The decay accelerating factor mutation I197V found in hemolytic uraemic syndrome does not impair complement regulation.
Hemolytic uremic syndrome is the clinical triad of thrombocytopenia, microangiopathic hemolytic anaemia and acute renal failure. Cases not associated with a preceding Shiga-like toxin producing Escherichia coli are described as atypical HUS (aHUS). Approximately 50% of patients with aHUS have mutations in one of three complement regulatory proteins, Factor H (CFH), membrane cofactor protein (MCP;CD46) or factor I (IF). A common feature of these three proteins is that they regulate complement by cofactor activity. Decay accelerating factor (DAF; CD55) regulates the complement system by disassociating the alternative and classical pathway convertases. Like CFH and MCP, the gene for DAF lies within the regulators of complement activation (RCA) gene cluster at 1q32. In 1998, we described linkage to this region in families with aHUS which led to the discovery of mutations in CFH and MCP. We therefore genotyped DAF in a panel of 46 aHUS patients including families with linkage to the RCA cluster. A mutation, I197V, was identified in one patient with familial HUS which was not found in 100 healthy controls. Molecular modelling of this mutation shows that the I197V mutation does not reside in an area which would be predicted to be important in decay accelerating activity. The expression of I197V on EBV-transformed B lymphocytes was equivalent to that of wild type controls. There was no significant decrease in decay acceleration activity of the recombinantly produced I197V mutant compared with wild type, as measured by a complement-mediated lytic assay. In conclusion, this study, identifies only one mutation in DAF in 46 patients with aHUS. This mutation, I197V, does not impair complement regulation and cannot be implicated in the pathogenesis of aHUS in this patient. This suggests that the complement regulatory abnormality in aHUS is principally one of deficient cofactor activity rather than of decay acceleration activity.


Protective effect of the olive hydroalcoholic extract on estrogen deficiency-induced bone loss in rats in comparison with estradiol.
Osteoporosis, as a skeletal disorder caused by aging, is considered a major health problem. This work was planned to assess the effect of the black olive hydroalcoholic extract on bone mineral density and biochemical parameters in ovariectomized rats. Ninety 6-month-old female Sprague Dawley rats were randomly assigned into 7 sets: control (received saline); sham-operated control, Ovariectomized (OVX) rats (received saline); 3 groups of black olive-supplemented OVX rats (respectively, receiving 250, 500, and 750 mg/kg body wt black olive extract orally); and estrogen group (receiving 3 mg/kg/day estradiol valerate). Blood samples were collected 2, 4 and 6 months after treatment to measure calcium (Ca), alkaline phosphatase (ALP), and phosphorus (P). Dual-energy X-ray absorptiometry (DEXA) was applied to measure the bone mineral density (BMD). Global, lumbar spine and lower limb BMD was measured. Ca concentration was significantly increased in the group treated with the highest dose of black olive hydroalcoholic compared to the OVX group (P<0.001). In addition, a significant decrease in ALP concentrations in the group treated with the highest dose of black olive hydroalcoholic comparing with the OVX group was observed (P<0.001). The global, tibia, femur and spine BMD in the group treated with the highest dose of black olive hydroalcoholic and estrogen group were significantly increased compared to the OVX group (P<0.05). Black olive hydroalcoholic extract at the dose of 750 mg/kg, prevented bone loss and augmented bone mineral density and could be a possible candidate for the management of osteoporosis.


Generation of semi-dwarf rice (Oryza sativa L.) lines by CRISPR/Cas9-directed mutagenesis of OsGA20ox2 and proteomic analysis of unveiled changes caused by mutations.
Plant height (PH) is one of the most important agronomic traits of rice, as it directly affects the yield potential and lodging resistance. Here, semi-dwarf mutant lines were developed through CRISPR/Cas9-based editing of OsGA20ox2 in an indica rice cultivar. Total 24 independent lines were obtained in T0 generation with the mean mutation rate of 73.5% including biallelic (29.16%), homozygous (47.91%) and heterozygous (16.66%) mutations, and 16 T-DNA-free lines (50%) were obtained in T1 generation without off-target effect in four most likely sites. Mutations resulted in a changed amino acid sequence of mutant plants and reduced gibberellins (GA) level and PH (22.2%), flag leaf length (FLL) and increased yield per plant (YPP) (6.0%), while there was no effect on other agronomic traits. Mutants restored their PH to normal by exogenous GA3 treatment. The expression of the OsGA20ox2 gene was significantly suppressed in mutant plants, while the expression level was not affected for other GA biosynthesis (OsGA2ox3 and OsGA3ox2) and signaling (D1, GIDI and SLR1) genes. The mutant lines showed decreased cell length and width, abnormal cell elongation, while increased cell numbers in the second internode sections at mature stage. Total 30 protein spots were exercised, and 24 proteins were identified, and results showed that OsGA20ox2 editing altered protein expression. Five proteins including, glyceraldehyde-3-phosphate dehydrogenase, putative ATP synthase, fructose-bisphosphate aldolase 1, S-adenosyl methionine synthetase 1 and gibberellin 20 oxidase 2, were downregulated in dwarf mutant lines which may affect the plant growth. Collectively, our results provide the insights into the role of OsGA20ox2 in PH and confirmed that CRISPR-Cas9 is a powerful tool to understand the gene functions.


Different roles of tumor marker monitoring after curative resections of gastric and colorectal cancers.
We previously demonstrated that false-positive findings for tumor markers are frequently observed, and that the sensitivity of marker monitoring for early detection of the recurrence is low after curative resection of gastric cancer. The aim of this study was to investigate whether such characters are specific to gastric cancer. Serum carcinoembryonic antigen and/or carbohydrate antigen 19-9 were periodically assessed in 258 patients who underwent curative gastrectomy for gastric cancer (n = 161) or curative resection for colorectal cancer (n = 97). The frequency of false-positive findings for the tumor markers, the sensitivity of the marker monitoring for detection of the recurrence, and the characteristics of such cases were compared between these two cancer groups. During the median follow-up period of 30 months, recurrence developed in 14% of gastric cancer and 23% of colorectal cancer patients. A false positive with the tumor marker was frequently observed in patients after gastrectomy compared with after colorectal surgery. The sensitivity of the marker monitoring regarding early detection of recurrence was higher in patients with colorectal cancer than those with gastric cancer, especially in cases of advanced stage. As a result, the accuracy of marker monitoring for the detection of recurrence was higher in patients after the resection of colorectal cancer than that of gastric cancer. Surgeons and oncologists should thus be aware that the role of the tumor marker monitoring after a curative operation differs between patients with gastric and colorectal cancers.


Application of Protection Motivation Theory to Quantify the Impact of Pandemic Fear on Anticipated Postpandemic Transit Usage.
The COVID-19 pandemic had an unprecedented impact on transit usage, primarily owing to the fear of infection. Social distancing measures, moreover, could alter habitual travel behavior, for example, using transit for commuting. This study explored the relationships among pandemic fear, the adoption of protective measures, changes in travel behavior, and anticipated transit usage in the post-COVID era, through the lens of protection motivation theory. Data containing multidimensional attitudinal responses about transit usage at several pandemic stages were utilized for the investigation. They were collected through a web-based survey in the Greater Toronto Area, Canada. Two structural equation models were estimated to examine the factors influencing anticipated postpandemic transit usage behavior. The results revealed that people taking relatively higher protective measures were comfortable taking a cautious approach such as complying with transit safety policies (TSP) and getting vaccinated to make transit trips. However, the intention to use transit on vaccine availability was found to be lower than in the case of TSP implementation. Conversely, those who were uncomfortable taking transit with caution and who were inclined to avoid travel and rely on e-shopping were most unlikely to return to transit in the future. A similar finding was observed for females, those with vehicle access, and middle-income individuals. However, frequent transit users during the pre-COVID period were more likely to continue to use transit after the pandemic. The study's findings also indicated that some travelers might be avoiding transit specifically because of the pandemic, implying they are likely to return in the future.


Upper airway. 4: Sarcoidosis of the upper respiratory tract (SURT).
Sarcoidosis of the upper respiratory tract (SURT) includes nasopharyngeal, laryngeal and tracheal disease. Documented SURT occurs in approximately 5% of patients, although upper airway symptoms are more common in patients with sarcoidosis. Wegener granulomatosis may have a similar appearance to SURT, but there are important differences in the manifestations of the disease locally as well as systemically. In some cases, topical treatment is adequate to control SURT. However, many patients with significant sinus or laryngeal disease require long-term systemic treatment. While corticosteroids are often the initial drug of choice, there have been several reports of the effectiveness of cytotoxic agents and anti-tumour necrosis factor antibodies.


Sudden Cardiac Death in Brugada Syndrome.
The Brugada syndrome is an inherited channelopathy that alters the main transmembrane ion currents that constitute the cardiac action potential. These changes not only modify the resting electrocardiogram but also predispose patients to develop malignant ventricular tachyarrhythmias that can lead to syncope, cardiac arrest, and sudden cardiac death. This syndrome is responsible for nearly 20% of all sudden cardiac deaths in patients with structurally normal hearts and up to 12% of all sudden cardiac deaths. Brugada syndrome is diagnosed by its characteristic electrocardiogram consisting of a coved-type ST-segment elevation of at least 2 mm followed by a negative T wave in either one of the right precordial leads. These changes can be observed spontaneously or after administration of a sodium channel blocker. While our understanding of this disease has increased tremendously since its first description in 1992, the primary therapeutic option remains implantation of an implantable cardioverter-defibrillator to avoid sudden cardiac death. Therefore, tremendous effort is being made to effectively risk stratify patients to determine who would benefit from implantable cardioverter-defibrillator implantation.


