Variability in leptin and adrenal response in juvenile Steller sea lions (Eumetopias jubatus) to adrenocorticotropic hormone (ACTH) in different seasons.
Eight free-ranging juvenile Steller sea lions (SSL; 6 males, 2 females; 14-20 months) temporarily held under ambient conditions at the Alaska SeaLife Center were physiologically challenged through exogenous administration of adrenocorticotropic hormone (ACTH). Four individuals (3 males, 1 female) underwent ACTH challenge in each of two seasons, summer and winter. Following ACTH injection serial blood and fecal samples were collected for up to 3 and 96 h, respectively. A radioimmunoassay (RIA) was validated for leptin, and using a previously validated RIA for cortisol, collected sera were analyzed for both cortisol and leptin. ACTH injection resulted in a 2.9-fold increase (P=0.164) in leptin which preceded a 3.2-fold increase (P=0.0290) in cortisol by 105 min in summer. In winter, a 1.7-fold increase in leptin (P=0.020) preceded a 2.1-fold increase (P=0.001) in serum cortisol by 45 min. Mean fecal corticosteroid maxima were 10.4 and 16.7-fold above baseline 28 and 12 h post-injection and returned to baseline 52 and 32 h post-injection, in summer and winter, respectively. Data indicate acute activity in juvenile adrenal glands is detectable in feces approximately 12-24 h post-stimulus in either season, with a duration of approximately 40 h in summer and 20 h in winter. Changes in serum cortisol proved statistically significant both seasons and elevated concentrations were detected by 30 min post-stimulus (baseline 64.8+/-4.2; peak 209.5+/-18.3 ng/ml: summer; baseline 87.0+/-15.7; peak 237.6+/-10.0 ng/ml: winter), whereas the changes that occurred in serum leptin proved to be significant only in winter (baseline 6.4+/-0.6; peak 18.7+/-7.0 ng/ml: summer; baseline 4.2+/-0.5; peak 7.5+/-0.6 ng/ml: winter). Changes in fecal corticosteroids proved significant only in summer (baseline 117.8+/-36.7; peak 1219.3+/-298.4 ng/g, P=0.038: summer; baseline 71.8+/-13.7; peak 1198.6+/-369.9 ng/g, P=0.053: winter) due to a high degree of individual variability in winter months. The data indicate that ACTH stimulates leptin production earlier than cortisol in both summer and winter, and that while the leptin response appears most variable in summer, fecal corticosteroids are most variable in winter.


Prediction of amphipathic helix-membrane interactions with Rosetta.
Amphipathic helices have hydrophobic and hydrophilic/charged residues situated on opposite faces of the helix. They can anchor peripheral membrane proteins to the membrane, be attached to integral membrane proteins, or exist as independent peptides. Despite the widespread presence of membrane-interacting amphipathic helices, there is no computational tool within Rosetta to model their interactions with membranes. In order to address this need, we developed the AmphiScan protocol with PyRosetta, which runs a grid search to find the most favorable position of an amphipathic helix with respect to the membrane. The performance of the algorithm was tested in benchmarks with the RosettaMembrane, ref2015_memb, and franklin2019 score functions on six engineered and 44 naturally-occurring amphipathic helices using membrane coordinates from the OPM and PDBTM databases, OREMPRO server, and MD simulations for comparison. The AmphiScan protocol predicted the coordinates of amphipathic helices within less than 3Å of the reference structures and identified membrane-embedded residues with a Matthews Correlation Constant (MCC) of up to 0.57. Overall, AmphiScan stands as fast, accurate, and highly-customizable protocol that can be pipelined with other Rosetta and Python applications.


Dropouts from nursing education: path analysis of a national sample.
Path analysis was used to test a theoretical model of college nursing student dropouts. Multiple regression was used to assess the relative importance of the predictor variables. Students' self-reported reasons for dropping out were studied by contingency and correlational analyses to determine the relationship between these reasons and individual difference variables. Factor analysis was used to develop scales to measure the variables of locus of control, self-esteem, social integration, and institutional commitment. The sample of students was drawn from the National Longitudinal Study of the High School Class of 1972. Included in the sample were students entering two- and four-year nursing programs full-time in the fall of 1972. These two groups of students were found to be significantly different in measures of cognitive ability and in aspirations for further education. Approximately 27 percent of the two-year and 41 percent of the four-year students withdrew from their nursing programs during this study. Reasons for withdrawal most frequently cited by both groups related to losing interest in nursing and becoming interested in other fields of study. Educational aspirations had the strongest direct effect on persistence in nursing for two-year students; for four-year students, academic ability was the most powerful predictor of persistence.


Expression of the axon guidance factor Slit2 and its receptor Robo1 in patients with Hirschsprung disease: An observational study.
Hirschsprung disease (HD) is a common form of digestive tract malformation in children. However, the pathogenesis of HD is not very clear. This study aimed to investigate the expression of slit guidance ligand 2 (Slit2) and roundabout 1 (Robo1) in patients with HD.From January 2018 to January 2019, 30 colon specimens from children with HD undergoing surgical resection at the Department of Surgery in Qilu Children's Hospital of Shandong University were obtained. These specimens were divided into the normal segment group, the transitional segment group and the spastic segment group. Immunohistochemical staining, Western blotting, and real-time polymerase chain reaction were used to measure the expression of Slit2 and Robo1 in the intestinal walls of normal, transitional, and spastic segments.Immunohistochemical staining and Western blot analyses showed high levels of the Slit2 and Robo1 proteins in normal ganglion cells in children with HD, lower levels in transitional ganglion cells, and no expression in spastic segments, with significant differences between groups (P < .05). Similarly, the real-time polymerase chain reaction results were consistent with the Western blot analysis results.The expression of Slit2 and Robo1 decreases significantly in the spastic segment of the intestinal tract in patients with HD.


Fifth toe deformities: overlapping and underlapping toe.
Overlapping fifth toe is thought to be a congenital deformity characterized by the proximal phalanx dorsally subluxating and adducting on the fifth metatarsophalangeal joint. Overlapping fifth toes may present as asymptomatic figments of parental concern, but not infrequently this deformity may be painful and disabling in both the pediatric and adult population. Pediatric overlapping fifth toe often corrects with normal ambulation and physicians only need to intervene if symptomatic deformity persists. Nonoperative optimization with strapping, splinting, and shoe modification would be reasonable first-line treatments. Surgical intervention including osteoclysis, percutaneous tenotomy, capsulotomy, syndacilization, tissue rearrangements, tendon transfers, phalangectomy, and toe amputation are indicated only after optimization of less invasive measures. Underlapping fifth toe (or "curly" toe) deformity is also felt to be congenital. In most cases, underlapping fifth toes are noticed by parents and family members early in infancy. The proximal phalanx in underlapping toes is typically in varus at the metatarsophalangeal joint with flexion. It is not uncommon for a rotational malalignment to be present (supination/pronation) as judged by the nailbeds. Similar to overlapping toes, pediatric underlappers commonly correct with reassurance and benign neglect up to age 6. Intervention is warranted in the setting of persistent pain and footwear difficulty. Accommodative shoes, absorbing cushions, and functional modification are the mainstays of nonoperative management. Operative intervention may consist of osteoclysis, percutaneous flexor tenotomy, capsulotomy, tissue rearrangements, tendon transfers, removal of symptomatic spurs, osteotomies, and amputation. After exhaustive review of the published literature, it is clear that fifth toe deformities (whether overlapping or underlapping) have not been extensively studied. No gold standard approach exists in treatment. Prospective research using larger numbers of patients with detailed outcome metrics are needed. Surgeons should carefully tailor surgical intervention to patient specific pathology. Expert Opinion, Level V.


Surgical treatment of pancreatic carcinoma.
We reviewed 75 patients operated on for carcinoma of the pancreas during the period 1973 to 1978. The role of surgery was examined in terms of contributing toward diagnosis, palliation, and cure. Computerized tomography, ultrasonography, upper gastrointestinal series, and arteriography were used to determine the presence or absence of a pancreatic mass. Arteriography and CT scanning were very helpful. Histologic confirmation was most often provided in conjunction with celiotomy. Endoscopy with cytology and percutaneous needle biopsy was quite specific but was rarely done. Palliative decompression of the biliary tree was done in 63% and biopsy alone in 21%, with a collective morbidity of 20% and a mortality of 3%. Potentially curative resection was done in only 8% with no immediate postoperative deaths. Although pancreaticoduodenectomy will continue to offer the only chance of cure in small numbers of patients, it is evident the present role of surgery is largely for diagnosis and palliation. In view of the mortality and morbidity of operation, increased emphasis should be placed on noninvasive diagnostic tests (CT scan, endoscopy with cytology, and direct needle biopsy). The future role of surgical reduction of the tumor mass in conjunction with adjuvant therapy is at present ill defined.


Acute oesophageal symptoms.
Acute oesophageal symptoms include acute dysphagia or food bolus impaction (most commonly due to strictures, Schatzki ring and eosinophilic oesophagitis), acute chest pain with odynophagia due to oesophageal infections, motility disorders and acute oesophageal rupture (of which oesophageal intramural haematoma is a subtype). Acute full thickness oesophageal rupture carries a high mortality if not recognised early; the clinical features and conditions with which this may be confused are presented and discussed.


Semiclassical ordering in the large-N pyrochlore antiferromagnet.
We study the semiclassical limit of the Sp(N) generalization of the pyrochlore lattice Heisenberg antiferromagnet by expanding about the N --> infinity saddlepoint in powers of a generalized inverse spin. To leading order, we write down an effective Hamiltonian as a series in loops on the lattice. Using this as a formula for calculating the energy of any classical ground state, we perform Monte Carlo simulations and find a unique collinear ground state. This state is not a ground state of linear spin-wave theory, and can therefore not be a physical (N = 1) semiclassical ground state.


