Association Between Common Vaginal Infections and Cervical Non-Human Papillomavirus (HPV) 16/18 Infection in HPV-Vaccinated Women.
How vaginal infections such as bacterial vaginosis, Candida spp, and Trichomonas vaginalis affect persistence of human papillomavirus (HPV) infection is not well established. Our study aimed to evaluate the association between common vaginal infections and cervical non-HPV16/18 infection, as risk factors associated with persistence of nonvaccine HPV types will become increasingly relevant in the setting of HPV vaccination. We performed an analysis in 2039 AS04-HPV16/18-vaccinated women enrolled in a phase II/III trial in China, who were HPV DNA negative at month 0 and 6 and had at least 1 subsequent follow-up visit. Vaginal infections were detected in liquid-based cytology according to the diagnostic criteria of the Bethesda System. Associations between vaginal infections and incident and 6-month persistent non-HPV16/18 infections in the cervix were evaluated using generalized estimating equations, adjusting for the age at initial vaccination, as well as HPV types in the persistence analysis. Study visits with any vaginal infection had a statistically significant increased risk of incident non-HPV16/18 infection compared to those without vaginal infections (odds ratio [OR], 1.44 [95% confidence interval {CI}, 1.09-1.92]). However, vaginal infections were not associated with 6-month persistent non-HPV16/18 infection (OR, 1.02 [95% CI, .62-1.69]). Our study suggests that common vaginal infections are not associated with persistence of non-HPV16/18 infection among HPV16/18-vaccinated women.


Graduate education in clinical psychology. "We're not in Kansas anymore".
In this article, the author addresses changes impacting graduate education in clinical psychology, including those in technology, the academy, and the marketplace, and discusses implications of these changes for psychology. Significant concerns are raised concerning issues of supply and demand as well as the nature of the product of graduate education and training.


Interleukin-6 and ratio of plasma interleukin-6/interleukin-10 as risk factors of symptomatic lumbar osteoarthritis.
To determine the role of cartilage oligomeric matrix protein (COMP), interleukin (IL)-6, IL-10 and ratio of IL-6/IL-10 as risk factors of symptomatic lumbar osteoarthritis (OA) in postmenopausal women with estrogen deficiency. Case-control study had been conducted in Sanglah General Hospital from October 2015 until March 2016. The blood samples were obtained and analyzed by enzyme-linked immunosorbent assay (ELISA). From 44 pairs of samples which divided into 44 samples as case group and 44 samples as control group showed that high level of COMP in estrogen deficiency postmenopausal women were not at risk (OR = 0.7; 95%CI: 0.261-1.751; P = 0.393) for symptomatic lumbar OA (cut-off point 0.946). Estrogen deficiency in postmenopausal women with the high level of IL-6 had 2.7 times risk (OR = 2.7; 95%CI: 0.991-8.320; P = 0.033) for symptomatic lumbar OA from the low level of IL-6 (cut-off point 2.264). At lower level of IL-10, there was no risk for symptomatic lumbar OA (OR = 0.6; 95%CI: 0.209-1.798; P = 0.345) than with the higher level of IL-10 (cut-off point 6.049). While the high ratio of IL-6/IL-10 level in estrogen deficiency postmenopausal women gave 3.4 times risk (OR = 3.4; 95%CI: 1.204-11.787; P = 0.011) for symptomatic lumbar OA than the low ratio of IL-6/IL-10 level (cut-off point 0.364). High ratio of IL-6/IL-10 plasma level was the highest risk factor for causing symptomatic lumbar OA in postmenopausal women with estrogen deficiency.


Sequential Shifting in T-helper and T-cytotoxic Subset Cell Population in Mild and Severe COVID-19 Patients Infected With Variant B.1.61.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) modulates antiviral immunity via T cells, but whether these cells are active or abundant in coronavirus disease 2019 (COVID-19) patients is unknown. The present study aimed to investigate the temporal shifting in the T-cell population and their subsets, T-Helper (Th) cell (CD4) and T-Cytotoxic (Tc) cell (CD8) in COVID-19 patients. Thirty confirmed COVID-19 patients (nasal swab reverse transcription-polymerase chain reaction (RT-PCR) confirmed) were enrolled. On the basis of oxygen saturation (SpO2) levels, patients were stratified into two categories: (i) mild (n=11) having fever and SpO2 level >95%, and (ii) severe (n=19) on the ventilator, and in the intensive care unit (ICU) as per the Indian Council of Medical Research (ICMR) guidelines. Thirty age-sex-matched controls without infectious diseases unrelated to COVID-19 were also enrolled in the study. Patients with inflammatory diseases and severe comorbidities that compromise immunity were excluded from the study. Immunophenotyping flow cytometry assay was used to evaluate T-cell viability, Th, and Tc cells population in mild and severe COVID-19 patients on day 1 (at admission) and day 4 (decreasing the infection load) in the second COVID-19 wave (variant: B.1.61). Categorical variables were expressed as frequency and percentage and p-values were calculated by Chi-square test. All the variables were represented in median and Q1 (25 percentile) and Q3 (75 percentile). The Mann-Whitney test was used to compare the study groups. The Δ mean differences were calculated by using the Paired samples t-test. The statistically significant level was taken as p<0.05. Hemoglobin, total leukocyte count (TLC), lymphocytes, monocytes, and eosinophils were significantly reduced in patients (p<0.05). A significant decrease of CD4 and CD8 cells in severe COVID-19 patients vs. controls (CD4, median 49; CD8, 40.12; p>0.05) was seen. Th-EM (effector memory)-Tim-3 (T-cell immunoglobulin domain and mucin domain 3)+ was significantly higher (p=0.002) however, Tc-EMRA (effector memory cells re-expressing)-Tim-3+, Tc-Naive-Tim-3+, Tc-EM-PD1+ and Tc-CM (central memory)-Tim-3+ significantly reduced (p<0.05) in mild COVID-19 patients than controls. Similarly, in severe COVID-19 patients, Th-EMRA-Tim-3+, Th-Naive-PD1+, Th-EM-PD1+, Th-EM-Tim 3+ and Th-CM-Tim-3+ showed a significant reduction (p<0.05) and Tc-EMRA-Tim-3+, Tc-Naive-Tim-3+, Tc-EM-PD1+, and Tc-CM-Tim-3+ showed similar results. In mild vs. severe group, decreased T-cells (p=0.001), Th-EMRA-Tim-3+ (p=0.024), and Th-Navie-Tim-3+ (p=0.005), and significantly increased (p<0.05) Tc-Naive-Tim3+ (p=0.001), Tc-EM-Tim-3+ (p=0.031), and Tc-CM-Tim-3+ (p=0.08) were observed. Severe COVID-19 patients showed a significant increase in Th-Naive-Tim3+ (day 4-day 1; δ43, p=0.019), Th-EM-Tim3+ (δ 16.24, p=0.033), and Th-CM-Tim3+ (δ 13.57, p=0.041). T-cell populations and CD8 subset help to differentiate the mild and severe COVID-19 patients. Monitoring T cells, especially CD8 subset changes, has important implications for diagnosing and treating mild and severe patients being critically ill.


Use of sensory information during postural control in children with cerebral palsy: systematic review.
Impairments in sensory processing in children with cerebral palsy (CP) appear to be a cause of the postural control deficits they present and may affect function and participation in daily activities. Understanding the role of sensory processing in postural control can better inform their rehabilitation. Thus, the authors aimed to systematically review the literature concerning effects of sensory information manipulation on postural control in children with CP. A tailored search strategy in relevant databases identified 11 full-text reports that fulfilled the predefined inclusion and exclusion criteria. Sensory information affects postural control in children with CP. These children are less responsive to sensory input, and therefore are less able to perform adjustments during sensory perturbation. They exhibit less postural stability in the presence of sensory conflicts. The most commonly studied sources of sensory data are visual and somatosensory information, particularly when processed under static conditions. There are no studies addressing sensory information manipulation on postural control during the performance of functional activities. Further studies addressing manipulation of new sources of sensory cues on postural control are required.


Augmented Quantum Yield of a 2D Monolayer Photodetector by Surface Plasmon Coupling.
Monolayer (1L) transition metal dichalcogenides (TMDCs) are promising materials for nanoscale optoelectronic devices because of their direct band gap and wide absorption range (ultraviolet to infrared). However, 1L-TMDCs cannot be easily utilized for practical optoelectronic device applications (e.g., photodetectors, solar cells, and light-emitting diodes) because of their extremely low optical quantum yields (QYs). In this investigation, a high-gain 1L-MoS2 photodetector was successfully realized, based on the surface plasmon (SP) of the Ag nanowire (NW) network. Through systematic optical characterization of the hybrid structure consisting of a 1L-MoS2 and the Ag NW network, it was determined that a strong SP and strain relaxation effect influenced a greatly enhanced optical QY. The photoluminescence (PL) emission was drastically increased by a factor of 560, and the main peak was shifted to the neutral exciton of 1L-MoS2. Consequently, the overall photocurrent of the hybrid 1L-MoS2 photodetector was observed to be 250 times better than that of the pristine 1L-MoS2 photodetector. In addition, the photoresponsivity and photodetectivity of the hybrid photodetector were effectively improved by a factor of ∼1000. This study provides a new approach for realizing highly efficient optoelectronic devices based on TMDCs.


