Thyroid function/antibodies in sudanese women with polycystic ovarian disease.
To evaluate thyroid function and hormonal profile in women with polycystic ovary syndrome (PCOS). A case-control study was conducted at Saad Abualila Center, Khartoum, Sudan. The cases were women with confirmed PCOS based on Rotterdam criteria. The controls were infertile women with no evidence of PCOS. The socio-demographic characteristics and medical history were gathered using a questionnaire. Thyroid hormones (thyroid-stimulating hormone, free tri-iodothyronine, and free thyroxine), anti-thyroid peroxidase, and anti-thyroglobulin antibodies were measured. While there were no significant differences in the age and haemoglobin levels of the two studied groups (55 women in each arm), body mass index was significantly higher in women with PCOS. There were no significant differences in the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone, luteinizing hormone/follicle stimulating hormone, anti-thyroid peroxidase, anti-thyroglobulin antibodies, cholesterol, triglycerides and low-density lipoprotein cholesterol between the cases and the controls. The mean±standard deviation of free tri-iodothyronine (3.50±0.2 vs. 3.38±0.3 pg/mL, P=0.040) and median (interquartile) high-density lipoprotein cholesterol (37.0 [34.0 to 42.0] vs. 35.80 [29.0 to 41.0] mg/dL, P=0.015) were significantly higher in PCOS patients compared with the control group. In linear regression, PCOS (0.151 pg/mL, P=0.023) and anti-thyroid peroxidase levels (-0.078 pg/mL, P=0.031) were significantly associated with free tri-iodothyronine. Free tri-iodothyronine was a significantly higher among PCOS patients compared with the control group.


Influence of Free Volume Determined by Positron Annihilation Lifetime Spectroscopy (PALS) on Gas Permeability of Cellulose Nanocrystal Films.
Cellulose nanocrystals (CNCs) are of increasing interest for packaging applications because of their biodegradability, low cost, high crystallinity, and high aspect ratio. The objective of this study was to use positron annihilation lifetime spectroscopy (PALS) to investigate the free volume of CNC films with different structural arrangements (chiral nematic vs shear-oriented CNC films) and relate this information to gas barrier performance. It was found that sheared CNC films with higher CNC alignment have lower free volume and hence have more tortuosity than chiral nematic self-assembled films, which lowers gas diffusion throughout the films. The overall barrier performance of the aligned CNC film obtained in this study has a higher barrier performance than high barrier polymer films like PVOH and EVOH. Furthermore, a modified model was developed for single-component CNC films to predict the gas permeability with variation of CNC alignment with validation by the data taken.


Originalarbeiten.
In 5 cases of polycythaemia vera and 2 cases with other myeloproliferative disorders accompanied by thrombocythaemia (megakaryocytic myelosis), the megakaryocytes were differentiated and studied by use of the combined application of cytophotometric determination of the DNA content and autoradiography with tritiated thymidine (3H-TdR) in vitro. A shift to the right of the megakaryocyte series, occurence of high polyploidy cells at 64c and a decrease of the 3H-TdR-labeling indices were observed. The data suggest a disturbance of the rhythmical polyploidization of the megakaryocytes, consisting of an elevated proportion of rest cells at the different ploidy stages. The maturation capacity of megakaryocytes may be related more to the resting than to the DNA synthesizing cells.


Evaluation of tonometric correction factors.
To investigate the efficacy of currently available correction factors in correcting intraocular pressure (IOP) measurements for the errors induced by the normal variations in corneal structural characteristics. Central corneal thickness (CCT) and corneal radius of curvature were measured on 324 individuals (175 normal: group 1 and 149 had either open angle glaucoma or ocular hypertension: group 2). IOP was measured in all normal subjects with the Goldmann applanation tonometer and the highest recorded IOP was obtained from patient charts for subjects with either open angle glaucoma or ocular hypertension. Regression analysis was performed on IOP, CCT, and corneal radius of curvature. The corrected IOP was also calculated using the models proposed by Ehlers and Orssengo and Pye. Linear regression analysis was used to calculate the residual association between corneal parameters and corrected IOP. There was a significant positive correlation between IOP measured using Goldmann applanation tonometer and the CCT in both groups. There was no significant correlation between corneal radius of curvature and IOP in either group. There was a significant negative correlation in both the groups between CCT and corrected IOP calculated using the models of Ehlers and Orssengo and Pye. This indicates that the Ehlers and Orssengo and Pye models may significantly overestimate the effect of CCT on IOP measurement. The effect of CCT and IOP as observed in the present study and by other studies in literature is less than predicted by both the Ehlers formula and the Orssengo and Pye model. Correcting IOP for the effect of CCT using these models could be erroneous and lead to overcorrection of IOP, thus resulting in erroneously low corrected IOP eyes with thicker cornea and erroneously high corrected IOP in eyes with thinner cornea.


Born Small for Gestational Age and Poor School Performance - How Small Is Too Small?
To assess the relationship between severity of small for gestational age (SGA) and the risk of poor school performance, and to investigate whether adult stature modifies this risk. 1,088,980 Swedish children born at term between 1973 and 1988 were categorized into severe SGA (less than -3 standard deviations (SD) of expected birth weight), moderate SGA (-2.01 to -3 SD), mild SGA (-1.01 to -2 SD), and appropriate for gestational age (-1 to 0.99 SD). The risk of poor school performance at the time of graduation from compulsory school (grades <10th percentile) was calculated using unconditional logistic regression models and adjusted for socio-economic factors. In a sub-analysis, we stratified boys by adult stature, and adjusted for maternal but not paternal height. All SGA groups were significantly associated with an increased risk of poor school performance, with adjusted odds ratios and 95% confidence intervals ranging from 1.85 (1.65-2.07) for severe SGA to 1.25 (1.22-1.28) for mild SGA. In the sub-analysis, all birth weight groups were associated with an increased risk of poor school performance among boys with short stature compared to those with non-short stature. Mild SGA is associated with a significantly increased risk of poor school performance, and the risk increases with severity of SGA. Further, this risk diminishes after adequate catch-up growth.


Comparison of serum CA 125, clinical impression, and ultrasound in the preoperative evaluation of ovarian masses.
The ability to differentiate a malignant from a benign ovarian mass was assessed for four diagnostic procedures: serum CA 125, clinical examination, original ultrasound, and reviewer ultrasound interpretation. When these tests were used individually, the sensitivity and specificity of CA 125 levels were equal to those of a review ultrasound. Overall, the sensitivity of clinical impression and original ultrasound was poor. Sensitivity and specificity were highest for CA 125 assays in postmenopausal patients, especially when these were used as the second diagnostic test. Positive and negative predictive values significantly increased among postmenopausal patients when CA 125 was added to any of the other diagnostic tests examined. In conjunction with such tests, measurement of serum CA 125 significantly increased diagnostic accuracy and may thus have an important role in the preoperative evaluation of women with ovarian masses.


Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.
Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.


Interactions between tumor cells and tumor infiltrating lymphocytes in human ovarian carcinoma.
The aim of our study was to investigate the lymphocytic infiltration rate of ovarian tumors and the possible use of tumor-infiltrating lymphocytes (TIL) as a therapeutic tool in gynecologic oncology. Twelve tumors were treated with digesting enzymes in order to isolate tumor-infiltrating lymphocytes as well as tumor cells, TIL were expanded by culture in the presence of human interleukin-2 (IL-2). Freshly prepared tumor cells were allowed to grow in culture medium for several days before the first investigations were performed. TIL could only be isolated from 50% of the investigated tumors. In contrast to this the isolated tumor cells could be largely expanded in 73% of the cases. The expression of the CA125 antigen in the culture supernatants served as control and could still be evaluated up to three months after isolation. In parallel the antigen expression on the cellular surface was estimated by immunocytochemistry. Evaluating the phenotypes of TIL showed predominantly CD3+, their expansion rate was only poor. Tumor cells were isolated and expanded in order to test the tumor-directed cytotoxic efficacy of TIL and for further use in transplantation to nude mice.


Impact of the surgical treatment for degenerative cervical myelopathy on the preoperative cervical sagittal balance: a review of prospective comparative cohort between anterior decompression with fusion and laminoplasty.
Cervical sagittal balance has received increased attention as an important determinant of radiological and clinical outcomes. However, no prospective studies have compared the impact of cervical sagittal balance between anterior and posterior surgeries. We previously conducted a prospective study comparing anterior decompression with fusion (ADF) and laminoplasty (LAMP) for degenerative cervical myelopathy (DCM) and reported; however, analysis of cervical alignment within the concept of sagittal balance has yet to be performed, because that concept has recently been proposed. This study aimed to review this prospective cohort, specifically focusing on cervical sagittal balance. We prospectively performed ADF or LAMP for DCM patients based on the year of enrollment: ADF was performed in odd-numbered years and LAMP in even-numbered years. Cervical lateral X-ray images taken in the neutral standing position were evaluated preoperatively and at a 1-year follow-up. The radiographic measurements included the following: (1) CL (cervical lordosis: C2-7 lordotic angle), (2) CGH (center of gravity of the head)-C7 SVA (sagittal vertical axis), and (3) C7 slope. The clinical results were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (C-JOA score). We analyzed the data for 66 patients (ADF n = 28, LAMP n = 38). While the CL and CGH-C7 SVA in the ADF were unchanged after the operation, those in the LAMP group worsened, especially in patients with preoperative cervical sagittal imbalance. The C7 slopes were not affected by the operation in either group. The postoperative decreases in the CL in the LAMP group correlated with the preoperative CGH-C7 SVA (r = 0.618, P < 0.01), but those in ADF group did not. In patients with preoperative cervical sagittal imbalance (CGH-C7 SVA ≥40 mm), the recovery rate of the C-JOA score in the ADF group was superior to that in the LAMP group (67.3 vs. 39.8 %). In contrast, for patients without cervical sagittal imbalance, the recovery rate of the C-JOA score showed no significant difference between the ADF and LAMP groups (64.5 vs. 58.7 %). Postoperative cervical sagittal alignment and balance were maintained after ADF but deteriorated following LAMP, especially in patients with preoperative CGH-C7 SVA ≥40 mm. In these patients, neurological recovery after LAMP was unsatisfactory. LAMP is not suitable for degenerative cervical myelopathy patients with preoperative cervical sagittal imbalance.


