Predicting walking-to-work using street-level imagery and deep learning in seven Canadian cities.
New 'big data' streams such as street-level imagery are offering unprecedented possibilities for developing health-relevant data on the urban environment. Urban environmental features derived from street-level imagery have been used to assess pedestrian-friendly neighbourhood design and to predict active commuting, but few such studies have been conducted in Canada. Using 1.15 million Google Street View (GSV) images in seven Canadian cities, we applied image segmentation and object detection computer vision methods to extract data on persons, bicycles, buildings, sidewalks, open sky (without trees or buildings), and vegetation at postal codes. The associations between urban features and walk-to-work rates obtained from the Canadian Census were assessed. We also assessed how GSV-derived urban features perform in predicting walk-to-work rates relative to more widely used walkability measures. Results showed that features derived from street-level images are better able to predict the percent of people walking to work as their primary mode of transportation compared to data derived from traditional walkability metrics. Given the increasing coverage of street-level imagery around the world, there is considerable potential for machine learning and computer vision to help researchers study patterns of active transportation and other health-related behaviours and exposures.


Closed crush injury of the metacarpophalangeal joint.
Closed crush injuries from direct blows to the dorsum of the hand may produce significant metacarpophalangeal (MCP) joint symptoms or dysfunction. We have treated 11 patients who had chronic pain and swelling, but without extensor tendon subluxation, for an average of 7.4 months. Only two responded to nonoperative treatment. The nine who had exploratory surgery had a consistent anatomic lesion that consisted of a partial, arcuate tear of the sagittal fibers. All the patients improved postoperatively. Cadaver dissections of the dorsal MCP tendon mechanism in 11 fresh specimens (44 MCP joints) demonstrated that neither partial nor complete transection of the ulnar sagittal fibers produces radial dislocation of extensor tendons. Radial sagittal fiber transections frequently produced ulnar tendon dislocation. Patients who have closed impact injuries of the MCP joints and present with longstanding pain, swelling, and limited mobility without extensor tendon migration may have sustained unrecognized partial ulnar sagittal fiber disruption. Repair of the partial sagittal fiber tear and exploration of the MCP joint is indicated.


It's not fiction if you believe it: How imaginary worlds are derived from imaginary realities.
Imaginary worlds are not a consequence of humans' exploratory tendencies as argued in the target article but a recent spinoff of a strong human tendency to create imaginary realities, that is, versions of how the world works that are fabricated (although we believe they are real) in order to allow us to believe we understand it and can control it.


Surgery in Castleman's disease: a systematic review of 404 published cases.
We undertook a systematic review of 404 published cases of Castleman's disease to identify the role of the surgeon beyond assistance in tissue-based diagnosis. Castleman's disease is a rare primary disease of the lymph node caused by infection with herpesviridae. Little is known about the role of surgery in this condition. Medline, Embase, Cochrane Database of Systematic Reviews, ISI Thompson Web of Knowledge, and hand search of articles' bibliography. Of the 1791 citations identified through the initial electronic search and screened for possible inclusion, 488 articles were retained after title and abstract reviews. Of these, 239 were accepted for this review. A complete dataset containing age, gender, centricity (unicentric vs multicentric), histopathologic type (hyaline vascular [HV] vs plasma cell [PC]), anatomical location of the only focus in unicentric Castleman's disease (UCD) or the dominant focus in multicentric Castleman's disease (MCD), nature of the surgical approach (resective vs diagnostic), and outcome (disease-free survival [DFS] vs death due to disease) was extracted. A resective or debulking surgical approach was described in 77.0% of all patients, but was far more common in unicentric (262/278; 94.2%) than multicentric (49/126; 38.9%) disease (χ² 146.8; P < 0.0001). Unicentric disease had a significantly higher overall survival (95.3% vs 61.1%; χ² 55.7; P < 0.0001), 3 year DFS (89.7% vs 55.6%; χ² 27.8; P < 0.0001), and 5 year DFS (81.2% vs 34.4%; χ² 28.6; P < 0.0001) than multicentric disease. Failure to treat unicentric disease by resective surgery resulted in a significant mortality (17.6% vs 3.8% χ²; P < 0.05). In multicentric disease, outcomes are comparable between debulking surgery alone, immunochemotherapy alone, or a combination of both (28.0% vs 28.9% vs 50.0%; P = nonsignificant). Surgery is the gold standard for treatment of unicentric Castelman's disease. The role of debulking surgery in human immunodeficiency virus (-) MCD needs to be evaluated in prospective studies.


Intragastric injection of botulinum toxin A for weight loss: A systematic review and meta-analysis of randomized controlled trials.
Intragastric botulinum toxin A (BTA) injection is a potential treatment for weight reduction in obese patients. Current studies yielded conflicting results. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the efficacy of intragastric BTA injection for weight management. We searched several databases to identify RCTs evaluating intragastric BTA injections for obesity. We applied random-effects models for all meta-analyses due to heterogeneity in the included studies. The mean difference (MD) and 95% confidence interval (CI) were calculated for continuous outcomes. A total of 6 RCTs including 192 subjects met the inclusion criteria and were included for the meta-analysis. Although the pooled data from six studies showed no difference in the absolute weight loss between intragastric BTA injection and control, subgroup analysis showed a significantly decreased absolute weight after a BTA injection dose ≥ 200 U (MD, -2.04 kg; 95% CI, -3.96 to -0.12) and after multiple injection regions in the stomach combined with diet control (MD, -4.44 kg; 95% CI, -6.54 to -2.33 kg) compared with the control. Regarding absolute weight loss, the impact of endoscopic ultrasound-guided injection and follow-up duration showed no difference. Intragastric BTA injection had a significant change in body mass index (MD, -1.25 kg/m2 ; 95% CI, -2.18 to -0.32 kg/m2 ) and prolonged gastric half-emptying time (MD, 11.37 min; 95% CI, -3.69 to 19.06 min). Intragastric BTA injection is effective for obesity treatment, and adequate doses (≥ 200 U), multiple gastric injection regions, and combined diet control are crucial. However, given the small sample size and limited power, caution should be exercised.


Sedentary behavior is associated with reduced cardiovagal baroreflex sensitivity in healthy adults.
Sedentary behavior is an established risk factor for cardiovascular disease; however, it remains unclear whether sedentary behavior is associated with the deterioration of arterial blood pressure regulation. The purpose of this study was to determine the association between the time spent in sedentary behavior and cardiovagal baroreflex sensitivity (cBRS) in healthy adults. We investigated the cross-sectional relationship between sedentary time and cBRS in 179 adults aged 22-81 years. Sedentary time was objectively measured using a triaxial accelerometer. cBRS was evaluated by the transfer function gain of beat-by-beat changes in systolic blood pressure and the R-R interval during 5 min of spontaneous resting. Glycemic, lipidemic, and vascular risk factors were measured as potential covariates of cBRS and sedentary behavior. Men had a longer sedentary time and lower cBRS than women (p = 0.001). In a simple correlation analysis, older age was negatively associated with cBRS and positively associated with sedentary time, but sedentary time was not correlated with cBRS. However, after adjustment for age and sex, a longer sedentary time was associated with a lower cBRS. Multiple linear regression analysis showed that sedentary time was independently associated with lower cBRS with adjustment for covariates (β = -0.325, p = 0.002). A significant association was also confirmed when the analysis was performed separately in the younger and older groups. This finding suggests that high sedentary behavior may have an adverse effect on arterial blood pressure regulation.


Radiography, abdominal CT and MRI compared with sacroiliac joint CT in diagnosis of structural sacroiliitis.
To assess the performance of pelvic plain radiograph (radiography), abdominal CT and sacroiliac joint MRI (MRI) compared with sacroiliac joints CT (SI joint CT) for the diagnosis of structural sacroiliitis in a population suffering from spondyloarthritis (SpA) meeting the New York or ASAS criteria. All SpA patients eligible for biologic treatment who received a pre-therapeutic check-up including the four imaging techniques in the same year were selected from 2005 to 2012. An assessment of sacroiliitis was based independently by a rheumatologist and a radiologist on radiography according to the modified New York criteria and on abdominal CT, MRI and SI Joint CT depending on the presence of erosion on at least two consecutive slices. A final diagnosis was established for conflicting exams. Of the 58 selected patients, sacroiliitis was diagnosed on radiography, abdominal CT, MRI and SI Joint CT in 32, 26, 34 and 35 patients, respectively. Inter-reader agreements for the grade of sacroiliitis were substantial with a weighted Kappa that varied between 0.60 and 0.76 and they were moderate for the diagnosis of sacroiliitis with a Kappa that varied between 0.45 and 0.55 for the four imaging modalities. The sensitivities of radiography, abdominal CT and MRI were 82.8%, 71.4% and 85.7% respectively and the specificities were 86.9%, 100% and 82.6% respectively with excellent accuracy and positive predictive value and good negative predictive value. This study demonstrates the relevance of MRI and abdominal CT for the diagnosis of structural sacroiliitis with good sensitivities and excellent specificities. These imaging modalities may also contribute for the diagnosis of structural sacroiliitis.


Kinetochore Function from the Bottom Up.
During a single human lifetime, nearly one quintillion chromosomes separate from their sisters and transit to their destinations in daughter cells. Unlike DNA replication, chromosome segregation has no template, and, unlike transcription, errors frequently lead to a total loss of cell viability. Rapid progress in recent years has shown how kinetochores enable faithful execution of this process by connecting chromosomal DNA to microtubules. These findings have transformed our idea of kinetochores from cytological features to immense molecular machines and now allow molecular interpretation of many long-appreciated kinetochore functions. In this review we trace kinetochore protein connectivity from chromosomal DNA to microtubules, relating new findings to important points of regulation and function.


The pseudouridine contents of the ribosomal ribonucleic acids of three vertebrate species. Numerical correspondence between pseudouridine residues and 2'-O-methyl groups is not always conserved.
The pseudouridine contents of the rRNA species of HeLa cells, mouse L-cells and Xenopus laevis cultured kidney cells were examined. Pseudouridine, like 2'-O-methylation, was found to occur relatively frequently in each of the high-molecular-weight rRNA species. However, the numerical data do not support the idea that there is a general one-to-one relationship between pseudoridine residues and 2'-O-methyl groups in vertebrate rRNA.