Osteonecrosis of the Jaws (ONJ) after Bisphosphonate Treatment in Patients with Multiple Myeloma: Decreasing ONJ Incidence after Adoption of Preventive Measures.
Bisphosphonates (BPs) are administered to Multiple Myeloma (MM) patients with bone lytic lesion. Osteonecrosis of the Jaw (ONJ) is a complication reported since 2003 in patients treated with intravenous (IV) BPs such as zoledronic acid and pamidronate, with 6%-26.3% frequency in early literature series, before some preventive measures were recommended. We evaluated the occurrence of ONJ with and without dental preventive measures in MM patients treated with BPs in our centre between 1996 and 2015. Since 2005, MM patients (already under treatment or before treatment) underwent a baseline mouth assessment (dental visit, Rx orthopantomography, and eventual tooth avulsion or dental care if necessary) and were followed by a multidisciplinary team. We reviewed the charts of 119 MM patients receiving IV BPs, classified into 3 groups: (a) "historic group" (21 patients who had started BP treatment in years before the awareness of ONJ); (b) "screening group" (20 patients starting BPs without baseline evaluation); and (c) "prevention group" (78 patients starting therapy only after baseline preventive assessment and eventual dental care measures). ONJ was observed in 3/21 patients (14.2%) from group a, in 2/20 patients (10%) from group b, and in no patients from group c (0%). Notably, the median number of IV BP administrations decreased after 2005. Our data confirmed a meaningful reduction of ONJ risk in MM patients treated with BPs if preventive measures are applied. Both implementation of prevention measures and reduction of cumulative doses of IV BPs could have contributed to a decreased incidence of ONJ.


Soluble CD14 and toll-like receptor-2 are potential salivary biomarkers for oral lichen planus and burning mouth syndrome.
Oral lichen planus (OLP) and burning mouth syndrome (BMS) are chronic conditions affecting the oral mucosa characterized by pain and burning sensation. Saliva plays a significant role in the maintenance of physical and functional integrity of normal oral mucosa. Identification of potential "salivary biomarkers" for early diagnosis and/or monitoring of human diseases is being explored. We investigated the soluble forms of innate immune associated proteins CD14 and toll-like receptor-2 in unstimulated whole saliva (UWS) as potential biomarkers for OLP and BMS. Our results suggest that the levels of sCD14 and sTLR-2 in UWS were upregulated in OLP and BMS respectively. In addition, oral epithelial cells in the saliva of patients with OLP and BMS exhibited elevated levels of CD14 mRNA and decreased levels of TLR-2 mRNA. Interestingly, presence of co-existent oral candidiasis nullified these changes.


The Assessment and Potential Implications of the Myocardial Performance Index Post Exercise in an at Risk Population.
The myocardial performance index (MPI) first described by Chuwa Tei in 1995 is a relatively new echocardiographic variable used for assessment of overall cardiac function. Previous studies have demonstrated the MPI to be a sum representation of both left ventricular systolic and diastolic function with prognostic value in patients with coronary artery disease as well as symptomatic heart failure. Ninety patients with either established coronary artery disease (CAD) or CAD risk factors underwent routine treadmill exercise stress testing with two-dimensional Doppler echocardiography using the standard Bruce protocol. Both resting and stress MPI values were measured for all 90 of the patients. Using a normal MPI cut off of ≤ 0.47, the prevalence of an abnormal resting MPI in our 90 subjects was 72/90 or 80% and the prevalence of an abnormal stress MPI in our 90 subjects was 48/90 or 53.33%. The average MPI observed in the resting portion of the stress test for the cohort was: 0.636 with a standard deviation of 0.182. The average MPI in the stress portion of the stress test for the cohort was 0.530 with a standard deviation of 0.250. The P value with the use of a one-tailed dependent T test was calculated to be < 0.05. We postulate that these findings reflect that the MPI (Tei) index assessed during exercise may be a sensitive indicator of occult coronary disease in an at risk group independent of wall motion assessment.


Discrimination and Health Among Taxi Drivers in New York and Toronto.
Immigrant taxi drivers in metropolitan cities are exposed to experiences of discrimination and occupation-based health risks. Given the structural differences in health care systems in the United States and Canada, we investigated the differences in reports of discrimination, health conditions and concern about health conditions between taxi drivers in New York City and Toronto, Ontario. Participants were recruited for a taxi driver Needs Assessment Survey as part of a Taxi Network needs assessment project using a street side convenience sampling technique in New York City and Toronto. The matched sample contained 33 drivers from Toronto and 33 drivers from NYC. All Toronto drivers in our sample reported having health insurance while over a quarter of NYC drivers did not have health insurance. Toronto drivers reported greater everyday and workplace discrimination. Drivers in both cities experienced higher rates than average, and reported concern about, major health conditions. We also found preliminary evidence suggesting a relationship between experiencing discrimination and reporting chronic pain. Our findings suggest the need for future research to more closely examine the associations between discrimination and health among the taxi driver population.


Lungeing on hard and soft surfaces: Movement symmetry of trotting horses considered sound by their owners.
Lungeing is often part of the clinical lameness examination. The difference in movement symmetry, which is a commonly employed lameness measure, has not been quantified between surfaces. To compare head and pelvic movement symmetry between surfaces and reins during lungeing. Quantitative gait analysis in 23 horses considered sound by their owners. Twenty-three horses were assessed in-hand and on the lunge on both reins on hard and soft surfaces with inertial sensors. Seven movement symmetry parameters were quantified and used to establish 2 groups, namely symmetrical (n = 9) and forelimb-lame horses (n = 14), based on values from straight-line assessment. Movement symmetry values for left rein measurements were side corrected to allow comparison of the amount of movement symmetry between reins. A mixed model (P<0.05) was used to study effects on movement symmetry of surface (hard/soft) and rein (inside/outside with respect to movement symmetry on the straight). In forelimb-lame horses, surface and rein were identified as significantly affecting all head movement symmetry measures (rein, all P<0.0001; surface, all P<0.042). In the symmetrical group, no significant influence of surface or rein was identified for head movement symmetry (rein, all P>0.245; surface, all P>0.073). No significant influence of surface or rein was identified for any of the pelvic movement symmetry measures in either group. While more symmetrical horses showed a consistent amount of movement symmetry across surfaces/reins, horses objectively quantified as lame on the straight showed decreased movement symmetry during lungeing, in particular with the lame limb on the inside of a hard circle. The variation within group questions straight-line movement symmetry as a sole measure of lameness without quantification of movement symmetry on the lunge, ideally on hard and soft surfaces to evaluate differences between reins and surfaces. In future, thresholds for lungeing need to be determined using simultaneous visual and objective assessment.


Prostate disease in older men: 1. Benign hyperplasia.
Medical therapy with alpha 1-adrenergic blockers or 5 alpha-reductase inhibitors offers an alternative to the traditional choices of watchful waiting and surgery. Patients with obstructive symptoms and a small prostate appear to respond to treatment with an alpha 1-adrenergic blocker, while a 5 alpha-reductase inhibitor may be the preferred agent for a large gland.


Scapular muscle dysfunction associated with subacromial pain syndrome.
Narrative Review. One of the shoulder pain disorders in which the function of the scapula is comprised is the subacromial pain syndrome. Several rehabilitation guidelines and exercises have been proposed to improve scapulothoracic muscle dysfunction. Consideration of muscle activation patterns may help to select the most appropriate rehabilitation exercise in these patients. To date, suggesting rehabilitation exercises is often based upon the knowledge of the superficial lying scapulothoracic muscles' activity. In the assumption that the deeper lying scapulothoracic muscles' activity may hinder normal scapular movement in case of tightness or hyperactivity, exercise protocols for patients with altered pattern in scapulothoracic muscles should also integrate knowledge on the deeper lying scapulothoracic muscle activity. To help clinicians choosing the most appropriate exercise in patients with subacromial pain syndrome related to scapulothoracic muscle dysfunction. First, a summary of key alterations in scapulothoracic (muscle) function in patients with subacromial pain was accomplished. Second, promising practical rehabilitation strategies toward restoring scapulothoracic muscle dysfunction (with a focus on scapulothoracic exercises) were developed, integrating current new research evidence (including information about the deeper lying scapulothoracic muscles) with clinical practice. This review details clinical exercises and their muscular activity to guide clinicians to optimize individualized scapulothoracic training and treatment programs by selecting the most appropriate exercise, based on knowledge from the clinical examination. Level 5.


Treatment of Chordomas and Chondrosarcomas With CyberKnife Robotic Hypofractionated Radiosurgery: A Single Institution Experience.
Introduction The aim of this study is to determine the efficacy and safety of CyberKnife® (Accuray, Inc., Sunnyvale, CA) hypofractionated radiosurgery (HfRS) in the treatment of chordomas and chondrosarcomas. Methods A total of 24 patients retrospectively identified with chordomas (19 patients) or chondrosarcomas (five patients) were treated between 2012 and 2019 with HfRS as monotherapy or an adjuvant, rescue, or combination therapy. Tumors were located in the skull base (75%) and vertebral spine (25%). Of these, 19 patients underwent previous partial resection and four patients received previous conventional external beam radiation therapy (EBRT) (60-74 Gy). Exclusive or rescue HfRS (20 patients) was administered in five fractions with a median dose of 37.5 Gy (30-40 Gy). Combined tomotherapy-EBRT treatment (median dose: 54 Gy) and HfRS (16.5-30 Gy in 3-12 fractions) were performed in four patients with bulky chordomas. Results The median follow-up from HfRS was 28 months. During clinical follow-up, no deaths were registered with overall survival (OS) of 100% and the actuarial local recurrence-free survival (LRFS) was 93% at one year, 85% at three years, and 68% at five years. Acute toxicity related to HfRS was present in a single patient. Conclusions It is seen that HfRS is effective and safe for chordomas and chondrosarcomas, with rates of LRFS comparable to other radiation modalities.