Captopril in heart failure.
The renin production, angiotensin II and aldosterone plasma levels have been proved to occur in heart failure. This pathological abnormalities can be stopped by the inhibition of ACE. This action of captopril is accompanied by a favourable clinical effects, the improvement of the symptoms of heart failure and the increase of sodium and water excretion and the increase of serum potassium level.


Simultaneous measurement of intracellular pH and contraction in uterine smooth muscle.
Changes in intracellular pH (pHi) are thought to produce large changes in force production in the uterus. There have however, been no simultaneous measurements of pHi and force in the uterus and therefore no direct information is available about the relation between the two. We have used carboxy-SNARF (a pH-sensitive fluorophore) in small strips of longitudinal myometrium and obtained simultaneous measurements of pHi and force. SNARF did not alter contractile function, and continuous measurements of pHi could be made for 2 hours. The mean resting pHi (7.16) was similar to that reported previously. Application of weak bases rapidly raised pHi, in a concentration-dependent manner, followed by a gradual restoration of pHi to resting levels. Alkalinization greatly increased the frequency of contractions, often accompanied by a small increase in their amplitude. Removal of base produced a rebound acidification which transiently abolished contractions. Direct acidification of the cytoplasm, by application of weak acid, also abolished contractions. However the alkalinization which accompanied removal of acid, produced variable effects on force.


When Precision Meets Penmanship: ChatGPT and Surgery Documentation.
ChatGPT (Chatbot Generative Pre-Trained Transformer) is an artificial intelligence with several potential applications in the field of medicine. As a large language model, it is particularly good at generating text. This study investigates the use of ChatGPT in constructing operation notes for laparoscopic appendicectomy, one of the most common surgical procedures in the UK. We prompted ChatGPT-4, the latest generation of ChatGPT, to produce operation notes for laparoscopic appendicectomy, which were then evaluated against 'Getting It Right First Time' (GIRFT) recommendations. GIRFT is an organisation that has collaborated with the National Health Service (NHS) to improve surgical documentation guidelines. Excluding certain items documented elsewhere in patient records, the generated notes were assessed against 30 key points in GIRFT recommendations. This process was repeated three times to obtain an average score. Our results showed that ChatGPT generated operation notes in seconds, with an average coverage of 78.8% (23.66 out of 30 points) of the GIRFT guidelines, surpassing average compliance with similar guidelines from the Royal College of Surgeons (RCS). However, the quality of ChatGPT's output was found to be dependent on the quality of the prompt, highlighting the need for verification of the generated content. Additionally, secure integration with electronic health records is required before ChatGPT can be adopted into the NHS.


Effects of pioglitazone on increases in visceral fat accumulation and oxidative stress in spontaneously hypertensive hyperlipidemic rats fed a high-fat diet and sucrose solution.
We examined oxidative stress and metabolic characteristics of the spontaneously hypertensive hyperlipidemic rat (SHHR) when it was fed a high-fat diet and sucrose solution (HFDS) after N(G)-nitro-L-arginine methyl ester ingestion to develop a rat model of metabolic syndrome. This study was carried out to assess the effects of pioglitazone on levels of lipid peroxide (LPO), Cu,Zn superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx), and non-esterified fatty acids (NEFA) in the plasma and liver tissue in HFDS-SHHR compared with Sprague-Dawley rats (SD). In the HFDS-treated groups, levels of LPO, CAT, GPx, and NEFA were elevated and levels of Cu,Zn-SOD were reduced in the plasma and liver tissue, with a marked accumulation of visceral fat. The changes induced by HFDS feeding were severe in the SHHR model that had essential hypertension and hyperlipidemia, when compared with SD that did not have these essential risk factors. Subcutaneous injection of 10 mg/kg per day of pioglitazone for 2 months significantly restored levels of LPO, CAT, GPx, Cu,Zn-SOD, and NEFA in the HFDS-SHHR group, and visceral fat accumulation was reduced. These results suggest that HFDS-SHHR is a suitable model of metabolic syndrome and that pioglitazone treatment can improve oxidative dysregulation in this rat model.


Protective Effect of Edaravone Against Aβ25-35-Induced Mitochondrial Oxidative Damage in SH-SY5Y Cells.
Amyloid-β (Aβ)-induced oxidative stress plays an important role in the pathogenesis of Alzheimer's disease (AD). Recent studies show that Aβ accumulation may lead to mitochondrial oxidative damage. In the present study, we investigated the protective effect of edaravone on mitochondrial damage in SH-SY5Y cells treated with Aβ25-35. SH-SY5Y cells were pre-treated with 20, 40 or 80 μM edaravone before treatment with 25 μM Aβ25-35. After 24h cell culture, cellular apoptosis, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), ATP levels and mitochondrial morphology were evaluated. SH-SY5Y cells exposed to Aβ25-35 had high levels of apoptosis and ROS; loss of ΔΨm, decreased ATP levels and presence of mitochondrial swelling. However, these effects were significantly inhibited by edaravone pre-treatment. These results indicate that edaravone prevents mitochondria oxidative damage caused by Aβ in SH-SY5Y cells, which suggests that it may have potential clinical application in AD therapy.


Induction of impaired membrane phospholipid asymmetry in mature erythrocytes after chemotherapy.
Senescent erythrocytes undergo a loss of phospholipid asymmetry in the plasma membrane and are removed from the circulation by phagocytosis.To examine the loss of phospholipid asymmetry in mature erythrocytes after chemotherapy, we monitored phosphatidylserine (PS)-exposing erythrocytes by using flow cytometry to detect annexin V-bound erythrocytes in the circulation of acute lymphoblastic leukemia patients after consolidation chemotherapy. Both the percentage and the absolute number of annexin V-positive erythrocytes gradually increased immediately after chemotherapy. This result paralleled the change in the serum levels of bilirubin, suggesting a direct induction of PS-externalization in mature erythrocytes and a subsequent increase in erythrocyte clearance by splenic macrophages. The PS-exposing erythrocyte counts showed negative correlations to platelet and reticulocyte counts, which reflect the hematopoietic potential in the bone marrow. This result suggests that bone marrow suppression could be responsible for the enlarged senescent population in the circulation. Moreover, PS-exposing erythrocytes in the circulation remained at relatively high levels even after the serum level of bilirubin normalized, indicating that the decreased clearance of senescent erythrocytes as a result of impaired phagocytosis following bone marrow suppression might also be involved in the increase in PS-exposing erythrocytes in the circulation late after chemotherapy.


Copy number variation in 19 Italian multiplex families with autism spectrum disorder: Importance of synaptic and neurite elongation genes.
Autism Spectrum Disorder (ASD) is endowed with impressive heritability estimates and high recurrence rates. Its genetic underpinnings are nonetheless very heterogeneous, with common, and rare contributing variants located in hundreds of different loci, each characterized by variable levels of penetrance. Multiplex families from single ethnic groups represent a useful means to reduce heterogeneity and enhance genetic load. We screened 19 Italian ASD multiplex families (3 triplets and 16 duplets, total N = 41 ASD subjects), using array-CGH (Agilent 180 K). Causal or ASD-relevant CNVs were detected in 36.6% (15/41) of ASD probands, corresponding to 36.8% (7/19) multiplex families with at least one affected sibling genetically positive. However, only in less than half (3/7) of positive families, affected siblings share the same causal or ASD-relevant CNV. Even in these three families, additional potentially relevant CNVs not shared by affected sib pairs were also detected. These results provide further evidence of genetic heterogeneity in ASD even within multiplex families belonging to a single ethnic group. Differences in CNV burden may likely contribute to the substantial clinical heterogeneity observed between affected siblings. In addition, Gene Ontology enrichment analysis indicates that most potentially causal or relevant ASD genes detected in our cohort belong to nervous system-specific categories, especially involved in neurite elongation and synaptic structure/function. These findings point toward the existence of genomic instability in these families, whose underlying genetic and epigenetic mechanisms deserve further scrutiny.


The carpal tunnel syndrome--a disease underlying Raynaud's phenomenon?
Forty patients with clinically and electromyographically proven carpal tunnel syndrome were examined for the frequency of concomitantly occurring Raynaud's phenomenon. The angiologic work-up was based on a detailed vascular history and examination, Doppler sonography to determine systolic digital artery pressures before and after exposure to the cold (10 degrees C for one minute), and thermoplate tests for recording heat convection of the hands at normal room temperature and measuring rewarming time after standardized cold exposure. Only 10% of the patients were found to have manifest Raynaud's phenomenon. The incidence was thus the same as in the general population. In addition, Raynaud's phenomenon and the carpal tunnel syndrome were poorly correlated with respect to their preliminary symptom appearances. Consequently, the carpal tunnel syndrome can no longer be regarded as a disease underlying Raynaud's phenomenon.


Healing predictors of stable juvenile osteochondritis dissecans knee lesions after 6 and 12 months of nonoperative treatment.
Nonoperative treatment of stable juvenile osteochondritis dissecans (JOCD) lesions of the knee fails in up to 50% of cases. Healing predictors are needed to identify potential failures and thus determine treatment options. A predictive model for healing potential after 6 and 12 months of nonoperative treatment of stable JOCD lesions based on sensitive magnetic resonance imagining (MRI) follow-up measurements was developed. Cohort study (diagnosis); Level of evidence, 2. A retrospective cross-sectional study was conducted to analyze 62 white patients (76 stable JOCD lesions) who were initially treated by restriction of activity until they were free of pain. The primary end point was healing investigated on MRI with follow-up measurements after 6 and 12 months of nonoperative treatment. Multivariate logistic regression was used to determine the influence of age, sex, JOCD lesion size, clinical symptoms, and the occurrence of cystlike lesions (CLLs) on healing potential. Additionally, optimal prognostic cutoffs were defined to differentiate failures from nonfailures. After 6 months of nonoperative treatment, 51 (67%) of 76 stable JOCD lesions showed no progression toward healing or showed signs of instability. Normalized lesion width and area and CLL occurrence differed significantly between failures and nonfailures (P < .05). A multivariate logistic regression best-predictors model that included age, CLL size, and normalized lesion width best predicted healing after 6 months and resulted in an area under the curve (AUC) of 0.779 (P < .001). A cutoff at 48% healing probability, as predicted by a nomogram based on age, normalized lesion width, and CLL size, differentiated failures from nonfailures (sensitivity, 60.0%; specificity, 83.7%). After 12 months, 37 lesions (49%) had progressed toward healing, and the sole observation of CLL size had the highest predictive validity (AUC, 0.766). The optimal cutoff was a healing probability of 61% (lesion size, 1.3 mm; sensitivity, 70.3%; specificity, 74.1%). A 6-month period of nonoperative treatment with or without casting might be appropriate if the healing potential is >48%. A 12-month period of nonoperative treatment may be successful if the CLL is <1.3 mm in length as assessed on MRI.


