Effects of Bifidobacterium infantis on cytokine-induced neutrophil chemoattractant and insulin-like growth factor-1 in the ileum of rats with endotoxin injury.
The digestive tract is the maximal immunizing tissue in the body, and mucosal integrity and functional status of the gut is very important to maintain a healthy organism. Severe infection is one of the most common causes of gastrointestinal dysfunction, and the pathogenesis is closely related to endotoxemia and intestinal barrier injury. Bifidobacterium is one of the main probiotics in the human body that is involved in digestion, absorption, metabolism, nutrition, and immunity. Bifidobacterium plays an important role in maintaining the intestinal mucosal barrier integrity. This study investigated the protective mechanism of Bifidobacterium during ileal injury in rats. To investigate the effects of Bifidobacterium on cytokine-induced neutrophil chemoattractant (CINC) and insulin-like growth factor 1 (IGF-1) in the ileum of rats with endotoxin injury. Preweaning rats were randomly divided into three groups: Control (group C), model (group E) and treatment (group T). Group E was intraperitoneally injected with lipopolysaccharide (LPS) to create an animal model of intestinal injury. Group T was intragastrically administered Bifidobacterium suspension 7 d before LPS. Group C was intraperitoneally injected with normal saline. The rats were killed at 2, 6 or 12 h after LPS or physiological saline injection to collect ileal tissue samples. The expression of ileal CINC mRNA was evaluated by reverse transcription-polymerase chain reaction (RT-PCR), and expression of ileal IGF-1 protein and mRNA was detected by immunohistochemistry and RT-PCR, respectively. The ileum of rats in Group C did not express CINC mRNA, ileums from Group E expressed high levels, which was then significantly decreased in Group T (F = 23.947, P < 0.05). There was no significant difference in CINC mRNA expression at different times (F = 0.665, P > 0.05). There was a high level of IGF-1 brown granules in ileal crypts and epithelial cells in Group C, sparse staining in Group E, and dark, dense brown staining in Group T. There was a significant difference between Groups C and E and Groups E and T (P < 0.05). There was no significant difference in IGF-1 protein expression at different times (F = 1.269, P > 0.05). IGF-1 mRNA expression was significantly different among the three groups (P < 0.05), though not at different times (F = 0.086, P > 0.05). Expression of CINC mRNA increased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium reduced CINC mRNA expression. IGF-1 protein and mRNA expression decreased in the ileum of preweaning rats with endotoxin injury, and exogenous administration of Bifidobacterium prevented the decrease in IGF-1 expression. Bifidobacterium may increase IGF-1 expression and enhance intestinal immune barrier function in rats with endotoxin injury.


Subdural hematoma in term infants.
Subdural hematomas are uncommon in term infants. The study objectives were to evaluate risk factors for and clinical significance of small subdural hematomas observed on computerized tomography. During a 3-year period, 26 near-term and term nonasphyxiated infants were found to have a subdural hematoma on computed tomography. Clinical indications for computed tomography were respiratory symptoms in 15 infants and neurologic symptoms in 10 infants; one infant had a skull fracture. Subdural hematomas were less than 3-mm maximum transverse dimensions in all infants: location was infratentorial (n = 7), supratentorial (n = 7), and in both sites (n = 12). Four infants also had evidence of edema and hemorrhage within the anterior temporal lobe. Delivery was vaginal in 25 of 26 infants, and forceps were used in 13 (50%) infants. Twenty-five infants were managed expectantly; one infant underwent surgical elevation of a depressed skull fracture. No infant required surgical evacuation of the subdural hematoma. At discharge, nine infants with subdural hematoma exhibited an abnormal examination, i.e., mild hypotonia (n = 7) and Erb's palsy (n = 2). The clinical syndrome attributed to subdural hematoma was most often a subtle clinical problem. The presence of subdural hematoma documented by computed tomography is not necessarily always indicative of birth trauma and may occur as sequelae of an otherwise uncomplicated delivery.


Immunosuppression and Opportunistic Infections: A Rare Case Report of Nocardia Osteomyelitis of the Pelvis.
Patients with a long-standing history of immunosuppression are at significantly increased risk of opportunistic infections. One such group of organisms that may cause these types of infections includes the Nocardia genus, a gram-positive, filamentous rod that demonstrates a branching pattern, is urease-producing and has acid-fast properties. The disease profile of Nocardia varies with manifestations ranging from cutaneous infection to severe pulmonary or central nervous system (CNS) infections, and rarely, osteomyelitis. In this case report, we present an 87-year-old female with persistent left gluteal and lumbar pain, generalized body aches, chills, and fevers diagnosed with Nocardia asiatica osteomyelitis of the pelvis, likely secondary to dissemination from pulmonary cavitary disease in an immunosuppressed host with chronic neutropenia. On magnetic resonance imaging (MRI), the patient was found to have heterogeneous enhancement, central necrosis, and loss of cortical margins of the left iliac wing, alongside a rim-enhancing soft tissue mass from the left iliac bone into the left gluteal soft tissues and left paraspinal musculature representing an abscess. She was promptly treated with surgical irrigation and drainage with surgical wound cultures growing Nocardia asiatica. She received treatment with trimethoprim-sulfamethoxazole antibiotics with symptom improvement and is following up with an infectious disease physician outpatient. Management of osteomyelitis, like in this case, involves long-term antibiotics with the potential need for surgical intervention. There are few reported cases of extrapulmonary Nocardia infections, particularly osteomyelitis, demonstrating the importance of their inclusion in the literature to better serve patients to allow for timely intervention for rare and life-threatening conditions. In immunocompromised hosts, the differential diagnosis should include opportunistic infections and less common pathogens, especially in those with atypical presentations, including gluteal and leg pain.


Lack of significant changes in nutrition-related parameters with tumor necrosis factor treatment of cancer.
Cancer and its therapies frequently produce anorexia and cachexia. In this study, the acute (3 days) and chronic (4 wks) nutrition-related effects of cancer therapy with recombinant human tumor necrosis factor (rHuTNF) were investigated and described. Nutritional status, as measured by body weight and body composition (body fat and lean-to-fat ratio) with use of bioelectrical impedance, did not appear to deteriorate. None of the serum lipids changed significantly, but triglycerides did rise modestly over four weeks of therapy. Glucose and the peptide hormones (insulin, C-peptide, glucagon, and pancreatic polypeptide) thought to affect appetite did not change with rHuTNF therapy. Therefore, although TNF is thought to contribute to wasting in animal models, it had no negative effect on nutritional status in our small sample. The lack of adverse effect noted in this study is possibly due to the low dose level of rHuTNF or to adaptation.


The public health threat of emerging viral disease.
"Emerging diseases" are those that either have newly appeared in the population or are rapidly increasing their incidence or expanding their geographic range. Emerging viruses usually have identifiable sources, often existing viruses of animals or humans that have been given opportunities to infect new host populations ("viral traffic"). Environmental and social changes, frequently the result of human activities, can accelerate viral traffic, with consequent increases in disease emergence. Host factors, including nutrition, have often received less attention in the past but are of considerable importance. These factors, combined with the ongoing evolution of viral and microbial variants, make it likely that emerging infections will continue to appear and probably increase, emphasizing the need for effective surveillance.


How few and far between? Examining the effects of probe rate on self-reported mind wandering.
We examined whether the temporal rate at which thought probes are presented affects the likelihood that people will report periods of mind wandering. To evaluate this possibility, we had participants complete a sustained-attention task (the Metronome Response Task; MRT) during which we intermittently presented thought probes. Critically, we varied the average time between probes (i.e., probe rate) across participants, allowing us to examine the relation between probe rate and mind-wandering rate. We observed a positive relation between these variables, indicating that people are more likely to report mind wandering as the time between probes increases. We discuss the methodological implications of this finding in the context of the mind-wandering literature, and suggest that researchers include a range of probe rates in future work to provide more insight into this methodological issue.


Does this older adult with lower extremity pain have the clinical syndrome of lumbar spinal stenosis?
The clinical syndrome of lumbar spinal stenosis (LSS) is a common diagnosis in older adults presenting with lower extremity pain. To systematically review the accuracy of the clinical examination for the diagnosis of the clinical syndrome of LSS. MEDLINE, EMBASE, and CINAHL searches of articles published from January 1966 to September 2010. Studies were included if they contained adequate data on the accuracy of the history and physical examination for diagnosing the clinical syndrome of LSS, using a reference standard of expert opinion with radiographic or anatomic confirmation. Two authors independently reviewed each study to determine eligibility, extract data, and appraise levels of evidence. Four studies evaluating 741 patients were identified. Among patients with lower extremity pain, the likelihood of the clinical syndrome of LSS was increased for individuals older than 70 years (likelihood ratio [LR], 2.0; 95% confidence interval [CI], 1.6-2.5), and was decreased for those younger than 60 years (LR, 0.40; 95% CI, 0.29-0.57). The most useful symptoms for increasing the likelihood of the clinical syndrome of LSS were having no pain when seated (LR, 7.4; 95% CI, 1.9-30), improvement of symptoms when bending forward (LR, 6.4; 95% CI, 4.1-9.9), the presence of bilateral buttock or leg pain (LR, 6.3; 95% CI, 3.1-13), and neurogenic claudication (LR, 3.7; 95% CI, 2.9-4.8). Absence of neurogenic claudication (LR, 0.23; 95% CI, 0.17-0.31) decreased the likelihood of the diagnosis. A wide-based gait (LR, 13; 95% CI, 1.9-95) and abnormal Romberg test result (LR, 4.2; 95% CI, 1.4-13) increased the likelihood of the clinical syndrome of LSS. A score of 7 or higher on a diagnostic support tool including history and examination findings increased the likelihood of the clinical syndrome of LSS (LR, 3.3; 95% CI, 2.7-4.0), while a score lower than 7 made the diagnosis much less likely (LR, 0.10; 95% CI, 0.06-0.16). The diagnosis of the clinical syndrome of LSS requires the appropriate clinical picture and radiographic findings. Absence of pain when seated and improvement of symptoms when bending forward are the most useful individual findings. Combinations of findings are most useful for identifying patients who are unlikely to have the diagnosis.


