Multimodal image-guided ablation on management of renal cancer in Von-Hippel-Lindau syndrome patients from 2004 to 2021 at a specialist centre: A longitudinal observational study.
To analyse the safety, technical feasibility, long-term renal function and oncological outcome of multimodal technologies in image-guided ablation (IGA) for renal cancer in Von-Hippel-Lindau (VHL) patients, and to evaluate factors that may influence the outcome. Retrospective analysis of a prospective database of VHL patients who underwent IGA at a specialist centre. Patient's demographics, treatment energy, peri-operative outcome and oncological outcomes were recorded. Statistical analysis was performed to determine factors associated with complication and renal function reduction. The overall, 5 and 10-year cancer specific (CS), local recurrence-free (LRF) and metastasis-free (MF) survival rates were presented with Kaplan-Meier Curves. From 2004 to 2021, 17 VHL patients (age 21-68.2) with a mean (±SD) RCC size of 2.06 ± 0.92 cm received IGA. Median (IQR) RCCs per patient was 3 (2-4) over the course of follow up. Fifty-four RCCs were treated using radiofrequency ablation (n = 11), cryoablation (n = 38) and irreversible electroporation (n = 8) in 50 sessions. Primary and overall technical success rate were 94.4% (51/54) and 98% (53/54). One CD-III complication with proximal ureteric injury. Five patients in seven treatment sessions experienced a >25% reduction of eGFR immediately post-IGA. All patients have preservation of renal function at a median follow-up of 79 (51-134) months. The 5 and 10-year CS, LRF and MF survival rates are 100%, 97.8% and 100%. Whilst, the 5 and 10-year overall survival rate are100% and 90%. Multimodal IGA of de novo RCC for VHL patients is safe and has provided long term preservation of renal function and robust oncological durability.


Surgical management of major renal trauma: a review of 102 cases treated by conservative surgery.
A review is presented of 102 patients with significant renal trauma seen in the last 5 years. All patients underwent exploratory laparotomy for abdominal trauma and had associated urologic injuries, which were managed by conservative surgery. Forty-eight patients had non-expanding retroperitoneal hematoma and were treated expectantly. Nine patients needed exploration and drainage only, while 18 had some form of renorrhaphy. Four patients underwent repairs of renal pelvic injuries, 12 underwent partial nephrectomy and 11 underwent repairs of renal pedicle injuries. A conservative approach to renal trauma is emphasized.


CT or not CT--that is the question. Whether 'tis better to evaluate clinically and x ray than to undertake a CT head scan!
To evaluate the usage of computed tomography (CT) head scanning in children at the Royal Aberdeen Children's Hospital after the publication of the National Institute of Clinical Excellence (NICE) guidelines on the management of head injury. The Accident and Emergency case records of all children presenting with a head injury over a three month period were reviewed and the number of attendances, radiographs, and CT head scans undertaken were noted. Also noted was the number of additional CT head scans that would have been performed if the NICE guidelines had been rigidly followed. Five hundred and thirty seven children were included in the study: 67% were boys. Two hundred and ten (39%) had skull radiographs: six demonstrated skull fractures and eight (1.5%) underwent CT head scan, with one positive report of a skull fracture. There were no reports of intracranial abnormalities. Ninety nine (18.4%) were admitted. Strictly applying all the NICE criteria for CT scanning would have resulted in an additional 54 patients being scanned. Rigid adherence to the NICE guidelines in all children with head injuries would have resulted in an almost eightfold increase in CT head scans performed. None of these children had clinical signs of intracranial injury and would have been exposed to a large amount of ionising radiation. The use of guidelines in practice must always be considered in conjunction with clinical judgement.


Drug interactions in a clinic using COSTAR.
In a study involving 1499 patients in a family office, prescription data obtained from a computerized record system (COSTAR) were analyzed to determine the drug interaction rate. While prior studies have adequately determined that drug interactions occur frequently in most medical offices this paper presents a methodology for performing such analyses in a very short period of time. By using a computer at all stages, the analysis was computed in less than four weeks and with more accuracy than would otherwise be possible. In addition to the demonstration of a method, the results of our analysis are also of interest. Overall 138 (9.2%) of the study patients were prescribed drugs with known interaction potential and among this group, 123 (72%) had interactions considered to be of "moderate" clinical significance and 36 (17%) had interactions considered to be of "major" significance.


How do (false) positively screened patients experience a screening programme for liver cirrhosis or fibrosis in Germany? A qualitative study.
This study aimed to explore psychosocial consequences of (false) positive liver screening results and to identify influencing factors for perceived strain within a multistage screening programme for liver cirrhosis and fibrosis in Germany. Between June 2018 and May 2019, all positively screened patients were asked to participate in the study (n = 158). N = 11 telephone interviews and n = 4 follow-up interviews were conducted. Semi-structured telephone interviews were carried out. The analysis followed a structuring content analysis approach. Thereby, categories were first defined deductively. Second, the categories were revised inductively based on the data. The main themes found regarding the consequences of the screening were categorised in emotional reactions and behavioural reactions. Few respondents described negative emotional consequences related to screening. Those seem to be mostly driven by suboptimal patient-provider communication and might be worsened when transparent information transfer fails to happen. As a result, patients sought information and support in their social environment. All patients reported positive attitudes towards liver screening. To reduce the potential occurrence of psychosocial consequences during the screening process, medical screening should be performed in the context of transparent information. Regular health communication on the side of health professionals and increasing patients' health literacy might contribute to avoiding negative emotions in line with screening. This study recognises the wide-ranging patients' perspectives regarding the consequences of liver screening which should be taken into consideration when implementing a new screening programme to ensure a patient-centred approach.


CHARACTERIZING FREQUENCY-SELECTIVE NETWORK VULNERABILITY FOR ALZHEIMER'S DISEASE BY IDENTIFYING CRITICAL HARMONIC PATTERNS.
Alzheimer's disease (AD) is a multi-factor neurodegenerative disease that selectively affects certain regions of the brain while other areas remain unaffected. The underlying mechanisms of this selectivity, however, are still largely elusive. To address this challenge, we propose a novel longitudinal network analysis method employing sparse logistic regression to identify frequency-specific oscillation patterns which contribute to the selective network vulnerability for patients at risk of advancing to the more severe stage of dementia. We fit and apply our statistical method to more than 100 longitudinal brain networks, and validate it on synthetic data. A set of critical connectome pathways are identified that exhibit strong association to the progression of AD.


New normative values for handgrip strength: results from the UK Biobank.
To develop normative values for right and left handgrip strength after stratification for confounders like gender, age, and height. Cross-sectional, descriptive. General population. A total of 502,713 people living in the United Kingdom. None. Handgrip strength was measured using a Jamar hydraulic hand dynamometer, which is considered to be an accurate instrument to measure handgrip strength. In addition, self-reported chronic conditions and ethnic background were registered, and lung function was assessed using spirometry. After exclusion of all individuals with missing data, a nonwhite ethnic background, the presence of 1 or more self-reported conditions, and/or an obstructive lung function (defined as FEV1/FVC <0.7), new normative values for right and left handgrip strength were derived from 224,830 and 224,852 individuals (54.2% women; age: 55.0 [8.0] years; height: 169.0 [9.2] cm; body mass index: 26.9 [4.4] kg/m(2)) with a nonobstructed spirometry (FEV1: 3.0 [0.8] L). Men were stronger than women. Moreover, significant associations were found between handgrip strength and height, and between handgrip strength and age. Finally, percentiles 5, 10, 25, 50, 75, 90, and 95 were calculated for right and left handgrip strength, after stratification for gender, age, and height. The UK Biobank dataset provided the opportunity to determine new normative values for handgrip strength in men and women aged 39 to 73 years. These normative values take into consideration age, height, and measurement side. Therefore, these new normative handgrip strength values are of broad clinical interest.


The conflict between research and mental health services.
Serious friction often results from the association between social scientists and providers of mental health care. Understanding the nature of this association and the types of conflict that exist may result in improved research and services.


Identification of anaerobic bacteria using high-performance liquid chromatography.
20 species of the genera Clostridium, Bacteroides, Fusobacterium and the type strains of Peptostreptococcus anaerobius, Peptococcus asaccharolyticus, Veillonella parvula and Propionibacterium acnes were examined for the production of volatile (VFA) and nonvolatile (NVFA) short-chain fatty acids using high-performance liquid chromatography (HPLC) with a column for organic acids (Aminex HPX-87H). 10 min are needed for sample preparation and the VFA and NVFA were detected simultaneously in a single chromatographic run. The total time required to run each chromatogram was approximately 60 min. With regard to the production of short-chain fatty acids in culture media it was possible to identify the species of the genera rapidly and clearly. The results illustrate the role of HPLC in determinating short-chain fatty acid products as an additional means for rapid differentiation between closely related anaerobic bacterial species. The aim of the method developed is to establish a complete automatization for the identification of anaerobic bacteria using an automatic sampling system and a microprocessor-controlled chromatography unit.


Designing, validation, and feasibility of a yoga module for patients with ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease that causes significant disability and reduced quality of life. Scientific studies on yoga have revealed its various health benefits in chronic conditions, including autoimmune diseases. However, whether yoga is feasible for AS patients or not is not studied. Further, no validated yoga module is available for AS patients. This study intended to develop a yoga module for AS patients and investigated its feasibility of use. The study was completed in three stages. In Stage I, six yoga experts prepared a list of 64 yoga practices based on the classical and contemporary yogic literature review. Of these practices, 41 were included in the designed yoga module. In Stage II, 41 experts with a minimum of five years of experience in yoga therapy were invited for yoga module validation. The usefulness of the practices was rated by experts on a 3-point scale (1: not at all useful, 2: moderately useful, and 3: very much useful). The Lawshe content validity ratio (CVR) method was used for the content validity of the yoga module. Practices with a CVR score of > 0.3 were retained in the final yoga module. In Stage III, a certified yoga instructor administered the validated yoga module to 19 AS patients (average age: 35.5 ± 10.7 years) thrice weekly for a month. Feasibility was assessed on the basis of the attrition rate, retention rate, attendance of the participants, and the subjective response on practical sessions using a structured checklist. Of the 41 practices in the module, 31 had a CVR score of > 0.3 and were included in the final yoga module. Of the 25 participants, 19 (76%) completed the study while six dropped out (24%). Nineteen patients reported greater improvement in pain and flexibility. They found yoga relaxing and easy to practice. Most participants (65%) were able to practice a minimum of 30 min/day. The present study offers a validated yoga module consisting of 31 practices for AS patients. The results of the pilot suggested that the module is feasible, acceptable, and easy to practice for AS patients. We recommend that AS patients should practice this yoga module for a minimum of 30 min every day under the supervision of a yoga expert.


