Transforming growth factor-β signaling promotes pulmonary hypertension caused by Schistosoma mansoni.
The pathogenic mechanisms underlying pulmonary arterial hypertension resulting from schistosomiasis, one of the most common causes of pulmonary hypertension worldwide, remain unknown. We hypothesized that transforming growth factor-β (TGF-β) signaling as a consequence of Th2 inflammation is critical for the pathogenesis of this disease. Mice sensitized and subsequently challenged with Schistosoma mansoni eggs developed pulmonary hypertension associated with an increase in right ventricular systolic pressure, thickening of the pulmonary artery media, and right ventricular hypertrophy. Rho-kinase-dependent vasoconstriction accounted for ≈60% of the increase in right ventricular systolic pressure. The pulmonary vascular remodeling and pulmonary hypertension were dependent on increased TGF-β signaling, as pharmacological blockade of the TGF-β ligand and receptor, and mice lacking Smad3 were significantly protected from Schistosoma-induced pulmonary hypertension. Blockade of TGF-β signaling also led to a decrease in interleukin-4 and interleukin-13 concentrations, which drive the Th2 responses characteristic of schistosomiasis lung pathology. Lungs of patients with schistosomiasis-associated pulmonary arterial hypertension have evidence of TGF-β signaling in their remodeled pulmonary arteries. Experimental S mansoni-induced pulmonary vascular disease relies on canonical TGF-β signaling.


Immunohistochemical localization of megalin and cubilin in the human inner ear.
Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications.


What do older patients know about their medication? A cross-sectional, interview-based pilot study.
This study sought to analyze the medication knowledge and awareness of medication adjustment options during intercurrent illness (sick day rules) of patients ≥ 70 years treated at a hospital for geriatric medicine in northern Germany. The study was designed as a cross-sectional, interview-based pilot study, was approved by the Ethics Committee of Hannover Medical School (No. 10274_BO_K_2022; date of approval: 11 March 2022), and enrolled a convenience sample of 100 patients between May and December 2022. The median of the average medication knowledge score in the study population (median age 82 years (IQR 75-87); 71% female) was 5 on a scale from 0 to 6 (IQR 3.8-5.6). Women achieved higher average medication knowledge scores than men (median 5.1 (IQR 4-5.6) vs. median 4.3 (IQR 3.6-5.1); p = 0.012), and patients < 80 years achieved higher average medication knowledge scores than patients ≥ 80 years (median 5.4 (IQR 4.9-5.7) vs. median 4.3 (IQR 3.2-5.3); p < 0.001). Sick day rules were known for only 1.1% of drugs for which sick day rules were applicable. Fifty-two percent of the patients reported that their general practitioner contributed most to their medication knowledge, and 66% considered their daily number of drugs to take adequate. Our study showed that medication knowledge of older patients was overall satisfying. Awareness of sick day rules, however, was poor. Future studies should evaluate the clinical benefits of sick day rules and ways of better communicating sick day rules to patients. In this regard, general practitioners may play a decisive role.


Mental health issues of gay and lesbian adolescents.
The mental health concerns of gay and lesbian adolescents are best understood within the context of cultural limitations, including a problematic conceptualization of adolescence, homophobia, and erotophobia. Within this framework, background information about homosexuality is presented; and the special social pressures and psychologic problems of gay and lesbian youth are discussed, with particular attention paid to internalized homophobia, developmental issues, and the "coming-out" process. Differences between gay and lesbian mental health issues are highlighted. Finally, practical suggestions regarding treatment planning are provided.


Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop.
The 2022 European Association for Haematopathology/Society for Hematopathology lymphoma workshop session on cavity-based lymphomas included sixty-eight cases in seven sections. The disease entities discussed include primary effusion lymphomas (PEL), extracavitary primary effusion lymphomas and confounding entities (ECPEL), HHV8-negative B-lineage lymphomas-effusion based (EBV-negative, EBV-positive, and plasmablastic types), diffuse large B-cell lymphoma associated with chronic inflammation, fibrin-associated diffuse large B-cell lymphoma (FA-DLBCL), breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and other lymphomas presenting as an effusion. All entities above are discussed; however, three are delved into greater detail given the challenges with classification: ECPEL, HHV8-negative effusion-based lymphomas, and FA-DLBCL. Cases exemplifying the diagnostic difficulty in differentiating ECPEL from HHV8-positive diffuse large B-cell lymphoma and germinotropic lymphoproliferative disorder were discussed. The more recently recognized effusion-based HHV8-negative large B-cell lymphoma is explored, with several cases submitted raising the question if this subset should be carved out as a specific entity, and if so, what should be the refining diagnostic criteria. Case submissions to the FA-DLBCL section yielded one of the largest case series to date, including classic cases, cases furthering the discussion on disease sites and prognosis, as well as novel concepts to be considered in this entity. The 2022 EA4HP/SH workshop cases allowed for further confirmation of the characteristics of some of the more historically accepted cavity-based lymphomas, as well as further inquiry and debate on relatively new or evolving entities.


Lignocellulosic hydrolysate inhibitors selectively inhibit/deactivate cellulase performance.
In this study, we monitored the inhibition and deactivation effects of various compounds associated with lignocellulosic hydrolysates on individual and combinations of cellulases. Tannic acid representing polymeric lignin residues strongly inhibited cellobiohydrolase 1 (CBH1) and β-glucosidase 1 (BGL1), but had a moderate inhibitory effect on endoglucanase 2 (EG2). Individual monomeric lignin residues had little or no inhibitory effect on hydrolytic enzymes. However, coniferyl aldehyde and syringaldehyde substantially decreased the activity of CBH1 and deactivated BGL1. Acetic and formic acids also showed strong inhibition of BGL1 but not CBH1 and EG2, whereas tannic, acetic and formic acid strongly inhibited a combination of CBH1 and EG2 during Avicel hydrolysis. Diminishing enzymatic hydrolysis is largely a function of inhibitor concentration and the enzyme-inhibitor relationship, rather than contact time during the hydrolysis process (i.e. deactivation). This suggests that decreased rates of hydrolysis during the enzymatic depolymerisation of lignocellulosic hydrolysates may be imparted by other factors related to substrate crystallinity and accessibility.


The computation of saturable and linear components of intestinal and other transport kinetics.
1. Published data for absorption kinetics have been fitted by non-linear regression to (i) a single Michaelis-Menten function, (ii) a Michaelis-Menten function plus a linear term and (iii) a sum of two Michaelis-Menten functions. A series of criteria have been drawn up to establish the goodness of fit in each case. 2. In 17 out of 35 cases the Michaelis-Menten function was the "best fit". In nine cases the "best-fit" model also included a linear term, but never was the sum of two Michaelis-Menten functions accepted to be the "best-fit" model. 3. Linearity of a Lineweaver-Burk plot was of unreliable diagnostic value in assessing goodness of fit. 4. Since the fit of a Michaelis-Menten function was often poor, simulated data sets with error were used to study the influence of experimental design etc. on Michaelis-Menten parameter estimation. 5. Precision of estimation of Km is increased by increasing the number of data points, reducing their variance, increasing the data range and by straddling Km in the observations. For a given constant number of observations there is no advantage in using replicate observations at few concentrations or single values at relatively many concentrations, or in using single values rather than means. 6. The caution necessary in interpretation of kinetic models is emphasized.


Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?
Advanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0-10), in cancer clinics. We explored the association between baseline patient-reported outcomes, via ESAS, and overall survival (OS). Advanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan-Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub-cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis. We identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub-cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS. Higher burden of patient-reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.


Singleton exome sequencing of 90 fetuses with ultrasound anomalies revealing novel disease-causing variants and genotype-phenotype correlations.
Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype-phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.


Distribution of skin surface pH on the forehead and cheek of adults.
The skin surface pH on the forehead and cheek of 574 men and women aged 18-95 was measured. No differences were found between men and women regarding forehead and cheek pH distribution. The group over the age of 80 showed higher pH values on both the forehead and the cheek. In 89% of the subjects measured, the skin surface pH on the cheek was higher than that on the forehead. The central 90%, i.e., the "representative range", for the population below the age of 80 is between 4.0-5.5 on the forehead and between 4.2-5.9 on the cheek.


Effect of alkali-treated HZSM-5 zeolite on the production of aromatic hydrocarbons from microwave assisted catalytic fast pyrolysis (MACFP) of rice husk.
We performed microwave-assisted catalytic fast pyrolysis (MACFP) of rice husk (RH) over an alkali-treated HZSM-5 zeolite, for production of hydrocarbons. The treatment consisted in the modification of the HZSM-5 by the organic base tetrapropylammonium hydroxide (TPAOH) solution at several concentrations. We characterized the resulting catalysts by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption-desorption, and temperature-programmed sorption of ammonia (NH3-TPD). The results suggest that the TPAOH treatment generated mesoporous structures in the HZSM-5, while preserving its microporous structure and crystallinity. We obtained the highest yield (45.9%) of hydrocarbons from MACFP of rice husk (RH) at 550 °C. As the TPAOH concentration increases, the relative content of BTEX hydrocarbons (benzene, toluene, ethylbenzene, and xylene) reaches a maximum value of 22.9% at 2.0 mol/L. A comparison of results obtained over the organic base TPAOH (HZSM-5 modified by 2.0 mol/L TPAOH solution) with those obtained over an inorganic base (HZSM-5 modified by 2.0 mol/L NaOH solution) shows a 4.3% increase in the relative content of monocyclic aromatic hydrocarbons for the TPAOH. In addition, the TPAOH-treated catalyst shows excellent selectivity of BTEX (58.5%), which is higher than the selectivity obtained with the parent HZSM-5 (51.2%) and NaOH-treated HZSM-5 (53.9%). The TPAOH-modified HZSM-5 catalyst effectively reduced coke formation by 4.6% compared to MACFP over the parent HZSM-5, most likely because TPAOH decreases the concentration of strong acidic sites on the outer surface of the catalyst, creating a mesoporous structure while retaining the weak acidic sites on the HZSM-5 inner surface. The new catalyst generated in this work contains a moderate amount of mesopores structures, which allows for effective upgrading of pyrolysis vapors while simultaneously reducing coke formation, thereby addressing a significant problem in the development of the catalytic fast pyrolysis process.


