish registry data, we show that large delivery centres as compared to small centres prefer regional anaesthesia for PPH procedures in opposed to general anaesthesia. Sevoflurane was used despite it causing uterine relaxation. The use of general anaesthesia was associated with younger parturients, larger blood loss, and larger Body-Mass Index. Aspiration was recorded in one case (0.02%). In the postoperative care-unit general anaesthesia was associated with a shorter stay, but also higher pain score at admission. Practice varies immensely between delivery centres with large centres preferring regional anaesthesia. Difference in practice might be explained by level of experience, here large centres might be more confident using regional anaesthesia. Knowledge is being extrapolated from literature on caesarean sections. Future studies should address the optimal choice of anaesthesia for PPH procedures.


Catalytic degradation of methylene blue using silver nanoparticles synthesized by honey.
This investigation displayed the good catalytic activity of silver nanoparticles (AgNPs) on the reduction of methylene blue dye. During this work, Honey was chosen for environmentally reducing and stabilizing agents for preparation of silver nanoparticles then characterized these nanoparticles by ultraviolet-visible spectroscopy (UV-Vis), functional biomolecules were confirmed by Fourier transform infrared spectroscopy (FTIR). Via transmission electron microscopy (TEM), the size and shape of silver nanoparticles revealed that the particles are spherical and monodispersed without major agglomeration, the particle size ranging from 5 to 25 nm, in addition, the largest particle density levels are 5-10 nm, ZETA Seizers studied the size distribution of the colloidal solution. UV/Vis spectrophotometer and HPLC were used to study and analyze the degradation performance of silver nanoparticles on methylene blue. The results show that 92% of methylene blue has been degraded after 72 h. additionally, several new peaks have appeared after treatment of the samples by using HPLC.


Lincomycin-induced cholecystitis and gallstones in guinea pigs.
Guinea pigs given lincomycin 60 mg per kg per day showed a striking increase in the renewal of epithelial cells in the gallbladder. This was detectable after only 24 hr of treatment. By 48 hr a precipitate consisting predominantly of calcium and bilirubin had formed in the gallbladder. Gallbladder bile glycoprotein concentrations rose progressively. At 8 days epithelial dysplasia was marked. Treatment was discontinued at 9 days. The guinea pigs that survived beyond 34 days showed that new tubuloalveolar glands had formed focally in the body and fundus of the gallbladder. Multiple calcium-containing stones were present. The failure to culture bacteria from bile, the failure of the bile salt pattern to change, and the progressive nature of the epithelial injury suggested that the changes resulted from a direct toxic effect and were not dependent on the antibiotic activity of this drug. It was concluded that damage to the epithelium of the gallbladder preceded the formation of a precipitate and initiated histological changes which culminated, at the time that the precipitate became organized into stones, in impressive glandular metaplasia.


Large cryptic genomic rearrangements with apparently normal karyotypes detected by array-CGH.
Conventional karyotyping (550 bands resolution) is able to identify chromosomal aberrations >5-10 Mb, which represent a known cause of intellectual disability/developmental delay (ID/DD) and/or multiple congenital anomalies (MCA). Array-Comparative Genomic Hybridization (array-CGH) has increased the diagnostic yield of 15-20%. In a cohort of 700 ID/DD cases with or without MCA, including 15 prenatal diagnoses, we identified a subgroup of seven patients with a normal karyotype and a large complex rearrangement detected by array-CGH (at least 6, and up to 18 Mb). FISH analysis could be performed on six cases and showed that rearrangements were translocation derivatives, indistinguishable from a normal karyotype as they involved a similar band pattern and size. Five were inherited from a parent with a balanced translocation, whereas two were apparently de novo. Genes spanning the rearrangements could be associated with some phenotypic features in three cases (case 3: DOCK8; case 4: GATA3, AKR1C4; case 6: AS/PWS deletion, CHRNA7), and in two, likely disease genes were present (case 5: NR2F2, TP63, IGF1R; case 7: CDON). Three of our cases were prenatal diagnoses with an apparently normal karyotype. Large complex rearrangements of up to 18 Mb, involving chromosomal regions with similar size and band appearance may be overlooked by conventional karyotyping. Array-CGH allows a precise chromosomal diagnosis and recurrence risk definition, further confirming this analysis as a first tier approach to clarify molecular bases of ID/DD and/or MCA. In prenatal tests, array-CGH is confirmed as an important tool to avoid false negative results due to karyotype intrinsic limit of detection.


Long non-coding RNA TUG1 sponges microRNA-381-3p to facilitate cell viability and attenuate apoptosis in cervical cancer by elevating MDM2 expression.
Based on the theory that long non-coding RNAs (lncRNAs) sponge microRNAs (miRNAs) to engage in cervical cancer development, this work was set out to investigate the possible role of lncRNA taurine upregulated gene 1 (TUG1) and miR-381-3p in the development of cervical cancer. TUG1, miR-381-3p and murine double minute 2 (MDM2) expression were measured in cervical cancer tissues and cells. The nexus between TUG1 and clinicopathological features of cervical cancer was discussed. The biological functions of TUG1, miR-381-3p and MDM2 on cervical cancer cell process were interpreted via gain- and loss-of-function experiments. Also, tumor xenograft in nude mice was conducted in vivo. The interactions between TUG1, miR-381-3p and MDM2 were identified. TUG1 and MDM2 raised while miR-381-3p reduced in cervical cancer. TUG1 expression was related to tumor size, differentiation, international federation of gynecology and obstetrics stage and lymph node metastasis of cervical cancer. Restored miR-381-3p, depleted TUG1 or reduced MDM2 decreased viability, colony-forming, migration and invasion abilities, and facilitated apoptosis of cervical cancer cells. Xenografted tumors grew slowly upon injection with restored miR-381-3p and depleted TUG1. TUG1 bound to miR-381-3p and miR-381-3p targeted MDM2. On all accounts, this present study provides evidence that silencing TUG1 depressed cervical cancer cell progression through miR-381-3p/MDM2 axis, highlighting a theoretical basis for cervical cancer treatment.


Retinal projections into the Zona Incerta of the rock cavy (Kerodon rupestris): a CTb study.
The Zona Incerta is a key neural substrate of higher brain functions. A neural population in the caudal ZI projects into the superior colliculus. This recently has been identified as an important structure for the saccades. Applying CTb, we describe a retinal projection into the caudal ZI and the distribution of its terminal varicosities in the rock cavy, a Brazilian rodent, which has been used as an anatomical model to enhance the comprehension about the phylogeny of the nervous system. Contrary to other investigated rodents, the retinal fibers in the rock cavy lie in the caudal Zona Incerta (ZIc), suggesting a functional specialization in the rock cavy. The high resolution and qualitative analysis of retinal fibers in the present work provide a substrate to interpretation of the visual system, and its phylogenetic pathways among species.


Effects of Neighborhood-level Data on Performance and Algorithmic Equity of a Model That Predicts 30-day Heart Failure Readmissions at an Urban Academic Medical Center.
Socioeconomic data may improve predictions of clinical events. However, owing to structural racism, algorithms may not perform equitably across racial subgroups. Therefore, we sought to compare the predictive performance overall, and by racial subgroup, of commonly used predictor variables for heart failure readmission with and without the area deprivation index (ADI), a neighborhood-level socioeconomic measure. We conducted a retrospective cohort study of 1316 Philadelphia residents discharged with a primary diagnosis of congestive heart failure from the University of Pennsylvania Health System between April 1, 2015, and March 31, 2017. We trained a regression model to predict the probability of a 30-day readmission using clinical and demographic variables. A second model also included the ADI as a predictor variable. We measured predictive performance with the Brier Score (BS) in a held-out test set. The baseline model had moderate performance overall (BS 0.13, 95% CI 0.13-0.14), and among White (BS 0.12, 95% CI 0.12-0.13) and non-White (BS 0.13, 95% CI 0.13-0.14) patients. Neither performance nor algorithmic equity were significantly changed with the addition of the ADI. The inclusion of neighborhood-level data may not reliably improve performance or algorithmic equity.


Clean Electrochemical Synthesis of Pd-Pt Bimetallic Dendrites with High Electrocatalytic Performance for the Oxidation of Formic Acid.
Pd-Pt bimetallic catalysts with a dendritic morphology were in situ synthesized on the surface of a carbon paper via the facile and surfactant-free two step electrochemical method. The effects of the frequency and modification time of the periodic square-wave potential (PSWP) on the morphology of the Pd-Pt bimetallic catalysts were investigated. The obtained Pd-Pt bimetallic catalysts with a dendritic morphology displayed an enhanced catalytic activity of 0.77 A mg-1, almost 2.5 times that of the commercial Pd/C catalyst reported in the literature (0.31 A mg-1) in acidic media. The enhanced catalytic activity of the Pd-Pt bimetallic catalysts with a dendritic morphology towards formic acid oxidation reaction (FAOR) was not only attributed to the large number of atomic defects at the edges of dendrites, but also ascribed to the high utilization of active sites resulting from the "clean" electrochemical preparation method. Besides, during chronoamperometric testing, the current density of the dendritic Pd-Pt bimetallic catalysts for a period of 3000 s was 0.08 A mg-1, even four times that of the commercial Pd/C catalyst reported in the literature (about 0.02 A mg-1).