High-Intensity Interval vs. Continuous Endurance Training: Preventive Effects on Hormonal Changes and Physiological Adaptations in Prediabetes Patients.
Safarimosavi, S, Mohebbi, H, and Rohani, H. High-intensity interval vs. continuous endurance training: Preventive effects on hormonal changes and physiological adaptations in prediabetes patients. J Strength Cond Res 35(3): 731-738, 2021-The aim of this study was to examine the effects of a 12-week high-intensity interval training (HIIT) intervention, or an isocaloric continuous endurance training (CET) intervention on insulin resistance indices and change in irisin and preptin in patients with prediabetes. Thirty-two prediabetic male patients (age = 38.7 ± 4; body mass index = 26.9 ± 1.4 kg·m-2; and V̇o2peak = 2.49 ± 0.22 L·min-1) were randomly assigned into 3 training groups (N = 8). These groups were matched based on the required energy expenditure (EE) for completing each protocol: (a) HIIT (10 × 60 seconds at 90% peak oxygen uptake [V̇o2peak], 1: 1 work to recovery at 50 W), (b) CET at an intensity equivalent to maximal fat oxidation (Fatmax) (CETFAT) (pedaling for a duration that expends an equivalent EE to an HIIT session [E ≈ HIIT]), (c) CET at an intensity equivalent to anaerobic threshold (CETAT) (E ≈ HIIT), and (d) the control group (CON): continued to perform their daily activities. After intervention, blood glucose levels were significantly (p < 0.05) lower in the HIIT group compared with CETAT group. Exercise training improved the insulin resistance index by 35, 28, and 37% in CETFAT, CETAT, and HIIT groups, respectively. Irisin concentrations in the HIIT and CETAT groups was significantly (p < 0.05) decreased compared with the pre-training values. Also, HIIT and CETFAT resulted in significant (p < 0.05) changes in preptin concentration compared with baseline. This study demonstrated that both HIIT and CETFAT protocols had similar effects on the insulin resistance index of prediabetic patients. Also, the intensity and type of exercise were effective factors in changing irisin and preptin concentrations.


Gender differences in adverse drug reactions: analysis of spontaneous reports to a Regional Pharmacovigilance Centre in France.
The aim of this study was to investigate putative gender-related differences in adverse drug reactions (ADRs). Data were ADRs recorded in the database of the French Midi-Pyrénées Pharmacovigilance Centre in 1998. A total of 927 ADRs were spontaneously reported to the Centre in 1998, of which 53.1% were in females (difference vs. males not statistically significant). There was no statistically significant difference in the incidence of reported ADRs in males (3.6/10,000 inhabitants) vs. females (3.9/10,000 inhabitants) for the total population of the Midi-Pyrénées area. The number of reported ADRs was similar across different age groups (10-year age ranges). However, 'serious' ADRs were more frequently reported in males in the 0-9 and 60-69 age groups (and in females between 20 and 29 years old). There were significantly more neuropsychiatric (69 vs. 43, P = 0.05) and fewer cardiovascular (8 vs. 2, P = 0.05) ADRs reported in females than in males. ADRs were more frequently reported in females for some classes of drugs (such as genito-urinary, sex hormone, antineoplastic, antiparasitic and respiratory drugs). These results confirm that female gender is a risk factor for the development of ADRs.


[Gastric mucosa in patients with fundic hyperplastic polyps].
To assess the functional and morphological characteristics of the gastric mucosa of patients with fundic hyperplastic polyps (FP), the determination of gastric acid secretion, serum gastrin levels, serum pepsinogen 1 (PG1) levels and histological examination were undertaken in 24 patients with FP, 34 with foveolar hyperplastic polyps (HP) and 62 controls, who had no gastric lesions. The following were the results of our investigation. 1) There were no differences between the patients with FP and the controls as to gastric acid secretion, serum gastrin levels, and serum PG1 levels. On the other hand, hypochlorhydria, hypergastrinemia and hypopepsinogenemia were common in those with HP. 2) Histological examination using gastric biopsy specimens showed almost normal gastric mucosa in patients with FP. However, severe atrophic gastritis of the fundus was common in patients with HP. 3) It was shown that there were definite differences between the patients with FP and those with HP with regard to the gastric function and morphology, although both types of gastric polyp were histologically classified as hyperplastic.


The Experience of Plague in East Kent, 1636–38.
On 2 July 1637 43-year-old Elizabeth Burgess, from Canterbury, was buried at Birchington, Kent, having died of the plague in the hamlet of Wood in that parish. She was the first victim of an outbreak of plague in 1637. This article firstly examines that outbreak in Birchington in detail; then it considers how far the parish's experience matched that in nearby Faversham and Sandwich. It finally discusses the extent to which the infection spread to the surrounding area.


ECG Variations in College Athletes.
At Georgia Institute of Technology, the sports preparticipation evaluation includes a cardiovascular questionnaire and careful examination of the heart, listening especially for systolic murmurs that intensify with Valsalva's maneuver and/or standing, which could indicate hypertrophic cardiomyopathy (1,2).


Brueckner doubles coupled cluster method with the polarizable continuum model of solvation.
We present the theory and implementation for computing the (free) energy and its analytical gradients with the Brueckner doubles (BD) coupled cluster method in solution, in combination with the polarizable continuum model of solvation (PCM). The complete model, called PTED, and an efficient approximation, called PTE, are introduced and tested with numerical examples. Implementation details are also discussed. A comparison with the coupled-cluster singles and doubles CCSD-PCM-PTED and CCSD-PCM-PTE schemes, which use Hartree-Fock (HF) orbitals, is presented. The results show that the two PTED approaches are mostly equivalent, while BD-PCM-PTE is shown to be superior to the corresponding CCSD scheme when the HF reference wave function is unstable. The BD-PCM-PTE scheme, whose computational cost is equivalent to gas phase BD, is therefore a promising approach to study molecular systems with complicated electronic structure in solution.


Acute kidney injury during treatment with high-dose cloxacillin: a report of 23 cases and literature review.
International guidelines recommend high-dose cloxacillin for endocarditis or osteoarticular infections due to methicillin-susceptible staphylococci. However, data on the tolerability of these regimens are scarce. We used the computerized registry of suspected drug-related adverse events in our institution. Cases of acute kidney injury (AKI), as defined by KDIGO, in patients receiving high-dose cloxacillin were retrospectively reviewed. Data were collected from medical charts on a standardized questionnaire. From 2009 to 2015, 23 consecutive patients (16 men, 7 women) with a median age of 75 years (interquartile range [IQR], 66-80) fulfilled inclusion criteria. By the time of AKI diagnosis, patients were treated with a median cloxacillin dose of 12 g/day (IQR, 10-12) after a median duration of 7 days (IQR, 4-10). Most patients (n=20) fulfilled RIFLE criteria for failure, with a median peak serum creatinine concentration of 339 µmol/L (IQR, 249-503). Urinalysis was indicative of tubular disease in 7 patients, 3 had hypereosinophilia and 8 had abnormal liver function tests. All patients presented at least one risk factor for AKI, including concomitant nephrotoxic drugs: gentamicin (n=19), diuretics (n=15), angiotensin-converting enzyme inhibitors (n=8) and angiotensin II receptor-blockers (n=6). Thirteen patients (57%) had cloxacillin plasma concentrations >50 µg/mL. Thirteen patients (57%) had complete recovery of renal function. AKI during high-dose cloxacillin treatment mostly occurs in elderly patients taking concomitant nephrotoxic drugs. The outcome is usually favourable after cloxacillin discontinuation. Therapeutic drug monitoring may decrease the risk of AKI in patients treated with high-dose cloxacillin.


Stable statistical representations facilitate visual search.
Observers represent the average properties of object ensembles even when they cannot identify individual elements. To investigate the functional role of ensemble statistics, we examined how modulating statistical stability affects visual search. We varied the mean and/or individual sizes of an array of Gabor patches while observers searched for a tilted target. In "stable" blocks, the mean and/or local sizes of the Gabors were constant over successive displays, whereas in "unstable" baseline blocks they changed from trial to trial. Although there was no relationship between the context and the spatial location of the target, observers found targets faster (as indexed by faster correct responses and fewer saccades) as the global mean size became stable over several displays. Building statistical stability also facilitated scanning the scene, as measured by larger saccadic amplitudes, faster saccadic reaction times, and shorter fixation durations. These findings suggest a central role for peripheral visual information, creating context to free resources for detailed processing of salient targets and maintaining the illusion of visual stability.


Predicting live weight using body volume formula in lactating water buffalo.
Live weight (LW) is an important piece of information within production systems, as it is related to several other economic characteristics. However, in the main buffalo-producing regions in the world, it is not common to periodically weigh the animals. We develop and evaluate linear, quadratic, and allometric mathematical models to predict LW using the body volume (BV) formula in lactating water buffalo (Bubalus bubalis) reared in southeastern Mexico. The LW (391.5 ± 138.9 kg) and BV (333.62 ± 58.51 dm3) were measured in 165 lactating Murrah buffalo aged between 3 and 10 years. The goodness-of-fit of the models was evaluated using the Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), coefficient of determination (R2), mean-squared error (MSE) and root MSE (RMSE). In addition, the developed models were evaluated through cross-validation (k-folds). The ability of the fitted models to predict the observed values was evaluated based on the RMSEP, R2, and mean absolute error (MAE). LW and BV were significantly positively and strongly correlated (r = 0.81; P < 0.001). The quadratic model had the lowest values of MSE (2788.12) and RMSE (52.80). On the other hand, the allometric model showed the lowest values of BIC (1319.24) and AIC (1313.07). The Quadratic and allometric models had lower values of MSEP and MAE. We recommend the quadratic and allometric models to predict the LW of lactating Murrah buffalo using BV as a predictor.


Brain Morphometric Correlates of Depressive Symptoms among Patients with and without Dementia.
Findings regarding brain morphometry among patients with dementia and concomitant depressive symptoms have been inconsistent. Thus, the aim of the present study was to test the hypothesis that dementia and concomitant depressive symptoms are associated with structural brain changes in the temporal lobe measured with structural magnetic resonance imaging (MRI). A sample of 492 patients from Norwegian memory clinics (n = 363) and Old Age Psychiatry services (n = 129) was studied. The assessment included the Cornell Scale for Depression in Dementia (CSDD), Instrumental Activities of Daily Living Scale, Mini Mental State Examination, and MRI of the brain, processed with FreeSurfer to derive ROI measures of cortical thickness, volume, and area using the Desikan-Killiany parcellation, as well as subcortical volumes. Dementia was diagnosed according to ICD-10 research criteria. Correlates of brain morphometry using multiple linear regression were examined. Higher scores on the CSDD were associated with larger cortical volume (β = 0.125; p value = 0.003) and area of the left isthmus of the cingulate gyrus (β = 0.151; p value = <0.001) across all patients. Inclusion of an interaction term (dementia × CSDD) revealed a smaller area in the left temporal pole (β = -0.345; p value = 0.001) and right-transverse temporal cortex (β = -0.321; p value = 0.001) in patients with dementia and depressive symptoms. We confirm the previous findings of structural brain changes in temporal regions among patients with dementia and concomitant depressive symptoms. This may contribute to a better understanding of the mechanisms underlying depression in dementia. To the best of our knowledge, this is the largest study conducted on this topic to date.


