Three vessel coronary artery-left ventricular multiple micro-fistulas: a rare angiographic finding.
A 54-year-old woman presents with a long history exertional chest pain and was found to have left ventricular systolic dysfunction on trans-thoracic echocardiogram. Coronary angiography revealed no evidence of atherosclerotic coronary artery disease and showed multiple micro-fistulae draining from all three major coronary arteries to the left ventricle. This rare abnormality is the result of failure of obliteration of intra-trabecular embryonic sinusoids and may cause myocardial ischemia through the coronary steal mechanism.


Serum uric acid, plasma glucose and diabetes.
The objective of this study was to investigate the association of serum UA with either FPG or 2hPG levels among Chinese adults in Qingdao, China. A population-based survey for diabetes was performed in 2006 in Qingdao. The survey included 1,490 men and 2,325 women aged 35-74 years who had data stored as required for the current data analysis. The association of mean UA with plasma glucose was tested using a linear regression model. Serum UA concentration raised with increasing FPG levels up to FPG of 7.0 mmol/l, but significantly decreased thereafter with further increase in FPG levels. The multivariate adjusted beta coefficient between FPG and UA in individuals with newly diagnosed diabetes was -0.20 for men and -0.27 for women (p<0.01 for both). A declining trend for the UA concentration was also observed at 2hPG of 10 mmol/l or higher in both genders. Fasting serum UA levels was higher in the pre-diabetic population but lower in people with diabetes than in normoglycaemic people. UA may serve as a potential biomarker of deterioration in glucose metabolism, but its clinical implication need to be further studied.


Cross-Sectional Association between Estimated Hardness of the Habitual Diet and Depressive Symptoms in Older Japanese Men.
This cross-sectional study aimed to investigate the association between dietary hardness and depressive symptoms in older Japanese men. Participants were 1487 men aged 60-69 years enrolled in the baseline survey of the Hitachi Health Study II (2017-2020). Habitual dietary intake was estimated by a brief-type, self-administered diet history questionnaire. Dietary hardness was defined as the magnitude of masticatory muscle activity necessary to consume solid foods. The participants who scored ≥ 9 points on a short version of the Center for Epidemiologic Studies Depression Scale were considered to have depressive symptoms. The prevalence of depressive symptoms was 12.7%. The ORs (95% CIs) for depressive symptoms in the third tertile of dietary hardness were significantly lower after adjustment for sociodemographic and lifestyle-related variables and mood-modulating nutrients (ORs [95% CIs]: 0.93 [0.63, 1.36] and 0.58 [0.35, 0.97] for the second and third tertile, respectively [p-value for trend = 0.04]). Dietary hardness was inversely associated with the prevalence of depressive symptoms in older Japanese men. Future studies should confirm these findings and clarify the role of consuming a hard diet in preventing depressive disorders.


Longitudinal pancreaticojejunostomy in chronic relapsing pancreatitis with onset in childhood.
Despite the rarity of chronic relapsing pancreatitis in children, in the last 15 years at Vanderbilt University Medical Center and its Children's Hospital we have used longitudinal pancreaticojejunostomy in treatment of eight patients whose symptoms began in childhood. Duration of symptoms ranged from 2 to 36 years. Seven of the eight patients had hereditary pancreatitis. Recurrent epigastric pain was characteristic and serum amylase was elevated in all patients on admission or shortly thereafter. Demonstration of an obstructed dilated pancreatic duct in all and stones in seven of eight patients by operative pancreatography in three early patients and by endoscopic retrograde cholangiopancreatography (ERCP) in five others established the therapeutic problem and facilitated treatment by removal of stones and longitudinal pancreaticojejunostomy. Results were uniformly excellent, both in the early postoperative period and in long-range follow-ups. Early diagnosis and early surgical drainage of the obstructed pancreatic duct by longitudinal pancreaticojejunostomy are desirable objectives in chronic relapsing pancreatitis with onset in childhood.


Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI.
Introducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration. Our primary objective was to investigate whether timing of infant complentary feeding with solid foods is associated with early childhood gut microbiota composition and BMI-z, and whether these associations differ by duration of breastfeeding. We used data from a Canadian pre-birth cohort followed till age 5 years. We examined timing of introduction to solid foods with the gut microbiota, determined by 16S rRNA gene sequencing of stool collected at 5 years of age, and age-and-sex specific BMI-z. We conducted analyses before and after stratifying by breastfeeding duration, and adjusted for delivery mode, gestational age and birth weight. Of the 392 children in the analysis, 109 (27.8%) had early (≤4 months) solids. The association between early (vs later) solids and BMI-z at 5 years was modified by breastfeeding status at 4 months (P = .06). Among children breastfed >4 months, early (vs later) solids were associated with differential relative abundance of 6 bacterial taxa, including lower Roseburia, and 0.30 higher BMI-z (95% CI: 0.05, 0.55) at 5 years. In children breastfed <4 months, early solids were associated with differential relative abundance of 9 taxa, but not with child BMI-z. Early (vs. later) introduction to solid foods in infancy is associated with altered gut microbiota composition and BMI in early childhood, however these associations differ by duration of breastfeeding.


[The thyroid gland and the breast].
The results of experimental clinical and epidemiological studies published so far from 1896 until today on the connection between thyroid and breast diseases doubtless require critical examination, since these results are highly contradictory. Without being able to go into details of the sources of methodological errors and the highly heterogenous investigation material, two pathophysiological mechanisms can be discussed in the investigation of the interrelationship between the thyroid and the breast: 1. A low level of thyroid hormone might make the breast hypersensitive to prolactin, which might induce dysplasia or neoplasia of the mammary epithelium. In addition, there is the almost identical neurohumoral regulation of the hormones of the thyrotropic and lactotropic cells in the anterior pituitary. 2. Thyroid hormones have an effect on peripheral androgenic and estrogenic metabolism. The hyperthyroid state may cause an increase in the concentration of sex hormone-binding globulins, which might give rise to an alteration of the beneficial effect of sex hormones on the cellular levels. Compared to this, the iodine deficit might lead to neoplastic transformation of the mammary epithelium via the enhanced gonadotropin stimulation and the subsequent chronic hyperestrogenism. For better understanding of the always topical problem of the not yet completely elucidated correlation between thyroid function and breast diseases, a two-track procedure is appropriate: 1. Thyroid receptor assay on animal and human breast tumor tissue and 2. prospective clinical studies on a large scale.(ABSTRACT TRUNCATED AT 250 WORDS)


