[Effect of 5-HT and postsynaptic 5-HT1 A on the mood and recogniztion of the repeated restraint stress in rats].
To explore the role of 5-HT and postsynaptic 5-HT1A receptors in the stress adaptation. p-PCA was used to deplete the 5-HT in rats. The 5-HT1A agonist 8-OH-DPAT and antagonist WAY100635 were used to determine the effect of postsynaptic 5-HT1A receptors on the ratso behaviors in the Elevated Plus-Maze test, the Forced Swimming test, and the Morris Water Maze test. Compared with the intact rats, the 5-HT depleted rats showed more seriously anxious behaviors in the Elevated Plus-Maze test and more obvious learned helplessness in the Forced Swimming test. After having been stressed the 5-HT depleted rats showed significantly impaired learning and memory compared with the intact rats according to Morris Water Maze test. Activation of postsynaptic 5-HT1A receptors by 8-OH-DPAT in the 5-HT depleted rats or the 5-HT depleted stress rats significantly decreased the symptoms of anxiety and learned helplessness behaviors which were prevented by the treatment of WAY100635. The 8-OH-DPAT and WAY100635 had no obvious effect on the 5-HT depletion or 5-HT depleted stress rats in the Morris Water Maze test. Deficiency of 5-HT in rats may suppress its ability to stress adaptation. Activation of post-synaptic 5-HT1A receptors can attenuate the anxiety and depressive behavior symptoms, and facilitate rats to adapt stress.


Fluoride-mediated activation of the respiratory burst in electropermeabilized neutrophils.
Electropermeabilization creates small pores in the plasma membrane allowing the introduction of low-molecular-weight modulatory components, such as ions and nucleotides, into the cytosol. The present study investigates fluoride-mediated stimulation of the signal transduction pathway that activates the respiratory burst in electropermeabilized neutrophils. In marked contrast to intact (i.e., non-electropermeabilized) neutrophils, cells permeabilized by this technique demonstrated an immediate and potent stimulation of the superoxide (O2-)-generating NADPH oxidase in response to the addition of fluoride. Furthermore, permeabilization of neutrophils in the presence of exogenously added ATP enhanced the rate of F(-)-mediated O2- production. Fluoride-stimulated O2- production in electropermeabilized neutrophils was antagonized by GDP beta S and dependent upon the presence of Mg2+ in the medium, but was insensitive to pertussis toxin treatment, consistent with the hypothesis that fluoride activates a G protein, probably Gp, by interacting with the nucleotide-binding site on the G alpha subunit. In addition, electropermeabilized neutrophil O2- release triggered by F- was blocked by staurosporine and H-7, indicating that this pathway proceeds largely through protein kinase C activation. However, nucleotide-enhanced O2- production was only partially blocked by these inhibitors, suggesting that under such conditions ATP either competes with the inhibitor-protein kinase interaction or affects the signaling pathway(s) in such a way that protein kinase C may no longer be necessary for the activation of NADPH oxidase.


The effects of IL-6 and TNF-alpha as molecular adjuvants on immune responses to FMDV and maturation of dendritic cells by DNA vaccination.
Various approaches have been developed to improve efficacy of DNA vaccination, such as the use of plasmid expressing cytokine as a molecular adjuvant. In this study, we investigated whether co-inoculation of a construct expressing either IL-6 or TNF-alpha as the molecular adjuvant with FMDV DNA vaccine, pcD-VP1, can increase immune responses. Compared to the group immunized with pcD-VP1 alone, the co-inoculation with either molecular adjuvant induced a higher ratio of IgG2a/IgG1, higher levels of expression of IFN-gamma in CD4+ and CD8+ T cells, IL-4 in CD4+ T cells, and in vivo antigen-specific cytotoxic response. Both adjuvants induced maturation of dendritic cells, suggesting a correlation between the initiating innate response and subsequent activating adaptive immune responses. Together, the results demonstrate that IL-6 and TNF-alpha used as molecular adjuvants can enhance the antigen-specific cell-mediated responses elicited by VP1 DNA vaccine.


Direct NMR evidence for Ca2+ ion binding to G-quartets.
We report the first 1H and 43Ca NMR characterization of Ca2+ ion binding to G-quartets.


Convergent evolution of bacterial ceramide synthesis.
The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently.


Metabolic activation of Trp-P-2, a tryptophan-pyrolysis mutagen, by isolated rat hepatocytes.
Metabolic activation of a tryptophan-pyrolysis product, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), by isolated rat hepatocytes was studied. The substrate (Trp-P-2) disappearance by hepatocytes from untreated rats was slow, but enhanced by 3-methylcholanthrene (MC) pretreatment of rats. The covalent binding of Trp-P-2 to cellular macromolecules was detected in hepatocytes from untreated rats. The amount of covalent binding of Trp-P-2 to protein and RNA was greater than that to DNA. The covalent binding to Trp-P-2 to DNA, RNA and protein in hepatocytes from untreated rats was about 5-10 times less than that in hepatocytes from MC-pretreated rats. 7,8-Benzoflavone strongly inhibited the substrate disappearance and the binding of Trp-P-2 to DNA in hepatocytes from MC-pretreated rats. These results indicate that Trp-P-2 is metabolically activated by the P-448 type of cytochrome P-450 which is induced by MC. Diethylmaleate enhanced by about 50% the binding of Trp-P-2 to DNA in hepatocytes from MC-pretreated rats. On the other hand, cysteine inhibited the binding of Trp-P-2 to DNA with a concomitant reduction in the accumulation of the active metabolite, N-hydroxy-Trp-P-2 (N-OH-Trp-P-2). Sulfhydryl compounds seemed to play important roles in the detoxification of Trp-P-2.


The influences of weather on patients with different ovarian responses in the treatment of assisted reproductive technology.
The purpose of this study was to evaluate the influences of tropical weather on patients with different ovarian responses in the treatment of assisted reproductive technology. Six-hundred fourty-seven women underwent their first treatment cycles were retrospectively analyzed. Patients received embryo transfer either 3 days or 5 days after oocyte retrieval, depending on the number and quality of embryos on day-2. Significant correlations were demonstrated in the top quality embryo rates of day-3 and day-5 embryo transfers with temperature, humidity, and atmosphere pressure. The cumulative light hours negatively correlated with the implantation and pregnancy rates of day-3 embryo transfer (-.282 and -.282, respectively), while they positively correlated with those of day-5 embryo transfer (.225 and .224, respectively). These results clearly suggest that weather may exert influences on the outcome of assisted reproductive technology. Patients with different ovarian responses or blastocyst culture and transfer may modify weather influences.


Unusual fracture of a maxillary second premolar.
Root fractures of posterior teeth are rare and occur as a result of severe trauma. This study describes a horizontal root fracture of a maxillary second premolar discovered during routine full-mouth radiographic examination. The tooth was asymptomatic and responded positively to electric pulp testing. The patient had no recollection of a causative event nor was there physical evidence of previous trauma. It is speculated that the fracture was caused when overzealous force was used in seating an overcontoured complete gold crown restoration of an adjacent tooth.


Diffuse noxious inhibitory controls (DNICs): psychophysical evidence in man for intersegmental suppression of noxious heat perception by cold pressor pain.
Counterirritation, the phenomenon of one painful stimulus reducing pain caused by a second noxious stimulus, has been recognized clinically for decades. Recently a physiological mechanism to explain counterirritation was described and termed diffuse noxious inhibitory controls (DNICs). Nevertheless, few psychophysical studies have examined systematically the effects of a noxious conditioning stimulus on pain perception. The present study examined the perception of painful heat stimuli on the face before, during and after the subject submerged a hand in painfully cold water (5 degrees C) for 5 min (cold pressor pain). We found that the subjects' ratings of the heat stimuli were significantly, although not completely, reduced during the cold pressor pain; this attenuation of pain perception continued after the noxious conditioning stimulus was withdrawn. Similarly, the pain threshold was significantly increased from 45.7 degrees C to 47.3 degrees C while the hand was in cold water and this threshold remained elevated after the cold water was terminated. Since DNICs have been found to completely and selectively inhibit the activity of only one type of pain transmission neuron (wide dynamic range), our data suggest that these neurons are involved in the perception of pain intensity. However, the persistence of residual pain perception in the presence of noxious conditioning stimuli indicates the importance of other nociceptive pathways.


Evaluation of loci to predict ear morphology using two SNaPshot assays.
Human ear morphology prediction with SNP-based genotypes is growing in forensic DNA phenotyping and is scarcely explored in Pakistan as a part of EVCs (externally visible characteristics). The ear morphology prediction assays with 21 SNPs were assessed for their potential utility in forensic identification of population. The SNaPshot™ multiplex chemistries, capillary electrophoresis methods and GeneMapper™ software were used for obtaining genotypic data. A total of 33 ear phenotypes were categorized with digital photographs of 300 volunteers. SHEsis software was applied to make LD plot. Ordinal and multinomial logistic regression was implemented for association testing. Multinomial logistic regression was executed to construct the prediction model in 90% training and 10% testing subjects. Several influential SNPs for ear phenotypic variation were found in association testing. The model based on genetic markers predicted ear phenotypes with moderate to good predictive accuracies demonstrated with the area under curve (AUC), sensitivity and specificity of predicted phenotypes. As an additional EVC, the estimated ear phenotypic profiles have the possibility of determining the human ear morphology differences in unknown biological samples found in crimes that do not result in a criminal database hit. Furthermore, this can help in facial reconstruction and act as an investigational lead.