Circulating unmetabolized folic acid and 5-methyltetrahydrofolate in relation to anemia, macrocytosis, and cognitive test performance in American seniors.
Folate deficiency has serious consequences for the fetus. Folic acid fortification of food addresses this problem. However, clinical consequences of vitamin B-12 deficiency may be worsened by high folic acid intakes, perhaps as a direct result of unmetabolized folic acid, which does not occur naturally in body tissues. We attempted to attribute associations that we previously found between higher folate status and anemia and cognitive test performance to circulating unmetabolized folic acid or 5-methyltetrahydrofolate (5MeTHF). The subjects (n = 1858) were senior participants in the US National Health and Nutrition Examination Survey (1999-2002) who had normal renal function and reported no history of stroke, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries. Subjects had undergone a phlebotomy, a complete blood count, and cognitive and dietary assessments. Circulating unmetabolized folic acid was detected in approximately 33% of the subjects and was related to an increased odds of anemia in alcohol users. In seniors with a serum vitamin B-12 concentration <148 pmol/L or a plasma methylmalonic acid concentration > or =210 nmol/L, the presence compared with the absence of detectable circulating unmetabolized folic acid was related to lower cognitive test scores and lower mean cell volume. In the same subgroup, higher serum 5MeTHF was related to an increased odds of anemia and a marginally significantly decreased odds of macrocytosis. In seniors with a normal vitamin B-12 status, a higher serum 5MeTHF concentration was related to higher cognitive test scores. Results of this epidemiologic study were somewhat consistent with reports on the folic acid treatment of patients with pernicious anemia, but some findings were unexpected.


Temporal constraints in the use of auditory action effects for motor optimization.
For quick ballistic movements the possibility of making online adjustments is limited. However, when the same action (e.g., pressing a button) is repeated multiple times, trial-by-trial adjustments are possible: Previous studies found that participants utilized auditory effects as feedback to optimize the applied force for such tone eliciting actions. In the current study, it was examined whether this action-effect-related motor adaptation also occurred if a delay was inserted between the action and its auditory effect. In 2 experiments, participants applied force impulses to a force-sensitive resistor in a self-paced schedule. Action-effect delay was manipulated between experimental blocks in the 0- to 1,600-ms range. The level of motor adaptation diminished as a function of action-effect delay, with no adaptation observable for delays longer than 200 ms, which indicates that action-effect contingency in itself is not sufficient to warrant that sensory effects will be useful for action control. A third experiment also showed that the observed temporal constraint was not absolute: Adaptation at 200-ms delay was stronger in a group of participants who were exposed to 400-ms action-tone delays before testing, than in a group exposed to a 0-ms action-tone delay, suggesting that action-effect-related motor adaptation is influenced by prior experience. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Phosphatidylinositol (4,5)-bisphosphate dynamically regulates the K2P background K+ channel TASK-2.
Two-pore domain K2P K+ channels responsible for the background K+ conductance and the resting membrane potential, are also finely regulated by a variety of chemical, physical and physiological stimuli. Hormones and transmitters acting through Gq protein-coupled receptors (GqPCRs) modulate the activity of various K2P channels but the signalling involved has remained elusive, in particular whether dynamic regulation by membrane PI(4,5)P2, common among other classes of K+ channels, affects K2P channels is controversial. Here we show that K2P K+ channel TASK-2 requires PI(4,5)P2 for activity, a dependence that accounts for its run down in the absence of intracellular ATP and its full recovery by addition of exogenous PI(4,5)P2, its inhibition by low concentrations of polycation PI scavengers, and inhibition by PI(4,5)P2 depletion from the membrane. Comprehensive mutagenesis suggests that PI(4,5)P2 interaction with TASK-2 takes place at C-terminus where three basic aminoacids are identified as being part of a putative binding site.


Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels.
Several studies indicate that mitochondrial ATP production as well as ADP/ATP exchange across mitochondrial membranes are impaired during apoptosis. We investigated whether Bcl-2 could protect against cell death under conditions in which ATP metabolism is inhibited. Inhibition of ATP production using antimycin A (AA) (complex III inhibition) combined with inhibition of ADP/ATP exchange by bongkrekic acid (BA) (adenine nucleotide translocator (ANT) inhibition) induced a sharp decrease in total cellular ATP in FL5.12 parental cells (to 35% of untreated controls after 24 h of incubation). Within 24 and 48 h, 38% and 75% of the cells had died, respectively. However, in stably transfected FL5.12 Bcl-2 subclones, no cell death occurred under these experimental conditions. Similar results were obtained with Jurkat and Bcl-2 overexpressing Jurkat cells. Total cellular ATP levels were equally affected in FL5.12 Bcl-2 overexpressing cells and FL5.12 parental cells. This indicates that Bcl-2 overexpressing cells are able to survive with very low cellular ATP content. Furthermore, Bcl-2 did not protect against cell death by restoring ATP levels. This suggests that, under these conditions, Bcl-2 acts by inhibiting the signalling cascade triggered by the inhibitors that would normally lead to apoptosis.


Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.
This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.


The Whiplash Disease Reconsidered.
The natural course of the whiplash disease is reconsidered in relation to the predominant view of its cause. It is assumed that a whiplash-type trauma is causing an acute tissue injury such as a distortion or sprain in the neck followed by neck pain and headache, which then tends to become a chronic pain condition. We conclude that the whiplash disease typically evolves following a minor trauma without any signs of a tissue injury. It presents with central neuromotor dysfunction, such as electromyography (EMG) hyperactivity and abnormal activation patterns associated with dyscoordination of the involved and adjacent muscle groups. This indicates a central neurological rather than a peripheral traumatic pathology. This view places the cause of the whiplash disease within the central nervous system, and, in concordance with the EMG abnormalities and motor dyscoordination, we suggest the term cervical spinal dyssynergia for this pathology. It provides a new paradigm for further investigations of this disease as well as a window for possible specific neuropharmacological therapy directed towards dysfunctional neuromotor control.


Effects of laparoscopic cholecystectomy on lung function: a systematic review.
To present and integrate findings of studies investigating the effects of laparoscopic cholecystectomy on various aspects of lung function. We extensively reviewed literature of the past 24 years concerning the effects of laparoscopic cholecystectomy in comparison to the open procedure on many aspects of lung function including spirometric values, arterial blood gases, respiratory muscle performance and aspects of breathing control, by critically analyzing physiopathologic interpretations and clinically important conclusions. A total of thirty-four articles were used to extract information for the meta-analysis concerning the impact of the laparoscopic procedure on lung function and respiratory physiopathology. The quality of the literature reviewed was evaluated by the number of their citations and the total impact factor of the corresponding journals. A fixed and random effect meta-analysis was used to estimate the pooled standardized mean difference of studied parameters for laparoscopic (LC) and open (OC) procedures. A crude comparison of the two methods using all available information was performed testing the postoperative values expressed as percentages of the preoperative ones using the Mann-Whitney two-sample test. Most of the relevant studies have investigated and compared changes in spirometric parameters.The median percentage and interquartile range (IQR) of preoperative values in forced vital capacity (FVC), forced expiratory volume in 1 s and forced expiratory flow (FEF) at 25%-75% of FVC (FEF25%-75%) expressed as percentage of their preoperative values 24 h after LC and OC were respectively as follows: [77.6 (73.0, 80.0) L vs 55.4 (50.0, 64.0) L, P < 0.001; 76.0 (72.3, 81.0) L vs 52.5 (50.0, 56.7) L, P < 0.001; and 78.8 (68.8, 80.9) L/s vs 60.0 (36.1, 66.1) L/s, P = 0.005]. Concerning arterial blood gases, partial pressure of oxygen [PaO2 (kPa)] at 24 or 48 h after surgical treatment showed reductions that were significantly greater in OC compared with LC [LC median 1.0, IQR (0.6, 1.3); OC median 2.4, IQR (1.2, 2.6), P = 0.019]. Fewer studies have investigated the effect of LC on respiratory muscle performance showing less impact of this surgical method on maximal respiratory pressures (P < 0.01); and changes in the control of breathing after LC evidenced by increase in mean inspiratory impedance (P < 0.001) and minimal reduction of duty cycle (P = 0.01) compared with preoperative data. Laparoscopic cholecystectomy seems to be associated with less postoperative derangement of lung function compared to the open procedure.


Transcription of intragenic CpG islands influences spatiotemporal host gene pre-mRNA processing.
Alternative splicing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during development and differentiation. Epigenetic marks such as trimethylation of histone H3 lysine 36 (H3K36me3) and DNA methylation play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes exhibit dynamic epigenetic and gene expression patterns during development and between different tissues. We hypothesise that iCGI-associated H3K36me3, DNA methylation and transcription can influence host gene AS and/or APA. We investigate H3K36me3 and find that this histone mark is not a major regulator of AS or APA in our model system. Genomewide, we identify over 4000 host genes that harbour an iCGI in the mammalian genome, including both previously annotated and novel iCGI/host gene pairs. The transcriptional activity of these iCGIs is tissue- and developmental stage-specific and, for the first time, we demonstrate that the premature termination of host gene transcripts upstream of iCGIs is closely correlated with the level of iCGI transcription in a DNA-methylation independent manner. These studies suggest that iCGI transcription, rather than H3K36me3 or DNA methylation, interfere with host gene transcription and pre-mRNA processing genomewide and contributes to the spatiotemporal diversification of both the transcriptome and proteome.


Prejunctional alpha 2-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries.
To study the influence of alpha-adrenergic stimuli on non-adrenergic non-cholinergic (NANC) neurogenic relaxation in isolated horse penile resistance arteries. Deep intracavernous penile arteries with an internal lumen diameter of 200-500 microns., isolated from the corpus cavernosum of young horses, were mounted in microvascular myographs for isometric tension recording and electrical field stimulation (EFS) of autonomic nerve terminals. In the presence of guanethidine (10(-5) M) and atropine (10(-7) M) tone of the arteries was raised by the thromboxane analogue, U46619. EFS (1, 4 and 32 Hz) induced frequency-dependent relaxations, which were abolished in the presence of tetrodotoxin, while NG-nitro-L-arginine (L-NOARG, 10(-4) M) abolished the relaxations to EFS at 1 Hz, and significantly reduced the relaxations at 4 Hz and 32 Hz by 82.5 +/- 10.2% and 52.9 +/- 4.7%, respectively (n = 6). EFS induced relaxations of a similar magnitude in penile arteries contracted with U46619 or the alpha 1-adrenoceptor agonist, phenylephrine, while the alpha 2-adrenoceptor agonist, BHT920 (10(-6) M), produced an inhibitory effect on the EFS-evoked relaxations which was inversely related to the stimulus frequency (1, 4 and 32 Hz). BHT920 had no effect on the relaxations induced by exogenous nitric oxide (NO), added as acidified sodium nitrite (10(-6)-10(-3) M). The inhibitory effect of BHT920 on NANC relaxations was reversed by 10(-7) M rauwolscine. These results suggest that the release of a NANC neurotransmitter primarily thought to be NO is inhibited by stimulation of prejunctional alpha 2-adrenoceptors in horse penile resistance arteries.


