Measuring the psychosocial, biological, and cognitive signatures of profound stress in humanitarian settings: impacts, challenges, and strategies in the field.
Evidence of 'what works' in humanitarian programming is important for addressing the disruptive consequences of conflict and forced displacement. However, collecting robust scientific evidence, and ensuring contextual relevance, is challenging. We measured the biological, psychosocial, and cognitive impacts of a structured psychosocial intervention, implemented by Mercy Corps with Syrian refugees and Jordanian host-community youth. In this paper, we present a case analysis of this evaluation study and reflect on the scientific contributions of the work, the challenges experienced in its delivery, and the strategies deployed to address them. We identified challenges with respect to study design, methods, and dissemination: these included the logistics and acceptability of implementing a randomized controlled trial in a humanitarian context, the selection and refinement of culturally-relevant research tools and community-based practices, and the dissemination of results to multiple stakeholders. We demonstrated beneficial and sustained impacts on self-reports of insecurity, stress, and mental health; developed a reliable and culturally-relevant measure of resilience; experimentally tested cognitive skills; and showed that levels of cortisol, a biomarker of chronic stress, reduced by one third in response to intervention. Using stress biomarkers offered proof-of-concept evidence, beyond self-reported data: interventions targeting mental health and psychosocial wellbeing can regulate physiological stress in the body as well as improve self-reported mental health and wellbeing. We built constructive dialogue between local communities, scholars, humanitarian practitioners, and policy-makers. Our work shows the value of rigorous research in humanitarian settings, emphasizing relevance for local communities and meaningful ways to build research ownership. Findings encourage the adoption of cognitive measures and stress biomarkers alongside self-report surveys in evaluating programme impacts. High-quality scientific research with youth can be feasible, useful, and ethical in humanitarian settings.


The changing demographic, legal, and technological contexts of political representation.
Three developments have created challenges for political representation in the U.S. and particularly for the use of territorially based representation (election by district). First, the demographic complexity of the U.S. population has grown both in absolute terms and in terms of residential patterns. Second, legal developments since the 1960s have recognized an increasing number of groups as eligible for voting rights protection. Third, the growing technical capacities of computer technology, particularly Geographic Information Systems, have allowed political parties and other organizations to create election districts with increasingly precise political and demographic characteristics. Scholars have made considerable progress in measuring and evaluating the racial and partisan biases of districting plans, and some states have tried to use Geographic Information Systems technology to produce more representative districts. However, case studies of Texas and Arizona illustrate that such analytic and technical advances have not overcome the basic contradictions that underlie the American system of territorial political representation.


A Parameter-Free Semilocal Exchange Energy Functional for Two-Dimensional Quantum Systems.
The method of constructing semilocal density functional for exchange in two dimensions using one of the premier approaches, i.e., density matrix expansion, is revisited, and an accurate functional is constructed. The form of the functional is quite simple and includes no adjustable semiempirical parameters. In it, the kinetic energy dependent momentum is used to compensate nonlocal effects of the system. The functional is then examined by considering the very well-known semiconductor quantum dot systems. And despite its very simple form, the results obtained for quantum dots containing a higher number of electrons agrees pretty well with that of the standard exact exchange theory. Some of the desired properties relevant for the two-dimensional exchange functional and the lower bound associated with it are also discussed. It is observed that the above parameter-free semilocal exchange functional satisfies most of the discussed conditions.


EDDS and EDTA-enhanced zinc accumulation by Solanum nigrum inoculated with arbuscular mycorrhizal fungi grown in contaminated soil.
The effect of two different chelating agents [EDTA and EDDS (S,S-ethylenediaminedissucinic acid)] on Zn tissue accumulation in Solanum nigrum L. grown in a naturally contaminated soil was assessed. Under those conditions, the response of the plant to the inoculation with two different isolates of arbuscular mycorrhizal fungi (AMF)--Glomus claroideum and Glomus intraradices--was also studied. Plants grown in the local contaminated soil (Zn levels of 433mg kg(-1)) accumulated up to 1191mg kg(-1) of Zn in the roots, 3747mg kg(-1) in the stems and 3409mg kg(-1) in the leaves. S. nigrum plants grown in the same soil spiked with extra Zn (Zn levels of 964mg kg(-1)) accumulated up to 4735, 8267 and 7948mg Zn kg(-1) in the leaves, stems and roots, respectively. The addition of EDTA promoted an increase in the concentration of Zn accumulated by S. nigrum of up to 231% in the leaves, 93% in the stems and 81% in the roots, while EDDS application enhanced the accumulation in leaves, stems and roots up to 140, 124 and 104%, respectively. In the stems, the presence of Zn was predominantly detected in the cortex collenchyma cells, the starch sheath and the internal phloem and xylem parenchyma, and the addition of chelating agents did not seem to have an effect on the localisation of accumulation sites. The devise of a chelate-enhanced phytoextraction strategy, using chelating agents and AMF, is discussed.


Hispidin rescues palmitate‑induced insulin resistance in C2C12 myotubes.
Skeletal muscle serves an important role in the utilization of glucose during insulin‑stimulated conditions. Excessive saturated fatty acids are considered to be a major contributing factor to insulin resistance in skeletal muscle cells. The present study investigated the effects of hispidin on palmitate‑induced insulin resistance in C2C12 skeletal muscle myotubes via an MTT assay, glucose uptake assay, Oil‑Red‑O staining and western blot analysis. Hispidin reversed the palmitate‑induced inhibition of glucose uptake, and inhibited palmitate‑induced intracellular lipid accumulation. Hispidin suppressed insulin receptor substrate‑1 Ser307 phosphorylation, and significantly promoted the activation of phosphatidylinositol‑3‑kinase and Akt, via inhibition of protein kinase C theta. Furthermore, hispidin treatment of C2C12 muscle cells increased glucose uptake via activation of adenosine monophosphate‑activated protein kinase. These findings indicated that hispidin may improve palmitate‑induced insulin resistance in skeletal muscle myotubes, and therefore hispidin treatment may be beneficial for patients with diabetes.


Histopathological features of autoimmune pancreatitis.
Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas characterised by lymphoplasmacytic infiltrates, interstitial fibrosis, periductal inflammation and periphlebitis. Although first described more than four decades ago, it has not gained widespread attention until the 1990s when new insights into its aetiology, clinical presentation and management were discovered. Although nowadays widely accepted as a form of chronic pancreatitis, recent evidence suggests that AIP might not be confined to the pancreas but rather be an inflammatory pancreaticobiliary disease (autoimmune pancreatocholangitis, AIPC) with possible systemic involvement and association with other autoimmune disorders. This article reviews current concepts of AIP with special focus on the histopathological features of the disease.


Cerebral amyloid in human prion disease.
The clinical and neuropathological features of 21 patients with prion disease were reviewed with special reference to the morphology and immunoreactivity of cerebral amyloid. Six cases had a mutation at codon 102 of the prion protein (PrP) gene and in these the characteristic pathology was the formation of multicentric amyloid plaques which were stained with PrP antibody, whereas spongiform changes were absent in one and minimal in two. In one case, with a 216 base-pair insertion in the PrP gene, there was no spongiform encephalopathy (SE) but cerebellar amyloid was a prominent feature of the pathology. One case with a PrP gene mutation at codon 200 had severe SE but no amyloid. Two iatrogenic and 11 sporadic cases had SE and some form of amyloid was identified in all but three. Amyloid angiopathy and senile neuritic plaques, which stained with antibody to beta-protein, were present in familial as well as in sporadic cases, including some who were rather young to be regarded as having Alzheimer's disease. Cerebellar amyloid and degeneration of granule and Purkinje cells were particularly common findings in sporadic as well as in genetically determined cases. This study serves to emphasize the association between prion disease and amyloid deposition in the brain. PrP is a component of some amyloid plaques in a high proportion of cases with inherited prion disease but may also be found in cases of sporadic SE without known mutations or base-pair insertions in the PrP gene.


Generation of symptomatic palatal tremor is not correlated with inferior olivary hypertrophy.
Although the generation of symptomatic palatal tremor (SPT) is thought to derive from the abnormal activity of hypertrophic inferior olivary neurones, the actual mechanism of SPT has not yet been elucidated. We therefore investigated the relationship between SPT and the pathological process of inferior olivary hypertrophy (IOH). We examined 16 autopsied subjects with cerebrovascular lesions of the dentate-olivary tracts. We analysed the size of the olives, the number of olivary neurones, synaptic, axonal and astrocytic changes in the olives and the clinical course in the subjects. SPT was observed in eight patients, in seven of whom it appeared 1-2 months after interruption of the afferents then progressed to reach a peak approximately 1-2 years from the onset. SPT persisted for the rest of the subjects' lives without decreasing in severity. Neuronal hypertrophic change began 20-30 days after the onset of the causative lesions and reached maximum size, accompanied by prominent astrocytosis and synaptic and axonal remodelling, 6-7 months later. The number of olivary neurones decreased to <10% of that in controls in patients who survived >6 years. Despite the persistence of SPT, both the myelin and the axons of efferent fibres from olivary neurones were severely degenerated in patients who survived several years. Therefore, the appearance of SPT may depend on the hyperactivity of olivary neurones released from inhibitory inputs until the peak of both IOH and SPT. However, the persistence of peak intensity and distribution of established SPT is probably due to both the disturbance of natural rhythmicity in the body and the lack of feedback from the abnormal movement resulting from the dysfunction of the olive.


Recent advances in the pathological understanding of eosinophilic esophagitis.
Eosinophilic esophagitis (EoE) is a chronic allergen-mediated inflammatory disease of the esophagus. This inflammation leads to feeding difficulties, failure to thrive and vomiting in young children, and causes food impaction and esophageal stricture in adolescents and adults. In the 20 years since EoE was first described, we have gained a great deal of knowledge regarding the genetic predisposition of disease, the inflammatory milieu associated with EoE and the long-term complications of chronic inflammation. Herein, we summarize the important breakthroughs in the field including both in vitro and in vivo analysis. We discuss insights that we have gained from large-scale unbiased genetic analysis, a multitude of genetically and chemically altered mouse models of EoE and most importantly, the results of clinical trials of various pharmacologic agents. Understanding these successes and failures may be the key to developing more effective therapeutic strategies.


