Radiological detection of sharp force skeletal trauma: an evaluation of the sensitivity of Lodox in comparison to CT and X-ray.
Victims of violent crime often have evidence of sharp force trauma (SFT) which needs to be examined to accurately investigate these cases. The abilities of CTs, X-rays, and Lodox to detect skeletal SFT defects and the minimum number of impacts were assessed, as were their abilities to macroscopically interpret SFT with the aim of identifying the class of weapon used. Ten pigs were, post-mortem, stabbed using a kitchen knife on one side of the body and chopped using a panga on the other side. They were then scanned and macerated. The number of SFT defects, type of SFT, and minimum number of impacts identifiable osteologically were recorded, as well as when using each imaging modality. CTs were most sensitive for detecting stab and chop defects (56.7% and 78.3%, respectively) and the minimum number of impacts (82.8%), while X-rays were least sensitive (17.2% for stab wounds, 46.5% for chop marks, and 43.5% for impacts). Lodox detected 26.8% of stab defects, 59.3% of chop marks, and 58.4% of impacts. The type of SFT for more than 70.0% of identified defects was correctly classified using all methods, while only Lodox had moderate sensitivities for stab wounds (52.4%). When radiological assessments of skeletal SFT are required, CTs should be performed, but Lodox can be used as an alternative. However, dry bone analyses still produce the best results and should be performed whenever possible. Macroscopic interpretations of skeletal SFT to broadly determine the class of weapon used is possible radiologically.


Associations of nonconforming gender expression and gender identity with bullying victimization: an analysis of the 2017 youth risk behavior survey.
Although gender nonconformity (GNC) and transgender identity are both linked to bullying victimization, few studies have examined them with bullying victimization simultaneously. Using a sample of Youth Risk Behavior Survey, we investigated the associations of GNC and transgender identity with bullying victimization within the same study. We analyzed data from the cross-sectional school-based Youth Risk Behavior Survey in 2017 (n = 25,378). The exposures were GNC and transgender identity. The main outcomes were traditional victimization, cyber victimization, and combined victimization. We calculated adjusted prevalence ratios (APRs) with 95% confidence intervals (CIs) using Poisson regression models. There were 22.15% of high school students with GNC, and 1.61% identified themselves as transgender. GNC is associated with traditional (APR,1.45;95%CI, 1.21-1.73), cyber (APR,2.00; 95%CI, 1.66-2.40) and combined victimization (APR,1.61;95%CI, 1.42-1.83) respectively among assigned male at birth (AMAB) students only. Transgender male and female students are both at higher risk of bullying victimization for all the three outcomes than cisgender peers. AMAB GNC and transgender identity are associated with a higher risk of bullying victimization. Providing support systems and celebrating gender diversity within and outside schools are important.


[Plurimucosal cicatricial pemphigoid. A case with involvement of the gingival, vulval and vaginal mucosa].
We have studied a 62 years old woman with the infrequent involvement of the gingiva (desquamative gingivitis), vulvar and vaginal mucouses in benign mucosal pemphigoid. The clinical features and pathology are exposed and we debate differential diagnosis principally with pemphigus and lichen planus.


Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention: a cost-effectiveness analysis.
Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs ≥ 5% were below $50,000/QALY gained. Intervening in those with ≥ 7% diabetes risk based on the GDRS or ≥ 9% on the ARIC 2009 score would be cost-effective. A risk score threshold ≥ 5% together with elevated FPG would also allow targeting interventions cost-effectively.


Invited commentary on … When unbearable suffering incites psychiatric patients to request euthanasia: a qualitative study.
Although the paper in this issue by Verhofstadt et al sheds some light on the features of unbearable suffering stemming from psychiatric disorder leading to a request for euthanasia, this is limited. The bulk of the paper illustrates the particular ethical challenges posed by the policy of making euthanasia available in these circumstances.


Clustering humans: on biological boundaries.
We inquire into the notions of 'boundary' and 'cluster' in the fields of medical genetics, pharmacogenetics, and population genetics. First we show that the two notions are not well discussed in literature. Then we propose a promising explication of them, in which we argue that clustering is always 'property laden', that is, fundamentally dependent on decisions about the properties to be taken into account. In particular we suggest three different kinds of properties (main properties, investigating properties, and catalyzing properties) that have a role in these decisions. That is, we conclude that boundaries and clusters among humans depend on our way of considering nature. Concepts of 'race' and 'ethnic group' are discussed too, since they are the most used clusters among humans.


In vivo multisite oximetry using EPR-NMR coimaging.
Coimaging employing electron paramagnetic resonance (EPR) imaging and MRI is used for rapid in vivo oximetry conducted simultaneously across multiple organs of a mouse. A recently developed hybrid EPR-NMR coimaging instrument is used for both EPR and NMR measurements. Oxygen sensitive particulate EPR probe is implanted in small localized pockets, called sites, across multiple regions of a live mouse. Three dimensional MRI is used to generate anatomic visualization, providing precise locations of implant sites. The pO₂ values, one for every site, are then estimated from EPR measurements. To account for radio frequency (RF) phase inhomogeneities inside a large resonator carrying a lossy sample, a generalization of an existing EPR data model is proposed. Utilization of known spectral lineshape, sparse distribution, and known site locations reduce the EPR data collection by more than an order of magnitude over a conventional spectral-spatial imaging, enhancing the feasibility of in vivo EPR oximetry for clinically relevant models.


In vivo characterization of nonribosomal peptide synthetases NocA and NocB in the biosynthesis of nocardicin A.
Two nonribosomal peptide synthetases (NRPS), NocA and NocB, together comprising five modules, are essential for the biosynthesis of the D,L,D configured tripeptide backbone of the monocyclic β-lactam nocardicin A. We report a double replacement gene strategy in which point mutations were engineered in the two encoding NRPS genes without disruption of the nocABC operon by placing selective markers in adjacent genes. A series of mutants was constructed to inactivate the thiolation (T) domain of each module and to evaluate an HHxxxDR catalytic motif in NocA and an atypical extended histidine motif in NocB. The loss of nocardicin A production in each of the T domain mutants indicates that all five modules are essential for its biosynthesis. Conversely, production of nocardicin A was not affected by mutation of the NocB histidine motif or the R828G mutation in NocA.


Primary care physician perceptions on caring for complex patients with medical and mental illness.
Mental illness is common and associated with poor outcomes for co-occurring medical illness. Since primary care physicians manage the treatment of complex patients with both mental and medical illnesses, their perspectives on the care of these patients is vital to improving clinical outcomes. To examine physician perceptions of patient, physician and system factors that affect the care of complex patients with mental and medical illness. Inductive, participatory, team-based qualitative analysis of transcripts of in-depth semi-structured interviews. Fifteen internal medicine physicians from two university primary care clinics and three community health clinics. Participant characteristics were balanced in terms of years in practice, practice site, and gender. Physicians identified contributing factors to the complexity of patient care within the domains of patient, physician and system factors. Physicians identified 1) type of mental illness, 2) acuity of mental illness, and 3) communication styles of individual patients as the principal patient characteristics that affected care. Physicians expressed concern regarding their own lack of medical knowledge, clinical experience, and communication skills in treating mental illness. Further, they discussed tensions between professionalism and emotional responses to patients. Participants expressed great frustration with the healthcare system centered on: 1) lack of mental health resources, 2) fragmentation of care, 3) clinic procedures, and 4) the national healthcare system. Physicians in this study made a compelling case for increased training in the treatment of mental illness and improvements in the delivery of mental health care. Participants expressed a strong desire for increased integration of care through collaboration between primary care providers and mental health specialists. This approach could improve both comfort in treating mental illness and the delivery of care for complex patients.


National distribution of child and adolescent psychiatrists.
To describe the national distribution of child and adolescent psychiatrists by state, community, and youth population. Data on child and adolescent psychiatrists were compiled for states and counties and compared by state, county characteristics, number of youth, percentage of youth living in poverty, and child and adolescent psychiatry residents. The number of child and adolescent psychiatrists per 100,000 youth varied greatly by state and county. Child and adolescent psychiatrists were significantly more likely to be located in metropolitan counties and counties with a low percentage of children living in poverty. The distribution of child and adolescent psychiatrists was not significantly related to the distribution of child and adolescent psychiatry residency training programs. The shortage of child and adolescent psychiatrists is accentuated for nonmetropolitan areas and youth at greatest risk for mental disorders by the current pattern of distribution.


Tetraketones: a new class of tyrosinase inhibitors.
Twenty-eight tetraketones (1-28) with variable substituents at C-7 were synthesized and evaluated as tyrosinase inhibitors. Remarkably compounds 25 (IC(50)=2.06 microM), 11 (IC(50)=2.09 microM), 15 (IC(50)=2.61 microM), and 27 (IC(50)=3.19 microM) were found to be the most active compounds of the series, even better than both standards kojic acid (IC(50)=16.67 microM) and L-mimosine (IC(50)=3.68 microM). This study may lead to the discovery of therapeutically potent agents against clinically very important dermatological disorders including hyperpigmentation as well as skin melanoma.


Most of it started with T4 phage and was then taken over.
Professor Fumio Arisaka is one of the famous leaders in bacteriophage research, especially in the areas of protein biophysics and structural biology. Autonomous phage morphogenesis is a self-assembly process controlled by subunit-subunit interaction. Under this principle, Fumio has studied T4 tail assembly and morphology. He has also contributed structural information about T4 phage through a combination of X-ray structural analysis and three-dimensional image reconstruction using cryo-electron microscopy. Most of the development of ultracentrifugation applications for molecular assembly and phage morphogenesis research was also performed in Fumio's laboratory. Fumio is a pioneer of supramolecular protein assembly study, and his science continues in the research work of the approximately 150 people who had attended his final lecture at the Tokyo Institute of Technology.