Rapid, sensitive spectrophotometric method for quantitative determination of sulfatides.
A rapid, sensitive spectrophotometric method for the analysis of sulfatides is described. The assay method is based upon the formation of a colored complex between the cationic dye azure A and (anionic) sulfolipids; the complex is extractable by a solution of chloroform-methanol 1:1. With the exception of some of the phospholipids, the reaction is specific for the sulfolipids. Cardiolipin was the most reactive of the non-sulfolipid compounds that were tested. Except for sphingosine and the mono- and dihexose derivatives of sphingosine, a wide variety of lipids did not interfere with the formation of color by standard sulfatides. Sulfur-containing amino acids, sugar sulfates, and sulfated polymers neither produced color nor interfered in its formation by sulfatide. Chloride and nitrate ions produced relatively little color. The method is much more sensitive (lower limit, about 0.002 micromole) than most methods currently employed for the analysis of sulfatides and has a high degree of precision. It is applicable to the analysis of sulfolipids in tissue extracts and gives values similar to those obtained by previously published procedures. The reliability of the method is increased when it is applied to partially purified lipid solutions. Sulfatides added to extracts of rabbit brain tissue were quantitatively accounted for by the assay. In addition, the method can be applied to samples obtained directly from thin-layer plates.


A 3d-printed composite electrode for sustained electrocatalytic oxygen evolution.
We report the facile design and fabrication of 3D-printed microstructured electrodes for electrocatalytic oxygen evolution. ABS polymer-based mesh scaffolds are chemically functionalized to enable electroless nickel metal deposition and subsequent catalyst (nickel iron hydroxide) immobilization. The resulting composites show sustained oxygen evolution with low overpotentials and high stability. The modular approach reported enables the scalable on-demand fabrication of microstructured composite electrodes.


Involvement of KCa3.1 channel activity in immediate perioperative cognitive and neuroinflammatory outcomes.
Potassium channels (KCa3.1; Kv1.3; Kir2.1) are necessary for microglial activation, a pivotal requirement for the development of Perioperative Neurocognitive Disorders (PNDs). We previously reported on the role of microglial Kv1.3 for PNDs; the present study sought to determine whether inhibiting KCa3.1 channel activity affects neuroinflammation and prevents development of PND. Mice (wild-type [WT] and KCa3.1-/-) underwent aseptic tibial fracture trauma under isoflurane anesthesia or received anesthesia alone. WT mice received either TRAM34 (a specific KCa3.1 channel inhibitor) dissolved in its vehicle (miglyol) or miglyol alone. Spatial memory was assessed in the Y-maze paradigm 6 h post-surgery/anesthesia. Circulating interleukin-6 (IL-6) and high mobility group box-1 protein (HMGB1) were assessed by ELISA, and microglial activitation Iba-1 staining. In WT mice surgery induced significant cognitive decline in the Y-maze test, p = 0.019), microgliosis (p = 0.001), and increases in plasma IL-6 (p = 0.002) and HMGB1 (p = 0.001) when compared to anesthesia alone. TRAM34 administration attenuated the surgery-induced changes in cognition, microglial activation, and HMGB1 but not circulating IL-6 levels. In KCa3.1-/- mice surgery neither affected cognition nor microgliosis, although circulating IL-6 levels did increase (p < 0.001). Similar to our earlier report with Kv1.3, perioperative microglial KCa3.1 blockade decreases immediate perioperative cognitive changes, microgliosis as well as the peripheral trauma marker HMGB1 although surgery-induced IL-6 elevation was unchanged. Future research should address whether a synergistic interaction exists between blockade of Kv1.3 and KCa3.1 for preventing PNDs.


Unrevealing Reliable Cortical Parcellation of Individual Brains Using Resting-State Functional Magnetic Resonance Imaging and Masked Graph Convolutions.
Brain parcellation helps to understand the structural and functional organization of the cerebral cortex. Resting-state functional magnetic resonance imaging (fMRI) and connectivity analysis provide useful information to delineate individual brain parcels in vivo. We proposed an individualized cortical parcellation based on graph neural networks (GNN) to learn the reliable functional characteristics of each brain parcel on a large fMRI dataset and to infer the areal probability of each vertex on unseen subjects. A subject-specific confidence mask was implemented in the GNN model to account for the tradeoff between the topographic alignment across subjects and functional homogeneity of brain parcels on individual brains. The individualized brain parcellation achieved better functional homogeneity at rest and during cognitive tasks compared with the group-registered atlas (p-values < 0.05). In addition, highly reliable and replicable parcellation maps were generated on multiple sessions of the same subject (intrasubject similarity = 0.89), while notable variations in the topographic organization were captured across subjects (intersubject similarity = 0.81). Moreover, the intersubject variability of brain parcellation indicated large variations in the association cortices while keeping a stable parcellation on the primary cortex. Such topographic variability was strongly associated with the functional connectivity variability, significantly predicted cognitive behaviors, and generally followed the myelination, cytoarchitecture, and functional organization of the human brain. This study provides new avenues to the precise individualized mapping of the cortical areas through deep learning and shows high potentials in the personalized localization diagnosis and treatment of neurological disorders.


