A qualitative study protocol of ageing carers' caregiving experiences and their planning for continuation of care for their immediate family members with intellectual disability.
Understanding the difficulties and needs of the family carers in taking care of a person with ID can facilitate the development of appropriate intervention programmes and services to strengthen their caring capacity and empower them to continue with their caring roles. This study aims to explore ageing family carers' caregiving experiences and the plans they have to provide care for themselves and their ageing children with mild or moderate intellectual disability (ID). A constructivist grounded theory will be used to interview around 60 carers who have a family member with mild or moderate ID and attending sheltered workshops in Hong Kong. Constant comparative analysis methods will be used for data analysis. The theory will capture family caregiving experiences and the processes of carers in addressing caregiving needs, support received and plans to continue to provide care for themselves and their relatives with ID in their later life. New insights into the emerging issues, needs and plights of family caregivers will be provided to inform the policies and practices of improving the preparation for the ageing process of the persons with ID, and to better support the ageing carers. The theoretical framework that will be generated will be highly practical and useful in generating knowledge about factors that influence the caregiving processes; and, tracking the caregiving journey at different time-points to clearly delineate areas to implement practice changes. In this way, the theoretical framework will be highly useful in guiding timely and appropriate interventions to target at the actual needs of family carers as they themselves are ageing and will need to continue to take care of their family members with ID in the community.


A novel protein, Xenopus p20, influences the stability of MeCP2 through direct interaction.
MeCP2 is the founder member of a family of methyl-CpG-binding proteins able to repress transcription from methylated DNA. To date, MeCP2 action seems to involve the delivery on modified DNA of histone deacetylase activity, followed by histone methylating activity. It has been recently demonstrated that MECP2 mutations cause Rett syndrome, a childhood neurological disorder that represents one of the most common causes of mental retardation in females. Here we show that a novel Xenopus laevis protein of 20 kDa, p20, is able to interact in vivo and in vitro with MeCP2. The p20 sequence revealed that it belongs to the family of the WAP (whey acidic protein) proteins, often functioning as a protease inhibitor. Therefore, we asked whether the p20 can influence the MeCP2 half-life. We demonstrate that, indeed, the xp20 not only can significantly increase the stability of an exogenously expressed MeCP2 in Xenopus oocytes but also can stabilize the human endogenous MeCP2. The capability of the mammalian methyl-CpG-binding protein to interact with p20 is confirmed by co-immunoprecipitation experiments performed overexpressing the WAP protein. Glutathione S-transferase pull-down assays reveal that the MeCP2 residues localized between the methyl-binding domain and the transcriptional repression domain is the primary interaction surface. Our data suggest that regulation of MeCP2 metabolism might be of relevant importance; in accordance with this, previous results have shown that some Rett syndrome mutations are characterized by a decrease in MeCP2 stability.


The Effect of dry Needling in Chronic Stroke with a complex Network Approach: A Case Study.
Background: Dry Needling (DN) has been demonstrated to be effective in improving sensorimotor function and spasticity in patients with chronic stroke. Electroencephalogram (EEG) has been used to analyze if DN has effects on the central nervous system of patients with stroke. There are no studies on how DN works in patients with chronic stroke based on EEG analysis using complex networks. Objective: The aim of this study was to assess how DN works when it is applied in a patient with stroke, using the graph theory. Methods: One session of DN was applied to the spastic brachialis muscle of a 62-year-old man with right hemiplegia after stroke. EEG was used to analyze the effects of DN following metrics that measure the topological configuration: 1) network density, 2) clustering coefficient, 3) average shortest path length, 4) betweenness centrality, and 5) small-worldness. Measurements were taken before and during DN. Results: An improvement of the brain activity was observed in this patient with stroke after the application of DN, which led to variations of local parameters of the brain network in the delta, theta and alpha bands, and inclined towards those of the healthy control bands. Conclusions: This case study showed the positive effects of DN on brain network of a patient with chronic stroke.


Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity.
XPC-hHR23B protein complex is specifically involved in nucleotide excision repair (NER) of DNA lesions on transcriptionally inactive sequences as well as the nontranscribed strand of active genes. Here we demonstrate that not only highly purified recombinant hHR23B (rhHR23B) but also a second human homolog of the Saccharomyces cerevisiae Rad23 repair protein, hHR23A, stimulates the in vitro repair activity of recombinant human XPC (rhXPC), revealing functional redundancy between these human Rad23 homologs. Coprecipitation experiments with His-tagged rhHR23 as well as sedimentation velocity analysis showed that both rhHR23 proteins in vitro reconstitute a physical complex with rhXPC. Both complexes were more active than free rhXPC, indicating that complex assembly is required for the stimulation. rhHR23B was shown to stimulate an early stage of NER at or prior to incision. Furthermore, both rhHR23 proteins function in a defined NER system reconstituted with purified proteins, indicating direct involvement of hHR23 proteins in the DNA repair reaction via interaction with XPC.


Rapid Weight Loss Practices in Elite Kickboxers.
The aim of this observational cross-sectional survey was to determine the prevalence of rapid weight loss (RWL) in elite kickboxers. Kickboxers (61 males; age = 24.2 ± 4.6 years, weight = 73.9 ± 12.8 kg, and height = 179.2 ± 7.9 cm) from eight European countries completed a Rapid Weight Loss Questionnaire regarding prevalence, magnitude, and methods of RWL. All athletes (100%) were practicing RWL before the competition with a Rapid Weight Loss Questionnaire score of 52.4 ±12.9. Most kickboxers 'usually lose between 2% and 5% of their body mass, whereas ∼30% lose between 6% and 8%. However, it is alarming that almost 30% reported cutting 10% of body weight or more sometime during their kickboxing career. Almost half of the athletes always practice gradual dieting (45.9%) and increased exercising (44.3%) to reduce body mass. Kickboxers usually reduce weight three to four times during a year, usually 7-15 days before a competition. More than a third (34.4%) started with RWL practice under the age of 17. There was no significant difference between weight divisions in weight management behaviors (p = .5, F = 0.6; η2 = .0) and no relation between the main characteristics of elite kickboxing athletes and the total RWL score. In conclusion, RWL practices in kickboxing athletes are somewhat specific and different when compared with other combat sports, which can be explained by greater number of weight classes and specific weigh-in protocol.


Sex estimation from sacrum and coccyx with discriminant analyses and neural networks in an equally distributed population by age and sex.
Sex estimation is an essential step in the process of the identification of the skeletal remains in forensic anthropology since it reduces the number of possible matches by half. In this study, sex estimation with 21 sacral and coccygeal metric parameters obtained from Computerized Tomography images of a Turkish population which consists of 480 patients that are equalized according to their sexes and ages, is performed. Univariate discriminant analysis, linear discriminant function analysis, stepwise discriminant function analysis, and multilayer perceptron neural networks are used in this study. A maximum of 67.1% accuracy for univariate discriminant analysis, 82.5% for linear discriminant function analysis, 78.8% for stepwise discriminant function analysis, and 86.3% for multilayer perceptron neural networks, were achieved. Although it does not reach an acceptable accuracy rate of 95% or more for sacrum and coccyx, sex estimation with neural networks is a promising field of research in corpses where identification is otherwise not possible, and further studies with other bones and with new techniques might give useful information.


Renal denervation in comparison with intensified pharmacotherapy in true resistant hypertension: 2-year outcomes of randomized PRAGUE-15 study.
The randomized, multicentre study compared the efficacy of renal denervation (RDN) versus spironolactone addition in patients with true resistant hypertension. We present the 24-month data. A total of 106 patients with true resistant hypertension were enrolled in this study: 52 patients were randomized to RDN and 54 patients to the spironolactone addition, with baseline SBP of 159 ± 17 and 155 ± 17 mmHg and average number of drugs 5.1 and 5.4, respectively. Two-year data are available in 86 patients. Spironolactone addition, as crossover after 1 year, was performed in 23 patients after RDN, and spironolactone addition followed by RDN was performed in five patients. Similar and comparable reduction of 24-h SBP after RDN or spironolactone addition after randomization was observed, 9.1 mmHg (P = 0.001) and 10.9 mmHg (P = 0.001), respectively. Similar decrease of office blood pressure (BP) was observed, 17.7 mmHg (P < 0.001) versus 14.1 mmHg (P < 0.001), whereas the number of antihypertensive drugs did not differ significantly between groups. Crossover analysis showed nonsignificantly better efficacy of spironolactone addition in 24-h SBP and office SBP reduction than RDN (3.7 mmHg, P = 0.27 and 4.6 mmHg, P = 0.28 in favour of spironolactone addition, respectively). Meanwhile, the number of antihypertensive drugs was significantly increased after spironolactone addition (+0.7, P = 0.001). In the settings of true resistant hypertension, spironolactone addition (if tolerated) seems to be of better efficacy than RDN in BP reduction over a period of 24 months. However, by contrast to the 12-month results, BP changes were not significantly greater.


Immune ligands for cytotoxic T Lymphocytes (CTLS) in cancer stem cells (CSCS).
The immune system has come to the forefront of cancer therapeutics in recent years with the success of immune blockade inhibitors in a variety of cancers whose list is increasing with a quick pace. Despite the efficacy of these drugs across a significant part of the cancer spectrum, responses are still seen only in a minority of patients, that implies that most patients are refractory or promptly develop resistance to these agents. Mechanisms of this resistance are important to decipher as this knowledge may lead to the introduction of additional therapies or manipulations to modulate resistance. The cancer stem cell theory stipulates that a minority of cancer cells in a given tumor are responsible for self-renewal and bulk tumor propagation. These cells, in most instances, are rare and less proliferative but give rise to highly proliferative progeny. In addition, they are, in general, resistant to therapies and endowed with metastatic potential through a process called EMT (Epithelial to Mesenchymal Transition). Cancer stem cells resistance to treatments may relate to inherent insensitivity to external apoptotic stimuli and, thus, may extend to immune therapies by inhibiting the actions of Cytotoxic T Lymphocytes (CTLs) in the tumor micro-environment. This paper examines available data on expression and regulation of immune co-modulatory (co-stimulatory and co-inhibitory) ligands on cancer stem cells in order to devise strategies to circumvent resistance.