Association of HCV Infection with C-Reactive Protein: National Health and Nutrition Examination Survey (NHANES), 2009⁻2010.
The relationship between hepatitis C virus (HCV) infection and C-reactive protein (CRP), which is an inflammatory biomarker, is limited in studies with the general population. It was hypothesized that changes in CRP levels are genotype-dependent in the general population with HCV infection. Thus, this study aimed to assess the prevalence of HCV infection and compare CRP levels with an anti-HCV antibody, HCV-RNA status, and HCV genotypes. A total of 5611 adult participants from the National and Health Nutrition Examination (NHANES), 2009⁻2010 survey were analyzed. Proc survey frequency, means, and multivariate regression were used due to the complex survey design of NHANES. The prevalence of HCV infection among the study population was 1.6%. There were lower mean CRP levels among people with anti-HCV antibody positive status compared to those with antibody negative status (0.12 ± 0.08 vs. 0.24 ± 0.02, p = 0.08, 95% Confidence Intervals, CI: -1.12 to 0.07). Mean CRP levels were also lower in people with HCV-RNA positive status compared to those with HCV-RNA negative status (0.56 ± 0.03 vs. 0.48 ± 0.05, p = 0.62 and 95% CI: -1.37 to 0.86). However, these differences were non-significant. With respect to HCV genotypes, significantly higher CRP levels were noted among people infected with HCV genotype 2 vs. genotype 1 (0.53 ± 0.06 vs. 0.23 ± 0.05, p < 0.01, 95% CI: -0.58 to -0.02) and those with HCV genotype 2 vs. HCV genotype 3 (0.53 ± 0.06, 0.28 ± 0.04, p < 0.01, 95% CI: 0.02 to 0.48). Further studies are needed to confirm this finding.


[Disordered fibrillar structure in ruptured tendons (author's transl)].
Areas of disordered fibrillar structure similar to kinking deformities have been observed in specimens from ruptured tendons. It seems possible to compare this phenomenon with experimentally produced deformations. The significance for the pathomechanics of tendon rupture is discussed.


Isolation, characterization and analysis of the expression of the Leishmania ribosomal PO protein genes.
Two tandemly linked genes are present in the Leishmania infantum genome that code for the acidic ribosomal PO protein. The genes are identical in the coding region, although a striking lack of nucleotide sequence conservation is observed when the boundaries of the coding regions between both genes are compared. The 3' untranslated regions of the two genes are, moreover, different in size. The deduced amino acid sequence of the L. infantum PO protein (LiPO) shows a high degree of sequence conservation, including the highly charged conserved C-terminal domain, with the ribosomal PO proteins of other eukaryotic organisms. Northern blot experiments showed that two different size class transcripts are expressed in the gene cluster and that the steady state level of each of the transcripts in logarithmic phase promastigotes is markedly different. The abundance of both transcripts is down-regulated in parasite cultures on reaching stationary phase. Since it seems that the two Leishmania ribosomal PO genes are expressed in a single polycistronic transcript, it is likely that the different levels of PO mRNAs observed in cultured cells is due to a postranscriptional regulatory mechanism.


An integrated model of epidermal growth factor receptor trafficking and signal transduction.
Endocytic trafficking of many types of receptors can have profound effects on subsequent signaling events. Quantitative models of these processes, however, have usually considered trafficking and signaling independently. Here, we present an integrated model of both the trafficking and signaling pathway of the epidermal growth factor receptor (EGFR) using a probability weighted-dynamic Monte Carlo simulation. Our model consists of hundreds of distinct endocytic compartments and approximately 13,000 reactions/events that occur over a broad spatio-temporal range. By using a realistic multicompartment model, we can investigate the distribution of the receptors among cellular compartments as well as their potential signal transduction characteristics. Our new model also allows the incorporation of physiochemical aspects of ligand-receptor interactions, such as pH-dependent binding in different endosomal compartments. To determine the utility of this approach, we simulated the differential activation of the EGFR by two of its ligands, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). Our simulations predict that when EGFR is activated with TGF-alpha, receptor activation is biased toward the cell surface whereas EGF produces a signaling bias toward the endosomal compartment. Experiments confirm these predictions from our model and simulations. Our model accurately predicts the kinetics and extent of receptor downregulation induced by either EGF or TGF-alpha. Our results suggest that receptor trafficking controls the compartmental bias of signal transduction, rather than simply modulating signal magnitude. Our model provides a new approach to evaluating the complex effect of receptor trafficking on signal transduction. Importantly, the stochastic and compartmental nature of the simulation allows these models to be directly tested by high-throughput approaches, such as quantitative image analysis.


The effect of embryonal amygdala grafts on the impairment of spatial working memory elicited in rats by kainate-induced amygdaloid damage.
The effect of epileptogenic lesion of amygdala on spatial working memory was examined in rats after unilateral (U, n = 9) or bilateral (B, n = 8) injection of 1 or 0.5 mu of 0.2% kainate into the amygdaloid complex. Another group of unilaterally lesioned rats (T, n = 9) received 8 days after kainate injection grafts of embryonal (E 20) amygdala into the damaged region. Twelve days after lesion the three experimental groups and an unoperated control group (C, n = 11) were trained during three weeks in the aversively motivated 8-arm radial water maze (RWM). Training decreased incidence of errors/8 choices from the initial 2.3 to 1.2 in the lesioned rats and to 0.4 in the controls. Transplantation did not enhance RWM acquisition but restored the symmetrical pattern of choices and normalized the emotionality of lesioned animals. Retraining the RWM task 3 months later revealed significant savings in the control group but not in the transplanted group. Histology showed in addition to large lesion at the injection site also distant lesions in the ipsilateral hippocampus, thalamus and neocortex and in the unilaterally injected rats also in the contralateral amygdala. Healthy, well integrated transplants found in 6 out of 9 transplanted rats reduced the incidence of remote lesions (particularly in the contralateral hemisphere). Performance of individual animals reflected the state of the transplant. It is concluded that the impairment of spatial working memory is due not only to destruction of amygdala but also to diffuse damage of the limbic system. The slowly developing seizure-induced distant lesions can be partly prevented by embryonal grafts.


Experimental determination of calibration settings for plastic syringes containing solutions of 90Y using commercial radionuclide calibrators.
Calibration factors for several makes (Capintec, AtomLab, and PTW) and models of commercially available re-entrant ionization chambers ("dose calibrators") were determined for solutions of 90Y using 10 ml plastic syringes that are used in the administration of the recently approved radioimmunotherapy drug Zevalin. Effects of filling volume on chamber response were studied for the anticipated prescription volume range of 3-9 ml in those syringes. A series of syringes were prepared over that range with accurately known volumes using a "standard" solution containing 90YCl3 in 1 moll(-1) HCl and approximately 50 microg of nonradioactive YCl3 per gram of solution. The respective calibration factors for the Capintec and AtomLab chambers required to give the correct activity reading were found to be "55+/-2 x 10" and 393+/-6, where the uncertainties are expanded (k = 2) uncertainties. The results indicated no significant effect of filling volume on the calibration setting to within the uncertainty on the activity measurement for all but the PTW chamber. In that case, a variation of about 5% was observed over the filling range. A direct comparison was also made between the actual 90Y Zevalin drug and the "standard" solution, with no differences in determined calibration settings observed within the uncertainties on the activity calibration.


Proximal realignment surgery for unilateral chronic patella dislocation in Morquio syndrome: a case report.
Mucopolysaccharidosis IVA (MPS IVA: Morquio A syndrome) is a lysosomal storage disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Patients with MPS IVA appear healthy at birth. Morquio-specific radiographic changes can be observed prior to clinical signs and symptoms. Patients are usually affected by a severe joint degeneration from the 2nd or 3rd decade. Hyperlaxity of the joints is prominent due to the excess of intermediate metabolites. We report a patient with inherited dwarfism, in which a proximal soft tissue realignment procedure was performed to treat chronic patellar dislocation.


Novel globoside-like oligosaccharide expression patterns in nontypeable Haemophilus influenzae lipopolysaccharide.
We report the novel pattern of lipopolysaccharide (LPS) expressed by two disease-associated nontypeable Haemophilus influenzae strains, 1268 and 1200. The strains express the common structural motifs of H. influenzae; globotetraose [beta-d-GalpNAc-(1-->3)-alpha-d-Galp-(1-->4)-beta-d-Galp-(1-->4)-beta-d-Glcp] and its truncated versions globoside [alpha-d-Galp-(1-->4)-beta-d-Galp-(1-->4)-beta-d-Glcp] and lactose [beta-d-Galp-(1-->4)-beta-d-Glcp] linked to the terminal heptose (HepIII) and the corresponding structures with an alpha-d-Glcp as the reducing sugar linked to the middle heptose (HepII) in the same LPS molecule. Previously these motifs had been found linked only to either the proximal heptose (HepI) or HepIII of the triheptosyl inner-core moiety l-alpha-d-Hepp-(1-->2)-[PEtn-->6]-l-alpha-d-Hepp-(1-->3)-l-alpha-d-Hepp-(1-->5)-[PPEtn-->4]-alpha-Kdo-(2-->6)-lipid A. This novel finding was obtained by structural studies of LPS using NMR techniques and ESI-MS on O-deacylated LPS and core oligosaccharide material, as well as electrospray ionization-multiple-step tandem mass spectrometry on permethylated dephosphorylated oligosaccharide material. A lpsA mutant of strain 1268 expressed LPS of reduced complexity that facilitated unambiguous structural determination. Using capillary electrophoresis-ESI-MS/MS we identified sialylated glycoforms that included sialyllactose as an extension from HepII, this is a further novel finding for H. influenzae LPS. In addition, each LPS was found to carry phosphocholine and O-linked glycine. Nontypeable H. influenzae strain 1200 expressed identical LPS structures to 1268 with the difference that strain 1200 LPS had acetates substituting HepIII, whereas strain 1268 LPS has glycine at the same position.