Inferring the mode and strength of ongoing selection.
Genome sequence data are no longer scarce. The UK Biobank alone comprises 200,000 individual genomes, with more on the way, leading the field of human genetics toward sequencing entire populations. Within the next decades, other model organisms will follow suit, especially domesticated species such as crops and livestock. Having sequences from most individuals in a population will present new challenges for using these data to improve health and agriculture in the pursuit of a sustainable future. Existing population genetic methods are designed to model hundreds of randomly sampled sequences but are not optimized for extracting the information contained in the larger and richer data sets that are beginning to emerge, with thousands of closely related individuals. Here we develop a new method called trio-based inference of dominance and selection (TIDES) that uses data from tens of thousands of family trios to make inferences about natural selection acting in a single generation. TIDES further improves on the state of the art by making no assumptions regarding demography, linkage, or dominance. We discuss how our method paves the way for studying natural selection from new angles.


Impact of relaxation training on patient-perceived measures of anxiety, pain, and outcomes after interventional electrophysiology procedures.
Electrophysiology procedures vary in invasiveness, duration, and anesthesia utilized. While complications are low and efficacy high, cases are elective and patient experiences related to anxiety, pain, and perceived outcomes are not well studied. We sought to determine if a 30-minute audio compact disc (CD) that teaches relaxation techniques and wellness perception prior to an elective procedure impacts validated measures of anxiety, pain, and procedural outcomes. Sixty-one patients were randomly assigned to a control group (CG) (N(CG) = 31) or interventional group (IG) (N(IG) = 30). Both groups answered a baseline Hospital Anxiety and Depression Scale (HADS-A) survey consisting only of anxiety assessment questions. The IG listened to the CD the night prior to their procedure. Heart rate and blood pressure were monitored on admission and prior to the procedure. Postprocedure, both groups completed two HADS-A surveys as well as two Patient Experience Surveys (PES). There was no statistical difference in the demographics and the rate of procedural complications between the groups. The statistical significance of our data was determined using a Student's t-test and χ(2) test. At baseline, both groups had equal amounts of anxiety prior to their procedures (P = 0.2). The patients in the IG had lower systolic blood pressures during admission and prior the administration of analgesics in comparison to the CG. Postprocedure, results from administering the HADS-A demonstrated that the IG had 33% lower anxiety (P = 0.02) than CG patients. The implementation of basic relaxation teaching techniques prior to planned electrophysiology procedures lowers systolic blood pressure and postprocedural anxiety.


Association of Treatment of Chorioamnionitis with Non-Beta Lactam Antibiotics and Postcesarean Infectious Morbidity.
Chorioamnionitis (CAM) is associated with postcesarean (CS) infectious morbidity (IM). Beta-lactam antibiotics (BLA) are used to treat CAM. It is uncertain if women who cannot receive BLA attain similar benefit from treatment of CAM with non-BLA. Retrospective cohort of women with CAM is delivered by CS in the maternal-fetal medicine units CS registry. We compared IM in women who received BLA versus women who received non-BLA. The primary outcome was a composite of endometritis, wound complication, necrotizing fasciitis, septic pelvic thrombophlebitis, and pelvic abscess. Multivariable logistic regression estimated odds ratios for the association of non-BLA treatment with IM outcomes. A total of 3,063 (93%) women received BLA, and 232 (7%) received non-BLA. Groups had similar rates of composite post-CS IM (10.6 vs. 12.1%, p = 0.5). After adjusting for confounders, treatment of CAM with non-BLA was not associated with post-CS IM (adjusted odds ratio [AOR] 1.1, 95% confidence interval [CI] 0.6-1.7), endometritis (AOR 1.1, 95% CI 0.7-1.8), or wound complications (AOR 1.2, 95% CI 0.5-3.2). Women with CAM who receive non-BLA and require CS may not be at increased risk of postoperative infections complications, compared to women who receive BLA.


Dexmedetomidine Reverses Postoperative Spatial Memory Deficit by Targeting Surf1 and Cytochrome c.
Anesthesia and surgery are associated with perioperative neurocognitive disorders (PND). Dexmedetomidine is known to improve PND in rats; however, little is known about the mechanisms. Male Sprague-Dawley rats were subjected to resection of the hepatic apex under propofol anesthesia to clinically mimic human abdominal surgery. The rats were divided into four groups: control group (C), anesthesia group (A), model group (M), and model + dex group (D). Cognitive function was evaluated with the Morris water maze (MWM). Neuronal morphology was observed with H&E staining, Nissl's staining and immunohistochemistry. Transcriptome analysis and quantitative real-time PCR were performed to investigate functional mitochondrial mRNA changes in the hippocampus. Protein levels were measured by Western blotting at 1, 3, and 7 days after surgery. Surgery-induced cognitive decline lasted for three days, but not seven days after surgery in the M group; however, rats in the D group were significantly improved by dexmedetomidine. No significant differences in the number of neurons were observed between the groups after surgery. Rats from the M group showed significantly greater expression levels of Iba-1 and GFAP compared with the C group and the D group. Rats in the M group demonstrated increased Surf1 and Cytochrome c expression on days 1 and 3, but not day 7; similar changes were not induced in rats in the D group. Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, and downregulate the expression of Surf1 and Cytochrome c protein in the hippocampus of rats in a PND model.


Comparison of the drug retention and reasons for discontinuation of tumor necrosis factor inhibitors and interleukin-6 inhibitors in Japanese patients with elderly-onset rheumatoid arthritis-the ANSWER cohort study.
This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of either tumor necrosis factor inhibitors (TNFi) or interleukin-6 inhibitors (IL-6i) in patients with elderly-onset rheumatoid arthritis (EORA). Patients with rheumatoid arthritis (RA) enrolled in a Japanese multicenter observational registry between 2011 and 2020 were included. EORA was defined as RA with onset at 60 or over. To adjust confounding by indication for treatment with TNFi or IL-6i, a propensity score based on multiple baseline characteristics variables was used to compare the drug retention and causes for discontinuation between TNFi and IL-6i. Adjusted cumulative incidence of drug discontinuation for each reason was compared between the two groups using the Fine-Gray model. Among a total of 9,550 patients in the registry, 674 TNFi and 297 IL-6i initiators with EORA were identified. Age, the proportion of females, disease duration, and baseline disease activity at the time of TNFi or IL-6i initiation were similar between the two groups. After adjusting for differences in baseline characteristics between the two groups, overall drug discontinuation was significantly lower in the IL-6i as compared to the TNFi (HR = 0.71, 95%CI = 0.59-0.86, p < 0.001). The adjusted cumulative incidence of discontinuation due to lack of effectiveness was lower with the IL-6i (HR = 0.46, 95%CI = 0.33-0.63, p < 0.001) while those due to adverse events (HR = 0.82, 95%CI = 0.56-1.18, p = 0.28) or achievement of clinical remission (HR = 1.09, 95%CI = 0.62-1.91, p = 0.76) were similar between the two groups. In EORA patients initiating a TNFi or IL-6i, significantly higher drug retention was observed with IL-6i. Discontinuation due to lack of effectiveness was significantly less frequent in IL-6i while discontinuations due to adverse event or achievement of clinical remission were similar between the two groups.


Respiratory virus infections.
The respiratory tract is a frequent site of infection with a wide range of viruses. Each family of viruses can cause differing clinical syndromes depending on the age of the patient and the immune response. As a corollary, different clinical syndromes can be caused by different families of viruses.


Analysis of the relationship between cellular thymidine kinase activity and virulence of thymidine kinase-negative herpes simplex virus types 1 and 2.
The virulence of thymidine kinase-negative herpes simplex virus type 1 (HSV-1; VRTK- strain) and type 2 (HSV-2; UWTK- strain) was studied in comparison with that of their parental strains (VR-3 and UW-268, respectively) in an encephalitis model of adult (4-week-old) and newborn (3-day-old) mice. Viral thymidine kinase (TK) activity was essential for the maximum expression of virulence of HSV-1, because the 50% lethal dose (LD50) of VRTK- was 60 times higher than that of VR-3 in the brains of newborn mice expressing high levels of cellular TK activity. However, the UWTK- strain showed that replication of the UWTK- strain was completely supported by cellular TK activity. This difference in the role of viral and cellular TKs for virus growth between HSV-1 and HSV-2 was¿ confirmed with the one-step growth of virus strains in L-M and L-M(TK-) cells.