Morphological and molecular characterization of Tarantobelus arachnicida gen. n., sp. n. (Nematoda, Rhabditida, Brevibuccidae), a parasitic nematode of tarantulas.
A new genus and new species, Tarantobelus arachnicida, was found in the oral opening of tarantula spiders bred in captivity in Poland. The new species is characterized by having a small body (0.77-0.95 mm long in females and 0.66-0.84 mm in males), cuticle poorly annulated by transverse incisures, lateral field inconspicuous, lips separated with small cuticular flaps topping each lip, stoma panagrolaimoid with gymnostom well developed with robust and refringent rhabdia, pharynx panagrolaimoid with isthmus slightly longer than the basal bulb, intestine with cardiac (anterior) and rectal (posterior) areas with narrower walls. Mature females with intestinal cells including needle crystal packs, excretory pore at isthmus level, female reproductive system panagrolaimoid with post-vulval sac 0.4-0.8 times the length of the corresponding body diameter and having very thick walls, vulva very prominent, female rectum 0.8-1.3 times the length of the anal body diameter, female tail conical with acute tip with phasmids at 58-62% of its length. Male tail conical with long and thin mucro, spicules ventrad bent having rounded manubrium and thick gubernaculum. Description, measurements and illustrations of the new species are provided. Molecular analyses show its relationship with Brevibucca and Cuticonema. On the other hand, Medibulla and its corresponding subfamily Medibullinae, previously in Osstellidae, are transferred to Panagrolaimidae, being Shahnematinae, the junior synonym of Medibullinae. Indocephalobus, recently proposed and located in the family Panagrolaimidae, is considered a junior synonym of Diplogastrellus (Diplogasteromorpha), and its only species, I. zebrae, is considered a junior synonym of D. gracilis. In addition, a key to identification of panagrolaimoid genera is included.


Simultaneous administration of G-CSF and GM-CSF for re-mobilization in patients with inadequate initial progenitor cell collections for autologous transplantation.
A proportion of candidates for high-dose chemotherapy with autologous PBPC support (HDC-PBPCS) will not provide an adequate PBPC yield from their first mobilization. The value of re-mobilization and the best regimen for re-mobilization in these patients is unclear. In 23 patients who failed to provide > or = 3 x 10(6) CD34+ cells/kg after their first mobilization, PBPC were re-mobilized using a regimen of simultaneous administration of G-CSF and GM-CSF (10 microg/kg/day each) with leukaphereses (LP) starting Day 4 or 5 of CSF administration. Yields of WBC/kg, MNC/kg and CD34+ cells/kg/L of processed blood were compared between the first and second mobilization in each patient. The ability of the combined yield from the two mobilizations to achieve the desired threshold PBPC yield and the tolerability of the re-mobilization were determined. The re-mobilization regimen was well-tolerated and no patient discontinued the regimen because of toxicity. Median collected WBC/kg/L (1.37 x 10(7) versus 2.62 x 10(7), p = 0.0065), MNC/kg/L (0.77 x 10(7) versus 1.97 x 10(7), p = 0.0003), CD34+ cells/kg/L (1.64 x 10(7) versus 4.18 x 10(7), p = 0.001) were significantly higher after the second mobilization (G-CSF/GM-CSF combination). Percentage of CD34+ cells in the leukapheresis was also significantly higher after the second mobilization (median 0.104% versus 0.195%, p = 0.036). Twelve of 22 patients achieved the target PBPC dose (> 3 x 10(6)/CD34+ cells/kg) after two mobilizations (six patients achieved the target from the second mobilization alone). A further eight underwent HDC-PBPCS without achieving the target PBPC dose. These patients experienced a significant delay in neutrophil and platelet engraftment when compared with those patients achieving the target dose. This study demonstrates that the combination of G-CSF and GM-CSF is an effective and tolerable method for re-mobilization of PBPC in patients who fail to provide an adequate yield from their first mobilization.


Mitochondrial encephalomyopathy: comparison of conventional MR imaging with diffusion-weighted and diffusion tensor imaging: case report.
Conventional MR imaging, MR spectroscopy, diffusion-weighted imaging, and diffusion tensor imaging were performed in a 5-month-old male patient with mitochondrial encephalomyopathy. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the temporoparietal white matter. A large lactate peak and decreased N-acetylaspartate were found in this region on proton MR spectroscopic images. Diffusion-weighted imaging showed increased apparent diffusion coefficient, representing vasogenic edema. Diffusion tensor imaging revealed decreased anisotropy, consistent with injury to the oligodendro-axonal unit. A muscle biopsy specimen revealed an isolated complex III enzyme respiratory chain deficiency. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the characterization of hyperintense lesions on T2-weighted MR images in cases of mitochondrial encephalomyopathy.


Adipose tissue in plastic surgery.
In this article I review the present state of knowledge about adipose tissue as it is relevant to the practical purposes of plastic surgery. Fat cells are normal constituents of loose connective tissue. Large numbers of fat cells organized into lobules are classified as adipose tissue. Adipose tissue is a special form of reticular connective tissue. The lobules are both morphologically and angiologically independent units. They are seen as well-vascularized structures supplied with blood through a pedicle. Severance of the lobule normally results in necrosis. The subcutaneous fat layer derives from the "primitive organs" identifiable in the hypodermis from the fourth fetal month onward. The primitive organs are the basis for individual fat lobules. The development of adipose tissue continues until physical growth is complete. The disposition of the subcutis to develop adipose tissue shows great variation in different regions of the body. The in-situ mechanical resistance of adipose tissue is provided by the supporting structures. The development, structural characteristics, and physiology of adipose tissue can provide an explanation for many of the observations plastic surgeons have made on this tissue. The processes involved in healing, grafting, and reduction of adipose tissue are analyzed and considered in relation to the clinical picture.


Developability studies before initiation of process development: improving manufacturability of monoclonal antibodies.
Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2-8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources.


Prospective risk factors for suicide attempts in a treated sample of patients with borderline personality disorder.
People with borderline personality disorder (BPD) are at high risk for attempting suicide. There are some data to suggest that risk factors for suicide attempts change over time. We conducted a prospective cohort study to examine risk factors for suicide attempts in a treated sample of patients with BPD. One hundred eighty participants with BPD were followed over a year-long course of dialectical behaviour therapy or general psychiatric management and then for 2 more years in naturalistic follow-up. Participants were assessed for suicidal and self-injurious behaviours at baseline, every 4 months over the 1-year treatment phase, and every 6 months over a 2-year follow-up period. Participants were classified as suicide or non-suicide attempters based on their behaviour at the end of the 1-year treatment phase and after the 2-year follow-up period. Groups were then compared on baseline clinical and demographic variables. Nearly 26% of participants made a suicide attempt during the 1-year treatment phase, while 16.7% reported a suicide attempt over the 2-year follow-up period. Baseline number of suicide attempts during the 4 months prior to study and severity of childhood sexual abuse predicted suicide attempts during the treatment year. Similarly, baseline suicide attempts, severity of childhood sexual abuse, and number of hospitalizations in the 4 months prior to study entry predicted suicide attempts during the 2-year follow-up. Risk factors for suicide attempts in this treated sample of patients with BPD were fairly stable, largely non-modifiable, and unrelated to psychopathology or psychosocial functioning at baseline.