The effect of kidney transplantation on left ventricular remodeling and global diastolic strain rate in end-stage renal disease.
Diastolic dysfunction is an early marker of cardiac pathology in end-stage kidney disease (ESKD) patients. The ratio of transmitral filling velocity (E) to early diastolic strain rate (E/e'sr) is a novel non-invasive marker of early left ventricular (LV) filling pressure obtained using two-dimensional speckle tracking echocardiography (2DSTE). In a prospective cohort of kidney transplant (KTX) recipients with echocardiograms performed pre-transplant we obtained repeat echocardiograms at 6 months following transplant. All echocardiograms were analyzed using 2DSTE where E/e'sr and global longitudinal strain were obtained. Paired tests were used to assess changes to cardiac structure and function following KTX. A total of 33 patients were included in the study (mean age was 46.6 ± 13.7 years and 42% were males). The primary causes of ESKD in the cohort were glomerular disease (33%), hypertension (30%), and polycystic kidney disease (12%). The median (IQR) time spent on dialysis was 5.4 years [2.9, 7.7 years]. A reverse remodeling of the LV was observed following KTX as LV mass decreased (189.2 ± 57.5 g vs 171.1 ± 56.8 g, P = 0.014). LV filling pressure decreased as assessed by E/e'sr (103.7 ± 51.1 cm vs 72.6 ± 35.5 cm, P = 0.009). E to early diastolic mitral annular tissue velocity (E/e') did not change following KTX (9.9 ± 4.5 vs 10.3 ± 4.1, P = 0.54). Additionally, both LV internal diastolic and systolic diameter decreased significantly. Reverse cardiac remodeling following KTX was observed as improvements in LV mass and LV dimensions. LV filling pressure improved as assessed by E/e'sr decreased following KTX, whereas E/e' did not change.


Use of the MCNPX to calculate the neutron spectra around the GE-PETtrace 8 cyclotron of the CDTN/CNEN, Brazil.
The Monte Carlo code MCNPX was used to calculate the neutron spectra in 4 points around the targets of the CDTN/CNEN cyclotron, Belo Horizonte, Brazil, during the production of the (18)FDG. Simulated data were compared with experimental data obtained with a Bonner multisphere spectrometry system (BSS) using TLD-600 and TLD-700 and the unfolding codes BUNKIUT, BUMS and NSDUAZ. In general, simulated spectra disagreed with those obtained by experimental means by a factor as high as 14. Measurements performed with a doserate meter in other 3 more shielded points, showed also an overestimation of the ambient dose equivalent rate by a factor as high as 20 in comparison with simulated results. Results are not conclusive and a more refined study is necessary. However, neutron emission rate of the source-term of radiation must be investigated and an special caution must be taken in the experimental measurements, by discriminating of the target selected for the irradiations and utilizing a matrix response suitable for the passive detectors (e.g. TLD) utilized in the experiments, instead of a matrix response (e.g. UTA4) developed for scintillation detectors.


Ovarian carcinoma during pregnancy: a study of 23 cases in Israel between the years 1960 and 1984.
Data from a study on malignant ovarian tumors in pregnancy in Israel are presented. During the 25-year period of the survey, 23 new cases of malignant ovarian tumors during pregnancy were diagnosed, representing an incidence of 0.12/100,000 females over the age of 14; over half of the patients were in their third decade of life at the time of diagnosis of the tumor. Ovarian malignant tumors during pregnancy are more prevalent in Jewish women of European-American origin than in those of Asian-African descent. Borderline carcinomas were found in 35% of our patients; epithelial invasive tumors were found in 30%; the other tumors were dysgerminoma (17%), granulosa cell tumor (13%), and undifferentiated carcinoma (5%). Most of the patients (74%) were diagnosed in stage I. In three cases, ovarian cancer was diagnosed during surgery for tubal pregnancy, and in two during cesarean section at term. In early-stage disease and low-potential-malignancy tumors, surgery can be conservative; thus, 14 of 23 bore a live child. In advanced disease, aggressive surgery, chemotherapy, and/or radiotherapy should be instituted. Factors affecting prognosis were age of patient, histologic type of tumor, and clinical stage of disease. Overall, the survival is much better than that for ovarian tumors in general, because most of the tumors are of low potential malignancy and are diagnosed at an early stage.


Spontaneously ruptured intraspinal epidermoid cyst causing chemical meningitis.
We report a 53-year-old woman with a rare ruptured lumbar intraspinal epidermoid cyst causing chemical meningitis evaluated with MRI (including diffusion-weighted imaging), with histopathologic correlation.


Metabolic responses of indigenous bacteria in chicken faeces and maggots to multiple antibiotics via heavy water labeled single-cell Raman spectroscopy.
The use of maggots derived from chicken faeces as fish diets might serve as a vehicle for the widespread of multiple antibiotic resistant bacteria (ARB) in the environment. Heavy water labeled single-cell Raman spectroscopy (D2O-Raman) was applied to detect the metabolic responses of indigenous bacteria in chicken faeces and maggots to different concentrations of combined colistin, kanamycin, and vancomycin. By incubating the samples with D2O and antibiotics, metabolically active bacterial cells to antibiotics were distinguished from those inactive by the exhibition of C-D Raman band. Using the C-D band as a universal metabolic biomarker, 96% and 100% of cells in chicken faeces and maggots were revealed to be metabolically active to 1 × minimum inhibition concentration (MIC) of the afore-mentioned antibiotics. A noticeable decrease in the percentage of active cells from 96% to 76% in faeces and 100% to 93% in maggots was observed at 5 × MIC of antibiotics. However, these ratios were still far above that obtained from the same faeces (1.84%) and maggots (0.51%) samples using a cultivation method, indicating the wide presence of nongrowing but metabolically active bacterial cells under antibiotic treatment. Conclusively, the culture-independent D2O-Raman approach detected and quantified a large portion of metabolically active indigenous bacteria to multiple antibiotics in their native environments, illustrating the great potential risks of these active cells to spread antibiotic resistance via food chain.


Educational support needs of injured children and their families: A qualitative study.
To explore the educational support needs of injured children and families. Thirteen injured children and/or their parents (n = 19) discharged from a major trauma centre within 12 months. Methods: Semi-structured interviews analysed with thematic analysis. Results: Theme 1: communication and information needs. Schools need help to understand the effects of children's injuries and the adjustments required for their return to school, such as how to involve chil-dren in the more active elements of the curriculum. Thus, effective communication between the injur-ed child, their family, health and education professionals and outside agencies is needed. A specialist key-worker could co-ordinate communication and school return. Theme 2: Educational support needs. Injured children experience changes to their appearance, new symptoms, and altered physical and cognitive abilities. Their absence from school often adversely affects their friendships. Consequently, injured children need continued access to education throughout recovery, support with learning, a flexible timetable, opportunities for social integration, involvement in all aspects of the curriculum, and environmen-tal adaptations to maintain their health and safety. Conclusion: Children with different types of injuries have similar needs for flexible learning and environmental accommodations. Social integration and participation in physical activity should be specific goals for school return.


Faecal carriage of Pseudomonas aeruginosa in newborn infants.
Carriage rates of Pseudomonas aeruginosa were studied using Solari medium and 1 g of faeces. The incidence in infants delivered at home was 6.0 per cent and 56.6 per cent in infants in hospital nursery. The carriage rate in healthy adults averaged 17.1 per cent an showed seasonal variations, high in summer an low in winter months. In 25 infants and two mothers the mean count of Ps. aeruginosa was 10(3)/g faeces.


Rapid response teams to support dementia care in Australian aged care homes: Review of the evidence.
To identify attributes of rapid response services designed to support people with very severe and extreme responsive behaviours, otherwise known as behavioural and psychological symptoms of dementia, in aged care homes. A rapid evidence assessment was conducted to inform the evaluation of the Severe Behaviour Response Team (SBRT) service, including a targeted search of peer-reviewed academic literature and an Internet-based search of government, service provider, peak body and university websites. A number of localised rapid response services targeting people with similar clinical profiles were identified, but none operated on the scale of the SBRT. Five operational attributes in common were as follows: clearly defined parameters and processes; provision of clinical expertise and knowledge translation activities; person-centred philosophy; relationship-oriented approach to stakeholders; and generalisable and sustainable outcomes. The five attributes provided a useful framework to guide the evaluation of the SBRT and clarify opportunities for continued service development.


Prospective assessment of vincristine-induced peripheral neuropathy in paediatric acute lymphoblastic leukemia.
Vincristine is a mainstay treatment for paediatric cancers, particularly acute lymphoblastic leukemia (ALL), with common toxicity including vincristine-induced peripheral neuropathy (VIPN). The present study comprehensively assessed VIPN outcomes in patients receiving vincristine treatment for ALL. Children diagnosed with ALL commencing vincristine treatment were prospectively evaluated (baseline, post-induction, pre-reinduction, post-reinduction, follow-up). VIPN was examined clinically using the Balis sensory/motor scale, neurophysiologically using axonal excitability techniques and quality-of-life using Pediatric Quality of Life Inventory. Thirty-one patients were recruited to this study (age = 6.8 ± 4.4; 61.3% female). Incidence of motor VIPN (motor Balis grade > 0) symptoms were higher than sensory VIPN (sensory Balis grade > 0) at post-induction (92.0% vs 36.0%) and post-reinduction (81.8% vs 22.7%) vincristine treatment. Neurophysiological assessment also demonstrated greater change in motor axonal excitability parameters compared to sensory parameters including changes in depolarising threshold electrotonus (P < 0.0125), superexcitability and subexcitability parameters (all P < 0.0125). Follow-up assessment demonstrated persisting VIPN symptoms with reduced quality-of-life scores compared to baseline. Clinical and neurophysiological evaluation of VIPN suggests vincristine produces a motor-prominent sensorimotor neuropathy in children which persisted at follow-up. VIPN signs and symptoms develop early in the treatment course, in line with axonal excitability profiles. Early detection of significant nerve changes may support timely implementation of neuroprotection strategies.


