Omsk haemorrhagic fever.
Omsk haemorrhagic fever is an acute viral disease prevalent in some regions of western Siberia in Russia. The symptoms of this disease include fever, headache, nausea, severe muscle pain, cough, and moderately severe haemorrhagic manifestations. A third of patients develop pneumonia, nephrosis, meningitis, or a combination of these complications. The only treatments available are for control of symptoms. No specific vaccine has been developed, although the vaccine against tick-borne encephalitis might provide a degree of protection against Omsk haemorrhagic fever virus. The virus is transmitted mainly by Dermacentor reticulatus ticks, but people are mainly infected after contact with infected muskrats (Ondatra zibethicus). Muskrats are very sensitive to Omsk haemorrhagic fever virus. The introduction of this species to Siberia in the 1930s probably led to viral emergence in this area, which had previously seemed free from the disease. Omsk haemorrhagic fever is, therefore, an example of a human disease that emerged owing to human-mediated disturbance of an ecological niche. We review the biological properties of the virus, and the epidemiological and clinical characteristics of Omsk haemorrhagic fever.


Regulation of NLRP3 inflammasome by zinc supplementation in Behçet's disease patients: A double-blind, randomized placebo-controlled clinical trial.
Overproduction of NLRP3 inflammasome complex is one of the causes of Behcet's disease's (BD) auto-inflammatory nature. The aim of current study was to examine the effect of zinc supplementation on NLRP3 inflammasome expression; as well as clinical manifestations of BD. In this double-blind parallel placebo-controlled randomized clinical trial, 50 BD patients were randomly allocated into either zinc gluconate (30 mg/day elemental zinc) or placebo groups for 12 weeks. The mRNA expression of NLRP3 and caspase-1 in the leukocytes, serum level of zinc and IL-1β, anthropometric measures, and clinical manifestations of patients were collected at pre- and post-intervention phase. The Iranian Behçet's disease dynamic activity measure (IBDDAM) was scored to measure the treatment effect using the calculation of number needed to treat (NNT). Analysis of covariance was performed to obtain the corresponding effect sizes. Zinc gluconate led to a significant improvement in genital ulcer (P = 0.019). Zinc supplementation decreased NLRP3 and caspase-1 genes expression compared with placebo group (baseline-adjusted P-value = 0.046 for NLRP3 and P-value = 0.003 for caspase-1), even after adjustment for the effect of confounding factors (baseline- and confounders-adjusted P-value = 0.032 for NLRP3 and P-value = 0.004 for caspase-1). Baseline and confounders adjusted effect size demonstrated that zinc was effective in reducing the serum level of IL-1β (P = 0.046). The NNT [95 %CI] for the rate of IBDDAM improvement was 3 [1.7-8.5]. Zinc gluconate supplementation (30 mg/day) for a 3-month period can be considered as an adjuvant therapy in alleviating inflammation and genital ulcer among BD patients.


Outcomes of iliofemoral conduits during fenestrated-branched endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms.
To describe the technical pitfalls and outcomes of iliofemoral conduits during fenestrated-branched endovascular repair (FB-EVAR) of complex abdominal aortic aneurysms (CAAAs) and thoracoabdominal aortic aneurysms (TAAAs). We retrospectively reviewed the clinical data of 466 consecutive patients enrolled in a previous prospective nonrandomized study to investigate FB-EVAR for CAAAs/TAAAs (2013-2021). Iliofemoral conduits were performed through open surgical technique (temporary or permanent) in patients with patent internal iliac arteries or endovascular technique among those with occluded internal iliac arteries. End points were assessed in patients who had any iliac conduit or no conduits, and in patients who had conduits performed prior or during the index FB-EVAR, including procedural metrics, technical success, and major adverse events (MAE). There were 138 CAAAs, 141 extent IV, and 187 extent I-III TAAAs treated by FB-EVAR with an average of 3.89 ± 0.52 vessels incorporated per patient. Any iliac conduit was required in 35 patients (7.5%), including 24 patients (10.4%) treated between 2013 and 2017 and 11 (4.7%) who had procedures between 2018 and 2021 (P = .019). Nineteen patients had permanent conduits using iliofemoral bypass, 11 had temporary iliac conduits, and 5 had endoconduits. Iliofemoral conduits were necessary in 12% of patients with extent I to III TAAA, in 6% with extent IV TAAA, and in 3% with CAAA (P = .009). The use of iliofemoral conduit was more frequent among women (74% vs 27%; P < .001) and in patients with chronic obstructive pulmonary disease (49% vs 28%; P = .013), peripheral artery disease (31% vs 15%; P = .009), and American Society of Anesthesiologists classification of III or higher (74% vs 51%; P = .009). There were no inadvertent iliac artery disruptions in the entire study. The 30-day mortality and MAE were 1% and 19%, respectively, for all patients. An iliofemoral conduit using retroperitoneal exposure during the index FB-EVAR was associated with longer operative time (322 ± 97 minutes vs 323 ± 110 minutes vs 215 ± 90 minutes; P < .001), higher estimated blood loss (425 ± 620 mL vs 580 ± 1050 mL vs 250 ± 400 mL; P < .001), and rate of red blood transfusion (92% vs 78% vs 32%; P < .001) and lower technical success (83% vs 87% vs 98%; P < .001), but no difference in intraoperative access complications and MAEs, compared with iliofemoral conduits without retroperitoneal exposure during the index FB-EVAR and control patients who had FB-EVAR without iliofemoral conduits, respectively. There were no differences in mortality or in other specific MAE among the three groups. FB-EVAR with selective use of iliofemoral conduits was safe with low mortality and no occurrence of inadvertent iliac artery disruption or conversion. A staged approach is associated with shorter operating time, less blood loss, and lower transfusion requirements in the index procedure.


[High clinical value of bone scintigraphy as a staging method for breast cancer].
Bone scintigraphy is a sensitive method for imaging bone metastases in patients with breast cancer. Despite its firm establishment in clinical routine, there are hardly any reliable data from larger homogeneous collectives on the value of bone scintigraphy in the context of staging of first diagnosed breast cancer patients. The aim of our work was to evaluate the real-life performance of bone scintigraphy as a staging examination in female patients with the initial diagnosis of breast cancer. We retrospectively evaluated the data of the patients examined in the year 2015 with the first diagnosis of breast cancer at the University Hospital Marburg by bone scintigraphy. In addition a follow-up over a period of 30 months after the first bone scintigraphy was performed. For this purpose we evaluated whether the results of this initial diagnostic could be confirmed in following diagnostic. 207/258 patients showed no suspicious findings in the initial bone scintigraphy, 48 had an unclear finding, which is why 42 patients received further diagnostics. In follow-up, new bone metastases were found in 4 patients, all of these had scintigraphic findings in the primary diagnosis, which were considered "unclear". Depending on the evaluation of the event (suspicious for metastasis/suspicious for metastasis and unclear), the sensitivity was 37.5%/100%, the specificity 100%/80%, the positive predictive value 100%/15.7% and the negative predictive value 98%/100%. By using bone scintigraphy and, if necessary, subsequent further imaging or histological clarification, a clinically significant diagnosis was obtained in 99,2% of the examined patients and confirmed in the follow-up. This result shows the good real-life performance of bone scintigraphy as a staging examination in patients with first diagnosed breast carcinomas.


Interaction in a dual-species biofilm of Candida albicans and Candida glabrata co-isolated from intravascular catheter.
The use of catheters for vascular access may be associated with colonization by Candida species and their biofilm-forming ability. The latter can harbor two or more species of Candida yeast. In the sense, we conducted our study at the University Hospital of Tlemcen in west Algeria at the neuro-surgery unit, that aims (or which aims) to evaluate the ability to form mixed biofilm by dual-species Candida albicans/Candida glabrata co-isolated from intravascular catheters and their interaction in biofilm. That is the first report in Algeria. During this study, we took photographic images by scanning electron microscopy of 3 catheters implanted before 48 h and co-colonized by dual-species. From all taken samples, 34 catheters were altered by yeasts from which three were co-colonized by two Candida species and C. albicans established synergistic and competitive interactions with C. glabrata species in mixed biofilm tested.


Health-enhancing physical activity during leisure time among adults in Germany.
Self-reported data from the GEDA 2014/2015-EHIS study was used to calculate the level of compliance among adults in Germany with the World Health Organization's (WHO) recommendations on physical activity. The WHO's recommendations distinguish between 'aerobic activity' and 'muscle-strengthening activity'. In Germany, 42.6% of women and 48.0% of men reported that they conduct at least 2.5 hours of aerobic physical activity per week, and therefore meet the WHO's recommendation on this form of activity. A higher level of education among women and men of all ages is associated with a higher frequency of meeting the WHO's recommendations on aerobic activity. In addition, 27.6% of women and 31.2% of men conduct muscle-strengthening activity at least twice a week, thereby meeting the WHO's recommendations on this form of activity. About one fifth of women (20.5%) and one quarter of men in Germany (24.7%) meet both of these recommendations. In summary, the results point to the value of encouraging people to conduct more physical activity during their leisure time. In fact, inactive people who begin to follow the WHO's recommendations can significantly reduce their long-term risk of premature mortality.


Stable numerical results to a class of time-space fractional partial differential equations via spectral method.
In this paper, we are concerned with finding numerical solutions to the class of time-space fractional partial differential equations: D t p u ( t , x ) + κ D x p u ( t , x ) + τ u ( t , x ) = g ( t , x ) , 1 < p < 2 , ( t , x ) ∈ [ 0 , 1 ] × [ 0 , 1 ] , under the initial conditions. u ( 0 , x ) = θ ( x ) , u t ( 0 , x ) = ϕ ( x ) , and the mixed boundary conditions. u ( t , 0 ) = u x ( t , 0 ) = 0 , where D t p is the arbitrary derivative in Caputo sense of order p corresponding to the variable time t. Further, D x p is the arbitrary derivative in Caputo sense with order p corresponding to the variable space x. Using shifted Jacobin polynomial basis and via some operational matrices of fractional order integration and differentiation, the considered problem is reduced to solve a system of linear equations. The used method doesn't need discretization. A test problem is presented in order to validate the method. Moreover, it is shown by some numerical tests that the suggested method is stable with respect to a small perturbation of the source data g ( t , x ) . Further the exact and numerical solutions are compared via 3D graphs which shows that both the solutions coincides very well.