Uterovesical fistula caused by cervical pessary placed for the prevention of preterm delivery - case report.
Uterovesical fistulas are the rarest of all urogenital fistulas, mostly occurring as a complication of cesarean section. We present a case of a 32-year-old woman, who noticed continuous vaginal urine leakage starting immediately after a vaginal delivery. The shortening of the uterine cervix was reported at 26th week of gestation, and a cervical pessary was placed. Shortly after delivery, the patient noticed the loss of urinary continence control, and she was diagnosed with urinary incontinence and hematuria. The office diagnostic hysteroscopy revealed uterovesical fistula. The correction procedure by transabdominal approach was performed by the team of gynecological and urological surgeons. One year of follow-up, the patient reports no symptoms related to lower urinary tract dysfunction. Based on the literature search, we believe that his is the first study of a uterovesical fistula followed by the use of a cervical pessary for the prevention of preterm delivery. Our case is a clear reminder that symptoms of urinary incontinence after vaginal delivery should be carefully managed.


Dual opposite injection electrokinetic chromatography: nonionic microemulsion pseudostationary phase and novel approach to electrokinetic sampling bias.
Dual opposite injection capillary electrophoresis (DOI-CE) is a family of CE techniques in which the sample is introduced into both ends of the capillary. For the analysis of compounds with widely varying pKa values using a voltage-driven separation scheme, DOI-CE is superior to conventional CE with sample introduction at only one end of the capillary due to DOI-CE's broader elution window. To enhance the DOI-CE separation, a running buffer with a microemulsion system was developed. Since DOI-CE works best under conditions of low electroosmotic flow (EOF), the suppression of EOF via the addition of a multiply charged cation (e.g., Zn2+) to the buffer was investigated, and was found to suppress the EOF effectively at moderate concentrations (2.5-10 mM). Three different dual opposite injection modes were studied: simultaneous electrokinetic injection, sequential electrokinetic injection, and sequential hydrodynamic injection. The injection bias in the first two electrokinetic injection modes was compared with the sequential hydrodynamic injection. Corrections in the bias of the electrokinetic injections were discussed, and an improved approach was suggested. Finally, the effect of the relative concentration of the multiply charged cation in the sample plug and running buffer on the peak shape of co-electroosmotic and counter-electroosmotic ions was examined, and found to be much more influential on the latter.


Proposal for an optical laser producing light at half the Josephson frequency.
We describe a superconducting device capable of producing laser light in the visible range at half of the Josephson generation frequency with the optical phase of the light locked to the superconducting phase difference. It consists of two single-level quantum dots embedded in a p-n semiconducting heterostructure and surrounded by a cavity supporting a resonant optical mode. We study decoherence and spontaneous switching in the device.


A 10-year comparison of mitral valve replacement with Carpentier-Edwards and Hancock porcine bioprostheses.
Two hundred fifty-three patients who underwent isolated mitral valve replacement with a porcine bioprosthesis had long-term evaluation. One hundred forty-seven patients received a Carpentier-Edwards porcine bioprosthesis and 106, a Hancock valve. There were no significant differences in preoperative clinical characteristics between the two groups. Cumulative follow-up was 1,375 patient-years. At 10 years, 93% +/- 2.5% of the patients in the Carpentier-Edwards group and 85% +/- 7.8% of those in the Hancock group were free from valve-related death (not significant), and 95% +/- 2% and 91% +/- 3.8%, respectively, were free from thromboembolism (not significant). At 10 years, 65% +/- 7.2% of the patients in the Carpentier-Edwards group and 66% +/- 7.2% of those in the Hancock group were free from structural valve deterioration (not significant), and 64% +/- 6% and 59% +/- 7.3%, respectively, were free from reoperation (not significant). We conclude that the first generation of Carpentier-Edwards and Hancock prostheses produce comparable long-term results in the mitral position.


Temporal characteristics of binocular rivalry: visual field asymmetries.
Very little is known about the mechanisms that drive the alternation between the two views during binocular rivalry. A key property of the rivalry process is the rate at which the two views alternate. Understanding the factors that affect the rate of the alternation is critical to the final understanding of the underlying process. Using a circular and a radial grating as the rivalry stimuli, we observed a significantly faster binocular rivalry when stimuli were presented in the right visual field than that in the left visual field for the right-handed observers, and a reversed asymmetry for the left-handed observers. In both groups, rivalry was faster for stimuli presented in the lower visual field than that in the upper visual field. This pattern of results suggests that (1) rivalry is likely a locally driven process and (2) the visual brain in the left hemisphere may be the faster one of the two hemispheres in right-handed people.


Positive and negative effects of herbivory on the population dynamics of Senecio jacobaea L. and Cynoglossum officinale L.
Herbivore effects were studied on populations of the biennial plant species Senecio jacobaea and Cynoglossum officinale. During a three year period (1985-1988) population characteristics (herbivory, number of seedlings, rosettes and flowering plants) were compared in-and outside exclosures, as well as parameters reflecting vegetation cover. In S. jacobaea, a strong negative effect of Tyria jacobaeae was found on seedling establishment, rosette growth and flowering. On the other hand, vertebrate herbivores (mainly rabbits) had an indirect positive effect by limiting the development of the surrounding vegetation (esp. grasses). The increasing vegetation cover in protected populations caused a reduction in germination, seedling- and rosette-growth. Herbivory on C. officinale was low (<10%), no direct effects of herbivores on plant populations were shown. Indirect effects of herbivory through an increasing vegetation were even more pronounced as in S. jacobaea. Therefore, although both plant species may first benefit from herbivore-exclusion, their populations are dependent on rabbits eating other plants (esp. grasses) and reducing competition.


Effects of estradiol on kisspeptin neurons during puberty.
The activation of the gonadotropin-releasing hormone (GnRH) neurons from a state of relative quiescence is critical for initiating puberty in mammals. Kisspeptin and its G-protein coupled receptor Gpr54 are essential for puberty, with disruption to either resulting in failed puberty in humans and mice. Robust data from several species indicate that Kiss1 mRNA and/or kisspeptin peptide expression within the hypothalamus increases during pubertal development. Kisspeptin fiber innervation of GnRH neurons and kisspeptin release within the hypothalamus also increase during pubertal development, indicating that there is increased kisspeptinergic drive to GnRH neurons during pubertal development. It is becoming increasingly apparent that gonadal steroids play important roles in the regulation of kisspeptin expression during pubertal development, and in particular, estradiol signaling through estrogen receptor alpha appears to be necessary for these changes to occur. This review focuses on the role that estradiol plays in the regulation of kisspeptin expression during pubertal development.


Urinary leukotriene E4 after exercise challenge in children with asthma.
To assess the role of sulfidopeptide leukotrienes in the pathogenesis of exercise-induced asthma (EIA), the urinary levels of leukotriene E4 (LTE4), a metabolite of LTC4 and LTD4, were measured by RIA before and after exercise in 13 children with EIA and 10 healthy children. Mass spectrometry was used to confirm the presence of LTE4 in urine and the specificity of the RIA. There was no significant difference in the urinary LTE4 levels before exercise between the children with asthma and healthy children (109 [21 to 265] versus 122 [45 to 156] pg/mg of creatinine; median and range). Urinary LTE4 levels increased significantly after exercise in the children with EIA (from 109 [21 to 265] to 196 [40 to 655] pg/mg of creatinine; median and range; p less than 0.05) but not in the healthy children. The children with asthma demonstrated no significant correlation between the LTE4 level after exercise and the degree of bronchoconstriction, as revealed by the maximal percent fall in the peak expiratory flow rate. Taken together with a recent study that pretreatment with a potent and selective LTD4 antagonist markedly attenuated EIA, our findings suggest that sulfidopeptide leukotrienes may play some role in the pathogenesis of this type of asthma with other factors also being involved in determining the overall airway response.


Implantation of an Atrial Flow Regulator in a Child on Venoarterial Extracorporeal Membrane Oxygenator as a Bridge to Heart Transplant: A Case Report.
Balloon dilation and stenting of the atrial septum are techniques used to unload left heart cavities in acute or end-stage heart failure in children. However, they carry significant risks such as tamponade or device embolization. We report the first case of a child with an end-stage mitochondrial cardiomyopathy on a venoarterial extracorporeal membrane oxygenator as a bridge to heart transplant where an atrial flow regulator device has been implanted. This case illustrates the feasibility and safety of atrial flow regulator implantation in this setting. This procedure allowed to wean inotropic support while awaiting heart transplantation.


Urinary tract infection caused by bacterial pathogens of the respiratory tract in children.
Urinary tract infections (UTIs) caused by bacterial pathogens of the respiratory tract such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are rare and little is known about their clinical features and potential host risk factors. The aim of this study is to reveal their clinical characteristics. We conducted a retrospective descriptive study on pediatric UTI due to S. pneumoniae, Haemophilus spp., or M. catarrhalis at a tertiary-care pediatric hospital. Pediatric patients diagnosed with UTI between 2002 and 2020 were included. Patient demographics, laboratory data, and microbiological findings were extracted from their electronic medical records and the infectious disease surveillance system. Among 46,332 urine samples, 76 bacteriuria (0.16%) and 22 UTI (0.05%) events due to the targeted species were identified (S. pneumoniae, n = 7, and Haemophilus spp., n = 15). Of the patients, 17 (85%) had underlying urinary tract abnormalities and 13 (60%) had vesicocutaneous fistula. All the UTI episodes caused by S. pneumoniae and Haemophilus spp. occurred after cystostomy. All the patients had satisfactory clinical outcomes. Although S. pneumoniae and Haemophilus spp. are rare causes of UTIs in children, they could be the true causative bacteria of UTI, particularly in the patients with urinary tract abnormalities and vesicocutaneous fistulas. Thus, clinicians should not ignore these pathogens as contaminations in special populations.