Amyotrophic lateral sclerosis and spinocerebellar ataxia type 2 in a family with full CAG repeat expansions of ATXN2.
A family with coexistence of spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis (ALS) is described. Intermediate or full CAG repeat expansions of ATXN2 are associated with ALS. However, no coexistence of spinocerebellar ataxia type 2 and ALS in a family has been reported in the literature.We describe a 47-year-old woman with an 11-year history of ataxia and her paternal uncle with ALS who were evaluated at Columbia University Medical Center since July 2006. Both our patient with ataxia and her uncle with ALS have full pathological CAG repeat expansions of ATXN2. The diverse clinical phenotypes of ATXN2 CAG expansions and their coexistence in a single family are highlighted. A clinician should consider the diagnosis of spinocerebellar ataxia type 2 when encountering a patient with ataxia and a family history of ALS.


Assessment of yeast Saccharomyces cerevisiae component binding to Mycobacterium avium subspecies paratuberculosis using bovine epithelial cells.
Since yeast Saccharomyces cerevisiae and its components are being used for the prevention and treatment of enteric diseases in different species, they may also be useful for preventing Johne's disease, a chronic inflammatory bowel disease of ruminants caused by Mycobacterium avium spp. paratuberculosis (MAP). This study aimed to identify potential yeast derivatives that may be used to help prevent MAP infection. The adherence of mCherry-labeled MAP to bovine mammary epithelial cell line (MAC-T cells) and bovine primary epithelial cells (BECs) co-cultured with yeast cell wall components (CWCs) from four different yeast strains (A, B, C and D) and two forms of dead yeast from strain A was investigated. The CWCs from all four yeast strains and the other two forms of dead yeast from strain A reduced MAP adhesion to MAC-T cells and BECs in a concentration-dependent manner after 6-h of exposure, with the dead yeast having the greatest effect. The following in vitro binding studies suggest that dead yeast and its' CWCs may be useful for reducing risk of MAP infection.


The effects of stress on salt and water balance.
The effect of 'stress' on salt and water balance is largely determined by intrinsic renal factors supported by a series of inter-related neuro-humoral mechanisms which serve to enhance salt and water reabsorption and to maintain arterial pressure. As shown by acute hypovolaemic stress, the hormone response is characterized by increased renin-angiotensin production and associated hyperaldosteronism, which is further augmented by states of Na+ depletion. As well as increasing aldosterone secretion, angiotensin II has a direct renal effect to increase Na+ retention, and may stimulate both thirst and arginine vasopressin secretion. Additional support to volume homeostasis is provided by increased secretion of hypothalamic hormones (arginine vasopressin and corticotrophin releasing factor) and activation of the sympathetic nervous system, which further enhances renin secretion. These mechanisms, in restoring extracellular fluid volume and renal perfusion pressure, eventually diminish the stimuli to renin once normovolaemia is achieved. A variety of other acute 'stressors', not associated with major changes in ECF volume or hypotension, also stimulate adrenocortical hormones (cortisol and aldosterone), renin and arginine vasopressin. The biological significance of these changes is uncertain, but their brief duration make it unlikely that the responses contribute significantly to changes in salt or water balance. Atrial peptide hormones could also be important in ECF volume regulation. However, recent studies show little if any change in basal plasma atrial natriuretic peptide levels during acute hypovolaemic stress, whereas severe treadmill exercise (but not surgical stress or acute hypoglycaemia) stimulates venous levels in man. The relevance of these findings to the regulation of salt and water balance during stress clearly requires further study.


Hg2+ detection and information encryption of new [1+1] lanthanide cluster.
The sensing of heavy metal ion and information encryption are two very important research areas. Therefore, developing multi-functional materials capable of sensing heavy metal ions and encrypting information is highly important. In this work, three [1 + 1] lanthanide clusters [Ln(TFBA)3(dmp) (H2O)2]2 (Ln = Tb3+Tb1+1, Eu3+Eu1+1, Gd3+Gd1+1, HTFBA = 2,3,4,5-tetrafluorobenzoic acid, dmp = 4,7-dimethyl-1,10-phenanthroline) were designed and synthesized. Among them, Tb1+1 shows excellent luminescence sensing towards Hg2+ (Ex = 350 nm, Em = 545 nm). Results demonstrates the sensing with high selectivity, strong anti-interference, 20-s response time, high accuracy, excellent linear relationship in 0-20.0 μM, and a very low limit of detection (0.02 ppb). Furthermore, paper strips based on Tb1+1 is fabricated for visual detection of Hg2+ in real samples of tap water, lake water, human urine, and human serum. More interestingly, a new method for confidentiality of information is realized through multi-color anti-counterfeiting patterns with the [1 + 1] lanthanide cluster ink, based on the luminescence "on-off" sensing towards Hg2+.


Responses of sap flow density of two shrub species to rainfall classes on the semiarid Loess Plateau of China.
Rainfall events can determine a cascade of plant physiological and ecological processes, and there is considerable interest in the way that rainfall modifies plant water flux dynamics. The sap flow density (SF) of the planted species of Vitex negundo and Hippophae rhamnoides, on the Loess Plateau of China was monitored using the heat balance method from 2015 to 2017. The results showed that SF responded differently to rainfall classes because of the changing meteorological and soil water content (SWC) conditions. For class 1: 0.2-2 mm, SF increased by 14.36-42.93% for the two species, which were mainly attributable to the effect of solar radiation and vapor pressure deficit after rainfall. For class 2: 2-10 mm, SF remained nearly stable for V. negundo and decreased for H. rhamnoides because of the relative humidity's effect. For class 3: > 10 mm, SF increased significantly because of increased SWC and the increasing response to solar radiation. The increased percentage of SF was relatively higher for V. negundo when rainfall was less than 20 mm, while the value was higher for H. rhamnoides when rainfall was greater than 10 mm. Further, V. negundo's water potential increased at the soil-root interface (ψ0) and ψL, indicating that the plant, which has shallower roots and a coarser of leaf and bark texture, considered as anisohydric species and used precipitation-derived upper soil water to survive. The relatively consistent ψL and ψ0 for H. rhamnoides, which has deep roots and leathery leaves, indicated that this species was considered as isohydric species and insensitive to the slight change in the soil water status. The differed response patter and water use strategies between the two species showed that species as V. negundo are more susceptible to frequent, but small rainfall events, while larger, but less frequent rainfall events benefit such species as H. rhamnoides. This study quantified the effect of environmental factors for SF variation. The results could help formulate a selection process to determine which species are more suitable for sustainable management in the afforestation activities under the context of more frequent and intense rainfall events.


Overcoming the framing problem-a critical-ethical perspective on the need to integrate social sciences and humanities and stakeholder contributions in EURATOM radiation protection research.
This paper introduces the 'framing problem' as the problem of the limited potential of critical reflection on the societal justification and use of nuclear energy technology as a contribution to European radiation protection research, given that the research is itself driven by EURATOM's pro-nuclear political position. The idea is that the problem of policy framing could in principle be 'overcome' by the integration of social sciences and humanities and stakeholder contributions in that research, taking into account that this approach could help to raise critical awareness with the involved researchers and policy makers of the issues of fairness of risk justification in society and of the consequences thereof for nuclear energy policy and policy-supportive research itself.


Retroperitoneal leiomyoma located in the broad ligament: A case report.
Retroperitoneal leiomyoma is a rare benign tumor. Retroperitoneal leiomyomas located in the latissimus uterine ligament are even rarer. Retroperitoneal leiomyomas have similar characteristics to uterine leiomyomas in terms of tissue, which results in confusion during diagnosis. A 47-year-old female with 3 years of pain in the right lower quadrant and discovery of a pelvic mass 13 d ago underwent open abdominal exploration. In the right broad ligament, a solid mass with well circumscribed boundaries, approximately 15 cm × 10 cm × 10 cm in size was bluntly peeled off. The pathological result was a spindle cell tumor, morphologically considered to originate from smooth muscle. Immunohistochemical results supported a deep soft tissue leiomyoma. Retroperitoneal leiomyoma is a rare benign tumor, and surgical treatment can have a good therapeutic effect.


Predictive factors of clinical response to treatment with anti-TNF agents in ulcerative colitis: what have we learned from our patients?
inhibitors of tumor necrosis factor alpha (anti-TNFs) are effective drugs for the treatment of moderate-to-severe ulcerative colitis (UC). However, many patients do not respond or lose therapeutic response during follow-up. to analyze the determining factors of clinical response to anti-TNFs in UC. a multicenter retrospective study was performed in 79 patients with UC who started treatment with anti-TNFs between 2009 and 2015. The primary endpoint was clinical remission (pMayo index ≤ 1) at 12 months. Furthermore, remission and clinical response (final pMayo score ≤ 3) and corticoids discontinuation were assessed at three, six and 12 months. An analysis was performed to identify variables predictive of clinical response. at 12 months, remission and clinical response were seen in 59.2 % and 77.8 % of patients, respectively. Corticoids could be discontinued in 82.4 % of patients. At 12 months, corticoids discontinuation (< 3 months) (OR 0.06; 95 % CI: 0.01-0.24) and clinical response at six months (OR 0.008; 95 % CI: 0.001-0.053) were independent factors predictive of clinical remission. in patients with active UC on anti-TNFs, corticoid discontinuation within three months and clinical response at six months after treatment onset are predictive of clinical disease remission.