Threat and uncertainty in the face of perceptual decision-making in anxiety.
Anxiety is defined as an anticipatory response to uncertain, future threats. It is unknown how anticipatory information regarding uncertainty about upcoming threatening and neutral stimuli impacts attention and perception in anxiety. Individuals with and without anxiety disorders performed two perceptual decision-making tasks in which they used threat or neutral prestimulus cues to discriminate between subsequent threatening and neutral faces. In one task, cues provided no probability information (high uncertainty). In the other, cues indicated a high probability of encountering threatening or neutral faces (low uncertainty). Under high uncertainty only, anxious apprehension was associated with worse discrimination between threatening versus neutral faces after threat cues. Additionally, anxious arousal was associated with worse discrimination after neutral cues in individuals with anxiety disorders. These findings will advance the field by spurring the development of more comprehensive and ecologically valid models in which anticipatory top-down factors influence threat perception in anxiety. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The relationship of approach/avoidance motivation and asymmetric frontal cortical activity: A review of studies manipulating frontal asymmetry.
The balance between activity in the left and right frontal cortex, commonly referred to as asymmetric frontal cortical activity, has served as a proxy for an organism's motivational direction (i.e., approach vs. avoidance). Many studies have examined the influence of the manipulation of motivational direction on asymmetrical frontal cortical activity and found results consistent with the idea that greater relative left (right) frontal cortical activity is associated with approach (avoidance) motivation. We critically review literature employing physical (versus psychological) manipulations of frontal asymmetry using a variety of methodologies including neurofeedback training, muscular contractions, and non-invasive brain stimulation. These reviewed methods allow us to make stronger causal inferences regarding the role of asymmetric frontal cortical activity in approach and avoidance motivation.


Modeling non-hereditary mechanisms of Alzheimer disease during apoptosis in yeast.
Impaired protein degradation and mitochondrial dysfunction are believed to contribute to neurodegenerative disorders, including Alzheimer disease (AD). In patients suffering from non-hereditary AD, UBB+1, the frameshift variant of ubiquitin B, accumulated in neurons affected by neurofibrillary tangles, which is a pathological hallmark. We established a yeast model expressing high levels of UBB+1, and could demonstrate that UBB+1 interfered with both the ubiquitin-proteasome system (UPS) and mitochondrial function. More precisely, UBB+1 promoted the mitochondrion-localized production of the basic amino acids arginine, ornithine, and lysine, which we identified as the decisive toxic event culminating in apoptosis. Inducing the UPS activity at mitochondria prevented the lethal basic amino acid accumulation and avoided UBB+1-triggered cell loss. The arginine/ornithine metabolism is altered in brains of AD patients, and VMS1, the mitochondrion-specific UPS component, co-existed with UBB+1 in neurofibrillary tangles. Therefore, our data suggest that aberrant basic amino acid synthesis is a crucial link between UPS dysfunction and mitochondrial damage during AD progression.


Factors associated with late antenatal care booking: population based observations from the 2007 Zambia demographic and health survey.
In spite of the extreme importance of an early antenatal care visit, more than 50% of Zambian pregnant women book for antenatal care late. We aimed to determine factors associated with late antenatal care booking in Zambia. Data stem from the 2007 Zambia Demographic and Health Survey where information on socio-demographic, social-economic, obstetrical characteristics and timing of the first antenatal visit were extracted on all women aged 15 to 49 years. A weighted survey analysis using STATA version 12 was applied. Firstly, we explored proportions of ANC booking at 0-3 months, 4-5 month and 6-9 months. Secondly, we investigated the association between predictor variables and late antenatal care booking using univariate and multivariate logistic regression. Overall (n= 3979), the proportion of late ANC booking (booking between 4th to 9th month) was 81% disaggregated as 56% and 19% at 4 to 5 months and 6 to 9 months respectively. Women who wanted their last child later were more likely to book late than those with wanted pregnancies then (AOR: 1.35 95% CI 1.10-1.66). Women with higher education were 55% less likely to book for ANC late compared to women with no education (AOR: 0.45 95%CI: 0.27-0.74). Women aged 20-34 years were 30% more likely to book earlier than women younger than 20 years (AOR: 0.69 95% CI 0.50-0.97). We found high proportion of late ANC booking associated with presence of unplanned or unwanted pregnancies in this population. The concentration of this problem in lower or no education groups may be an illustration of existing inequalities which might further explain limitations in health promotion messages meant to mitigate this challenge. There is thus urgent need to re-pack health promotion message to specifically target this and related poor groups.


[Neuroradiological studies in diving accidents].
In case of a type II decompression sickness (with cerebrospinal injury), the decision on how to structure a prompt hyperbaric treatment rests on an anamnesis and the clinical investigation. In looking for an associated contingent barotrauma, one has to be satisfied with an X-ray of thorax and abdomen. The myelopathy which results from a decompression mishap with medullary involvement forms a very peculiar clinical entity defined by a fascicular injury at several levels. For several years now, clinical radiologists resort to a new medical imaging technique: Nuclear Magnetic Resonance (NMR-)Imaging. For the first time, this technique allows the imaging of intramedullary lesions due to a decompression accident. Other neuroradiological investigations (such as myelography, spinal tomodensitometry, medullary angiography, isotopic tests) are without merit for evaluating decompression accidents with medullary involvement. NMR-Imaging has the potential too, of revealing ischemic cerebral injuries, even if the clinical brain impairment is often silent and therefore overlooked. The role of NMR-Imaging for evaluating cerebrospinal aspect of decompression accidents is not yet finalized. However, NMR-Imaging will give without any doubt a boost to the pathophysiological knowledge of decompression mishaps.


Engineering of clinical glioma treatment: prediction of pro-invasive molecular events in treated gliomas.
The diffusely infiltrative nature of malignant gliomas is the main obstacle to successful treatment approaches. Advanced simulation models of the in vivo response to therapy conditions are expected to improve malignant glioma treatment substantially. In parallel experiments, human malignant glioma cells underwent either radiation or chemotherapy treatment (chemotreatment) with temozolomide alone, or combined chemoradiation. Cells were treated according to diverse, clinically relevant, therapeutic algorithms. Quantitative 'real-time' polymerase chain reaction (PCR) measurements were performed for target genes, namely vascular endothelial growth factor, p53, and cyclooxygenase-2, which allow a comparative evaluation of pro-invasive molecular events in treated gliomas. The proof-of-principle study simulated variable intratumoural regional conditions. Pro-invasive molecular patterns were strongly dependent on the treatment algorithm, cellular density, and drug delivery. The highest pro-invasive potential was demonstrated for simulated peripheral regions under continued chemoradiation. This result strongly supports the clinical observations of increased aggressiveness and relatively poor response to second-line therapies in post-operatively chemoradiation-treated malignant gliomas at the time of relapse. Individualized and potentially the most effective treatment algorithms can be designed using established gene expression patterns applied on primary cell cultures obtained from individual patients. Individual drug toxicity and response to anti-cancer therapy can be predicted.


[Do we Isolate Patients or Bugs? Challenging Isolation Precautions].
Isolation of patients with multidrug-resistant organisms (MRGN) has been recommended since years. Recent evidence suggests no benefit by this isolation procedure. Furthermore, isolation precautions may have potential negative effects on patient well-being and may increase therapeutic error.Rather than blocking patients up in a room, implementing and continuous education about standard precautions as hand washing and contact awareness may decrease spread of MRGN and other resistant bacteria. In this context, evidence about mechanism of resistance transfer between bacteria is still expanding. Education about these mechanisms inside and outside the body may help to corroborate the appreciation about implementation of standard precautions. In addition, the awareness of antibiotic stewardship in this context has to be underlined. Prevention of spreading bacteria is not done by isolation in room. In fact, it is a multifactorial continuous cycle of planning, teaching, surveillance and transfer of knowledge. Combination of education, compliance to standard precautions and continuous education may be a big step forward in fighting MRGN transmission and progression.


Hybrid treatment of a huge complex aortic pseudo-aneurysm subsequent to a coarctation.
Endovascular treatment of pseudo-aneurysms subsequent to a pre-existing aortic coarctation is becoming a well-accepted technical solution especially in patients presenting anatomical challenges involving the aortic arch. We report the case of a 65-year-old woman with a huge pseudo-aneurysm of the descending thoracic aorta. Diagnostic imaging assessment documented also the presence of an aneurysmatic aberrant right subclavian artery. Due to patient's anatomical arterial condition, we decided to treat the aneurysm applying a hybrid approach.


Depressive moods and marital happiness: within-person synchrony, moderators, and meaning.
Recent studies using within-persons designs conceptually replicate and substantively extend prior research that has shown marital distress to be a robust risk factor for depression. The present investigation further extends this within-persons research tradition by increasing the frequency of assessments and by adding new moderators and measures in a sample of both newlywed (n = 24) and maritally distressed (n = 31) wives. In both samples, the average within-persons association between 21 daily assessments of wives' depressed mood and marital happiness approximated previous estimates of analogous effects (overall r = -.54). Wives reported worse depressive mood symptoms on days they experienced lower marital happiness, even after accounting for time and between-person variation in marital happiness. Each participant's within-persons mood and marital happiness association was then treated as a dependent variable to be predicted from theoretically relevant individual differences. Multilevel modeling showed that the negative within-person association between daily depressed mood and daily marital happiness was especially strong for women who were relatively high in depressive symptoms, who had avoidant attachment styles, and who were relatively low in marital adjustment.


Molecular genetics of a three-gene cluster in the Amy region of Drosophila.
Analysis of amylase RNA levels in the anterior and posterior midgut regions of flies from the Amy1,6 mapA and c Amy2,3 mapC strains of D. melanogaster, reared on yeast and on yeast supplemented with glucose, indicates that the trans-acting map gene controls the abundance of amylase RNA tissue-specifically, i.e., in the adult posterior midgut. This is consistent with the view that its role in controlling Amy expression is that of a transcription factor. Dietary glucose represses Amy expression in the anterior and posterior midgut regions of adults, reducing the abundance of amylase RNA, which suggests that it also controls Amy transcriptional activity. However, the mechanism for glucose repression appears to act systemically in the midgut, in a manner that is independent of the effects of map on Amy expression. A new glucose repressible TU was identified that is located just proximal to the Amy locus in region 54A of polytene chromosome 2R. It is transcribed in the direction opposite to that of the proximal Amy gene and encodes an RNA about 1500 bases long. Its RNA is expressed in both larvae and adults of the above strains of D. melanogaster, but the nature of the product it encodes is unknown. We speculate that all three genes in the cluster at 54A, namely the two Amy gene copies and the new glucose repressible TU, are coordinately controlled by the same mechanism that regulates Amy gene expression in response to dietary glucose. Somatic transformation experiments suggest that 5' cis-regulatory mechanisms required for the correct spatial expression of the proximal and distal Amylase genes from a Canton-S strain of D. melanogaster, Amy-p1 and Amy-d3, are located within 450 bp and 463 bp of their respective translation start sites. These regions also contain sequences responsive to dietary glucose repression, which is mediated at the DNA level of exogenous Amy genes in somatically transformed larvae reared on a yeast + glucose diet. A positive activator is located in the upstream region of Amy-d3 between the nucleotide pairs at -365 and -252 from the translation start site, but a comparable activator does not appear to exist in the upstream region of Amy-p1. Deletion analysis of the 5' sequence flanking the coding region of Amy-d3 indicates 125 nucleotide pairs of flanking DNA is sufficient for its functional activity. A model is proposed for coordinate control, in part, of the duplicated Amy genes.