From laboratory studies to clinical trials: past benefits and future directions in hyperthermia.
Three examples of clinical research trials that were direct outgrowths of hyperthermia laboratory investigations performed at Stanford University, as well as elsewhere, are reviewed and directions for future studies presented. The first series of laboratory-clinical studies investigated the influence of the number of hyperthermia treatments on tumour response in combined radiotherapy-hyperthermia regimens. A prospective randomized clinical trial was performed and showed no difference in response rate or duration of local control in combined radiation therapy-hyperthermia regimens comparing two versus six hyperthermia treatments. The results were in agreement with the laboratory studies in RIF murine tumours which suggested that persistent thermotolerance limited the effectiveness of multiple heat treatments in fractionated hyperthermia treatment regimens. The second prospective clinical trial was undertaken to investigate the influence of pretreatment tumour temperatures on subsequent response to radiotherapy and hyperthermia. In agreement with the laboratory studies, low (< 37 degrees C) pretreatment temperatures sensitized superficially located tumours to subsequent hyperthermia treatment. Lower pretreatment temperatures and larger differentials between minimum treatment temperatures and pretreatment maximum or mean temperatures were correlated with the duration of local control. The final studies investigated thermosensitizing agents, agents which were non-toxic at 37 degrees C but became cytotoxic at elevated temperatures. Thermosensitizers such as sulphydryl compounds have demonstrated up to 10,000-fold enhancement of cell killing at exposure to 43 degrees C for 1 h and may be considered for tumour sensitization. However, normal tissue may also be sensitized as was noted for topical anaesthetics such as lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)


Dose escalation study of docetaxel and nedaplatin in patients with relapsed or refractory squamous cell carcinoma of the esophagus pretreated using cisplatin, 5-fluorouracil, and radiation.
Definitive chemoradiation with cisplatin (CDDP) and 5-fluorouracil (5FU) has been playing an important role in the treatment of esophageal cancer, but some patients are not curable or have recurrent lesions. However, few chemotherapeutic regimens are available for such patients. Docetaxel and nedaplatin are active for esophageal cancer. We conducted a dose-escalation study of docetaxel and nedaplatin as second line-chemotherapy after definitive chemoradiation in patients with relapsed or refractory squamous cell carcinoma of the esophagus after chemoradiation. Nedaplatin was administered on day 1 and docetaxel was administered on days 1 and 15, every 4 weeks. Dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Twelve patients were enrolled. At a docetaxel dose of 30 mg/m(2) and a nedaplatin dose of 80 mg/m(2), one grade 4 neutropenia occurred and caused one treatment break longer than 2 weeks, but there were few DLTs. At doses of 35 and 80 mg/m(2), respectively, two grade 4 neutropenias and one grade 2 thrombopenia occurred and caused three treatment breaks longer than 2 weeks. Therefore, the maximum tolerated dose was established at this dose level. Two grade 3 anorexias and one grade 3 nausea occurred, but other non-hematological toxicities were generally mild. Responses were seen in one-fourth of the 12 patients, including one complete remission. The recommended doses of docetaxel and nedaplatin were 30 and 80 mg/m(2), respectively. This combination could be a potential second-line treatment for this target population.


Impact of improved staffing on seclusion/restraint reliance in a public psychiatric hospital.
This study examines the association between gradual improvements in direct care staffing and seclusion/restraint reliance at a public psychiatric hospital. Over a 2-year period, increases in the number of staff members relative to the number of persons receiving care were significantly related to decreases in reliance on seclusion and mechanical restraint for managing challenging behavior problems. The results provide support for the premise that, in addition to education, training and competence of direct care staff the simple number of staff members in relation to number of individuals they assist, is a relevant area of concern.


[Degeneration of dermoid cysts: a case study of malignant transformation].
Malignant transformation of ovarian dermoid cyst (mature cystic teratoma) is rare and most often established in postmenopausal women after surgery by sample anatomopathological analysis. We report the case of a 58-year-old woman showing abdominal pain associated with constipation episodes. The diagnosis of dermoid cyst was established upon ultrasonographic and tomodensitometric criteria. Its histopathological analysis confirmed the presence of a well differentiated epidermoid carcinoma. In line with the literature, our study highlights the importance of the age of the patient, the size of dermoid cyst and its growth rate as well as squamous cell carcinoma (SCC) antigen serum level. These date are collected in order to establish a correct diagnosis and provide an appropriate cure. When a cyst is discovered these data must pathological event, mostly observed in menopaused women. Certainty diagnosis is collected in order to establish a correct diagnosis and provide an appropriate cure.


Krogius tenoplasty for recurrent dislocation of the patella. Failure associated with joint laxity.
Thirty-three patients treated with a Krogius tenoplasty for recurrent dislocation of the patella have been followed for an average of 3 years; the knees were classified according to Rünow. In 14 of 34 operated knees dislocations had recurred. Most of the recurrences were found in patients with generalized joint laxity, whereas only one of nine knees with only a high Insall index had redislocated. Patients with generalized joint laxity should not be treated with the Krogius tenoplasty as the sole procedure.


[Late results of testis autotransplantation].
Seven patients with bilateral undescended testes (9 intraabdominal testes and 5 inguinal testes), aged 7 to 29 years, were treated surgically. Testis autotransplantation was done for 9 intra-abdominal testes, and cryptorchidopexy was done for 5 inguinal testes. Follow-up for 5 to 9 years showed that the transplanted testes survived except 1 atrophied helf a year after operation. The size of the transplanted was as big as that of international testis model 15, and their hardness was moderate. Obvious improvement of secondary sex character and sexual function were observed in 6 of the 7 patients. The value of serum testosterone was norma (1450-600ng/dl) in 4 patients. In 4 patients, sperms were found in semen. The wives of 2 of those patients bore a boy and a girl respectively in 2-3 years after operation. Operative treatment and optimal age for testis autotransplantation are discussed.


Pedersen fetuin contains three adipogenic factors with distinct biochemical characteristics.
Crude Pedersen fetuin, derived from fetal bovine serum, contains adipogenic activity. Biochemical characterization was undertaken by following the differentiation of the 1246 adipogenic cell line. The present paper provides evidence that crude fetuin contains distinct proteins with adipogenic activity. By molecular sieve fractionation using Sephacryl S-300, the majority of adipogenic activity eluted in two distinct peaks, FI (molecular weight greater than 669 kDa) and FII (molecular weight ranging from 445 and 232 kDa). In addition a minor activity was found in a third peak, FIII (molecular weight around 69 kDa). Partial purification and biochemical characterization indicate that FI and FII are two distinct factors. FI has a PI higher than 9.4, is destroyed by alkaline treatment, and is stable when treated with acid. FII has a PI lower than 4.0, is alkali stable, but is destroyed completely by treatment with acid. Moreover, our data show that adipogenic factors are distinct from another protein alpha 2 macroglobulin known to be found in crude Pedersen fetuin. These results suggest that serum contains two large molecular weight proteins bearing adipogenic activity which could play an important role in the control of the adipose differentiation process.


Establishment of a Bernard-Soulier syndrome model in zebrafish.
Platelets play an essential role in thrombosis and hemostasis. Abnormal hemostasis can cause spontaneous or severe post-traumatic bleeding. Bernard-Soulier syndrome (BSS) is a rare inherited bleeding disorder caused by a complete quantitative deficiency in the GPIb-IX-V complex. Multiple mutations in GP9 lead to the clinical manifestations of BSS. Understanding the roles and underlying mechanisms of GP9 in thrombopoiesis and establishing a proper animal model of BSS would be valuable to understand the disease pathogenesis and to improve its medical management. Here, by using CRISPR-Cas9 technology, we created a zebrafish gp9SMU15 mutant to model human BSS. Disruption of zebrafish gp9 led to thrombocytopenia and a pronounced bleeding tendency, as well as an abnormal expansion of progenitor cells. The gp9SMU15 zebrafish can be used as a BSS animal model as the roles of GP9 in thrombocytopoiesis are highly conserved from zebrafish to mammals. Utilizing the BSS model, we verified the clinical GP9 mutations by in vivo functional assay and tested clinical drugs for their ability to increase platelets. Thus, the inherited BSS zebrafish model could be of benefit for in vivo verification of patient-derived GP9 variants of uncertain significance and for the development of potential therapeutic strategies for BSS.


Initial Psychometric Development of the Fear and Anxiety to COVID-19 Scale in Nursing Professionals: An Occupational Health Assessment Tool.
The effects caused by COVID-19 on the physical and mental health show the need to renew and create tools that specifically measure the fear and anxiety caused by the pandemic in healthcare professionals. The aim of the study was to measure fear and anxiety of COVID-19 in the nursing population group using a specific assessment scale. A descriptive, cross-sectional study was carried out in Spain based on questionnaires. The sample was selected by non-probabilistic snowball sampling. Univariate and bivariate descriptive analyses were performed. For qualitative variables, a categorical regression analysis was performed. The sample consisted of 1012 nurses residing in Spain, 86.6% of whom were women, with a mean age of 40.84 years (SD = 11.51). The bivariate analysis revealed statistically significant differences in the mean score of the scale and the variables sex, level of education, m2 of the dwelling, and work area. The validation of this scale provides a new management tool that should enable managers to assess anxiety and fear among their nurses, whether in the current COVID-19 pandemic or in other possible epidemiological situations to come.


General anaesthesia for caesarean section in severe pre-eclampsia. Comparison of the renal and hepatic effects of enflurane and halothane.
In a randomized study of patients undergoing Caesarean section, either enflurane (mean 0.24 MAC-h) or halothane (mean 0.23 MAC-h) and 50% nitrous oxide in oxygen were administered to women (n = 12) with severe pre-eclampsia-eclampsia and to 16 healthy pregnant patients with normal renal and hepatic function. No evidence of nephrotoxicity was found in any pre-eclamptic or normal patient. Metabolism of enflurane resulted in plasma inorganic fluoride concentrations (max 15 mumol litre -1) which were well below the toxic value. Postoperative liver function tests showed no important changes from preoperative values, although reductive metabolites of halothane were not measured. In patients with severe pre-eclampsia there appears no contraindication to enflurane or, probably, halothane as volatile supplements during general anaesthesia.


CD4 T cell-independent antibody response promotes resolution of primary influenza infection and helps to prevent reinfection.
It is generally believed that the production of influenza-specific IgG in response to viral infection is dependent on CD4 T cells. However, we previously observed that CD40-deficient mice generate influenza-specific IgG during a primary infection, suggesting that influenza infection may elicit IgG responses independently of CD4 T cell help. In the present study, we tested this hypothesis and show that mice lacking CD40 or CD4 T cells produce detectable titers of influenza-specific IgG and recover from influenza infection in a manner similar to that of normal mice. In contrast, mice completely lacking B cells succumb to influenza infection, despite the presence of large numbers of functional influenza-specific CD8 effector cells in the lungs. Consistent with the characteristics of a T-independent Ab response, long-lived influenza-specific plasma cells are not found in the bone marrow of CD40-/- and class II-/- mice, and influenza-specific IgG titers wane within 60 days postinfection. However, despite the short-lived IgG response, CD40-/- and class II-/- mice are completely protected from challenge infection with the same virus administered within 30 days. This protection is mediated primarily by B cells and Ab, as influenza-immune CD40-/- and class II-/- mice were still resistant to challenge infection when T cells were depleted. These data demonstrate that T cell-independent influenza-specific Ab promotes the resolution of primary influenza infection and helps to prevent reinfection.


Singlet-oxygen oxidation of 5-hydroxymethylfurfural in continuous flow.
Singlet-oxygen oxidation of 5-hydroxymethylfurfural (5-HMF) was performed in continuous flow mode using rose Bengal as photosensitizer. The resulting butenolide (H(2) MF) was formed selectively in high yield. The procedure proved to be scalable and applicable to related bio-based furfurals. Furthermore, preliminary data show that H(2) MF can be readily isomerized thermally to 5-hydroxy-4-keto-pentenoic acid oligomers.


