Agallolides A-M, including two rearranged ent-atisanes featuring a bicyclo[3.2.1]octane motif, from the Chinese Excoecaria agallocha.
Thirteen new diterpenoid compounds, named agallolides A-M (1-13), including ten ent-atisanes, were isolated from the stems and twigs of the Chinese semi-mangrove plant, Excoecaria agallocha. Most notably, agallolides A (1) and B (2) are two rearranged ent-atisanes featuring a unique 6/6/5/7 tetracyclic carbon skeleton. Agallolides C-J (3-10) are ent-atisanes, among which agallolide C (3) represents the first example of 3,4-seco-17-nor-ent-atisane. Agallolides K (11) and L (12) are two ent-isopimaranes, whereas agallolide M (13) is a rare 3,4-seco-ent-trachylobane. The structures of these diterpenoid compounds were established by HR-ESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of agallolide A (1) and agallolides I-K (9-11) were further confirmed by single-crystal X-ray diffraction analyses with Cu Kα radiation. The plausible biogenetic pathways for agallolides A (1), B (2), and I (9) were proposed. Agallolides I (9) and J (10) exhibited NF-κB inhibitory activity with inhibition rates of 23.4% and 19.4%, respectively, at the concentration of 100.0 µM.


Isolation and Preparation of Extracellular Proteins from Lignocellulose-Degrading Fungi for Comparative Proteomic Studies Using Mass Spectrometry.
Fungi utilize a unique mechanism of nutrient acquisition involving extracellular digestion. To understand the biology of these microbes, it is important to identify and characterize the function of proteins that are secreted and involved in nutrient acquisition. Mass spectrometry-based proteomics is a powerful tool to study complex mixtures of proteins and understand how the proteins produced by an organism change in response to different conditions. Many fungi are efficient decomposers of plant cell walls, and anaerobic fungi are well recognized for their ability to digest lignocellulose. Here we outline a protocol for the enrichment and isolation of proteins secreted by anaerobic fungi after growth on simple (glucose) and complex (straw and alfalfa hay) carbon sources. We provide detailed instruction on generating protein fragments and preparing these for proteomic analysis using reversed-phase chromatography and mass spectrometry. The interpretation of results and their relevance to a particular biological system is study-dependent and beyond the scope of this protocol.


Relationship between foot pressure and spinal parameters in healthy adults - A systematic review.
Foot pressure has an essential impact on the entire musculoskeletal chain. So far, the direct influence of foot pressure onto the spinal posture and vice versa is still unclear. The aim of this study was to determine the relationship between foot pressure and spinal posture in healthy adults under static and dynamic conditions. Systematic research was conducted using PubMed to demonstrate the relationship between foot pressure and spinal posture. The search strategy was based on the PICOS selection criteria. The risk of bias within the studies was assessed using SIGN rankings. Based on the search strategy, 719 articles were identified by screening title and abstract. 11 studies with moderate methodological quality partially showed a relationship between foot pressure and spinal posture (SIGN:2-1- and B-D). Apart from the foot pressure, the included studies analyzed parameters of muscle thickness (sonography), trunk displacement, head position, posterior tilt angle, trunk tilt, pelvic rotation, spinal range of motion, or spinal motion. Strength training and increased muscle thickness in the lumbar spine ensure decreased foot pressure. The head position partly induces a change of foot pressure under static conditions. No correlation was identified between spinal posture and foot pressure during forward and backward walking without manipulation. The static and dynamic measurements only show statistical correlations between foot and back muscles. Foot pressure and spinal posture seem to be interrelated under static and dynamic conditions. Static and dynamic measurements are necessary for body posture analysis, as the conditions do not always show consistent results. Due to the small number of studies and low sample sizes, further investigations are necessary to gain more precise perception of the interplay of the spine and foot pressure. For better comparison, more homogeneous studies investigating similar spine parameters are needed.


Fecal chymotrypsin levels in children with pancreatic insufficiency.
The fecal chymotrypsin (FC) levels in samples collected over 24 h were determined by a new commercial colorimetric method from Boehringer Mannheim in 82 children suffering from various pancreatic disorders. The patients were divided into 4 groups, in accordance with the following etiologies: cystic fibrosis of the pancreas (CFP), chronic severe hepatic disorders (CSH), primary malabsorption syndrome (PMS) and malnutrition due to nondigestive causes (M). The control group comprised 48 children of similar ages. The 24th FC levels as U/g (mean +/- SD) were: 34 +/- 6 in the control group, 2 +/- 2 in the CFP group, 15 +/- 6 in the M group, 19 +/- 9 in the CSH group and 43 +/- 13 in the PMS group. The differences between the CFP patients and all the other groups were statistically significant. These results indicate that the FC levels may be suitable as a diagnostic indication of CFP and capable of differentiating between this disorder and other causes of pancreatic insufficiency.


Prevalence of metabolic syndrome, its risk factors and associated lifestyles in Myanmar adult people: A community based cross-sectional study.
Metabolic syndrome (MetS) is the constellation of cardio-metabolic risk factors, and it can illustrate the coming burden of cardiovascular diseases and diabetes mellitus. Myanmar faces larger pressure from cardio-metabolic diseases and there is no existing data to understand the magnitude of MetS in adult population. This study aimed to investigate the extent of existing people with MetS in the community and to know the related lifestyle factors to MetS. A community based cross-sectional study was performed in convenient sample of 302 Myanmar adult people. Prevalence of MetS and associated risk factors were identified by collecting sociodemographic information, anthropometric measurements, and blood investigation of glucose and lipid profiles. Logistic regression analysis was performed for developing statistical models to estimate the odd ratios (OR) and confidence intervals (CI). Prevalence of MetS is 29.1%, and there is no significant difference between male and female prevalence. Abdominal obesity is the highest component of MetS (OR: 28.37, CI: 12.41-64.85, p < 0.001) especially for female (OR: 44.52, CI: 17.19-115.31, p < 0.001), and hypertriglyceridemia (OR: 11.05, CI: 6.20-19.66, p < 0.001) is the commonest in male. Age is the constant risk for developing MetS (OR: 4.06, CI: 1.91-8.64, p < 0.001) whereas the practice of midday nap is the behavior related to increased occurrence of MetS (OR: 1.97, CI: 1.16-3.38, p < 0.05). Dietary pattern, smoking status, drinking alcoholic beverages and physical activity involvement do not impact on the development of MetS. Education, occupation, income and other sociodemographic factors do not produce significant effect on cardio-metabolic status. Obesity, diabetes, and hypertensive conditions of community residents are also explored. Modifiable pathophysiological conditions such as abdominal obesity, and obesity play a vital role in preventing MetS before it occurs while unmodifiable risk factor such as getting older and female sex are not as much important as changeable lifestyle habits.


Causative and Sanative dynamicity of ChREBP in Hepato-Metabolic disorders.
ChREBP is the master regulator of carbohydrate dependent glycolytic and lipogenic flux within metabolic tissues. It plays a vital role in hyper-calorific milieu by activating glycolysis, lipogenesis along with pentose phosphate shunt and glycogen synthesis, fostering immediate reduction in the systemic glycemic levels. Liver being the primary organ to sense disproportionate dietary intake and linked physiological stress, stimulates ChREBP to perform the aforementioned processes. Activated ChREBP also inhibits lipolysis and encourages proper disposal of excessive triglycerides into adipocytes from the liver ablating hepatic intracellular lipid trafficking. Chronic overeating or onset of positive energy balance, hyper-activates ChREBP and signals development, intensification of hepato-metabolic disorders, and allied discrepancies in the whole-body metabolic functioning. ChREBP thus gets negatively connotated as the primary regulator of hepatic disorders, owing to its inherent features as the primary glycemic sensor and the only transcription factor that can transduce glucose-dependent glycolytic and lipogenic signals. Through this review, we - try to recapitulate and emphasize on the sanative events coordinated by ChREBP in several pathophysiological states. In totality, we aim to uncouple the disease-causing aspects of ChREBP from its positive attributes evoked during a metabolic crisis, in hepato-metabolic diseases.


Construction and evaluation of live attenuated vaccine strains of Shigella flexneri and Shigella dysenteriae 1.
Shigellosis is an invasive disease of the human colon which is particularly prevalent among children of the developing world. No proper vaccine is available to protect against this enteric disease. It is currently accepted that only live strains with attenuated virulence administered orally may elicit protective immunity at the level of the colonic mucosa, which is the exclusive site of multiplication of causative microorganisms such as Shigella flexneri and Shigella dysenteriae 1. We have constructed such vaccine candidates based on the destruction of virulence genes responsible for selected steps of the infection process. In S. flexneri, a combination of two mutations impairing cell-to-cell spread (icsA) and aerobactin production and transport (iuc, iut) which support growth within tissues provide a well tolerated and protective vaccine prototype against shigellosis in macaque monkeys. In S. dysenteriae 1, similar mutations are currently being introduced, in addition to one which eliminates the catalytic activity of Shiga toxin. These mutants and others will be tested soon in human phase I trials.


Nanoparticles prepared by polysaccharides extracted from Biyang floral mushroom loaded with resveratrol: Characterization, bioactivity and release behavior under in vitro digestion.
Resveratrol (RES) is a common active factor in the functional food field, but poor water solubility and low bioavailability have limited its application. In the present study, the novel nanoparticles (RES-CBFMP NPs) using floral mushroom polysaccharide as the wall material have been developed for delivering RES, aiming to overcome its application shortcomings. After ratio optimization, RES-CBFMP NPs (RES-CBFMP,1:8 w/w), which combined through the hydrogen bonds between RES and CBFMP, showed the best overall performance, with the encapsulation efficiency (EE) of 49.74 ± 0.16%, loading efficiency (LE) of 5.53 ± 0.02%, particle size of 158.56 ± 1.97 nm and zeta-potential of -17.56 ± 0.24 mV. In addition, RES-CBFMP NPs exhibited good physicochemical stabilities, sustained gastrointestinal digestive release property, as well as improved in vitro antioxidant and anticancer activities. This study may contribute to the development of RES oral delivery systems and the application of hydrophobic active molecules in the functional food field.