Land use regression model for ultrafine particles in Amsterdam.
There are currently no epidemiological studies on health effects of long-term exposure to ultrafine particles (UFP), largely because data on spatial exposure contrasts for UFP is lacking. The objective of this study was to develop a land use regression (LUR) model for UFP in the city of Amsterdam. Total particle number concentrations (PNC), PM10, PM2.5, and its soot content were measured directly outside 50 homes spread over the city of Amsterdam. Each home was measured during one week. Continuous measurements at a central urban background site were used to adjust the average concentration for temporal variation. Predictor variables (traffic, address density, land use) were obtained using geographic information systems. A model including the product of traffic intensity and the inverse distance to the nearest road squared, address density, and location near the port explained 67% of the variability in measured PNC. LUR models for PM2.5, soot, and coarse particles (PM10, PM2.5) explained 57%, 76%, and 37% of the variability in measured concentrations. Predictions from the PNC model correlated highly with predictions from LUR models for PM2.5, soot, and coarse particles. A LUR model for PNC has been developed, with similar validity as previous models for more commonly measured pollutants.


Deep lamellar endothelial keratoplasty in 10 horses.
To describe and evaluate a surgical technique utilized for the therapy of deep corneal stromal abscesses (DSA) in horses. The DSA is excised and replaced with a partial thickness corneal lamellar allograft. A retrospective clinical study describing the indications for the surgical technique utilized and the outcomes of this procedure in 10 eyes of 10 horses. Each affected eye had a discrete DSA within the posterior stroma. An initial partial thickness semicircular corneal incision was made at the limbus, followed by anterior stromal lamellar dissection over the lesion. After excision of the DSA and replacement with a larger diameter split-thickness donor button, the anterior stroma was replaced into its original position and the initial corneal incision was repaired. All of the animals that underwent deep lamellar endothelial keratoplasty (DLEK) procedure healed appropriately and with subjectively less postoperative scarring and complications than previously described surgical approaches to DSA. This procedure is an effective technique for surgical removal of DSA in horses and, in most cases, results in a visual and cosmetically acceptable globe. The advantages of this technique compared to other surgical approaches to DSA are the peripheral location of the incision, shortened anesthesia times, the resultant minimal scarring and shorter healing times associated with DLEK.


Impaired autonomic nervous system activity during sleep in family caregivers of ambulatory dementia patients in Japan.
The number of dementia patients requiring care is rapidly increasing in Japan. Consequently, a large percentage of family members, including spouses and children of those with dementia, are assuming the role of primary caregiver. Many caregivers develop health problems including sleep disorders. Some report poor quality of sleep even when sleep duration is normal. In the present study, we used actigraphy and heart rate variability spectral analysis to assess autonomic nervous system activity and quality of sleep in family caregivers of people with ambulatory dementia. The 20 caregivers who participated in our study exhibited significantly higher levels of sympathetic nervous system activity during sleep than noncaregivers. This abnormal activity was most prominent during the first half of the sleep period and was not related to overall sleep duration. We propose that relaxation is inhibited during the first half of the sleep period in this caregiver population. This may be due to increased stress, as caregivers of people with ambulatory dementia may worry about their patients waking and wandering at night, potentially injuring themselves. Our findings indicate a need for increased support for caregivers of people with dementia, including the assessment and treatment of sleep disorders.


SUS1 introns are required for efficient mRNA nuclear export in yeast.
Efficient coupling between mRNA synthesis and export is essential for gene expression. Sus1/ENY2, a component of the SAGA and TREX-2 complexes, is involved in both transcription and mRNA export. While most yeast genes lack introns, we previously reported that yeast SUS1 bears two. Here we show that this feature is evolutionarily conserved and critical for Sus1 function. We determine that while SUS1 splicing is inefficient, it responds to cellular conditions, and intronic mutations either promoting or blocking splicing lead to defects in mRNA export and cell growth. Consistent with this, we find that an intron-less SUS1 only partially rescues sus1Δ phenotypes. Remarkably, splicing of each SUS1 intron is also affected by the presence of the other and by SUS1 exonic sequences. Moreover, by following SUS1 RNA and protein levels we establish that nonsense-mediated decay (NMD) pathway and the splicing factor Mud2 both play a role in SUS1 expression. Our data (and those of the accompanying work by Hossain et al.) provide evidence of the involvement of splicing, translation, and decay in the regulation of early events in mRNP biogenesis; and imply the additional requirement for a balance in splicing isoforms from a single gene.


Ovarian cysts in young girls with hypothyroidism: follow-up and effect of treatment.
Ovarian cysts have been reported in girls with longstanding uncompensated primary hypothyroidism. Restoration of euthyroid state has been associated with resolution of these cysts; long-term follow-up of these patients is however lacking. We evaluated the outcome in ten girls with ovarian cysts and hypothyroidism managed at our hospital with special emphasis on subsequent pubertal development and ovarian imaging. Patients were diagnosed at the age of 8.6 +/- 2.3 years (mean +/- SD) with severe uncompensated primary hypothyroidism (TSH levels >100 mIU/l in all; 509.3 +/- 651 mIU/l) and growth retardation (height SDS -4.1 +/- 1.8). Nine girls had vaginal bleeding at diagnosis; five also had thelarche. LH and FSH levels were prepubertal in all patients. Ovarian cysts were bilateral in eight girls (80%); internal septation was noted in six. Thyroxine replacement (4.1 +/- 0.7 microg/kg/day) led to normalization of TSH levels with reversal of pubertal changes and regression of ovarian cysts in all patients 2.2 +/- 1.0 months after treatment. At last follow-up 3.5 +/- 2.6 years after initiation of treatment at the age of 12.0 +/- 2.3 years, all patients had normal ovarian size in ultrasound evaluation with six girls progressing to normal puberty. Our study emphasizes the need to exclude hypothyroidism in young girls with ovarian cysts. Identification of hypothyroidism in these girls obviates the need for extensive investigations.


Bixa orellana leaf extract suppresses histamine-induced endothelial hyperpermeability via the PLC-NO-cGMP signaling cascade.
Histamine is established as a potent inflammatory mediator and it is known to increased endothelial permeability by promoting gap formation between endothelial cells. Previous studies have shown that aqueous extract of Bixa orellana leaves (AEBO) exhibits antihistamine activity in vivo, yet the mechanism of its action on endothelial barrier function remains unclear. Therefore, the current study aimed to determine the protective effect of AEBO against histamine-induced hyperpermeability in vitro. The endothelial protective effect of AEBO was assess using an in vitro vascular permeability assay kit. Human umbilical vein endothelial cells (HUVEC) were used in the current study. HUVEC were pre-treated with AEBO for 12 h before histamine induction. Vascular permeability was evaluated by the amount of FITC-dextran leakage into the lower chamber. In order to elucidate the mechanism of action of AEBO, phospholipase C (PLC) activity, intracellular calcium level, nitric oxide (NO) concentration, cyclic guanosine monophosphate (cGMP) production and protein kinase C (PKC) activity were determined following histamine challenge. Histamine-induced increased HUVEC permeability was significantly attenuated by pretreatment with AEBO in a time- and concentration-dependent manner. Upregulation of PLC activity caused by histamine in HUVEC was suppressed by pretreatment with AEBO. Pretreatment with AEBO also blocked the production of intracellular calcium induced by histamine in HUVEC. In addition, AEBO suppressed the NO-cGMP signaling cascade when HUVEC were challenged with histamine. Moreover, PKC activity was significantly abolished by pretreatment with AEBO in HUVEC under histamine condition. In conclusion, the present data suggest that AEBO could suppress histamine-induced increased endothelial permeability and the activity may be closely related with the inhibition of the PLC-NO-cGMP signaling pathway and PKC activity.


Emotional processing in Parkinson's disease and schizophrenia: evidence for response bias deficits in PD.
Deficits in facial emotion recognition in Parkinson's disease (PD) patients has been well documented. Nevertheless, it is still not clear whether facial emotion recognition deficits are secondary to other cognitive impairments. The aim of this study was to answer the question of whether deficits in facial emotion recognition in PD result from impaired sensory processes, or from impaired decision processes. To address this question, we tested the ability to recognize a mixture of basic and complex emotions in 38 non-demented PD patients and 38 healthy controls matched on demographic characteristics. By using a task with an increased level of ambiguity, in conjunction with the signal detection theory, we were able to differentiate between sensitivity and response bias in facial emotion recognition. Sensitivity and response bias for facial emotion recognition were calculated using a d-prime value and a c index respectively. Our study is the first to employ the EIS-F scale for assessing facial emotion recognition among PD patients; to test its validity as an assessment tool, a group comprising schizophrenia patients and healthy controls were also tested. Patients with PD recognized emotions with less accuracy than healthy individuals (d-prime) and used a more liberal response criterion (c index). By contrast, patients with schizophrenia merely showed diminished sensitivity (d-prime). Our results suggest that an impaired ability to recognize facial emotions in PD patients may result from both decreased sensitivity and a significantly more liberal response criteria, whereas facial emotion recognition in schizophrenia may stem from a generalized sensory impairment only.