Tritiated-thymidine labeling of rectal epithelial cells in 'non-prep' biopsies of individuals at increased risk for colonic neoplasia.
Recent measurements have shown increased proliferation of colonic epithelial cells in individuals at heightened risk for cancer of the large intestine. This biomarker has facilitated measurements of the effects of nutritional intervention in studies that are attempting to inhibit tumor development in high-risk individuals. In this study, further measurements were made of the proliferation of rectal epithelial cells, when biopsies were removed from mucosa that had not previously been disturbed by any tapwater or other enema preparations. Progressive increases were found in the numbers of [3H]dThd-labeled epithelial cells in rectal crypts, and in labeling index profiles, in patients having previous sporadic adenomas or colon cancer, compared to individuals who had not developed colonic neoplasms. The most quiescent proliferative equilibrium was found in individuals without previous colonic disease. Findings indicated that 'non-prep' rectal biopsies obtained from the most accessible region of the large intestine, show modifications in the biomarker of cell proliferation paralleling colon cancer risk.


Effect of anaesthetic maintenance with isoflurane or propofol on ease of endoscopic duodenal intubation in dogs.
To compare the ease of endoscopic duodenal intubation (EDI) in dogs during maintenance of general anaesthesia with isoflurane or propofol infusion. Prospective, randomized, partially blinded clinical trial. A total of 22 dogs undergoing upper gastrointestinal tract endoscopy to include EDI were recruited. Dogs were randomly assigned isoflurane (ISO; n = 10) or propofol (PROP; n = 11) for maintenance of general anaesthesia. Following anaesthetic premedication with intramuscular medetomidine (0.005 mg kg-1) and butorphanol (0.2 mg kg-1), general anaesthesia was induced with propofol, to effect, maintained with 1.5% (vaporizer setting) isoflurane in 100% oxygen or 0.2 mg kg-1 minute-1 propofol. The dose of both agents was adjusted to maintain general anaesthesia adequate for the procedure. Degree of sedation 20 minutes post-anaesthetic premedication, propofol induction dose, anaesthetist and endoscopist training grade, animal's response to endoscopy, presence of gastro-oesophageal and duodenal-gastric reflux, spontaneous opening of the lower oesophageal and pyloric sphincters, antral movement and time to achieve EDI were recorded. EDI was scored 1 (immediate entry with minimal manoeuvring) to 4 (no entry after 120 seconds) by the endoscopist, blinded to the agent in use. Data were tested for normality (Shapiro-Wilk test) and differences between groups analysed using independent t test, Mann-Whitney U test and Fisher's exact test as appropriate. There were no significant differences between groups for EDI score [median (interquartile range): 2 (3) ISO, 2 (3) PROP] or time to achieve EDI [mean ± standard deviation: 52.50 ± 107.00 seconds (ISO), 70.00 ± 196.00 seconds (PROP)]. Significantly more dogs responded to passage of the endoscope into the oesophagus in group PROP compared with group ISO (p = 0.01). Maintenance of general anaesthesia with either isoflurane or propofol did not affect EDI score or time to achieve EDI.


[Induction of anaesthesia and intubation in children with a full stomach. Time to rethink!].
Classical adult type rapid sequence induction (RSI) intubation is not always appropriate in children. In newborns, infants and small children, limited cooperation during pre-oxygenation, reduced respiratory oxygen reserves, increased oxygen demand and a tendency for airway collapse, easily lead to hypoxaemia after induction of anaesthesia. Gentle mask ventilation with pressures not exceeding 10-12 degrees cm H(2)O allows oxygenation without the risk of gastric inflation and aspiration. Risk factors leading to pulmonary aspiration are bucking, coughing and straining during induction or tracheal intubation and active regurgitation and vomiting during laryngoscopy under light anaesthesia and incomplete muscle paralysis. Gentle mask ventilation allows tracheal intubation under optimised oxygenation, haemodynamics, depth of anaesthesia and complete muscle relaxation. Application of cricoid pressure does not reliably prevent pulmonary aspiration. In children cricoid pressure clearly interferes with smooth induction of anaesthesia, results in difficult mask ventilation and intubation as well as provokes bucking and straining and, therefore, should not be routinely used. Key features of RSI intubation for children are effective induction of deep anaesthesia followed by profound muscle paralysis, careful mask ventilation and gentle tracheal intubation under optimised conditions.


Corneal arcus, case finding and definition of individual clinical risk in heterozygous familial hypercholesterolaemia.
Premature corneal arcus may identify individuals with hyperlipidaemia and increased cardiovascular risk. We have attempted to quantitate relationships through determination of graded prevalence of corneal arcus with age for 81 males and 73 females suffering from heterozygous familial hypercholesterolaemia (HFH) at presentation, and for 280 male and 353 female unselected patients (age range 16-76 years) attending a country general practice. Some degree of arcus affected 50% of HFH patients by age 31-35 years, and 50% of practice patients by age 41-45 years. Complete full ring arcus affected 50% of the familial hypercholesterolaemia (FH) group by age 50 years, with only 5% similarly affected in the non-FH group. Arcus grade with age was advanced by some 5 years in males versus females. Premature arcus potentially alerting to HFH can be broadly defined for males and females combined, as heavy full ring by age 50 years, or any degree of arcus by age 30-35 years. Arcus grade was not related to the presence of coronary disease. Accelerated development of corneal arcus with age is an indicator of HFH, but premature arcus is not an additional marker of premature coronary disease for individual cases of HFH.


Novel cross-linked polyacrylamide matrices: an investigation using gradient gel electrophoresis.
Gradient gel electrophoresis was used to examine the separation properties of novel cross-linking compounds for polyacrylamide (PAAm). At low %T and at the same %C protein migration difference is accentuated for bismethacrylamide cross-linked networks relative to bisacrylamide cross-linked networks. Similar properties were observed for cyclic monomers at low %T. This trend is maintained throughout the gradient. However, at higher %T migration differential relative to N,N'-methylenebisacrylamide (Bis) was less pronounced. Evidence from gradient gels suggests that reactivity and functionality of vinyl groups impose an overriding control over network formation.


Vasoactive intestinal peptide administration after stroke in rats enhances neurogenesis and improves neurological function.
The aim of this study was to investigate the effects of vasoactive intestinal peptide (VIP) on neurogenesis and neurological function after cerebral ischemia. Rats were intracerebroventricular administered with VIP after a 2h middle cerebral artery occlusion (MCAO) and sacrificed at 7, 14 and 28 days after MCAO. Functional outcome was studied with the modified neurological severity score. The infarct volume was evaluated via histology. Neurogenesis, angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were measured by immunohistochemistry and Western blotting analysis, respectively. The treatment with VIP significantly reduced the neurological severity score and the infarc volume, and increased the numbers of bromodeoxyuridine (BrdU) immunoreactive cells and doublecortin immunoreactive area in the subventricular zone (SVZ) at 7, 14 and 28 days after ischemia. The cerebral protein levels of VEGF and VEGF expression in the SVZ were also enhanced in VIP-treated rats at 7 days after stroke. VIP treatment obviously increased the number of BrdU positive endothelial cells in the SVZ and density of cerebral microvessels in the ischemic boundary at 28 days after ischemia. Our study suggests that in the ischemic rat brain VIP reduces brain damage and promotes neurogenesis by increasing VEGF. VIP-enhanced neurogenesis is associated with angiogenesis. These changes may contribute to improvement in functional outcome.


1 alpha,20R-dihydroxyecdysone from Axyris amaranthoides.
Bioassay/RIA-directed phytochemical examination of the seeds of Axyris amaranthoides afforded a new ecdysteroid: 1 alpha,20R-dihydroxyecdysone [1-epi-integristerone A], together with 20-hydroxyecdysone and polypodine B. The structure of 1 alpha,20R-dihydroxyecdysone was determined unequivocally by UV, LSIMS, and a combination of 1D and 2D NMR techniques.


Incidence and microbiological profile of mycotic keratitis in a tertiary care eye hospital: A retrospective analysis.
To determine the incidence and microbiological profile of mycotic keratitis seen at a tertiary care eye hospital. A retrospective review of microbiology records of patients presenting with suspected microbial keratitis seen between January 2006 and December 2009 was performed. Patients with positive fungal cultures were further analyzed for the type of fungus isolated and associated bacterial pathogens. Microbiology records of 2300 patients with suspected microbial keratitis were reviewed. A microbiological diagnosis of mycotic keratitis was established in 87 (3.8%) patients over a four year period based on positive fungal cultures. The yearly incidence of mycotic keratitis was 3.2% (2006), 4.9% (2007), 3.3% (2008) and 3.6% (2009). Filamentous fungi were isolated more often than yeasts. Aspergillus species followed by Fusarium species and Trichophyton species were the commonest filamentous fungi isolated while Candida albicans was the most frequently encountered yeast. Mixed infections due to fungal and bacterial pathogens were seen in 25/87 (28.7%) patients. Cumulative incidence of mycotic keratitis was 3.8% over a four year period. Aspergillus species and Candida albicans were the most frequent pathogenic organisms causing mycotic keratitis in this part of the world. Mixed infections were seen in 28.7% of the patients. Knowledge of the "local" etiology within a region may be valuable in the management of mycotic keratitis in instituting an empirical therapy, especially when facilities for microscopy, cultures and antifungal susceptibility are not readily available. The baseline information presented will also be helpful in the planning of a corneal ulcer management strategy and for future studies on mycotic keratitis.


Mapping putative hubs in human, chimpanzee and rhesus macaque connectomes via diffusion tractography.
Mapping anatomical brain networks with graph-theoretic analysis of diffusion tractography has recently gained popularity, because of its presumed value in understanding brain function. However, this approach has seldom been used to compare brain connectomes across species, which may provide insights into brain evolution. Here, we employed a data-driven approach to compare interregional brain connections across three primate species: 1) the intensively studied rhesus macaque, 2) our closest living primate relative, the chimpanzee, and 3) humans. Specifically, we first used random parcellations and surface-based probabilistic diffusion tractography to derive the brain networks of the three species under various network densities and resolutions. We then compared the characteristics of the networks using graph-theoretic measures. In rhesus macaques, our tractography-defined hubs showed reasonable overlap with hubs previously identified using anterograde and retrograde tracer data. Across all three species, hubs were largely symmetric in the two hemispheres and were consistently identified in medial parietal, insular, retrosplenial cingulate and ventrolateral prefrontal cortices, suggesting a conserved structural architecture within these regions. However, species differences were observed in the inferior parietal cortex, polar and medial prefrontal cortices. The potential significance of these interspecies differences is discussed.