The therapeutic efficacy of glutamine for rats with smoking inhalation injury.
Smoke inhalation injury represents a major cause of mortality in burn patients and is associated with a high incidence of pulmonary complications. Glutamine (GLN) is considered a conditionally essential amino acid during critical illness and injury. However, whether GLN could attenuate lung injury caused by smoke inhalation is still unknown. The purpose of this study is to investigate whether GLN has a beneficial effect on smoke inhalation induced lung injury. In our present work, rats were equally randomized into three groups: Sham group (ambient air inhalation plus GLN treatment), Control group (smoke inhalation plus physiological saline) and GLN treatment group (smoke inhalation injury plus GLN treatment). At sampling, bronchoalveolar lavage fluid was performed to determine total protein concentration and pro-inflammatory cytokine levels. Lung tissues were collected for wet/dry ratio, histopathology, hydroxyproline and Western blotting measurement. Our results exhibited that GLN attenuated the lung histopathological alterations, improved pulmonary oxygenation, and mitigated pulmonary edema. At 28days post-injury, GLN mitigated smoke inhalation-induced excessive collagen deposition as evidence by Masson-Goldner trichrome staining and hydroxyproline content. GLN mitigated smoke inhalation-induced lung inflammatory response, and further prevented the activity of NF-kappa-B. More importantly, results from Western blotting and Immunohistochemistry exhibited that GLN enhanced the expression of HSF-1, HSP-70 and HO-1 in lung tissues. Our data demonstrated that GLN protected rats against smoke inhalation-induced lung injury and its protective mechanism seems to involve in inhibition inflammatory response and enhancing HSP expression.


MicroRNAs in cardiac regeneration and cardiovascular disease.
microRNAs (miRNAs) are a class of small non-coding RNAs, which have been shown important to a wide range of biological process by post-transcriptionally regulating the expression of protein-coding genes. miRNAs have been demonstrated essential to normal cardiac development and function. Recently, numerous studies indicate miRNAs are involved in cardiac regeneration and cardiac disease, including cardiac hypertrophy, myocardial infarction and cardiac arrhythmia. These observations suggest miRNAs play important roles in cardiology. In this review, we summarize the recent progress of studying miRNAs in cardiac regeneration and cardiac disease. We also discuss the diagnostic and therapeutic potential of miRNAs in heart disease.


Systematic review of factors affecting pharmaceutical expenditures.
To systematically identify the main factors contributing to the increase in pharmaceutical expenditures. A systematic search of published studies was conducted utilising major widely used electronic databases using the search terms 'factors,' 'financing,' 'pharmaceutical,' and 'expenditures.' To be included, the studies needed to: (1) measure at least one of the following outcomes: total growth in pharmaceutical expenditures, price growth or quantity growth; (2) mention a clear method for analysing the impact of factors affecting the increases in drug expenditures; (3) be written in English. Nonprimary articles that were published only as an abstract, a review, a commentary or a letter were excluded. From a total of 2039 studies, only 25 were included in the full review. The main determinant categories that were identified in the review were factors related to price, utilisation, therapeutic choice, demand and health care system. The major cost drivers were found to be changes in drug quantities and therapies as well as new drugs. It is important for policymakers to understand pharmaceutical spending trends and the factors that influence them in order to formulate effective cost containment strategies and design optimum drug policy.


HEALER: homomorphic computation of ExAct Logistic rEgRession for secure rare disease variants analysis in GWAS.
Genome-wide association studies (GWAS) have been widely used in discovering the association between genotypes and phenotypes. Human genome data contain valuable but highly sensitive information. Unprotected disclosure of such information might put individual's privacy at risk. It is important to protect human genome data. Exact logistic regression is a bias-reduction method based on a penalized likelihood to discover rare variants that are associated with disease susceptibility. We propose the HEALER framework to facilitate secure rare variants analysis with a small sample size. We target at the algorithm design aiming at reducing the computational and storage costs to learn a homomorphic exact logistic regression model (i.e. evaluate P-values of coefficients), where the circuit depth is proportional to the logarithmic scale of data size. We evaluate the algorithm performance using rare Kawasaki Disease datasets. Download HEALER at http://research.ucsd-dbmi.org/HEALER/ CONTACT: email@example.com Supplementary data are available at Bioinformatics online.


Effects of the Omicron variant on perinatal outcomes in full-term neonates.
Research of coronavirus disease (COVID-19) effects on newborns is ongoing. But the research of specific variant's effects is none. This study analyzed the effects of the Omicron variant on the perinatal outcomes of full-term newborns during the Omicron wave period. METHODS: Between December 2021 and April 2022, this study was conducted on all newborns who visited a single center. We investigated due to the Omicron maternal infection maternal pregnancy complications, delivery methods, birth week, Apgar scores, neonatal resuscitation program requirement, whether respiratory support was required until 12 h after childbirth, suspicious infectious status, and mortality depending on maternal Omicron infection. A total of 127 neonates were enrolled, and 12 were excluded based on exclusion criteria. Sixteen neonates were born to mothers with a history of Omicron COVID-19, and 99 were born to non-infectious mothers. All infected mothers became infected in the 3rd trimester. Of the 16 mothers, seven were symptomatic, and four met the isolation criteria, according to Korean guidelines. The birth weight of newborns to mothers with a history of COVID and those without was 2.958 ± 0.272 kg and 3.064 ± 0.461 kg (p = 0.049), respectively. The 5-min Apgar score at childbirth was 9.29 ± 0.756 and 9.78 ± 0.460 for neonates born to symptomatic and asymptomatic mothers (p = 0.019), respectively. When compared with or without maternal self-isolation, neonates requiring respiratory support 12 h after birth demonstrated a significant difference (p = 0.014; OR, 10.275). Additionally, the presence or absence of transient tachypnea of the newborn showed a significant value (p = 0.010; OR 11.929). Owing to Omicron COVID-19, newborns were born with lower birth weight, low 5-min Apgar scores, and required respiratory support until 12 h after birth.


Characteristics of patients aged over 75 years with hepatitis C virus infection treated with direct-acting antivirals in Japan: Evidence based on the nationwide, real-world database in Japan.
Direct-acting antivirals (DAAs) have dramatically changed the treatment of chronic hepatitis C. Their high efficacy helps in eradicating hepatitis C virus with few adverse events. Information on real-world use of DAAs therapy in patients aged 75 years and older is inadequate. The Japanese DAAs database was constructed in 2014 as a cooperative system between 18 prefectures. The medical reports filled in by doctors and anonymized at the local government office were collected. The patients' demographic features, viral factors, and treatment characteristics were compared among three groups stratified by age when therapy was initiated: Group A (<60 years old), Group B (60-74 years old), and Group C (≥75 years old). Out of the 22,454 patients whose age upon starting therapy could be identified, 24.8% (n = 5597) belonged to Group C, which was ten times the number in the Japanese Interferon Database. Female patients, advanced stages of liver fibrosis, and past history of hepatocellular carcinoma treatment were significantly higher in the older age groups (Group A < B < C), whereas sustained virologic response (SVR) rates were not different (91%-93%). In Group C, multivariate logistic regression analysis revealed that predicting factors for virologic response varied among DAAs regimens. However, the completion of DAAs therapy commonly contributed to SVR, regardless of DAAs regimen. DAAs therapy is associated with high SVR rates, even in the oldest age group, and therapy should not be withheld on the basis of old age.


Optical coherence tomography angiography aspects of the retinal and optic disc microvascular morphology in erythemato-telangectatic rosacea.
To investigate retinal and optic disc (OD) microvascular morphological changes in erythemato-telangiectatic rosacea (ETR) patients using optical coherence tomography angiography (OCTA), and compare the findings to age- and gender-matched healthy individuals. This study included newly diagnosed 31 ETR patients (31 right eyes, group 1) who were clinically diagnosed by two experienced dermatologists. A control group had 32 healthy individuals (32 right eyes, group 2). Demographic data, including age and gender were collected, followed by a thorough ophthalmologic exam. A 6 × 6 mm macular OCTA analysis of superficial and deep capillary plexus (SCP and DCP) vessel densities (VDs), as well as foveal avascular zone (FAZ) area, FAZ perimeter (PERIM), foveal VDs 300 µm area around FAZ (FD-300), and flow areas in the outer retinal and choriocapillaris, was then performed. Mean age in groups 1 and 2 was 43.70 ± 13.02 and 43.62 ± 12.30 years, respectively (p=0.979). Male-to-female ratio in group 1 was 4:27 and 4:28 in group 2. Capillary flow analysis revealed slightly higher values in group 1 than in group 2, with the former having a significantly higher select area in the outer retinal layer (p=0.001) and flow area in the choriocapillaris (p=0.002). Despite slightly higher values in group 1, there were no significant differences in SCP and DCP VDs (p > 0.05), FAZ area (p=0.471), PERIM (p=0.778), or FD-300 (p=0.527). ETR appears to be associated with posterior segment changes, especially retinal microvascular morphology, even in asymptomatic ocular conditions. Given the disease's high rate of misdiagnosis, understanding rosacea-induced ocular manifestations is critical for ophthalmologists.


[Place of laparoscopic radical cystectomy in the treatment of invasive bladder urothelial carcinoma].
Radical cystectomy is the reference treatment for recurrent superficial or invasive bladder tumours. The most standardized incision is midline infra-umbilical laparotomy. The first laparoscopic cystectomy was performed in 1992 in a patient with neurogenic bladder and several teams have subsequently described this incision for the treatment of bladder tumours. The advantages of laparoscopy have been reported in terms of morbidity and earlier return to daily activities. The current oncological results of this incision are difficult to compare with those of conventional open surgery due to the insufficient follow-up. However, published series have not reported any significant difference in the intermediate term. Until convincing results become available, it therefore appears legitimate to allow teams skilled in laparoscopy to demonstrate the oncological efficacy of this approach. At the present time, the reference treatment for invasive bladder cancer remains open cystectomy.


Microglia-derived IGF-2 prevents TNFalpha induced death of mature oligodendrocytes in vitro.
Insulin-like growth factor-2 (IGF-2) present in media conditioned by non-activated and interferon gamma (IFN gamma)-treated microglia reduces galactocerebroside(+) (GalC) oligodendrocyte apoptosis in cultures derived both from the CG4 cell line and primary rat cortices. Microglia-derived IGF-2 also acts in each culture system to block GalC(+) oligodendrocyte toxicity resulting from soluble microglial-derived tumour necrosis factor alpha (TNF alpha). IGF-2 inhibits TNF alpha-induced c-Jun kinase (JNK) activation of the CG4 cell line. Microglial activation results in the release of soluble factors that are potentially toxic to oligodendrocytes but this may be offset by the production of soluble factors that protect these vulnerable cells. Allowing for extrapolation of these in vitro findings to intact tissue, our observations suggest one mechanism for limiting bystander damage in the context of inflammatory brain disease.