The effect of current pulp capping materials against intrapulpal temperature increase in primary teeth. An in-vitro study by pulpal microcirculation simulation model.
Widespread use of light-cured materials has raised the issue of possible thermal effects on pulp tissue. It was aimed to investigate the effectiveness of pulp capping materials (PCM) against intrapulpal temperature increases (ITI) in primary teeth during light-curing of compomers in this study. A Class-I cavity was prepared on the primary mandibular second molar tooth. An experimental mechanism was used for pulpal microcirculation and temperature regulation of the tooth. There are eight groups in the study: in Groups 1-6: MTA-Angelus, Biodentine, TheraCal LC, Dycal, conventional Glass Ionomer Cement (GIC) and resin-modified GIC were used as PCM, respectively. In Group-7 no PCM was used. In Group-8 only light was applied to the cavity without any PCM or compomer. Compomer restorations were applied in Groups 1-7 with the same material (Dyract XP, DENTSPLY, Weybridge, UK) and light cured for 10sec with the same light-curing unit (Kerr, Demi Plus, 1200 mW/cm2). Temperature changes (Δt) in the pulp chamber were measured and statistically analysed with Kruskal-Wallis and Mann Whitney U tests. The highest Δt-value (4.57 ± 0.11 °C) was measured in Group-4 and 7. The lowest Δt-value (3.94 ± 0.4 °C) was measured in Group-8. Δt-values measured in the Groups 2, 3 and 6 were significantly lower than the values measured in Group-4 and 7 (p = 0.001). ITI during the light-curing of the PCM used in Group-3 and 6 exceeded the critical value (5.5 °C) reported in the literature. In protecting the pulp from the harmful thermal effects of restorative procedures Biodentine which is a self-cured material, may be most acceptable choice as an indirect PCM.


The dynamic changes of Nrf2 mediated oxidative stress, DNA damage and base excision repair in testis of rats during aging.
Accumulation of oxidative stress, DNA damage and impaired DNA repair appear to play critical roles in the decline of testicular function with aging. However, when those factors begin to lose control in testis during aging has not yet been well understood. This study was designed to assess the changes of oxidative stress and DNA damage status, and DNA repair capacity in testis during aging. Thus, male Sprague-Dawley rats at 3, 9, 15 and 24 months of age were used to delineate the dynamic changes in testicular weight and index, testosterone concentration, testicular histology, Nrf2-mediated oxidative stress, DNA damage, DNA repair and apoptosis. Results showed that testicular weight and index, testosterone concentration and spermatid number progressively declined from 9 to 24 months of age. Similarly, seminiferous tubule diameters and seminiferous epithelium heights gradually diminished with aging. Nrf2-mediated antioxidant defense ability was significantly impaired in testis with increasing age including decreased the activity of SOD and the expression levels of Nrf2, HO-1 and NQO-1, and increased the contents of MDA. In addition, DNA damage including DNA single-strand breaks (SSBs) and DNA double-strand breaks (DSBs) also progressively increased accompanied by increased levels of 8-hydroxydeoxyguanosine (8-OHdG) and γ-H2AX, and activated ATM/Chk2 and ATR/Chk1 pathway. Consistent with the results of Nrf2 pathway, the expression levels of APE1, OGG1 and XRCC1 involved in base excision DNA repair (BER) pathway increased from 3 to 9 months of age, and then gradually decreased after 9 months of age. Finally, TUNEL and Western blot results further confirmed germ cell apoptosis progressively increased from 3 to 24 months of age as evidenced by decreased ratio of Bcl-2/Bax and levels of Bcl-2 expression, and increased Bax expression levels. Taken together, our results suggest that downregulation of antioxidant ability mediated by Nrf2 pathway and impairment of BER capacity might correlate with increased DNA damage, and then induce declining testicular function during aging after adult.


The contribution of intrinsic activity to the action of opioids in vitro.
The effects of opioids were compared in five field-stimulated isolated tissue models, the guinea-pig ileum and vasa deferentia from rat, rabbit and mice of the Alderley Park and C57BL/6 strains. Although the mu-receptor agonist [D-Ala2, MePhe4, Gly-ol5] enkephalin appeared to act at similar receptors in the guinea-pig ileum, rat vas deferens, mouse vas deferens and C57BL/6 mouse vas deferens preparations, its potency varied considerably between these preparations. Similar potency differences were also observed with the kappa-agonist, ethylketocyclazocine. It is proposed that these variations in potency reflect differences in the number of spare receptors present in each model. The finding that some drugs which have agonist activity in the more sensitive preparations behave as antagonists in the less sensitive tissues supports this proposal and highlights the importance of intrinsic activity in determining the action of opioids. Many of the prototypic opioid agonists were found to be either partial agonists (eg. morphine and bremazocine) or to possess affinity for more than one receptor type (eg. ethylketocyclazocine, Mr 2034).


Functional investigation of AfsKRS regulatory system for pristinamycin biosynthesis in Streptomyces pristinaespiralis.
Three genes encoding AfsK, AfsR, AfsS homologues in Streptomyces pristinaespiralis were studied, respectively, to investigate regulatory role of AfsKRS system for pristinamycin biosynthesis. Transcription change and gene inactivation analysis indicated that these genes had active transcription and positive regulation for the improvement of pristinamycin production in S. pristinaespiralis. The analysis of AfsKRS-defective mutagenesis indicated that there might be a positive correlation between the product of afsK and pristinamycin I biosynthesis, and a negative correlation to pristinamycin II biosynthesis. However, both afsR and afsS might have negative correlation to pristinamycin I production and positive correlation to pristinamycin II production. The effects on pristinamycin production of AfsKRS disruptants by protein kinase inhibitor K252a indicated that AfsR, both not AfsK and AfsS, was the inhibition target of K252a in S. pristinaespiralis, and AfsR should serve as a pleiotropic regulator to have differential regulation on biosynthesis of pristinamycin I and II components. Based on above study, it might be deduced that different signal transduction patterns via AfsK, AfsR, AfsS of AfsKRS system should be involved in respective regulation for biosynthesis of pristinamycin I and II in S. pristinaespiralis. In conclusion, the investigation could give some valuable clues for exploring furtherly regulatory function of AfsKRS system in S. pristinaespiralis.


Granulomatous and lymphocytic thyroiditis associated with a follicular adenoma.
A 44-year-old woman came to medical attention with right thyroid lobe enlargement and weight loss. Thyroid scan and ultrasound demonstrated a nodule in the right thyroid lobe; a right hemithyroidectomy was performed. Histologic examination documented granulomatous and lymphocytic thyroiditis associated with a follicular adenoma. No inflammation was apparent within the adenoma. The parallels between granulomatous thyroiditis and lymphocytic thyroiditis, including presumed viral initiation and deranged immunologic function, suggest that granulomatous thyroiditis may evolve into chronic lymphocytic thyroiditis; this case may be an example of such a transition. It is proposed that thyroid follicular adenomas have different antigenicity, which may account for the conspicuous absence of inflammation within the tumor.


Immuno-electronmicroscopic study of human EA rosettes.
The immuno-electronmicroscopic study of human EA rosettes, using ferritin-labelled anti-human IgG antiserum, showed clusters of ferritin granules at the points of contact between erythrocytes and lymphoid cells, indicating that the links between Fc fragment of IgG on the surface of erythrocytes and specific receptor on the surface of lymphoid cell correspond to the sites of morphological interaction between the 2 cell types.


Mechanical characteristics of lyophilized human saphenous vein valves.
We investigated the mechanical characteristics of lyophilized human saphenous vein valves to determine their suitability for use as allogeneic transplants to treat chronic venous insufficiency. Fresh cadaveric veins were lyophilized in vacuum bottles within 24 hours of harvest and were stored at room temperature. The veins were reconstituted in saline solution and then were placed in an in vitro flow circuit for evaluation. At varied flow rates, pressures proximal and distal to valves during prograde and retrograde flow were measured. Valve closure times were determined with Doppler examination and spectral analysis. The valves were also stressed to 350 mm Hg on a separate apparatus. All pressures proximal and distal to the valves remained less than 10 mm Hg during prograde flow. A pressure gradient developed immediately on the reversal of flow. Pressure as high as 200 mm Hg applied against the closed valves was not transmitted beyond the valve. Valve closure times had a mean of 0.31 +/- 0.03 seconds and 0.21 +/- 0.01 seconds for the Doppler examination and spectral analysis, respectively. All valves withstood stress pressures to 350 mm Hg. The in vitro mechanical characteristics of the valves of lyophilized veins are similar to known values for normal in vivo valves.


Increased risk of carotid atherosclerosis for long-term exposure to indoor coal-burning pollution in rural area, Hebei Province, China.
Smoky coal burning is a predominant manner for heating and cooking in most rural areas, China. Air pollution is associated with the risk of atherosclerosis, however, the link between indoor air pollution induced by smoky coal burning and atherosclerosis is not very clear. Therefore, we designed a cross-sectional study to evaluate the association of long-term exposure to smoky coal burning pollutants with the risk of atherosclerosis. 426 and 326 participants were recruited from Nangong, China and assigned as the coal exposure and control group according to their heating and cooking way, respectively. The indoor air quality (PM2.5, CO, SO2) was monitored. The association between coal burning exposure and the prevalence of atherosclerosis was evaluated by unconditional logistic regression analysis, adjusted for confounding factors. The inflammatory cytokines mRNAs (IL-8, SAA1, TNF-α, CRP) expression in whole blood were examined by qPCR. People in the coal exposure group had a higher risk of carotid atherosclerosis compared with the control (risk ratio [RR], 1.434; 95% confidence interval [95%CI], 1.063 to 1.934; P = 0.018). The association was stronger in smokers, drinkers and younger (<45 years old) individuals. The elevation of IL-8 (0.24, 95%CI, 0.06-0.58; P < 0.05), CRP (0.37, 95%CI, 0.05-0.70; P < 0.05), TNF-α (0.41, 95%CI, 0.14-0.67; P < 0.01) mRNAs expression in whole blood were positively related to coal exposure. Our results suggested long-term exposure to smoky coal burning emissions could increase the risk of carotid atherosclerosis. The potential mechanism might relate that coal burning emissions exposure induced inflammatory cytokines elevation which had adverse effects on atherosclerotic plaque, and then promoted the development of atherosclerosis.


