Economic Evaluation of a Pre-Hospital Protocol for Patients with Suspected Acute Stroke.
In regional and rural Australia, patients experiencing ischemic stroke do not have equitable access to an intravenous recombinant tissue plasminogen activator (tPA). Although thrombolysis with tPA is a clinically proven and cost-effective treatment for eligible stroke patients, there are few economic evaluations on pre-hospital triage interventions to improve access to tPA. To describe the potential cost-effectiveness of the pre-hospital acute stroke triage (PAST) protocol implemented to provide priority transfer of appropriate patients from smaller hospitals to a primary stroke center (PSC) in regional New South Wales, Australia. The PAST protocol was evaluated using a prospective and historical control design. Using aggregated administrative data, a decision analytic model was used to simulate costs and patient outcomes. During the implementation of the PAST protocol (intervention), patient data were collected prospectively at the PSC. Control patients included two groups (i) patients arriving at the PSC in the 12 months before the implementation of the PAST protocol and, (ii) patients from the geographical catchment area of the smaller regional hospitals that were previously not bypassed during the control period. Control data were collected retrospectively. The primary outcome of the economic evaluation was the additional cost per disability adjusted life years (DALYs) averted in the intervention period compared to the control period. The intervention was associated with a 17 times greater odds of eligible patients receiving tPA (adjusted odds ratio, 95% CI 9.42-31.2, p < 0.05) and the majority of the associated costs were incurred during acute care and rehabilitation. Overall, the intervention was associated with an estimated net avoidance of 93.3 DALYs. The estimated average cost per DALY averted per patient in the intervention group compared to the control group was $10,921. Based on our simulation modeling, the pre-hospital triage intervention was a potentially cost-effective strategy for improving access to tPA therapy for patients with ischemic stroke in regional Australia.


Hypersecretion of luteinizing hormone and ovarian steroids in women with recurrent early miscarriage.
Polycystic ovary syndrome is associated with hypersecretion of luteinizing hormone (LH) which has been implicated in the aetiology of early pregnancy loss. Although 82% of women with recurrent early loss have polycystic ovaries on ultrasound imaging, random serum LH concentrations are normal. In the present study, we have obtained further information from serial samples concerning the cyclical patterns of gonadotrophin and sex steroid secretion in these women. Twenty-one women with recurrent early pregnancy loss and 10 multiparous controls were investigated; 81% of them and one of ten control subjects had polycystic ovaries. Mean mid-follicular and mid-luteal serum LH and follicle stimulating hormone (FSH) levels were similar in both groups. Seventeen women with pregnancy loss had either raised urinary LH excretion or a premature LH surge; one control subject had a premature LH surge. Total LH excretion during the cycle and mean follicular phase serum testosterone was significantly greater with early pregnancy loss than in the control group, the difference in LH being greatest in the early luteal phase. Urinary oestrone-3-glucuronide excretion was raised in the early luteal phase of the cycle in the group with early pregnancy loss; there was no difference between the groups in pregnanediol-3 alpha-glucuronide excretion. These data demonstrate abnormalities in LH secretion in 81% of women with recurrent fetal loss. Inappropriately raised LH levels may have adverse effects on the developing oocyte or endometrium either directly, or indirectly by causing an elevation in testosterone and oestrogen levels.


Advanced Glycation End Products and Bone Metabolism in Patients with Chronic Kidney Disease.
Advanced glycation end products (AGEs) accumulation may be involved in the progression of CKD-bone disorders. We sought to determine the relationship between AGEs measured in the blood, skin, and bone with histomorphometry parameters, bone protein, gene expression, and serum biomarkers of bone metabolism in patients with CKD stages 3 to 5D patients. Serum levels of AGEs were estimated by pentosidine, glycated hemoglobin (A1c), and N-carboxymethyl lysine (CML). The accumulation of AGEs in the skin was estimated from skin autofluorescence (SAF). Bone AGEs accumulation and multiligand receptor for AGEs (RAGEs) expression were evaluated by immunohistochemistry; bone samples were used to evaluate protein and gene expression and histomorphometric analysis. Data are from 86 patients (age: 51 ± 13 years; 60 [70%] on dialysis). Median serum levels of pentosidine, CML, A1c, and SAF were 71.6 pmol/mL, 15.2 ng/mL, 5.4%, and 3.05 arbitrary units, respectively. AGEs covered 3.92% of trabecular bone and 5.42% of the cortical bone surface, whereas RAGEs were expressed in 0.7% and 0.83% of trabecular and cortical bone surfaces, respectively. AGEs accumulation in bone was inversely related to serum receptor activator of NF-κB ligand/parathyroid hormone (PTH) ratio (R = -0.25; p = 0.03), and RAGE expression was negatively related to serum tartrate-resistant acid phosphatase-5b/PTH (R = -0.31; p = 0.01). Patients with higher AGEs accumulation presented decreased bone protein expression (sclerostin [1.96 (0.11-40.3) vs. 89.3 (2.88-401) ng/mg; p = 0.004]; Dickkopf-related protein 1 [0.064 (0.03-0.46) vs. 1.36 (0.39-5.87) ng/mg; p = 0.0001]; FGF-23 [1.07 (0.4-32.6) vs. 44.1 (6-162) ng/mg; p = 0.01]; and osteoprotegerin [0.16 (0.08-2.4) vs. 6.5 (1.1-23.7) ng/mg; p = 0.001]), upregulation of the p53 gene, and downregulation of Dickkopf-1 gene expression. Patients with high serum A1c levels presented greater cortical porosity and Mlt and reduced osteoblast surface/bone surface, eroded surface/bone surface, osteoclast surface/bone surface, mineral apposition rate, and adjusted area. Cortical thickness was negatively correlated with serum A1c (R = -0.28; p = 0.02) and pentosidine levels (R = -0.27; p = 0.02). AGEs accumulation in the bone of CKD patients was related to decreased bone protein expression, gene expression changes, and increased skeletal resistance to PTH; A1c and pentosidine levels were related to decreased cortical thickness; and A1c levels were related to increased cortical porosity and Mlt. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Pharmacological effect of beta toxin of Clostridium perfringens type C on rats.
The biological effect of purified beta toxin of Clostridium perfringens type C in vivo was investigated. After intravenous injection of the purified beta toxin into rats, a rise in blood pressure and a simultaneous fall in heart rate were observed. After the blood pressure reached a maximum, the heart rate recovered gradually, and electrocardiographic and respiratory changes began. The rise in blood pressure induced by beta toxin tended to be proportional to the amount of toxin. The latent period between the injection of toxin and the onset of the increase, and also the time between the injection and the maximum pressure induced by the toxin decreased with increasing concentration of the toxin. A good correlation was found between the factor producing the rise in blood pressure and beta toxin. Alpha adrenergic and ganglionic blocking agents reduced blood pressure levels elevated by beta toxin. The data suggest that the toxin causes a release of catecholamines, and that the increase in blood pressure was induced by released catecholamines.


[Delayed Copying of Unfamiliar Contour Shapes: Does Reaction Time Decrease with Growing Delay Reflect a Change in Internal Representation Of Fothcoming Movement?].
Group of 24 adults has performed the delayed reproduction (copying) of unfamiliar contour shapes (trajectory templates). Templates were shown for 250 ms and the participants were asked to reproduce them upon detecting acoustical go signal (short click). Go signal was delayed relatively to the end of a visual template exposure by T = 0, 500, 1000, 2000 or 4000 ms. Block design of the experiment was used when delay T was held constant within a block consisted of 32 trials. We analyzed reaction time (RT), mean movement time (MT) along a single segment of trajectory, and the mean dwell time (DT) in the vertices of the template. It is shown that RT does not depend monotonically on the delay T showing a decrease at T ≤ 1000 ms and increase at T ≤ 2000 ms. The RT of T curve is well described by a simple additive model that includes a linearly growing and an exponentially decaying terms. The linear growth reflects the foreperiod effect, i.e., decreasing capacity to predict an exact moment of go signal with the growing delay T [Niemi, Naatanen, 1981; Meulenbroek, Van Galen, 1988]. We suggested that exponentially decaying term may be caused by the internal representation of a trajectory undergoing some transformation during retention in the working memory.


Development of clinical prediction rule for the requirement of endoscopic papillary large balloon dilation (EPLBD) on endoscopic CBD stone clearance.
To develop a simplified scoring system for clinical prediction of difficulty in CBD stone removal to assist endoscopists working in resource-limited settings in deciding whether to proceed with an intervention or refer patients to a center capable of performing additional procedures and interventions. This study included patients with CBD stones who underwent ERCP at Pattani Hospital between August 2017 and December 2021. Retrospective cohort data was collected and patients were categorized into two groups: bile duct stones successfully treated by endoscopic biliary sphincterotomy and extraction compared to the former method combined with EPLBD. We explored potential predictors using multivariable logistic regression. The chosen logistic coefficients were transformed into a scoring system based on risk with internal validation via bootstrapping procedure. Among the 155 patients who had successful endoscopic therapy for bile duct stones, there were 79 (50.97%) cases of endoscopic biliary sphincterotomy, EPLBD and extraction versus 76 (49.03%) cases without EPLBD. The factors used to derive a scoring system included the size of CBD stones >15 mm, the difference between the stone and distal CBD diameter >2mm, distal CBD arm length <36 mm and stone shape. The score-based model's area under ROC was 0.88 (95% CI: 0.83, 0.93). For clinical use, the range of scores from 0 to 16, was divided into two subcategories based on CBD stone removal difficulty requiring EPLBD to derive the PPV. For scores <5 and ≥ 5, the PPV was 23.40 (p <0.001) and 93.44 (p <0.001) respectively. The Bootstrap sampling method indicated a prediction ability of 0.88 (AuROC, 95% CI: 0.83, 0.94). This scoring system has acceptable prediction performance in assisting endoscopists in their choice of stone removal procedure.


Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.
The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. Complete remission (CR) was seen in 39.2% of patients with NLR < 2.95 compared to 20% in the group with NLR ⩾ 2.95 (P= 0.094). NLR was lower in CR patients in comparison to Non-CR subjects (P= 0.044). Patients with a NLR ⩾ 2.95 experienced inferior median survival compared to those with NLR < 2.95 (4-year OS rates were 30.9% and 64.8%, respectively, P= 0.029). In multivariate analysis, only elevated LDH and IgA MM were factors predicting inferior OS. Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.


Alterations in sheep peripheral blood mononuclear cell proliferation and cytokine release by polyunsaturated fatty acid supplementation in the diet under high ambient temperature.
The aim of this study was to investigate the effects of polyunsaturated fatty acid (PUFA) supplementation from different sources in the diet of dairy sheep under high ambient temperatures on ex vivo lymphocyte proliferation and inflammatory responses. The experiment was carried out during summer: 32 Comisana ewes were divided into 4 groups of 8. The FS group was supplemented with whole flaxseed, the AG group was supplemented with Ascophyllum nodosum, the FS+AG group was supplemented with a combination of flaxseed and A. nodosum. The fourth group (CON group) was a control and received a diet containing no supplement. The average maximum temperature was around 33°C during wk 2 and 3, whereas the mean temperature never decreased below 26°C. Following 15 d of treatment with respective diets, peripheral blood mononuclear cells (PBMC) from sheep who received a diet supplemented with A. nodosum had impaired cell proliferation responses and IL-6 production after mitogen stimulation compared with PBMC from FS+AG sheep. In addition, PBMC from AG sheep displayed impaired cell proliferation compared with cells from the CON group. The FS+AG cells produced lower levels of IL-10 than CON cells, and higher IL-6 than AG and CON cells. Results demonstrated that the supplementation with PUFA from different sources in a sheep's diet can influence their immunological responses under high ambient temperatures depending on the composition of fatty acid supplementation. In particular, synergistic effects of different PUFA from flaxseed and A. nodosum, simultaneously administrated in the sheep diet, were observed on activation of inflammation response.


Influence of the 3D inverse dynamic method on the joint forces and moments during gait.
The joint forces and moments are commonly used in gait analysis. They can be computed by four different 3D inverse dynamic methods proposed in the literature, either based on vectors and Euler angles, wrenches and quaternions, homogeneous matrices, or generalized coordinates and forces. In order to analyze the influence of the inverse dynamic method, the joint forces and moments were computed during gait on nine healthy subjects. A ratio was computed between the relative dispersions (due to the method) and the absolute amplitudes of the gait curves. The influence of the inverse dynamic method was negligible at the ankle (2%) but major at the knee and the hip joints (40%). This influence seems to be due to the dynamic computation rather than the kinematic computation. Compared to the influence of the joint center location, the body segment inertial parameter estimation, and more, the influence of the inverse dynamic method is at least of equivalent importance. This point should be confirmed with other subjects, possibly pathologic, and other movements.


Zinc in the anterior pituitary of rat: a histochemical and analytical work.
Recent studies have suggested zinc to be a possible modulator of hormone secretion from the anterior pituitary. The three aims of the present study were: to estimate the total amount of zinc in the gland by instrumental analysis; to visualize the zinc at light and electron microscopical levels, and to estimate the amount of zinc that can be visualized by histochemical techniques. PIXE measurement showed the total amount of zinc to be 74 ng/mg dry weight in males and 100 ng/mg dry weight in females, which is a highly significant difference. Histochemically, the zinc was shown by a modified Timm method and the selenium method to be localized to the secretory granules, and to a smaller extent to the Golgi apparatus of the somatotrophs, corticotrophs and thyrotrophs. Chelation of tissue zinc by intravital dithizone treatment effectively blocked subsequent selenium and Timm staining in the secretory granules, and PIXE assays of the chelated metal (extracted into CCl4) showed it constituted less than 5% of the total zinc in the tissue. It is concluded from the study that zinc is present in the anterior pituitary of rats in rather high amounts and that loosely bound zinc, which is suggested to exert a biological effect by itself, can be located to the parts of the cells responsible for production, storing and release of hormones.


Magnetic resonance imaging for characterizing myocardial diseases.
The National Institute of Health defined cardiomyopathy as diseases of the heart muscle. These myocardial diseases have different etiology, structure and treatment. This review highlights the key imaging features of different myocardial diseases. It provides information on myocardial structure/orientation, perfusion, function and viability in diseases related to cardiomyopathy. The standard cardiac magnetic resonance imaging (MRI) sequences can reveal insight on left ventricular (LV) mass, volumes and regional contractile function in all types of cardiomyopathy diseases. Contrast enhanced MRI sequences allow visualization of different infarct patterns and sizes. Enhancement of myocardial inflammation and infarct (location, transmurality and pattern) on contrast enhanced MRI have been used to highlight the key differences in myocardial diseases, predict recovery of function and healing. The common feature in many forms of cardiomyopathy is the presence of diffuse-fibrosis. Currently, imaging sequences generating the most interest in cardiomyopathy include myocardial strain analysis, tissue mapping (T1, T2, T2*) and extracellular volume (ECV) estimation techniques. MRI sequences have the potential to decode the etiology by showing various patterns of infarct and diffuse fibrosis in myocarditis, amyloidosis, sarcoidosis, hypertrophic cardiomyopathy due to aortic stenosis, restrictive cardiomyopathy, arrythmogenic right ventricular dysplasia and hypertension. Integrated PET/MRI system may add in the future more information for the diagnosis and progression of cardiomyopathy diseases. With the promise of high spatial/temporal resolution and 3D coverage, MRI will be an indispensible tool in diagnosis and monitoring the benefits of new therapies designed to treat myocardial diseases.


Decreased taurine concentration in skeletal muscles after exercise for various durations.
To examine the changes of taurine concentrations in blood and skeletal muscles after transient exercise. Rats were placed on a treadmill set at 25 m.min-1. The animals were divided into four groups: control (no exercise) and exercise groups 1, 2, and 3. The exercise duration for groups 1, 2, and 3 was 30, 60, and 100 +/- 12.5 min (to exhaustion: mean +/- SD), respectively. We examined the plasma concentrations of taurine and lactate, the serum concentrations of sodium and chloride ions, as well as the skeletal muscle taurine content in the soleus (slow-twitch fiber dominant type), gastrocnemius (slow- and fast-twitch fiber mix type), and plantaris and extensor digitorum longus (fast-twitch fiber dominant type) muscles. Although the plasma taurine concentration was not affected by the increased exercise duration, that in skeletal muscles was significantly decreased. The gastrocnemius and plantaris muscles from the exercise group 3 had a significantly lower concentration of taurine than those of the control group. The extensor digitorum longus taurine concentration from the different exercise groups was significantly decreased compared with that from the control group. However, there was no significant difference among the exercise groups. Taurine concentration was decreased in all skeletal muscles after exercise, regardless of the duration. Moreover, this decrease was specific to fast-twitch dominant fibers. However, under these conditions, the plasma taurine concentration remained unchanged.


Inflamed urachal cyst containing calculi in an adult.
The urachus is an embryonic structure that persists after birth in some individuals and can cause various problems. We report a case of an inflamed urachal cyst filled with a thick yellow fluid and several calculi in a woman with a 1-month history of dysuria. Physical examination revealed a fist-sized tumor located infraumbically in the midline. The patient's erythrocyte sedimentation rate was elevated; the results of all other routine laboratory studies were normal. Sonography showed a regularly shaped, ovoid, hypoechoic cystic area in the abdominal wall measuring 8 x 4 x 3 cm and containing several hyperechoic masses associated with acoustic shadowing. The wall of the cyst was inhomogeneous, and a thin hypoechoic linear tract linked the superior aspect of the mass to the umbilicus. The results of excretory urography, voiding cystography, and cystoscopy excluded an abnormality of the urinary system. A urachal cyst was diagnosed, and the mass was surgically removed. The surgical specimen was sent for histopathologic analysis, which confirmed the diagnosis.


Extrasynaptic effects of GABA (gamma-aminobutyric acid) agonists on myelinated axons of peripheral nerve.
Effects of the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (> or = 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


[Intra-abdominal torsion of the testis with seminoma].
A 38-year-old man presented with acute onset of left iliac fossa pain. He had never noticed a left testis. An ultrasound scan showed a solid pelvic mass. Alfafoetoprotein and HCG were normal. Laparotomy for an acute abdomen was performed and revealed torsion of the left intra-abdominal testis. A left orchiectomy was performed. The patient made an uneventful recovery. Histology showed seminoma and carcinoma in situ. A testicular biopsy from the right testis showed no malignancy. A detailed examination of the genitalia should be part of the usual abdominal examination.


Unfolded protein response is required for Aspergillus oryzae growth under conditions inducing secretory hydrolytic enzyme production.
Unfolded protein response (UPR) is an intracellular signaling pathway for adaptation to endoplasmic reticulum (ER) stress. In yeast UPR, Ire1 cleaves the unconventional intron of HAC1 mRNA, and the functional Hac1 protein translated from the spliced HAC1 mRNA induces the expression of ER chaperone genes and ER-associated degradation genes for the refolding or degradation of unfolded proteins. In this study, we constructed an ireA (IRE1 ortholog) conditionally expressing strain of Aspergillus oryzae, a filamentous fungus producing a large amount of amylolytic enzymes, and examined the contribution of UPR to ER stress adaptation under physiological conditions. Repression of ireA completely blocked A. oryzae growth under conditions inducing the production of hydrolytic enzymes, such as amylases and proteases. This growth defect was restored by the introduction of unconventional intronless hacA (hacA-i). Furthermore, UPR was observed to be induced by amylolytic gene expression, and the disruption of the transcriptional activator for amylolytic genes resulted in partial growth restoration of the ireA-repressing strain. In addition, a homokaryotic ireA disruption mutant was successfully generated using the strain harboring hacA-i as a parental host. These results indicated that UPR is required for A. oryzae growth to alleviate ER stress induced by excessive production of hydrolytic enzymes.