Investigation of chlorine tolerance profile of dominant gram negative bacteria recovered from secondary treated wastewater in Jaipur, India.
Management of bacterial survival post chlorine disinfection is vital for safe wastewater reuse for irrigation, as the presence of microorganisms in large numbers may lead to subsequent contamination of the surface and ground water reservoirs. Even after satisfying the current norms of coliform counts after disinfection (less than 1000 MPN per 100 mL), chlorine tolerant bacteria surviving in inadequately treated wastewater may pose a public health threat as many of these bacteria are able to re-grow upon storage. The current study is aimed to assess the magnitude of the problem posed by chlorine tolerant bacteria during chlorine disinfection and attempts to derive a strategy for safe disinfection. The chlorine tolerance was examined in the dominant gram negative bacteria (GNB) recovered from secondary treated sewage from a treatment plant located at Jaipur, India. Bacterial survival and re-growth (after 24 h) studies on test species (n = 11) with reference to E.coli ATCC 25922 reveal that, while the lethal doses of isolates ranged from 0.5 to 1.25 mgL-1,the chlorine doses for complete inhibition of re-growth were much higher (0.75-1.75 mgL-1).The isolates showing highest lethal dose and re-growth inhibition dose, identified as Citrobacter freundii, Klebsiella sp. and Stenotrophomonas maltophilia also exhibited very low log effective reduction (0.72-1.90) values and were selected as chlorine tolerant bacteria. Results of inactivation kinetics experiments on chlorine tolerant bacteria reveal a strong correlation (R2 > 0.89-0.99) between log reduction values and contact time. In re-growth kinetics experiments, maximum re-growth was observed after 6 h exposure following which, only marginal increase was registered up to 24 h. The study indicates that the existing approach of bacterial elimination post chlorine treatment may be grossly inadequate to assess the performance of the disinfection process adopted for drinking water treatment. It further brings out a novel approach to arrive at meaningful chlorine doses that take bacterial re-growth into account for achieving safe disinfection.


The arachidonic acid pathway and its role in prostate cancer development and progression.
The arachidonic acid pathway incorporates phospholipase, cyclooxygenase, lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major role in the development and progression of a number of cancers, including prostate cancer. We discuss the current status of research of this pathway in the area of prostate cancer, ranging from preclinical in vitro studies to human clinical trials. We performed an online search of the current and past peer reviewed literature on prostate cancer and arachidonic acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet activating factor, prostaglandin and eicosanoid. We retrieved and evaluated all full-length articles published in English from the 1980s to January 2007. Epidemiological evidence suggested that nonsteroidal anti-inflammatory drugs may decrease the risk of prostate cancer. This effect, presumably through the inhibition of cyclooxygenase-2, has been validated in preclinical studies. Cyclooxygenase-2 inhibition has also decreased the rate of prostate specific antigen increase in men with biochemical recurrence after treatment for prostate cancer. Although lipoxygenase and secretory phospholipase A2 inhibition was also effective for decreasing prostate cancer growth in preclinical studies, to our knowledge these strategies have not yet been used in clinical trials. Cytosolic phospholipase A2, platelet activating factor and epoxygenase need further investigation to determine a role in prostate cancer. Evolving data suggest a significant role for some areas of the arachidonic acid pathway in prostate cancer. Inhibiting 1 or a number of these enzymes in combination may hold promise for future prostate cancer treatment.


Mechanical evaluation of novel spinal interbody fusion cages made of bioactive, resorbable composites.
Osteoconductive and totally bioresorbable spinal/cervical interbody fusion cages were fabricated from a forged composite of raw particulate hydroxyapatite/poly L-lactide (u-HA/PLLA) with an u-HA 40wt% fraction (F-u-HA 40). The mechanical strengths of three types of cages, designed for open-box, screw and cylinder constructs, were compared with those of existing metal and carbon-fiber/polymer cages. Compressive strengths of these composite cages surpassed those of existing metal and carbon-fiber cages. Fatigue resistance to alternate and static compressive loading persisted for longer than the minimum period (6 months) necessary for spinal devices in simulated body fluid (SBF) at 37 degrees C. These novel interbody fusion cages await clinical application in humans.


Strategies for controlling axial shoulder rotation change shoulder muscle activity during external rotation exercises.
The infraspinatus muscle has a crucial role in shoulder stability. Although axial shoulder rotation is useful for selective activation of the infraspinatus, no study has examined the influence of exercise position on axial shoulder rotation during shoulder external rotation (ER) exercises. Thus, this study investigated the muscle activity in the infraspinatus, posterior deltoid, and middle trapezius during shoulder ER exercises performed with and without controlled axial shoulder rotation in 2 different positions. Twenty healthy subjects performed prone external rotation (PER) exercises with and without pressure biofeedback and seated external rotation (SITER) exercises with and without posterior humeral head gliding. Muscle activity during each ER exercise was measured using surface electromyography. Exercise strategy (P < .001) and position (P < .001) had a significant main effect on muscle activity in the infraspinatus and posterior deltoid. However, no significant interaction between strategy and position was observed. For muscle activity in the middle trapezius, strategy and position had a significant interaction effect (P = .014). Muscle activity in the infraspinatus increased significantly with the use of strategies to control axial shoulder rotation, whereas muscle activity in the posterior deltoid and middle trapezius decreased significantly. For all 3 muscles, greater activity was observed in the prone position than the seated position. We suggest that PER with pressure biofeedback can be useful to improve selective activation of the infraspinatus muscle while further eliciting infraspinatus muscle activity.


Advances in aptamer-based nuclear imaging.
Aptamers are short oligonucleotides that bind to specific target molecules. They have been extensively explored in biomedical applications, including biosensing, medical imaging, and disease treatment. Their adjustable affinity for specific biomarkers stimulates more translational efforts, such as nuclear imaging of tumors in preclinical and clinical settings. In this review, we present recent advances of aptamer-based nuclear imaging and compare aptamer tracers with other biogenic probes in forms of peptides, nanobodies, monoclonal antibodies, and antibody fragments. Fundamental properties of aptamer-based radiotracers are highlighted and potential directions to improve aptamer's imaging performance are discussed. Despite many translational obstacles to overcome, we envision aptamers to be a versatile tool for cancer nuclear imaging in the near future.


Overweight and obesity as markers for the evaluation of disease risk in older adults.
To explore disease risk through the measurement of BMI scores and waist circumferences in older Mexican adults with favorable health statuses and to determine how this risk is associated with sociodemographic characteristics. Using data from the National Health and Nutrition Survey of 2006, we created a cross-sectional design and selected 878 participants (60 years or older) who had favorable health statuses. The demographic data, health status, body mass index (BMI), waist circumference (WC), and an estimation of disease risk (arterial hypertension, diabetes type 2, and metabolic syndrome) were obtained through the survey. The prevalence of overweight, obesity, and abdominal obesity were 42.1%, 29.7%, and 80.9%, respectively. Disease risks, which were classified as least, increased, high, or very high, were 14.7%, 17.5%, 38.7%, and 29.1%, respectively. We observed that younger age has a higher risk for disease and that this decreases as age increases until it becomes minimal. After controlling for some risk factors such as tobacco, alcohol, and physical activity, we observed that being female, younger, and married are all factors significantly associated with a high and very high risk for disease. On the other hand, being indigenous, having a low education level, living in a rural setting are all protective factors with a minimum disease risk. The prevalence rates of overweight, obesity, and abdominal obesity are high among older Mexican adults. We observed that as age increases, disease risk decreases, which also occurs with some lifestyle factors such as living in a rural setting, being indigenous, having a low education level, and being married.


Genetic dissection of sesquiterpene biosynthesis by Fusarium fujikuroi.
A treasure trove of terpenes: The products of two fungal sesquiterpene synthases from the rice pathogen Fusarium fujikuroi were identified by gene-knockout experiments, genetic engineering of the fungus for production optimization, isolation of the sesquiterpenes, and structure elucidation by spectroscopic methods.


Individualized CT Angiography Protocols for the Evaluation of the Aorta: A Feasibility Study.
Ionizing radiation and iodinated contrast media are potential drawbacks to repetitive follow-up CT angiography in current practice. The aim of the present study was to optimize radiation dose and contrast agent volume by using individualized CT angiography protocols. Eighty consecutive patients referred for CT angiography of the whole aorta were prospectively evaluated. Patients were divided into groups of patients with a body mass index (BMI) < 28 kg/m(2) (group 1; n = 50) and those with a BMI ≥ 28 kg/m(2) (group 2; n = 30). A control group consisted of 50 consecutive patients who were retrospectively evaluated. CT angiography parameters on a second-generation dual-source scanner were 128 × 0.6-mm collimation, pitch of 0.9, rotation time of 0.33 seconds, tube voltages of 80/100/120 kVp (group 1/group 2/control), reference tube current of 400 mA, and image reconstruction at 1-mm/0.8-mm slice thickness (kernels, B30f [control] and I30f/strength 3 [groups 1/2]). The control group received 120 mL of contrast agent (300 mgI/mL) at 4.8 mL/s; groups 1 and 2 received 44 mL and 53 mL at 3.3 mL/s and 4 mL/s, respectively. Effective dose was evaluated for each patient. Image quality was determined by qualitative image analysis at the levels of the thoracic, abdominal, and pelvic aorta as nondiagnostic, diagnostic, good, or excellent, and quantitative image analysis was performed, including attenuation values and contrast-to-noise ratio (CNR). Mean effective radiation dose values for CT angiography of the aorta were 3.7 mSv ± 0.7 in group 1, 6.7 mSv ± 1.4 in group 2, and 8.7 mSv ± 1.9 in the control group (P < .001). Mean attenuation values and CNR levels were 334 HU ± 66 and 16 ± 8, respectively, in group 1, 277 HU ± 56 and 14 ± 5 in group 2, and 305 HU ± 77 and 11 ± 4 in the control group. Iterative reconstruction algorithms resulted in 23%-57% less radiation in combination with 55%-63% less contrast agent volume compared with standard CT protocols.