The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling.
Repair mechanisms after acetaminophen (APAP) hepatotoxicity are poorly understood. We recently discovered that phosphatidic acid (PA) increases in mice and humans after APAP overdose, and is critical for liver regeneration. Here, we hypothesized that PA inhibits glycogen synthase kinase-3β (GSK3β), a component of canonical Wnt/β-catenin signaling, after APAP overdose. To test that, we treated mice with 300 mg/kg APAP at 0 h followed by vehicle or 20 mg/kg of the glycerol 3-phosphate acyltransferase inhibitor FSG67 at 3, 24 and 48 h. Some mice also received the GSK3 inhibitor L803-mts. Blood and liver were collected at multiple time points. Consistent with our earlier results, FSG67 did not affect toxicity (ALT, histology), APAP bioactivation (total glutathione), or oxidative stress (oxidized glutathione), but did reduce expression of proliferating cell nuclear antigen (PCNA) at 52 h. We then measured GSK3β phosphorylation and found it was dramatically decreased by FSG67 at 24 h, before PCNA dropped. Expression of cyclin D1, downstream of Wnt/β-catenin, was also reduced. To determine if the effect of FSG67 on GSK3β is important, we treated mice with FSG67 and L803-mts after APAP. Importantly, L803-mts rescued hepatocyte proliferation and survival. Our data indicate PA and lysoPA may support recovery after APAP overdose by inhibiting GSK3β.


Effect of growth implant regimen on health, performance, and immunity of high-risk, newly received stocker cattle.
Growth implant efficacy may be affected when administered to nutritionally stressed calves, whereas the procedure may alter health or the humoral immune response to respiratory vaccination. The study objective was to determine the effect of different administration times (d 0, 14, or 28) of a growth implant containing 200 mg progesterone and 20 mg estradiol benzoate on health, performance, and metabolic and immunologic variables in high-risk, newly received beef calves used in a 120-d receiving/grazing stocker system. Crossbred bull and steer calves ( = 203) were weighed (initial BW = 203 ± 2.7 kg), stratified by castrate status on arrival, and randomly assigned to experimental treatments consisting of 1) negative control (no growth implant administered), 2) growth implant administered on d 0, 3) growth implant administered on d 14, and 4) growth implant administered on d 28. There were no differences ( ≥ 0.16) in BW or ADG during the 42-d receiving period. However, ADG during the subsequent grazing period and overall was greater ( ≤ 0.01) for implanted calves versus the negative control. Growth implant timing did not affect the rate of clinical bovine respiratory disease morbidity ( = 0.52; 94% morbidity overall) or bovine viral diarrhea virus type 1a antibody titer concentration ( = 0.61). Indicative of an overall negative energy balance on arrival, NEFA decreased sharply subsequent to d 0 (day effect, < 0.001), but was not affected ( = 0.47) by the timing of growth implantation. Blood urea N concentrations increased transiently (day effect, < 0.001); however, no treatment effect was observed ( = 0.72). Therefore, under conditions of this study, the timing of growth implant administration did not affect growth implant efficacy, health, or metabolic or immunologic variables in newly received, high-risk beef stocker calves. Overall, our observations suggest that there is not a clear benefit to delaying growth implantation and that a growth implant does not affect health or vaccine response in newly received beef calves.


Regenerable Cu-intercalated MnO2 layered cathode for highly cyclable energy dense batteries.
Manganese dioxide cathodes are inexpensive and have high theoretical capacity (based on two electrons) of 617 mAh g-1, making them attractive for low-cost, energy-dense batteries. They are used in non-rechargeable batteries with anodes like zinc. Only ∼10% of the theoretical capacity is currently accessible in rechargeable alkaline systems. Attempts to access the full capacity using additives have been unsuccessful. We report a class of Bi-birnessite (a layered manganese oxide polymorph mixed with bismuth oxide (Bi2O3)) cathodes intercalated with Cu2+ that deliver near-full two-electron capacity reversibly for >6,000 cycles. The key to rechargeability lies in exploiting the redox potentials of Cu to reversibly intercalate into the Bi-birnessite-layered structure during its dissolution and precipitation process for stabilizing and enhancing its charge transfer characteristics. This process holds promise for other applications like catalysis and intercalation of metal ions into layered structures. A large prismatic rechargeable Zn-birnessite cell delivering ∼140 Wh l-1 is shown.


Vaccine Hesitancy Among General Practitioners and Its Determinants During Controversies: A National Cross-sectional Survey in France.
This study aimed to assess: 1) vaccine hesitancy (VH) prevalence among French general practitioners (GPs) through the frequency of their vaccine recommendations, and 2) the determinants of these recommendations. Cross-sectional observational study in 2014 nested in a national panel of 1712 randomly selected GPs in private practice in France. We constructed a score of self-reported recommendation frequency for 6 specific vaccines to target populations. 16% to 43% of GPs sometimes or never recommended at least one specific vaccine to their target patients. Multivariable logistic regressions of the dichotomized score showed that GPs recommended vaccines frequently when they felt comfortable explaining their benefits and risks to patients (OR = 1.87; 1.35-2.59), or trusted official sources of information highly (OR = 1.40; 1.01-1.93). They recommended vaccines infrequently when they considered that adverse effects were likely (OR = 0.71; 0.52-0.96) or doubted the vaccine's utility (OR = 0.21; 0.15-0.29). Our findings show that after repeated vaccine controversies in France, some VH exists among French GPs, whose recommendation behaviors depend on their trust in authorities, their perception of the utility and risks of vaccines, and their comfort in explaining them. Further research is needed to confirm these results among health care workers in other countries.


Complete Genome Sequence of Thiostrepton-Producing Streptomyces laurentii ATCC 31255.
Streptomyces laurentii ATCC 31255 produces thiostrepton, a thiopeptide class antibiotic. Here, we report the complete genome sequence for this strain, which contains a total of 8,032,664 bp, 7,452 predicted coding sequences, and a G+C content of 72.3%.


The chemical and antiviral properties of the somatic antigen of Phase II Shigella sonnei.
1. The somatic antigen of Phase II Shigella sonnei can be isolated by extracting phenol-killed microorganisms with water. This substance inactivates all T phages to which this bacillus is susceptible. 2. The Phase II antigen is constituted from a protein and a phosphorylated lipocarbohydrate. The major portion of the protein component can be removed by digestion with pancreatin. The enzymatically degraded antigen thus obtained can be further dissociated into its protein and lipocarbohydrate components by treatment with 90 per cent phenol. Glucose, galactose, glucosamine, and an aldoheptose have been identified as the monosaccharide constituents of the lipocarbohydrate.


New Constraint on Primordial Lepton Flavor Asymmetries.
A chiral chemical potential present in the early Universe can source helical hypermagnetic fields through the chiral plasma instability. If these hypermagnetic fields survive until the electroweak phase transition, they source a contribution to the baryon asymmetry of the Universe. In this Letter, we demonstrate that lepton flavor asymmetries above |μ|/T∼9×10^{-3} trigger this mechanism even for vanishing total lepton number. This excludes the possibility of such large lepton flavor asymmetries present at temperatures above 10^{6} GeV, setting a constraint which is about 2 orders of magnitude stronger than the current CMB and BBN limits.


Advancing Pharmacogenomics as a Component of Precision Medicine: How, Where, and Who?
Pharmacogenomics is an important element of precision medicine. Advances in pharmacogenomics implementation have been made but significant barriers remain, including evidence, reimbursement, and clinician knowledge, among others. Widespread adoption of pharmacogenomics requires overcoming these barriers, a clinician champion group, which we propose will be pharmacists, and an easily accessible setting, which may be the community pharmacy. Whatever the path, it must be evidence-driven and pharmacogenomics must improve drug-related outcomes to become a standard of care.


Effect of low levels of dietary available phosphorus on phosphorus utilization, bone mineralization, phosphorus transporter mRNA expression and performance in growing pigs.
A study was conducted to examine the effects of different dietary levels of available phosphorus (aP) on P excretion, bone mineralization, performance and the mRNA expression of sodium-dependent P transporters in growing pigs. Sixty-day old growing pigs (n = 54) with an average initial BW of 19.50 ± 1.11 kg were randomly allocated to a control diet (C) containing 0.23% available phosphorus (aP), T1 containing 0.17% aP and T2 containing 0.11% aP. There were 6 pens per treatment with 3 pigs per pen. Body weight and feed intake were measured weekly. At the end of each week, one pig from each pen was housed in a metabolic crate for 24 h to collect fecal and urine samples and then sacrificed to obtain third metacarpal (MC3) bones and jejunal and kidney samples. Bones were scanned by Dual Energy X-ray Absorptiometry (DEXA). Fecal and urine samples were sub-sampled and analyzed for P content. The expression of P transporter mRNA in jejunum and kidney samples was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Data were analyzed using GLM procedure of the Statistical Analysis System (SAS Institute version 9.2). Pigs fed the T2 diet had reduced (P < 0.05) average daily gain (ADG) and gain to feed (G:F) compared to those fed the C diet during week 2. Overall, ADG and G:F were also reduced (P < 0.05) in pigs fed the T2 diet compared to those fed the C and T1 diets. Bone mineral density (BMD) and bone mineral content (BMC) were reduced (P < 0.05) in pigs fed the T2 diet compared to those fed the C diet throughout the experiment. At week 1, jejunal mRNA expression of Na (+)-dependent phosphate transporter 2 (SLC34A2) was increased (P < 0.01) in pigs fed the T2 diet compared to C diet. Renal mRNA expression of Na(+)-dependent phosphate transporter 1 (SLC34A1) and SLC34A3 were increased (P < 0.05) in pigs fed the T2 diet compared to those fed the C diet at week 2 and was accompanied by lower (P < 0.05) urinary P in pigs fed the T2 diet during week 2 and week 3. In conclusion, growing pigs are highly sensitive to low dietary P as shown by reduced ADG, bone mineralization and urinary P level, but moderate reduction in dietary P up to 0.17% aP in the diet has the potential to reduce environmental pollution by reducing P concentration in swine manure and without compromising performance.