White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors.
We studied 52 asymptomatic subjects using magnetic resonance imaging, and we compared age-matched groups (51-70 years old) with and without white matter lesions with respect to carotid ultrasonography, cerebral blood flow (xenon-133 injection), and cerebrovascular risk factors. In the group with white matter signal abnormalities, we noted a higher frequency of extracranial carotid artery disease, a lower mean gray matter blood flow (F1), and a significant reduction (p less than 0.05) in blood flow of the slow-flowing (F2) compartment. Hypertension, diabetes mellitus, and cardiac diseases (p less than 0.002) were found more often in this group. Our results indicate that a higher incidence of changes known to be associated with an increased risk for stroke exists in the presence of white matter lesions in normal elderly individuals.


How do women talk about self-funded breast cancer genetic testing?: Small stories and stance-taking strategies.
Genetic testing for breast cancer genes is an experience which is inextricably linked with health communication practices and the broader social context in which it occurs. Linguistic approaches can provide perspective on how women seeking self-funded BRCA1/2 gene testing represent their experiences, knowledge, roles, choices and emotions through the way they talk. A discursive constructionist epistemology and narrative theoretical framework informed the applied linguistics methodology. Analysis of 'small stories' and stance-taking was performed on eight transcripts of audio-recorded telephone interviews with women at low to moderate risk of carrying BRCA1/2 pathogenic variants who self-funded genetic testing. We found a high prevalence of 'small stories' including accounts of events, hypotheticals, habitual narratives, and stories which combined multiple genres. Stance-taking was a means by which participants constructed personal identities in the conversational context, such as that of a responsible person. Via stance-taking strategies, participants also actively negotiated the conversational agenda, for example expressing different degrees of alignment with the interviewer's orientation towards emotions. This study provides a basis for recognizing linguistic markers in genetic counseling interactions about genetic testing for breast cancer genes. Enhanced awareness of client language choice, and the ways in which small stories and stance can signify the client's evaluation of experience and choices, alignment with the genetic counselor's questions/statements, and investment in the conversation, has potential to improve the therapeutic interaction.


ACTH secretion, circadian variations of salivary free and total serum cortisol and urinary 17-OHCS excretion in active acromegaly following bromocriptine treatment.
The serum levels of ACTH, PRL, GH, somatomedin-C and cortisol (also in saliva) and urinary 17-OHCS excretion were investigated in 37 acromegalic males after radiotherapy. According to bromocriptine test (BC) 20 subject were classified as responders, and 17 as non-responders. ACTH concentration was normal in all acromegalic patients and remained unchanged after BC administration. Mean 24-h level of serum total cortisol was lower in untreated patients and it increased after BC treatment only in responders. No disturbances in circadian rhythm of free cortisol were observed in any of patients. A significantly elevated excretion of 17-OHCS was found in responders before and in non-responders before and after BC administration. In untreated responders significantly increased levels of GH were found which decreased significantly after bromocriptine. In non-responders no difference was found between the values before and after BC, both being significantly higher than those in controls. In both groups of patients significantly increased levels of PRL were observed which after BC decreased to the control values. The levels of somatomedin-C were changing in parallel to those of GH described above.


Anabolic beta-2-agonist clenbuterol fails to modify muscle atrophy due to femur fracture.
Unilateral femur fracture in rats resulted in a significant reduction in body weight gain and food intake. The former was reversed by addition of the beta 2-adrenoceptor agonist clenbuterol to the diet (4 mg/kg) but food intake was unaffected. Neither resting oxygen consumption (VO2) nor brown adipose tissue GDP binding (measured on day 4) was affected either by femur fracture or by administration of clenbuterol. Femur fracture caused reductions in the mass, protein, and RNA content of gastrocnemius muscle from the fractured leg but not from the intact leg. Clenbuterol did not modify the reduction in the mass or protein content of muscle from the fractured leg, but stimulated these parameters in the intact leg and in heart. The ratio of RNA to protein was enhanced by clenbuterol in gastrocnemius muscle from both legs and heart. These data confirm the anabolic effect of clenbuterol in intact limb muscle but suggest that this agent is unable to prevent muscle atrophy at the site of femur fracture in the rat.


Demineralized bone matrix used for direct pulp capping in rats.
To evaluate the wound healing process following direct pulp capping with demineralized bone matrix (DBM) and calcium hydroxide (Ca(OH)2). Fifty 8-weeks-old SPF Wistar male rats were divided into two groups: one was the DBM treated group, and the other was the Ca(OH)2 treated group. Pulpotomy was performed on the maxillary first molar of one side of each rat, and the another side was left as the blank control. Rats were sacrificed after each observation period (1, 3, 7, 14 and 28 days) and specimen slices were made. Hematoxylin-Eosin (HE) staining was used for observing the changes of pulp tissue, and immunohistochemical staining was used for observing the expression of reparative dentinogenesis-related factors runt transcription factor 2 (Runx2), type I collagen (COL I), osteocalcin (OCN) and dentin sialoprotein (DSP). Inflammatory cell infiltration (ICI) and pulp tissue disorganization (PTD) could be observed in both the DBM and Ca(OH)2 groups at all observation periods. The DBM group showed slighter ICI on 1 and 28 days and milder PTD on 28 days, with a significant difference (P<0.05). Reparative dentin formation (RDF) could initially be observed on 14 days postoperatively, and the DBM group showed more regular and thinner RDF with significant differences on 14 and 28 days compared with the Ca(OH)2 group (P<0.05). In both groups, the expression of Runx2, COL I, DSP and OCN were positive. Generally, the expression of these four factors in the DBM group was stronger than the Ca(OH)2 group on the same observation periods. DBM had the ability of inducing odontoblast differentiation and promoting dentinogenesis. DBM could initiate physiologic wound healing in pulp and had the ability to promote reparative dentin formation. Consequently, DBM may be an acceptable alternative for direct pulp capping.


The relationship between airways responsiveness and chronic airflow limitation.
In 84 subjects with varying degrees of chronic airflow limitation (CAL), airways responsiveness (AR) measured by the response to an inhaled bronchodilator was negatively correlated with pulmonary function. Correlation coefficients were AR and FEV1, r = -0.39, p less than .001; AR and FEV1 percent predicted, r = -0.41, p less than .001; and between AR and FVC percent predicted, r = -0.28, p less than .006. This confirms the findings of others who used bronchoprovocation techniques to measure AR. Previously reported associations between AR and annual rate of change (ARC) of the FVC and FEV1 were reevaluated to determine if they are independent of any relationship between AR and baseline pulmonary function. Baseline FVC and FEV1 were not significantly correlated with ARC, while AR retained its significant association when evaluated by Pearson correlation coefficients and partial correlation coefficients adjusting for baseline FVC and FEV1, and when baseline values were included in liner regression models. Thus, AR in these subjects is a predictor of ARC of the FVC and FEV1 independent of baseline pulmonary function values.


Prevalence of use and perceptions of risk of novel and other alternative tobacco products among sexual minority adults: Results from an online national survey, 2014-2015.
Sexual minority (lesbian, gay, and bisexual [LGB]) populations experience disparities in cigarette use, but sparse evidence exists about novel and other alternative tobacco product use. In this study, we compared rates of novel and other alternative tobacco product use, risk perceptions, and worldview between LGB and heterosexual (HET) adults. An online survey administered in 2014-2015, using a weighted probability sample of 11,525 U.S. adults, assessed awareness of tobacco products; ever and current use of e-cigarettes, cigars, little cigars and cigarillos, and hookahs; perceptions of e-cigarettes; and worldview (individualism vs. communitarianism). Bivariate and adjusted multivariable analyses were performed to determine differences between LGB and HET groups. In the adjusted analyses, LGB adults were 1.5 times more likely to have ever used e-cigarettes (95% CI 1.2-1.9) and 1.9 times more likely to have ever used hookahs (95% CI 1.5-2.4) as compared to HET adults. A lower percentage of LGB adults, as compared to HET adults (16.7% vs. 19.2%), believed that exposure to vapors from e-cigarettes was "harmful" and reported that they "did not know" of any harm (35.1% vs. 39.8%). LGB were 20% less likely than were HET adults to endorse an individualistic worldview. These results suggest that a disparity exists, whereby LGB adults are more likely to have used e-cigarettes and hookahs. In addition, although vapor from e-cigarettes contains nicotine and other chemicals, LGB adults are less likely to perceive exposure to secondhand vapor as harmful. Tailored awareness campaigns and interventions are needed to convey the risks and curb use of these products.


Proteinuria and microalbuminuria in adults: significance, evaluation, and treatment.
This paper reviews current concepts regarding the pathophysiology, diagnostic evaluation, and treatment of microalbuminuria and proteinuria in adults. Microalbuminuria (in diabetics) and proteinuria are early markers for potentially serious renal disease, and are associated with increased risk of atherosclerotic cardiovascular disease. Proteinuria also contributes to renal scarring, and accelerates the progression of chronic kidney disease to end-stage renal failure. Screening of diabetics for microalbuminuria, and the initial workup of proteinuria, should occur in the primary care setting. Reduction of microalbuminuria in diabetics may retard its progression to overt diabetic nephropathy. Therapy of renal diseases should aim for optimal blood pressure control and the maximum possible reduction in urinary protein excretion. Angiotensin-converting enzyme inhibitor (ACE-I) and/or angiotensin-receptor blocker (ARB) therapy is the most effective measure to achieve this. These drugs also provide protection against the cardiovascular problems that are highly prevalent in this patient population.


Cis-platin-Mecy as salvage chemotherapy in recurrent advanced ovarian carcinoma.
Cis-platin (DDP) has proved to be highly active in the treatment of ovarian adenocarcinoma. The Authors have treated 12 patients with istologically proven advanced ovarian carcinoma with a type of alternating regimen consisting of four weekly DDP courses (1 mg/kg b.w./week) followed by monthly courses high-dose methotrexate (750 mg/mq i.v.) plus cyclophosphamide (250 mg/mq for 5 days) (Mecy). The alternating regimen DDP + Mecy proved to have significant activity as a salvace chemiotherapy regimen for patients with advanced ovarian carcinoma.