Fistula complications of diverticular disease.
Right-sided sliding inguinal hernias usually involve the cecum and occasionally the ascending colon. Colocutaneous fistulas secondary to diverticular disease are rare and usually present with a short tract to the anterior abdominal wall. The authors describe a case of colocutaneous fistula secondary to diverticular disease in an inguinal hernia and review fistula formation after diverticular disease.


Drug-drug interactions evaluated by a highly active reconstituted native human cytochrome P4503A4 and human NADPH-cytochrome P450 reductase system.
Catalytic activities of native human CYP3A4-mediated reactions as well as drug interactions were directly evaluated by isolated reconstituted human CYP3A4: NADPH-cytochrome P450 reductase systems. The SDS-PAGE pure CYP3A4 and human NADPH-cytochrome P450 reductase had been incorporated into a binary vesicular phospholipid system of dilauroyl-phosphatidyl-choline and phosphatidyl-serine which had proven to achieve optimal nifedipine oxidase activity (19.6 nmol nifedipine oxidized x min(-1) x nmol CYP3A4(-1)). The IC50 values of ketoconazole (CAS 65 277-42-1) (approximately 3 micromol/l), quinidine (CAS 56-54-2) (approximately 5 micromol/l), mifepristone (CAS 84 371-65-3) (-8 micromol/l), 17alpha-ethinylestradiol (CAS 57-63-6) (approximately 17 micromol/l), cimetidine (CAS 51 481-61-9) (approximately 46 micromol/l), FK 506 (tacrolimus) (CAS 104 987-11-3) (approximately 53 micromol/l), naringenin (CAS 480-41-1) (approximately 87 micromol/l), and cyclosporine A (CAS 59 865-13-3) (approximately 90 micromol/l) indicate that all these drugs have an inhibitory effect on nifedipine (CAS 21 829-25-4) metabolism, whereas the drug quinine (CAS 130-95-0) did not elicit any significant inhibition.


Immunopharmacological profile of a novel isoxazol derivative, HWA 486, with potential antirheumatic activity--I. Disease modifying action on adjuvant arthritis of the rat.
The new isoxazol derivative, N-(4-Trifluoro-methylphenyl)-5-methylisoxazol-4-carboxamide (HWA 486) has been investigated as to its disease modifying activity on adjuvant arthritis of the Lewis rat. This compound was able to prevent the onset of the adjuvant disease, provided the therapy was started within the first 12 days after its induction, reflecting properties similar to that of immunosuppressive agents. If therapy started later than 12 days, the substance was still able to reduce the degree of inflammation and arrest its progress as long as it was administered, i.e. termination of the therapy, after the establishment of adjuvant arthritis, allowed the disease to progress, a property similar to classical anti-inflammatory agents such as indomethacin. The stimulation of lymphocytes from adjuvant arthritic rats with ConA, PHA, and LPS was suppressed. Treatment of these animals with HWA 486 returned the mitogenic response to normal values. However, the lymphocytes from non-diseased animals were not affected by treatment with this substance. Cyclophosphamide, on the other hand, which also can prevent the establishment of the disease, reduces the proliferative response to mitogens in healthy animals. The characteristics of HWA 486 distinguish it from either classical anti-inflammatory drugs, such as phenylbutazone, or classical immunosuppressive agents, such as cyclophosphamide.


Dexamethasone therapy and Candida sepsis in neonates less than 1250 grams.
To determine whether dexamethasone use increases the risk for Candida sepsis (CS) in very low birth weight premature infants (<1250 g). Retrospective chart review of all infants with a birth weight <1250 g, admitted to the neonatal intensive care unit of the MetroHealth Medical Center, Cleveland, Ohio between January 1, 1996 and December 31, 1999. Infant groups with (n=65) and without (n=229) CS were compared. Two hundred and ninety four infants with a birth weight <1250 g were identified. CS was diagnosed at a median age of 18 days, and 6 of 65 (10%) infants died directly from Candida-related complications. Candida albicans (n=30, 60%) and Candida parapsilosis (n=14, 25%) were the predominant isolates. Use of dexamethasone in infants at risk for chronic lung disease before 14 days of age (p=0.001), duration of antibiotics (p=0.001), and total duration of parenteral nutrition and intralipid (p=0.0001) were all significantly greater in infants who developed CS. Regression analysis showed that duration of antibiotics before the diagnosis of Candida infection (r(2)=0.69, p=0.0002) and duration of dexamethasone (r(2)=0.93, p=0.0002) correlated with Candida infection. Early dexamethasone use was also related to the age at diagnosis of Candida infection (r(2)=0.51, p=0.01). Dexamethasone therapy and prolonged duration of antibiotics are associated with Candida infection in premature infants.


Renal arterial embolization in cases of renal neoplasms. Own experiences.
Observations of 17 embolizations of the renal artery carried out in cases of renal neoplasms are reported. In the light of intraoperative observations the optimal timing of the operation after embolization was established to be 48-72 hours. Attention is called to the possibility of complications in the form of spinal cord damage after renal arterial embolization.


Response to Comment on "No consistent ENSO response to volcanic forcing over the last millennium".
Robock claims that our analysis fails to acknowledge that pan-tropical surface cooling caused by large volcanic eruptions may mask El Niño warming at our central Pacific site, potentially obscuring a volcano-El Niño connection suggested in previous studies. Although observational support for a dynamical response linking volcanic cooling to El Niño remains ambiguous, Robock raises some important questions about our study that we address here.


Studies on photochemical reactions of air pollutants. XIV.Photooxidation of sulfur dioxide in air by various air pollutants.
Upon exposure to sunlight, or to artificial light at wavelengths longer than 290 nm, sulfur dioxide in air underwent oxidation to give sulfur trioxide in the presence of air pollutants such as biacetyl (2,3-butanedione), benzaldehyde and nitrogen dioxide, but not in their absence. Only nitrogen dioxide completely oxidized sulfur dioxide to sulfur trioxide.


Investigation of non-motor symptoms in patients with amyotrophic lateral sclerosis.
[Objective] Few studies have comprehensively investigated the non-motor symptoms of amyotrophic lateral sclerosis (ALS). We aimed to investigate this aspect of ALS. [Methods] We held a nationwide webinar, titled "ALS Café," and distributed self-report questionnaires to ALS patients. In addition to the frequency of non-motor symptoms such as fatigue, pain, sleep disorders, defecation disorders, sialorrhea, and sexual problems, we evaluated the quality of life (QoL), ALS Functional Rating Scale-Revised (ALSFRS-R), and Patient Health Questionnaire-9 (PHQ-9). [Results] The average age of the 33 respondents (19 male, 14 female) was 60.8 ± 11.2; 96.7% of respondents had some non-motor symptoms. The median ALSFRS-R was 32.0, and seven (21.2%) of the respondents had a PHQ-9 score of 10 or higher. Fatigue was the most common non-motor symptom (81.8%), followed by pain (60.6%), defecation disorders (57.6%), sleep disorders (48.5%), sialorrhea (48.5%), and sexual problems (24.2%). Fatigue was more frequent in females (P = 0.03). Among the non-motor symptoms, pain was the most common factor affecting QoL, followed by fatigue. More than 90% of ALS patients answered that they had never consulted a physician/counselor about sexual problems. Patients with pain had higher PHQ-9 scores than those without (P = 0.01). There was no correlation between the ALSFRS-R score and QoL and PHQ-9. [Conclusions] Most patients with amyotrophic lateral sclerosis had non-motor symptoms, and fatigue and pain were the most common. We showed that many non-motor symptoms affected QoL without correlating with ALSFRS-R score. Attention should be paid to those even if the motor symptoms of ALS are mild.


Orbital diseases mimicking graves' orbitopathy: a long-standing challenge in differential diagnosis.
Graves' orbitopathy (GO) is the most common cause of orbital tissue inflammation, accounting for ~ 60% of all orbital inflammatory conditions in the population aged 21-60 years, and for ~ 40% in the population aged > 60 year. GO is observed in 25-30% of patients with Graves' hyperthyroidism and more rarely in association with hypothyroid autoimmune thyroiditis. In addition, a small proportion of GO patients (1-2%) do not have a clinically overt thyroid dysfunction. Clinically, GO is characterized by proptosis, inflammation involving the eyelids and the conjunctiva, extraocular muscle hypertrophy, with consequent reduction of ocular motility and diplopia, and in the most severe cases, compression of the optic nerves at the orbital apex, with reduction of visual acuity. At CT scan or MRI, a muscle increase involving the superior, medial and inferior rectus is quite typical. In the most severe forms, compression of the optic nerves at the orbital apex can be observed. Euthyroid GO is usually an early sign of a full-blown Graves' disease; however, in some cases, the orbital disease can remain isolated. Moreover, euthyroid GO can rarely be unilateral, which makes the picture even more confusing. Under those circumstances, the diagnostic process becomes obviously quite difficult, having other conditions mimicking GO been excluded. A number of inflammatory conditions affecting orbital tissue can mimic GO, thereby requiring an accurate evaluation for a proper differential diagnosis. The majority of these conditions are immune mediated. Most of them are benign, but they can be rather aggressive and some can cause visual loss. The most common inflammatory condition affecting orbital tissues and mimicking GO is idiopathic orbital inflammation. Other, more rare, orbital diseases that should be considered in the differential diagnosis are infections, orbital manifestations of systemic diseases, primitive and secondary orbital neoplasms, and orbital vascular alterations. In most instances, when an orbitopathy occurs in the absence of hyperthyroidism, the diagnosis of the disease underlying the ocular symptoms and signs is based on exclusion of the other conditions. Here we review the conditions that can mimic GO and how to distinguish them from this obnoxious eye disease.


Differences in the inhibitory effects of N-(1-n-dodecyl)-heterocycles on the 2,3-oxidosqualene lanosterol-cyclase of rat liver and yeast.
The ability of thirteen N-(1-n-dodecyl)-heterocyclic compounds and one N-(1-n-fluoroalkyl)-heterocyclic compound to inhibit the 2,3-oxidosqualene lanosterol-cyclase of rat liver and yeast has been tested. Eight of the N-(1-n-dodecyl)-heterocycles inhibited the rat liver enzyme well but none inhibited the yeast enzyme at 100 microM concentrations. The N-(1-fluoroalkyl)-heterocycle inhibited the rat liver enzyme mildly but did not inhibit the yeast enzyme at 100 microM concentration. It is evident that the rat liver and yeast cyclases are different; the possible nature of these differences is discussed.