Self-mode-locking semiconductor disk laser.
The development of mode-locked semiconductor disk lasers received striking attention in the last 14 years and there is still a vast potential of such pulsed lasers to be explored and exploited. While for more than one decade pulsed operation was strongly linked to the employment of a saturable absorber, self-mode-locking emerged recently as an effective and novel technique in this field - giving prospect to a reduced complexity and improved cost-efficiency of such lasers. In this work, we highlight recent achievements regarding self-mode-locked semiconductor devices. It is worth to note, that although nonlinear effects in the active medium are expected to give rise to self-mode-locking, this has to be investigated with care in future experiments. However, there is a controversy whether results presented with respect to self-mode-locking truly show mode-locking. Such concerns are addressed in this work and we provide a clear evidence of mode-locking in a saturable-absorber-free device. By using a BBO crystal outside the cavity, green light originating from second-harmonic generation using the out-coupled laser beam is demonstrated. In addition, long-time-span pulse trains as well as radiofrequency-spectra measurements are presented for our sub-ps pulses at 500 MHz repetition rate which indicate the stable pulse operation of our device. Furthermore, a long-time-span autocorrelation trace is introduced which clearly shows absence of a pedestal or double pulses. Eventually, a beam-profile measurement reveals the excellent beam quality of our device with an M-square factor of less than 1.1 for both axes, showing that self-mode-locking can be achieved for the fundamental transverse mode.


Comparison of Omadacycline and Tigecycline Pharmacokinetics in the Plasma, Epithelial Lining Fluid, and Alveolar Cells of Healthy Adult Subjects.
The steady-state concentrations of omadacycline and tigecycline in the plasma, epithelial lining fluid (ELF), and alveolar cells (AC) of 58 healthy adult subjects were obtained. Subjects were administered either omadacycline at 100 mg intravenously (i.v.) every 12 h for two doses followed by 100 mg i.v. every 24 h for three doses or tigecycline at an initial dose of 100 mg i.v. followed by 50 mg i.v. every 12 h for six doses. A bronchoscopy and bronchoalveolar lavage were performed once in each subject following the start of the fifth dose of omadacycline at 0.5, 1, 2, 4, 8, 12, or 24 h and after the start of the seventh dose of tigecycline at 2, 4, 6, or 12 h. The value of the area under the concentration-time curve (AUC) from time zero to 24 h postdosing (AUC0-24) (based on mean concentrations) in ELF and the ratio of the ELF to total plasma omadacycline concentration based on AUC0-24 values were 17.23 mg · h/liter and 1.47, respectively. The AUC0-24 value in AC was 302.46 mg · h/liter, and the ratio of the AC to total plasma omadacycline concentration was 25.8. In comparison, the values of the AUC from time zero to 12 h postdosing (AUC0-12) based on the mean concentrations of tigecycline in ELF and AC were 3.16 and 38.50 mg · h/liter, respectively. The ratio of the ELF and AC to total plasma concentrations of tigecycline based on AUC0-12 values were 1.71 and 20.8, respectively. The pharmacokinetic advantages of higher and sustained concentrations of omadacycline compared to those of tigecycline in plasma, ELF, and AC suggest that omadacycline is a promising antibacterial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens.


Effect of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, on experimental Chlamydophila pneumoniae infection.
Chlamydophila pneumoniae is a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniae and alpha(v)beta(3) integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniae and treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P > 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 10(6) inclusion-forming units of C. pneumoniae were treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniae counts versus those for the controls; this finding did not differ significantly (P > 0.05) from the results observed for the antibiotic-treated group. Integrin alpha(v)beta(3) plays an important role in C. pneumoniae infection. Blockage of integrin activation led to a significant inhibition of C. pneumoniae infection in HeLa cells. Moreover, CHO(DHFR) alpha(v)beta(3)-expressing cells were significantly (P < 0.001) more susceptible to C. pneumoniae infection than CHO(DHFR) cells. These results offer new perspectives on the treatment of C. pneumoniae infection and indicate that alpha(v)beta(3) could be a promising target for new agents developed for activity against this pathogen.


Kinetic studies on the specificity of chelate-iron uptake in Aspergillus.
Three strains of the fungus Aspergillus, Aspergillus quadricinctus (E. Yuill), A. fumigatus (Fresenius), and A. melleus (Yukawa), each producing different iron-chelating compounds during iron-deficient cultivation, were used for 55Fe3+ uptake measurements. Iron from chelates of the ferrichrome-type family was taken up by young mycelia of all strains tested, irrespective of the ferrichrome-type compound these strains predominantly produce in low-iron cultures. Ferrichrysin-producing strains, however, seem to favor ferrichrysin iron uptake, whereas ferrichrome, ferricrocin, and even ferrirubin showed similar iron transport properties in all of these strains. Compared to iron uptake from ferrichrome-type compounds (Km approximately 4 uM) iron uptake from fusigen revealed completely different kinetic values (Km approximately 50 to 80 muM). Iron from exogenous chelates, e.g., from coprogen produced by Neurospora crassa for ferrioxamine B produced by Streptomyces pilosus, can obviously not be taken up by Aspergillus, confirming the pronounced specificity of chelate-iron transport in fungi.


[Value of quantitative tissue velocity imaging in the evaluation of cardiac function and diagnosis of left heart failure].
To investigate the value of quantitative tissue velocity imaging (QTVI) echocardiography in the evaluation of cardiac function and the diagnosis of left heart failure. 30 heart failure (HF) patients, aged 66 +/- 12 (39 - 86), and 32 normal controls, 66 +/- 12 (40 - 82) underwent conventional echocardiography, and QTVI. Left ventricular ejection fraction (LVEF) was calculated by Simpson's formula. Mitral annulus peak systolic velocity (Vs) and systolic displacement (Ds) from posteroseptal, lateral, anteroseptal, posterior, anterior, and inferior segments were determined by QTVI, and the mean Vs and Ds were calculated. The values of mean Vs and Ds of the HF patients and those of the normal controls, and the values of mean Vs and Ds of the HF patients before and after treatment were compared. The correlation of the mean Vs and Ds with LVEF was analyzed. The mean Vs of the HF patients was 2.8 cm/s +/- 0.6 cm/s, significantly lower than that of the normal controls (6.4 cm/s +/- 0.9 cm/s, P < 0.01). The mean Vs of the HF patients after treatment was 3.5 cm/s +/- 1.1 cm/s, significantly higher than that before treatment (2.8 cm/s +/- 0.6 cm/s, P < 0.01). The mean Ds of the HF patients was 5.2 mm +/- 1.5 mm, significantly lower than that of the normal controls (11.6 mm +/- 1.5 mm, P < 0.01). The mean Ds of the HF patients after treatment was 6.5 mm +/- 2.0 mm, significantly higher than that before treatment (5.2 mm +/- 1.5 mm, P < 0.01). The mean Vs and mean Ds were positively correlated with LVEF (r = 0.87, P < 0.01, and r = 0.89, P < 0.01). The area under the curve (AUC) of receiver operator characteristic (ROC) was 0.95 for the mean Vs to diagnose HF. The mean Vs < or = 4.42 cm/s was used as a cut-off point to diagnosis left HF with a sensitivity of 97.5% a specificity of 90.2%, and an accuracy rating of 95.1%. The AUC of ROC was 0.96 for the mean Ds to diagnose HF. The mean Ds < or = 8.49 mm was used as a cut-off point to diagnose left HF with a sensitivity of 97.5%, a specificity of 87.8%, and an accuracy rating was 95.1%. The mean systolic velocity and mean systolic displacement of mitral annulus determined by QTVI help evaluate the left ventricular systolic function. The value of the diagnosis is significant in left HF.


Effects of heparin and its 6-O-and 2-O-desulfated derivatives with low anticoagulant activity on proliferation of human neural stem/progenitor cells.
Heparin binds various growth factors and activates them to interact with high-affinity cell surface receptors; a specific array of sulfate groups in the heparin backbone structure is very important for this interaction. In the present study, we evaluated the effects of two novel heparin derivatives, 6-O-desulfated heparin (6-DSH) and 2-O-desulfated heparin (2-DSH), on blood coagulation and the proliferation of human neural stem/progenitor cells (NSPCs). 6-DSH showed lower anticoagulant activity than intact heparin or 2-DSH, as measured by the activated partial thromboplastin time and thrombin time. In the presence of FGF-2, 6-DSH and 2-DSH promoted approximately the same rate of proliferation of human NSPCs, without noticeably changing the expression of nestin. The mitotic effects of 6-DSH and 2-DSH on human NSPCs were different from their effects on mouse hematopoietic stem cells and fibroblasts. These findings indicate that 6-DSH and 2-DSH have the same ability to promote the growth of human NSPCs as intact heparin. Our results suggest that these two novel heparin derivates, especially 6-DSH, could be used in clinical applications for ex vivo human NSPC culture, as a lower-risk growth co-adjuvant than intact heparin.


Orthostatic hypoxaemia in dialysed adult polycystic kidney disease patients.
Recently we observed a unique clinical phenomenon, namely, orthostatic or postural hypoxaemia in a 72-year-old female adult polycystic kidney disease (APKD) patient, maintained on CAPD. Extensive investigations failed to yield a satisfactory explanation for her ambulatory hypoxaemia. To validate our observation, 15 dialysed patients underwent blood gases analyses in both the supine and ambulatory positions (SpO2 and ApO2 respectively). Patients were divided into two groups: group 1 (n-7) whose end-stage renal failure (ESRF) was due to APKD and group 2 (n-8) in whom ESRF was due to other causes. Both haemodialysed (HD) and CAPD patients were included. ApO2 was determined as the pO2 immediately upon standing up. Readings in HD patients were taken at the end of the dialysis session, that is, at the patients' dry weight. Respective SpO2 and ApO2 of the two groups were 85 +/- 17.1 and 78 +/- 20.5 vs 85.8 +/- 19 and 91 +/- 21 mmHg. Delta change in pO2 defined as the mean decrease (negative value) or mean increase (positive value) of ApO2 in relation to SpO2 was -7.85 (group 1) vs + 5.2 mmHg (group 2), P < 0.005. In group 1, six of seven patients demonstrated a negative delta. In group 2, four of eight showed a positive delta whilst the remaining four had no change in the delta value. Orthostatic hypoxaemia may occur in dialysed patients whose ESRF is due to APKD.