Contribution of complement activation to the rise in blood levels of 6-oxo-prostaglandin F1 alpha during endotoxin-induced hypotension in rabbits.
Administration of endotoxin (lipopolysaccharide W E. coli O111 B4, 0.5 mg/kg i.v.) induced about 20% activation of the complement system (measured as CH50 and C3), a biphasic hypotension, thrombocytopenia and a significant rise in blood levels of 6-oxo-PGF1 alpha. Complement depletion (CH50 and C3 less than 3%) with Cobra Venom Factor significantly reduced the initial fall in blood pressure and the rise in 6-oxo-PGF1 alpha, and abolished the second phase of hypotension and the thrombocytopenia, due to subsequent injection of endotoxin. It is concluded that activation of about 20% of the complement system by endotoxin is a prerequisite for the occurrence of thrombocytopenia and secondary hypotension, and that it is involved in the increase in blood levels of 6-oxo-PGF1 alpha. The results of histamine determinations in rabbit blood and plasma indicate that, besides products derived from prostaglandin endoperoxides, other vasoactive substances, possibly released during complement-mediated adherence aggregation of platelets, might contribute to the endotoxin-induced hypotension.


Mood recognition in bipolar patients through the PSYCHE platform: preliminary evaluations and perspectives.
Bipolar disorders are characterized by a series of both depressive and manic or hypomanic episodes. Although common and expensive to treat, the clinical assessment of bipolar disorder is still ill-defined. In the current literature several correlations between mood disorders and dysfunctions involving the autonomic nervous system (ANS) can be found. The objective of this work is to develop a novel mood recognition system based on a pervasive, wearable and personalized monitoring system using ANS-related biosignals. The monitoring platform used in this study is the core sensing system of the personalized monitoring systems for care in mental health (PSYCHE) European project. It is comprised of a comfortable sensorized t-shirt that can acquire the inter-beat interval time series, the heart rate, and the respiratory dynamics for long-term monitoring during the day and overnight. In this study, three bipolar patients were followed for a period of 90 days during which up to six monitoring sessions and psychophysical evaluations were performed for each patient. Specific signal processing techniques and artificial intelligence algorithms were applied to analyze more than 120 h of data. Experimental results are expressed in terms of confusion matrices and an exhaustive descriptive statistics of the most relevant features is reported as well. A classification accuracy of about 97% is achieved for the intra-subject analysis. Such an accuracy was found in distinguishing relatively good affective balance state (euthymia) from severe clinical states (severe depression and mixed state) and is lower in distinguishing euthymia from the milder states (accuracy up to 88%). The PSYCHE platform could provide a viable decision support system in order to improve mood assessment in patient care. Evidences about the correlation between mood disorders and ANS dysfunctions were found and the obtained results are promising for an effective biosignal-based mood recognition.


Engaging the Houston Community in Research: An Early Case Study of a Community Engagement Core in the University of Houston's HEALTH Center for Addictions Research and Cancer Prevention.
The National Institute on Minority Health and Health Disparities-funded U54 Research Center at the University of Houston addresses disparate racial/ethnic health outcomes related to cancer and substance abuse. Of its 4 cores, the Community Engagement Core involves the impacted community in affiliated research. Strategies include implementing community advisory boards, assisting with study design and execution, maintaining a social media presence, and publishing health-related videos for the community. We examine the early effectiveness of these strategies. Data collection included surveying investigators and community advisory board members and monitoring traffic to videos and social media posts. On a Likert scale survey of investigators (4 = "agree" and 5 = "strongly agree"), the mean rating for a prompt expressing satisfaction with services received was 4.67 (SD = 0.52; N = 6). On a Likert scale survey of community advisory board members, the mean rating for a prompt expressing belief that feedback was taken seriously was 5.00 (SD = 0.00; N = 9). The Community Engagement Core is building trusting relationships between researchers and community members. We discuss lessons learned that may inform both our growth and others' efforts to implement community-engaged research.


Characterization of radiation-induced luminescence properties and free radicals for the identification of different gamma-irradiated teas.
Two kinds (20 each) of gamma-irradiated (0, 5, and 10 kGy) tea samples, blended powders and packed in sachets (tea bags), were investigated using photostimulated luminescence (PSL), thermoluminescence (TL), and electron spin resonance spectroscopy (ESR) to identify their irradiation status. PSL-based rapid screening was possible for all the control samples except for one packed and two powdered samples. The irradiated samples presented a good dose-dependent PSL count except two powdered samples with very low PSL sensitivity. TL analysis provided the most reliable results, in which all the irradiated samples were identified using a well-defined high-intensity TL glow curve in a temperature range of 150-250 °C. The TL results were also confirmed by determining the TL ratio (TL1/TL2), which was <0.1 in all the non-irradiated samples and >0.1 in the irradiated ones. ESR spectroscopy was effective for only 3 packed and 6 powdered samples showing the radiation-induced cellulosic and sugar radical signals, respectively.


Surgical techniques for medial Patellofemoral ligament reconstruction: a systematic review and meta-analysis of level I and II studies.
To determine the most optimal surgical technique for medial patellofemoral ligament reconstruction (MPFLR). Three databases MEDLINE, PubMed, and EMBASE were searched from inception to December 13th, 2022, for level I or II studies comparing MPFLR techniques. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on patient-reported outcome measures were recorded. Quality assessment was carried out using the MINORS and Cochrane Risk of Bias assessment tools. Certainty of evidence was carried out with the GRADE assessment tool. Ten studies comprising 723 patients (723 knees) were included in this review. The weighted mean difference in Kujala, Lysholm, and IKDC scores comparing single- and double-tunnel patellar drilling techniques was 2.66 (95% CI -1.05-6.37, p = 0.16, I2 = 0%) with moderate certainty, 0.78 (95% CI -9.02-10.58, p = 0.88, I2 = 87%) with low certainty, and 1.71 (95% CI -2.43-5.86, p = 0.42, I2 = 0%) with low certainty, respectively. Double-suture anchor patellar fixation demonstrated greater Kujala scores than transpatellar fixation (87.1 ± 2.8 vs 84.0 ± 3.8, p < 0.001) with moderate certainty. Y-shaped graft patellar fixation demonstrated superior Kujala scores to C-shaped graft patellar fixation (95.9 ± 4.7 vs 91.3 ± 9.7, p = 0.001) with moderate certainty. Augmentation of femoral fixation with polyester sutures demonstrated superior Kujala scores (97.8 ± 6.4. vs 88.0 ± 6.3, p < 0.005) with low certainty. Four-stranded grafts demonstrated greater Kujala scores than two-stranded grafts (93.5 ± 2.6 vs 91.6 ± 3.5, p = 0.01) with low certainty. The optimal MPFLR surgical technique is likely to utilize a four-stranded graft using either endobutton, double-suture anchor, or transosseous suture patellar fixation with polyester suture augmented interference screw femoral fixation. Orthopedic surgeons can consider employing such a technique to improve patient outcomes by conferring greater graft stability, strength, and function. Level of evidence Level II.


Control of production of insulin-like growth factor I by pig Leydig and Sertoli cells cultured alone or together. Cell-cell interactions.
The production of insulin-like growth factor I (IGF-I) by pig Leydig cells and pig Sertoli cells cultured alone or together was investigated. Human chorionic gonadotropin (hCG) and basic fibroblast growth factor (FGF) stimulate in a dose-dependent manner IGF-I production by Leydig cells. At maximal concentrations the effects of both factors were almost additive. Insulin at micromolar concentrations enhanced IGF-I production and potentiated the effects of hCG and FGF. The secretion of IGF-I by Sertoli cells was stimulated by FSH and FGF. Under basal conditions, the production of IGF-I by the coculture was similar to the addition of the production by each cell cultured alone. In contrast, in the presence of hCG, FSH or FGF, the production of IGF-I by the coculture largely exceeded that expected from the monocultures. Moreover, stimulation of the coculture with both hCG and FSH resulted in a further increase in IGF-I production. These results indicate that Leydig as well as Sertoli cells secrete IGF-I and that the secretion of both cell types is stimulated by the corresponding gonadotropin. In addition, they indicate that Leydig-Sertoli interactions play a role in the control of IGF-I production, supporting the contention that this growth factor plays an important role in the paracrine and autocrine control of testicular functions.


A long-term survivor case of malignant mesothelioma treated by recombinant tumor necrosis factor-SAM2 (TNF-alpha mutein) and 5-fluorouracil (5-FU): a new therapeutic approach based on host-tumor relationship.
The prognosis of mesothelioma is very poor, and there is no established method to suppress tumor growth. Immunological approaches have recently been thought to be effective for mesothelioma and several studies using cytokines have been performed. We used a novel recombinant tumor necrosis factor-alpha (rTNF-alpha) we called rTNF-SAM2, in the treatment of a patient with this disease. A 48-year old male patient with ascites was diagnosed with malignant mesothelioma by cytological examination. TNF-SAM2 in an amount of 264 to 576 micrograms (1 to 2.2 x 10(6) U) was injected via a catheter several times. Five hundred mg of 5 fluorouracil (5-FU) was also given via catheter once a week and 5-FU derivative was given orally every day. No apparent tumor progression was observed for 6 years and 6 months and the patient led a normal life. During the therapy, the malignancy of tumor cells from the ascites changed from class V to class VI. TNF based therapy may be promising treatment for the suppression of malignant mesothelioma.


An analysis of rod outer segment adaptation based on a simple equivalent circuit.
This model of rod outer segment adaptation is based on the hypothesis that transmitter substance released by bleached rhodopsin closes sodium channels in the outer segment plasma membrane, leading to hyperpolarization of the receptor. The outer segment adaptation processes of the model are associated with the transmitter release, the transmitter background concentration and the plasma membrane leakage. Changes in the three model parameters correspond to the three types of outer segment adaptation process. According to the model the stimulus-response function is in every adaptational state U/Umax = I/(I + IH). The model predicts how each adaptation process affects IH and Umax. Specifically, when the number of liberated transmitter molecules per isomerizing quantum decreases, the amplitude Umax remains constant but IH increases. A short description of this model has been published in a paper reporting experimental results on background adaptation (Hemilä, 1977).


