The effect of an enrolled nursing registration pathway program on undergraduate nursing students' confidence level: A pre- and post-test study.
In the latter half of the 20th century, registered nurse education moved to university degree level. As a result, there has been a reduction in access for students to clinical experience. In numerous studies, nursing graduates have reported that they do not feel prepared for practice. The importance of maximising every learning opportunity during nursing school is paramount. At Edith Cowan University, a program was initiated that allows students to become enrolled nurses at the midway point of their degree to enable them to work and therefore gain experience in the clinical practice setting during their education. This study investigated the effect of the program on the nursing students' perception of their clinical abilities and explored their ability to link theory to practice. The research design for this study was a quasi-experimental, prospective observational cohort study. The study included 39 second-year nursing students not enrolled in the program (Group 1), 45 second-year nursing students enrolled in the program (Group 2), and 28 third-year nursing students who completed the program and are working as enrolled nurses (Group 3). Participants were asked to complete a Five Dimension of Nursing Scale questionnaire. The quantitative analyses showed that students in Group 1 had statistically significant higher pre-questionnaire perceived abilities across all domains, except in two dimensions when compared to Group 2. The post-questionnaire analysis showed that Group 1 had statistically significant lower perceived abilities in four of the five dimensions compared to Group 2. Group 1 also had significantly lower abilities in all dimensions compared to Group 3. Group 3 had a significantly higher perception of their clinical abilities compared to Group 2. This study highlights the value of meaningful employment for undergraduate nursing students by providing opportunities to increase confidence in clinical abilities.


Gondwanan evolution of the grass alliance of families (Poales).
Phylogenetic interrelationships among all 18 families of Poales were assessed by cladistic analysis of chloroplast DNA rbcL and atpB sequences from 65 species. There are two well-supported main clades; the graminoid clade with Poaceae (grasses), Anarthriaceae, Centrolepidaceae, Ecdeiocoleaceae, Flagellariaceae, Joinvilleaceae, and Restionaceae; and the cyperoid clade with Cyperaceae, Juncaceae, and Thurniaceae. A sister group relationship between Poaceae and Ecdeiocoleaceae is identified with strong support. The sister group of this pair is Joinvilleaceae. These relationships help in elucidating the evolution of grasses and the grass spikelet. Dating of the tree was done by nonparametric rate smoothing of rbcL molecular evolution. Most Poales families date back to the Cretaceous >65 million years ago (mya). Dispersal-vicariance analysis indicates that the Poales originated in South America, the cyperoid clade in West Gondwana (South America or Africa), and the graminoid clade in East Gondwana (Australia). The Trans-Antarctic connection between South America and Australia, and its breakup about 35 mya, probably influenced the evolution of the Poales and the graminoid clade in particular, leading to vicariance between the continents, but the separation of Africa from the other Gondwanan areas, completed about 105 mya, is too old for such a relation.


Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer.
Cannabinoids have been reported to possess antitumorogenic activity. Not much is known, however, about the effects and mechanism of action of synthetic nonpsychotic cannabinoids on breast cancer growth and metastasis. We have shown that the cannabinoid receptors CB1 and CB2 are overexpressed in primary human breast tumors compared with normal breast tissue. We have also observed that the breast cancer cell lines MDA-MB231, MDA-MB231-luc, and MDA-MB468 express CB1 and CB2 receptors. Furthermore, we have shown that the CB2 synthetic agonist JWH-133 and the CB1 and CB2 agonist WIN-55,212-2 inhibit cell proliferation and migration under in vitro conditions. These results were confirmed in vivo in various mouse model systems. Mice treated with JWH-133 or WIN-55,212-2 showed a 40% to 50% reduction in tumor growth and a 65% to 80% reduction in lung metastasis. These effects were reversed by CB1 and CB2 antagonists AM 251 and SR144528, respectively, suggesting involvement of CB1 and CB2 receptors. In addition, the CB2 agonist JWH-133 was shown to delay and reduce mammary gland tumors in the polyoma middle T oncoprotein (PyMT) transgenic mouse model system. Upon further elucidation, we observed that JWH-133 and WIN-55,212-2 mediate the breast tumor-suppressive effects via a coordinated regulation of cyclooxygenase-2/prostaglandin E2 signaling pathways and induction of apoptosis. These results indicate that CB1 and CB2 receptors could be used to develop novel therapeutic strategies against breast cancer growth and metastasis.


Retinohypothalamic tract synapses in the rat suprachiasmatic nucleus demonstrate short-term synaptic plasticity.
The master circadian pacemaker located in the suprachiasmatic nucleus (SCN) is entrained by light intensity-dependent signals transmitted via the retinohypothalamic tract (RHT). Short-term plasticity at glutamatergic RHT-SCN synapses was studied using stimulus frequencies that simulated the firing of light sensitive retinal ganglion cells. The evoked excitatory postsynaptic current (eEPSC) was recorded from SCN neurons located in hypothalamic brain slices. The eEPSC amplitude was stable during 0.08 Hz stimulation and exhibited frequency-dependent short-term synaptic depression (SD) during 0.5 to 100 Hz stimulus trains in 95 of 99 (96%) recorded neurons. During SD the steady-state eEPSC amplitude decreased, whereas the cumulative charge transfer increased in a frequency-dependent manner and saturated at 20 Hz. SD was similar during subjective day and night and decreased with increasing temperature. Paired-pulse stimulation (PPS) and voltage-dependent Ca(2+) channel (VDCC) blockers were used to characterize a presynaptic release mechanism. Facilitation was present in 30% and depression in 70% of studied neurons during PPS. Synaptic transmission was reduced by blocking both N- and P/Q-type presynaptic VDCCs, but only the N-type channel blocker significantly relieved SD. Aniracetam inhibited AMPA receptor desensitization but did not alter SD. Thus we concluded that SD is the principal form of short-term plasticity at RHT synapses, which presynaptically and frequency-dependently attenuates light-induced glutamatergic RHT synaptic transmission protecting SCN neurons against excessive excitation.


A positron emission tomography study of visual and mental spatial exploration.
We measured normalized regional cerebral blood flow (NrCBF) using positron emission tomography (PET) and oxygen-15-labeled water in eight young right-handed healthy volunteers selected as high-imagers. during 2 runs of 3 different conditions: 1, rest in total darkness 2; visual exploration of a map 3; mental exploration of the same map in total darkness. NrCBF images were aligned with individual magnetic resonance images (MRI), and NrCBF variations between pairs of measurements (N = 15) were computed in regions of interest having anatomical boundaries that were defined using a three-dimensional (3-D) reconstruction of each subject MRI. During visual exploration, we found bilateral activations of primary visual areas, superior and inferior occipital gyri, fusiform and lingual gyri, cuneus and precuneus, bilateral superior parietal, and angular gyri. The right lateral premotor area was also activated during this task while superior temporal gyri and Broca's area were deactivated. By contrast, mental exploration activated the right superior occipital cortex, the supplementary motor area, and the cerebellar vermis. No activation was observed in the primary visual area. These results argue for a specific participation of the superior occipital cortex in the generation and maintenance of visual mental images.


Pathogenesis of hypertension in rats with chronic aortic baroreceptor deafferentation.
In an attempt to produce a form of chronic neurogenic hypertension without the increased blood pressure lability which is characteristic of total baroreceptor removal, selective aortic baroreceptor deafferentation (ABD) was performed in rats. Blood pressure, blood pressure variability, heart rate, plasma and extracellular fluid volumes, and the effect of total autonomic blockade were determined in male rats 1 month following ABD. Rats with ABD had significantly higher systolic, diastolic, and mean arterial blood pressures than did sham-operated animals, but the standard deviation of pressure measured repetitively over a 1-hour period was not significantly greater. Total autonomic blockade with atropine, propranolol, and phentolamine lowered blood pressure and heart rate to a similar level in ABD and sham-operated rats. Extracellular fluid volume was not different in the two groups of rats, but plasma volume was significantly lower in rats with ABD. Despite the overall reduction in plasma volume, there was a significant positive correlation between plasma volume and blood pressure in ABD rats; no such correlation was observed in sham-operated rats. It was concluded that ABD produces a mild, chronic hypertension in rats without marked pressure lability. Although the hypertension appears to be Neurogenic in that it is ABOLIshed by autonomic blockade, volume factors also may contribute to the increased blood pressure.


Unwrapping the diagnosis of tuberculosis in primary care: a qualitative study.
Although tuberculosis (TB) is relatively rare in the UK, its diagnosis is important because diagnostic delays can result in worse outcomes for patients and expose others to the risk of infection. Atypical presentations may be common, and patients' help-seeking behaviour may influence the diagnostic process in primary care. Little is known about the process of diagnosing TB in primary care in developed countries. To understand the process of diagnosing TB in UK primary care. Qualitative inductive study with paired semi-structured interviews. Communities and general practices in south-east Wales. Interviews were conducted with 17 patients diagnosed with TB in the previous 6 months and 16 GPs involved with their care. Data were analysed thematically. In response to expected classical features, GPs generally ordered specific tests. Both GPs and patients reported atypical presentations, and then the diagnostic and referral net was appropriately widened in most cases. Identified barriers to prompt diagnosis included atypical presentations and low clinical suspicion of TB, lack of continuity of care, workload demands that limit time with patients, and suboptimal clinician-patient communication. GPs recognised the growing problem of TB nationally and the need for improved education among health professionals. GPs' and patients' accounts about the process of diagnosing TB suggest that delays can occur, although they are not typical. Where diagnosis is clear, GPs generally test specifically and refer appropriately; where diagnosis is less clear, the diagnostic net is cast further. It is only when certain core values of general practice are not applied (including continuity of care, considering context appropriately, and eliciting and responding appropriately to patients' explanatory models) that clinicians and patients identify a suboptimal diagnostic process.