Brand substitution or multiple switches per patient? An analysis of pharmaceutical brand substitution in Australia.
To determine the number of times patients have brand and generic products substituted under Australia's Pharmaceutical Benefits Scheme (PBS) brand substitution policy. A retrospective cohort study was conducted using Repatriation Pharmaceutical Benefits Scheme (RPBS) pharmacy claims data. Department of Veterans' Affairs (DVA) treatment card holders with at least two dispensings of atenolol, citalopram, enalapril, metformin, omeprazole or ramipril between 1 January 2001 and 28 February 2006 were included. Patients were followed from first dispensing until death, cessation or study end. The main outcome measure was the number of substitutions per patient during follow-up. Based on this, patients were defined as non-switchers, brand substitution or multiple switchers. Data for 160,145 patients were analysed. Overall more than 80% of patients either had no switches or demonstrated brand substitution. For all study drugs, patients were more likely to be non-switchers than have a brand substitution (RR range 2.6-9.4, p < 0.0001) and were more likely to be non-switchers than multiple switchers (RR range 3.2-35.9, p < 0.0001). Patients who switched were more likely to have a brand substitution than multiple switches (RR range 1.2-3.8, p < 0.0001). Multivariate logistic regression showed greater odds of being a multiple switcher with increasing number of prescribers and dispensing pharmacies, and increasing length of follow-up. Most patients in this study did not substitute products, and those who did were more likely to demonstrate brand substitution than have multiple switches. These results suggest that the brand substitution policy is having its intended effect for most patients.


Psychologists' Contributions to Medical Education and Interprofessional Education in Medical Schools.
Recognition of the importance of behavioral and psychological phenomena has grown. Patients and physicians are receptive to psychological insights and processes in health and healthcare. Psychologists serve in diverse roles in medical schools, spanning activities such as didactics, rounds, precepting, supervising, mentoring, participating in educational projects, directing courses, and serving on educational committees. They address multiple content areas fundamental to medicine. Their participation in medical education and professional development activities for faculty are well-regarded. As healthcare becomes more interprofessional, with services delivered via interprofessional teams, opportunities for psychologists to contribute to, and play leadership roles in, interprofessional education (IPE) are expanding. It is critical that psychologists seize them. This article reviews psychologists' historic roles in medical education and provides a snapshot of their educational, faculty development, and IPE activities based on the 2017 survey of members of the Association of Psychologists in Academic Health Centers and their colleagues.


The relation between tidal volume and inspiratory and expiratory times during steady-state carbon dioxide inhalation in man.
1. Ambiguities and discrepancies in the published descriptions of the patterns of breathing in man have been re-investigated.Steady-state hyperpnoea during rest was induced in normal subjects of both sexes by means of CO(2) inhalation, usually in high O(2), but sometimes in low (P(A, O2) approximately 200 and 55 torr respectively).2. The relations between mean tidal volume V(T) and mean times for inspiration T(I) and expiration T(E) were satisfactorily divided into lower and upper parts (ranges 1 and 2) in nineteen out of thirty-three experiments using an objective least-squares method, and polynomials were fitted separately to each of the following pairs of variables V(T,lower), T(I); V(T,lower), T(E); V(T,upper), T(I); V(T,upper), T(E).3. The breakpoints occurred when V(T) was about one third of vital capacity, but there was much variation between subjects.4. In range 2, V(T) was inversely related to both T(I) and T(E) and there appeared to be linkage between T(I) and T(E), all as described by Clark & Euler (1972). The relation suggested by Hey, Lloyd, Cunningham, Jukes & Bolton (1966) over range 2 was not confirmed.5. The main part of the relation described by Hey et al. (1966) is concerned with range 1. Here the relation between V(T) and T(I) was variable; slight, but significant negative correlation predominated. V(T) was, on the other hand, strongly and inversely related to T(E), and plots of (T(E) - T(I)) against V(T) over both ranges showed even less scatter. Hence (a) T(E) is probably related to V(T) through two mechanisms, one involving a link with T(I) and another prominent one being quite independent of T(I), (b) most changes of respiratory frequency in normal man are brought about by change of T(E) rather than of T(I), and (c) there is no region of constant frequency as implied by Clark & Euler (1972).


Ovarian aging and the perimenopausal transition: the paradox of endogenous ovarian hyperstimulation.
The purpose of this review is to put into a useful clinical context the changing over time of basic ovarian-pituitary-hypothalamic relationships during perimenopause. "Perimenopause" means changes in ovarian hormones, feedback relationships, and clinical experiences beginning in women ages 35-50 with regular flow and ending 1 yr after the final menstrual flow. A key observation must be explained--estradiol levels are increased in perimenopause. Inhibin B levels are lower and activin may be higher in midlife, menstruating women. These changes probably cause higher follicular phase FSH levels--"endogenous ovarian hyperstimulation" results. The positive estradiol feedback on LH is also disturbed--midcycle LH peaks and mid-luteal slow-frequency, high-amplitude LH pulses are less frequent. In addition to higher levels, estradiol receptors may increase in tissues of symptomatic women. Despite hyperstimulation of follicles, progesterone levels and luteal phase lengths are paradoxically decreased--reasons probably include LH peak disruptions and estrogen-stimulated greater corticotrophin-mediated reproductive suppression. In summary, disturbed feedback relationships causing higher and unpredictable estrogen and lower progesterone levels occur throughout perimenopause, especially during regular cycles. Prospective, population-based research is needed to systematically relate these feedback hormonal changes to clinical characteristics and to allow a diagnosis of perimenopause in regularly cycling midlife women.


A bibliometric analysis of the 100 most influential papers on peritoneal dialysis.
We aimed to identify the 100 most cited articles published on peritoneal dialysis (PD) and analyze their characteristics to provide information on the achievements and developments of PD research over the past decades. The Science Citation Index Expanded (SCIE) in the Web of Science Core Collection was comprehensively searched from 2000 to 2018, using the keywords "Peritoneal dialysis" or "Dialyses, Peritoneal" or "Dialysis, Peritoneal" or "Peritoneal Dialyses". The top 100 cited articles were retrieved by reading titles and abstracts. Significant information was further elicited, including the authors, journals, countries, institutions, and publication year. The United States was the most productive country (n = 51), Li Pkt published the highest number of papers (n = 7), the Journal of the American Society of Nephrology produced the highest number of contributions (n = 28), and Baxter International Inc., the University of California System, and the University of Toronto were the institutions with the highest number of articles (n = 10). This is the first bibliometric study to identify the most influential papers in PD research. This report describes the major changes and advances in research regarding PD as a guide for writing a citable article.


18F-Fluorodeoxyglucose positron emission tomography in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors: a systematic review.
To systematically review the role of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) in evaluating treatment response to imatinib or other drugs in gastrointestinal stromal tumors (GIST). A comprehensive literature search of published studies through February 2011 in PubMed/MEDLINE and EMBASE databases was performed. We identified 19 studies including 628 patients with GIST. Main findings of included studies are presented. (18)F-FDG PET has a significant value in assessing treatment response to imatinib or other drugs in GIST patients. (18)F-FDG PET allows an early assessment of treatment response and is a strong predictor of clinical outcome.


When English proposes what Greek presupposes: the cross-linguistic encoding of motion events.
How do we talk about events we perceive? And how tight is the connection between linguistic and non-linguistic representations of events? To address these questions, we experimentally compared motion descriptions produced by children and adults in two typologically distinct languages, Greek and English. Our findings confirm a well-known asymmetry between the two languages, such that English speakers are overall more likely to include manner of motion information than Greek speakers. However, mention of manner of motion in Greek speakers' descriptions increases significantly when manner is not inferable; by contrast, inferability of manner has no measurable effect on motion descriptions in English, where manner is already preferentially encoded. These results show that speakers actively monitor aspects of event structure, which do not find their way into linguistic descriptions. We conclude that, in regard to the differential encoding of path and manner, which has sometimes been offered as a prime example of the effects of language encoding on non-linguistic thought, surface linguistic encoding neither faithfully represents nor strongly constrains our mental representation of events.


Analysis of the relationship of insulin-like growth factor-1 to the growth velocity and feeding of healthy infants.
Infancy is the fastest growth period in a child's development after birth, but little is known about hormonal regulation mechanism for the growth and development of this period. The objective of this study is to analyze the trend of serum IGF-1 levels in healthy infants and the relationship of IGF-1 to the growth velocity and feeding method of infants. Population-based birth cohort study. The study was conducted in the Third Hospital of Peking University. Study participants were 484 healthy infants, all of whom were full-term and appropriate for gestational age (238 boys and 246 girls). Interventions were anthropometrical measurements, feeding methods recorded every 1 to 2 months and serum samples (2, 4, 6, 8, 10,12 months). Height, weight, feeding methods and serum IGF-1 were the main outcome measures. Serum IGF-1 levels decreased in the following 2 months in boys but in females levels remained relatively high between 2 to 3 months after birth and then started to decrease. It reached the lowest point at Months 7-8, and was on a slow rise in both male infants and female infants thereafter. Serum IGF-1 levels were significantly higher in female infants [112.65 ng/ml (CI 91.82, 133.89)] than in male infants [74.38 ng/ml (CI 53.14, 95.61)] at early infancy. Infants fed with human milk had lower serum IGF-1 levels than infants fed with formula milk or human milk plus formula milk (66.94 ± 45.85 ng/ml, 72.56 ± 36.55 ng/ml, 79.89 ± 51.79 ng/ml, respectively; P = 0.019). IGF-1 levels were positively correlated to the growth velocity of body length (P<0.01). This study provides the trend for IGF-1 levels at infancy. It is highly possible that IGF-1 plays an important role in the regulation and control of length increases in infants, and feeding method influences serum IGF-1 levels.