Myocardial blood flow and metabolism in patients with hypertrophic cardiomyopathy--a study with carbon-11 acetate and positron emission tomography.
The underlying pathophysiology of hypertrophic cardiomyopathy (HCM) is still unclear. positron emission tomography is a suitable and promising technique for the detection of possible metabolic consequences of the disease. To assess regional myocardial blood flow and metabolism, 19 asymptomatic or only mildly symptomatic patients with HCM and 10 normal control subjects were studied using carbon-11 acetate and fluorine-18-labelled deoxyglucose (FDG) as tracers of myocardial blood flow (Ao), oxygen consumption (k), and exogenous glucose utilization. In the patients, regional Ao in the hypertrophied septum and apex (H) was similar to that in the nonhypertrophied free wall (N) (91.3 +/- 3.9% vs 92.9 +/- 3.1%; p = NS). However, the k values were significantly lower in H than in N (0.044 +/- 0.012 vs 0.060 +/- 0.016/min, p < 0.0001). The k value in N and normal control subjects (0.062 +/- 0.013) was similar. Postprandial FDG uptake was lower in H than in N (70 +/- 16 vs 91 +/- 7%; p < 0.0001) in 16 patients and slightly higher in 3 patients. Fasting FDG study showed increased FDG uptake in H in 3 out of 13 patients, suggesting a disorder of the myocardial microvascular circulation. A relative decrease in hypertrophied septal and apical oxidative metabolism and glucose utilization without any corresponding perfusion defect could reflect abnormal regional aerobic metabolism in the disproportionately thickened myocardium in patients with HCM. This suggests that a primary myocardial metabolic defect might be present in patients with HCM.


Aroma composition of shalgam: a traditional Turkish lactic acid fermented beverage.
Shalgam, a traditional red, cloudy and sour soft beverage, is produced by lactic acid fermentation of black carrot, sourdough, salt, bulgur flour, turnip and adequate water. The present study was designed to characterize the volatile compounds of shalgam obtained from different methods. The aroma compounds of shalgams produced by traditional and direct methods, and addition of Lactic acid bateria (LAB) cultures were examined. Volatile components of shalgam samples were extracted by liquid-liquid extraction technique with pentane/dichloromethane and analyzed by gas chromatography-mass spectrometry (GC-MS). Sixty aroma compounds were identified in shalgam samples including 20 terpenes, 9 esters, 9 alcohols, 5 volatile acids, 6 volatile phenols, 5 lactones, 3 naphthalenes, 2 carbonyl compounds and 1 C13-norisoprenoids. It was found that the aroma profiles of shalgams were quite similar. However, the total volatile content of the shalgam samples increased with addition of Lb. plantarum.


Pharmacological management of dermatomyositis.
Dermatomyositis is a rare heterogeneous systemic autoimmune disease with multiple organ involvement which can result in significant disability and mortality. Despite the lack of placebo-controlled trials, glucocorticoids are considered to be the mainstay of initial management. Treatment strategies are mainly based on uncontrolled studies, evidence based guidelines for treatments do not exist. Areas covered: This review provides an overview of the currently available pharmacological treatments in the field of dermatomyositis including conventional immunosuppressants, biologics and topical agents. The role of antibodies in different treatment responses of dermatomyositis related clinicoserological syndromes is also discussed. A PubMed search was performed in order to find relevant literature for this review. Expert commentary: Early recognition and intervention is essential to ameliorate disease outcome. Determination of antibodies provide a useful key in diagnosis, clinical manifestations, malignancy, prognosis, and treatment response and may lead to wider acceptance of personalized medicine. Corticosteroids with adjunctive steroid-sparing immunosuppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. Combinations of second-line therapies or newer third-line therapies are used in severe, refractory, or corticosteroid-dependent diseases. Further research is required to assess the role of new therapies.


Evidence-based nursing-sensitive indicators for patients hospitalized with depression in Thailand.
The aim of this study was to develop and validate nursing-sensitive indicators for patients hospitalized with depression in Thailand. The initial draft, consisting of 12 categories with 37 subcategories, was then evaluated by experts in the US and Thailand. Hospital records were then utilized to evaluate the feasibility and efficacy of the indicators. The finalized instrument consisted of 11 categories with 43 items with a validity of .98 and internal consistency of .88. This is the first set of indicators developed to evaluate nursing-sensitivity for patients hospitalized with a diagnosis of depression in Thailand. Having nursing indicators for depressed patients provides nurses with concrete tools to evaluate their work with depressed patients, allowing these staff to assess their work in a very specific, methodical, and consistent manner. When problems are discovered, both the staff and administration can work to address these issues through training, procedural changes, and departmental shifts.


Controlling the termination and photochemical reactivity of the SrTiO3(110) surface.
SrTiO3(110) orientated crystals have been heated to temperatures between 1000 °C and 1200 °C in air, alone or in the presence of powder reservoirs of TiO2 or Sr3Ti2O7. In these conditions, the surface is terminated by two types of atomically flat terraces. One has a relatively higher surface potential and promotes the photochemical reduction of silver (it is photocathodic) and the other has a relatively lower surface potential and promotes the photochemical oxidation of lead (it is photoanodic). Measurements of the step heights between the terraces indicate that the surfaces with different properties have different terminations. By adjusting the time and temperature of the anneal, and in some cases including reservoirs of TiO2 or Sr3Ti2O7, it is possible to change the surface area fraction from 98% photocathodic to 100% photoanodic. The surface is more photocathodic when the annealing temperature is lower, the duration shorter, and if Sr3Ti2O7 is present. The surface is more photoanodic if the temperature is higher, the annealing duration longer, and if TiO2 is present. The results make it possible to control the surface potential and the ratio of photocathodic to photoanodic area on the SrTiO3(110) surface.


[The influence of training on rehabilitation and keep-fit tables on the chosen parameters of body weight].
More and more people in the world contend with overweight or obesity, and this phenomenon at the moment is being recognized as one of the most important problems of modern civilization observed in many developed countries. Change of the lifestyle connected with turning from the active life to the more sedentary one and bad eating habits led to the development of overweight and obesity at an alarmingly fast rate with the parallel development of interests directed on conducting the research and looking for the effective methods of fighting against the overweight and obesity. The aim of the study was to evaluate some parameters of body weight among people being put on the healthy training on the rehabilitation and keep-fit tables Slender-Life. A group of 50 patients treated in sanatorium were included into the observation. Double measurement of body weight and thickness of the skin and fat were performed during the first and last days of the fifteen day training on the formerly mentioned tables. The statistically important decrease of examined parameters including the real body weight, fat mass, the BMI indication and the thickness of the skin and fat folds was detected. The healthy training on the rehabilitation and keep-fit tables Slender-Life causes the increase of the body fat-free weight. The positive acceptation of the rehabilitation on tables Slender-Life proves it should be applied.


[The approach to bone and joint disease for extending the healthy life expectancy].
In Japan, the super-aged society, the difference between the healthy life expectancy and life expectancy is large, it has become a social problem. For the extension of healthy life expectancy, measures to bone and joint disease are important. Lower limb muscle strengthening is useful to decrease in pain and improvement of walking ability. Further, in order to maintain a balance function, improvement in range of motion is important. On the other hand, for patients who had joint destruction, decreased ability of exercise, muscle weakness, balance dysfunction has already occurred, it is necessary for extension of healthy life expectancy including surgical treatment. We believe that by performing the appropriate therapeutic intervention, extending healthy life expectancy would be possible.


Combined neurodevelopmental exposure to deltamethrin and corticosterone is associated with Nr3c1 hypermethylation in the midbrain of male mice.
Attention-Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders and manifests inattention, hyperactivity, and impulsivity symptoms in childhood that can last throughout life. Genetic and environmental studies implicate the dopamine system in ADHD pathogenesis. Work from our group and that of others indicates that deltamethrin insecticide and stress exposure during neurodevelopment leads to alterations in dopamine function, and we hypothesized that exposure to both of these factors together would lead to synergistic effects on DNA methylation of key genes within the midbrain, a highly dopaminergic region, that could contribute to these findings. Through targeted next-generation sequencing of a panel of cortisol and dopamine pathway genes, we observed hypermethylation of the glucocorticoid receptor gene, Nr3c1, in the midbrain of C57/BL6N males in response to dual deltamethrin and corticosterone exposures during development. This is the first description of DNA methylation studies of Nr3c1 and key dopaminergic genes within the midbrain in response to a pyrethroid insecticide, corticosterone, and these two exposures together. Our results provide possible connections between environmental exposures that impact the dopamine system and the hypothalamic-pituitary-adrenal axis via changes in DNA methylation and provides new information about the presence of epigenetic effects in adulthood after exposure during neurodevelopment.


[Yeast mitochondrial transfer RNA. Structure, coding properties and genome organization].
The up-to-date data on mitochondrial tRNAs of yeast, their structures and peculiarities of these structures, anomalies of the mitochondrial genetic code and anticodons of tRNAs, the structure and number of tRNA genes are reviewed in the present paper. New information concerning 17 types of yeast mitochondrial tRNAs, deciphered by the authors of the paper are given; among them 8 types are first published. The likeness and differences of yeast mitochondrial tRNAs from their cytoplasmic counterparts are discussed by comparison with other organisms.


Effect of dietary supplementation with fructo-oligosaccharides on fecal flora of healthy cats.
To investigate changes in the fecal flora of healthy cats after dietary supplementation with fructo-oligosaccharides (FOS). 12 healthy, barrier-maintained, specific-pathogen-free-derived adult cats. Fresh fecal samples for quantitative and qualitative bacteriologic examination were collected from each cat after ingestion of a replete dry (basal) diet for a minimum of 8 weeks. The diet was then supplemented with 0.75% FOS, and another fecal sample was collected after 12 weeks. Mean +/- SD fecal aerobic, anaerobic, and total bacterial counts (log10 colony-forming units per gram of feces [CFU/g]) did not differ significantly between diets (8.3 +/- 0.8, 9.2 +/- 0.6, 9.4 +/- 0.4, respectively, for the basal diet; and 8.4 +/- 0.8, 9.7 +/- 0.7, and 9.8 +/- 0.7, respectively, for the FOS diet), although there was a trend for higher numbers of anaerobes and total bacteria associated with the FOS diet. Members of the genus Bacteroides, Clostridium perfringens, Escherichia coli, lactobacilli, and Plesiomonas shigeloides were the most prevalent bacteria isolated. Compared with samples from cats fed basal diet, there was a trend for increased mean counts of lactobacilli (P = 0.02) and Bacteroides spp (P = 0.05) after FOS supplementation, and a trend for decreased mean numbers of Escherichia coli (P = 0.03) and Clostridium perfringens (P = 0.08) to be associated with the FOS diet. Supplementation of FOS resulted in a median 164-fold increase in numbers of lactobacilli, 13.2-fold increase in Bacteroides spp, 98% reduction in numbers of C perfringens, and 75% reduction in numbers of E coli. Supplementation of the diet with FOS resulted in alteration of the fecal flora of cats.