Three residues in HIV-1 matrix contribute to protease inhibitor susceptibility and replication capacity.
Other than cleavage site mutations, there is little data on specific positions within Gag that impact on HIV protease inhibitor susceptibility. We have recently shown that non-cleavage site mutations in gag, particularly within matrix protein can restore replication capacity and further reduce protease inhibitor drug susceptibility when coexpressed with a drug-resistant (mutant) protease. The matrix protein of this patient-derived virus was studied in order to identify specific changes responsible for this phenotype. Three amino acid changes in matrix (R76K, Y79F, and T81A) had an impact on replication capacity as well as drug susceptibility. Introduction of these three changes into wild-type (WT) matrix resulted in an increase in the replication capacity of the protease mutant virus to a level similar to that achieved by all the changes within the mutant matrix and part of the capsid protein. Pairs of changes to wild-type matrix led to an increased replication capacity of the protease mutant (although less than with all three changes). Having only these three changes to matrix in a wild-type virus (with wild-type protease) resulted in a 5- to 7-fold change in protease inhibitor 50% effective concentration (EC₅₀). Individual changes did not have as great an effect on replication capacity or drug susceptibility, demonstrating an interaction between these positions, also confirmed by sequence covariation analysis. Molecular modeling predicts that each of the three mutations would result in a loss of hydrogen bonds within α-helix-4 of matrix, leading to the hypothesis that more flexibility within this region or altered matrix structure would account for our findings.


Evolutionary trajectory of organelle-derived nuclear DNAs in the Triticum/Aegilops complex species.
Organelle-derived nuclear DNAs, nuclear plastid DNAs (NUPTs) and nuclear mitochondrial DNAs (NUMTs) have been identified in plants. Most, if not all, genes residing in NUPTs/NUMTs (NUPGs/NUMGs) are known to be inactivated and pseudogenized. However, the role of epigenetic control in silencing NUPGs/NUMGs and the dynamic evolution of NUPTs/NUMTs with respect to organismal phylogeny remain barely explored. Based on the available nuclear and organellar genomic resources of wheat (genus Triticum) and goat grass (genus Aegilops) within Triticum/Aegilops complex species, we investigated the evolutionary fates of NUPTs/NUMTs in terms of their epigenetic silencing and their dynamic occurrence rates in the nuclear diploid genomes and allopolyploid subgenomes. NUPTs and NUMTs possessed similar genomic atlas, including (i) predominantly located in intergenic regions and preferential integration to gene regulation regions and (ii) generating sequence variations in the nuclear genome. Unlike nuclear indigenous genes, the alien NUPGs/NUMGs were associated with repressive epigenetic signals, namely high levels of DNA methylation and low levels of active histone modifications. Phylogenomic analyses suggested that the species-specific and gradual accumulation of NUPTs/NUMTs accompanied the speciation processes. Moreover, based on further pan-genomic analyses, we found significant subgenomic asymmetry in the NUPT/NUMT occurrence, which accumulated during allopolyploid wheat evolution. Our findings provide insight into the dynamic evolutionary fates of organelle-derived nuclear DNA in plants.


Role of AUX1 in the control of organ identity during in vitro organogenesis and in mediating tissue specific auxin and cytokinin interaction in Arabidopsis.
Classic plant tissue culture experiments have shown that exposure of cell culture to a high auxin to cytokinin ratio promotes root formation and a low auxin to cytokinin ratio leads to shoot regeneration. It has been widely accepted that auxin and cytokinin play an antagonistic role in the control of organ identities during organogenesis in vitro. Since the auxin level is highly elevated in the shoot meristem tissues, it is unclear how a low auxin to cytokinin ratio promotes the regeneration of shoots. To identify genes mediating the cytokinin and auxin interaction during organogenesis in vitro, three allelic mutants that display root instead of shoot regeneration in response to a low auxin to cytokinin ratio are identified using a forward genetic approach in Arabidopsis. Molecular characterization shows that the mutations disrupt the AUX1 gene, which has been reported to regulate auxin influx in plants. Meanwhile, we find that cytokinin substantially stimulates auxin accumulation and redistribution in calli and some specific tissues of Arabidopsis seedlings. In the aux1 mutants, the cytokinin regulated auxin accumulation and redistribution is substantially reduced in both calli and specific tissues of young seedlings. Our results suggest that auxin elevation and other changes stimulated by cytokinin, instead of low auxin or exogenous auxin directly applied, is essential for shoot regeneration.


Widespread dissemination in The Netherlands of the epidemic berlin methicillin-resistant Staphylococcus aureus clone with low-level resistance to oxacillin.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen and represents a growing public health burden due to the emergence and spread of epidemic strains, particularly within the hospital environment. An epidemic MRSA clone, with characteristic low-level resistance to oxacillin, emerged in the year 2000 and became endemic in the Netherlands. Multilocus sequence typing characterized the strain as sequence type 45, which was previously designated the Berlin epidemic MRSA clone. In 2 years, this strain has become the predominant MRSA clone in the Netherlands.


Prior medical conditions and the risk of adult leukemia in Shanghai, People's Republic of China.
A population-based case-control interview study of 486 adult leukemia cases and 502 healthy controls was carried out in Shanghai, People's Republic of China during 1987-89 to evaluate the etiologic role of prior medical conditions, medications, and diagnostic X-rays. Risks were examined separately for 236 cases with acute non-lymphocytic leukemia (ANLL), 79 with chronic myeloid leukemia (CML), 81 with acute lymphocytic leukemia (ALL), and 21 with chronic lymphocytic leukemia (CLL). Little difference was found between cases and controls for prior history of diabetes, hypertension, allergic conditions, most medications, and diagnostic X-rays. A few significant associations were observed for appendectomy, tuberculosis, and for several other chronic disorders with specific leukemia cell types, but the odds ratio estimates for most of these ranged from two to three and, with the exception of the two specified above, were based generally on five or fewer exposed controls. In contrast to an association with childhood leukemia in Shanghai, prior use of chloramphenicol was not linked with ANLL or other forms of adult leukemia. Further research is needed to clarify the relation of specific medical conditions and exposures with particular subtypes of leukemia, and to examine reasons for the low incidence of CLL in China and other Asian populations.


Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.
Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the CNS, enables rapid nerve impulse conduction and sustains neuronal health. The signals exchanged between axons and oligodendrocytes in myelin remain to be fully elucidated. Here we provide genetic evidence for multiple and critical functions of Contactin-1 in central myelin. We document dynamic Contactin-1 expression on oligodendrocytes in vivo, and progressive accumulation at nodes of Ranvier and paranodes during postnatal mouse development. Nodal and paranodal expression stabilized in mature myelin, but overall membranous expression diminished. Contactin-1-deficiency disrupted paranodal junction formation as evidenced by loss of Caspr, mislocalized potassium Kv1.2 channels, and abnormal myelin terminal loops. Reduced numbers and impaired maturation of sodium channel clusters accompanied this phenotype. Histological, electron microscopic, and biochemical analyses uncovered significant hypomyelination in Contactin-1-deficient central nerves, with up to 60% myelin loss. Oligodendrocytes were present in normal numbers, albeit a minor population of neuronal/glial antigen 2-positive (NG2(+)) progenitors lagged in maturation by postnatal day 18, when the mouse null mutation was lethal. Major contributing factors to hypomyelination were defects in the generation and organization of myelin membranes, as judged by electron microscopy and quantitative analysis of oligodendrocyte processes labeled by GFP transgenically expressed from the proteolipid protein promoter. These data reveal that Contactin-1 regulates both myelin formation and organization of nodal and paranodal domains in the CNS. These multiple roles distinguish central Contactin-1 functions from its specific role at paranodes in the periphery, and emphasize mechanistic differences in central and peripheral myelination.


Association between ALDH2 Polymorphism and Gastric Cancer Risk in a Korean Population.
The association between alcohol and gastric cancer is stronger in East Asians than in other ethnic groups, presumably due to an aldehyde dehydrogenase 2 (ALDH2) polymorphism. Therefore, we investigated the relationship between the ALDH2 rs671 polymorphism and gastric cancer in a Korean population. This case-control study included 3,245 hospital patients newly diagnosed with gastric cancer and 8,732 population controls. The ALDH2 rs671 genotype was classified as inactive ALDH2 (GG) or active ALDH2 (GA/AA). The risk of gastric cancer was higher in men with the inactive ALDH2 than in those with active ALDH2 (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.09-1.39), whereas no significant association was found between ALDH2 genotype and gastric cancer in women (OR, 1.00; 95% CI, 0.99-1.02). In men, the association between ALDH2 genotype and gastric cancer was stronger in current drinkers. Our findings support the previously reported association between inactive ALDH2 and high risk of gastric cancer.


Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia.
Combined hyperlipidemia is a common disorder, characterized by a highly atherogenic lipoprotein profile and a substantially increased risk of coronary heart disease. The purpose of this study was to establish whether variations of apolipoprotein A5 (APOA5), a newly discovered gene of lipid metabolism located 30 kbp downstream of the APOA1/C3/A4 gene cluster, contributes to the transmission of familial combined hyperlipidemia (FCHL). We performed linkage and association tests on 128 families. Two independent alleles, APOA5c.56G and APOC3c.386G, of the APOA1/C3/A4/A5 gene cluster were overtransmitted in FCHL (P=0.004 and 0.007, respectively). This was paired with reduced transmission of the common APOA1/C3/A4/A5 haplotype (frequency 0.4461) to affected subjects (P=0.012). The APOA5c.56G genotype accounted for 7.3% to 13.8% of the variance in plasma triglyceride levels in probands (P<0.004). The APOC3c.386G genotypes accounted for 4.4% to 5.1% of the variance in triglyceride levels in FCHL spouses (P<0.007), suggesting that this allele marks a FCHL quantitative trait as well as representing a susceptibility locus for the condition. A combined linkage and association analysis establishes that variation at the APOA1/C3/A4/A5 gene cluster contributes to FCHL transmission in a substantial proportion of northern European families.