Large-scale mapping of human protein interactome using structural complexes.
Although the identification of protein interactions by high-throughput (HTP) methods progresses at a fast pace, 'interactome' data sets still suffer from high rates of false positives and low coverage. To map the human protein interactome, we describe a new framework that uses experimental evidence on structural complexes, the atomic details of binding interfaces and evolutionary conservation. The structurally inferred interaction network is highly modular and more functionally coherent compared with experimental interaction networks derived from multiple literature citations. Moreover, structurally inferred and high-confidence HTP networks complement each other well, allowing us to construct a merged network to generate testable hypotheses and provide valuable experimental leads.


Splenic storage volume in the unanesthetized resting beagle.
Determination of the dog's splenic storage volume without surgical procedures requires measurement of both circulating and total red cell volumes. The estimation of circulating red cell volume by radioisotope techniques is impeded by the rapid uptake of tagged cells in the spleen. The circulating cell volume might be calculated from plasma volume and large vessel hematocrit, provided that the latter is corrected for the unequal distribution of red cells in the circulatory system. However, the correction factor can only be estimated in the splenectomized dog. We describe here a method to determine the factor in the intact dog, "physiologically splenectomized" by the severe exercise. The values obtained by this method slightly exceed those in the resting dog, as shown by studies in splenectomized exercising beagles in which splenic function was simulated by infusion of packed cells. The method was tested in beagles exercised by swimming and treadmill running and it was concluded that in the unanesthetized resting beagle about one-third of all erythrocytes is stored in the spleen. Labeled cells are equilibrated with about one-half of the splenic storage volume within 10 min after their injection. During maximal exertion the mean increase in large vessel hematocrit was 38.6 +/- 3.3%, the mean decrease in plasma volume 13.6 +/- 1.7% and the mean increase in plasma osmolarity 2.8 +/- 0.9% (percentages of control values).


To GP or not to GP: a natural experiment in children triaged to see a GP in a tertiary paediatric emergency department (ED).
To evaluate the impact of integrating a general practitioner (GP) into a tertiary paediatric emergency department (ED) on admissions, waiting times and antibiotic prescriptions. Retrospective cohort study. Alder Hey Children's NHS Foundation Trust, a tertiary paediatric hospital in Liverpool, UK. From October 2014, a GP was colocated within the ED, from 14:00 to 22:00 hours, 7 days a week. Children triaged green on the Manchester Triage System without any comorbidities were classed as 'GP appropriate'. The natural experiment compared patients triaged as 'GP appropriate' and able to be seen by a GP between 14:00 and 22:00 hours (GP group) to patients triaged as 'GP appropriate' seen outside of the hours when a GP was available (ED group). Intention-to-treat (ITT) analysis was used to assess the main outcomes. 5223 patients were designated as 'GP appropriate'-18.2% of the total attendances to the ED over the study period. There were 2821 (54%) in the GP group and 2402 (46%) in the ED group. The median duration of stay in the ED was 94 min (IQR 63-141) for the GP group compared with 113 min (IQR 70-167) for the ED group (p<0.0005). Using the ITT analysis equivalent, we demonstrated that the GP group were less likely to: be admitted to hospital (2.2% vs 6.5%, OR 0.32, 95% CI 0.24 to 0.44), wait longer than 4 hours (2.3% vs 5.1%, OR 0.45, 95% CI 0.33 to 0.61) or leave before being seen (3.1% vs 5.7%, OR 0.53, 95% CI 0.41 to 0.70), but more likely to receive antibiotics (26.1% vs 20.5%, OR 1.37, 95% CI 1.10 to 1.56). Sensitivity analyses yielded similar results. Introducing a GP to a paediatric ED service can significantly reduce waiting times and admissions, but may lead to more antibiotic prescribing. This study demonstrates a novel, potentially more efficient ED care pathway in the current context of rising demand for children's emergency services.


Blended fabric with integrated neural network based on attention mechanism qualitative identification method of near infrared spectroscopy.
Near Infrared spectroscopy (NIRS) qualitative analysis technology has shown excellent development potential in the field of blend fabrics. However, the qualitative detection method based on the convolutional neural network (CNN) is difficult to accurately extract the feature of the spectral data, which will lead to missing detection or false detection; when using deep learning to build a qualitative detection model, due to interference of the external environment and other factors, the spectral data collected may have outliers, this means that the knowledge generalization on anomalous testing data, which may have a different distribution of that of the training set, is not trivial, which will also lead to missing detection or false detection. To solve the above problems, this paper proposes a novel qualitative detection neural network by analyzing the near infrared spectral data of blend fabrics. Firstly, we remove the convolutional layer and pooling layer of the CNN, making full use of the feature to enhance the feature representation ability of the model. Secondly, adding the L1 norm of the feature coefficients as a penalty term to the loss function to force those features with high redundancy to become weaker. Thirdly, in order to improve the recognition accuracy of the anomalous spectral data and minimize the model uncertainty, an ensemble machine learning approach utilizing 5 neural networks in parallel is used. To show the superiority of our proposed method, the existing methods are used as competitive methods to compare with our method. Our homemade dataset contains 3482 samples of blend fabrics with 9 different compositions. The results show that the Micro-F1-score, Micro-Specificity, Weight-F1-score, and Weight-Specificity of this method respectively 99.71%, 99.96%, 99.73%, and 99.99%, the results further confirm the method has higher analysis accuracy and stability. In addition, the method proposed in this paper can greatly improve the recognition accuracy of the anomalous spectral data. It has important practical value in the qualitative detection of blend fabrics.


3 Tesla turbo-FLASH magnetic resonance imaging of deglutition.
In this article we describe a methodology for obtaining high-quality dynamic magnetic resonance imaging (MRI) sequences of the swallow sequence in healthy volunteers. The study includes comparison to previous work done in our lab using a 1.5 Tesla (T) magnet. Case series. Three healthy volunteers underwent turbo-fast low angle shot MRI at 3T while swallowing liquid boluses delivered via intravenous tubing to the oral cavity. Imaging was performed in the sagittal and axial planes. Imaging provided by this sequence provided high temporal resolution, with the ability to depict deglutition in the axial and sagittal planes. Comparison with imaging at 1.5 T demonstrated benefits in temporal resolution and signal-to-noise. Anatomic information provided differed from comparative videofluoroscopy. MRI of swallowing using the described technique is reliable and provides a unique evaluation of the swallowing sequence.


[Enzyme arrangement of various tissues in swine. 1. Studies of the effect of 32 hours of fasting, administration of actinomycin D, and fasting in combination with administration of actinomycin D on crude protein level, activities of GOT, GTP, fructose-1,6-diphoaphatase as well as ATPase of liver, kidneys and semitendinous muscle in newborn piglets].
The effects of sufficient milk intake as well as of 32 hours of fasting after birth, administration of actinomycin D (intraperitoneal application of 1 mg/kg five weight), and fasting in combination with actinomycin D on the development of body and liver weights, crude protein levels in homogenate and supernatant of liver, kidneys, and M. semitendinosus as well as on the activities of certain tissue enzymes were analysed with four groups of piglets (n = 4). Fasting, administration of actinomycin, and fasting in combination with actinomycin D resulted in rapid reduction in body and liver weights, while the crude protein levels in those tissues were not affected with significance. GOT and fructose-1,6-diphosphatase activities in supernatant from liver tended to decline under fasting conditions. The ATPase activity in the homogenate of the above tissues did not change in response to differentiated treatment.


Effect of ingesting caffeine and ephedrine on 10-km run performance.
The ingestion of either caffeine (C) or ephedrine (E) has been shown to improve performance during high-intensity aerobic activity lasting 10-20 min, with an additive effect being found when the combination (C + E) was ingested. It was the purpose of this study to determine if the addition of E to C would improve performance in activity lasting longer than 20 min. One and one half hours after ingesting a placebo (P), C (4 mg/kg), E (0.8 mg/kg), or C + E, 12 subjects performed a 10-km run while wearing a helmet and backpack weighing 11 kg. The trials were performed in a climatic suite at 12-13 degrees C, on a treadmill where the speed was regulated by the subject. VO(2), VCO(2), V(E), heart rate (HR), and rating of perceived exertion (RPE) were measured during the run at 15 and 30 min, and again when the individual reached 9 km. Blood was sampled at 15 and 30 min and again at the end of the run and assayed for lactate, glucose, and catecholamines. Run times (mean +/- SD), in minutes, were for C (46.0 +/- 2.8), E (45.5 +/- 2.9), C + E (45.7 +/- 3.3), and P (46.8 +/- 3.2). The run times for the E trials (E and C + E) were significantly reduced compared with the non-E trials (C and P). Pace was increased for the E trials compared with the non-E trials over the last 5 km of the run. VO(2) was not affected by drug ingestion. HR was elevated for the ephedrine trials (E and C + E). RPE remained similar for all trails. Caffeine increased the epinephrine and norepinephrine response associated with exercise and also increased blood lactate, glucose, and glycerol levels. Ephedrine reduced the epinephrine response but increased dopamine and FFA levels. The previously seen additive nature of E and C was not evident in this study, with the primary ergogenic effect being attributed to E.


Adaptive hypersensitivity to estradiol: potential mechanism for secondary hormonal responses in breast cancer patients.
Women with hormone dependent breast cancer initially respond to hormone deprivation therapy with tamoxifen or oophorectomy for 12-18 months but later relapse. Upon secondary therapy with aromatase inhibitors, patients often experience further tumor regression. The mechanisms responsible for secondary responses are unknown. We postulated that hormone deprivation induces hypersensitivity to estradiol. Evidence of this phenomenon was provided in a model system involving MCF-7 cells grown in vitro and in xenografts. To determine if the ER transcriptional process is involved in hypersensitivity, we examined the effect of estradiol on ER reporter activity, PgR, PS2, and c-myc as markers and found no alterations in hypersensitive cells. Next, we examined whether MAP kinase may be upregulated in the hypersensitive cells as a reflection of increased growth factor secretion or action. Basal MAP kinase activity was increased both in vitro and in vivo in hypersensitive cells. Proof of principle studies indicated that an increase in MAP kinase activity induced by TGFalpha administration caused a two- to three-fold shift to the left in estradiol dose response curves in wild type cells. Blockade of MAP kinase with PD98059 returned the shifted curve back to baseline. These data suggested that MAP kinase overexpression could induce hypersensitivity. To determine why MAP kinase was increased, we excluded constitutive receptor activity and growth factor secretion by the demonstration that the pure anti-estrogen, ICI 182780, could inhibit MAP kinase activation. We also excluded hypersensitivity to estradiol induced growth factor secretion, and thus MAP kinase activation, since estradiol stimulated MAP kinase at 24, 48, and 72 h at the same concentrations in hypersensitive as in wild type cells. Surprisingly, a series of experiments suggested that MAP kinase increased in hypersensitive cells as a result of estrogen activation via a non-genomic pathway. We examined the classical signal pathway in which SHC is phosphorylated and binds to SOS and GRB-2 to activate Ras, Raf, and MAP kinase. With 5-20 min of exposure, estradiol caused binding of SHC to the estrogen receptor, phosphorylation of SHC, binding of GRB-2 to SOS, and activation of MAP kinase. All of these affects could be blocked by ICI 182780. Taken together, these observations suggest that the cell membrane ER pathway may be responsible for upregulation of MAP kinase and hypersensitivity in cells adapted to estradiol deprivation.