Vesicoureteral reflux in end stage renal disease.
Of 85 adults with end stage renal disease examined consecutively for renal transplantation 25 (29.4 per cent) had vesicoureteral reflux. Of these 25 patients 11 had a nephropathy as the cause of renal failure that was unrelated to reflux (for example glomerulonephritis) and 12 had, in addition to vesicoureteral reflux, a history of urinary tract infections and chronic pyelonephritis, which seems to be significant in the etiology of terminal renal failure in our patients (14 per cent). Only 2 of the 25 patients had severe, sterile reflux: 1 had bilateral megaureter with reflux into 1 side after ureteroneocystostomy and 1 had bilateral grade IV sterile reflux complicated by megacystitis. We had no case of uncomplicated, sterile reflux, which, in our experience, seems to be a rare cause of renal failure.


Learning style and instructional preformances of family physicians.
The learning styles and instructional preferences of two groups of family physicians were compared. One group of physicians attended a refresher course sponsored by a medical school; the other group did not attend the course.


Usefulness of paired samples for the Serodiagnosis of toxoplasmosis infection in a tertiary teaching Hospital in Malaysia.
Accurate diagnosis of Toxoplasma gondii (T. gondii) infection remains elusive and requires a comprehensive assessment through laboratory and clinical investigation. In this study, a diagnostic algorithm based on paired serum samples and clinical data was developed and evaluated. A total of 1267 suspected cases of Toxoplasma infection were enrolled in this study from January 2016 to December 2016. The cases were screened for anti-Toxoplasma IgM and IgG by electrochemiluminiscence immunoassay (ECLIA) method. Based on the serological profiles, all cases with first seropositive serum samples were considered as suggestive cases of Toxoplasma infection. Thus, second serum samples were obtained after an interval of 2 weeks. The diagnosis was made based on laboratory results and clinical data. A total of 482 T. gondii seroreactive cases were selected. The patient's records were traced and the data were analysed. Accordingly, 152 cases were diagnosed as clinically confirmed cases; 198 cases were clinically asymptomatic and 132 cases were newborn babies or infants who did not have toxoplasmosis and only acquired passive immunity from their mothers. The paired serum algorithm allowed classifying the seroreactive cases as follows: early (0.6%), acute (1.9%), reactivation (13.5%), recent (1.5%), passive immunity from mother (27.3%) and possible congenital infections (1.2%). In addition, cases of reactivated toxoplasmosis were detected among the pregnant mothers (13/82; 15.8%), children aged above 1 year (2/8; 25.0%) and immunocompetent mothers (5/135; 3.7%). Furthermore, the application of the paired serum analysis resulted in remarkably improved treatment initiation. Toxoplasmosis diagnosis and treatment can be improved through the use of paired serum diagnostic algorithm.


[Ammonium-selective disc-electrode with the carrier-antibiotic nonactin. A method for the continuous enzymatic, electrochemical determination of urea, I (author's transl)].
An ammonium-selective disc-electrode is described; the membrane consists of a polyvinylchloride-matrix with an active phase of nonactin in tris (2-ethylhexyl)phosphate and diphenyl ether as the ion-selective plastic. One side of the membrane is in contact with the solution to be measured and the other with the front surface of a platinum wire, which is enclosed in acrylic glass. This arrangement results in a very low drift potential.


Improving Wellbeing After Acute Coronary Syndrome.
Cardiovascular disease is the leading cause of death globally, primarily due to ischemic heart disease and subsequent acute coronary syndrome (ACS). ACS not only impacts physical function, but also psychological wellbeing. Patients who experience acute cardiovascular events are at elevated risk for experiencing symptoms of anxiety and depression. Further, increased levels of depression and anxiety following ACS is associated with amplified morbidity and mortality. Secondary prevention focusing on psychological well-being must be prioritized in this population to improve quality of life and cardiovascular health. The purpose of the present review is to summarize the literature on secondary prevention following ACS via interventions aimed at reducing depression and anxiety. Due to the heterogeneity of programs identified, a large, randomized control trial comparing their efficacy is vital to improving outcomes in this population.


Identification of Safe and Effective Intravenous Dose of AAVrh.10hFXN to Treat the Cardiac Manifestations of Friedreich's Ataxia.
Friedreich's ataxia (FA) is a life-threatening autosomal recessive disorder characterized by neurological and cardiac dysfunction. Arrhythmias and heart failure are the main cause of premature death. From prior studies in murine models of FA, adeno-associated virus encoding the normal human frataxin gene (AAVrh.10hFXN) effectively treated the cardiac manifestations of the disease. However, the therapeutic dose window is limited by high level of human frataxin (hFXN) gene expression associated with toxicity. As a therapeutic goal, since FA heterozygotes have no clinical manifestations of FA, we estimated the level of frataxin (FXN) necessary to convert the heart of a homozygote to that of a heterozygote. In noncardiac cells, FA heterozygotes have 30-80% of normal FXN levels (17.7-47.2 ng/mg, average 32.5 ng/mg) and FA homozygotes 2-30% normal levels (1.2-17.7 ng/mg, average 9.4 ng/mg). Therefore, an AAV vector would need to augment endogenous in an FA homozygote by >8.3 ng/mg. To determine the required dose of AAVrh.10hFXN, we administered 1.8 × 1011, 5.7 × 1011, or 1.8 × 1012 gc/kg of AAVrh.10hFXN intravenously (IV) to muscle creatine kinase (mck)-Cre conditional knockout Fxn mice, a cardiac and skeletal FXN knockout model. The minimally effective dose was 5.7 × 1011 gc/kg, resulting in cardiac hFXN levels of 6.1 ± 4.2 ng/mg and a mild (p < 0.01 compared with phosphate-buffered saline controls) improvement in mortality. A dose of 1.8 × 1012 gc/kg resulted in cardiac hFXN levels of 33.7 ± 6.4 ng/mg, a significant improvement in ejection fraction and fractional shortening (p < 0.05, both comparisons) and a 21.5% improvement in mortality (p < 0.001). To determine if the significantly effective dose of 1.8 × 1012 gc/kg could achieve human FA heterozygote levels in a large animal, this dose was administered IV to nonhuman primates. After 12 weeks, the vector-expressed FXN in the heart was 17.8 ± 4.9 ng/mg, comparable to the target human levels. These data identify both minimally and significantly effective therapeutic doses that are clinically relevant for the treatment of the cardiac manifestations of FA.


Recovery potential of aerobic sludge biomass from Co (II) stress in sequencing batch reactors.
Heavy metals in higher concentrations are often encountered in domestic sewage of developing and under-developed countries. High metallic concentrations can stress reactor sludge biomass morphology impeding its performance in organics reduction. However, the extent of damage and ability of sludge biomass to recover from the metallic stress is not fully understood. Also, there is no protocol to identify and prevent the sludge biomass from metallic stress in fully functional sewage treatment plants (STPs). This study investigates performance, metabolic activity, morphology, and settling characteristics of the sludge biomass under different Co(II) stress conditions. The extent of recovery in biomass, when the supply of Co(II) metal ion was discontinued in the inlet stream, was explored. The study also proposed a protocol based on simple settling characteristics of sludge biomass to get an early indication of metal infiltration to prevent potential damage to the biomass morphology. Four sequencing batch reactors (SBRs) with Co(II) ion concentrations of 0 (designated as RCo0), 5 (RCo5), 25 (RCo25), and 75 mg/L (RCo75) in the feed were operated with a cycle time of 12 h. Reactors were operated for 35 days with Co(II) in the feed (termed as stressed phase operation) followed by 24 days of operation without Co(II) in the feed (termed as recovery phase operation). Results show that COD removal in reactor RCo75 reduced to 48% on the 10th day of stressed phase operation, showing a lag in COD removal due to metallic stress. The activity of biomass in reactors RCo5, RCo25, and RCo75 was reduced by 39%, 45%, and 49%, respectively, in the stressed phase compared to the biomass in control reactor. Recovery in COD removal efficiency and specific biomass activity were observed in all the reactors after the removal of metallic stress. The settleability of sludge biomass in reactors RCo25 and RCo75 was significantly affected. Transformation in the shape of flocs in reactor RCo25 and RCo75 biomasses revealed the prolonged effect of metallic stress, which was observed to be irreversible even during the recovery phase operation.


Oral clonidine premedication reduces the EC50 of propofol concentration for laryngeal mask airway insertion in male patients.
Oral clonidine, an alpha2-adrenergic receptor agonist, reduces the dose of propofol required for laryngeal mask airway (LMA) insertion. Target-controlled infusion (TCI) is becoming increasingly popular for propofol infusion. There is no information, however, on the propofol blood concentrations required for LMA insertion and the effect of oral clonidine premedication on these values. Propofol at target effect-site concentrations from 4.0 to 12.0 microg/ml were randomly administered using TCI in three groups of healthy male patients (n=35 each) who were undergoing elective orthopedic surgery: control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups. Nothing was administered to the control group. Clonidine(2.5 microg/kg or 5.0 microg/kg) was administered orally 90 min before arrival at the operating room in the clonidine groups. After equilibration between the blood- and effect-site for 15 min, insertion of the LMA was attempted. The EC50 for LMA insertion (measured propofol serum concentration in equilibrium with the effect-site at which 50% of patients do not respond to the insertion of the LMA) was determined by logistical regression. EC50+/-standard error values in the control, 2.5 microg/kg clonidine, and 5.0 microg/kg clonidine groups were 8.72+/-0.55, 7.76+/-0.60, and 5.84+/-0.58 microg/ml, respectively. The EC50 in the 5.0 microg/kg clonidine group was significantly lower than that in the control group (P < 0.01). The propofol concentration required for LMA insertion in healthy male patients is reduced by premedication with 5.0 microg/kg oral clonidine.