Reduced hexokinase activity in renal medullary tissue from rabbits with inferior vena caval constriction.
Caval constriction in rabbits results in reduced blood flow to outer cortical tissue but blood flow to juxtamedullary cortex and outer medullary tissue is increased. The present study indicates that this shift in tissue perfusion is accompanied by a reduction in hexokinase activity.


Cerebrospinal fluid xenin levels during body mass reduction: no evidence for obesity-associated defective transport across the blood-brain barrier.
Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism. To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin. Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay. As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin. Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.


Rapid and efficient degradation of bisphenol A by chloroperoxidase from Caldariomyces fumago: product analysis and ecotoxicity evaluation of the degraded solution.
To degrade enzymatically bisphenol A (BPA) that causes serious environmental concerns and is difficult to be degraded by chemical or physical methods. BPA (150 mg l(-1)) was completely degraded by chloroperoxidase (CPO)/H2O2 within 7 min at room temperature, atmospheric pressure with the enzyme at 6 μg CPO ml(-1). The degradation products were identified by HPLC-MS, which suggested involvement of multiple steps. Enzymatic treatment followed by existing bioremediation technologies (activated sludge) enhanced removal of COD from 9 to 54 %. Using an ecotoxicity evaluation with Chlorella pyrenoidosa, the degradation products had a lower toxicity than BPA. BPA can be degraded rapidly and efficiently under mild conditions with chloroperoxidase at 6 μg ml(-1). The degradation products had a lower toxicity than BPA.


Dental scaling and lower risk of spontaneous intracranial hemorrhage.
-Spontaneous intracranial hemorrhage (ICH) has high fatality while has few proven treatments. We aim at investigating the association between dental scaling (DS) and the risk of ICH. -In this cohort study, two cohorts were matched by propensity score based on potential confounders. Data from ICH between January 2008 and December 2014 in Taiwan were analyzed. The subjects underwent DS at least 6 times between January 1, 2002, and December 31, 2007, while the matched controls did not undergo any DS during the same period. Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing confounders. -Each cohort consisted of 681,126 subjects. Compared with the non-DS cohort, the regular-DS cohort had a significantly lower incidence of ICH (0.8% vs 1.2%; P < 0.0001), and the adjusted hazards ratio (aHR) of 7-year ICH was 0.61 (95% confidence interval, CI, 0.59-0.63; P < 0.0001). The 30-39-year age group of the regular-DS cohort had the lowest HR (0.57; 95% CI, 0.52-0.61; P < 0.0001) of 7-year ICH when compared with similar controls. Compared with the controls, the regular-DS cohort also had significantly lower HR (0.82; 95% CI, 0.81-0.82; P < 0.0001) of 7-year hypertension. Compared with those without DS, the lowest risk of intracerebral hemorrhage was observed in the male participants with regular DS (0.43; 95% CI, 0.40-0.47; P < 0.0001). -Regular DS was consistently associated with lower ICH risk in subjects aged 30-59 years, which may benefit from the decreased HBP risk. DS had a potential role in the prophylaxis for ICH, a condition with a high disability or mortality.


Does the absence of ABCC6 (multidrug resistance protein 6) in patients with Pseudoxanthoma elasticum prevent the liver from providing sufficient vitamin K to the periphery?
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by a progressive mineralization of connective tissue, resulting in skin, arterial and eye disease. Classical PXE is caused by mutations in the ABCC6 gene, which encodes a member of the ABCC (MRP) family of organic anion transporters. Recent studies on Abcc6(-/-) mice show that the absence of ABCC6 in the liver is crucial for PXE and confirm the "metabolic disease hypothesis" for PXE, which states that tissue calcification is due to the absence of a plasma factor secreted from the basolateral hepatocyte membrane. We propose that this plasma factor is vitamin K (precursor). We propose that vitamin K (precursor) is secreted by ABCC6 from the liver as a glutathione--(or glucuronide)--conjugate and that this supplements the vitamin K need of peripheral tissues that receive insufficient vitamin from the diet, because dietary vitamin K is effectively extracted from blood by the liver. Peripheral tissue vitamin K is needed for the gamma-carboxylation of glutamate residues in proteins known to be required for counteracting calcification of connective tissue throughout the body. Our hypothesis explains the known facts of PXE and also explains why PXE-like symptoms can occur in patients with mutations in the gamma-glutamyl carboxylase gene (encoding the enzyme responsible for protein carboxylase) and in rats treated with vitamin K antagonists. The hypothesis implies that the symptoms of PXE can be prevented or mitigated by providing patients (intravenously) with a form of plasma vitamin K (precursor) that can be used by peripheral tissues.


Mucoepidermoid carcinoma of the external auditory canal: case report.
This study reports a case of mucoepidermoid carcinoma (MEC) of the external auditory canal, which to date has only been described once in literature. Because the lesion is extremely rare, it is particularly difficult to classify it into stages following normal diagnostic parameters. This obviously limits the possibilities of treatment that consequently are either empirical or based on those of squamous cell carcinoma. The problems in the diagnosis and the possible methods of treatment of mucoepidermoid carcinoma are discussed.


Change in bacterial aetiology of peritoneal dialysis-related peritonitis over 10 years: experience from a centre in South-East Asia.
This study reviewed 1787 episodes of peritoneal dialysis (PD)-related peritonitis in 544 patients between 1994 and 2003. The overall rate of peritonitis was 0.68 episodes/year of PD, but decreased from 1.10 to 0.46 episodes/year between 1994 and 2003. The incidence of peritonitis caused by coagulase-negative staphylococci declined between 1994 and 1998 from 0.21 to 0.06 episodes/year of PD, coinciding with a reduction in the use of spike PD sets. There was a 60.1% response rate to antibiotics throughout the period, but the percentage of cases that required modification of the initial empirical antibiotic regimen rose from 13.6% to 58.7%, indicating that treatment should be individualised.


Accumulation of a cellular protein bearing c-myc-like antigenicity in hepatic and non-hepatic delta antigen expressing cells.
Patients with chronic but not acute hepatitis delta virus infection undergo a strong accumulation of a protein of cellular origin which specifically reacts with a panel of anti-c-myc antibodies and which is expressed in the same nuclei that express the delta antigen. In this paper we report on the in vitro characterization of this phenomenon. The delta antigen induced c-myc antigen accumulation can occur in vitro upon transfection of HBsAg positive and negative cell lines with HDAg expression vectors. Using recombinant vaccinia viruses expressing only p24 or p27 we demonstrate that structures common to the two isoforms of HDAg are responsible for the phenomenon, which is not restricted to cells of hepatic origin.


Early effects of inhalation injury on lung mechanics and pulmonary perfusion.
We investigated the early effects of a rather large amount of cotton-smoke on lung mechanics and pulmonary perfusion. Under halothane anesthesia 18 ewes were intubated with a double-lumen tube. In 6 sheep the left lung was exposed to smoke, in another 6 the right lung. A sham group of 6 sheep was insufflated with air instead of smoke. Prior to and 30-45 min following the smoking- (sham-) procedure the following parameters were determined for the smoke- (sham-) exposed and the contralateral lung: static compliance, inspiratory airway resistance, and physiologic dead space ratio. In addition MAP, MPAP, WP, and CO were recorded. The data indicate that inhalation of large amounts of smoke has no major direct effects on pulmonary mechanics and perfusion in the early post-injury period. Only an increase in airway resistance of the smoke exposed lungs was found, which must be attributed to a local reflex mechanism.


[Embryonic stem cell research in Brazil and the (un)constitutionality of article 5 of the biosafety act (Part I)].
The Brazilian Law on Biosafety was approved on March 2005. Subsequently, in May of this same year, the Attorney General of the Republic filed a lawsuit challenging the constitutional grounds of article 5 of the aforementioned Law. This article allows the use of embryonic stem cells in research and therapies obtained from surplus human embryos from techniques of in vitro fertilisations.


Unifocal Langerhans cell histiocytosis of bone: percutaneous navigational bipolar radiofrequency ablation for curative treatment.
In this report, the initial clinical experience of authors is described on the novel application of a navigational bipolar radiofrequency ablation electrode system for curative treatment of a painful unifocal Langerhans cell histiocytosis involving the supra-acetabular iliac bone. The technical success and safety of the radiofrequency ablation procedure to achieve cure suggests that this intervention may be utilized in clinical practice as a viable and minimally invasive alternative option, for management of unifocal Langerhans cell histiocytosis.


In-vitro antibacterial activity of commercially available probiotics on food-borne pathogens along with their synergistic effects with synthetic drugs.
Probiotics are put forward as food to ensure the maintenance of the equilibrium of the intestinal flora. Prolonged usage of probiotics in food ingredients for human as well as in animal feed has not exposed any side effects yet. Present study attempted to justify the effects of some commercially available probiotics (Good-gut, Lubenna, Probio and Protein restro) and commonly used antibiotics (Streptomycin, Gentamycin, Ampicillin, Methicillin, Azithromycin, Erythromycin, Ceftrizone, Imepenem, Ciprofloxacin and Tetracycline) on the bacteria which were previously isolated from food samples. The anti-bacterial potential of the probiotics was aimed to be checked through the agar well diffusion method and the antibiogram of the synthetic drugs was determined by disc-diffusion method (Kirby Bauer technique). The minimum inhibitory concentration (MIC) of the probiotics were examined through broth micro dilution assay. Almost all the probiotic samples exhibited antibacterial activity against the tested bacteria within the range of 10 mm-30 mm except Bacillus spp. and Salmonella spp. The lowest MIC values 3 mg/ml was determined with Luvena for Pseudomonas spp. and Shigella spp. while the maximum MIC 20 mg/ml was recorded for Good gut and Probio against Salmonella spp. and E. coli. Meanwhile, majority of the tested pathogens were detected to be resistant against more than one antibiotic as MDR strains except gentamycin, streptomycin and azithromycin. During the combination method, the zone diameter increased remarkably with a clear indication of synergistic effects compared to their individual activity. This study substantiated that the deployment of a combination of two antibacterial medications in order to combat the multi-drug resistant bacteria would rather be efficacious than the application of either antimicrobial agent alone.