Enzymes and sensitization via skin exposure: A critical analysis.
Some proteins, including enzymes, can induce allergic sensitization of various types, including allergic sensitization of the respiratory tract. There is now an increased understanding of the role that the skin plays in the development of IgE-mediated allergy and this prompts the question whether topical exposure to enzymes used widely in consumer cleaning products could result in allergic sensitization. Here, the evidence that proteins can interact with the skin immune system and the way they do so is reviewed, together with a consideration of the experience gained over decades of the use of enzymes in laundry and cleaning products. The conclusion drawn is that although transcutaneous sensitization to proteins can occur (typically through compromised skin) resulting in IgE antibody-mediated allergy, in practice such skin contact with enzymes used in laundry and cleaning products does not appear to pose a significant risk of allergic disease. Further, the evidence summarized in this publication support the view that proteins do not pose a risk of allergic contact dermatitis.


Reporting Policies in Neurosurgical Journals: A Meta-Science Study of the Current State and Case for Standardization.
Reporting quality within the neurosurgical literature is low, limiting the ability of journals to act as gatekeepers for evidence-based neurosurgical care. Journal policies during article submission aim to improve reporting quality. We conducted a meta-science study characterizing the reporting policies of neurosurgical journals and other related peer-reviewed publications. Journals were retrieved in 7 searches using Journal Citation Reports and Google Scholar. Characteristics, impact metrics, and submission policies were extracted. Of 486 results, 54 journals were included, including 27 neurosurgical and 27 related topical journals. Thirty-eight (70.4%) adopted authorship guidelines and 20 (37.0%) disclosure standards of the International Council of Medical Journal Editors. Twenty-six (48.1%) required data availability statement and 33 (61.1%) clinical trials registration. Twenty-one (38.9%) required and 11 (20.4%) recommended adherence to reporting guidelines. Twenty (37.0%) endorsed EQUATOR network guidelines. PRISMA was mentioned by 30 (55.6%) journals, CONSORT by 28 (51.9%), and STROBE by 18 (33.3%). Among neurosurgical journals, factors associated with a requirement or recommendation to follow reporting guidelines among neurosurgical journals included impact factor (P = 0.0013), Article Influence Score (P = 0.0236), SCImago h-index (P = 0.0152), SCImago journal rank (P = 0.002), and CiteScore (P = 0.0023), as well as recommendations pertaining to International Council of Medical Journal Editors authorship guidelines (P = 0.0085), ORCID (P = 0.014), clinical trials registration (P = 0.0369), or data availability statement (P = 0.0047). CONSORT, PRISMA, or STROBE delineations were significantly associated with the mention of another guideline (P < 0.01). Neurosurgical journal submission policies are inconsistent. Frameworks to improve reporting quality are uncommonly used. Increasing rigor and standardization of reporting policies across journals publishers may improve quality.


HIV in adolescents: what we know and what we need to know.
HIV, the cause of AIDS, has infected more than 65 million people worldwide, including 1 million children. An estimated 39.5 million people are living with HIV. As of 2006, 4.3 million were newly infected, with 2.8 million occurring in sub-Saharan Africa. Rates of infection have risen more than 50% in Eastern Europe and Central Asia. Mother-to-child transmission occurs rarely with antiretroviral treatments in the United States, and congenitally infected children are living to adulthood. HIV is now a "youth-driven disease" worldwide. In the United States, 40% of new HIV infections occur in individuals less than 25 years old, and HIV is the sixth-leading cause of death among adolescents. Young people with HIV/AIDS live with this chronic condition and its associated medical and psychological morbidities while coping with identity and maturation issues. In this paper, we review what we know about HIV and psychiatric disorders among adolescents.


An improved sedimentation technique for the cytologic preparation of cerebrospinal fluid cells.
The conventional CSF cell preparation methods suffer from a poor cell recovery rate (mean rates of 10-50% with the sedimentation techniques, which makes it unlikely, that the cell sampling on the slide is representative) or from suboptimal cell visualization (filter techniques). An improved sedimentation technique is described with a mean recovery rate of 80% and excellent cell visualization.


Changes in the inducibility of a hepatic aldehyde dehydrogenase by various effectors.
A hepatic soluble aldehyde dehydrogenase (ALDH), inducible by polycyclic aromatic hydrocarbons, was studied in Wistar rats in connection with substances known to affect drug metabolism or aldehyde dehydrogenase activity, such as phenobarbital (PB), disulfiram (DS), beta-diethylaminoethyl diphenylpropylacetate (SKF 525A) and calcium cyanamide (CC). 3-Methylcholanthrene (MC) was given as a model inducer of ALDH (100 mg/kg, i.p., as a single dose) and the animals were killed after 3 days. Pretreatment with PB (1 g/l drinking water, for 2 weeks) enhanced the inducing effect of MC. On the contrary, pretreatment with DS (100 mg/kg, i.p., daily x 4) reduced by 70% the expected increase in ALDH activity. Neither SKF 525A (25 mg/kg, i.p., daily x 4), nor CC (5 mg/kg, i.p., daily x 4) could affect the action of the inducer. At the above doses, basal ALDH activity was inhibited by DS (30%) and CC (70%), but was not affected at all by PB or SKF 525A. The results were somewhat different when the various effectors tested were administered to animals already treated with MC (20 mg/kg, i.p., daily x 6). In this case, DS did not affect the already induced ALDH activity. On the contrary, CC was still an effective inhibitor. Unexpectedly, post-treatment with SKF 525A further enhanced the initial induction brought about by MC. Our findings show that substances affecting microsomal drug metabolism can interfere with the process of ALDH induction by MC. The additive result of PB pretreatment is probably due to the enhanced accumulation of an active metabolite of MC.(ABSTRACT TRUNCATED AT 250 WORDS)


Central nervous system blast crisis in chronic myeloid leukemia on imatinib mesylate therapy: report of two cases.
Chronic myeloid leukaemia is a chronic myeloproliferative disorder characterised by a reciprocal translocation between chromosomes 9 and 22 and thereby formation of the Philadelphia chromosome. Imatinib mesylate (STI-571) is a potent and selective inhibitor of BCR-ABL tyrosine kinase and has emerged as a treatment of choice in chronic myeloid leukaemia (CML) patients in chronic phase. It has shown activity in CML patients in the chronic phase or blastic phase. However there is poor penetration of the central nervous system (CNS) by the drug or its active metabolites. Therefore the CNS acts as a sanctuary site for malignant cells for CML patients treated with Imatinib. We report cases of two CML patients on Imatinib therapy, who were in haematological remission but developed CNS disease.


Clinical characteristics of visual motion hypersensitivity: a systematic review.
This qualitative systematic review presents an overview of the state of the research relating to visual motion hypersensitivity (VMH) and offers a reference tool for future studies in the field. The study set out to identify and collate articles investigating risk groups with aberrant responses to visual motion as compared to healthy control groups, presenting evidence for risk factors associated with visual motion hypersensitivity. Data were synthesized into the state of the research and analyzed in the context of the clinical characteristics of each risk factor. Literature searches were performed on Medline Ovid, EMBASE, Web of Science, and Cinahl, identifying a total of 586 studies of which 54 were finally included. Original articles published between the dates of commencement for each database and 19th January 2021 were included. JBI critical appraisal tools were implemented for each corresponding article type. In total, the following number of studies was identified for each respective risk factor: age (n = 6), migraines (n = 8), concussions (n = 8), vestibular disorders (n = 13), psychiatric conditions (n = 5), and Parkinson's disease (n = 5). Several studies described VMH as the primary concern (n = 6), though these primarily included patients with vestibulopathies. There were considerable differences in the nomenclature employed to describe VMH, depending largely on the investigating group. An overview of investigated risk factors and their evaluation methods was presented in a Sankey diagram. Posturography was the most implemented methodology but due to diverse measurements meta-analyses were not possible. One may however note that while the easily implemented Vestibular Ocular Motor Screening (VOMS) was designed for concussed patients, it may prove useful for other risk groups.


Withholding or withdrawal of life sustaining treatment for newborn infants.
In the last two decades the survival of extreme preterm infants and sick newborn infants has improved significantly due to the advances in perinatal medicine. Despite this advance, for some babies, withholding or withdrawal of life sustaining treatment may be the best option in the interest of the baby. An overview of when to consider withholding or withdrawal of life sustaining treatment is described. The decision making process and factors influencing parents decision, how to resolve disagreement, what treatment can be withheld or withdrawn are explained. High quality palliative care must be provided after withholding or withdrawal of life sustaining treatment.