Detector for organophosphorus compounds in liquid chromatography based on the cholinesterase inhibition reaction.
A sensitive method for the post-column reaction detection of organophosphorus compounds is described. The method relies on cholinesterase and is particularly suitable for the analysis of potent inhibitors such as sarin, soman and tabun. The compounds are separated by reversed-phase chromatography with methanol-water as the mobile phase in a linear gradient system. The reactor used for the detection comprises conventional autoanalyzer equipment with air segmentation of the reactor stream. The detection limits are 10 pg for sarin and soman and 60 pg for tabun. A quantitation method is presented, based on the linear correlation between the residual enzyme activity and the inhibitor concentration. The repeatability is +/- 1%. As a test of the system, the model compounds were detected against a background of urban air.


Visual Neuroscience: The Puzzle of Perceptual Stability.
Our world appears stable, although our eyes constantly shift its image across the retina. What brain mechanisms allow for this perceptual stability? A recent study has brought us a step closer to answering this millennial question.


Nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017-2018): Congenital hyperinsulinism, insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata's disease).
We aimed to investigate the nationwide incidence, treatment details and outcomes of patients with endogenous hyperinsulinemic hypoglycemia (EHH), including those with transient/persistent congenital hyperinsulinism (CHI), insulinoma, non-insulinoma pancreatogenous hypoglycemia syndrome and insulin autoimmune syndrome (Hirata's disease) in Japan. A nationwide, questionnaire-based survey was carried out to determine the number of patients with EHH who were treated for hypoglycemia or hypoglycemia-related complications in 2017-2018. The questionnaires were sent to all hospitals in Japan with >300 beds, and with pediatric and/or adult clinics likely managing EHH patients. The secondary questionnaires were sent to obtain the patients' date of birth, sex, age at onset, treatment details and post-treatment outcomes. A total of 447 patients with CHI (197 transient CHI, 225 persistent CHI and 25, unknown histology), 205 with insulinoma (118 benign, 18 malignant and 69 unknown subtype), 111 with non-insulinoma pancreatogenous hypoglycemia syndrome (33 post-gastric surgery HH, 57 postprandial HH, 10 nesidioblastosis and 11 unknown subtype) and 22 with insulin autoimmune syndrome were identified. Novel findings included: (i) marked improvement in the prognosis of persistent CHI over the past 10 years; (ii) male dominance in the incidence of transient CHI; (iii) non-insulinoma pancreatogenous hypoglycemia syndrome emerging as the second most common form of EHH in adults; (iv) frequent association of diabetes mellitus with insulin autoimmune syndrome; and (v) frequent post-treatment residual hypoglycemia and impaired quality of life. The first nationwide, all age group survey of EHH showed the current status of each type of EHH disorder and the unmet needs of the patients.


Prognostic factors and treatment of penetrating gunshot wounds to the head.
In an attempt to evaluate the predictive factors of morbidity and mortality in patients who suffered from civilian gunshot wounds to the head, we reviewed a series of 319 patients admitted to the Hospital Santa Marcelina, São Paulo, Brazil, between 1994 and 2000. Clinical and cranial computed tomography (CT) results are described. The initial Glasgow Coma Scale (GCS), the presence of an unilateral dilated pupil or medium fixed pupils, and five different findings in the CT scan were considered as variables. The Qui-Square Fisher test was utilized to verify the correlation between the presence of the variables and the occurrence of an increased mortality rate and of an unfavorable outcome (Glasgow Outcome Scale = 2 and 3). In 265 cases the missile penetrated the dura (83%). In our study there was a significant correlation between the low GCS scores on admission and a higher mortality (p < 0.001). This kind of correlation was also noted with patients admitted with unilateral dilated pupil and medium fixed pupil. There were 187 patients (70.5%) evaluated by CT scan. There was a significant correlation between the presence of transventricular or bihemispheric central type trajectory and high mortality. The patients admitted with unilobar supratentorial wounds resulted in better outcome when compared to those with bilobar or multilobar wounds (p < 0.001). A group of 156 patients was submitted to an aggressive surgical protocol. The best results were seen in patients admitted with initial GCS score higher than 8. We conclude that low GCS scores at admission, unilateral dilated pupil or medium fixed pupil, transventricular or bihemispheric central type trajectory, and bilobar or multilobar wounds noted through CT scan are predictive factors of high morbidity and mortality in patients with gunshot wounds to the head, in our clinical experience. We also conclude that surgical treatment is not recommended for patients with penetrating wounds and GCS score of 3 to 5 in the absence of hematoma causing a mass effect.


Head and neck manifestations of distant carcinomas.
Metastatic tumors to the head and neck from distant carcinomas are rare lesions that epitomize the "zebras." They represent a diagnostic and therapeutic challenge for clinicians and health providers. These lesions usually rank low in the differential diagnosis list, but a history of cancer should prompt clinicians about the possibility of a metastatic lesion from a distant carcinoma. The presence of these lesions usually represents a poor prognosis. The surgeon's role in treating these lesions is to improve or maintain the patient's quality of life, taking into consideration the overall prognosis.


Deep vein thrombosis and brain metastases. Case report and systematic review.
Secondary brain tumours, also known as brain metastasis, are a group of neoplasias which constitute the most frequent type of brain tumour in adults. Up to 20% patients with brain metastasis present venous thromboembolism (VTE). The management of VTE in these patients is complicated by multiple factors including intracranial haemorrhage, among others. We evaluated the case fatality rate (the proportion of patients who die due to a particular condition) of haemorrhage and recurrent VTE in patients with deep vein thrombosis (DVT) and brain metastasis to compare the risk/benefits of anticoagulant treatment. We also describe a clinical case and a systematic review of the literature on the management of anticoagulant treatment in patients with brain metastases and DVT. The principal objective of this review was to clarify the main questions about the management of this type of patient based on a clinical case.


The sensitivity to light of solutions of phenazine methosulphate: a quantitative cytochemical study.
The ability of phenazine methosulphate to transfer electrons from reduced coenzymes to a tetrazolium salt, neotetrazolium chloride, after exposure to light for various periods of time has been studied. Enzymes assayed for this purpose were: glucose-6-phosphate dehydrogenase been studied. Enzymes assayed for this purpose were: glucose-6-phosphate dehydrogenase (NADP+-dependent); lactate dehydrogenase (NAD+-dependent) and succinate dehydrogenase (flavoprotein-dependent). Enzyme activity was measured in sections of rodent liver by scanning and integrating microdensitometry. Phenazine methosulphate in solution was found to be sufficiently stable in light for up to two hours for reproducible quantitative measurements of cytochemical dehydrogenase activity to be obtained over this period.


Polypharmacy and Unplanned Hospitalizations in Patients with Rheumatoid Arthritis.
Polypharmacy (PP), the prescribing of multiple drugs for an individual, is rising in prevalence. PP associates with an increased risk of adverse drug reactions (ADR) and hospital admissions. We investigated the relationship between PP, characteristics of rheumatoid arthritis (RA), and the risk of unplanned hospital admissions. Patients from a hospital RA cohort were retrospectively analyzed. Information was collected from electronic medical records. Cox proportional hazards were used to compare hospitalization risk according to levels of PP. Admissions were adjudicated to determine whether an ADR was implicated. The study included 1101 patients; the mean number of all medications was 5. PP correlated with increasing age, disease duration, disease activity, and disability. At least 1 unplanned admission occurred for 16% of patients. Patients taking ≥ 10 medications had an adjusted HR for hospitalization of 3.1 (95% CI 2.1-4.5), compared to those taking 0-5 medications. Corticosteroid use associated with a doubling in adjusted risk of admission of 1.7 (95% CI 1.2-2.4). The most common reason for hospitalization was infection (28%). While in half of all admissions an ADR was a possible contributing factor, only 2% of admissions were found to directly result from an ADR. PP is common in RA and is a prognostic marker associated with increased risk of acute hospitalizations. Our data suggest that PP may be an indicator of comorbidity burden rather than a contributing cause of a drug-related toxicity. PP should be monitored to minimize inappropriate combination of prescribed medications. PP may be a useful predictor of clinical outcomes in epidemiologic studies.


Fibroblast phenylalanine concentration as a surrogate biomarker of cellular number.
Metabolomics studies in human dermal fibroblasts can elucidate the biological mechanisms associated with some diseases, but several methodological issues that increase variability have been identified. We aimed to quantify the amino acid levels in cultured fibroblasts and to apply different sample-based normalization approaches. Forty-four skin biopsies from control subjects were collected. Amino acids were measured in fibroblasts supernatants by UPLC-MS/MS. Statistical supervised and unsupervised studies were used. Spearman's test showed that phenylalanine displayed the second highest correlation with the remaining amino acids (mean r = 0.8), whereas the total protein concentration from the cell pellet showed a mean of r = 0.67. The lowest percentage of variation was obtained when amino acids were normalized by phenylalanine values, with a mean of 42% vs 57% when normalized by total protein values. When amino acid levels were normalized by phenylalanine, Principal Component Analysis and clustering analyses identified different fibroblasts groups. In conclusion, phenylalanine may be a suitable biomarker to estimate cellular content in cultured fibroblasts.


Activation of type-1 protein phosphatase by cdc2 kinase.
Purified cdc2 or cdc2 obtained from HeLa cells in association with p13suc1 activate inactive type-1 protein phosphatase (PP1) (catalytic subunit.inhibitor-2 complex, purified from skeletal muscle). Likewise in the case of PP1 activation by FA/GSK3, activation by cdc2 is accompanied by phosphorylation of inhibitor-2 (I2) and free I2 can be phosphorylated as well. Correlation between PP1 activation and I2 phosphorylation is suggested by the fact that both activation and phosphorylation (a) increase in parallel during incubation with cdc2, (b) decrease in parallel upon subsequent cdc2 inhibition by EDTA, and (c) are inhibited by the cdc2 inhibitor 5,6-dichlorobenzimidazole riboside. cdc2 also phosphorylates the catalytic subunit of PP1, whether in the complex with I2 or as free molecule. The activation of PP1 by cdc2 and by FA/GSK3 is compared.