Tetracycline resistance of Escherichia coli isolated from water, human stool, and fish gills from the Lake Sevan basin.
The ecological state of Lake Sevan, the largest drinking water reservoir for the South Caucasus, formed under the influence of climatic and social changes. This study assesses the bacteriological quality of water in the rivers of the Lake Sevan basin and tetracycline-resistant bacteria isolated from fish and people living near the rivers of the Lake Sevan basin in Armenia in autumn 2019 and spring 2020. No differences have been shown for the tetracycline resistance of the investigated E. coli isolated from the human gut and the Masrik, Argichi, and Gavaraget Rivers. Horizontal gel electrophoresis revealed the same plasmid bands in most of the investigated E. coli with the same tetracycline resistance from the different sources of the Argichi River (obtained from people/fish/water sources where the fish were caught). The results also showed that most of the waters carried Edwardsiella spp., Erwinia spp., Morganella spp., and Proteus spp. in addition to E. coli; the coliform index did not exceed the standard level of 5 × 104 CFU mL-1 there. These findings highlight the importance of multidisciplinary studies of bacteria from "interacting" ecosystems, which might serve as a basis for the suggestion of microbial antibiotic resistance as another indicator of water pollution.


Primary and postoperative retroperitoneal fibrosis-experience with 18 cases.
Retroperitoneal fibrosis (RPF) is an uncommon disease complicated by ureteral entrapment. Its etiology includes several medications, periaortic inflammation, abdominal and retroperitoneal operations, radiotherapy, and malignancy. We present 18 patients, 14 of whom developed RPF after surgery and radiotherapy. During the past 12 years, we treated 7 women and 11 men. The diagnosis was based on intravenous urography, retrograde pyelography, and computed tomography features. Computed tomography-guided or intraoperative biopsies were taken to differentiate benign from malignant fibrosis. In all patients, percutaneous stent nephrostomies or internal stents were inserted before surgery. The operation included ureterolysis with an omental flap or ureteral reimplantation. Follow-up included renal function tests, intravenous urography, and computed tomography. The mean patient age was 57.3 years (range 36 to 85). Fourteen patients developed RPF after abdominal or retroperitoneal surgery. Three had primary RPF and one malignant RPF due to metastatic disease. Six patients also underwent radiotherapy. The mean time between the insults to the diagnosis of RPF was 18.6 months (range 1 to 96). Ten patients had bilateral obstruction. Fourteen patients underwent surgery and four were treated with stenting only. Of the 14 patients who underwent surgery, 10 had a normal intravenous urogram postoperatively and 4 had decreased function of the formerly obstructed kidney. In 1 patient, re-entrapment of the ureter appeared owing to pelvic recurrence of tumor. At last follow-up, 1 patient waits with stents. The mean follow-up time was 22 months (range 4 to 52). The etiology of RPF varies. The unique feature of our series was the high incidence of patients who developed RPF after surgery and radiotherapy to the retroperitoneum. Nephrostomy drainage and ureteral stenting facilitated surgery. Ureterolysis combined with wrapping the ureter with an omental flap or re-implantation ensured good anatomic and functional results.


Older Adults' Perspectives on Voluntary Assisted Death: An In-Depth Qualitative Investigation in Australia.
Interest in voluntary assisted death (VAD) has been growing among researchers, policy makers and the public. This study aimed to explore older adults' perspectives on VAD in Australia. Using purposive sampling, 15 adults ≥65 years participated in in-depth semi-structured interviews. Interpretative phenomenological analysis identified four themes: cultural reflections; beliefs and worldviews; health aspects; and fabric of life. Participants expressed a desire to have control over end-of-life options, challenged by religious beliefs. Participants expressed concern that VAD legislation could leave people vulnerable to coercion and saw a need for safeguards. Reasons for and against supporting and utilising VAD were discussed. Physical illness was seen a more compelling reason for VAD than mental ill-health. Finally, connections to life and other were discussed, and being able to do the things one loved were named aspects of what it meant to live a good life. Implications are discussed along with future research directions.


Meaning and centrality of caring activities among older women.
This article explores the meaning and conditions of caring activities for older women. Taped, in-person interviews were conducted with 53 ethnically and economically diverse women, 55-84 years old. The interview guide contained open-ended questions regarding the process of taking on caring activities and the centrality of care to personal identity. Past activities were automatically assumed, in contrast to the present experience of choice. Caring activities provided meaning and continuity throughout the life course. Participants reported becoming more self-protective over the life course and offered seven explanations for their increased ability to be self-protective.


Japanese children's understanding of notational systems.
This study examined Japanese children's understanding of two Japanese notational systems: hiragana and kanji. In three experiments, 126 3- to 6-year-olds were asked to name words written in hiragana or kanji as they appeared with different pictures. Consistent with Bialystok (Journal of Experimental Child Psychology, 2000, Vol. 76, pp. 173-189), 3- and 4-year-olds' identification of written words varied according to the picture with which they appeared, and older children named the words with different pictures more accurately. The 4-year-olds who could read words written in hiragana but could not read words written in kanji named both hiragana words and kanji words with different pictures more accurately than those who could not read hiragana and kanji words. The interrelationship between the symbol-sound relationships and the symbol-referent relationships of notational systems is discussed.


[Anesthetics responsible for anaphylactic shock. A French multicenter study].
Combined allergological and anaesthetic consultations have been started in the last few years in eight French Teaching Hospitals so as to explore peranaesthetic anaphylactoid shocks. A survey was carried out in these centers in order to collect patients investigated with the same protocol, for the assessment of the incidence of anaphylaxis in France, as well as the involved drugs. Investigations were always carried out at least 6 to 8 weeks after the accident. The tests used to diagnose IgE-dependent anaphylaxis were skin tests (prick and intradermal tests, carried out in all eight centers), the radioimmunological assay of specific anti-quaternary ammonium IgE, together with an inhibition test with thiopentone and propofol (six centers), leukocyte histamine release (five centers) and human basophil degranulation tests (three centers) for those drugs for which no specific antibody assay exists. The collected data involved 1,240 patients, investigated within the last four years. Anaphylaxis was diagnosed in 821 patients (66.2%). Muscle relaxants were responsible in 668 cases (80% of cases of anaphylaxis). Suxamethonium was the main cause (54.3% of shocks due to muscle relaxants), followed by vecuronium (15.3%). General anaesthetics (hypnotics and benzodiazepines) were responsible for 9.2% of all cases of anaphylaxis opioids for 2.6%. There were only three cases of shock due to local anaesthetic agents. Latex and ethylene oxide are becoming increasingly involved. It would therefore seem mandatory to carry out after any anaphylactoid accident an assessment with sensitive and specific tests for anaphylaxis. Diagnosing anaphylaxis means that the involved drug should be used never again in that patient. Because muscle relaxants are by far the most involved drugs, anaesthetists should use them only when really required.


Effect of exercise on the kidney of aging mice.
Quantitative light microscopic and ultrastructural kidney changes were studied in young and old mice subjected to moderate exercise. While there was little or no change in the glomeruli of the young animals, the older age-group showed progressive and statistically significant mesangial sclerosis with obliteration of capillary lumina. Electron microscopy also showed electron dense deposits in both the mesangium and subendothelium. Kidney weight in the young mice subjected to exercise was decreased when compared with the controls, while old animals showed a higher kidney weight after 6 weeks of running exercise. Our results of progressive kidney changes in old exercising animals, together with previous studies on myocardial and skeletal muscle showing parallel changes, stress the need for careful clinical studies on the possible damage of these organs in older people who engage in jogging and heavy exercise.


Exotic superconducting properties in the electron-hole-compensated heavy-fermion "Semimetal" URu2Si2.
We show that the charge and thermal transport measurements on ultraclean crystals of URu2Si2 reveal a number of unprecedented superconducting properties. The uniqueness is best highlighted by the peculiar field dependence of thermal conductivity including the first-order transition at Hc2 with a reduction of entropy flow. This is a consequence of multiband superconductivity with compensated electronic structure in the hidden order state of this system. We provide strong evidence for a new type of unconventional superconductivity with two distinct gaps having different nodal topology.


Inadvertent radical nephrectomy leads to worse prognosis in renal pelvic urothelial carcinoma patients: A propensity score-matched study.
To compare overall survival (OS) and cancer-specific survival (CSS) in renal pelvic urothelial carcinoma (RPUC) patients treated with radical nephroureterectomy (NU) and inadvertent radical nephrectomy (RN). In this retrospective study, patients with RPUC who underwent NU or RN diagnosed between 2004 and 2017 were identified from the Surveillance, Epidemiology, and End Results database. To adjust the confounders, the propensity score-matched analysis was conducted. The Kaplan-Meier method and log-rank test were performed to explore the effect of different surgical methods on OS and CSS. A total of 2197 cases were finally included in this analysis, among which, 187 (8.5%) patients were treated with RN and 2010 (91.5%) patients were treated with NU. Before matching, the survival analysis revealed that the OS (HR: 1.444, 95%CI: 1.197, 1.741) and CSS (HR: 1.522, 95%CI: 1.211, 1.914) of patients who received RN were worse than that of patients who received NU (p = 0.0001 and p = 0.0003, respectively). After matching, the RN group had a worse OS (HR: 1.298, 95%CI: 1.002, 1.682) than the NU group (p = 0.048). No significant difference was observed in CSS between the RN and NU groups (p = 0.282). The hierarchical analysis showed that there was no significant difference observed in OS and CSS in patients with tumor size ≤4.2 cm (p = 0.884 and p = 0.496, respectively). In tumor size >4.2 cm, both OS (HR: 1.545, 95%CI: 1.225, 1.948) and CSS (HR: 1.607, 95%CI: 1.233, 2.095) of patients who received RN were worse than those of patients who received NU (p = 0.0002 and p = 0.0005). RN could lead to worse oncological outcomes than NU in patients with renal pelvis urothelial carcinoma. Accurate diagnosis of renal pelvis urothelial carcinoma is extremely important.