Passive immunization with convalescent serum, or oral immunization with formalin-killed organisms, does not protect mice against gastrointestinal challenge with Listeria monocytogenes.
Listeria monocytogenes is an important foodborne pathogen in both humans and animals. In addition, murine listeriosis is a widely used model for studying the molecular pathogenesis of an intracellular pathogen, and the regulation of protective cellular immunity. Little attention has been paid to protective immunity against L. monocytogenes in the gastrointestinal tract, where a secretory immune response might prevent attachment of the bacteria to the intestinal epithelium. In this study we found that neither opsonization of L. monocytogenes with immune serum, nor repeated oral administration of killed L. monocytogenes, protected mice against gastrointestinal challenge with L. monocytogenes.


Enterocytozoon bieneusi in fecal samples from calves and cows in Austria.
Enterocytozoon bieneusi is an obligate intracellular pathogen that infects livestock, companion animals, and wildlife and has the potential to cause severe diarrhea especially in immunocompromised humans. In the underlying study, fecal samples from 177 calves with diarrhea and 174 adult cows originating from 70 and 18 farms, respectively, in Austria were examined for the presence of E. bieneusi by polymerase chain reaction targeting the Internal Transcribed Spacer 1 (ITS1) region. All positive samples were further sequenced for genotype determination. Overall, sixteen of the 351 (4.6%) samples were positive for E. bieneusi, two of the 174 samples from cows (1.2%) and 14 of the 177 samples from calves (7.9%). In total, four genotypes, J (n = 2), I (n = 12), BEB4 (n = 3), and BEB8 (n = 1), were identified. The uncorrected p-distance between the four ITS1 lineages (344 bp) ranges from 0.3% to 2.9%. The lineages differ by 1 bp (I and J), 2 bp (J and BEB4), and 3 bp (I and BEB4), respectively, and BEB8 differs by 7 to 10 bp from the latter three lineages. Two of the E. bieneusi-positive calves showed an infection with two different genotypes. E. bieneusi occurred significantly more often in calves > 3 weeks (8/59) than in calves ≤ 3 weeks (6/118), respectively (p = 0.049). Calves with a known history of antimicrobial treatment (50 of 177 calves) shed E. bieneusi significantly more often than untreated calves (p = 0.012). There was no statistically significant difference in E. bieneusi shedding in calves with or without a medical history of antiparasitic treatment (p = 0.881). Calves showing a co-infection with Eimeria spp. shed E. bieneusi significantly more often than uninfected calves (p = 0.003). To our knowledge, this is the first report of E. bieneusi in cattle in Austria. Cattle should be considered as a reservoir for human infection since potentially zoonotic E. bieneusi genotypes were detected.


Hydrothermal synthesis of meso/macroporous BiVO4 hierarchical particles and their photocatalytic degradation properties under visible light irradiation.
An ordered hierarchical meso/macroporous monoclinic bismuth vanadate (BiVO4) particle was fabricated for the first time by a simple two-step melamine template hydrothermal method followed by calcination. The physiochemical parameters of as-prepared porous materials were characterized by means of X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy, Raman, Barrett-Emmett-Teller, and UV-vis techniques. The nitrogen adsorption-desorption measurement and pore size distribution curve suggest that meso/macropores exist in these hierarchical microarchitectures. Further, it is found that melamine plays a significant role in the formation of porous BiVO4 particles, and when a known amount of melamine was added, the surface area and pore size of such porous BiVO4 particles were increased. The photocatalytic activities of the as-prepared hierarchical BiVO4 samples were measured for the photodegradation of Congo red aqueous dye solution under visible light irradiation. Surprisingly, the porous BiVO4 particles showed outstanding photocatalytic activities than polycrystalline BiVO4 sample. The possible enhancement of such catalytic performance has also been further discussed.


Hypertriglyceridaemic waist phenotype and waist circumference triglyceride index are associated with higher incidence of acute pancreatitis: a nationwide population-based retrospective cohort study.
The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort. A retrospective, nationwide cohort study. Registry of health check-up result from Korean National Health Insurance Service. A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study. Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L). The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated. During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile). The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis.


Characterization of [hydroxyproline9]luteinizing hormone-releasing hormone and its smallest precursor forms in immortalized luteinizing hormone-releasing hormone-secreting neurons (GT1-7), and evaluation of their mode of action on pituitary cells.
[Hydroxyproline9]luteinizing hormone-releasing hormone ([Hyp9]LHRH), an endogenous hydroxylated post-translational product of the LHRH sequence, has been isolated from mammalian hypothalamus. Using the LHRH-hypothalamic cell line (GT1-7) of fetal origin, we attempted to define the substrates available for the hydroxylation process during LHRH synthesis and to characterize immunologically the [Hyp9]LHRH and pro-[Hyp9]LHRH forms with anti-LHRH antibodies of different specificities after separation by HPLC. Their biological activity and mode of action were evaluated and compared to that of LHRH and LHRH intermediate precursors in normal pituitary cells and in a gonanodotrope cell line alpha T3-1. immunoreactivity was progressively increased in cells and media during cell culture. [Hyp9]LHRH and its two smallest precursor forms ([Hyp9]LHRH-(Gly11) and -(11-13)) were detected in cells and in media. They were simultaneously detected with the homologous LHRH molecular forms indicating that the hydroxylation occurs early in the processing of pro-LHRH. [Hyp9]LHRH-like molecules were more abundant than LHRH forms in media. This predominant release may thus represent a physiological process occurring during fetal life. Free acid forms of both decapeptides were detected only in cells. Furthermore, the results obtained suggest that conversion of Gln1 in pyroGlu1 occurs before or during processing into the hydroxylated or non-hydroxylated LHRH intermediate (11-13)-precursors. The biosynthetic pathway is thus common for both decapeptides and it is not altered by the hydroxylation process. LHRH and [Hyp9]LHRH shared the same receptor for their biological activity, as assessed by measuring luteinizing hormone release and activation of phospholipase C and A2. [Hyp9]LHRH was, however, less potent than LHRH.


Challenges and common weaknesses in case-control studies on drug use and road traffic injury based on drug testing of biological samples.
To determine and discuss common weaknesses and errors in case-control studies on the association between drug use and road traffic crash injury among drivers and recommend improvements for future studies. A search for case-control studies published between 2000 and 2016 was performed using PubMed and other databases in addition to manual search. The used methodologies were compared with requirements and recommendations for case-control studies as well as current knowledge on the interpretation of drug concentrations in biological samples. Seventeen studies were identified. The major difficulties in the studies were related to likely selection bias, information bias, and confounding. In some studies, the definition of drug exposure was different for controls than for cases, generating potentially serious errors in the odds ratio estimations. Other weaknesses include lacking explanation of the assessment of drug exposure, missing covariates, lacking description of statistical methods, and lack of discussion of bias and confounding. Many of the observed challenges and weaknesses can be overcome or reduced. Recommendations for future studies are presented.


Study of intestinal immunity against V. cholerae: role of antibody to V. cholerae haemagglutinin in intestinal immunity.
Cell-bound haemagglutinin as an adhesive factor of Vibrio cholerae has been partially purified from E1 Tor vibrios using 0.05 M cyclohexylaminopropane sulfonic acid buffer pH 9.5 and gel filtration column chromatography. Rabbits were immunized with the precipitin complexes of the haemagglutinin and its antibody. The antiserum is tested for the protective ability against the oral challenge with Vibrio cholerae strain of which the haemagglutinin has been prepared. The results indicate definite protection of the haemagglutinin antiserum.


Humeral Lengthening with the PRECICE Magnetic Lengthening Nail.
Different types of external fixators have been used for humeral lengthening with successful outcomes reported in literature. Motorized intramedullary (IM) lengthening nails have been developed as an alternative to external fixators for long bone lengthening in the lower extremity. This case series reports on using the new technology of IM lengthening nails for humeral lengthening. We assessed the radiological healing and functional outcomes after using the PRECICE IM nail for humeral lengthening. This multicenter retrospective study included a total of six humeri in five patients (mean age was 20 years) that underwent lengthening with the magnetic IM PRECICE nail in two centers in the USA. The etiology was humeral growth arrest post-bone cyst (two segments), post-septic growth arrest (two segments), and multiple hereditary exostosis (bilateral segments in one patient). The outcomes measured were the length achieved, distraction index (DI; the length achieved in mm divided by the duration of lengthening in days), consolidation index (CI; number of days from surgery until consolidation divided by the length of the regenerate in cm), complications encountered, and functional outcomes (shoulder and elbow range of motion, the upper extremity functional index (UEFI), and QuickDASH functional scores). The mean follow-up period was 1.8 years (0.9 to 2.4 years). All segments achieved the goal of lengthening; the mean was 5.1 cm (4.5 to 5.8 cm). Mean DI was 0.7 mm/day (0.5 to 0.8). Mean CI was 36 days/cm (25 to 45 days/cm). No complications were observed. At the last follow-up, all patients maintained their preoperative range of motion (ROM) except one patient had reduced shoulder ROM. QuickDASH score and upper extremity functional index showed postoperative improvement compared to the preoperative scores. IM lengthening nails can provide successful and safe humeral lengthening. Specifically, the PRECICE nail has accurate control over the lengthening process.


Not all the infected develop the disease - A "Lotus and Cactus" model.
The immunogenetic dictum "not all the infected develop the disease" can best be explained by a "Lotus and Cactus" model. Lotuses grow in ponds and cacti in deserts: analogously, we can say that tubercle patient's lung (genetic makeup) functions as an ideal 'broth' for Mycobacterium tuberculosis (M.tb) germs to grow, but not the lungs of an endemic control. HLA association studies from Europe to Asia since 1983 till date, have shown a persistent HLA DR2 (15) association. Further, HLA DR2 and non-DR2 endemic controls showed disparate patterns of immune responses and gene expressions. The host and pathogen MHC diversities, Th1-Th2 paradigm and cytokine circuits all may play a crucial role in TB susceptibility. It is possible to decipher the protective immunity by controlling the known confounders - epidemiological, demographic, socio-biological and also host and pathogen diversities. This has become significant with our understanding on the 'out of Africa' migration and neolithic co-dispersal of M.tb with modern human. Divergence and expansion of various MHCs (eg HLA-DRB1*15, HLA-B*57) and non-MHC alleles in various continents might be responsible for the skewed transmission and distribution of the infectious diseases around the globe. The 'Lotus and Cactus' model proposed here exemplifies this. A holistic genetic epidemiology approach employing modern tools is the need of the hour to better understand infectious disease susceptibility.