Navigating nursing curriculum change during COVID-19 pandemic: A systematic review and meta-synthesis.
To consolidate the evidence around the experiences of nursing undergraduates and faculty members navigating through remote and online education during the COVID-19 pandemic. The Coronavirus disease 2019 caused by the SARS-CoV-2 Virus (COVID-19) has placed massive pressure on healthcare, economic and education systems globally. Restrictive social distancing policies and public health measures necessitated educational institutions to switch from face-to-face to remote and online education to sustain the learning process. These changes have created an uncertain path and undue stress for healthcare learners and faculty, especially for professional roles that traditionally require more hands-on and access to clinical practice particularly pre-licensure nursing students. As such, there is an urgent need to consolidate evidence on the experiences of nursing undergraduates and faculty members as they navigate the rapid transition from face-to-face to remote and online education to ensure continuity of learning in achieving optimal learning outcomes and to support them during current and future public health crises. A systematic review and meta-synthesis of the qualitative literature was undertaken using Sandelowski and Barroso's approach. Six electronic databases, CINAHL, Embase, ERIC, PsycINFO, PubMed and Scopus, were searched systematically using the eligibility criteria from December 2019 to September 2022. The Critical Appraisal Skills Program checklist for qualitative studies was used to conduct the critical appraisal of the selected articles. Forty-seven studies were included in this review, which encapsulates the experiences of 3052 undergraduates and 241 faculty members. An overarching meta-theme 'Remote and online education: a rollercoaster ride', emerged along with three main meta-themes: (1) Transition to remote and online education: A turbulent road, (2) Acceptance of the untravelled road, (3) Hopes and recommendations for the road ahead. To improve nursing undergraduates' and faculty member's navigation of remote and online education, more institutions should move towards establishing hybrid education as the new 'normal' and exercise prudence in the organisation and delivery of curriculum, teaching, well-being and clinical attachment contingencies of their healthcare courses.


Rapidly enlarging hepatobiliary cystadenoma.
An unusual case of a hepatobiliary cystadenoma caused severe abdominal pain and obstructive jaundice by rapid enlargement in a woman aged 73 years. Magnetic resonance imaging revealed a 12 cm cystic lesion in the left medial segment of the liver and dilatation of the intrahepatic bile ducts. The abdominal pain was worse 4 days later, when magnetic resonance imaging demonstrated enlargement of the cystic lesion, to 14 cm in diameter. Laboratory tests on admission revealed serum alkaline phosphatase, 1342 IU/L; gamma glutamic transpeptidase, 672 IU/L; total serum bilirubin, 7.4 mg/dL; direct bilirubin, 5.8 mg/dL; and carbohydrate antigen 19-9, 37U/mL. Serosanguineous fluid was obtained by emergency percutaneous transhepatic drainage of the cyst, which resolved the patient's abdominal pain. Culture and cytologic examination of the fluid were nondiagnostic. The discharged fluid through dramage tube turned brown, and the total serum bilirubin concentration gradually decreased. Cystography and endoscopic retrograde cholangiography demonstrated communication between the cyst and the intrahepatic bile ducts on the left side of the liver. The cyst was removed by left hepatectomy 14 days after it had been drained. Pathologic examination of the resected specimen confirmed the presence of a hepatobiliary cystadenoma. Although hepatobiliary cystadenoma is a rare benign cystic tumor of the liver, it can become malignant and should thus be excised.


The silent epidural abscess as a complication of acute otitis media in children.
Acute otitis media with complications is a persistent problem in the modern antibiotic era with a relatively high mortality rate. Acute mastoiditis is a serious complication of acute otitis media with potentially grave consequences and the epidural abscess constitutes the commonest of all intracranial complications, arising from middle ear infections. We report two cases of children with acute mastoiditis without evidence of intracranial complication or subperiosteal abscess, in whom the early evaluation with computed tomography (CT) disclosed an unsuspected epidural abscess. Therefore, we stress the use of CT as a rule of thumb for every child with acute mastoiditis.


Nuclear and mitochondrial DNA repair: similar pathways?
Mitochondrial DNA (mtDNA) alterations are implicated in a broad range of human diseases and alterations of the mitochondrial genome are assumed to be a result of its high susceptibility to oxidative damage and its limited DNA repair compared to nuclear DNA (nDNA). Characterization of DNA repair mechanisms has generally focused on these processes in nDNA but increasing interest and research effort have contributed to our knowledge of the mechanisms underlying DNA repair in mitochondria. In this review, we make comparisons between nDNA and mtDNA repair pathways and propose a model for how these pathways interact in mitochondria.


Acute kidney injury in patients with cirrhosis: Prospective longitudinal study in 405 patients.
Acute kidney injury (AKI) is common in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed new definitions of AKI in order to improve the prediction of outcomes. Our aim was to assess the prevalence and prognostic value of ICA 2015 - AKI criteria in hospitalised patients with cirrhosis. We prospectively collected data from 405 consecutive cirrhotic patients admitted to the hospital between November 2016 and November 2017. AKI was diagnosed at inclusion according to ICA 2015 criteria, and was assessed to predict 30-day and 90-day in-hospital mortality. AKI was diagnosed in 78 (19.3%) patients. AKI was independently associated with 90-day death (HR 7.61; 95% CI 4.75-12.19; p < 0.001). In hospital, 30-day and 90-day survival was lower in the group of patients with AKI compared to the group with no AKI (72% vs. 98%, p < 0.001; 64% vs. 96%, p < 0.001; and 49% vs. 81%, p < 0.001, respectively). Patients with stage 1a AKI had a lower 30-day and 90-day survival compared to the group of patients who did not develop AKI (71% vs. 96%, p < 0.001, and 71% vs. 91%, p < 0.01, respectively) and better survival than patients with more severe AKI (71% vs. 40%, p < 0.01). AKI was independently associated with mortality in patients with cirrhosis, even at the very early 1a stage. Response to treatment improved survival, and was inversely proportional to the stage of AKI, which suggests that treatment should be started at the earliest stage of AKI.


Evidence for the use of Levomepromazine for symptom control in the palliative care setting: a systematic review.
Levomepromazine is an antipsychotic drug that is used clinically for a variety of distressing symptoms in palliative and end-of-life care. We undertook a systematic review based on the question "What is the published evidence for the use of levomepromazine in palliative symptom control?". To determine the level of evidence for the use of levomepromazine in palliative symptom control, and to discover gaps in evidence, relevant studies were identified using a detailed, multi-step search strategy. Emerging data was then scrutinized using appropriate assessment tools, and the strength of evidence systematically graded in accordance with the Oxford Centre for Evidence-Based Medicine's 'levels of evidence' tool. The electronic databases Medline, Embase, Cochrane, PsychInfo and Ovid Nursing, together with hand-searching and cross-referencing provided the full research platform on which the review is based. 33 articles including 9 systematic reviews met the inclusion criteria: 15 on palliative sedation, 8 regarding nausea and three on delirium and restlessness, one on pain and six with other foci. The studies varied greatly in both design and sample size. Levels of evidence ranged from level 2b to level 5, with the majority being level 3 (non-randomized, non-consecutive or cohort studies n = 22), with the quality of reporting for the included studies being only low to medium. Levomepromazine is widely used in palliative care as antipsychotic, anxiolytic, antiemetic and sedative drug. However, the supporting evidence is limited to open series and case reports. Thus prospective randomized trials are needed to support evidence-based guidelines.


Radiation therapy for the treatment of non-eight nerve intracranial neurilemmoma.
The records of 19 patients treated for intracranial neurilemmomas, other than of the eighth nerve, at the University of California, San Francisco from 1945 through 1983 were reviewed. One patient who died within 30 days following surgery was excluded from the analysis. The 5th and the 9/10/11th nerve complex were the most common sites of tumor origin. Patients were classified by the extent of surgical resection: total (90-99% resection, NTR), subtotal (less than 90% resection, STR) and biopsy. Five patients had total excision of their tumor without post-operative irradiation and none had recurred. One of the 2 patients who had STR and did not receive post-operative irradiation recurred, while 2 of the 3 patients who received post-operative irradiation following STR recurred. One of the 2 patients who had NTR and did not receive post-operative irradiation recurred, while 1 of the 3 patients who received post-operative irradiation following NTR recurred. Two patients were treated with post-operative irradiation following biopsy and one recurred. One patient was treated with planned preoperative irradiation to reduce tumor vascularity, followed by total resection. Because of the small number of patients, no firm conclusion regarding the efficacy of irradiation for non-eighth nerve intracranial neurilemmoma can be made.


Patient-treatment interactions among alcoholics.
The ratins of the different aspects of an alcoholism treatment program by patients before discharge revealed differences in views of the program that were related to differences in personality.


Anatomic variants of the paranasal sinuses in patients with recurrent acute rhinosinusitis.
The incidence and potential disease impact of paranasal sinus anatomic variants in patients with recurrent acute rhinosinusitis (RARS) has important implications for management, including surgery, but is incompletely defined. A retrospective review of 26 patients with RARS who had undergone computed tomography (CT) was performed. Patient demographics, RARS severity and comorbidities were reviewed. CT scans were reviewed for the incidence of anatomic variants in all patients. The pattern of inflammatory changes was explored in the subset of patients with acute rhinosinusitis at the time of CT. Potential correlation between the presence of anatomic variants and disease severity were investigated. In the patient cohort who met inclusion criteria, the most common variants included agger nasi cell (88.5%), concha bullosa (53.8%), infraorbital cell (50%), and deviated nasal septum with middle meatus obstruction (42%). In exploring correlations with RARS severity, type 2 frontal cells correlated with a greater number of years with RARS (0.0363). In the 23 patients who underwent CT at the time of an acute infection, no statistically significant correlation was found between severity or location of inflammatory changes and the presence of anatomic variants. This study describes the incidence of anatomic variants in a cohort of patients with RARS. A correlation between the presence of anatomic variants and the pattern of inflammatory changes was not identified.


On the validity of remember-know judgments: evidence from think aloud protocols.
The use of remember-know judgments to assess subjective experience associated with memory retrieval, or as measures of recollection and familiarity processes, has been controversial. In the current study we had participants think aloud during study and provide verbal reports at test for remember-know and confidence (i.e., sure-probably) judgments. Results indicated that the vast majority of remember judgments for studied items were associated with recollection from study (87%), but this correspondence was less likely for high-confidence judgments (72%). Instead, high-confidence judgments were more likely than remember judgments to be associated with incorrect recollection and a lack of recollection. Know judgments were typically associated with a lack of recollection (62%), but still included recollection from the study context (33%). Thus, although remember judgments provided fairly accurate assessments of retrieval including contextual details, know judgments did not provide accurate assessments of retrieval lacking contextual details.