Brownian dynamics simulations on the self-assembly behavior of AB hybrid dendritic-star copolymers.
The micellization behavior of hybrid dendritic-star copolymers with solvophilic dendritic units is studied by means of Brownian dynamics simulations. The critical micelle concentration and the micelle size and shape are examined for different solvophobic/solvophilic ratios r as a function of the number of the dendritic and linear arms. Hybrid dendritic-star copolymers with one dendritic and up to three solvophobic linear branches form spherical micelles with preferential aggregation number. Those with two dendritic arms and three solvophobic branches form micelles with wide aggregation numbers only for small values of r. For hybrid dendritic-star copolymers with three dendritic arms and two or three solvophobic linear arms, micelles with wide aggregation numbers are also formed but for slightly higher values of r. Our results for the aggregation number are compared with existing results of other architectures obtained at the same temperature, and an inequality for the aggregation number is proposed.


Augmented desensitization to epidermal growth factor (EGF) immediate actions: a novel mechanism for altered EGF growth response in mutant A431 cells.
Epidermal growth factor (EGF) may either stimulate or inhibit cell growth. To elucidate the mechanism of these varied effects, we compared EGF action in parental A431 cells in which cell growth is inhibited, and clone 15, a mutant of these cells resistant to EGF growth inhibition. In both lines, EGF receptor was present in similar concentrations and underwent tyrosine phosphorylation to the same extent. Likewise, in both lines, acute exposure to EGF stimulated an increase in free cytoplasmic [Ca2+], as well as a similar increase in phosphorylation of lipocortin 1, a major substrate for the EGF receptor kinase whose phosphorylation is calcium-dependent. On the other hand, pretreatment of clone 15 cells with EGF for 72 h abolished EGF-induced phosphorylation of lipocortin 1 and led to a loss of the increase in cytoplasmic free [Ca2+], whereas no such desensitization was seen in the parental A431 cells. These data indicate a link between EGF-induced increase in cytoplasmic calcium, lipocortin phosphorylation, and cell growth and suggest that differences in mechanisms of desensitization to these immediate actions of EGF may lead to altered growth response to this hormone.


Role of immune-checkpoint inhibitors in lung cancer.
Immune checkpoint inhibitors, mainly drugs targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways, represent a remarkable advance in lung cancer treatment. Immune checkpoint inhibitors targeting PD-1 and PD-L1 are approved for the treatment of patients with non-small-cell lung cancer, with impressive clinical activity and durable responses in some patients. This review will summarize the mechanism of action of these drugs, the clinical development of these agents and the current role of these agents in the management of patients with lung cancer. In addition, the review will discuss the role of predictive biomarkers for optimal patient selection for immunotherapy and management of autoimmune side effects of these agents.


Seasonal variation of IgE antibody specific for ragweed antigen E (IgE-a-AgE) from the basophil surface in patients with ragweed pollenosis.
Seasonal elevation in total serum IgE and IgE antibody specific for antigen E (IgE-a-AgE) are well recognized in patients with ragweed pollenosis. We found that the ratio of specific IgE-a-AgE to total IgE in plasma was the only measure predictive of the number of specific IgE-a-AgE molecules per basophil. Although both total and specific IgE rose with season, the ratio did not change, the number of IgE-a-AgE molecules per basophil did not change, and histamine release in response to AgE did not increase.


Clinical magnetic resonance imaging of brain tumors at ultrahigh field: a state-of-the-art review.
With the advancement of the magnetic resonance (MR) technology, the whole-body ultrahigh field MR system operated from 7 to 9.4 T becomes feasible for the routine patient imaging in clinical settings. The associated potentials and challenges from the perspectives of technology, physics, and biology as well as clinical application of the ultrahigh field MR systems are different from those systems operated at 3 T, 1.5 T, or lower field strength. In this article, we will present our initial experiences of brain tumor imaging using the 7 and 8 T whole-body MR systems at the Ohio State University Medical Center and provide a brief overview pertinent to the ultrahigh field clinical MR systems.


Production of bioactive and aroma volatile compounds of Lawsonia inermis L. cultivated under different growth conditions.
The present study aimed to investigate the influence of different growing conditions on the amount of leaf pigments (chlorophylls, carotenoids), bioactive metabolites, such as polyphenols, flavonoids, lawsone and volatile organic compounds (VOCs) of Lawsonia inermis L. (henna) plants. Young henna plants were cultivated for two months in a growth chamber (GC) and in open-air conditions during summer under the Mediterranean climate (OF), and leaves were analysed to evaluate their adaptive responses. The different growth conditions modified the carbon allocation priorities, increasing antioxidant metabolites (e.g. phenolic and flavonoid compounds) while decreasing lawsone in GC conditions. Quali-quantitative changes were observed for VOCs. This study revealed that GC conditions permit an alternative use of Lawsonia cultivation, because of the increase in the endogenous content of bioactive secondary metabolites with many potential biological activities.


Primary health care services utilization and satisfaction among the elderly in Asir region, Saudi Arabia.
Use of primary health care (PHC) services and satisfaction among elderly people (60 + years) in Asir was studied in 26 PHC centres. They visited PHC centres significantly less often than younger adults but they were referred significantly more often to secondary and tertiary care and for more laboratory tests. A random sample of 253 elderly people attending the centres was interviewed about accessibility, continuity, humaneness, informativeness and thoroughness of care. Overall, 79.0% were satisfied with the services provided. The leading 3 items of dissatisfaction were: not enough audiovisual means for health education (65.1%), long time spent in the centre (46.4%), and not enough specialty clinics (42.5%).


Validity of parental report of influenza vaccination in children 6 to 59 months of age.
The objective of this study was to assess the validity of parental report of influenza vaccinations. A cross-sectional study of children who were 6 to 59 months of age and presented to a large, pediatric residency clinic from February through April 2005 was performed. A standardized, parental questionnaire ascertained the influenza vaccination status of children during the 2004-2005 influenza season and was compared with the medical chart, the criterion standard. Children were classified as being at high risk when they had a specific influenza vaccine recommendation in 2004-2005 by age (6-23 months of age) or by chronic medical condition. Of 218 parents approached in the pediatric residency clinic, 198 (95%) children who were 6 to 59 months of age were enrolled, and 84 (42%) were vaccinated according to the medical chart. More children who were 6 to 23 months than those who were 24 to 59 months of age were vaccinated (63% vs 21%). Children with chronic medical conditions were more likely to be vaccinated than healthy children who were 24 to 59 months of age (57% vs 11%), but no difference was observed for children who were 6 to 23 months of age (79% vs 60%). In comparison with the medical chart, parental report of influenza vaccination had a sensitivity of 88%, a specificity of 90%, and a kappa coefficient of 0.78. For children who were 6 to 23 months of age or had a chronic medical condition (n = 123), parental report had a sensitivity of 89%, a specificity of 81%, and a kappa coefficient of 0.71. Parental report of influenza vaccination among children who were 6 to 59 months of age had reasonable sensitivity, specificity, and reliability as compared with the medical chart in this study population.


Gene Therapy for Lung Cancer.
Gene therapy was originally conceived to treat monogenic diseases. The replacement of a defective gene with a functional gene can theoretically cure the disease. In cancer, multiple genetic defects are present and the molecular profile changes during the course of the disease, making the replacement of all defective genes impossible. To overcome these difficulties, various gene therapy strategies have been adopted, including immune stimulation, transfer of suicide genes, inhibition of driver oncogenes, replacement of tumor-suppressor genes that could mediate apoptosis or anti-angiogenesis, and transfer of genes that enhance conventional treatments such as radiotherapy and chemotherapy. Some of these strategies have been tested successfully in non-small-cell lung cancer patients and the results of laboratory studies and clinical trials are reviewed herein.


Electrochemical Generation of Steady-State Linear Concentration Gradients within Microfluidic Channels Perpendicular to the Flow Field.
A new design of microelectrode was introduced to generate electrochemically steady-state linear concentration gradients perpendicular to the flow direction throughout the cross section of microchannels. The shape and geometry of the electrode were established based on operating regimes at microchannel electrodes. Before implementation, optimal conditions were preliminary delineated by numerical simulations according to the flow velocity and microchannel dimensions. To assess experimentally these predictions, a specific microfluidic platform was developed with optimized geometry to simultaneously allow the generation of linear concentration gradients and the mapping of concentration profiles by confocal fluorescence microscopy. As a model, the electrochemical reduction of a quinone in the presence of fluorescein was selected to both generate and monitor a linear proton gradient. A good agreement was observed between theoretical and experimental data, establishing the proof of concept. These results should broaden the performance and applications of electrochemical platforms, particularly in the field of active control of microenvironments in biology, biochemistry, and analytical chemistry.


Social identification with animals: Unpacking our psychological connection with other animals.
Our relations with other animals are ubiquitous in human life, yet the psychological structure of our connection with animals is just beginning to receive empirical attention. Drawing on theories of social identification and intergroup relations, we investigate the various ways that people identify with animals. Across 7 studies, we introduce the Identification with Animals Measure (IWAM) and uncover 3 dimensions by which humans identify with animals as a group: solidarity with animals, animal pride, and human-animal similarity. First, we establish the reliability, factorial structure, and predictive validity of the 3-factor IWAM. Next, we find that these factors predict a distinct set of attitudes and behaviors toward animals. Solidarity with animals is defined by feeling connected to other animals and is associated with more contact with animals (i.e., pets) and a greater desire to help animals and to engage in collective actions on their behalf, even if this implies withdrawing privileges to humans. Human-animal similarity is defined by the perception that animals share similarities with humans; this dimension is associated with increased moral concern for their welfare and a greater attribution of typically human traits to other animals. Finally, animal pride is defined by a direct recognition and positive endorsement of the social category that includes all animals, and is associated with viewing humans as more animal-like, and with more competitive and instrumental intergroup relations. The findings confirm that identification with animals is a multidimensional construct that is colored by the unique and complex nature of our relations with nonhuman animals. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Effects of mass loading on the viability of assessing the state of healing of a fixated fractured long bone.
This paper aims to evaluate the effects of mass loading on the healing assessment of an internally fixated femur by vibrational means. The presence of soft tissue surrounding a femur increases damping and mass of a system, and hence affects the vibrational response of a mechanical structure by obscuring the coherent modes. This may compromise vibration-based monitoring strategies in identifying modes associated with fracture healing. This paper presents a series of experimental works to address this issue. Two osteotomised composite femurs were internally fixated using a plate-screw system and an intramedullary nail. Soft tissue is approximated by surrounding an artificial Sawbone femur with modelling clay. The femur is excited by an instrumented impact hammer and instrumented with two accelerometers to record bending and torsion modes between 0 and 600 Hz. A 30-min epoxy was applied to simulate the healing of the fractured femur in the osteotomised region. The resonant frequencies and its modes are monitored while union is being formed and a healing index is calculated at various times to quantify the degree of healing. The results demonstrate that the effect of modelling clay compressed the natural modes along the frequency axis. It is observed that frequency bandwidth in the vicinity of 150 Hz and 500 Hz is sensitive to the state of healing of the fixated femurs, which is due to the increase in stiffness of the osteotomised region. These findings were used to formulate the healing index which assists in identifying the initial, later and complete healing stages in conjunction with the index derivative. In this study, a two-sensor measurement strategy to quantify fixated femur healing is investigated. It is shown that the mass loading effect did not affect this vibrational analysis method ability to assess the state of healing, and both coherent bending and twisting modes associated with healing were easily identified. The proposed healing index, its derivative, and the cross-spectra are a viable tool for quantitative healing assessment.