Defensive secretion of the tenebrionid beetle, Blaps mucronata: physical and chemical determinants of effectiveness.
The primary components of the defensive secretions of Blaps mucronata (Tenebrionidae) are two quinones (methyl-p-benzoquinone and ethyl-p-benzoquinone) and the hydrocarbon 1-n-tridecene. The hydrocarbon is shown, by comparison with longer- and shorter-chain n-alkanes and 1-n-alkenes, to be optimally suited as carrier of the quinones, and as a surfactant that promotes spread of secretion over the beetle's body following discharge from the gland openings at the abdominal tip. As shown from repellency tests with ants (Monomorium pharaonis) and topical irritancy tests with cockroaches (Periplaneta americana), the anti-insectan potency of the secretion derives as much from the hydrocarbon as from the quinones.


Wild animals as an underused treasure trove for studying the genetics of cancer.
Recent years have seen an emergence of the field of comparative cancer genomics. However, the advancements in this field are held back by the hesitation to use knowledge obtained from human studies to study cancer in other animals, and vice versa. Since cancer is an ancient disease that arose with multicellularity, oncogenes and tumour-suppressor genes are amongst the oldest gene classes, shared by most animal species. Acknowledging that other animals are, in terms of cancer genetics, ecology, and evolution, rather similar to humans, creates huge potential for advancing the fields of human and animal oncology, but also biodiversity conservation. Also see the video abstract here: https://youtu.be/UFqyMx5HETY.


Review: Why screen for severe combined immunodeficiency disease?
Newborn screening for severe combined immunodeficiency (SCID) is now routinely performed in many countries across Europe and around the world. The number of T-cell receptor excision circles (TRECs) reflects T cell levels. TREC quantification is possible using dried blood spot (DBS) samples already collected from newborns to screen for other conditions. This method is very sensitive and highly specific. Data in the literature show that the survival rate for children with SCID is much higher when the disease is detected through early screening, as opposed to a later diagnosis. Newborns diagnosed with SCID may receive the appropriate care quickly, before the onset of serious infectious complications, which raises survival rates, improves quality of life, and limits side effects and treatment costs. At the request of the French Ministry of Health, France's National Authority for Health (Haute Autorité de Santé) is expected to issue recommendations on this topic soon. The nationwide DEPISTREC study, involving 48 maternity units across France, showed that routine SCID screening is feasible and effective. Such screening offers the additional benefit of also diagnosing non-SCID lymphopenia within the infant population.


[Separation and determination, using a gas-chromatographic method, of vinyl acetate, methyl acetate and methyl alcohol in industrial environments].
The AA. have defined a simple and rapid method for sampling and subsequent simultaneous determination of ppm of vinyl acetate, methyl acetate and methyl alcohol present in work environments. The methods for drawing air and for performing the gaschromatographic analysis by two columns are illustrated.


Metrological characterization of the ADONIS system used in gamma-ray spectrometry.
In gamma-ray spectrometry, new acquisition systems based on digital signal processing are now commercially available. In order to determine their performance at high count rates, the Commissariat à l'Energie Atomique (CEA), Laboratoire National Henri Becquerel has tested several of these systems. These tests have clearly shown that the performance levels announced by the manufacturers were generally not met. It was therefore a logical step to include the Atelier de DévelOppement Numérique pour l'Instrumentation en Spectrométrie (ADONIS) system in these tests. ADONIS is the new numerical system for gamma-ray spectrometry, developed by the CEA Service d'Instrumentation et d'Application des Rayonnements.


Effects of Saccharomycopsis fibuligera and Saccharomyces cerevisiae inoculation on small fermentation starters in Sichuan-style Xiaoqu liquor.
Xiaoqu liquor is a type of distilled spirit in China prepared on a small scale from a small solid starter culture. Although this liquor is popular in southwestern China, it can have a dull taste, limiting its market. To improve the flavour profile of Xiaoqu liquor, we selected two functional yeast strains (Saccharomycopsis fibuligera and Saccharomyces cerevisiae) from Zaopei (fermented grain) of Baijiu liquor and used them for Xiaoqu liquor fermentation. Compared with traditional Xiaoqu (Starter), bioaugmentation inoculation increased the glucoamylase and acidic protease activities and the ethanol synthesis rate, while decreasing the acidity of the Zaopei (fermented grains) in the early stage of fermentation. By the end of the fermentation process, the alcohol and ester content had also increased by 42.5% and 11.8%, respective, and that of aldehydes and ketones, and heterocyclic compounds decreased by 73.7% and 77.1%, respectively. Traditional isolation and high-throughput sequencing were employed to analyse the microorganisms in the Zaopei. Bioaugmentation inoculation increased the microbial diversity of Xiaoqu liquor during the fermentation process. The dominant fungus during fermentation using the two types of starter cultures was S. cerevisiae, whereas the dominant bacteria was Pseudomonas, followed by Bacillus, Weissella, Lactobacillus, and Bacteroides. Principal component analysis of the bacterial community structure and flavour substances in the Zaopei produced using the two strains revealed that there were few differences between the two liquors and that inoculation with functional yeasts may not change the flavour substances in Xiaoqu liquor. However, correlation analysis showed that Escherichia Shigella, Terrisporobacter, Bacillus, Clostridium, and Prevotellaceae are the main microorganisms in the Xiaoqu liquor fermentation process. These results lay the foundation to improve the quality of Xiaoqu liquor.


An effective simulation- and measurement-based workflow for enhanced diagnostics in rhinology.
Physics-based analyses have the potential to consolidate and substantiate medical diagnoses in rhinology. Such methods are frequently subject to intense investigations in research. However, they are not used in clinical applications, yet. One issue preventing their direct integration is that these methods are commonly developed as isolated solutions which do not consider the whole chain of data processing from initial medical to higher valued data. This manuscript presents a workflow that incorporates the whole data processing pipeline based on a Jupyter environment. Therefore, medical image data are fully automatically pre-processed by machine learning algorithms. The resulting geometries employed for the simulations on high-performance computing systems reach an accuracy of up to 99.5% compared to manually segmented geometries. Additionally, the user is enabled to upload and visualize 4-phase rhinomanometry data. Subsequent analysis and visualization of the simulation outcome extend the results of standardized diagnostic methods by a physically sound interpretation. Along with a detailed presentation of the methodologies, the capabilities of the workflow are demonstrated by evaluating an exemplary medical case. The pipeline output is compared to 4-phase rhinomanometry data. The comparison underlines the functionality of the pipeline. However, it also illustrates the influence of mucosa swelling on the simulation. Graphical Abstract Workflow for enhanced diagnostics in rhinology.


Tumor microenvironment remodeling in oral cancer: Application of plant derived-natural products and nanomaterials.
Oral cancers consist of squamous cell carcinoma (SCC) and other malignancies in the mouth with varying degrees of invasion and differentiation. For many years, different modalities such as surgery, radiation therapy, and classical chemotherapy drugs have been used to control the growth of oral tumors. Nowadays, studies have confirmed the remarkable effects of the tumor microenvironment (TME) on the development, invasion, and therapeutic resistance of tumors like oral cancers. Therefore, several studies have been conducted to modulate the TME in various types of tumors in favor of cancer suppression. Natural products are intriguing agents for targeting cancers and TME. Flavonoids, non-flavonoid herbal-derived molecules, and other natural products have shown promising effects on cancers and TME. These agents, such as curcumin, resveratrol, melatonin, quercetin and naringinin have demonstrated potency in suppressing oral cancers. In this paper, we will review and discuss about the potential efficacy of natural adjuvants on oral cancer cells. Furthermore, we will review the possible therapeutic effects of these agents on the TME and oral cancer cells. Moreover, the potential of nanoparticles-loaded natural products for targeting oral cancers and TME will be reviewed. The potentials, gaps, and future perspectives for targeting TME by nanoparticles-loaded natural products will also be discussed.


Is postoperative flexion angle genuinely better in unicompartmental knee arthroplasty than in total knee arthroplasty? A comparison between the knees in the same patients.
The aim of this retrospective study was to clarify if unicompartmental knee arthroplasty (UKA) can acquire a greater postoperative flexion angle than total knee arthroplasty (TKA) in the same individuals after adjusting for the preoperative flexion angle and if the preoperative flexion angle correlates with the change in flexion postoperatively. Thirty-five patients between 2011 and 2017 who had undergone simultaneous TKA on one knee and UKA on the other knee were included in the study. Range of motion was measured preoperatively and at one year after the surgery. The relationship between the pre- and postoperative flexion angles was evaluated. UKA can acquire approximately 10° greater flexion postoperatively when compared to TKA, even after adjustment for the preoperative flexion angle. The preoperative flexion angle is strongly and negatively correlated with the change in flexion angle in both the TKA and UKA knees. A preoperative knee with a smaller flexion angle will gain greater flexion postoperatively, whereas a preoperative knee with a greater flexion angle tends to lose flexion angle. The thresholds of gain/loss are estimated as 123° and 135° in TKA and UKA knees, respectively. These results provide an evidence that the UKA can acquire a greater postoperative flexion angle than the TKA and valuable information for patients who demand a deep postoperative flexion angle.


EmbryoNet: using deep learning to link embryonic phenotypes to signaling pathways.
Evolutionarily conserved signaling pathways are essential for early embryogenesis, and reducing or abolishing their activity leads to characteristic developmental defects. Classification of phenotypic defects can identify the underlying signaling mechanisms, but this requires expert knowledge and the classification schemes have not been standardized. Here we use a machine learning approach for automated phenotyping to train a deep convolutional neural network, EmbryoNet, to accurately identify zebrafish signaling mutants in an unbiased manner. Combined with a model of time-dependent developmental trajectories, this approach identifies and classifies with high precision phenotypic defects caused by loss of function of the seven major signaling pathways relevant for vertebrate development. Our classification algorithms have wide applications in developmental biology and robustly identify signaling defects in evolutionarily distant species. Furthermore, using automated phenotyping in high-throughput drug screens, we show that EmbryoNet can resolve the mechanism of action of pharmaceutical substances. As part of this work, we freely provide more than 2 million images that were used to train and test EmbryoNet.