Suicides on farms in South Australia, 1997-2001.
Despite much having been written, both nationally and internationally, about rural suicides, no one in Australia knows either the number of residents on farms or the suicide rate for this group of people. This paper seeks to determine the number of residents on farms in South Australia, along with the suicide rate. A retrospective audit review of the files of suicides completed between the 1 January 1997 and 31 December 2001 was undertaken in the South Australian Coroner's Office. There were 1033 cases examined for sociodemographic details and 380 files were explored in detail. Estimating both the number of agricultural establishments in South Australia and the resident population on farms for 2001, and determining the number of suicides on farms between 1997 and 2001, the farm suicide rate was found to be 33.8 for men, 6.7 for women and 21.6 per 100,000 for persons, much higher than the rural suicide rate for South Australia in 2001 (23.8 for men, 5.6 for women and 14.5 per 100,000 for persons) according to the Australian Bureau of Statistics. This study provides an estimate of the number of farm residents in South Australia in 2001, the number and rate of suicides on farms in South Australia in 2001, and shows that this rate is significantly higher than the overall rate of suicide in South Australia in 2001.


Solution of the boundary value problem for optimal escape in continuous stochastic systems and maps.
Topologies of invariant manifolds and optimal trajectories are investigated in stochastic continuous systems and maps. A topological method is introduced that simplifies the solution of boundary value problems: The activation energy is calculated as a function of a set of parameters characterizing the initial conditions of the escape path. The method is applied explicitly to compute the optimal escape path and the activation energy for a variety of dynamical systems and maps.


[Time-Temperature indicators (TTI). A means of quality control of produce].
The author, after having dwelt on the mediatic importance of bacterial food poisonings, analyses their reasons, insisting on the importance of the temperature as a factor of bacterial growth. Among the cures for the association temperature-bacterial growth, the author draws attention to the benefits of the use of the time temperature indicators (TTI). He describes the purposes, the required qualities, the principles of activity. The "Lifelines TTI" proves to be interesting. The author describes the principles of activity, the directions for reading the results, the practical application. Finally he describes the remarks following on its use in large scale in a group of chain-stores. In the conclusion, the author points that these TTI are an attractive technical innovation regarding to the fresh foods, for the control of coldness in the human nutrition.


Retinal pathology and function in a Cln3 knockout mouse model of juvenile Neuronal Ceroid Lipofuscinosis (batten disease).
Batten disease or JNCL, is the juvenile form of Neuronal Ceroid Lipofuscinosis (NCL) an autosomal recessive neurodegenerative disorder. Since retinal degeneration is an early consequence of Batten disease, we examined the eyes of Cln3 knockout mice (1-20 months of age), along with heterozygotes and appropriate controls, to determine whether or not the Cln3 defect would lead to characteristic retinal degeneration and visual loss. Accumulation of autofluorescent material and intracellular inclusions were markedly increased in Cln3 knockout retinal ganglion cells, as well as most other nuclear layers. Nerve fiber density was also significantly decreased in Cln3 knockout retinae. Apoptosis was observed in the photoreceptor layer of Cln3 knockout. However, the degree of retinal degeneration up to age 20 months was not extensive. Fundus examinations of Cln3 knockout mice showed no significant abnormalities, while electroretinograms remained robust through 11 months of age. In summary, it appears that accumulation of autofluorescent material, carbohydrate storage material, as well as apoptotic cell death are retinal manifestations of the Cln3 defect that do not appear to extinguish retinal function in this mouse model of Batten disease.


Muscular contributions to hip and knee extension during the single limb stance phase of normal gait: a framework for investigating the causes of crouch gait.
Crouch gait, a troublesome movement abnormality among persons with cerebral palsy, is characterized by excessive flexion of the hips and knees during stance. Treatment of crouch gait is challenging, at present, because the factors that contribute to hip and knee extension during normal gait are not well understood, and because the potential of individual muscles to produce flexion or extension of the joints during stance is unknown. This study analyzed a three-dimensional, muscle-actuated dynamic simulation of walking to quantify the angular accelerations of the hip and knee induced by muscles during normal gait, and to rank the potential of the muscles to alter motions of these joints. Examination of the muscle actions during single limb stance showed that the gluteus maximus, vasti, and soleus make substantial contributions to hip and knee extension during normal gait. Per unit force, the gluteus maximus had greater potential than the vasti to accelerate the knee toward extension. These data suggest that weak hip extensors, knee extensors, or ankle plantar flexors may contribute to crouch gait, and strengthening these muscles--particularly gluteus maximus--may improve hip and knee extension. Abnormal forces generated by the iliopsoas or adductors may also contribute to crouch gait, as our analysis showed that these muscles have the potential to accelerate the hip and knee toward flexion. This work emphasizes the need to consider how muscular forces contribute to multijoint movements when attempting to identify the causes of abnormal gait.


Oral efficacy of an attenuated rabies virus vaccine in skunks and raccoons.
Raccoons and skunks are major rabies reservoirs in North America. Oral vaccination is one method to consider for disease control in these carnivores. Under field conditions in the USA, only one oral rabies vaccine has been used. It is efficacious in wildlife such as raccoons (Procyon lotor), coyotes (Canis latrans), and foxes (Vulpes vulpes) but not in skunks (Mephitis mephitis). The objectives of this study were to evaluate an attenuated SAG-2 rabies virus vaccine for safety, immunogenicity, and efficacy by the oral route in skunks and raccoons. Two of five skunks and three of five raccoons developed virus neutralizing antibodies (VNA) by day 14 following oral administration of SAG-2 vaccine. All animals remained healthy. Upon challenge, naive controls succumbed to rabies. Among vaccinated animals, four of five skunks and all five raccoons had VNA on day 7 post-challenge and all survived. Given these results, SAG-2 is a promising candidate vaccine that may satisfy both safety and efficacy concerns for oral rabies immunization of major North American rabies reservoirs.


Soft tissue composition, quadriceps strength, bone quality and bone mass in rheumatoid arthritis.
To examine differences in soft tissue composition, bone quality, bone mass and quadriceps strength between women with rheumatoid arthritis (RA) and healthy controls. 79 women with RA (median disease duration 10 yrs) were studied. Most were or had been on steroids. 67 healthy age-matched women served as controls. The lean tissue mass (LTM) and fat mass (FM) of the total body and of the major body subregions, as well as the bone mineral density (BMD, g/cm2) of the femoral neck, spine (L2-L4) and distal forearm were measured by dual energy x-ray absorptiometry (DXA). Bone quality expressed as the speed of sound (SOS m/sec), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness was assessed by an Achilles ultrasound device, and isometric quadriceps strength by an isokinetic dynamometer. No between-group differences were found for the body mass index (BMI, weight/height2), total or regional percentage fat, LTM and FM. However, women with RA had 20% lower quadriceps strength than controls. BMD at the femoral neck and distal forearm, and SOS, BUA and stiffness were significantly lower in patients than in controls. No difference was found for spine BMD. In the RA group, z-scores for SOS and stiffness were significantly more reduced than those for BMD. Multiple regression analyses indicated negative associations between ultrasound parameters and the cumulative steroid dose. Reductions in BMD and muscle strength in RA were not accompanied by changes in soft tissue composition, Bone quality assessed by ultrasonography was compromised in RA and may be modified by steroids.


Top five legal pitfalls in retinopathy of prematurity.
This review highlights the common areas of medicolegal risk during retinopathy of prematurity (ROP) screening. Most malpractice risk in ROP comes from systemic errors that ultimately result in failure to screen the patient in a timely fashion, resulting in failures to intervene and/or refer in a timely fashion. Currently, the emphasis is engaging the family members, the hospital staff, and clinic staff to pro-actively manage ROP patients and ensure that they are screened in a timely fashion. Coordinating care between multiple caregivers can minimize risk. Risk increases when practitioners do not stay up to date on current screening and treatment guidelines or on the most recent study recommendations. Finally, it is important to maintain a high level of suspicion when dealing with infants is known to be predisposed to poor outcomes. Premature infants with short gestation and very low birthweights need to have structured screening coordinated between the hospital, the clinic, the physicians, and the family in order to minimize medicolegal risk and maximize beneficial outcomes.


A Larger Body Mass Index is Associated with Increased Atherogenic Dyslipidemia, Insulin Resistance, and Low-Grade Inflammation in Individuals with Metabolic Syndrome.
The consequences of increased body mass index (BMI) on the metabolic disorders associated with metabolic syndrome (MetS) have not been thoroughly examined. We analyzed data from 262 individuals, 97 men and 165 women (aged 18-70 years), classified with MetS to investigate whether variations in BMI could be associated with parameters of dyslipidemia, insulin resistance, or low-grade inflammation. We hypothesized that increases in BMI would positively correlate with the major dysregulations in metabolism that define MetS. For this purpose, individuals were separated into four subgroups based on their BMI: normal weight (<25 kg/m(2)), overweight (≥25 to <30 kg/m(2)), obese (≥30 to <40 kg/m(2)), and morbidly obese (≥40 kg/m(2)). As expected, body weight and waist circumference increased significantly as BMI increased (P < 0.0001). Both systolic and diastolic blood pressure were lower in the normal BMI group compared with the other three BMI groups (P = 0.001). Markers of HDL metabolism were adversely impacted in elevated BMI groups, as both high-density lipoprotein cholesterol (HDL-C) and large HDL decreased as BMI increased (P = 0.01). BMI was negatively correlated with HDL-C (r = -0.193, P = 0.002), HDL size (r = (-)0.227, P = 0.002), and large HDL (r = -0.147, P = 0.037). In addition, plasma insulin was highest in subjects classified as morbidly obese (P < 0.0001). There was also a strong positive correlation between BMI and plasma insulin (r = 0.413, P < 0.0001), whereas adiponectin, a marker of insulin sensitivity, was negatively correlated with BMI (r = -0.288, P = 0.001). Finally, BMI was positively correlated with proinflammatory C-reactive protein (r = 0.312, P = 0.0001) and interleukin-6 (r = 0.238, P = 0.001). The data from this study suggest that the physiological factors associated with increased BMI exacerbate the metabolic abnormalities characteristic of MetS.