Randomised clinical trial on the effect of the Dutch obstetric peer review system.
The project "Obstetric Peer Review Interventions" (Verloskundige Onderlinge Kwaliteitsspiegeling Interventies, VOKSINT) was set-up in The Netherlands in 1994. It provided annual comparison data (quality ranking, league tables) for secondary care obstetric departments adjusted for population differences, based on the data registered in the Perinatal Database of The Netherlands (Landelijke Verloskunde Registratie, LVR). The aim of the so-called VOKS reports was to influence obstetricians' interventions in such a way that they led to a more homogeneous policy. To assess this influence, a trial was set-up, with departments randomly assigned to be or not to be informed about the VOKS results. Obstetric intervention rates and the morbidity of newborns including neonatal neurological examinations (NNEs) were assessed. Obstetric intervention rates were similar in the report group and the control group. Practice in the report group became more homogeneous (adjusted for population differences) than in the control departments, but this was only statistically significant for term caesarean section.


Impact of inhomogeneous static magnetic field (31.7-232.0 mT) exposure on human neuroblastoma SH-SY5Y cells during cisplatin administration.
Beneficial or adverse effects of Static Magnetic Fields (SMFs) are a large concern for the scientific community. In particular, the effect of SMF exposure during anticancer therapies still needs to be fully elucidated. Here, we evaluate the effects of SMF at induction levels that cisPt-treated cancer patients experience during the imaging process conducted in Low field (200-500 mT), Open field (300-700 mT) and/or inhomogeneous High field (1.5-3 T) Magnetic Resonance Imaging (MRI) machines. Human adrenergic neuroblastoma SH-SY5Y cells treated with 0.1 µM cisPt (i.e. the lowest concentration capable of inducing apoptosis) were exposed to SMF and their response was studied in vitro. Exposure of 0.1 µM cisPt-treated cells to SMF for 2 h decreased cell viability (30%) and caused overexpression of the apoptosis-related cleaved caspase-3 protein (46%). Furthermore, increase in ROS (Reactive Oxygen Species) production (23%) and reduction in the number of mitochondria vs controls were seen. The sole exposure of SMF for up to 24 h had no effect on cell viability but increased ROS production and modified cellular shape. On the other hand, the toxicity of cisPt was significantly prevented during 24 h exposure to SMF as shown by the levels of cell viability, cleaved caspase-3 and ROS production. In conclusion, due to the cytoprotective effect of 31.7-232.0 mT SMF on low-cisPt-concentration-treated SH-SY5Y cells, our data suggest that exposure to various sources of SMF in cancer patients under a cisPt regimen should be strictly controlled.


Accessory nerve injury.
A series of 13 patients with an injury of the accessory nerve in the posterior cervical triangle is reported. In 11 patients the nerve was damaged during a lymph node biopsy and in two cases there was a sharp glass injury. Paralysis of the trapezius muscle occurred with resulting deformity and loss of function of the shoulder. Nine patients were operated on. In five cases neurolysis, in two cases neurorrhaphy and in two cases reconstruction with a sural nerve graft were performed 3-17 months after the injury. The result was good or fair in six operative cases. Five of these were neurolyses. In one instance good and in three cases fair recovery was achieved without operation. All but one of the patients were able to return to their former employment. The mean follow-up time was 20 months.


Omental transposition for Alzheimer 's disease.
A patient with Alzheimer's disease of long standing was treated with omental transposition to his brain. The rational for the procedure was to use the omentum to increase cerebral blood flow and to augment cholinergic neurotransmission activity. The patient improved for a year following surgery but after that time slowly began to decline neurologically and cognitively. However, according to Alzheimer's specialists who have followed the patient pre and postoperatively, he still maintains, 2.5 years after surgery, a higher level of performance than expected. There is theoretical and now a clinical suggestion that the omentum might play some role in the treatment of Alzheimer's disease. In view of the devastating nature of the disease, it seems reasonable to suggest that a limited controlled study be carried out to support or negate the benefit of the operation.


Tissues of the Laron dwarf are sensitive to insulin-like growth factor I but not to growth hormone.
Tissues from patients with Laron dwarfism are resistant to the actions of endogenous or exogenous GH. As a result, insulin-like growth factor I (IGF-I) levels are low, possibly contributing to the severe growth deficiency that occurs in patients with this syndrome. In this study, we found that erythroid progenitor cells and permanently transformed T-cell lines from two patients with Laron dwarfism responded in vitro to added IGF-I in concentrations ranging between 1-10 ng/mL despite no stimulatory response to added GH in concentrations of up to 500 ng/mL. Normal or near-normal responsiveness to insulin was also demonstrated. The persistence of GH resistance in the cultured T-cell lines confirms the primary genetic nature of the defect in Laron dwarfism. The preservation of in vitro growth responsiveness to IGF-I in hematopoietic tissue from the Laron dwarfs suggests that affected individuals are sensitive to this factor and may respond to it in vivo.


Monomeric Camelus dromedarius GSTM1 at low pH is structurally more thermostable than its native dimeric form.
Glutathione S‒transferases (GSTs) are multifunctional enzymes that play an important role in detoxification, cellular signalling, and the stress response. Camelus dromedarius is well-adapted to survive in extreme desert climate and it has GSTs, for which limited information is available. This study investigated the structure-function and thermodynamic properties of a mu-class camel GST (CdGSTM1) at different pH. Recombinant CdGSTM1 (25.7 kDa) was expressed in E. coli and purified to homogeneity. Dimeric CdGSTM1 dissociated into stable but inactive monomeric subunits at low pH. Conformational and thermodynamic changes during the thermal unfolding pathway of dimeric and monomeric CdGSTM1 were characterised via a thermal shift assay and dynamic multimode spectroscopy (DMS). The thermal shift assay based on intrinsic tryptophan fluorescence revealed that CdGSTM1 underwent a two-state unfolding pathway at pH 1.0-10.0. Its Tm value varied with varying pH. Another orthogonal technique based on far-UV CD also exhibited two-state unfolding in the dimeric and monomeric states. Generally, proteins tend to lose structural integrity and stability at low pH; however, monomeric CdGSTM1 at pH 2.0 was thermally more stable and unfolded with lower van't Hoff enthalpy. The present findings provide essential information regarding the structural, functional, and thermodynamic properties of CdGSTM1 at pH 1.0-10.0.


Modeling and Analysis of Data-Driven Systems through Computational Neuroscience Wavelet-Deep Optimized Model for Nonlinear Multicomponent Data Forecasting.
Complex time series data exists widely in actual systems, and its forecasting has great practical significance. Simultaneously, the classical linear model cannot obtain satisfactory performance due to nonlinearity and multicomponent characteristics. Based on the data-driven mechanism, this paper proposes a deep learning method coupled with Bayesian optimization based on wavelet decomposition to model the time series data and forecasting its trend. Firstly, the data is decomposed by wavelet transform to reduce the complexity of the time series data. The Gated Recurrent Unit (GRU) network is trained as a submodel for each decomposition component. The hyperparameters of wavelet decomposition and each submodel are optimized with Bayesian sequence model-based optimization (SMBO) to develop the modeling accuracy. Finally, the results of all submodels are added to obtain forecasting results. The PM2.5 data collected by the US Air Quality Monitoring Station is used for experiments. By comparing with other networks, it can be found that the proposed method outperforms well in the multisteps forecasting task for the complex time series.


The effects of epilepsy surgery on the sensorimotor function of children.
The motor and sensory functions of 50 children were investigated before and six months after epilepsy surgery; 34 infants were assessed 24 months after surgery. Postoperatively, 20 children were seizure-free and 22 had a significant reduction of seizures. Epilepsy surgery was found to be an effective mode of treatment for intractable seizures in childhood, even in multiply handicapped individuals. Motor and sensory functions did not deteriorate after surgery; in fact, significant improvements were found in more than half of the children, including those with multiple handicaps. Improvements were most obvious in the seizure-free group, but were also noted in those with reduced seizure frequency. The younger children benefited more from surgery as regards sensorimotor function than did older children and adolescents.


How does overcoordination create ion selectivity?
Some biological molecules can distinguish between ions of similar nature, which may be achieved by enforcing specific coordination numbers on ions in the binding site. It is suggested that when this number is favourable for one ion type, but too large for another, this creates ion selectivity through the proposed mechanism of 'overcoordination'. Much debate has occurred about the role overcoordination plays, and suggestions made as to how molecules can enforce particular coordination numbers, but there has not been an examination of the microscopic underpinning of ion selectivity by overcoordination. Here we use molecular-dynamics to systematically investigate how the number of ligands affects the ion-ligand and ligand-ligand interaction energies, and thus the thermodynamic ion selectivity, of a combination of model systems: three ions (Li(+)/Na(+)/K(+)) with three different ligands (water/formaldehyde/formamide). We find that the ligand-ligand repulsion controls the changes in geometry of each system with changing ligand number. Ion selectivity by overcoordination is achieved as smaller ions exhibit anomalous geometrical changes with the addition of extra ligands, whilst larger ions do not.


Folic acid binding by human plasma albumin.
Binding of [3H]folate to pure human plasma albumin was studied by Sephadex G-200 gel filtration in a steady-state system. The experiments showed the presence of two binding sites per molecule of albumin and an equilibrium constant of 0.9x10(3) 1/mol. With normal human plasma, only albumin bound exogenous [3H]folate with nearly the same equilibrium constant. In human blood plasma at concentrations of less than 10(-5) mol/1, 50% of folate was free, and 50% was bound to albumin. Binding was maximal at about pH 6 and negligible above pH 8 and below pH 4.5. Neither human transferrin nor Cohn fraction II was able to bind [3H]folate.