Exploring the Intertwined Nexus between Globalization, Energy Usage, Economic Complexity, and Environmental Quality in Emerging Asian Economies: A Pathway Towards a Greener Future.
The study aims to examine the relationship between carbon emissions and ecological footprints with economic complexity, core pollution indicators, urbanization, globalization, and renewable and non-renewable energy consumption in eight emerging Asian economies from 1971 to 2020. A panel data framework that considers cross-sectional dependence and heterogeneity was used for analysis. The Pedroni and Johnsen Fisher cointegration showed that carbon emission, ecological footprint, renewable and non-renewable energy consumption, economic complexity, globalization, and urbanization confirmed the presence of cointegration. Moreover, fully modified ordinary least squares (FMOLS) and dynamic ordinary least squares (DLOS) indicated that globalization, non-renewable energy consumption, and economic complexity increase emission and ecological footprint in the long run, whereas renewable energy generated through biomass, solar, and wind decreases environmental degradation. Furthermore, urbanization also negatively affects the environment. From a policy perspective, policymakers in these countries may manage their natural resources efficiently by escalating the share of renewables in total energy production, offering tax holidays, incentives and encouraging companies to install clean energy plant, and providing support to research and development-oriented companies to engage in research activities to reduce the cost of production of renewable energy.


Evaluation of occupational ocular trauma: are we doing enough to promote eye safety in the workplace?
The aim of this study was to document the use of eye personal protective equipment (PPE) by patients who had sustained an eye injury in the workplace and to evaluate the characteristics and outcomes of these patients. Case-control study. All adult patients who had sustained an eye injury in the workplace and presented to the urgent ophthalmology clinic of a tertiary care hospital from October 1, 2013, to November 30, 2014, were eligible for inclusion. Medical records were reviewed to obtain occupational eye injury data, including etiology, type, and severity of injury as per the Ocular Trauma Score. Use of eye PPE at the time of injury was recorded. Outcome data, including disposition, duration of follow-up, and return to baseline best-corrected visual acuity, were also recorded. One hundred sixty-nine patients were included in this study. The median age of the cohort was 31 years (range, 17-68 years), and 92.9% were male. Chemical exposure (31.4%), grinding (17.9%), and injuries sustained by a sharp-object, metal, or nail (13.1%) were overall the most common etiologies of injury. Eye PPE was not worn by 66.9% of the cohort, with 33.1% of the cohort sustaining an occupational eye injury despite the use of eye PPE. Use of eye PPE among workers who sustain an eye injury in the workplace remains low; yet, its use does not preclude a significant proportion of such workers from injury. Increasingly advocating for both the use and appropriate selection of eye PPE in the workplace is an important public health initiative that should therefore be encouraged.


Failure to immortalise human AML cells using human recombinant GMCSF in vitro and in vivo.
We have failed to find any evidence that human recombinant GM-CSF can immortalize human AML cells grown in liquid culture or as nodules in immune deprived mice. In previous clinical studies and a controlled trial currently underway there is no evidence of irreversible acceleration of the disease.


[Experimental analysis of human specific protein coding open reading frame c11orf72].
Gene c11orf72 (also known as FLJ90834) included in human gene reference list was previously predicted on the basis oftranscriptome analysis. We show that c11orf72 predicted protein coding open reading frame is specific for human genome and that it is absent from DNAs of other investigated primate species (chimpanzee, macaque). For the first time, we systematically analyzed c11orf72 expression in five normal and two cancerous human tissues (testicles, heart, brain, lung, bladder, bladder tumor and testicular tumor) and found no transcriptional activity there. Promoter of c11orf72, located close to promoter of a housekeeping gene NDUFV1, has shown high methylation level, whereas NDUFV1 promoter was almost free from methylation. The protein product for cllorf72 was analyzed using heterologous expression in human cell lines NT2/D1 (Tera2) and HepG2, in N- and C-terminal fusion constructs with the fluorescent protein TurboGFP. C11orf72 protein showed no cytotoxic or promitotic activity and was distributed diffusely through the cell. Our data confirm the possibility of gain of new protein-coding genes during human evolution due to simple accumulation of point mutations. However, we found no evidence for the functional significance of gene c11orf72.


Prognostic Value of Venous to Arterial Carbon Dioxide Difference during Early Resuscitation in Critically Ill Patients with Septic Shock.
The partial pressure of venous to arterial carbon dioxide gradient (PCO2 gap) is considered as an alternative marker of tissue hypoperfusion and has been used to guide treatment for shock. The aim of this study was to investigate the prognostic value of venous-to-arterial carbon dioxide difference during early resuscitation of patients with septic shock and compared it with that of lactate clearance and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. Forty patients admitted to one Intensive Care Unit were enrolled. APACHE-II score was calculated on admission. An arterial blood gas, central venous, and lactate samples were obtained on admission and after 6 h, and lactate clearance was calculated. Patients were classified retrospectively into Group I (survivors) and Group II (nonsurvivors). Pv-aCO2 difference in the two groups was evaluated. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. At T0, Group II showed high PCO2 gap (8.37 ± 1.36 mmHg) than Group I (7.55 ± 0.95 mmHg) with statistically significant difference (P = 0.030). While at T6, Group II showed higher PCO2 gap (9.48 ± 1.47 mmHg) with statistically significant difference (P < 0.001) and higher mean lactate values (62.71 ± 23.66 mg/dl) with statistically significant difference (P < 0.001) than Group I where PCO2 gap and mean lactate values became much lower, 5.91 ± 1.12 mmHg and 33.61 ± 5.80 mg mg/dl, respectively. Group I showed higher lactate clearance (25.42 ± 6.79%) with statistically significant difference (P < 0.001) than Group II (-69.40-15.46%). High PCO2 gap >7.8 mmHg after 6 h from resuscitation of septic shock patients is associated with high mortality.


Lymphohematopoietic cancer mortality among Korean semiconductor manufacturing workers.
We aimed to examine the lymphohematopoietic cancer mortality in a cohort of workers at a semiconductor manufacturing company in South Korea according to their jobs. A retrospective cohort was constructed using the personnel records of semiconductor manufacturing workers who were employed in a semiconductor company in South Korea in 1998-2012. Data on their vital status and causes of death were obtained from the National Statistical Office of South Korea. The standardized mortality ratios (SMRs) of lymphohematopoietic cancer were calculated. A total of 288 deaths were reported, of which 22 were caused by lymphohematopoietic cancer, among 65,782 workers in 878,325 person-years. The SMRs for lymphohematopoietic cancer were 0.78 (95% confidence interval [CI] = 0.39-1.40; the number of observed cases [Obs] = 11) among male workers and 1.71 (95% CI = 0.85-3.06; Obs = 11) among female workers. Among female operators, excess deaths due to lymphohematopoietic cancer (SMR = 2.59, 95% CI = 1.24-4.76) and leukemia (SMR = 2.92, 95% CI = 1.26-5.76) were observed. However, they were not observed among office workers, facility managers, utility managers, or process managers. Female operators involved in the semiconductor wafer fabrication process had higher risk of mortality from lymphohematopoietic cancer.


Pharmacologic inhibition of mast cell degranulation prevents left ventricular remodeling induced by chronic volume overload in rats.
Left ventricular (LV) hypertrophy and dilation are important compensatory responses to chronic volume overload; however, the mechanisms responsible for this LV remodeling have not been well characterized. Previous observations that the number of myocardial mast cells are increased in congestive heart failure (CHF) suggested the hypothesis that mast cells might be involved in the ventricular remodeling induced by a chronic volume overload. Accordingly, the intent of this study was to determine the contribution of mast cells to LV remodeling, dysfunction, and morbidity/mortality secondary to CHF in the infrarenal aortocaval fistula model of sustained volume overload. To this end, LV end-diastolic pressure, size, and function (ie, isovolumetric pressure-volume relations in the blood-perfused isolated heart) were assessed in both nedocromil sodium treated and untreated rats at 8 weeks after fistula and compared with age-matched controls. Nedocromil, a mast cell-stabilizing drug, effectively prevented the LV dilation and decreased contractility seen in the untreated fistula group in a dose-dependent fashion, resulting in a significant reduction in the incidence of morbidity/mortality from CHF. The ability of mast cell stabilization to prevent ventricular dilation induced by chronic volume overload identifies a key role for mast cells in the regulation of myocardial remodeling.


Azithromycin versus Sulfadiazine and Pyrimethamine for non-vision-threatening toxoplasmic retinochoroiditis: a pilot study.
The purpose of this pilot study is to compare the efficacy and tolerance of azithromycin alone as opposed to standard treatment with sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. We conducted a prospective, randomized, institutional clinical study comparing azithromycin to sulfadiazine and pyrimethamine for active, non-vision-threatening toxoplasmic retinochoroiditis. Nineteen out of 75 patients fulfilled inclusion criteria and were randomized into 2 treatment regimens. Nine patients were treated with sulfadiazine and pyrimethamine and 10 patients with azithromycin at a dose of 500 mg qd. Main outcome measures assessed were time to sharpening of lesion borders, time to lesion scarring, time to disease inactivity, and treatment tolerance. Azithromycin monotherapy achieved lesion scarring and disease inactivity in all but 1 patient. Although no statistically significant difference was found between the 2 patient groups as regards main outcome measures for treatment efficacy, all median times to endpoints (days) were longer for the azithromycin group - time to sharpening of lesion borders on clinical evaluation (25.5 vs. 24) and masked evaluation of photographs (30.5 vs. 24), time to lesion scarring on clinical evaluation (73 vs. 47) and masked evaluation of photographs (71.5 vs. 36) and time to disease inactivity (73 vs. 49). Treatment tolerance was significantly better for the azithromycin group (p=0.0005). Azithromycin monotherapy at a dose of 500 mg per day was shown to be effective and well-tolerated for the treatment of active, non-vision-threatening toxoplasmic retinochoroiditis. Duration of treatment was clinically longer for the azithromycin group.