Predictors of endoscopic inflammation in patients with ulcerative colitis in clinical remission.
Patients with ulcerative colitis (UC) who are in clinical remission may still have underlying endoscopic inflammation, which is associated with inferior clinical outcomes. The goal of this study was to determine the prevalence of active endoscopic disease, and factors associated with it, in patients with UC who are in clinical remission. Prospective observational study in a single center. Patients with UC in clinical remission (by Simple Clinical Colitis Activity Index) were enrolled prospectively at the time of surveillance colonoscopy. Disease phenotype, endoscopic activity (Mayo subscore), and histologic score (Geboes) were recorded, and blood was drawn for peripheral blood biomarkers. Overall, 149 patients in clinical remission were prospectively enrolled in this cohort; 81% had been in clinical remission for >6 months, and 86% were currently prescribed maintenance medications. At endoscopy, 45% of patients in clinical remission had any endoscopic inflammation (Mayo endoscopy subscore >0), and 13% had scores >1. In a multivariate model, variables independently associated with a Mayo endoscopic score >1 were remission for <6 months (P = 0.001), white blood count (P = 0.01), and C-reactive protein level (P = 0.009). A model combining these 3 variables had a sensitivity of 94% and a specificity of 73% for predicting moderate-to-severe endoscopic activity in patients in clinical remission (area under the curve, 0.86). In an unselected subgroup of patients who had peripheral blood mononuclear cell messenger RNA profiling, GATA3 messenger RNA levels were significantly higher in patients with endoscopic activity. Duration of clinical remission, white blood count, and C-reactive protein level can predict the probability of ongoing endoscopic activity, despite clinical remission in patients with UC. These parameters could be used to identify patients who require intensification of treatment to achieve mucosal healing.


Migration load and the coexistence of ecologically similar sexuals and asexuals.
The frozen niche variation hypothesis suggests that sexuals can coexist with closely related, ecologically similar asexuals because sexuals and narrowly adapted asexual clones use different resources. However, because a collection of clones can potentially dominate the entire resource axis, such coexistence is not stable. We show that if the sexual population inhabits multiple selection regimes and asexuals are intrinsically slightly less fit than sexuals, migration load in the sexual population allows sexuals and asexuals to coexist stably at the regional level. By decreasing sexuals' fitness, migration load allows asexuals to invade the sexual population. However, as the sexuals' range contracts, migration load decreases, preventing asexuals from driving sexuals to extinction. This "buffering" effect of migration load is even more relevant in models that include more realistic conditions, such as demographic asymmetries or explicit spatial structure.


An infrastructure for cooperation and communication in an advanced clinical information system.
In a research project, organizational and technological requirements for an advanced clinical information system have been analysed, and a concept has been developed. From the application's perspective, medical personnel is more actively relieved from routine tasks by support of organizational tasks and by coordination of distributed activities. Program development is supported by a concept of simple and complex services with well-defined interfaces, and by the use of activity templates, i.e. pre-modeled activities describing possible sequences of services. The concept is based on an open systems approach, with a reliable and secure communication infrastructure. In addition, monitoring facilities are provided.


Phosphoproteomics study on the activated PKCδ-induced cell death.
The proteolytic activation of protein kinase Cδ (PKCδ) generates a catalytic fragment called PKCδ-CF, which induces cell death. However, the mechanisms underlying PKCδ-CF-mediated cell death are largely unknown. On the basis of an engineering leukemic cell line with inducible expression of PKCδ-CF, here we employ SILAC-based quantitative phosphoproteomics to systematically and dynamically investigate the overall phosphorylation events during cell death triggered by PKCδ-CF expression. Totally, 3000 phosphorylation sites were analyzed. Considering the fact that early responses to PKCδ-CF expression initiate cell death, we sought to identify pathways possibly related directly with PKCδ by further analyzing the data set of phosphorylation events that occur in the initiation stage of cell death. Interacting analysis of this data set indicates that PKCδ-CF triggers complicated networks to initiate cell death, and motif analysis and biochemistry verification reveal that several kinases in the downstream of PKCδ conduct these networks. By analysis of the specific sequence motif of kinase-substrate, we also find 59 candidate substrates of PKCδ from the up-regulated phosphopeptides, of which 12 were randomly selected for in vitro kinase assay and 9 were consequently verified as substrates of PKCδ. To our greatest understanding, this study provides the most systematic analysis of phosphorylation events initiated by the cleaved activated PKCδ, which would vastly extend the profound understanding of PKCδ-directed signal pathways in cell death. The MS data have been deposited to the ProteomeXchange with identifier PXD000225.


Antinuclear antibodies with nucleosome-restricted specificity for targeted delivery of chemotherapeutic agents.
Circulating antinuclear autoantibodies (ANAs) are well known to accompany various pathological conditions and can be artificially induced by immunization. Research and clinical data permit us to hypothesize a definite connection between cancer and ANAs. Based on the available data, my group's research suggested that exogenous ANAs may be used as anticancer therapeutics. Among these ANAs, nucleosome-specific ANAs may be particularly useful. Advances in cancer immunotherapy with monoclonal antibodies re-emphasized the role of humoral immunity in neoplasia control. The development of a universal antibody targeting diverse cancers is of clear importance. We showed that certain natural ANAs recognize the surface of numerous tumor cells but not normal cells via cell surface-bound nucleosomes originating from the apoptotically dying neighboring tumor cells, mediate antibody-dependent cellular cytotoxicity of tumor cells in vitro and inhibit the development of murine tumor in syngeneic mice. A single monoclonal antinuclear nucleosome-specific autoantibody, mAb 2C5, specifically recognizes multiple unrelated human tumor cell lines and accumulates at a high tumor-to-normal cell ratio in various human tumors in nude mice. Immunotherapy with mAb 2C5 resulted in significant suppression of the growth of several human tumors. In addition, mAb 2C5, when used in subtherapeutic quantities, can serve as a highly efficient specific ligand to target various drug- or diagnostic agent-loaded pharmaceutical nanocarriers, such as liposomes and polymeric micelles, to various tumors. Here, the data (accumulated predominantly in our laboratory over several years) on mAb 2C5-mediated tumor targeting of chemotherapeutic agents is reviewed.


[Postgraduate trainings program in pathology and laboratory medicine at teaching hospitals of Japan].
It is meaningful to propose a postgraduate training program in pathology and laboratory medicine to select the course after graduation and promote recognition of the roles of pathologists(AP) and laboratory physicians(CP). It is desirable that the training program be common to both AP and CP, although this would be difficult in practice. So author proposes a practical training program that should involve making rounds with AP and CP. The desirable period of training is 3 or 4 years. In the program of laboratory medicine for AP, conferences and CPC are essential and other courses are elective. In the selective program, laboratory management is very important because it will be useful when the graduate becomes a laboratory manager. In the pathology program for CP, autopsy and CPC(as a pathologist) are essential. Training in surgical pathology and cytology are desirable to set limits in materials, for example, liver, kidney, bone marrow, and other tissues. Key points of successful training are good relationships chiefs of AP and CP, high level performance and give-and-take in routine work. It is very difficult to study and maintain the knowledge and technique necessary in all fields of pathology and laboratory medicine. So the author emphasizes that the training program should be constructed to focus on useful issues in routine work and management of laboratory.


Left atrial diameter, aortic mean gradient, and hemoglobin for risk stratification in patients undergoing transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is an alternative treatment of severe symptomatic aortic stenosis (AS) in patients with high operative risk. In spite of favorable entire results, long-term mortality of patients is high. The present study aims to identify independent preprocedural risk factors to improve risk stratification in these highly selected patients. This prospective study included 202 consecutive patients with severe symptomatic AS and high operative risk (mean logistic European System for Cardiac Operative Risk Evaluation, 22±17%; mean age, 79±6 years; 107 female). Preprocedural comprehensive examinations were performed (laboratory, electrocardiography, echocardiography, cardiac catheterization). All patients received transfemoral or transaxillary TAVI with a CoreValve prosthesis (Medtronic, Minneapolis, MN). During a follow-up of 535±333 days, 56 patients (28%) reached the primary study end point (all-cause mortality). Independent predictors of long-term mortality were as follows: hemoglobin<12.5 g/dL (hazard risk [HR], 3.62; 95% confidence interval [CI], 2.025-6.468; P<0.001), aortic mean gradient≤41 mm Hg (HR, 2.16; 95% CI, 1.272-3.655; P=0.004), and left atrial diameter>42 mm (HR, 3.09; 95% CI, 1.588-6.019; P=0.001). Our risk-stratification model based on these independent predictors separated patients into 4 groups with high (74%), intermediate (37%), low (18%), and very low (3%) all-cause mortality. In patients undergoing TAVI, preprocedural assessment of hemoglobin, aortic mean gradient, and left atrial diameter provides independent prognostic information and therefore contributes to improved risk stratification in TAVI.


A comprehensive and comparative review of optimal cut-points selection methods for diseases with multiple ordinal stages.
Cut-points selection is a key topic in the field of diagnostic studies. For binary classification, there exist several well-developed methods, some of which have been extended to three-class settings and beyond. This paper focuses on optimal cut-points selection methods for diseases with multiple ordinal stages. The purpose of this paper is two-fold: 1) to propose three new cut-points selection methods; and 2) to present a comprehensive simulation study to assess and compare the performance of all the available methods. Two real data sets, one from ovarian cancer and the other from pancreatic cancer, are analyzed.