Hepatocellular carcinoma in explanted livers of patients with genotype d HBV cirrhosis: report of the first experience from Iran.
This study was conducted to determine the impact of hepatitis B virus (HBV) as a cause of hepatocellular carcinoma (HCC) in a single liver transplant center in Iran. We included all hepatectomy specimens from patients with HBV-related cirrhosis who underwent transplants from May 1993 until January 2012 in this study. From these, we determined the number that had HBV-induced HCC. Nested PCR results were used to determine the HBV genotype from sections of the hepatectomy pathology specimens. During this time period there were 1361 cirrhotic livers transplanted in our center. Of these, 249 were attributed to HBV cirrhosis. Overall, HCC was detected in 40 (2.9%) subjects, of which 29 (1.2%) had HBV-related HCC. Genotype D was only genotype observed in all HBV subjects. The results revealed that although HBV-related cirrhosis was the most frequent single cause for liver transplant, the frequency of HBV-induced HCC was very low among transplant recipients. Out of 1361 transplant recipients, only 29 (2.1%) were diagnosed with HBV-related HCC. All HBV subjects had genotype D.


Watermelons, Syringes, and Regulation: Instagram Marketing by Cosmetic Clinics in the UK and the Netherlands.
Cosmetic clinics use social media to inform and market to prospective patients. Evidence from social media posts by the UK and Dutch cosmetic clinics illustrates the precarious balance between professionalism and commercialism, and raises important questions for the regulation of these marketing communication efforts. A random selection of Instagram posts by Dutch and the UK clinics which offer (non-) invasive cosmetic procedures were selected for a qualitative content analysis. The corpus of data comprised 395 posts by six Dutch and four UK clinics, published between January 2018 and July 2019. The method of analysis was inspired by previous qualitative studies into the marketing of cosmetic procedures and can be described as a (discursive) thematic analysis. The tension between the medical-professional and commercial nature of cosmetic procedures was evident in the Instagram posts by Dutch and UK clinics. Despite calls for 'ethical' marketing on social media, this study illustrates that marketing materials are not always in line with current advertising guidelines. Whereas advertising standards authorities have warned against the trivialization of cosmetic procedures, posts by clinics backgrounded the medical nature of procedures in favor of more commercial advertising appeals. Furthermore, the posts demonstrated little diversity in terms of models' gender, ethnicity and body type, which reinforces narrow contemporary beauty ideals. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


The relationship of maternal separation anxiety and differentiation of self to children's separation anxiety and adjustment to kindergarten: a study in Druze families.
The study explores relationships between preschoolers' separation anxiety and adjustment to kindergarten and their mothers' separation anxiety and levels of differentiation. It also examines the universality of several theoretical and clinical notions in Bowen's [Bowen, M. (1978). Family therapy in clinical practice. Aronson: New York] Family Systems Theory, by testing them in the Eastern-collectivist Israeli-Druze society. The main findings were positive correlations between mothers' and children's separation anxiety, as well as negative correlations between children's separation anxiety and maternal differentiation (for total DSI score and for emotional cutoff), so that lower differentiation and higher cutoff were associated with higher levels of anxiety. Another interesting finding was that teachers perceived the children of Druze working mothers as having more problematic behaviors than non-working mothers, pointing to poorer adjustment to kindergarten. Results suggest that a crucial balance of separation and closeness provides an optimal context for meeting the needs and promoting the healthy development of both mother and child. The present study is the first to indicate relations between mothers' differentiation and preschoolers' separation anxiety among Druze participants, partially supporting the universality of Bowen's theory "in all families and in all cultures" [Kerr, M., & Bowen, M. (1988). Family evaluation. New York: Norton, p. 202].


Human glucagon receptor antagonists based on alkylidene hydrazides.
A series of alkylidene hydrazide derivatives containing an alkoxyaryl moiety was optimized. The resulting hydrazide-ethers were competitive antagonists at the human glucagon receptor. Pharmacokinetic experiments showed fast clearance of most of the compounds tested. A representative compound [4-hydroxy-3-cyanobenzoic acid (4-isopropylbenzyloxy-3,5-dimethoxymethylene)hydrazide] with an IC50 value of 20 nM was shown to reduce blood glucose levels in fasted rats.


Incidence and risk factors for COVID-19 associated candidemia (CAC) in ICU patients.
Critically ill COVID-19 patients have a high risk for the development of candidemia due to being exposed to both well-defined classical risk factors and COVID-19-specific risk factors in ICU. In this study, we investigated the incidence of candidemia in critically COVID-19 patients, and the independent risk factors for candidemia. COVID-19 patients hospitalised in ICU during 1-year period (August 2020 to August 2021) were included. Clinical and laboratory characteristics of all COVID-19 patients, applied treatments, and invasive procedures that may predispose to candidemia were recorded. Of 1229 COVID-19 patients, 63 developed candidemia. Candidemia incidence rate was 4.4 episodes per 1000 ICU days. The most common species was Candida albicans (52.3%). Only 37 patients (58.7%) received antifungal therapy. The presence of central venous catheter (OR 4.7, 95% CI 1.8-12.2, p < .005), multifocal candida colonisation (OR 2.7, 95% CI 1.4-5.2, p < .005), a prolonged ICU stay (≥14 days) (OR 1.9, 95% CI 1.08-3-37, p < .05), the absence of chronic lung disease (OR 0.4, 95% CI 0.1-0.9, p < .05) and the absence of corticosteroid use (OR 0.3, 95% CI 0.14-0.52, p < .0001) were significantly associated with candidemia. Our study filled the knowledge gap in the literature about the impact of COVID-19-associated risk factors for the development of candidemia. The classical risk factors for candidemia had a significant effect on candidemia, and contrary to expectations, corticosteroids had a protective effect against the development of candidemia. The results of these studies showing interesting effects of corticosteroids in critically ill COVID-19 patients should be confirmed by further studies.


Fertile Ground: Work at MIT?s Center for Gynepathology Research is Revealing How Tissue Engineering Can Help Address Gynecological Disorders.
At the age of 14, Linda Griffith experienced such abnormally painful periods that her doctor had already put her on birth control pills. They helped but only a little. In graduate school, a boyfriend convinced her to go off the pills, and her periods became so painful, she couldn't walk.


Evaluating pediatric intussusception using 24-hour ultrasound.
Although ultrasound is often the preferred pediatric imaging modality for the evaluation of intussusception in children, many institutions lack access to ultrasound at night. This study characterized the day- and nighttime use of radiographic imaging for evaluation of intussusception. The charts of pediatric patients evaluated for intussusception between January 2010 and December 2010 were reviewed retrospectively to evaluate the day- and nighttime use of radiographic imaging. Patients were stratified into day and night groups according to when the imaging studies were performed, and differences in the clinical characteristics, imaging studies, cost, and final diagnosis were compared. Pediatric consultations were performed for 86 suspected intussusceptions: 40 (46.5%) during the day [38 (95%) ultrasounds and 33 (82.5%) plain abdominal X-rays] and 46 at night [3 (6.5%) computed tomography and 39 (84.7%) plain abdominal X-rays]. The rate of positive enemas was significantly higher during the day than at night (97.5% vs. 52.2%, p < 0.001). The radiation dose during the initial survey was significantly lower during the day than at night (0.63 ± 0.48 vs. 2.06 ± 1.48 mSv, p < 0.001). Radiographic imaging at night results in higher radiation exposure and negative enema findings. Twenty-four-hour ultrasound availability would decrease the radiation exposure and unnecessary enemas for intussusceptions suspected clinically.


Precordial electrocardiographic mapping technique.
Using an original device, unipolar electrograms in 36 points on the anterior thoracic wall were recorded. The equal intensity contour lines of the amplitudes of electrical events were drawn as precordial maps, by mathematical procedures.


Contribution of forests to the carbon sink via biologically-mediated silicate weathering: A case study of China.
During silicate weathering, atmospheric carbon dioxide (CO2) is consumed and base cations are released from silicate minerals to form carbonate and bicarbonate ions, which are finally deposited as carbonate complexes. Continental silicate weathering constitutes a stable carbon sink that is an important influence on long-term climate change, as it sequesters atmospheric carbon dioxide at a million-year time scale. Traditionally, CO2 sequestered through silicate weathering is estimated by measuring the flux of the base cations to watersheds. However, plants also absorb considerable amounts of base cations. Plant biomass is often removed from ecosystems during harvesting. The base cations are subsequently released after decomposition of the harvested plant materials, and thereby enhance CO2 consumption related to weathering. Here, we analyze plant biomass storage-harvest fluxes (production and removal of biomass from forests) of base cations in forests across China to quantify the relative contribution of forest trees to the terrestrial weathering-related carbon sink. Our data suggest that the potential CO2 consumption rate for biomass-related silicate weathering (from the combined action of with afforestation/reforestation, controlled harvesting and rock powder amendment) in Chinese forests is 7.9±4.1Tg CO2yr-1. This represents ~34% of the chemical weathering rate in China. Globally, forests may increase CO2 sequestration through biologically-mediated silicate weathering by ~32%.


Potent antiperoxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: the amine moiety is responsible for its pH-dependent radical scavenge activity.
The bisbenzylisoquinoline alkaloid cepharanthine, which has been considered to exhibit antiperoxidation activity due to its membrane stabilizing effect, was found to scavenge radicals such as .OH and DPPH (1,1-diphenyl-2-picrylhydrazyl) in solution, and to inhibit lipid peroxidation in mitochondria and liposomes by Fe2+/ADP. The antiperoxidation activity of cepharanthine in rat liver mitochondria initiated by Fe2+/ADP at pH 7.4 was much greater than that of alpha-tocopherol, its half-inhibitory concentration being about 23 microM. However, cepharanthine was effective only at neutral pH values such as pH 7.4, not in a moderately acidic pH region below pH 6.5. Accordingly, the neutral form of the deprotonated amine moiety in the tetrahydroisoquinoline ring is concluded to be responsible for the radical scavenging activity of cepharanthine. There are two amine moieties in the cepharanthine molecule, but we specified the effective amine moiety from the antiperoxidation activities of the imine analogs of cepharanthine.