Reconstruction of the temporal contour for traumatic tissue loss using a CAD/CAM-prefabricated titanium implant-case report.
A 16-year-old Arab boy had suffered from a severe head injury including an intracranial haematoma. Despite replantation of the bone flap later on, the cosmetic result was very unfavourable due to partial resorption of the reinserted bone and atrophy of the right temporalis muscle. For contour reconstruction of both soft and hard tissues the boy was transferred from Saudi Arabia. A spiral CT was obtained and the contour was reconstructed using a new algorithm for surface generation. The resulting titanium implant was inserted without complications or the need for revision. The cosmetic result was good and corresponded to the preoperative digital planning. Techniques of computer-assisted implant prefabrication and surgery may include special algorithms for considering soft tissues including contour deficits of the temporalis muscle.


Computational investigation reveals that the mutant strains of SARS-CoV2 have differential structural and binding properties.
Remarkable infectivity of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) is due to the rapid emergence of various strains which enable the virus to ruling the world. Over the course of SARS-CoV2 pandemic, the scientific communities worldwide are responding to newly emerging genetic variants. However, mechanism behind the persistent infection of these variants is still not known due to the paucity of study of these variants at molecular level. In this scenario, computational methods have immense utility in understanding the molecular and functional properties of different variants. The various mutants (MTs) of SpikeS1 receptor binding domain (RBD) of highly infectious SARS-CoV2 strains were manifested and elucidated the protein structure and binding strength using molecular dynamics (MD) simulation and protein-protein docking approaches. MD simulation study showed that all MTs exhibited stable structures with altered functional properties. Furthermore, the binding strength of different MTs along with WT (wildtype) was revealed that MTs showed differential binding affinities to host protein with high binding strength exhibited by V367F and V483A MTs. Hence, this study shed light on the molecular basis of infection caused by different variants of SARS-CoV2, which might play an important role in to cease the transmission and pathogenesis of virus and also implicate in rational designing of a specific drug.


Clinical outcome comparison of polymethylmethacrylate bone cement with and without mineralized collagen modification for osteoporotic vertebral compression fractures.
A retrospective study of consecutive patients.The purpose of this study was to compare the clinical effect of biomimetic mineralized collagen (MC) modified polymethylmethacrylate (PMMA) bone cement and traditional PMMA bone cement for the treatment of osteoporotic vertebral compression fractures (OVCF).New fracture on adjacent level is the major postoperative complication of percutaneous vertebroplasty (PVP). The clinical incidence was 12.4% to 27.7%. The increased stiffness of the treated vertebral body caused by filling bone cement is considered as one of the main reasons.A total of 30 patients treated with traditional PMMA bone cement from June 2013 to March 2016 were selected as the traditional group, while 50 patients treated with MC modified PMMA bone cement from July 2014 to March 2016 were selected as the modified group. The 2 groups were compared by injection time of the bone cements, postoperative pain relief effects, vertebral height restoration, CT value changes of the treated vertebral bodies, and postoperative complications in the clinical observations.The surgeries were successfully completed in both groups. In the treatment of OVCF, the MC modified bone cement was able to achieve the same pain relief and vertebral height restoration effects compared to traditional bone cement during the follow-ups, although the injection time of the cement was prolonged in the operation. MC modified bone cement significantly reduced the incidence of postoperative adjacent vertebral fracture from 13.3% to 2%, and significantly increased bone density of the treated vertebral bodies.The MC modified PMMA bone cement showed good clinical outcomes and better mechanical properties than the traditional bone cements.


Effect of sinomenine on collagen-induced arthritis in mice.
The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from sinomenium acutum on collagen-induced arthritis (CIA) in mice. For this investigation, mice were s.c. immunized with type II collagen (CII) emulsified with complete Freund's adjuvant (day 0). Varying doses of SIN were orally administered daily commencing on day 0 daily over a period of 55 days. The severity of arthritis was evaluated according to clinical score, the effect of SIN on immune responses were determined by measurement of proliferative responses of spleen cells, antibody levels in serum and cytokine assays. Anti-CII IgG2a and IFN-gamma were measured as indicators of Th1 immune responses and anti-CII IgG1, IgE and IL-5 as those of Th2 responses. IL-10 and TGF-beta were measured as indicators of T cell regulator responses. The results showed that treatment with SIN was followed by decreases in the incidence and severity of CIA, anti-CII IgG and the antigen-specific splenocyte proliferation. Production of all isotypes of antibodies including anti-CII IgG2a, IgG1 and IgE as well as secretion of cytokines such as IFN-gamma and IL-5 were suppressed by SIN. In addition, SIN enhanced the secretion of TGF-beta while it had no obvious effect on production of IL-10. These results suggest that the anti-arthritic effect of SIN may be related to the suppression of both Th1 and Th2 immune responses. TGF-beta may at least in part contribute to the suppression of Th1 as well as Th2 immune responses.


A comparison of perioperative charges and outcome between open and mini-open approaches for anterior lumbar discectomy and fusion.
The objectives of this study were to examine charge data and long-term outcomes of two approaches for anterior lumbar interbody fusion: a mini-open lateral approach (extreme lateral interbody fusion, XLIF) and an open anterior approach (anterior lumbar interbody fusion, ALIF) through retrospective chart review. A total of 202 patients underwent surgery: 87 with ALIF (Open) and 115 with XLIF (Mini-open) procedures, all with transpedicular fixation. Complications occurred in 16.7% of Open, and 8.2% of Mini-open, procedures (p = 0.041). The mean charges ($US) for one-level Mini-open and Open procedures were $91,995 and $102,146, and for two-level procedures were $124,540 and $144,183, respectively. All differences were statistically significant (p < 0.05). This represents a 10% cost-savings, based on charges, for one-level and 13.6% for two-level Mini-open compared to Open procedures. Functional outcomes improved significantly at two years for both cohorts, although the difference between groups was not statistically significant. In conclusion, the Mini-open approach, compared to the Open, resulted in clinical as well as cost benefits with similar long-term outcomes.


Comparison of parameters from Heidelberg Retina Tomographs 2 and 3.
To compare stereometric parameters and classification results from the Heidelberg Retina Tomograph version 2 (HRT2); HRT3; and HRT3 Glaucoma Probability Score (GPS), an automated method of obtaining optic nerve head analysis without the need for manual definition of disc margin. Retrospective cross-sectional study. Five hundred four eyes from 281 consecutive subjects (glaucoma, glaucoma suspect, and healthy) evaluated in a glaucoma clinic. All participants had HRT2 scanning of the optic nerve head. Inclusion criteria were scans with good centration and focus, even illumination, an overall quality score by HRT3 of acceptable or better, and standard deviation < 50 mum. A Bland-Altman analysis was used for the comparison of HRT2 and HRT3. From these results, calibration equations were determined to permit conversion of the measurements between devices. The agreement between HRT2 and HRT3 Moorfields regression analysis (MRA) and HRT3 GPS classification methods was measured using kappa statistics. Heidelberg Retina Tomograph version 2 and HRT3 stereometric parameters, MRA, and global GPS. There was a statistically significant difference between HRT2 and HRT3 global disc area, rim area, cup area, rim volume, cup volume, height variation contour, and retinal nerve fiber layer cross-sectional area stereometric parameters. All of those parameters were smaller using HRT3, due to a manufacturer-reported horizontal scaling error of 4% in HRT2 that was corrected in HRT3. kappas for agreement were 0.60 between classifications (within normal limits, borderline, and outside normal limits) of MRA by HRT2 and HRT3 and 0.47 between HRT3 MRA and GPS. The HRT3 generally provided smaller stereometric disc measurements than HRT2. There was no clear conversion between HRT3 and GPS parameters, as the 2 methods for measuring the stereometric parameters differ.


Cannabinoid receptors in acute and chronic complications of atherosclerosis.
Atherosclerosis is a chronic inflammatory disease that is the primary cause of myocardial infarction and stroke, which occur after sudden thrombotic occlusion of an artery. A growing body of evidence suggests that cannabinoid signalling plays a fundamental role in atherosclerosis development and its clinical manifestations. Thus, CB2 receptors are protective in myocardial ischaemia/reperfusion and implicated in the modulation of chemotaxis, which is crucial for the recruitment of leukocytes during inflammation. Delta-9-Tetrahydrocannabinol (THC)-mediated activation has been shown to inhibit atherosclerotic plaque progression in a CB2 dependent manner. Although CB1 and CB2 expression has been reported on platelets, their involvement in thrombus formation is still controversial. While several reports suggest that CB1 receptors may have a relevant role in neuroprotection after ischaemic stroke, recent studies show the protective effects in various forms of neuroprotection are not related to CB1 stimulation, and a protective role of CB1 blockade has also been reported. In addition, vascular and myocardial CB1 receptors contribute to the modulation of blood pressure and heart rate. It is tempting to suggest that pharmacological modulation of the endocannabinoid system is a potential novel therapeutic strategy in the treatment of atherosclerosis. For these purposes, it is important to better understand the complex mechanisms of endocannabinoid signalling and potential consequences of its pharmacological modulation, as it may have both pro- and anti-atherosclerotic effects.


[Functional role of pulmonary surface-active substances].
Freshly prepared from the rat lung solution of the surfactant active substances (SA1) accelerated oxygen absorption at the borderline of the phases. The oxidized SA1 solutions produced an inhibitory effect. As suggested, functional role of SA1 in the realization of external respiration is not limited to reduction of surface tension and alveoli stabilization, but also includes participation in oxygen absorption and its transport regulation through the aerohematic barrier.