Contribution of catechol-O-methyltransferase Val158Met polymorphism to endometrial cancer risk in postmenopausal women: a meta-analysis.
Catechol-O-methyltransferase (COMT) is a critical enzyme to detoxify the carcinogenic catechol estrogen and the Val158Met polymorphism of COMT could influence its enzymatic activity. Recent epidemiological studies have investigated the correlation of COMT Val158Met polymorphism with endometrial cancer risk; however, the results are inconsistent. To better evaluate the role of COMT Val158Met in endometrial carcinogenesis, we performed this meta-analysis, considering menopausal status, study quality, ethnicity, and source of controls. Eight eligible studies including 5109 subjects were collected from PubMed, CNKI, and Chinese Biomedicine Database (updated until September 21, 2012). Although no obvious associations were detected between COMT Val158Met and endometrial cancer susceptibility in the pooled analysis, we noted significantly decreased endometrial cancer risk for Val/Met versus Val/Val, and Met/Met + Val/Met versus Val/Val genetic models in the postmenopausal female (OR = 0.795, 95%CI = 0.656-0.962, P = 0.019; and OR = 0.819, 95%CI = 0.683-0.983, P = 0.032; respectively), and similar results existed in high-quality studies (OR = 0.835, 95%CI = 0.726-0.961, P = 0.012; and OR = 0.853, 95%CI = 0.747-0.974, P = 0.019; respectively). However, no evidence of association was noted in different ethnic groups and sources of controls. In conclusion, our results suggested that the COMT Val/Val genotype might act as a potential endometrial cancer risk factor in postmenopausal women. Further studies are needed to investigate the interactions between COMT Val158Met polymorphism and endometrial cancer in a specific population.


Computed tomography of testicular feminization.
Testicular feminization is a rare genetic disease characterized by an XY karyotype, bilateral functional testes, female external genitalia, blind vagina, and absence of müllerian derivatives. The presurgical localization of the testes is critical and is particularly well suited to the cross-sectional imaging capability of CT.


Dermal Collagen Stabilization by Polyphenols and Spray Drying as an Encapsulation Strategy.
Collagen, the most abundant component in mammalian tissues, has a crucial impact at skin level. Both promotion and maintenance of cross-linked collagen at the skin are critical to sustain the functionality and appearance of that tissue. Lysyl oxidases, also known as LOX enzymes, are the major collagen cross-linking enzymes that play a pivotal role in homeostasis. This minireview summarizes evidence that describes an amino oxidase-like activity, which could be attributed to polyphenols, or where polyphenols could be required. We also discuss some available collagen formulations and the scientific evidence that describes the impact on dermal extracellular matrix. In addition, information about encapsulation strategies to carry polyphenols, and some examples are also provided.


Electrical properties and synaptic connections to neurons in parasympathetic colonic ganglia of the cat.
Intracellular recording techniques were used in vitro to analyze the electrophysiological properties and synaptic connections to cat parasympathetic neurons in ganglia located on the serosal surface of the distal colon. Neurons were classified into two types. The first type exhibited spontaneous action potentials at regular and irregular interspike intervals. Spontaneous action potentials were 1) not abolished by superfusion of the ganglia with a modified Krebs solution containing low Ca2+, high Mg2+, or nicotinic ganglionic blocking agents, 2) reduced or abolished by intracellular injection of hyperpolarizing current, and 3) increased by intracellular injection of depolarizing current. We suggest that the generation of spontaneous action potentials may be due to an endogenous depolarizing mechanism and not to cholinergic synaptic input from other neurons located in the ganglia. The second type of neuron termed "quiescent" exhibited a stable transmembrane potential and elicited action potentials in response to electrical stimulation of nerve trunks. Both quiescent and spontaneously discharging neurons receive synaptic input from preganglionic fibers in the pelvic nerve and project their postganglionic axons to colonic nerve fibers that innervate effector structures in the colon.


Altered growth, pigmentation, and antimicrobial susceptibility properties of Staphylococcus aureus due to loss of the major cold shock gene cspB.
An insertional mutation made in the major cold shock gene cspB in Staphylococcus aureus strain COL, a methicillin-resistant clinical isolate, yielded a mutant that displayed a reduced capacity to respond to cold shock and many phenotypic characteristics of S. aureus small-colony variants: a growth defect at 37 degrees C, a reduction in pigmentation, and altered levels of susceptibility to many antimicrobials. In particular, a cspB null mutant displayed increased resistance to aminoglycosides, trimethoprim-sulfamethoxazole, and paraquat and increased susceptibility to daptomycin, teicoplanin, and methicillin. With the exception of the increased susceptibility to methicillin, which was due to a complete loss of the type I staphylococcal cassette chromosome mec element, these properties were restored to wild-type levels by complementation when cspB was expressed in trans. Taken together, our results link a stress response protein (CspB) of S. aureus to important phenotypic properties that include resistance to certain antimicrobials.


The action of Pseudomonas aeruginosa biofilms in intrinsic drug resistance.
There is a growing interest in studying the relationship between intrinsic resistance and biofilms resistance to drugs. However, the relationship still remains unclear in the macroscopic bacterial growth. Our study is to illuminate the change of bacterial drug resistance of gyrA mutant and active efflux pump during the development of Pseudomonas aeruginosa (P. aeruginosa) biofilms. The strains of type II topoisomerase gene mutant (gyrA mutant) and multidrug resistance (MDR) efflux pump were clinical isolates and detected by polymerase chain reaction (PCR). The process of bacterial biofilms development was observed by scanning electron microscope. Triparental mating experiments were performed to transfer report gene of green fluorescent protein (GFP) into P. aeruginosa biofilms strains and followed by analysis of bacterial survival rate between intrinsic resistance and biofilms resistance. The fluorescent strains with pGFPuv could develop mature biofilms on Teflon surface. Before a period of 72 hours, the survival rate of biofilms bacteria and intrinsic resistance strains in ciprofloxacin solution was significantly different (P < 0.05). The survival number of intrinsic resistance strains (gyrA mutation and active efflux pump) was illustriously higher than biofilm strain in the initial stage of biofilms development. After 72 hours incubation, there was no clearly difference between mutants and biofilms strains in the survival rate (P > 0.05). The carbonyl cyanide m-chlorophenylhydrazone and azithromycin could significantly reduce the drug resistance of biofilm strains and efflux pump strains. In the development of P. aeruginosa biofilms, the strains of gyrA mutation and MDR efflux could be conferred with new level of drug resistance. When co-cultured mutated strains with biofilm strains, biofilms may play a major role in bacterial resistance. But after 72 hours incubation (a mature biofilms had been developed), there was no clearly difference between the number of mutant strains and biofilm strains.


Concepts, electrode configuration, characterization, and data analytics of electric and electrochemical microfluidic platforms: a review.
Microfluidic cytometry (MC) and electrical impedance spectroscopy (EIS) are two important techniques in biomedical engineering. Microfluidic cytometry has been utilized in various fields such as stem cell differentiation and cancer metastasis studies, and provides a simple, label-free, real-time method for characterizing and monitoring cellular fates. The impedance microdevice, including impedance flow cytometry (IFC) and electrical impedance spectroscopy (EIS), is integrated into MC systems. IFC measures the impedance of individual cells as they flow through a microfluidic device, while EIS measures impedance changes during binding events on electrode regions. There have been significant efforts to improve and optimize these devices for both basic research and clinical applications, based on the concepts, electrode configurations, and cell fates. This review outlines the theoretical concepts, electrode engineering, and data analytics of these devices, and highlights future directions for development.


Role of BMI and hormone therapy in melanoma risk: a case-control study.
Currently, the association between body mass index (BMI) and hormone therapies and Cutaneous Melanoma (CM) development is strongly debated. This study was carried out to assess the association between BMI, hormone therapies, and CM risk. The present study is a hospital-based case-control study with 605 consecutive CM patients and 592 controls treated for non-neoplastic conditions at the Department of Dermatology in Florence. The associations of melanoma risk with BMI and hormone therapies were assessed performing unconditional logistic regression to estimate odds ratios (OR) and their 95% confidence intervals, adjusting for potential confounders. We found a significant interaction of BMI with age (P < 0.0001): being overweight significantly increased CM risk among individuals less than 50 years old (OR = 1.85 with 95% CI 1.14-2.94), whereas the association was not significant for individuals over 50 years old (OR = 1.15 with 95% CI 0.77-1.71). For oestrogen therapy, women taking oral contraceptives (OCs)/hormone replacement therapy (HRT) showed a lower CM risk than men (OR = 0.63, 95% CI 0.44-0.89), with risk estimates significantly lower (P < 0.0001) than in non OCs/HRT users, which had an increased risk compared to men (OR = 1.81, 95% CI 1.29-2.53). Being overweight was significantly associated with CM risk, and this relationship was highly age-conditioned; the second finding was the protective effect of oestrogen therapies for women. Both findings may have a significant impact on melanoma prevention, as the prevalence of obesity and hormone therapy use is increasing worldwide.


[Possibilities and limitations of minimally invasive methods in thoracic surgery].
First experiences with minimal invasive thoracic surgery are presented. Between November 1991 and September 1992 37 intrathoracic operations--3 lobectomies among them--have been performed by their modified method. A special surgical thoracoscope was inserted through a 6-7 cm-s incision into the thorax. This instrument provides a direct view with excellent distal illumination and it also can be applied by video-thoracoscopic system. It is emphasized that their method needs further development. It's practical value and result depend on the appropriate consideration of possibilities and limits, and on careful selection of the patients.