The early estimation of circulating drug metabolites in humans.
An evolution in bioanalytical methodologies to identify and quantify drug metabolites has led to a wealth of biotransformation information during preclinical and early clinical testing phases. However, this abundance of metabolism data has not clarified how to select the most important circulating human metabolites for safety assessment. Consequently, more stringent regulatory expectations for a comprehensive approach to human metabolism have led pharmaceutical sponsors to employ a variety of novel methods to estimate circulating drug metabolites in humans and animals. This review provides context for 'why' human circulating metabolites must be qualified for safety in animals. A detailed overview is also presented concerning 'where,' 'how' and 'when' to conduct these assessments during drug development. A human metabolite qualification strategy is now a required element of the drug safety package submitted with a new drug application (NDA). The important question is whether or not this additional information, about metabolite safety, is making human drugs any safer. Currently, this is a debatable issue, especially because stand-alone metabolite testing is fraught with its own challenges. As drug development moves into the twenty-first century, there is a pressing need for more sophisticated methodologies to address human drug and metabolite safety.


Demonstration of central nervous system tolerance to ethanol in mice: consequent effects on smooth muscle in vitro.
Mice were given ethanol (9 g/kg) or saline (57 ml/kg) daily in three divided doses for periods of 1 and 4 days to study the effects of such ethanol (ETOH) exposure on central nervous system (CNS) and peripheral smooth muscle (vasa deferentia) function. After 1 day, ETOH-treated mice were functionally tolerant to the hypothermic (3 g/kg, intraperitoneal), but not to the hypnotic (3.25 g/kg, intraperitoneal) effect of ETOH. Functional tolerance to both CNS effects of ETOH was demonstrated in mice after the 4-day ETOH exposure. Norepinephrine (NE) and high K+-depolarizing solutions each elicited dose-dependent contractions in the mouse vasa deferens preparation in vitro that consisted of a phasic and tonic component. The tonic components of the NE and K+ responses were more dependent upon extracellular Ca2+ (Ca2+ext) than the phasic components. Addition of ETOH (120 to 480 mM) or the Ca2+ channel-antagonist nifedipine (1 X 10(-9) to 3 X 10(-7) M) to the preparation selectively inhibited the tonic component of the NE and K+ responses, suggesting that both agents acted to inhibit the responses by interfering with the translocation of Ca2+ext. Vasa deferentia isolated from ETOH-treated mice did not exhibit altered reactivity to NE in the phasic or tonic component of the response. The isolated smooth muscle from mice centrally tolerant to ETOH did not appear to be tolerant to inhibitory effect of ETOH or cross-tolerant to the inhibitory effect of nifedipine on stimulant-induced contractions.


Aquaporin regulation in roots controls plant hydraulic conductance, stomatal conductance, and leaf water potential in Pinus radiata under water stress.
Stomatal regulation is crucial for forest species performance and survival on drought-prone sites. We investigated the regulation of root and shoot hydraulics in three Pinus radiata clones exposed to drought stress and its coordination with stomatal conductance (gs ) and leaf water potential (Ψleaf ). All clones experienced a substantial decrease in root-specific root hydraulic conductance (Kroot-r ) in response to the water stress, but leaf-specific shoot hydraulic conductance (Kshoot-l ) did not change in any of the clones. The reduction in Kroot-r caused a decrease in leaf-specific whole-plant hydraulic conductance (Kplant-l ). Among clones, the larger the decrease in Kplant-l , the more stomata closed in response to drought. Rewatering resulted in a quick recovery of Kroot-r and gs . Our results demonstrated that the reduction in Kplant-l , attributed to a down regulation of aquaporin activity in roots, was linked to the isohydric stomatal behaviour, resulting in a nearly constant Ψleaf as water stress started. We concluded that higher Kplant-l is associated with water stress resistance by sustaining a less negative Ψleaf and delaying stomatal closure.


Secukinumab improves scalp pain, itching, scaling and quality of life in patients with moderate-to-severe scalp psoriasis.
Scalp psoriasis adversely affects patients' lives and is often resistant to treatment; however, it has not been a major focus of a clinical study. This analysis assessed the effect of secukinumab on patient-reported outcomes (PRO) of scalp psoriasis. A randomized, double-blind, placebo-controlled, multicenter study was conducted in 102 adult patients with moderate-to-severe scalp psoriasis. Patients were randomized 1:1 to secukinumab 300 mg or placebo. Patients rated their scalp-related pain, itching and scaling using a 0-10 numeric rating scale (higher scores indicate greater severity). Scalp dermatitis-related quality of life (QOL) was assessed at baseline and then every 4 weeks using the Scalpdex. Analysis of covariance models examined PRO effect up to 12 weeks. Baseline scalp pain, itching and scaling mean (SD) values were 3.1 (3.00), 6.7 (2.60) and 7.3 (2.02) and similar for both treatment groups. At week 12, patients treated with secukinumab reported greater reduction in scalp pain (-1.98 vs. 0.61), itching (-4.07 vs. -0.04) and scaling (-5.76 vs. -0.95) as well as greater improvements in Scalpdex total scores (-39.62 vs. -7.91) compared with placebo (all p < .001). Secukinumab in moderate-to-severe scalp psoriasis reduces scalp pain, itching, and scaling and improves patients' QOL.