α-actinin is required for the proper assembly of Z-disk/focal-adhesion-like structures and for efficient locomotion in Caenorhabditis elegans.
The actin binding protein α-actinin is a major component of focal adhesions found in vertebrate cells and of focal-adhesion-like structures found in the body wall muscle of the nematode Caenorhabditis elegans. To study its in vivo function in this genetic model system, we isolated a strain carrying a deletion of the single C. elegans α-actinin gene. We assessed the cytological organization of other C. elegans focal adhesion proteins and the ultrastructure of the mutant. The mutant does not have normal dense bodies, as observed by electron microscopy; however, these dense-body-like structures still contain the focal adhesion proteins integrin, talin, and vinculin, as observed by immunofluorescence microscopy. Actin is found in normal-appearing I-bands, but with abnormal accumulations near muscle cell membranes. Although swimming in water appeared grossly normal, use of automated methods for tracking the locomotion of individual worms revealed a defect in bending. We propose that the reduced motility of α-actinin null is due to abnormal dense bodies that are less able to transmit the forces generated by actin/myosin interactions.


Responses to COVID-19, small and medium enterprises' corporate social responsibility and psychological capital of employees: From the mediating perspective of affective commitment.
The influence of corporate social responsibility (CSR) on employees' positive psychological capital in stressful situations remains unexplored in the literature for small and medium enterprises (SMEs). This study aims to examine how CSR could assist employees in developing psychological capital during the COVID-19 pandemic. In order to understand the aforesaid relationship, an attempt is made to study the mediation effect of affective commitment. Structural equation modelling (AMOS 21.0) was used for data analysis and hypothesis testing on a sample of 545 employees from 356 Malaysian SMEs. The results of this study showed that SMEs' CSR policies helped to improve the positive psychological capital of their employees during the COVID-19 pandemic. Also, affective commitment complementary mediates the relationship between CSR and psychological capital. During the COVID-19 pandemic, SMEs should come up with a consistent way to implement CSR policies and procedures to improve employees' psychological capital and increase their affective commitment toward the enterprise. There are two main contributions to the literature from this study, in addition to enriching previous empirical research on CSR. As a first contribution to the CSR literature, it examines how CSR impacts employees' psychological capital during a pandemic. COVID-19 is one of the recent pandemics that offers an opportunity to examine its effects on employee psychological state. Secondly, the results of the study add to the growing body of empirical research that supports affective commitment's significant relationship with CSR and enhances employees' psychological capital during a pandemic in a developing market.


Who are the patients with extrapulmonary tuberculosis?
Tuberculosis (TB) remains a major global public health problem and 20% of all cases are extrapulmonar. The purpose of this study was to identify risk factors associated with extrapulmonar tuberculosis. We carried out a transversal study which included all patients with extrapulmonary tuberculosis registered in a TB reference center in northern Portugal, between January 2008 and January 2012. We evaluated demographic data, comorbidities, BCG vaccination and previous tuberculosis treatments. Multivariable logistic regression was used to identify independent risk factors (p<0.05). Among the 386 patients studied, 260 (67.4%) had pulmonary tuberculosis (PTB) and 126 (32.6%) extrapulmonary TB (EPTB). Age over 40 years old (OR=2.09; 95%CI: 1.29-3.38), female gender (OR=1.63; 95%CI=1.02-2.6) and HIV infection (OR=2.72, 95%CI=1.25-5.93) were independent risk factors for EPTB. Alcoholism (OR=2.22, 95%CI: 1.00-4.95) was associated with higher risk for PTB. Previous liver disease (OR=22.30; 95%IC: 1.89-263.57) was an independent risk factor for peritoneal TB. HIV co-infection (OR=12.97; 95%IC: 1.71-48.42) and the presence of previous TB treatment (OR=7.62; 95%IC: 1.00-57.9) increase the risk of disseminated disease. We identified independent risk factors for EPTB. Recognizing risk factors associated with EPTB is essential for suspicion of disease and may help make an accurate diagnosis.


Synaptic circuit remodelling by matrix metalloproteinases in health and disease.
Matrix metalloproteinases (MMPs) are extracellularly acting enzymes that have long been known to have deleterious roles in brain injury and disease. In particular, widespread and protracted MMP activity can contribute to neuronal loss and synaptic dysfunction. However, recent studies show that rapid and focal MMP-mediated proteolysis proactively drives synaptic structural and functional remodelling that is crucial for ongoing cognitive processes. Deficits in synaptic remodelling are associated with psychiatric and neurological disorders, and aberrant MMP expression or function may contribute to the molecular mechanisms underlying these deficits. This Review explores the paradigm shift in our understanding of the contribution of MMPs to normal and abnormal synaptic plasticity and function.


Relationship of stress-reactive cortisol to suicidal intent of prior attempts in major depression.
Higher intent suicide attempts carry elevated risk of future suicidal behavior. Abnormal functioning of the hypothalamic-pituitary-adrenal (HPA) axis is both linked to nonfatal suicidal behavior and suicide deaths in major depressive disorder. Few studies, however, have identified biological markers of a high-intent suicidal subgroup. We examined HPA axis output and reactivity to the Trier Social Stress Test (TSST) via salivary cortisol in depressed individuals (N=68) with a suicide attempt (SA) history. A median split of higher and lower suicidal intent scores was used to define groups. Individuals with high intent SA had attenuated total cortisol output (AUCg), F(1,60)=10.04, SE=5.095, p=.003, and lower HPA-axis stress responsivity to the TSST (AUCi), F(1,60)=4.50, SE=4.604, p=.039, compared with the low intent SA group. The high intent group also reported more pronounced negative affect than the low intent group (F[1,61]=6.413, SE=10.55, p=.014) both at baseline (meandiff=22.32, p=.038) and in response to the stressor task (meandiff=37.62, p=.003). Vulnerability to suicidal behavior in high-intent individuals may be related to the combined profile of impaired physiological responses to stress and greater negative affectivity. This clinical and biologic subgroup may benefit from targeted suicide prevention interventions.


Hormetic and anti-inflammatory properties of oxidized phospholipids.
Oxidized phospholipids are generally recognized as deleterious factors involved in disease pathogenesis. This review summarizes the data suggesting that under certain biological conditions the opposite is correct, namely that OxPLs can also induce protective effects. Examples that are discussed in the review include upregulation of antioxidant genes, inhibition of inflammatory signaling pathways through Nrf2-dependent and -independent mechanisms, antagonism of Toll-like receptors, immuno-modulating and immuno-suppressive action of OxPLs in adaptive immunity and autoimmune disease, activation of PPARs known for their anti-inflammatory action, as well as protective action against lung edema in acute lung inflammation. The data support the notion that oxidation of phospholipids provides a negative feedback preventing damage to host tissues due to uncontrolled inflammation and oxidative stress.


A new anoscope for transanal surgery.
Although stapled mucosectomy has several advantages over hemorrhoidectomy for hemorrhoidal prolapse, complications such as hemorrhage, pain, and life-threatening pelvic sepsis may occur, often due to poorly executed purse-string suture. We describe a simple new anoscope that makes it easy to correctly perform and position the purse-string suture that is an integral part of stapled mucosectomy. The apex of the middle part of the new anoscope consists of digitiform projections separated by spaces. After insertion of the instrument into the anus, the inner part is removed, allowing strips of rectal mucosa to protrude through the spaces between the digitiform projections. The purse-string suture is made through these protrusions. The suture catches the mucosa and submucosa but not the deeper muscle layer, which does not protrude through the spaces. Preliminary histologic studies in the pig suggest that the design of the anoscope prevents inclusion of the muscular layer in the pursestring.


Hepatitis C virus-associated decompensated liver cirrhosis with refractory hepatic encephalopathy successfully treated by balloon-occluded retrograde transvenous obliteration after sofosbuvir/velpatasvir.
Sofosbuvir/velpatasvir (SOF/VEL) is expected to be highly effective, even in patients with decompensated liver cirrhosis. However, portal hypertension can be problematic after achieving a sustained viral response (SVR), especially in patients with hepatic encephalopathy (HE) associated with large portal-systemic shunt. Although balloon-occluded retrograde transvenous obliteration (BRTO) is a useful option, whether BRTO or SOF/VEL therapy should be initially performed in patients with a poor liver function reserve is controversial. We herein report a case of refractory HE caused by decompensated liver cirrhosis due to hepatitis C virus (HCV) classified as Child-Pugh class C that was treated by BRTO after SVR with SOF/VEL. A 64-year-old woman with HCV-associated decompensated cirrhosis developed refractory HE. Dynamic contrast-enhanced computed tomography (CT) revealed large portal-systemic shunt. We treated the patient with 12 weeks of SOF/VEL, and she achieved SVR. Although the serum albumin level, edema, and ascites were improved, intractable HE remained. Her general condition had been improved after SVR, so HE was suspected to have been caused by portal-systemic shunting. We, therefore, treated the patient by BRTO. On dynamic contrast-enhanced CT, partial obstruction of the shunt vessel was confirmed after BRTO. Thereafter, her serum ammonia level rapidly improved, and HE did not recur. Interventional radiology such as BRTO following SOF/VEL therapy may be a useful option even in patients with decompensated HCV-associated cirrhosis accompanied by portal-systemic shunt.


T cells in the pathogenesis of type 1 diabetes.
T lymphocytes' crucial role in the autoimmune process leading to insulin-dependent type 1 diabetes is now universally recognized. Research focuses on identifying pathogenic and nonpathogenic T cells, understanding how they are primed and expanded, characterizing their antigen specificity, and ultimately on devising strategies to blunt their autoaggressive action. In this review, we focus on recent progress identified in three different areas. Results obtained with transgenic mice acknowledge proinsulin's unique role in triggering autoimmunity and suggest that other beta-cell proteins are recognized as a result of epitope spreading, at least in the nonobese diabetic mouse. Progress has also been achieved by developing and validating reliable CD4+ and CD8+ T-cell tests that may prove valuable for diagnostic and prognostic purposes in the near future. Finally, recent results provide novel and important guidance for manipulating autoreactive T-cell responses against beta-cell antigens.