Descent of the right renal vein.
A new operation is described, in which the right renal vein outlet is moved to a lower level on the vena cava, helping to decrease the distance between the kidney and the bladder. This procedure permits treatment of extensive obstructive wounds of the pyeloureteral junction or lumbar ureteral junction, caused by lithiasis and ureteral and renal operations, that cannot be treated with conventional operations. Renal circulation is not altered with this procedure. The operation is simple, does not cause complications and provides excellent results.


Different components of 3H-imipramine binding in rat brain membranes: relation to serotonin uptake sites.
In the present paper we confirm and extend previous studies showing heterogeneous 3H-imipramine (3H-IMI) binding sites. Inhibition curves of various drugs (serotonin, imipramine, desmethyl-imipramine, d-fenfluramine, d-norfenfluramine and indalpine, a potent serotonin uptake inhibitor) obtained using 2 nM 3H-IMI and in presence of 120 mM NaCl, confirmed the presence of at least three 3H-IMI binding sites: two of these (high and low affinities) were serotonin-insensitive while the third one was selectively inhibited by serotonin and indalpine with nanomolar affinities. Moreover, this last component was found to be selectively modulated by chronic imipramine treatment thus suggesting a closer relation to serotonin uptake mechanism. These data indicate that the use of a more selective inhibitors of the serotonin-sensitive component (like indalpine or serotonin itself) to define non specific 3H-IMI, may be of help in understanding its relation with serotonin uptake system.


Analysis of eighteen antidepressants, four atypical antipsychotics and active metabolites in serum by liquid chromatography: a simple tool for therapeutic drug monitoring.
Therapeutic drug monitoring necessitates efficient, fast and reliable analytical methods validated by external quality control. We therefore devised an isocratic reversed-phase HPLC method with ultraviolet detection and optimised this to quantify mirtazapine, reboxetine, moclobemide, venlafaxine, O-desmethylvenlafaxine, paroxetine, fluvoxamine, fluoxetine, norfluoxetine, sertraline, citalopram, amitriptyline, nortriptyline, imipramine, desipramine, doxepin, nordoxepin, clomipramine, norclomipramine, trimipramine, mianserine, maprotiline, normaprotiline, amisulpride, clozapine, norclozapine, quetiapine, risperidone and 9-OH-risperidone in human serum. After solid-phase extraction of the drugs and metabolites, the chromatographic separation was achieved on a Nucleosil 100-Protect 1 column with acetonitrile-potassium dihydrogenphosphate buffer as mobile phase. The method was validated for therapeutic and toxic serum ranges. A linear relationship (r>0.998) was obtained between the concentration and the detector signal. Recoveries were between 75 and 99% for the drugs and metabolites. The accuracy of the quality control samples, expressed as percent recovery, ranged from 91 to 118%; intra- and inter-assay-relative standard deviations were 0.9-10.2% and 0.9-9.7%, respectively. Additional external quality control is carried out since 3 years. This method is applicable to rapidly and effectively analyze serum or plasma samples for therapeutic drug monitoring of about 30 antidepressants and atypical antipsychotics.


Super-Resolution Imaging of Competitive Unlabeled DNA Hybridization Reveals the Influence of Fluorescent Labels on Duplex Formation and Dissociation Kinetics.
Single-molecule fluorescence imaging is a powerful method to measure reversible reaction kinetics, allowing one to monitor the bound state of individual probe molecules with fluorescently labeled targets. In the case of DNA hybridization, previous studies have shown that the presence of a fluorescent label on a target strand can exhibit significant influence on the stability of a DNA duplex that is formed. In this work, we have developed a super-resolution imaging method to measure the hybridization kinetics of unlabeled target DNA that compete with a fluorescently labeled tracer DNA strand to hybridize with an unlabeled probe DNA immobilized at a surface. The hybridization of an unlabeled DNA target cannot be detected directly, but its presence blocks the immobilized probe DNA, influencing the measured time intervals between labeled DNA hybridization events. We derive a model for competitive hybridization kinetics to extract the association and dissociation rate constants of the unlabeled species from the distribution of time intervals between hybridization events of the labeled tracer DNA at individual localized DNA probe sites. We use this methodology to determine the hybridization kinetics of a model 11-mer unlabeled target DNA strand and then determine how five different fluorescent labels attached to the same target DNA strand impact the hybridization kinetics. Compared to the unlabeled target, these labels can slow the association and dissociation rates by as much as a factor of 5. The super-resolution time-interval methodology provides a unique approach to determining fundamental (label-free) rates of DNA hybridization, revealing the significant influence of fluorescent labels on these kinetics. This measurement concept can be extended to studies of other reversible reaction systems, where kinetics of unlabeled species can be determined from their influence on the reaction of a labeled species with localized probe molecules on a surface.


Biomass and domestic waste: a potential resource combination for bioenergy generation and water treatment via benthic microbial fuel cell.
The benthic microbial fuel cell (BMFC) is one of the most efficient types of bioelectrochemical fuel cell systems. Modern bioelectrochemical fuel cells have several drawbacks, including an unstable organic substrate and a microorganism-unfriendly atmosphere. The recent literature to encounter such issues is one of the emerging talks. Researchers are focusing on the utilization of biomass and waste to encounter such challenges and make the technique more feasible at the pilot scale. This study investigated the combination of local bakery waste as an organic substrate with lignocellulosic biomass material. The whole experiment was conducted for 45 days. At an external resistance of 1000 ῼ and an internal resistance of 677 ῼ, the power density was found to be 3.51 mW/m2. Similarly, for Pb2+, Cd2+, Cr3+, Ni2+, and Co2+, the degradation efficiency was 84.40%, 81.21%, 80%, 89.50%, and 86.0%, respectively. The bacterial identification results showed that Liquorilactobacillus nagelii, Proteus mirabilis, Pectobacterium punjabense, and Xenorhabdus thuongxuanensis are the most prominent species found on anode biofilm. The method of electron generation in this study, which includes the degradation of metal ions, is also well described. Lastly, optimising the parameters showed that pH 7 provides a feasible environment for operation. A few future suggestions for practical steps are enclosed for the research community.


Left coronary artery calcification patterns after coronary bypass graft surgery: An in-vivo optical coherence tomography study.
We sought to evaluate the severity and patterns of calcifications in the left main coronary artery (LMCA) and proximal segments of left anterior descending coronary artery (LAD) and left circumflex artery (LCX) using optical coherence tomography (OCT) in patients with and without prior coronary artery bypass grafting (CABG). CABG may accelerate upstream calcium development. OCT images (n = 76) of the LMCA bifurcation from either the LAD or LCX in 76 patients with at least one patent left coronary graft, on average 7.0 ± 5.6 years post-CABG, were compared with 148 OCT images in propensity-score-matched non-CABG controls. Minimum lumen areas in the LMCA, LAD, and LCX in post-CABG patients were smaller than non-CABG controls. Maximum calcium arc and thickness as well as calcium length were greater in the LMCA and LCX, but not in the LAD in post-CABG patients versus non-CABG controls. Calcium located at the carina of a bifurcation, calcified nodules (CN), thin intimal calcium, and lobulated calcium were more prevalent in post-CABG patients. After adjusting for multiple covariates, prior CABG was an independent predictor of calcification at the carina of a bifurcation (odds ratio [OR] 5.77 [95% confidence interval, CI: 1.5-21.6]), thin intimal calcium (4.7 [1.5-14.4]), and the presence of a CN (15.60 [3.2-76.2]). Prior CABG is associated with greater amount of calcium in the LMCA and the proximal LCX, as well as higher prevalence of atypical calcium patterns, including CN, thin or lobulated calcium, and calcifications located at the carina of a bifurcation, compared with non-CABG controls.


The effect of sex differences on neointimal characteristics of in-stent restenosis in drug-eluting stents: An optical coherence tomography study.
Previous studies have demonstrated that there are sex-related differences in atherosclerosis. However, in terms of the nature of in-stent restenosis (ISR) neointima, the effect of gender on the results is unclear. Patients with ISR of drug-eluting stents (DES) who underwent OCT examination in Senior Department of Cardiology of the Chinese People's Liberation Army General Hospital from March 2010 to March 2022 were included. The patients were divided into male and female groups. In this study, a total of 230 DES-ISR patients and 249 DES-ISR target lesions were analyzed. OCT data showed that compared to females, males have a higher incidence of thin-cap fibrous atherosclerosis (TCFA) (37.4% [n = 77] vs. 9.3% [n = 4], p < 0.001) and in-stent neoatherosclerosis (ISNA) (82.0% [n = 169] vs. 62.8% [n = 27]). p = 0.005). In addition, a multivariate logistic regression analysis demonstrated that male was independently associated with a higher incidence of ISNA (OR: 2.659, 95% CI: 1.239-5.707; p = 0.012) and TCFA (OR: 4.216, 95% CI: 1.370-12.976; p = 0.012). For DES-ISR patients, the incidence of ISNA in female was significantly lower than that in male and vulnerability of neointimal pattern is lower in female than in male.


Antibody Responses to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients.
We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.


Same-day or next-day sentinel node biopsy after lymphoscintigraphy for melanoma using 99m Tc-labelled antimony sulphide colloid.
Two recent publications have reported that a shorter interval between preoperative lymphoscintigraphy and sentinel node biopsy (SNB) is associated with improved survival of patients with primary cutaneous melanoma. The aims of this study were to analyse prospectively collected survival data for patients who had SNB on the same day as lymphoscintigraphy or the day after; and to assess tracer migration from sentinel nodes to second-tier nodes after lymphoscintigraphy on the previous day. Outcome data were obtained for patients who had lymphoscintigraphy and SNB on the same day (time interval less than 8 h) or the next day (interval more than 16 h). In a separate prospective cohort, same-day and next-day lymphoscintigraphic images of sentinel nodes and second-tier nodes were compared. Following lymphoscintigraphy, 2848 patients had same-day and 3328 had next-day SNB. Survival outcomes did not differ between these groups. In a prospectively studied cohort of 30 patients, none had significant tracer migration from sentinel nodes to second-tier nodes on imaging the following day. No difference in survival after same- or next-day sentinel node biopsy is seen when 99m Tc-labelled antimony sulphide colloid is used. This may be because of less tracer migration to second-tier nodes.