The ESO Diffuse Interstellar Bands Large Exploration Survey: EDIBLES I. Project description, survey sample and quality assessment.
The carriers of the diffuse interstellar bands (DIBs) are largely unidentified molecules ubiquitously present in the interstellar medium (ISM). After decades of study, two strong and possibly three weak near-infrared DIBs have recently been attributed to the [Formula: see text] fullerene based on observational and laboratory measurements. There is great promise for the identification of the over 400 other known DIBs, as this result could provide chemical hints towards other possible carriers. In an effort to systematically study the properties of the DIB carriers, we have initiated a new large-scale observational survey: the ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES). The main objective is to build on and extend existing DIB surveys to make a major step forward in characterising the physical and chemical conditions for a statistically significant sample of interstellar lines-of-sight, with the goal to reverse-engineer key molecular properties of the DIB carriers. EDIBLES is a filler Large Programme using the Ultraviolet and Visual Echelle Spectrograph at the Very Large Telescope at Paranal, Chile. It is designed to provide an observationally unbiased view of the presence and behaviour of the DIBs towards early-spectral type stars whose lines-of-sight probe the diffuse-to-translucent ISM. Such a complete dataset will provide a deep census of the atomic and molecular content, physical conditions, chemical abundances and elemental depletion levels for each sightline. Achieving these goals requires a homogeneous set of high-quality data in terms of resolution (R ~ 70 000 - 100 000), sensitivity (S/N up to 1000 per resolution element), and spectral coverage (305-1042 nm), as well as a large sample size (100+ sightlines). In this first paper the goals, objectives and methodology of the EDIBLES programme are described and an initial assessment of the data is provided.


Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters.
Despite the relevance of Argonaute proteins in RNA silencing, little is known about the structural steps of small RNA loading to form RNA-induced silencing complexes (RISCs). We report the 1.9 Å crystal structure of human Argonaute4 with guide RNA. Comparison with the previously determined apo structure of Neurospora crassa QDE2 revealed that the PIWI domain has two subdomains. Binding of guide RNA fastens the subdomains, thereby rearranging the active-site residues and increasing the affinity for TNRC6 proteins. We also identified two water pockets beneath the nucleic acid-binding channel that appeared to stabilize the mature RISC. Indeed, mutating the water-pocket residues of Argonaute2 and Argonaute4 compromised RISC assembly. Simulations predict that internal water molecules are exchangeable with the bulk solvent but always occupy specific positions at the domain interfaces. These results suggest that after guide RNA-driven conformational changes, water-mediated hydrogen-bonding networks tie together the converged domains to complete the functional RISC structure.


Rapid, noninvasive detection of diabetes-induced retinal metabolic stress.
To test whether subjects with diabetes mellitus (DM) have enhanced retinal flavoprotein autofluorescence compared with age-matched control subjects using a rapid, noninvasive clinical imaging method. Twenty-one subjects with DM and 21 healthy age-matched control volunteers were subjected to retinal imaging using 1-ms flashes of 467-nm light. Flavoprotein autofluorescence for each flash at 535 nm was recorded using an electron-multiplying charged-coupled device camera with a 512x512-pixel chip. The average intensity and the average curve width of retinal flavoprotein autofluorescence were determined by analyzing histograms of pixel intensities plotted for each eye. When stratified by age, the mean average intensity and average curve width levels in subjects with DM were significantly greater than those in controls across all 3 consecutive decades of life studied (P < or = .004 and P < or = .006, respectively). An overall comparison of the mean average intensity and average curve width levels in all subjects with DM vs all controls, with adjustment for age, was consistent with the results found in each age category (P =.001 and P < .001, respectively). Subjects having DM with retinopathy in at least 1 eye had significantly greater average intensity and average curve width than subjects having DM without retinopathy in either eye (P =.002 and P =.005, respectively). Flavoprotein autofluorescence measurements may be clinically useful to rapidly and noninvasively identify diabetic metabolic tissue stress and disease severity. Development of flavoprotein autofluorescence technology is likely to result in a tool that will improve DM screening and disease management.


Surface hydrophobicity of spores of Bacillus spp.
The surface hydrophobicity of 12 strains of Bacillus spp. was examined in a hexadecane-aqueous partition system. Mature and germinated spores of Bacillus megaterium QM B1551 transferred to the hexadecane layer, while vegetative and sporulating cells did not. Wild-type spores were more hydrophobic than spores of an exosporium-deficient mutant of B. megaterium QM B1551, although the mutant spores were shown to be hydrophobic to some extent by using increased volumes of hexadecane. This result suggests that the exosporium is more hydrophobic than the spore coat and that the surface hydrophobicity of spores depends mainly on components of the exosporium. The surface hydrophobicity of spores of nine other species of Bacillus was also examined, and spores having an exosporium were more hydrophobic than those lacking an exosporium. Thus measurement of the hydrophobicity of spores by the hexadecane partition method may provide a simple and rapid preliminary means of determining the presence or absence of an exosporium.


Preservation of bursal-sided tendon in partial-thickness articular-sided rotator cuff tears: a novel arthroscopic transtendon anatomic repair technique.
The purpose of this study was to introduce a novel arthroscopic transtendon anatomic repair technique that spares the intact bursal-sided tendon in articular-sided partial-thickness rotator cuff tears (PTRCT) and to present shoulder functional outcomes in patients with symptomatic articular-sided PCRCT that involves more than 50 % of its thickness after arthroscopic repair using a novel technique. Eighteen patients with symptomatic articular-sided PCRCT involving more than 50 % of the tendon's thickness underwent arthroscopic repair using a devised technique. The devised technique restores only the torn articular portion of the rotator cuff at the anatomical footprint using a suture anchor, and preserves the integrity of the corresponding bursal-sided tendon by tying knots at the most lateral bursal side on the subacromial space. Clinical and functional outcome using ASES and Constant scores were evaluated. The structural integrity of the rotator cuff was evaluated by MRI at 6 months postoperatively. Pain relief and shoulder functional outcomes were encouraging during the recovery phase after operation. ASES (preoperative 54.0 ± 10.3 to postoperative 92.6 ± 8.0), Constant score (61.2 ± 8.5-88.0 ± 5.3), VAS for pain (4.9 ± 2.6-0.6 ± 0.7) improved significantly after arthroscopic transtendon anatomic repair (p < 0.001). No patients had rotator cuff retears on 6-month MRI. No complications related to surgical procedures had occurred. The devised technique of arthroscopic transtendon repair provided satisfactory functional outcomes without postoperative discomforts. This technique minimizes over-tightening of the articular layer and reduces tension mismatches between the articular and bursal layers, which are considered as important factors for improvement of postoperative shoulder motion.


Silent myocardial ischemia in patients with diabetes: who to screen.
Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present.


Jig-assisted modified Harrington reconstruction for metastatic bone destruction of the acetabulum.
We developed a technique using an indigenously designed jig to assist pin placement in producing a stable and long-lasting construct to augment the acetabulum combined with a cemented hip replacement in cases of metastatic destruction of the acetabulum. We describe our novel modified Harrington technique and retrospectively assess our cohort's clinical outcomes and complications. Between 2006 and 2019, 27 patients with a median age of 69 (49-81) years and a median ASA grade of III (II-IV) were managed using our modified 'Harrington' technique. We assessed outcomes on the following criteria: mechanical complications, post-surgery mobility, and functional outcome using Musculoskeletal Tumour Society Score (MSTS). At the last follow-up, ten patients were alive with disease [median follow-up of 26 months (12-74)], and 17 patients died of their oncological disease [median follow-up of 15 months (9-22)]. There were no perioperative deaths or intra-operative complications in our series. In total, ten complications were noted in nine patients (33%). Mobility-wise, 13 patients (48%) mobilised unaided, ten patients (37%) required a stick or crutch, two patients (7%) required a frame and two patients (7%) were wheel chair-dependent. The median MSTS score of all patients during their latest follow-up was 18 (8-26). Our jig-aided modified Harrington reconstruction technique assists in safe placement of antegrade pins in acetabulum during surgery and offers a long-lasting solution to these high-risk patients. The use of large diameter pins, appropriate patient selection, and cage used during construction in the acetabulum demonstrated relief of pain, improved mobility, and favorable functional outcomes with minimal complication rates.


Impaired osteoblast function in osteoporosis: comparison between calcium balance and dynamic histomorphometry.
Osteoblast function was investigated in 27 patients with idiopathic osteoporosis. Transiliac bone biopsy specimens were taken after double labelling with tetracycline, and metabolic calcium balance was studied almost simultaneously. Many of the patients showed poor double labelling of their otherwise unremarkable trabecular osteoid, suggesting impaired formation of bone at many of these surfaces. This phenomenon was not accompanied by increased width of osteoid seams (as seen in osteomalacia), indicating that formation of the matrix and its mineralisation were in equilibrium. For the first time, highly significant positive correlations (p less than 0.01) were found between indices of bone formation, determined by labelling with tetracycline, and calcium balance. Thus some patients with osteoporosis who are rapidly losing bone have low rates of formation of trabecular bone both by individual osteoblasts and in relation to available bone surfaces. As histological indices of bone resorption also independently correlated strongly and inversely (p less than 0.01) with calcium balance the rate of initiation of new basic multicellular units by osteoclastic resorption of trabecular surfaces (or the depth of resorption at these surfaces) also appears to be an important determinant of mineral balance. The mechanisms that regulate the effective life span of mature osteoblasts require further investigation, particularly as some promising treatments that can increase trabecular bone volume in osteoporosis, such as parathyroid peptide hPTH (1-34) and sodium fluoride, must work through a reversal of osteoblastic depression.