Surgical outcomes of single stage surgery for Tandem spinal stenosis (TSS) in elderly and younger patients: A comparative study.
Retrospective study. To evaluate and compare the outcomes of single stage surgery for Tandem Spinal Stenosis (TSS) in elderly (Age ≥65 years) and younger patients (Age <65 years). Tandem spinal stenosis among elderly is common and often missed diagnosed with delayed presentation. Literature evaluating efficacy and safety of single staged surgery for TSS in elderly patients is scanty. Analysis of 74 patients with TSS managed with single stage posterior surgery from 2007 to 2016 was done. A total of 62 patients who satisfied our inclusion criteria were evaluated and subdivided into two groups based on age; Study group (age ≥65years)] (n = 32) and control group (age <65years) (n = 30). Perioperative, clinical/radiological parameters and postoperative complications and recovery rate were noted. The Mean ODI and mJOA showed significant improvement post-operatively in both groups however there was no significant difference between the two groups at final follow-up. There was no statistical difference in operative time, blood loss and hospital stay between the groups. As per Odom's criteria, 78.1% had excellent to good results in study group, while 83.3% had excellent to good results in control group. Postoperative complications were more in elderly group however, there was no significant difference among neurological or cardiopulmonary complications between both groups. Single stage surgery is safe & efficacious modality with less morbidity and optimal results in elderly patients with proper preoperative risk assessment. Our study showed that increased age does not proved to be deterrent in the outcome of single staged surgery in tandem spinal stenosis.


Comparison of body structure, function, activity, and participation levels according to ankle foot orthosis wearing time in children with spastic cerebral palsy.
Ankle foot orthoses (AFOs) are usually recommended to prevent deformities and to increase the standing and walking performance in children with spastic cerebral palsy (CP). To compare the body functions and structures, activity and participation levels, and environmental factors according to AFO-wearing time in children with spastic CP. Prospective, cross-sectional-observational-clinical study. Eighty children with spastic CP (Gross Motor Function Classification System I-III; mean age 7.3 ± 3.9 years) were divided into two groups with equal ages and duration of AFO usage, which is provided as a part of routine clinical care: 6-12 hours per day group (n = 40) and 12-24 hours per day group (n = 40). The outcomes measured were calf muscle's spasticity with the modified Ashworth Scale (MAS), passive ankle dorsiflexion angle (DA), 66-item Gross Motor Function Measurement, Pediatric Berg Balance Scale, and Pediatric Quality of Life Inventory (PedsQL). Parental satisfaction was measured with a Visual Analog Scale. Multifactorial ANOVA was used to compare the groups, corrected for 66-item Gross Motor Function Measurement. No significant differences for the Pediatric Berg Balance Scale, MAS, and DA were found between the groups. Significant differences for the PedsQL (76.99 vs. 57.63; mean difference [MD], 15.60; 95% confidence interval [CI], 10.99∼20.22), daily living activities (65.30 vs. 35.92; MD, 25.72; 95% CI, 17.58∼33.86), fatigue (76.9 vs. 56.85; MD, 23.11; 95% CI, 16.87∼29.35), and satisfaction (8.08 vs. 5.21; MD, 2.46; 95% CI, 1.64∼3.27) were found between the groups; 6-12 hour group had superiority for each outcome (P < 0.001). Wearing time was significantly correlated with PedsQL (r = -0.524, P < 0.001) and satisfaction (r = -0.521, P < 0.001) but not with MAS or DA. AFO-wearing time seems to depend on the child's activity and participation levels rather than body functions and structures in children with spastic CP. Prolonged AFO-wearing time was negatively correlated with both the activity-participation level and parental satisfaction.


Application of a CNN to the Boda Claystone Formation for high-level radioactive waste disposal.
Nations relying on nuclear power generation face great responsibilities when designing their firmly secured final repositories. In Hungary, the potential host rock [the Boda Claystone Formation (BCF)] of the deep geological repository is under extensive examination. To promote a deeper comprehension of potential radioactive isotope transport and ultimately synthesis for site evaluation purposes, we have efficiently tailored geospatial image processing using a convolutional neural network (CNN). We customized the CNN according to the intricate nature of the fracture geometries in the BCF, enabling the recognition process to be particularly sensitive to details and to interpret them in the correct tectonic context. Furthermore, we set the highest processing scale standards to measure the performance of our model, and the testing circumstances intentionally involved various technological and geological hindrances. Our presented model reached ~ 0.85 precision, ~ 0.89 recall, an ~ 0.87 F1 score, and a ~ 2° mean error regarding dip value extraction. With the combination of a CNN and geospatial methodology, we present the description, performance, and limits of a fully automated workflow for extracting BCF fractures and their dipping data from scanned cores.


Antibacterial poly (ethylene glycol) diacrylate/chitosan hydrogels enhance mechanical adhesiveness and promote skin regeneration.
Various functional active hydrogels have been widely applied in tissue regeneration, especially in fields of wound repair as they are similar to the natural extracellular matrix (ECM) and can maintain moist at the wound site. However, preparing a hydrogel with multifunctional properties including high mechanical properties, excellent biocompatibility and long-term antibacterial activity is still a challenge. Herein, we developed a series of double network hydrogels based on poly (ethylene glycol) diacrylate (PEGDA) and chitosan (CS) or thiolated chitosan (TCS). The hydrogels presented in situ forming properties, good mechanical strength, adhesiveness, antibacterial activity and biocompatibility. The sample with the optimal formula of 15 wt% of PEGDA and 2 wt% of CS or TCS showed excellent mechanical adhesiveness, sustained release of antibacterial peptide and plasmid DNA, and it significantly accelerated in vivo wound healing process in a full-thickness skin defect model by reducing the inflammation and promoting the angiogenesis, meaning that the prepared hydrogels are excellent candidates for wound dressing.


Utility of quantitative ultrasound in community screening for hepatic steatosis.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Quantitative ultrasound facilitates clinical grading of hepatic steatosis (the early stage of NAFLD). However, the utility of quantitative ultrasound as a first-line method for community screening of hepatic steatosis remains unclear. Therefore, this study aimed to investigate the utility of quantitative ultrasound to screen for hepatic steatosis and for metabolic evaluation at the community level. In total, 278 participants enrolled from a community satisfied the study criteria. Each subject underwent anthropometric and biochemical examinations, and abdominal ultrasound imaging was performed to measure the controlled attenuation (CAP), integrated backscatter (IB), and information Shannon entropy (ISE). The assessment outcomes were compared with the fatty liver index (FLI), hepatic steatosis index (HSI), metabolic syndrome (MetS), and insulin resistance to evaluate the screening performance through the area under the receiver operating characteristic curve (AUROC) and Delong's test. Ultrasound ISE, CAP, and IB were effective in screening hepatic steatosis, MetS, and insulin resistance. In screening for hepatic steatosis, the AUROCs of ISE, CAP, and IB were 0.85, 0.83, and 0.80 (the cutoff FLI = 60), respectively, and 0.84, 0.75, 0.77 (the cutoff HSI = 36), respectively, and those for the evaluation of MetS and insulin resistance were 0.79, 0.75, 0.79, respectively, and 0.83, 0.76, 0.78, respectively. Delong's test revealed that ISE outperformed CAP and IB for the detection of hepatic steatosis and insulin resistance (P < .05). Based on the present results, ultrasound ISE is a potential imaging biomarker during first-line community screening of hepatic steatosis and insulin resistance.


Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions.
Cellular protrusion formation capacity is a key feature of developing neurons and many eukaryotic cells. However, the mechanisms underlying membrane growth in protrusion formation are largely unclear. In this study, photo-reactive unnatural amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nε-l-lysine was incorporated by a genetic code expansion strategy into protrudin, a protein localized in acidic endosomes and in the endoplasmic reticulum, that induces cellular protrusion and neurite formation. The modified protrudin was used for covalent trapping of protrudin-interacting proteins in living cells. Fatty acid synthase (FASN), which synthesizes free fatty acids, was identified to transiently interact with protrudin. Further characterization revealed a unique cooperation mechanism in which protrudin cooperates with FASN to facilitate cellular protrusion formation. This work reveals a novel mechanism involved in protrusion formation that is dependent on transient interaction between FASN and protrudin, and establishes a creative strategy to investigate transient protein-protein interactions in mammalian cells.


Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients.
The effects of a 48-hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady-state plasma level of 1798 +/- 481 ng/ml. Biphasic, rapid elimination of pirmagrel was observed with a distribution half-life of 6.7 minutes and a terminal half-life of 73 minutes. Plasma clearance and the volume of distribution of the drug were 300 +/- 87 ml/hr/kg and 497 +/- 232 ml/kg, respectively. The pharmacodynamic effects of pirmagrel were marked by a mean 96% suppression of serum thromboxane B2 (TXB2), which coincided with a suppression of urinary excretion of TXB2, 2,3-dinor-TXB2, and 11-dehydro-TXB2 of 85% +/- 8%, 91% +/- 5%, and 89% +/- 9%, respectively. Urinary excretion of all thromboxane metabolites measured at the end of 1 week after termination of infusion was returned to the baseline. In conclusion, pirmagrel caused effective and sustained suppression of all thromboxane derived metabolites in plasma and urine during continuous infusion in kidney transplant patients receiving cyclosporine.