Discovery and Characterization of Phage Display-Derived Human Monoclonal Antibodies against RSV F Glycoprotein.
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in infants, the elderly and in immunosuppressed populations. The vast majority of neutralizing antibodies isolated from human subjects target the RSV fusion (F) glycoprotein, making it an attractive target for the development of vaccines and therapeutic antibodies. Currently, Synagis® (palivizumab) is the only FDA approved antibody drug for the prevention of RSV infection, and there is a great need for more effective vaccines and therapeutics. Phage display is a powerful tool in antibody discovery with the advantage that it does not require samples from immunized subjects. In this study, Morphosys HuCAL GOLD® phage libraries were used for panning against RSV prefusion and postfusion F proteins. Panels of human monoclonal antibodies (mAbs) against RSV F protein were discovered following phage library panning and characterized. Antibodies binding specifically to prefusion or postfusion F proteins and those binding both conformations were identified. 3B1 is a prototypic postfusion F specific antibody while 2E1 is a prototypic prefusion F specific antibody. 2E1 is a potent broadly neutralizing antibody against both RSV A and B strains. Epitope mapping experiments identified a conformational epitope spanning across three discontinuous sections of the RSV F protein, as well as critical residues for antibody interaction.


Advanced molecular profiling in vivo detects novel function of dickkopf-3 in the regulation of bone formation.
A bioinformatics-based analysis of endochondral bone formation model detected several genes upregulated in this process. Among these genes the dickkopf homolog 3 (Dkk3) was upregulated and further studies showed that its expression affects in vitro and in vivo osteogenesis. This study indicates a possible role of Dkk3 in regulating bone formation. Endochondral bone formation is a complex biological process involving numerous chondrogenic, osteogenic, and angiogenic proteins, only some of which have been well studied. Additional key genes may have important roles as well. We hypothesized that to identify key genes and signaling pathways crucial for bone formation, a comprehensive gene discovery strategy should be applied to an established in vivo model of osteogenesis. We used in vivo implanted C3H10T1/2 cells that had been genetically engineered to express human bone morphogenetic protein-2 (BMP2) in a tetracycline-regulated system that controls osteogenic differentiation. Oligonucleotide microarray data from the implants (n = 4 repeats) was analyzed using coupled two-way clustering (CTWC) and statistical methods. For studying the effects of dickkopf homolog 3 (Dkk3) in chondrogenesis and osteogenesis, C3H10T1/2 mesenchymal progenitors were used. The CTWC revealed temporal expression of Dkk3 with other chondrogenesis-, osteogenesis-, and Wnt-related genes. Quantitative RT-PCR confirmed the expression of Dkk3 in the implants. C3H10T1/2 cells that expressed Dkk3 in the presence of BMP2 displayed lower levels of alkaline phosphatase and collagen I mRNA expression than control C3H10T1/2 cells that did not express Dkk3. Interestingly, the levels of collagen II mRNA expression, Alcian blue staining, and glucose aminoglycans (GAGs) production were not influenced by Dkk3 expression. In vivo microCT and bioluminescence imaging revealed that co-expression of Dkk3 and BMP2 by implanted C3H10T1/2 cells induced the formation of significantly lower quantities of bone than cells expressing only BMP2. A bioinformatics analysis enabled the identification of Dkk3 as a pivotal gene with a novel function in endochondral bone formation. Our results showed that Dkk3 might have inhibitory effects on osteogenesis, but no effect on chondrogenesis, indicating that Dkk3 plays a regulatory role in endochondral bone formation. Further mechanistic studies are required to reveal the mechanism of action of Dkk3 in endochondral bone formation.


Sustaining and scaling a clinic-based approach to address health-related social needs.
Scaling evidence-based interventions (EBIs) from pilot phase remains a pressing challenge in efforts to address health-related social needs (HRSN) and improve population health. This study describes an innovative approach to sustaining and further spreading DULCE (Developmental Understanding and Legal Collaboration for Everyone), a universal EBI that supports pediatric clinics to implement the American Academy of Pediatrics' Bright Futures™ guidelines for infants' well-child visits (WCVs) and introduces a new quality measure of families' HRSN resource use. Between August 2018 and December 2019, seven teams in four communities in three states implemented DULCE: four teams that had been implementing DULCE since 2016 and three new teams. Teams received monthly data reports and individualized continuous quality improvement (CQI) coaching for six months, followed by lighter-touch support via quarterly group calls (peer-to-peer learning and coaching). Run charts were used to study outcome (percent of infants that received all WCVs on time) and process measures (percent of families screened for HRSN and connected to resources). Integrating three new sites was associated with an initial regression of outcome: 41% of infants received all WCVs on time, followed by improvement to 48%. Process performance was sustained or improved: among 989 participating families, 84% (831) received 1-month WCVs on time; 96% (946) were screened for seven HRSN, 54% (508) had HRSN, and 87% (444) used HRSN resources. An innovative, lighter-touch CQI approach to a second phase of scale-up resulted in sustainment or improvements in most processes and outcomes. Outcomes-oriented CQI measures (family receipt of resources) are an important addition to more traditional process-oriented indicators.


Evaluation of effluents from bench-scale treatment combinations for landfill leachate in Ibadan, Nigeria.
The removal of pollutants in landfill leachate was investigated using constructed wetlands, a trickling filter, alum flocculation and coagulation, and a sequencing batch reactor in various combinations. Thirteen combined operations were investigated involving three out of the four unit treatment methods in series. The study was conducted because unit operations, though achieved reductions in pollutants concentrations had effluent values above the national regulatory guideline values. The suspended solids of effluents were permissible in most treatment processes, while reductions in 5-day biochemical oxygen demand (BOD5), chemical oxygen demand (COD) and ammonia (NH3) of leachates ranged from 80% to 97%; 86% to 97% and 92% to 98% respectively. However, there were significant increases in nitrate (85%) and dissolved oxygen of treatment (218%). In addition, the characteristics of the recommended treatment sequence, involving constructed wetlands, alum and trickling filter produced effluents with reductions in colour (97%), alkalinity (97%), BOD (97%), COD (97%) and NH3 (98%), and in metals, except nickel (29% reduction from the influent values). The recommended treatment combination is suitable for effective leachate management at the landfill. The cost of constructing and operating the recommended treatment combination at the facility, for 5 years, would be NGN6,009,750.00 ($38,036.39). The performance should be monitored on site prior to full adoption if effluent characteristics remain consistently low over dry and wet seasons.