Comparative dietary therapy effectiveness in remission of pediatric eosinophilic esophagitis.
Eosinophilic esophagitis is a chronic, immune-mediated inflammatory disorder that responds to dietary therapy; however, data evaluating the effectiveness of dietary therapeutic strategies are limited. This study compared the effectiveness of 3 frequently prescribed dietary therapies (elemental, 6-food elimination, and skin prick and atopy patch-directed elimination diets) and assessed the remission predictability of skin tests and their utility in directing dietary planning. A retrospective cohort of proton-pump inhibitor-unresponsive, non-glucocorticoid-treated patients with eosinophilic esophagitis who had 2 consecutive endoscopic biopsy specimens associated with dietary intervention was identified. Biopsy histology and remissions (<15 eosinophils/high-power field) after dietary therapy and food reintroductions were evaluated. Ninety-eight of 513 patients met the eligibility criteria. Of these 98 patients, 50% (n= 49), 27% (n= 26), and 23% (n= 23) received elemental, 6-food elimination, and directed diets, respectively. Remission occurred in 96%, 81%, and 65% of patients on elemental, 6-food elimination, and directed diets, respectively. The odds of postdiet remission versus nonremission were 5.6-fold higher (P= .05) on elemental versus 6-food elimination diets and 12.5-fold higher (P= .003) on elemental versus directed diets and were not significantly different (P= .22) on 6-food elimination versus directed diets. After 116 single-food reintroductions, the negative predictive value of skin testing for remission was 40% to 67% (milk, 40%; egg, 56%; soy, 64%; and wheat, 67%). All 3 dietary therapies are effective; however, an elemental diet is superior at inducing histologic remission compared with 6-food elimination and skin test-directed diets. Notably, an empiric 6-food elimination diet is as effective as a skin test-directed diet. The negative predictive values of foods most commonly reintroduced in single-food challenges are not sufficient to support the development of dietary advancement plans solely based on skin test results.


Retracted: Advanced Deep Learning Human Herpes Virus 6 (HHV-6) Molecular Detection in Understanding Human Infertility.
[This retracts the article DOI: 10.1155/2022/1422963.].


Calbindin controls release probability in ventral tegmental area dopamine neurons.
Relatively little is known about the molecular control of midbrain dopamine release. Using high-fidelity imaging of pHluorin-tagged vesicular monoamine transporter 2 in dopamine neurons, we found that exocytosis was more loosely coupled to calcium entry than in fast synapses. In ventral tegmental area neurons, this allows exocytosis to be efficiently controlled by a native fast calcium buffer, calbindin-D28k, maintaining a lower vesicular release probability compared with substantia nigra neurons.


Organized Management of Diabetes Mellitus in Lung Transplantation: Study of Glycemic Control and Patient Survival in a Single Center.
To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.


[Characteristics of the afferent activity of the cardiac nerves of Agrionemys horsfieldi turtles].
On the basis of changes in afferent impulsation emerging from the heart of the tortoise A. horsfieldi under various conditions of cardiac haemodynamics, it was shown that bursting activity of the superior cardiac nerves belongs to mechanoreceptors which are located in the ventricle and the adjacent arterial vessels. The discharge in these mechano-receptors coincides with ventricular systole. The second, predominant, type of afferentation is presented by irregular continued activity in both the superior and inferior vagal branches. The origin of this activity remains uncertain.


[Aspects of health economic evaluations as a contribution to the priority-setting debate in Germany].
Decision-making in healthcare is a priority-setting process. Tools used in health economic evaluation support decision-making by outlining complex interdependences, simulating short- and long-term consequences, and quantifying formal comparisons of health technologies. Key elements in health economic evaluations are patient-relevant outcomes and cost parameters. Costing of healthcare services is demanding and reflects only an approximation to reality, particularly in Germany, as the reimbursement schemes neither fully provide all details nor the different costing perspectives. Hence, in order to obtain uniform and cross-indication applicable cost parameters, a German standard cost dataset is necessary. In addition, patient-relevant and indication-specific sets of outcomes parameters should be agreed upon in order to also enable a reliable clinical product development. Economic aspects could be applied in a two-step decision-making approach, where initially the anticipated indication-specific technical efficiency level in terms of cost per adjusted life years would be assessed from a health system perspective. The second step would employ prioritization based on indication-relevant outcomes and ranking criteria in the individual patient decision situation. Health economic evaluations are relevant tools to support prioritization of health technologies, both on an individual as well as public health level.


Impact of the Food and Drug Administration Safety Communication on the Use of Power Morcellator in Daily Clinical Practice: An Italian Survey.
To assess the impact of the Food and Drug Administration (FDA) warning about power morcellation use on the daily clinical practice of Italian gynecologists. Electronic survey mailed to the main gynecologic centers (Canadian Task Force Classification type III). Unit of Obstetrics and Gynecology, IRCCS - Arcispedale S. Maria Nuova di Reggio Emilia (Italy). The study did not include patient data. There was no intervention. From 490 surveys sent out, 426 replies were included in the final analysis (return rate = 86.9%). Four hundred of the 426 (93.9%) gynecologists were aware of the FDA warning. One hundred fifty of 302 (49.7%) of experienced gynecologists and 176 of 349 (50.4%) of oncology gynecologists considered laparoscopy the best approach for myomectomy. The FDA communication was considered overly restrictive by experienced and oncology gynecologists who declared that they had no intention of changing their surgical approach. Two hundred fifty of the 426 (58.7%) gynecologists declared that they would change their surgical approach only to prevent legal litigation. The FDA warning also affected Italian gynecologists. Particularly, less experienced gynecologists and those without oncologic practice seem to be more interested in avoiding legal litigation rather than a real clinical risk of upstaging an unexpected leiomyosarcoma. Fear of undiagnosed sarcoma could increase the number of laparotomies.


Joint Task Force Algorithm and Annotations for Diagnosis and Management of Rhinitis.
The algorithm and text annotations in this document are intended to assist clinical decision making about patients who present with symptoms of rhinitis. This document complements the Executive Summary of Joint Task Force Practice Parameters for Diagnosis and Management of Rhinitis (Ann Allergy, Asthma, Immunol 1998; 81:463-468) and Diagnosis and Management of Rhinitis: Complete Guidelines of the Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology (Ann Allergy, Asthma, Immunol 1998;81:478-578). The Joint Task Force on Practice Parameters in Allergy, Asthma and Immunology is co-sponsored by the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology and the Joint Council of Allergy, Asthma and Immunology.


From ligand binding to gene expression: new insights into the regulation of G-protein-coupled receptors.
Transmembrane signaling systems relay information from the exterior to the interior of a cell, through a series of complex protein-protein interactions and second messenger cascades. One such system consists of the G-protein-coupled receptors, which interact with G proteins upon ligand binding, and in turn activate an effector molecule. The receptor is the first component in this signaling cascade and is subject to considerable regulation. Recent studies have shown that these regulatory events can occur at the levels of receptor protein modification and receptor gene expression. Interestingly, some of these processes appear to be mediated by the same second messenger systems that these receptors activate, which leads to various forms of positive and negative feedback regulation.


High volume is the key for improving in-hospital outcomes after radical prostatectomy: a total population analysis in Germany from 2006 to 2013.
Outcomes of radical prostatectomy are prone to publication bias, because most of the data originated from highly specialized centers. We assessed in-hospital outcomes of all radical prostatectomies in Germany from 2006 to 2013 focusing on caseload volume, surgical approach, and certification status. We analyzed the nationwide German hospital billing data covering 221,331 radical prostatectomies from 2006 to 2013. Outcomes were in-hospital mortality, surgical revision, and transfusion rates and the length of stay. Multivariate models described the impact of these factors. The yearly number of radical prostatectomies declined from 28,374 to 21,850. While shares of all other approaches decreased, shares for robot-assisted prostatectomy increased from 0.6 to 25.2%. Hospitals with ≥100 cases a year reported lower in-hospital mortality with 0.08 versus 0.17% for hospitals with <50 cases a year. On multivariate analysis, the odds for an individual death were doubled in hospitals with <50 cases a year. All other factors showed no significant impact on mortality. Concerning blood transfusion, the surgical approach was the strongest predictor with minimally invasive surgery (26% of the odds of conventional surgery) followed by caseload volume. Surgical revision was frequent in hospitals with lower rates of minimally invasive approaches (OR 1.6) and smaller caseloads (OR 1.4). Length of stay was reduced by 3 days for caseloads ≥200 a year, 2 days with minimally invasive approaches, and 1 day in certified prostate cancer centers. Lacking clinical information is a major limitation. Annual caseload volume of hospitals is the most important factor for improved in-hospital outcomes.


[Positive contrast in the detection of magnetically labeled cells by MRI--in vitro experiments].
Magnetically labeled cells (MLC) cause local field inhomogenities within the single voxels as well as on a macroscopic scale. The related Larmor frequency shift near MLC was exploited to obtain bright visualization applying spectral selective saturation (SSS). SK-Mel28 cells were labeled with the superparamagnetic iron oxide contrast agent SHU 555A. Low cell concentrations (0, 5, 20, 30, 50, 75, and 150 MLC/microl) and high cell concentrations (10 x 10(3), 30 x 10(3), 60 x 10(3), and 100 x 10(3) MLC/10 microl) were examined at 3 Tesla. Shimming and frequency adjustment to spectrometer reference frequency v0 was performed with the built in routine of the scanner. A 2D spin echo sequence with broadband excitation and refocusing pulses was used (BWex = 1.000 Hz). Prior to each TR, a non-selective saturation sinc pulse centred at v0 was applied. Bandwidth (BWsat) of this pulse was varied from 100 Hz to 800 Hz in logarithmic steps. Without SSS the highest value of Crel (i.e. relative MR contrast between labeled to unlabeled samples) was found for 150 MLC/microl and was given by 10%. Applying SSS led to positive contrast of the complete labeled volumes and to remarkable improvements in Crel. With increasing cell concentrations Crel raised to maximum, that was given by 52% (BWsat=100 Hz) and 28% (BWsat = 200 Hz) found for 75 MLC/microl. For 150 MLC/microl Crel decreased. A contrast clarification could also be detected near cell aggregations despite saturation. Using SSS positive contrast can be achieved for voxels containing MLC and voxels close to cell clusters. Under in vitro conditions positive contrast improved the sensitivity to detect MLC as compared to negative contrast imaging techniques. It seems reasonable, that positive contrast approaches can be applied in vivo as the underlying physical mechanism are comparable.