A dynamic study in two new cases of X chromosome translocations.
The authors discuss the clinical and cytogenetic problems raised in two new cases of X-chromosome translocations. The first case involves a child who presented marked malformations at age 3 months. Chromosome analysis revealed the presence of a translocation between a 22 and X chromosome resulting in partial X monosomy and partial trisomy 22: 46,X,der(X),t(X:22)(q112;q13)mat. The balanced translocation form was detected in the mother. Dynamic study after 5-Brdu treatment revealed inactivation of the translocated X chromosome in the proband, while in the mother the normal X chromosome was inactivated. In addition to magnesium dependent hypocalcemia resulting from a specific absorption anomaly, Case 2 presented discrete malformations and psychomotor retardation. Chromosome analysis revealed an apparently balanced translocation between a 9 and X chromosome: 46,X,t(9;X)(q12;p22). Treatment with 5-Brdu demonstrated that the translocated X chromosome was inactivated but that inactivation did not extend to the translocated part of chromosome 9. Finally, a pericentric inversion of a 9 chromosome was detected in the father, grandfather, and brother of the proband.


Sexual differences in spatio-temporal interaction among badgers.
I tested the following hypotheses of territorial polygyny on badgers (Taxidea taxus: Carnivora; Mustelidae): Competition among adult females for food should result in intrasexual territoriality, while male competition for females should result in larger territories that encompass multiple female territories. The sagebrush-grassland study area (Wyoming, USA) contained a depauperate terrestrial fauna with a dense badger population preying on high densities of ground squirrels (Spermophilus armatus). Implant telemetry generated locations for analysis of home range and spatio-temporal interaction. During the summer breeding season males doubled movement rates and nearly tripled home range areas to overlap those of females. Before and after the breeding season, males reduced their home ranges to sizes nearer those of stable female ranges ([Formula: see text]=2.82 km2). Unexpectedly, home range overlap between males and females was no different than intrasexual overlap. However, analysis of spatio-temporal interaction revealed that females spatially avoided one another, while males were spatially and temporally attacted to one another, similar to that of male-female interactions. Presumably, olfactory mechanisms allow resource tracking and lagged communication. Male-male territoriality was not viable, most likely because the high density of badgers, combined with the severely male-biased sex ratio (1.75:1), effectively increased intruder pressure - as a resource, receptive females were too mobile and spatially unpredictable within their home ranges. Consequently, males monitored and searched widely for relatively scarce females during the breeding season with the effect of attracting each other. Male mobility, home range size, and possibly aggression increased with age, suggesting age-related breeding tactics, although dominance could only be surmised. This and other studies suggest how the spatial, temporal, and dominance components of carnivore resource partitioning and sociality will be understood better by unraveling the interplay of olfactory processes, attributes of disparate resources (e.g., food vs. females), seasonality, and population density and age-sex structure.


Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects.
Short-hairpin RNAs (shRNAs) are widely used to produce small-interfering RNAs (siRNAs) for gene silencing. Here we design an alternative siRNA precursor, named single-stranded, Argonaute 2 (Ago2)-processed interfering RNA (saiRNA), containing a 16-18 bp stem and a loop complementary to the target transcript. The introduction of a self-cleaving ribozyme derived from hepatitis delta virus to the 3' end of the transcribed saiRNA dramatically improves its silencing activity by generating a short 3' overhang that facilitates the efficient binding of saiRNA to Ago2. The same ribozyme also enhances the activity of Dicer-dependent shRNAs. Unlike a classical shRNA, the strand-specific cleavage of saiRNA by Ago2 during processing eliminates the passenger strand and prevents the association of siRNA with non-nucleolytic Ago proteins. As a result, off-target effects are reduced. In addition, saiRNA exhibits less competition with the biogenesis of endogenous miRNAs. Therefore, ribozyme-enhanced saiRNA provides a reliable tool for RNA interference applications.


Icatibant use in Brazilian patients with hereditary angioedema (HAE) type 1 or 2 and HAE with normal C1-INH levels: findings from the Icatibant Outcome Survey Registry Study.
Hereditary angioedema can be caused by C1-Inhibitor (C1-INH) deficiency and/or dysfunction (HAE-1/2) or can occur in patients with normal C1-INH (HAE nC1-INH). The Icatibant Outcome Survey (IOS; NCT01034969) registry monitors the safety and effectiveness of icatibant for treating acute angioedema. Present findings from Brazilian patients with HAE-1/2 and HAE nC1-INH participating in IOS. 42 patients were enrolled (HAE-1/2, n = 26; HAE nC1-INH, n = 16). Median age at symptom onset was significantly lower with HAE-1/2 vs. HAE nC1-INH (10.0 vs. 16.5y, respectively; p = 0.0105), whereas median age at diagnosis (31.1 vs. 40.9y; p = 0.1276) and the median time between symptom onset and diagnosis (15.0 vs. 23.8y; p = 0.6680) were numerically lower vs. HAE nC1-INH, respectively. One icatibant dose was used for > 95% of HAE attacks. Median (range) time-to-event outcomes were shorter for patients with HAE nC1-INH vs. HAE-1/2, including time to first administration (0.5 [0-96.0] vs. 1.0 [0-94.0]h, respectively), time from first administration to complete resolution (1.0 [0-88.0] vs. 5.5 [0-96.0]h, respectively), and total attack duration (7.0 [0.3-99.0] vs. 18.5 [0.1-100.0]h, respectively). Mean (SD) time from attack onset to resolution was significantly shorter for patients with HAE nC1-INH vs. HAE-1/2 (9.8 [18.7] vs. 19.6 [24.0]h, respectively; p = 0.0174). 83 adverse events (AEs) in 42 patients were reported; most were mild (66.3%) or moderate (13.3%) and non-serious (75.9%). The most common icatibant-related AE was injection site erythema (HAE-1/2, 34.6%; HAE nC1-INH, 18.8%). This was an observational study without a treatment comparator and that relied on patient recall. Findings demonstrate effectiveness and tolerability of icatibant in Brazilian HAE patients.


Self-proxy agreement and correlates of health-related quality of life in young adults with epilepsy and mild intellectual disabilities.
This study investigated health-related quality of life (HRQOL) in young adults with epilepsy and intellectual disabilities. First, agreement between self-reports and proxy reports of HRQOL was examined. Second, medical and psychological contributions to HRQOL were explored. Thirty-six patients were interviewed using the Quality of Life in Epilepsy inventory (QOLIE-31), the Hospital Anxiety and Depression Scale, and the Neuroticism and Extraversion scales of the NEO Five-Factor Inventory. Medical data were taken from files. Professional caregivers completed rephrased QOLIE-31-questionnaires. The perspectives on HRQOL differed systematically: Caregivers underrated their clients' HRQOL on average. Few correlations with medical characteristics emerged, whereas all psychological variables were strongly related to HRQOL. Neuroticism, Age at Disability Onset, and their interaction explained 71% of the HRQOL variance. Results indicate that proxy reports do not provide valid substitutes for most of the self-reported HRQOL subscales. Psychological treatment of negative affectivity and after critical life events in adolescence may improve HRQOL in young adults with epilepsy and mild intellectual disabilities.


Identification of a genetic locus for autosomal dominant disseminated superficial actinic porokeratosis on chromosome 1p31.3-p31.1.
Disseminated superficial actinic porokeratosis (DSAP) is a chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Two genetic loci for DSAP were identified, but no specific genes were reported to date. The pathogenic mechanism of this disorder remains to be elucidated. In this study, a large, five-generation Chinese family with DSAP was genetically characterized. Two known DSAP loci, DSAP1 and DSAP2, two DSAP candidate genes (SART3 and SSH1), one DSP-linked locus and one PPPD-linked locus were first excluded in the family. The family was then characterized by genome-wide linkage analysis and a new DSAP locus was identified on chromosome 1p31.3-p31.1 with a maximum two-point LOD score of 5.09 with marker D1S2897 (theta = 0). Fine mapping showed that the disease gene was located within an 8.2 cM or 11.9 Mb region between markers D1S438 and D1S464. This is the third locus identified for DSAP (DSAP3). Eight candidate genes including GNG12, IL12RB2, ITGB3BP, DNAJ6, PIN1L, GADD45A, RPE65 and NEGR1 were sequenced, but found to be negative for functional sequence variants. Further mutational analysis of the candidate genes in the region will identify the specific gene for DSAP, which will provide insights into the pathogenesis of DSAP.


Morphological characterization of marginal (lamina I) neurons immunoreactive for substance P, enkephalin, dynorphin and gamma-aminobutyric acid in the rat spinal cord.
Neurons of the rat spinal cord were immunostained for substance P, enkephalin and dynorphin in colchicine-treated animals, and for gamma-aminobutyric acid (GABA). Lamina I stained cells were classified in the four neuronal groups of our previous morphological classification of marginal cells (See Lima and Coimbra, 1986), according to their configuration in the three main anatomical planes. Most lamina I cells exhibiting substance P-immunoreactivity belonged in the group of flattened neurons. Most enkephalinergic cells were pyramidal neurons, while GABA-immunoreactive cells included all multipolar stained neurons and some fusiform neurons. Dynorphin-immunoreactive cells could be fusiform, pyramidal or flattened. The different neurochemical nature and supraspinal projection patterns are suggestive of functional specificity for each group. It is likely that each immunocytochemical subset in each cell group includes tract cells acting at their projection target and intrinsic neurons with local functional roles.


Thought for application and application with thought: issues in theoretical thinking and practical wisdom.
Both theoretical thinking and practical wisdom are used by health professionals in their clinical practice. Lately, discussion has centered on the abstract phrase "theory-practice gap." The health profession is not the only discipline that seeks unity in theory and practice issues. Education is also building bridges in this arena. One reoccurring myth is the notion that theory and practice are separate; as a result, this gives a mistaken impression that theory serves no purpose in practice. Discussion of the issues in this paper includes definitions of theoretical thinking and practical wisdom, theoretical and practical knowledge development, and relevance to health professional's education, practice and science. These issues must be communicated to practitioners, educators and theorists. A collective definition to begin communication is proposed and suggestions are offered for addressing key issues.