[Flow cytofluorometric DNA analysis in fresh bladder specimens and its correlations between cytology and mitotic index].
From 1986 to 1987, cell materials of 50 patients with a suspicious history of bladder tumor were determined by flow cytofluorometric DNA measurement and compared with conventional cytogenetic analysis in the institution. The frequency of DNA aneuploid was found 47.6 per cent positive in 42 consecutive cases investigated by means of flow cytometry whereas in 47 cases by cytology and 42 cases by mitotic index (MI) profile a comparable 44.7% and 52.5% of positive findings were observed respectively, showing that there was good correlation between flow cytometry and conventional cytology. In a combined analysis of these 3 potential indices for tumor marker a 74 per cent positive rate could be reached and a good consistency of the 3 indices was observed by 69.7%. The study of DNA distribution pattern by FCM would definitely be of clinical significance in daily practice only if a disagreement appears a reevaluation should then be made. Cytological studies require a high level of skill and experience and it is time-consuming with subjective bias, comparing to FCM which sever as a valuable method with much more diagnostic sensitivity, objectivity and rapidity. Flow cytometry is now developed to the point as a particularly valuable adjuvant for bladder tumor detection.


Dietary advanced glycation end products and their role in health and disease.
Over the past 2 decades there has been increasing evidence supporting an important contribution from food-derived advanced glycation end products (AGEs) to the body pool of AGEs and therefore increased oxidative stress and inflammation, processes that play a major role in the causation of chronic diseases. A 3-d symposium (1st Latin American Symposium of AGEs) to discuss this subject took place in Guanajuato, Mexico, on 1-3 October 2014 with the participation of researchers from several countries. This review is a summary of the different presentations and subjects discussed, and it is divided into 4 sections. The first section deals with current general knowledge about AGEs. The second section dwells on mechanisms of action of AGEs, with special emphasis on the receptor for advanced glycation end products and the potential role of AGEs in neurodegenerative diseases. The third section discusses different approaches to decrease the AGE burden. The last section discusses current methodologic problems with measurement of AGEs in different samples. The subject under discussion is complex and extensive and cannot be completely covered in a short review. Therefore, some areas of interest have been left out because of space. However, we hope this review illustrates currently known facts about dietary AGEs as well as pointing out areas that require further research.


Polysomnographic phenotype as a risk factor for cardiovascular diseases in patients with obstructive sleep apnea syndrome: a retrospective cohort study.
Obstructive sleep apnea syndrome (OSAS) is associated with the development of cardiovascular diseases caused by hypoxemia during sleeping. We classified OSAS phenotypes based on polysomnographic findings and aimed to evaluate that the unique phenotypes would be differentially associated with risk of cardiovascular disease. This retrospective and observational study assessed adult patients who underwent polysomnography at the Wonju Severance Christian Hospital from November 2008 to February 2018. The OSAS phenotypes were classified as apnea-predominant, hypopnea-predominant, and respiratory effort-related arousal (RERA)-predominant based on the polysomnography results. The polysomnographic data were collected and analysed, and clinical features such as medical history and comorbidities were assessed by a review of the electronic medical records. A total of 860 adult patients were classified as apnea-predominant (n=220), hypopnea-predominant (n=119), or RERA-predominant (n=275). The hypopnea-predominant group had significantly higher rates of hyperlipidaemia (P<0.001), heart failure (15.5%, P<0.001), and coronary artery disease (20.9%, P=0.005) than the other groups. After classifying the patients according to severity of the hypopnea index, logistic regression analyses adjusted for age, sex, and smoking history revealed that the hypopnea index increased the risk for coronary artery disease and heart failure. The hypopnea-predominant group would be a specific phenotype that has a differential association with the risks for coronary artery disease and heart failure.


Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.
The directed study of the functional proteome in colorectal cancer (CRC) has identified critical protein markers and signaling pathways; however, the prognostic relevance of many of these proteins remains unclear. We determined the prognostic implications of the functional proteome in 263 CRC tumor samples from patients treated at MD Anderson Cancer Center (MDACC) and 462 patients from The Cancer Genome Atlas (TCGA) to identify patterns of protein expression that drive tumorigenesis. A total of 163 validated proteins were analyzed by reverse phase protein array (RPPA). Unsupervised hierarchical clustering of the tumor proteins from the MDACC cohort was performed, and clustering was validated using RPPA data from TCGA CRC. Cox regression was used to identify predictors of tumor recurrence. Clustering revealed dichotomization, with subtype A notable for a high epithelial-mesenchymal transition (EMT) protein signature, while subtype B was notable for high Akt/TSC/mTOR pathway components. Survival data were only available for the MDACC cohort and were used to evaluate prognostic relevance of these protein signatures. Group B demonstrated worse relapse-free survival (hazard ratio 2.11, 95% confidence interval 1.04-4.27, p = 0.039), although there was no difference in known genomic drivers between the two proteomic groups. Proteomic grouping and stage were significant predictors of recurrence on multivariate analysis. Eight proteins were found to be significant predictors of tumor recurrence on multivariate analysis: Collagen VI, FOXO3a, INPP4B, LcK, phospho-PEA15, phospho-PRAS40, Rad51, phospho-S6. CRC can be classified into distinct subtypes by proteomic features independent of common oncogenic driver mutations. Proteomic analysis has identified key biomarkers with prognostic importance, however these findings require further validation in an independent cohort.


The influence of cognitive reserve on psychosocial and neuropsychological functioning in bipolar disorder.
Cognitive reserve (CR) refers to the hypothesized capacity of an adult brain to cope with brain pathology in order to minimize symptomatology. CR was initially investigated in dementia and acute brain damage, but it is being applied to other neuropsychiatric conditions. The present study aims at examining the fit of this concept to a sample of euthymic bipolar patients compared with healthy controls in order to investigate the role of CR in predicting psychosocial and cognitive outcome in bipolar disorder (BD). The sample included 101 subjects: 52 patients meeting DSM-IV-TR criteria for BD type I or II and 49 healthy controls (HC) matched for age and gender. They were all assessed with a cognitive battery tapping into executive and memory functioning. CR was obtained using three different proxies: education-occupation, leisure activities and premorbid IQ. Psychosocial functioning was evaluated by means of the Functioning Assessment Short Test (FAST). MANCOVAs were performed to determine differences in cognitive and functioning variables. Linear regression analyses were carried out to predict neuropsychological and psychosocial outcomes. Euthymic bipolar patients showed worse neuropsychological performance and psychosocial functioning than HC. The linear regression models revealed that CR was significantly predictive of FAST score (β = -0.47, p < 0.0001), Executive Index (β = 0.62, p < 0.0001) and Visual Memory Index (β = 0.44, p = 0.0004), indicating that CR is a significant predictor of cognitive and psychosocial functioning in euthymic bipolar outpatients. Therefore, CR may contribute to functional outcome in BD and may be applied in research and clinical interventions to prevent cognitive and functional impairment.


Experimental evaluation of four airway devices in anaesthetized New Zealand White rabbits.
To compare airway management during induction of anaesthesia, spontaneous ventilation (SV) and controlled mechanical ventilation (CMV), using an endotracheal tube (ETT), laryngeal mask (LM), rabbit-specific supraglottic airway device (v-gel) or facemask (FM). Prospective randomized crossover experiment. Ten New Zealand White rabbits. After premedication, rabbits were randomly allocated to four groups: 1) ETT; 2) LM; 3) v-gel or 4) FM. The required dose of propofol, duration and number of attempts to place an airway device and leakage during SV and CMV at different peak inspiratory pressures (6, 10, 12, 14 and 16 cmH2O) were recorded. Computed tomography (CT) of the head, neck and abdomen were performed before and after CMV. Significantly less propofol and time [2.0±0.5 mg kg-1, 82±34 seconds, p<0.001] were needed to place the FM compared to the three other groups [v-gel 5.1±2.1 mg kg-1, 302±124 seconds; LM 4.8±1.2 mg kg-1, 275±89 seconds; ETT 5.5±1.4 mg kg-1, 315±147 seconds]. A leak > 25% of the tidal volume occurred at the lowest pressure in FM [median (range), 6 (6-8) cmH2O], which was significantly lower than with v-gel [16 (6-no leak at 16) cmH2O], LM [>16 (6-no leak at 16)] or ETT [>16 (no leak at 16) cmH2O] (p<0.001). On CT images, the height and width of the larynx were significantly smaller with v-gel in comparison to FM and LM (p=0.004). A significant increase in the amount of gas in the stomach (p=0.007), but not gastric volume, was detected in FM and LM. The v-gel is a practical alternative to LM and ETT for airway management and CMV, but can compress the larynx. The FM is easily placed, but significant leakage occurs during CMV.


Lavendamycin antitumor agents: structure-based design, synthesis, and NAD(P)H:quinone oxidoreductase 1 (NQO1) model validation with molecular docking and biological studies.
A 1H69 crystal structure-based in silico model of the NAD(P)H:quinone oxidoreductase 1 (NQO1) active site has been developed to facilitate NQO1-directed lavendamycin antitumor agent development. Lavendamycin analogues were designed as NQO1 substrates utilizing structure-based design criteria. Computational docking studies were performed using the model to predict NQO1 substrate specificity. Designed N-acyllavendamycin esters and amides were synthesized by Pictet-Spengler condensation. Metabolism and cytotoxicity studies were performed on the analogues with recombinant human NQO1 and human colon adenocarcinoma cells (NQO1-deficient BE and NQO1-rich BE-NQ). Docking and biological data were found to be correlated where analogues 12, 13, 14, 15, and 16 were categorized as good, poor, poor, poor, and good NQO1 substrates, respectively. Our results demonstrated that the ligand design criteria were valid, resulting in the discovery of two good NQO1 substrates. The observed consistency between the docking and biological data suggests that the model possesses practical predictive power.


Isolation and Synthesis of a Bacterially Produced Inhibitor of Rosette Development in Choanoflagellates.
The choanoflagellate Salpingoeca rosetta is a microbial marine eukaryote that can switch between unicellular and multicellular states. As one of the closest living relatives of animals, this organism has become a model for understanding how multicellularity evolved in the animal lineage. Previously our laboratories isolated and synthesized a bacterially produced sulfonolipid that induces S. rosetta to form multicellular "rosettes." In this study, we report the identification of a bacterially produced inhibitor of rosettes (IOR-1) as well as the total synthesis of this molecule and all of its stereoisomers. Our results confirm the previously noted specificity and potency of rosette-modulating molecules, expand our understanding of the complex chemical ecology between choanoflagellates and rosette-inducing bacteria, and provide a synthetic probe template for conducting further mechanistic studies on the emergence of multicellularity.