Mumps in a boarding school: description of an outbreak and control measures.
The number of cases of mumps in the UK has increased during 2004-2005. Understanding why some people are more susceptible to mumps infection will help target vaccination and other control measures in the future. This paper describes a mumps outbreak in a boarding school in Scotland (October to November 2004). To describe the characteristics of cases in a mumps outbreak; and to conduct a case-control study looking at the effect of previous measles-mumps-rubella (MMR) vaccination. Descriptive epidemiology. Clinical, laboratory and surveillance data. A private school with 600 boarding and day pupils. Fifty cases were notified to the public health department as having mumps. Twenty of the cases (40%) were confirmed virologically, all born between 1987-1991. A matched case-control study was conducted to explore the effect of prior MMR vaccination. Compared to no vaccine, MMR protected against mumps (odds ratio = 0.7), two doses offering best protection (odds ratio = 0.5), but the study was not large enough to detect a statistically significant difference. Some children and young people in the UK are currently incompletely vaccinated. This outbreak illustrates the potential of a mumps outbreak to disrupt the medical, educational and social life of a school. All children should be vaccinated with two doses of MMR vaccine before school entry. Children and young people born between 1979-1991 should be given the necessary additional dose(s) of MMR vaccine.


An efficient method for the prediction of deleterious multiple-point mutations in the secondary structure of RNAs using suboptimal folding solutions.
RNAmute is an interactive Java application which, given an RNA sequence, calculates the secondary structure of all single point mutations and organizes them into categories according to their similarity to the predicted structure of the wild type. The secondary structure predictions are performed using the Vienna RNA package. A more efficient implementation of RNAmute is needed, however, to extend from the case of single point mutations to the general case of multiple point mutations, which may often be desired for computational predictions alongside mutagenesis experiments. But analyzing multiple point mutations, a process that requires traversing all possible mutations, becomes highly expensive since the running time is O(nm) for a sequence of length n with m-point mutations. Using Vienna's RNAsubopt, we present a method that selects only those mutations, based on stability considerations, which are likely to be conformational rearranging. The approach is best examined using the dot plot representation for RNA secondary structure. Using RNAsubopt, the suboptimal solutions for a given wild-type sequence are calculated once. Then, specific mutations are selected that are most likely to cause a conformational rearrangement. For an RNA sequence of about 100 nts and 3-point mutations (n = 100, m = 3), for example, the proposed method reduces the running time from several hours or even days to several minutes, thus enabling the practical application of RNAmute to the analysis of multiple-point mutations. A highly efficient addition to RNAmute that is as user friendly as the original application but that facilitates the practical analysis of multiple-point mutations is presented. Such an extension can now be exploited prior to site-directed mutagenesis experiments by virologists, for example, who investigate the change of function in an RNA virus via mutations that disrupt important motifs in its secondary structure. A complete explanation of the application, called MultiRNAmute, is available at [1].


The dissatisfied patient with chronic pain.
Patients with chronic pain may become dissatisfied because of their lack of improvement. Thirteen such patients, encountered in a pain-management program, registered formal complaints of their dissatisfaction. From their histories they were found to be the most chronic and treatment-refractory patients encountered, with problems of medication dependency, accident proneness, and dissatisfaction with previous treatment efforts. During hospitalization they opposed psychologic approaches, further manifested their dependency on medication, and some of them had circumscribed delusions. The pain-management program was difficult to apply to these patients; and further, they resisted other recommendations for treatment and even resisted discharge in in some instances. Further psychiatric screening is necessary to avoid the complications presented by this type of patient.


To develop a regional ICU mortality prediction model during the first 24 h of ICU admission utilizing MODS and NEMS with six other independent variables from the Critical Care Information System (CCIS) Ontario, Canada.
Intensive care unit (ICU) scoring systems or prediction models evolved to meet the desire of clinical and administrative leaders to assess the quality of care provided by their ICUs. The Critical Care Information System (CCIS) is province-wide data information for all Ontario, Canada level 3 and level 2 ICUs collected for this purpose. With the dataset, we developed a multivariable logistic regression ICU mortality prediction model during the first 24 h of ICU admission utilizing the explanatory variables including the two validated scores, Multiple Organs Dysfunctional Score (MODS) and Nine Equivalents Nursing Manpower Use Score (NEMS) followed by the variables age, sex, readmission to the ICU during the same hospital stay, admission diagnosis, source of admission, and the modified Charlson Co-morbidity Index (CCI) collected through the hospital health records. This study is a single-center retrospective cohort review of 8822 records from the Critical Care Trauma Centre (CCTC) and Medical-Surgical Intensive Care Unit (MSICU) of London Health Sciences Centre (LHSC), Ontario, Canada between 1 Jan 2009 to 30 Nov 2012. Multivariable logistic regression on training dataset (n = 4321) was used to develop the model and validate by bootstrapping method on the testing dataset (n = 4501). Discrimination, calibration, and overall model performance were also assessed. The predictors significantly associated with ICU mortality included: age (p < 0.001), source of admission (p < 0.0001), ICU admitting diagnosis (p < 0.0001), MODS (p < 0.0001), and NEMS (p < 0.0001). The variables sex and modified CCI were not significantly associated with ICU mortality. The training dataset for the developed model has good discriminating ability between patients with high risk and those with low risk of mortality (c-statistic 0.787). The Hosmer and Lemeshow goodness-of-fit test has a strong correlation between the observed and expected ICU mortality (χ (2) = 5.48; p > 0.31). The overall optimism of the estimation between the training and testing data set ΔAUC = 0.003, indicating a stable prediction model. This study demonstrates that CCIS data available after the first 24 h of ICU admission at LHSC can be used to create a robust mortality prediction model with acceptable fit statistic and internal validity for valid benchmarking and monitoring ICU performance.


The effects of particulate matters on allergic rhinitis in Nanjing, China.
Particulate matter pollution is a serious environmental problem. Individuals exposed to particulate matters have an increased prevalence to diseases. In the present study, we performed an epidemiological study to investigate the effects of particulate matter less than 10 μm in aerodynamic diameter (PM10) and particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) on allergic rhinitis in Nanjing, China. Daily numbers of allergic rhinitis patients (33,063 patients), PM10, PM2.5, and weather data were collected from January 2014 to December 2016 in Nanjing, China. Generalized additive models (GAM) were used to evaluate the effects of PM10 and PM2.5 on allergic rhinitis. We found that the interquartile range (IQR) increases in PM10 (difference of estimates, 5.86%; 95% CI, 3.00-8.81%; P = 4.72 × 10-5) and PM2.5 (difference of estimates, 5.39%; 95% CI, 2.73-8.12%; P = 5.67 × 10-5) concentrations were associated with the higher increased numbers of allergic rhinitis patients with 3-day cumulative effects in single-pollutant model. In addition, we found that the IQR increase in PM10 (age ≥ 18 years: 7.37%, 3.91-10.96%, 2.14 × 10-5; 0-17 years: 0.83%, - 4.00-5.91%, 0.740) and PM2.5 (age ≥ 18 years: 7.00%, 3.78-10.32%, 1.40 × 10-5; 0-17 years: 0.40%, - 4.10-5.10%, 0.866) increased the number of allergic rhinitis patients in adults, but not in children. In summary, our findings suggested that exposure to PM10 and PM2.5 was associated with the risk of allergic rhinitis.


Male sexuality and regulation of emotions: a study on the association between alexithymia and erectile dysfunction (ED).
Alexithymia is a multidimensional construct that describes a constellation of personality features characterised by difficulties in differentiating, identifying and communicating emotions. The purpose of the present study was to investigate prevalence of alexithymia in outpatients with erectile dysfunction (ED), both in the psychogenic lifelong type (PLED) and in the acquired one (PAED). ED severity was evaluated with the International Index of Erectile Function (IIEF) and alexithymia was measured using the Italian version of the 20-item Toronto Alexithymia Scale (TAS-20). The results suggest a high incidence of alexithymic characteristics in patients with psychogenic ED, a positive correlation between the alexithymia level and ED severity in patients with PAED and statistically significant differences in the alexithymia level between the two subgroups PLED and PAED. We assumed that alexithymia contributes to the origin of the PLED, and to a more severe manifestation of ED, once it appears in the acquired form.


Selective nonresponse bias in population-based survey estimates of drug use behaviors in the United States.
There is a trend of decreasing response rates in population surveys, and selective nonresponse represents a major source of potential bias in population-based survey estimates of drug use behaviors, especially estimates based on longitudinal designs. This study compared baseline substance use behaviors among initial respondents who did respond (n = 34,653) and did not respond (n = 8440) to a 3-year follow-up interview in a prospective study of the general U.S. adult population. Differences in nonresponse rates were assessed as a function of past-year drug use behaviors both before and after adjustment for socio-demographic differences potentially associated with these behaviors, and the effects of interactions of the socio-demographic characteristics with the drug use behaviors were assessed in multivariate logistic regression models for response at the 3-year follow-up. Weighted and unweighted nonresponse rates varied between alcohol users and users of other drugs such as cocaine and marijuana, with rates of nonresponse being higher in the latter drug categories. There were also significant differences in nonresponse rates as a function of frequency of use and demographics. More specifically, being married tends to reduce the probability of non-response, while older age, being male, being Asian or Hispanic, and having lower education all substantially increase the probability of nonresponse at Wave 2, even after controlling for relevant covariates. This study provides the substance abuse field with a methodology that users of longitudinal data can apply to test the sensitivity of their inferences to assumptions about attrition patterns.


Is dependence on phonological information in children's reading a product of instructional approach?
Eight-year-old British children were found to be less accurate at rejecting pseudohomophones than ordinary nonwords in a lexical decision task, but 8-year-old New Zealand children did not show this effect. A subsequent homophone decision task showed that this difference was not due to the New Zealand children being unable to distinguish pseudohomophones from other nonwords. The New Zealand children, however, were less accurate than the British children in pronouncing the pseudohomophones they had identified. It was argued that the British children tended to sound out the items before making a choice in the lexical decision task, which gave salience to phonological rather than visual information, resulting in increased errors to the pseudohomophones. It was concluded that where the British children showed this dependency on use of phonological information it was a product of the teaching approach they had experienced.


Synthesis of benzofurans with remote bromide functionality by domino "ring-cleavage-deprotection-cyclization" reactions of 2-alkylidenetetrahydrofurans with boron tribromide.
[reaction: see text] Bromination and subsequent Suzuki reactions of 2-alkylidenetetrahydrofurans, readily available by [3+2] cyclizations, afforded 1'-(2''-methoxyphenyl)-2-alkylidenetetrahydrofurans. Treatment of the latter with boron tribromide and subsequent addition of water resulted in the chemoselective formation of functionalized benzofurans containing a remote bromide functionality. The products are formed by a new domino "ring-cleavage-deprotection-cyclization" reaction. The addition of an aqueous solution of potassium tert-butoxide, rather than water, afforded saturated analogues of calycine by a "ring-cleavage-deprotection-ring-closure-lactonization" reaction.