Coriolis and centrifugal forces drive haltere deformations and influence spike timing.
The halteres of flies are mechanosensory organs that serve a crucial role in the control of agile flight, providing sensory input for rapid course corrections to perturbations. Derived from hind wings, halteres are actively flapped and are thus subject to a variety of inertial forces as the fly undergoes complex flight trajectories. Previous analyses of halteres modelled them as a point mass, showing that Coriolis forces lead to subtle deflections orthogonal to the plane of flapping. By design, these models could not consider the effects of force gradients associated with a mass distribution, nor could they reveal three-dimensional spatio-temporal patterns of strain that result from those forces. In addition, diversity in the geometry of halteres, such as shape and asymmetries, could not be simply modelled with a point mass on a massless rod. To study the effects of mass distributions and asymmetries, we examine the haltere subject to both flapping and body rotations using three-dimensional finite-element simulations. We focus on a set of simplified geometries, in which we vary the stalk and bulb shape. We find that haltere mass distribution gives rise to two unreported deformation modes: (i) halteres twist with a magnitude that strongly depends on stalk and bulb geometry and (ii) halteres with an asymmetric mass distribution experience out-of-plane bending due to centrifugal forces, independent of body rotation. Since local strains at the base of the haltere drive deformations of mechanosensory neurons, we combined measured neural encoding mechanisms with our structural analyses to predict the spatial and temporal patterns of neural activity. This activity depends on both the flapping and rotation dynamics, and we show how the timing of neural activity is a viable mechanism for rotation-rate encoding. Our results provide new insights in haltere dynamics and show the viability for timing-based encoding of fly body rotations by halteres.


Proton Pump Inhibitors Intake and Iron and Vitamin B12 Status: A Prospective Comparative Study with a Follow up of 12 Months.
Proton pump inhibitors (PPIs) represent the most widely prescribed antisecretory agents, but their prolonged use, may influence iron and vitamin B12 status, which could have important implications for clinical practice. We undertook this study aiming to investigate the association between PPIs use for 12 months and potential changes in iron and vitamin B12 status, as well as whether this potential association varies among four specific PPI drugs used in the study. A total of 250 adult subjects were recruited into this study, of which 200 subjects were PPIs users while 50 subjects belonged to the control group. Serum iron, ferritin, vitamin B12, and homocysteine (Hcy) levels were measured before the start of the study and after 12 months. Mann - Whitney U test and Kruskal - Wallis test was used to compare the baseline characteristics of the study groups, while Wilcoxon test was used to analyse post - pre differences. Statistical analysis showed significant changes within PPIs group and specific PPIs subgroups between the two-time points in serum ferritin and vitamin B12 levels, respectively, while no significant changes in serum iron and homocysteine levels were shown. However, subsequent diagnosis of hypoferremia and hypovitaminosis B12 in the whole study sample at 12 months was established in only 3.8% and 2.9% of the subjects, respectively. PPIs use for 12 months did not result in clinically significant iron and/or vitamin B12 deficiency; thus, these findings argue routine screening under normal circumstances, although monitoring in elderly and malnourished may be of precious value.


Single-nucleus transcriptional profiling of GAD2-positive neurons from mouse lateral habenula reveals distinct expression of neurotransmission- and depression-related genes.
Glutamatergic projection neurons of the lateral habenula (LHb) drive behavioral state modulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that modulate LHb output is of interest for understanding control of motivated behaviors. A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic synthesizing enzyme GAD2, and they can inhibit nearby LHb projection neurons; however, these neurons lack markers of classic inhibitory interneurons and they co-express the vesicular glutamate transporter VGLUT2. To determine the molecular phenotype of these neurons, we genetically tagged the nuclei of GAD2-positive cells and used fluorescence-activated nuclear sorting to isolate and enrich these nuclei for single nuclear RNA sequencing (FANS-snRNAseq). Our data confirm that GAD2+/VGLUT2+ neurons intrinsic to the LHb co-express markers of both glutamatergic and GABAergic transmission and that they are transcriptionally distinct from either GABAergic interneurons or habenular glutamatergic neurons. We identify gene expression programs within these cells that show sex-specific differences in expression and that are implicated in major depressive disorder (MDD), which has been linked to LHb hyperactivity. Finally, we identify the Ntng2 gene encoding the cell adhesion protein Netrin-G2 as a marker of LHb GAD2+/VGLUT+ neurons and a gene product that may contribute to their target projections. These data show the value of using genetic enrichment of rare cell types for transcriptome studies, and they advance understanding of the molecular composition of a functionally important class of GAD2+ neurons in the LHb.


Condyloma acuminata on the nipple and coronary sulcus of the penis: A case report.
Condyloma acuminatum (CA) is a benign tumor primarily caused by infection with human papillomavirus (HPV) type-6 or type-11, lesions of which are most frequently found on the genital and perianal squamous mucosa and skin. CA outside the genitals is not common. A 29-year-old male presented with lesions on the left nipple and coronary sulcus after heterosexual contact. Histopathological examination and HPV detection made a definite diagnosis of CA. The patient was treated with microwave and topical imiquimod cream. After 6 months follow-up, there was no sign of recurrence. This case shows that we should pay more attention to CA outside the genitals in the process of diagnosis and treatment.


GAIT DEFICITS UNDER DUAL - TASK CONDITIONS IN THE CONCUSSED ADOLESCENT AND YOUNG ATHLETE POPULATION: A SYSTEMATIC REVIEW.
There are no current sport concussion assessments that capture the effects of dual-task conditions on gait. Multiple studies have evaluated changes, but none have comprehensively examined literature related to the adolescent and young adult population.Purpose: The purpose of this systematic review is to synthesize documented changes in gait under dual-task conditions in adolescents and young adults after sustaining a concussion.Study Design: Systematic Review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was consulted to guide this systematic review. Six databases were searched: Cinahl, ProQuest, PubMed, Scopus, SPORTdiscus, and Web of Science. Concussion, gait, and dual-task, along with their synonymous terms were the search terms used. Inclusion criteria consisted of adolescent and young adult age groups, acute concussion, dual-tasking, and matched controls. Quality assessment was performed using The Joanna Briggs Institute Critical Appraisal Checklist for Case Control Studies. Ten full-text articles were selected for inclusion. Concussed individuals demonstrated longer stride times with shorter stride lengths, increased mediolateral displacement with corresponding increases in sagittal and frontal plane peak velocity, and decreased sagittal plane Center of Mass (COM) and Center of Pressure (COP) displacement. The majority of included studies demonstrated moderate to large effect sizes in these gait characteristics. Concussed individuals demonstrated decreased gait stability while ambulating with a dual-task condition. Though statistically significant differences between concussed individuals and matched controls lasted only 72 hours, concussed individuals demonstrated continued improvements in gait for up to two months post-injury, which has the potential to affect an athlete's ability to perform. Further research is needed to determine if a gait examination with a dual-task condition is a realistic, reliable, and valid measure to be included in return to sport testing. 2a.


Using Game Theory to Understand Systemic Acquired Resistance as a Bet-Hedging Option for Increasing Fitness When Disease Is Uncertain.
Systemic acquired resistance (SAR) is a mechanism through which plants may respond to initial challenge by a pathogen through activation of inducible defense responses, thereby increasing resistance to subsequent infection attempts. Fitness costs are assumed to be incurred by plants induced for SAR, and several studies have attempted to quantify these costs. We developed a mathematical model, motivated by game-theoretic concepts, to simulate competition between hypothetical plant populations with and without SAR to examine conditions under which the phenomenon of SAR may have evolved. Data were gathered from various studies on fitness costs of induced resistance on life history traits in different plant hosts and scaled as a proportion of the values in control cohorts in each study (i.e., healthy plants unprimed for SAR). With unprimed healthy control plants set to a fitness value of 1, primed healthy plants incurred a fitness cost of about 10.4% (0.896, n = 157), primed diseased plants incurred a fitness cost of about 15.5% (0.845, n = 54), and unprimed diseased plants incurred a fitness cost of about 28.9% (0.711, n = 69). Starting from a small proportion of the population (0.5%) and competing against a population with constitutive defenses alone in stochastic simulations, the SAR phenotype almost always dominated the population after 1000 generations when the probability of disease was greater than or equal to 0.5 regardless of the probability for priming errors.


N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-[4-(methyl-sulfan-yl)phen-yl]acetamide.
In the title compound, C(20)H(21)N(3)O(2)S, the 2,3-dihydro-1H-pyrazole ring is nearly planar (r.m.s. deviation = 0.023 Å) and forms dihedral angles of 16.96 (6) and 38.93 (6)° with the benzene and phenyl rings, respectively. The dihedral angle between the benzene and phenyl rings is 55.54 (6)°. The mol-ecular conformation is consolidated by an intra-molecular C-H⋯O hydrogen bond, which forms an S(6) ring. In the crystal, inversion dimers linked by pairs of N-H⋯O(p) (p = pyrazole) hydrogen bonds generate R(2) (2)(10) loops. The dimers are linked by C-H⋯O hydrogen bonds into sheets lying parallel to (100).