Hepatoprotective and antioxidant activity of hydromethanolic extract of Daniella oliveri leaves in carbon tetrachloride-induced hepatotoxicity in rats.
Daniella oliveri is a deciduous plant that is commonly found in savanna and open grassland. Various parts of the plant is used by herbalist in the management of different ailments. The present study aims at investigating the hepatoprotective and antioxidant activity of the methanolic extract of D. oliveri leaves. The hepatoprotective activity was investigated using carbon tetrachloride (CCl4)-induced hepatotoxicity in albino rats. The antioxidant activity was determined using both in vitro (2, 2-diphenyl-1-picrylhydrazine photometric assay) and in vivo (malondialdehyde and catalase level assay) models. The pretreatment with extract (100, 200, and 400 mg/kg) and silymarin (100 mg/kg) produced a significant (p<0.05) dose-dependent increase in hepatoprotective activity when compared with the negative control group. The extract (25-400 μg/mL concentration) produced a concentration-dependent increase in antioxidant activity in 2, 2-diphenyl-1-picrylhydrazine (DPPH) photometric assay. The IC50 of the extract in DPPH photometric assay was 400 μg/mL concentrations. The extract and silymarin showed a significant (p<0.05) dose-dependent increase in catalase level in treated rats when compared with the negative control group. Also, the extract and silymarin produced a significant (p<0.05) dose-dependent decrease in malondialdehyde level in treated rats when compared with the negative control group. The results of the study suggest that D. oliveri leaves has a potent hepatoprotective activity that may be linked to its antioxidant activities and validates its use in the traditional management of liver disorders.


[Effectiveness of the Federal Inspectorate for the Protection of Consumer Rights and Human Welfare in the Novosibirsk Region in 2007 to 2009].
A system for monitoring and analyzing the effectiveness and efficiency of the performance of the Board of the Federal Inspectorate for the Protection of Consumer Rights and Human Welfare in the Novosibirsk Region was introduced into its activities to estimate the provision of the Novosibirsk Region's population with sanitary epidemiological wellbeing in 2007-2009. The introduction of monitoring was ascertained to increase the effectiveness of budgetary fund surveillance and spending, by predicting the effectiveness and choice of priority lines of activities, by increasing the quality of budgetary services rendered in the provision of sanitary and epidemiological well-being to the population.


Why use a mirror to assess visual pursuit in prolonged disorders of consciousness? Evidence from healthy control participants.
Evidence of reliable smooth visual pursuit is crucial for both diagnosis and prognosis in prolonged disorders of consciousness (PDOC). However, a mirror is more likely than an object to elicit evidence of smooth pursuit. Our objective was to identify the physiological and/or cognitive mechanism underlying the mirror benefit. We recorded eye-movements while healthy participants simultaneously completed a visual pursuit task and a cognitively demanding two-back task. We manipulated the stimulus to be pursued (two levels: mirror, ball) and the simultaneous cognitive load (pursuit only, pursuit plus two-back task) within subjects. Pursuit of the reflected-own-face in the mirror was associated with briefer fixations that occurred less uniformly across the horizontal plane relative to object pursuit. Secondary task performance did not differ between pursuit stimuli. The secondary task also did not affect eye movement measures, nor did it interact with pursuit stimulus. Reflected-own-face pursuit is no less cognitively demanding than object pursuit, but it naturally elicits smoother eye movements (i.e. briefer pauses to fixate). A mirror therefore provides greater sensitivity to detect smooth visual pursuit in PDOC because the naturally smoother eye movements may be identified more confidently by the assessor.


[Senile amyloidosis of the heart].
A morphologic study of 376 hearts from individuals who died between 75 and 98 years of age demonstrated senile amyloidosis of the heart in 307 (82%) of the cases, using the Congo red stains for polarized light studies and the thiosine red for luminescent microscopy. The frequency of cardiac amyloidosis detection increased with age, and reached 100% in those above 90. Clinico-anatomical correlations showed repolarization changes to be the most common findings (80%), followed by arrhythmia (over 50%), conductivity disorders and reduced voltage of electrocardiographic waves. Chronic heart failure was less common (about 10%). In most cases, moderately marked coronary atherosclerosis was also found at autopsy. Amyloidosis was thought to be making a more significant contribution towards myocardial lesions, as compared to atherosclerosis, in elderly people above 85 years of age.


Silica-stimulated monocytes release fibroblast proliferation factors identical to interleukin 1. A potential role for interleukin 1 in the pathogenesis of silicosis.
Previous study strongly suggests that silicotic fibrosis is mediated by macrophages and their soluble mediators. The biochemical properties of the mediators involved in silicotic fibrosis, however, are as yet ill defined. The current study, therefore, determined whether human monocyte-macrophages treated with fibrogenic silica dust released factors capable of activating fibroblasts as measured by an increase in fibroblast proliferation. Silica, but not nonfibrogenic diamond dust, stimulated the release of fibroblast proliferation factors. Moreover, the level of fibroblast proliferation activity was comparable with the level of thymocyte proliferation (interleukin-1) activity in the same culture supernatants. The factors responsible for these seemingly diverse activities were found to behave identically when analyzed by gel filtration chromatography, size exclusion chromatography, isoelectrofocusing, ion exchange chromatography, and hydrophobic chromatography. Moreover, the response of these factors to four different proteases and heat (56 degrees C) was also identical, which shows that their comigration on various separation media could not be explained by noncovalent interaction between otherwise unrelated species. The data demonstrate that a monocyte-derived thymocyte proliferation factor having the molecular properties of interleukin 1 is capable of regulating fibroblast proliferation. In silicosis and other fibrotic diseases, the local release of interleukin 1 may contribute to abnormal connective tissue deposition by stimulating fibroblast proliferation, and thereby, amplifying other signals stimulating the synthesis of connective tissue components.


Hepatoid carcinoma of the ovary. A newly described tumor.
Five cases of ovarian carcinoma with hepatoid features, three of them primary and two probably primary, are described. The tumor cells were arranged predominantly in sheets and contained moderate to abundant amounts of eosinophilic cytoplasm; varying numbers of tumor cells stained immunohistochemically for alpha fetoprotein. In contrast to the much younger age range of patients with ovarian hepatoid yolk sac tumors, the ages of the five patients with hepatoid carcinomas ranged from 42 to 78 (average, 63 years), and none of them had gonadal dysgenesis or recognizable germ cell components within their tumors. All the tumors presented as adnexal masses; in four cases they were Stage III and in one case, Stage IIB; this last tumor spread to the upper abdomen within 4 years. In three cases the clinical course and pathology findings indicated that the tumor had originated in the ovary; in the remaining two cases the tumors were interpreted as only probably primary in the ovary. Hepatoid carcinomas must be distinguished from other ovarian neoplasms, especially from hepatoid yolk sac tumors.


The role of resilience in healthcare transitions among adolescent kidney transplant recipients.
AYAs with KTs experience high rates of premature allograft loss during the HCT. There is a critical need to identify protective factors associated with stable HCT. Resilience-the ability to adapt and thrive in the setting of adversity-has known positive impact on health outcomes. This study explored the novel role of resilience constructs as protective factors in securing stable HCT among AYA with KT. We conducted semi-structured interviews of adolescents and young adults who transitioned from a single pediatric transplant center to multiple adult nephrology centers between 2010 and 2017. Interviews explored the role of key resilience constructs in participants' lives around the time of HCT. Participants were stratified into stable or unstable HCT groups based on biological markers of allograft function and clinical data from chart review. Content analyses of interview transcripts were reviewed and compared among HCT groups. Thirty-two participants enrolled (17 stable; 15 unstable). Key resilience constructs more salient in the stable versus unstable HCT group were confidence in and connection to one's healthcare team. Reports of healthcare self-management competencies were similar across both HCT groups. Confidence in and connection to one's healthcare team appear to be linked with a stable HCT among AYA with KT. This suggests that interdependence, the ability to foster connections with and elicit support from healthcare providers, as opposed to complete independence or autonomy, which is often advised in the HCT process, is a critical component of resilience linked to stable HCT.


Fistula development after anal abscess drainage-a multicentre retrospective cohort study.
Anal abscesses are common and, despite correct treatment with surgical drainage, carry the risk of developing fistulas. Studies identifying risk factors for the development of anal fistulas are sparse. This study aimed to identify the risk factors for anal fistulas after anal abscess surgery. This was a multicentre, retrospective cohort study of patients undergoing acute surgery for anal abscesses in the Capital Region of Denmark between 2018 and 2019. The patients were identified using ICD-10 codes for anal abscesses. Predefined clinicopathological factors and postoperative courses were extracted from patient records. A total of 475 patients were included. At a median follow-up time of 1108 days (IQR 946-1320 days) following surgery, 164 (33.7%) patients were diagnosed with an anal fistula. Risk factors for developing fistulas were low intersphincteric (OR 2.77, 95CI 1.50-5.06) and ischioanal (OR 2.48, 95CI 1.36-4.47) abscesses, Crohn's disease (OR 5.96, 95CI 2.33-17.2), a history of recurrent anal abscesses (OR 4.14, 95CI 2.47-7.01) or repeat surgery (OR 5.96, 95CI 2.33-17.2), E. coli-positive pus cultures (OR 4.06, 1.56-11.4) or preoperative C-reactive protein (CRP) of more than 100 mg/L (OR 3.21, 95CI 1.57-6.71). Several significant clinical risk factors were associated with fistula development following anal abscess surgery. These findings are clinically relevant and could influence the selection of patients for specialised follow-up, facilitate expedited diagnosis, and potentially prevent unnecessarily long treatment courses.


The P10K database: a data portal for the protist 10 000 genomes project.
Protists, a highly diverse group of microscopic eukaryotic organisms distinct from fungi, animals and plants, exert crucial roles within the earth's biosphere. However, the genomes of only a small fraction of known protist species have been published and made publicly accessible. To address this constraint, the Protist 10 000 Genomes Project (P10K) was initiated, implementing a specialized pipeline for single-cell genome/transcriptome assembly, decontamination and annotation of protists. The resultant P10K database (https://ngdc.cncb.ac.cn/p10k/) serves as a comprehensive platform, collating and disseminating genome sequences and annotations from diverse protist groups. Currently, the P10K database has incorporated 2959 genomes and transcriptomes, including 1101 newly sequenced datasets by P10K and 1858 publicly available datasets. Notably, it covers 45% of the protist orders, with a significant representation (53% coverage) of ciliates, featuring nearly a thousand genomes/transcriptomes. Intriguingly, analysis of the unique codon table usage among ciliates has revealed differences compared to the NCBI taxonomy system, suggesting a need to revise the codon tables used for these species. Collectively, the P10K database serves as a valuable repository of genetic resources for protist research and aims to expand its collection by incorporating more sequenced data and advanced analysis tools to benefit protist studies worldwide.