Academic Radiologist Subspecialty Identification Using a Novel Claims-Based Classification System.
The objective of the present study is to assess the feasibility of a novel claims-based classification system for payer identification of academic radiologist subspecialties. Using a categorization scheme based on the Neiman Imaging Types of Service (NITOS) system, we mapped the Medicare Part B services billed by all radiologists from 2012 to 2014, assigning them to the following subspecialty categories: abdominal imaging, breast imaging, cardiothoracic imaging, musculoskeletal imaging, nuclear medicine, interventional radiology, and neuroradiology. The percentage of subspecialty work relative value units (RVUs) to total billed work RVUs was calculated for each radiologist nationwide. For radiologists at the top 20 academic departments funded by the National Institutes of Health, those percentages were compared with subspecialties designated on faculty websites. NITOS-based subspecialty assignments were also compared with the only radiologist subspecialty classifications currently recognized by Medicare (i.e., nuclear medicine and interventional radiology). Of 1012 academic radiologists studied, the median percentage of Medicare-billed NITOS-based subspecialty work RVUs matching the subspecialty designated on radiologists' own websites ranged from 71.3% (for nuclear medicine) to 98.9% (for neuroradiology). A NITOS-based work RVU threshold of 50% correctly classified 89.8% of radiologists (5.9% were not mapped to any subspecialty; subspecialty error rate, 4.2%). In contrast, existing Medicare provider codes identified only 46.7% of nuclear medicine physicians and 39.4% of interventional radiologists. Using a framework based on a recently established imaging health services research tool that maps service codes based on imaging modality and body region, Medicare claims data can be used to consistently identify academic radiologists by subspecialty in a manner not possible with the use of existing Medicare physician specialty identifiers. This method may facilitate more appropriate performance metrics for subspecialty academic physicians under emerging value-based payment models.


Phosphorylation of Deinococcus radiodurans RecA Regulates Its Activity and May Contribute to Radioresistance.
Deinococcus radiodurans has a remarkable capacity to survive exposure to extreme levels of radiation that cause hundreds of DNA double strand breaks (DSBs). DSB repair in this bacterium depends on its recombinase A protein (DrRecA). DrRecA plays a pivotal role in both extended synthesis-dependent strand annealing and slow crossover events of DSB repair during the organism's recovery from DNA damage. The mechanisms that control DrRecA activity during the D. radiodurans response to γ radiation exposure are unknown. Here, we show that DrRecA undergoes phosphorylation at Tyr-77 and Thr-318 by a DNA damage-responsive serine threonine/tyrosine protein kinase (RqkA). Phosphorylation modifies the activity of DrRecA in several ways, including increasing its affinity for dsDNA and its preference for dATP over ATP. Strand exchange reactions catalyzed by phosphorylated versus unphosphorylated DrRecA also differ. In silico analysis of DrRecA structure support the idea that phosphorylation can modulate crucial functions of this protein. Collectively, our findings suggest that phosphorylation of DrRecA enables the recombinase to selectively use abundant dsDNA substrate present during post-irradiation recovery for efficient DSB repair, thereby promoting the extraordinary radioresistance of D. radiodurans.


Thymoquinone and curcumin attenuate gentamicin-induced renal oxidative stress, inflammation and apoptosis in rats.
The present study was aimed to investigate the possible protective effects of thymoquinone (TQ) and curcumin (Cur) on gentamicin (GM)-induced nephrotoxicity in rats. Rats were divided into four groups as follows: group 1 received normal saline and served as normal controls, group 2 received GM only, group 3 concurrently received GM and TQ and group 4 concurrently received GM and Cur. At day 21, rats were sacrificed and samples were collected for assaying serum tumor necrosis factor alpha (TNF-α), urea and creatinine levels, and renal lipid peroxidaion, glutathione (GSH) content as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. In addition, kidneys were collected for histopathological examination and immunohistochemical determination of the antiapoptotic protein, B-cell lymphoma 2 (Bcl-2). The biochemical results showed that GM-induced nephrotoxicity was associated with a significant increase in serum TNF-α, urea and creatinine as well as renal lipid peroxidation. On the other hand, renal GSH content and GPx and SOD activities were significantly declined. Concomitant administration of either TQ or Cur efficiently alleviated the altered biochemical and histopathological features. In conclusion, both TQ and Cur showed more or less similar marked renoprotective effect against GM-induced nephrotoxicity through their antioxidant, anti-inflammatory and anti-apoptotic efficacies.


Perforation of terminal ileum and appendix in typhoid enteritis: report of two cases.
Two cases of simultaneous typhoid perforation of terminal ileum and appendix are reported from Harare Central Hospital. These findings have not been reported before. Perforations were associated with schistosomiasis and HIV/AIDS. Definitive diagnosis was made only after laparotomy, serology and histopathology. With early diagnosis, effective resuscitation and timely intervention, this life-threatening condition is not necessarily fatal. Septic shock is however, an ominous sign of poor prognosis. In the tropics, bradycardia, leukopaenia and perforation in a febrile patient with right iliac fossa tenderness should arouse suspicion. Perforations may occur in patients with underlying diseases.


PER2 Promotes Odontoblastic/Osteogenic Differentiation of Dental Pulp Stem Cells by Modulating Mitochondrial Metabolism.
Human dental pulp stem cells (hDPSCs) possess remarkable self-renewal and multilineage differentiation ability. PER2, an essential circadian molecule, regulates various physiological processes. Evidence suggests that circadian rhythm and PER2 participate in physiological functions of DPSCs. However, the influence of PER2 on DPSCs' differentiation remains largely unknown. This study aimed to explore the effect and potential mechanism of PER2 on hDPSCs' differentiation. Dental pulp tissues were extracted, and hDPSCs were cultured for in vitro and in vivo experiments. Dorsal subcutaneous transplantation was performed in 6-week-old male BALB/c mice. The hDPSCs' odontoblastic/osteogenic differentiation was assessed, and mitochondrial metabolism was evaluated. The results indicated PER2 expression increasing during hDPSCs' odontoblastic/osteogenic differentiation. Gain- and loss-of function studies confirmed that PER2 promoted alkaline phosphatase (ALP) activity, mineralized nodules deposition, mRNA expression of DSPP, DMP1, COL1A1 and protein expression of DSPP and DMP1 in hDPSCs. Furthermore, PER2 enhanced collagen deposition, osteodentine-like tissue formation and DSPP expression in vivo. Mitochondrial metabolic evaluation aimed to investigate the mechanism of PER2-mediated hDPSC odontoblastic/osteogenic differentiation, which showed that PER2 increased ATP synthesis, elevated mitochondrial membrane potential and changed expression of proteins regulating mitochondrial dynamics. This study demonstrated that PER2 promoted hDPSCs' odontoblastic/osteogenic differentiation, which involved mitochondrial metabolic change.


Topography and synaptology of mamillary body projections to the mesencephalon and pons in the rat.
The anterograde and retrograde transport of horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was used to study the anatomical organization of descending projections from the mamillary body (MB) to the mesencephalon and pons at light and electron microscopic levels. Injections of WGA-HRP into the medial mamillary nucleus resulted in dense anterograde and retrograde labeling in the ventral tegmental nucleus, while injections in the lateral mamillary nucleus resulted in dense anterograde labeling in the dorsal tegmental nucleus pars dorsalis and dense anterograde and retrograde labeling in the pars ventralis of the dorsal tegmental nucleus. Anterogradely labeled fibers in the mamillotegmental tract diverged from the principal mamillary tract in an extensive dorsocaudally oriented swath of axons which extended to the dorsal and ventral tegmental nuclei, and numerous axons turned sharply ventrally and rostrally to terminate topographically in the dorsomedial nucleus reticularis tegmenti pontis and rostromedial pontine nuclei. The anterograde labeling in these two precerebellar relay nuclei was distributed near the midline such that projections from the lateral mamillary nucleus terminated mainly dorsomedial to the terminal fields of projections from the medial mamillary nucleus. In the dorsal and ventral tegmental nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites and to a lesser extent with neuronal somata. A few labeled terminals contained pleomorphic vesicles and formed symmetric synaptic junctions with dendrites and neuronal somata. Labeled axon terminals were also frequently found in synaptic contact with retrogradely labeled dendrites and neuronal somata in the dorsal and ventral tegmental nuclei. These findings indicate that neurons in the dorsal and ventral tegmental nuclei are reciprocally connected with MB projection neurons. In the nucleus reticularis tegmenti pontis and medial pontine nuclei, labeled axon terminals contained round synaptic vesicles and formed asymmetric synaptic junctions primarily with small diameter dendrites. The present study demonstrates that projections from the medial and lateral nuclei of the MB are topographically organized in the mesencephalon and pons. The synaptic morphology of mamillotegmental projections suggests that they may have excitatory influences primarily on the distal dendrites of neurons in these brain regions.


Hidden from plain sight: Novel Simkaniaceae and Rhabdochlamydiaceae diversity emerging from screening genomic and metagenomic data.
Chlamydiota are an ancient and hyperdiverse phylum of obligate intracellular bacteria. The best characterized representatives are pathogens or parasites of mammals, but it is thought that their most common hosts are microeukaryotes like Amoebozoa. The diversity in taxonomy, evolution, and function of non-pathogenic Chlamydiota are slowly being described. Here we use data mining techniques and genomic analysis to extend our current knowledge of Chlamydiota diversity and its hosts, in particular the Order Parachlamydiales. We extract one Rhabdochlamydiaceae and three Simkaniaceae Metagenome-Assembled Genomes (MAGs) from NCBI Short Read Archive deposits of ciliate and algal genome sequencing projects. We then use these to identify a further 14 and 8 MAGs respectively amongst existing, unidentified environmental assemblies. From these data we identify two novel clades with host associated data, for which we propose the names "Sacchlamyda saccharinae" (Family Rhabdochlamydiaceae) and "Amphrikana amoebophyrae" (Family Simkaniaceae), as well as a third new clade of environmental MAGs "Acheromyda pituitae" (Family Rhabdochlamydiaceae). The extent of uncharacterized diversity within the Rhabdochlamydiaceae and Simkaniaceae is indicated by 16 of the 22 MAGs being evolutionarily distant from currently characterised genera. Within our limited data, there was great predicted diversity in Parachlamydiales metabolism and evolution, including the potential for metabolic and defensive symbioses as well as pathogenicity. These data provide an imperative to link genomic diversity in metagenomics data to their associated eukaryotic host, and to develop onward understanding of the functional significance of symbiosis with this hyperdiverse clade.


Dynamic Contrast Magnetic Resonance Lymphangiography Localizes Lymphatic Leak to the Duodenum in Protein-Losing Enteropathy.
Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. Nineteen patients 0.3-58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12 of 17 (71%), and IM-DCMRL detected duodenal leak in 5 of 6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.