Circadian time structure of endocrine and biochemical parameters in adult onset (type II) diabetic patients.
Forty-one endocrine and biochemical serum parameters were studied over a 24-hour span with 6 samples at 4-hour intervals in 20 non-insulin dependent (Type II) diabetics and in 20 non-diabetic subjects matched for sex, age, height and weight. Circadian rhythms were verified by cosinor analysis. Group-synchronized circadian rhythms were detected in diabetic and non-diabetic subjects with no statistically significant difference in any of the rhythm parameters (rhythm adjusted mean, amplitude and acrophase) in: Aldosterone, cortisol, insulin, 17-OH progesterone, prolactin, testosterone, TSH, and in serum albumin, creatine phosphokinase (CPK), serum iron, inorganic phosphate and total protein. Statistically significant (p less than .05) circadian rhythms in both groups with a difference in some parameters between the diabetic and the non-diabetic subjects, which were verified by the Bingham Test (p less than .05) were found with a difference in the mesor in cholesterol, glucose, urea nitrogen (BUN), in the amplitude in C-peptide and in the acrophase in triglycerides, globulin and reverse T3 (rT3). Statistically significant circadian rhythms were detected as a group phenomenon for the diabetics only in progesterone, free and total T4, chloride, calcium, bilirubin and LDH and in the non-diabetic subjects only in ACTH, LH, total T3, alkaline phosphatase, uric acid and potassium. In the remainder of the functions studied, a circadian rhythm was detectable with statistical significance by cosinor analysis as a group phenomenon neither in the diabetics nor in the matched non-diabetic controls (DHEA-S, estradiol, FSH, GH, glucagon, free T3, sodium, GOT and gamma GT). In the absence of a detectable circadian rhythm as group phenomenon, the circadian mean was different between the diabetics and the non-diabetic subjects in sodium, chloride and calcium which were higher in the diabetic patients and serum LDH which was lower. In a comparison of endocrine determinations in the two groups, the circadian mean or mesor in T3 was lower in the diabetics and ACTH higher, without corresponding changes in TSH or in corticosteroids. The circadian time structure of Type II diabetic patients thus seems to be very similar to that seen in non-diabetic subjects of the same sex, age, weight and height. The minor differences found in some rhythm parameters will have to be confirmed or excluded in larger numbers of subjects. The higher circadian mean ACTH concentrations without change in steroid rhythm parameters observed in this group is interesting but will also require confirmation.(ABSTRACT TRUNCATED AT 400 WORDS)


Zebrafish models for dyskeratosis congenita reveal critical roles of p53 activation contributing to hematopoietic defects through RNA processing.
Dyskeratosis congenita (DC) is a rare bone marrow failure syndrome in which hematopoietic defects are the main cause of mortality. The most studied gene responsible for DC pathogenesis is DKC1 while mutations in several other genes encoding components of the H/ACA RNP telomerase complex, which is involved in ribosomal RNA(rRNA) processing and telomere maintenance, have also been implicated. GAR1/nola1 is one of the four core proteins of the H/ACA RNP complex. Through comparative analysis of morpholino oligonucleotide induced knockdown of dkc1 and a retrovirus insertion induced mutation of GAR1/nola1 in zebrafish, we demonstrate that hematopoietic defects are specifically recapitulated in these models and that these defects are significantly reduced in a p53 null mutant background. We further show that changes in telomerase activity are undetectable at the early stages of DC pathogenesis but rRNA processing is clearly defective. Our data therefore support a model that deficiency in dkc1 and nola1 in the H/ACA RNP complex likely contributes to the hematopoietic phenotype through p53 activation associated with rRNA processing defects rather than telomerase deficiency during the initial stage of DC pathogenesis.


[Roles of ATP receptors in the regulation of various functions in spinal microglia].
It is shown that glial cells have a pivotal influence on the formation of neuronal network in central nerve system. Moreover, spinal microglia has some important roles in the development and progression of various neurological disorders. Therefore, it is possible that modulation of microglial activity may be sufficient to alleviate those harmful responses. ATP is one of signaling molecules in the spinal cord, and involved in regulation of several microglial functions through the binding of P2X and P2Y receptors. Thus, I focused on the ATP-mediated regulation mechanisms for the two important proteins, which are p38 MAP kinase and excitatory amino acid transporters (EAATs), in cultured spinal microglia. Mounting evidence indicates that p38 in spinal microglia has crucial roles in some neurological diseases. Furthermore, it is recently suggested that microglial EAATs might participate in the homeostasis of glutamate in synapses. This review summarizes our finding regarding the involvement of P2Y receptors and β-adrenergic receptors in the regulation of p38 phosphorylation, and the mechanism of P2X7 receptor-mediated downregulation of EAATs function.


Thin Films of Metal-Organic Framework Interfaces Obtained by Laser Evaporation.
Properties such as large surface area, high pore volume, high chemical and thermal stability, and structural flexibility render zeolitic imidazolate frameworks (ZIFs) well-suited materials for gas separation, chemical sensors, and optical and electrical devices. For such applications, film processing is a prerequisite. Herein, matrix-assisted pulsed laser evaporation (MAPLE) was successfully used as a single-step deposition process to fabricate ZIF-8 films. By correlating laser fluency and controlling the specific transfer of lab-synthesized ZIF-8, films with user-controlled physical and chemical properties were obtained. Films' characteristics were evaluated by scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The analysis showed that frameworks of ZIF-8 can be deposited successfully and controllably to yield polycrystalline films. The deposited films maintained the integrity of the individual ZIF-8 framework, while undergoing minor crystalline and surface chemistry changes. No significant changes in particle size were observed. Our study demonstrated control over both the MAPLE deposition conditions and the outcome, as well as the suitability of the listed deposition method to create composite architectures that could potentially be used in applications ranging from selective membranes to gas sensors.


Antifungal susceptibilities of bloodstream isolates of Candida species from nine hospitals in Korea: application of new antifungal breakpoints and relationship to antifungal usage.
We applied the new clinical breakpoints (CBPs) of the Clinical and Laboratory Standards Institute (CLSI) to a multicenter study to determine the antifungal susceptibility of bloodstream infection (BSI) isolates of Candida species in Korea, and determined the relationship between the frequency of antifungal-resistant Candida BSI isolates and antifungal use at hospitals. Four hundred and fifty BSI isolates of Candida species were collected over a 1-year period in 2011 from nine hospitals. The susceptibilities of the isolates to four antifungal agents were determined using the CLSI M27 broth microdilution method. By applying the species-specific CBPs, non-susceptibility to fluconazole was found in 16.4% (70/428) of isolates, comprising 2.6% resistant and 13.8% susceptible-dose dependent isolates. However, non-susceptibility to voriconazole, caspofungin, or micafungin was found in 0% (0/370), 0% (0/437), or 0.5% (2/437) of the Candida BSI isolates, respectively. Of the 450 isolates, 72 (16.0%) showed decreased susceptibility to fluconazole [minimum inhibitory concentration (MIC) ≥4 μg/ml]. The total usage of systemic antifungals varied considerably among the hospitals, ranging from 190.0 to 7.7 defined daily dose per 1,000 patient days, and fluconazole was the most commonly prescribed agent (46.3%). By Spearman's correlation analysis, fluconazole usage did not show a significant correlation with the percentage of fluconazole resistant isolates at hospitals. However, fluconazole usage was significantly correlated with the percentage of fluconazole non-susceptible isolates (r = 0.733; P = 0.025) or the percentage of isolates with decreased susceptibility to fluconazole (MIC ≥4 μg/ml) (r = 0.700; P = 0.036) at hospitals. Our work represents the first South Korean multicenter study demonstrating an association between antifungal use and antifungal resistance among BSI isolates of Candida at hospitals using the new CBPs of the CLSI.


Relationships in the Caryophyllales as suggested by phylogenetic analyses of partial chloroplast DNA ORF2280 homolog sequences.
Phylogenetic relationships within the angiosperm order Caryophyllales were investigated by comparative sequencing of two portions of the highly conserved inverted repeat (totaling some 1100 base pairs) coinciding with the region occupied by ORF2280 in Nicotiana, the largest gene in the plastid genomes of most land plants. Data were obtained for 33 species in 11 families within the order and for one species each of Plumbaginaceae, Polygonaceae, and Nepenthaceae. These data, when analyzed along with previously published ORF (open reading frame) sequences from Nicotiana. Spinacia. Epifagus, and Pelargonium using parsimony, neighbor-joining, and maximum likelihood methods, reveal that: (1) Amaranthus, Celosia, and Froelichia (all Amaranthaceae) do not comprise a monophyletic group; (2) Amaranthus may be nested within a paraphyletic Chenopodiaceae; (3) Sarcobatus (Chenopodiaceae) is allied with Nyctaginaceae + Phytolaccaceae (the latter family excluding Stegnosperma but including Petiveria); and (4) Caryophyllaceae (with Corrigiola basal within the clade) are sister group to Chenopodiaceae + Amaranthaceae. Basal relations within the order remain obscure. Sequence divergence values in pairwise comparisons across all Caryophyllales taxa ranged from 0.1 to 5% of nucleotides. However, despite these low values, 23 insertion and deletion events were apparent, of which five were informative phylogenetically and bolstered several of the relationships listed above. A polymerase chain reaction (PCR) survey for ORF homolog length variants in representatives from 70 additional angiosperm families revealed major deletions, of 100 to 1400 base pairs, in 19 of these families. Although the ORF is located within the mutationally retarded inverted repeat region of most angiosperm chloroplast DNAs, this gene appears particularly prone to length mutation.


Stable N-heterocyclic carbene adducts of arylchlorosilylenes and their germanium homologues.
The first N-heterocyclic carbene adducts of arylchlorosilylenes are reported and compared with the homologous germanium compounds. The arylsilicon(II) chlorides SiArCl(Im-Me(4)) [Ar=C(6)H(3)-2,6-Mes(2) (Mes=C(6)H(2)-2,4,6-Me(3)), C(6)H(3)-2,6-Trip(2) (Trip=C(6)H(2)-2,4,6-iPr(3))] were obtained selectively on dehydrochlorination of the arylchlorosilanes SiArHCl(2) with 1,3,4,5-tetramethylimidazol-2-ylidene (Im-Me(4)). The analogous arylgermanium(II) chlorides GeArCl(Im-Me(4)) were prepared by metathetical exchange of GeCl(2)(Im-Me(4)) with LiC(6)H(3)-2,6-Mes(2) or addition of Im-Me(4) to GeCl(C(6)H(3)-2,6-Trip(2)). All compounds were fully characterized. Density functional calculations on ECl(C(6)H(3)-2,6-Trip(2))(Im-Me(4)), where E=Si, Ge, at different levels of theory show very good agreement between calculated and experimental bonding parameters, and NBO analyses reveal similar electronic structures of the two aryltetrel(II) chlorides. The low gas-phase Gibbs free energy of bond dissociation of SiCl(C(6)H(3)-2,6-Trip(2))(Im-Me(4)) (Delta(calcd) degrees=28.1 kJ mol(-1)) suggests that the carbene adducts SiArCl(Im-Me(4)) may be valuable transfer reagents of the arylsilicon(II) chlorides SiArCl.