[Subcutaneous infection by Curvularia pallescens in a lung transplant recipient: First report in Spain].
Curvularia is a filamentous dematiaceous fungus increasingly recognized as a pathogen in immunocompromised patients. The most common clinical entities associated with this fungus are allergic sinusitis, cutaneous infection and keratitis. In this article, a report on the first clinical case of Curvularia pallescens cutaneous infection in Spain and its treatment is described. A 68 year-old man with a history of lung transplantation presented to Dermatology Unit due to a skin lesion in the knee that had been evolving for 6 months. A skin biopsy was performed for its study. In the histopathological study, an intense and non-specific inflammatory reaction in the dermis was observed, and with Grocott stain and periodic acid Schiff abundant septate hyphae and spores were found in the dermis. The culture of the sample revealed a filamentous fungus whose microscopic examination allowed to identify the genus as Curvularia. Using MALDI-TOF mass spectrometry and molecular identification, the fungus was finally identified as Curvularia pallescens. The patient underwent surgical resection of the lesion and was treated with posaconazole, evolving favorably. The species of Curvularia should be considered causal agents of fungal skin infections in immunosuppressed patients. This clinical case, which showed good clinical response after surgical resection and treatment with posaconazole, is the first described in Spain due to this species.


Molecular Correlates of Topiramate and GRIK1 rs2832407 Genotype in Pluripotent Stem Cell-Derived Neural Cultures.
There is growing evidence that the anticonvulsant topiramate is efficacious in reducing alcohol consumption. Further, an intronic single nucleotide polymorphism (rs2832407, C A) in the GRIK1 gene, which encodes the GluK1 subunit of the excitatory kainate receptor, predicted topiramate's effectiveness in reducing heavy drinking in a clinical trial. The molecular correlates of GRIK1 genotype that may relate to topiramate's ability to reduce drinking remain unknown. We differentiated induced pluripotent stem cells (iPSCs) characterized by GRIK1 rs2832407 genotype from 8 A/A and 8 C/C donors into forebrain-lineage neural cultures. Our differentiation protocol yielded mixed neural cultures enriched for glutamatergic neurons. Basal mRNA expression of the GRIK1 locus was examined via quantitative polymerase chain reaction (qPCR). The effects of acute topiramate exposure on excitatory spontaneous synaptic activity were examined via whole-cell patch-clamp electrophysiology. Results were compared and contrasted between iPSC donor genotypes. Although characterization of the GRIK1 locus revealed no effect of rs2832407 genotype on GRIK1 isoform mRNA expression, a significant difference was observed on GRIK1 antisense-2 expression, which was greater in C/C neural cultures. Differential effects of acute exposure to 5 μM topiramate were observed on spontaneous synaptic activity in A/A versus C/C neurons, with a smaller reduction in excitatory event frequency observed in C/C donor neurons. This work highlights the use of iPSC technologies to study pharmacogenetic treatment effects in psychiatric disorders and furthers our understanding of the molecular effects of topiramate exposure in human neural cells.


Acute human immunodeficiency virus syndrome presenting with hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) has been described in patients with advanced stages of human immunodeficiency virus (HIV) infection, but rarely occurs during the seroconversion stage of acute HIV infection. We report a case of acute HIV syndrome that presented with virus-associated HLH. The patient recovered spontaneously without any immunomodulating therapy. This case suggests that acute HIV infection should be included in the differential diagnosis of HLH and indicates that HLH associated with acute HIV infection can have a favorable outcome.


What is the optimal approach to the administration of intraperitoneal chemotherapy in ovarian cancer?
Three well-designed and conducted randomized phase 3 trials have revealed that the intraperitoneal administration of cisplatin-based chemotherapy as primary treatment of small-volume residual advanced ovarian cancer improves both progression-free and overall survivals compared to an all intravenous cisplatin-based regimen. Based on very reasonable extrapolations from existing evidence-based data, a number of possible "options" can be proposed that use the intraperitoneal route for delivery of chemotherapy in this clinical setting.


Mechanisms of multi-strain coexistence in host-phage systems with nested infection networks.
Bacteria and their viruses (bacteriophages) coexist in natural environments forming complex infection networks. Recent empirical findings suggest that phage-bacteria infection networks often possess a nested structure such that there is a hierarchical relationship among who can infect whom. Here we consider how nested infection networks may affect phage and bacteria dynamics using a multi-type Lotka-Volterra framework with cross-infection. Analysis of similar models has, in the past, assumed simpler interaction structures as a first step towards tractability. We solve the proposed model, finding trade-off conditions on the life-history traits of both bacteria and viruses that allow coexistence in communities with nested infection networks. First, we find that bacterial growth rate should decrease with increasing defense against infection. Second, we find that the efficiency of viral infection should decrease with host range. Next, we establish a relationship between relative densities and the curvature of life history trade-offs. We compare and contrast the current findings to the "Kill-the-Winner" model of multi-species phage-bacteria communities. Finally, we discuss a suite of testable hypotheses stemming from the current model concerning relationships between infection range, life history traits and coexistence in complex phage-bacteria communities.


[Study on computer aided design system of anterior prosthesis in terms of artificial neural network].
This study was to develop computer aided design system of anterior prosthesis, which can improve information communication among doctors, technicians, patients and raise anterior prosthesis cosmetic effect. Digital camera was used for image capture; Space field method, neighboring field average method, midst value filter method, and image average method were used for image pre-process; sample teeth were constructed; anterior prosthesis were automatically designed through tooth feature extraction. 86 patients were prosthetically designed through this CAD system with excellent results. This system implemented anterior prosthesis CAD rapidly, guided clinical application and promoted information process in the field of prosthetics.


FDA's Factored Food Vocabulary for food product description.
The Food and Drug Administration's Factored Food Vocabulary (FFV) uses standardized language to describe characteristics of food products that are important for food safety and nutritional quality. Each food product is described by a set of descriptors from the following factors: product type; food source; part of plant or animal; physical state, shape, or form; degree of preparation; cooking method; treatment applied; preservation method; packing medium; container or wrapping; food contact surface; and user group. The purpose of the vocabulary is to facilitate retrieval of food composition, food consumption, food contamination, and other food-related data relative to these factors. The major advantages of this system are flexibility with specificity, enhanced searchability with economy, and ease of change and updating.


Modelling heme d1. The spectral properties of copper(II) porphyrindiones.
The heme d1 macrocycle of Ps. aeruginosa dissimilatory nitrite reductase is an iron porphyrin-3,8-dione with a 17-acrylate substituent. We have compared the RR properties of Cu-d1, the copper(II) TME of extracted heme d1, with those of models that differ only with respect to the acrylate: Cu-17-acrylate mesoporphyrin-3,8-dione (2) and Cu-mesoporphyrin-3,8-dione (3). The RR spectrum of Cu-d1 is very similar to that of 2, including v(C = O) at approximately 1720 cm-1. Replacement of the acrylate with propionate changes the spectrum markedly. For example, the v(C = O) mode of 3 shifts to 1712 cm-1, and peaks of Cu-d1 and 2 at approximately 1400 and approximately 1535 cm-1 are shifted or absent from the spectrum of 3. FTIR spectra of 2 and 3 also differ in their voxo(C = O) frequencies. The acrylate thus has a surprisingly strong influence on the electronic structural and spectral properties of heme d1. These data provide a foundation for studies of the novel biological porphyrindione macrocycles.


Loss of synchronization in partially coupled Hodgkin-Huxley equations.
We study the loss of synchronization of two partially coupled space-clamped Hodgkin-Huxley equations, with symmetric coupling. This models the coupling of two cells through an electrical synapse. For strong enough coupling it is known that all solutions of the equations approach a state where the two cells are perfectly synchronized, having the same behaviour at each moment. We describe the local bifurcations that arise when the coupling strength is reduced, using a mixture of analytical and numerical methods. We find that perfect synchrony is retained for very small positive values of the coupling strength, for almost all initial conditions. Although perfect synchrony is lost for negative values of the coupling constant, the system always retains some degree of synchronization until it becomes totally unstable. This happens in two ways: in many cases for almost all initial conditions the solutions still approach a perfectly synchronized state. Even when this is not true, the attracting solutions are still synchronized, with a half-period phase shift.


Maternal Intake of Probiotics to Program Offspring Health.
Probiotics intake may be considered beneficial by prospective and pregnant mothers, but their effects on offspring development are incompletely understood. The purpose of this review was to examine recent pre-clinical and clinical studies to understand how maternal probiotics exposure affects offspring health outcomes. Effects were investigated in the context of supporting offspring growth, intestinal health, and gut microbiota, preventing allergic diseases, supporting neurodevelopment, and preventing metabolic disorders in pre-clinical and clinical studies. Most human studies focused on infancy outcomes, whereas pre-clinical studies also examined outcomes at adolescence and young adulthood. While still understudied, both pre-clinical and clinical studies propose epigenetic modifications as an underlying mechanism. Optimal timing of intervention remains unclear. Administration of selected probiotics to mothers has programming potential for sustaining life-long health of offspring. Administration protocols, specific windows of susceptibility, and individual-specific responses need to be further studied.


Ultrastructural localization of a peroxisomal protein in rat liver using the specific antibody against the non-specific lipid transfer protein (sterol carrier protein 2).
An antibody against the non-specific lipid transfer protein from rat liver was purified by immunoabsorbent affinity chromatography. This antibody in conjunction with protein A-colloidal gold was used to localize the transfer protein in rat liver by electron microscopy. Labeling by this immunocytochemical technique was found to be mainly restricted to the peroxisomes; low labeling was observed in the cytoplasm. Subsequent analysis of isolated peroxisomes by immunoblotting indicated that the non-specific lipid transfer protein (mol. wt. 14800) was absent from this organelle and that a protein of molecular weight 58000 was responsible for the immunological response. Immunoblotting of the membrane-free cytosol showed the presence of both proteins. It remains to be established to what extent the non-specific lipid transfer protein in the cytosol and the high-molecular weight protein in the peroxisomes are related.