Weight fluctuations and risk for metabolic syndrome in an adult cohort.
Weight gain is a risk factor for metabolic syndrome (MS). However, it is not known whether weight fluctuations (WF) have a deleterious effect upon MS risk. In the present study, we investigated this association in subjects participating in the SU.VI.MAX cohort. MS status was assessed at baseline (1994/1995) and at the end of follow-up (2001/2002) using the National Cholesterol Education Program-Adult Treatment Panel III criteria. WF were estimated with four weight measures during follow-up. Odds ratio (OR, 95% confidence interval (CI)) for incident MS cases was evaluated according to four WF groups (no WF and tertiles of WF) in 3553 middle-aged subjects. The OR (95% CI) for MS was 2.06 (1.20-3.52) for the third WF tertile compared to the first tertile. This association was independent of confounding variables, especially relative weight change during follow-up. Subjects without WF had a 2.72-fold increase (1.64-4.53) for MS risk compared to the first tertile of WF. For MS components taken separately, similar associations were found for raised blood pressure, low high-density lipoprotein-cholesterol and increased waist circumference. Our results showed that WF was an independent risk factor for MS after 7 years of follow-up. Moreover, subjects without WF were also at risk for MS, due to the highest weight gain during follow-up. These results support the benefits of weight stability and emphasize the importance of weight gain prevention starting from early adulthood.


In vivo screening of essential oils of Skimmia laureola leaves for antinociceptive and antipyretic activity.
To study the screening of essential oils of Skimmia laureola leaves (SLO) for acute toxicity, antinociceptive, antipyretic and anticonvulsant activities in various animal models. SLO were extracted using modified Clevenger type apparatus. Acute toxicity test was used in mice to observe its safety level. Antinociceptive activity of SLO was evaluated in acetic acid induced writhing and hot plate tests. Yeast induced hyperthermic mice and pentylenetetrazole induced convulsive mice were used for the assessment of its antipyretic and anticonvulsant profile respectively. Substantial safety was observed for SLO in acute toxicity test. SLO showed a high significant activity in acetic acid induced writhing test in a dose dependent manner with maximum pain attenuation of 68.48% at 200 mg/kg i.p. However, it did not produce any relief in thermal induced pain at test doses. When challenged against pyrexia evoked by yeast, SLO manifested marked amelioration in hyperthermic mice, dose dependently. Maximum anti-hyperthermic activity (75%) was observed at 200 mg/kg i.p. after 4 h of drug administration. Nevertheless, SLO had no effect on seizures control and mortality caused by pentylenetetrazole. In vivo studies of SLO showed prominent antinociceptive and antipyretic activities with ample safety profile and thus provided pharmacological base for the traditional uses of the plant in various painful conditions and pyrexia. Additional detail studies are required to ascertain its clinical application.


Temperature study of indole, tryptophan and N-acetyl-L-tryptophanamide (NATA) triplet-state quenching by iodide in aqueous solution.
In this study, the temperature dependence of the measured phosphorescence lifetimes of aqueous indole, tryptophan and N-acetyl-L-tryptophanamide (NATA) between 6 and 55 °C in the absence and in the presence of iodide, a suitable intersystem crossing enhancer, has been determined. The obtained results suggest the existence of one process for the temperature-dependent, non-radiative deactivation of triplet states of the aqueous indoles in the absence of iodide. This process may be associated with the high sensitivity of indole triplet state lifetime to the subtle changes in the local viscosity of the surrounding aqueous environment or may be attributed to diffusional quenching by solvent molecules and/or by possible impurities present in water. However, the steep decrease in the measured phosphorescence lifetimes of indole and tryptophan with temperature suggests that diffusion-mediated quenching processes are not prevailing. Upon increasing concentration of iodide (up to 0.1 M), the obtained Arrhenius plots for the deactivation rate (1/τph) of the triplet states of the studied indoles were linear, which provided strong support for the hypothesis of the existence of one temperature dependent non-radiative process for the de-excitation of indoles triplet state. Our results showed that this process is attributed to the diffusion-controlled solute-quenching by iodide and, most probably, proceeds via reversibly formed exciplex. At concentration of iodide higher than 0.1M highly curved Arrhenius plots were obtained, which may indicate a change in the rate determining step with a change in temperature. This change most probably is associated with a transition from diffusion-controlled exciplex formation followed by rate-determining exciplex deactivation at high temperature.


Applications of high pressure to pre-rigor rabbit muscles affect the functional properties associated with heat-induced gelation.
High pressure (HP) was applied to pre-rigor rabbit muscles (PRRMs) for the manufacture of value-added gel-type products. A 2×3 factorial design was adopted for HP-treatment (100, 200 and 300MPa for 15 or 180s) to PRRMs. The HP-treated meat was used for gel preparation and determination of water mobility properties and textural profiles. Salt-soluble meat proteins (SSMP) were then extracted from meat for estimating the tertiary conformational changes (hydrophobic and sulfhydryl groups). The water-holding capacity of treated samples increased significantly (P<0.05) except for those treated at 300-180 (MPa-s). The hardness, cohesiveness and chewiness were significantly improved (P<0.05) by moderate HP-treatments (100-200MPa for 15 or 180s). HP-induced the de-polymerization of some protein components, together with unfolding and refolding of protein tertiary conformations, partly explaining the observed functionality changes. In conclusion, application of moderate HP to PRRM modified the protein conformation in a manner that improved the functional properties of gels.


Extramedullary relapse following total marrow and lymphoid irradiation in patients undergoing allogeneic hematopoietic cell transplantation.
Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.


Induction of sister-chromatid exchanges by procarcinogens in metabolically competent Chinese hamster epithelial liver cells.
An epithelial cell strain has been established from the livers of male Chinese hamsters (CHEL cells). These cells, which proliferate in culture and retain their metabolic enzymatic activities during several subcultures, were used in a sister-chromatid exchange assay to evaluate the effectiveness of polycyclic aromatic hydrocarbons (PAHs), aflatoxin B1 (AFB1) and cyclophosphamide (CP). The results obtained demonstrate that CHEL cells are metabolically competent to activate different classes of procarcinogens into biologically active metabolites. Moreover, they showed a selective capacity to discriminate chemical carcinogens from noncarcinogens. Thus, the CHEL cell system appears to be a promising alternative to the short-term tests that include cell-free rodent liver homogenate to evaluate new promutagens and/or procarcinogens.


Effect of UV254 disinfection on the photoformation of reactive species from effluent organic matter of wastewater treatment plant.
UV254 is one of the main disinfection methods used in wastewater treatment plants (WWTPs) for the inactivation of pathogens in the effluents before being discharged into the receiving waters. The effluent organic matters (EfOM) are well-known photosensitizers for the generation of reactive species, mainly including the triplet states of EfOM (3EfOM*), singlet oxygen (1O2) and hydroxyl radical (•OH), which contribute to the removal of trace pollutants in water. However, the effect of UV254 disinfection on the photoreactivity of EfOM remains unclear. Here we investigated the photophysical and photochemical properties variation of EfOM after UV254 disinfection, along with humic substances (HS) as comparison. The UV254 disinfection caused a decrease of aromaticity, fluorescence intensity and molecular weight for all samples, while a reduction formation of triplet state of these dissolved organic matters (3DOM*), 1O2, hydrogen peroxide (H2O2), and superoxide anions (O2•-) under simulated sunlight was observed. In contrast, the generation of •OH was increased after UV254 disinfection. The quantum yield of 1O2 was positively correlated with triplet quantum yield coefficient (fTMP) in all cases. However, the quantum yield of •OH exhibited positive and negative correlations with fTMP for EfOM and HS, respectively. The quantum yields showed positive correlations with E2/E3 (ratio of the absorbance at 254 to 365 nm) for untreated DOM samples, while for the first time we found the trends differ distinctly after UV254 disinfection. These findings indicate that UV254 disinfection in WWTPs significantly increases the potential of •OH photoproduction from effluents and the cost-effective solar irradiation after UV254 disinfection is expected to be a novel technique for further removal of pathogen and trace organic pollutants in wastewater effluents and receiving waters.


Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy.
Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure. A double blinded randomized trial. The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR). The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (-52.0±26.4 vs -17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were -60.2±28.2%, -62.2±33.9%, -48.5±29.8%, and -55.5±24.0%, and, in the control group, -6.8±32.2%, -2.5±35.9%, -12.7±34.2%, and -21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable. Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication. Clinicaltrial.gov NCT1224028.


A streptavidin-biotin system combined with magnetic actuators for remote neuronal guidance.
The ability to control neuronal mobility and organization is of great importance in developing neuronal interfaces and novel therapeutic approaches. An emerging promising method is the manipulation of neuronal cells from afar via magnetic forces. Nevertheless, using magnetic iron oxide nanoparticles as internal actuators may lead to biotoxicity, adverse influence on intracellular processes, and thus requires prerequisite considerations for therapeutic approaches. Magnetizing the cells via the incorporation of magnetic particles that can be applied extracellularly is advantageous. Herein, we have developed a magnetic system based on streptavidin-biotin interaction to decorate cellular membrane with magnetic elements. In this model, superparamagnetic microparticles, coated with streptavidin, were specifically bound to biotinylated PC12 cells. We demonstrated that cell movement can be directed remotely by the forces produced by pre-designed magnetic fields. First, using time lapse imaging, we analyzed the kinetics of cell migration towards the higher flux zone. Next, to form organized networks of cells we designed and fabricated micro-patterned magnetic devices. The fabricated devices were composed of a variety of ferromagnetic shapes, sputter-deposited onto glass substrates. Cells that were conjugated to the magnetic particles were plated atop the micro-patterned substrates, attracted to the magnetic actuators and became fixed onto the magnetic patterns. In all, our study presents a novel system based on a well-known molecular technology combined with nanotechnology that may well lead to the expansion of implantable magnetic actuators to organize and direct cellular growth.