Salicylates and 12-lipoxygenase activity in human washed platelets.
In vitro salicylates /aspirin, salicylic acid, salicylamide and gentisic acid/ inhibited formation of 12-lipoxygenase products in intact human washed platelets which were stimulated with thrombin or arachidonic acid. Salicylates did not affect 12-lipoxygenase activity in platelet lysates. Ex vivo aspirin or salicylamide at a dose of 1 g given orally to healthy volunteers potentiated formation of 12-lipoxygenase products in washed platelets. It is concluded that the effect of salicylates on 12-lipoxygenase pathway is independent from their influence on cyclooxygenase activity in platelets and aspirin cannot be considered as a selective inhibitor of platelet cyclooxygenase.


Retinopathy of prematurity (ROP) and indomethacin therapy in premature infants with patent ductus arteriosus (PDA).
Recent studies suggested that prostaglandins (PGs) may play a role in the pathogenesis of retinopathy of prematurity (ROP). To evaluate if PGs inhibitor, indomethacin, would affect the incidence or severity of the ROP, an analysis was performed on 47 infants who participated in a double-blind controlled study of indomethacin for the closure of PDA. Twenty-three were in the control group and 24 in the indomethacin group. Indirect ophthalmoscopic examinations were performed from about 4 weeks of postnatal age and onward as needed. There was no significant difference between the groups with respect to birth weight, gestational age, postnatal age, Apgar score, and cardiopulmonary status shortly after birth and at the time of study. Six in the control and 2 in the indomethacin group (p = 0.58) developed active ROP; one in each group developed cicatricial ROP. It appears that with current doses of therapy, indomethacin does not increase the incidence or severity of ROP.


Spatial patterns in tactile perception: is there a tactile field?
Previous studies of tactile spatial perception focussed either on a single point of stimulation, on local patterns within a single skin region such as the fingertip, on tactile motion, or on active touch. It remains unclear whether we should speak of a tactile field, analogous to the visual field, and supporting spatial relations between stimulus locations. Here we investigate this question by studying perception of large-scale tactile spatial patterns on the hand, arm and back. Experiment 1 investigated the relation between perception of tactile patterns and the identification of subsets of those patterns. The results suggest that perception of tactile spatial patterns is based on representing the spatial relations between locations of individual stimuli. Experiment 2 investigated the spatial and temporal organising principles underlying these relations. Experiment 3 showed that tactile pattern perception makes reference to structural representations of the body, such as body parts separated by joints. Experiment 4 found that precision of pattern perception is poorer for tactile patterns that extend across the midline, compared to unilateral patterns. Overall, the results suggest that the human sense of touch involves a tactile field, analogous to the visual field. The tactile field supports computation of spatial relations between individual stimulus locations, and thus underlies tactile pattern perception.


James Smith Turner (1832-1904) and the British Dental Association.
Together with John Tomes, J. S. Turner was a leading campaigner in the fight to advance dentistry from a trade to a profession. Through the Dental Reform Committee he promoted the establishment of a Dentists Register and then the British Dental Association. As first secretary of the BDA he guided it through its first days. He became president in 1891.


Effect of various exposure scenarios on the biological monitoring of organic solvents in alveolar air. II. 1,1,1-Trichloroethane and trichloroethylene.
The purpose of the present study was to investigate the influence of different exposure scenarios on the elimination of trichloroethylene (TRI) and 1,1,1-trichloroethane (1,1,1-TRI) in alveolar air and other biological fluids in human volunteers. In addition, it was sought to establish an interactive process between experimental data gathering and simulation modeling in an attempt to predict the influence of the different scenarios of exposure to TRI and 1,1,1-TRI on their respective biological monitoring indices and thus to establish the flexibility and validity of simulation models. Two adult male and two adult female Caucasian volunteers were exposed by inhalation, in a dynamic controlled exposure chamber, to various concentrations of TRI (12.5-25 ppm) or 1,1,1-TRI (87.5-175 ppm) in order to establish the influence of exposure concentration, duration of exposure, variation of concentration within day, and work load on biological exposure indices. The concentrations of unchanged solvents in end-exhaled air and in blood as well as the urinary excretion of trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined. The results show that doubling the exposure concentration for both solvents led to a proportional increase in the concentrations of unchanged solvents in alveolar air and blood at the end of a 7-h exposure period; this proportionality was still observable in 1,1,1-TRI expired air samples 16 h after the end of the third exposure day. In the case of urinary excretion of TCE and TCA, the proportionality between excretion and exposure concentration was not as good. It was once again observed that the slow excretion of both metabolites leads to progressive cumulation and that their urinary determination is subject to considerable interindividual variations. After adjustment (lowering) of the exposure concentration to account for a prolongation of the duration of exposure (from 8 to 12 h) it was observed that the concentrations of TRI or 1,1,1-TRI towards the end of both exposure periods are more a reflection of the actual exposure concentration than of the exposure duration. Despite important interindividual variations, these adjusted and nonadjusted exposures led to almost identical average total urinary excretion over 24 h) of TCE and TCA after exposure to 1,1,1-TRI, as was also the case for TCE but not for TCA after exposure to TRI. Induced within-day variations in the exposure concentration led to corresponding but not proportional changes in alveolar air concentrations for both solvents. After exposure to peak concentrations there was a lag period before alveolar air concentrations returned to prepeak levels. At the end of repeated 10-min periods of physical exercise at 50 W, alveolar air concentrations of TRI were increased by 50% while those of 1,1,1-TRI increased by only 12%. After optimization of the physiologically based toxicokinetic model parameters with experimental data collected during the first exposure scenario, results pertaining to the three other scenarios were adequately simulated by the optimized models. Overall, the results of the present study suggest that alveolar air solvent concentration is a reliable index of exposure to both TRI and 1,1,1-TRI under various experimental exposure scenarios. These results also suggest that urinary excretion of TCE and TCA must be interpreted with caution when assessing exposure to either solvents. For exposure situations likely to be encountered in the workplace, physiologically based toxicokinetic modeling appears to be a useful tool both for developing strategies of biological monitoring of exposure to volatile organic solvents and for predicting alveolar air concentrations under a given set of exposure conditions.


A kinematic study of luno-triquetral dissociations.
An analysis of carpal motion after sectioning the ligamentous support of the luno-triquetral joints was done by use of stereoradiographic methods. The ligaments were sectioned in two stages. In stage I, a complete sectioning of both the dorsal and palmar luno-triquetral ligaments and the interosseous membrane was done. Stage II consisted of further sectioning of both the dorsal radio-triquetral and dorsal scapho-triquetral ligaments. After both stage I and stage II ligament sectioning, all of the intercarpal joints exhibited altered kinematics. The changes were especially marked at the luno-triquetral joint where motion was increased in all planes of wrist motion. The essential lesion in producing a static palmar flexed intercalated segment instability was division of the dorsal radio-triquetral and dorsal scapho-triquetral ligaments in association with the luno-triquetral ligaments and interosseous membrane sectioning.


Patterns and predictors of HIV/STI risk among Latino migrant men in a new receiving community.
The purpose of this study was to examine patterns and predictors of HIV/STI risk over time among Latino migrant men in a new receiving community. Latino men (N = 125) were interviewed quarterly for 18 months and HIV/STI tested annually. Selected individual, environmental and cultural factors by partner type and condom use were explored longitudinally and in a cross-section. Sex with female sex workers (FSWs) and multiple partners decreased, sex with main partners and abstinence increased, while the number of casual partners remained stable. Consistent condom use was highest with FSWs, lowest with main partners and midrange with casual partners with no trends over time. STI morbidity was low; no HIV was detected. Drug use and high mobility were associated with inconsistent condom use with FSW, whereas having family in the household was protective. HIV/STI prevention efforts should focus on drug using Latino migrants who are highly mobile and should foster healthy social connections.


Prospective study of interleukin-6 and the risk of malignant ventricular tachyarrhythmia in ICD-recipients--a pilot study.
We investigated the relationship between interleukin-6 (IL-6) and the risk of experiencing spontaneous ventricular tachyarrhythmia (VT/VF) in patients with an implantable cardioverter-defibrillator (ICD). Cytokine levels predict outcome in patients with advanced heart failure and are elevated in patients with coronary artery disease (CAD). Regarding heart rhythm disturbances, proinflammatory activity could predict the occurrence of atrial fibrillation. There is no data on cytokine levels and the risk of spontaneous VT/VF. IL-6 serum concentrations were determined at baseline and follow-up in 47 consecutive ICD-patients with CAD and idiopathic dilated cardiomyopathy (IDC). Data were prospectively correlated with VT/VF-incidence. Thirty-six patients (76.6%) suffered from CAD and 11 (23.4%) from IDC. Mean serum concentrations of IL-6 at baseline and at 9 months follow-up were 6.12+/-4.98 and 4.63+/-6.97. 88 spontaneous VT/VF-events occurred in 13/47 patients (27.7%). Patients with VT/VF had significantly higher IL-6 levels as compared to patients without VT/VF (8.96+/-5.97 vs. 5.04+/-4.16pg/ml at baseline (p =0.03), 7.8+/-4.88 vs. 3.42+/-6.32pg/ml at follow-up (p =0.01)). Elevated IL-6 serum concentrations were prospectively associated with an increased risk of spontaneous VT/VF-events in ICD-patients with CAD or IDC. These preliminary findings support a possible association of proinflammatory activity and an increased susceptibility to spontaneous VT/VF-events.