International Myeloma Working Group molecular classification of multiple myeloma: spotlight review.
Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinicopathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of chromosomes 13 and 17 and abnormalities of chromosome 1 (1p deletion and 1q amplification). Other key drivers of cell survival and proliferation have also been identified such as nuclear factor- B-activating mutations and other deregulation factors for the cyclin-dependent pathways regulators. Further understanding of the biological subtypes of the disease has come from the application of novel techniques such as gene expression profiling and array-based comparative genomic hybridization. The combination of data arising from these studies and that previously elucidated through other mechanisms allows for most myeloma cases to be classified under one of several genetic subtypes. This paper proposes a framework for the classification of myeloma subtypes and provides recommendations for genetic testing. This group proposes that genetic testing needs to be incorporated into daily clinical practice and also as an essential component of all ongoing and future clinical trials.


Ca2+-calmodulin binding to caldesmon and the caldesmon-actin-tropomyosin complex. Its role in Ca2+ regulation of the activity of synthetic smooth-muscle thin filaments.
We measured the concentration of calmodulin required to reverse inhibition by caldesmon of actin-activated myosin MgATPase activity, in a model smooth-muscle thin-filament system, reconstituted in vitro from purified vascular smooth-muscle actin, tropomyosin and caldesmon. At 37 degrees C in buffer containing 120 mM-KCl, 4 microM-Ca2+-calmodulin produced a half-maximal reversal of caldesmon inhibition, but more than 300 microM-Ca2+-calmodulin was necessary at 25 degrees C in buffer containing 60 mM-KCl. The binding affinity (K) of caldesmon for Ca2+-calmodulin was measured by a fluorescence-polarization method: K = 2.7 x 10(6) M-1 at 25 degrees C (60 mM-KCl); K = 1.4 x 10(6) M-1 at 37 degrees C in 70 mM-KCl-containing buffer; K = 0.35 x 10(6) M-1 at 37 degrees C in 120 mM-KCl- containing buffer (pH 7.0). At 37 degrees C/120 mM-KCl, but not at 25 degrees C/60 mM-KCl, Ca2+-calmodulin bound to caldesmon bound to actin-tropomyosin (K = 2.9 x 10(6) M-1). Ca2+ regulation in this system does not depend on a simple competition between Ca2+-calmodulin and actin for binding to caldesmon. Under conditions (37 degrees C/120 mM-KCl) where physiologically realistic concentrations of calmodulin can Ca2+-regulate synthetic thin filaments, Ca2+-calmodulin reverses caldesmon inhibition of actomyosin ATPase by forming a non-inhibited complex of Ca2+-calmodulin-caldesmon-(actin-tropomyosin).


Gaussian Process Domain Experts for Modeling of Facial Affect.
Most of existing models for facial behavior analysis rely on generic classifiers, which fail to generalize well to previously unseen data. This is because of inherent differences in source (training) and target (test) data, mainly caused by variation in subjects' facial morphology, camera views, and so on. All of these account for different contexts in which target and source data are recorded, and thus, may adversely affect the performance of the models learned solely from source data. In this paper, we exploit the notion of domain adaptation and propose a data efficient approach to adapt already learned classifiers to new unseen contexts. Specifically, we build upon the probabilistic framework of Gaussian processes (GPs), and introduce domain-specific GP experts (e.g., for each subject). The model adaptation is facilitated in a probabilistic fashion, by conditioning the target expert on the predictions from multiple source experts. We further exploit the predictive variance of each expert to define an optimal weighting during inference. We evaluate the proposed model on three publicly available data sets for multi-class (MultiPIE) and multi-label (DISFA, FERA2015) facial expression analysis by performing adaptation of two contextual factors: "where" (view) and "who" (subject). In our experiments, the proposed approach consistently outperforms: 1) both source and target classifiers, while using a small number of target examples during the adaptation and 2) related state-of-the-art approaches for supervised domain adaptation.


Evidence-based pharmacotherapy for attention-deficit hyperactivity disorder.
There is a substantial body of literature documenting the efficacy of multiple unrelated pharmacological agents in attention-deficit hyperactivity disorder (ADHD) individuals throughout the life-cycle. The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. The literature documents that stimulants not only improve abnormal behaviours of ADHD, but also improves self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbidities. In addition there is a large body of literature documenting the efficacy of atomoxetine which shows improvement in these same domains. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-aged Caucasian boys. Further, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.


The complexity of the Fragaria x ananassa (octoploid) transcriptome by single-molecule long-read sequencing.
Strawberry (Fragaria x ananassa) is an allopolyploid species with diverse and complex transcripts. The regulatory mechanisms of fruit development and maturation have been extensively studied; however, little is known about the signaling mechanisms that direct this process in octoploid strawberry (Fragaria x ananassa). Here, we used long-read sequencing (LRS) technology and RNA-seq analysis to investigate the diversity and complexity of the polyploid transcriptome and differentially expressed transcripts along four successive fruit developmental stages of cultivated strawberry. We obtained a reference transcriptome with 119,897 unique full-length isoforms, including 2017 new isoforms and 2510 long noncoding RNAs. Based on the genome of the plausible progenitor (Fragaria vesca), 20,229 alternative splicing (AS) events were identified. Using this transcriptome, we found 17,485 differentially expressed transcripts during strawberry fruit development, including 527 transcription factors (TFs) belonging to 41 families. The expression profiles of all members of the auxin, ABA pathway, and anthocyanin biosynthesis gene families were also examined, and many of them were highly expressed at the ripe fruit stage, strongly indicating that the role of those genes is in the regulation of fruit ripening. We produce a high-quality reference transcriptome for octoploid strawberry, including much of the full-length transcript diversity, to help understand the regulatory mechanisms of fruit development and maturation of polyploid species, particularly via elucidation of the biochemical pathways involved in auxin, ABA, and anthocyanin biosynthesis.


Evaluation of an Organisational Intervention to Promote Integrated Working between Health Services and Care Homes in the Delivery of End-of-Life Care for People with Dementia: Understanding the Change Process Using a Social Identity Approach.
In the United Kingdom, approximately a third of people with dementia live in long-term care facilities for adults, the majority of whom are in the last years of life. Working arrangements between health services and care homes in England are largely ad hoc and often inequitable, yet quality end-of-life care for people with dementia in these settings requires a partnership approach to care that builds on existing practice. This paper reports on the qualitative component of a mixed method study aimed at evaluating an organisational intervention shaped by Appreciative Inquiry to promote integrated working between visiting health care practitioners (i.e. General Practitioners and District Nurses) and care home staff. The evaluation uses a social identity approach to elucidate the mechanisms of action that underlie the intervention, and understand how organisational change can be achieved. We uncovered evidence of both (i) identity mobilisation and (ii) context change, defined in theory as mechanisms to overcome divisions in healthcare. Specifically, the intervention supported integrated working across health and social care settings by (i) the development of a common group identity built on shared views and goals, but also recognition of knowledge and expertise specific to each service group which served common goals in the delivery of end-of-life care, and (ii) development of context specific practice innovations and the introduction of existing end-of-life care tools and frameworks, which could consequently be implemented as part of a meaningful bottom-up rather than top-down process. Interventions structured around a Social Identity Approach can be used to gauge the congruence of values and goals between service groups without which efforts to achieve greater integration between different health services may prove ineffectual. The strength of the approach is its ability to accommodate the diversity of service groups involved in a given area of care, by valuing their respective contributions and building on existing ways of working within which practice changes can be meaningfully integrated.


The genes of the sulphoquinovose catabolism in Escherichia coli are also associated with a previously unknown pathway of lactose degradation.
Comparative genomics analysis of conserved gene cassettes demonstrated resemblance between a recently described cassette of genes involved in sulphoquinovose degradation in Escherichia coli K-12 MG1655 and a Bacilli cassette linked with lactose degradation. Six genes from both cassettes had similar functions related to carbohydrate metabolism, namely, hydrolase, aldolase, kinase, isomerase, transporter, and transcription factor. The Escherichia coli sulphoglycolysis cassette was thus predicted to be associated with lactose degradation. This prediction was confirmed experimentally: expression of genes coding for aldolase (yihT), isomerase (yihS), and kinase (yihV) was dramatically increased during growth on lactose. These genes were previously shown to be activated during growth on sulphoquinovose, so our observation may indicate multi-functional capabilities of the respective proteins. Transcription starts for yihT, yihV and yihW were mapped in silico, in vitro and in vivo. Out of three promoters for yihT, one was active only during growth on lactose. We further showed that switches in yihT transcription are controlled by YihW, a DeoR-family transcription factor in the Escherichia coli cassette. YihW acted as a carbon source-dependent dual regulator involved in sustaining the baseline growth in the absence of lac-operon, with function either complementary, or opposite to a global regulator of carbohydrate metabolism, cAMP-CRP.


Testicular tumors in children and adolescents.
To perform a comparative assessment of the clinical and epidemiological aspects of testicular tumors in childhood and adolescence. Retrospective analysis of medical records of patients with testicular or paratesticular neoplasms. Patients under 10 years were classified as children and patients between 10 and 20 were classified as adolescents. The obtained results were compared through the two-sample test for proportions: non-parametric Mann-Whitney test and log-rank test. 60 patients were admitted in the period from January 1992 to July 2009: 34 children and 26 adolescents with testicular or paratesticular neoplasms. The main manifestations were testicular tumor and scrotal pain. Pain complaints were more common in adolescents (p = 0.006), who presented a mean time from disease onset to diagnosis of 4.9 months, longer than children, who presented a period of 2.3 months from disease onset to diagnosis (p = 0.01). Histological types were as follows: germ cell tumors in 32/60 (53%), rhabdomyosarcomas (RMSs) in 23/60 (38.3%), and other in 5/60 (8.3%). Adolescents presented a higher incidence of RMSs, lymph node metastases (p = 0.003) and distant metastases (p = 0.035). Differences in survival rates among the studied patients were not statistically significant, the only indicative being that survival in RMS cases is longer for children (p = 0.072). Compared to children, adolescents with testicular tumor presented longer time from disease onset to diagnosis, aggressive histological type and advanced illness at diagnosis, despite the small sample analyzed.