Three-dimensional arrangement of the cell wall protein of Sulfolobus acidocaldarius.
The three-dimensional structure of the S-layer that surrounds the bacterium Sulfolobus acidocaldarius is described in detail. Pieces of the S-layer, which are two-dimensional crystals with p6 symmetry, have been studied by crystallographic analysis of electron micrographs of tilted specimens. In the density map, each asymmetric unit appears to consist of several domains connected by strong hinges. On the basis of the ragged appearance of the structure at torn edges, we now suggest that the single species of polypeptide is in a highly extended conformation, with much overlap between different molecules, and show how such molecules might be weaved together to produce the morphological domains. We show that the closed surface lattice of the intact cell wall contains 5-fold and 7-fold vertices and show how the subunit structure appears to be well suited to form 5-fold and 7-fold symmetric rings at these points in place of the 6-fold rings of the hexagonal lattice.


Biomechanical action of a corrective brace on thoracic idiopathic scoliosis: Cheneau 2000 orthosis.
To provide a detailed description of the mechanisms responsible for the corrective effect of the rigid brace Cheneau 2000. Morphology of thoracic scoliosis is presented, including surface trunk asymmetries and radiological deformation. Biomechanical rules, applied to achieve curve correction in the three planes, are the subject of a comprehensive review. Tissue transfer in the three dimensions, elongation effect, rib cage 'derotation' and bending are the passive mechanisms of correction. Restoring of physiological thoracic kyphosis is promoted by a special combination of pads and free spaces in the brace. Hypercorrection is achievable in some clinical situations, especially for the trunk imbalance. Attention is attached to the active mechanisms of corrective bracing, comprising the modeling of vertebral growth, asymmetrically guided respiratory movements, repositioning of the spatial arrangement of trunk muscles and the anti-gravitational effect. Contemporary corrective orthosis for idiopathic scoliosis should take advantage of specific passive and active mechanisms. Preservation of the function of the vertebral column as a flexible framework for the human body, as well as the preservation of the respiratory function of the thorax stay ambitious goals to approach, and a significant progress over recent years has been observed.


Necrosulfonamide ameliorates intestinal inflammation via inhibiting GSDMD-medicated pyroptosis and MLKL-mediated necroptosis.
Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract, while the present therapeutic efficacy is insufficient. In recent years, numerous studies have shown that necrosulfonamide (NSA) played a protective role in many inflammatory diseases by blocking mixed lineage kinase domain-like protein (MLKL) polymerization. However, the protective effect of NSA in dextran sodium sulfate (DSS)-induced colitis has not been reported. In the present study, we used DSS to establish mouse models of acute colitis to explore the proactive effect of NSA. Our study showed that NSA alleviated symptoms of DSS-induced colitis through reducing weight loss and disease activity index (DAI) score. Furthermore, NSA inhibited macrophages and CD4+/CD8 + T-cell accumulation in colon tissue caused by DSS. In addition, we found that NSA had the therapeutic effects on DSS-induced colitis. Mechanistically, we detected the expression level of phosphorylated MLKL, the release of LDH, cytokines, and N-gasdermin D (N-GSDMD) to examine necroptosis and pyroptosis pathways. We found NSA alleviated the severity of DSS-induced colitis by inhibiting the expressions of phosphorylated MLKL and N-GSDMD in vivo. In vitro experiments, we found NSA inhibited the release of inflammatory factors and LDH and the expressions of N-GSDMD in bone marrow-derived macrophages. Furthermore, we found NSA inhibited the expression of phosphorylated MLKL and necroptosis of NCM460 cell through western blot and flow cytometer. In general, this study reveals that NSA inhibits pyroptosis and necroptosis pathways to eventually alleviate intestinal inflammation, which may serve as a potential candidate for IBD therapy.


[Role of calcium in the mechanism of the change in vascular reactivity under the action of reserpine].
Reserpine induces an appreciable reduction of the calcium content in the segments of the distal aorta and rabbit femoral arteries incubated in a saline. These changes develop simultaneously to those in the reaction pattern of the vascular segment to direct electric stimulation (decline of constrictor responses and their subsequent replacement by relaxation). It is postulated that the decreased calcium content in the vascular wall may be one of the causes of altered vascular reactivity.


Effects of Speaking Rate on Breathing and Voice Behavior.
The objective of this study was to investigate the effects of speaking rate (habitual and fast) and speech task (reading and spontaneous speech) on seven dependent variables: Breath group size (in syllables), Breath group duration (in seconds), Lung volume at breath group initiation, Lung volume at breath group termination, Lung volume excursion for each breath group (in % vital capacity), Lung volume excursion per syllable (in % vital capacity) and mean speaking Fundamental frequency (fO). Ten women and seven men were included as subjects. Lung volume and breathing behaviors were measured by respiratory inductance plethysmography and fO was measured from audio recordings by the Praat software. Statistical significance was tested by analysis of variance. For both reading and spontaneous speech, the group increased mean breath group size and breath group duration significantly in the fast speaking rate condition. The group significantly decreased lung volume excursion per syllable in fast speech. Females also showed a significant increase of fO in fast speech. The lung volume levels for initiation and termination of breath groups, as well as lung volume excursions in % vital capacity, showed great individual variations and no significant effects of rate. Significant effects of speech task were found for breath group size and lung volume excursion per syllable, where reading induced more syllables produced per breath group and less % VC spend per syllable as compared to spontaneous speech. Interaction effects showed that the increases in breath group size and breath group duration associated with fast rate were significantly larger in reading than in spontaneous speech. Our data from 17 vocally untrained, healthy subjects showed great individual variations but still significant group effects regarding increased speaking rate, where the subjects seemed to spend less air per syllable and inhaled less often as a consequence of greater breath group sizes in fast speech. Subjects showed greater changes in breath group patterns as a consequence of fast speech in reading than in spontaneous speech, indicating that effects of speaking rate are dependent on the speech task.


Pituitary adenylate cyclase-activating polypeptide causes increased tyrosine phosphorylation of focal adhesion kinase and paxillin.
The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin were investigated using lung cancer cells. Addition of PACAP-27 or PACAP-38 but not vasoactive intestinal peptide to NCI-H838 or NCI-H1299 human lung cancer cells significantly increased the tyrosine phosphorylation of FAK or paxillin. The increase in FAK or paxillin tyrosine phosphorylation caused by addition of PACAP-27 to NCI-H838 cells was inhibited by PACAP(6-38), a PAC1-receptor (R) antagonist. The increase in FAK or paxillin tyrosine phosphorylation caused by 100 nM PACAP-27 was maximal 2 min after addition to NCI-H838 cells. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by cytochalasin D and genistein which inhibit actin polymerization and tyrosine kinase activity, respectively. The effects of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed by U-73122 but not H89 which inhibit phospholipase C and protein kinase A, respectively. The results show that PAC1-R regulates FAK and paxillin tyrosine phosphorylation in lung cancer cells as a result of increased phosphatidylinositol turnover but not adenylyl cylase stimulation.


Neurocomputational models of basal ganglia function in learning, memory and choice.
The basal ganglia (BG) are critical for the coordination of several motor, cognitive, and emotional functions and become dysfunctional in several pathological states ranging from Parkinson's disease to Schizophrenia. Here we review principles developed within a neurocomputational framework of BG and related circuitry which provide insights into their functional roles in behavior. We focus on two classes of models: those that incorporate aspects of biological realism and constrained by functional principles, and more abstract mathematical models focusing on the higher level computational goals of the BG. While the former are arguably more "realistic", the latter have a complementary advantage in being able to describe functional principles of how the system works in a relatively simple set of equations, but are less suited to making specific hypotheses about the roles of specific nuclei and neurophysiological processes. We review the basic architecture and assumptions of these models, their relevance to our understanding of the neurobiological and cognitive functions of the BG, and provide an update on the potential roles of biological details not explicitly incorporated in existing models. Empirical studies ranging from those in transgenic mice to dopaminergic manipulation, deep brain stimulation, and genetics in humans largely support model predictions and provide the basis for further refinement. Finally, we discuss possible future directions and possible ways to integrate different types of models.


Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E(2) in laying hen ovaries.
Prevention of ovarian cancer is the best approach for reducing the impact of this deadly disease. The laying hen is a robust model of spontaneous ovarian cancer that recapitulates the human disease. Dietary intervention with flaxseed, the richest vegetable source of omega-3 fatty acids (OM-3FAs) and phytoestrogen lignans, demonstrate the potential for effective prevention and amelioration of ovarian cancer by targeting inflammatory prostaglandin pathways. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. Our objective was to investigate the effect of flaxseed supplementation for one year on ovarian cancer and correlate its effects to expression of COX enzymes and concentrations of prostaglandins. White Leghorn hens were fed 10% flaxseed-enriched or standard diet for one year. The severity of ovarian cancer was determined by gross pathology and histology. COX-1 and COX-2 localization and protein and mRNA expression and PGE2 and PGE3 concentrations in ovaries were measured by IHC, western blot, quantitative real-time PCR and LC-MS-MS, respectively. The results demonstrated a significant reduction in late stage ovarian tumors in the flaxseed-fed hens compared with the control diet-fed hens. In correlation with decreased ovarian cancer severity, concentrations of PGE2 and expression of COX-2 were diminished in ovaries of flaxseed-fed hens. PGE3 concentrations were below the level of detection. The results demonstrated that in normal ovaries, COX-1 was localized to the granulosa cell layer surrounding the follicles and ovarian surface epithelium (OSE) whereas COX-2 protein was localized to the granulosa cell layer in the follicle. Extensive COX-1 and COX-2 protein expression was found throughout the ovarian carcinoma. Our findings suggest that the flaxseed-mediated reduction in the severity of ovarian cancer in hens is correlated to the reduction in PGE2 in the ovaries of flaxseed-fed hens. These findings may provide the basis for clinical trials of dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.