Syn- and anticlinal isomers of 2a'-acetoxy-1,7'-diacetyl-7',7a'-dihydro-2-oxospiro[1H-indole-3(2H),2'(2a'H)-oxeto[3,2-b]indole].
In the syn- and anticlinal isomers of the title compound, C(22)H(18)N(2)O(6), the indole moiety is not completely planar, with the pyrrolidine ring being distorted very slightly towards a conformation intermediate between half-chair and envelope. The molecular and packing structures in the crystals of these isomers are stabilized by C-H...O interactions.


The trihelix family of transcription factors--light, stress and development.
GT factors are the founding members of the trihelix transcription factor family. They bind GT elements in light regulated genes, and their nature was uncovered in a burst of activity in the 1990s. Study of the trihelix family then slowed. However, interest is now re-awakening. Genomic studies have revealed 30 members of this family in Arabidopsis and 31 in rice, falling into five clades. Newly discovered functions involve responses to salt and pathogen stresses, the development of perianth organs, trichomes, stomata and the seed abscission layer, and the regulation of late embryogenesis. Thus the time is ripe for a review of the genomic and functional information now emerging for this neglected family.


Minimally invasive approaches to axillary osmidrosis treatment: A comparison between superficial liposuction with automatic shaver curettage, subcutaneous laser treatment, and microwave-based therapy with a modified technique.
Minimally invasive techniques, including superficial liposuction with automatic shaver curettage (LC), subcutaneous laser treatment, and microwave-based therapy have been developed to treat osmidrosis. Few studies have compared these three techniques in relation to clinical efficacy, life quality improvement, and downtime. We aim to evaluate clinical results and life quality improvement, in addition to downtime and complications, between these three techniques. Clinical records of patients treated with these three minimally invasive techniques for axillary osmidrosis were retrospectively reviewed. Hyperhidrosis disease severity scale, Dermatology Life of Quality Index, clinical improvement, complication, and recurrence were assessed. Among 403 patients, 168 received microwave-based therapy, 119 received subcutaneous laser treatment, and 116 received LC. All treatments showed significant improvements (P < 0.001) in HDSS, DLQI and clinical result after 3 and 12 months comparing to the baseline. But the improvements of subcutaneous laser were significantly inferior to microwave-base therapy and LC. Patients who received LC had a significantly longer downtime (P < 0.001) than those who received other treatments. The recurrence rate was significantly higher in the subcutaneous laser treatment group, and the microwave-based therapy group exhibited a longer recurrence duration (P < 0.001). LC group presented higher complication rate than other treatments. Comparing to other treatments, microwave-based therapy was effective in treating osmidrosis with minimal downtime, recurrence, and complications. It could be a durable and effective therapeutic modality for osmidrosis and is less operator-dependent. It may be considered as a first-line treatment for axillary osmidrosis.


Isolation and characterization of parasites and host cell ghosts from erythrocytes infected with Plasmodium chabaudi.
A new procedure has been developed which allows the concomitant isolation of viable parasites and host cell plasma membranes from erythrocytes infected with Plasmodium chabaudi trophozoites. The average final yield of parasites is 56%. Free parasites reveal a well preserved ultrastructure, incorporate [14C]isoleucine for at least 3 h, and synthesize about the same proteins as parasites within erythrocytes as monitored by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)-autoradiography. The host cell plasma membranes can be isolated in the form of ghosts with an average yield of 27%. The ghosts possess a structurally intact plasma membrane as revealed by freeze-etch electron microscopy. The ghosts are regularly associated with seven neo-proteins as identified by SDS-PAGE and isoelectric focusing (IEF)/SDS-PAGE. These neo-proteins have the following apparent molecular masses: 154 kDa, 145 kDa, 90 kDa, 72 kDa (pI 4.5), 67 kDa, 52 kDa, and 33 kDa (pI 5.7), respectively. The contamination of ghosts by parasite material and, conversely, the contamination of parasites by host cell plasma membranes is very low as demonstrated by light and electron microscopy, lactoperoxidase-mediated radioiodination and the distribution of the typical parasite marker enzymes such as choline kinase, cholinephosphotransferase and ethanolaminephosphotransferase.


Synthesis of a specific oligodeoxyribonucleotide probe and its use for studying proenkephalin A gene expression.
A 44-mer, complementary to the coding region of bovine adrenal medullary proenkephalin A mRNA (ProEnkA mRNA) has been synthesized as a specific probe for this mRNA. Northern-blot hybridization analysis identified a single band in an RNA extract from bovine, ovine and porcine adrenal medullae. The molecular size of these hybridized bands (1400-1600 nucleotides) was in excellent agreement with that reported previously using cloned cDNA probes. In situ hybridization on bovine and ovine adrenal sections revealed that ProEnkA mRNA was localized selectively in cells at the outer margin of the medulla, a region rich in adrenaline-containing cells. This study both confirms and extends previous findings with cloned cDNA probes on the presence of high concentrations of ProEnkA mRNA in cells at the periphery of the adrenal medulla. In addition, it demonstrates the usefulness of synthetic oligodeoxyribonucleotides as specific and sensitive probes for the study of proenkephalin A gene expression.


Pilot testing model to uncover industrial symbiosis in Brazilian industrial clusters.
The main objective of this study was to create a pilot model to uncover industrial symbiosis practices in Brazilian industrial clusters. For this purpose, a systematic revision was conducted in journals selected from two categories of the ISI Web of Knowledge: Engineering, Environmental and Engineering, Industrial. After an in-depth revision of literature, results allowed the creation of an analysis structure. A methodology based on fuzzy logic was applied and used to attribute the weights of industrial symbiosis variables. It was thus possible to extract the intensity indicators of the interrelations required to analyse the development level of each correlation between the variables. Determination of variables and their weights initially resulted in a framework for the theory of industrial symbiosis assessments. Research results allowed the creation of a pilot model that could precisely identify the loopholes or development levels in each sphere. Ontology charts for data analysis were also generated. This study contributes to science by presenting the foundations for building an instrument that enables application and compilation of the pilot model, in order to identify opportunity to symbiotic development, which derives from "uncovering" existing symbioses.


Identification of Actinobacillus pleuropneumoniae biovars 1 and 2 in pigs using a PCR assay.
Actinobacillus pleuropneumoniae causes swine pleuropneumonia worldwide. Previously, we described a gene sequence of approximately 800bp in A. pleuropneumoniae serotype 1 that encodes a metalloprotease of 24kDa, (Genbank accession no. AY217757). We selected primers carrying the forward and reverse 5'-terminal sequences of this region of the gene for the development of a species-specific PCR assay. The primers amplified an 800bp sequence from isolated DNA and lysed bacteria of the 13 A. pleuropneumoniae biovar 1 serotypes, with the exception of subtype 1b. The primers also amplified the sequence in nasal secretion cultures from pigs with chronic and acute experimental pleuropneumonia. No PCR products were detected when A. pleuropneumoniae serotypes of biovar 2 were used. Internal primers from this gene sequence detected biovar 2 and subtype 1b, leading to the production of a 350bp PCR product. The primers did not amplify DNA from other related species from the Pasteurellaceae family. The 800bp PCR assay was sensitive in vitro, with a detection limit of 5.5pg of extracted DNA, and an average of 120CFU. The specificity and sensitivity of this PCR assay make it a useful method for the rapid identification and diagnosis of A. pleuropneumoniae.


Single nucleotide polymorphisms of PIN1 promoter region and cancer risk: evidence from a meta-analysis.
Peptidylprolyl cis/trans isomerase NIMA-interacting 1 (PIN1) is involved in the process of tumorigenesis. The two single nucleotide polymorphisms (-677T>C, -842G>C) in the PIN1 promoter region have been suspected of being associated with cancer risk for years, but the conclusion is still inconclusive. Eligible case-control studies were retrieved by searching databases and references of related reviews and studies. Genotype distribution data, adjusted odds ratios (ORs) and 95% confidence (CIs) intervals were extracted to calculate pooled ORs. A total of 4619 cancer cases and 4661 controls were included in this meta-analysis. Overall, the PIN1 -667T>C polymorphism was not associated with cancer risk, while the -842C allele was significantly associated with reduced cancer risk (CC+GC vs. GG, OR = 0.725, 95% CI: 0.607-0.865; P(heterogeneity) = 0.012 and GC vs. GG: OR = 0.721, 95% CI: 0.591-0.880; P(heterogeneity) = 0.003). Results from genotype distribution data were in agreement with those calculated with adjusted ORs and 95% CIs. No publication bias was detected. Results of this meta-analysis suggest that the PIN1 -842G>C polymorphism is associated with decreased cancer risk, but that the -667T>C polymorphism is not.


Antagonism by nalmefene of systemic and intrathecal morphine-induced analgesia in mice.
Nalmefene is an orally active opiate antagonist structurally related to naloxone and naltrexone. In this study using two different strains of mice (Swiss Cox and ICR), the antagonist activity of nalmefene given subcutaneously (sc) was quantified by determination of the apparent pA2 values against the antinociceptive activity (tail flick and hot plate tests) of morphine given sc or intrathecally (lumbar spinal cord). The apparent pA2 values (constrained to a slope of -1) were 8.06 (7.79-8.33) in Swiss Cox mice and 7.81 (7.62-8.00) in ICR mice in the tail flick test with sc morphine. These values were larger than the corresponding value for naloxone in ICR mice, 7.35 (7.10-7.60). The hot plate test provided similar results: the apparent pA2 values for nalmefene with sc morphine were 8.14 (7.89-8.39) in Swiss Cox mice and 7.81 (7.65-7.97) in ICR mice, values which were different from naloxone 7.33 (7.23-7.42) in ICR mice. Apparent pA2 values for nalmefene with intrathecal morphine were not different from those for naloxone in the tail flick test. Thus, these sets of results suggest that it may be worthwhile to further determine whether systemic nalmefene might possibly possess an advantage over naloxone in antagonizing systemic side effects of morphine arising from local spinal morphine administration.