Are CD8 T cells involved in control of African trypanosomiasis in a natural host environment?
Murine models have suggested that CD8 T cells might play a major parasite-promoting role in African trypanosomiasis. To assess the role of these cells in a natural host environment, we have depleted CD8 cells from Boran cattle in vivo and subsequently infected these animals with Trypanosoma congolense by tsetse fly challenge. Following administration of a mouse monoclonal anti-bovine CD8 antibody, we have been able to achieve a depletion of more than 99.9% in peripheral blood, spleen, prescapular lymph nodes, prefemoral lymph nodes, mesenteric lymph nodes and Peyer's patches. Depletion could be maintained over a 4-5-week infection period. Despite the almost total absence of CD8 cells, no effect whatsoever was observed on parasitemia. In addition, anemia, which is the main factor determining the mean survival time in cattle was not affected by the CD8 depletion.


Effects of Piezoelectric Surgery on Bone Regeneration Following Distraction Osteogenesis of Mandible.
The aim of this study is to compare the bone healing in the distraction gap following the osteotomy performed with piezoelectric and conventional devices for the distraction osteogenesis in the rabbit mandibles. Twelve rabbits were randomly divided into 2 groups; 6 for piezoelectric device and 6 for rotary instruments. After 3 days of latency period, distraction was started at a rate of 1 mm per day for 10 days. All the animals were sacrificed after 4 weeks of consolidation phase for histological and histomorphological evaluation. Histological evaluation revealed thick trabecular bone formation in all of the specimens. Inflammation scores were chronic minimal. The mean percentages of the bone area in distraction gap are 62% in group P and 57% in group R. However, the difference between 2 groups was not statistically significant (P > 0.05). Our results revealed a slight increase in bone formation in the distraction gap in piezo-osteotomy groups histologically though not statistically supported. However, there is still a need for more histological studies with larger sample sizes evaluating the bone structure following piezo-osteotomies.


Fulminant demyelinating encephalomyelitis: Insights from antibody studies and neuropathology.
Antibodies to myelin oligodendrocyte glycoprotein (MOG) are detectable in inflammatory demyelinating CNS diseases, and MOG antibody-associated diseases seem to have a better prognosis despite occasionally severe presentations. We report the case of a 71-year-old patient with acute visual and gait disturbance that dramatically worsened to bilateral amaurosis, tetraplegia, and respiratory insufficiency within a few days. MRI showed multiple progressive cerebral and spinal lesions with diffusion restriction (including both optic nerves) and marginal contrast enhancement. Routine blood and CSF measures including oligoclonal bands were normal. At disease onset, MOG immunoglobulin G was detected (serum titer 1:1,280, corresponding CSF titer was 1:20) and remained positive in patient serum. Aquaporin-4 antibodies were absent at disease onset but seroconverted to positive at week 9. In addition, CSF glial fibrillary acid protein and myelin basic protein levels were very high at onset but decreased during disease course. After 4 months, the patient died despite immunomodulatory treatment. Postmortem neuropathologic examination revealed an acute multiple sclerosis (MS) defined by multiple demyelinating lesions with a pronounced destructive component and loss of astrocytes. Lesion pattern of optic chiasm met MS pattern II characterized by antibody and complement-mediated demyelination. The case with the clinical presentation of an acute demyelinating encephalomyelitis with predominant optic and spinal involvement, absent oligoclonal bands, a histopathology of acute MS pattern II and development of aquaporin-4 antibodies extends the spectrum of MOG antibody-associated encephalomyelitis. Although, MOG antibodies are suspected to indicate a favorable prognosis, fulminant disease courses are possible and warrant an aggressive immunotherapy.


Attitudes toward colon cancer gene testing: survey of relatives of colon cancer patients.
Various studies have identified psychosocial factors that may influence attitudes toward colon cancer gene testing. Whereas family history of colon cancer has been associated with interest in gene testing, this has not been examined extensively. We hypothesized that the strength of family history of colon cancer is associated with risk perception and willingness to undergo gene testing. We evaluated attitudes toward colon cancer gene testing among persons who had at least one first-degree relative with colon cancer. A total of 2680 at-risk relatives in 863 kindreds were identified and mailed an extensive survey regarding sociodemographic variables, family history, health behaviors and knowledge, and willingness to take a colon cancer gene test. A total of 56.6% of persons completed and returned surveys. We conducted a brief telephone survey of a random sample of 200 persons who did not respond to the mail survey. The combined study sample of 1373 people was 42% male, had a mean age of 55 +/- 15 years, was 96% white, and had moderate-to-high SES. A total of 77.4% were very likely to take the gene test, and 92.4% were somewhat or very likely to take the gene test. A total of 78% of the sample perceived a higher colon cancer risk, although patterns of risk perception and worry differed significantly between mail survey and telephone survey respondents. More of the telephone survey respondents were also somewhat unlikely or very unlikely to take the gene test compared to the mail survey respondents (13.7% versus 6.9%). In the combined sample, concern about developing colon cancer and risk perception increased with number of relatives with colon cancer (P < 0.0001). Eight percent expressed no concern about developing colon cancer; 4.8% felt their chance of developing colon cancer was lower than others of the same age, sex, and race; and 3.3% felt that they were very unlikely to develop colon cancer in their lifetime. However, there was strong interest in gene testing regardless of the number of affected relatives, and persons with more affected relatives were generally willing to pay more for the gene test (up to $1000). The strength of family history of colon cancer is associated with risk perception but not with willingness to undergo gene testing.


Dynamic Maternal Gradients Control Timing and Shift-Rates for Drosophila Gap Gene Expression.
Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are involved in segment determination during early embryogenesis. They are activated by maternal morphogen gradients encoded by bicoid (bcd) and caudal (cad). These gradients decay at the same time-scale as the establishment of the antero-posterior gap gene pattern. We use a reverse-engineering approach, based on data-driven regulatory models called gene circuits, to isolate and characterise the explicitly time-dependent effects of changing morphogen concentrations on gap gene regulation. To achieve this, we simulate the system in the presence and absence of dynamic gradient decay. Comparison between these simulations reveals that maternal morphogen decay controls the timing and limits the rate of gap gene expression. In the anterior of the embyro, it affects peak expression and leads to the establishment of smooth spatial boundaries between gap domains. In the posterior of the embryo, it causes a progressive slow-down in the rate of gap domain shifts, which is necessary to correctly position domain boundaries and to stabilise the spatial gap gene expression pattern. We use a newly developed method for the analysis of transient dynamics in non-autonomous (time-variable) systems to understand the regulatory causes of these effects. By providing a rigorous mechanistic explanation for the role of maternal gradient decay in gap gene regulation, our study demonstrates that such analyses are feasible and reveal important aspects of dynamic gene regulation which would have been missed by a traditional steady-state approach. More generally, it highlights the importance of transient dynamics for understanding complex regulatory processes in development.


Weight gain management in patients with schizophrenia during treatment with olanzapine in association with nizatidine.
Weight gain is associated with treatment with many psychotropic agents. Nizatidine, H2 receptor antagonist, has been proposed to have weight-reducing effects. This was a 12-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of nizatidine in reducing/limiting weight gain in patients with schizophrenia who have been under treatment with olanzapine. Patients receiving olanzapine (2 to 6 months) and weight gain >or= 5% of their body weight during olanzapine treatment were randomly assigned to receive nizatidine 600 mg or placebo for up to 12 weeks. Change in psychopathology was assessed using Brief Psychiatric Rating Scale scores from baseline to endpoint. Safety was assessed using the Safety Assessed Software, assessment of glucose and lipid blood levels, and treatment-emergent adverse events. Out of 54 patients enrolled in this analysis, 45 completed the protocol. The mean weight change prior randomization was 7.6 kg and 7.3 kg for those randomized to placebo and nizatidine, respectively (p = 0.828). Patients receiving placebo and nizatidine had a mean weight gain of 12.3% (0.7 kg) and 12% (1.1 kg) from baseline to endpoint, respectively (p = 0.9). Patients from both groups experienced a statistically significant decrease on the Brief Psychiatric Rating Scale mean score from baseline to endpoint. Treatment-emergent adverse events were reported by 18.5% and 25.9% on the placebo and nizatidine group, respectively. There were no statistically significant differences in glucose and lipid blood levels from baseline to endpoint and between groups. The concomitant use of olanzapine with nizatidine was not effective in controlling weight gain in patients who had previously gained weight during treatment with olanzapine when compared to placebo.


Socio-demographic characteristics, treatment coverage, and self-rated health of individuals who reported six chronic diseases in Brazil, 2003.
The Brazilian World Health Survey, carried out in 2003, included questions about diagnosis of six chronic diseases: arthritis, angina, asthma, depression, schizophrenia and diabetes mellitus. The probabilistic sample of 5,000 adults was selected in 250 census tracts. We analyzed the socio-demographic profile, the coverage of treatment, and self-rated health of the individuals that reported diagnosis of one of these diseases. To control for age and sex, logistic regression models were used. Among the 5,000 participants, 39.1% reported medical diagnosis of at least one of the six diseases. Depression was the most prevalent (19.2%), followed by asthma (12.0%), arthritis (10.5%), angina (6.7%), diabetes (6.2%) and schizophrenia (1.7%). Significant differences by age were found for all diseases, except for asthma. All diseases were more prevalent among women, except angina. Analysis by educational level showed that the diabetes prevalence rate was significantly larger among those with incomplete schooling. Although the six diseases presented different treatment coverage rates, for individuals with diagnosis of any one of the six diseases, the self-rated health was always worst, even after controlling for age and sex.