Incrimination of Aedes (Stegomyia) hensilli Farner as an epidemic vector of Chikungunya virus on Yap Island, Federated States of Micronesia, 2013.
Two species of Aedes (Stegomyia) were collected in response to the first chikungunya virus (CHIKV) outbreak on Yap Island: the native species Ae. hensilli Farner and the introduced species Ae. aegypti (L.). Fourteen CHIKV-positive mosquito pools were detected. Six pools were composed of female Ae. hensilli, six pools were composed of female Ae. aegypti, one pool was composed of male Ae. hensilli, and one pool contained female specimens identified as Ae. (Stg.) spp. Infection rates were not significantly different between female Ae. hensilli and Ae. aegypti. The occurrence of human cases in all areas of Yap Island and the greater number of sites that yielded virus from Ae. hensilli combined with the ubiquitous distribution of this species incriminate Ae. hensilli as the most important vector of CHIKV during the outbreak. Phylogenic analysis shows that virus strains on Yap are members of the Asia lineage and closely related to strains currently circulating in the Caribbean.


Metastases suppressor NM23-H2 interaction with G-quadruplex DNA within c-MYC promoter nuclease hypersensitive element induces c-MYC expression.
Regulatory influence of the G-quadruplex or G4 motif present within the nuclease hypersensitive element (NHE) in the promoter of c-MYC has been noted. On the other hand, association of NM23-H2 to the NHE leads to c-MYC activation. Therefore, NM23-H2 interaction with the G4 motif within the c-MYC NHE presents an interesting mechanistic possibility. Herein, using luciferase reporter assay and chromatin immunoprecipitation we show NM23-H2 mediated c-MYC activation involves NM23-H2-G4 motif binding within the c-MYC NHE. G4 motif complex formation with recombinant NM23-H2 was independently confirmed using fluorescence energy transfer, which also indicated that the G4 motif was resolved to an unfolded state within the protein-bound complex. Taken together, this supports transcriptional role of NM23-H2 via a G4 motif.


Signs of beta-cell autoimmunity in nondiabetic schoolchildren: a comparison between Russian Karelia with a low incidence of type 1 diabetes and Finland with a high incidence rate.
We sought to study the prevalence of autoantibodies to various islet cell antigens in the background population of two neighboring countries with a sixfold difference in the incidence of type 1 diabetes. Serum samples were obtained from 3,652 nondiabetic schoolchildren in Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of Russia. The Karelian children were divided into three groups (Finns/Karelians, Russians, and others) based on the ethnic background of their mother. The samples were analyzed for islet cell antibodies (ICAs), insulin autoantibodies (IAAs), GAD antibodies (GADAs), and the tyrosine phosphatase-like insulinoma antigen 2 (IA-2A) protein and HLA class II genotypes. The frequency of ICAs, IAAs, and GADAs did not differ significantly between the Karelian (3.5, 0.6, and 0.9%, respectively) and Finnish children (2.8, 0.9, and 0.5%, respectively). Similarly, the frequency of multiple (> or = 2) autoantibodies was similar in both countries (0.5 vs. 0.6%). The frequency of IA-2A was, however, four times higher in Finland (0.6 vs. 0.15% in Russian Karelia; P = 0.03). There were no significant differences in autoantibody prevalence among the three ethnic groups in Russian Karelia. There was a falling frequency of GADAs and of positivity for multiple autoantibodies along with decreasing HLA-conferred disease susceptibility among the Finnish schoolchildren. These data indicate that beta-cell autoimmunity among schoolchildren is as frequent in Russian Karelia as in Finland, although the incidence of clinical type 1 diabetes is six times higher in Finland. However, in contrast to this general trend, IA-2As were more common in Finland. Since IA-2As usually appear late in the preclinical process, this suggests that progressive beta-cell autoimmunity is more rare in Russian Karelia.


Hypothalamic secretion of somatostatin and growth hormone-releasing factor into the hypophysial-portal circulation is reduced in streptozotocin diabetic male rats.
Growth hormone (GH) secretory patterns are disrupted in streptozotocin (STZ) diabetic rats. Alterations in hypothalamic growth hormone-releasing factor (GRF) or hypothalamic somatostatin (SRIF) secretion, increased systemic SRIF secretion, and changes in somatotroph sensitivity to these hypothalamic factors have been advanced as potential underlying mechanisms for the observed attenuation of GH secretion after STZ treatment. Two weeks after STZ treatment, the mean circulating GH level was attenuated by 58%, plasma glucose concentration was 4-fold higher, and systemic SRIF concentration was elevated 6.8-fold with respect to vehicle (VEH)-treated rats. The hypothalamic content of neither SRIF nor GRF was significantly different between VEH and STZ groups. Total hypophysial-portal SRIF concentration, which represents the sum of both peripheral and hypothalamic SRIF contributions, was significantly elevated in the STZ versus VEH group (p less than 0.007). However, when corrected for the contribution of peripheral SRIF, the mean portal SRIF concentration in STZ rats was only 44% of the mean portal SRIF in VEH rats. A reduction in hypophysial-portal GRF concentration in STZ diabetic rats was also observed. Overall, these observations suggest that elevated peripheral SRIF levels characteristic of STZ diabetic rats play a major role in mediating the suppression of GH secretion in this model. Furthermore, the data are suggestive of an inhibitory effect of peripheral SRIF on hypothalamic SRIF release.


Glycosylation of SARS-CoV-2: structural and functional insights.
The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to other coronaviruses, its particles are composed of four structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. S, E, and M proteins are glycosylated, and the N protein is phosphorylated. The S protein is involved in the interaction with the host receptor human angiotensin-converting enzyme 2 (hACE2), which is also heavily glycosylated. Recent studies have revealed several other potential host receptors or factors that can increase or modulate the SARS-CoV-2 infection. Interestingly, most of these molecules bear carbohydrate residues. While glycans acquired by the viruses through the hijacking of the host machinery help the viruses in their infectivity, they also play roles in immune evasion or modulation. Glycans play complex roles in viral pathobiology, both on their own and in association with carrier biomolecules, such as proteins or glycosaminoglycans (GAGs). Understanding these roles in detail can help in developing suitable strategies for prevention and therapy of COVID-19. In this review, we sought to emphasize the interplay of SARS-CoV-2 glycosylated proteins and their host receptors in viral attachment, entry, replication, and infection. Moreover, the implications for future therapeutic interventions targeting these glycosylated biomolecules are also discussed in detail.


Synapse efficiency diverges due to synaptic pruning following overgrowth.
In the development of the brain, it is known that synapses are pruned following overgrowth. This pruning following overgrowth seems to be a universal phenomenon that occurs in almost all areas-visual cortex, motor area, association area, and so on. It has been shown numerically that the synapse efficiency is increased by systematic deletion. We discuss the synapse efficiency to evaluate the effect of pruning following overgrowth, and analytically show that the synapse efficiency diverges as O(|ln c|) at the limit where connecting rate c is extremely small. Under a fixed synapse number criterion, the optimal connecting rate, which maximizes memory performance, exists.


Population-based epidemiological study of primary intracranial tumors in childhood.
Brain tumors are the most common solid tumors in children and their prognosis is poor. Epidemiologic data from a population-based cancer registry provide the information necessary to determine the incidence rate of pediatric brain tumors. The aim of this study was to determine the epidemiology of childhood primary intracranial tumors in Kumamoto Prefecture, Japan. We surveyed 210 patients younger than 15 years who were diagnosed with primary intracranial tumors between 1989 and 2008; 159 (75.7%) of the tumors were confirmed microscopically. The age-adjusted annual incidence rate was 36.1 cases per million children. The boys/girls ratio was 1.31. The age-specific annual incidence rate was 28.5-, 40.9-, and 38.4 cases per million for the 0- to 4-, 5- to 9-, and 10- to 14-year age group, respectively. The incidence was highest in 10- to 14-year-old boys (53.6 per million) and lowest in 10- to 14-year-old girls (22.6 per million). The most common tumor was astrocytoma (35.7%) with an annual incidence rate of 13.2 per million, followed by germ cell tumor (14.3%, 5.0 per million), craniopharyngioma (10.5%, 3.8 per million), medulloblastoma (10.0%, 3.7 per million), and ependymoma (4.8%, 1.5 per million). The distribution of the tumor type varied with the patient age and gender. Although there were no germ cell tumors in 0- to 4-year-old boys, they were the second-most common tumor in 10- to 14-year-old boys. Conversely, while there were no medulloblastomas in 10- to 14-year-old girls, their incidence was high in 0- to 4-year-old girls. In this Kumamoto survey, the incidence rate of primary intracranial tumors in children was similar to that in Western countries. However, the incidence and relative frequency of particular histological types of childhood brain tumors such as germ cell tumors and craniopharyngiomas were different between Japan and Western countries.


Biologic transplantation and neurotrophin-induced neuroplasticity after traumatic brain injury.
In this review, we analyze progress in the treatment of traumatic brain injury with neurotrophins, growth factors and cell and tissue neurotransplantation. The primary objective of these therapies is to reduce neurologic deficits associated with the trauma by inducing neuroplasticity. These therapies are restorative and not necessarily neuroprotective. An extensive literature on administration of neurotrophics factors and cell and tissue cerebral transplantation is reviewed. The effects of these therapeutic approaches on brain biochemical, molecular, cellular, and tissue responses are summarized. The cumulative data indicate that cell therapy shows substantial promise in the treatment of neural injury.