Co-expression of steroid hormone receptors (estrogen receptor alpha and/or progesterone receptors) and Her2/neu (c-erbB-2) in breast cancer: clinical outcome following tamoxifen-based adjuvant therapy.
In breast cancer patients, the expression of steroid hormone receptors (HR:ERalpha/PR) appears inversely correlated with Her2/neu (not all reports agree on this negative correlation). Moreover, some but not all studies suggest that HR+/Her2/neu+ patients have a poor response to endocrine therapy, making this special group a matter of debate. In this prospective study we have analyzed the clinical outcome of our HR+/Her2/neu+ patients (n=51) selected from 516 consecutive stages I-II cases, with a follow-up 5-10 years (mean 7.3), treated with standard adjuvant therapy with tamoxifen (TAM) (TAM alone or TAM after chemotherapy). This group was compared with the HR+/Her-2/neu- patients (n=129) treated also with TAM. The tumor biopsies were studied by immunohistochemistry. We found that the association HR+/Her2/neu- was 2.5 times higher than the association HR+/Her2/neu+ (25% versus 9.9%, respectively). Our study also showed that the disease free survival (DFS) of the patients co-expressing HR and Her2/neu was significantly lower than those expressing HR but lacking of Her2/neu (p<0.001). A similar result was obtained when the overall survival (OS) was evaluated (p=0.001). All of these patients received hormone therapy with TAM, alone or after chemotherapy. When the analysis was performed in the patients treated with TAM alone, again the expression of Her-2/neu had a negative impact on both the DFS and the OS (p<0.05).


Senotherapeutics for mesenchymal stem cell senescence and rejuvenation.
Mesenchymal stem cells (MSCs) are susceptible to replicative senescence and senescence-associated functional decline, which hampers their use in regenerative medicine. Senotherapeutics are drugs that target cellular senescence through senolytic and senomorphic functions to induce apoptosis and suppress chronic inflammation caused by the senescence-associated secreted phenotype (SASP), respectively. Therefore, senotherapeutics could delay aging-associated degeneration. They could also be used to eliminate senescent MSCs during in vitro expansion or bioprocessing for transplantation. In this review, we discuss the role of senotherapeutics in MSC senescence, rejuvenation, and transplantation, with examples of some tested compounds in vitro. The prospects, challenges, and the way forward in clinical applications of senotherapeutics in cell-based therapeutics are also discussed.


Kinetics of primidone metabolism and excretion in children.
The metabolism and excretion of orally administered primidone was studied in 12 children, aged 7 to 14 yr during long-term dosing. Plasma concentrations of primidone (Pr) peaked at 4 to 6 hr and declined exponentially from 6 to 24 hr, with half-life (t1/2) values ranging from 4.5 to 11 hr. A mean of 92% (72% to 123%) of the administered dose was recovered within 24 hr from the urine as Pr and its metabolites. Of the total Pr daily dose, 42.3% (15.2% to 65.9%) was recovered as unchanged drug, 45.2% (16.3% to 65.3%) as phenylethylmalonamide (PEMA), and 4.9% (1.1% to 8.0%) as phenobarbital (Pb). The mean rate constant for conversion of Pr to PEMA (K1) was 0.0424 hr-1, for conversion of Pr to Pb (K2) was 0.0045 hr-1, and for excretion of unchanged Pr (K3) was 0.0389 hr-1. Of Pb excreted, 43% (13% to 100%) was unchanged, 15% (0% to 27%) was unconjugated p-OH Pb, 20% (0% to 44%) was conjugated p-OH Pb, and 22% (0% to 33%) was conjugated 3,4-OH Pb. KE appears to be important determinant of the steady-state plasma concentration of Pb, but interindividual differences in K2 have little influence on the overall rate constant for elimination of Pr.


Closing the Loop with Ambulatory Staff on Safety Reports.
A commonly cited reason among nurses and physicians for not reporting safety events is a perceived lack of feedback from management on filed safety reports. This suggests that the value of a safety reporting system could be improved with a closed-loop feedback system between management and frontline staff on filed safety reports in which feedback was requested. Ambulatory staff were surveyed on barriers to reporting to assess this challenge at an academic medical center. In response, system changes were implemented to the electronic safety reporting system, gained leadership buy-in, incorporated managers into a work group tasked with enhancing feedback to staff, established project management support, and developed a safety star manager recognition program. Ultimately, a process was developed to measure and ensure that feedback was provided to staff who requested it through a series of Plan-Do-Study-Act cycles termed the Feedback to Reporter program. At baseline in 2013, the team found that staff who indicated they wanted feedback on safety reports received it less than 50% of the time. By the end of fiscal year 2018, the monthly feedback to reporter rate was consistently 90% or higher. The percentage of safety reports in which feedback was requested ranged from 35.0% to 49.7% of all safety reports submitted. Ultimately, a multidimensional approach improved closed-loop communication from local managers to frontline staff and between managers of different departments on ambulatory safety reports when feedback was requested. Improvements were sustained for more than one year.


Inbreeding in Norway.
In Norway specified information of marriages between second cousins and closer relations has been recorded in the marriage certificates since January 1889. In addition, information was collected in the 1891 census and in the Medical Registration of Births (established in 1967). A ratio of second- to first-cousin marriages equal to or greater than 2 has been taken as some evidence indicating reliability of the source of data. Using this criterion, the information in the Medical Registration of Births seems most reliable, and that in the 1891 census possibly of similar accuracy. On the other hand, from 1890 the marriage certificates are unreliable with regard to the proportion of second-cousin marriages (ratio less than 1), and with regard to the proportion of first-cousin marriages from 1919. The present inbreeding in Norway is low (alpha4 = 0-000242), approximately one-eighth of the estimated level according to the 1891 census. The greatest reduction in inbreeding probably occurred after 1920.


Retracted: Application of Neural Network Model Based on Multispecies Evolutionary Genetic Algorithm to Planning and Design of Diverse Plant Landscape.
[This retracts the article DOI: 10.1155/2021/9031366.].


Primary care incidence and treatment of four neuropathic pain conditions: a descriptive study, 2002-2005.
Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain. A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005. Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27-30) for post-herpetic neuralgia, 27 (95%CI 26-29) for trigeminal neuralgia, 0.8 (95%CI 0.6-1.1) for phantom limb pain and 21 (95%CI 20-22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain. The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.


Pollution of the Niger Delta with total petroleum hydrocarbons, heavy metals and nutrients in relation to seasonal dynamics.
The African Niger Delta is among the world's most important wetlands in which the ecological effects of intensive oil exploitation and global change are not well documented. We characterized the seasonal dynamics and pollution with total-petroleum-hydrocarbons (TPHs), heavy-metals (HMs) and nutrient-loads in relation to climate-driven variables. High TPH concentrations up to 889 mg/L and HMs up to 13.119 mg/L were found in water samples, with pronounced spatio-temporal variation throughout the year. HM pollution index and contamination factor indicate serious ecological and human health hazards, especially for Cd, Cu, Hg, and Ni. Significant differences in TPHs/HMs were observed between sites and seasons, with correlations between TPHs-HMs, and climate-variables and TPHs-HMs. Nutrient levels, turbidity, salinity, temperature, and SO42- were high and interlinked with the variability of TPHs/HMs being greatest during wet season. These findings suggest an urgent need for improved pollution control in the Niger Delta taking into account the observed spatio-temporal variation and the exacerbation of effects in light of climate change. Given the high levels of contamination, further assessments of exposure effects and bioaccumulation in biota should include future climate change scenarios and effects on humans who intensively depend on the system for drinking water, food supply and livelihood.


Commissurotomy subjects show lateralized difference between manual and oral responding.
This study investigates the influence of the mode of response on the right ear advantage in verbal dichotic testing. Four complete commissurotomy subjects were tested on an ascending digits tape with oral response and manual response by the dominant hand with the volume equal and raised in each ear. Oral response elicited right ear report in all tests under all conditions at all levels of task difficulty. Pointing and writing responses elicited left ear report when the volume was raised in the left ear and the number of digits to report was small. Right ear performance increased and left ear performance decreased as the number of digits to process increased. Results indicate that response modes differ significantly in the degree to which they engage the left hemisphere or to which they suppress the ipsilateral pathways within the left hemisphere. Use of an oral response may obscure the lateralized contribution of the cognitive activity under investigation.


Functioning human insulinomas. An immunohistochemical analysis of intracellular insulin processing.
Sixty-seven insulinomas were investigated by immunohistochemistry using site-directed antibodies against insulin, proinsulin, chromogranin A, HISL-19, and four proteins directly or indirectly involved in the proteolytic processing of proinsulin: the prohormone convertases PC2 and PC3, carboxypeptidase H (CPH) and 7B2. Results were expressed in a six-grade score according to the frequency of immunoreactive tumour cells. Insulin was expressed by all tumours, appearing in either a diffuse or a polarized pattern and being detected in more than 30% of tumour cells in all cases but three. Proinsulin was also expressed in all tumours, with more than 50% of tumour cells immunoreactive in all cases but 5. It was consistently localized in the Golgi apparatus. In about half the cases, moreover, it also showed diffuse cytoplasmic staining, usually with a very sparse distribution. Trabecular and solid insulinomas did not present specific, homogeneous patterns of insulin immunostaining. However, insulin immunoreactivity was much more abundant in trabecular than in solid neoplasms, being present in virtually all tumour cells (score 6) in 50% and 8% of cases, respectively. Virtually all insulinomas expressed PC2, PC3, CPH and 7B2, usually in 30-100% of tumour cells, with a frequency significantly related to that of insulin. However, detection of PC2 and 7B2 was slightly less frequent than that of PC3 and CPH. In consecutive sections these proteins were found to be mostly co-localized with insulin and chromogranin A but not with proinsulin. They were heavily expressed in all 10 tumours with more than 10% of cells showing cytoplasmic proinsulin immunoreactivity, indicating that the leakage of proinsulin from the Golgi compartment is not associated with faulty expression of converting enzymes and possibly reflects a saturated processing capacity. HISL-19 immunoreactivity was found in both Golgi apparatus and insulin stores, indicating that the relevant antigen is different from all other proteins investigated. These results do not support a defect in expression or localization of proinsulin-processing enzymes in most insulinomas.