Neurodevelopment and Cognition Across the Lifespan in Patients With Single-Ventricle Physiology: Abnormal Brain Maturation and Accumulation of Brain Injuries.
The proportion of adults with single-ventricle physiology (SVP) has significantly increased over time. Improved longevity, however, may be associated with increased risks to brain health in adulthood. Children with SVP are at risk for neurodevelopmental impairment early in life and neurocognitive impairment as they age, and existing epidemiologic evidence suggests that adults with complex congenital heart disease, including SVP, are at increased risk of stroke and dementia, as compared with age-matched controls. Mechanisms that could contribute to increased potential for cognitive impairment in adults with SVP include the following: (i) baseline brain dysmaturation beginning in utero; (ii) subsequent acquired injury occurring in early childhood from staged surgeries; and (iii) pathophysiologic factors related to SVP itself, both in childhood and potentially throughout the lifespan as new arrhythmias, heart failure, and other issues may develop. Associated pathophysiologic mechanisms may include thromboembolism, hypercoagulability, hypoxia, hypoperfusion, and inflammation. Despite increasingly robust pediatric literature with neuroradiologic-neuropsychology correlates in SVP, there is a dearth of similar research in adults, with respect to both complex congenital heart disease overall and SVP specifically. Unanswered questions in adults with SVP include the following: (i) what is the prevalence of baseline brain injury and neurocognitive impairment in adulthood; (ii) what is the incident risk of these issues over time; and (iii) how much may be mediated by incident brain injury across the lifespan in adulthood, as opposed to from underlying susceptibility from dysmaturation and early childhood insults. In this review, we describe what is known regarding the brain health in individuals with SVP across the lifespan, and identify priority areas for future research.


Direct electrochemistry and electrochemical catalysis of immobilized hemoglobin in an ethanol-water mixture.
Hemoglobin (Hb) was immobilized on a glassy carbon electrode (GCE) surface by konjac glucomannan (KGM). KGM hydrogel films on GCE have relatively high stabilities in aqueous-ethanol mixtures. The entrapped hemoglobin undergoes fast direct electron transfer reactions in aqueous-organic solvent mixtures. The peak current is bigger, the peak-to-peak separation smaller and the formal potential observed in the cyclic voltammogram is more negative for Hb-KGM/GCE in ethanol-PBS compared to Hb-KGM/GCE in PBS. The electrochemical properties of the Hb in aqueous-organic solution are almost unchanged from with those observed for the purely aqueous solution, suggesting that water pools in the KGM hydrogel play an important role in preventing changes in conformation and making proteins unreactive with polar organic solvents. The immobilized Hb was able to catalyze the reduction of nitric oxide, peroxides (hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide, 2-butanone peroxide), and the dehalogenation of haloethanes (hexachloroethane, pentachloroethane, tetrachloroethane, etc.). The stability and reproducibility of the modified electrode meant that it could be used to determine these substances.


Survival and prognostic factors in patients undergoing the resection of solitary brain metastasis from non-small cell lung cancer: a retrospective cohort study.
Neurosurgery is the standard of care for resectable solitary brain metastasis (BM) from non-small cell lung cancer (NSCLC), but still with a poor outcome. Postoperative whole-brain radiotherapy (WBRT) was reported to reduce local recurrence, whether it could prolong survival was uncertain. In this study, we attempted to evaluate WBRT and other prognostic for overall survival (OS) in these patients. In this retrospective study, NSCLC patients with a solitary BM and controlled primary tumor who underwent neurosurgical resection were selected from the medical records database between January 2014 and December 2018. Clinical data, disease control/progression results and survival outcomes were obtained from the medical records, regular outpatient follow-up and telephone interviews. Univariable and multivariable Cox analyses of potential prognostic factors including patients' characteristics, BM features, tissue-based parameters and postoperative treatments were conducted. OS was illustrated using Kaplan-Meier curves, and group differences were assessed using the log-rank test. The subgroup analysis compared each variable between the WBRT group and the untreated control by the hazard ratio and its 95% confidence interval (CI). A total of 94 patients were included, with a median OS of 812 days. Univariable analysis showed that postoperative WBRT and targeted therapy were associated with OS. Multivariable analysis demonstrated that postoperative WBRT [P<0.001, hazard ratio (HR) 0.357], chemotherapy (P=0.008, HR 0.512), targeted therapy (P<0.001, HR 0.265), and smaller tumor size (P=0.018, HR 0.553) were independent prognostic factors for prolonged OS. However, tissue-based parameters (Ki67 tumor cell proliferation index, epidermal growth factor receptor, and checkpoint levels) were identified as statistically insignificant factors. In the subgroup analysis, the beneficial effect of WBRT was only observed in patients that did not receive systematic treatments. Postoperative WBRT and systematic treatments after solitary BM resection improve the prognosis of NSCLC patients with a controlled primary tumor. Postoperative WBRT could be considered, especially for those who not receive systematic chemotherapy or targeted therapy treatments, as they might be more likely to benefit from it.


Simulation in surgical education.
Simulation is becoming an important tool in surgical education. Surgical faculty have been forced to modify how they teach technical skills. Instead of a complete reliance on teaching in the operating room, a structured curriculum and dedicated time in the simulation center are being used in many centers. Some of the advantages of this approach include the ability to learn and practice new procedures in a safe and nurturing environment. The disadvantages include the significant cost of virtual reality simulators and the competition, between various training programs, to gain access to simulation.


Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia.
Des-tyr1-gamma-endorphin (DT gamma E) was administered intramuscularly in a dose of 1 mg/day for 10 days to 18 neuroleptic-free schizophrenic patients in a double-blind crossover design. Six patients showed either a slight or no antipsychotic response; seven patients showed a moderate antipsychotic response; and the remaining five patients showed a marked antipsychotic response. DT gamma E led to a decrease of plasma prolactin levels in patients treated with DT gamma E in the first period of experimental treatment as compared to those treated with placebo. Neither plasma levels of growth hormone and cortisol nor cerebrospinal fluid concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and 3-methoxy-4-hydroxyphenylglycol were affected by DT gamma E. Patients suffering from a hebephrenic or paranoid type of schizophrenia and those presenting relatively fewer negative symptoms were most susceptible to treatment with DT gamma E. These data confirm and extend previous findings that DT gamma E has antipsychotic properties in a number of schizophrenic patients.


Hepatic microsomal metabolism of androst-4-ene-3,17-dione: relative importance of ring hydroxylation and aromatization in control and induced rat liver.
The purpose of these studies was to determine whether oestrogen production is a quantitatively important pathway in the hepatic microsomal metabolism of androst-4-ene-3,17-dione. The effects of the enzyme inducing agents phenobarbitone and beta-naphthoflavone on microsomal cytochrome P-450-mediated androst-4-ene-3,17-dione hydroxylation and aromatization was investigated in the rat in vitro. In microsomal fractions from untreated rats the ratio of hydroxylated products to aromatized (oestrogenic) metabolites was 33:1. Phenobarbitone pretreatment of rats increased total hydroxylation by about 20% but did not change the ratio of hydroxylated to aromatized products (27:1). In contrast, beta-naphthoflavone induction decreased total hydroxylation to about 35% of control but did not affect total aromatization. Thus the ratio of hydroxylation to aromatization was significantly lower than in control microsomes (17:1). The principal aromatized products were oestriol and 2-hydroxyoestradiol-17 beta, with oestradiol-17 beta and its 4-hydroxy metabolite as minor products; no oestrone was observed. In further studies of the microsomal metabolism of oestrone, the major product was oestradiol-17 beta whereas hydroxylated metabolites were only minor products. Oestradiol-17 beta, in contrast, was hydroxylated to a considerable extent. These findings suggest that oestrone is a better substrate for the microsomal 17 beta-oxidoreductase than it is for cytochrome P-450. It therefore appears likely that any oestrone formed from the aromatization of androst-4-ene-3,17-dione would be readily converted to oestradiol-17 beta which, in turn, is subject to cytochrome P-450-mediated hydroxylation. Although the liver is a site of C19-steroid aromatization, it appears unlikely that this organ could contribute significantly to serum oestrogen levels since microsomal hydroxylases are readily able to convert aromatized products to biologically inactive metabolites.


Investigation on the "In vitro" degradation of zearalenone in rumen fluid.
Ruminal zearalenone (ZEA) degradation in "in vitro" digestion was examined in different variants using the Hohenheimer Gas Test. First, the mycotoxin degradation was measured using squeezed rumen fluid from solid digesta of the dorsal sack and free rumen fluid from the ventral sack, respectively. Then free rumen, fluid of the ventral sac was used with addition of concentrate and mixtures of concentrate with sun-flower oil and starch, respectively. Within 24 hours ZEA was degraded down to 63% and 49% of the initial concentration when incubated with solid and fluid rumen digesta, respectively. Using additives and rumen fluid concentrate for incubation, concentrate, concentrate with oil and concentrate with starch, respectively, a reduction of ZEA to 46, 56 and 37% of the initial toxin concentration was observed.