Grassroots Intervention to Increase Appointment of Pediatric Emergency Care Coordinators in Massachusetts Emergency Departments.
Appointment of a pediatric emergency care coordinator (PECC) is considered the single best intervention to improve pediatric emergency care and has been recommended for all U.S. general emergency departments (EDs) for more than a decade. Unfortunately, many EDs do not adhere with this recommendation. In 2017, we performed a grassroots intervention to establish a PECC in every Massachusetts ED. We conducted annual surveys of all 73 Massachusetts EDs from 2014 to 2018. Data collection included ED visit volumes, presence of a pediatric area, and PECC status. The intervention in 2017-2018 included e-mails and telephone calls to every ED director to not only assess PECC status but also encourage him/her to appoint one as needed. Survey response rates were > 85% in all years and 100% during 2016 to 2018. While Massachusetts EDs did not materially change over time (in terms of visit volumes or presence of a pediatric area), the 2017 intervention increased the percentage of EDs with an appointed PECC. Specifically, PECCs were present in approximately 30% of EDs during 2014 to 2016, climbed to 85% in 2017, and reached 100% in 2018. Most of the newly appointed PECCs were physicians. Through a relatively simple grassroots intervention, we increased the appointment of PECCs in Massachusetts EDs from 30% to 100%. In addition to providing PECCs with online educational materials, ongoing work is focused on building community, identifying best practices, and implementing interventions at the local level.


Modifications in the handling in vitro of 125I-labelled keyhole limpet haemocyanin by peritoneal macrophages from mice pretreated with the adjuvant Corynebacterium parvum.
Peritoneal macrophages were isolated from C. parvum-pretreated (CP) and normal CBAT6T6 mice and their in vitro handling of 125I-labelled Keyhole limpet haemocyanin (125I-labelled KLH) studied in relation to the humoral anti-KLH responses induced in corresponding animals. CP pretreatment exerted an adjuvant effect on the production of anti-KLH antibodies, both IgM and IgG, which was also demonstrable with a normally subimmunogenic dose of antigen. There was a clear difference between the handling of 125I-labelled KLH by CP and normal macrophages. The initial uptake of the antigen by CP macrophages was slower than that by normal ones. Moreover, 125I-labelled KLH was degraded to a lesser extent within CP macrophages, although the rates of antigen digestion were similar in both kinds of cells. The lower extent of 125I-labelled KLH degradation within the CP macrophages was due to a larger amount of antigen being retained on the cell membrane, where it escapes digestion. The findings suggest that intensified presentation to lymphocytes of antigen on the macrophage surface could be a causal factor in the adjuvant action of CP.


Stability of latanoprost in generic formulations using controlled degradation and patient usage simulation studies.
To evaluate the stability of latanoprost in generic formulations by using controlled degradation and patient usage simulation studies Standard latanoprost was subjected to controlled degradation studies. Latanoprost content was assessed by using MRM, and generated Degradation Products (DP) were analysed by using the Information Dependent Acquisition (IDA) protocol of positive ESI-LC-MS/MS. Latanoprost content and formation of DP were assessed in generic formulations and were compared with Xalatan(®) in a controlled patient usage simulation studies. The last few drops of latanoprost, present in containers used by patients were also evaluated. Extreme pH conditions, oxidation, light and heat were found to be the significant factors for high degree of latanoprost degradation. Systematic analysis of 7 selected generics revealed that the latanoprost content varied from 90-330%. Concentration of the latanoprost in Xalatan was found to be 97% of the label claim. Degradation studies showed the formation of 3 novel and 3 already known impurities. Upon simulated patient usage, 2 of the generic formulations showed significant degradation of latanoprost. Generic formulations having thermally sealed gas tight packing showed good stability during patient usage. Overage of latanoprost was observed in generics with other than thermal sealing. Latanoprost bottles used by patients showed concentrations ranging from 20 to 250% of label claim (144% median). This study revealed the presence of overage of latanoprost in some generic formulations and formation of degradation products. Packaging with gas tight containers may be one of the important factors for latanoprost stability, along with its storage at low temperature during patient usage.


Hypercoagulation and Antithrombotic Treatment in Coronavirus 2019: A New Challenge.
The novel coronavirus 2019 (COVID-19) is clinically characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for a high number of patients needing mechanical ventilation or intensive care units treatment and for the elevated mortality risk. A link between COVID-19 and multiorgan failure may be dependent on the fact that most COVID-19 patients are complicated by pneumonia, which is known to be associated with early changes of clotting and platelet activation and artery dysfunction; these changes may implicate in thrombotic-related events such as myocardial infarction and ischemic stroke. Recent data showed that myocardial injury compatible with coronary ischemia may be detectable in SARS-CoV-2 patients and laboratory data exploring clotting system suggest the presence of a hypercoagulation state. Thus, we performed a systematic review of COVID-19 literature reporting measures of clotting activation to assess if changes are detectable in this setting and their relationship with clinical severity. Furthermore, we discussed the biologic plausibility of the thrombotic risk in SARS-CoV-2 and the potential use of an antithrombotic treatment.


SERS- and Electrochemically Active 3D Plasmonic Liquid Marbles for Molecular-Level Spectroelectrochemical Investigation of Microliter Reactions.
Liquid marbles are emergent microreactors owing to their isolated environment and the flexibility of materials used. Plasmonic liquid marbles (PLMs) are demonstrated as the smallest spectroelectrochemical microliter-scale reactor for concurrent spectro- and electrochemical analyses. The three-dimensional Ag shell of PLMs are exploited as a bifunctional surface-enhanced Raman scattering (SERS) platform and working electrode for redox process modulation. The combination of SERS and electrochemistry (EC) capabilities enables in situ molecular read-out of transient electrochemical species, and elucidate the potential-dependent and multi-step reaction dynamics. The 3D configuration of our PLM-based EC-SERS system exhibits 2-fold and 10-fold superior electrochemical and SERS performance than conventional 2D platforms. The rich molecular-level electrochemical insights and excellent EC-SERS capabilities offered by our 3D spectroelectrochemical system are pertinent in charge transfer processes.