Contrasting effects of mu opioid receptor and delta opioid receptor deletion upon the behavioral and neurochemical effects of cocaine.
Conventional brain microdialysis was used to assess basal and cocaine-induced dopamine (DA) levels in the nucleus accumbens of wildtype (WT) C57BL/6J mice and mice with constitutive deletion of ether mu- or delta-opioid receptors (MOR or DOR knockout [KO], respectively). Locomotor activity was assessed in these same animals. Basal locomotor activity of DOR KO was elevated relative to MOR KO, but did not differ from that of WT mice. DOR mice, but not WT or MOR KO, exhibited a significant increase in activity in response to an injection of saline. The acute administration of cocaine produced a dose-related increase in locomotor activity in the three genotypes. The locomotor activating effects of a low dose (10 mg/kg) of cocaine were enhanced in DOR KO mice whereas the locomotor activating effects of both a low and higher (20 mg/kg) dose of cocaine were reduced in MOR KO animals. Microdialysis studies revealed no difference between genotypes in basal DA levels. Acute administration of cocaine, but not saline, increased DA levels in WT and KO animals. Paradoxically, however, the magnitude of this effect was smaller in DOR KO as compared with that in either WT or MOR KO. These data indicate that constitutive deletion of either MOR or DOR results in contrasting effects upon responsiveness to cocaine, which is consistent with the distinct phenotypes previously described for these mutants.


Aortic root reconstruction: from principles to numerical modeling.
Reconstructing the aortic root represents a formidable task for modern cardiac surgery. By the time an individual reaches 75 years of age his or her aortic apparatus has been submitted to more than three billion cardiac cycles, leaving no place for engineering flaws or misconception. The rules that have been established through millions of years of evolution are strict and demanding. During the past two decades, the cardiovascular community has manifested a growing interest in this topic, especially in patients with medial degenerative disease. However, the ideal reconstruction is still to be devised. To achieve a physiological root reconstruction that preserves the diastolic and systolic function of the valve as well as prevents premature degeneration, a few principles have to be respected. Neglecting any one of them has consequences on the normal functioning of the aortic valve. Current surgical techniques have limitations due to the limited availability of biomaterial and the lack of useful tools to assess pathophysiological conditions and assist surgeons in designing better custom-made reconstructions of the aortic root. The authors present a review of the principles behind the physiology of the reconstruction of the aortic root, and review the literature on computerized models exploring the biomechanics and kinetics of the ascending aorta.


Role of immunochemotherapy in the treatment of chronic lymphocytic leukemia.
Major advances have been made in our understanding of the biology and opportunities for treatment of chronic lymphocytic leukemia in recent times. Newer treatment regimens incorporating purine nucleoside analogs have increased the rate of successful remission induction in chronic lymphocytic leukemia patients. Moreover, recent combination chemoimmunotherapy regimens have produced more frequent complete molecular remissions, and early evidence seems to suggest that this could result in prolonged duration of responses, although this association remains to be clearly demonstrated. This review will summarize recent advances in the biology and the management of chronic lymphocytic leukemia, including prognostic factors, pointing mainly on combination chemotherapy based on nucleoside analogs and monoclonal antibodies. In our opinion, in the future a significant improvement of clinical benefits in chronic lymphocytic leukemia will be obtained through the administration of cocktails of monoclonal antibodies combined with chemotherapy in different modalities.


[Prognosis of fractures of the lower end of the femur in children and adolescents. Apropos of 96 cases].
A multicentre study undertaken in a number of orthopaedic and traumatology departments of hospitals in the East of France have made it possible to bring together, over 10 consecutive years, 96 fractures of the lower end of the femur in children and adolescents. The analysis of this retrospective series agrees with the findings in the literature both in its clinical features and the methods of treatment. The results were very good in 84 per cent of cases. The authors feel that the standard scoring systems are too optimistic and they prefer an analytic description of the complications which presented in 54 per cent of cases with 13 per cent of malunions, 16 per cent of epiphysiodeses and 7 per cent of inequalities of limb length greater than 10 mm. The etiology and pathology of these diverse complications is reviewed. Vascular lesions seem to play an unimportant role. The prognosis, as defined, seems to be realistic since this work has taken account of a large proportion of the fractures occurring during the same period in the same region.


Identification of SEPP1 polymorphisms is not a genetic risk factor for preeclampsia in Chinese Han women: A clinical trial and experimental study.
SEPP1 encodes selenoprotein P, which involved in oxidative stress and plays an important role in the development of preeclampsia (PE). The aim of this study was to investigate the association between PE and genetic variants of SEPP1 in Chinese Han women. In all, 2434 unrelated pregnant women were recruited, including 1034 PE cases and 1400 normal pregnant controls. TaqMan allelic discrimination real-time PCR method was used to genotype the 2 polymorphisms of rs7579 and rs230813 in SEPP1. No statistically significant difference in genotypic or allelic frequencies were found at the 2 genetic variants in SEPP1 between PE patients and controls (rs7579: genotype χ = 2.417, P = .299 and allele χ = 0.197, P = .761, odds ratio 1.049, 95% confidence interval 0.744-1.151; rs230813: genotype χ = 3.273, P = .195 and allele χ = 0.252, P = .615, odds ratio 0.971, 95% confidence interval 0.864-1.091). There were also no statistically significant differences in genetic distributions between mild/severe PE or early/late-onset PE and control subgroups. Our data indicate that the 2 genetic variants of rs7579 and rs230813 in SEPP1 may not play a role in the pathogenesis of PE in Chinese Han Women.


Bone marrow-derived dendritic cells, infection with human immunodeficiency virus, and immunopathology.
Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may become productive as they mature. The distribution of DC within genital mucosa and their susceptibility to infection particularly with clade E viruses could be reflected in the ease of heterosexual transmission. Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protective immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infected DC and T cells. In asymptomatic infection, fewer dendritic cells with reduced capacity to stimulate CD4 T cell proliferation are found before evidence of T cell abnormalities, and these early changes in antigen-presenting cells may result in a decline in the production of CD4 memory T cells. However, DC fuel ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus underlie two major features of early HIV infection--loss in CD4+ memory T cells and persistence of antibody production. In AIDS, infected dendritic and epithelial cells within the thymus may affect maturation and contribute to loss of the "naive" T cell population. Further loss of memory T cells may occur through syncytium formation with infected DC. Finally, in AIDS patients, there is a failure in the development and the function of DC from CD34+ stem cells. In conclusion, the infection of dendritic cells, loss in their numbers, and changed signaling to T cells may shape the pattern of immunity during infection with HIV-1. Conversely, treatments that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.


Circular flow formation triggered by Marangoni convection in nematic liquid crystal films with a free surface.
We demonstrate circular flow formation at a surface in homeotropically oriented nematic liquid crystals with a free surface using focused laser beam irradiation. Under a weak laser power, a pit together with an associated circular bulge is formed: the Marangoni effect. Here a diverging molecular flow from the pit (thermocapillary flow) also induces director tilt in the radial direction. Upon increasing the laser power, the pit becomes deeper, and eventually evolves into a circular flow associated with a deeper pit and a subsidiary circular bulge or valley structure. This phenomenon is induced by escaping from excess deformation energy due to a bend deformation of the director. Actually, we confirmed that the circular flow is never formed in the isotropic phase. The handedness of the vortex cannot be controlled by circular polarisation, but is controllable by doping with chiral molecules. This rotational motion (a nematic micro-rotor) is a unique phenomenon only exhibited by anisotropic liquids, and is expected to be applied for novel devices.


A Case of Rapidly Deteriorating Lymphangitic Carcinomatosis in a Patient with Stage IV Pancreatic Cancer.
Pulmonary lymphangitic carcinomatosis (PLC) is defined as a tumor in the lung lymphatic vessels. It is rarely seen as a result of malignancy and generally carries a poor prognosis. Proper knowledge of the clinical presentation is important for physicians to be aware of in order to consider a diagnosis of PLC. We present the case of a 52-year-old Caucasian gentleman who initially came to the hospital with a three-week history of dyspnea. In the hospital, a diagnosis of Stage 4 pancreatic cancer with a lymphangitic spread of the tumor to the lungs was made. Despite optimal treatment, the patient required mechanical ventilation for acute hypoxic respiratory failure. PLC is a relatively rare manifestation of malignancy; yet, it generally carries a poor prognosis. It may occur during the course of malignancy or may represent as the first findings in malignancy. It is important for physicians to be aware of the clinical presentations of PLC in order to ensure timely treatment. Oftentimes, PLC can be diagnosed through clinical judgment alone without the need for radiological support and other invasive measures.


Vitamin E and C levels in infants during the first year of life.
The considerably lower vitamin E level found in cord blood and in newborns at birth than those found in the venous blood of mothers at delivery are not yet fully explained. In a group of 217 not selected newborns, we attempted to establish the relation between vitamin E and C levels at delivery and the changes during the first year of life. The mean serum vitamin E level rose from 0.37 mg/ml at 3 days to 0.80 mg/100 ml at 6 months and to 0.72 mg/100 ml at 12 months. On the other hand vitamin C mean levels lowered from 0.93 mg/100 ml in cord blood to 0.77 mg/100 ml at 6 months and to 0.73 mg/100 ml at 12 months. The rise of vitamin E values could be explained by the early use of infant solid foods with high vitamin and mineral content and by the increase of serum lipoproteins. Except at 3 days after delivery there were no individual values of serum vitamin E below the acceptable 0.35 mg/100 ml limit. However, serum vitamin C levels compatible with a moderate risk were very often observed, i.e., in 27.1% of infants at 6 months and in 30.5% at 1 year. Thus, vitamin E intake in infants was satisfactory with the usual diet but not vitamin C for which blood levels were not adequate. In view of these findings it appears necessary to evaluate periodically the vitamin E as well as vitamin C status in the infant population.


Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients.
Nucleos(t)ide analogues are utilized for the treatment of chronic HBV infection, and HBe seroconversion and HBV DNA levels are commonly used as markers of viral status and as primary treatment endpoints. Recently, a new assay was prepared for the detection of serum HBV core-related antigen (HBcrAg), consisting of HBcAg, HBeAg, and p22cr, which is a precore protein from amino acid -28 to at least amino acid 150, by coding the precore/core region. In this study, we examined the correlation between serum HBcrAg concentration and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients. Intrahepatic cccDNA was detected in all 57 patients, 42 patients were HBcrAg-positive, and serum HBcrAg concentration level was closely correlated with cccDNA. Additionally, positive HBcrAg concentration level results were observed in 6 out of 13 HBsAg seroclearance patients and 20 out of 31 HBV DNA-negative patients. Moreover, the correlation between HBcrAg and cccDNA in these 31 HBV DNA-negative patients was statistically significant (r = 0.482, P = 0.006). These data suggest that serum HBcrAg concentration is well correlated with intrahepatic cccDNA level, and that the measurement of serum HBcrAg may be clinically useful for monitoring intrahepatic HBV viral status, especially in patients under treatment with nucleos(t)ide analogues.


[Primary malignant non-Hodgkin's lymphoma of the stomach in the Kiel classification].
Resection preparations from 30 cases of primary malignant non-Hodgkin lymphomas of the stomach were reclassified using the Kiel-classification. In 17 cases centroblastic malignant lymphomas were found a further 4 were centroblastic-centrocytic, 4 were immunoblastic malignant lymphomas, and 5 immunocytic malignant lymphomas. Although preoperative gastroscopies and biopsies were carried out in 22 cases, certain diagnoses of lymphoma were possible in 9 cases only. Seven patients died within a month postoperatively. The two-year survival rate was more than one-third, and the five-year survival rate, less than one-fourth of all cases. The results are compared with data from the literature.


Adolescents' and school nurses' perceptions of using a health and lifestyle tool in health dialogues.
To describe and explore adolescents' and nurses' perceptions of using a health and lifestyle tool in health dialogues in the School Health Service. In Sweden, dialogues concerning health and lifestyle are offered to adolescents aged 14 years with the purpose of encouraging an interest in a healthy lifestyle. A health and lifestyle tool including a health questionnaire and a health profile has recently been developed, with the aim of facilitating the communication about health and lifestyle in these dialogues. Qualitative descriptive design. Twenty-nine adolescents and 23 nurses participated in focus group interviews, which were subjected to qualitative content analysis. The health and lifestyle tool was perceived as constituting a structure for the dialogues and as a clear and applicable starting point, focusing on individual aspects. The tool contributed to an understanding of the health situation and to the transmittal of health information on an individual as well as a group level. The tool was perceived as constituting a useful structure for the dialogues about health and lifestyle. When it was used the individual's health and lifestyle were concretised, which opened up for a dialogue and different aspects of health and lifestyle were detected. However, in some cases the outcome of the tool could be conceived as a stringent assessment and thereby complicate the dialogues. The use of a tool, such as the one used in this study, is one way to improve the dialogues in the School Health Service, allowing them to be more focused on the individual's needs and to detect aspects that would otherwise not be so easily detected. The implications of this study include using the findings to guide counselling sessions in the schools and other health care settings.


Design and Modular Construction of a Polymeric Nanoparticle for Targeted Atherosclerosis Positron Emission Tomography Imaging: A Story of 25% (64)Cu-CANF-Comb.
To assess the physicochemical properties, pharmacokinetic profiles, and in vivo positron emission tomography (PET) imaging of natriuretic peptide clearance receptors (NPRC) expressed on atherosclerotic plaque of a series of targeted, polymeric nanoparticles. To control their structure, non-targeted and targeted polymeric (comb) nanoparticles, conjugated with various amounts of c-atrial natriuretic peptide (CANF, 0, 5, 10 and 25%), were synthesized by controlled and modular chemistry. In vivo pharmacokinetic evaluation of these nanoparticles was performed in wildtype (WT) C57BL/6 mice after (64)Cu radiolabeling. PET imaging was performed on an apolipoprotein E-deficient (ApoE(-/-)) mouse atherosclerosis model to assess the NPRC targeting efficiency. For comparison, an in vivo blood metabolism study was carried out in WT mice. All three (64)Cu-CANF-comb nanoparticles showed improved biodistribution profiles, including significantly reduced accumulation in both liver and spleen, compared to the non-targeted (64)Cu-comb. Of the three nanoparticles, the 25% (64)Cu-CANF-comb demonstrated the best NPRC targeting specificity and sensitivity in ApoE(-/-) mice. Metabolism studies showed that the radiolabeled CANF-comb was stable in blood up to 9 days. Histopathological analyses confirmed the up-regulation of NPRC along the progression of atherosclerosis. The 25% (64)Cu-CANF-comb demonstrated its potential as a PET imaging agent to detect atherosclerosis progression and status.


Evaluation of the onset and intubation conditions of rocuronium bromide.
Rocuronium 0.6, 0.75, or 0.9 mg kg-1, was given after supramaximal train-of-four stimulation of the ulnar nerve, measuring the compound action potential of the hypothenar muscles, Intubation conditions, onset time, recovery to 25% and recovery index of the three doses of rocuronium bromide were determined in 60 ASA I or II consenting patients, who were receiving propofol, alfentanil and N2O/O2 for ophthalmic surgery. Intubation conditions were randomly assessed either 45 s or 60 s after injection. In general, intubation conditions were excellent or good; in only three patients were poor conditions obtained, always at 45 s. For total intubation score a borderline difference was found in favour of the 60 s subgroups. No difference could be shown between the three dose groups. The onset time was longer (P < 0.01) in the 0.6 mg kg-1 group, compared to that in the 0.9 mg kg-1 group. The recovery to 25% and spontaneous recovery index were shorter in the 0.6 mg kg-1 group (P < 0.01).


Factors Affecting MoO4(2-) Inhibitor Release from Zn2Al Based Layered Double Hydroxide and Their Implication in Protecting Hot Dip Galvanized Steel by Means of Organic Coatings.
Zn2Al/-layered double hydroxide (LDH) with intercalated MoO4(2-) was investigated as a potential source of soluble molybdate inhibitor in anticorrosion coatings for hot dip galvanized steel (HDG). The effect of solution pH, soluble chlorides, and carbonates on the release kinetics of the interleaved MoO4(2-) ions from the LDH powder immersed in solutions containing different anions was studied by X-ray diffraction, in situ attenuated total reflectance infrared (ATR-IR) spectroscopy, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The effect of the solution composition on the total release and the release kinetics was demonstrated. Less than 30% of the total amount of the intercalated MoO4(2-) was released after 24 h of the immersion in neutral 0.005-0.5 M NaCl and 0.1 M NaNO3 solutions whereas the complete release of MoO4(2-) was observed after 1 h in 0.1 M NaHCO3 or Na2SO4 and in alkaline solutions. The in situ ATR-IR experiments and quantification of the released soluble species by ICP-AES demonstrated the release by an anion exchange in neutral solutions and by the dissolution of Zn2Al/-LDH in alkaline solutions. The anion exchange kinetics with monovalent anions was described by the reaction order n = 0.35 ± 0.05 suggesting the diffusion control; for divalent anions, n = 0.70 ± 0.06 suggested the control by a surface reaction. Dissolution of Zn from coated HDG with and without Zn2Al/-MoO4(2-) fillers, leaching of MoO4(2-) from the coating, and the electrochemical impedance spectroscopy response of the coated systems were measured during the immersion in 0.5 M NaCl solutions with and without 0.1 M NaHCO3. Without carbonates, the release of soluble MoO4(2-) was delayed for 24 h with no inhibiting effect whereas with 0.1 M NaHCO3 the immediate release was accompanied by the immediate and strong inhibiting effect on Zn dissolution. The concept of controlling the inhibition performance of LDH hybrid coatings by means of the environment composition is discussed.


Efficient Synthesis of Fused Oxazepino-isoquinoline Scaffolds via an Ugi, Followed by an Intramolecular Cyclization.
A mild and efficient protocol was developed for the synthesis of oxazepino-isoquinolines via a one-pot Ugi four-component reaction, followed by the intramolecular addition of the resulting alcohol to an alkyne moiety under microwave irradiation conditions. Notably, this process only required one purification step, providing facile access to two series of complex and potentially interesting biologically active scaffolds.


Seborrheic keratosis in an adolescent: A rare presentation.
Seborrheic keratosis is a common benign epidermal lesion that typically occurs in the elderly population. Its occurrence in childhood and adolescence is rare and can pose a diagnostic challenge for clinicians and dermatopathologists. We report a case of a 16-year-old boy with multiple brown, black oval-shaped stuck-on lesions on his face, which were diagnosed as seborrheic keratosis based on histological findings. The patient had no significant medical history or family history of seborrheic keratosis. In this report, we discuss the differential diagnoses of seborrheic keratosis-like lesions in childhood and adolescence and explain why they were not compatible with our case. We also review the available treatment options. Our case emphasizes the need for dermatologists to consider seborrheic keratosis in the differential diagnosis of cutaneous lesions in young patients.


[Successful treatment of a primary racemose hemangioma using ligation and transection of the bronchial artery decided on the basis of the intra-operative arterial pressure].
An 80-year-old woman presented with hemoptysis. Fiberoptic bronchoscopy revealed a blue, non-pulsatile, polypoid lesion at the orifice of the left upper division bronchus. Bronchial arteriography demonstrated convolution, dilatation, and pooling of contrast material in the left upper lobe. Since the bronchial arterial pressure decreased to the predicted pulmonary artery pressure after transient interruption between the aorta and proximal bronchial artery, the racemose hemangioma was presumed to be supplied mainly from the bronchial artery. She underwent ligation and transaction of the left bronchial artery, and had no further hemoptysis. Measurement of the bronchial arterial pressure is important for determining how to treat racemose hemangioma.