Covalent immobilization of delipidated human serum albumin on poly(pyrrole-2-carboxylic) acid film for the impedimetric detection of perfluorooctanoic acid.
The immobilization of biomolecules at screen printed electrodes for biosensing applications is still an open challenge. To enrich the toolbox of bioelectrochemists, graphite screen printed electrodes (G-SPE) were modified with an electropolymerized film of pyrrole-2-carboxilic acid (Py-2-COOH), a pyrrole derivative rich in carboxylic acid functional groups. These functionalities are suitable for the covalent immobilization of biomolecular recognition layers. The electropolymerization was first optimized to obtain stable and conductive polymeric films, comparing two different electrolytes: sodium dodecyl sulphate (SDS) and sodium perchlorate. The G-SPE modified with Py-2-COOH in 0.1 M SDS solution showed the required properties and were further tested. A proof-of-concept study for the development of an impedimetric sensor for perfluorooctanoic acid (PFOA) was carried out using the delipidated human serum albumin (hSA) as bioreceptor. The data interpretation was supported by size exclusion chromatography and small-angle X-ray scattering (SEC-SAXS) analysis of the bioreceptor-target complex and the preliminary results suggest the possibility to further develop this biosensing strategy for toxicological and analytical studies.


Intratympanic gentamicin therapy for Ménière's disease: a meta-analysis.
This study compared the effectiveness of five different techniques of intratympanic gentamicin administration for Ménière's disease. A MEDLINE search of the English language literature from 1978 to 2002 was performed using the key words "intratympanic," "gentamicin," "therapy," "Ménière's," and "disease." Inclusion criteria to select articles for meta-analysis were clear description of gentamicin delivery technique, clearly reported vertigo control results, and report of hearing loss posttreatment. Seven studies (n = 218) describing the multiple daily dosing technique (delivery three times per day for >or=4 d), two studies (n = 84) describing the weekly dosing technique (weekly injections for four total doses), eight studies (n = 253) of the low-dose technique (one to two injections with retreatment for recurrent vertigo), four studies (n =156) of continuous microcatheter delivery, and six studies (n =269) of the titration technique (daily or weekly doses until onset of vestibular symptoms, change in vertigo, or hearing loss) were entered into the model. Vertigo control results were stratified into complete, substantial, or poor control. Hearing results were separated by profound, partial, or no hearing loss. Individuals undergoing caloric testing were separated by degree of vestibular ablation (complete versus partial) and analyzed for vertigo control (n = 301) and hearing loss (n = 333) after treatment. Comparisons between the rates of complete vertigo control, effective vertigo control (complete plus substantial control), overall hearing loss (partial plus profound), and profound hearing loss by delivery method were based on a parametric empirical Bayes analysis using binomial generalized linear models and backward variable selection (joining). Relative risk for vertigo control and hearing loss by partial or complete ablation was examined study by study using residual maximum likelihood to carry out a parametric empirical Bayes analysis. The titration method of gentamicin delivery demonstrated significantly better complete (81.7%, p = 0.001) and effective (96.3%, p < 0.05) vertigo control compared with other methods. The low-dose method of delivery demonstrated significantly worse complete vertigo control (66.7%, p < 0.001) and trends toward worse effective vertigo control (86.8%, p = 0.05) compared with other methods. The weekly method of delivery trends toward less overall hearing loss (13.1%, p = 0.08), and the multiple daily method demonstrated significantly more overall hearing loss (34.7%, p < 0.01) compared with other groups. No significant difference in profound hearing loss was found between groups. Degree of vestibular ablation after gentamicin therapy is not significantly correlated with the resulting vertigo control or hearing loss status.


CsMYB15 positively regulates Cs4CL2-mediated lignin biosynthesis during juice sac granulation in navel orange.
'Lane Late', a late-maturing navel orange cultivar, is mainly distributed in the Three Gorges Reservoir area, which matures in the late March of the next year and needs overwintering cultivation. Citrus fruit granulation is a physiological disorder, which is characterized by lignification and dehydration of juice sac cells, seriously affecting the commercial value of citrus fruits. The pre-harvest granulation of late-maturing navel orange is main caused by low temperature in the winter, but its mechanism and regulation pattern remain unclear. In this study, a SG2-type R2R3-MYB transcription factor, CsMYB15, was identified from Citrus sinensis, which was significantly induced by both juice sac granulation and low temperature treatment. Subcellular localization analysis and transcriptional activation assay revealed that CsMYB15 protein was localized to the nucleus, and it exhibited transcriptional activation activity in yeast. Over-expression of CsMYB15 by stable transformation in navel orange calli and transient transformation in kumquat fruits and navel orange juice sacs significantly increased lignin content in the transgenic lines. Further, Yeast one hybrid, EMSA, and LUC assays demonstrated that CsMYB15 directly bound to the Cs4CL2 promoter and activated its expression, thereby causing a high accumulation of lignin in citrus. Taken together, these results elucidated the biological function of CsMYB15 in regulating Cs4CL2-mediated lignin biosynthesis, and provided novel insight into the transcriptional regulation mechanism underlying the juice sac granulation of late-maturing navel orange.


Melatonin as a local regulator of human placental function.
Melatonin plays a critical role in a variety of mammalian reproductive processes not only acting on the central nervous system but also behaving as a peripheral physiologic regulator. To address the relevance of melatonin to the maintenance of pregnancy at the feto-maternal interface, we investigated the expression of two types of membrane melatonin receptors, MT1 and MT2, as well as arylalkylamine N-acetyltransferase (AA-NAT) and hydroxyindole-O-methyltransferase (HIOMT), the two enzymes required for the conversion of serotonin to melatonin, in the human placenta and the effect of melatonin on the release of human chorionic gonadotropin (hCG) from cultured human trophoblast cells. RT-PCR analysis and DNA sequencing revealed that transcripts of MT1, MT2, AA-NAT, and HIOMT were present in the first-trimester human placenta. We also found that melatonin significantly potentiated hCG secretion at optimal concentrations. These results suggest that melatonin may regulate human placental function in a paracrine/autocrine manner, providing evidence for a novel role in human reproduction.


Planning keypress and reaching responses: effects of response location and number of potential effectors.
In previous work the authors argued that the potential number of effectors in the response set is crucial in discriminating (multiple-effector) keypress from (single-effector) reaching responses. It is not clear, however, what influence the locus of responding (on vs. off the stimulus location for reaching and keypressing, respectively) has on reaction time (RT) performance. In 3 experiments, the authors systematically manipulated response location and response type using a spatial precuing task. The results consistently showed that even though response location did influence the RTs of keypress and reaching responses, the effect of the number of potential effectors was dominant in shaping the prototypical RT profiles of the 2 response types. These outcomes underscore the importance of the anatomical identity, in addition to response location, in response coding and corroborate the notion that distinct mechanisms dominate performance in single- and multiple-effector visuomotor tasks.


Preemptive meloxicam for postoperative pain relief after abdominal hysterectomy.
This study was conducted to evaluate the analgesic efficacy of meloxicam in abdominal hysterectomy. The study population consisted of 52 patients scheduled for total abdominal hysterectomy who were ASA 1 or 2 physical status female. Patients were allocated randomly to receive orally either 15 mg of meloxicam (Group M, n = 27) or placebo (Group P, n = 25) before anesthesia induction. After intravenous administration of 1.5 mg kg(-1) of tramadol, anesthesia was induced with an intravenous loading dose of 1-2 mg kg(-1) propofol. Anesthesia was maintained on intravenous infusion of propofol at 6-12 mg kg(-1) h plus tramadol at 1 mg kg(-1) h(-1), vecuronium, and a 2:1 nitrous oxide-oxygen mixture. The relative propofol consumption was lower in Group M than in Group P, (p < 0.05). The time for analgesic rescue decreased in the order Group M > Group P (p < 0.01). The degree of sedation was similar between the groups (p > 0.05) and the visual analog scores (10-cm scale) and verbal rating scale data differences were present in the first 2 h only (p < 0.05). When side-effects were evaluated nausea and vomiting were found to be lower in group M than in group P (p < 0.05). Preemptive meloxicam provided better postoperative analgesia than placebo.


[Rehabilitation of patients with vestibular disorders].
The connections between the two vestibular nuclei permit vestibular compensation after unilateral lesions. The interactions between the vestibular and the visual and proprioceptive system can support vestibular compensation. Our physical training program for the treatment of vertigo is based on these mechanisms. The training consists of fixation exercises, smooth pursuit and motor learning by proprioceptive cognition. The results are very convincing.


Youth experiences with and perspectives on long covid.
Research on the long-term effects of COVID-19 infection is ongoing, and the psychological and physical impacts of Long Covid on youth is poorly understood. To assess these impacts, we surveyed youth regarding their experiences with, and perspectives on, the long-term effects of COVID-19. We conducted a nationwide text message survey of youth ages 14-24 years in the United States. The survey asked four open ended questions regarding their experiences and perceptions regarding the long-term effects of COVID-19. Qualitative data was analyzed independently by three investigators using thematic analysis. Prevalence of codes were summarized using descriptive statistics. Among 1150 participants, 991 responded to at least one survey question (response rate 86.1%). The vast majority of our sample had COVID-19 or knew someone who did (75%), and approximately one third (32%) of youth indicated that they knew someone who had experienced symptoms consistent with Long Covid. Many youth (50%) reported worry and concern about Long Covid even if they, or someone they knew, did not have Long Covid. Among youth who were not concerned about Long Covid, the most commonly reported reasons were having received the vaccine (29%) and not having a prior COVID-19 infection (24%). Our findings suggest that among younger populations, there is significant concern regarding the long-term effects of COVID-19. Vaccination campaigns and youth-centered public health communication about Long Covid may not only reduce COVID-19 transmission, but also alleviate worries and concerns about Long Covid among youth.


Optimization of pH, temperature and CaCl2 concentrations for Ricotta cheese production from Buffalo cheese whey using Response Surface Methodology.
The recovery of milk constituents from cheese whey is affected by various processing conditions followed during production of Ricotta cheese. The objective of the present investigation was to optimize the temperature (60-90 °C), pH (3-7) and CaCl2 concentration (2·0-6·0 mm) for maximum yield/recovery of milk constituents. The research work was carried out in two phases. In 1st phase, the influence of these processing conditions was evaluated through 20 experiments formulated by central composite design (CCD) keeping the yield as response factor. The results obtained from these experiments were used to optimize processing conditions for maximum yield using response surface methodology (RSM). The three best combinations of processing conditions (90 °C, pH 7, CaCl2 6 mm), (100 °C, pH 5, CaCl2 4 mm) and (75 °C, pH 8·4, CaCl2 4 mm) were exploited in the next phase for Ricotta cheese production from a mixture of Buffalo cheese whey and skim milk (9 : 1) to determine the influence of optimized conditions on the cheese composition. Ricotta cheeses were analyzed for various physicochemical (moisture, fat, protein, lactose, total solids, pH and acidity indicated) parameters during storage of 60 d at 4 ± 2 °C after every 15 d interval. Ricotta cheese prepared at 90 °C, pH 7 and CaCl2 6 mm exhibited the highest cheese yield, proteins and total solids, while high fat content was recorded for cheese processed at 100 °C, pH 5 and 4 mm CaCl2 concentration. A significant storage-related increase in acidity and NPN was recorded for all cheese samples.