Interstitial lung disease - An approach to diagnosis and management.
Interstitial lung disease (ILD) is a term that describes a diverse range of lung conditions, which are an important cause of morbidity and mortality in all age groups. Idiopathic pulmonary fibrosis is the most common ILD in older adults and generally has a poor prognosis. Sarcoidosis is more common in younger adults and generally has a more benign prognosis. This article aims to increase the reader's understanding of the aetiology of ILD and to provide a general approach to diagnosis along with the basic principles of management of these conditions. As ILDs can progress to pulmonary fibrosis, early detection is important. The clinical course of ILD varies considerably, largely determined by the underlying cause. While some forms of ILD remain essentially untreatable, many forms respond well to treatment. It is therefore imperative that a prompt and accurate diagnosis of the underlying cause is made so that appropriate management can be instituted.


Evaluation of the diagnostic accuracy of prototype rapid tests for human African trypanosomiasis.
Diagnosis of human African trypanosomiasis (HAT) remains a challenge both for active screening, which is critical in control of the disease, and in the point-of-care scenario where early and accurate diagnosis is essential. Recently, the first field deployment of a lateral flow rapid diagnostic test (RDT) for HAT, "SD BIOLINE HAT" has taken place. In this study, we evaluated the performance of "SD BIOLINE HAT" and two new prototype RDTs. The performance of "SD BIOLINE HAT" and 2 prototype RDTs was tested using archived plasma from 250 Trypanosoma brucei gambiense patients, and 250 endemic controls. As well as comparison of the sensitivity and specificity of each device, the performance of individual antigens was assessed and the hypothetical performance of novel antigen combinations extrapolated. Neither of the prototype devices were inferior in sensitivity or specificity to "SD BIOLINE HAT" (sensitivity 0.82±0.01, specificity 0.97±0.01, 95% CI) at the 5% margins, while one of the devices (BBI) had significantly superior sensitivity (0.88±0.03). Analysis of the performance of individual antigens was used to model new antigen combinations to be explored in development of the next generation of HAT RDTs. The modelling showed that an RDT using two recombinant antigens (rLiTat1.5 and rISG65) would give a performance similar to the best devices in this study, and would also offer the most robust performance under deteriorating field conditions. Both "SD BIOLINE HAT" and the prototype devices performed comparably well to one another and also to the published performance range of the card agglutination test for trypanosomiasis in sensitivity and specificity. The performance of individual antigens enabled us to predict that an all-recombinant antigen RDT can be developed with an accuracy equivalent to " SD BIOLINE HAT." Such an RDT would have advantages in simplified manufacture, lower unit cost and assured reproducibility.


Disrupted cell adhesion but not proliferation mediates cyst formation in polycystic liver disease.
The pathogenesis of polycystic liver disease is not well understood. The putative function of the associated proteins, hepatocystin and Sec63p, do not give insight in their role in cystogenesis and their tissue-wide expression does not fit with the liver-specific phenotype of the disease. We designed this study with the specific aim to dissect whether pathways involved in polycystic kidney diseases are also implicated in polycystic liver disease. Therefore, we immunohistochemically stained cyst tissue specimen with antibodies directed against markers for apoptosis, proliferation, growth receptors, signaling and adhesion. We analyzed genotyped polycystic liver disease cyst tissue (n=21) compared with normal liver tissue (n=13). None of the cysts showed proliferation of epithelial cells. In addition, anti-apoptosis marker Bcl-2 revealed slight increase in expression, with variable increase of apoptosis marker active caspase 3. Growth factor receptors, EGFR and c-erbB-2, were overexpressed and mislocalized. We found EGFR staining in the nuclei of cyst epithelial cells regardless of mutational state of the patient. Further, in hepatocystin-mutant polycystic liver disease patients, apical membranous staining of c-erbB-2 and adhesion markers, MUC1 and CEA, was lost and the proteins appeared to be retained in cytoplasm of cyst epithelia. Finally, we found loss of adhesion molecules E-cadherin and Ep-CAM in cyst epithelium of all patients. Nevertheless, we observed normal beta-catenin expression. Our results show that polycystic liver disease cystogenesis is different from renal cystogenesis. Polycystic liver disease involves overexpression of growth factor receptors and loss of adhesion. In contrast, proliferation or deregulated apoptosis do not seem to be implicated. Moreover differential findings for PRKCSH- and SEC63-associated polycystic liver disease suggest a divergent mechanism for cystogenesis in these two groups.


Thermophilin 13, a nontypical antilisterial poration complex bacteriocin, that functions without a receptor.
A novel broad host range antimicrobial substance, Thermophilin 13, has been isolated and purified from the growth medium of Streptococcus thermophilus. Thermophilin 13 is composed of the antibacterial peptide ThmA (Mr of 5776) and the enhancing factor ThmB (Mr of 3910); the latter peptide increased the activity of ThmA approximately 40 x. Both peptides are encoded by a single operon, and an equimolar ratio was optimal for Thermophilin 13 activity. Despite the antilisterial activity of Thermophilin 13, neither ThmA nor ThmB contain the YGNGV-C consensus sequence of Listeria-active peptides, and post-translational modifications comparable to that in the lantibiotics are also absent. Mass spectrometry did reveal the apparent oxidation of methionines in ThmA, which resulted in a peptide that could not be enhanced any longer by ThmB, whereas the intrinsic bactericidal activity was normal. Thermophilin 13 dissipated the membrane potential and the pH gradient in liposomes, and this activity was independent of membrane components from a sensitive strain (e.g. lipid or proteinaceous receptor). Models of possible poration complexes formed are proposed on the basis of sequence comparisons, structure predictions, and the functional analysis of Thermophilin 13.


Paired donor interchange to avoid ABO-incompatible living donor liver transplantation.
We report an emergency paired donor interchange living donor liver transplant performed on January 13, 2009. The 4 operations (2 liver transplants) were performed simultaneously. The aim was to avoid 2 ABO-incompatible liver transplants. One recipient in acute liver failure underwent transplantation in a high-urgency situation. The abdomen of the other recipient had severe adhesions from previous spontaneous bacterial peritonitis that rendered the recipient operation almost impossible. The ethical and logistical issues are discussed. Approaches adopted in anticipation of potential adverse outcomes are explained in view of the higher donor and recipient mortality and morbidity rates in comparison with kidney transplantation.


Comparison of meta-analysis versus analysis of variance of individual patient data.
Meta-analysis is a method of synthesizing the results of independent studies. We consider the case in which there are multiple treatments and a control, with the goal of estimating the relative effect of each treatment based on continuous outcomes. Even when all data are available, rather than only summary data, it has become common to use meta-analytic estimators of treatment contrasts. Alternatively, we could use a two-way analysis of variance model with no interaction in which one factor is study and one factor is treatment. For the unbalanced case, we obtain the surprising result that the standard meta-analysis estimates of treatment contrasts are identical to the least squares estimators of treatment contrasts in the linear model. Because a meta-analysis of individual patient data can be considerably more costly in terms of data retrieval than a meta-analysis of summary data, this equivalence provides for cost-efficient analysis.


Neurological sequelae after cerebral anoxia.
Cardiac arrest can cause neurological impairment. The aim of this study is to confirm the disability and the predominant part of executive and behavioural impairments after cardiac arrest. A retrospective study is proposed. All consecutive patients admitted to the Department of Rehabilitation for Neurological Impairments following cerebral anoxia after cardiac arrest between 1995-2007 were included. Clinical and neuropsychological assessment was proposed. Thirty patients, 19 men, were examined. Ages ranged from 16-58 (mean = 39.5). Fourteen patients presented with severe disability and 16 patients presented with moderate disability. In the first group (severe disability) no patients were autonomous for daily life activities. They presented with dysexecutive syndrome and behavioural disorders associated with amnesia syndrome; 64% of them presented with motor disorders. In the second group, patients with moderate disability were autonomous in daily life but not for the complex activities or functioning. They had no motor impairment but suffered from executive and memory impairments. Behavioural changes were noted. Medical history or demographic data did not differ between the two groups. The study confirms the predominant part of executive, memory and behavioural impairments after cardiac arrest. This retrospective study cannot provide prognosis factors and further prognosis studies are needed.


Abolished tubuloglomerular feedback and increased plasma renin in adenosine A1 receptor-deficient mice.
The hypothesis that adenosine acting on adenosine A1 receptors (A1R) regulates several renal functions and mediates tubuloglomerular feedback (TGF) was examined using A1R knockout mice. We anesthetized knockout, wild-type, and heterozygous mice and measured glomerular filtration rate, TGF response using the stop-flow pressure (P(sf)) technique, and plasma renin concentration. The A1R knockout mice had an increased blood pressure compared with wild-type and heterozygote mice. Glomerular filtration rate was similar in all genotypes. Proximal tubular P(sf) was decreased from 36.7 +/- 1.2 to 25.3 +/- 1.6 mmHg in the A1R+/+ mice and from 38.1 +/- 1.0 to 27.4 +/- 1.1 mmHg in A1R+/- mice in response to an increase in tubular flow rate from 0 to 35 nl/min. This response was abolished in the homozygous A1R-/- mice (from 39.1 +/- 4.1 to 39.2 +/- 4.5 mmHg). Plasma renin activity was significantly greater in the A1R knockout mice [74.2 +/- 14.3 milli-Goldblatt units (mGU)/ml] mice compared with the wild-type and A1R+/- mice (36.3 +/- 8.5 and 34.1 +/- 9.6 mGU/ml), respectively. The results demonstrate that adenosine acting on A1R is required for TGF and modulates renin release.