[The Phenomenon of Short PQ Interval in Children].
Data of analysis of the clinical course of a natural phenomenon of short PQ interval in 300 children are presented. During the period.


Disperse-and-Collect Approach for the Type-Selective Detection of Matrix Metalloproteinases in Porous Silicon Resonant Microcavities.
We report on the design and testing of photonic biosensors for the type-selective detection of different types of matrix metalloproteinases (MMPs). The ability to detect a panel of different MMP types has important implications for prognosis of wound healing. We combine the immunocapture of MMPs on dispersed magnetic nanoparticles modified with antibodies specific for target MMPs (immuno-magNPs) with subsequent MMP detection upon fluorogenic peptide cleavage in porous silicon resonant microcavity (pSiRM) architectures. We report fast, sensitive, and type-selective detection of MMPs directly in wound fluid. This study sets the scene for downstream developments of multiparametric biosensors as point-of-care (POC) prognostic tools that may step-change chronic wound management.


Daily ingestion of immunologic components in human milk during the first four months of life.
The amounts of lactoferrin, lysozyme, SIgA and SIgA antibodies to E. coli somatic antigens in human milk ingested per day and per kg per day by breast-fed infants were determined during the first four months of life. A gradual decline in the amounts of lactoferrin, SIgA, and SIgA antibodies ingested per day or per kg per day was found, whereas the quantities of lysozyme ingested by the infants rose during that period. These data suggest that the production and secretion of these immunologic factors by the mammary gland may be linked to the ontogeny of the production or catabolism of those components at mucosal tissues of the recipient infant.


A student proposal for ethical guidelines in anatomical education: Ethical and policy considerations.
The recent publication of a story regarding anatomical dissection in a medical school has revealed the need for increased attention to the ethical and policy aspects of anatomical education. While most of the attention devoted to these questions thus far has been focused on procedures before and after dissection, from the perspective of medical students, there are important considerations during the process of dissection itself. This proposal was developed by two third-year medical students through a review of the relevant published literature, reflection upon their personal experiences in anatomy courses in two separate institutions, and informal discussion of these topics with peers. The proposal is that basic ethical guidelines should be established and monitored by an independent committee tasked with reviewing them. The proposed guidelines include: First, a clear set of expectations about what the student is expected to learn with respect to anatomical knowledge and dissection technique; second, the establishment by schools or national bodies of minimal ethical standards regarding respectful behavior toward the donor bodies, and the communication of these standards to teachers and students involved in educational dissections; third, the use of materials that encourage students to view their donors with respect and ensure proper treatment of them; and fourth, the establishment of an oversight group (at each medical school and at national level) comprising students, faculty, community members, and staff, who will regularly review the anatomical education program and update these ethical guidelines as appropriate. While many of these proposals are already implemented in some anatomy departments, the establishment of clear guidelines at a national as well as a school-by-school level will permit students the freedom to participate fully in their education, knowing they have met the highest ethical standards as they prepare for a career as a humanistic physician.


INTENSE SELECTION OF MITE CLONES IN A HETEROGENEOUS ENVIRONMENT.
Genetic diversity within obligatorily parthenogenic species can be high, contrary to common views of the evolutionary consequences of this reproductive system. How this clonal diversity is maintained within populations is not clearly understood. Previous studies showing high clonal diversity have used parthenogenic organisms with known sexual forms or relatives. Here we report significant spatial and temporal clonal diversity within two populations of an obligatorily parthenogenic mite, Penthaleus major, which has no known sexual form or close sexual relative. Fitness estimates from temporal sampling at two sites and manipulated field plots reveal intense natural selection acting on ecologically different clones. We propose that environmental heterogeneity contributes to the maintenance of clonal diversity within populations of P. major and that selection is strong enough to overcome the problems of relative niche size.


Three-dimensional interferometric scattering microscopy via remote focusing technique.
Interferometric scattering (iSCAT) microscopy enables us to track nm-sized objects with high spatial and temporal resolutions and permits label-free imaging of biomolecules. Its superb sensitivity, however, comes at a cost by several downsides, such as slow three-dimensional imaging and limited vertical tracking. Here, we propose a new method, Remote Focusing-iSCAT (RF-iSCAT) microscopy, to visualize a volume specimen by imaging sections at different depths without translation of either the objective lens or sample stage. We demonstrate the principle of RF-iSCAT by determining the z-position of submicrometer beads by translating the reference mirror instead. RF-iSCAT features an unprecedentedly long range of vertical tracking and permits fast but vibration-free vertical scanning. We anticipate that RF-iSCAT would enhance the utility of iSCAT for dynamics study.


Evidence for the Deregulation of Protein Turnover Pathways in Atm-Deficient Mouse Cerebellum: An Organotypic Study.
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ < Atm+/- < Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans.


Cosensitivity of vagal mucosal afferents to histamine and 5-HT in the rat jejunum.
A complex sensitivity of afferent nerves in the mesentery of the rat jejunum to systemic administration of histamine has recently been demonstrated. In the present study, we aimed to characterize subpopulations of mesenteric afferents that mediate this afferent nerve response. Multiunit afferent discharge was recorded from mesenteric nerves supplying the proximal jejunum in anesthetized rats. The majority of mesenteric bundles (84%) exhibited biphasic responses to histamine (8 micromol/kg), and these bundles also responded to 2-methyl-5-HT (2m5HT). In contrast, monophasic responses lacked a short-latency component, and these bundles failed to respond to 2m5HT. Single-unit analysis revealed a population of afferents that possessed cosensitivity for 2m5HT and histamine. This population of afferents was absent in chronically vagotomized animals, whereas mucosal anesthesia with luminal lidocaine reversibly converted the biphasic profile to a monophasic one. Ondansetron (500 microg/kg) blocked the response to 2m5HT with no effect on the profile of the histamine response, whereas pyrilamine (5 mg/kg) blocked the histamine response without affecting the response to 2m5HT. We conclude that histamine-sensitive afferents exist in the rat proximal jejunum that also respond to 5-HT via the 5-HT3 receptor. These fibers appear to be vagal afferents originating in the intestinal mucosa and may be involved in the organization of mast cell-mediated responses.