White-light interferometer with dispersion: an accurate fiber-optic sensor for the measurement of distance.
We present a fiber-optical sensor for distance measurement of smooth and rough surfaces that is based on white-light interferometry; the sensor measures the distance from the sample surface to the sensor head. Because white light is used, the measurement is absolute. The measurement uncertainty depends not on the aperture of the optical system but only on the properties of the rough surface and is commonly approximately 1 microm. The measurement range is approximately 1 mm. The sensor includes no mechanical moving parts; mechanical movement is replaced by the spectral decomposition of light at the interferometer output. The absence of mechanical moving parts enables a high measuring rate to be reached.


The difference in kinematics of horses walking, trotting and cantering on a flat and banked 10 m circle.
Locomotion adaptation mechanisms have been observed in horses, but little information is available in relation to banked and nonbanked curve locomotion, which might be important to optimise training environments. To determine if adaptation mechanisms in horses existed when moving on a banked compared to a flat curve and whether adaptation was similar in different gaits. Eight infrared cameras were positioned on the outside of a 10 m lungeing circle and calibrated. Retroreflective markers were used to define left and right metacarpus (McIII) and proximal phalanges (P1), metatarsus (MtIII), head and sacrum. Data were recorded at 308 Hz from 6 horses lunged at walk, trot and canter on a flat and 10° banked circle in a crossover design. Measurements extracted were speed, stride length, McIII inclination, MtIII inclination, relative body inclination and duty factor. Data were smoothed with a fourth order Butterworth filter with 30 Hz cut-off. ANOVA was used to determine differences between conditions and limbs. Adaptation mechanisms were influenced by gait. At canter inside forelimb duty factor was significantly longer (P<0.05) on a flat curve compared to a banked curve; at walk this was reversed. McIII inclination, MtIII inclination and relative body inclination were significantly greater (P<0.05) at trot and canter on a flat curve, so more inward tilt was found relative to the bearing surface. Adaptation to curved motion is gait specific. At faster gaits it appears that horses negotiate a banked curve with limb posture closer to body posture and probably with demands on the musculoskeletal system more similar to straight canter.


Economic and epidemiological impact of different intervention strategies for clinical contagious mastitis.
The overall aim of this study was to compare different intervention strategies for clinical intramammary infections (IMI). We conducted a simulation study to represent a Danish dairy cattle herd with IMI caused mostly by Staphylococcus aureus and 9 different intervention strategies for clinical IMI. A standard intervention of 3 d of treatment consisting of intramammary injections for all clinical cases was used. Two of the strategies reflected the use of more antibiotics and 6 strategies reflected cow-specific treatment or culling decisions. For these strategies, we assessed the cost and effectiveness of culling as an IMI intervention. Our results showed that nearly all strategies could reduce the number of IMI cases [e.g., a median of 37 clinical cases with the extended intramammary treatment over 5 d strategy (Basic5) and 30 clinical cases with the cow culled with recovery probability below 50% (Before50)] compared with the standard intervention (median of 42 clinical cases). This happened alongside either increased antibiotic usage (e.g., from a median of 123 treatment days up to 179 treatment days with strategy Basic5) or an increased number of cows culled in relation to IMI (e.g., from a median of 16 up to 24 cows with strategy Before50). Strategies with more antibiotics or reactive culling had a slightly higher net income (e.g., €190,014 median net income with strategy Basic5 or €196,995 with strategy Before50 compared with €187,666 with the standard strategy). This shows that a cow-specific clinical intervention approach can be cost-effective in reducing IMI incidence.


Wolf reintroduction to Scotland: public attitudes and consequences for red deer management.
Reintroductions are important tools for the conservation of individual species, but recently more attention has been paid to the restoration of ecosystem function, and to the importance of carrying out a full risk assessment prior to any reintroduction programme. In much of the Highlands of Scotland, wolves (Canis lupus) were eradicated by 1769, but there are currently proposals for them to be reintroduced. Their main wild prey if reintroduced would be red deer (Cervus elaphus). Red deer are themselves a contentious component of the Scottish landscape. They support a trophy hunting industry but are thought to be close to carrying capacity, and are believed to have a considerable economic and ecological impact. High deer densities hamper attempts to reforest, reduce bird densities and compete with livestock for grazing. Here, we examine the probable consequences for the red deer population of reintroducing wolves into the Scottish Highlands using a structured Markov predator-prey model. Our simulations suggest that reintroducing wolves is likely to generate conservation benefits by lowering deer densities. It would also free deer estates from the financial burden of costly hind culls, which are required in order to achieve the Deer Commission for Scotland's target deer densities. However, a reintroduced wolf population would also carry costs, particularly through increased livestock mortality. We investigated perceptions of the costs and benefits of wolf reintroductions among rural and urban communities in Scotland and found that the public are generally positive to the idea. Farmers hold more negative attitudes, but far less negative than the organizations that represent them.


Mortality patterns and site heterogeneity of severe malaria in African children.
In this study we aimed to assess site heterogeneity of early, intermediate, and late mortality prediction in children with severe Plasmodium falciparum malaria in sub-Saharan Africa. Medical records of 26,036 children admitted with severe Plasmodium falciparum malaria in six hospital research centers between December 2000 to May 2005 were analyzed. Demographic, clinical and laboratory data of children who died within 24 hours (early), between 24 and 47 hours (intermediate) and thereafter (48 hours or later, late mortality) were compared between groups and survivors. Overall mortality was 4·3% (N = 1,129). Median time to death varied across sites (P<0·001), ranging from 8 h (3 h-52 h) in Lambaréné to 40 h (10 h-100 h) in Kilifi. Fifty-eight percent of deaths occurred within 24 hours and intermediate and late mortality rate were 19% and 23%, respectively. Combining all sites, deep breathing, prostration and hypoglycemia were independent predictors for early, intermediate and late mortality (P<0·01). Site specific independent predictors for early death included prostration, coma and deep breathing at all sites (P<0·001). Site specific independent predictors for intermediate and late death largely varied between sites (P<0·001) and included between 1 and 7 different clinical and laboratory variables. Site heterogeneity for mortality prediction is evident in African children with severe malaria. Prediction for early mortality has the highest consistency between sites.


Outcomes research in the ICU: an aid in defining the role of physiotherapy.
The economic reality of consumers, funders, and regulatory agencies demanding evidence regarding the quality of care patients are receiving in the intensive care unit (ICU) will have an effect on many of the routinely used practices in ICU, including physiotherapy. Outcomes research is a method that has been used to obtain evidence for the medical and respiratory management of patients in ICU. An overview of the literature was conducted to answer the following questions: 1. What is outcomes research? 2. Which outcomes should be measured in the adult critical care environment? 3. Which outcomes are physiotherapists currently including in research reports? Outcomes research is recognized by critical care specialists as a cost-effective method of determining what works in the real world. The value of physiologic measures is questioned, whereas the importance of patient centered, economic, and traditionally accepted outcome measures is increasingly being recognized. Most physiotherapy research reports still include physiologic measurements as the primary outcome of an intervention. Outcomes research provides researchers with the tools to define the role of the physiotherapist in the critical care environment. The outcomes measured must be relevant to patients, families, and funders.


Origination of the muscular branches of the median nerve: an electrophysiological study.
In lower brachial plexus injury, finger flexion after brachialis motor branch transfer is relatively weak. We sought to screen potential branches of the median nerve from the upper trunk for strengthening finger flexion in addition to the brachialis motor branch. However, the spinal origin of the muscular branches of the median nerve based on electrophysiological study was unclear. To determine the spinal origin of the muscular branches of the median nerve. An intraoperative electrophysiological study was carried out in 18 patients who underwent contralateral C7 nerve transfer. After exposure of the brachial plexus nerve roots on the healthy side, the amplitude of the compound muscle action potential of each median nerve-innervated muscle was recorded while the different nerve roots were stimulated. The pronator teres received fibers from C5, C6, and C7. It had more contribution from C5 and C6 than from C7 (P<.05). The flexor carpi radialis was innervated mainly by C6 and C7. The nerve branches of the palmaris longus and flexor digitorum superficialis stemmed primarily from C7 and the lower trunk, and no significant difference was found between them (P>.05). The flexor digitorum profundus, flexor pollicis longus, pronator quadratus, and abductor pollicis brevis were innervated predominantly by the lower trunk (P<.05). This electrophysiological study indicates that the pronator teres branch might be the most feasible alternative donor nerve to supplement the brachialis motor branch and strengthen finger flexion after lower brachial plexus injury.


SPHK1 Is a Novel Target of Metformin in Ovarian Cancer.
The role of phospholipid signaling in ovarian cancer is poorly understood. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of sphingosine that has been associated with tumor progression through enhanced cell proliferation and motility. Similarly, sphingosine kinases (SPHK), which catalyze the formation of S1P and thus regulate the sphingolipid rheostat, have been reported to promote tumor growth in a variety of cancers. The findings reported here show that exogenous S1P or overexpression of SPHK1 increased proliferation, migration, invasion, and stem-like phenotypes in ovarian cancer cell lines. Likewise, overexpression of SPHK1 markedly enhanced tumor growth in a xenograft model of ovarian cancer, which was associated with elevation of key markers of proliferation and stemness. The diabetes drug, metformin, has been shown to have anticancer effects. Here, we found that ovarian cancer patients taking metformin had significantly reduced serum S1P levels, a finding that was recapitulated when ovarian cancer cells were treated with metformin and analyzed by lipidomics. These findings suggested that in cancer the sphingolipid rheostat may be a novel metabolic target of metformin. In support of this, metformin blocked hypoxia-induced SPHK1, which was associated with inhibited nuclear translocation and transcriptional activity of hypoxia-inducible factors (HIF1α and HIF2α). Further, ovarian cancer cells with high SPHK1 were found to be highly sensitive to the cytotoxic effects of metformin, whereas ovarian cancer cells with low SPHK1 were resistant. Together, the findings reported here show that hypoxia-induced SPHK1 expression and downstream S1P signaling promote ovarian cancer progression and that tumors with high expression of SPHK1 or S1P levels might have increased sensitivity to the cytotoxic effects of metformin. IMPLICATIONS: Metformin targets sphingolipid metabolism through inhibiting SPHK1, thereby impeding ovarian cancer cell migration, proliferation, and self-renewal.