Dacarbazine-encapsulated solid lipid nanoparticles for skin cancer: physical characterization, stability, in-vivo activity, histopathology, and immunohistochemistry.
This study examined the use of solid lipid nanoparticles (SLNs) to administer Dacarbazine (DTIC) to skin melanoma cells with minimal adverse effects. Melanoma is a tricky skin cancer to cure, and standard chemotherapy has many negative effects. Encapsulating DTIC in SLNs may allow the drug to target melanoma cells without harming healthy cells. The study developed and tested DTIC-loaded SLNs for skin melanoma treatment. This study encapsulated Dacarbazine (DTIC) in solid lipid nanoparticles (SLNs). SLNs with reversed micelles were produced utilizing specified ratios of the surfactant Kolliphor® P188 and phosphatidylcholine. To track SLN drug localisation, gold nanoparticles were conjugated to the DTIC. Nanoparticle size and form were examined using DLS and TEM. These approaches ensured SLNs had the correct size and shape for drug delivery. In the study, various parameters of the developed solid lipid nanoparticles (SLNs) were evaluated, including particle size, zeta potential, polydispersity index (PDI), entrapment efficacy, and cumulative drug permeation. The values for these parameters varied across the different formulations, with particle size ranging from 146 ± 4.71 nm to 715 ± 7.36 nm, zeta potential from -12.45 ± 2.78 mV to -30.78 ± 2.83 mV, PDI from 0.17 ± 0.013 to 0.51 ± 0.023, entrapment efficacy from 37.78 ± 2.78% to 87.45 ± 4.78%, and cumulative drug permeation from 117 ± 4.77 μg/cm2 to 275 ± 5.67 μg/cm2. To determine the optimal anti-cancer formulation, the DTIC-SLNs-8 nanoparticles were mixed with an optimized concentration of Gellan gum (0.01% w/v) and applied to DMBA-induced skin tumors in rats for six weeks, twice daily. Histopathology demonstrated that DTIC-SLNs-8-treated rats had less keratosis, inflammatory responses, and angiogenesis than free DTIC-treated rats. The development of SLNs may be a promising approach for melanoma treatment due to their improved drug retention over the skin. The optimised anti-cancer formulation DTIC-SLNs-8 showed improved efficacy with minimal side effects as compared to free DTIC.


[Analysis of teicoplanin impurities by two-dimensional ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry].
A two-dimensional ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (2D-UPLC-Q/TOF-MS) method was established for the separation and structural analysis of the components in teicoplanin. This method effectively solved the problems associated with chromatographic systems, such as liquid chromatography-mass spectrometry (LC-MS), which used a non-volatile phosphate buffer as the mobile phase and were not suitable for the rapid identification of impurities. Moreover, this method circumvented the complexities associated with locating and identifying impurities using the original method by re-establishing a chromatographic system suitable for LC-MS. In this study, for one-dimensional (1D) chromatography, the chromatographic separation was performed on an Octadecyl silica (ODS) hypersil column (250 mm×4.6 mm, 5 μm) with gradient elution using 3.0 g/L sodium dihydrogen phosphate buffer (pH 6.0)/acetonitrile=9/1 (v/v) as mobile phase A and 3.0 g/L sodium dihydrogen phosphate buffer (pH 6.0)/acetonitrile=3/7 (v/v) as mobile phase B. The column temperature was maintained at 30 ℃ and an ultraviolet detector was used at 254 nm for analysis. For 2D chromatography, desalting was performed on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) with gradient elution using ammonium formate buffer (pH 6.0) and acetonitrile as the mobile phases. The column temperature was maintained at 45 ℃. The MS data for the components and impurities were collected by positive ion electrospray ionization (ESI) using the full-information tandem MS mode (MSE). The cone and nebulizer gas flow rates were set at 50 and 900 L/h, respectively. The ion source and nebulizer gas temperatures were set at 120 ℃ and 500 ℃, respectively. The ESI and cone needle voltages were set at 2500 and 60 V, respectively. The collision energy was set at 20-50 eV. The molecular formulas of the components and impurities were determined using their exact masses and isotope distributions, and the structural components and impurities of teicoplanin were deduced from their fragment ions according to the fragmentation pathway of the TA2-2 component. Moreover, the 10 components reported in the European Pharmacopoeia 10.0 were analyzed and 22 impurities of teicoplanin were identified by 2D-UPLC-Q/TOF-MS. Three new impurities and two characteristic fragment ions of the teicoplanin parent nucleus were detected, and the fragmentation pathway of TA2-2 was deduced. Using this method, 1D-UPLC is applicable for the accurate qualification of components based on relative retention times, and 2D-UPLC-Q/TOF-MS is suitable for the rapid identification of the structure of components based on their fragment ions. The results indicate that 2D-UPLC-Q/TOF-MS may be used to analyze the structure of impurities in teicoplanin based on their exact masses, isotope distributions, and fragment ions. The method is rapid, simple, and sensitive, which provides a novel strategy for the quality control and process optimization of teicoplanin.


Preparation, characterization, and in vivo pharmacodynamic evaluation of parenteral diclofenac submicron lipid emulsions.
The aim of the present study was to develop stable parenteral submicron lipid emulsions (SLEs) for sustained delivery of diclofenac acid, used to treat arthritic conditions, to minimize dosing frequency. The SLEs of diclofenac acid were prepared using soybean oil, egg lecithin, and cholesterol. They were heated and processed by homogenization and ultrasonication. The influence of formulation variables, such as the change in proportion of oil and cholesterol, were studied, and optimized formulations were developed. The stability of the optimized formulations SM-A (no cholesterol), SM-I (0.05% cholesterol), and SM-II (0.1% cholesterol) was studied during autoclaving, centrifugal stress, desorption stress (dilution effect), and on storage. The creaming volume percentage was found during the storage and centrifugal stress studies. The effect of dilution on zeta potential and size was noted in the desorption studies. The total drug content and entrapment efficiency was determined using high-performance liquid chromatography. In vitro release studies were performed in phosphate buffer using dialysis method for 12 h. The in vivo anti-inflammatory activity (reduction in paw volume of optimized SLEs) was tested in a 1% carrageenan-induced rat paw oedema model and compared with a diclofenac injection (Voveran). Stable SLEs of diclofenac were developed with a mean size ranging from 200-250 nm and a zeta potential of -31 +/- 1 mV. The cholesterol concentration did not significantly affect the prepared SLEs' size and zeta potential. The optimized formulations, SM-A, SM-I, and SM-II, were relatively stable during centrifugal stress, dilution stress, and storage. The drug content was found to be 2.45 +/- 0.26 mg/mL for SM-A, 2.46 +/- 0.34 mg/mL for SM-I, and 2.42 +/- 0.01 mg/mL for SM-II. The entrapment efficiency was 98.91 +/- 0.13%, 99.01 +/- 0.12%, and 99.27 +/- 0.1% for SM-A, SM-I and SM-II, respectively. The in vitro drug release was zero-order and the cumulative amount of drug released within 12 h was 80% (SM-A), 57% (SM-I), and 42% (SM-II. During in vivo studies, the optimized formulations initially revealed a sustained anti-inflammatory activity occurring up to 12 h, with a maximum activity occurring after 2 h. In the case of the diclofenac injection, the maximum activity persisted up to 5 h and then gradually decreased. No such decrease was noticed regarding the optimized formulations for a period extending up to 12 h. Beyond 12 h, activity persisted up to 24 h with a slight reduction in effect.


Anti-adhesion and anti-biofilm activity of slightly acidic electrolyzed water combined with sodium benzoate against Streptococcus mutans: A novel ecofriendly oral sanitizer to prevent cariogenesis.
Streptococcus mutans (S. mutans) can promote the establishment of high acidic biofilms and therefore have contribution to the development of dental caries. Alleviating the acidic environment and/or disrupting the structure of S. mutans biofilm are effective approaches against dental caries, rather than killing the microorganisms. The anti-biofilm effect of slightly acidic electrolyzed water (SAEW) is entirely based on the hypochlorous acid and ROS generation. In this study, sodium benzoate (NaB) acts as a pH adjuster and enhances SAEW's anti-biofilm activity. The results showed that the SAEW combined with NaB (SAEW + NaB) is highly effective in controlling biofilm. The adhesive strength of biofilm was significantly reduced by SAEW, and NaB was found to have a synergy effect with SAEW. Biofilm treated by SAEW + NaB was entirely removed by 60 s of ultrasonic wave, whereas the untreated biofilm can only be removed to a lesser extent. Atomic force microscope (AFM) analysis revealed that SAEW and NaB reduced the height of S. mutans biofilm. The metabolites derived from biofilm positively changed during the periodic 1-min treat, the production of lactic acid was hindered by the treatment. Altogether, these findings suggested a novel therapeutic intervention against S. mutans biofilm by targeting the cariogenic action.


Susceptibility to faking of a sentence completion test of ego development.
Effects of faking on a sentence completion test. of ego development, explored in five experiments, partially confirmed the developmental hypothesis that persons can lower their ego level test scores but not increase them. When faking high on retest, subjects scores either stayed the same or increased by about a half step. Only intensive study of ego development seemed genuinely to increase scores. When faking a bad impression or a low ego level, subjects' scores decreased, typically to the pre-Conformist level. Unexpectedly, attempts to make a good impression lowered high scores, especially for women, Because the test is susceptible to factors which can artificially lower scores, careful planning and evaluation of testing conditions must accompany test use.