Sprouty4 regulates endothelial cell migration via modulating integrin β3 stability through c-Src.
Angiogenesis is mediated by signaling through receptor tyrosine kinases (RTKs), Src family kinases and adhesion receptors such as integrins, yet the mechanism how these signaling pathways regulate one another remains incompletely understood. The RTK modulator, Sprouty4 (Spry4) inhibits endothelial cell functions and angiogenesis, but the mechanisms remain to be fully elucidated. In this study, we demonstrate that Spry4 regulates angiogenesis in part by regulating endothelial cell migration. Overexpression of Spry4 in human endothelial cells inhibited migration and adhesion on vitronectin (VTN), whereas knockdown of Spry4 enhanced these behaviors. These activities were shown to be c-Src-dependent and Ras-independent. Spry4 disrupted the crosstalk between vascular endothelial growth factor-2 and integrin αVβ3, the receptor for VTN. Spry4 overexpression resulted in decreased integrin β3 protein levels in a post-transcriptional manner in part by modulating its tyrosine phosphorylation by c-Src. Conversely, knockdown of Spry4 resulted in increased integrin β3 protein levels and tyrosine phosphorylation. Moreover, in vivo analysis revealed that Spry4 regulated integrin β3 levels in murine embryos and yolk sacs. Our findings identify an unanticipated role for Spry4 in regulating c-Src activity and integrin β3 protein levels, which contributes to the regulation of migration and adhesion of endothelial cells. Thus, targeting Spry4 may be exploited as a target in anti-angiogenesis therapies.


Hepatic dysfunction in peroxisomal disorders.
The peroxisomal compartment in hepatocytes hosts several essential metabolic conversions. These are defective in peroxisomal disorders that are either caused by failure to import the enzymes in the organelle or by mutations in the enzymes or in transporters needed to transfer the substrates across the peroxisomal membrane. Hepatic pathology is one of the cardinal features in disorders of peroxisome biogenesis and peroxisomal β-oxidation although it only rarely determines the clinical fate. In mouse models of these diseases liver pathologies also occur, although these are not always concordant with the human phenotype which might be due to differences in diet, expression of enzymes and backup mechanisms. Besides the morphological changes, we overview the impact of peroxisome malfunction on other cellular compartments including mitochondria and the ER. We further focus on the metabolic pathways that are affected such as bile acid formation, and dicarboxylic acid and branched chain fatty acid degradation. It appears that the association between deregulated metabolites and pathological events remains unclear.


Efficacy of Preoperative Biopsy in Predicting the Newly Proposed Histologic Grade of Resected Lung Adenocarcinoma.
A novel histologic grading system for invasive lung adenocarcinomas (LUAD) has been newly proposed and adopted by the World Health Organization (WHO) classification. We aimed to evaluate the concordance of newly established grades between preoperative biopsy and surgically resected LUAD samples. Additionally, factors affecting the concordance rate and its prognostic impact were also analyzed. In this study, surgically resected specimens of 222 patients with invasive LUAD and their preoperative biopsies collected between January 2013 and December 2020 were used. We determined the histologic subtypes of preoperative biopsy and surgically resected specimens and classified them separately according to the novel WHO grading system. The overall concordance rate of the novel WHO grades between preoperative biopsy and surgically resected samples was 81.5%, which was higher than that of the predominant subtype. When stratified by grades, the concordance rate of grades 1 (well-differentiated, 84.2%) and 3 (poorly differentiated, 89.1%) was found to be superior compared to grade 2 (moderately differentiated, 66.2%). Overall, the concordance rate was not significantly different from biopsy characteristics, including the number of biopsy samples, biopsy sample size, and tumor area size. On the other hand, the concordance rate of grades 1 and 2 was significantly higher in tumors with smaller invasive diameters, and that of grade 3 was significantly higher in tumors with larger invasive diameters. Preoperative biopsy specimens can predict the novel WHO grades, especially grades 1 and 3 of surgically resected specimens, more accurately than the former grading system, regardless of preoperative biopsy or clinicopathologic characteristics.


Irisin acts as a regulator of macrophages host defense.
Irisin, the adipomyokine, released mainly by exercised muscles, participate in the browning of adipose tissue and contribute to the restriction of insulin resistance and diabetes mellitus 2 development. Because of the limited reports describing the effect of irisin on inflammation and immunocompetent cells activation, the present study attempted to assess the influence of various irisin concentrations on basic macrophage activity. Studies were carried out on murine RAW 264.7 macrophages cultured in medium enriched with irisin (0nM, 10nM, 50nM, or 100nM). General cell activity, viability, and proliferation were assessed along with phagocytosis process, and respiratory burst generation. Irisin level positively correlates with general cell activity and cell cycle progression as well as with phagocytosis intensity, but negatively correlates with the intensity of respiratory burst generation. No influence of irisin on quiescent cell viability, including apoptosis or necrosis, was observed. This research is the first to show that irisin modulates macrophage activity by reducing reactive oxygen species (ROS) overproduction, which could suggest its potential anti-inflammatory properties. Therefore, further studies are needed for the evaluation of influence of irisin on immunocompetent cell function.


Hypertrophic cardiomyopathy secondary to tacrolimus therapy in a kidney transplant patient: A case report and focused review of the literature.
Calcineurin inhibitors have become a pillar of immunosuppressive treatment in solid organ transplant recipients. Several case reports have shown hypertrophic and dilated cardiomyopathy as an adverse effect to tacrolimus therapy. We present the case of a kidney transplant recipient woman who developed hypertrophic cardiomyopathy due to tacrolimus therapy.


Extraction of pertechnetates from HNO3 solutions into ionic liquids.
The extraction of pertechnetate ions from aquous solutions containing various concentrations of nitric acid into hydrophobic ionic liquids (ILs) has been examined at 25, 50 and 70 °C. The results show that the distribution ratio of Tc (DTc) between both phases weakly depends on the temperature and HNO3 concentration when IL's with relatively short aliphatic chains are used. The DTc obtained for all examined ILs, except methyltrioctylammonium bis(trifluoromethylsulfonyl)imide and 1-butyl-3-methylimidasolium hexafluorophosphate, are lower than 1.5. In the case of methyltrioctylammonium bis(trifluoromethylsulfonyl)imide a decrease of Tc concentration in aqueous solutions facilitates pertechnetate extraction into the organic phase.


Role of ictal baseline shifts and ictal high-frequency oscillations in stereo-electroencephalography analysis of mesial temporal lobe seizures.
To assess the role of ictal baseline shifts (IBS) and ictal high-frequency oscillations (iHFOs) in intracranial electroencephalography (EEG) presurgical evaluation by analysis of the spatial and temporal relationship of IBS, iHFOs with ictal conventional stereo-electroencephalography (icEEG) in mesial temporal lobe seizures (MTLS). We studied 15 adult patients with medically refractory MTLS who underwent monitoring with depth electrodes. Seventy-five ictal EEG recordings at 1,000 Hz sampling rate were studied. Visual comparison of icEEG, IBS, and iHFOs were performed using Nihon-Kohden Neurofax systems (acquisition range 0.016-300 Hz). Each recorded ictal EEG was analyzed with settings appropriate for displaying icEEG, IBS, and iHFOs. IBS and iHFOs were observed in all patients and in 91% and 81% of intracranial seizures, respectively. IBS occurred before (22%), at (57%), or after (21%) icEEG onset. In contrast, iHFOs occurred at (30%) or after (70%) icEEG onset. The onset of iHFOs was 11.5 s later than IBS onset (p < 0.0001). All of the earliest onset of IBS and 70% of the onset of iHFOs overlapped with the ictal onset zone (IOZ). Compared with iHFOs, interictal HFOs (itHFOs) were less correlated with IOZ. In contrast to icEEG, IBS and iHFOs had smaller spatial distributions in 70% and 100% of the seizures, respectively. An IBS dipole was observed in 66% of the seizures. Eighty-seven percent of the dipoles had a negative pole at the anterior/medial part of amygdala/hippocampus complex (A-H complex) and a positive pole at the posterior/lateral part of the A-H complex. The results suggest that evaluation of IBS and iHFOs, in addition to routine icEEG, helps in more accurately defining the IOZ. This study also shows that the onset and the spatial distribution of icEEG, IBS, and iHFOs do not overlap, suggesting that they reflect different cellular or network dynamics.


Enhanced expression of HLA class I by inhibited replication of hepatitis B virus.
HLA class I display on hepatitis B virus (HBV)-infected hepatocytes is important for limiting HBV infection. However, the effect of HBV replication on HLA class I expression on host cells has not been determined. Since acyclovir is known to inhibit HBV replication of the novel cell line HB611, which was transfected with HBV genome using human hepatoblastoma cells as the recipient and continuously replicates HBV DNA, we analyzed HLA class I expression on acyclovir-treated HB611 by quantitative flow cytometry. The results demonstrated that acyclovir treatment clearly increases the level of HLA class I on HB611, and suggested that HBV replication inhibits expression of HLA class I on infected hepatocytes. This effect of HBV replication on the host cell may be a means by which HBV evades immune surveillance to maintain chronic infection.


The preparative separation of sialic acid-containing lipids from sulphate group-containing glycolipids from small intestine of different animals. Analysis by thin-layer chromatography and detection of novel species.
Acidic glycolipids (gangliosides and glycolipid sulphates) were purified from non-glycolipid contaminants by silicic acid chromatography of their acetylated derivatives. Acetylation converted gangliosides into non-polar neutral and weakly acidic derivatives. These were separated from acetylated sulphate-containing glycolipids by chromatography on DEAE-cellulose. The fractions thus isolated from small intestine of 7 different animals were analyzed by thin-layer chromatography. This revealed a considerable species-related variation of both gangliosides and sulphoglycolipids. Mass spectrometry demonstrated a novel ganglioside in guinea-pig small intestine and a novel sulphoglycolipid in mouse small intestine.