Adiponectin inhibits the binding of low-density lipoprotein to biglycan, a vascular proteoglycan.
The aim of this study was to test the possibility that adiponectin has an antiatherogenic effect through the inhibition of LDL binding to proteoglycans, an initial event in atherogenesis. Both full-length and globular adiponectin inhibited LDL binding in a dose-dependent manner. Both types of adiponectin bound to biglycan in a dose-dependent manner. Immunoprecipitation and immunoblotting analysis showed interaction of full-length adiponectin with LDL. Pretreatment of biglycan with globular adiponectin prior to LDL addition diminished the inhibitory effect, while pretreatment with full-length adiponectin retained the effect. This is a new antiatherogenic property that appears independent of the receptor-mediated hormonal action of adiponectin.


Crossover comparison of climate-change adaptation measures taken in the Gdansk (Baltic-sea) and Rotterdam (Nord-sea) deltas.
Gdansk in Poland and the Netherlands share a long-term relationship that started with the establishment of Dutch Mennonites in the Vistula delta in the 16 th Century. Climate-change figures show that both the Polish Gdansk and DutchRotterdam deltas will suffer flooding due to sea level rise, with accumulating severe rainfall accompanied by high river levels; reasons that led to a comparison of the adaptation measures taken. On the basis of the crossover comparison studied, it can be concluded that Poland and the Netherlands have a virtually identical approach when it comes to climate-change impacts on their current situation. With regard to the long-term climate-change trend, the Netherlands in exploring for the future more 'anticipatory' measures with the development of new scenarios for the protection of land and cities. In the Netherlands the use of Hackathon approach is thereby used more often to explore such scenarios. The interaction between the experts and stakeholders of different expertise in this methodology show to lead to creative and new perspectives. This approach may also be recommended for the situation in Gdansk.


Growth factor release and enhanced encapsulated periodontal stem cells viability by freeze-dried platelet concentrate loaded thermo-sensitive hydrogel for periodontal regeneration.
Periodontium regeneration is a highly challenging process as it requires the regeneration of three different tissues simultaneously. The aim of this study was to develop a composite material that can be easily applied and can sufficiently deliver essential growth factors and progenitor cells for periodontal tissue regeneration. Freeze-dried platelet concentrate (FDPC) was prepared and incorporated in a thermo-sensitive chitosan/β-glycerol phosphate (β-GP) hydrogel at concentrations of 5, 10, or 15 mg/ml. The viscosity of the hydrogels was investigated as the temperature rises from 25 °C to 37 °C and the release kinetics of transforming growth factor (TGF-β1), platelet-derived growth factor (PDGF-BB) and insulin-like growth factor (IGF-1) were investigated at four time points (1 h, 1 day, 1 week, 2 weeks). Periodontal ligament stem cells (PDLSCs) were isolated from human third molars and encapsulated in the different hydrogel groups. Their viability was investigated after 7 days in culture in comparison to standard culture conditions and non FDPC-loaded hydrogel. Results showed that loading FDPC in the hydrogel lowered the initial viscosity in comparison to the unloaded control group and did not affect the sol-gel transition in any group. All FDPC-loaded hydrogel groups exhibited sustained release of TGF-β1 and PDGF-BB for two weeks with significant difference between the different concentrations. The loading of 10 and 15 mg/ml of FDPC in the hydrogel increased the PDLSCs viability significantly compared to the unloaded hydrogel and was comparable to the standard culture conditions. Accordingly, it may be concluded that loading FDPC in a chitosan/β-GP hydrogel can offer enhanced injectability, a sustained release of growth factors and increased viability of encapsulated stem cells which can be beneficial in periodontium tissue regeneration.


The BDNF Val66Met polymorphism predicts rumination and depression differently in young adolescent girls and their mothers.
A single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene Val66Met has been associated with depression. However, the relationship between this SNP and depression has been mixed, especially when comparing studies of child and adult depression. We examined whether Val66Met would predict depression differentially in mothers versus their daughters. We also examined whether rumination, the tendency to brood and repetitively think about negative information, might serve as a mediator in the path between genotype and depressive symptoms. Participants included 200 individuals (100 mother-daughter pairs) from a high-risk population. The BDNF Val66Met polymorphism was examined in DNA samples from the mothers and daughters, and measures of depressive symptoms and rumination were also obtained. Among the young adolescent girls (ages 10-14), the Val/Val genotype was associated with more depressive symptoms and higher rumination scores compared to the Val/Met genotype. Furthermore, rumination mediated the relationship between genotype and depressive symptoms. However, in the mothers with adult-onset depression the Val/Met genotype was associated with more depressive symptoms, and rumination again mediated the relationship between genotype and depression. Rumination may be an endophenotype in the pathway from the BDNF Val66Met polymorphism to depression. Future work should further explore this mechanism and pursue explanations for its effects at different times in development.


Orthogonal Versatile Interacting Peptide Tags for Imaging Cellular Proteins.
Genetic tags are transformative tools for investigating the function, localization, and interactions of cellular proteins. Most studies today are reliant on selective labeling of more than one protein to obtain comprehensive information on a protein's behavior in situ. Some proteins can be analyzed by fusion to a protein tag, such as green fluorescent protein, HaloTag, or SNAP-Tag. Other proteins benefit from labeling via small peptide tags, such as the recently reported versatile interacting peptide (VIP) tags. VIP tags enable observations of protein localization and trafficking with bright fluorophores or nanoparticles. Here, we expand the VIP toolkit by presenting two new tags: TinyVIPER and PunyVIPER. These two tags were designed for use with MiniVIPER for labeling up to three distinct proteins at once in cells. Labeling is mediated by the formation of a high-affinity, biocompatible heterodimeric coiled coil. Each tag was validated by fluorescence microscopy, including observation of transferrin receptor 1 trafficking in live cells. We verified that labeling via each tag is highly specific for one- or two-color imaging. Last, the self-sorting tags were used for simultaneous labeling of three protein targets (i.e., TOMM20, histone 2B, and actin) in fixed cells, highlighting their utility for multicolor microscopy. MiniVIPER, TinyVIPER, and PunyVIPER are small and robust peptide tags for selective labeling of cellular proteins.


Time to re-envisage culturally responsive care: Intersection of participatory health research and implementation science.
In the context of widening societal diversity, culturally and linguistically diverse patients continue to experience inequities in healthcare access and deficiencies in standards of nursing care. Re-framing culturally responsive care as a complex intervention spanning multiple interacting factors at micro, meso and macro levels is an essential prerequisite for addressing knowledge translation gaps into everyday nursing practice. To this end, this paper proposes and explicates the potential of applying synergistic participatory implementation methodologies for developing effective implementation strategies with impact at individual and wider structural levels. Discussion Paper. A co-design case study is presented as an example of combining normalization process theory and participatory learning and action to investigate and support the implementation of culturally responsive care in general practice nursing. Enacting culturally responsive health care is inherently complex in that it is influenced by multiple interacting factors. Viewing culturally responsive care as a complex intervention and incorporating a synergistic participatory implementation science approach offers possibilities for addressing the documented shortcomings in the implementation of culturally responsive nursing care. There is a need to move away from conventional approaches to conceptualizing and generating evidence on culturally responsive care. Incorporating participatory implementation methodologies can provide a new lens to investigate and support whole system implementation strategies. The combination of participatory and implementation methodologies is both theoretically and empirically informed. Engaging stakeholders in the co-design and co-production of evidence and solutions to long standing problems has the potential to increase the likelihood of influencing iterative and sustainable implementation and changes to clinical practice and systems. This work is part of a wider programme of participatory health research on migrant health, partnering with a non-governmental organization that supports migrants.


N-acetyl-L-tryptophan (NAT) provides protection to intestinal epithelial cells (IEC-6) against radiation-induced apoptosis via modulation of oxidative stress and mitochondrial membrane integrity.
Ionizing radiation generates oxidative stress in biological systems via inducing free radicals. Gastro-intestinal system has been known for its high radiosensitivity. Therefore, to develop an effective radiation countermeasure for gastrointestinal system, N-acetyl L-tryptophan was evaluated for its radioprotective efficacy using intestinal epithelial cells-6 (IEC-6) cells as the experimental model. Cellular metabolic and lysosomal activity of L-NAT and L-NAT treated irradiated IEC-6 cells were assessed by MTT and NRU staining, respectively. ROS and mitochondrial superoxide levels along with mitochondrial disruption were detected using specific fluorescent probes. Endogenous antioxidants (CAT, SOD, GST, GPx) activities were determined using calorimetric assay. Apoptosis and DNA damage were assessed using flow cytometery and Comet assay, respectively. Results of the study were demonstrated that L-NAT pre-treatment (- 1 h) to irradiated IEC-6 cells significantly contribute to ensuring 84.36% to 87.68% (p < 0.0001) survival at 0.1 μg/mL concentration against LD50 radiation dose (LD50; 20 Gy). Similar level of radioprotection was observed with a clonogenic assay against γ radiation (LD50; 5 Gy). L-NAT was found to provide radioprotection by neutralizing radiation-induced oxidative stress, enhancing antioxidant enzymes (CAT, SOD, GST, and GPx), and protecting DNA from radiation-induced damage. Further, significant restoration of mitochondrial membrane integrity along with apoptosis inhibition was observed with irradiated IEC-6 cells upon L-NAT pretreatment.


Clinical diagnostic approach for oral lymphomas: a multi-institutional, observational study based on 107 cases.
To evaluate oral lymphomas' clinical manifestations and investigate whether clinical features are associated with lymphoma subtypes. Oral lymphomas with at least 1 representative clinical image were evaluated. They were classified according to their microscopic grade (high vs low), predominant cell size (small vs medium/large), and cellular lineage (B cell vs T cell). Clinical images were described according to tumor location, number, swelling, ulcer, necrosis, telangiectasia, predominant color, and lobulation. Lymphomas affecting the palate were compared with salivary gland tumors (SGTs) affecting this location. Data from 107 cases were included. High-grade subtypes (80.4%), with medium/large-sized cells (52.3%), and diagnosed as diffuse large B cell lymphomas (29%) predominated. High-grade lymphomas often presented as painful, ulcerative, and osteolytic diseases (P < .05). Tumors predominantly composed of medium/large-sized cells were associated with painful lesions, ulcerated, with necrosis and bone destruction (P < .05). When only palate tumors were considered, multiple and bilateral lesions, the presence of pain, ulceration, and necrosis were significantly more associated with a diagnosis of lymphoma than SGT (P < .001). High-grade oral lymphomas are more associated with destructive presentation than low-grade subtypes, and bilateral lesions in the palate are more associated with a lymphoma diagnosis than SGT.