[Three-dimensional echocardiography in the diagnosis of cardiopathies].
The ability to visualize with dynamic 3D views the images obtained from the 2D study was the obviously next step in the evolution of echocardiography. Today, thanks to the technological evolution, the capability of obtaining and processing images with computers support has emerged with a great potential. Three-dimensional echocardiography facilitates spatial recognition of intracardiac structures, is surpassing the experimental phase quickly and its accuracy has been validated in vivo.


The characteristics and capabilities of the available open source health information technologies supporting healthcare: A scoping review protocol.
Due to the many advantages of open source software (OSS), including reduced cost of licensing, more flexibility in terms of customisation and redistribution, better quality and no vendor lock-in, OSS in healthcare is increasingly gaining importance. Various open source health information technologies (OS-HITs) are continuously being designed and developed for different areas of healthcare to increase organisational efficiencies and quality of care at minimum costs. The objective of this scoping review is to identify the kinds of existing OS-HITs, their characteristics (e.g. functions) and capabilities (e.g. advantages/disadvantages) for various healthcare stakeholders (physicians and patients) and healthcare sectors (e.g. clinical, administrative). We will conduct a scoping review to identify the range of available OS-HITs in international literature from 1980 to September 2018. Searches will be conducted in six major international databases, namely: Cumulative Index to Nursing and Allied Health Literature Plus, Excerpta Medica Database, Global Health, Library Information Science and Technology Abstracts, Medline and Web of Science to identify relevant published research. We will also search the Google search engine and Google Scholar for on-going and unpublished work and the grey literature. Searches will be peer-reviewed by two independent reviewers and will not be limited by methodology or language. Next, selected references will be tabulated for study characteristics by author affiliation, country of origin, the name of OS-HIT, healthcare area/sector, system requirements, stakeholders, complete solution and web link. Furthermore, functions, benefits/advantages, disadvantages and outcomes (e.g. usability) of OS-HITs will be extracted. Narrative and interpretative synthesis of data will be undertaken. We will report our findings in a peer-reviewed journal.


Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning.
Gonadal failure is a health and quality-of-life concern in hematopoietic cell transplant (HCT) survivors. While ovarian dysfunction is nearly universal following myeloablative (MA) conditioning, the risk is unclear after reduced-intensity conditioning (RIC). Gonadotropin-releasing hormone agonists decrease ovarian failure rates following conventional chemotherapy, but little is known about its effectiveness with HCT. We investigated the impact of leuprolide on ovarian function after MA conditioning and monitored ovarian function after RIC in this descriptive pilot study. Post-menarchal females <50 years undergoing HCT with adequate baseline ovarian function (follicle-stimulating hormone (FSH) level <40 mIU/mL and normal menstruation) were eligible. Prior to MA conditioning, leuprolide was administered. Those undergoing RIC were observed. FSH was measured at various time points. Seventeen women aged 12-45 years were evaluated (7 in the intervention group and 10 in the observation group). Compared to the historical high rate of ovarian failure after MA conditioning, 3 of 7 evaluable Lupron recipients had ovarian failure at a median of 703 days post transplant. Ovarian failure occurred in 1 of 10 recipients of RIC at a median follow-up of 901 days. In conclusion, leuprolide may protect ovarian function after MA conditioning. Additionally, RIC with cyclophosphamide, fludarabine and low-dose TBI has a low risk of ovarian failure.


The expression of Smads in human endometrium and regulation and induction in endometrial epithelial and stromal cells by transforming growth factor-beta.
Human endometrium expresses TGF-beta and TGF-beta receptors where they regulate several endometrial biological activities implicated in embryo implantation, irregular bleeding, endometriosis, and cancer. In the present study, we determined the expression of Smads, intracellular signals that mediate TGF-beta receptors signals from the cell surface to the nucleus, in the endometrium as well as isolated endometrial epithelial (EEC) and stromal (ESC) cells. We also determined whether TGF-beta regulates the expression Smads and activates Smad3 in these cells and endometrial surface epithelial cell line (HES). Using semiquantitative RT-PCR, Western blot analysis, and immunohistochemistry, we found that endometrium, EEC, ESC, and HES express Smad3, -4, and -7 mRNA and protein and contain phosphorylated Smad3 (pSmad3). Smads and pSmad3 were localized in the epithelial and stromal cells with cytoplasmic/nuclear localization. TGF-beta in a dose- and time-dependent manner increased the expression of Smads mRNA and protein, the rate of pSmad3 activation, and Smad3 translocation into the nucleus in ESC and HES. The effect of TGF-beta on pSmad3 induction was, in part, abrogated by the pretreatment of HES and ESC with TGF-beta type II receptor antisense oligonucleotides. We conclude that human endometrium expresses the necessary components of Smad signaling pathway, whose expression and induction in endometrial epithelial and stromal cells are regulated by TGF-beta.


RNA landscape of the emerging cancer-associated microbe Fusobacterium nucleatum.
Fusobacterium nucleatum, long known as a constituent of the oral microflora, has recently garnered renewed attention for its association with several different human cancers. The growing interest in this emerging cancer-associated bacterium contrasts with a paucity of knowledge about its basic gene expression features and physiological responses. As fusobacteria lack all established small RNA-associated proteins, post-transcriptional networks in these bacteria are also unknown. In the present study, using differential RNA-sequencing, we generate high-resolution global RNA maps for five clinically relevant fusobacterial strains-F. nucleatum subspecies nucleatum, animalis, polymorphum and vincentii, as well as F. periodonticum-for early, mid-exponential growth and early stationary phase. These data are made available in an online browser, and we use these to uncover fundamental aspects of fusobacterial gene expression architecture and a suite of non-coding RNAs. Developing a vector for functional analysis of fusobacterial genes, we discover a conserved fusobacterial oxygen-induced small RNA, FoxI, which serves as a post-transcriptional repressor of the major outer membrane porin FomA. Our findings provide a crucial step towards delineating the regulatory networks enabling F. nucleatum adaptation to different environments, which may elucidate how these bacteria colonize different compartments of the human body.


Home-Based HIV Testing and Counseling for Male Couples (Project Nexus): A Protocol for a Randomized Controlled Trial.
HIV prevalence remains high among men who have sex with men (MSM) in the United States, yet the majority of research has focused on MSM as individuals, not as dyads, and has discussed HIV risks primarily in the context of casual sex. Nexus is an online prevention program that combines home-based HIV testing and couples HIV testing and counseling (CHTC). It allows partners in dyadic MSM relationships to receive HIV testing and care in the comfort of their designated residence, via video-based chat. By using video-based technologies (eg, VSee video chat), male couples receive counseling and support from a remote online counselor, while testing for HIV at home. This randomized control trial (RCT) aims to examine the effects of video-based counseling combined with home-based HIV testing on couples' management of HIV risk, formation and adherence to explicit sexual agreements, and sexual risk-taking. The research implements a prospective RCT of 400 online-recruited male couples: 200 self-reported concordant-negative couples and 200 self-reported discordant couples. Couples in the control arm will receive one or two home-based HIV self-testing kits and will be asked to report their results via the study's website. Couples in the experimental arm will receive one or two home-based HIV self-testing kits and will conduct these tests together under the facilitation of a remotely located counselor during a prescheduled VSee-based video CHTC session. Study assessments are taken at baseline, as well as at 3- and 6-month follow-up sessions. Project Nexus was launched in April 2016 and is ongoing. To date, 219 eligible couples have been enrolled and randomized. Combining home-based HIV testing with video-based counseling creates an opportunity to expand CHTC to male couples who (1) live outside metro areas, (2) live in rural areas without access to testing services or LGBTQ resources, or (3) feel that current clinic-based testing is not for them (eg, due to fears of discrimination associated with HIV and/or sexuality). ClinicalTrials.gov NCT02335138; https://clinicaltrials.gov/ct2/show/NCT02335138 (Archived by WebCite at http://www.webcitation.org/6qHxtNIdW).


Karnofsky Memorial Lecture. Marrow transplantation for malignant diseases.
Marrow grafting, once undertaken only after failure of all other forms of therapy, is now the preferred therapy for some malignant diseases. Chemoradiotherapy and marrow grafting for patients with acute leukemia who have failed chemotherapy results in cure rates of 10%-30%. For patients under the age of 50 with acute nonlymphoblastic leukemia transplanted in first remission, the cure rate is approximately 50% with better results in younger patients. Marrow grafting is now being explored in a variety of types of malignant diseases having in common a steep dose-response curve to therapy, therapy limited by marrow toxicity, and the availability of a suitable marrow donor. Current research in the field of marrow transplantation is reviewed and provides a basis for a reasonable expectation that results of marrow transplantation will continue to improve. The use of partially matched family members or phenotypically histocompatibility leukocyte antigen-identical unrelated donors will make marrow grafting available to a larger fraction of patients. Marrow grafting, developed for the treatment of malignant disease, has found an important application to nonmalignant diseases, including immunodeficiency syndromes, aplastic anemia, and thalassemia and other genetic disorders of hematopoiesis.


Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer.
Tetrahydroisoquinoline 40 has been identified as a potent ERα antagonist and selective estrogen receptor degrader (SERD), exhibiting good oral bioavailability, antitumor efficacy, and SERD activity in vivo. We outline the discovery and chemical optimization of the THIQ scaffold leading to THIQ 40 and showcase the racemization of the scaffold, pharmacokinetic studies in preclinical species, and the in vivo efficacy of THIQ 40 in a MCF-7 human breast cancer xenograft model.


In vitro antifungal and antibacterial potentials of organic extracts of Avicennia marina collected from Rabigh Lagoon, Red Sea Coasts in Saudi Arabia.
Mangrove shrub Avicennia marina (Forsk.) Vierh was used to test the antifungal and antibacterial activities of aerial fractions in vitro. Aspergillus sp, Candida sp and Gram positive bacteria have all been found to be sensitive to mangrove extracts, whereas Gram negative bacteria have been found to be resistant to them. Agar disc diffusion and well-cut diffusion were employed to conduct antifungal and antibacterial activities. The MICs (minimum inhibitory concentrations) for each assay have been established. Several extracts from Mangrove reduced fungus growth (diameters fluctuated between 11 and 41 mm). The Ethyl acetate fraction showed particularly strong inhibition of C. tropicalis, C. albicanis, and A. fumigatus. They had 41, 40, and 25 mm-diameter inhibition zones, respectively. Nesoral, a synthetic antifungal medication, showed no significant changes in its MICs compared to different extracts. Enterococcus faecalis and Bacillus subtilis were inhibited by Petroleum Ether extracts at MICs of 0.78 and 0.35 mg/mL, respectively. It is possible that A. marina extracts may be exploited as a viable natural alternative that may be employed in the management of various infections, notably nosocomial bacterial infections, as anti-candidiasis and as anti-aspergillosis agents.