Sex-specific differences in organic anion transporting polypeptide 1a4 (Oatp1a4) functional expression at the blood-brain barrier in Sprague-Dawley rats.
Targeting endogenous blood-brain barrier (BBB) transporters such as organic anion transporting polypeptide 1a4 (Oatp1a4) can facilitate drug delivery for treatment of neurological diseases. Advancement of Oatp targeting for optimization of CNS drug delivery requires characterization of sex-specific differences in BBB expression and/or activity of this transporter. In this study, we investigated sex differences in Oatp1a4 functional expression at the BBB in adult and prepubertal (i.e., 6-week-old) Sprague-Dawley rats. We also performed castration or ovariectomy surgeries to assess the role of gonadal hormones on Oatp1a4 protein expression and transport activity at the BBB. Slco1a4 (i.e., the gene encoding Oatp1a4) mRNA expression and Oatp1a4 protein expression in brain microvessels was determined using quantitative real-time PCR and western blot analysis, respectively. Oatp transport function at the BBB was determined via in situ brain perfusion using [3H]taurocholate and [3H]atorvastatin as probe substrates. Data were expressed as mean ± SD and analyzed via one-way ANOVA followed by the post hoc Bonferroni t-test. Our results showed increased brain microvascular Slco1a4 mRNA and Oatp1a4 protein expression as well as increased brain uptake of [3H]taurocholate and [3H]atorvastatin in female rats as compared to males. Oatp1a4 expression at the BBB was enhanced in castrated male animals but was not affected by ovariectomy in female animals. In prepubertal rats, no sex-specific differences in brain microvascular Oatp1a4 expression were observed. Brain accumulation of [3H]taurocholate in male rats was increased following castration as compared to controls. In contrast, there was no difference in [3H]taurocholate brain uptake between ovariectomized and control female rats. These novel data confirm sex-specific differences in BBB Oatp1a4 functional expression, findings that have profound implications for treatment of CNS diseases. Studies are ongoing to fully characterize molecular pathways that regulate sex differences in Oatp1a4 expression and activity.


A rapid autolytic method for the preparation of protein hydrolysate from poultry viscera.
Protein hydrolysate was prepared from poultry viscera by a procedure involving autolysis for 6h at pH 2.8 and 55 degrees C followed by heat inactivation, filtration and drying. Recovery of nitrogen in the product was 87%. The process reduced the viable count of bacteria by 5-6logcfu/g. The product contained 84% protein, 6.5% ash and 8.8% moisture. Peptide analysis by gel filtration chromatography showed size in the range of 0.5-5kDa. RPHPLC exhibited the presence of hydrophilic peptides in higher concentration than that in trypsin digest of casein. Protein hydrolysate exhibited presence of all essential amino acids in comparison with reference protein except for methionine and threonine. The product possesses excellent solubility (>93%) over a pH range of 1-12. Efficacy of the product as a bacteriological media or feed supplement is discussed.


Feasibility of a New Pulley Repair: A Cadaver Study.
In this study, the feasibility of a new pulley reconstruction in which the tendon graft is pulled through a tunnel in the proximal phalanx, was evaluated using a cadaver model, with particular attention paid to the weakening of the bone structure by the drill hole. Nine fingers from 6 cadaver hands with intact pulley systems were compared with 9 fingers from 6 cadaver hands with missing A2 to A4 pulleys but that included a repair using the new surgical technique. Each finger was fixed to an isokinetic loading device. The forces in the flexor tendons were recorded in each finger using a force transducer. The forces recorded in the flexor tendons of the control group were significantly higher than in the reconstructed fingers. The most common event in the reconstructed fingers was graft failure. A fracture of the bone due to the drill hole was not observed. The new pulley reconstruction could represent an alternative to existing reconstructive techniques. The cause for the higher forces recorded in the control group could be attributed to sutures used in the operated fingers. The new pulley reconstruction method may enable reduced extensor tendon irritation because it avoids contact with the extensor hood and could possibly prohibit cortical bone loss, a serious side effect in the "one and one-half loop" technique.


Carcinogenicity testing of chemicals with particular reference to organochlorine pesticides.
The organochlorine chemicals comprise a large number of pesticides that are used widely throughout the world. The organochlorine pesticides given in the diet to mice are carcinogenic for the liver. They induce not only carcinomas of the liver, particularly at the higher doses, but also carcinomas and sarcomas in other organs in rats. They cause acute and chronic liver and kidney injury, which interferes with the development of carcinomas and sarcomas in rats. The testing of chemicals for carcinogenicity, with particular reference to organochlorine pesticides, includes discussions on the following topics: classification of hepatic lesions in mice and rats, toxicity versus carcinogenicity in the testing of chemicals, a comparison of carcinomas and cirrhosis of the liver in experimental animals and humans, and the significance of laboratory carcinogenicity findings to human health.


Efficacy of closed reduction for nasal fractures in children.
The aim of this study was to evaluate the efficacy of closed reduction and the effects of the time of intervention on young patients' satisfaction. Patients older than 16 years and those with additional maxillofacial fractures were excluded. All patients were treated by closed reduction and external fixation. The patients and parents were asked about their satisfaction in a survey 6 months' postoperatively. They were divided into groups according to the time of intervention, and the results. Twenty-four patients, age range 4-16 years, with isolated nasal fractures were included in the study. The mean (SD) time before intervention was 5.5 (1.8) days. The first group comprised 16 patients whose fractures were reduced between days 1 and 5 after the injury, and the second the 8 whose fractures were reduced between days 6 and 10. At 6 months 15 of the 24 were satisfied with the result, and 9 were not. In the group treated between days 1-5, 12/16 were happy with the result, and in the group treated between days 6-10, 3/8 were satisfied. Closed reduction gives good results in the treatment of nasal fractures in children. Early intervention increases the rate of satisfaction.


Feline 'C'-type terminals possess synaptic sites associated with a hypolemmal cistern and Nissl body.
Previous findings suggest that axosomatic 'C'-type terminals on rat spinal motoneurones possess 'active' synaptic sites associated with the characteristic subsynaptic cistern and postsynaptic Nissl body, but 'C'-terminals in cat do not. A re-examination of feline 'C'-terminals undertook to compare the synaptic ultrastructure in aldehyde-fixed material stained by either osmium or ethanolic phosphotungstic acid (E-PTA). In agreement with previous findings osmicated cat 'C'-terminals failed to reveal synaptic complexes in regions possessing the subsynaptic cistern ('cisternal regions'). In contrast, cisternal regions of E-PTA stained 'C'-terminals exhibited a linear array of presynaptic dense projection all opposed by a single extended postsynaptic density which abutted directly onto both postsynaptic membrane and the cistern. This close topographical relationship is suggested to be functionally significant in the trans-synaptic trophism previously demonstrated for feline 'C'-terminals.


Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat.
We investigated the ability of 3-(15 hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (N-hexacosanol), a neurotrophic substance, to reverse diabetes-induced cystopathy in the rat. Eight-week-old male Sprague-Dawley rats were divided randomly into four age-matched groups. In three of these groups, diabetes was induced by streptozotocin (STZ; 50mg/kg intraperitoneal [IP]). Four weeks after the induction of diabetes, the three groups received another 4 weeks of treatment by vehicle or N-hexacosanol (2 or 8 mg/kg IP every day). The serum glucose and serum insulin levels were determined, and the bladder functions were estimated by voiding behavior studies, cystometric studies, and functional studies using carbachol and KCl. The participation levels of M(2) and M(3) receptors were investigated by real-time polymerase chain reaction and immunohistochemical staining. Typical hematoxylin-eosin staining was also performed. Treatment with N-hexacosanol did not alter the rats' diabetic status, but did significantly improve the diabetes-induced dysfunction of the detrusor in a dose-dependent manner. Furthermore, N-hexacosanol significantly reversed the upregulation of muscarinic M(2) and M(3) receptor messenger RNAs (mRNAs) in STZ-diabetic rats. Muscarinic M(2) and M(3) receptors were localized in detrusor and urothelium, and there was no difference between any of the groups in the distribution of muscarinic M(2) and M(3) receptors. These results indicate that N-hexacosanol has a beneficial effect on hyperreactivity in the diabetic detrusor by ameliorating overexpression of muscarinic M(2) and M(3) receptor mRNAs.


Exploration of G-quadruplex function in c-Myb gene and its transcriptional regulation by topotecan.
Our bioinformatics research shows that there are four G-rich sequences (S1-S4) in the upstream region of the transcription start site of c-Myb gene, and we have proved that these sequences have the ability to form G-quadruplex structures. This work mainly focuses on G-quadruplex function, recognition and transcription regulation in c-Myb gene, revealing a novel regulatory element in c-Myb proximal promoter region, and its transcription regulation by G-quadruplex binder. The research has identified that the enhancer effect in c-Myb transcription was primarily affected by the G-quadruplex formed by S1 sequence, and the up-regulation effect may due to the removal of repressive progress of MZF-1 by stabilizing G-quadruplex. Attentions were being paid to the development of G-quadruplex binders for selective recognition, and topotecan was found to have high binding affinity in vitro and could effectively affect the c-Myb transcription activities in cells. The regulation of G-quadruplex with binders in transcriptional, translational levels by Q-RT-PCR and western blot was in expectation of providing a strategy for gene expression modulation. In conclusion, our study revealed a G-quadruplex structure in c-Myb proximal promoter region, which was of great importance in the regulation of c-Myb function.


Hierarchical use of cues in the missing object recognition task by rats (Rattus norvegicus).
This study investigated rats' preferences for using non-spatial and spatial cues in a missing-object recognition task. Rats were trained to find a sunflower seed under any one of four previously missing adjacent objects, the test array of a trial, after having found seeds under three of them in the 'study' array of that trial. On some trials the study and test arrays consisted of a different object at each baited food site and on other trials, of identical objects. A previously missing object's position and orientation within its array and its global position within the large foraging chamber varied over trials but not within trials. Following training, rats received interspersed non- or partially rewarded probe trials with transformed test arrays of dissociated non-spatial (object-specific) and spatial cues on test array feeders. Results from these probe trials revealed that rats preferred to search for a missing object based first on its specific non-spatial features before searching for it based on its local spatial features; that is, its local position followed by its orientation, and finally based on its global position. This hierarchical sequence for using spatial cues was preserved under the identical-objects cueing condition. Rats reversed their preferences between object-specific and local position cues, however, when novel objects replaced the same four different objects in a supplementary experiment. We discussed the implications of these findings in terms of the influence of ecological- and context-dependent factors on information use or retrieval from animals' visuo-spatial working memory.