Post-traumatic anterior hypopituitarism.
Reports of anterior pituitary insufficiency following closed head trauma are unusual. In those cases reported, extensive endocrinologic evidence to support the clinical syndrome is often lacking. The present report documents a case of anterior pituitary insufficiency in a 14-year-old girl following a skull fracture. Endocrine evaluation one year after her automobile accident revealed hypopituitarism minifested by cachexia, hypothyroidism, hypoadrenocorticism, and hypogonadism with regression of secondary sex characteristics. Laboratory studies demonstrated deficiencies of both trophic and peripheral anterior pituitary hormones. The patient has responded to replacement therapy and is clinically well. A review of previously described cases is included.


Sales of systemic anti-infective agents in Cyprus in comparison with four other European countries.
To determine the pattern of systemic antibiotic sales in Cyprus during the years 1990-1993 and 1996 and make a comparison with other four European countries. The Anatomical Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD) methodology according to the WHO (World Health Organization) guidelines were employed and data in wholesales were used. The results were presented as DDD/1000 inhabitants/day and were compared with similar results from Sweden, Norway, Denmark and Greece. Data from two independent surveys (1990 and 2001/2002), which covered a total sample of 166,979 persons regarding medicine taking in Cyprus were also used. The overall sales of systemic anti-infective agents in Cyprus were 22.1, 20.6, 24.5 and 24.2 DDD/1000 inhabitants/day for 1990, 1991, 1992 and 1993 respectively. The sales number increased to 30.2 by 1996. Penicillins, cephalosporins and tetracyclines had the greatest share. The above numbers were higher than the respective ones in the reference countries. The first independent survey conducted in 1990 showed that 4.2% of the population reported to take antibiotics without prescription. The second survey provided evidence about the kind of antibiotics taken by the sample (mainly amoxicillin and ciprofloxacin). These data reveal that the sales of antibiotics in Cyprus are higher than in Sweden, Norway, Denmark and Greece. The broad-spectrum antibiotics in Cyprus have higher sales than the other antibiotics. This study describes for the first time the pattern of systemic anti-infective agent sales in Cyprus. Further investigations are needed in order to determine the possible factors that might be implicated or explain the high antibiotic sales in Cyprus.


[Molecular characterization of 71 cases of glucose-6-phosphate dehydrogenase deficiency in Hainan province].
To molecularly analyze in Han and Li individuals of glucose-6-phosphate dehydrogenase deficiency in Hainan, China. The amplification refractory mutation system (ARMS) was employed to detect G1376T, G1388A and A95G mutations. The coding regions and flanking intronic regions from the second to the thirteenth exons of G6PD gene was analyzed by DNA sequencing to characterize the gene mutations in samples without G1376T, G1388A and A95G mutations. Among 29 Han cases of G6PD deficiency, 11 had G1376T (37.9%), 2 G1388A (6.9%), 1 G1376T and G1388A (3.4%) and 1 G1376T and A95G (3.4%) were identified. Mutations of G1376T, G1388A, A95G and their complex accounted for 51.7% of G6PD deficiency in the Han individuals. Among 42 Li cases of G6PD deficiency, 25 had G1376T (59.5%), 6 G1388A (14.3%), 2 A95G (4.8%), 4 G1376T and G1388A (9.5%), 1 G1376T and A95G (2.4% )were identified. These mutations accounted for 90.5% of the Li individuals. Gene mutation of 18 cases (14 Han and 4 Li individuals) remained unknown. Sequencing results of the 18 samples indicated that one case had a single base of T deletion at nucleotide 636 or 637 in the 5th intron (IVS-5 636 or 637 T del) and two cases had C1311T with IVS-11 T93C mutation. G6PD G1376T and G1388A are the most common mutations in the populations of the Han and Li nationalities in Hainan. The IVS-5 636 or 637 T del mutation is first reported in Chinese, and the complex mutation of G1376T/A95G is first found in the Li nationality.


The Foxc2 transcription factor regulates angiogenesis via induction of integrin beta3 expression.
Forkhead transcription factor Foxc2 is an essential regulator of the cardiovascular system in development and disease. However, the cellular and molecular functions of Foxc2 in vascular endothelial cells are still not fully understood. Here, through gene expression profiling in endothelial cells, we identified molecules associated with cell-extracellular matrix interactions, integrin beta3 (Itgb3), integrin beta5 (Itgb5), and fibronectin, as downstream targets of Foxc2. We found that Itgb3 expression is directly regulated by Foxc2 through multiple Forkhead-binding elements within two high homology regions in the Itgb3 promoter. Because Itgb3 is known to regulate angiogenesis, we further tested whether Foxc2 is directly involved in angiogenesis by regulating Itgb3 expression by in vitro experiments. Overexpression of Foxc2 significantly enhanced endothelial cell migration and adhesion, whereas this effect was strongly inhibited by Itgb3 neutralization antibody. In accordance with these results, pulmonary microvascular endothelial cells isolated from Foxc2 heterozygous mutant mice showed a marked reduction in Itgb3 expression and cell migration. Finally, ex vivo aortic ring assay to test the sprouting and microvessel formation revealed enhanced microvessel outgrowth by Foxc2 overexpression. Conversely, microvessel outgrowth from aortas of Foxc2 heterozygous mutant mice was reduced. Taken together, these results suggest that Foxc2 directly induces Itgb3 expression and regulates angiogenesis by Itgb3-mediated endothelial cell adhesion and migration.


The Effectiveness of an Interpersonal Cognitive Problem-Solving Strategy on Behavior and Emotional Problems in Children with Attention Deficit Hyperactivity.
This study was designed to evaluate the effectiveness of the "I Can Problem Solve" (ICPS) program on behavioral and emotional problems in children with attention deficit hyperactivity disorder (ADHD). The subjects were 33 children with ADHD aged between 6 to 11 years. The study used a pre- and post-test quasi-experimental design with one group. The researchers taught 33 children with ADHD how to apply ICPS over a period of 14 weeks. The Child Behavior Checklist for Ages 6-18 (Teacher Report Form) and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition Text Revision (DSM-IV-TR) Based Disruptive Behavior Disorders Screening and Rating Scale (parents' and teacher's forms) were used to evaluate the efficacy of the program. The scales were applied to parents and teachers of the children before and after the ICPS program. The findings indicated that the measured pre-training scores for behavioral and emotional problems (attention difficulties, problems, anxious/depressed, withdrawn/depressed, oppositional defiant problems, rule breaking behaviors, and aggressive behaviors) were significantly decreased in all children post-training. In addition, children's total competence scores increased (working, behaving, learning and happy) after the ICPS program. According to the results, it is likely that, ICPS would be a useful program to decrease certain behavioral and emotional problems associated with ADHD and to increase the competence level in children with ADHD. An additional benefit of the program might be to empower children to deal with problems associated with ADHD such as attention difficulties, hyperactivity-impulsivity, and oppositional defiant problems.


Thyroid hormone receptor alpha is a molecular switch of cardiac function between fetal and postnatal life.
Thyroid hormones are involved in the regulation of many physiological processes and regulate gene transcription by binding to their nuclear receptors TRalpha and TRbeta. In the absence of triiodothyronine (T3), the unliganded receptors (aporeceptors) do bind DNA and repress the transcription of target genes. The role of thyroid hormone aporeceptors as repressors was observed in hypothyroid adult mice, but its physiological relevance in nonpathological hypothyroid conditions remained to be determined. Here we show that, in the normal mouse fetus, TRalpha aporeceptors repress heart rate as well as the expression of TRbeta and several genes encoding ion channels involved in cardiac contractile activity. Right after birth, when T3 concentration sharply increases, liganded TRalpha (holoreceptors) turn on the expression of some of these same genes concomitantly with heart rate increase. These data describe a physiological situation under which conversion of TRalpha from apo-receptors into holo-receptors, upon changes in T3 availability, plays a determinant role in a developmental process.


Novel formulation of a reconstituted high-density lipoprotein (CSL112) dramatically enhances ABCA1-dependent cholesterol efflux.
The ability of high-density lipoprotein (HDL) to remove cholesterol from atherosclerotic plaque is thought to underlie its inverse correlation with cardiovascular risk. Our objective was to produce and characterize a human apolipoprotein AI (apoA-I) product optimized to treat clinical atherosclerotic disease. A new formulation of full length, plasma-derived human apoA-I termed CSL112 was designed to maximize the cholesterol efflux from cells and exhibit favorable pharmacological properties. CSL112 is a disc-shaped particle that strongly elevates cholesterol esterification and shows good pharmacokinetics in rabbits. Infusion of CSL112 into rabbits caused a strong and immediate increase in the ATP binding cassette transporter A1 (ABCA1)-dependent efflux capacity of plasma, an increase in plasma unesterified cholesterol and rapid subsequent cholesterol esterification. In the presence of human plasma, CSL112 was significantly more potent than native HDL at enhancing cholesterol efflux from macrophages, and the efflux elevation was predominantly via the ABCA1 transporter. Consistent with this observation, addition of CSL112 to plasma led to generation of high levels of HDL-VS, a favorable substrate for ABCA1. The lipid profile of plasma did not affect these behaviors. In studies with whole human blood, CSL112 reduced expression of intercellular adhesion molecule 1 and cytokine secretion, and as with cholesterol efflux, these activities were substantially greater than those of native HDL assayed in parallel. CSL112 has favorable pharmacological properties and strongly elevates the ability of plasma to withdraw cholesterol from cells. Preferential elevation of ABCA1-dependent efflux may target atherosclerotic plaque for cholesterol removal and this property makes CSL112 a promising candidate therapy for acute coronary syndrome.


Impotence and its non-surgical management.
Impotence is a common symptom which can cause considerable distress to both the sufferer and his partner. The use of pharmacotherapy to improve erectile function will continue to increase as safe and effective drugs are developed. However, restoring erectile function should not be the only treatment objective. It is also essential to address personal and emotional factors in the sufferer, conflicts in his relationship with his partner, and sexual problems in his partner, all of which may be instrumental in causing or maintaining the presenting impotence. We advocate a combined approach with appropriate medical treatment and sex and couple therapy.