Closed-Shell Organic Compounds Might Form Dimers at the Surface of Molecular Clusters.
The role of covalently bound dimer formation is studied using high-level quantum chemical methods. Reaction free energy profiles for dimer formation between common oxygen-containing functional groups are calculated, and based on the Gibbs free energy differences between transition states and reactants, we show that none of the studied two-component gas-phase reactions are kinetically feasible at 298.15 K and 1 atm. Therefore, the catalyzing effect of water, base, or acid molecules is calculated, and sulfuric acid is identified to lower the activation free energies significantly. We find that the reactions yielding hemiacetal, peroxyhemiacetal, α-hydroxyester, and geminal diol products occur with activation free energies of less than 10 kcal/mol with sulfuric acid as a catalyst, indicating that these reactions could potentially take place on the surface of sulfuric acid clusters. Additionally, the formed dimer products bind stronger onto the pre-existing cluster than the corresponding reagent monomers do. This implies that covalent dimerization reactions stabilize the existing cluster thermodynamically and make it less likely to evaporate. However, the studied small organic compounds, which contain only one functional group, are not able to form dimer products that are stable against evaporation at atmospheric conditions. Calculations of dimer formation onto a cluster surface and the clustering ability of dimer products should be extended to large terpene oxidation products in order to estimate the real atmospheric significance.


Reflex sympathetic dystrophy syndrome.
Reflex sympathetic dystrophy is a condition characterized by unrelenting pain, swelling, discoloration, temperature, and physical changes in the affected body part that are life-altering for the patient and the family. Early diagnosis and treatment are essential to minimize the progressive disability from this disorder that results in limb pain, physical changes, and deformity. This article considers the current understanding of RSDS in terms of historical perspective, clinical features, pathophysiologic theories, diagnostic evaluation, treatment options, and nursing care.


[Changes of the dermal-fascial autograft after transplantation on the vascular-nervous connections using a microsurgical technique].
In 56 dogs 86 microsurgical operations on transplantation of free dermal-facial autografts from the internal knee surface have been performed on the hidden vascular-nervous bundle. The animals have been observed for 1 day up to 1 year. The implanted grafts (63) have been studied, using a complex of anatomical, histological and roentgenological methods. During early time (up to 7 days) after the operation in the flap signs of edema, dystrophy and inflammatory infiltration of tissues predominate. The graft gets blood at the expense of the restored main artery and has no vascular connections with the surrounding tissues. Its nervous conductors are fragmented. During 2 weeks--1 month epidermis completely regenerates along the line of the dermal suture. In the flap bed mature granulations result in vascular connections with its surrounding tissues. These connections become stable by the end of the first month, this means that the graft has implanted. Its nervous fibers are also restored. Long-term observations demonstrate that the adaptive changes of the flap and its vascular bed are near to completion. By the end of the 1st year restoration of the main innervational connections of the graft takes place. According to the data obtained, the nervous conductors grow into it along the sewed hidden nerve and along the course of paravasal nerve plexuses. Across the scar from the surrounding tissues the dermal-fascial autograft does not reinnervate.


Inflammatory Profiles in Depressed Adolescents Treated with Fluoxetine: An 8-Week Follow-up Open Study.
Changes in cytokine levels in major depression and during treatment have been reported in adults. However, few studies have examined cytokine levels in an adolescent sample despite this being a common age of onset. Methods. We measured proinflammatory (IL-2, IFN-γ, IL-1β, TNF-α, IL-6, IL-12, and IL-15) and anti-inflammatory (IL-4, IL-5, IL-13, IL-1Ra, and IL-10) cytokine serum levels in 22 adolescents with major depression and 18 healthy volunteers. Cytokines were measured by multiplex bead-based immunoassays at baseline, and 4 and 8 weeks after commencement of fluoxetine administration in the clinical group. Results. Compared to healthy volunteers, adolescents with major depression at baseline showed significant increases in all pro- and anti-inflammatory cytokines, except IL-1Ra and IL-10. Significant changes were observed in fluoxetine treatment compared to baseline: proinflammatory cytokines IFN-γ, IL-1β, TNF-α, IL-6, IL-12, and IL-15 were decreased only at week 4 whereas IL-2 was increased only at week 8; anti-inflammatory cytokines IL-4 and IL-5 were increased at week 8 while IL-1Ra was reduced only at week 4. There were no significant correlations between cytokine levels and symptomatic improvement in HDRS. Discussion. The results suggest a significant interplay between cytokine levels, the depressive state, and the stage of treatment with an SSRI. To the best of our knowledge, this is the first report in depressed adolescents with elevated IL-12, IL-13, and IL-15 levels. Further studies are necessary to clarify the role and mechanisms of altered cytokine levels in the pathogenesis and physiopathology of major depressive disorder.


Leading the Dental Quality Movement: A Dental Quality Alliance Perspective.
Changing regulatory priorities set forth by the Affordable Care Act and recent activities of the Centers for Medicare and Medicaid Services clearly prioritize the need to improve the quality of health care in both the public and private sectors. As the largest multistakeholder organization focused on oral health care quality measurement and improvement, the Dental Quality Alliance is leading the way in establishing standardized and valid quality measures applicable in both private and public sectors.


Price fixing in general practice.
Dr Bev Young has just finished packing up her office. This is her last day in her Preston practice of 19 years. Bev enjoys the autonomy of being a solo general practitioner, but lately she finds managing the practice increasingly stressful. Teaming up with a fellow GP seemed a good alternative.


The clinical and biochemical study of pesticide sprayers.
Clinical, haematological and biochemical studies of 34 subjects, occupationally exposed to different types of pesticides, were conducted. The findings have been compared with those observed in 14 control subjects. Inhibition of cholinesterase activity was observed in the exposed group. Serum alkaline phosphatase was also found to be raised. Radiological examination revealed pneumonitic patches in the chest skiagrams of three exposed subjects. Paraesthesia with hyporeflexia was also found in 8.8% of exposed subjects. The findings suggest that exposure to multiple pesticides over many years affects the normal functioning of different organ systems and may produce characteristic clinical effects.


Drinking problems: mechanisms of macropinosome formation and maturation.
Macropinocytosis is a mechanism for the nonspecific bulk uptake and internalisation of extracellular fluid. This plays specific and distinct roles in diverse cell types such as macrophages, dendritic cells and neurons, by allowing cells to sample their environment, extract extracellular nutrients and regulate plasma membrane turnover. Macropinocytosis has recently been implicated in several diseases including cancer, neurodegenerative diseases and atherosclerosis. Uptake by macropinocytosis is also exploited by several intracellular pathogens to gain entry into host cells. Both capturing and subsequently processing large volumes of extracellular fluid poses a number of unique challenges for the cell. Macropinosome formation requires coordinated three-dimensional manipulation of the cytoskeleton to form shaped protrusions able to entrap extracellular fluid. The following maturation of these large vesicles then involves a complex series of membrane rearrangements to shrink and concentrate their contents, while delivering components required for digestion and recycling. Recognition of the diverse importance of macropinocytosis in physiology and disease has prompted a number of recent studies. In this article, we summarise advances in our understanding of both macropinosome formation and maturation, and seek to highlight the important unanswered questions.


Attachment anxiety, disinhibited eating, and body mass index in adulthood.
Several studies report a relationship between body mass index (BMI) and disinhibited eating (a failure to restrict intake and to overeat). However, the aetiology of disinhibited eating has received scant attention. In this study, we consider a role for 'attachment orientation', a trait that reflects the quality of bonding in early life and remains stable throughout adulthood. Participants (N = 200, females = 135, BMI range from 17.4 to 41.1 kg m(-2)) completed measures of disinhibition and attachment orientation. 'Attachment anxiety' was a good predictor of disinhibited eating (P<0.001). Furthermore, mediation analysis confirmed that it is through this relationship that attachment anxiety also predicts BMI (P=0.02). These findings are consistent with other studies, showing an association between attachment orientation and other disinhibited behaviours, including alcohol and substance abuse. Our interpretation is that disinhibited eaters engage in external affect regulation. In doing so, they seek to mitigate the anxiety associated with poor interpersonal attachments.


Chromosomal alterations among age-related haematopoietic clones in Japan.
The extent to which the biology of oncogenesis and ageing are shaped by factors that distinguish human populations is unknown. Haematopoietic clones with acquired mutations become common with advancing age and can lead to blood cancers1-10. Here we describe shared and population-specific patterns of genomic mutations and clonal selection in haematopoietic cells on the basis of 33,250 autosomal mosaic chromosomal alterations that we detected in 179,417 Japanese participants in the BioBank Japan cohort and compared with analogous data from the UK Biobank. In this long-lived Japanese population, mosaic chromosomal alterations were detected in more than 35.0% (s.e.m., 1.4%) of individuals older than 90 years, which suggests that such clones trend towards inevitability with advancing age. Japanese and European individuals exhibited key differences in the genomic locations of mutations in their respective haematopoietic clones; these differences predicted the relative rates of chronic lymphocytic leukaemia (which is more common among European individuals) and T cell leukaemia (which is more common among Japanese individuals) in these populations. Three different mutational precursors of chronic lymphocytic leukaemia (including trisomy 12, loss of chromosomes 13q and 13q, and copy-neutral loss of heterozygosity) were between two and six times less common among Japanese individuals, which suggests that the Japanese and European populations differ in selective pressures on clones long before the development of clinically apparent chronic lymphocytic leukaemia. Japanese and British populations also exhibited very different rates of clones that arose from B and T cell lineages, which predicted the relative rates of B and T cell cancers in these populations. We identified six previously undescribed loci at which inherited variants predispose to mosaic chromosomal alterations that duplicate or remove the inherited risk alleles, including large-effect rare variants at NBN, MRE11 and CTU2 (odds ratio, 28-91). We suggest that selective pressures on clones are modulated by factors that are specific to human populations. Further genomic characterization of clonal selection and cancer in populations from around the world is therefore warranted.