Sampling Transgenic Corn Producing Bt Toxins for Corn Earworm Injury.
Transgenic corn, Zea mays L., hybrids expressing insecticidal proteins from Bacillus thuringiensis (Bt) and non-Bt near isolines were sampled for injury from Helicoverpa zea (Boddie) in North and South Carolina from 2012 to 2017. A total of 7,260 ears were sampled, with an average kernel injury from H. zea feeding of 1.22 ± 0.02 (SEM) cm2. The χ2 statistics for observed and Poisson predicted distributions of the area of kernel injury indicated nonrandom distributions for all hybrids (P < 0.0001), which were confirmed by all variance to mean ratios (ID) being significantly greater than one. Slopes b of Taylor's power law and β of Iwao's patchiness regressions for the area of kernel injury were all either not significantly (P > 0.05) different from a value of one or significantly (P < 0.05) less than a value of one. Within each family of hybrids, relationships between proportions of ear samples with injury and area of kernel injury were similar among Bt and non-Bt hybrids. For the same level of injury, to reach a population estimate within 10% of the mean (Dx = 0.1), the number of sample units required was large (>100), particularly at low levels of injury. Sample sizes for estimates within 30% of the mean (Dx = 0.3) were considerable smaller. Sample size for Bt hybrids relative to non-Bt hybrids varied with the levels of injury and with family. Our study has provided the first sampling recommendations for population estimates of H. zea injury to corn ears.


[Precocious puberty].
Precocious puberty is an early sexual maturation before the age of 8 in case of girls and 9 in boys. There are two types: isosexual precocious puberty--characteristic are appropriate for the child's genetic and gonadal sex; and heterosexual precocious puberty--sexual characteristic are inappropriate for the genetic sex (feminizing syndrome in boys or virilizing syndrome in girls). Precocious puberty is an important problem in childhood gynecology pediatrics, endocrinology and psychology.


Qualitative differences in T-cell activation by dendritic cell-derived extracellular vesicle subtypes.
Exosomes, nano-sized secreted extracellular vesicles (EVs), are actively studied for their diagnostic and therapeutic potential. In particular, exosomes secreted by dendritic cells (DCs) have been shown to carry MHC-peptide complexes allowing efficient activation of T lymphocytes, thus displaying potential as promoters of adaptive immune responses. DCs also secrete other types of EVs of different size, subcellular origin and protein composition, whose immune capacities have not been yet compared to those of exosomes. Here, we show that large EVs (lEVs) released by human DCs are as efficient as small EVs (sEVs), including exosomes, to induce CD4+ T-cell activation in vitro When released by immature DCs, however, lEVs and sEVs differ in their capacity to orient T helper (Th) cell responses, the former favouring secretion of Th2 cytokines, whereas the latter promote Th1 cytokine secretion (IFN-γ). Upon DC maturation, however, these functional differences are abolished, and all EVs become able to induce IFN-γ. Our results highlight the need to comprehensively compare the functionalities of EV subtypes in all patho/physiological systems where exosomes are claimed to perform critical roles.


[Catatonia].
This review summarises the knowledge of catatonia, which is a neuropsychiatric syndrome with altered psychomotor and behavioural symptoms as well as autonomic dysfunction seen in a variety of psychiatric, neurologic and medical conditions. However, catatonia frequently remains unrecognised by clinicians. The classification of catatonia differs significantly in the international classifications, reflecting the controversy regarding the concept of catatonia and its complex symptomatology. Different rating scales are developed to diagnose catatonia in clinical practice. First-choice treatment is benzodiazepines and ECT regardless of underlying condition.


[Psychosocial interventions for high-risk family members with mental health problems--concepts and results].
Systematic review of psychosocial interventions for high-risk family members with mental health problems in highly developed industrialized countries. Systematic search in electronic databases as well as manual search for intervention studies. Interventions were effective in significantly reducing symptoms of depression and anxiety and strengthening social skills. Backing in situations of distress, as well as elements of selective primary and secondary psychosocial prevention, has temporary effectiveness among high-risk group members.


Eosinophils contribute to IL-4 production and shape the T-helper cytokine profile and inflammatory response in pulmonary cryptococcosis.
Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ΔdblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ΔdblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis.


How are you investing your time?
Reflections at the beginning of this year stand worlds apart from those of a year ago. In the past 12 months we've seen a rapid decline in global stability, terrorist acts on American soil unparalleled in magnitude or horror, an economic recession, and the virtual dissolution of Internet start-up companies. As we bid adieu to 2001, prospects of improvement are, thankfully, brighter.


COVID-19 in celiac disease: a multicentric retrospective cohort study.
Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.


Disposition of phenytoin in analbuminemic rats.
The disposition characteristics of phenytoin were investigated in analbuminemic rats to study the effect of plasma protein binding on phenytoin disposition. Blood and plasma phenytoin concentration determinations, measurement of plasma protein phenytoin binding, and whole-body autoradiography were performed after intravenous bolus injection of 10 mg kg-1 of phenytoin. When plasma phenytoin was assayed, total body phenytoin clearance (CL) was faster and its apparent volume of distribution (Vd) greater in the analbuminemic rats in comparison to the controls. The plasma protein binding of phenytoin was significantly lower in the analbuminemic rats, suggesting the disposition characteristics of phenytoin were altered in the presence of low plasma albumin concentrations due to reduced plasma phenytoin protein binding. On the other hand, when blood phenytoin levels were analyzed, no difference in CL and a less pronounced difference in Vd were noted between the two groups of rats. The red blood cell-to-plasma phenytoin concentration ratios were greater in analbuminemic rats, suggesting that the distribution of phenytoin into red blood cells was greater in the mutant rats.


Notch signaling in the developing cardiovascular system.
The Notch proteins encompass a family of transmembrane receptors that have been highly conserved through evolution as mediators of cell fate. Recent findings have demonstrated a critical role of Notch in the developing cardiovascular system. Notch signaling has been implicated in the endothelial-to-mesenchymal transition during development of the heart valves, in arterial-venous differentiation, and in remodeling of the primitive vascular plexus. Mutations of Notch pathway components in humans are associated with congenital defects of the cardiovascular system such as Alagille syndrome, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and bicuspid aortic valves. This article focuses on the role of the Notch pathway in the developing cardiovascular system and congenital human cardiovascular diseases.


1,3-Dithianes as Assembling Ligands for the Construction of Copper(I) Coordination Polymers. Investigation of the Impact of the RC(H)S2C3H6 Substituent and Reaction Conditions on the Architecture of the 0D-3D Networks.
The parent compound 1,3-dithiane (L1) was reacted with CuI providing the 1D coordination polymer [{Cu(μ2-I)2Cu}(μ2-L1)2] n (CP1), an isostructural compound [{Cu(μ2-Br)2Cu}(μ2-L1)2] n (CP2) was isolated upon treatment of CuBr with L1. In contrast, treatment of L1 with CuCl results in the formation of 2D polymeric [{Cu(μ2-Cl)2Cu}(μ2-L1)] n (CP3), in which each sulfur atom acts as a 4-electron donor. The 1D compounds [{Cu(μ2-X)2Cu}(μ2-L2)2] n (CP7, X = Br, and CP8, X = Cl) resulting from treatment of 2-methyl-1,3 dithiane (L2) with CuBr and CuCl are isostructural with their CuI homologue [{Cu(μ2-I)2Cu}(μ2-L2)2] n (CP5), reported previously. Using CuCN, a 2D CP of composition [{Cu(μ2-CN)2Cu}(μ2-L2)2] n (CP9) has been isolated. Complexation of 2-isobutyl-1,3-dithiane (L3) on CuI generates a 2D material [{Cu3(μ3-I)(μ2-I)2(μ2-L3)2}] n (CP10), incorporating the usual trinuclear μ3-I-capped Cu clusters as SBUs, whereas 2D-polymeric compounds [{Cu(μ2-Br)2Cu}(μ2-L3)2] n (CP11) and [{Cu(μ2-Cl)2Cu}(μ2-L3)2] n (CP12) were obtained with CuBr and CuCl. Treatment of 2-Me3Si-1,3-dithiane (L4) with CuX yields the series [{Cu2(μ4-X)(μ2-X)}(μ2-L4)] n (CP13-CP15). With 2-phenyl-1,3-dithiane (L5), the outcome of the reaction with CuI depends on the reaction conditions. Reaction with CuI in MeCN provides a 1D ribbon [{Cu(μ2-I)2Cu}(MeCN)2(μ2-L5)2] n (CP16), whereas treatment of CuI with L5 in hot EtCN yields 2D-polymeric[{Cu3(μ3-I)(μ2-I)2(μ2-L5)2}] n (CP17). A reversible phase transition from triclinic P1̅ to monoclinic P21/ m is observed when recording the structure of CP16 at five different temperatures in the 100-300 K range. Ligand L6 containing a ferrocenyl function at the 2-position was also probed as organometallic dithioether ligand. Reaction of L6 with 1 equiv of CuI produces the 0D dinuclear complex [{Cu(μ2-I)2Cu}(η1-L6)2(MeCN)2] (D1), whereas treatment with 2 equiv of CuI affords the novel 1D CP [{Cu(μ3-I)2Cu}(μ-L6)] n (CP18), in which both S atoms of one L6 molecule span two copper centers of the infinite (CuI) n ribbon. Some selected results of thermal analyses and luminescence measurements are also presented.


Financial Relationships Between Pharmaceutical Companies and Rheumatologists in Japan Between 2016 and 2019.
Given the increasing number of novel and expensive drugs for rheumatoid diseases, the financial relationships between pharmaceutical companies and rheumatologists could be prevalent and substantial. However, little was known about the information in Japan. Using payment data publicly disclosed by 92 major pharmaceutical companies, we evaluated the financial relationships between pharmaceutical companies and rheumatologists who were board certified by the Japan College of Rheumatology between 2016 and 2019. The trends in payments were estimated by the generalized estimating equations with 4-year payment data. Differences in payments between general and leading rheumatologists including the board members, clinical practice guideline authors, and medical journal editors were assessed. Of the board-certified rheumatologists, 70.7% (3563 of 5038) received a total of $55,246,485 in personal payments for lecturing, writing, and consulting from 79 pharmaceutical companies between 2016 and 2019. The median payments per rheumatologist receiving payments were $3447 (interquartile range, $1124-$11,974) in payment amounts. There were increasing trends in the payments per rheumatologist and the number of rheumatologists with payments, with average yearly change rates of 5.9% (95% confidence interval, 3.9%-7.9%; p < 0.001) and 1.2% (95% CI, 0.3%-2.0%; p = 0.008). The leading rheumatologists such as the society board members, clinical practice guideline authors, and medical journal editors received much more payments than other rheumatologists. Most rheumatologists increasingly received personal payments for lecturing, consulting, and writing reimbursements from pharmaceutical companies in Japan. These payments were significantly concentrated on rheumatologists in authoritative and influential positions.