Comparative Safety of Sulfonylureas and the Risk of Sudden Cardiac Arrest and Ventricular Arrhythmia.
To examine the association between individual antidiabetic sulfonylureas and outpatient-originating sudden cardiac arrest and ventricular arrhythmia (SCA/VA). We conducted a retrospective cohort study using 1999-2010 U.S. Medicaid claims from five large states. Exposures were determined by incident use of glyburide, glimepiride, or glipizide. Glipizide served as the reference exposure, as its effects are believed to be highly pancreas specific. Outcomes were ascertained by a validated ICD-9-based algorithm indicative of SCA/VA (positive predictive value ∼85%). Potential confounding was addressed by adjustment for multinomial high-dimensional propensity scores included as continuous variables in a Cox proportional hazards model. Of sulfonylurea users under study (N = 519,272), 60.3% were female and 34.9% non-Hispanic Caucasian, and the median age was 58.0 years. In 176,889 person-years of sulfonylurea exposure, we identified 632 SCA/VA events (50.5% were immediately fatal) for a crude incidence rate of 3.6 per 1,000 person-years. Compared with glipizide, propensity score-adjusted hazard ratios for SCA/VA were 0.82 (95% CI 0.69-0.98) for glyburide and 1.10 (0.89-1.36) for glimepiride. Numerous secondary analyses showed a very similar effect estimate for glyburide; yet, not all CIs excluded the null. Glyburide may be associated with a lower risk of SCA/VA than glipizide, consistent with a very small clinical trial suggesting that glyburide may reduce ventricular tachycardia and isolated ventricular premature complexes. This potential benefit must be contextualized by considering putative effects of different sulfonylureas on other cardiovascular end points, cerebrovascular end points, all-cause death, and hypoglycemia.


THE PROPERTIES OF T ANTIGENS EXTRACTED FROM GROUP A HEMOLYTIC STREPTOCOCCI.
1. T antigens of group A hemolytic streptococci have been obtained in soluble form by digestion of the bacterial cells with pepsin or trypsin. Large quantities of this antigen were readily extracted from type 1 strains, whereas only small amounts could be obtained from strains of other types. 2. The T antigen, prepared in this way from a type 1 strain, was partially purified by chemical precipitation and further enzymatic digestion. An active fraction, apparently protein in nature, was separated electrophoretically at pH 7.00. The separated material, pooled and analyzed at the same pH, gave only a single peak. The isoelectric point of this substance was about pH 4.50. An elementary analysis was obtained. Although the T antigen was resistant to digestion with proteolytic enzymes and ribonuclease, it was readily inactivated by heat, especially in acid media and in strong salt solutions. The serological activity of this purified T substance was lost after exposure to ultraviolet radiation. 3. Analysis by means of the ultracentrifuge showed that the material was polydisperse and therefore probably impure. 4. The soluble form of the T substance was active in the precipitin reaction, in the fixation of complement, in inhibition of T agglutination, and as an antigen when injected into rabbits. The antibodies produced did not protect mice against infection with virulent strains of hemolytic streptococci containing the same T antigen. 5. The immunological specificity of T antigen in soluble form is the same as that of the T antigen in the intact streptococcus from which it was derived.


Considerations for the use of functional principal components analysis in sports biomechanics: examples from on-water rowing.
The proliferation of new biomechanical technology in laboratory and field settings facilitates the capture of data-sets consisting of complex time-series. An understanding of the appropriate statistical approaches for analysing and interpreting these data-sets is required and the functional data analysis (FDA) family of statistical techniques has emerged in the biomechanical literature. Given the use of FDA is currently in its infancy with biomechanical data, this paper will form the first of a two part series aiming to address practical issues surrounding the application of FDA techniques in biomechanics. This work focuses on functional principal components analysis (fPCA), which is explored using existing literature and sample data from an on-water rowing database. In particular methodological considerations for the implementation of fPCA such as temporal normalisation of data, removal of unwanted forms of variation in a data-set and documented methods for preserving the original temporal properties within a set of curves are explored in detail as a part of this review. Limitations and strengths of the technique are outlined and recommendations are provided to encourage the appropriate use of fPCA within the field of applied sports biomechanics.


Hypermethylation of p16 gene promoter correlates with loss of p16 expression that results in poorer prognosis in esophageal squamous cell carcinomas.
The purpose of this study was to analyze loss of p16 expression and its relationship to hypermethylation, clinicopathological parameters and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Tissue samples from 60 ESCC were subjected to histological analysis. Immunohistochemical staining for p16 expression was performed. DNA was extracted from these primary esophageal tumors and from sera from another 38 ESCC patients. The DNA was modified with bisulfite and analyzed for p16 promoter methylation by methylation-specific polymerase chain reaction. Twelve out of the 60 tumors (20%) were methylated at the p16 promoter and 48 tumors (80%) were unmethylated. There were no significant correlations between the methylation of the p16 promoter and clinicopathological parameters. Immunohistochemical staining revealed that 41 of the 60 tumors (68.3%) were p16-negative and 19 tumors (31.7%) were p16-positive. The correlation between negative p16 immunohistochemical staining and methylation was statistically significant (P = 0.0084). No instances of p16 methylation and p16 positive immunostaining were found. There was a close correlation between loss of p16 expression and poorer prognosis in ESCC (P = 0.0517 in overall survival, P = 0.0478 in disease-free survival). The p16 gene promoter hypermethylation was detected in the serum of two of 38 (5.2%) patients with ESCC. This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC. The present results may lead to the development of new therapeutic strategies, such as p16(INK4A) gene therapy, to treat patients with ESCC.


Correlation of phenotype with genotype and protein structure in RYR1-related disorders.
Variants in the skeletal muscle ryanodine receptor 1 gene (RYR1) result in a spectrum of RYR1-related disorders. Presentation during infancy is typical and ranges from delayed motor milestones and proximal muscle weakness to severe respiratory impairment and ophthalmoplegia. We aimed to elucidate correlations between genotype, protein structure and clinical phenotype in this rare disease population. Genetic and clinical data from 47 affected individuals were analyzed and variants mapped to the cryo-EM RyR1 structure. Comparisons of clinical severity, motor and respiratory function and symptomatology were made according to the mode of inheritance and affected RyR1 structural domain(s). Overall, 49 RYR1 variants were identified in 47 cases (dominant/de novo, n = 35; recessive, n = 12). Three variants were previously unreported. In recessive cases, facial weakness, neonatal hypotonia, ophthalmoplegia/paresis, ptosis, and scapular winging were more frequently observed than in dominant/de novo cases (all, p < 0.05). Both dominant/de novo and recessive cases exhibited core myopathy histopathology. Clinically severe cases were typically recessive or had variants localized to the RyR1 cytosolic shell domain. Motor deficits were most apparent in the MFM-32 standing and transfers dimension, [median (IQR) 85.4 (18.8)% of maximum score] and recessive cases exhibited significantly greater overall motor function impairment compared to dominant/de novo cases [79.7 (18.8)% vs. 87.5 (17.7)% of maximum score, p = 0.03]. Variant mapping revealed patterns of clinical severity across RyR1 domains, including a structural plane of interest within the RyR1 cytosolic shell, in which 84% of variants affected the bridging solenoid. We have corroborated genotype-phenotype correlations and identified RyR1 regions that may be especially sensitive to structural modification.


Patterns of Adverse Childhood Experiences in Juveniles Who Sexually Offended.
Juveniles who sexually offended (JSOs) are differentially burdened with adverse childhood experiences (ACEs). The present study used Latent Class Analysis (LCA) to derive subtypes of JSOs according to their patterns of 10 different ACEs. An extensive file analysis of 322 male JSOs ( M = 14.14, SD = 1.94) revealed five subtypes with (a) multiple (9.0%), (b) mainly family related (17.1%), (c) mainly peer related (21.7%), (d) mainly neglectful (18.6%), and (e) little/no (33.5%) ACEs. Differences among ACE subtypes with regard to several offense and victim characteristics (e.g., the use of penetration or violence, the choice of a child, a male, a stranger, or multiple victims) were examined. Whereas no differences were found for the use of physical violence or the choice of male, stranger, or multiple victims, binary logistic regressions revealed associations of the multiple-ACE subtype with the choice of a child victim, the family-ACE subtype with the use of penetration as well as further nonsexual delinquency, the peer-ACE subtype with the use of penetration and the choice of a child victim, and the neglect-subtype with the choice of a child victim. Additional analyses including single ACE categories instead of LCA-derived subtypes supported these results. Findings highlight the need for a comprehensive consideration of ACEs in research and clinical work to understand developmental pathways to juvenile sexual offending.


Radioassay of UDP-glucuronyltransferase-catalysed formation of bilirubin monoglucuronides and bilirubin diglucuronide in liver microsomes.
A radioassay for specific determination of the rates of UDP-glucuronic acid-dependent conversion of bilirubin into the two isomeric (C-8, C-12) bilirubin monoglucuronides and bilirubin diglucuronide is described and illustrated by its application to rat liver microsomes. The method is based on measurement of the relative amounts of radiolabel in unesterified bilirubin and its mono- and di-esterified reaction products after incubation with [14C]bilirubin as substrate. This analysis is performed by the alkaline-methanolysis procedure, combined with one of two t.l.c. systems developed in order to enhance the sensitivity, accuracy and precision of the radioassay. Results for rates of total bilirubin glucuronide formation obtained with the new assay and the standard enzyme assay based on the ethyl anthranilate diazo-method were identical. However, the sensitivity of the latter technique is approx. 10-fold lower than that of the radioassay.