Analysis of cellular expression of gangliosides by gene transfection. I: GD3 expression in myc-transfected and transformed 3Y1 correlates with anchorage-independent growth activity.
Transfection of c-myc DNA into rat fibroblastic 3Y1 cell line resulted in the neosynthesis of GD3 ganglioside, as has been previously shown to occur after transfection of 3Y1 cells with adeno El (Nakakuma, H., Sanai, Y., Shiroki, K., and Nagai, Y. (1984) J. Biochem. 96, 1471-1480); in both cases, the products are expressed intranuclearly. Moreover, a clear correlation was identified between levels of GD3 expression and colony-forming activity (in soft agar) of myc-transformed 3Y1 cells, implying that GD3 plays some specific role in myc-induced transformation of 3Y1 cell line.


Quantitative analysis of the effects of volatile anaesthetics on cortical electroencephalographic activity.
Methoxyflurane, halothane and enflurane were compared in respect of their ability to modify cortical activity in Sprague-Dawley rats with chronically implanted electrodes. An analytical instrumentation system for analysis of the electroencephalogram (e.e.g), equipped with a memory unit and capable of obtaining on-line analysis of time histograms of the e.e.g. was used. Methoxyflurane was found to be four times as potent as enflurane, and 2.6 times as potent as halothane 15 to 25 min after the commencement of anesthesia. Halothane was found to be 1.5 times as potent as enflurane.


Scaling a Dpp Morphogen Gradient through Feedback Control of Receptors and Co-receptors.
Gradients of decapentaplegic (Dpp) pattern Drosophila wing imaginal discs, establishing gene expression boundaries at specific locations. As discs grow, Dpp gradients expand, keeping relative boundary positions approximately stationary. Such scaling fails in mutants for Pentagone (pent), a gene repressed by Dpp that encodes a diffusible protein that expands Dpp gradients. Although these properties fit a recent mathematical model of automatic gradient scaling, that model requires an expander that spreads with minimal loss throughout a morphogen field. Here, we show that Pent's actions are confined to within just a few cell diameters of its site of synthesis and can be phenocopied by manipulating non-diffusible Pent targets strictly within the Pent expression domain. Using genetics and mathematical modeling, we develop an alternative model of scaling driven by feedback downregulation of Dpp receptors and co-receptors. Among the model's predictions is a size beyond which scaling fails-something we observe directly in wing discs.


Can nutrition-sensitive intervention and programmes reduce household's food insecurity among the communities affected by Boko-Haram insurgency in Nigeria?
Dwindling food security situations that arose from Boko-haram insurgence experienced in the northeast of Nigeria has led to an urgent need to respond to the food and livelihood requirements of families who were affected by the conflicts in this region. This is necessary in order to enhance their food and nutritional security and livelihood activities. Thus, examining the status of malnutrition of households in the intervening communities is imperative. Therefore, primary data were collected from some selected households within the region using multi-stage sampling procedure. Descriptive statistics, Dietary Diversity Score (DSS), Heckman and Tobit Models were the analytical tools employed. The study revealed that food aid constitutes an integral proportion of the total expenditure of households on food in the intervening communities. Level of malnutrition also reduces from 40.58 to 16.7% due to the impact of the sensitization programme on households' consumption of nutritious foods. However, there is still a high level of malnutrition (68.79%) among the children that are 5 years and below. Social capital formation and group-specific nutritional policy strategies directed at the internally displaced persons (IDPs) and children that are 5 years and below are panacea to reducing malnutrition in the region.


beta-Glucosidases as detonators of plant chemical defense.
Some plant secondary metabolites are classified as phytoanticipins. When plant tissue in which they are present is disrupted, the phytoanticipins are bio-activated by the action of beta-glucosidases. These binary systems--two sets of components that when separated are relatively inert--provide plants with an immediate chemical defense against protruding herbivores and pathogens. This review provides an update on our knowledge of the beta-glucosidases involved in activation of the four major classes of phytoanticipins: cyanogenic glucosides, benzoxazinoid glucosides, avenacosides and glucosinolates. New aspects of the role of specific proteins that either control oligomerization of the beta-glucosidases or modulate their product specificity are discussed in an evolutionary perspective.


Inhibition of vascular angiotensin-converting enzyme by telmisartan via the peroxisome proliferator-activated receptor gamma agonistic property in rats.
The angiotensin receptor blocker (ARB) telmisartan is a partial agonist of peroxisome proliferator-activated receptor gamma (PPARgamma). Typical PPARgamma agonists suppress the gene expression of angiotensin-converting enzyme (ACE) in vascular tissues. However, it remains unclear whether or not PPARgamma activation by telmisartan can inhibit vascular ACE activity. We compared the effects of PPARgamma agonistic telmisartan and non-agonistic valsartan on ACE, vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP) and in sodium (1% NaCl)-loaded SHR-SP. SHR-SP and sodium-loaded SHR-SP received placebo, 1 mg/kg telmisartan, or 10 mg/kg valsartan for 2 weeks. Systolic blood pressure (SBP) was equally reduced in SHR-SP given either telmisartan or valsartan compared with SHR-SP given placebo. However, neither telmisartan nor valsartan suppressed SBP in sodium-loaded SHR-SP. Acetylcholine induced significantly less vasorelaxation in SHR-SP than in Wistar-Kyoto rats, but telmisartan and valsartan each significantly prevented such vasorelaxation. However, telmisartan significantly attenuated acetylcholine-induced vasorelaxation in sodium-loaded SHR-SP, whereas valsartan did not. Telmisartan significantly attenuated NADPH oxidase subunit p22(phox) gene expression in both SHR-SP and sodium-loaded SHR-SP, whereas valsartan did not. Likewise, telmisartan also significantly attenuated the significantly increased vascular ACE activity in sodium-loaded SHR-SP, whereas valsartan did not. In conclusion, the partial PPARgamma agonist telmisartan might inhibit vascular ACE activity, and result in the prevention of oxidative stress and endothelial dysfunction more effectively than non-agonistic valsartan.


Differential infectivity and immunopathology in murine experimental infections by two natural clones belonging to the Trypanosoma cruzi I lineage.
Immunopathology of Chagas' disease in Balb/c mice infected with 2 Trypanosoma cruzi clones, belonging to the T. cruzi I lineage and presenting different in vitro virulence (P/209 cl1 > SO34 c14) was compared. In the acute phase, evading mechanisms such as parasite-induced lymphocyte polyclonal activation and T cell immunosuppression were higher in mice infected with the clone giving a higher parasitaemia (P/209 cl1). A similar increase of non-specific isotypes was observed in both infections with IgG2a prevalence. Interestingly, CD8+ cell hypercellularity and lymphocyte immunosuppression were observed during the chronic phase (245 days post-infection) in mice infected by the most virulent clone. In the same way, the parasite-specific antibody response was more intense in P/209 cl1-infected mice over the acute phase. During the chronic phase this response remarkably dropped down in SO34 cl4-infected mice exclusively. Finally, P/209 cl1-infected mice presented a more severe inflammation and tissue damage in heart and quadriceps than SO34 cl4-infected mice. This comparative study showed differences between the two clones: a higher virulence in vivo being clearly associated with a greater ability to induce evasion mechanisms and severe tissue damage.


Is the experience of meaningful activities understood in nursing homes? A qualitative study.
Lack of occupation can lead to boredom, apathy, social exclusion and solitude. Occupation should incorporate meaningful activities. The aim of this study is to describe how Spanish Nursing Home residents experienced and made sense of meaningful activities. A qualitative phenomenological approach was followed. Data were collected over an 18-month period between 2012 and 2014. Purposeful sampling was conducted with Spanish residents in nursing homes in Madrid. Data were collected using unstructured and semi-structured interviews. The data were analyzed using the Giorgi proposal. Thirty-eight residents (20 female and 18 male) participated. Three main themes describing the significance of meaningful activity in nursing homes emerged from the data: Feeling the passage of time, Seeking an occupation, and Living with restrictions. Nursing homes should strive to develop diverse and meaningful activity programs for residents in order to occupy their time and provide them with a greater sense of purpose.


Three new ant-eating spiders of the family Zodariidae Thorell, 1881 (Araneae, Zodariidae) from Xishuangbanna, China.
Three new zodariid spiders from the Xishuangbanna Tropical Botanical Garden in Yunnan, China are described. A new species of the genus Euryeidon Dankittipakul & Jocqué, 2004, E.diansp. nov. (♂♀), and two new species of the genus Mallinella Strand, 1906, M.bannasp. nov. (♂) and M.menglasp. nov. (♂), are described. Euryeidon is reported for the first time in China.


Forensic application of blood stains and polymorphism of the sixth component of human complement (C6).
Blood samples from 340 unrelated individuals in Fukui prefecture in the central part of Japan were tested in order to determine the gene frequencies of the C6 common alleles. The gene frequencies calculated were as follows: C6 A, 0.478, C6 B, 0.464, C6 B2, 0.052 and rare alleles, 0.006. It was demonstrated that C6 phenotyping from blood stains aged over a period of 1 year, could be performed correctly. The quantity of detectable whole blood after this period amounted to less than 2 microliter.


Maternal vaccination with a type-III glycoconjugate protects mouse neonates against Group B Streptococcus intranasal infection.
Group B Streptococcus (GBS) is generally an asymptomatic colonizer of human mucosa but it occasionally infects pregnant women and neonates through vertical transmission, causing disease during the first weeks of life with frequent and severe complications. Preclinical studies have shown that maternal vaccination with polysaccharide-based vaccines protects mothers and offspring from GBS mucosal colonization and consecutive infection. In these models, bacteria were inoculated in mouse either intravaginally in the last trimester of pregnancy or systemically in pups. Here, we investigated whether maternal vaccination with glycoconjugate vaccines may also prevent GBS-mediated colonization and disease in neonates using an infection route that more closely mimics inhalation or ingestion of bacteria during human delivery. To address this point, mice aged less than two days were intranasally challenged with epidemiologically relevant GBS strains. Bacteria were found to colonize nose and intestine, reaching in some cases lungs and blood during the first days of life. Bacteria were also found in vagina of a fraction of colonized female mice within the first month of life. GBS-specific IgG induced by maternal vaccination with a glycoconjugate vaccine formulation were found in blood and mucosal tissues of newborns. Finally, when intranasally challenged with GBS serotype III strains, pups delivered by vaccinated mothers were partially protected against mucosal colonization and deeper infection.