A mild and efficient extraction method for polysaccharides from Sinonovacula constricta and study of their structural characteristic and antioxidant activities.
The aim of this paper is to develop a mild and efficient extraction method for polysaccharides from Sinonovacula constricta (SCP) using enzyme extraction, and analyze the structural characteristics and antioxidant activities of the two purified polysaccharide fractions (SCP-1 and SCP-2). Firstly, enzyme extraction conditions were optimized, and the conditions were found to be, as follows: enzymolysis time 173.0 min, pH 8.2, enzymolysis temperature 50.0 ℃ and enzyme content 4.0%. Comparison between enzymatic extraction and water extraction was obtained from visual, UV-visible and IR spectrum images. The results clearly indicate that there is no significant difference between them with regard to the composition of the SCP fraction, but the polysaccharide content produced by enzymatic extraction is higher. Then, the physicochemical properties and structural characteristics of SCP-1 and SCP-2 were investigated using FT-TR, UV, GC and HPGPC. The carbohydrate content, sulfuric radicals and uronic acids of the two fractions were detected. Both SCP-1 and SCP-2 were mainly consisted of glucose, but their molecular weights were different. In addition, compared the Fe2+ chelating activity, ABTS+ radical and superoxide radical scavenging activity, and lipid peroxidation inhibition activity of SCP-1 and SCP-2, it turned out that SCP-2 had stronger antioxidant activity than SCP-1.


One-Day Bayesian Cloning of Type 1 Diabetes Subjects: Toward a Single-Day UVA/Padova Type 1 Diabetes Simulator.
The UVA/Padova Type 1 Diabetes (T1DM) Simulator has been shown to be representative of a T1DM population observed in a clinical trial, but has not yet been identified on T1DM data. Moreover, the current version of the simulator is "single meal" while making it "single-day centric," i.e., by describing intraday variability, would be a step forward to create more realistic in silico scenarios. Here, we propose a Bayesian method for the identification of the model from plasma glucose and insulin concentrations only, by exploiting the prior model parameter distribution. The database consists of 47 T1DM subjects, who received dinner, breakfast, and lunch (respectively, 80, 50, and 60 CHO grams) in three 23-h occasions (one open- and one closed-loop). The model is identified using the Bayesian Maximum a Posteriori technique, where the prior parameter distribution is that of the simulator. Diurnal variability of glucose absorption and insulin sensitivity is allowed. The model well describes glucose traces (coefficient of determination R2 = 0.962 ± 0.027 ) and the posterior parameter distribution is similar to that included in the simulator. Absorption parameters at breakfast are significantly different from those at lunch and dinner, reflecting more rapid dynamics of glucose absorption. Insulin sensitivity varies in each individual but without a specific pattern. The incorporation of glucose absorption and insulin sensitivity diurnal variability into the simulator makes it more realistic. The proposed method, applied to the increasing number of long-term artificial pancreas studies, will allow to describe week/month variability, thus further refining the simulator.


A novel periplasmic protein (Slr0280) tunes photomixotrophic growth of the cyanobacterium, Synechocystis sp. PCC 6803.
Cyanobacteria are among the main contributors to global photosynthesis and show a high degree of metabolic plasticity. Synechocystis sp. PCC 6803 can grow under photoautotrophic, photomixotrophic or photoheterotrophic conditions. We have characterized a novel periplasmic protein (Slr0280) that tunes the photomixotrophic growth of Synechocystis sp. PCC 6803. Slr0280 is a multi-domain protein consisting mainly of β-sheets. Several proteins that interact with Slr0280 were identified via bacterial two-hybrid screening. Slr0280 may interact through its DUF2233 domain with partners that participate in sugar metabolism, thereby coordinating the respective regulations. When slr0280 was deleted, the mutant grew more slowly than wild-type in the presence of glucose, which is ascribed to the down-regulation of glycolysis, glycogen catabolism, oxidative pentose phosphate pathway, Calvin cycle and glucose utilization. A positive regulation of Slr0280 on these sugar catabolic enzymes was confirmed by transcript (qPCR) analyses. Based on these findings, we proposed a speculative model that Slr0280 plays a coordinating regulatory role in sugar metabolism.


Differential effects of conifer and broadleaf litter inputs on soil organic carbon chemical composition through altered soil microbial community composition.
A strategic selection of tree species will shift the type and quality of litter input, and subsequently magnitude and composition of the soil organic carbon (SOC) through soil microbial community. We conducted a manipulative experiment in randomized block design with leaf litter inputs of four native subtropical tree species in a Pinus massoniana plantation in southern China and found that the chemical composition of SOC did not differ significantly among treatments until after 28 months of the experiment. Contrasting leaf litter inputs had significant impacts on the amounts of total microbial, Gram-positive bacterial, and actinomycic PLFAs, but not on the amounts of total bacterial, Gram-negative bacterial, and fungal PLFAs. There were significant differences in alkyl/O-alkyl C in soils among the leaf litter input treatments, but no apparent differences in the proportions of chemical compositions (alkyl, O-alkyl, aromatic, and carbonyl C) in SOC. Soil alkyl/O-alkyl C was significantly related to the amounts of total microbial, and Gram-positive bacterial PLFAs, but not to the chemical compositions of leaf litter. Our findings suggest that changes in forest leaf litter inputs could result in changes in chemical stability of SOC through the altered microbial community composition.


Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells.
Bisphenol-A (BPA) shows proliferative actions in uterus and mammary glands and may influence the development of male and female reproductive tracts in utero or during early postnatal life. Because of its ability to function as an estrogen receptor (ER) agonist, BPA has the potential to disrupt normal endocrine signaling through regulation of ER target genes. Some genes are regulated by both estradiol (E2) and BPA, but those exclusive to either agent have not been described. Using a yeast strain incorporating a vitellogenin A2 ERE-LacZ reporter gene into the genome, we found that BPA induced expression of the reporter in colonies transformed with the ERalpha expression plasmid, illustrating BPA-mediated regulation within a chromatin context. Additionally, a reporter gene transiently transfected into the endometrial cancer (Ishikawa) cell line also showed BPA activity, although at 100-fold less potency than E2. To compare global gene expression in response to BPA and E2, we used a variant of the MCF-7 breast cancer cell line stably expressing HA-tagged ERalpha. Cultures were treated for 3h with an ethanol vehicle, E2 (10(-8)M), or BPA (10(-6)M), followed by isolation of RNA and microarray analysis with the human U95A probe array (Affymetrix, Santa Clara, CA, USA). More than 300 genes were changed 2-fold or more by either or both agents, with roughly half being up-regulated and half down-regulated. A number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFbeta-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. We used quantitative real-time PCR to verify regulation of the HOXC6 gene, which showed decreased expression of approximately 2.5-fold by BPA. These results reveal novel effects by BPA and E2, raising interesting possibilities regarding the role of endocrine disruptors in sexual development.


The parallel process of resistance by clients and therapists to starting groups: a guide for nurses.
Group psychotherapy is well recognized as a treatment modality with a powerful healing capacity. Yet, as experienced group therapists will attest, it is immensely difficult to begin a group. Assembling clients who have sufficiently dealt with their resistance to join a psychotherapy group is a painstaking process. Students in group psychotherapy training programs also find beginning a new group an arduous and frustrating task. The authors have had the benefit of postgraduate group psychotherapy training program to build on the expertise and skills already familiar to the Clinical Nurse Specialist. Our understanding of the parallel process in the resistance to beginning a group grew out of our training experience. We will explore within the parallel process framework some of the factors that make the development of a group psychotherapy practice as complex. Parallels will be drawn between clinician resistance to beginning a new group and client resistance to joining a group.


In Vitro Antihaemolytic Activity.
In this assay, the rat erythrocytes are induced with hydroxyl radical damage by the addition of H2O2. This causes the rupture of the RBC and the contents leak out giving the red colour of the haemoglobin to the medium. Hence, anti-haemolytic activity has been presented here in a brief and easy manner using the rat erythrocytes.


Regulation of immunity and inflammation by hypoxia in immunological niches.
Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.


Efficacy of pharmacists' assessment and intervention based on Screening Tool for Older Persons' Appropriate Prescriptions for Japanese compared with Screening Tool of Older Persons' potentially inappropriate Prescriptions criteria version 2 in older patients with cardiovascular disease.
This study aimed to evaluate the efficacy of pharmacists' assessment and intervention using the Screening Tool for Older Persons' Appropriate Prescriptions for Japanese (STOPP-J) to detect and correct potentially inappropriate medications (PIM) compared with the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP) criteria version 2. A prospective observational study was carried out at a medical unit of Cardiovascular Surgery and Cardiovascular Internal Medicine in a Japanese university hospital involving new inpatients aged ≥65 years prescribed one or more daily medication. Pharmacists detected PIM based on STOPP-J and STOPP criteria version 2, and corrected them with physicians. The number of patients with PIM, the content and changes in PIM were compared between both criteria. Overall, 230 patients were included (mean age 75.4 years, 162 men, mean number of medications 8.3). STOPP-J detected significantly more patients with PIM than STOPP criteria version 2 (122 [53%] vs 75 [33%], P < 0.001). The number of PIM based on STOPP-J was 232, the physicians were recommended to change 61 (26%) and 50 (22%) were changed. Meanwhile, the number of PIM based on STOPP criteria version 2 was 133, the physicians were recommended to change 61 (46%) and 54 (41%) were changed. Several medications detected as PIM using STOPP-J were not detected using STOPP criteria version 2. STOPP-J detected significantly more patients with PIM than STOPP criteria version 2, and pharmacists' assessment and intervention based on STOPP-J were suggested to be effective for detecting and correcting PIM. Geriatr Gerontol Int 2019; 19: 1101-1107.