Toxoplasma gondii infection in first-episode and inpatient individuals with schizophrenia.
A high seroprevalence of Toxoplasma gondii infection has been detected in psychiatric patients, particularly in schizophrenia cases. In the present study 98 patients suffering from schizophrenia (58 inpatients and 40 first-episode patients) and 96 control patients (50 healthy volunteers and 46 with a depressive disorder) were examined for the presence of both IgG and IgM antibodies against T. gondii by enzyme-linked immunosorbent assay (ELISA). We applied the Bradford Hill criteria to identify the weight of causal inference. The positivity rate of anti-T. gondii IgG antibodies among individuals with schizophrenia (57.1%) was significantly higher than in healthy controls (29.2%). There were no associations between immune status ratio (ISR) values and the risk of schizophrenia. The weight of evidence approach using the Bradford Hill criteria revealed a 92% probability of a causal association. Our results show that exposure to T. gondii may lead to schizophrenia.


Genetic and environmental contributions to the covariance between occupational status, educational attainment, and IQ: a study of twins.
Scores of occupational status, educational attainment, and IQ were obtained for 507 monozygotic and 575 dizygotic male twin pairs born 1931-1935 and 1944-1960. A multivariate genetic analysis with statistics from different cohorts showed heterogeneity between cohorts, and analyses were performed in four separate cohorts. The only set of results which departed clearly from the rest was found for the group born 1931-1935, where the ratio of environmental to genetic effects exceeded those of the other groups. Typical heritability values in the three youngest groups (weighted means) were .43, .51, and .66 for occupation, education, and IQ, respectively. The values in the oldest group were .16, .10, and .37, but this sample is small and the estimates are unstable. Genetic variance influencing educational attainment also contributed approximately one-fourth of the genetic variance for occupational status and nearly half the genetic variance for IQ. The values for the between-families variances (reflecting family environment and assortative mating) varied from 2 to 35% in the three youngest groups but were higher for education (62%) and IQ (45%) in the oldest groups. All the between-families variance was common to all three variables. For educational attainment and IQ, the bulk of this between-families variance is probably genetic variance due to assortative mating. The common-factor environmental within-family variances were generally small, and the specific estimates seemed to contain mainly measurement error.


Real-time bioelectronic sensing of environmental contaminants.
Real-time chemical sensing is crucial for applications in environmental and health monitoring1. Biosensors can detect a variety of molecules through genetic circuits that use these chemicals to trigger the synthesis of a coloured protein, thereby producing an optical signal2-4. However, the process of protein expression limits the speed of this sensing to approximately half an hour, and optical signals are often difficult to detect in situ5-8. Here we combine synthetic biology and materials engineering to develop biosensors that produce electrical readouts and have detection times of minutes. We programmed Escherichia coli to produce an electrical current in response to specific chemicals using a modular, eight-component, synthetic electron transport chain. As designed, this strain produced current following exposure to thiosulfate, an anion that causes microbial blooms, within 2 min. This amperometric sensor was then modified to detect an endocrine disruptor. The incorporation of a protein switch into the synthetic pathway and encapsulation of the bacteria with conductive nanomaterials enabled the detection of the endocrine disruptor in urban waterway samples within 3 min. Our results provide design rules to sense various chemicals with mass-transport-limited detection times and a new platform for miniature, low-power bioelectronic sensors that safeguard ecological and human health.


HIV-1 Rev transactivator: a beta-subunit directed substrate and effector of protein kinase CK2.
The phosphorylation of HIV-1 Rev by protein kinase CK2 is strictly dependent on the regulatory beta subunit of the kinase and is deeply affected by conformational changes of the substrate outside the phosphorylation site. Here we show that Rev modulates a variety of CK2 properties, including autophosphorylation, catalytic activity toward calmodulin, and susceptibility to polycationic effectors, whose common denominator is the involvement of the beta subunit. Rev's two major CK2 sites are located at its N-terminus, immediately adjacent to a helix-loop-helix motif. By comparing the behaviour of full-size Rev with that of synthetic peptides reproducing, with suitable modifications, its N-terminal 26 amino acids including the phosphoacceptor site (Ser 5, Ser 8) and amphipathic helix-1, it appears that the functional interaction of the N-terminal portion of Rev with the N-terminal domain of the beta subunit must rely on both electrostatic and hydrophobic interactions. The former mainly involve Rev's arginine-rich domain (residues 35-50) in helix-2, while the latter are mostly mediated by residues 12-24 of helix-1. These data disclose the possibility that, besides displaying protective, regulatory and targeting properties with respect to the catalytic subunit, the CK2 beta subunit also plays a role as a docking site for a subset of CK2 substrates.


Discrepancies between Turkish mothers' and adolescents' reports of adolescents' emotion regulation difficulties.
The aim of the present study was to examine discrepancies between Turkish mothers' and adolescents' reports in terms of adolescents' difficulties in emotion regulation. In addition, the mediating role of mothers' own emotion regulation difficulties between mothers' psychological symptoms and the discrepancy on reports of adolescents' difficulties in emotion regulation was examined. A total of 595 first-year high school students (300 females and 295 males) whose ages ranged between 14 and 17 years participated in the study. In addition, 365 mothers (61.34%) completed the questionnaires. Mean age of mothers was 41.86 years (standard deviation = 5.02) ranging from 32 to 61 years. The results revealed that adolescents tended to report higher levels of difficulties in emotion regulation for themselves as compared with mothers' report, and girls reported more difficulties for their emotion regulation than boys. It was also found that mothers' own emotion regulation difficulties mediated the relation between mothers' psychological symptoms and discrepancy on reports of adolescents' emotion regulation difficulties. Mothers may be less likely to endorse their children's emotion regulation difficulties since they cannot observe various aspects of their children's emotion regulation. On the other hand, the mothers' perception of their children's emotion regulation could be affected from their own emotion regulation difficulties, which could be a result of their psychological problems.


Size-dependent activity of silver nanoparticles on the morphological switch and biofilm formation of opportunistic pathogenic yeasts.
Dimorphism and biofilm formation are important virulence factors of some opportunistic human pathogenic yeasts. Such species commensally colonize skin or mucosal surfaces generally in yeast form, but under particular circumstances, convert into virulent hyphae and disseminate internal organs or cause mucocutaneous infections. The yeast-to-hypha shape-conversion promotes the development of a biofilm, a thick extracellular matrix with sessile cells within. The biofilm is capable to prevent the penetration of antifungal drugs, rendering the surviving biofilm-resident cells intrinsic sources of recurrent infections. The aim of this study was to evaluate the ability of silver nanoparticles (AgNPs) to attenuate the morphological switch and biofilm formation of several opportunistic pathogenic yeasts and to determine whether this feature depends on the nanoparticle size. AgNPs in three different sizes were prepared by chemical reduction approach and characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and dynamic light scattering. The antifungal activity was evaluated by the microdilution method, the inhibitory capacity on biofilm formation and the biofilm degradation ability of differently sized AgNPs was assessed by viability assay. The morphological state of opportunistic pathogenic yeast cells in monoculture and in co-culture with human keratinocytes in the presence of AgNPs was examined by flow cytometry and scanning electron microscopy. All the three AgNPs inhibited the growth of the examined opportunistic pathogenic yeasts, nevertheless, AgNPs with the smallest diameter exhibited the most prominent toxic activities. AgNPs attenuated the biofilm formation in a nanoparticle size-dependent manner; however, their biofilm destruction capacity was negligible. AgNPs with the smallest size exerted the most significant effect on suppressing the morphological change of pathogens in monoculture as well as in a co-culture with keratinocytes. Our results confirm that AgNPs are capable to hinder yeast-to-hypha morphological conversion and biofilm formation of opportunistic pathogens and this biological effect of AgNPs is size-dependent.


Purification of aspartase and aspartokinase-homoserine dehydrogenase I from Escherichia coli by dye-ligand chromatography.
Improved purification schemes are reported for the enzymes L-aspartase and aspartokinase-homoserine dehydrogenase I from Escherichia coli. Dye-ligand chromatography on commercially available dye matrices are incorporated as key steps in these purifications. Red A-agarose has a high affinity for L-aspartase, which is then eluted as a homogeneous protein fraction with 1 mM L-aspartic acid. Green A-agarose shows a high binding affinity for the bifunctional enzyme aspartokinase-homoserine dehydrogenase I. Purification is accomplished by elution with NADP+, followed by formation of a ternary complex with NADP and cysteine, a good competitive inhibitor of the homoserine dehydrogenase activity, and rechromatography on Green A-agarose. The final specific activity of each purified enzyme equaled or exceeded previously reported values, the overall yield of enzymes obtained was significantly higher, and these improved purification schemes were found to be more amenable to being scaled up for the production of large quantities of purified enzyme.


Semi-permanent transcorneal filter support and in vivo surgical implantation technique for open-angle glaucoma treatment.
Primary open-angle glaucoma is a progressive disease affecting nearly 60 million people worldwide which, if left untreated, can lead to optic nerve head damage and complete loss of sight. Current interventions include: pharmaceutical drops, laser surgery, shunts, and bleb; however, these methods provide insufficient long-term efficacy in intraocular pressure management. We developed a semi-permanent, implantable transcorneal duct as a new aid in the treatment of this disease. The duct, composed of an intracorneal stabilizing washer and hollow screw, creates an interface between the anterior chamber and the external environment, allowing for the outflow of excess aqueous humor. We discuss the fluid mechanics behind designing and implementing a filter material capable of preventing the ingress of bacteria and viruses while modifying aqueous humor outflow resistances to pre-glaucomatous levels, finding the effective radius of such a material to be 10.44 μm. After performing surgical implantation in four rabbit eyes, subsequent testing showed successful integration between the screw and washer. Colored saline injections highlighted fluid flow progression out of the eye through the duct, suggesting that the device may be a viable approach to treating high intraocular pressure created by open-angle glaucoma.


Unbalanced translocation between chromosomes 2 and 7 with de novo deletion of band 35 on the long arm of chromosome 2.
Clinical and cytogenetical findings are described in an infant with a de novo deletion of the long arm of chromosome 2. The boy's karyotype is 46,XY, rec(2)delq,t(2;7) (2pter----2q34::7p21----7pter) (7qter----7p21::2q36----2qter). He showed developmental retardation, low-set ears, micrognathia, short, neck, abundant skin of the neck, tetralogy of Fallot, bipartite labialike scrotum, clitorislike penis, cryptorchism, and deformities of the hands and feet.