Selective surgical treatment of patients with rectal carcinoma and unresectable synchronous metastases based on response to preoperative chemotherapy.
The time schedule for chemotherapy and primary tumor resection in patients with rectal carcinoma (RC) and unresectable synchronous metastases (USM) is not well defined. We evaluated whether response to chemotherapy is an appropriate criterion for deciding to perform surgery. We treated 22 patients with RC and USM who received chemotherapy and were regularly evaluated. After documentation of a partial remission (PR) or stable disease (SD), patients were offered resection of the primary tumor. Results were compared with those of a historical control group of 42 patients who underwent immediate surgery. Seven patients had a PR, four showed SD, and 11 progressed under chemotherapy. Seven patients underwent resection of the primary tumor (no perioperative mortality). The median survival for all 22 patients was 20.2 months. Patients with primary tumor resection survived 27.2 months, whereas patients without resection survived only 12.4 months (p = 0.017). The median survival in the control group was 13.5 months (perioperative mortality, 9.5%). Chemotherapy and response-dependent resection of the primary tumor results in the same survival time as that attained with immediate surgery. Patients who face a poor prognosis due to progressive disease are thereby spared the risks of major rectal surgery.


Cu2+-modulated cysteamine-capped CdS quantum dots as a turn-on fluorescence sensor for cyanide recognition.
A new fluorescence sensor for detection of cyanide ions (CN(-)) in aqueous media based on the recovered fluorescence of cysteamine capped CdS quantum dots [Cys-CdS QDs]-Cu(2+) system was proposed. The fluorescence intensity of Cys-CdS QDs was quenched by Cu(2+) due to the binding of Cu(2+) to cysteamine on the surface of the QDs. The degree of fluorescence quenching was proportional to the concentration of Cu(2+). However, in the presence of CN(-), the fluorescence intensity of Cys-CdS QDs was found to be efficiently recovered. Experimental results showed that the pH of the buffer solution and the concentration of Cu(2+) affected the fluorescence intensity upon adding CN(-). Under the optimal condition, the recovered fluorescence intensity was linearly proportional to the increasing CN(-) concentration in the range 2.5-20 μM. The limit of detection and the limit of quantification were found to be 1.13 μM and 3.23 μM, respectively. In addition, among the tested ions, only CN(-) could turn on the fluorescence intensity suggesting that the [Cys-CdS QDs]-Cu(2+) system was a highly selective sensor for CN(-). Moreover, this proposed sensor was demonstrated to detect CN(-) in drinking water with satisfactory results.


Analysing lumbar pedicle morphometry observed via traditional and recent modalities.
The present study was conducted to collect morphometric data on the lumbar vertebrae pedicles of the adult population from the eastern parts of India and analyse the variations, if any, with other parts of the country and the world. The retrospective cross-sectional study where lumbar pedicle morphometric data was obtained via dried bone, the 3D Lumbar vertebrae images were obtained by scanning the dried lumbar vertebrae, and the 3D lumbar vertebrae model was generated from a 1 mm thin CT scan slice of the Lumbar spine of patients who were advised to have a CT scan of the abdomen for reasons other than related to the vertebral column. Both linear and angular measurements in the lumbar pedicles were made bilaterally. The transverse pedicle width is widest at L3 and the narrowest at L2 vertebra bilaterally. The sagittal pedicle width at L4 vertebrae was observed to be the widest bilaterally, while L3 had the narrowest pedicle. The pedicular and body length along the pedicular axis is longer than the central axis at all the lumbar levels. The linear measurement along the pedicular axis was longest at L5 bilaterally via both modes, with a range of 18.2-47.31 mm for bones and 21.03-49.28 mm for CT scan morphometry. The transverse pedicular angle on analysis was observed to increase as one goes down the spine from L1 to L5, with a steep rise between L4 and L5. In contrast, the sagittal pedicular angle decreased as we went caudally toward the L5 vertebrae. The present study data had significant differences among the values reported in the literature from the different populations for the parameters studied. The data obtained by this study will be highly beneficial for the success of the free-hand technique of pedicle screw insertion.


Towards an understanding of the biological function of histone acetylation.
A model is presented which explains the biological function of posttranslational acetylation of core histones in chromatin. Along the lines of this model histone acetylation serves as a general mechanism to destabilize nucleosome core particles during various processes occurring in chromatin. Acetylation acts as a signal that modulates histone-protein and histone-DNA interactions and finally leads to the displacement of particular histones from nucleosome cores. The high specificity of the acetylation signal for different processes (DNA replication, transcription, differentiation-specific histone replacement) is achieved by site specificity and asymmetry of acetylation in nucleosomes. The essential features of this model are in accord with the more recent results on histone acetylation.


Internal jugular phlebectasia.
Varicose veins are a common venous anomaly, but rarer varieties also occur including phlebectasia, which is an abnormal dilatation of an isolated vein. Phlebectasia may affect any vein and is usually asymptomatic. When the internal jugular vein is involved, it presents as a cervical swelling that closely mimics the signs of either a pharyngocoele or a laryngocoele and, due to its rarity, is frequently misdiagnosed. A review of the English literature demonstrates that the diagnosis has generally been confirmed either by invasive contrast radiographic techniques, or surgical exploration, though many authors had made a tentative clinical diagnosis prior to surgical confirmation. No treatment is indicated for this benign self-limiting condition, except for the few patients who complain of symptoms and require surgical removal of the affected vein, and therefore, if a diagnosis cannot be made with certainty from the clinical features, investigations should be as non-invasive as possible, employing either a CAT scan or Digital Subtraction Angiography, though the latter is not yet universally available.


Catches in pitfall traps in relation to mean densities of carabid beetles.
Based on continuous pitfall catches summed over the whole activity period for the carabid beetles Pterostichus versicolor Sturm and Calathus melanocephalus L., a satisfactorily linear relationship is presented between the mean densities in several habitats and in different years and the numbers of beetles trapped. This means that with the help of continuous pitfall sampling a reliable relative measure of the sizes of carabid populations can be obtained.Simulation experiments show that for individuals of P. versicolor the distances covered each day should be represented by strips of some width instead of by lines to obtain numbers trapped that equal the field data. The influence on numbers trapped of the high mobility of beetles in unfavorable habitats is probably not significant. Simulation experiments with C. melanocephalus indicate that a much lower capture efficiency than for P. versicolor has to be programmed to fit the simulation results with the field data.The catch from different types of pitfalls is not always proportional to trap perimeter due to different vegetation cover of the immediate trap surroundings and to different kinds of roofs placed over the pitfalls. For the same species the capture efficiency of a pitfall can also change throughout the season.Simulation experiments show that the number and shape of the pitfalls need not influence the catches, provided that the traps keep the same total perimeter and are broadly spaced.Remodelling of some data from the literature reveals that the linear relationship between mean densities and year-catches in pitfalls is probably a general one among carabid species. This leads to the hypothesis that carabid beetles have to work through a fixed reproductive program each year by means of an almost constant total amount of locomotory activity which is realized step by step during spells of suitable weather.Some recommendations are given for intraspecific and interspecific comparisons of pitfall catches between sites and years.


Usefulness of 64-detector computed tomographic angiography for diagnosing in-stent restenosis in native coronary arteries.
The purpose of this study was to evaluate the accuracy of detector computed tomographic angiographic qualitative and quantitative analyses for the detection of in-stent restenosis (ISR) Previous studies have used qualitative analyses exclusively and have excluded "unevaluable" stents. Multidetector computed tomographic angiography (MDCT) was performed before quantitative coronary angiography in 67 patients with 132 stents that were evaluated by 2 techniques: (1) qualitative, on the basis of degree of visual hypodensity, and (2) quantitative, comparing in-stent with prestent Hounsfield units. All stents were evaluated, irrespective of image quality. The incidence of ISR was 12.5%. The sensitivity (94%), specificity (74%), and positive predictive value (39%) of the qualitative evaluation were superior to the quantitative technique (82%, 54%, and 21%, respectively); negative predictive values were similar (99% vs 95%). Accuracies were equal in stents located in proximal and distal vessels. In conclusion, ISR can be evaluated qualitatively by 64-slice MDCT with excellent sensitivity and negative predictive accuracy without exclusion of unevaluable stents and with reasonable specificity but low positive predictive value. Quantitative analysis was less accurate.


Choroidal changes associated with Bruch membrane pathology in pseudoxanthoma elasticum.
To investigate the impact of Bruch membrane pathology on the choroid in pseudoxanthoma elasticum (PXE). Monocenter cross-sectional prospective case series. The study included 61 eyes of 51 patients with PXE and 54 eyes of 54 normal subjects. The diagnosis of PXE was based on skin biopsy, genetic analysis or both. Eyes with PXE were subdivided into 3 groups: eyes without choroidal neovascularization (CNV) or chorioretinal atrophy (Group 1); eyes with active or fibrotic CNV (Group 2); and eyes with chorioretinal atrophy only (Group 3). Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT). Compared to controls (331 μm ± 24; mean ± 95% CI), mean subfoveal choroidal thickness in eyes of patients with PXE was significantly reduced within all 3 groups (Group 1: 243 μm ± 29; Group 2: 184 μm ± 28; Group 3: 104 μm ± 28; P < 0.001). Associated structural changes included apparent loss of small choroidal vessels. The difference of PXE compared to control eyes was largest close to the optic disc and approximated the level of controls toward the periphery. Within the PXE subgroups, eyes without CNV or chorioretinal atrophy (Group 1) showed the least reduction of choroidal thickness, while it was most pronounced in Group 3. The results indicate that changes of Bruch membrane can be associated with choroidal alterations, which are most pronounced in the presence of advanced disease. A role of Bruch membrane in choroidal homeostasis may reflect a possible contribution of Bruch membrane alterations to CNV and geographic atrophy development in age-related macular degeneration.