Prevalence of wheeze, bronchial hyper-responsiveness and asthma in the elderly Chinese.
Asthma is a common health problem affecting patients of all ages. Because of the ease of sampling, epidemiological studies have concentrated mainly on the paediatric and general population. This study aimed to determine the prevalence of wheeze, bronchial hyper-responsiveness and asthma amongst our elderly population and deduce any clinical and laboratory risk factors that might identify elderly asthmatics at an earlier stage. Two thousand and thirty-two elderly Chinese aged > or = 70 years, randomly selected from a registered list of all recipients of Old Age and Disability Allowances in Hong Kong, were administered a questionnaire on lung health. Two hundred and fifty subjects were invited to attend our laboratory for skin tests and pulmonary function tests and 179 agreed. Of these, 173 (96.6%) and 176 (98.3%) had eosinophil count and serum IgE levels measured, respectively. Two definitions of asthma were used: (1) bronchial hyper-responsiveness (BHR) plus current wheeze, and (2) history of wheezing without previous diagnostic labels of emphysema or chronic bronchitis. Fifteen patients (out of 179: 8.4%) reported wheezing over the past 1 year. Fifty-one patients (28.5%) demonstrated BHR on spirometry or histamine challenge tests. Seven patients had both symptoms of wheezing and evidence of BHR. The prevalence of asthma using this definition is therefore 3.9% (95% CI 1.6-7.9%). Nine patients had symptoms of wheezing without previous diagnostic labels of chronic bronchitis or emphysema and, using this definition, the prevalence is 5.0% (95% CI 2.3-9.3%). Using multiple logistic regression studies, sex, social class, age, smoking habits, serum IgE levels and eosinophil counts did not predict a diagnosis of asthma using either definition. We found no association between a positive skin test and any respiratory symptoms or illnesses including asthma. Wheeze, bronchial hyper-responsiveness and asthma are prevalent amongst our elderly population. However, there were no identifiable demographic and laboratory risk factors in this study that may help us predict a diagnosis of asthma.


[Time-series analysis of particulate matter and daily hospital visits for coronary heart disease in Yinzhou district, Ningbo area].
Objective: To explore the association between particulate matter (PM) and daily hospital visits of coronary heart diseases in Ningbo. Methods: Daily data of hospital visits from January 2014 to June 2015 (516 days in total) were obtained from the Yinzhou Health Information System in Ningbo. Daily air pollution data for PM and meteorological data were collected from the database of Ningbo Environmental Monitoring Center and Ningbo Meteorological Bureau. Time-series analysis by quasi-Poisson generalized additive model was used to examine the association between air pollution and hospital visits for coronary heart diseases by adjustment of long-term trends, seasonal patterns and meteorological variables (temperature, humidity), and day of week. Results: An increase of an IQR of PM2.5 accounted for 1.98% (95%CI:-0.59%-4.63%) increase of hospital visits for coronary heart diseases. The associations between PM2.5 and hospital visits for coronary heart diseases among female and the elderly (≥75 years) were stronger (ER=2.70%,95% CI:0.01%-5.47%; ER=3.35%, 95% CI: 0.12%-6.69%). The effects of PM2.5~10 attenuated after adjustment for PM2.5.Conclusion: PM2.5 had short-term effects on daily hospital visits for coronary heart diseases in Ningbo, and such association was stronger among female and the elderly.


Antonio Scarpa (1752-1832) and his study on ocular cancer.
Antonio Scarpa (1752-1832) is known in the history of medicine as a distinguished anatomist and surgeon. Apart from his anatomical studies that established him and especially in clinical anatomy, he focused also his interest on ophthalmology, therefore he was considered as the "father of ophthalmology in Italy". His study on ocular cancer is of particular interest, because he not only reviewed older approaches on this issue enriching them with his own clinical observations but his study served as a bridge connecting the previous tradition to the scientific study of ocular cancer which began at the second third of 19th century.


Associations Between Spousal Relationship, Husband Involvement, and Postpartum Depression Among Postpartum Mothers in West Java, Indonesia.
Indonesia is actively promoting husband involvement in maternal health care, since it has been claimed to impact the wellbeing of mothers. This study aims to investigate the extent to which spousal relationship, husband involvement, and maternal health behavior affect postpartum depression among Indonesian mothers. A survey was carried out among 336 postpartum mothers who received maternal care in 27 independent midwifery clinics in 7 regions of West Java Province, Indonesia. The measurement model of husband involvement comprising 4 dimensions, namely maternity care engagement, instrumental support, emotional support, and informational support were developed and validated using confirmatory factor analysis. The Quality of Marriage Index (QMI) and the Edinburgh Postnatal Depression Scale (EPDS) were also validated and used to measure spousal relationship and postpartum depressive symptoms. A structural equation model was specified to examine the association between spousal relationship, husband involvement, maternal healthy behavior, and postpartum depression. The study confirms the assumption that the quality of the spousal relationship could determine husband's involvement during pregnancy, childbirth, and postpartum (γ = .60, P < .001), eventually leading to better maternal healthy behavior (γ = .015, P < .001) and a decrease in postpartum depressive symptoms among mothers (γ = -.21, P < .001). The study results suggest the needs to promote comprehensive husband involvement to enhance the wellbeing of mothers. This can be achieved through couple interventions at the community level and the inclusion of a supportive role for husbands in the maternal and childcare guidebook offered during ANC visits.


Rare Presentation of Small Bowel Obstruction Secondary to Intestinal Leiomyoma in a Patient with Crohn's Disease.
Small bowel obstructions (SBOs) are surgical emergencies that can occur with mechanical blockage of the intestinal lumen. These blockages are most commonly caused by adhesions or hernias, but can also result from intestinal neoplasms. This case report documents the rare occurrence of SBO due to a submucosal leiomyoma. This case was complicated by the patient's longstanding history of Crohn's disease, which has a considerable overlap in symptomatology with SBOs. This may have resulted in a delay in the patient's diagnosis. Leiomyomas should always be considered as a potential, albeit rare, cause of SBO.


Cranial translation of the elevated prepuce in dogs before and after two modifications: A cadaveric study.
To quantify cranial translation of the prepuce after elevating it from the ventral body wall and to compare it to the cranial translation achieved after each of two modifications expected to increase cranial translation. Cadaveric study. Ten male dogs. All procedures were performed with dogs in dorsal recumbency. A urinary catheter with an attached millimeter scale was secured in the urethra and the penis was sutured to the ventral body wall to eliminate relative movement between the penis and prepuce. Three preplaced sutures between the prepuce and linea alba, at increasing distances from the prepuce, were used to translate the prepuce cranially. The prepuce was tested after elevating it from the ventral body wall, and after sequentially releasing the skin caudal to the prepuce (modification 1) and the attachment of the lamina interna to the penis (modification 2). The preplaced sutures were tightened and loosened sequentially from caudal to cranial, and the location of the dorsal aspect of the preputial opening on the millimeter scale was noted prior to, and after tightening each of the sutures. Maximum mean (range) cranial translation of the prepuce after elevating the prepuce, and after modifications 1 and 2, was 15 mm (5-26 mm), 25 mm (15-30 mm), and 37 mm (24-50 mm), respectively. Modifications described increased cranial translation of the prepuce. Modifications described in this study may provide alternate strategies for the treatment of dogs with severe paraphimosis.


[Apoptosis and necrosis of lymphocytes induced by UV-radiation in the presence of autological plasma].
The influence of UV-light (240-390 nm) in doses 151-3020 J/m2 on the nature of the death of lymphocytes cells of donor's blood (using markers of apoptotic and necrotic death of cells) and on the level of expression of the marker of apoptotic pre-preparation--CD95-receptor has been investigated. We have shown that UV-radiation increases expression of CD95-receptors which is caused mainly by de novo synthesis of the receptors. It has been revealed that during daily incubation of photo-modified lymphocytes (151 and 755 J/m2) without autological blood cell death occurs by receptor-involved apoptosis. Exposure to high doses of radiation (1510 and 3020 J/m2) causes massive necrotic death of immunocytes. The use of autologous blood plasma during incubation of photo-modified lymphocytes allows decreasing the number of both apoptotic and necrotic cells.


Animal models of contraception: utility and limitations.
Appropriate animal modeling is vital for the successful development of novel contraceptive devices. Advances in reproductive biology have identified novel pathways for contraceptive intervention. Here we review species-specific anatomic and physiologic considerations impacting preclinical contraceptive testing, including efficacy testing, mechanistic studies, device design, and modeling off-target effects. Emphasis is placed on the use of nonhuman primate models in contraceptive device development.


Deglycosylated bleomycin induces apoptosis in lymphoma cell via c-jun NH2-terminal kinase but not reactive oxygen species.
Bleomycin (BLM) has demonstrated potent activity in treating malignant lymphomas but its therapeutic efficacy is hampered by induction of lung fibrosis. This side effect is related to the ability of the drug to generate reactive oxygen species in lung cells. In the present study, we evaluated the consequences of deglycosylation of BLM in term of cytotoxic activity and generation of reactive oxygen species. When tested on U937 human lymphoma cells, both compounds generated a typical apoptotic phenotype. Cell death induction was associated with Bax oligomerization, dissipation of the mitochondrial membrane potential, release of cytochrome c, caspase activation, chromatin condensation and internucleosomal degradation. Whereas both reactive oxygen species and c-jun NH(2)-terminal kinase (JNK) inhibitors prevented BLM-induced U937 cell death, only JNK inhibition prevented deglycosylated BLM-mediated cell death. Both compounds induced clustering of TRAIL receptors (DR4 and DR5) and Fas at the cell surface but neither a chimeric soluble DR5 receptor that inhibits TRAIL-induced cell death nor a dominant negative version of the adaptor molecule Fas-associated death domain prevented BLM-induced cytotoxicity. These observations indicate that deglycosylation of BLM does not impair the ability of the drug to trigger cell death through activation of the intrinsic pathway but prevents induction of reactive oxygen species. This observation suggests that deglycosylated BLM could exhibit less toxic side effects and could warrant its use in clinic.