Solid tissue culture for cytogenetic analysis: a collaborative survey for the Association of Clinical Cytogeneticists.
To survey the diagnostic service provided by UK laboratories for the culture of solid tissue samples (excluding tumours) and in particular to examine the variation in culture success rates and the problems of maternal cell overgrowth. Twenty seven laboratories took part in a collaborative survey during 1992. Each laboratory submitted data on up to a maximum of 60 consecutive specimens (n = 1361) over a six month period. Skin specimens, the largest category received (n = 520), were the most problematic (51% success rate). Culture success rates were significantly lower (43%) when skin specimens (n = 140) were transported dry to the laboratory. Success rates for skin specimens also varied, depending on the origin of the specimen, from 18% for intra-uterine deaths (IUD) (n = 94) to 85% for neonatal deaths (n = 33) and 83% for live patients (n = 54). Culture of selected extra-fetal tissues from IUD, stillbirths and following elective termination of pregnancy (TOP) gave comparable success rates to those achieved for skin samples from neonatal deaths and live births. Skewed sex ratios, female > male, were identified for products of conception (POC) (n = 298) and placental biopsy specimens (n = 97). By appropriate selection, transport and processing of tissues, and in particular by avoiding relying solely on skin samples from IUD, stillbirths and TOP, an increase in culture success rates for solid tissue samples submitted for cytogenetic analysis could be achieved. The high risk of maternal cell contamination from POC and placental biopsy specimens was also identified in this survey.


Cation mediation of radical transfer between Trp48 and Tyr356 during O2 activation by protein R2 of Escherichia coli ribonucleotide reductase: relevance to R1-R2 radical transfer in nucleotide reduction?
A tryptophan 48 cation radical (W48(+)(*)) forms concomitantly with the Fe(2)(III/IV) cluster, X, during activation of oxygen for tyrosyl radical (Y122.) production in the R2 subunit of class I ribonucleotide reductase (RNR) from Escherichia coli. W48(+)(*) is also likely to be an intermediate in the long-range radical transfer between R2 and its partner subunit, R1, during nucleotide reduction by the RNR holoenzyme. The kinetics of decay of W48(+)(*) and formation of tyrosyl radicals during O(2) activation (in the absence of R1) in wild-type (wt) R2 and in variants with either Y122, Y356 (the residue thought to propagate the radical from W48(+)(*) into R1 during turnover), or both replaced by phenylalanine (F) have revealed that the presence of divalent cations at concentrations similar to the [Mg(2+)] employed in the standard RNR assay (15 mM) mediates a rapid radical-transfer equilibrium between W48 and Y356. Cation-mediated propagation of the radical from W48 to Y356 gives rise to a fast phase of Y. production that is essentially coincident with W48(+)(*) formation and creates an efficient pathway for decay of W48(+)(*). Possible mechanisms of this cation mediation and its potential relevance to intersubunit radical transfer during nucleotide reduction are considered.


Exendin-4 improves ER stress-induced lipid accumulation and regulates lipin-1 signaling in HepG2 cells.
Lipin-1 performs dual function during lipid metabolism, i.e., it functions as a transcriptional coactivator and as a phosphatidate phosphatase during triglyceride biosynthesis. We investigated whether exendin-4 prevented endoplasmic reticulum (ER) stress-induced hepatic steatosis and whether the protective effects of exendin-4 were associated with lipin-1 signaling. Tunicamycin and thapsigargin, ER stress inducers, increased triglycerides (TG) content and expression of genes encoding lipid droplet surface proteins. Exendin-4 decreased the expression of ER stress markers phosphorylated PKR like ER kinase (PERK), phosphorylated inositol-requiring enzyme 1 alpha (IRE1α), and glucose-regulated protein 78 kDa (GRP78) proteins and spliced X-box binding protein 1 (XBP-1s) mRNA and increased the expression of genes encoding lipolytic enzymes hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) and VLDL assembly-associated proteins microsomal triglyceride transfer protein (MTP) and apolipoprotein B (APOB) in tunicamycin-pretreated cells. Moreover, exendin-4 significantly decreased lipin-1β/α ratio by increasing SFRP10 and increased lipin-1 nuclear localization. The decrease in lipin-1β/α ratio was also observed in SIRT1 and AMPK agonist-treated cells. These data suggest that exendin-4 improves ER stress-induced hepatic lipid accumulation by increasing lipolysis and VLDL assembly, which is partially mediated by the regulation of lipin-1 signaling.


Hierarchy and Reliability of the Preschool Language Scales-Fifth Edition: Mokken Scale Analysis.
Purpose This study examined the psychometric properties of the Preschool Language Scales-Fifth Edition (PLS-5 English) among preschool children from low-socioeconomic status (SES) families. Method The PLS-5 was administered individually to 169 3- to 4-year-old children enrolled in Head Start programs. We carried out a Mokken scale analysis (MSA), which is a nonparametric item response theory analysis, to examine the hierarchy among items and the reliability of test scores of the PLS-5 Auditory Comprehension (AC) and Expressive Communication (EC) scales. Results The PLS-5 EC items retained a moderate Mokken scale with the inclusion of all the items. On the other hand, the PLS-5 AC items formed a moderate Mokken scale only with the exclusion of five unscalable items. The latent class reliability coefficients for the AC and the EC scale scores were both above .90. Several items that violated the invariant item ordering assumption were found for both scales. Conclusions MSA can be used to examine the relationship between the latent language ability and the probability of passing an item with ordinal responses. Results indicate that for preschool children from low-SES families, it is appropriate to use the PLS-5 EC scale scores for comparing individuals' expressive language abilities; however, researchers and speech-language pathologists should be cautious when using the PLS-5 AC scale scores to evaluate individuals' receptive language abilities. Other implications of the MSA results are further discussed.


Enhanced resin titanium adhesion with silane primers using tribochemical silica-coating.
Experimental silane primers and a urethane dimethacrylate resin were prepared to resin titanium bonding. Commercially pure 2 Ti coupons were pretreated and randomly assigned into groups: group-SM (ESPE Sil™+Multilink® Speed), group-SE (ESPE Sil™+experimental resin), group-AM (1.0 vol% 3-acryloxypropyltrimethoxysilane+Multilink® Speed), group-AE (1.0 vol% 3-acryloxypropyltrimethoxysilane+experimental resin), group-BM (1.0 vol% 3-acryloxypropyltrimethoxysilane+0.5 vol% bis-(1,2-triethoxysilyl)ethane+Multilink® Speed), and group-BE (1.0 vol% 3-acryloxypropyltrimethoxysilane+0.5 vol% bis-(1,2-triethoxysilyl) ethane+experimental resin). Specimens were stored in a desiccator for 24 h, and artificially aged by thermo-cycling (6,000 and 12,000 cycles). According to ANOVA and the Tukey's test (n=10, α=0.05), the mean enclosed mold shear bond strength after 24 h was highest in group-AE (26.2±4.0 MPa). After 12,000 thermo-cycles, the group-BM exhibited the highest adhesion strength (13.4±3.2 MPa). This study suggests that a silane primer (3-acryloxypropyltrimethoxysilane+0.5 vol% bis-(1,2-triethoxysilyl)ethane) might enhance adhesion strength.


Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons.
1. The interaction between inhibitory interneurons and cortical pyramidal neurons was studied by use of computer simulations to test whether inhibitory interneurons could assist in phase-locking postsynaptic cells. Two models were used: a simplified model, which included only 3 membrane channels, and a detailed 11-channel model. 2. The 11-channel model included most of the ion channels known to be present in neocortical pyramidal neurons as well as calcium diffusion and other membrane mechanisms. The kinetics for the channels were obtained from voltage-clamp studies in a variety of preparations. The parameters were then adjusted to produce repetitive bursting similar to that seen in some cortical pyramidal cells entrained during visual stimulation. 3. Phase-locking to a train of inhibitory postsynaptic potentials (IPSPs) located on or near the soma was observed in the 3-channel model cell subjected to random synaptic bombardment. In the 11-channel model, phase-locking due to multiple IPSPs was compared with phase-locking due to multiple excitatory postsynaptic potentials (EPSPs). Phase-locking began to occur when 20% of the IPSPs (20/100) or 40% of the EPSPs (4,000/10,000) were synchronized. The exact percentages differed with different 11-channel models, but either EPSPs or IPSPs would generally produce entrainment with approximately 40% synchronization. Thus 40 inhibitory boutons had an effect equivalent to 4,000 excitatory boutons in producing phase-locking. 4. Phase-locking with IPSPs in these models was possible because the IPSPs could cause either an increase or a decrease in firing rate over a limited range. The IPSPs served a modulatory role, increasing the rate of firing in some cases and decreasing it in others, depending on the state of the cell. 5. We examined frequency entrainment by IPSPs. In the 3-channel model, frequency entrainment of a postsynaptic cell was observed with a rapid train of strong (20-100 nS), brief, compound IPSPs. A 40-Hz compound IPSP train of 60 nS entrained cells having initial firing rates between 32 and 47 Hz. Below this range, cells could be partially entrained. Above the range, entrainment would fail. Frequency entrainment in the 3-channel model generally occurred on the first cycle after onset of the IPSPs. 6. Phase-locking and frequency entrainment were less robust in the 11-channel model. This was partly because bursts rather than individual spikes were being entrained. A 40-Hz, 90-nS compound IPSP train entrained a model cell upward from 34 Hz. Downward frequency entrainment also occurred.(ABSTRACT TRUNCATED AT 400 WORDS)


[Microorganisms synthesizing enzymes with thrombolytic action].
The literary and experimental data obtained by the authors concerning the ability of various microorganisms to synthesize exoproteases lysing the thrombi of human blood are presented in the article. Various methods of enhancing the thrombolytic activity of microorganisms cultures, the properties of some isolated and purified preparations, methods of enlarging the specificity of the enzymes to fibrin and of reduction of their toxicity are considered.