Translation and validation of the Persian version of the STarT Back Screening Tool in patients with nonspecific low back pain.
To translate the STarT Back Screening Tool (SBT) into Persian and to investigate the psychometric properties of the new version in a group of patients with Non-Specific Low Back Pain (NSLBP). The STarT is a validated questionnaire used for subgrouping LBP patients at three levels of low-, medium-, and high-risk, based on the risk of chronicity. It has previously been translated and validated in different languages. The translation and validation of the original questionnaire were carried out in accordance with the standard guidelines. To approve the construct validity, 295 patients with NSLBP completed a questionnaire package. The package comprised of the STarT, Roland-Morris Disability questionnaire (RMDQ), Tampa Scale for Kinesiophobia (TSK), Coping Strategies Questionnaire (CSQ), and Hospital Anxiety and Depression Scale (HADS). To evaluate test-retest reliability, 35 randomly selected NSLBP patients completed the STarT questionnaire within min. 24-hour interval. Factor analysis confirmed two subscales of the STarT. The Cronbach α was .83 and .81 for the STarT and the subscale, respectively. This questionnaire showed excellent test-retest reliability (ICC = .85) (p < 0.01). The correlations between the STarT and RMDQ, CSQ, TSK, and the two subscales of HADS were estimated to be .81, .70, .71, .74, and .71, respectively. The Area under the Curve was also calculated for 6 items and the range was between .734 and .860. The Persian version of the STarT is reliable and valid, and consistent with the original questionnaire. Therefore, clinicians to subgroup Persian-speaking NSLBP patients can use it.


Ruthenium-Catalyzed Reductive Cleavage of Unstrained Aryl-Aryl Bonds: Reaction Development and Mechanistic Study.
Cleavage of carbon-carbon bonds has been found in some important industrial processes, for example, petroleum cracking, and has inspired development of numerous synthetic methods. However, nonpolar unstrained C(aryl)-C(aryl) bonds remain one of the toughest bonds to be activated. As a detailed study of a fundamental reaction mode, here a full story is described about our development of a Ru-catalyzed reductive cleavage of unstrained C(aryl)-C(aryl) bonds. A wide range of biaryl compounds that contain directing groups (DGs) at 2,2' positions can serve as effective substrates. Various heterocycles, such as pyridine, quinoline, pyrimidine, and pyrazole, can be employed as DGs. Besides hydrogen gas, other reagents, such as Hantzsch ester, silanes, and alcohols, can be employed as terminal reductants. The reaction is pH neutral and free of oxidants; thus a number of functional groups are tolerated. Notably, a one-pot C-C activation/C-C coupling has been realized. Computational and experimental mechanistic studies indicate that the reaction involves a ruthenium(II) monohydride-mediated C(aryl)-C(aryl) activation and the resting state of the catalyst is a η4-coordinated ruthenium(II) dichloride complex, which could inspire development of other transformations based on this reaction mode.


A suprasellar arachnoid cyst resulting from an intraventricular haemorrhage and showing complete resolution following endoscopic fenestration.
We present the case of a premature neonate who developed a large, acquired arachnoid cyst as a consequence of intraventricular haemorrhage. The child was managed with endoscopic fenestration and made an excellent recovery.


Do we really need tranexamic acid in total hip arthroplasty? A meta-analysis of nineteen randomized controlled trials.
Studies have shown that tranexamic acid reduces blood loss and transfusion need in patients undergoing total hip arthroplasty. However, no to date, no study has been large enough to determine definitively whether the drug is safe and effective. We examined whether intravenous tranexamic acid, when compared with placebo, was safe and effective in total hip arthroplasty. The literature search was conducted using the PubMed, Cochrane Library, MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases. Data were evaluated using the generic evaluation tool designed by the Cochrane Bone, Joint and Muscle Trauma Group. Ultimately, 19 randomized controlled trials involving 1,030 patients were included. The use of tranexamic acid significantly reduced total blood loss by a mean of 305.27 mL [95 % confidence interval (CI) -397.66 to -212.89, p < 0.001], intraoperative blood loss by a mean of 86.33 mL(95 % CI -152.29 to -20.37, p = 0.01), postoperative blood loss by a mean of 176.79 mL (95 % CI -236.78 to -116.39, p < 0.001), and "hidden" blood loss by a mean of 152.70 mL (95 % CI -187.98 to -117.42, p < 0.001), resulting in a meaningful reduction in the proportion of patients requiring blood transfusion (odds ratio 0.28, 95 % CI 0.19 to 0.42, p < 0.001). There was no significant difference in occurrence of deep vein thrombosis, pulmonary embolism, or other complications among the study groups, or cost or hospitalization duration. The data from this meta-analysis indicate that intravenous tranexamic acid may reduce blood loss and transfusion need in patients undergoing total hip arthroplasty without increasing the risk of complications. However, high-quality randomized controlled trials are required to validate the results.


Short sleep duration and obesity among children: A systematic review and meta-analysis of prospective studies.
Previous epidemiology studies have demonstrated that short sleep duration may be associated with the development of obesity, although the effects remain controversial. This study aimed to assess epidemiologic evidence systematically on the relation between sleep duration and obesity in children. We searched the Medline, Cochrane Library, EMBASE and Science Citation Index databases and reference lists of the included articles. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using a random-effects model. Fifty cohorts from thirteen studies were included in the pooled analysis. They included 35,540 participants from around the world. In children/adolescents the pooled OR was 1.71 (1.36-2.14; I2=91.3%), the positive association was consistent after omitting any of the studies. In subgroup analyses, the results indicated that the heterogeneity of effect may due to differences in geographical location, cut-off for short sleep duration and definition of obesity/overweight. The publication bias tests indicated a no evidence of publication bias. This meta-analysis provides evidence that short sleep duration in children is associated with a significantly increased risk of obesity. Enough sleep duration is potentially important for the prevention of obesity among children.


Fetal Vascular Ectasia Can be an Artifact of Placental Fixation.
Placentas from outlying hospitals are formalin-fixed en route to our laboratory. We identified that chorionic, stem villus, and umbilical vessels in these fixed placentas are ectatic with greater frequency than in our in-house fresh placentas. We searched our LIS for third trimester placentas using keywords "ectasia" or "ectatic" over a 12-month period. We fixed incoming in-house placentas over a 2-week period for 24-72 hours and tabulated the presence or absence of vascular ectasia as defined by Parast et al, 2008. The LIS search identified 61% of placental cases from outlying hospitals that had ectatic vessels vs 3% of in-house placentas (P < .001). Of 38 placentas fixed in a 2-week period, 45% had ectatic chorionic or stem villus vessels and 21% had umbilical vessel ectasia. In comparison, in the 2 subsequent weeks, 3.8% (P < .001) of fresh placentas had vascular ectasia. These data suggest that large fetal vessels in the placenta become engorged with blood at delivery and, if fixed soon after delivery, remain ectatic and congested when processed for pathology. The identification of artifactual ectasia is important because fetal vessel ectasia can suggest the presence of fetal vascular malperfusion (FVM) if diagnostic signs of FVM are present.


Trace metal accumulation is infrapopulation-dependent in acanthocephalans parasites of the white mullet (Mugil curema) from an estuarine environment of southeastern Brazil coast.
Here, in an estuarine canal in southeast Brazil, we evaluated the potential for trace metal accumulation of the acanthocephalan parasite Floridosentis mugilis, which infects the fish host Mugil curema. The quantities of the trace metals were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS), which was used to analyze samples of the fish's muscle, intestine, and liver as well as the parasites. The parasites and the host's tissues had significantly different trace metal concentrations, according to our data. Furthermore, some metals have quite high bioconcentration factors, including Al, Cr, Ni, and Cd. We also found that the trace metal concentrations in the parasites were impacted by the sizes of the parasitic infrapopulations, with smaller infrapopulations tending to accumulate more metals. This study shows this acanthocephalan species' effective ability to store metals and is the first to investigate metal accumulation using it as a model.


Assortative mixing in spatially-extended networks.
We focus on spatially-extended networks during their transition from short-range connectivities to a scale-free structure expressed by heavy-tailed degree-distribution. In particular, a model is introduced for the generation of such graphs, which combines spatial growth and preferential attachment. In this model the transition to heterogeneous structures is always accompanied by a change in the graph's degree-degree correlation properties: while high assortativity levels characterize the dominance of short distance couplings, long-range connectivity structures are associated with small amounts of disassortativity. Our results allow to infer that a disassortative mixing is essential for establishing long-range links. We discuss also how our findings are consistent with recent experimental studies of 2-dimensional neuronal cultures.


Giardia intestinalis thymidine kinase is a high-affinity enzyme crucial for DNA synthesis and an exploitable target for drug discovery.
Giardiasis is a diarrheal disease caused by the unicellular parasite Giardia intestinalis, for which metronidazole is the main treatment option. The parasite is dependent on exogenous deoxyribonucleosides for DNA replication and thus is also potentially vulnerable to deoxyribonucleoside analogs. Here, we characterized the G. intestinalis thymidine kinase, a divergent member of the thymidine kinase 1 family that consists of two weakly homologous parts within one polypeptide. We found that the recombinantly expressed enzyme is monomeric, with 100-fold higher catalytic efficiency for thymidine compared to its second-best substrate, deoxyuridine, and is furthermore subject to feedback inhibition by dTTP. This efficient substrate discrimination is in line with the lack of thymidylate synthase and dUTPase in the parasite, which makes deoxy-UMP a dead-end product that is potentially harmful if converted to deoxy-UTP. We also found that the antiretroviral drug azidothymidine (AZT) was an equally good substrate as thymidine and was active against WT as well as metronidazole-resistant G. intestinalis trophozoites. This drug inhibited DNA synthesis in the parasite and efficiently decreased cyst production in vitro, which suggests that it could reduce infectivity. AZT also showed a good effect in G. intestinalis-infected gerbils, reducing both the number of trophozoites in the small intestine and the number of viable cysts in the stool. Taken together, these results suggest that the absolute dependency of the parasite on thymidine kinase for its DNA synthesis can be exploited by AZT, which has promise as a future medication effective against metronidazole-refractory giardiasis.


Addressing the Need for a Better Understanding of Foot and Ankle Pathology Relevant to the Adolescent Athlete.
Foot and ankle pathology in the adolescent athlete is a growing area of basic science, translational, and clinical research [...].