Real-time Observation of Deep Lithiation of Tungsten Oxide Nanowires by In Situ Electron Microscopy.
An in-depth mechanistic understanding of the electrochemical lithiation process of tungsten oxide (WO3 ) is both of fundamental interest and relevant for potential applications. One of the most important features of WO3 lithiation is the formation of the chemically flexible, nonstoichiometric Lix WO3 , known as tungsten bronze. Herein, we achieved the real-time observation of the deep electrochemical lithiation process of single-crystal WO3 nanowires by constructing in situ transmission electron microscopy (TEM) electrochemical cells. As revealed by nanoscale imaging, diffraction, and spectroscopy, it is shown that the rapid and deep lithiation of WO3 nanowires leads to the formation of highly disordered and near-amorphous Lix WO3 phases, but with no detectable traces of elemental W and segregated Li2 O phase formation. These results highlight the remarkable chemical and structural flexibility of the Lix WO3 phases in accommodating the rapid and deep lithiation reaction.


Alternation of heart microRNA-mRNA network by high-intensity interval training and proanthocyanidin in myocardial ischemia rats: Artificial intelligence and validation experimental.
Heart ischemia is an irreversible condition that occurs via decreased blood flow in vessels by genetic factors, molecular regulators, and environmental conditions. The microRNAs binding to 3´UTR of target genes can influence gene expression and play pivotal roles in several mechanisms identified as a potential biomarker to the pathogenesis. We have screened a pool of microRNAs and mRNAs according to their potential correlation to myocardial ischemia based on artificial intelligence. We constructed the hub genes and mRNA-microRNA networks by R programing language and in silico analysis. Moreover, we calculated the binding affinity of the 3D structure of proanthocyanidin on VEGFα and GATA4 to ameliorate heart tissue after ischemia. Then we treated rats with 300 mg/kg proanthocyanidins and exercised in different intensity and duration times (low, moderate, and high-intensity interval training) for 14 weeks. In the second step, after 14 weeks, isoproterenol hydrochloride was injected into the rats, and myocardial ischemia was induced. We indicated that VEGFα, GATA4, and GJA1 axis associated with miR-27a-3p, miR-499-5p, miR-206-3p, miR-208a-3p are regulatable after 14 weeks of exercise training and proanthocyanidin extract consumption and could prevent myocardial injuries in ischemia. Moreover, we revealed different intensity and duration times, and proanthocyanidin modulated the microRNA-mRNA interaction in rats with myocardial ischemia. Proanthocyanidin consumption as a bioactive compound may significantly ameliorate myocardial dysfunction and offset pathological hallmarks of myocardial ischemia. Moreover, exercise has protective effects on myocardial tissue by reprograming genes and genetic regulator factors. PRACTICAL APPLICATIONS: Complimentary medicine identified Proanthocyanidin and exercise are recognized as effective methods to prevent and improve Myocardial ischemia. According to medical biology servers, we explored the VEGFα, GATA4, and GJA1 axis associated with miR-27a-3p, miR-499-5p, miR-206-3p, miR-208a-3p as a vital pathomechanism of myocardial ischemia. Furthermore, proanthocyanidin extract is the effective compound that could has protective effects on myocardial tissue by reprograming genes and genetic regulator factors. Furthermore, proanthocyanidin and swimming training might recover myocardial dysfunction and regulate the hub genes and mRNA-microRNA networks.


Utility of a pre-optimized kit for random amplified polymorphic DNA in typing Candida albicans.
The utility of a pre-optimized kit for random amplified polymorphic DNA (RAPD) was assessed in typing diverse strains of Candida albicans from epidemiologically unrelated inpatients (interpatient analysis) and in detecting clonal variations that maybe present within individual patient isolates (intrapatient analysis). Stool samples from inpatients were cultured on Inhibitory Mold agar. Nine individual colonies from all patients with > or =9 colonies of C. albicans (n = 18) were selected, frozen, and karyotyped using CHEF genomic DNA plug kits and CHEF-DRIII. Each of the selected colonies was then analyzed by RAPD, utilizing the selected kit, with 6 primers. Interpatient analysis revealed 9 karyotypes and 17 RAPD composites. RAPD discrimination was significantly better (p < 0.001). Intrapatient analysis revealed 34 (21%) and 33 (20.4%) variants among 162 colonies tested by RAPD and karyotyping, respectively. The results were discordant in 25 variants, all with differences of 1-3 bands. These results illustrate that this pre-optimized kit for RAPD provides excellent discrimination of genetically unrelated strains. Its performance in delineating subtle clonal differences was comparable with karyotyping; both methods failed to detect all minor genetic variations. The ease of use and quick turnaround time of this kit offer a practical and reliable method for typing diverse strains of C. albicans, but may be inadequate for assessing microevolution.


Prognostic significance of seminal vesicle invasion on the radical prostatectomy specimen. Rationale for seminal vesicle biopsies.
The prognostic significance of seminal vesicle invasion on the radical prostatectomy specimen was evaluated according to the proximal or distal site of this invasion. 52 consecutive patients undergoing radical prostatectomy for stage pT3b N0 M0 prostatic cancer were classified into two groups: group A (18 patients): patients with invasion limited to the proximal part of the seminal vesicles (stage T3b limited); group B (34 patients): patients with invasion extending to the free part of the seminal vesicles (stage T3b extensive). The PSA progression-free curves were compared between the two groups. A multivariable regression model was performed to determine independent prognostic factors. Overall, the 5-year PSA progression free rate of the 52 patients was 14.4%. The 5-year PSA progression-free rate of the patients in group A was 45.4 vs. 4.2% at 4 years in group B (p = 0.0004). The stage of seminal vesicle invasion and the Gleason score were the only independent predictive factors of PSA progression (p = 0.02 and p = 0.04, respectively). The prognostic significance of seminal vesicle invasion is not constant and depends on the site of invasion. Preoperative seminal vesicles biopsies can select patients with invasion extending to the free part of seminal vesicles and who have a poor prognosis in terms of PSA progression after radical prostatectomy.


Influence of social anxiety on recognition memory for happy and angry faces: Comparison between own- and other-race faces.
The reported experiment investigated memory of unfamiliar faces and how it is influenced by race, facial expression, direction of gaze and observers' level of social anxiety. In total, 87 Japanese participants initially memorized images of Oriental and Caucasian faces displaying either happy or angry expressions with direct or averted gaze. They then saw the previously seen faces and additional distractor faces displaying neutral expressions and judged whether they had seen them before. Their level of social anxiety was measured with a questionnaire. Regardless of gaze or race of the faces, recognition for faces studied with happy expressions was more accurate than for those studied with angry expressions (happiness advantage), but this tendency weakened for people with higher levels of social anxiety, possibly due to their increased anxiety for positive feedback regarding social interactions. Interestingly, the reduction in the happiness advantage observed for the highly anxious participants was more prominent for the own-race faces than for the other-race faces. The results suggest that angry expression disrupts processing of identity-relevant features of the faces, but the memory for happy faces is affected by the social anxiety traits, and the magnitude of the impact may depend on the importance of the face.


Hidradenitis suppurativa tarda: defining an understudied elderly population.
Hidradenitis suppurativa (HS) is a chronic, devastating multifactorial skin disease. Patients generally develop HS after puberty and the prevalence of the disease is assumed to decrease with higher age. Data outside the usual age range is limited, especially for elderly patients. To investigate the prevalence, clinical characteristics, and associated comorbidities among the elderly HS population. Data was collected through a population-wide survey-based study within the Lifelines Cohort Study in the Netherlands. The clinical characteristics of elderly HS patients (≥60y) were compared to an adult HS (<60y) population. The comorbidities in elderly HS patients were compared to a non-HS sex- and age-matched elderly population in a 1:4 ratio. HS in elderly was defined as active HS in patients aged 60 years and older. Within the HS elderly, two subgroups were defined, late-onset HS (HS developed after 60 years of age) and persistent HS (HS developed at younger age but continued after 60 years). Within the Lifelines cohort 209 elderly patients with HS were identified as well as an adult (<60y) HS group (n = 793) and a non-HS sex- and age-matched control elderly group (N = 810). The prevalence of HS among the elderly population was 0.8% [95% CI 0.4 to 1.2]. A significantly higher age of HS symptom onset was found compared to the adult HS group (respectively, 40.0 years vs. 23.0 years [OR = 1.056; 95%CI 1.05-1.07]). Among the elderly HS cohort a female-to-male ratio of 1.7:1.0 and a higher family history for HS were found. Moreover, elderly HS patients had a significantly higher risk of having HS associated comorbidities compared to the sex-and age-matched controls. The prevalence of HS in elderly is not rare. Among the elderly a shift from female predominance towards a lower female-to-male ratio in HS is observed. Besides, HS in the elderly showed significant variation in age of onset and involved body areas. Moreover, elderly HS patients were more susceptible to multimorbidity. At last, we propose defining HS in elderly as "HS tarda" and subdividing it as late-onset and persistent HS tarda.


Disulfide-linked high molecular weight protein associated with human cataract.
A major high molecular weight disulfide-linked protein has been isolated from cataractous lenses. It is only present in the water-insoluble protein fractions. This species has not been found in normal lenses of comparable age. Upon reduction of this fraction, polypeptides having molecular weights of approximately 60,000, 43,000, and 20,000 as well as a noncharacterized heterogeneous species are released. Similar sized polypeptides have been found in various noncovalently linked aggregates in both normal and cataractous lenses. Examination of the disulfide-linked protein fraction indicates that approximately 70% of the sulfhydryl groups are in the oxidized state. Although little change in the sizes of the other major polypeptides in the water-insoluble fraction is observed upon reduction, these components were also found to contain an appreciable disulfide content. Such results indicate that the only major lens fraction containing disulfide-linked polypeptide is the high molecular weight species and that the disulfides present in the remaining fractions are either intrachain disulfides or link polypeptides to small peptides.