A level set approach for shape-driven segmentation and tracking of the left ventricle.
Knowledge-based segmentation has been explored significantly in medical imaging. Prior anatomical knowledge can be used to define constraints that can improve performance of segmentation algorithms to physically corrupted and incomplete data. In this paper, the objective is to introduce such knowledge-based constraints while preserving the ability of dealing with local deformations. Toward this end, we propose a variational level set framework that can account for global shape consistency as well as for local deformations. In order to improve performance, the problems of segmentation and tracking of the structure of interest are dealt with simultaneously by introducing the notion of time in the process and looking for a solution that satisfies that prior constraints while being consistent along consecutive frames. Promising experimental results in magnetic resonance and ultrasonic cardiac images demonstrate the potentials of our approach.


Problems in comprehension of informed consent in rural and peri-urban Mali, West Africa.
Clinical trials undertaken by industrialized nations in undeveloped nations pose several critical ethical dilemmas. One key potential problem concerns misunderstandings of the consent process by participants. Though other reports have begun to explore this area, needs remain to identify specific areas of misunderstanding. To identify deficits in comprehension during consent processes in Mali, West Africa. After obtaining informed consent for participation for a malaria vaccine trial being conducted in two West African villages, we administered to participants a nine-item questionnaire testing their understanding of information relevant for their consent. After testing their ability to understand a multiple choice format, 78 of 100 subjects were administered the questionnaire in one village and 85 of 100 in the other. Participants had difficulty comprehending several concepts relevant to informed consent: 90% of respondents did not understand withdrawal criterion, 93% did not understand the existence of study side effects, and 74% did not understand that they were enrolled in an investigation as opposed to receiving therapy. The response rate and percentage of correct answers was generally much higher in the village nearer an urban center than the more rural village. The percent of correct answers exceeded 50% for five questions in the urban village and for only two question in the more rural setting. Potential limitations of this study are relating to translation, cultural differences in the notion of informed consent, staff differences between each village, the proportion who could not understand the survey instrument and the fact that the study explored participants' understanding of the consent process but did not observe the process itself. This study illustrates potential areas of miscomprehension in the consent process in a developing country. The degree of miscomprehension found in this study appeared to be more than that found in similar studies conducted in industrialized nations. Despite efforts to obtain truly informed consent, several factors make it more challenging in the developing world. This research highlights the need for more comprehensive studies of consent in developing countries. Such studies may eventually aid investigators in identifying, targeting and addressing specific areas of miscomprehension and thereby improve the informed consent process in the developing world.


Left vocal cord paralysis associated with long-standing patent ductus arteriosus.
Left vocal cord paralysis in association with patent ductus arteriosus is unusual. We report a patient with long-standing patent ductus arteriosus (PDA) in whom CT studies obtained before and after paralysis developed showed an interval increase in size of the pulmonary trunk. The pathogenesis of left vocal cord paralysis in association with long-standing PDA is discussed.


Impact of the COVID-19 pandemic on uveitis patient care.
The COVID-19 pandemic has significantly changed practice of medicine and patient care worldwide. The impact of the pandemic on patients with uveitis is unknown. We developed the COVID-19 Practice Patterns Study Group to evaluate the effect of the pandemic on uveitis patient care. This is a multicentre, cross-sectional survey of uveitis specialists practising worldwide. A web-based survey was distributed through the mailing lists of international uveitis societies to assess modifications in patient care, and use of immunomodulatory therapies (IMTs),aswell as considerations regarding COVID-19 vaccination. A diverse group consisting of 187 uveitis specialists from six continents participated in this survey. Most of these experts noted a disruption in clinical management of patients, including clinic closures or decrease in volume, patients missing in-person visits due to the fear of infection and difficulties obtaining laboratory testing. Most participants initiated (66.8%) and continued (93.3%) IMTs based on clinical presentation and did not modify their use of immunosuppressives. In cases of reported exposure to COVID-19 infection, most participants (65.3%) recommended no change in IMTs. However, 73.0% of the respondents did recommend holding all or select IMTs in case of COVID-19 infection. COVID-19 vaccine was recommended universally by almost all the specialists and 52% stated that they would counsel patients regarding the decreased immunogenicity and effectiveness of the vaccine in immunocompromised patients. Uveitis patient care has changed significantly since the beginning of the pandemic. The recommendations will continue to evolve as new data on IMTs and vaccination become available.


Open and shut: crystal structures of the dodecylmaltoside solubilized mechanosensitive channel of small conductance from Escherichia coli and Helicobacter pylori at 4.4 Å and 4.1 Å resolutions.
The mechanosensitive channel of small conductance (MscS) contributes to the survival of bacteria during osmotic downshock by transiently opening large diameter pores for the efflux of cellular contents before the membrane ruptures. Two crystal structures of the Escherichia coli MscS are currently available, the wild type protein in a nonconducting state at 3.7 Å resolution (Bass et al., Science 2002; 298:1582-1587) and the Ala106Val variant in an open state at 3.45 Å resolution (Wang et al., Science 2008; 321:1179-1183). Both structures used protein solubilized in the detergent fos-choline-14. We report here crystal structures of MscS from E. coli and Helicobacter pylori solubilized in the detergent β-dodecylmaltoside at resolutions of 4.4 and 4.2 Å, respectively. While the cytoplasmic domains are unchanged in these structures, distinct conformations of the transmembrane domains are observed. Intriguingly, β-dodecylmaltoside solubilized wild type E. coli MscS adopts the open state structure of A106V E. coli MscS, while H. pylori MscS resembles the nonconducting state structure observed for fos-choline-14 solubilized E. coli MscS. These results highlight the sensitivity of membrane protein conformational equilibria to variations in detergent, crystallization conditions, and protein sequence.


Quantum-dot-in-perovskite solids.
Heteroepitaxy-atomically aligned growth of a crystalline film atop a different crystalline substrate-is the basis of electrically driven lasers, multijunction solar cells, and blue-light-emitting diodes. Crystalline coherence is preserved even when atomic identity is modulated, a fact that is the critical enabler of quantum wells, wires, and dots. The interfacial quality achieved as a result of heteroepitaxial growth allows new combinations of materials with complementary properties, which enables the design and realization of functionalities that are not available in the single-phase constituents. Here we show that organohalide perovskites and preformed colloidal quantum dots, combined in the solution phase, produce epitaxially aligned 'dots-in-a-matrix' crystals. Using transmission electron microscopy and electron diffraction, we reveal heterocrystals as large as about 60 nanometres and containing at least 20 mutually aligned dots that inherit the crystalline orientation of the perovskite matrix. The heterocrystals exhibit remarkable optoelectronic properties that are traceable to their atom-scale crystalline coherence: photoelectrons and holes generated in the larger-bandgap perovskites are transferred with 80% efficiency to become excitons in the quantum dot nanocrystals, which exploit the excellent photocarrier diffusion of perovskites to produce bright-light emission from infrared-bandgap quantum-tuned materials. By combining the electrical transport properties of the perovskite matrix with the high radiative efficiency of the quantum dots, we engineer a new platform to advance solution-processed infrared optoelectronics.


Trait Impulsivity Is Independent of Mild Cognitive Impairment in a Parkinson's Disease Cohort.
Patients with Parkinson's disease (PD) commonly experience cognitive deficits and some also develop impulse control disorders (ICDs); however, the relationship between impulsivity and cognitive dysfunction remains unclear. This study investigated whether trait impulsivity associates with mild cognitive impairment (MCI), or is altered in a PD patient cohort with MCI. A total of 302 patients with idiopathic PD were recruited sequentially from three Australian Movement Disorder clinics. Based on cognitive scores, participants were divided into two groups, one defined as having mild cognitive impairment (PD-MCI; n = 113) and the other with normal cognitive function (PD-C; n = 189). Trait impulsivity was evaluated using the Barrett Impulsiveness Scale 11 (BIS-11). Total impulsivity scores, as well as subscale scores, were compared between PD-C and PD-MCI groups. The PD-MCI cohort had significantly lower scores in all cognitive domains, and mirrored expected clinical differences in medication, motor symptoms, and disease duration, when compared to the PD-C cohort. Self-reported impulsivity was not significantly different between groups, nor was there a difference within first-order subscale scores: attention (p=0.137), cognitive instability (p=0.787), self-control (p=0.503), cognitive complexity (p=0.157), motor impulsivity (p=0.559), or perseverance (p=0.734) between the PD-MCI and PD-C groups. These findings suggest that impulsive traits and behaviors are independent of changes in cognitive state and are not altered in PD patients with mild cognitive impairment.


Myocardial and Cardiocirculatory Reserve in Asymptomatic Aortic Stenosis and Preserved Ejection Fraction.
Managing patients with asymptomatic severe aortic stenosis (AS) remains a major challenge. Myocardial as well as cardiocirculatory reserve have been hypothesized to predict outcome in patients with asymptomatic AS. A total of 48 patients (indexed aortic valve area 0.39 +/- 0.12 cm2/m2; ejection fraction (EF) 67 +/- 7%) underwent spiroergometry and dobutamine stress echocardiography. Death or valve surgery served as a combined endpoint for follow up. Thirty-seven patients reached the endpoint after a mean of 756 days (range: 100-2146 days). Age- and gender-corrected univariate Cox proportional analysis revealed the presence of mild obstructive lung disease, stroke work loss (SWL), end-systolic diameter index, and E/Flow propagation velocity as the best predictive clinical, valvular, cardiostructural, and left ventricular filling pressure parameters, respectively. After inclusion of these parameters into a baseline multivariable Cox proportional hazard model, SWL (HR 1.21 per rise of 1 unit, CI 1.08-1.35, p = 0.0005) and female gender (HR 3.37, CI 1.50-7.59, p = 0.0044) were independently predictive. Similarly, the best-performing myocardial parameter, EF after dobutamine, was independently predictive (HR 0.75 per 5 units, CI 0.57-0.99, p = 0.035) after inclusion. The best-performing exercise capacity parameter, Watt(max), was of borderline significance (HR 0.93 per 5 units, CI 0.86-1.00, p = 0.0505). For each parameter, cut-off values were determined by time-dependent receiver-operator characteristics. The Kaplan-Meier curves of the patients above versus below the cut-offs differed significantly for SWL (p = 0.001), Wattm (p = 0.001), and gender (p = 0.013). Besides SWL and female gender, the EF after dobutamine as well as highest exercise stress intensity reached are helpful in determining the prognosis of asymptomatic patients with moderate-severe AS.