The science of salt: A regularly updated systematic review of salt and health outcomes (December 2015-March 2016).
The purpose of this review was to identify, summarize, and critically appraise studies on dietary salt relating to health outcomes that were published from December 2015 to March 2016. The search strategy was adapted from a previous systematic review on dietary salt and health. Overall, 13 studies were included in the review: one study assessed cardiovascular events, nine studies assessed prevalence or incidence of blood pressure or hypertension, one study assessed kidney disease, and two studies assessed other health outcomes (obesity and nonalcoholic fatty liver disease). Four studies were selected for detailed appraisal and commentary. One study met the minimum methodologic criteria and found an increased risk associated with lower sodium intake in patients with heart failure. All other studies identified in this review demonstrated positive associations between dietary salt and adverse health outcomes.


The Iowa Gambling Task in Parkinson's disease: A meta-analysis on effects of disease and medication.
Decision-making under uncertainty as measured by the Iowa Gambling Task has frequently been studied in Parkinson's disease. The dopamine overdose hypothesis assumes that dopaminergic effects follow an inverted U-shaped function, restoring some cognitive functions while overdosing others. The present work quantitatively summarizes disease and medication effects on task performance and evaluates evidence for the dopamine overdose hypothesis of impaired decision-making in Parkinson's disease. A systematic literature search was performed to identify studies examining the Iowa Gambling Task in patients with Parkinson's disease. Outcomes were quantitatively combined, with separate estimates for the clinical (patients ON medication vs. healthy controls), disease (patients OFF medication vs. healthy controls), and medication effects (patients ON vs. OFF medication). Furthermore, using meta-regression analysis it was explored whether the study characteristics drug level, disease duration, and motor symptoms explained heterogeneous performance between studies. Patients with Parkinson's disease ON dopaminergic medication showed significantly impaired Iowa Gambling Task performance compared to healthy controls. This impairment was not normalized by short-term withdrawal of medication. Heterogeneity across studies was not explained by dopaminergic drug levels, disease durations or motor symptoms. While this meta-analysis showed significantly impaired decision-making performance in Parkinson's disease, there was no evidence that this impairment was related to dopamine overdosing. However, only very few studies assessed patients OFF medication and future studies are needed to concentrate on the modulation of dopaminergic drug levels and pay particular attention to problems related to repeated testing. Furthermore, short- vs. long-term medication effects demand further in-depth investigation.


Spatio-temporal dynamics and laterality effects of face inversion, feature presence and configuration, and face outline.
Although a crucial role of the fusiform gyrus (FG) in face processing has been demonstrated with a variety of methods, converging evidence suggests that face processing involves an interactive and overlapping processing cascade in distributed brain areas. Here we examine the spatio-temporal stages and their functional tuning to face inversion, presence and configuration of inner features, and face contour in healthy subjects during passive viewing. Anatomically-constrained magnetoencephalography (aMEG) combines high-density whole-head MEG recordings and distributed source modeling with high-resolution structural MRI. Each person's reconstructed cortical surface served to constrain noise-normalized minimum norm inverse source estimates. The earliest activity was estimated to the occipital cortex at ~100 ms after stimulus onset and was sensitive to an initial coarse level visual analysis. Activity in the right-lateralized ventral temporal area (inclusive of the FG) peaked at ~160 ms and was largest to inverted faces. Images containing facial features in the veridical and rearranged configuration irrespective of the facial outline elicited intermediate level activity. The M160 stage may provide structural representations necessary for downstream distributed areas to process identity and emotional expression. However, inverted faces additionally engaged the left ventral temporal area at ~180 ms and were uniquely subserved by bilateral processing. This observation is consistent with the dual route model and spared processing of inverted faces in prosopagnosia. The subsequent deflection, peaking at ~240 ms in the anterior temporal areas bilaterally, was largest to normal, upright faces. It may reflect initial engagement of the distributed network subserving individuation and familiarity. These results support dynamic models suggesting that processing of unfamiliar faces in the absence of a cognitive task is subserved by a distributed and interactive neural circuit.


Effect of gaze orientation on tactilo-kinesthetic performance.
Twenty-two normal right-handed subjects indicated with their index finger the midpoint of a horizontal rod that they could not see. Subjects performed this task while directing their gaze either centrally or toward four different locations (5 degrees or 30 degrees to the left or to the right of the midline). Results showed an overall leftward bias in rod bisection, which increased when subjects used their right hand and fixated a right-sided visual target. Thus, orienting of gaze can affect a nonvisual, tactilo-kinesthetic spatial task. The possible mechanisms of this interaction are discussed with respect to activation-orienting theories egocentric hypotheses and directional trends.


The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis.
Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model. Two different doses of rhBMP-2 (LD low dose, HD high dose) with a HA/TCP carrier were injected into the femoral intramedullary canal of rats with T1DM-related osteoporosis. Two more diabetic rat groups were injected with saline alone and with HA/TCP carrier alone. Radiographs and micro-computed tomography were utilized for qualitative assessment of bone mineral density (BMD). Biomechanical testing occurred at 4- and 8-week time points; parameters tested included torque to failure, torsional rigidity, shear stress, and shear modulus. At the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences. Groups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment. Not applicable.


Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer.
Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015. In the FOLFIRINOX group, patients received 85 mg/m2 oxaliplatin followed by 180 mg/m2 irinotecan and 200 mg/m2 L-leucovorin, and by 400 mg/m2 fluorouracil as a bolus and 2,400 mg/m2 fluorouracil as a 46-h continuous infusion every 14 days. In the GnP group, patients received 125 mg/m2 nab-PTX followed by 1 g/m2, and gemcitabine on days 1, 8 and 15, repeated every 28 days. Response rate was 6.3% in the FOLFIRINOX group and 40.9% in the GnP group (P=0.025). Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 3.0-4.5] in the FOLFIRINOX group and 6.5 months (95% CI, 6.2-6.9 months) in the GnP group (P=0.031). Drug toxicity in the GnP group was less than in the FOLFIRINOX group. Efficacy and safety of GnP compare favorably to those of FOLFIRINOX in patients with pancreatic cancer. Additional prospective trials are warranted.


Paraneoplastic syndrome simulating encephalitis in the course of testicular seminoma.
A case of paraneoplastic syndrome diagnosed post mortem in a 68-year-old man with a single submandibular lymphatic metastasis of testicular seminoma is presented. The syndrome developed 3 years after orchidectomy and clinically combined the features of limbic and bulbar encephalitis together with signs of cerebellar degeneration. Histological examination revealed marked loss of cerebellar Purkinje and granular cells and to a lesser extent of cerebral cortical neurons. Additionally axonal injury (spheroids) and multifocal demyelination with sparse lymphocytic infiltrations was observed. Immunohistochemically, strong reaction with monoclonal anti-human IgG in some neurons of cerebellum was detected whereas the reaction with anti-complement (C3b) receptor in corresponding sections was negative. It is suggested that the presented case may represent a "burn out" stage of paraneoplastic syndrome associated with anti-neuronal antibodies, however the isolation of specific antibodies was not performed.


Pivotal involvement of Fcgamma receptor IIA in the neutralization of lipopolysaccharide signaling via a potent novel anti-TLR4 monoclonal antibody 15C1.
The mammalian Toll-like receptor (TLR) family has evolved to sense pathogens in the environment and protect the host against infection. TLR4 recognizes lipopolysaccharide (LPS) from Gram-negative bacteria and induces a signaling cascade that, when exaggerated, has been associated with severe sepsis. We have generated a TLR4-specific monoclonal antibody, 15C1, which neutralizes LPS-induced TLR4 activation in a dose-dependent manner. 15C1 potently blocks the effects of LPS on a panel of primary cells and cell lines in vitro. The binding of 15C1 was mapped to an epitope in the second portion of the extracellular region of TLR4, which has been shown previously to be functionally important in the recognition of LPS. Furthermore, we demonstrate a novel mechanism of inhibition, as the effects of 15C1 are partially Fc-dependent, involving the regulatory Fcgamma receptor IIA (CD32A). In addition to introducing 15C1 as a potent clinical candidate for use in the treatment of LPS-mediated indications, our work demonstrates a newly discovered pathway whose manipulation is pivotal in achieving optimal neutralizing benefit.


Giant intracavernous carotid aneurysm in a child. Case report.
The occurrence of intracranial aneurysm in the pediatric population is a rare phenomenon. A case of giant aneurysm of the intracavernous carotid artery in a child is reported. Clinicoradiological findings are presented and the surgical procedure is illustrated. Authors stress the value of monitoring the cerebral collateral blood flow before and during the operation.


[Effect of butorphanol tartrate on cross-fostering in rats].
In the preceding study, neonatal deaths were observed when an analgesic, butorphanol tartrate (BT), was administered subcutaneously to female rats during the perinatal and lactating periods. In the present study, cross-fostering using CRJ:CD (Sprague-Dawley) rats was employed to clarify the cause of death. When the litters naturally delivered from dams receiving BT (25 mg/kg/day, s.c.) during the perinatal period were switched among one another within the BT-treated dams or placed with control (saline-treated) dams, the viability of newborns on postpartum day 3 was significantly lowered. Since some of the BT-treated dams were observed to neglect the delivery cares that were fundamental to dams such as removing amnions, umbilical cords and placentas, as well as gathering and lactating to newborns immediately after natural delivery, it was considered that death after cross-fostering was the result of the pups being emaciated before cross-fostering. This finding was supported by the fact that a significant elevation in the viability was revealed when the newborns Cesarean-delivered from BT-treated dams were placed with control or untreated dams. No significant effects of BT were observed on the viability and body weight of newborns at birth and on those of pups from postpartum day 3 through the weaning day.