Reduced cortical surface area globally and in reward-related cortex is associated with elevated depressive symptoms in preschoolers.
Elevated depressive symptoms in early childhood strongly predict depression onset in youth. Nevertheless, little is known about the neural correlates of these symptoms, information that is key for understanding the early development of depression. As a result, the present study conducted a novel investigation of the association between cortical structure and depressive symptoms in preschoolers. Forty-six preschool age children (Mage = 5.90, SD = 0.75), some (N = 15) at high risk for depression, participated in the study. Data included parent-report of child depressive symptoms and measures of child whole brain and regional cortical structure acquired via 3T MRI. After adjustment for maternal depression, socio-economic status, child age, child sex, and intracranial volume, reduced total cortical surface area and reduced surface area of the lateral orbitofrontal cortex were associated with elevated depressive symptoms. Cortical thickness was not associated with depressive symptoms. The present data are cross-sectional, limiting any causal interpretations. Results suggest that reduced cortical surface area, rather than thickness, is a neural correlate of depressive symptoms in preschoolers. Findings highlight the importance of surface area in reward processing regions (i.e., lateral orbitofrontal cortex) in particular. The present results provide novel insight into early emerging associations between brain structure and features of depression in young children and underscore early childhood as an important developmental period for understanding depression.


Improved survival in pregnancy and pulmonary hypertension using a multiprofessional approach.
Pregnancy in women with pulmonary hypertension (PH) is reported to carry a maternal mortality rate of 30-56%. We report our experience of the management of pregnancies using a strategy of early introduction of targeted pulmonary vascular therapy and early planned delivery under regional anaesthesia. Retrospective observational study. Specialist quaternary referral pulmonary vascular unit. Nine women with PH who chose to proceed with ten pregnancies. A retrospective review of the management of all women who chose to continue with their pregnancy in our unit during 2002-2009. Maternal and fetal survival. All women commenced nebulised targeted therapy at 8-34 weeks of gestation. Four women required additional treatment or conversion to intravenous prostanoid therapy. All women were delivered between 26 and 37 weeks of gestation. Delivery was by planned caesarean section in nine cases. All women received regional anaesthesia and were monitored during the peripartum period in a critical care setting. There was no maternal mortality during pregnancy and all infants were free from congenital abnormalities. One woman died 4 weeks after delivery following patient-initiated discontinuation of therapy. All remaining women and infants were alive after a median of 3.2 years (range, 0.8-6.5 years) of follow-up. Although the risk of mortality in pregnant women with PH remains significant, we describe improved outcomes in fully counselled women who chose to continue with pregnancy and were managed with a tailored multiprofessional approach involving early introduction of targeted therapy, early planned delivery and regional anaesthetic techniques.


Postoperative complications of anterior cruciate ligament reconstruction after ambulatory surgery.
To study postoperative complications of arthroscopic anterior cruciate ligament (ACL) reconstruction performed as an outpatient compared with same surgery performed as a regular admission (inpatient). A study was conducted on a historical cohort of 342 patients (115 outpatients vs 227 inpatients) who underwent arthroscopic ACL primary ligamentoplasty (2004-2012). A review was performed on the demographic, surgical and hospital variables. A study was made of early complications (60 days postoperative) including visits to emergency department and readmissions. A descriptive and bivariate distribution analysis was performed between groups, with the grouping criterion: performing of the surgery with or without admission. The Chi-square test was used for qualitative variables and Mann-Whitney U test for quantitative. Limit significance p<0.05. Overall, there were 13.2% emergency department visits (mean of 1.24 visits) with an average delay of 8.22 days after discharge. pain not controlled with analgesia (6.7%), hemarthrosis that required arthrocentesis (4.4%), fever (3.2%), deep vein thrombosis (0.6%), cellulitis (0.6%), septic arthritis that required arthroscopic debridement (0.3%), and others (1.2%) including problems with immobilization. The hospital readmissions (2.3%) were for surveillance and monitoring of the surgical wound. In the bivariate analysis no statistically significant differences were found between groups as regards the sociodemographic characteristics of the patients or the complications recorded. The most frequent complications recorded were acute pain, hemarthrosis and fever. Serious complications (deep vein thrombosis, septic arthritis or need for hospital readmission) were rare. Outpatient arthroscopic ACL repair is a common technique that can be performed safely by surgery without admission, with an overall low complication rate with no differences between outpatients and inpatients.


Endovascular Aortic Repair in Nonagenarian Patients.
The increasing proportion of elderly patients being treated for abdominal aortic aneurysm (AAA) in the endovascular era is controversial. This study compared 30-day outcomes of endovascular aortic repair (EVAR) in nonagenarians (NAs) with non-nonagenarians (NNAs). This retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database included EVAR procedures performed from 2011 to 2017. Multivariate logistic regression in the unadjusted cohort, followed by propensity-score matching (PSM), was performed. Primary outcomes were 30-day mortality and 30-day major adverse events. A total of 12,267 patients were included (365 NAs). Ruptured aneurysms accounted for 6.7% (n = 819): 15.7% (n = 57) in NAs versus 6.5% (n = 762) in NNAs (p < 0.001). Mean aneurysm diameter was 6.5 ± 1.8 cm in NAs versus 5.8 ± 1.7 cm in NNAs (p < 0.001). The unadjusted 30-day mortality was 9.9% in NA versus 2.2% in NNAs (p < 0.001). Multivariate analysis revealed age ≥90 years (odds ratio [OR]: 3.36), male sex (OR: 1.78), functional status (OR: 4.22), pre-operative ventilator dependency (OR: 3.80), bleeding disorders (OR: 1.52), dialysis (OR: 2.56), and ruptured aneurysms (OR: 17.21) as independent predictors of mortality. After PSM, no differences in 30-day mortality (intact AAA [iAAA]: 5.3% NA vs. 3% NNA [p = 0.15]; ruptured AAA [rAAA]: 38% NA vs. 28.6% NNA [p = 0.32]) or 30-day major adverse events (iAAA: 7% NA vs. 4.6% NNA [p = 0.22]; rAAA: 28% NA vs. 36.7% NNA [p = 0.35]) were observed. Age was identified as an independent predictor of 30-day mortality after EVAR on multivariate analysis. However, no differences were found after PSM, suggesting that being ≥90 years of age but with similar comorbidities to younger patients is not associated with a higher short-term mortality after EVAR. Age ≥90 years alone should not exclude patients from EVAR, and tailored indications and carefully balanced risk assessment are advised.


Interleukin-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum.
Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response. Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed. At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated lipocalin-2 (LCN2) in the skin or IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12. IL-17RA inhibition by brodalumab decreases several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin or IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab.


"Who maltreats? Distinct pathways of intergenerational (dis)continuity of child maltreatment".
Maltreatment victimization history is an established risk factor for child maltreatment across generations. However, many parents with a victimization history do not maltreat, and many parents with no victimization history do have victimized children. To understand differences in demographic and maltreatment risk factors across the following intergenerational patterns of maltreatment: cycle maintainers, cycle breakers, cycle initiators, and a comparison group (no maltreatment). Data were drawn from a large population-based cohort in Queensland, Australia and included 32,574 biological parents and their children. Maltreatment experiences as a victim or person responsible for harm towards a child were obtained from the Queensland Child Protection System. Multinomial regression was completed with the full sample to compare the three maltreatment groups with the comparison group. Logistic regressions were conducted on all pairwise combinations of maltreatment groups. Models accounted for several demographic and maltreatment factors. Compared with breakers, maintainers were more likely to be Indigenous (OR = 1.86), never married (OR = 0.34), younger at first birth (OR = 0.87), have ≥3 children (OR = 1.99), be younger at first-and older at last-maltreatment victimization (ORs = 0.97 and 1.07, respectively), and experience a higher frequency of victimization (OR = 1.05). Amongst maltreaters, males were significantly more likely to be initiators while females were more likely to be maintainers (OR = .62). There were few other differences between initiators and maintainers. Meaningful differences among the three maltreatment groups were revealed suggesting that research should focus on the intergenerational discontinuity of maltreatment.