Venus lower atmospheric composition: analysis by gas chromatography.
The first gas chromatographic analysis of the lower atmosphere of Venus is reported. Three atmospheric samples were analyzed. The third of these samples showed carbon dioxide (96.4 percent), molecular nitrogen (3.41 percent), water vapor (0.135 percent), molecular oxygen [69.3 parts per million (ppm)], argon (18.6 ppm), neon (4.31 ppm), and sulfuir dioxide (186 ppm). The amounts of water vapor and sulfur dioxide detected are roughly compatible with the requirements of greenhouse models of the high surface temperature of Venus. The large positive gradient of sulfur dioxide, molecular oxygen, and water vapor from the clould tops to their bottoms, as implied by Earth-based observations and these resuilts, gives added support for the presence of major quantities of aqueous sulfuric acid in the clouds. A comparison of the inventory of inert gases found in the atmospheres of Venus, Earth, and Mars suggests that these components are due to outgassing from the planetary interiors.


[Pressor response to the stimulation of peripheral sympathetic nerves and the posterior hypothalamus in the presence of tricyclic antidepressive agents and nomifensine in dogs].
Acute experiments documented the peripheric action of tricyclic antidepressives (imipramine, chlorimipramine and amitriptyline). They evoked a significant hypotensive action (P less than 0.02), baroreceptor blockade and higher intensity and duration of pressor responses to exogenous noradrenaline, electric stimulation of the sympathetic nerves of the spleen, posterior hypothalamus or the central extremity of vagus nerve. These effects could be produced by the inhibition of noradrenaline reuptake and are antagonized by noradrenergic blockade with phentolamine. Nomifensine does not change arterial pressure, but its analeptic effect is able to awake anesthetized dogs. The pressor noradrenergic response is greater than that obtained with tricyclic antidepressives. The potentiation showed by the injection of dopamine was similar to that produced by imipramine. Injected into the cerebral ventricles of the dog, it did not changed arterial pressure, but crossed the blood-brain barrier. High doses of tricyclic antidepressives and nomifensine evoked inhibitory effects on adrenergic responses.


Sustainability of an enhanced recovery after surgery program (ERAS) in colonic surgery.
Between 2006 and 2008 the enhanced recovery after surgery (ERAS) program was implemented in colonic surgery in one-third of all hospitals in the Netherlands (n = 33). This resulted in enhanced recovery and a decrease in hospital length of stay (LOS) from a median of 9 days at baseline to 6 days at one-year follow-up. The present study assessed the sustainability of the ERAS program 3-5 years after its implementation. From the 33 ERAS hospitals, 10 initially successful hospitals were selected, with success defined as a median LOS of 6 days or lower and protocol adherence rates above 70 %. In 2012 a retrospective audit of 30 consecutive patients was performed in each of these hospitals. Sustainability of the ERAS program was assessed on hospital level, using median hospital LOS, protocol adherence rates and time to functional recovery. Data were compared with the implementation phase data. Overall median LOS in the selected hospitals increased from 5.25 days (interquartile range [IQR] 4.75-6.00; min, 4.00-max, 6.00) to 6 days (IQR 5.00-7.00; min, 5.00-max, 8.00), but this change was not significant (p = 0.052). Time to functional recovery was equal in both phases: median 3.00 days (p = 0.26). Protocol adherence decreased from 75 to 67 % (p = 0.32). Especially adherence to postoperative care elements dropped considerably. Despite a slight decrease in protocol adherence, the ERAS program was sustained reasonably well in the 10 selected hospitals, although there was quite some variation between the hospitals.


Trophic ecology of Atlantic bluefin tuna Thunnus thynnus larvae.
Feeding intensity, diet composition, selectivity, energy ingestion and dietary niche breadth of larval Atlantic bluefin tuna Thunnus thynnus were studied on the eastern (Mediterranean) spawning grounds of the species. Larval T. thynnus were collected in the Balearic Archipelago (north-west Mediterranean Sea) during 2004 and 2005 using surveys specific for larval scombrids. Larvae between 2·6 and 8·7 mm standard length (L(S) ) are diurnal feeders, and 94% of the guts collected during daylight hours were full. The mean ±s.d. number of prey per gut was 7·1 ± 5·7, with mean ±s.d. ranging from 3·0 ± 1·6 in the smallest T. thynnus larvae to 11·1 ± 5·8 in 5·0-6·0 mm L(S) larvae. Up to 21 prey were found in a single larval gut (5·0-6·0 mm L(S) ) at the end of the day. Larvae progressively selected larger prey and exhibited increased carbon content concurrent with preflexion development of feeding and locomotory structures. Larvae of 5·0-6·0 mm L(S) exhibited positive selection of cladocerans over other prey (Chesson's index), whereas copepod nauplii dominated the diets of earlier stages. The dietary niche breadth measured increased initially but decreased at c. 5·5 mm L(S) . Appendicularians were found in the diet of larger larval sizes, but no piscivory was observed. Results are discussed in light of the sparse existing data for larval T. thynnus and other larval tuna species.


Ergonomics: safe patient handling and mobility.
This article reviews and investigates the issues surrounding ergonomics, with a specific focus on safe patient handling and mobility. The health care worker of today faces many challenges, one of which is related to the safety of patients. Safe patient handling and mobility is on the forefront of the movement to improve patient safety. This article reviews the risks associated with patient handling and mobility, and informs the reader of current evidence-based practice relevant to this area of care.


Modulatory effects of NDP-MSH in the regenerating liver after partial hepatectomy in rats.
Melanocortins are endogenous peptides that exert protective actions on the host physiology. The broad modulatory effects of these molecules suggest that they might influence the mediator network induced during liver regeneration. The research aim was to determine if melanocortin treatment alters liver molecular changes induced by partial hepatectomy (PH). Rats under isoflurane anesthesia were subjected to standard 70% PH or sham surgery. Animals received a single i.v. injection of Nle4, DPhe7-α-melanocyte stimulating hormone (NDP-MSH) or saline 30 min before surgery. Sacrifice was performed at time intervals between 4 and 72 h. A preliminary screening based on TaqMan low-density array (TLDA) identified 71 transcripts altered by PH. Real-time PCR analysis revealed that NDP-MSH modulated the expression of a substantial proportion of these transcripts including several chemokines and their receptors. The critical signaling pathway interleukin-6 (IL-6)/signal transducer and activator of transcription (STAT)/suppressor of cytokine signaling (SOCS) was significantly enhanced by NDP-MSH. Further, peptide treatment considerably reduced the decline of IκBα protein caused by PH. Although the final organ regeneration was not substantially affected, NDP-MSH modulated expression of cell cycle mediators and exerted subtle influences on hepatocyte replication. Most of the changes brought about by NDP-MSH, a peptide approved for clinical use, should be salutary during liver regeneration.


SIEA versus DIEP Arterial Complications: A Cohort Study.
The authors analyzed arterial complications in patients undergoing breast reconstruction with superficial inferior epigastric artery (SIEA) flaps compared with deep inferior epigastric artery perforator (DIEP) flaps. The variability, caliber, and angiosome of the SIEA are cited as limitations. Experts currently limit SIEA reconstruction to cases with favorable arterial anatomy on preoperative imaging. In this retrospective cohort study, consecutive flaps for breast reconstruction from the initial 7 years of a single microsurgeon's practice (2007 to 2013) were reviewed. Preoperative imaging was not used. Consistent intraoperative criteria for SIEA flap selection were used. All complications were abstracted independently in duplicate using a standardized form and a priori criteria. One hundred sixty-nine free flaps (SIEA, n = 44; DIEP, n = 125) were performed on 112 patients for unilateral or bilateral breast reconstruction. Significantly more SIEA flaps required reexploration versus DIEP flaps (20 percent versus 7 percent; p = 0.03). Arterial insufficiency was significantly higher among SIEA flaps (14 percent versus 1 percent; p = 0.001). There was no difference in venous insufficiency (p = 0.92). Significantly more SIEA flaps had necrosis requiring intervention (p = 0.03). Ultimately, significantly more SIEA flaps failed completely (14 percent versus 2 percent; p < 0.01). All SIEA flap failures were attributable to arterial thrombosis. Compared with DIEP flaps, SIEA flaps had significantly higher proportions of reexploration, arterial complication, necrosis, and failure. No difference in venous complications was found. DIEP outcomes agree with existing literature from specialized centers. Complications and failures in SIEA flaps were attributed to arterial thrombosis. Given the authors' practice setting, SIEA flaps are no longer performed. Therapeutic, III.


Effect of inducer and inhibitor probes on DNA adduction of benzo[a]pyrene and 2-acetylaminofluorene and their roles in defining bioactivation mechanism(s).
In this study, we used DNA adducts as the endpoint to reflect on the type and amount of electrophilic metabolites formed in a cell-free system, which were 'trapped' with DNA and the resultant adducts analyzed by a highly sensitive (32)p- postlabeling assay. Incubation of benzo[a]pyrene (BP) (10 mu M) with liver microsomes and S-9 fractions from uninduced and beta-naphthoflavone (beta-NF)-induced rats and NADPH-generating system resulted in two major adducts, one derived from the interaction of benzo[a]pyrene diolepoxide with deoxyguanosine (BPDE-dG) and the other from further activation of 9-OH-BP. beta-NF treatment increased the microsomal DNA adduction capability: both BPDE-dG and 9-OH-BP adducts were enhanced to 19,600 and 26,600 adducts/10(9) nucleotides compared to 2,800 and 1,700 adducts/10(9) nucleotides with uninduced microsomes, respectively. An even greater enhancement of both adducts was observed when S-9 was substituted for microsomes. These results suggest the involvement of CYP1A1 in BP activation because of the known role of beta-NF in the induction of this enzyme. Further, evidence of the involvement of CYP1A1 was obtained by using alpha-naphthoflavone (alpha-NF), a known inhibitor of CYP1A family. Addition of alpha-NF (50 mu M) to the activation system almost completely (>95%) abolished both the adducts. These results are consistent with selective inhibition of CYP1A1, the isozyme involved in the conversion of BP to BP-7,8-diol. Further, cyclohexene oxide (Chox) (100 mu M), a known inhibitor of epoxide hydrolase reduced BPDE-dG adduct by 55% over that in the absence of the inhibitor, suggesting its epoxide origin; 9-OH-BP adduct was, however slightly increased. Enhanced DNA adduction of another class of carcinogen, 2-acetylaminofluorene (2-AAF) (20 mu M) with induced S-9 and microsomes, and inhibition in the presence of alpha-NF was also observed which is consistent with the involvement of CYP1A2 in the initial activation of aromatic amines. Results from these experiments suggest that the approach of using a battery of inducer/inhibitor probes and their influence on DNA adduction capability of subcellular fractions coupled with P-32-postlabeling can be fully exploited as important tools in defining metabolic pathway(s) that may be involved in the bioactivation of unknown compounds.