Global Burden of Cutaneous Melanoma in 2020 and Projections to 2040.
Despite many cases being preventable, cutaneous melanoma remains the most serious skin cancer worldwide. Understanding the scale and profile of the disease is vital to concentrate and reinforce global prevention efforts. To examine global patterns of cutaneous melanoma in 2020 and to provide projected estimates of cases and deaths by 2040. This population-based study used the GLOBOCAN 2020 database for global epidemiological assessment of new cases and deaths due to invasive melanoma. Age-standardized incidence and mortality rates were calculated per 100 000 person-years by country, world region, and 4-tier level of human development. Estimated numbers of cases and deaths were calculated for the year 2040. A worldwide total of 325 000 new melanoma cases (174 000 males, 151 000 females) and 57 000 deaths (32 000 males, 25 000 females) was estimated for 2020. Large geographic variations existed across countries and world regions, with the highest incidence rates among males (42 per 100 000 person-years) and females (31 per 100 000 person-years) observed in Australia/New Zealand, followed by Western Europe (19 per 100 000 person-years for males and females), North America (18 per 100 000 person-years for males, 14 per 100 000 person-years for females), and Northern Europe (17 per 100 000 person-years for males, 18 per 100 000 person-years for females). Melanoma continued to be rare in most African and Asian countries, with incidence rates commonly less than 1 per 100 000 person-years. Mortality rates peaked at 5 per 100 000 person-years in New Zealand, and geographic variations were less pronounced than for incidence. Melanoma was more frequent among males than females in most world regions. If 2020 rates continue, the burden from melanoma is estimated to increase to 510 000 new cases (a roughly 50% increase) and to 96 000 deaths (a 68% increase) by 2040. This epidemiological assessment suggests that melanoma remains an important challenge to cancer control and public health globally, especially in fair-skinned populations of European descent.


Friction-induced energy-loss rainbows in atom surface scattering.
The rainbow is due to extrema of the angular deflection function of light impinging on water drops. Generically, extrema of suitably defined deflection functions lead to rainbows. These include angular and rotational rainbows in surface scattering and more. Here we introduce the concept of an "energy-loss deflection function" for scattering of particles from a periodic surface whose extrema lead to a new form-the "energy-loss rainbow" which appears as multiple maxima in the final energy distribution of the scattered particle. Energy-loss rainbows are caused by frictional phonon effects which induce structure in the energy-loss distribution instead of "washing it out." We provide evidence that they have been observed in Ne scattering on self-assembled monolayers.


The operational costs of spraying residual insecticides: a case-study from Nepal.
Little attention has been paid to the cost implications of different insecticides for malaria control, particularly to the local (non-insecticide) costs. This study in Nepal explored the significance of operational costs in relation to insecticide cost and examined the extent to which operational costs varied for DDT, malathion and Ficam. A detailed analysis was done of costs relating to spraying, transport and safety. The study found that the operational cost differences were relatively small in comparison with the costs of the chemicals themselves and the cost of transporting them to Nepal, though DDT and Ficam had significantly lower operational costs than malathion. Operational costs were paid mainly by the Nepalese government and insecticide and external freight costs by donors.


Tracing the phase diagram of the four-site water potential (TIP4P).
We present here the phase diagram for one of the most popular water models, the four-point transferable intermolecular potential (TIP4P) model. We show that TIP4P model, does indeed provide a qualitatively correct description of the phase diagram of water. The melting line of the five-point transferable intermolecular potential (TIP5P) at low pressures is also presented.


Interfacing Branching Random Walks with Metropolis Sampling: Constraint Release in Auxiliary-Field Quantum Monte Carlo.
We present an approach to interface branching random walks with Markov chain Monte Carlo sampling and to switch seamlessly between the two. The approach is discussed in the context of auxiliary-field quantum Monte Carlo (AFQMC) but can be applied to other Monte Carlo calculations or simulations. In AFQMC, the formulation of branching random walks along imaginary-time is needed to realize a constraint to control the sign or phase problem. The constraint is derived from an exact gauge condition and is in practice implemented approximately with a trial wave function or trial density matrix, which can break exactness in the algorithm. We use the generalized Metropolis algorithm to sample a selected portion of the imaginary-time path after it has been produced by the branching random walk. This interfacing allows a constraint release to follow seamlessly from constrained-path sampling, which can reduce the systematic error from the latter. It also provides a way to improve the computation of correlation functions and observables that do not commute with the Hamiltonian. We illustrate the method in atoms and molecules, where improvements in accuracy can be clearly quantified and near-exact results are obtained. We also discuss the computation of the variance of the Hamiltonian and propose a convenient way to evaluate it stochastically without changing the scaling of AFQMC.


The role of menopausal hormone therapy in the management of osteoporosis.
It is now 75 years since Fuller Albright published his observations on the causal relationship between menopausal estrogen deficiency and osteoporosis. He introduced the concept of menopausal hormone therapy (MHT) for the prevention of osteoporosis. Most of his remarkable observations have stood the test of time and scientific scrutiny. Unfortunately, the uptake of MHT for the prevention of osteoporosis and related fractures remains very low. This can be ascribed to several factors. The availability of new drugs, supported by randomized clinical trials, has increased therapeutic options and created the impression that all new drugs are better compared to MHT. Confusion exists as to the benefit/risk profile of menopausal hormone therapy, limitations on the age of initiation of treatment, limitations on the length of treatment, and the need for treatment in the young menopausal woman with low bone density.


Outbreak of measles in a teenage school population: the need to immunize susceptible adolescents.
An outbreak of measles occurred in a community school and the surrounding area in Crowborough, East Sussex, UK, from December 1992 to February 1993. There were 96 suspected cases reported: 66 cases among 1673 students at one school and 30 community cases. The majority of suspected cases were in those aged 11-17 (78%), 2 cases occurred in infants < 1 year old and 8 cases in adults aged 18 years or over. Data collected on 60 (91%) of the 66 suspect school cases showed 56 (93%) had an illness which met a case definition of measles. Eighteen had confirmatory IgM measles antibody. Two cases were hospitalized. The local percentage uptake for measles immunization for the school age years affected varied between 64% and 84%. A survey of parents showed that approximately 74% of the students attending the school had a history of measles immunization. The immunization rates reported by parents for children who developed measles was 21%, (29% based on GP records) compared with 77% for those who remained well. Vaccine efficacy was estimated to be 92%. This outbreak, along with others recently reported in older unimmunized children in the UK, reinforces the need for catch-up immunization programmes to reach this susceptible group of adolescents.


Acute arsenic intoxication presenting as Guillain-Barré-like syndrome.
Arsenic-induced polyneuropathy is traditionally classified as an axonal-loss type, electrodiagnostically resulting in low amplitude or absent sensory and motor responses, relatively preserved proximal and distal motor conduction rates, and distal denervation. We report four patients with a subacute onset progressive polyradiculoneuropathy following high-dose arsenic poisoning. In three patients, early electrodiagnostic testing demonstrated findings suggestive of an acquired segmental demyelinating polyradiculoneuropathy. Serial testing confirmed evolution into features of a distal dying-back neuropathy. We hypothesize that arsenic toxicity and the resultant biochemical derangement of the peripheral nerve cell leads to subtle changes in axonal function that produce, initially, segmental demyelination and eventually distal axonal degeneration. Acute arsenic toxicity must be suspected in patients with clinical and electrodiagnostic features supporting Guillain-Barré syndrome.


New medicines for spontaneous preterm birth prevention and preterm labour management: landscape analysis of the medicine development pipeline.
There are few medicines in clinical use for managing preterm labor or preventing spontaneous preterm birth from occurring. We previously developed two target product profiles (TPPs) for medicines to prevent spontaneous preterm birth and manage preterm labor. The objectives of this study were to 1) analyse the research and development pipeline of medicines for preterm birth and 2) compare these medicines to target product profiles for spontaneous preterm birth to identify the most promising candidates. Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched to identify candidate medicines (including drugs, dietary supplements and biologics) and populate the Accelerating Innovations for Mothers (AIM) database. This database was screened for all candidates that have been investigated for preterm birth. Candidates in clinical development were ranked against criteria from TPPs, and classified as high, medium or low potential. Preclinical candidates were categorised by product type, archetype and medicine subclass. The AIM database identified 178 candidates. Of the 71 candidates in clinical development, ten were deemed high potential (Prevention: Omega-3 fatty acid, aspirin, vaginal progesterone, oral progesterone, L-arginine, and selenium; Treatment: nicorandil, isosorbide dinitrate, nicardipine and celecoxib) and seven were medium potential (Prevention: pravastatin and lactoferrin; Treatment: glyceryl trinitrate, retosiban, relcovaptan, human chorionic gonadotropin and Bryophyllum pinnatum extract). 107 candidates were in preclinical development. This analysis provides a drug-agnostic approach to assessing the potential of candidate medicines for spontaneous preterm birth. Research should be prioritised for high-potential candidates that are most likely to meet the real world needs of women, babies, and health care professionals.


Ethnic differences in the severity of varicella in adults in northern Saudi Arabia.
The severity of varicella infection in 124 expatriates from the Asian continent was compared to that in 120 Saudi nationals, seen in Arar Central Hospital, Arar, Saudi Arabia, between January 1992 and December 1994. Persistent fever (defined as a raised body temperature more than 37.4 degrees C lasting more than 5 days), extensive skin eruptions (defined as extensive, when more than 50% of the body surface was affected) and transient elevation of hepatic enzymes (aspartate transaminases > 37 U/L and alanine transaminases > 40 U/L) after excluding other possible causes, occurred significantly more in expatriates than in Saudis. The mean duration of the illness in expatriates was 15.9 +/- 3.41 days as compared to a mean duration of 13.1 +/- 3.52 days in Saudis. This difference was statistically significant (p < 0.01 Student's t-test). The findings in this study suggest that varicella infection runs a more severe course in expatriates from the Asian continent as compared to the Saudis. Treatment with the antiviral agent acyclovir may be indicated in this group of expatriates with varicella infection.