L-dopa treatment increases oscillatory power in the motor cortex of Parkinson's disease patients.
Parkinson's disease (PD) is a movement disorder caused by dopaminergic neurodegeneration. Levodopa (L-dopa) is an effective medication for alleviating motor symptoms in PD that has been shown previously to reduce subcortical beta (13-30 Hz) oscillations. How L-dopa influences oscillations in the motor cortex is unclear. In this study, 21 PD patients were recorded with magnetoencephalography (MEG) in L-dopa ON and OFF states. Oscillatory components of resting-state power spectra were compared between the two states and the significant effect was localized using beamforming. Unified Parkinson's Disease Rating Scale (UPDRS) III akinesia and rigidity sub-scores for the most affected hemibody were correlated with source power values for the contralateral hemisphere. An L-dopa-induced power increase was found over the central sensors significant in the 18-30 Hz range (F(1,20) > 14.8, PFWE corr < 0.05, cluster size inference with P = 0.001 cluster-forming threshold). Beamforming localization of this effect revealed distinct peaks at the bilateral sensorimotor cortex. A significant correlation between the magnitude of L-dopa induced 18-30 Hz oscillatory motor-cortical power increase and the degree of improvement in contralateral akinesia and rigidity was found (F(2, 19) = 4.9, pone-tailed = 0.02, R2 = 0.2). Power in the same range was also inversely correlated with combined akinesia and rigidity scores in the L-dopa OFF state (F(2, 19) = 9.2, ptwo-tailed = 0.007, R2 = 0.33) but not in the L-dopa ON state (F(2, 19) = 0.27, ptwo-tailed = 0.6, R2 = 0.01). These results suggest that the role of motor cortical beta oscillations in PD is distinct from that of subcortical beta.


Proteome profiling of Extracellular Vesicles in Pseudomonas aeruginosa endophthalmitis: Prognostic and therapeutic significance in a mouse model.
Endophthalmitis is a sight-threatening infection and a serious consequence of complications during intraocular surgery or penetrating injury of which Pseudomonas aeruginosa is an important etiology. Extracellular vesicles (EVs) have evolved as a promising entity for developing diagnostic and therapeutic biomarkers due to their involvement in intracellular communication and pathogenesis of diseases. We aimed to characterise the protein cargo of extracellular vesicles, isolated from a murine (C57BL/6) model of P. aeruginosa endophthalmitis by LC-MS/MS at 24 h post infection (p.i). EVs were extracted by ultracentrifugation, characterized by Dynamic Light Scattering (DLS) and western blotting with tetraspannin markers, CD9 and CD81 and quantified by the ExoCet quantification kit. Multiplex ELISA was performed to estimate the levels of TNF-α, IL-6, IFN-γ and IL-1β. Proteomic analysis identified 2010 proteins (FDR ≤0.01) in EVs from infected mice eyes, of which 137 were differentially expressed (P-value ≤ 0.05). A total of 101 proteins were upregulated and 36 were downregulated. Additionally, 43 proteins were exclusive to infection set. KEGG and Gene Ontology revealed, Focal adhesion, Phagosome pathway, Complement cascade and IL-17 signalling pathway are crucial upregulated pathways involving proteins such as Tenascin, caveolin 1, caveolin 2, glutamine synthetase, microtubule-associated protein, C1, C8 and IL-17. Tenascin and caveolins are known to suppress anti-inflammatory cytokines further exacerbating the disease. The result of this study provides insight into the global extracellular vesicle proteome of P. aeruginosa endophthalmitis with their functional correlation and distinctive pattern of expression and tenascin, caveolin 1 and caveolin 2 are attractive biomarkers for P. aeruginosa endophthalmitis.


Electrocatalysis in DNA Sensors.
Electrocatalysis is often thought of solely in the inorganic realm, most often applied to energy conversion in fuel cells. However, the ever-growing field of bioelectrocatalysis has made great strides in advancing technology for both biofuel cells as well as biological detection platforms. Within the context of bioelectrocatalytic detection systems, DNA-based platforms are especially prevalent. One subset of these platforms, the one we have developed, takes advantage of the inherent charge transport properties of DNA. Electrocatalysis coupled with DNA-mediated charge transport has enabled specific and sensitive detection of lesions, mismatches and DNA-binding proteins. Even greater signal amplification from these platforms is now being achieved through the incorporation of a secondary electrode to the platform both for patterning DNA arrays and for detection. Here, we describe the evolution of this new DNA sensor technology.


Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes.
We have previously reported that Fas activation induces apoptosis of anterior pituitary cells from rats at proestrus but not at diestrus and in an estrogen-dependent manner. In this study, we evaluated the effect of Fas activation on apoptosis of lactotropes and somatotropes during the estrous cycle and explored the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether changes in Fas expression are involved in the apoptotic response of anterior pituitary cells. Fas activation increased the percentage of TUNEL-positive lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered apoptosis of somatotropes only when cells from ovariectomized rats were cultured in the presence of 17 β-estradiol (E2). Progesterone (P4) blocked the apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the cell membrane. Our results show that Fas activation induces apoptosis of lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids may be involved in the apoptotic response of lactotropes and somatotropes, suggesting that Fas activation is implicated in the renewal of these pituitary subpopulations during the estrous cycle. The effect of gonadal steroids on Fas expression may be only partially involved in regulation of the Fas/FasL apoptotic pathway in the anterior pituitary gland.


Changing pattern of desmocollin 3 expression accompanies epidermal organisation during skin development.
The adhesive core of the desmosome is composed of cadherin-like glycoproteins of 2 families, desmocollins and desmogleins. The desmosomal cadherins show distinct patterns of expression in adult epidermis, and we have suggested that the desmocollins have a functional role in regulating the differentiation and/or morphogenesis of that epithelium (North et al. [1996] Proc. Natl. Acad. Sci. USA 93:7701-7705.). To examine this hypothesis, we cloned murine desmocollins and examined the induction patterns of desmocollins 1 and 3 during skin and skin appendage development. Desmocollins 3 and 1 were first expressed in epidermis in highly regional patterns at embryonic days 13.0 and 13.5, respectively, and both were up-regulated in general body epidermis at day 14.5. At this stage, epidermis is undifferentiated and the desmocollins showed an unexpected expression pattern. However, by day 18.5 when skin had undergone terminal differentiation, desmocollin 1 and 3 expression resembled that found in the adult. Thus, the establishment of the adult pattern of desmocollin expression corresponds to the adult pattern of epidermal stratification. We suggest that it is the ratio of desmocollin 1 to desmocollin 3 expression at different levels in the epidermis that is fundamental in establishing this pattern of differentiation.


A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.
The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.


Immune-mediated syndromes following intravenous bisphosphonate therapy.
Intravenous (IV) infusion of aminobisphosphonates (ABP) induces cytokine release by peripheral blood Vγ9δ2 T cells, resulting in an immediate short-term inflammatory response in up to 50% of patients. We evaluated possible long-term pro-inflammatory effects of IV ABP. Retrospective case-series study from one rheumatology specialist's clinic. 2261 electronic charts were reviewed for administration of 'zoledronate' or different brand names of zoledronic acid, and relevant clinical data was retrieved for patients who had received the infusion. Thirteen patients had recieved zoledronate. In six, new-onset or exacerbation of a previous inflammatory/autoimmune disorder was diagnosed within 3 months following infusion. Of these, one patient developed new-onset rheumatoid arthritis (RA), two polymyalgia rheumatica (PMR), two suffered a flare of Crohn's disease-related and aromatase inhibitor-induced arthralgias, and one patient acquired autoimmune hemophilia. Pre-existing malignancy and immediate inflammatory response following zoledronate were more frequent in patients experiencing new or worsening immunologic manifestations (3/6 vs. 0/7, and 5/6 vs. 2/7, respectively). Intravenous ABP may trigger induction of persistent autoimmune syndromes, especially when accompanied by an immediate adverse reaction or pre-existing malignancy.


Effect of chain length on binding of fatty acids to Pluronics in microemulsions.
We investigated the effect of fatty acid chain length on the binding capacity of drug and fatty acid to Pluronic F127-based microemulsions. This was accomplished by using turbidity experiments. Pluronic-based oil-in-water microemulsions of various compositions were synthesized and titrated to turbidity with concentrated Amitriptyline, an antidepressant drug. Sodium salts of C(8), C(10), or C(12) fatty acid were used in preparation of the microemulsion and the corresponding binding capacities were observed. It has been previously determined that, for microemulsions prepared with sodium caprylate (C(8) fatty acid soap), a maximum of 11 fatty acid molecules bind to the microemulsion per 1 molecule of Pluronic F127 and a maximum of 12 molecules of Amitriptyline bind per molecule of F127. We have found that with increasing the chain length of the fatty acid salt component of the microemulsion, the binding capacity of both the fatty acid and the Amitriptyline to the microemulsion decreases. For sodium salts of C(8), C(10) and C(12) fatty acids, respectively, a maximum of approximately 11, 8.4 and 8.3 molecules of fatty acid molecules bind to 1 Pluronic F127 molecule. We propose that this is due to the decreasing number of free monomers with increasing chain length. As chain length increases, the critical micelle concentration (cmc) decreases, thus leading to fewer monomers. Pluronics are symmetric tri-block copolymers consisting of propylene oxide (PO) and ethylene oxide (EO). The polypropylene oxide block, PPO is sandwiched between two polyethylene oxide (PEO) blocks. The PEO blocks are hydrophilic while PPO is hydrophobic portion in the Pluronic molecule. Due to this structure, we propose that the fatty acid molecules that are in monomeric form most effectively diffuse between the PEO "tails" and bind to the hydrophobic PPO groups.