Effective simulations of gas diffusion through kinetically accessible tunnels in multisubunit proteins: O2 pathways and escape routes in T-state deoxyhemoglobin.
The diffusion of small gases to special binding sites within polypeptide matrices pivotally defines the biochemical specificity and reactivity of proteins. We investigate here explicit O(2) diffusion in adult human hemoglobin (HbA) as a case study employing the recently developed temperature-controlled locally enhanced sampling (TLES) method and vary the parameters to greatly increase the simulation efficiency. The method is carefully validated against standard molecular dynamics (MD) simulations and available experimental structural and kinetic data on ligand diffusion in T-state deoxyHbA. The methodology provides a viable alternative approach to traditional MD simulations and/or potential of mean force calculations for: (i) characterizing kinetically accessible diffusion tunnels and escape routes for light ligands in porous proteins; (ii) very large systems when realistic simulations require the inclusion of multiple subunits of a protein; and (iii) proteins that access short-lived conformations relative to the simulation time. In the case of T-state deoxyHbA, we find distinct ligand diffusion tunnels consistent with the experimentally observed disparate Xe cavities in the α- and β-subunits. We identify two distal barriers including the distal histidine (E7) that control access to the heme. The multiple escape routes uncovered by our simulations call for a review of the current popular hypothesis on ligand escape from hemoglobin. Larger deviations from the crystal structure during simulated diffusion in isolated α- and β-subunits highlight the dampening effects of subunit interactions and the importance of including all subunits of multisubunit proteins to map realistic kinetically accessible diffusion tunnels and escape routes.


Implementing the severe sepsis care bundles outside the ICU by outreach.
Sepsis is not a new challenge facing the health care team, it remains a complex disease, which is difficult to identify and treat. Mortality from sepsis remains high and continues to be a common cause of death among critically ill patients, despite advances in critical care. Sepsis accounts for an estimated 27% of all intensive care admissions in England, Wales and Northern Ireland, and accounted for 46% of all intensive care bed days. Recent research studies and the surviving sepsis campaign have shown that identifying and providing key interventions to patients with severe sepsis and septic shock prior to their admission to the intensive care unit significantly improve outcomes. The aim of this paper was to identify how the Critical Care Outreach Team at one local hospital implemented the severe sepsis resuscitation care bundle for patients in the emergency department (ED) and on the general wards. It will include a presentation on the various ways the team raised the profile of severe sepsis and the care bundle at hospital and at national level. It also includes audit data that have been collected. The results showed that if the resuscitation care bundle was implemented within the first 24 h of hospital admission, mortality was 29%, whereas if the care bundle was instigated after this time mortality was more than at 49%. Audit data showed that the commonest sign of severe sepsis seen in patients in the ED and on wards was tachypnoea. This article discusses the successful implementation of the severe sepsis resuscitation care bundle and the positive impact an Outreach team can have in changing practice in the way patients are managed with severe sepsis. The audit data support the need for regular physiological observations and the use of a Patient At Risk Trigger scoring tool to identify patients at risk of deterioration. This allows referral to the Outreach team, who assess the patient and if appropriate initiate the care bundle.


Fatigue and the cancer patient.
Chronic fatigue is a phenomenon frequently experienced by patients with cancer. This article reviews the literature, paying particular attention to the nature, aetiology and effects of chronic fatigue on the patient. While many of the findings are interesting and relevant when planning care for a patient experiencing fatigue, there remains a lack of knowledge as to the aetiology. The research findings are inconsistent and therefore nursing practice cannot be guided by them.


Acute effects of concentric and eccentric exercise on glucose metabolism and interleukin-6 concentration in healthy males.
Acute muscle-damaging eccentric exercise (EE) negatively affects glucose metabolism. On the other hand, long-term eccentric endurance exercise seems to result in equal or superior positive effects on glucose metabolism compared to concentric endurance exercise. However, it is not known if acute non-muscle-damaging EE will have the same positive effects on glucose metabolism as acute concentric exercise (CE). Interleukin-6 (IL-6) released from the exercising muscles may be involved in the acute adaptations of glucose metabolism after CE and non-muscle-damaging EE. The aim of this study was to assess acute effects of uphill walking (CE) and non-muscle-damaging downhill walking (EE) on glucose metabolism and IL-6 secretion. Seven sedentary non-smoking, healthy males participated in a crossover trial consisting of a 1 h uphill (CE) and a 1 h downhill (EE) walking block on a treadmill. Venous blood samples were drawn before (pre), directly after (acute) and 24 h after (post) exercise. An oral glucose tolerance test (OGTT) was performed before and 24 h after exercise. Glucose tolerance after 1 and 2 hours significantly improved 24 hours after CE (-10.12±3.22%: P=0.039; -13.40±8.24%: P=0.028). After EE only the 1-hour value was improved (-5.03±5.48%: P=0.043). Acute IL-6 concentration rose significantly after CE but not after EE. We conclude that both a single bout of CE and a single bout of non-muscle-damaging EE elicit positive changes in glucose tolerance even in young, healthy subjects. Our experiment indicates that the overall metabolic cost is a major trigger for acute adaptations of glucose tolerance after exercise, but only the IL-6 production during EE was closely related to changes in glycaemic control.


Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix.
We wanted to investigate the clinical usefulness of determining the pretreatment levels of multiple serum tumor markers in predicting lymph node status and the prognosis for patients with cervical carcinoma. The preoperative serum levels of squamous cell carcinoma antigen (SCC), cancer antigens CA125 and CA19-9 were assayed simultaneously in 103 patients with stages IB to IIB cervical SCC undergoing radical hysterectomy. The cut-off values of SCC, CA125, and CA19-9 in this study were 1.5 ng/ml, 35 U/ml, and 37 U/ml, respectively. The relation between preoperative tumor marker levels and histopathologic prognostic factors including lymph node metastasis and patient survival was studied. Preoperative serum SCC, CA125, and CA19-9 levels were significantly related to the FIGO stage. In addition, serum SCC and CA125 levels were significantly related to tumor diameter, depth of cervical stromal invasion, lymph-vascular space invasion, and lymph node metastasis. We subsequently created a double-tumor-marker (DTM) index, which incorporated the number of positive markers of SCC and CA125. The DTM index was strongly related to the number of positive pelvic lymph nodes (p = 0.0002) and to the site of positive nodes (none vs. pelvic only vs. common iliac/paraaortic) (p = 0.0005). Probability of lymph node metastasis according to the DTM index = 0, 1, and 2 was 6/48 (12.5%), 14/45 (31.1%), and 8/10 (80.0%), respectively. The rate of common iliac/paraaortic node metastasis according to the DTM index = 0, 1, and 2 was 1/48 (2.1%), 2/45 (4.4%), and 3/10 (30.0%), respectively. By logistic regression analysis, it was shown that the DTM index and tumor diameter were independently related to lymph node metastasis. Using multivariate Cox regression analysis including singly determined serum SCC and CA125 levels, clinical stage (IB/IIA vs. IIB), tumor diameter (<or= 2 vs. 2-4 vs. > 4 cm), parametrial invasion, lymph node metastasis, and the DTM index, the DTM index was found to be the most important prognostic factor (p = 0.0005). However, when the sites of positive nodes were included in the multivariate analysis, only the sites of positive nodes (p = 0.0008) and parametrial invasion (p = 0.041) showed independent prognostic significance. Combination assay of pretreatment serum SCC and CA125 levels seems to be useful in estimating lymph node status and the prognosis for patients with cervical SCC in a preoperative setting.


Students' perception about logbooks: advantages, limitation and recommendation - a qualitative study.
To identify students' perception concerning advantages, limitations and recommendations about logbooks. In this qualitative-phenomenology study, conducted from January to December 2010, 14 undergraduate nursing students were selected by random sampling. The study was done in the neonatal intensive care unit and paediatrics ward of a regional hospital in Bojnord, Iran. At the beginning of the courses, the tutor explained the specific objectives of the core curriculum and how to complete the logbooks. During the course, formative assessment and related feedback were noted down. At the end, two semi-structured focus groups were generated. All interviews were recorded, transcribed and analysed for emerging themes and concepts. Based on content analysis, three advantages and four limitations of logbooks were identified and recommendations were noted. An appropriate logbook should be inexpensive, feasible and acceptable to students and should allow rapid collection of valid, relevant and reliable data. However, its methodology needs to be revised.


The effects of decreased inspiratory capacity on postural stability during backward reach.
[Purpose] The purpose of this study is to investigate the effect of decreased inspiratory capacity on the backward reach distance in healthy young individuals, as patients with chronic obstructive pulmonary disease have a high risk of falling. [Participants and Methods] Thirteen healthy volunteers (age, 19.2 ± 0.4 years: mean ± SD) participated in this study. We recorded the backward reach distance at the resting expiration level and at two different inspiratory capacity levels: -1/3 and -2/3 of inspiratory capacity, when the air is inhaled at resting expiration level. We assessed the backward reach distance for each inspiratory capacity, using one-way repeated measures analysis of variance and post-hoc analysis. [Results] We found that inspiratory capacity has a significant effect on backward reach distance. The backward reach distance was significantly decreased in participants with a -2/3 inspiratory capacity, compared with the backward reach distance in participants with a resting expiration level. [Conclusion] Patients with lung volume fractionation and decreased inspiratory capacity lack postural stability during backward reach. Therefore, the link between decreased inspiratory capacity and loss of balance in patients with chronic obstructive pulmonary disease may, in part, be due to decreased postural stability, and the resulting tendency to plan movements, which create a loss of balance.


Loudness Dependence of Auditory-evoked Potentials, a Marker of Central Serotonergic Activity, is Affected by Fasting and Selective Uptake of Food.
Serotonin is an important neuromodulator involved in many physiological processes including mood and satiety. In the brain, serotonin is manufactured from tryptophan, as serotonin itself cannot cross the blood-brain barrier. Previous research has shown that blood-tryptophan levels increase upon ingestion of carbohydrates and decrease upon protein consumption. How this translates into serotonin availability is as yet under-researched. Therefore, we examined the effect of fasting versus consuming carbohydrates or protein on central serotonergic activity using a repeated-measures crossover design in a sample of 37 healthy men. The loudness dependence of auditory-evoked potentials (LDAEP) serves as a noninvasive method to study central serotonergic activity. Blood-glucose levels and mood changes were also monitored before and after the nutritional intervention. The intervention had a significant nutrition-specific effect on LDAEP and blood-glucose levels. A significant difference emerged between the fasting condition and satiety, with LDAEP being lower during satiety, irrespective of the type of food. Thus, this indicator of serotonergic activity increased after food consumption, which was further related to mood improvement. Moreover, the LDAEP differed between the 2 measurements only for the carbohydrate testing day, suggesting that LDAEP can be selectively modulated by the type of nutrition consumed. Our data further indicate a high intraindividual stability of LDAEP, as the electrophysiological signals were very similar in the fasting condition across the 2 testing days. Together, these findings demonstrate that the LDAEP can serve as a biological marker for central serotonergic activity, while at the same time being sensitive to nutritional changes.