Loss of protein kinase C theta, Bcl10, or Malt1 selectively impairs proliferation and NF-kappa B activation in the CD4+ T cell subset.
The cytosolic proteins protein kinase Ctheta (PKCtheta), Bcl10, and Malt1 play critical roles in TCR signaling to the transcription factor NF-kappaB. Our data confirm that CD4(+) T cells from PKCtheta, Bcl10, and Malt1 knockout mice show severe impairment of proliferation in response to TCR stimulation. Unexpectedly, we find that knockout CD8(+) T cells proliferate to a similar extent as wild-type cells in response to strong TCR signals, although a survival defect prevents their accumulation. Both CD4(+) and CD8(+) knockout T cells express activation markers, including CD25, following TCR stimulation. Addition of exogenous IL-2 rescues survival of knockout CD4(+) and CD8(+) T cells, but fails to overcome the proliferation defect of CD4(+) T cells. CD4(+) T cells from knockout mice are extremely deficient in TCR-induced NF-kappaB activation, whereas NF-kappaB activation is only partially impaired in CD8(+) T cells. Overall, our results suggest that defects in TCR signaling through PKCtheta, Bcl10, and Malt1 predominantly impair NF-kappaB activation and downstream functional responses of CD4(+) T cells. In contrast, CD8(+) T cells maintain substantial NF-kappaB signaling, implying the existence of a significant TCR-regulated NF-kappaB activation pathway in CD8(+) T cells that is independent of PKCtheta, Bcl10, and Malt1.


Chronic treatment with the opioid antagonist naltrexone favours the coupling of spinal cord μ-opioid receptors to Gαz protein subunits.
Sustained administration of opioid antagonists to rodents results in an enhanced antinociceptive response to agonists. We investigated the changes in spinal μ-opioid receptor signalling underlying this phenomenon. Rats received naltrexone (120 μg/h; 7 days) via osmotic minipumps. The antinociceptive response to the μ-agonist sufentanil was tested 24 h after naltrexone withdrawal. In spinal cord samples, we determined the interaction of μ-receptors with Gα proteins (agonist-stimulated [(35)S]GTPγS binding and immunoprecipitation of [(35)S]GTPγS-labelled Gα subunits) as well as μ-opioid receptor-dependent inhibition of the adenylyl cyclase (AC) activity. Chronic naltrexone treatment augmented DAMGO-stimulated [(35)S]GTPγS binding, potentiated the inhibitory effect of DAMGO on the AC/cAMP pathway, and increased the inverse agonist effect of naltrexone on cAMP accumulation. In control rats, the inhibitory effect of DAMGO on cAMP production was antagonized by pertussis toxin (PTX) whereas, after chronic naltrexone, the effect became resistant to the toxin, suggesting a coupling of μ-receptors to PTX-insensitive Gα(z) subunits. Immunoprecipitation assays confirmed the transduction switch from Gα(i/o) to Gα(z) proteins. The consequence was an enhancement of the antinociceptive response to sufentanil that, in consonance with the neurochemical data, was prevented by Gα(z)-antisense oligodeoxyribonucleotides but not by PTX. Such changes in opioid receptor signalling can be a double-edged sword. On the one hand, they may have potential applicability to the optimisation of the analgesic effects of opioid drugs for the control of pain. On the other hand, they represent an important homeostatic dysregulation of the endogenous opioid system that might account for undesirable effects in patients chronically treated with opioid antagonists. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.


Delivery of self training and education for stressful situations (DESTRESS-PC): a randomized trial of nurse assisted online self-management for PTSD in primary care.
This randomized controlled trial examined the effectiveness of a nurse assisted online cognitive-behavioral self-management intervention for war-related posttraumatic stress disorder (PTSD), compared to optimized usual primary care PTSD Treatment (OUC) to reduce PTSD symptoms. Participants were 80 veterans of recent military conflicts with PTSD as assessed by the PTSD Checklist (PCL) seeking primary care treatment at one of three Veterans Affairs (VA) and four Army clinics. DESTRESS-PC consisted of logins to a secure website three times per week for 6 weeks with monitoring by a study nurse. All participants received nurse care management in the form of phone check-ins every two weeks and feedback to their primary care providers. Blinded raters assessed outcomes 6, 12, and 18 weeks post-randomization. DESTRESS-PC was associated with a significantly greater decrease in PTSD symptoms compared to OUC (F(3, 186)=3.72, p=.012). The effect was largest at the 12-week assessment (∆PCL=12.6±16.6 versus 5.7±12.5, p<0.05) with the treatment effect disappearing by the 18-week follow-up. Notably, there was a dose effect; number of logins correlated significantly with PTSD outcomes, with more logins associated with greater PTSD symptom improvement. None of the secondary outcomes (depression, anxiety, somatic symptoms, and functional status) showed statistically significant improvement; however, the treatment effect on depression approached significance (F(3, 186)=2.17, p=.093). DESTRESS-PC shows promise as a means of delivering effective, early PTSD treatment in primary care. Larger trials are needed.


mHealth Interventions to Promote Anti-Retroviral Adherence in HIV: Narrative Review.
Antiretrovirals (ARVs) are key in the management of HIV. Although no cure exists, ARVs help patients live healthy lives and prevent transmission to others. Adherence to complex regimens is paramount to outcomes and in avoiding the emergence of drug-resistant viruses. The goal of therapy is to reach an undetectable viral load. However, adherence is a common problem, stemming from issues such as mental health, chaotic home situations, and busy work schedules. Mobile health (mHealth) represents a new approach in improving medication adherence, and multiple studies have been performed in this area. This study aims to review the current implementation of mHealth in the management of HIV among different groups of patients. We used PubMed, Academic Search Elite, and 1 journal database with various search terms to review the current implementation of mHealth in HIV care. Titles and abstracts were screened, and 61 papers were identified and fully reviewed. The literature was divided into lower- and higher-income nations, as defined by the United Nations. A total of 20 studies with quantitative results were identified, with 10 being text- and SMS-based interventions (the majority of these being in lower-income countries) and 8 being smartphone-based apps (primarily in higher-income countries). The majority of these studies determined whether there was an effect on adherence or biochemical parameters (viral load and CD4 count). Various qualitative studies have also been conducted, and many have focused on determining the specific design of interventions that were successful (frequency of messaging, types of messages, etc) as well as priorities for patients with regard to mHealth interventions. There seems to be a role of mHealth in the management of HIV in lower-income nations; however, the optimal design of an intervention needs to be delineated. In higher-income countries, where the 2 significant risk factors were injection drugs and men who have sex with men, the benefit was less clear, and more research is needed.


Factor VIII and transmissible spongiform encephalopathy: the case for safety.
Haemophilia A is the most common inherited bleeding disorder, caused by a deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A is based on repeated infusions of plasma-derived FVIII concentrate or of recombinant FVIII, which may be exposed to plasma-derived material of human or animal origin used in its tissue culture production process. We review epidemiological and experimental studies relevant to blood infectivity in the transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and evaluate the hypothetical risk of TSE transmission through treatment with plasma-derived or recombinant FVIII.


Nonatherosclerotic coronary artery disease in young women.
Nonatherosclerotic coronary artery disease (NACAD) is an important cause of myocardial infarction (MI) in young women but is often missed on coronary angiography, especially spontaneous coronary artery dissection (SCAD). The prevalence of NACAD in young women has not been described. We retrospectively reviewed all coronary angiograms of women aged 50 years and younger at Vancouver General Hospital from December 1, 2009 to November 30, 2011. The angiograms were reviewed by 2 experienced interventional cardiologists, and reported as normal (<30% stenosis), atherosclerotic coronary artery disease (ACAD), or NACAD. NACAD was further characterized as SCAD, coronary fibromuscular dysplasia (FMD), ectasia, vasculitis, embolism, congenital anomaly, or unclear etiology. Of 7605 coronary angiograms performed, 177 were done in women aged 50 years and younger. The mean age was 45.4 ± 4.9 (range, 31-50) years, 76 of 177 (42.9%) presented with acute coronary syndrome, and 66 were troponin-positive. Ninety-seven (54.8%) women had normal arteries, 54 (30.5%) had ACAD, 23 (13.0%) had NACAD, and 3 (1.7%) had unclear etiology. Of those with NACAD, SCAD was observed in 16 (all troponin-positive and 13 of 16 had noncoronary FMD), and 2 had irregular beading suspicious of coronary FMD. Coronary vasculitis was suspected in 2, and 5 had coronary ectasia. Among women with MI (66/177), 19 (28.8%) had normal arteries (3 Takotsubo cardiomyopathy), 24 (36.4%) had ACAD, 20 (30.3%) had NACAD, 16 (24.2%) had SCAD, and 3 had unclear etiology. NACAD was not rare among young women (aged 50 years and younger) undergoing coronary angiography and was an important cause of MI, accounting for 30%. SCAD was the most commonly encountered NACAD in young women, causing 24% of MIs.


Effects of modulators of the production and degradation of hydrogen peroxide on erythropoietin synthesis.
Erythropoietin (Epo) synthesis is suppressed in normoxia and stimulated in hypoxia. To test the hypothesis that the cellular H2O2 level is important in the control of Epo synthesis, we have studied effects of modulators of H2O2 generation and degradation on Epo production in human hepatic cell cultures (hepatoma lines HepG2 and Hep3B). In addition, we measured the activities of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) in cultures following hypoxia exposure or H2O2 treatment. The results show that the formation of immunoreactive Epo was stimulated in normoxic cultures by treatment with exogenous catalase thus mimicking the effect of hypoxia (24 h incubation periods). Epo production was also stimulated when scavengers of reactive O2 species (tetramethylthiourea, dihydrorhodamine) were added to the cells. On the other hand, stimulators of H2O2 generation (xanthine oxidase, glucose oxidase, NADH, NADPH) lowered Epo production in hypoxic cultures. Hypoxia exposure decreased superoxide dismutase activity and H2O2 treatment reduced catalase activity thus influencing the endogenous antioxidant defense system. These findings support the concept that reactive O2 species, primarily H2O2, act as messengers in the O2-dependent control of the hepatic production of Epo. Changes in the cellular activities of antioxidant enzymes appear to play only a minor role in this process.


RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function.
RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders.