Effects of concentration and temperature on gustatory persistence.
The effects of concentration and temperature on the perceived persistence of citric acid, sodium chloride, sucrose, and urea were determined. The results obtained by a modified magnitude-estimation procedure suggest that power functions of the form P = K X Cn related the perceived persistence (P in seconds) to the concentration (C in % W/V) at each temperature and for each taste compound. Furthermore, the relative persistence (K) and the slope of the functions of persistence (n) showed changes when the temperature of taste stimuli varied.


Depression in patients with coronary artery disease.
Depression is more prevalent in patients with coronary artery disease (CAD) than in the general elderly population. Although CAD patients with depression have higher mortality rates, depression is often not recognized and treated in these patients. We administered structured psychiatric diagnostic interviews to 99 inpatients with CAD and diagnosed 23% with a major depressive episode (MDE) by DSM-IV criteria. Severity of medical illness and family history of psychopathology were indicators for increased risk for MDE. These findings may facilitate the recognition of CAD patients at greater risk for MDE.


System Identification Algorithm for Non-Uniformly Sampled Data.
Considerable effort has been devoted to the development of algorithms for identification of parsimonious discrete time models from noisy input/output data sets since this facilitates controller design. Several methods, such as nuclear norm minimization, have been used to provide approximate solutions to this non-convex problem. However, even though the field of continuous time system identification is now mature, results on parsimonious model identification of continuous time systems are still very limited. In this paper, an atomic norm minimization method is proposed for this purpose that can handle non-uniformly sampled data without preprocessing. The proposed approach provides an efficient way to use noisy, non-uniformly sampled data to determine a reliable, low-order continuous time model. Numerical performance is illustrated using academic examples and simulated behavioral data from a smoking cessation study.


Bone marrow transplantation: economic, ethical, and social issues.
Bone marrow transplantation is a useful model for the controversies surrounding medical technologies that involve high cost, mortality, and complications. This essay first delineates the economic circumstances of bone marrow transplantation, comparing it with other organ transplantations. Although children represent a significant proportion of bone marrow transplantation patients, little research has focused on the economic impact for this population. Next, the financial, social, and ethical motivations and controversies that surround bone marrow transplantation are explored, along with current allocation mechanisms. Finally, recommendations are offered for guiding discussions regarding the appropriate use of bone marrow transplantation. In making transplantation decisions, physicians must consider the costs and benefits of bone marrow transplantation for each patient. Such analyses, whether based on medical or socioeconomic criteria, are insufficient to resolve the fundamental cultural dilemmas posed by this procedure and other expensive medical technologies, however. The goal is to foster broader discussion of these issues to achieve more candid decisions in allocating resources among competing health priorities.


Biomechanical changes in the head associated with penetrating injuries of the maxilla and mandible: an experimental investigation.
In this experiment, we studied the craniocerebral injury that occurs due to the transmission of forces when maxillofacial gunshot wounds are sustained by the facial bones and cranium. Forty fresh pigs' heads were wounded by one of the following methods: steel spheres weighing 1.03 g at an impact velocity of 1,400 m/s, steel spheres weighing 1.03 g at an impact velocity of 800 m/s, M193 military bullets, or M56 military bullets. Pressure waves in the brain, acceleration of the head, and stress changes in the facial bones and cranium at the moment of the impact were recorded by pressure and acceleration transducers and strain gauges and were statistically compared. Some obvious differences between the mechanical values obtained from high-and low-velocity missile wounds were found. A negative relationship between the peak value of the pressure wave in the brain and the distance from the point of impact to the transducer was obtained. The acceleration of the head in the direction of the ballistic path was the strongest in absolute value. There were differences in the stress values between the mandible and the temporal bone. Acceleration of the head, pressure wave changes in the brain, and injury from bony stress conduction all play important roles in associated craniocerebral damage after maxillofacial firearm wounds.


Periodontal disease in Kuna albinism: a comparative study.
In classic albinism, all parts of the body are normal except for the absence of melanin. It is believed that lack of this pigment in periodontal tissues might influence periodontal disease progression. This study was designed to determine the relationship between periodontal diseases and albinism by comparing the clinical periodontal status of a group of native Panamanian Kuna albinos (from San Blas, Panama) to Kuna non-albinos of the same communities. An experimental group of 30 subjects (Kuna albinos aged > or =12 years) was selected and divided into three subgroups according to age. Likewise, a control group of 30 subjects (Kuna non-albinos) was selected and divided in subgroups. Assessment of oral hygiene and gingival inflammation in albinos by the Silness and Löe plaque index and Löe and Silness gingival index, respectively, was unremarkable compared to control groups. No statistically significant differences were found for number of teeth present, gingival index, plaque index, clinical attachment loss (CAL), probing depth, or gingival recession. As expected, age was a factor in the severity of the periodontal disease; 58% of individuals aged > or =36 years had at least one site with CAL > or =7 mm. Based on the overwhelming similarity of results found between experimental and control groups, albinism does not represent a clinical risk factor in the pathogenesis or exacerbation of periodontal diseases for these individuals.


Terpenoids and Bio-Functions of Essential Oils Hydrodistilled Differently from Freshly Immature and Mature Blumea balsamifera Leaves.
The volatiles and antioxidant capacity of essential oils (EOs) extracted from freshly immature and mature leaves of Blumea balsamifera at various hydrodistillation times were investigated. Seven major terpenoids were identified: two monoterpenes, camphor and L-borneol, and five sesquiterpenes, silphiperfol-5-ene, 7-epi-silphiperfol-5-ene, ß-caryophyllene, ɤ-eudesmol, and α-eudesmol. The quantity and terpenoid composition of the EOs were impressed by leaf maturity and hydrodistillation times. The yield of EOs from the immature leaves was 1.4 times that of mature leaves, with 73% of the yield acquired within the first 6 hours (hrs) of hydrodistillation. Approximately 97% of camphor and L-borneol, 80% of ß-caryophyllene, silphiperfolene, and 7-epi-silphiperfolene, 32% of ɤ-eudesmol, and 54% α-eudesmol were collected in the first 6 hrs of hydrodistillation. More ß-caryophyllene, ɤ-eudesmol, and α-eudesmol were found in the mature leaf EOs. The antioxidant capacity of the EOs was proportionally related to their terpenoid contents. The EOs extracted from immature leaves at 0-6 hrs of hydrodistillation demonstrated distinctive antibacterial activity against Staphylococcus aureus, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.5 mg/mL and 1 mg/mL, respectively.


Nonconjugate quantum subsystems.
We introduce an alternative way to understand the decomposition of a quantum system into interacting parts and show that it is natural in several physical models. This enables us to define a reduced density operator for a working system interacting with a thermal bath that is consistent with the inclusion of the interaction Hamiltonian within the working system's energy. We subsequently provide a self-consistent formulation of quantum thermodynamics that incurs nontrivial physical corrections to thermodynamic relations and quantities previously defined within the literature.


Characterisation of bubble detectors for aircrew and space radiation exposure.
The Earth's atmosphere acts as a natural radiation shield which protects terrestrial dwellers from the radiation environment encountered in space. In general, the intensity of this radiation field increases with distance from the ground owing to a decrease in the amount of atmospheric shielding. Neutrons form an important component of the radiation field to which the aircrew and spacecrew are exposed. In light of this, the neutron-sensitive bubble detector may be ideal as a portable personal dosemeter at jet altitudes and in space. This paper describes the ground-based characterisation of the bubble detector and the application of the bubble detector for the measurement of aircrew and spacecrew radiation exposure.


Antidysrhythmic and dose-related hemodynamic effects of manganese in perfused isolated rabbit hearts.
Hemodynamic and antidysrhythmic studies were performed to determine the effects of manganese (Mn) on inotropy and chronotropy in normally perfused isolated rabbit hearts (IRHs), and the efficacy of Mn in suppressing and terminating ventricular dysrhythmias (VDs) in regionally ischemic IRHs. Four groups of eight hearts were perfused with Krebs-Ringer bicarbonate solution (KRB) during the control period, followed by 10 min of perfusion with either KRB, as control, or KRB containing 1.0 mM (A), 0.1 mM (B), or 0.01 mM (C) MnCl2. All hearts were then again perfused, for 10 min, with KRB alone (washout). A caused marked depression of heart rate (HR), peak left ventricular (LV) systolic pressure (PSP) and peak LV dP/dt, B resulted in significant depression of HR alone, and C resulted in significant increases in PSP and dP/dt, with a slight fall in HR. Negative effects of Mn were rapidly reversed during washout. Sustained (greater than 2 min) VDs were induced in five of six by sequential bolus injections of isoproterenol and procaine, following ligation of the left marginal coronary artery. A second group of identically treated hearts developed identical VDs with the same frequency, but were reverted to sinus rhythm by a 2-mol bolus of 10 mM MnCl2, without induction of AV block. In a third group of hearts, treated as described for the two groups above, but perfused with KRB containing 0.1 mM Mn, only one of six developed a sustained VD. These results encourage further work, in ischemic whole animal models, to determine the antidysrhythmic efficacy of manganese.