A novel ejection protein from bacteriophage 80α that promotes lytic growth.
Many staphylococcal bacteriophages encode a minor capsid protein between the genes for the portal and scaffolding proteins. In Staphylococcus aureus bacteriophage 80α, this protein, called gp44, is essential for the production of viable phage, but dispensable for the phage-mediated mobilization of S. aureus pathogenicity islands. We show here that gp44 is not required for capsid assembly, DNA packaging or ejection of the DNA, nor for generalized transduction of plasmids. An 80α Δ44 mutant could be complemented in trans by gp44 expressed from a plasmid, indicating that gp44 plays a post-injection role in the host. Our results show that gp44 is an ejection (pilot) protein that is involved in deciding the fate of the phage DNA after injection. Our data are consistent with a model in which gp44 acts as a regulatory protein that promotes progression to the lytic cycle.


Nonspecific snail muscle adenylate deaminase: simplified purification, characterization and use for the preparation of deamino derivatives of NAD, NADH and AMP-P(NH)P.
Chromatography on phosphocellulose P-11 under conditions different from those applicable for deaminases specific to 5' AMP resulted in homogeneous preparation of snail foot muscle enzyme. Snail deaminase is a tetramer with molecular weight of 240,000, composed of four apparently identical subunits. Its amino acid composition is remarkably different from deaminases of higher animals, it was not inhibited by EDTA, but zinc became inhibitory to the snail enzyme. Unlike deaminases specific to 5' AMP, nonspecific deaminase is not a zinc-containing enzyme. It was adopted further for the preparation of hypoxanthine derivatives of adenosine-containing nucleotides such as NAD, NADH, AMP-P(NH)P, AMP, ADP and ATP.


Development of a wound-management formulary for use in clinical practice.
A wound-management formulary is an important aid to health-care professionals looking for the most appropriate product for a particular patient. Some of the basic principles of compiling such a formulary are described, providing a step-by-step guide, and concentrating principally on one for wound dressings.


Psychopathology and social functioning of 42 subjects from a Danish ultra high-risk cohort.
To make a thorough characterization of the co-morbidity, psychopathology and demographics in the first Danish ultra high-risk (UHR) sample. Forty-two UHR subjects went through comprehensive interviews assessing their psychopathology, psychiatric disorders, substance use and family history of psychiatric disorders. All UHR subjects met the criteria of at least 1 axis I diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and met on average four diagnoses (both axis I and II), mostly within the areas of depression, anxiety and substance abuse. A total of 48% had schizotypal personality disorder and 19% had borderline personality disorder. Level of functioning was low with a mean score on the Social and Occupational Functioning Assessment Scale corresponding to "major impairment in several areas," and mean scores in the Global Functioning: Social and Role scales between "moderate impairment in social functioning" and "very serious impairment independently." Forty-seven percent were unemployed and 29% on sick leave. Fifty-five percent relied financially on public support. As seen in previous UHR populations, Danish UHR subjects had low function socio-economically and met criteria of several psychiatric diagnoses, suggesting that they require pharmacological and non-pharmacological psychiatric treatment as well as vocational and educational guidance and support.


The Impact of Sociocultural Influences on the COVID-19 Measures-Reflections From Singapore.
The coronavirus disease 2019 (COVID-19) pandemic presents unique challenges to Asian countries like Singapore with a predominantly Confucian culture. Palliative care providers play an important role in supporting their patients and family members in these difficult times.


Hemodynamics of the carotid-artery circulation in the elderly "dizzy" patient.
One hundred and one consecutive patients complaining of dizziness were assessed by noninvasive carotid-artery testing, including oculoplethysmography, supraorbital directional Doppler and direct carotid flow Doppler. Hemodynamically significant carotid disease was found in 8 of 34 patients with the nonspecific complaint of "lightheadedness," in 4 of 21 patients with syncope, in 3 of 12 patients with vertebrobasilar insufficiency, and in 7 of 27 patients with associated focal cerebral signs or symptoms. None of 7 patients with vertigo alone were affected. In summary, 21 of the 101 patients with dizziness had hemodynamically significant obstruction to flow in the carotid-artery circulation. These findings suggest that in a fairly large proportion of patients complaining of dizziness, the symptoms may be the result of decreased cerebral perfusion due to carotid-artery occlusive disease. In these patients, noninvasive carotid-artery testing appears to be useful in identifying those with significant obstruction to blood flow in the carotid-artery circulation.


Tetracycline-induced pleural symphysis for recurrent hydrothorax complicating cirrhosis. A new approach to treatment.
Two patients with cirrhosis and ascites complicated by extensive unilateral pleural transudates refractory to therapy with dietary sodium restriction, diuretics, and repeated thoracentesis were successfully managed by tetracycline-induced pleural symphysis. The intrapleural instillation of this antibiotic prevented the recurrence of the effusion and substantially relieved the patients' symptoms with minimal undesirable side effects.


Complementary psychocutaneous therapies in dermatology.
The skin and the nervous system develop side by side in the fetus and remain intimately interconnected and interactive throughout life. Because of the skin-nervous system interactions, there is a significant psychosomatic or behavioral component to many dermatologic conditions. This permits complementary nonpharmacologic psychotherapeutic interventions, such as acupuncture, aromatherapy, biofeedback, cognitive-behavioral therapy, hypnosis, placebo, and suggestion, to have positive impacts on many dermatologic diseases. Complementary pharmacologic psychotherapeutic interventions, such as herbs and supplements, also may help improve some dermatologic disorders.


Seasonal variability in multimedia transport and fate of benzo[a]pyrene (BaP) affected by climatic factors.
The impact of meteorological factors on the transport behavior and distribution of volatile and semi-volatile organic pollutants has become an area of increasing concern. Here, we analyzed seasonal variation in climatic variables including wind, temperature, and precipitation to quantitatively assess the impact of these factors on the multimedia transport and fate of BaP in the continental region of China using a Berkeley-Trent (BETR) model. The advective rates of air exhibited an increasing trend of autumn (1.830 mol/h) < summer (1.975 mol/h) < winter (2.053 mol/h) < spring (2.405 mol/h) in association with increasing wind speed, indicating that lower atmospheric BaP concentrations are present in regions with high wind speeds and advective rates. The air-soil transport rates (0.08-45.55 mol/h) in winter were higher than in summer (0.07-32.41 mol/h), while low winter temperatures accelerate BaP accumulation in terrestrial ecosystems due to cold deposition. Cold deposition effects were more evident in northern regions than in southern regions. Further, increasing precipitation enhanced air-soil and soil-freshwater transport rates with the correlation coefficients of r = 0.445 and r = 0.598 respectively, while decreasing the air-vegetation transport rates (r = 0.475), thereby contributing to the accumulation of BaP in soils and freshwaters. In the light of the potential dispersion of BaP pollution at regional and global scales affected by these key climatic factors, this indirectly indicated the impact of future climate change on the BaP transport. Thus, flexible policy interventions should be enacted to slow future climate change.


Hypertrophic mononeuritis clinically presenting with painful legs and moving toes.
A 40-year-old woman presented with progressive lower leg pain and spontaneous toe movement. The EMG showed a posterior tibial nerve mononeuropathy and continuous myokymic discharges in posterior tibial-innervated muscles. The MRI revealed a markedly enlarged posterior tibial nerve. Toe movements and myokymia were unaffected by the proximal transection of the lesion but ceased abruptly when the distal end of the fusiform "tumor" was resected, suggesting that spontaneous electrical foci may have been located along the nerve lesion. The markedly enlarged nerve segment contained edematous, swollen fascicles with marked Schwann cell onion-bulb lesions and angiocentric, lymphocytic, and lymphofollicular infiltration. This nerve lesion is an example of a newly recognized entity called hypertrophic mononeuritis.


Thyrotropin-releasing hormone inputs are preferentially directed towards respiratory motoneurons in rat nucleus ambiguus.
In the present study, we assessed the extent of the thyrotropin-releasing hormone (TRH) input to motoneurons in the ambigual, facial, and hypoglossal nuclei of the rat using a combination of intracellular recording, dye filling, and immunohistochemistry. Twelve motoneurons in the rostral nucleus ambiguus were labelled by intracellular injection in vivo of Neurobiotin (Vector). Seven out of 12 ambigual motoneurons displayed rhythmic fluctuations of their membrane potential in phase with phrenic nerve discharge, whereas the other five had no modulations of any kind. Seven facial motoneurons and seven hypoglossal motoneurons were also filled with Neurobiotin. All three motor nuclei contained TRH-immunoreactive varicosities, with the largest numbers found in the nucleus ambiguus. Close appositions were seen between TRH-immunoreactive boutons and every labelled motoneuron. Respiratory-related motoneurons in the nucleus ambiguus received the largest number of TRH appositions with 74 +/- 38 appositions/neuron (mean +/- S.D.; n = 7). In contrast, nonrespiratory ambigual motoneurons received significantly fewer TRH appositions (11 +/- 5; n = 5; P < 0.05; Mann-Whitney U test). Facial motoneurons received about the same number of TRH appositions as nonrespiratory ambigual motoneurons, with 13 +/- 4 (n = 7). Hypoglossal motoneurons received the fewest appositions from TRH-containing boutons, with 8 +/- 2 (n = 7). There were no differences in the TRH inputs to respiratory and nonrespiratory motoneurons in the facial and hypoglossal nuclei. These results demonstrate that, among motoneurons in the medulla, respiratory motoneurons in the rostral nucleus ambiguus are preferentially innervated by the TRH-immunoreactive boutons.