Chronic desipramine alters stress-induced behaviors and regional expression of the immediate early gene, c-fos.
This experiment examined the effects of acute or chronic administration of the antidepressant drug desipramine on conditioned stress-induced behaviors and regional c-fos expression in the brain. To this end, rats were exposed to three sequential daily sessions of uncontrollable foot-shock and matched, on the basis of crouching, into one of four groups. Two of these groups were exposed to saline injections twice daily and two were exposed to injections of desipramine (5 mg/kg, SC) twice per day, for 9 days. On the 10th day one of the saline groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Likewise, on the 10th day one of the desipramine groups received saline and the other received desipramine before being exposed to the shock chamber without shock. Detailed behavioral analysis showed that compared to the saline-treated controls only the group treated chronically with desipramine, including on the test day, exhibited statistically significant reductions in crouching and increases in exploration during the test session. Similarly, Fos immunohistochemistry revealed that the chronic desipramine group showing positive behavioral effects was the only group in which there were significant reductions in the number of stress-induced Fos-positive neurons in five of 60 structures surveyed. These structures included the anterior cingulate cortex, anterior claustrum, central nucleus of the amygdala, dentate gyrus of the dorsal hippocampus, and paraventricular nucleus of the thalamus. To the extent that repeated exposure to uncontrollable stress is an animal model of depression, these and previous results suggest that these structures are potentially important neural targets for the antidepressant effects of desipramine.


Prevalence, management and outcomes of medically complex vulnerable elderly patients with urinary incontinence in the United States.
To assess the prevalence, patient-physician communication, treatment and health outcomes associated with urinary incontinence (UI) among the medically complex vulnerable elderly (MCVE) in the United States (US). Data from the 2006 to 2012 Medicare Health Outcomes Survey (HOS) were used. MCVE patients were aged 65+ years with a HOS VE score ≥ 3. UI was reported as a small, big or no problem. Descriptive statistics were used to assess patient-physician communication and treatment. Multivariable regression analyses were performed to assess the association of small or big UI problems with various outcomes. The annual UI prevalence increased among MCVE [from 35.8% (2006) to 38.6% (2012)]. MCVE with big UI problems communicated with their physicians more often than those with small UI problems (77.9% and 49.6%, respectively); however, treatment of UI remained low (48.5% and 29.1%, respectively). Physical component summary (PCS) and mental component summary (MCS) scores were lower among MCVE with small or big UI problems compared with those with no UI problems, respectively. The decrements in PCS and MCS scores associated with big UI problems were greater than the decrements associated with any of the other assessed conditions. MCVE with small or big UI problems, respectively, were more likely to report past falls, depression and activity daily living limitations vs. those without UI. The odds of having experienced these outcomes were greater for those with big UI vs. small UI problems. Urinary incontinence prevalence in the USA increased among MCVE from 2006 to 2012, although treatment of UI remained low. UI problems, particularly big UI problems, adversely impact health outcomes. Efforts to better identify and manage UI among the MCVE are needed.


Effects of postganglionic nerve section on synaptic transmission in the superior cervical ganglion of the guinea-pig.
In sympathetic neurons, axotomy induces a marked depression in synaptic transmission. We asked whether the decrease in synaptic efficacy observed in a given axotomized cell is more severe if most of the postsynaptic neurons are also injured. Accordingly, we studied if the synaptic depression induced by axotomy in neurons with axons running in a postganglionic nerve is influenced by section of other postganglionic nerves. The excitatory postsynaptic potentials evoked by preganglionic stimulation were recorded intracellularly in an in vitro preparation of the superior cervical ganglion. Eight days after cutting the inferior postganglionic nerve, postsynaptic potentials recorded from neurons projecting through this nerve were smaller (median = 6 mV, n = 62) than the controls (median = 34 mV, n = 89), but were similar to those found after sectioning the inferior nerve plus most postganglionic nerves (median = 5 mV, n = 70). If the inferior nerve was left intact, but most postganglionic branches were cut, the synaptic potentials recorded from inferior nerve neurons were normal (median = 33 mV, n = 77). It is concluded that the synaptic depression induced by axotomy in a sympathetic neuron is not affected by axotomy of nearby ganglion cells, even if they share part of their presynaptic axons. This suggests that the effect of axotomy is restricted to the synaptic terminals on the injured neuron.


Surgical pathology of mitral valves--the Indian scene.
Of the 75 cardiac valves excised at surgery over a 2 year period, 54 were mitral valves. Using simple morphological criteria along with clinical data, the valves were assigned to 2 major groups, rheumatic and non-rheumatic. The group with rheumatic disease accounted for 90% of cases. Mitral stenosis, incompetence and combined stenosis with incompetence were encountered with equal frequency (38, 38 and 24%). Mitral insufficiency of rheumatic etiology, no longer considered to be a major problem in the west, continues to be frequent in India. An increased incidence of mitral regurgitation in young females is an important feature noticed in this series.


Protoplast fusion and gene recombination in the uncommon Actinomycete Planobispora rosea producing GE2270.
An efficient method for protoplast generation for the uncommon actinomycete Planobispora rosea, the producer of the thiazolylpeptide antibiotic GE2270, was developed using a combination of hen egg white lysozyme and Streptomyces globisporus mutanolysin. This method converted more than 70% of vegetative mycelium to protoplasts, which were then regenerated with 50% efficiency in an optimized medium. When P. rosea protoplasts were efficiently fused, recombination between different antibiotic (streptomycin and gentamicin) resistance markers originated sensitive strains (str(s)gen(s)) at frequencies as high as 18% and double resistant fusants (str(r)gen(r)) at frequencies as high as 29%. Double resistant fusants showed GE2270 productivity intermediate between the productivity of the parental strains. Protoplast generation and fusion in P. rosea makes whole genome shuffling feasible as an approach to be used alternately with classical random mutagenesis in industrial strain improvement programs.


Expression of L cone pigment gene subtypes in females.
Spectral subtypes of L pigment are produced by a serine/alanine dimorphism at amino acid position 180. X-chromosomes that carry genes for the different subtypes occur with about equal frequency in normal men. Females have two X-chromosomes: thus, about 50% of women will inherit genes for both L pigment subtypes, although on different X-chromosomes. In these women, X-inactivation is expected to produce about equal numbers of LS180 and LA180 cones in addition to middle (M) and short (S) wavelength-sensitive cones to total four spectrally distinct cone types. Consistent with this expectation we found nearly equal expression of genes for two spectrally distinct subtypes of L pigment in five of nine female retinas examined.


[Analysis of circadian rhythm influence to heart rate turbulence in patients post myocardial infarction with left ventricular dysfunction].
Some study reported circadian occurence of sudden cardiac death, ventricle ectopic activity, acute coronary syndromes and heart rate variability. Heart rate turbulence (HRT) is one of a new markers of noninvasive stratification of sudden cardiac death. We have evaluated HRT in 120 consecutive patiens post myocardial infarction in mean age 62.7+/-12.4 years (90 M, 30 W), indicated for ecg Holter monitoring with LVEF 0.45+/-0.12 in 2hours interval during 24 hours. We have analysed circadian variation of the HRT. The statistically significant circadian patterns were found in turbulence slope parameter of HRT. No significant changes for turbulence onset parameter were described.


Expression of galectin-3 in adenoid cystic carcinoma of the head and neck and its relationship with distant metastasis.
Adenoid cystic carcinoma (ACC) is one of the most common malignant tumours of the salivary glands characterized by multiple recurrences and distant metastasis resulting in significantly worsening prognosis. Galectin-3, a member of the beta-galactoside-binding lectin family, has been implicated in tumour progression, metastasis, and found to have prognostic value. The aim of the study was to determine galectin-3 expression in ACC and correlate it with clinicopathological features and patient survival. Galectin-3 expression was investigated in paraffin sections of 35 ACC of the head and neck. Patients were divided into two groups based on a threshold of 5% positivity in the tumour cell population. The mean follow-up period for all patients was 90.1 months (range 3-300.1 months). Seventeen (48.6%) tumour specimens were considered galectin-3-positive. Galectin-3 reactivity was significantly associated with regional and distant metastasis (P=0.045 and P<0.001, respectively). There was no statistical significance in the correlation of galectin-3 expression and disease-free survival and overall survival rate (P=0.095 and 0.102, respectively). Galectin-3 may be used as an indicator in the prediction of metastatic spread in ACC.


High-frequency electromagnetic dynamics properties of THP1 cells using scanning microwave microscopy.
Microwave measurements combined with scanning probe microscopy is a novel tool to explore high-localized mechanical and electrical properties of biological species. Complex permittivities and permeabilities are detected through slight variations of an incident microwave signal. Here we report the high-frequency dependence of the electromagnetic dynamic characteristics in human monocytic leukemia cells (THP1) through local measurements by scanning microwave microscopy (SMM). The amplitude and phase images were shown to depend on the applied resonance frequency. While the amplitude yields information about the resistivity determined by the water and the ionic strength, the phase information reflects the dielectric losses arising from the fluid density.


The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.
This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.


Line scan diffusion spectrum of the denervated rat skeletal muscle.
To detect the earlier changes of the skeletal muscle of rats after peripheral nerve injury by measuring the apparent diffusion coefficient (ADC) on diffusion MR spectroscopy. The posterior tibial nerve was transected in six rats (nerve transection group) and was only dissected in six rats (control group). At one, three, five, seven, 14, and 28 days after the surgery, both the T2 value and the ADC of gastrocnemius muscle were measured using a line-scan diffusion spectrum on a 1.5T clinical MR imager on both groups. In the nerve transection group, the T2 ratio compared to the contralateral side increased gradually over four weeks after the transection, while the ADC ratio increased right after the surgery and began to decrease at five days. Four weeks after the transection, the ADC ratio returned to normal while the T2 ratio stayed at a high value. The control group indicated an almost constant T2 and ADC ratio during the experimental periods. The ADC of the skeletal muscle increased quickly after the transection of the dominant peripheral nerve and was detectable one day after the surgery. Diffusion MRI can be a useful tool for early detection of peripheral nerve injury instead of T2-weighted MRI or electromyography (EMG).