Impact of Moderate Aerobic Training on Physical Capacities of Hypertensive Obese Elderly.
The association of old age and chronic conditions, such as hypertension and obesity, can lead to larger decreases in the physical capacities of elderly, compared with their healthy counterparts. Physical exercise has been demonstrated to be efficient in postponing this phenomenon, mainly strength training. However, little is known about the effect of aerobic training on this condition. The aim of this work was to investigate the impact of 12 weeks of moderate-intensity aerobic training on the physical capacities of hypertensive obese older women. Aerobic power, lower limb muscle power, upper limb muscle strength, endurance, and flexibility of 19 hypertensive obese elders were evaluated. Afterward, patients were blindly randomized into control group (CG) and exercise group (EG). EG underwent three sessions/week of 60 min of moderate-intensity aerobic training, during 12 weeks. EG showed increases in VO2max compared with CG (p = .03) and increases in flexibility compared with basal moment (+21.6%; p = .01) after 12 weeks, whereas CG did not show any significant alterations. Moderate aerobic training is capable of inducing increases in maximal aerobic power and flexibility in hypertensive obese elderly. However, other essential physical capacities associated with independence in elderly people (i.e., muscle power and strength) were not responsive to this kind of protocol.


In vitro acylation of okadaic acid in the presence of various bivalves' extracts.
The dinoflagellate Dinophysis spp. is responsible for diarrhetic shellfish poisoning (DSP). In the bivalves exposed to the toxic bloom of the dinoflagellate, dinophysistoxin 3 (DTX3), the 7-OH acylated form of either okadaic acid (OA) or DTX1, is produced. We demonstrated in vitro acylation of OA with palmitoyl CoA in the presence of protein extract from the digestive gland, but not other tissues of the bivalve Mizuhopecten yessoensis. The yield of 7-O-palmitoyl OA reached its maximum within 2 h, was the highest at 37 °C followed by 28 °C, 16 °C and 4 °C and was the highest at pH 8 in comparison with the yields at pH 6 and pH 4. The transformation also proceeded when the protein extract was prepared from the bivalves Corbicula japonica and Crassostrea gigas. The OA binding protein OABP2 identified in the sponge Halichondria okadai was not detected in the bivalve M. yessoensis, the bivalve Mytilus galloprovincialis and the ascidian Halocynthia roretzi, though they are known to accumulate diarrhetic shellfish poisoning toxins. Since DTX3 does not bind to protein phosphatases 1 and 2A, the physiological target for OA and DTXs in mammalian cells, the acylation of DSP toxins would be related to a detoxification mechanism for the bivalve species.


International overview on the treatment of prostate cancer--Scandinavian experience.
The Scandinavian countries, especially Sweden and Norway, have a high incidence of prostate cancer. The tumor classification has been mainly uniform in recent years, according to the TNM system. Transrectal fine-needle biopsy and cytologic malignancy grading were introduced in Sweden and were gradually accepted in other countries. The treatment of prostate cancer has been mainly conservative as it is in most parts of Europe. For a long period endocrine therapy was given in the vast majority of cases. In recent years radiotherapy has also been used in cancer of low differentiation with no evidence of dissemination. In poorly differentiated and disseminated disease, Estracyt is the standard therapy. Estracyt is also given in disseminated carcinoma nonresponsive to ordinary hormone therapy. In this category of patients other chemotherapy is the second therapeutic alternative. Various techniques of endocrine therapy, chemotherapy, and radical surgery are subject to controlled trials.


Angiotensin II receptors and angiotensin converting enzyme in the medulla oblongata.
Quantitative in vitro autoradiography was used to map angiotensin II (ANG II) receptors and angiotensin converting enzyme (ACE) in sections from rat, rabbit, sheep, and human medulla oblongata and to follow changes in receptor and ACE density after disruption of vagal projections by nodose ganglionectomy in the rat. ANG II receptors and ACE are both concentrated in the nucleus of the solitary tract and dorsal motor nucleus of vagus of the rat, rabbit, sheep, and human. An ANG II receptor-containing band connecting the nucleus of the solitary tract with the dorsolateral medulla was seen in rabbit and human tissue, providing evidence for association of ANG II receptors with vagal afferent fibers. ANG II receptors were found to be concentrated in the rostral and caudal ventrolateral medulla, which corresponded to the region of C1 and A1 catecholamine-containing cell groups in the rabbit. This localization was also evident in rat and human tissue. In all four species, a prominent, ANG II receptor-rich band in the intermediate reticular nucleus was found to connect the ventrolateral medulla and the dorsal vagal complex. In humans and sheep, this band contains puncta that overlie cell bodies. One week after nodose ganglionectomy in the rat, the density of ANG II receptors in the ipsilateral dorsal vagal complex fell markedly. This fall was most prominent in the rostral dorsal motor nucleus of vagus (to 46% of control density) and in the nucleus of the solitary tract (to 56% of control). ACE levels and calcitonin gene-related peptide receptor density were unchanged in both nuclei after ganglionectomy.(ABSTRACT TRUNCATED AT 250 WORDS)


Predictors of patient satisfaction in an emergency care centre in central Saudi Arabia: a prospective study.
This study aimed to (i) assess the level of patient satisfaction and its association with different sociodemographic and healthcare characteristics in an emergency care centre (ECC) in Saudi Arabia and (ii) to identify the predictors of patients' satisfaction. A prospective cohort study of 390 adult patients with Canadian triage category III and IV who visited ECC at King Abdulaziz Medical City, Riyadh, Saudi Arabia, between 1 July and end of September 2011 was conducted. All patients were followed up from the time of arrival at the front desk of ECC until being seen by a doctor, and were then interviewed. Patient satisfaction was measured using a previously validated interview-questionnaire, within two domains: clarity of medical information and relationship with staff. Patient perception of health status after as compared with before the visit, and overall life satisfaction were also measured. Data on patient characteristics and healthcare characteristics were collected. Multiple linear regression analysis was used, and significance was considered at p≤0.05. One-third (32.8%) of patients showed high level of overall satisfaction and 26.7% were unsatisfied, with percentage mean score of 70.36% (17.40), reflecting moderate satisfaction. After adjusting for all potential confounders, lower satisfaction with the ED visit was significantly associated with male gender (p<0.001), long waiting time (p=0.032) and low perceived health status compared with status at admission (p<0.001). Overall life satisfaction was not a significant predictor of patient satisfaction. An appreciation of waiting time as the only significant modifiable risk factor of patient satisfaction is essential to improve the healthcare services, especially at emergency settings.


Influence diagnostics in meta-regression model.
This paper studies the influence diagnostics in meta-regression model including case deletion diagnostic and local influence analysis. We derive the subset deletion formulae for the estimation of regression coefficient and heterogeneity variance and obtain the corresponding influence measures. The DerSimonian and Laird estimation and maximum likelihood estimation methods in meta-regression are considered, respectively, to derive the results. Internal and external residual and leverage measure are defined. The local influence analysis based on case-weights perturbation scheme, responses perturbation scheme, covariate perturbation scheme, and within-variance perturbation scheme are explored. We introduce a method by simultaneous perturbing responses, covariate, and within-variance to obtain the local influence measure, which has an advantage of capable to compare the influence magnitude of influential studies from different perturbations. An example is used to illustrate the proposed methodology.


Air gun dangers.
The handgun debate in the UK has heard arguments about the use of air guns, which assumes small lead pellets have a limited tissue penetration and do not cause significant tissue damage unless a vital structure is directly hit. A study of air gun injuries in paediatric patients treated at the University of Louisville contradicts this belief.


[Comparison of transcription factors repressing epithelial phenotype in two different prostate cancer EMT models and its significance].
To screen and compare the specific transcription factors that repress the epithelial phenotype in epithelial-mesenchymal transition (EMT) in two different human prostate cancer models LNCaP/HIF1alpha and ARCaP. We established two different prostate cancer EMT models, LNCaP/HIF1alpha and ARCaP, cultured LNCaP, LNCaP/HIF1alpha, IF11 and IA8 cells in vitro, and detected the five transcription factors Snail, Slug, ZEB1, SIP1 and Twist1 in these cells by RT-PCR. Different levels of Snail, Slug, ZEB1, SIP1 and Twist1 were detected in both LNCaP and LNCaP/HIF1alpha cells, with significant differences only in the expressions of Slug and Twist1 between the two cells. The expression of Slug was increased, but that of Twist1 decreased in the LNCaP/HIF1alpha cells. All the five transcription factors but Twist1 were expressed in both the IF11 and IA8 cells, but only the express- sions of ZEB1 and Slug were increased significantly in the IA8 cells. There are different mechanisms underlying transcriptional regulation in different prostate cancer EMT models. Slug may be one of the key transcription factors involved in the HIF1alpha-induced EMT of LNCaP cells, while ZEB1 and Slug may play an important role in repressing the epithelial phenotype of the ARCaP model.


Role of immunotherapy in allergic fungal rhinosinusitis.
Our understanding of the pathogenesis and treatment of allergic fungal rhinosinusitis (AFRS) continues to evolve. This article serves to update the reader on the diagnosis and management of AFRS and pays particular attention to the recent literature regarding efficacy and safety of immunotherapy in this patient population. The mainstay of treatment of AFRS remains a thorough surgery; however, adjunctive medical management is also critical to achieve optimal outcomes. Oral steroid use in AFRS remains recommended. Immunotherapy, both fungal and nonfungal, may be considered for patients exhibiting a type I hypersensitivity to specific allergens. To date, limited studies do show improvement with reduction of postoperative exacerbations and revision surgeries. There remains no evidence of unusual side-effects or formation of immune complexes from immunotherapy in AFRS patients. Double-blind placebo controlled trials on immunotherapy and AFRS are lacking, and ultimately, conclusive evidence of efficacy is not present to date. Treatment of AFRS requires multimodality therapy with immunotherapy playing a significant, yet inconclusive, role. Further studies remain warranted.