Tissue engineered vessel from a biodegradable electrospun scaffold stimulated with mechanical stretch.
A tissue engineered vessel has the potential to provide an alternative small diameter vascular graft for patients with cardiovascular disease in need of surgical revascularization. In this study, a polyglycolic acid (PGA) electrospun scaffold seeded with human dermal fibroblasts was stimulated with circumferential mechanical stretch by a pulsatile perfusion system. The PGA scaffold was fabricated using a custom electrospinning set-up to co-electrospray a sacrificial polyethylene oxide microparticle to increase pore size and bulk porosity. The tissue engineered vessel exposed to circumferential mechanical stretch was compared to an engineered vessel cultured under static conditions without any mechanical stimulation. The histology cross-sections demonstrated a similar thickness of engineered vessels with mechanical stretch and static, but on Masson's Trichrome stain there was nearly twice the amount of staining for collagen. The collagen content was quantified, and the collagen content was 60% greater in the human tissue engineered vessel exposed to mechanical stretch compared to the static vessel. The total collagen cross-linking was similar, but on a per collagen basis there was significantly more cross-linking in the static vessel over the stretch vessel. The stress-strain curve of the tissue engineered vessel with mechanical stretch demonstrated a statistically significantly greater ultimate tensile strength (UTS) of 1.86 ± 0.14 MPa (n = 6) and elastic modulus (EM) of 7.62 ± 0.39 MPa (n = 6) versus the static engineered vessel UTS of 0.31 ± 0.07 MPa (n = 5) and EM of 1.37 ± 0.21 MPa (n = 5). The primary determinant of the mechanical properties of the tissue engineered vessel correlated to the collagen content with minimal contribution of the collagen cross-linking. Therefore, the versatile properties of an electrospun scaffold are ideal in combination with a biomimetic culture system to generate a tissue engineered vessel composed of extracellular matrix suitable as a vascular graft.


Intracranial meningiomas in French West Indies and French Guiana.
Studies toward the end of the 20th century and in the first decade of the millennium show that meningioma represents the most common brain tumor of all types. There are no data available regarding meningiomas in the French West Indies and French Guiana. The author aimed to determine clinical and epidemiological features and provide data of meningiomas in French West Indies and French Guiana. I reviewed the files of 358 patients who underwent surgery between January 2000 and December 2008. I found a sex ratio of 2.5 to 1-256 (71.5%) female to 102 (28.5%) male. Meningiomas were encountered mostly in the sixth decade of life and the most common anatomical location was cerebral convexities (29.32% of patients) followed by parasagittal and parafalcine (20.11%). The third most common was sphenoid wing meningioma. The incidence of meningiomas was 6.31 per 100,000 inhabitants. The current study attempts to estimate frequency and peculiarities of meningiomas in the French West Indies and French Guiana and is the first of its kind.


Tungsten Promoted Ni/Al2O3 as a Noble-Metal-Free Catalyst for the Conversion of 5-Hydroxymethylfurfural to 1-Hydroxy-2,5-Hexanedione.
The conversion of 5-hydroxymethylfurfural (HMF) to 1-hydroxy-2,5-hexanedione (HHD) represented a typical route for high-value utilization of biomass. However, this reaction was often catalyzed by the noble metal catalyst. In this manuscript, W promoted Ni/Al2O3 was prepared as a noble-metal-free catalyst for this transformation. The catalysts were characterized by XRD, XPS, NH3-TPD, TEM, and EDS-mapping to study the influence of the introduction of W. There was an interaction between Ni and W, and strong acid sites were introduced by the addition of W. The W promoted Ni/Al2O3 showed good selectivity to HHD when used as a catalyst for the hydrogenation of HMF in water. The influences of the content of W, temperature, H2 pressure, reaction time, and acetic acid (AcOH) were studied. NiWOx/Al2O3-0.5 (mole ratio of W:Ni = 0.5) was found to be the most suitable catalyst. The high selectivity to HHD was ascribed to the acid sites introduced by W. This was proved by the fact that the selectivity to HHD was increased a lot when AcOH was added just using Ni/Al2O3 as catalysts. 59% yield of HHD was achieved on NiWOx/Al2O3-0.5 at 393 K, 4 MPa H2 reacting for 6 h, which was comparable to the noble metal catalyst, showing the potential application in the production of HHD from HMF.


[Ectopic bone formation of bone marrow mesenchymal stem cells with gene transfer of human bone morphogenetic protein-9 gene in rabbit].
To investigate the method combining hBMP-9 gene therapy with tissue-engineering techniques to improve osteogenesis in an ectopic bone formation model in rabbits. Rabbit marrow MSCs were transferred with BMP-9 gene by cationic liposome, and then were subjected to a series tests including fluorescent microscope, Flow cytometer (FCM), ALP activity quantitative assay and Von Kossa's calcium nodus staninig; MSCs transfected with BMP-9 gene successfully were seeded onto scaffolds of polylactide-co-glycolide (PLGA). Cell-matrix interactions were observed with fluorescent microscopy and scanning electronic microscopy. The tissue-engineered bones with MSCs seeded on PLGA were further subcutaneously implanted into rabbits. The implants were evaluated with histological staining at 4 and 8 weeks after surgery. The gene transfer efficiency of MSCs transfected with BMP-9 gene was 34.15%, which was measured by FCM. The ALP activity of MSCs with BMP-9 gene transfer was higher than that of non-transfered cells (P < 0.01). The calcium nodus formation of MSCs was enhanced by the gene modification of BMP-9 gene. MSCs seeded onto PLGA showed high level of cell proliferation, and efficient synthesis of cell matrix was observed with, scanning electronic microscopy. In the ectopic bone formation model, new bone area was also significantly improved by BMP-9 gene modified MSCs seeded on PLGA (P < 0.05). hBMP-9 gene modified MSCs could enhance ectopic new bone formation in rabbits. These results indicated that the strategy combining BMP-9 gene modified MSCs with PLGA might be suitable for bone tissue engineering applications.


Critical Review of the Test of Gross Motor Development.
The Test of Gross Motor Development (TGMD) is designed to be both a norm-referenced and criterion-referenced assessment of gross motor skills in 3-to 10- year-old children, normal to moderately handicapped. Whether the TGMD thoroughly covers the total domain of gross motor function with its two subtests of locomotor and object control is questioned. The TGMD appears promising as a test the is easily learned and administered by a wide variety of professionals. Studies are reviewed that address the issues if the TGMD's reliability and validity. As with any formal assessment, testers need to be aware of the TGMD's strengths and weaknesses in interpreting test scores.


The influence of simulated clinical use on the flexibility of rotary ProTaper Universal, K3 and EndoSequence nickel-titanium instruments.
To investigate the influence of cyclic flexural and torsional loading on the flexibility of ProTaper Universal, K3 and EndoSequence nickel-titanium instruments, in view of the hypothesis that these types of loading would decrease the flexibility of the selected NiTi rotary files. The instruments evaluated were S2 and F1 ProTaper Universal, sizes 20 and 25, .06 taper K3, and sizes 20 and 25, .06 taper EndoSequence. Flexibility was determined by 45° bending tests according to ISO 3630-1 specification. Values of the bending moment (MB ) obtained with new instruments were considered as the control group (CG). Bending tests were then conducted in instruments previously fatigued to one-fourth and three-fourths of their average fatigue life (fatigue groups, FG¼ and FG¾), as well as after cyclic torsional loading (torsional group, TG). Fatigue tests were carried out in a bench device that allowed the files to rotate freely inside an artificial canal with an angle of curvature of 45° and a radius of 5 mm. Cyclic torsional loading tests were performed that entailed rotating the instrument from zero angular deflection to 180° and then returning to zero applied torque in 20 cycles. Data were analysed using one-way analysis of variance at a significance level of 5%. Simulated clinical use by means of flexural fatigue tests did not affect the flexibility of the instruments, except for a significant increase in flexibility observed in a few instruments (P < 0.05). In addition, comparative statistical analyses between the values of MB measured in new instruments and after cyclic torsional loading showed no significant differences between them (P > 0.05). The flexibility of rotary ProTaper Universal, K3 and EndoSequence NiTi instruments, measured in bending tests, was not adversely affected by simulated clinical use in curved root canals.


Imaging of lumbar spinal surgery complications.
Lumbar spine surgery for spinal stenosis is a frequently performed procedure and was the fastest growing type of surgery in the US from 1980 to 2000. With increasing surgical invasiveness, postoperative complications also tend to be higher. Cross-sectional imaging techniques (CT and MRI) are more sensitive than radiographs and play an increasingly important role in evaluation of patients with lumbar spine surgery. Their use in patients with metallic implants is somewhat limited by artefacts, which can obscure pathology and decrease accuracy and reader confidence. Metal artefact reduction techniques have been developed, which can significantly improve image quality and enable early detection of postoperative complications. Complications can occur throughout postoperative course. Early complications include hardware displacement, incidental durotomy, postoperative collections-most commonly seroma, and less likely haematoma and/or infection. Incidental durotomy with CSF leak causing intracranial hypotension has characteristic MR brain findings and diagnosis of occult leak sites have been improved with use of dynamic CT myelography. Haematomas, even when compressing the thecal sac, are usually asymptomatic. Early infection, with nonspecific MR findings, can be diagnosed accurately using dual radiotracer studies. Delayed complications include loosening, hardware failure, symptomatic new or recurrent disc herniation, peri-/epidural fibrosis, arachnoiditis, and radiculitis. • CT and MRI play an increasingly important role in evaluation of patients with lumbar spine surgery • Complications can occur throughout the postoperative course and early detection is critical • Artefact reduction techniques can improve image quality for early and improved detection of complications.


Neural pathways for the processing of alarm pheromone in the ant brain.
Social insects like ants exhibit sophisticated communication by means of pheromones, one example of which is the use of alarm pheromones to alert nestmates for colony defense. In the ant Camponotus obscuripes, we have reported that information about formic acid and n-undecane, alarm pheromone components, is processed in a set of specific glomeruli in the antennal lobe (primary olfactory center). Alarm pheromone signals are then transmitted, mainly via uniglomerular projection neurons (uni-PNs), to the protocerebrum (PR), where sensory signals are integrated to form motor commands for behavioral responses. In this study, we physiologically and morphologically characterized 63 alarm pheromone-sensitive PR neurons in ants by using intracellular recording and staining techniques. Most of the pheromone-sensitive PR neurons had dendrites in the mushroom body (MB), the lateral horn, or the medial PR. Some neurons with dendrites in these areas responded specifically to formic acid or n-undecane and may participate in the control of specific behavioral responses to each pheromone component. Other neurons responded also to non-pheromonal odors, in contrast to uni-PNs, most of which responded specifically to alarm pheromones. Responses to non-pheromonal odors were most prominent in efferent neurons of the MB lobe, suggesting that they may participate in integration of pheromonal and non-pheromonal information. We found a class of PR neurons that receives input in all of these pheromone-processing areas and terminates in a variety of premotor areas. These neurons may participate in the control of pheromone-sensitized aggressive behavior, which is triggered by non-pheromonal sensory stimuli associated with a potential enemy.