Sinapic acid attenuates kainic acid-induced hippocampal neuronal damage in mice.
Excitotoxin induces neurodegeneration via glutamatergic activation or oxidative stress, which means that the blockade of glutamate receptors and the scavenging of free radicals are potential therapeutic targets in neurodegenerative diseases. Sinapic acid (SA) has a GABA(A) receptor agonistic property and free radical scavenging activity. We investigated the neuroprotective effects of SA on kainic acid (KA)-induced hippocampal brain damage in mice. SA (10 mg/kg) by oral administration has an anticonvulsant effect on KA-induced seizure-like behavior. Moreover, SA (10 mg/kg) significantly attenuated KA-induced neuronal cell death in the CA1 and CA3 hippocampal regions when administered as late as 6 h after KA. In addition, flumazenil, a GABA(A) antagonist, blocked the effect of SA administered immediately after KA but not the effect of SA administered 6 h after KA. This late protective effect of SA was accompanied by reduced levels of reactive gliosis, inducible nitric oxide synthase expression, and nitrotyrosine formation in the hippocampus. In the passive avoidance task, KA-induced memory impairments were ameliorated by SA. These results suggest that the potential therapeutic effect of SA is due to its attenuation of KA-induced neuronal damage in the brain via its anti-convulsive activity through GABA(A) receptor activation and radical scavenging activity.


Complete recovery following hyperbaric oxygen therapy in idiopathic sudden sensorineural hearing loss--a report of two cases.
Idiopathic sudden sensorineural hearing loss (ISSHL), a common otologic emergency, presents mostly as an abrupt onset unilateral hearing loss, aural fullness, often with vertigo and tinnitus, usually upon awakening in the morning. Its etiopathogenesis is multifactorial, so a number of different therapeutic regimens are in practice, hyperbaric oxygen (HBO2) therapy being an effective yet underutilized one. Not all cases recover completely even after treatment. Here we describe two cases of ISSHL, diagnosed on the basis of clinical examination and pure-tone audiometry, who had a complete recovery following administration of HBO2 therapy in addition to medical treatment. These cases are reported to highlight the effectiveness of this modality in a physician's armamentarium.


Psychiatry and the need for mental health care in Australia: findings from the National Survey of Mental Health and Wellbeing.
This paper describes the pattern of consultations reported with psychiatrists and primary mental health care providers in the Australian adult population. It explores whether inequalities found in utilization of psychiatric services according to area are different in degree from inequalities in utilization of medical and surgical specialists,and describes the meeting of perceived needs for mental health care within those seen by psychiatrists. The National Survey of Mental Health and Wellbeing (NSMHW) was a community survey employing clustered probability sampling, with a computerized field questionnaire which included sections of the composite international diagnostic interview (CIDI), as well as self-reported service utilization and perceived needs for care. By survey estimates, 1.8% of the Australian population consulted a psychiatrist in the last year. Among people with an ICD 10-diagnosed mental disorder, 7.3% consulted a psychiatrist. Only about one in five people seen by a psychiatrist report the psychiatrist as the only mental health care provider. Disadvantaged areas of the cities and remote areas, when compared with the least deprived areas of the cities, showed lower rates of utilization. This effect is stronger in psychiatry than in other specialties. Patients seeing psychiatrists seem to be a more satisfied group than those seeing only other providers; nonetheless, some needs are not well met, and the role of the psychiatrist cannot be isolated as the cause of this satisfaction. Most care delivered by psychiatrists is de facto shared care. Psychiatrists as clinical professionals need to be continually mindful of the need to communicate with others providing care. Psychiatric services in Australia are not delivered in an equitable manner,and the inequalities are greater for psychiatric services than for other medical specialties.


Interaction of GM2 activator protein with glycosphingolipids.
GM2 activator protein is a protein cofactor that stimulates the hydrolysis of the GalNAc and the NeuAc in GM2 by beta-hexosaminidase A and sialidase, respectively. To understand the mechanism of action of GM2 activator, the interaction of this protein with GM2 and/or beta-hexosaminidase A has been the subject of interest since the purified GM2 activator became available. Numerous techniques including ultracentrifugation, isoelectric a focusing, polyacrylamide gel electrophoresis, gel filtration, thin layer chromatogram overlay, and fluorescence dequenching assay have been used to investigate the binding and the affinity of GM2 activator to various glycosphingolipids. It has been generally accepted that GM2 activator must have a very weak binding with the enzyme, because they can be easily separated from each other by gel filtration. Therefore, the interaction of GM2 and GM2 activator has been the focus for most of he study. Although preferential association of GM2 activator with GM2 was detected by some methods, GM2 activator was found also to bind other glycosphingolipids. Isolation of the specific complex that consists of only GM2 activator and GM2 from incubation mixture containing the activator protein and mixed glycosphingolipids has not been successfully carried out. Ultracentrifugation and gel-filtration are the mildest methods for the isolation of the complexes. However, these methods do not separate the complexes formed by specific interaction from that formed by non-specific association. In fluorescence dequenching assay, the attempt to isolate the complex of R18 lipid probe with GM2 activator was also not successful. Since GM2 activator and glycosphingolipids contain hydrophobic domains in their molecules, the non-specific hydrophobic interactions between the two components can greatly interfere with the isolation of true functional complexes. Among the reported methods, thin layer chromatography overlay and the assay based on the inhibition of fluorescence dequenching by various glycosphingolipids are more informative than the others on the binding between GM2 activator and the carbohydrate head groups of glycosphingolipids.


Epithelialization of the corneal endothelium in posterior polymorphous dystrophy.
The unusual cell type present on the posterior corneal surface of posterior polymorphous dystrophy patients has been characterized. In addition to microvilli and desmosomes, these cells contain abundant 10 nm filaments which by immunofluorescent staining were shown to consist of keratin proteins, a marker for epithelial cells.


Domestic laundry and microfiber pollution: Exploring fiber shedding from consumer apparel textiles.
Synthetic fibers are increasingly seen to dominate microplastic pollution profiles in aquatic environments, with evidence pointing to textiles as a potentially important source. However, the loss of microfibers from textiles during laundry is poorly understood. We evaluated microfiber release from a variety of synthetic and natural consumer apparel textile samples (n = 37), with different material types, constructions, and treatments during five consecutive domestic laundry cycles. Microfiber loss ranged from 9.6 mg to 1,240 mg kg-1 of textile per wash, or an estimated 8,809 to > 6,877,000 microfibers. Mechanically-treated polyester samples, dominated by fleeces and jerseys, released six times more microfibers (161 ± 173 mg kg-1 per wash) than did nylon samples with woven construction and filamentous yarns (27 ± 14 mg kg-1 per wash). Fiber shedding was positively correlated with fabric thickness for nylon and polyester. Interestingly, cotton and wool textiles also shed large amounts of microfibers (165 ± 44 mg kg-1 per wash). The similarity between the average width of textile fibers here (12.4 ± 4.5 μm) and those found in ocean samples provides support for the notion that home laundry is an important source of microfiber pollution. Evaluation of two marketed laundry lint traps provided insight into intervention options for the home, with retention of up to 90% for polyester fibers and 46% for nylon fibers. Our observation of a > 850-fold difference in the number of microfibers lost between low and high shedding textiles illustrates the strong potential for intervention, including more sustainable clothing design.


Pyridine-2,6-dicarboxaldehyde bis[(diphenylmethylidene)hydrazone].
The title compound, C(33)H(25)N(5), belongs to the family of pyridine-2,6-dicarboxaldehyde Schiff bases which possess a terdentate coordinating site (-N=C-C=N-C-C=N-) similar to terpyridine derivatives. The dihedral angles between pairs of terminal rings are 69.67 (9) and 66.23 (9)°. The shortest distance between the centroids of aromatic rings in neighbouring mol-ecules is 3.8080 (14) Å.


[Elucidating the molecular mechanism of prostate cancer progression under chronic hypoxia and development of the novel therapeutic approach].
Cancer cells encounter a hypoxic microenvironment during tumor growth and progression. In addition, androgen-deprivation therapy against prostate cancer can develop secondary to a hypoxic condition caused by drastic blood supply reduction because androgen drives angiogenic inducers including vascular endothelial growth factor (VEGF) and inhibits angiogenesis inhibitor prostatic pigment epithelium-derived factor (PEDF). Extreme hypoxic conditions are not suitable for cancer survival, however, cancer cells soon adapt to a hypoxic environment and survive. We established a prostate cancer cell line cultured under chronic hypoxia and analyzed a castration-resistant phenotype. Here, the Vav3 was identified as a key oncogenic molecule associated with castration-resistance under chronic hypoxia. We analyzed the functions of Vav3 and Vav3-mediated signaling to establish a novel therapeutic target for castration-resistant prostate cancer.


[Problems in quality standard research of new traditional Chinese medicine compound].
The new traditional Chinese medicine compound is the main part of the research of new drug of traditional Chinese medicine (TCM), and the new Chinese herbal compound reflects the characteristics of TCM theory. The new traditional Chinese medicine compound quality standard research is one of the main content of pharmaceutical research, and is also the focus of the new medicine pharmaceutical evaluation content. Although in recent years the research level of new traditional Chinese medicine compound has been greatly improved, but the author during the review found still some common problems existing in new traditional Chinese medicine compound quality standard research data, this paper analyzed the current quality standards for new traditional Chinese medicine compound and the problems existing in the research data, respectively from measurement of the content of index selection, determine the scope of the content, and the quality standard design concept, the paper expounds developers need to concern. The quality of new traditional Chinese medicine compound quality standard is not only itself can be solved, but quality standards is to ensure the key and important content of product quality, improving the quality of products cannot do without quality standards. With the development of science and technology, on the basis of quality by design under the guidance of the concept, new traditional Chinese medicine compound quality standard system will be more scientific, systematic and perfect.


Survey on prevalence of lower urinary tract symptoms in an Asian population.
Lower urinary tract symptoms (LUTS) have a strong effect on socio-economic and individual quality of life. The aim of the present study was to investigate the prevalence of LUTS in an Asian population. A telephone survey of individuals aged ≥40 years and of Chinese ethnicity was conducted. The survey included basic demographics, medical and health history, drinking habits, International Prostate Symptom Score, overactive bladder symptom score, Patient Health Questionnaire (PHQ-9) score, and Short Form (SF)-12v2 score. From March to May 2017, 18 881 calls were made, of which 1543 fulfilled the inclusion criteria. In the end, 1000 successful respondents were recruited (302 men and 698 women). Age-adjusted prevalence of overactive bladder syndrome was 15.1%. The older the respondent, the more prevalent the storage symptoms and voiding symptoms (storage symptoms: r=0.434, P<0.001; voiding symptom: r=0.190, P<0.001). Presence of hypertension and diabetes were found to be significantly and positively correlated with storage and voiding symptoms. Storage and voiding symptoms were found to affect PHQ-9 scores (storage symptoms: r=0.257, P<0.001; voiding symptoms: r=0.275, P<0.001) and SF-12v2 scores (storage symptoms: r=0.467, P<0.001; voiding symptoms: r=0.335; P<0.001). Nocturia was the most prominent symptom among patients who sought medical help for their LUTS. Lower urinary tract symptoms are common in Asian populations. Both storage and voiding symptoms have a negative impact on mental health and general well-being of individuals.