LincRNA Plays a Role in the Effect of CYP46A1 Polymorphism in Alzheimer's Disease - Related Pathology.
Polymorphism of the cholesterol-24S-hydroxylase (CYP46A1) gene is thought to be a risk factor for Alzheimer's disease (AD). A single nucleotide polymorphism (T/C) in intron 2, rs754203, has been confirmed to be implicated in AD. Rs754203 is located in the long intronic non-coding RNA (LincRNA) sequence, which has previously been shown to be involved in the pathology of many diseases. Thus, the present study aimed to investigate the role of LincRNA in the CYP46A1 gene expression and related AD pathology. SH-SY5Y cells with overexpressed TT or CC genotype CYP46A1 were used. Through RT-PCR, Western blot and ELISA assays, we found that LincRNA can affect the CYP46A1 gene expression and the production of 24-OHC and Aβ. Overexpression of LincRNA can significantly inhibit CYP46A1 expression and 24-OHC production, as well as increasing the Aβ expression level. Silencing of LincRNA confirmed the role that it plays in the regulation of CYP46A1, as well as the production of 24-OHC and Aβ. In addition, this effect was stronger in the A type LincRNA than in the G type LincRNA. Results from dual luciferase assays show that LincRNA inhibited the activity of the CYP46A1 gene promoter. This study indicates a possible novel role of LincRNA and provides a new way to look into the relationship between CYP46A1 polymorphism and AD pathology. This may identify a novel pathway through which to explore AD therapy.


[Generation of new cardiomyocytes in the adult heart: Prospects of myocardial regeneration as an alternative to cardiac transplantation].
The classic dogma, still prevalent in cardiology, that the adult myocardium is a terminally differentiated tissue unable to produce new cardiomyocytes needs to be revised in light of recent results. In human and experimental animals there is now incontrovertible evidence that new myocytes are continuously generated throughout life in response to physiological and pathological stimuli. Moreover, the elucidation of mechanisms responsible for the hypertrophic response indicate similarity and overlap with the mechanisms involved in cell death by apoptosis as well as cell growth. During cardiac development, from birth to adulthood, there is a balance between the stimuli induce cell growth -by hypertrophy and hyperplasia- on one hand and those that induce programmed cell death on the other. In human and experimental animals it has been well documented that pathological conditions, such as diabetes and hypertension, can increase dramatically the rate of cell death. Moreover, high rates of cell death have been measured in normal adult human hearts and those of mice and rats. No surprisingly, these values increase significantly with age and high in senescence. By themselves, these high rates of normal cell death provide a very compelling argument in favor of cardiomyocyte regeneration. Without cell renewal, these rates of cell death would be incompatible with survival because the heart would disappear before early adulthood. As expected, direct measurement of rates of new cell formation in adult hearts demonstrate high rates of cell renewal that compensate for cell death. Thus, the heart is in continuous cellular turnover with new myocardial cells replacing the older ones. Experiments with fetal mouse cardiocytes shows that the retinoblastoma protein is responsible for the cardiocyte withdrawal from the cell cycle during development. The identification in the adult heart of a subpopulation of quiescent cells that have many of the characteristics of stem cells able to rapidly enter the cell cycle and generate new cardiocytes is yet another evidence that the heart continuously produces new cardiocytes to replace those that disappear either by apoptosis or necrosis.Surprisingly, stem cells other that those from the heart are able to produce new cardiocytes and repopulate the myocardium. We have used bone marrow stem cells injected into the border zone of post-coronary occlusion necrosis. Remarkably, these cells have proven to be very effective in generating new myocardium in the necrotic zone that is integrated to the rest of the muscle and irrigated by new vessels. These results demonstrate that stem cells provide a new avenue for the generation of new contractile tissue. This approach could prove useful in the treatment of chronic cardiac failure and post-ischemic necrosis.


The spectrum of disease and tau pathology of nodding syndrome in Uganda.
Nodding syndrome is an enigmatic recurrent epidemic neurologic disease that affects children in East Africa. The illness begins with vertical nodding of the head and can progress to grand mal seizures and death after several years. The most recent outbreak of nodding syndrome occurred in northern Uganda. We now describe the clinicopathologic spectrum of nodding syndrome in northern Uganda. The neuropathologic findings of 16 children or young adults with fatal nodding syndrome were correlated with the onset, duration and progression of their neurological illness. The affected individuals ranged in age from 14 to 25 years at the time of death with a duration of illness ranging from 6-15 years. All 16 cases had chronic seizures. In 10 cases, detailed clinical histories were available and showed that three individuals had a clinical course that was predominantly characterized by epilepsy, whereas the other seven individuals had progressive cognitive, behavioural and motor decline, in addition to epilepsy. The main neuropathologic findings included: tau pathology (16/16 cases), cerebellar degeneration (11/16 cases) and white matter degeneration (7/16 cases). The tau pathology was characterized by filamentous tau-positive deposits in the form of neurofibrillary tangles, pre-tangles and dot-like grains and threads in the neuropil. All cases showed some degree of tau pathology in the neocortex and in the locus coeruleus with frequent involvement of the substantia nigra and tegmental nuclei and lesser involvement of other grey matter sites, but there was a lack of glial tau pathology. The tau pathology in the neocortex showed a multifocal superficial laminar pattern. We conclude that nodding syndrome is a clinicopathological entity associated consistently with tau pathology, but our observations did not establish the cause of the disease, or an explanation for the tau pathology.


Routine HIV testing in health care settings: the deterrent factors to maximal implementation in sub-Saharan Africa.
The sub-Saharan region of Africa is the most severely affected HIV/AIDS region in the world. The population of this region accounts for 67% of all people living with HIV/AIDS and 72% of all AIDS-related deaths. As international collaboration makes access to HIV treatment more widely available in this region the need to increase the population's awareness of its serostatus becomes greater. The incorporation of provider-initiated HIV testing and counseling (routine HIV testing model) as part of a routine medical care would not only increase the population's serostatus awareness but also lead to a better understanding of HIV prevention and treatment and ultimately, increased utilization of available HIV/AIDS prevention programs on a much larger scale. This mini-review summarizes some important regional, sociocultural, economic, legal, and ethical issues that may be deterrent factors to maximal implementation and integration of provider initiated HIV testing and counseling as part of routine medical care in the sub-Saharan African region.


[Value of an ostomy club for patient followup after total cystectomy].
Patients using stoma appliances after a total cystectomy undergo a considerable psychological shock. The creation of groups of ostomates helps in the dissemination of information concerning the use of stomal appliances and in the building up of user confidence, thereby facilitating a return to a normal everyday life. Our main aim is to organize regular meetings of stoma appliance users, with frequent visits from former cystectomy patients. The usefulness of these clubs has been amply demonstrated by the introduction of the training of enterostomal therapists, the collaboration offered by the appliance manufacturers and the interest manifested by surgeons and urologists.


[Chronic pain in cancer patients].
Cancer pain relief is a public health problem. A WHO method has been developed, which provides for drugs to be administered immediately if there is pain, to be given "by the clock" rather than "on demand" and to be increased from nonopioids to weak opioids and then to strong opioids until the patient is free from pain.


Structural Characterization of a Pleurotus sajor-caju Polysaccharide and Its Neuroprotection Related to the Inhibition of Oxidative Stress.
A novel polysaccharide PSP2-1 was isolated and purified from Pleurotus sajor-caju. The structural characterization data displayed that the molecular weight of PSP2-1 was 44.9 kDa, and PSP2-1 consisted of fucose, galactose, glucose, and mannose. The methylation results showed that the glycosidic bonds of PSP2-1 included T-Fuc, 1,6-Gal, T-Glc, 1,6-Glc, 1,3,6-Glc, 1,3-Man, 1,2,6-Man, and T-Man. Neuroprotective studies indicated that PSP2-1 significantly improved the cell viability of the H2O2-induced oxidatively damaged neuronal cell HT22, reduced the release of LDH, inhibited apoptosis and release of cytochrome c, and alleviated the decline of mitochondrial membrane potential and ROS accumulation. Furthermore, PSP2-1 decreased the phosphorylation levels of cleaved PARP and cleaved caspase-3, and increased the ratio of bcl-2/bax. Additionally, PSP2-1 could inhibit the phosphorylation of MAPK family members including JNK, p38, and Erk. Finally, animal experiments showed that PSP2-1 could improve the oxidative stress injury and the learning and memory ability of mice with aging induced by D-galactose. Our results confirmed that PSP2-1 significantly ameliorated the oxidative stress injury, inhibited the apoptosis in H2O2-induced neuronal cells via MAPK pathway, and also improved cognition in mice with aging induced by D-galactose. Our research gives the foundation for the functional food application of P. sajor-caju polysaccharides in the future.


Social implications of immobility.
The patient who loses his or her independence in the community inevitably forfeits the will to live. One factor that repeatedly surfaces is the inability of our society to realistically deal with immobility of the elderly. Of the estimated 95 per cent of the elderly who do not live in institutional settings (nursing homes), 43 per cent require assistance in some aspect of their daily lives.


Utility of anaerobic bottles for the diagnosis of bloodstream infections.
Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI). We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied. A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient. Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.


Role of myocardial gated SPECT scintigraphy in the clinical suspicion of ischemic cardiomyopathy: discussion of an unusual case.
The case of a 72-year-old patient affected by myasthenia gravis under pyridostigmine therapy, admitted to the hospital for the onset of oppressive thoracic pain associated with mild enzyme increase, electrocardiographic and echocardiographic disorders, is discussed. Dypiridamole/gated SPECT perfusion scintigraphy at rest evidenced reduced coronary reserve at the level of the lateral wall with apical akinesia and normokinesia of mediobasal left ventricle. On coronarography, coronary arteries were free of significant stenoses and left ventricular apical akinesia. The diagnostic approach to ischemic cardiomyopathy with the correct sequence of performed diagnostic imaging led to the presumptive identification of a rare syndrome.