Learning from Ambiguously Labeled Face Images.
Learning a classifier from ambiguously labeled face images is challenging since training images are not always explicitly-labeled. For instance, face images of two persons in a news photo are not explicitly labeled by their names in the caption. We propose a Matrix Completion for Ambiguity Resolution (MCar) method for predicting the actual labels from ambiguously labeled images. This step is followed by learning a standard supervised classifier from the disambiguated labels to classify new images. To prevent the majority labels from dominating the result of MCar, we generalize MCar to a weighted MCar (WMCar) that handles label imbalance. Since WMCar outputs a soft labeling vector of reduced ambiguity for each instance, we can iteratively refine it by feeding it as the input to WMCar. Nevertheless, such an iterative implementation can be affected by the noisy soft labeling vectors, and thus the performance may degrade. Our proposed Iterative Candidate Elimination (ICE) procedure makes the iterative ambiguity resolution possible by gradually eliminating a portion of least likely candidates in ambiguously labeled faces. We further extend MCar to incorporate the labeling constraints among instances when such prior knowledge is available. Compared to existing methods, our approach demonstrates improvements on several ambiguously labeled datasets.


Pancreatographic investigation of embryology of complete and incomplete pancreas divisum.
To investigate embryology of complete and incomplete pancreas divisum (PD). We analyzed anatomy of the pancreatic duct system in 44 cases of complete PD and 41 cases of incomplete PD. Under the concept of branch fusion between the ventral and dorsal pancreatic ducts, incomplete PD was divided into 3 types: fusion of the extreme end of the upper branch of the ventral pancreatic duct with the dorsal pancreatic duct (type 1); fusion of the lower branch of the dorsal pancreatic duct with the lower branch of the ventral pancreatic duct (type 2); and fusion of the lower branch of the dorsal pancreatic duct with the ventral pancreatic duct (type 3). Complete PD showing no ventral pancreatic duct radiologically might be induced by complete regression of the ventral pancreatic duct near the orifice in the pancreas with communication between the ventral and dorsal pancreatic ducts. Embryological mechanism of incomplete PD (type 1, n = 16; type 2, n = 10; and type 3, n = 15) was confirmed by measurement in pancreatograms. Some cases of complete PD might be induced by complete regression of the ventral pancreatic duct near the orifice. Embryology of incomplete PD can be accounted by concept of branch fusion.


Co-immunoprecipitation for Assessing Protein-Protein Interactions in Agrobacterium-Mediated Transient Expression System in Nicotiana benthamiana.
The characterization of protein-protein interactions (PPI) often provides functional information about a target protein. Yeast-two-hybrid (Y2H) and luminescence/fluorescence-based detections, therefore, have been widely utilized for assessing PPI. In addition, a co-immunoprecipitation (co-IP) method has also been adopted with transient protein expression in Nicotiana benthamiana (N. benthamiana) infiltrated with Agrobacterium tumefaciens. Herein, we describe a co-IP procedure in which structural maintenance of chromosome 1 (SMC1), identified from a Y2H screening, was verified as an interacting partner for microchidia 1 (MORC1), a protein well known for its function in plant immunity and epigenetics. SMC1 and MORC1 were transiently expressed in N. benthamiana when infiltrated by Agrobacterium with the respective genes. From this approach, we identified a region of SMC1 responsible for interacting with MORC1. The co-IP method, of which outputs are mainly from immunoblot analysis, provided information about target protein expression as well, which is often useful for troubleshooting. Using this feature, we showcased a PPI confirmation from our SMC1-MORC1 study in which a full-length SMC1 protein was not detectable, and, therefore, a subsequent truncated mutant analysis had to be employed for PPI verification.


Piezosurgery in hemifacial microsomia: a promising exemption from conventional peri-osteotomy suffering.
Mandibular distraction osteogenesis, a recommended therapy for hemifacial microsomia, has brought much agony because of its traumatic procedures and peri-osteotomy complications. Our study aims to retrospectively compare piezoelectric osteotome with conventional reciprocal bone saw for hemifacial microsomia patients and validate its meliority in operability, surgical risks and patient outcomes. All patients included underwent osteotomies conducted by either piezosurgery or bone saw. Information of intraoperative blood loss, operation duration, postoperative pain and complications was collected from patient files, ward round inspections and follow-ups. Among all 40 patients, 13 underwent piezo-osteotomy. Piezosurgery performed better than conventional reciprocal bone saw in decreasing intraoperative blood loss (p < 0.001) and operation duration (p = 0.030). No significant difference was found in hospitalization duration, total expenses or complication rates between two groups. There were positive relations between operation duration and intraoperative blood loss (p = 0.042), and between hospitalization duration and total expenses (p = 0.0096). Postoperative pain scores of both groups declined over time while the piezosurgery group had a statistically significant tendency (p = 0.006) to suffer less than the conventional group. Piezosurgery diminishes intraoperative blood loss, operative duration, and postoperative pain, making an alternative to conventional osteotomes to mitigate patients' and families' peri-osteotomy sufferings, and a more humane solution to HFM.


Enhancement of fluorescence development of end products by use of a fluorescence developer solution in a rapid and sensitive fluorescent spot test for specific detection of microbial beta-lactamases.
A fluorescent spot test method for specific detection of microbial beta-lactamases as previously published (K. C. S. Chen, J. S. Knapp, and K. K. Holmes, J. Clin. Microbiol. 19:818-825, 1984) was improved by the use of a fluorescence developer solution. The fluorescence developer solution used in this study consisted of 0.78 M sodium tartrate buffer containing 12% formaldehyde at a final pH of 4.5. An addition of 1 volume of fluorescence developer solution to 5 volumes of ampicillin or cephalex substrate solution incubated with beta-lactamase-producing organisms, followed by heating the mixture at 45 degrees C for 10 min resulted in enhancement of fluorescence of the end products of beta-lactamase activity. This provides a more sensitive assay for microbial beta-lactamases and offers the potential for direct detection of beta-lactamases in clinical specimens.


Potential of Nonfullerene Small Molecules with High Photovoltaic Performance.
Over the past decades, fullerene derivatives have become the most successful electron acceptors in organic solar cells (OSCs) and have achieved great progress, with power conversion efficiencies (PCEs) of over 11 %. However, fullerenes have some drawbacks, such as weak absorption, limited energy-level tunability, and morphological instability. In addition, fullerene-based OSCs usually suffer from large energy losses of over 0.7 eV, which limits further improvements in the PCE. Recently, nonfullerene small molecules have emerged as promising electron acceptors in OSCs. Their highly tunable absorption spectra and molecular energy levels have enabled fine optimization of the resulting devices, and the highest PCE has surpassed 12 %. Furthermore, several studies have shown that OSCs based on small-molecule acceptors (SMA) have very efficient charge generation and transport efficiency at relatively low energy losses of below 0.6 eV, which suggests great potential for the further improvement of OSCs. In this focus review, we analyze the challenges and potential of SMA-based OSCs and discuss molecular design strategies for highly efficient SMAs.


Low-flow, Low-gradient Severe Aortic Stenosis: A Review.
Aortic stenosis (AS) is a common valve pathology experienced by patients worldwide. There are limited population-based studies assessing its prevalence; however, epidemiological studies emphasize that the burden of disease is growing. Recognizing AS relies on accurate clinical assessment and diagnostic investigations. Patients who develop severe AS are often referred to the heart team for assessment of aortic valve intervention. Although echocardiography has traditionally been used to screen and monitor the progression of AS, there can be discordance between measurements in a low-flow state. Such patients may have truly severe AS and potentially derive long-term benefit from aortic valve intervention. Accurately identifying these patients with the use of ancillary testing has been the focus of research for several years. In this article, we discuss the contemporary approaches and challenges in identifying and managing patients with low-flow, low-gradient severe AS.


High incidence of low vitamin B12 levels in Estonian newborns.
Vitamin B12 deficiency seems to be more common worldwide than previously thought. However, only a few reports based on data from newborn screening (NBS) programs have drawn attention to that subject. In Estonia, over the past three years, we have diagnosed 14 newborns with congenital acquired vitamin B12 deficiency. Therefore, the incidence of that condition is 33.8/100,000 live births, which is considerably more than previously believed. None of the newborns had any clinical symptoms associated with vitamin B12 deficiency before the treatment, and all biochemical markers normalized after treatment, which strongly supports the presence of treatable congenital deficiency of vitamin B12. During the screening period, we began using actively ratios of some metabolites like propionylcarnitine (C3) to acetylcarnitine (C2) and C3 to palmitoylcarnitine (C16) to improve the identification of newborns with acquired vitamin B12 deficiency. In the light of the results obtained, we will continue to screen the congenital acquired vitamin B12 deficiency among our NBS program. Every child with aberrant C3, C3/C2 and C3/C16 will be thoroughly examined to exclude acquired vitamin B12 deficiency, which can easily be corrected in most cases.


Product branching from the CH2CH2OH radical intermediate of the OH + ethene reaction.
Using a crossed laser-molecular beam scattering apparatus and tunable photoionization detection, these experiments determine the branching to the product channels accessible from the 2-hydroxyethyl radical, the first radical intermediate in the addition reaction of OH with ethene. Photodissociation of 2-bromoethanol at 193 nm forms 2-hydroxyethyl radicals with a range of vibrational energies, which was characterized in our first study of this system ( J. Phys. Chem. A 2010 , 114 , 4934 ). In this second study, we measure the relative signal intensities of ethene (at m/e = 28), vinyl (at m/e = 27), ethenol (at m/e = 44), formaldehyde (at m/e = 30), and acetaldehyde (at m/e = 44) products and correct for the photoionization cross sections and kinematic factors to determine a 0.765:0.145:0.026:0.063:<0.01 branching to the OH + C(2)H(4), H(2)O + C(2)H(3), CH(2)CHOH + H, H(2)CO + CH(3), and CH(3)CHO + H product asymptotes. The detection of the H(2)O + vinyl product channel is surprising when starting from the CH(2)CH(2)OH radical adduct; prior studies had assumed that the H(2)O + vinyl products were solely from the direct abstraction channel in the bimolecular collision of OH and ethene. We suggest that these products may result from a frustrated dissociation of the CH(2)CH(2)OH radical to OH + ethene in which the C-O bond begins to stretch, but the leaving OH moiety abstracts an H atom to form H(2)O + vinyl. We compare our experimental branching ratio to that predicted from statistical microcanonical rate constants averaged over the vibrational energy distribution of our CH(2)CH(2)OH radicals. The comparison suggests that a statistical prediction using 1-D Eckart tunneling underestimates the rate constants for the branching to the product channels of OH + ethene, and that the mechanism for the branching to the H(2)O + vinyl channel is not adequately treated in such theories.