Establishment of a national quality improvement process on oxygen delivery index during cardiopulmonary bypass.
Targeted oxygen delivery during cardiopulmonary bypass (CPB) has received significant attention due to its influence on patient outcomes, especially in mitigating acute kidney injury. While it has gained popularity in select institutions, there remains a gap in establishing it globally across multiple centers. The purpose of this investigation was to describe the development of a quality improvement process of targeted oxygen delivery during CPB across hospitals throughout the United States. A systematic approach to utilize oxygen delivery index (DO2i) as a key performance indicator within hospitals serviced by a national provider of perfusion services. The process included a review of the current literature on DO2i, which yielded a target nadir value (272 mL/min/m2) and an area under the curve (DO2i272AUC) cut off of 632. All data is displayed on a dashboard with results categorized across multiple levels from system-wide to individual clinician performance. From January 2020 through December 2022, DO2i data from 91 hospitals and 11,165 coronary artery bypass graft procedures were collected. During this period the monthly proportion of DO2i measurements above the target nadir DO2i272 ranged from 60.5% to 78.4% with a mean+/-SD of 70.8 +/- 4.2%. Binary logistic regression for the first 7 months following monthly DO2i performance reporting has shown a statistically significant positive linear trend in the probability of achieving the target DO2i272 (p < .001), with a crude increase of approximately 7.8% for DO2i272AUC, and a 73.8% success rate (p < .001). A survey was sent to all individuals measuring oxygen delivery during CPB to assess why a target DO2i272 could not be reached. The two most common responses were an 'inability to improve CPB flow rates' and 'restrictive allogeneic red blood cell transfusion policies'. This study demonstrates that targeting a minimum level of oxygen delivery can serve as a key performance indicator during CPB using a structured quality improvement process.


Low birth-weight and the relationship to developmental problems.
A general introduction is provided into the causes, prevalence and long term consequences of low birth-weights. Although the vast majority of low birth-weight children have normal outcomes, as a group they have higher rates of subnormal growth, illness and neurodevelopmental problems. An increased awareness of the consequences of low birth-weight is needed as dentists provide services for this population of youngsters.


Risk of hypertension with multicystic kidney disease: a systematic review.
Children with multicystic kidney disease (MCKD) are increasingly managed conservatively, and are followed up throughout childhood because of the risk of hypertension highlighted in some reports. With this risk still poorly defined, the strategy and the duration of follow up do not seem to be based on evidence. Systematic review of the literature for all published cohort studies (prospective and retrospective) of children diagnosed to have unilateral MCKD and managed conservatively. Exclusion criteria were bilateral MCKD, and nephrectomy (not for hypertension) during the follow up period. For children with MCKD, the probability of developing hypertension during the follow up period was estimated. From 29 reviewed studies, six cases of hypertension developed in 1115 eligible children. The mean probability of a child with unilateral MCKD developing hypertension was therefore 5.4 per 1000 (95% CI estimated at 1.9 to 11.7 per 1000). Although the risk of hypertension in MCKD is low, the results of this study do not allow firm recommendations on the frequency and duration of blood pressure measurement follow up for these children. Large prospective cohort studies with a very long duration of follow up are needed.


Immunogenicity and efficacy of a bivalent vaccine against infectious bronchitis virus.
Infectious bronchitis (IB) is a highly contagious viral disease and is responsible for considerable economic losses in the poultry industry, worldwide. To mitigate the IB-associated losses, multiple vaccines are being applied in the sector with variable successes and thus necessitating the development of a potent vaccine to protect against the IB in the poultry. In the present study, we investigated a bivalent live attenuated vaccine consisting of IB virus (IBV) strain H120 (GI-1 lineage) and D274 (GI-12 lineage) to evaluate its protection against heterologous variant of IBV (GI-23 lineage) in chicken. Protection efficacy was evaluated based on the serology, clinical signs, survival rates, tracheal and kidney histopathology and the viral shedding. Results demonstrated that administering live H120 and D274 (named here Classivar®) vaccine in one day-old and 14 days-old provided 100 % protection. We observed a significant increase in the mean antibody titers, reduced virus shedding, and ameliorated histopathology lesions compared to routinely used vaccination regimes. These results revealed that usage of different IBV vaccines combination can successfully ameliorate the clinical outcome and pathology in vaccinated chicks especially after booster vaccination regime using Classivar®. In conclusions, our data indicate that Classivar® vaccine is safe in chicks and may serve as an effective vaccine against the threat posed by commonly circulating IBV strains in the poultry industry.


Hypersensitivity to DNA double-strand breaks associated with PARG deficiency is suppressed by exo-1 and polq-1 mutations in Caenorhabditis elegans.
Deficiency of either of the two homologs of poly(ADP-ribose) glycohydrolase (PARG), PARG-1 and PARG-2, in Caenorhabditis elegans leads to hypersensitivity to ionizing radiation (IR). In the germ cells of parg-2 mutant worms, the dissipation of recombinase RAD-51 foci was slower than in wild-type (WT) cells, suggesting defects in DNA double-strand break (DSB) repair via homologous recombination (HR). Nevertheless, RPA-1, the large subunit of replication protein A, accumulated faster in parg-2 worms and disappeared earlier than in WT worms. This accelerated RPA-1 accumulation may result from the enhanced expression of exonuclease-1 (EXO-1) after IR treatment. Accordingly, an exo-1 mutation reduced IR sensitivity and accumulation of RPA-1 in parg-2 worms. A mutation of polq-1, encoding for a key factor in the alternative end-joining (Alt-EJ) pathway, suppressed the IR hypersensitivity phenotype of parg-2 worms and normalized the kinetics of RAD-51 dissipation. This indicates that error-prone Alt-EJ may mediate DSB repair in parg-2 worms, causing hypersensitivity to IR. In summary, PARG-2 deficiency in C. elegans causes hyperactive DSB end resection likely through EXO-1 overproduction. DSBs with long single-stranded DNA ends in parg-2 worms are thought to be repaired by Alt-EJ instead of HR, causing genomic instability.


Fatal poisoning by butane sniffing: A forensic analysis and immunohistochemical detection of myocardial hypoxic damage.
Although less widespread than twenty years ago, inhalant abuse remains an on-going problem, whose incidence among U.S. teenagers and young adults ranges from 10 to 15%. Death due to the inhalation of vapor from halogenated hydrocarbons is a well-known phenomenon, yet few cases of fatal butane-gas poisoning have been described. Many cases of volatile substance abuse in prison populations have been reported: drug-addicted inmates often resort to this alternative practice when unable to get their habitual drugs of abuse. A similar pattern occurs especially among adolescents. The study herein described was conducted including all cases of fatal acute intoxication of butane gas examined from 2007 to 2015 at the Institute of Legal Medicine and Forensic Sciences of the University of Genoa. In the absence of overt and specific macroscopic and histological findings indicating cause and pathological mechanism of death, we aimed to assess whether recent cardiac lesions were detectable by way of immunohistochemical (IHC) analysis. Specifically, fibronectin and troponin C expression in myocardial tissues were investigated in deaths from acute butane-gas poisoning so as to better define the underlying pathological mechanisms. IHC findings were indicative of hypoxic cardiac damage. In all cases, positivity to fibronectin and mildly to moderately reduced troponin C expression in cardiac muscle cells were immunohistochemically ascertained.


Bread Sourdough Lactic Acid Bacteria-Technological, Antimicrobial, Toxin-Degrading, Immune System-, and Faecal Microbiota-Modelling Biological Agents for the Preparation of Food, Nutraceuticals and Feed.
This review intends to highlight the fact that bread sourdough is a very promising source of technological, antimicrobial, toxin-degrading, immune system-, and faecal microbiota-modelling biological agents for the preparation of food, nutraceuticals, and feed, which has great potential at industrial biotechnology scale. There are many applications of sourdough lactic acid bacteria (LAB), which are the main microorganisms in spontaneous sourdough. In addition to their application as pure technological strains in the food and feed industries, taking into consideration the specific properties of these microorganisms (antimicrobial, antifungal, immuno-, and microbiota-modulating, etc.), they are used as valuable ingredients in higher-value food as well as nutraceutical formulations. Additionally, a very promising application of LAB is their use in combination with plant- and/or animal-based ingredients to increase the functional properties of the whole combination due to different mechanisms of action, as well as desirable symbiotic activity. In addition to traditional foods prepared using sourdough microorganisms (bread, biscuits, meat products, dairy, beverages, etc.), they could find application in the preparation of added-value ingredients for the food, nutraceutical, and feed industries. Finally, this mini-review gives a brief introduction to the possible applications of sourdough LAB in the food, feed, and nutraceutical industries.


Displaced stress fracture of the femoral neck in young active adults.
Stress fractures of the femoral neck in healthy individuals are rare and most prevalent among long-distance runners and military recruits. Women seem to be at higher risk of developing stress fractures because of possible eating disorders and, thereby, following amenorrhoea and osteoporosis. The majority of fractures of the femoral neck are undisplaced. However, they might progress into displaced fractures with avascular necrosis of the femoral head and following development of osteoarthritis as a probable consequence even when treated properly. Early diagnosis with MRI or radionuclide scanning in patients with a history of pain in the groin region during training might be crucial in detecting the fractures at early stages; thereby preventing possible complications following surgical treatment of displaced fractures. The authors present a report of two young adults who developed displaced fractures of the femoral neck and were treated with closed reduction and internal fixation.


Effects of Salt Treatment Time on the Metabolites, Microbial Composition, and Quality Characteristics of the Soy Sauce Moromi Extract.
Salt is one of the most important factors for fermented foods, but the effect of salt treatment time on the quality of fermented foods has rarely been studied. In this study, the effect of different salt treatment times (0, 48, and 96 h) after the start of fermentation on the quality of the soy sauce moromi extract (SSME) was investigated. As the salt treatment time was delayed, the population of Aspergillus oryzae, Lactobacillaceae, and Enterococcaecea in SSME increased, whereas the population of Staphylococcaceae and Bacillaceae decreased, leading to changes in the enzymatic activity and metabolite profiles. In particular, the contents of amino acids, peptides, volatile compounds, acidic compounds, sugars, and secondary metabolites were significantly affected by the salt treatment time, resulting in changes in the sensory quality and appearance of SSME. The correlation data showed that metabolites, bacterial population, and sensory parameters had strong positive or negative correlations with each other. Moreover, based on metabolomics analysis, the salt treatment-time-related SSME metabolomic pathway was proposed. Although further studies are needed to elucidate the salt treatment mechanism in fermented foods, our data can be useful to better understand the effect of salt treatment time on the quality of fermented foods.