Connor-Davidson Resilience Scale: validation study in a Portuguese sample.
The objective of this paper was to evaluate the structural validity and convergent validity of the first Portuguese version of the Connor-Davidson Resilience Scale (CD-RISC). The data sets come from two studies conducted in Portugal, respectively, from the Resilience Effect in Coping with Trauma (RECT) project and from the Health Impact Assessment of Employment Strategies (HIAES) project. The sample is composed of 476 participants from the RECT project and 405 participants from the HIAES project. In both projects, convenience samples were used. The original CD-RISC items were translated to Portuguese and were used in a survey along with additional psychosocial and biomedical measures. Independent exploratory factorial analysis (EFA) with each of the two samples revealed that the best solution in both samples had three factors consistent with the self-efficacy, spirituality and social support factors from the original scale. A Confirmatory factor analysis using the two samples together and specifying the three factors from the EFA revealed a good overall fit and, comparatively, better fit than a model specified with the five factors from the original scale. The study of the convergent validity revealed that bivariate correlations between the three factors and validated measures of stress, life satisfaction, mental health and physical health are globally consistent with previous research. This study makes available to the broad Community of Portuguese Language Countries a validated measure of resilience extensively used for research and intervention. The results encourage future studies using this translated version of CD-RISC to explore further the three-factor structure found here and to test the convergent validity with new samples.


Hansen's disease with McCune-Albright syndrome.
McCune-Albright syndrome (MAS) comprises a triad of fibrous dysplasia of bone, café-au-lait macule, and endocrinopathy. The disease is due to activating mutation of G protein-coupled receptor leading to hyperfunction of glands. Hansen's disease is caused by infection with Mycobacterium leprae and is seen with underlying immunosuppressed conditions in genetically predisposed individuals. We recently encountered a patient with Hansen's disease along with underlying MAS and report the same in this report.


The Regulation of Homologous Recombination by Helicases.
Homologous recombination is essential for DNA repair, replication and the exchange of genetic material between parental chromosomes during meiosis. The stages of recombination involve complex reorganization of DNA structures, and the successful completion of these steps is dependent on the activities of multiple helicase enzymes. Helicases of many different families coordinate the processing of broken DNA ends, and the subsequent formation and disassembly of the recombination intermediates that are necessary for template-based DNA repair. Loss of recombination-associated helicase activities can therefore lead to genomic instability, cell death and increased risk of tumor formation. The efficiency of recombination is also influenced by the 'anti-recombinase' effect of certain helicases, which can direct DNA breaks toward repair by other pathways. Other helicases regulate the crossover versus non-crossover outcomes of repair. The use of recombination is increased when replication forks and the transcription machinery collide, or encounter lesions in the DNA template. Successful completion of recombination in these situations is also regulated by helicases, allowing normal cell growth, and the maintenance of genomic integrity.


Synthesis of Pyridobenzazepines Using a One-Pot Rh/Pd-Catalyzed Process.
In recent years, our group has been developing multicatalytic reactions for the synthesis of biologically relevant heterocyclic compounds. An efficient dual-metal catalyzed reaction of electron-deficient o-chlorovinylpyridines with o-aminophenylboronic esters to access pyridobenzazepines is described. Combining a RhI-catalyzed arylation followed by a Pd0-catalyzed C-N coupling, in a one-pot procedure, provides a simplified method to access heterocycles without workup and purification after each step. The substrate scope encompasses a variety of N-H and N-alkylated pyridobenzazepine variants with yields up to 93%.


Health-related quality of life among dialysis patients on three continents: the Dialysis Outcomes and Practice Patterns Study.
Assessing health-related quality of life (HRQOL) can provide information on the types and degrees of burdens that afflict patients with chronic medical conditions, including end-stage renal disease (ESRD). Several studies have shown important international differences among ESRD patients treated with hemodialysis, but no studies have compared these patients' HRQOL. Our goal was to document international differences in HRQOL among dialysis patients and to identify possible explanations of those differences. We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational, international study of hemodialysis patients. We performed a cross-sectional analysis of DOPPS data from the United States, five countries in Europe (France, Germany, Italy, Spain, and the United Kingdom), and Japan. Linear mixed models were used to analyze differences in HRQOL, using the KDQOL-SFTM. Norm-based scores were used to minimize cultural response bias. Linear regression analysis was used to adjust for confounding factors. Other variables included demographic variables, comorbidities, primary cause of ESRD, complications of ESRD and treatment, and socioeconomic status. In all generic HRQOL subscales, patients on all three continents had much lower scores than their respective population norm values. Patients in the United States had the highest scores on the mental health subscale and the highest mental component summary scores. Japanese patients reported better physical functioning than did patients in the United States or Europe, but they also reported the greatest burden of kidney disease. Overall, these differences remained even after adjusting for possible confounders. On all three continents, ESRD and hemodialysis profoundly affect HRQOL. In the United States, the effects on mental health are smaller than in other countries. Japanese hemodialysis patients perceived that their kidney disease imposes a greater burden, but their physical functioning was significantly higher. Different distributions of socioeconomic factors and major comorbid conditions could explain little of this difference in physical functioning. Other possible factors, such as quality of dialysis and related health care, deserve careful study.


Does attention redirection contribute to the effectiveness of attention bias modification on social anxiety?
Attention bias modification (ABM) is designed to modify threat-related attention bias and thus alleviate anxiety. The current research examined whether consistently directing attention towards targeted goals per se contributes to ABM efficacy. We randomly assigned 68 non-clinical college students with elevated social anxiety to non-valence-specific attend-to-geometrics (AGC), attention modification (AMC), or attention control (ACC) conditions. We assessed subjective, behavioral, and physiological reactivity to a speech task and self-reported social anxiety symptoms. After training, participants in the AMC exhibited an attention avoidance from threat, and those in the AGC responded more rapidly toward targeted geometrics. There was a significant pre- to post-reduction in subjective speech distress across groups, but behavioral and physiological reactivity to speech, as well as self-report social anxiety symptoms, remained unchanged. These results lead to questions concerning effectiveness of ABM training for reducing social anxiety. Further examination of the current ABM protocol is required.


Polyamine-like actions of peptides derived from conantokin-G, an N-methyl-D-aspartate (NMDA) antagonist.
Conantokins-T and -G are highly conserved polypeptides derived from Conus venoms. The N-methyl-D-aspartate (NMDA) antagonist properties of these compounds have been attributed to a potent noncompetitive inhibition of polyamine responses. Substitution of the highly conserved gamma-carboxyglutamate residues as well as modification of the N and C termini of conantokin-G abolished the inhibition of polyamine responses at the NMDA receptor complex. However, several of these modified polypeptides closely mimicked the neurochemical profile of polyamines at the NMDA receptor complex. One of these derivatives, Tyr0-conantokin-G, was found to be the most potent compound exhibiting polyamine-like actions at the NMDA receptor complex described to date, approximately 7-fold more potent than spermine. Circular dichroism studies demonstrate a significant alpha-helical content in conantokin-G (27% in aqueous medium). However, this alpha-helicity is not sufficient for the NMDA antagonist action of the parent peptide and is neither necessary nor sufficient for the polyamine-like behavior of several conantokin-G analogs. The modified conantokin-G derivatives described in this report should be useful probes for examining the role of both polyamines and the polyamine recognition site in the operation of the NMDA receptor complex.


Binding studies of RU486 in different Reuber hepatoma variants.
The synthetic steroid RU486, which displays antiprogestin and antiglucocorticoid properties in different systems, inhibits cell growth in dexamethasone-sensitive H56 cells containing glucocorticoid receptors, as well as in dexamethasone-resistant S-H56-125 cells displaying a very low level of dexamethasone binding. In order to better understand the mechanism of the antiproliferative effect, the binding of RU486 to these hepatoma cells was examined. Results revealed the presence of two different kinds of binding sites for RU486 in dexamethasone-sensitive H56 cells whereas only one type of site was detected in the dexamethasone-resistant cells. These peculiar sites were also recognized by cortivazol during competition experiments. Thus, it seems that S-H56-125 cells contain an altered glucocorticoid receptor that binds RU486 and cortivazol but virtually not dexamethasone. The ability of RU486 to inhibit the growth of dexamethasone-resistant cells suggests this steroid may be used to treat tumor cells that develop glucocorticoid resistance after long-term treatment.


Ultrastructural changes in the gastric mucosa following hemorrhagic shock in pigs.
Ultrastructural changes in the gastric mucosa of 14 piglets subjected to transient hemorrhagic shock (3 hr duration; mean arterial pressure 40 mmHg) are described. After 30 min there was mucosal edema and extravasation of red blood cells. Microthrombi with degranulating thrombocytes and fibrin strands were seen in the capillaries. These changes were also seen in the antral mucosa where no subsequent ulceration usually occurs. At this stage the cells of the neck region of the gastric glands showed mitochondrial dilatation and their apical parts were seen to bulge into the lumen of the gastric glands. Other cell types were affected later and necrosis progressed from the surface into deeper parts of the mucosa. Mast cells and mucosal endocrine cells were relatively resistant, being mostly undamaged at the end of the shock period and later. The findings suggest that, during the shock, local formation of thrombi contributes to mucosal ischemia and ulcer formation, and that the cells at the neck region of the gastric glands form the locus of limited resistance to ulcerogenic effects.


The role of the left hemisphere in motor control of touch: a functional magnetic resonance imaging analysis.
Previous research using a simple finger-touching task has shown greater blood oxygenation level dependent (BOLD) activation volume in the motor cortex of the right hemisphere for contralateral finger touching compared to ipsilateral finger touching, but no significant contralateral advantage for the left hemisphere. Such equal involvement of the left hemisphere for both contralateral and ipsilateral finger touching suggests a special role of the left hemisphere for finger touching. In contrast, we found a contralateral advantage in the motor cortex of both hemispheres in a majority of participants (14/16) when consistently activated BOLD volumes were examined. However, participants who did not show a clear contralateral advantage for the left hemisphere did show activation in the left inferior frontal gyrus (IFG; Broca's Area) and in the left insular cortex, which suggests that verbally mediated sequencing of finger movements can account for our less frequent result.