Patient information in dentistry: the standard dental treatment form, a French health policy
In France, the information provided to the patient by the dentist is ensured by the mandatory delivery of a standard dental treatment form (SDTF). This form has undergone a certain number of changes, in particular as a result of legislative interventions. More recently, the implementation of the 100% health reform has confirmed the place of the SDTF in the political ambition to improve access to dental care. This article presents the issues and changes of the SDTF in France over a period of 25 years. The study is based on a literature review supplemented by a qualitative analysis using semi-directed interviews with actors involved in oral health policies. The ambition of a SDTF is the result of a common approach initiated by the dental profession and insurers at the end of the 1990s. Subsequently, lawmakers became involved in the design of the form, making it mandatory. Over the years, the SDTF become particularly exhaustive, making its application and understanding by patients complex. According to the public control authority, the rate of non-application of the SDTF by dental surgeons remains high. The SDTF now occupies an essential place in dental health services in France. However, this study highlights the difficulties for the actors involved in oral health policies to reach a lasting consensus allowing its full application, in the interest of patients.


Ultrasound screening of the abdominal aorta in patients with intermittent claudication.
The presence of abdominal aortic dilatations and aneurysms (AAA) among 372 patients (302 men and 70 women) who originally presented with intermittent claudication was studied. The cohort was analysed in two ways, first retrospectively from the date of diagnosis of intermittent claudication until 1st of August 1985 (mean follow-up time being 70 months), second those alive at that date and who had not been operated on were offered ultrasound screening of their aorta. Retrospectively nine male patients were found to have had an operation for an aneurysm, one because of a rupture. Of the 110 patients who died and had not had surgery, 88 (73 men, 15 women) were autopsied and AAA was found at autopsy in six males and one female. Two males died of rupture. Ultrasonographic screening of the abdominal aorta was performed in 183 patients (147 men and 36 women) and dilatation was found in 25 patients (24 men, 1 woman). In the male part of the total material (n = 257) there were 39 patients (15%) with aneurysm or dilatation. Male patients with AAA or dilated aortas were significantly heavier, with a lower ankle arm index and higher serum cholesterol values than patients without AAA or aortic dilatation.


Differences in the acquisition process and the effect of scopolamine on radial maze performance in three strains of rats.
The acquisition process and the effect of scopolamine (SCOP) on the radial maze task were studied in 3 strains of male rats, Fischer 344 (F344), Sprague-Dawley (SD) and Wistar. The pretraining level of locomotor activity was measured and performance was quantitatively and qualitatively evaluated. The highest pretraining locomotor activity was observed in Wistar rats. In this experiment, rats were allowed to select each arm successively. The changes in the number of correct choices during the first eight selections, error choice in a trial and the total duration of a trial differed with the strain in the first 5 training sessions. Acquisition curve for F344 rats gradually rose. Wistar rats made many error choices. However, during the final 5 sessions, only the total duration of a trial differed with the strain. Wistar rats took the shortest time to finish a trial, but the number of sessions taken to acquire this task was the fewest with F344 rats, and the most with Wistar rats. The effect of SCOP differed among strains in all the above 3 indexes. Generally, the Wistar rat was the most affected by the injection of SCOP. Moreover, the change of the choice accuracy and the spatial strategy by the administration of SCOP were investigated. SD and Wistar rats showed a dose-dependent decrease in choice accuracy in the earlier selection. The spatial strategy was changed in every strain by the injection of SCOP. These findings do not support the previous finding that a high level of locomotor activity yields fast acquisition of this task or that Wistar rats are better in learning than SD, but indicates that SCOP affects not only the working memory but also the motivational factor.


Dexamethasone enhances oxidative stress-induced cell death in murine neural stem cells.
Glucocorticoids (GCs) are essential for normal brain development; however, there is consistent evidence that prenatal exposure of the fetal brain to excess GCs permanently modifies the phenotype of neuronal cells. In this paper, the murine-derived multipotent stem cell line C17.2 was used, as an in vitro model, to investigate the impact of GCs on neural stem cell survival. Our results indicate that dexamethasone (Dex) increases the sensitivity of murine neural stem cells (NSCs) to 2,3-methoxy-1,4-naphthoquinone-induced apoptosis, and this effect could be blocked by the glucocorticoid-receptor (GR) antagonist mifepristone, strongly suggesting the involvement of the GR. Furthermore, our results show that Dex decreases cell number and induces a G1-arrest. We hypothesized that the mitochondria are the main target of Dex. Interestingly, after treatment with Dex, 72% of the investigated genes involved in the mitochondrial respiratory chain are down-regulated, as well as 29% of the genes encoding for antioxidant enzymes. In conclusion, using the C17.2 cell line as a model to study developmental neurotoxicity in vitro, we have shown that GCs can increase cellular sensitivity to oxidative stress and alter the phenotype of NCSs.


Deep Learning and Computational Chemistry.
Within the context of the latest resurgence in the application of artificial intelligence approaches, deep learning has undergone a renaissance over recent years. These methods have been applied to a number of problems in computational chemistry. Compared to other machine learning approaches, the practical performance advantages of deep neural networks are often unclear. However, deep learning does appear to offer a number of other advantages such as the facile incorporation of multitask learning and the enhancement of generative modeling. The high complexity of contemporary network architectures represents a potentially significant barrier to their future adoption due to the costs of training such models and challenges in interpreting their predictions. When combined with the relative paucity of very large datasets, it is interesting to reflect on whether deep learning is likely to have the kind of transformational impact on computational chemistry that it is commonly held to have had in other domains such as image recognition.


Interstitial laser coagulation with temporary hepatic artery occlusion for patients with cirrhosis and irresectable hepatoma.
The aim was to determine the degree of local control of hepatocellular carcinoma (HCC) in patients with cirrhotic liver disease when treated with ultrasonographically guided interstitial laser coagulation (ILC) with temporary hepatic artery occlusion. Sixteen patients with 24 HCC tumours were treated. Follow-up was by computed tomography or magnetic resonance imaging every 3 months. Nineteen of 24 tumours showed complete necrosis immediately after treatment, and there was no tumour recurrence during follow-up (mean 14 months, median 12 months). No effect on liver function was observed after 1 week and there was no death. In 13 of the 16 patients, new HCC foci developed at other sites. Percutaneous ILC combined with temporary hepatic artery occlusion during a single session is an effective local treatment for HCC nodules smaller than 5 cm. However, new HCC lesions develop in the majority of patients, which underscores the need for adjuvant therapy or repeated treatment in these patients.


Glutamine uptake and catabolism is required for myofibroblast formation and persistence.
Fibrosis and extracellular matrix remodeling are mediated by resident cardiac fibroblasts (CFs). In response to injury, fibroblasts activate, differentiating into specialized synthetic and contractile myofibroblasts producing copious extracellular matrix proteins (e.g., collagens). Myofibroblast persistence in chronic diseases, such as HF, leads to progressive cardiac dysfunction and maladaptive remodeling. We recently reported that an increase in αKG (alpha-ketoglutarate) bioavailability, which contributes to enhanced αKG-dependent lysine demethylase activity and chromatin remodeling, is required for myofibroblast formation. Therefore, we aimed to determine the substrates and metabolic pathways contributing to αKG biosynthesis and their requirement for myofibroblast formation. Stable isotope metabolomics identified glutaminolysis as a key metabolic pathway required for αKG biosynthesis and myofibroblast formation, therefore we tested the effects of pharmacologic inhibition (CB-839) or genetic deletion of glutaminase (Gls1-/-) on myofibroblast formation in both murine and human cardiac fibroblasts. We employed immunofluorescence staining, functional gel contraction, western blotting, and bioenergetic assays to determine the myofibroblast phenotype. Carbon tracing indicated enhanced glutaminolysis mediating increased αKG abundance. Pharmacological and genetic inhibition of glutaminolysis prevented myofibroblast formation indicated by a reduction in αSMA+ cells, collagen gel contraction, collagen abundance, and the bioenergetic response. Inhibition of glutaminolysis also prevented TGFβ-mediated histone demethylation and supplementation with cell-permeable αKG rescued the myofibroblast phenotype. Importantly, inhibition of glutaminolysis was sufficient to prevent myofibroblast formation in CFs isolated from the human failing heart. These results define glutaminolysis as necessary for myofibroblast formation and persistence, providing substantial rationale to evaluate several new therapeutic targets to treat cardiac fibrosis.


Outcome of gastric bypass patients.
The authors analyzed previously studied outcomes of Roux-en-Y gastric bypass (RYGBP), examined pre-surgical factors of post-surgical outcomes, and examined some of the psychosocial benefits. A retrospective chart review was conducted of 138 patients who underwent RYGBP between 1997 and 2000. Pre-surgical BMI, cholesterol, blood pressure, creatinine, number of antidepressant/glycemic drugs, and hemoglobin were recorded. Post-surgical follow-up was reviewed to examine changes. Statistically significant changes were found in BMI, hypertension, cholesterol and glycemic control. Surgery was found to reduce creatinine from a pre-surgery average of 1.14 to 1.01 (n = 11, p = .0015)). Patients with early post-operative complications (defined as length of stay > 6 days or re-hospitalization within 1 month following surgery) had an average BMI of 57.58 (n = 23) vs a BMI of 49.9 (n = 103) in those who did not experience any complications (p = 0.0004). There was a statistically significant decrease in the rate of anti-depressant use following surgery. 49 patients were on antidepressants before surgery vs 38 following surgery (p = .0016). RYGBP significantly improves hypertension, hyperlipidemia and type II diabetes, and may also improve kidney function. Patients with higher pre-surgical BMIs are at greater risk for post-surgical complications. Postoperative antidepressant use appears to decrease.