Tuberous sclerosis complex with autosomal dominant polycystic kidney disease: a rare duo.
Tuberous sclerosis complex (TSC) is an autosomal dominant condition characterised by the presence of multiple hamartomas in various organ systems in the body. The kidneys are affected in 80% of patients, usually in the form of renal angiomyolipomas, renal cysts or renal cell carcinoma. Although extremely rare, TSC and autosomal dominant polycystic kidney disease (ADPKD) can co-exist in the same patient as a result of concurrent deletion of both polycystic kidney disease (PKD) 1 and TSC2 genes present on the chromosome 16p13.3. These patients develop end-stage renal disease at an earlier age and have an increased risk of malignancy. We present a case of a 30-year-old man with a history of tuberous sclerosis, presenting with loin pain and subsequently diagnosed to have ADPKD.


Pineal tumors: experience with 48 cases over 10 years.
The authors retrospectively reviewed 48 patients treated at Seoul National University Hospital (SNUH) between 1986 and 1995. There were 35 children and 13 adults, accounting for 10.1% of 345 pediatric and 0.68% of 1914 adult brain tumors in SNUH during the same period. The 48 cases consisted of 33 cases of germ cell tumor (69%, GCT); 6 of pineoblastoma (PB, 12.5%); 3 of pineocytoma (PC, 6.3%); 3 of anaplastic astrocytoma (6.3%); 1 of astrocytoma; 1 of glioblastoma; and 1 of ependymoma. The median age was 13 years (range 1-59) and the male-to-female ratio was 3.36:1. The most frequent presenting symptom was due to increased intracranial pressure (90%), followed by Parinaud syndrome or diplopia (50%). Patients with a benign tumor, such as teratoma (TE), astrocytoma, or ependymoma, underwent surgery by the occipital transtentorial approach (OTT) for attempted radical resection without adjuvant therapy, while patients with immature teratoma (imTE), PC, and anaplastic astrocytoma underwent regional radiotherapy (RT) after debulking via OTT. Seven patients with nongerminomatous malignant GCT (NG-MGCT) and 3 with germinoma (GE) underwent craniospinal radiation only, 6 with GE, a NG-MGCT, and 2 with GE+TE received craniospinal radiotherapy (CSRT) after debulking via OTT. Three patients with GE, 4 with NG-MGCT, and 3 with PB underwent radiochemotherapy after debulking via OTT. Forty-four patients were followed up after treatment. The median follow-up period was 36 months. All patients with GE were alive after RT at 36 months (median) of follow-up (range 7-70 months). All with GE+TE and TE were alive. Three patients with PC or astrocytoma were also alive with stable or no evidence of disease. In 1 of the 3 cases of imTE there was a recurrence. However, 4 patients with NG-MGCT died, all of whom had undergone CSRT only; 2 PB patients were alive (12, 19 months), 1 in a moribund status (36 months), and 2 were dead (6, 60 months). The overall mean survival time with pineal tumors was 66 months and the 3-year survival rate was 84% with minimal posttreatment complications. It is concluded that pineal region tumors have male and childhood predominances, and the most common tumor is GCT. The majority of pineal region tumors are malignant. Pineal region tumors can be approached safely and effectively and the surgical complications are mostly transient. Their prognosis is dependent on the pathologies and treatment modalities.


Expression of differentiated function by hepatocytes in primary culture: variable effects of glucagon and insulin on gluconeogenesis during cell growth.
Hormonal effects on gluconeogenesis from lactate were studied during the growth cycle of adult rat parenchyma liver cells using a primary monolayer culture system previously described [25]. Basal and glucagon-stimulated gluconeogenic ability were found to decline rapidly during log phase, insulin-stimulated growth. A progressive recovery of gluconeogenesis activity was observed after cell division subsided. Rates of lactate-gluconeogenesis were found also to decline in the absence of prior insulin exposure. This decline was not as rapid as the loss observed in cells cultured with insulin. However, in insulin-deficient cultures gluconeogenesis was completely abolished after 12 days and did not reelevate with further incubation unless cells were washed and exposed to glucagon. Decreasing growth rates of insulin-supplemented cultures by decreasing serum concentrations resulted in comparatively higher gluconeogenic activity. The results presented here are consistent with previous observations of hepatic parenchymal expression of 'differentiated function' during cellular growth phases in culture (i.e., differentiated functions are generally lost during rapid growth and regained as cells become quiescent). The present study, however, presents unexpected effects of insulin on the apparent growth-state dependent gluconeogenic recovery. Our data imply that although insulin has long been known to inhibit gluconeogenesis, its presence in culture may facilitate long-term basal maintenance of gluconeogenic enzyme activity. Insulin also functions as a growth factor whose initial mitogenic effect correlates with decreased gluconeogenic function. These changes show no simple or predictive correlation with cyclic nucleotide metabolism.


Detection of Schistosoma japonicum antigen (Sj31/32) in sera of Chinese patients using a sandwich ELISA based on monoclonal antibody.
A sandwich-ELISA was developed using IgG from rabbits infected with Schistosoma japonicum as capture antibody and a monoclonal antibody as detecting reagent for circulating Sj 31/32 in patient sera. The assay detected circulating antigen in 36 of 53 sera from Chinese schistosomiasis japonica patients, but not in sera from healthy persons or patients with paragonimiasis, trichinosis or cysticercosis. This is the first demonstration that Sj 31/32 proteins may be used for circulating antigen-based serodiagnosis of schistosomiasis.


Enhancement of molecular ions in mass spectrometry using an ultrashort optical pulse in multiphoton ionization.
The spectral domain of an ultraviolet femtosecond laser was expanded by stimulated Raman scattering/four-wave Raman mixing, and the resulting laser pulse was compressed using a pair of gratings. The pulse width was then measured using an autocorrelator comprised of a Michelson interferometer equipped with a multiphoton ionization/mass spectrometer which was used as a two-photon detector. A gas chromatograph/mass spectrometer was employed to analyze triacetone triperoxide (TATP), and the molecular ion induced by multiphoton ionization was substantially enhanced by decreasing the laser pulse width.


A case of amiodarone-induced thyrotoxicosis successfully treated with prednisolone.
We describe a patient who was treated with amiodarone for ventricular arrhythmia based on arrhythmogenic right ventricular dysplasia and who subsequently developed severe amiodarone-induced thyrotoxicosis. Discontinuation of amiodarone resulted in sustained ventricular tachycardia, which was successfully treated with a DC electrical shock, and subsequently atrial fibrillation, leading to brain embolism due to occlusion of the left middle cerebral artery. Combination treatment with amiodarone and prednisolone was effective both in reducing the serum concentration of thyroid hormones and in improving the patient's general condition. As the use of amiodarone becomes more widespread, treatment with prednisolone for this kind of thyrotoxicosis, which is resistant to conventional treatment, will be required increasingly frequently because iodine overload of the thyroid gland persists for some time after discontinuation of amiodarone treatment.


Vesicular stomatitis virus in Drosophila melanogaster cells: lack of leader RNA transport into the nuclei and frequent abortion of the replication step.
In cultured Drosophila melanogaster cells, vesicular stomatitis virus (VSV) establishes a persistent, noncytopathic infection. No inhibition of host macromolecular synthesis occurs. We studied the synthesis of VSV plus-strand leader RNA, which may be directly involved in vertebrate host synthesis shut-off. Leader RNA accumulated in Drosophila cell cytoplasm, but in low amounts, it was either free or associated to structures larger than the leader RNA-N protein complexes found in vertebrate cells. Only a few leader RNA copies migrated into the cell nucleus; no increase of this transport was observed at any time during the virus cycle. Viral RNAs complementary to the 3' end of the genome and ranging in size from the leader to several hundred nucleotides were found to accumulate in Drosophila cell cytoplasm. Their synthesis was inhibited in the presence of cycloheximide, which blocks all protein synthesis and VSV replication. Correlation between the absence of VSV cytopathogenicity in Drosophila cells and the lack of leader RNA transport into their nuclei is discussed, as well as the possible relationship between the restriction of viral synthesis and the frequent initiation of an abortive replication step.


Multidisciplinary treatment of colorectal cancer in New Zealand: survival rates from 1997-2002.
The surgical and oncological treatment of colorectal cancer has undergone steady evolution over the last 20 years, however nationally derived survival figures have been disappointingly slow to improve. This study is an analysis of prospectively collected data (taken over a 6-year period) on the outcome of colorectal cancer management from a single university surgical unit in New Zealand. A comprehensive dataset was prospectively collected on all patients seen with colorectal cancer by a single surgical team, and complete follow-up was obtained. Details of surgical and oncology treatment of the primary lesion and of any subsequent disease and treatment were recorded. Survival was analysed by clinical and pathological variables. Over 6 years, 244 new patients with a total of 263 primary colorectal cancers were seen.; 97% of these patients had an operation and 95% had the primary tumour resected. The mortality after elective operation was 0.5% (1/197) and 8% (3/39) after urgent or emergency surgery. After a median follow-up of 32 months, recurrence in the pelvis was apparent in 1 of 72 patients after curative resection of rectal cancer and 4 of 18 after palliative resection, thus giving a total pelvic recurrence rate of 6% at 30 months. The 5-year survival rate of all new patients seen with a rectal cancer was 58% and 56.5 % for patients with a colon cancer. A combination of low operative mortality rates, low local recurrence rates in rectal cancer, the increasing use of adjuvant therapies, and careful follow up to detect (and where possible resect) metastatic disease at an early stage is associated with good cancer-specific survival figures. However further improvement in survival will need a shift to earlier stage at diagnosis and more effective chemotherapy (both in the adjuvant setting and for advanced disease) if significant gains in survival are to be made.