EFFECT OF AN ALDOSTERONE ANTAGONIST (SPIRONOLACTONE) ON PATIENTS WITH SEVERE CONGESTIVE HEART FAILURE.
Spironolactone was evaluated as a diuretic in the therapy of six patients with chronic severe congestive heart failure, during which metabolic balance studies were performed. Two of the patients showed a clear-cut although moderate diuresis and natriuresis in response to spironolactone in the presence of other diuretics. Two patients had slight unsustained responses and two showed no response. No significant change in potassium excretion was observed. A decrease in the serum sodium level was noted in four patients, associated with a rise in serum potassium. Urinary aldosterone excretion was normal or low in all patients and showed no correlation with the diuretic response to spironolactone.It is concluded that spironolactone has definite but limited usefulness in the therapy of some but not all patients with chronic congestive heart failure.


Ultrafast transient absorption measurements of photocarrier dynamics in PdSe2.
We investigate the photocarrier dynamics in bulk PdSe2, a layered transition metal dichalcogenide with a novel pentagonal structure and unique electronic and optical properties. Using femtosecond transient absorption microscopy, we study the behavior of photocarriers in mechanically exfoliated bulk PdSe2 flakes at room temperature. By employing a 400 nm ultrafast laser pulse, electron-hole pairs are generated, and their dynamics are probed using an 800 nm detection pulse. Our findings reveal that the lifetime of photocarriers in bulk PdSe2 is approximately 210 ps. Furthermore, by spatially resolving the differential reflection signal, we determine a photocarrier diffusion coefficient of about 7.3 cm2 s-1. Based on these results, we estimate a diffusion length of around 400 nm and a photocarrier mobility of approximately 300 cm2 V-1 s-1. These results shed light on the ultrafast optoelectronic properties of PdSe2, offer valuable insights into photocarriers in this emerging material, and enable design of high-performance optoelectronic devices based on PdSe2.


Inheritance of downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) resistance in grapevines.
Downy mildew (Plasmopara viticola) and anthracnose (Sphaceloma ampelinum) are two of the major diseases of most grapevine (Vitis vinifera L.) cultivars grown in Thailand. Therefore, breeding grapevines for improved downy mildew and anthracnose resistance is crucial. Factorial crosses were made between three downy mildew and/or anthracnose resistant lines ('NY88.0517.01', 'NY65.0550.04', and 'NY65.0551.05'; male parents) and two or three susceptible cultivars of V. vinifera ('Black Queen', 'Carolina Black Rose', and/or 'Italia'; female parents). F1 hybrid seedlings were evaluated for downy mildew and anthracnose resistance using a detached/excised leaf assay. For both diseases, the general combining ability (GCA) variance among male parents was significant, while the variance of GCA among females and the specific combining ability (SCA) variance were not significant, indicating the prevalence of additive over non-additive gene actions. The estimated narrow sense heritabilities of downy mildew and anthracnose resistance were 55.6 and 79.2%, respectively, suggesting that downy mildew/anthracnose resistance gene(s) were highly heritable. The 'Carolina Black Rose x NY65.0550.04' cross combination is recommended for future use.


A new route to meso-formyl porphyrins.
Prior syntheses of porphyrins bearing meso-formyl groups have generally employed the Vilsmeier formylation of an acid-resistant copper or nickel porphyrin. A new approach for the synthesis of free base porphyrins bearing one or two (cis or trans) meso-formyl substituents entails the use of a dipyrromethane bearing an acetal group at the 5-position, a dipyrromethane-1-carbinol bearing an acetal group at the 5-position or carbinol position, or a dipyrromethane-1,9-dicarbinol bearing an acetal group at a carbinol position. Treatment of the resulting meso-acetal-substituted free base porphyrin to gentle acidic hydrolysis yields the corresponding meso-formyl porphyrin.


Ultrasensitive Electrochemiluminescence Biosensor for MicroRNA Detection by 3D DNA Walking Machine Based Target Conversion and Distance-Controllable Signal Quenching and Enhancing.
In this study, an electrochemiluminescence (ECL) regenerated biosensor was reported to sensitively detect microRNA through 3D DNA walking machine and "on-off-super on" strategy. First, 3D DNA walking machine with higher efficiency of payload releasing and superior signal amplification than those of the traditional DNA walking machine was initially introduced in the ECL system for converting target microRNA to intermediate DNA and achieving significant signal amplification. Second, the distance between CdS:Mn quantum dots and Au nanoparticles was increased with the hybridization of intermediate DNA and Au nanoparticles modified S2, which weakened the energy transfer for ECL signal recovering and excited the surface plasma resonance for further enhancing the signal to construct the on-off-super on biosensor. Such an on-off-super on strategy not only reduced the ECL background signal but also increased the detection sensitivity. Impressively, the elaborately designed biosensor could be regenerated by Lambda exonuclease hydrolyzing the intermediate DNA to make Au nanoparticles modified S2 recover to their original hairpin structure. With the amazing signal amplification of 3D DNA walking machine and sensitive distance control of the on-off-super on strategy, the biosensor showed excellent performance for microRNA-141 detection with a low detection limit of 3.3 fM and could be applied to human prostate cancer cells analysis. Furthermore, this work established a foundation to apply 3D walker in ECL methodology and provided an effective way for analysis of other microRNA or cancer cells.


Post traumatic malocclusion and its prosthetic treatment.
Mandible fractures belong to the most common fractures encountered in maxillofacial trauma. Because mandible is such a unique structure with hinge joint and masticatory muscles attached to the body of mandible, attention must be paid to avoid displacement during treatment. Displacement during fracture reduction leads to malocclusion. Many TMJs function with complete comfort and apparent normalcy in adapted centric posture, even though they have undergone deformation caused by trauma. This clinical report describes the patient with post traumatic malocclusion and its prosthetic treatment. His fractured mandible was openly reduced in changed position, as a result his occlusion has been changed. He was treated by prosthetic method in so-called adapted centric posture.


Defining the Structural Basis for Allosteric Product Release from E. coli Dihydrofolate Reductase Using NMR Relaxation Dispersion.
The rate-determining step in the catalytic cycle of E. coli dihydrofolate reductase is tetrahydrofolate (THF) product release, which can occur via an allosteric or an intrinsic pathway. The allosteric pathway, which becomes accessible when the reduced cofactor NADPH is bound, involves transient sampling of a higher energy conformational state, greatly increasing the product dissociation rate as compared to the intrinsic pathway that obtains when NADPH is absent. Although the kinetics of this process are known, the enzyme structure and the THF product conformation in the transiently formed excited state remain elusive. Here, we use side-chain proton NMR relaxation dispersion measurements, X-ray crystallography, and structure-based chemical shift predictions to explore the structural basis of allosteric product release. In the excited state of the E:THF:NADPH product release complex, the reduced nicotinamide ring of the cofactor transiently enters the active site where it displaces the pterin ring of the THF product. The p-aminobenzoyl-l-glutamate tail of THF remains weakly bound in a widened binding cleft. Thus, through transient entry of the nicotinamide ring into the active site, the NADPH cofactor remodels the enzyme structure and the conformation of the THF to form a weakly populated excited state that is poised for rapid product release.


Facile Integration between Si and Catalyst for High-Performance Photoanodes by a Multifunctional Bridging Layer.
Designing high-quality interfaces is crucial for high-performance photoelectrochemical (PEC) water-splitting devices. Here, we demonstrate a facile integration between polycrystalline n+p-Si and NiFe-layered double hydroxide (LDH) nanosheet array by a partially activated Ni (Ni/NiOx) bridging layer for the excellent PEC water oxidation. In this model system, the thermally deposited Ni interlayer protects Si against corrosion and makes good contact with Si, and NiOx has a high capacity of hole accumulation and strong bonding with the electrodeposited NiFe-LDH due to the similarity in material composition and structure, facilitating transfer of accumulated holes to the catalyst. In addition, the back illumination configuration makes NiFe-LDH sufficiently thick for more catalytically active sites without compromising Si light absorption. This earth-abundant multicomponent photoanode affords the PEC performance with an onset potential of ∼0.78 V versus reversible hydrogen electrode (RHE), a photocurrent density of ∼37 mA cm-2 at 1.23 V versus RHE, and retains good stability in 1.0 M KOH, the highest water oxidation activity so far reported for the crystalline Si-based photoanodes. This bridging layer strategy is efficient and simple to smooth charge transfer and make robust contact at the semiconductor/electrocatalyst interface in the solar water-splitting systems.


Coassociation of CD26 (dipeptidyl peptidase IV) with CD45 on the surface of human T lymphocytes.
In the present report, we demonstrated that modulation of CD26 from T cell surface induced by antiCD26 (1F7) led to enhanced phosphorylation of CD3 zeta tyrosine residues and increased CD4 associated p56lck tyrosine kinase activity. We further showed that CD26 was comodulated on the T cell surface with CD45, a known membrane-linked protein tyrosine phosphatase and that anti-CD26 was capable of precipitating CD45 from T cell lysates. These findings strongly suggest that CD26 may be closely associated with the CD45 protein tyrosine phosphatase on T cell surface and further support the notion that the interaction of CD26 with CD45 results in enhanced tyrosine kinase activity, zeta chain phosphorylation, and T cell activation.


Skusella Freeman (Diptera: Chironomidae): new species, immature stages from Africa, Asia and Australia, and expanded distributions.
Skusella Freeman, 1961 (Diptera: Chironomidae, Chironominae), known previously from adults from Australia and Africa, is revised with extended descriptions, including for immature life stages. Skusella is diagnosed based on its type species S. subvittata (Skuse, 1889) from Australia, S. pallidipes (Kieffer, 1921) from the Afrotropical region (the only other originally included species), a second African species S. freemani Harrison, 2002, and S. silingae Tang, sp. n., newly described here from the pupa and adult males from China. The immature stages of Skusella have been known informally for several decades, notably for a characteristic fringe of setae on one or more abdominal pleurae of the pupa, shared only with newly described Paraskusella Cranston, 2018 within the Chironominae. Amongst larvae of Chironomini with 6-segmented antenna, alternate Lauterborn organs and a well-demarcated ventromentum, those of Skusella are distinguishable only with caution due to insufficient reared associations. Unassociated pupal exuviae, tentatively belonging to three unknown new species, are described informally from China, as is a larval type from Africa. Range extensions include for S. freemani, with pupae (newly described here) from Nigeria and Cameroon, at least 5000 km from the type locality in South Africa. A wider distribution of S. subvittata in Australia and Asia is revealed by extensive pupal exuviae sampled from drift.