Climate and the meristem temperatures of plant communities near the tree-line.
Temperatures of terminal meristems of forest, krummholz and dwarf shrub vegetation were measured at altitudes of 450, 600, 650 and 850 m in the Cairngorm Mountains of Scotland. Simultaneously, the air temperature above the vegetation was recorded, so that it was possible to calculate the difference between meristem and air temperature, sometimes called the excess temperature. This temperature increased linearly with the net radiation absorbed at each station, and the slope was dependent on wind speed and the height of the vegetation. In the extreme cases the slopes were practically zero for forest and 0.028° C W-1 m2 for dwarf shrubs. The latter implies a temperature excess of about 15° C in bright sunshine and low wind speeds. A model is developed to calculate the excess temperature from a knowledge of vegetational height and climatological variables.


Insulin sensitizes FGF21 in glucose and lipid metabolisms via activating common AKT pathway.
Previous studies reveal that fibroblast growth factor 21 (FGF21) sensitizes insulin to achieve a synergy in regulating glucose metabolism. Here, we report that insulin sensitizes FGF21 in regulating both glucose and lipid metabolisms. db/db diabetic mice were subcutaneously administrated once a day for 6 weeks. Effective dose of insulin (1 U) could control blood glucose level of the db/db mice for maximum of 2 h, increased the body weight of the db/db mice and did not improve serum lipid parameters. In contrast, effective dose of FGF21 (0.5 mg/kg) could maintain blood glucose of the db/db mice at normal level for at least 24 h, repressed the weight gain of the mice and significantly improved lipid parameters. Ineffective doses of FGF21 (0.125 mg/kg) and insulin had no effect on blood glucose level of the db/db mice after 24 h administration, body weight or lipid parameters. However, combination of the two ineffective doses could maintain blood glucose level of the db/db mice for at least 24 h, suppressed weight gain and significantly improved lipid parameters. These results suggest that insulin sensitizes FGF21 in regulating both glucose and lipid metabolism. The results aimed to study the molecular basis of FGF21 sensitization indicates that combination of the two ineffective doses increased the mRNA expression of glut1, glut4, β-Klotho, sirt1, pgc-1α, ucp-1 and AKT phosphorylation, decreased fasn. The results demonstrate that insulin sensitizes FGF21 through elevating the phosphorylation of common gene Akt and amplifying FGF21 downstream signaling, including increasing expression of glut1 sirt1, pgc-1α, ucp-1, and decreasing fasn expression. In summary, we reports herein for the first time that insulin sensitizes FGF21 to achieve a synergy in regulating glucose and lipid metabolism. Along with previous studies, we conclude that the synergistic effect between FGF21 and insulin is realized through mutual sensitization.


Examining determinants of gender attitudes: evidence among Tanzanian adolescents.
The shaping of gender beliefs and attitudes in early adolescence affects the way young people internalize and self-enforce prevalent notions of masculinity and femininity, with lifelong consequences for sexual and reproductive health. This cross-sectional study examines determinants of gender attitudes among some of the poorest and most vulnerable adolescents in Tanzania using an ecological model. Data come from baseline interviews with 2458 males and females aged 14-19 years conducted as part of a larger impact evaluation. Structural equation models are used to examine how factors at the community-, household-, and individual-levels influence gender attitudes in the four domains measured by the Gender Equitable Men (GEM) Scale (i.e. violence, sexual relationships, reproductive health and disease prevention, and domestic chores and daily life). A structural equation model of the four latent domains of the GEM scale regressed on individual, social-interactional and structural level characteristics indicated that secondary school attendance was associated with more equitable gender attitudes, while females held less equitable attitudes than males in the sample. Having had sexual intercourse was associated with more gender equitable attitudes among females, but the reverse was true among males. Addressing gender inequity requires understanding gender socialisation at the socio-interactional level. As females had more inequitable gender attitudes than males in the study, a special emphasis on highlighting the rights of women to girls should be considered. This study will inform future analysis of programme impacts on gender attitudes and sexual and reproductive health.


Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm.
High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (AAA) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of AAA patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from AAA patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in AAA were oxidative stress and immune-inflammatory responses. In AAA tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in AAA (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and AAA diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in AAA, identifying the antioxidant PRDX6 as a novel systemic biomarker of AAA.


Successful lactation in Plgrkt-deficient female mice caused by a 1-bp deletion of exon4.
Plasminogen (Pg) activation on the cell surface is important for various (patho)physiologic conditions, and Plg-RKT is a cell membrane protein that binds to Pg and promotes its activation. To evaluate the role of Plg-RKT in atherosclerosis, Plgrkt gene in Ldlr-/-/Apobec1-/- was modified using in vivo CRISPR/Cas9. Synthetic RNA for Plgrkt and Cas9 complex was electroporated into the fertilized eggs in the oviducts. Plgrkt deficient mice were established through a 1-bp deletion, and in this research communication we report their lactational ability. In contrast to Plgrkt-/- mice developed by a conventional method, these newly developed mice did not suffer lactation failure and could maintain their pups until weaning. The major obvious difference between these lines is the area of gene modification. The conventionally developed mouse possesses about 10 kb deletion of Plgrkt, which might relate to the lactation failure. Lactation failure is a lethal phenotype in mammals, and analyses of causative genes are especially important for dairy industries. Further genome-wide analyses with both Plgrkt-/- mice may help to establish causative genes for lactation failure.


Sodium is neither a risk nor a protective factor in urolithiasis?
The effect of changes in urinary sodium, induced by dietary manipulation in normal subjects (NS) and in stone formers (SF) was studied by observing crytalluria qualitatively and by determining calcium, oxalate and phosphate crystallization quantitatively in an experimental model. In SF the calcium crystallization was significantly higher than in NS at all the three levels of urinary sodium studied. However, no difference was observed in oxalate and phosphate crystallization rates between these two groups. Calcium and oxalate (p less than 0.05) and oxalate and phosphate (p less than 0.001) were found to be correlated in NS but were non-significant in SF. The wide changes in the urinary sodium induced by dietary changes did not influence the crystallization rate of calcium, nor of oxalate and phosphate in NS as well as in SF. The results suggested that a sodium intake with lower and upper limits of 124 mg and 6,009 mg respectively did not act as "inhibitor" of crystallization rate nor did it induce hypercalciuria severe enough to pose a "risk" of stone formation. The results did not suggest that a high urinary sodium increases the solubility of calcium phosphate.


Effects of sodium azide on platelet function.
Sodium azide in low concentrations (0.1-10 micrometer) was found to have inhibitory effects on human platelet function. Primary aggregation induced by ADP, epinephrine, thrombin and the ionophore A 23187 was decreased. To evaluate the effect of azide apart from secondary processes, the platelets were treated with indomethacin to prevent prostaglandin/thromboxane synthesis for all inducers; in addition, effects of secreted ADP, in the case of thrombin and A 23187, was prevented by the presence of creatine phosphate plus creatine phosphokinase ADP, epinephrine and A 23187, but not thrombin-induced primary aggregates, dispersed immediately upon addition of azide. Azide powerfully inhibited dense granule secretion induced by collagen, ADP and epinephrine as measured both by 14C-serotonin secretion and as judged by secondary aggregation. Shape change induced by ADP, thrombin or A 23187 was not affected. Azide had no effect on energy metabolism. Since the aggregation experiments were performed in the presence of indomethacin, and malondialdehyde formation from arachidonic acid was not affected by azide, it seemed unlikely that the inhibition by azide of platelet function was related to inhibition of synthesis of prostaglandins and thromboxanes. It is concluded that azide exerts its effects directly on the common pathway for platelet responses.


Safety of high-energy neodymium:YAG laser pulses in YAG sclerostomy.
YAG sclerostomy was performed in 15 eyes of nine cynomolgus monkeys. Individual pulse energies ranged between 10 and 135 millijoules. Total pulse energy ranged between 2,000 and 36,000 millijoules in order to test the extreme range of energy that might be required. Both acute effects and chronic effects were studied in the corneal endothelium, the lens capsule, the iris, the ciliary body, the retina, and the sclera. Techniques included flat preparations of the corneal endothelium, paraffin sections for light microscopy, and scanning and transmission electron microscopy. Our conclusion is that individual pulse energies of up to 135 millijoules with a total of up to 36 joules of energy are safe in monkey eyes when performing YAG sclerostomy.


Psychiatric presentation of medical illness.
A 37-year-old woman was seen in the emergency department for symptoms of depression. A careful mental status examination resulted in the discovery of an organic basis for the "psychiatric" presentation. As with any patient demonstrating behavioral abnormalities, this case illustrates the importance of an adequate history, physical, and mental status evaluation in ruling out organic etiology prior to labeling a patient's complaints as functional. Medical illnesses that can present as apparent psychiatric disease and the clinical clues that lead to the diagnosis of such cases are discussed.


The regulation of cell proliferation by calcium and cyclic AMP.
Calcium, in partnership with cyclic AMP, controls the proliferation of non-tumorigenic cells in vitro and in vivo. While it does not seem to be involved in the proliferative activation of cells such as hepatocytes (in vivo) or small lymphocytes (in vitro), it does control two later stages of prereplicative (G1) development. It must be one of the very many regulatory and permissive factors affecting early prereplicative development, because severe calcium deprivation reversibly arrests some types of cell early in the G1 phase of their growth-division cycle in vitro. However, calcium more specifically and much more often regulates a later (mid or late G1) stage of prereplicative development. Thus, regardless of its severity or the type of cell, calcium deprivation in vitro or in vivo reversibly stops proliferative development at that part of the G1 phase in which the cellular cyclic AMP content transiently rises and the synthesis of the four deoxyribonucleotides begins. The evidence points to calcium and the cyclic AMP surge being co-generators of the signal committing the cell to DNA synthesis. The evidence is best explained so far by the cyclic AMP surge causing a surge of calcium ions which combine with molecules of the multi-purpose, calcium-dependent, regulator protein calmodulin (CDR) somewhere between the cell surface and the cytosol. The resulting Ca-calmodulin complexes then stimulate many different (and possibly membrane-associated) enzymes such as protein kinases, one of which produces the DNA-synthetic initiator. Calcium has little or no influence on the proliferation of tumor cells. Some possible explanations of this very important loss of control are considered.