Relationship between blood pressure and subcortical lesions in healthy elderly people.
The relationship between blood pressure (BP) and heart rate (HR) and MRI assessments of subcortical T2 hyperintensities was evaluated in healthy elderly men and women. Casual and 24-hour ambulatory BPs and HR measurements were taken of 144 elderly individuals, aged 55 to 79 years. Subjects had no evidence of previous health disorders. MRI scans of white matter, subcortical gray matter, and insular subcortex were coded for severity of hyperintensities. Mean casual BP for the group was 120/72 mm Hg. With age and sex accounted for, individuals with the highest severity rating of white matter hyperintensities had higher casual, awake, and sleep systolic BPs; higher awake diastolic BPs; greater awake systolic BP variability; and a smaller nocturnal fall in systolic and diastolic BPs than individuals with less severe ratings. Higher severity ratings for subcortical gray matter hyperintensities were associated with elevations in casual, awake, and asleep systolic BPs and a smaller HR drop during sleep. Subjects with higher ratings for the insular subcortex had higher systolic and diastolic BPs (casual, awake, and asleep), greater HR variability during sleep, and a smaller nocturnal fall in HR. Casual and 24-hour ambulatory BPs and some ambulatory HR measures are associated with subcortical lesions of the brain. Longitudinal studies are needed to further explore the relationship between white matter lesions and cardiovascular measures, as well as the significance of these lesions for cerebrovascular disease in healthy elderly subjects.


Blood-derived lysophospholipid sustains hepatic phospholipids and fat storage necessary for hepatoprotection in overnutrition.
The liver has a high demand for phosphatidylcholine (PC), particularly in overnutrition, where reduced phospholipid levels have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). Whether other pathways exist in addition to de novo PC synthesis that contribute to hepatic PC pools remains unknown. Here, we identified the lysophosphatidylcholine (LPC) transporter major facilitator superfamily domain containing 2A (Mfsd2a) as critical for maintaining hepatic phospholipid pools. Hepatic Mfsd2a expression was induced in patients having NAFLD and in mice in response to dietary fat via glucocorticoid receptor action. Mfsd2a liver-specific deficiency in mice (L2aKO) led to a robust nonalcoholic steatohepatitis-like (NASH-like) phenotype within just 2 weeks of dietary fat challenge associated with reduced hepatic phospholipids containing linoleic acid. Reducing dietary choline intake in L2aKO mice exacerbated liver pathology and deficiency of liver phospholipids containing polyunsaturated fatty acids (PUFAs). Treating hepatocytes with LPCs containing oleate and linoleate, two abundant blood-derived LPCs, specifically induced lipid droplet biogenesis and contributed to phospholipid pools, while LPC containing the omega-3 fatty acid docosahexaenoic acid (DHA) promoted lipid droplet formation and suppressed lipogenesis. This study revealed that PUFA-containing LPCs drive hepatic lipid droplet formation, suppress lipogenesis, and sustain hepatic phospholipid pools - processes that are critical for protecting the liver from excess dietary fat.


Pharmacist's Demand for Optimal Primary Care Service Delivery in a Community Pharmacy: The OPTiPharm Study.
The US population continues to expand providing the need for primary health care services. Community pharmacies integrated with medicine may provide greater access while providing high quality care. To gauge pharmacists' demand for primary health care services delivered through community pharmacies. An online survey was administered to determine community pharmacists' preferences for varying primary care services that could be offered in the community pharmacy setting. A Discrete Choice Experiment was employed to show pharmacists competing scenarios with varied primary care service offerings in the community pharmacy setting. Attributes evaluated were operation hours, service provider, medical records, service logistics, physical examinations, point-of-care diagnostic testing, preventative care, and drug prescribing. Respondents chose the scenario most likely to induce switching employment from base pharmacy to one providing advanced services. The optimal service delivery model from 291 community pharmacists comprised: inclusion of patient prescriptions and health information into the patient's medical record; provision of point of care testing and vital sign, including blood pressure, heart rate and breathing rate, and blood sugar and cholesterol measurement; and pharmacists prescribing (under physician oversight). Pharmacists were 4 times more likely to switch employment from their current pharmacy to their choice for advanced pharmacy services. Pharmacist demand was highest among those with a PharmD, less experience, working >40 hours per week, and in rural areas. This study provides empirical support for the model of pharmacists playing a greater role in the provision of primary care health services through community pharmacy settings.


[Alimentary thyrotoxcicosis in two dogs].
Two dogs with increased thyroxin concentrations compatible with hyperthyroidism were referred for further examinations. One dog displayed clinical signs of hyperthyroidism. Based on history, clinical examination, laboratory evaluation and scintigraphy an alimentary thyrotoxicosis was identified. It was caused by feeding a BARF diet containing thyroidal tissue in one dog and by conventional dog food in the other patient. After changing the diet the clinical signs resolved in the affected dog. A control examination revealed thyroxin concentrations within the reference range in both dogs.


Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2.
There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.


Contrasting effects of nutlin-3 on TRAIL- and docetaxel-induced apoptosis due to upregulation of TRAIL-R2 and Mcl-1 in human melanoma cells.
Wild-type p53 is commonly expressed in melanoma but does not appear to be effective in the induction of apoptosis. One explanation is that p53 is targeted for degradation by the E3 ligase MDM2. However, we found in this study that blockade of the interaction of p53 and MDM2 by the MDM2 antagonist nutlin-3 in melanoma cells did not induce apoptosis, even though it upregulated p53 and its proapoptotic targets. Nevertheless, nutlin-3 enhanced TRAIL-induced apoptosis as a result of p53-mediated upregulation of TRAIL-R2. Unexpectedly, nutlin-3 upregulated Mcl-1, which attenuated apoptotic signaling triggered by TRAIL, and inhibited apoptosis induced by the microtubule-targeting drug docetaxel. The increase in Mcl-1 was related to a p53-independent transcriptional mechanism, but stabilization of the Mcl-1 protein played a dominant role, as nutlin-3 upregulated the Mcl-1 protein to a much greater extent than the Mcl-1 mRNA, and this was associated with prolonged half-life time and reduced ubiquitination of the protein. Knockdown of p53 blocked the upregulation of the Mcl-1 protein, indicating that p53 plays a critical role in the stabilization of Mcl-1. The contrasting effects of nutlin-3 on TRAIL- and docetaxel-induced apoptosis were confirmed in fresh melanoma isolates. Collectively, these results show that nutlin-3 may be a useful agent in combination with TRAIL and, importantly, uncover a novel regulatory effect of p53 on the expression of Mcl-1 in melanoma cells on treatment with nutlin-3, which may antagonize the therapeutic efficacy of other chemotherapeutic drugs in addition to docetaxel in melanoma.


Effects of adding high-intensity training during an 8-week period on maximal oxygen uptake in 12-year-old youth athletes.
Maximal oxygen uptake (V̇O2max ) increases during adolescence parallel to the increase in fat-free mass (FFM). How much endurance training adds to this effect is still controversial. Our aim was to investigate if inclusion of high-intensity training (HIT) during an 8-week training period was superior to low-intensity strength and coordination training in 12-year-old youth athletes concerning the effect on V̇O2max . Thirty-five cross-country skiers were randomized into a HIT group (ET) and a strength and coordination group (SC), while 29 less active peers served as controls for growth and maturation (C). Anthropometrics and V̇O2max were assessed before and after the training period, and level of physical activity and training were monitored with accelerometers, training logs and a questionnaire. The number of weekly training sessions were higher for ET (4.6 ± 1.2) and SC (4.1 ± 1.0) compared with C (1.8 ± 2.0) (p < 0.01), with only ET conducting HIT sessions (1.9 ± 0.2 per week). C spent more time sedentary and less time in moderate and vigorous activity compared with ET (p < 0.05). All groups had a similar %-change pre-post in absolute V̇O2max (mL min-1 ) of 6% ± 6% for ET (p < 0.01), 5% ± 7 for SC (p = 0.14), and 5% ± 13% for C (p = 0.03), with no significant differences between groups. V̇O2max relative to FFM did not change significantly for any groups. The change in V̇O2max paralleled the change in FFM for all groups, questioning the effect of HIT on V̇O2max over an 8-week period in youth athletes.


Galanin-mediated anxiolytic effect in rat central amygdala is not a result of corelease from noradrenergic terminals.
Galanin is colocalized extensively with norepinephrine in brain. Although this suggests possible activity-dependent neurotransmitter interactions, the functional significance of such colocalization remains elusive. Previously, we showed that enhancing stress-activation of the noradrenergic system by yohimbine pretreatment released galanin in central amygdala, attenuating the anxiety-like behavioral response to stress on the elevated plus-maze. The present study was conducted to determine, in this context, whether galanin was indeed coreleased from noradrenergic terminals, or instead from another galanin afferent or local stress-responsive galanin neurons in the amygdala. In experiment 1, galanin-mediated anxiolytic effects on the plus-maze following yohimbine + stress were unaltered by lesioning the noradrenergic innervation of central amygdala. In experiment 2, combining immunohistochemistry and in situ hybridization, galanin neurons specifically activated by yohimbine + stress treatment were found only in the locus coeruleus and intraamygdalar bed nucleus of the stria terminalis, adjacent to central amygdala. In experiment 3, retrograde tracing combined with in situ hybridization revealed few if any galanin cells projecting to central amygdala in locus coeruleus or nucleus tractus solitarius, sources of noradrenergic innervation. Indeed, few retrogradely-labeled galanin neurons were observed anywhere in the brain, including a small number in the intraamygdalar bed nucleus. Together, these results suggest that stress following yohimbine may have induced galanin release from an afferent to central amygdala originating in the bed nucleus, or from local neurons in the intraamygdalar bed nucleus, but that anxiolytic effects exerted by galanin in this context of elevated noradrenergic activity were not the result of corelease from noradrenergic terminals innervating central amygdala.


Widespread bacterial protein histidine phosphorylation revealed by mass spectrometry-based proteomics.
For decades, major difficulties in analyzing histidine phosphorylation have limited the study of phosphohistidine signaling. Here we report a method revealing widespread and abundant protein histidine phosphorylation in Escherichia coli. We generated an extensive E. coli phosphoproteome data set, in which a remarkably high percentage (∼10%) of phosphorylation sites are phosphohistidine sites. This resource should help enable a better understanding of the biological function of histidine phosphorylation.