Dynamic analysis of vascular morphogenesis using transgenic quail embryos.
One of the least understood and most central questions confronting biologists is how initially simple clusters or sheet-like cell collectives can assemble into highly complex three-dimensional functional tissues and organs. Due to the limits of oxygen diffusion, blood vessels are an essential and ubiquitous presence in all amniote tissues and organs. Vasculogenesis, the de novo self-assembly of endothelial cell (EC) precursors into endothelial tubes, is the first step in blood vessel formation. Static imaging and in vitro models are wholly inadequate to capture many aspects of vascular pattern formation in vivo, because vasculogenesis involves dynamic changes of the endothelial cells and of the forming blood vessels, in an embryo that is changing size and shape. We have generated Tie1 transgenic quail lines Tg(tie1:H2B-eYFP) that express H2B-eYFP in all of their endothelial cells which permit investigations into early embryonic vascular morphogenesis with unprecedented clarity and insight. By combining the power of molecular genetics with the elegance of dynamic imaging, we follow the precise patterning of endothelial cells in space and time. We show that during vasculogenesis within the vascular plexus, ECs move independently to form the rudiments of blood vessels, all while collectively moving with gastrulating tissues that flow toward the embryo midline. The aortae are a composite of somatic derived ECs forming its dorsal regions and the splanchnic derived ECs forming its ventral region. The ECs in the dorsal regions of the forming aortae exhibit variable mediolateral motions as they move rostrally; those in more ventral regions show significant lateral-to-medial movement as they course rostrally. The present results offer a powerful approach to the major challenge of studying the relative role(s) of the mechanical, molecular, and cellular mechanisms of vascular development. In past studies, the advantages of the molecular genetic tools available in mouse were counterbalanced by the limited experimental accessibility needed for imaging and perturbation studies. Avian embryos provide the needed accessibility, but few genetic resources. The creation of transgenic quail with labeled endothelia builds upon the important roles that avian embryos have played in previous studies of vascular development.


Excessive daytime sleepiness in young adults: a 20-year prospective community study.
Excessive daytime sleepiness (EDS) is a symptom with high clinical and public health importance because of its association with increased risk for accidents, decreased productivity, and impaired quality of life. Little information is available regarding the longitudinal course or clinical correlates of EDS. The aim of this study was to explore associations between self-reported EDS, sleep disorder symptoms, major depression, and anxiety in a longitudinal community study of young adults. A prospective single-age community study of young adults (Zurich Cohort Study) was conducted from 1978 through 1999. Information was derived from 6 interviews administered when participants (N = 591) were ages 20, 22, 27, 29, 34, and 40 years. Trained health professionals administered a semistructured interview for health habits and psychiatric and medical conditions. The presence of either or both of 2 symptoms-accidentally falling asleep or excessive need for sleep during the day-was used to establish the presence of EDS. EDS was a common complaint among the study participants, with increasing prevalence with age. Cross-sectionally, EDS was associated with insomnia symptoms, nocturnal hypersomnia, anxiety disorders, somatization, and reduced quality of life. Longitudinally, impaired sleep quality, waking up too early, and anxiety were associated with later EDS. Conversely, EDS was not significantly associated with later anxiety or depressive disorders. Insomnia symptoms and anxiety are associated with the subsequent occurrence of EDS. Although these findings do not demonstrate causality, insomnia and anxiety disorders are prevalent and treatable conditions, and our results may have important clinical implications for the prevention and treatment of EDS. Whether the results of this study are limited to populations with elevated levels of psychopathology remains to be tested.


Hybrid optical system for three-dimensional shape acquisition.
Hybrid concepts are often used to improve existing methods in many fields. We developed a hybrid optical system that consists of multiple color cameras and one depth camera to make up the concavity problem of the visual hull construction. The heterogeneous data from the color cameras and the depth camera is fused in an effective way. The experimental results show that the proposed hybrid system can reconstruct concave objects successfully by combining the visual hull and the depth data.


Plasmodium knowlesi infection: a diagnostic challenge.
Plasmodium knowlesi malaria is an uncommon, but highly prevalent parasitic infection in parts of Malaysia. This is the case of a 14-year-old Singaporean boy presenting to our emergency department with an 11-day history of fever following a school trip to Malaysia. Hepatosplenomegaly was the only clinical finding; laboratory tests showed thrombocytopaenia, lymphopaenia, mild anaemia and liver transaminitis. Specific malaria antigen tests were negative, but the peripheral blood film showed plasmodia with atypical features, with a parasite load of 0.5%. PCR confirmed the diagnosis of P knowlesi. The patient was successfully treated with chloroquine. The clinical course of P knowlesi malaria is indistinguishable from that of Plasmodium falciparum. This case highlights the importance of taking detailed travel history, careful examination of malaria blood films and judicious use of molecular techniques. Antigen tests alone may have missed a malaria diagnosis altogether, while blood film examination may wrongly identify the species as Plasmodium malariae or P falciparum. Third-generation PCR assays can be used to reliably identify P knowlesi.


Attenuation of compulsive-like behavior by fluvoxamine in a non-induced mouse model of obsessive-compulsive disorder.
The current study evaluated the role of strain and compulsive trait differences in response to fluvoxamine, a common obsessive-compulsive disorder (OCD) drug, in two different mouse strains (BIG1 and BIG2) with a spontaneous compulsive-like phenotype. For compulsive-like nest-building behavior, dose-dependent attenuation of nesting by fluvoxamine was observed for the BIG1 compulsive-like strain during the first hour after administration. No significant differences were found for the BIG2 strain during the first hour, although a dose-dependent trend similar to that in the BIG1 strain was observed. Fluvoxamine dose dependently decreased the number of marbles buried in both strains 1 h after administration. For anxiety-like behaviors in the open field, no significant drug effects were found for the latency to leave the center and the number of line crossings. Significant strain differences were observed, with the BIG2 strain showing higher anxiety-like behaviors and reduced locomotor activity compared with the BIG1 strain. Consequently, this study adds predictive validity to our mouse model of OCD, whereas the anxiety-like differences between the strains add heterogeneity to our mouse model, similar to the heterogeneity observed in OCD.


Intracellular maturation and localization of the tumour necrosis factor alpha convertase (TACE).
Tumour necrosis factor alpha convertase (TACE) is a metalloprotease/disintegrin involved in the ectodomain shedding of several proteins, a process thought to be important in inflammation, rheumatoid arthritis and murine development. The characterization of the intracellular maturation and subcellular localization of endogenous TACE is decribed in the present study. Similarly to other proteolytically active metalloprotease/disintegrins, two forms of TACE are found in cells; a full-length precursor and a mature form lacking the prodomain. Prodomain removal occurs in a late Golgi compartment, consistent with the proposed role of a furin type proprotein convertase in this process. An additional form of TACE, lacking the pro and cytoplasmic domains, is detected when cell lysates are prepared in the presence of EDTA instead of a hydroxamate-based metalloprotease inhibitor or 1,10-phenanthroline. This form appears to be generated by mature TACE cleaving its own cytoplasmic tail and may explain why little mature TACE has been detected in previous studies. In cell-surface labelling experiments, mature TACE was detected on the cell surface but immunofluorescence data indicate that TACE is predominantly localized to a perinuclear compartment similar to that described for tumour necrosis factor (TNF)alpha. This raises the possibility that TACE-mediated ectodomain shedding may occur in an intracellular compartment in addition to the cell surface.


T lymphocyte colony assay in hemophiliacs.
Unexplained lymphadenopathy, with or without accompanying symptoms, known as the "lymphadenopathy syndrome," has been recognized in groups at risk for acquired immune deficiency syndrome (AIDS), namely, homosexuals and hemophiliacs. To date, however, no test has been defined that discriminates between asymptomatic individuals and those with adenopathy in these high-risk groups. The T colony assay, which measures T lymphocyte growth in soft agar and which allows selective T cell proliferation with minimal cell-cell contact, was evaluated in asymptomatic hemophiliacs. Significantly lower mean colony counts were found in eight hemophiliacs with adenopathy (HA), 763 +/- 348 (+/- SEM), than in 16 healthy hemophiliacs (HH) 3,044 +/- 661 (P less than .005), or than in 24 heterosexual control subjects, 3,964 +/- 395 (P less than .005). The in vitro addition of exogenous interleukin-2 (IL-2) restored normal colony growth in the HA population. These results indicate that the T colony assay can detect abnormal cell-mediated immunity among hemophiliacs and specifically discriminates between asymptomatic hemophiliacs (HH) and those with adenopathy (HA). In addition, IL-2 may be of potential benefit in improving T cell defects in AIDS or the "lymphadenopathy syndrome"; however, this remains to be proven.


Dissociative adsorption dynamics of nitrogen on a Fe(111) surface.
We study the dissociative adsorption dynamics of N2 on clean bcc Fe(111) surfaces. We base our theoretical analysis on a multidimensional potential energy surface built from density functional theory. The dissociative sticking probability is computed by means of quasi-classical trajectory calculations. For normal incidence and impact energies of the order of a few eV, our theoretical results agree well with existing experimental values. For these energies, the dynamics of the dissociated molecules shows that dissociation is a direct process that follows narrow paths in the multidimensional space. For lower energies of the beam, this direct process is not enough to explain the measured values. A better agreement with the experiment is obtained if we increase the surface temperature to promote the transfer to dissociation of molecules previously trapped. Most of the molecules dissociate very close to the Fe(111) third layer atoms and with an orientation parallel to the surface. A comparison between the dissociation of N2 on Fe(111) and Fe(110) highlights the role of the different energy barriers in both surfaces.