Effect of vitamin C or beta-carotene on SCE induction by gamma rays in radiosensitized murine bone marrow cells in vivo.
The in vivo effect of vitamin C or beta-carotene on sister chromatid exchange (SCE) radio-induction was determined in murine bone marrow cells sensitized by BrdU incorporation. Pre- or post-treatment with 100 mg/kg body wt vitamin C did not cause a significant reduction in SCE induced by the exposure to 0.63 Gy gamma-rays. Treatment with a double dose of vitamin C and with 0.45 Gy radiation did not cause a significant reduction in SCE frequency. However, due to the fact that vitamin C per se is capable of SCE induction, if an additive effect of radiation and vitamin C is considered, the expected frequency is higher than that observed. This implies that vitamin C could have a slight radioprotective activity. With regard to beta-carotene, it has been demonstrated that 50 mg/kg body wt causes a statistically significant increase per se, although pre- and post-treatment with the same dose has an additive effect on SCE frequency induced by 0.62 Gy radiation. This indicates that beta-carotene does not have radioprotective activity under the conditions used in the present study.


Overview of current pharmacotherapeutic options in benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) represents the histological entity of prostate cell proliferation, which inflicts a gradually increasing obstruction of the bladder outlet and is accompanied by a progressing manifestation of lower urinary tract symptoms (LUTS). BPH management algorithm includes conservative measures, pharmaceutical agents, and surgical procedures. A comprehensive literature review was performed using PubMed, Scopus, and Google Scholar databases to identify publications written in English, analyzing BPH pharmaceutical treatment. The search was conducted from January 2000 to January 2023. Six main drug classes can be administered, either as monotherapy or in combination. Furthermore, the authors provide current direction of research on future medications, which focuses on a more etiological interference to the BPH pathophysiological mechanism. The available medications represent an effective first-line step of BPH/LUTS therapy. Currently, the administration of BPH medications is tailored to patient/disease characteristics and entails long-time adherence to therapy. The emergence of new surgical modalities, which combine significantly lower morbidity compared to standard procedures and more durable effects than the available medications, seems to challenge the current treatment algorithm. More direct comparisons and the increasing experience with these surgical modalities will delineate the switch points between various therapy levels along the BPH management sequence.


Antisense-induced blockade of GATA-3 expression could inhibit Th2 excursion of tumor cells in vitro and in vivo.
Previous studies have shown that tumor cells predominantly express Th2 type cytokines and transcription factors. GATA-3, as a Th2-specific transcription factor, plays a central role in positive-regulating Th2 development. So whether the expression of GATA-3 in tumor cells has any effect on tumor development is a question of interest. In the present study, we inhibited the expression of GATA-3 in tumor cells through antisense RNA blockade technique, and observed its effects on tumor in vitro and in vivo. Our results showed that antisense GATA-3 treatment could inhibit the expression of TNF-alpha and Th2 cytokines in tumor cells, and antisense-induced blockade of GATA-3 could also depress tumor growth in tumor-bearing mice. We suggest that the ratio of T-bet/GATA-3 can be evaluated as a more important marker of the status of Th1/Th2 type. And our results might provide some evidence about the molecular regulatory mechanisms in tumor cell development.


VITAMIN D AND TISSULAR EXPRESSION OF VITAMIN D RECEPTOR IN OBESITY.
Vitamin D (VitD), a lipid-soluble hormone, is able to regulate the transcription of many genes through vitamin D receptor (vitD receptor-VDR). It has been shown that VitD deficiency is associated with obesity, characterized by a low degree inflammatory state, which contribute to the pathogeny of metabolic syndrome and type 2 diabetes mellitus. VitD deficiency is a public health problem, at the same time the global prevalence of obesity and cardiovascular diseases is continuously growing. Evidence from recent studies on animal models suggest that VitD or VDR deficiency promotes cardiomyocyte hypertrophy, which can be one of the mechanisms for increasing cardiovascular risk. The heart is one of the target organs of action for VitD, because VDR is expressed in cardiomyocytes. Also, previous in vitro studies have shown that VitD is able to inhibit the production of monocyte chemotactic factors (MCP-1) and other pro-inflammatory mediators in human preadipocytes and mature adipocytes. Inflammation is an important factor in the pathogenesis of atherosclerosis. In obesity there are not known data about correlations between plasma levels of VitD and VDR expression in the subcutaneous fat tissue, epicardial visceral adipose tissue, and in particular in myocardium. Also, there are still no studies to test VDR expression in myocardial cells and to investigate the results of dietary VitD supplementation on the expression of VDR in the epicardial adipose tissue and myocardium.


Myocardial substrate utilization in perfused hearts isolated from adrenalectomizedcats.
Isolated hearts form chronically adrenalectomized cats were perfused with Krebs-Henseleit buffer plus either glucose (10mM) or palmitate (0.4 mM) under various conditions of constant pressure and constant flow. Glucose uptake in adrenalectomizedhearts was not diminished from control values under conditions of constant pressure, constant flow, anoxia, or insulin stimulation. Palmatic acid uptake and oxygen consumption were significantly reduced (P less than 0.02) in adrenalectomized hearts. This diminished fatty acid utilization was also reflected in a significantly lower CO'2 production and incorporation of the palmitate into myocardial triglycerides. The decreased fatty acid uptake by adrenalectomized cat hearts may represent aserious defect in myocardial metabolism since lipids are the major energy substrate forthe heart. Whether the defect occurs in fatty acid transport or activation cannot beelucidated by this study. However, it is unlikely that this defect has a major contributory effect on the dysfunction of adrenalectomized hearts since the myocardium iscabable of using other energy substrates readily.


[European Association of Urology guidelines on assessment and nonsurgical management of urinary incontinence].
The previous European Association of Urology (EAU) guidelines on urinary incontinence comprised a summary of sections of the 2009 International Consultation on Incontinence. A decision was made in 2010 to rewrite these guidelines based on an independent systematic review carried out by the EAU guidelines panel, using a sustainable methodology. We present a short version of the full guidelines on assessment, diagnosis, and nonsurgical treatment of urinary incontinence, with the aim of increasing their dissemination. Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches, based on Population, Intervention, Comparator, Outcome questions. Appraisal of papers was carried out by an international panel of experts, who also collaborated on a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. The full version of the guidelines is available online (http://www.uroweb.org/guidelines/online-guidelines/). The guidelines include algorithms that refer the reader back to the supporting evidence, and they are more immediately useable in daily clinical practice. These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where such evidence does not exist, they present a consensus of expert opinion.


Ultrastructural localization of coenzyme A phosphatase (CoA-Pase) activity to the GERL system in secretory ameloblasts of the rat incisor.
Enzymatic hydrolysis of the monoester phosphate group from coenzyme A (CoA) was studied in rat incisor ameloblasts by incubating specimens from glutaraldehyde-fixed teeth in a cytochemical medium prepared with acetyl-CoA as substrate and lead ions as capture agent for phosphate. Ameloblasts incubated for 1 hr at 37 degrees C and at pH 5.0 in this medium showed reaction product localized almost exclusively along the trans (mature) aspect of the Golgi apparatus within a network of small granules and interconnecting tubular channels that comprise the GERL system in this cell. Reaction product was otherwise seen in trace amounts only within some Golgi saccules, a few lysosomal dense bodies and, in rare instances, within an occasional focal area of the endoplasmic reticulum. No selective staining of the GERL system was seen in control ameloblasts incubated at either pH 7.2 or pH 9.0 with acetyl-CoA as substrate, or incubated at pH 5.0 with dephospho-CoA as substrate. Control experiments at pH 5.0 also revealed that reaction product selectively stained the GERL system in ameloblasts when other molecules resembling CoA were used as substrate (e.g., crotonyl-CoA, 3'-NADP+), but not when adenosine 3'-monophosphate (3'-AMP) was used as substrate. That is, ameloblasts incubated at pH 5.0 with 3'-AMP showed heavy deposits of reaction product at many sites throughout the cell, including most lysosomal dense bodies, the Golgi saccules, the GERL system, most secretory granules, the nucleus, and extensively throughout the endoplasmic reticulum. These findings suggest that the GERL system of ameloblasts contains a CoA-specific phosphatase activity that may function to convert CoA to dephospho-CoA at acid pH. Biochemical studies included with this investigation further indicate that CoA-Pase activity saturates at exceptionally low concentrations of substrate (KM = 30 microM CoA) compared to other acid-dependent phosphatases.


A Psychophysiological Model of Firearms Training in Police Officers: A Virtual Reality Experiment for Biocybernetic Adaptation.
Crucial elements for police firearms training include mastering very specific psychophysiological responses associated with controlled breathing while shooting. Under high-stress situations, the shooter is affected by responses of the sympathetic nervous system that can impact respiration. This research focuses on how frontal oscillatory brainwaves and cardiovascular responses of trained police officers (N = 10) are affected during a virtual reality (VR) firearms training routine. We present data from an experimental study wherein shooters were interacting in a VR-based training simulator designed to elicit psychophysiological changes under easy, moderate and frustrating difficulties. Outcome measures in this experiment include electroencephalographic and heart rate variability (HRV) parameters, as well as performance metrics from the VR simulator. Results revealed that specific frontal areas of the brain elicited different responses during resting states when compared with active shooting in the VR simulator. Moreover, sympathetic signatures were found in the HRV parameters (both time and frequency) reflecting similar differences. Based on the experimental findings, we propose a psychophysiological model to aid the design of a biocybernetic adaptation layer that creates real-time modulations in simulation difficulty based on targeted physiological responses.


Cas9-based tools for targeted genome editing and transcriptional control.
Development of tools for targeted genome editing and regulation of gene expression has significantly expanded our ability to elucidate the mechanisms of interesting biological phenomena and to engineer desirable biological systems. Recent rapid progress in the study of a clustered, regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) protein system in bacteria has facilitated the development of newly facile and programmable platforms for genome editing and transcriptional control in a sequence-specific manner. The core RNA-guided Cas9 endonuclease in the type II CRISPR system has been harnessed to realize gene mutation and DNA deletion and insertion, as well as transcriptional activation and repression, with multiplex targeting ability, just by customizing 20-nucleotide RNA components. Here we describe the molecular basis of the type II CRISPR/Cas system and summarize applications and factors affecting its utilization in model organisms. We also discuss the advantages and disadvantages of Cas9-based tools in comparison with widely used customizable tools, such as Zinc finger nucleases and transcription activator-like effector nucleases.