Evolution of paternal care in diploid and haplodiploid populations.
W. D. Hamilton famously suggested that the inflated relatedness of full sisters under haplodiploidy explains why all workers in the social hymenoptera are female. This suggestion has not stood up to further theoretical scrutiny and is not empirically supported. Rather, it appears that altruistic sib-rearing in the social hymenoptera is performed exclusively by females because this behaviour has its origins in parental care, which was performed exclusively by females in the ancestors of this insect group. However, haplodiploidy might still explain the sex of workers if this mode of inheritance has itself been responsible for the rarity of paternal care in this group. Here, we perform a theoretical kin selection analysis to investigate the evolution of paternal care in diploid and haplodiploid populations. We find that haplodiploidy may either inhibit or promote paternal care depending on model assumptions, but that under the most plausible scenarios it promotes - rather than inhibits - paternal care. Our analysis casts further doubt upon there being a causal link between haplodiploidy and eusociality.


The kinetics of binding of oxygen and carbon monoxide to Gastrophilus haemoglobin.
The dimeric haemoglobin in the tracheal cells of the Gastrophilus larva was extracted and purified, and the spectral properties of its oxy- and carbon monoxide adducts are recorded. In dilute solutions the kinetic parameters of binding of oxygen and carbon monoxide were determined. In solutions between 0.1 and 50mum for oxygen k(on) is 1x10(7)m(-1).s(-1) and k(off) is 1s(-1); for carbon monoxide l(on) is 6.5x10(5)m(-1).s(-1) and l(off) is 0.14s(-1). These values are in agreement with previous equilibrium results on oxygen binding and carbon monoxide/oxygen partition. These results are discussed and compared with the known values for other monomeric protohaem proteins.


Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial.
This study was conducted to demonstrate the efficacy and safety of LixiLan (iGlarLixi), a novel, titratable, fixed-ratio combination of insulin glargine (iGlar) (100 units) and lixisenatide, compared with iGlar in patients with type 2 diabetes inadequately controlled on basal insulin with or without up to two oral glucose-lowering agents. After a 6-week run-in when iGlar was introduced and/or further titrated, and oral antidiabetic drugs other than metformin were stopped, 736 basal insulin-treated patients (mean diabetes duration 12 years, BMI 31 kg/m2) were randomized 1:1 to open-label, once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose <100 mg/dL (<5.6 mmol/L) up to a maximum dose of 60 units/day. The primary outcome was change in HbA1c levels at 30 weeks. HbA1c decreased from 8.5% (69 mmol/mol) to 8.1% (65 mmol/mol) during the run-in period. After randomization, iGlarLixi showed greater reductions in HbA1c from baseline compared with iGlar (-1.1% vs. -0.6%, P < 0.0001), reaching a mean final HbA1c of 6.9% (52 mmol/mol) compared with 7.5% (58 mmol/mol) for iGlar. HbA1c <7.0% (53 mmol/mol) was achieved in 55% of iGlarLixi patients compared with 30% on iGlar. Mean body weight decreased by 0.7 kg with iGlarLixi and increased by 0.7 kg with iGlar (1.4 kg difference, P < 0.0001). Documented symptomatic hypoglycemia (≤70 mg/dL) was comparable between groups. Mild gastrointestinal adverse effects were very low but more frequent with iGlarLixi. Compared with iGlar, a substantially higher proportion of iGlarLixi-treated patients achieved glycemic targets with a beneficial effect on body weight, no additional risk of hypoglycemia, and low levels of gastrointestinal adverse effects in inadequately controlled, basal insulin-treated, long-standing type 2 diabetes.


[Clinical significance of Willebrand's factor antigen in patients with primary Sjogren's syndrome].
Concentration of von Willebrand's factor antigen (WFAg) was measured by solid phase enzyme immunoassay in the blood serum of 17 female patients (mean age 56.7 +/- 12.1 years) with primary Sjogren's syndrome (PSS) lasting, on the average, 4.1 +/- 1.5 years. Mean WFAg level in patients with PSS was equal to 2.56 +/- 1.4 IU/ml and exceeded significantly that of donors' (1.06 +/- 0.34, p < 0.001). In 9(53%) of 17 patients WFAg concentration was higher than normal (> 2.1 IU/ml). WFAg mean levels and frequency of its elevation did not differ significantly in patients with chronic parotitis, enlarged salivary glands, arthralgia/arthritis, lymphadenopathy, lung lesions, polyneuropathy and patients free of the above symptoms. In patients with myalgia, Raynaud's syndrome, skin vasculitis and vascular diseases WFAg concentrations were higher than in patients without them. There was no significant correlation between WFAg level and ESR, concentration of C-reactive protein, presence of rheumatoid and antinuclear factors.


Manifestation of cerebral malaria-like symptoms in the WM/Ms rat infected with Plasmodium berghei strain NK65.
Conditions required for the induction of cerebral malaria (CM)-like symptoms were investigated using 12 strains of rats and 5 murine malaria strains. Among various combinations, only inbred WM/Ms rats infected with P. berghei (NK65) developed neuropathological complications that closely resembled human CM cases. When young WM/Ms rats were infected with the parasites, neurologic signs were induced followed by death in 5-10 days with almost 100% incidence, whereas aged hosts revealed strong resistance. Histologically, edematous changes, occlusion of vessels, and petechial hemorrhages were found in the brain. There was an optimum dose of parasites to induce the manifestations, and a low incidence was obtained by increased or decreased inoculum size. No correlation was found between the level of parasitemia and incidence of the disease. The other 11 rat strains inoculated with this parasite showed high levels of parasitemia, but most of their infections were self-limiting or malarial death occurred without CM-like signs. Inoculation into WM/Ms rats with other murine malaria parasites, including P. chabaudi, P. vinckei, P. yoelii (17X), and P. yoelii (nigeriensis) failed to induce CM-like manifestations irrespective of the inoculation size and the degree of parasitemia. These results indicated that P. berghei (NK65)-infected WM/Ms rats represent an experimental model for CM and certain appropriate conditions are needed for its development in both parasite and host sides.


The mediational role of neurocognition in the behavioral outcomes of a social-emotional prevention program in elementary school students: effects of the PATHS Curriculum.
Neuropsychology is one field that holds promise in the construction of comprehensive, developmental models for the promotion of social competence and prevention of problem behavior. Neuropsychological models of behavior suggest that children's neurological functioning affects the regulation of strong emotions, as well as performance in social, cognitive, and behavioral spheres. The current study examines the underlying neurocognitive conceptual theory of action of one social-emotional development program. Hypothesized was that inhibitory control and verbal fluency would mediate the relationship between program condition and teacher-reported externalizing and internalizing behavior problems. Participants were 318 regular education students enrolled in the second or third grade. A series of regression analyses provided empirical support for (a) the effectiveness of the PATHS Curriculum in promoting inhibitory control and verbal fluency and (b) a partial mediating role for inhibitory control in the relation between prevention condition and behavioral outcomes. Implications are that programs designed to promote social and emotional development should consider comprehensive models that attend to neurocognitive functioning and development. Lack of consideration of neurocognitive pathways to the promotion of social competence may ignore important mechanisms through which prevention affects youth outcomes. Furthermore, the findings suggest that developers of social-emotional preventions should design curricula to explicitly promote the developmental integration of executive functioning, verbal processing, and emotional awareness. Doing so may enhance prevention outcomes particularly if those preventions are implemented during a time of peak neurocognitive development.


Acute Effects of Partial-Body Cryotherapy on Isometric Strength: Maximum Handgrip Strength Evaluation.
De Nardi, M, Pizzigalli, L, Benis, R, Caffaro, F, and Cremasco, MM. Acute effects of partial-body cryotherapy on isometric strength: maximum handgrip strength evaluation. J Strength Cond Res 31(12): 3497-3502, 2017-The aim of the study was to evaluate the influence of a single partial-body cryotherapy (PBC) session on the maximum handgrip strength (JAMAR Hydraulic Hand dynamometer). Two hundred healthy adults were randomized into a PBC group and a control group (50 men and 50 women in each group). After the initial handgrip strength test (T0), the experimental group performed a 150-second session of PBC (temperature range between -130 and -160° C), whereas the control group stayed in a thermo neutral room (22.0 ± 0.5° C). Immediately after, both groups performed another handgrip strength test (T1). Data underlined that both groups showed an increase in handgrip strength values, especially the experimental group (Control: T0 = 39.48 kg, T1 = 40.01 kg; PBC: T0 = 39.61 kg, T1 = 41.34 kg). The analysis also reported a statistical effect related to gender (F = 491.99, P ≤ 0.05), with women showing lower handgrip strength values compared with men (women = 30.43 kg, men = 52.27 kg). Findings provide the first evidence that a single session of PBC leads to the improvement of muscle strength in healthy people. The results of the study imply that PBC could be performed also before a training session or a sport competition, to increase hand isometric strength.


The application of near infrared spectroscopy to study lipid characteristics and deterioration of frozen lean fish muscles.
Near infrared spectroscopy (NIR) was applied to estimate lipid composition and degradation of two lean fish species, saithe (Pollachius virens) and hoki (Macruronus novaezelandiae). Calibration models were developed, using partial least squares (PLS) regression, for total lipid content and composition, free fatty acids (FFA), thiobarbituric acid reactive substances (TBARS) and fluorescent interaction compounds (OFR). Coefficients of determination for calibration (R(2)cv) and root-mean-square error of cross validation (RMSECV) ranged from 0.82 to 0.99 and 0.66 to 3.69 for hoki and from 0.64 to 0.99 and 0.06 to 2.65 for saithe, respectively. The validations of the calibrations indicated that lipid composition and FFA of hoki and saithe can be estimated by NIR with good accuracy. Furthermore, NIR differentiate fish muscles with low, medium and high concentration of OFR and TBARS. Overall, the results demonstrate the potential for use of NIR spectroscopy as an objective and non-destructive method to inspect the lipid characteristics and quality of frozen lean fish.


Cytotoxic Activity of Organotin(IV) Derivatives with Triazolopyrimidine Containing Exocyclic Oxygen Atoms.
In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO- ligands belonging to adjacent chains were also detected that resemble the "base-pairing" assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.