Regulation of urinary phosphate excretion in camels.
Urinary inorganic phosphorus (P) excretion was measured in 16 adult female non-pregnant, non-lactating daily watered camels. They were randomly divided into four groups of four animals. Groups 1, 2, and received either an i.v. infusion of phosphate or synthetic human parathyroid hormone (PTH) or PTH-related peptide (PTHrP), respectively. The fourth group was used as a control. Intravenous P loading induced a significant increase in phosphatemia and in P renal clearance. Both PTH and PTHrP increased calcemia and decreased phosphatemia. They had no significant effect on urinary calcium excretion, but they increased P renal clearance and phosphaturia. Thus, the regulation of urinary P excretion in normally watered camels looks similar to that already described in other ruminants.


Using a Systematic Framework of Interventions to Improve Early Discharges.
Late-afternoon hospital discharges can lead to admission bottlenecks and negatively affect the flow of patients needing hospital admission. Delays in discharge are a prevalent health care problem and have been linked to increased length of stay, lower patient satisfaction scores, and adverse outcomes. As a result, hospitals are placing a renewed emphasis on early discharge as a way to reduce admission delays and achieve optimal patient flow. This study shows that the Model for Improvement (MFI) is an effective approach for complex improvement efforts. A needs assessment identified four common barriers to early discharge: (1) lack of communication between nurses, case managers, and teams about discharge planning; (2) obtaining home services, equipment, and oxygen early in the morning; (3) arranging transportation to facilities earlier in the day; and (4) communicating discharge expectations with patients and family members. Using the MFI, we tested and implemented interventions in three key areas: education, process changes, and audit and feedback. Key interventions included an educational campaign on the safety implications of reducing emergency department boarding time, an afternoon huddle with MDs and case managers, and a Web-based dashboard to provide real-time discharge by noon (DBN) audit and feedback. The DBN rate increased from a baseline of 10.4% to an average of 19.7% during a 24-month time frame, with significant improvements in average length of stay (5.88 to 5.60) and length of stay index (1.18 to 1.10) (p <0.05). Improving hospital throughput is becoming imperative, and a structured approach to improvement can lead to rapid and sustainable results.


Factors affecting the conversion of apple polyphenols to phenolic acids and fruit matrix to short-chain fatty acids by human faecal microbiota in vitro.
Proanthocyanidins (PAs) in apples are condensed tannins comprised mostly of (-)-epicatechin units with some terminal (+)-catechins. PAs, especially those having a long chain-length, are absorbed in the upper intestine only to a small extent and are passed to the colon. In the colon they are subjected to microbial metabolism by colonic microbiota. In the present article, the ability of human microbiota to ferment apple PAs is studied. Freeze-dried fruit preparations (apple, enzymatically digested apple, isolated cell-walls, isolated PAs or ciders) from two varieties, Marie Ménard and Avrolles, containing PAs of different chain lengths, were compared. Fermentation studies were performed in an in vitro colon model using human faecal microbiota as an inoculum. The maximal extent of conversion to known microbial metabolites, was observed at late time point for Marie Ménard cider, having short PAs. In this case, the initial dose also contributed to the extent of conversion. Long-chain PAs were able to inhibit the in vitro microbial metabolism of PAs shown as low maxima at early time points. Presence of isolated PAs also suppressed SCFA formation from carbohydrates as compared with that from apple cell wall or faecal suspension without substrates. The low maximal extents at early time points suggest that there is a competition between the inhibitory effect of the PAs on microbial activity, and the ability to convert PAs by the microbiota.


The hereditary hyperbilirubinaemias.
The presence of jaundice in the neonate, infant or young child presents a broad differential diagnosis. The 'disease' may be benign, as in breast-milk jaundice, or potentially fatal, as in hereditary fructose intolerance. The cause of the jaundice may be a primary hepatic disorder, such as extrahepatic biliary atresia, or secondary to a non-hepatic cause, such as haemolysis or sepsis. There may be significant hepatic injury and dysfunction, as in fulminant viral hepatitis, or simply elevation of plasma bilirubin, as in Gilbert's syndrome. In this chapter we will discuss the familial hyperbilirubinaemia syndromes. This diverse group of disorders is characterized by hepatic dysfunction in the absence of hepatocellular injury. The first section of the chapter will discuss the unconjugated hyperbilirubinaemias: Crigler-Najjar syndrome I, Crigler-Najjar syndrome II and Gilbert's syndrome. The discovery of the gene for bilirubin uridine diphosphate glucuronosyltransferase has increased our understanding of the genetic heterogeneity and clinical presentation of the Crigler-Najjar syndromes. The remainder of the chapter will discuss the conjugated hyper-bilirubinemias: Rotor syndrome and Dubin-Johnson syndrome. These rare diseases share many clinical features; however, they can be readily distinguished by biochemical markers in the urine and bile.


Piezo1 regulates shear-dependent nitric oxide production in human erythrocytes.
Mature circulating red blood cells (RBCs) are classically viewed as passive participants in circulatory function, given erythroblasts eject their organelles during maturation. Endogenous production of nitric oxide (NO) and its effects are of particular significance; however, the integration between RBC sensation of the local environment and subsequent activation of mechano-sensitive signaling networks that generate NO remain poorly understood. The present study investigated endogenous NO production via the RBC-specific nitric oxide synthase isoform (RBC-NOS), connecting membrane strain with intracellular enzymatic processes. Isolated RBCs were obtained from apparently healthy humans. Intracellular NO was compared at rest and following shear (cellular deformation) using semiquantitative fluorescent imaging. Concurrently, RBC-NOS phosphorylation at its serine1177 (Ser1177) residue was measured. The contribution of cellular deformation to shear-induced NO production in RBCs was determined by rigidifying RBCs with the thiol-oxidizing agent diamide; rigid RBCs exhibited significantly impaired (up to 80%) capacity to generate NO via RBC-NOS during shear. Standardizing membrane strain of rigid RBCs by applying increased shear did not normalize NO production, or RBC-NOS activation. Calcium imaging with fluo-4 revealed that diamide-treated RBCs exhibited a 42% impairment in Piezo1-mediated calcium movement when compared with untreated RBCs. Pharmacological inhibition of Piezo1 with GsMTx4 during shear inhibited RBC-NOS activation in untreated RBCs, whereas Piezo1 activation with Yoda1 in the absence of shear stimulated RBC-NOS activation. Collectively, a novel, mechanically activated signaling pathway in mature RBCs is described. Opening of Piezo1 and subsequent influx of calcium appear to be required for endogenous production of NO in response to mechanical shear, which is accompanied by phosphorylation of RBC-NOS at Ser1177.NEW & NOTEWORTHY The mechano-sensitive ion channel Piezo1 is expressed in enucleated red blood cells and provides a mechanism of shear-induced red cell nitric oxide production via nitric oxide synthase phosphorylation. Thiol oxidation of red cells decreases Piezo1-dependent calcium movement and thus impairs nitric oxide generation in response to mechanical force. The emerging descriptions of exclusively posttranslational signaling networks in circulating red cells as acute regulators of cell function support that these cells play an important role in cardiovascular physiology that extends beyond passive oxygen transport.


Corrosion and wear behavior of Ti-5Cu-xNb biomedical alloy in simulated body fluid for dental implant applications.
The present study examined the corrosion and tribological behavior of novel Ti-5Cu-xNb alloy synthesized via powder metallurgy as a new biomedical material in a simulated bodily fluid (SBF) solution. The electrochemical impedance spectroscopy (EIS) study reveals the formation of two protective layers on the surface of alloys during the test. The alloys spontaneously produce a passivating oxide coating on their surfaces, and the breakdown potential (1.14-1.17 V) and re-passivation current density (2.07-3.04 μAcm-2) were observed during the potentiodynamic polarization test. The highest corrosion resistance was observed for the alloy Ti-5Cu-10Nb (icorr = 21.44 nA-cm-2). The SEM and XPS analysis of the corroded surface showed the formation of oxide on the surfaces of the alloys. The samples were tested at 10 N, 15 N, and 20 N loads against the zirconia counterpart to investigate the effect of loading on friction and wear. The lowest coefficient of friction was obtained for Ti-5Cu-5Nb (0.25-0.41) at 20 N loading, while the maximum for Ti-5Cu-10Nb at 15 N load falls in the range of (0.71-0.25). Additionally, they present the wear rate in the range of (5.3 × 10-8-1.45 × 10-6 mm3/mm), in accordance with the change in microstructure and mechanical properties. However, the wear rate increases with the addition of niobium and reaches the maximum for Ti-5Cu-15Nb at 20 N loading condition, but it is relatively deficient compared to commonly used implant material. Therefore, it is suggested that this β-type Ti-5Cu-xNb alloy is a promising candidate, more suitable than the commercially used Ti and Ti-6Al-4V for dental applications.


Efficacy of crude extract of Aloe secundiflora against Salmonella gallinarum in experimentally infected free-range chickens in Tanzania.
The ethnoveterinary use of Aloe species extract in free-range local chickens against fowl typhoid was investigated. Five-months-old local chickens, free of antibodies against fowl typhoid were used. The chickens were randomly assorted into five groups including pretreated and infected (G1, n=21), infected and untreated (G2, n=21), infected and treated (G3, n=21), untreated and uninfected (G4, n=10) and treated uninfected (G5, n=10). Groups 1, 2 and 3 were inoculated with 5.0 x 10(8) c.f.u/ml of Salmonella gallinarum, following which the chickens were monitored for 15 days. There was a delay on the occurrence of the clinical signs and reduced severity of the disease in the Aloe treated chickens (G1 and G3). The mortality rates were 23.8% (5/21) in G1 (pretreated and infected), 42.8% (9/21) in G2 (infected and untreated) and 14.2% (3/21) in G3 (infected and treated). Antibody levels were raised among the infected and untreated group (G2) while they remained relatively low in the Aloe treated groups (G1 and G3). However, there was a sharp increase in the levels of interleukin 6 (IL-6) in the Aloe treated groups (G1 and G3) as compared to the untreated group (G2) until day 9 post-infection. The results of this work indicate that the extract of Aloe secundiflora may be used in the control of fowl typhoid in chickens. Studies to determine the active ingredients of the plant extract are in progress.


LRRC6 regulates biogenesis of motile cilia by aiding FOXJ1 translocation into the nucleus.
LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription. We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings. The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor. Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. Video Abstract.