Use of Antipsychotics: The Experiences, Views, and Monitoring Practices of Child and Adolescent Psychiatrists in Turkey.
Objectives: The aim of this study is to evaluate the antipsychotics prescribed by child psychiatrists and their applications on the follow-up of these drugs. Methods: The universe of this research included consultant physicians and child psychiatry residents working in the field. A questionnaire has been created that assesses the use of antipsychotics and follow-up processes of physicians. The survey involved 19 questions. Contents of the survey were sociodemographic data, short-term and long-term follow-up of antipsychotic drugs, side-effect intervention strategies, and diagnoses of the most commonly preferred antipsychotic medications. The survey was delivered via e-mail and sent as a message to the child and adolescent psychiatrists in Turkey. Results: One hundred sixty-one physicians working in the field of child and adolescent psychiatry participated in the study. Aripiprazole (32.2%), risperidone (30.4%), and quetiapine (14.9%) were three most commonly prescribed antipsychotics. Disruptive behavior-related disorders (28.9%), behavior problems related to autism spectrum disorder (20.7%), behavior problems related to intellectual disability (14.5%), and attention-deficit/hyperactivity disorder (12.4%) were the most common diagnoses requiring antipsychotics medications. Before starting antipsychotic treatment, the most commonly evaluated parameters were body mass index (BMI) (47.2%), waist circumference (10.5%), blood pressure (28.5%), lipid profile (37%), and blood glucose level (41.6%). When the evaluations made at least in a year after starting antipsychotic drug therapy were examined, 80.2% of physicians reported blood glucose, 79.6% lipid profile, 65.7% BMI, 59.1% blood pressure, and 26.6% waist circumference measurement almost always done. Conclusions: The results showed that the adherence to recommendations in guidelines for the screening of antipsychotic-related side effects was low. This study suggests that interventions should be made about antipsychotic monitoring training to physicians.


Evaluation of an efficient method for training staff to implement stimulus preference assessments.
We used a brief training procedure that incorporated feedback and role-play practice to train staff members to conduct stimulus preference assessments, and we used group-comparison methods to evaluate the effects of training. Staff members were trained to implement the multiple-stimulus-without-replacement assessment in a single session and the paired-stimulus method in another single session. In all 16 cases (2 assessments for 8 trainees), correct responding increased to over 80% accuracy; in 14 of those 16 cases, it increased to over 90% accuracy. Thus, training produced mastery-level performance in a single training session in almost all cases.


SYMPATRIC SPECIATION VIA HABITAT SPECIALIZATION DRIVEN BY DELETERIOUS MUTATIONS.
Theoretical studies have suggested that the evolution of habitat (host) races, regarded as a prelude to sympatric speciation, requires strong trade-offs in adaptation to different habitats: alleles that improve fitness in some habitats and have deleterious effects of similar magnitude in other habitats must be segregating in the population. I argue that such trade-offs are not necessary; the evolution of habitat races can also be driven by genetic variation due to loci that affect fitness in one habitat and are neutral or nearly so in others, that is, when performance in different habitats is genetically independent. One source of such genetic variation are deleterious mutations with habitat-specific fitness effects. I use deterministic two-locus and multilocus models to show that the presence of such mutations in the gene pool results in indirect selection favoring habitat fidelity or habitat preference over acceptance of both suitable habitats. This leads to the evolution of largely genetically isolated populations that use different habitats, from a single panmictic population of individuals accepting both habitats. This study suggests that the conditions favoring habitat race formation, and thus possibly sympatric speciation, are much less stringent than previously thought.


Comprehensive characterization of the Hsp70 interactome reveals novel client proteins and interactions mediated by posttranslational modifications.
Hsp70 interactions are critical for cellular viability and the response to stress. Previous attempts to characterize Hsp70 interactions have been limited by their transient nature and the inability of current technologies to distinguish direct versus bridged interactions. We report the novel use of cross-linking mass spectrometry (XL-MS) to comprehensively characterize the Saccharomyces cerevisiae (budding yeast) Hsp70 protein interactome. Using this approach, we have gained fundamental new insights into Hsp70 function, including definitive evidence of Hsp70 self-association as well as multipoint interaction with its client proteins. In addition to identifying a novel set of direct Hsp70 interactors that can be used to probe chaperone function in cells, we have also identified a suite of posttranslational modification (PTM)-associated Hsp70 interactions. The majority of these PTMs have not been previously reported and appear to be critical in the regulation of client protein function. These data indicate that one of the mechanisms by which PTMs contribute to protein function is by facilitating interaction with chaperones. Taken together, we propose that XL-MS analysis of chaperone complexes may be used as a unique way to identify biologically important PTMs on client proteins.


Perindopril: possible use in cancer therapy.
Since angiogenesis is essential for the growth of any solid tumor, emerging efforts are being made to develop antiangiogenic therapy. To date, however, no antiangiogenic agent has become widely available for the clinical setting. Angiotensin I-converting enzyme (ACE) inhibitors are commonly used as antihypertensive agents and it has recently been suggested that they decrease the risk of cancer. Studies have found that an ACE inhibitor, perindopril, is a potent inhibitor of experimental tumor development and angiogenesis at a clinically comparable dose. The potent angiogenic factor, vascular endothelial growth factor (VEGF), is significantly suppressed by perindopril and also inhibits VEGF-induced tumor growth. In vitro studies showed that perindopril is not cytotoxic to either tumor cells or endothelial cells. Since perindopril is already in widespread clinical use without serious side effects, it may represent a potential new strategy for anticancer therapy.


Lipidomic fingerprint of almonds (Prunus dulcis L. cv Nonpareil) using TiO₂ nanoparticle based matrix solid-phase dispersion and MALDI-TOF/MS and its potential in geographical origin verification.
A matrix solid-phase dispersion (MSPD) procedure with titanium dioxide (TiO2) nanoparticles (NP) as sorbent was developed for the selective extraction of phospholipids from almond samples, and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) was employed for analysis. A remarkable increase in the signals of phospholipid accompanied by a decrease in those of triacylglycerols and diacylglycerols was observed in the relevant mass spectra. The proposed method was applied to five batches of almonds originating from four geographical areas, whereas principal component analysis (PCA) was utilized to normalize the relative amounts of the identified phospholipid species. The results indicated that the lipidomic fingerprint of almonds was successfully established by the negative ion mode spectrum, and the ratio of m/z 833.6 to 835.6 as well as m/z 821.6 could be introduced as potential markers for the differentiation of the tested almonds with different geographical origins. The whole method is of great promise for selective separation of phospholipids from nonphospholipids, especially the glycerides, and superior in fast screening and characterization of phospholipids in almond samples.


Update on the etiopathogenesis of psoriasis (Review).
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, involving hyperproliferative keratinocytes and infiltration of T cells, dendritic cells, macrophages, and neutrophils. Multiple factors appear to play important roles in the pathogenesis of psoriasis. These environmental (e.g., infectious agents and trauma), genetic, and immunologic factors are reviewed in this article. Although the pathogenesis of psoriasis remains to be established, data suggesting immune cell dysregulation in the skin are available. The involvement of the immune system, particularly T cells, in the etiopathogenesis of psoriasis is discussed in this review, indicating a potential justification for innovative treatment intervention. Besides describing pathogenic T cells, the aim of the review was to assess the function of newly identified antimicrobial peptides (AMPs), interleukin (IL)-23, IL-17, and tissue resident memory cells (TRMs), and their role in psoriasis. Furthermore, new insights were presented regarding TRMs, a recently identified subset of memory T cells, and the role they play in the local memory of disease, making them a potential new therapeutic target in psoriasis. Finally, current developments in T-cell research and cytokine-targeted therapy for psoriasis treatment are reviewed.


High mobility group box 1 and kidney diseases (Review).
High mobility group box 1 (HMGB1), a non-histone DNA-binding protein, regulates nucleosome function and transcription in the nuclei of all metazoans and plants. However, extracellular HMGB1, which is actively or passively released under different conditions, can act as a key inflammatory mediator through MyD88/mitogen-activated protein kinase signaling by binding to its receptors including the receptor for advanced glycation end products or Toll-like receptors. A growing body of evidence indicates that HMGB1 plays an important role in kidney diseases, such as glomerulonephritis, lupus nephritis, antineutrophilic cytoplasmatic antibody-associated vaculitis, diabetic nephropathy, renal allograft rejection and acute kidney injury. In this review, we focus on the biology of HMGB1 and the association of HMGB1 with kidney diseases.


Immunomodulating properties of Minthostachys verticillata on human lymphocytes and basophils.
Minthostachys verticillata (Griseb.) Epling is a South American traditional medicinal herb used as digestive, anti-spasmodic, anti-inflammatory and bronchial dilator agent among other uses. Its anti-microbial activity against staphylococcal strains and its anti-viral properties against HVS-1 and strain RC/79 of PrV have been demonstrated. To determine the immunomodulating ability of M. verticillata decoction and essential oil. As a complementary study, the main constituents of the essential oil were identified. Lymphocyte-proliferating activity of both vegetal derivatives was tested and compared with cellular expansion induced by PHA, Pokeweed, CGB in cytomorphological study. A non-stimulate culture was used as control reference. The score of lymphocyte clusters and colonies was performed using the method described by Lange. Among proliferated cells, LT CD8+ subpopulation was characterized by direct immunofluorescence. The in vitro degranulant ability of the vegetal fractions was tested on basophils from allergic and non-allergic individuals sensitized to environmental fungi. Essential oil components of M. verticillata were identified by gas chromatography technique. M. verticillata derivatives reached higher proliferation levels compared to non-stimulated cultures, showed mitogenic activity and induced cluster and colony formation similar to PHA, Pokeweed and CGB. Cells that proliferated after stimulation with derivatives showed 40% of LT CD8+. Tested concentrations of decoction and essential oil did not reach minimum degranulation indexes over basophils, from both allergic and non-allergic individuals. Gas chromatography analysis revealed the presence of pulegone and menthone as the main constituents. M. verticillata derivatives were mitogenic over LT, inducing significant cluster and colony formation. There was no evidence of degranulating ability over basophils at the concentrations tested. We assume that the derivatives from M. verticillata would induce Th1 deviation in cellular cultures from allergic patients, which would diminish hypersensitivity reactions. Some of the compounds of the essential oil revealed by gas chromatography analysis may be responsible of the biological activity of these products.