Monitoring Theileria orientalis (Ikeda)-associated bovine anaemia in affected cattle over time.
The aim of the study was to observe changes in haematocrit (HCT) over time in a New Zealand South Island dairy herd affected by an outbreak of Theileria-associated bovine anaemia (TABA; Ikeda). A secondary aim was to relate individual cow HCTs to the amount of Theileria orientalis Ikeda DNA present in the blood, as measured by cycle threshold values, using a quantitative PCR (qPCR). Over a 6 month period, blood samples from 19 randomly selected cattle were monitored from a herd of 600 dairy cows. The sampling interval was approximately fortnightly for the first six weeks, followed by sampling at between four and six week intervals. At the initial report of the outbreak, two from six cattle were anaemic (HCT<0.25L/L). Blood collected from 14 cattle 11 days later showed that 57% (95% CI 33-77%) of the cattle sampled were anaemic. Of the 19 cattle that went on to be monitored, 12 (63% 95% CI=41-81%) developed anaemia at some point during the period of monitoring. One of the anaemic animals did not meet the case definition for TABA Ikeda. For individual cattle, the average number of days between when cattle were first detected as anaemic and when HCT returned to normal was 53days (median=47 days, range=6-92 days). At the point of notification the amount of T. orientalis Ikeda DNA in the blood of the six cattle tested was low (Cq median=36), but 11days later the amount of DNA in blood of 14 additional cows tested was relatively high (Cq median=24). Levels of all 19 cows monitored continued to remain moderately high through the period of testing (Cq median=29). This was despite a general improvement in the HCT of affected cattle. In four of the 15 cattle positive to T. orientalis Ikeda where blood fractions (plasma and whole blood) were tested, it appeared that T. orientalis Ikeda (as measured by qPCR) dropped more rapidly in plasma fractions than in whole blood at the point that HCT started to return to normal levels. Despite the assumption that tick populations were low in the Canterbury region of the South Island the impact of TABA (proportion of herd affected and the average period that animals remained anaemic) on the case herd was still relatively high.


Shear deformation effects in enzyme catalysis. Metal ion effect in the shear inactivation of urease.
The mechanism of the inactivation of the enzyme urease produced by subjecting its dilute solutions to hydrodynamic shear stresses in the range 0.5-2.5 Pa has been determined. By studying the kinetics of urease-catalyzed urea hydrolysis during application of hydrodynamic shear under varying chemical environments, we demonstrate that micromolar quantities of metal ions, in this case adventitious Fe, can accelerate the oxidation of thiol groups on urease and thus inactivate it when the protein is subjected to a shearing stress of order 1.0 Pa. In the absence of metal ion this stress level is ineffectual. It is proposed that this type of synergy between deformation and chemical environment may be crucial in many situations where biological macromolecules are subjected to mechanical stress.


Prevention and treatment of motor fluctuations.
The symptoms of Parkinson's disease can become increasingly difficult to control as the disease advances, particularly with the development of motor complications, such as end-of-dose wearing-off and dyskinesias, following long-term therapy. At this stage, the patient is frequently referred to a Parkinson's disease specialist for advice on the management of their disease. In this review we provide an overview of the Parkinson's disease specialist's strategies for coping with such problems. This includes strategy to prevent or delay motor fluctuations and the concept of the long duration response. The paper also includes establishing the optimum and most rational levodopa treatment schedule, improving levodopa absorption, use of COMT-inhibition, the addition of oral dopaminergic agonists, and the use of subcutaneous injections or infusions of apomorphine or lisuride. Finally, we highlight the increasing importance of treatment strategies that stimulate dopamine receptors in a more continuous, less pulsatile manner as a way of reducing the risk of developing treatment-associated motor complications.


Inflammation, heart disease, and depression.
Morbidity and mortality of cardiovascular disease is exceedingly high worldwide. Depressive illness afflicts a significant portion of the population worldwide. Epidemiological studies have confirmed the high co-morbidity between these two entities and the co-morbidity is bidirectional. Systems that contribute to this co-morbidity include the central and autonomic nervous systems, the neuroendocrine, immune, vascular and hematologic systems. Specific pathophysiologic factors include imbalance between the sympathetic and the parasympathetic systems, sympathoadrenal activation, hypothalamic-pituitary-adrenal axis activation, immune system dysregulation with release of pro-inflammatory cytokines and chemokines, platelet activation and hypercoaguability. Inflammation occurs in cardiac and cardiovascular pathology independent of the presence or absence of depression and in depression. Inflammation is closely associated with endothelial dysfunction which is a preamble to atherosclerosis and atherothrombosis. A likely common instigator underlying this co-morbidity is mental stress leading to sustained sympathetic overdrive and diminished vagal tone. Diminished vagal tone contributes to a pro-inflammatory status which affects neurotransmitter regulation, specifically serotonergic transmission. Stress hormones and certain pro-inflammatory substances released by macrophages and microglia upregulate the rate-limiting enzymes in the metabolic pathway of tryptophan. This results in a shunt in tryprophan metabolism away from serotonin formation and down the kynurenine pathway with resulting formation of neurotoxic metabolites.


Synthesis and evaluation of novel bifunctional chelating agents based on 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid for radiolabeling proteins.
Detailed synthesis of the bifunctional chelating agents 2-methyl-6-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (1B4M-DOTA) and 2-(p-isothiocyanatobenzyl)-5, 6-cyclohexano-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (CHX-DOTA) are reported. These chelating agents were compared to 2-(p-isothiocyanatobenzyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (C-DOTA) and 1, 4, 7, 10-Tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N', N", N"'-tris(acetic acid) cyclododecane (PA-DOTA) as their (177)Lu radiolabeled conjugates with Herceptin. In vitro stability of the immunoconjugates radiolabeled with (177)Lu was assessed by serum stability studies. The in vivo stability of the radiolabeled immunoconjugates and their targeting characteristics were determined by biodistribution studies in LS-174T xenograft tumor-bearing mice. Relative radiolabeling rates and efficiencies were determined for all four immunoconjugates. Insertion of the 1B4M moiety into the DOTA backbone increases radiometal chelation rate and provides complex stability comparable to C-DOTA and PA-DOTA while the CHX-DOTA appears to not form as stable a (177)Lu complex while exhibiting a substantial increase in formation rate. The 1B4M-DOTAmay have potential for radioimmunotherapy applications.


Levels of HIV Testing Among Young Men Who Have Sex with Men in Bulgaria: Very Low Testing by Ethnic Minority Roma (Gypsy) Men.
Little is known about HIV testing among young men who have sex with men (MSM) in Southeastern European countries, nor about differences in testing by young ethnic majority and young Roma MSM, the region's most disadvantaged minority population. 271 young MSM (153 non-Roma and 118 Roma) were recruited in Sofia, Bulgaria and completed measures of HIV testing, psychosocial characteristics related to testing, sexual behavior, and substance use. While 74% of ethnic majority MSM had an HIV test (and 56% had multiple prior tests), only 4% of Roma MSM had ever been tested. Roma MSM had lower knowledge about HIV testing, perceived greater barriers and weaker social norms for testing, and held more negative testing attitudes and intentions. Although all had male partners, no Roma MSM self-identified as gay and most reported transactional sex. Efforts are urgently needed to increase HIV testing uptake by young Roma MSM.


Impact of elicited mood on movement expressivity during a fitness task.
The purpose of the present study was to evaluate the impact of four mood conditions (control, positive, negative, aroused) on movement expressivity during a fitness task. Motion capture data from twenty individuals were recorded as they performed a predefined motion sequence. Moods were elicited using task-specific scenarii to keep a valid context. Movement qualities inspired by Effort-Shape framework (Laban & Ullmann, 1971) were computed (i.e., Impulsiveness, Energy, Directness, Jerkiness and Expansiveness). A reduced number of computed features from each movement quality was selected via Principal Component Analyses. Analyses of variance and Generalized Linear Mixed Models were used to identify movement characteristics discriminating the four mood conditions. The aroused mood condition was strongly associated with increased mean Energy compared to the three other conditions. The positive and negative mood conditions showed more subtle differences interpreted as a result of their moderate activation level. Positive mood was associated with more impulsive movements and negative mood was associated with more tense movements (i.e., reduced variability and increased Jerkiness). Findings evidence the key role of movement qualities in capturing motion signatures of moods and highlight the importance of task context in their interpretations.


The serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble gp130 (sgp130) in different tumour stages. Correlation between the two parameters in progression of malignancy.
Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. In this study we measured serum levels of the soluble intercellular adhesion molecule-1 (sICAM-1) in 74 patients with various tumours, divided into four groups according to tumour stage and previous therapy. Serum values of sgp130 were determined in the same patients. As controls we took healthy persons (n=18 for sICAM-1; n=28 for sgp130). Two parameters were determined by ELISA. The serum values of sICAM-1 were significantly elevated compared to controls in stages III + IV both without and after previous chemo/radiotherapy (P<0.05). In stages I + II without or with previous therapy there was no significance. The serum values of sgp130 were increased significantly at each tumour stage both without and after therapy. There were significant correlations between the values of sICAM-1 and sgp130 in patients with progression (tumour stage III + IV without therapy P<0.01; after chemo/radiotherapy P<0.05). To our knowledge this relationship between the two serum parameters has never before been reported. The simultaneous measurement of sICAM-1 and sgp130 could be important in the evaluation of the clinical progression of malignant diseases.


AI molecular property prediction for Parkinson's Disease reveals potential repurposing drug candidates based on the increase of the expression of PINK1.
Parkinson's Disease (PD), a common neurodegenerative disorder and one of the major current challenges in neuroscience and pharmacology, may potentially be tackled by the modern AI techniques employed in drug discovery based on molecular property prediction. The aim of our study was to explore the application of a machine learning setup for the identification of the best potential drug candidates among FDA approved drugs, based on their predicted PINK1 expression-enhancing activity. Our study relies on supervised machine learning paradigm exploiting in vitro data and utilizing the scaffold splits methodology in order to assess model's capability to extract molecular patterns and generalize from them to new, unseen molecular representations. Models' predictions are combined in a meta-ensemble setup for finding new pharmacotherapies based on the predicted expression of PINK1. The proposed machine learning setup can be used for discovering new drugs for PD based on the predicted increase of expression of PINK1. Our study identified nitazoxanide as well as representatives of imidazolidines, trifluoromethylbenzenes, anilides, nitriles, stilbenes and steroid esters as the best potential drug candidates for PD with PINK1 expression-enhancing activity on or inside the cell's mitochondria. The applied methodology allows to reveal new potential drug candidates against PD. Next to novel indications, it allows also to confirm the utility of already known antiparkinson drugs, in the new context of PINK1 expression, and indicates the potential for simultaneous utilization of different mechanisms of action.