Leukotic spread: an unusual tumor transition.
This report concerns a case of lung cancer, which is of interest because it proves that an epithelial tumor is capable of spreading in a manner morphologically identical to that of a malignant lymphoreticular tumor.


Biochar amendment controlled bacterial wilt through changing soil chemical properties and microbial community.
Long-term continuous cropping has led to epidemic of bacterial wilt disease in Southern China. Bacterial wilt disease is caused by Ralstonia solanacearum and difficult to control. In order to control bacterial wilt, rice hull biochar was applied to soil with different doses (0, 7.5, 15, 30 and 45 t ha-1) in a field trial. After three years, the influence of biochar on soil properties, incidence of bacterial wilt and microbial community were characterized. Biochar amendment significantly suppressed bacterial wilt through changing soil chemical properties and microbial composition. Compared with control, disease incidence and index of biochar amendments (7.5, 15, 30, and 45 t ha-1) significantly decreased. Disease incidence and index of biochar amendment (15 t ha-1) were the lowest. Compared to the unamended control, contents of soil organic matter in biochar amendments (15, 30 t ha-1), available nitrogen in biochar amendment (15 t ha-1), and urease activity in biochar amendments (7.5, 15 t ha-1) significantly increased. Biochar amendments (15, 30, and 45 t ha-1) increased the relative abundances of potential beneficial bacteria (Aeromicrobium, Bacillus, Bradyrhizobium, Burkholderia, Chlorochromatium, Chthoniobacter, Corynebacterium, Geobacillus, Leptospirillum, Marisediminicola, Microvirga, Pseudoxanthomonas, Telmatobacter). Biochar amendments (7.5, 30, and 45 t ha-1) reduced the relative abundances of denitrifying bacteria (Noviherbaspirillum, Reyranella, Thermus). Biochar amendments (7.5, 15, and 45 t ha-1) significantly decreased pathogen Ralstonia abundance. Overall, application of biochar effectively controlled bacterial wilt through sequestering more carbon and nitrogen, enriching specific beneficial bacteria and decreasing pathogen abundance. This study revealed the potential of biochar in control of bacterial wilt.


Molecular Cloning and Differential Gene Expression Analysis of 1-Deoxy-D-xylulose 5-Phosphate Synthase (DXS) in Andrographis paniculata (Burm. f) Nees.
Andrographis paniculata 1-deoxy-D-xylulose-5-phosphate synthase (ApDXS) gene (GenBank Accession No MG271749.1) was isolated and cloned from leaves for the first time. Expression of ApDXS gene was carried out in Escherichia coli Rosetta cells. Tissue-specific ApDXS gene expression by quantitative RT-PCR (qRT-PCR) revealed maximum fold expression in the leaves followed by stem and roots. Further, the differential gene expression profile of Jasmonic acid (JA)-elicited in vitro adventitious root cultures showed enhanced ApDXS expression compared to untreated control cultures. A. paniculata 3-hydroxy-3-methylglutaryl-coenzyme A reductase (ApHMGR) gene expression was also studied where it was up-regulated by JA elicitation but showed lower expression compared to ApDXS. The highest expression of both genes was found at 25 µm JA elicitation followed by 50 µm. HPLC data indicated that the transcription levels were correlated with increased andrographolide accumulation. The peak level of andrographolide accumulation was recorded at 25 μM JA (9.38-fold) followed by 50 µM JA (7.58-fold) in elicitation treatments. The in silico generated ApDXS 3D model revealed 98% expected amino acid residues in the favored and 2% in the allowed regions of the Ramachandran plot with 92% structural reliability. Further, prediction of conserved domains and essential amino acids [Arg (249, 252, 255), Asn (307) and Ser (247)] involved in ligand/inhibitor binding was carried out by in silico docking studies. Our present findings will generate genomic information and provide a blueprint for future studies of ApDXS and its role in diterpenoid biosynthesis in A. paniculata.


A physiologically relevant culture platform for long-term studies of in vitro gingival tissue.
There is a clinical need to understand the etiologies of periodontitis, considering the growing socio-economic impact of the disease. Despite recent advances in oral tissue engineering, experimental approaches have failed to develop a physiologically relevant gingival model that combines tissue organization with salivary flow dynamics and stimulation of the shedding and non-shedding oral surfaces. Herein, we develop a dynamic gingival tissue model composed of a silk scaffold, replicating the cyto-architecture and oxygen profile of the human gingiva, along with a saliva-mimicking medium that reflected the ionic composition, viscosity, and non-Newtonian behavior of human saliva. The construct was cultured in a custom designed bioreactor, in which force profiles on the gingival epithelium were modulated through analysis of inlet position, velocity and vorticity to replicate the physiological shear stress of salivary flow. The gingival bioreactor supported the long-term in vivo features of the gingiva and improved the integrity of the epithelial barrier, critical against the invasion of pathogenic bacteria. Furthermore, the challenge of the gingival tissue with P. gingivalis lipopolysaccharide, as an in vitro surrogate for microbial interactions, indicated a greater stability of the dynamic model in maintaining tissue homeostasis and, thus, its applicability in long-term studies. The model will be integrated into future studies with the human subgingival microbiome to investigate host-pathogen and host-commensal interactions. STATEMENT OF SIGNIFICANCE: The major societal impact of human microbiome had reverberated up to the establishment of the Common Fund's Human Microbiome Project, that has the intent of studying the role of microbial communities in human health and diseases, including periodontitis, atopic dermatitis, or asthma and inflammatory bowel disease. In addition, these chronic diseases are emergent drivers of global socioeconomic status. Not only common oral diseases have been shown to be directly correlated with several systemic conditions, but they are differentially impacting some racial/ethnic and socioeconomic groups. To address this growing social disparity, the development of in vitro gingival model would provide a time and cost-effective experimental platform, able to mimic the spectrum of periodontal disease presentation, for the identification of predictive biomarkers for early-stage diagnosis.


[Hypothyroidism with leading myopathy in a patient suffering from systemic lupus erythematosus and Hashimoto's thyroiditis].
Muscle weakness with or without elevation of serum creatine kinase (CK) is a common complaint, which is a diagnostic challenge for the treating physician. Either infectious, neurologic, iatrogenic, genetic or endocrinologic and rheumatologic causes should be considered. A 66-year-old female patient with a history of systemic lupus erythematosus (SLE) currently in remission presented herself with muscle weakness, myalgias and elevated CK (1618 U/l) to the authors' hospital. A flare of the SLE as cause of the symptoms could be ruled out diagnostically. Instead, a Hashimoto's-associated hypothyroidism was detected. Treatment with L-thyroxine resulted in rapid improvement of symptoms, and CK levels returned to normal. Although a myositis can be observed in SLE patients suffering from muscle weakness with elevated CK levels, a careful evaluation is warranted. In the presented case, hypothyroidism due to Hashimoto's thyroiditis was the real culprit of the symptoms.


Absence of expression of a human endogenous retrovirus is correlated with choriocarcinoma.
We examined the RNA expression of a human endogenous provirus, termed ERV3, in 170 human tissue and cell specimens. The highest expression was found in normal placental chorionic villi as mRNAs of 9, 7.3, and 3.5 kb. The 7.3-kb RNA species was found only in the placenta. ERV3 mRNA was expressed in most other normal and malignant tissues at a level which was 2-10% of that seen in placenta. However, several tissues and tumor cell lines had higher transcriptional levels, equal to 10-60% of the placental level. In contrast, an almost complete abrogation of ERV3 mRNA expression was noted in choriocarcinoma cell lines and in an invasive hydatidiform mole tissue biopsy. This abrogation was not linked to deletions or rearrangements of the ERV3 genome. It appeared to be unassociated with methylation because the ERV3 provirus was similarly methylated in the DNA of placental chorionic villi and choriocarcinoma cells, and ERV3 transcription in choriocarcinoma cells was not induced by 5-azacytidine. These results suggest that the loss of ERV3 mRNA expression is associated with susceptibility to choriocarcinoma.


Hyperactivity, hyper-reactivity, and sensorimotor deficits induced by low doses of the N-methyl-D-aspartate non-competitive channel blocker MK801.
Three doses of MK801 (0.05 mg/kg, 0.3 mg/kg and 1.0 mg/kg) were given systemically to adult male rats, which were then tested on a battery of previously learned, reactive and spontaneous behaviors. Hyperactivity, hyper-reactivity, reductions in rearing behavior and deficits in tongue extension were found at the 0.05 mg/kg dose. Similar, but more severe results were found at the 0.3 mg/kg dose, with the addition of difficulties in climbing, balancing on a beam, and abnormalities in orienting to tactile stimuli. A number of tasks could not be performed at the 1.0 mg/kg dose including tongue extension, orienting, balancing on a beam, and climbing. Additionally, abnormal postures, gaits, and swimming behaviors were observed at this dose. These results characterize the behavioral effects of MK801 as a syndrome of hyperactivity, hyper-reactivity, and sensorimotor deficits. Evidence of this syndrome was present at all three doses, including the 0.05 mg/kg dose, which previously has been claimed to induce deficits similar to hippocampal lesions. Learning literature employing MK801 is discussed in the context of the behavioral deficits found in this study.


2-(N-acyl) and 2-N-acyl-N(6)-substituted analogues of adenosine and their affinity at the human adenosine receptors.
A series of 2-(N-acyl) and 2-(N-acyl)-N(6)-alkyladenosine analogues have been synthesized from the intermediate 2-amino-6-chloroadenosine derivatives (2b and 7) and evaluated for their affinity at the human A(1), A(2A), and A(3) receptors. We found that 2-(N-acyl) derivatives of adenosine showed relatively low affinity at A(2A) and A(3) receptors, while the N(6)-cyclopentyl substituent in 4h and 4i induced high potency [A(1) (K(i))=20.7 and 31.8 nM respectively] at the A(1) receptor and resulted therefore in increased selectivity for this subtype. The general synthetic methods and their binding studies are presented herein.


Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: implications for studies concerned with quantifying epicatechin bioavailability.
Epicatechin is a widely consumed dietary flavonoid and there is substantial evidence that it contributes to the health benefits reported for flavanol-rich cocoa products including dark chocolate. Numerous reports have described the appearance of epicatechin and epicatechin phase-2 conjugates (sulfates and glucuronides of epicatechin and methylepicatechin) in blood and urine samples of subjects following ingestion of epicatechin. The most widely reported method of quantifying total epicatechin in plasma and urine samples involves hydrolysis with a mixture of β-glucuronidase and sulfatase to convert the conjugates to epicatechin aglycone which is subsequently quantified. We observed a lack of hydrolysis of epicatechin sulfates and methylepicatechin sulfates using commercial sulfatases and investigated this further. Samples of urine or plasma from subjects who had consumed epicatechin were subjected to enzyme hydrolysis and then analysed using LC-MS/MS, or analysed without enzyme hydrolysis. Attempts to increase the extent of hydrolysis of epicatechin conjugates were made by increasing the amount of enzyme, hydrolysis pH and length of incubations, and using alternative sources of enzyme. The standard hydrolysis conditions failed to hydrolyse the majority of epicatechin sulfates and methylepicatechin sulfates. Even when the quantity of enzyme and incubation period was increased, the pH optimised, or alternative sources of sulfatases were used, epicatechin monosulfates and methylepicatechin monosulfates remained as major peaks in the chromatograms of the samples. An assessment of literature data strongly suggested that the majority of reports where enzyme hydrolysis was used had significantly underestimated epicatechin bioavailability in humans. Methods for quantifying epicatechin concentrations in blood and urine need to take account of the lack of hydrolysis of (methyl)epicatechin-sulfates, for example by quantifying these directly using LC-MS/MS.


Hypoalgesia induced by microinjection of a norepinephrine antagonist in the raphe magnus: reversal by intrathecal administration of a serotonin antagonist.
Microinjection of phentolamine in the nucleus raphe magnus produces hypoalgesia as assessed by both the tail flick and hot plate tests. The elevation of tail flick latency appears to result from activation of serotonergic raphe-spinal projections, while the elevation of hot plate latency appears to be mediated by activation of non-serotonergic raphe-spinal neurons and/or by activation of raphe neurons which project to supraspinal nuclei.


Bipolar I affective disorder: predictors of outcome after 15 years.
Robust predictors of long-term outcome in bipolar affective disorder would have substantial importance to both clinicians and researchers. Such predictors are not available, however, perhaps because of the limitations of previous efforts to find them. In this study, 113 patients with bipolar affective disorder were followed semiannually for 5 years and annually for a subsequent 15 years. Of these, 23 (20.4%) had a poor long-term outcome indicated by the presence of mania or major depressive disorder throughout the 15th year. Among the baseline demographic and clinical variables tested, only active alcoholism and low levels of optimum functioning in the preceding 5 years characterized poor outcome patients. The persistence of depressive symptoms in the first 2 years of follow-up predicted depressive symptoms 15 years later but the early persistence of manic symptoms seemed to have no predictive value. A regression analysis eliminated alcoholism as an independent predictor. Thus, only poor optimal functioning in the 5 years before baseline assessment, and the persistence of depressive symptoms in the two subsequent years, were independently associated with poor, long-term prognosis. Patients were recruited at tertiary care centers and sampling was therefore biased toward greater severity and chronicity. As is true of all naturalistic studies of course, treatment was not controlled. These findings suggest the existence of a poor outcome, depression-prone subtype of bipolar affective disorder.


Development and analysis of quality assessment tools for different types of patient information - websites, decision aids, question prompt lists, and videos.
Our working group has developed a set of quality assessment tools for different types of patient information material. In this paper we review and evaluate these tools and their development process over the past eight years. We compared the content and structure of quality assessment tools for websites, patient decision aids (PDAs), question prompt lists (QPLs), and videos. Using data from their various applications, we calculated inter-rater concordance using Kendall's W. The assessment tools differ in content, structure and length, but many core aspects remained throughout the development over time. We found a relatively large variance regarding the amount of quality aspects combined into one item, which may influence the weighting of those aspects in the final scores of evaluated material. Inter-rater concordance was good in almost all applications of the tool. Subgroups of similar expertise showed higher concordance rates than the overall agreement. All four assessment tools are ready to be used by people of different expertise. However, varying expertise may lead to some differences in the resulting assessments when using the tools. The lay and patient perspective needs to be further explored and taken into close consideration when refining the instruments.


Factors affecting stresses in cortical bone around miniscrew implants: a three-dimensional finite element study.
To evaluate various types of stress in cortical bone around miniscrew implants using finite element analysis. Twenty-six three-dimensional assemblies of miniscrew models placed in alveolar bone blocks were constructed using Abaqus (Dassault Systèmes Simulia Corp, Providence, RI), a commercial finite element analysis software package. The model variables included implant design factors and bone-related factors. All miniscrew implants were loaded in the mesial direction with a linear force equal to 2 N. Peak von Mises and principal stress values in cortical bone were compared between the different models for each factor. The results demonstrated that some factors affected the stresses in bone (implant diameter, implant head length, thread size, and elastic modulus of cancellous bone), while other factors did not (thread shape, thread pitch, and cortical bone thickness). Miniscrew implant diameter, head length, and thread size as well as the elastic modulus of cancellous bone affect the stresses in cortical bone layer surrounding the miniscrew implant and may therefore affect its stability.


Socioeconomic inequalities in health status and survival: a cohort study in Rome.
To analyse the association between individual and contextual socioeconomic position (SEP) with health status and to investigate the role of SEP and baseline health status on survival. Cross-sectional and cohort study. Rome, Italy. We selected the 25-99 year-olds included in the Rome 2011 census cohort. As a measure of health status on the census reference date (09 October 2011), we used the presence of chronic or rare conditions from the Disease-Related Co-payment Exemption Registry, a database implemented to provide free care to people with chronic or rare diseases. We used logistic regression to analyse the association between both individual (educational attainment) and contextual SEP (neighbourhood real estate price quintiles) with baseline health status. We analysed the role of SEP and the presence of chronic or rare conditions on 5-year survival (until 31 December 2016) using accelerated failure time models with Weibull distribution, reporting time ratios (TRs; 95% CI). In middle-aged, subjects with low SEP (either individual or contextual) had a prevalence of chronic conditions comparable with the prevalence in high SEP individuals 10 years older. Adjusted logistic models confirmed the direct association between SEP and baseline health status in both women and men. The lowest educated were up to 67% more likely to have a chronic condition than the highest educated, while the difference was up to 86% for lowest versus highest contextual SEP. Low SEP and the presence of chronic conditions were associated with shorter survival times in both sexes, lowest versus highest educated TR was TR=0.79 for women (95% CI: 0.77 to 0.81) and TR=0.71 for men (95% CI: 0.70 to 0.73). The contextual SEP shrunk survival times by about 10%. Inequalities were present in both baseline health and survival. The association between SEP and survival was independent of baseline health status.


Revision of the pulchella-group of Alona s. lato leads to its translocation to Ovalona Van Damme et Dumont, 2008 (Branchiopoda: Anomopoda: Chydoridae).
The pulchella-group of Alona s.l. (Cladocera: Anomopoda: Chydoridae) is transferred to Ovalona Van Damme et Dumont, 2008, and an emended diagnosis is provided. Ovalona meridionalis (Sinev, 2006) is removed from Ovalona due to differences in thoracic limb morphology. At the moment, Ovalona consists of 17 species, and is the largest natural genus of Aloninae. A key for the world fauna and diagnosis for all species is provided. The morphology of O. nuragica (Margaritora, 1971) is studied for the first time. The position of Ovalona within subfamily Aloninae and the distribution of the genus are discussed.


Alcohol consumption and socioeconomic status associated with the risk of kidney cancer in a large Australian cohort study.
Studies have shown an inverse association between alcohol consumption and kidney cancer risk. We postulate that this inverse association may be further influenced by other risk factors. We used an Australian cohort, the 45 and Up Study, recruited between 2005 and 2009 to investigate the association between alcohol consumption, and other potential risk factors and kidney cancer incidence. The median follow-up was 5.4 years. Of the 267,357 participants aged ≤45 years living in New South Wales, 497 were diagnosed with kidney cancer. There was a significant inverse association between alcohol consumption and risk of kidney cancer (P = .027), and a significant inverse dose-response relationship (P = .011). There was a significant interaction between alcohol consumption and socioeconomic status (P interaction = .001). Participants residing in higher socioeconomic areas (the two most advantaged quintiles) who consumed 8-10 drinks or greater than 10 drinks per week, respectively, had a lower risk of kidney cancer compared to the group who consumed 1-4 drinks per week (hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, HR 0.51, 95% CI 0.31-0.83) with a dose-response trend of HR 0.62 (95% CI 0.42-0.93) per 7 drink increase in weekly alcohol consumption. There could be an inverse association between alcohol consumption and risk in those residents in higher socioeconomic areas.


Application of an asymmetrical flow field-flow fractionation channel to the separation and characterization of proteins, plasmids, plasmid fragments, polysaccharides and unicellular algae.
The asymmetrical flow field-flow fractionation channel has been improved by introduction of a different sample loading method, downstream central injection, which reduces sample relaxation and focusing time considerably and allows the concentrations of material in the channel, thereby enabling the loading of very large sample volumes. The performance of the channel was demonstrated by the separation of a protein from its dimer, retention of nucleic acids, i.e., plasmids and enzymatically cleaved plasmids, hyaluronate and unicellular algae.


Reciprocal Schwann cell-axon interactions.
This article describes the reciprocal interactions between neurones and Schwann cells with particular reference to the role of growth factors and neurokines as signalling molecules between these cells and of the extracellular matrix as a conduit for such signalling. Major recent advances have identified molecules produced by neurones that are responsible for Schwann cell proliferation, as well as some of the Schwann cell factors regulating the expression of molecules shown to play an important role in neuronal survival and differentiation.


Controlled protein release from monodisperse biodegradable double-wall microspheres of controllable shell thickness.
Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-μm thick PDLL shell, an extended period of constant-rate release was achieved.