Age differences in recognition memory of the rhesus monkey (Macaca mulatta).
Aging is accompanied by a gradual decline in memory in both humans and nonhuman primates. To determine whether the impairment in nonhuman primates extends to recognition memory, which is a sensitive index of the integrity of the limbic system, we trained rhesus monkeys of four different age groups (3-6, 14-17, 20-24, and 25-29 years of age) on a delayed nonmatching-to-sample task with trial-unique objects. After the animals had learned the task, which required recognition of single objects presented ten seconds earlier, memory demands were increased by gradually lengthening delay intervals (to 120 seconds) and list lengths (to ten objects). With increasing age, only marginal impairments in learning the basic task were observed. However, clear age-related differences did emerge when either delays or list lengths were increased, with the oldest group of monkeys demonstrating the greatest impairments. The decline in visual recognition ability in aging monkeys parallels the decline in memory observed with advancing age in humans.


Graft fixation is highest with anatomic tunnel positioning in acromioclavicular reconstruction.
The purposes were to determine the bone density at specific bone tunnel locations in the clavicle and to determine ultimate load to failure of a graft fixed with an interference screw at specific areas. Bone mass densitometry was tested at 5-mm intervals from the lateral to the medial end of 11 clavicles (mean age, 70.0 ± 17.7 years). Tunnels were drilled in 10-mm increments from the lateral edge, and tenodesis screws were used to fix semitendinosus grafts in the tunnel. Grafts were cyclically loaded, followed by load to failure. The bone mineral density (BMD) of the cadaveric clavicles increased from lateral (0.304 ± 0.078 g/cm(2) at 10 mm) to medial (0.760 ± 0.103 g/cm(2) at 50 mm). Load to failure increased from lateral to medial, and most specimens failed by tendon pullout. The load was 125.3 ± 42.5 N at the most lateral tunnel and 349.3 ± 120.3 N at the most medial tunnel. The Pearson correlation coefficient was 0.653 between tunnel position and load to failure, 0.659 between bone density and load to failure, and 0.803 between tunnel position and bone density. These all showed strong correlation. BMD shows that optimal bone density is found in the anatomic insertion area of the coracoclavicular ligaments between 20 mm and 50 mm from the lateral end of the clavicle. Low BMD correlated with decreased load to failure. Failure at the lateral bone tunnel in coracoclavicular ligament reconstruction may be a result of poor bone quality. When one is drilling bone tunnels for this surgery, consideration should be given to both anatomic position and bone quality.


Biosynthesis of intestinal microvillar proteins. Translational evidence in vitro that aminopeptidase N is synthesized as a Mr-115000 polypeptide.
A crude RNA fraction, prepared from pig small intestine, was found to be more efficient than a fraction enriched in polyadenylated RNA in directing translation of polypeptides with Mr greater than 100000 in a rabbit reticulocyte lysate system. Aminopeptidase N (EC 126.96.36.199) synthesized in vitro was immunopurified from the translation mixture and analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. It was found to have an apparent Mr of 115000 regardless of whether the translation was performed in the absence or presence of proteinase inhibitors. This result contradicts the possibility of aminopeptidase N being synthesized as a large single-chain precursor polypeptide.


Threshold dynamics of a HCV model with virus to cell transmission in both liver with CTL immune response and the extrahepatic tissue.
In this paper, a deterministic model characterizing the within-host infection of Hepatitis C virus (HCV) in intrahepatic and extrahepatic tissues is presented. In addition, the model also includes the effect of the cytotoxic T lymphocyte (CTL) immunity described by a linear activation rate by infected cells. Firstly, the non-negativity and boundedness of solutions of the model are established. Secondly, the basic reproduction number R01 and immune reproduction number R02 are calculated, respectively. Three equilibria, namely, infection-free, CTL immune response-free and infected equilibrium with CTL immune response are discussed in terms of these two thresholds. Thirdly, the stability of these three equilibria is investigated theoretically as well as numerically. The results show that when R01<1 , the virus will be cleared out eventually and the CTL immune response will also disappear; when R02<1<R01 , the virus persists within the host, but the CTL immune response disappears eventually; when R02>1 , both of the virus and the CTL immune response persist within the host. Finally, a brief discussion will be given.


Polysomnographic findings, video-based sleep analysis and sleep perception in progressive supranuclear palsy.
To compare subjective sleep perception, sleep architecture, rapid eye movement (REM) sleep without atonia, and REM sleep behavior disorder (RBD) in patients with progressive supranuclear palsy (PSP) to patients with Parkinson's disease (PD). A comparative sleep study using the Parkinson's Disease Sleep Scale (PDSS), the Mini-Mental State Examination (MMSE), and cardiorespiratory polysomnography on two consecutive nights with synchronized video recording. The study was undertaken in a sleep laboratory in a movement disorder center. Forty patients matched for age and cognition with probable PSP (n=20, aged 71+/-8 years, MMSE < or = 24 in n=7) and PD (n=20, aged 69+/-5 years, MMSE < or = 24 in n=8). PDSS sum scores showed no difference between PSP and PD. PSP patients had significantly lower sleep efficiency (43.0+/-15.0%) compared to PD patients (62.8+/-19.1%) (p<0.0008). Seventeen PSP patients and 19 PD patients had REM without atonia (RWA). Seven PSP patients and 13 PD patients had clinical RBD. The amount of RWA was lower in PSP (14.5+/-17.3%) than in PD (44.6+/-31.3%) (p<0.0007). Eleven PSP and 11 PD patients were newly identified with sleep-disordered breathing (SDB). Polysomnographically recorded sleep is more severely impaired in PSP than in PD. PDSS ratings do not reflect the poorer sleep quality in PSP, possibly pointing to a specific neuropsychological profile. RWA and RBD are present in both neurodegenerative diseases. So far undetected SDB affects more than half of all patients in this study.


Usefulness of an aura for classification of a first generalized seizure.
In 67 of 149 patients with a generalized first seizure, the occurrence of some kind of sensation immediately preceding the loss of consciousness was the only clue that possibly indicated focal onset of the seizure. We studied the interobserver agreement between six neurologists regarding the interpretation of these preceding feelings as either a nonspecific symptom or an aura implicating a focal onset of the seizure. The observers also classified the seizures as generalized from onset, undetermined, or partial secondarily generalized. To assess the accuracy of the classification, we obtained a standard EEG, an EEG after partial sleep deprivation, a computed tomography (CT) scan, and a follow-up report after 1 year. The subclassification on clinical grounds of a generalized first seizure is too unreliable and probably too invalid as well to be useful in clinical practice or in epidemiologic research.


Effect of education based on the Common-Sense Model of Self-Regulation on blood pressure and self-management of hypertensive patients: A clinical trial study.
This study aimed to determine the impact of training based on the Common-Sense Model of Self-Regulation (CSM) on blood pressure and self-management of patients with hypertension. This randomized controlled trial study was conducted. Seventy-two hypertensive patients were referred to the Farshchian Hospital clinic in Hamadan from April 2021 to March 2022. Samples were selected and randomly assigned to the intervention group (n = 36) and control group (n = 36). The intervention group participated in a training program based on the CSM in five sessions of 30-45 min for one month. Phone follow-up was also done once every three days. The control group only received routine clinic education. The clinic's nurse measured the patients' blood pressure, and the participants completed the self-management questionnaire before and three months after the start of the study. A total of 68 participants completed the study. Results showed that before the intervention, there was no statistically significant difference in the mean scores of self-management and its dimensions, systolic, diastolic, and mean arterial pressure between intervention and control groups (P > 0.05). However, after the intervention, the mean of systolic blood pressure (116.21 ± 14.52 vs. 128.62 ± 16.88) mmHg, mean arterial pressure (88.03 ± 8.47 vs. 98.11 ± 11.69) mmHg and the scores of self-management and its dimensions among patients in the intervention group were decreased comparison with control group (P < 0.05). Education based on the CSM improved self-management and blood pressure reduction in hypertensive patients, so nurses should use it as an effective educational model.


Potassium currents in rat prevertebral and paravertebral sympathetic neurones: control of firing properties.
1. Intracellular recordings were made from rat sympathetic neurones in isolated superior cervical ganglia (SCG), coeliac ganglia (CG) and superior mesenteric ganglia (SMG). 2. Based on their response to a maintained depolarizing current stimulus, neurones were classified as 'phasic' or 'tonic'. All neurones in the SCG were phasic, 85% of the neurones in the SMG and 58% of the neurones in the CG were tonic, and the remainder were phasic. 3. The voltage response of phasic and tonic neurones around threshold to a constant current step was markedly different. The response of phasic neurones was biphasic with an initial depolarizing response followed by significant repolarization of the membrane potential. In contrast, tonic neurones became more depolarized during a prolonged current step. 4. The underlying currents were studied using single-electrode voltage-clamp recording. The M-current was present in all phasic neurones, but was very weak or absent in tonic neurones. 5. An A-current was apparent in both phasic and tonic neurones. The voltage-dependent activation, steady- state inactivation, and current density of the A-current were all similar in phasic and tonic cells. 6. A low- threshold, slowly inactivating outward current (D2-current) was observed exclusively in tonic neurones. The slow inactivation of this current appeared to underlie the slow depolarizing ramp seen in response to a maintained depolarizing current step. 7. Computer simulations, based on the voltage-clamp data, suggested that the different firing properties of phasic and tonic neurones could be accounted for by differential expression of the M-current.