ALS-linked TDP-43 mutations produce aberrant RNA splicing and adult-onset motor neuron disease without aggregation or loss of nuclear TDP-43.
Transactivating response region DNA binding protein (TDP-43) is the major protein component of ubiquitinated inclusions found in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions. Two ALS-causing mutants (TDP-43(Q331K) and TDP-43(M337V)), but not wild-type human TDP-43, are shown here to provoke age-dependent, mutant-dependent, progressive motor axon degeneration and motor neuron death when expressed in mice at levels and in a cell type-selective pattern similar to endogenous TDP-43. Mutant TDP-43-dependent degeneration of lower motor neurons occurs without: (i) loss of TDP-43 from the corresponding nuclei, (ii) accumulation of TDP-43 aggregates, and (iii) accumulation of insoluble TDP-43. Computational analysis using splicing-sensitive microarrays demonstrates alterations of endogenous TDP-43-dependent alternative splicing events conferred by both human wild-type and mutant TDP-43(Q331K), but with high levels of mutant TDP-43 preferentially enhancing exon exclusion of some target pre-mRNAs affecting genes involved in neurological transmission and function. Comparison with splicing alterations following TDP-43 depletion demonstrates that TDP-43(Q331K) enhances normal TDP-43 splicing function for some RNA targets but loss-of-function for others. Thus, adult-onset motor neuron disease does not require aggregation or loss of nuclear TDP-43, with ALS-linked mutants producing loss and gain of splicing function of selected RNA targets at an early disease stage.


Effect of caffeine supplementation on repeated sprint running performance.
This study examined the effects of 6 mgxkg(-1) caffeine ingestion in team-sport players (N.=10) on repeated-sprint running performance (5 sets of 6 x 20 m) and reaction times, 60 min after caffeine or placebo ingestion. Best single sprint and total set sprint times, blood lactate and simple and choice reaction times (RT) were measured. Total sprint times across sets 1, 3 and 5 (departure every 25 s) were significantly faster after caffeine (85.49+/-5.55 s) than placebo (86.98+/-5.78 s) (P<0.05). Similarly, total sprint times across sets 2 and 4 (departure every 60 s), were significantly faster after caffeine (55.99+/-3.64 s) than placebo (56.77+/-3.74 s) (P<0.05). Significantly higher blood lactates were recorded in caffeine compared to placebo after set 3 (13.1+/-1.2 vs 10.3+/-1.4 mmolxL(-1)) (P<0.05) and set 5 (13.1+/-1.3 vs 10.3+/-1.6 mmolxL(-1)) (P<0.01). There were no significant effects on simple or choice RT, although effect sizes suggested improved post-exercise times after caffeine. Caffeine ingestion 60 min prior to exercise can enhance repeated sprint running performance and is not detrimental to reaction times.


Nutraceuticals, nutritional therapy, phytonutrients, and phytotherapy for improvement of human health: a perspective on plant biotechnology application.
Plants are one of the most important resources of human foods and medicines. Rapidly increasing knowledge on nutrition, medicine, and plant biotechnology has dramatically changed the concepts about food, health and agriculture, and brought in a revolution on them. Nutritional therapy and phytotherapy have emerged as new concepts and healing systems have quickly and widely spread in recent years. Strong recommendations for consumption of nutraceuticals, natural plant foods, and the use of nutritional therapy and phytotherapy have become progressively popular to improve health, and to prevent and treat diseases. With these trends, improving the dietary nutritional values of fruits, vegetables and other crops or even bioactive components in folk herbals has become targets of the blooming plant biotechnology industry. This review attempts to display and remark on these aspects. It summarizes the progress made on nutraceuticals, nutritional therapy, phytonutrients, phytotherapy, and their related epidemiological investigations and clinical studies. It also covers markets of these health-promoting products and disease-preventing or healing systems, as well as regulations behind them that direct the development of biotechnology study and application. Finally, related patents are listed and briefly analyzed, regarding of plant biotechnological research and progress on transgenic crops to improve nutritional value, phytotherapy efficiency, or to produce pharmaceutically important secondary metabolites or high-valued protein medicines such as vaccines and antibodies.


Temporal Patterns of Pre- and Post-Natal Target Organ Damage Associated Wih Hypertensive Pregnancy: A Systematic Review.
Hypertensive pregnancy is associated with increased risks of developing a range of vascular disorders in later life. Understanding when hypertensive target organ damage first emerges could guide optimal timing of preventive interventions. This review identifies evidence of hypertensive target organ damage across cardiac, vascular, cerebral, and renal systems at different time points from pregnancy to postpartum. Systematic review of Ovid/MEDLINE, EMBASE and ClinicalTrials.gov up to and including February 2023 including review of reference lists. Identified articles underwent evaluation via a synthesis without meta-analysis using a vote-counting approach based on direction of effect, regardless of statistical significance. Risk of bias was assessed for each outcome domain and only higher quality studies were used for final analysis. From 7644 articles, 76 studies, including data from 1,742,698 pregnancies, were identified of high quality that reported either blood pressure trajectories or target organ damage during or after a hypertensive pregnancy. Left ventricular hypertrophy, white matter lesions, proteinuria and retinal microvasculature changes were first evident in women during a hypertensive pregnancy. Cardiac, cerebral and retinal changes were also reported in studies performed during the early and late post-partum period despite reduction in blood pressure early post-partum. Cognitive dysfunction was first reported late post-partum. The majority of target organ damage reported during a hypertensive pregnancy remains evident throughout the early and late post-partum period despite variation in blood pressure. Early peri-partum strategies may be required to prevent or reverse target organ damage in women who have had a hypertensive pregnancy.


Plaque production by arboviruses in Singh's Aedes albopictus cells.
We report plaquing tests of 124 virus strains, mostly arboviruses of 21 serological groups, in Singh's line of Aedes albopictus cells. Thirty of these plaqued: all were arboviruses of six groups and were known or presumed to be mosquito borne. Failing to plaque were 86 strains of arboviruses, mostly tick borne, two strains of insect pathogens, and six animal viruses not classified as arboviruses. Among mosquito-borne agents, plaquing ability appeared related to serological classification. California group and most A-group viruses failed to plaque, but nearly all members of B and Bunyamwera groups readily plaqued. Within serological group B, 14 of 16 mosquito-borne agents plaqued, but none of 13 tick-borne or vector-unassociated viruses did so. Some implications of these results for recognition and classification of arboviruses are discussed.


Allergic conjunctivitis in Jos-Nigeria.
Allergic conjunctivitis (AC) may follow seasonal or perennial pattern. There are climatic and racial risk factors involved in some types of AC. It is more prevalent in warm climatic conditions and among Afro-Caribbeans, Arabs and Asians and less among the White populations. Clinical presentations also seem to follow climatic and genetic predisposition. The purpose of this study is to determine the prevalence of AC and its clinical presentations in a hospital setting in this region in people of all ages. This is a hospital-based retrospective study of new patients seen at Adoose Specialist Hospital, Jos the capital city of Plateau State in North Central Nigeria with clinical diagnosis of AC from 2000 to 2009. There were 972 subjects, 474 (48.8%) males and 498 (51.2%) females with M:F ratio of 1:1.05. The most common symptom was itching followed by redness, pains, watery/mucoid discharge, sticky eyes, puffy eyes and photophobia. The presence of papillae in the upper tarsal or lower conjunctiva, a discrete or confluent gelatinous hypertrophy of the limbal conjunctiva (Trantas dots), hyperpigmentation, hyperemia/chemosis of the conjunctiva were the common signs. AC was more prevalent in those aged 1-16 years 38.4% decreasing to 4.9% in the age group above 50 years. The presentation followed perennial pattern, with a peak around July. The most prevalent ocular comorbid condition was refractive error (distant RE and presbyopia) in 15.4%, followed by pterygium/pinguecula 3.6%, bacterial conjunctivitis in 2.2%, glaucoma 2.1% and eyelid disorders 1.7%. Cataract was present in 1.3%, and keratopathy 1.1%. Other conditions such as episcleritis, dry eye, vitamin A deficiency and posterior segment disease were also present in decreasing order. Systemic association were few with generalised body atopy in 0.3%. The prevalence of AC was 32% and is similar to what pertains in some of the African hospital studies, but differs in presentation from the Caucasians.


Infant Nutritional Status, Feeding Practices, Enteropathogen Exposure, Socioeconomic Status, and Illness Are Associated with Gut Barrier Function As Assessed by the Lactulose Mannitol Test in the MAL-ED Birth Cohort.
The lactulose mannitol (LM) dual sugar permeability test is the most commonly used test of environmental enteropathy in developing countries. However, there is a large but conflicting literature on its association with enteric infection and host nutritional status. We conducted a longitudinal cohort using a single field protocol and comparable laboratory procedures to examine intestinal permeability in multiple, geographically diverse pediatric populations. Using a previously published systematic review to guide the selection of factors potentially associated with LM test results, we examined the relationships between these factors and mucosal breach, represented by percent lactulose excretion; absorptive area, represented by percent mannitol excretion; and gut barrier function, represented by the L/M ratio. A total of 6,602 LM tests were conducted in 1,980 children at 3, 6, 9, and 15 months old; percent lactulose excretion, percent mannitol excretion, and the L/M ratio were expressed as age- and sex-specific normalized values using the Brazil cohort as the reference population. Among the factors considered, recent severe diarrhea, lower socioeconomic status, and recent asymptomatic enteropathogen infections were associated with decreased percent mannitol excretion and higher L/M ratios. Poorer concurrent weight-for-age, infection, and recent breastfeeding were associated with increased percent lactulose excretion and increased L/M ratios. Our results support previously reported associations between the L/M ratio and factors related to child nutritional status and enteropathogen exposure. These results were remarkably consistent across sites and support the hypothesis that the frequency of these exposures in communities living in poverty leads to alterations in gut barrier function.