[Prolonged intubation in children (author's transl)].
217 cases of prolonged intubation in children are described, with its manipulation and complications. They are more frequent when the reason for intubation is infection of the upper airway, in which case it should not be applied for longer than a week. It is very important to use tubes that provide an adequate airway with the smallest possible caliber.


The management of HIV and hepatitis B coinfection.
Coinfection with HIV and hepatitis B virus has a significant impact on the natural history of hepatitis B disease with faster rates of progression to cirrhosis and end stage liver disease. An increasing number of hepatitis B virus active drugs are now available, many of which have dual anti-HIV activity. This review highlights the most important recent developments in the management of HIV and hepatitis B virus coinfection. Natural history studies continue to confirm the increased rate of liver-related mortality in coinfected individuals and the importance of hepatocellular carcinoma in this population. The most recent studies of adefovir and tenofovir in open label use in coinfected individuals are discussed and new data on the activity of emtricitabine, entecavir and pegylated interferon are presented. Strategies for use of these new options for anti-hepatitis B virus therapy in coinfected individuals are discussed. Prevention of end stage liver disease and hepatocellular carcinoma in the coinfected population is vital and the increasing availability of drugs with potent anti-hepatitis B activity is encouraging. Appropriate diagnosis and monitoring of hepatitis B, coupled with better understanding of the mechanisms of drug resistance, will enable clinicians to manage coinfection more effectively.


Short report: elevated levels of alanine aminotransferase and hepatitis A in the context of a pediatric malaria vaccine trial in a village in Mali.
A Phase 1 study of the apical membrane antigen malaria vaccine AMA1-C1/Alhydrogel was conducted in 2-3-year-old children in a village in Mali. A high frequency of elevated levels of alanine aminotransferase (ALT) caused by hepatitis A was seen, with 8 of 36 children diagnosed by specific IgM antibody over the course of the study. Hepatitis A is a common cause of asymptomatic elevations of ALT levels in children, particularly in less-developed settings. Investigators should be aware of the frequency of hepatitis A in this age group to guard against inadvertently facilitating transmission at study facilities and to properly evaluate symptomatic or asymptomatic elevations of ALT levels.


A novel correction scheme for DFT: a combined vdW-DF/CCSD(T) approach.
A system-specific but very accurate density functional theory (DFT) correction scheme is proposed for precise calculations of adsorbent-adsorbate interactions by combining the non-empirical van der Waals density functional (vdW-DF) method and the empirical DFT/CC correction scheme to reach accuracy of the coupled clusters method with single, double and perturbative triple excitations (CCSD(T)). The new approach is applied to small molecules (CH4, CO2, H2, H2O, N2) interacting with silica surfaces and purely siliceous microporous solids. The vdW-DF/CC results for a perfectly reconstructed α-quartz surface are consistent with other dispersion-corrected DFT methods. Corrected for ZPVE, the vdW-DF/CC enthalpies of adsorption in pure-silica zeolite LTA (ΔHads(0 K)) of 3.6 and 5.2 kcal/mol for methane and carbon dioxide, respectively, are in excellent agreement with experimental values of 3.6 and 5.0 kcal/mol. The very high accuracy of the new scheme and its relatively easy use and numerical stability as compared to the earlier DFT/CC scheme offer a straightforward solution for obtaining reliable predictions of adsorption energies.


Novel therapeutic strategies for injured endometrium: intrauterine transplantation of menstrual blood‑derived cells from infertile patients.
Menstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which need to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. We collected menstrual blood-derived cells from volunteers and infertile patients and confirmed their mesenchymal stem cell phenotype by flow cytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. Menstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis, and improved fertility outcomes without any apparent complications. In our pre-clinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.


Research on the Effect of the Foot Bath and Foot Massage on Residual Schizophrenia Patients.
Researchers performed foot baths and massages for residual schizophrenia patients to gauge the effects on psychiatric symptoms. Subjects were six residual schizophrenia patients hospitalized in a psychiatric hospital. Three times a week for 4weeks, they received an 8-minute effleurage massage to their legs after a 10-minute foot bath. The effect of physiological relaxation was identified by a significant decline in heart rate in all cases. The results of the Positive and Negative Symptom Scale are as follows: a mean score of 29.0 was measured before treatment, which lowered to 21.5 after treatment, indicating that foot care improved their negative symptoms (p<0.05).The results of the Quality of Life Scale before the foot care intervention, were 10.5 and increased to 34.0 after the intervention, indicating improvement in their quality of life (p<0.05). The results of the two measurements indicate that foot baths and massages were effective in improving psychiatric symptoms.


Maternal nutrition induces gene expression changes in fetal muscle and adipose tissues in sheep.
Maternal nutrition during different stages of pregnancy can induce significant changes in the structure, physiology, and metabolism of the offspring. These changes could have important implications on food animal production especially if these perturbations impact muscle and adipose tissue development. Here, we evaluated the impact of different maternal isoenergetic diets, alfalfa haylage (HY; fiber), corn (CN; starch), and dried corn distillers grains (DG; fiber plus protein plus fat), on the transcriptome of fetal muscle and adipose tissues in sheep. Prepartum diets were associated with notable gene expression changes in fetal tissues. In longissimus dorsi muscle, a total of 224 and 823 genes showed differential expression (FDR ≤0.05) in fetuses derived from DG vs. CN and HY vs. CN maternal diets, respectively. Several of these significant genes affected myogenesis and muscle differentiation. In subcutaneous and perirenal adipose tissues, 745 and 208 genes were differentially expressed (FDR ≤0.05), respectively, between CN and DG diets. Many of these genes are involved in adipogenesis, lipogenesis, and adipose tissue development. Pathway analysis revealed that several GO terms and KEGG pathways were enriched (FDR ≤0.05) with differentially expressed genes associated with tissue and organ development, chromatin biology, and different metabolic processes. These findings provide evidence that maternal nutrition during pregnancy can alter the programming of fetal muscle and fat tissues in sheep. The ramifications of the observed gene expression changes, in terms of postnatal growth, body composition, and meat quality of the offspring, warrant future investigation.


Radiotherapy-Induced Vitiligo in a Patient with Carcinoma Buccal Mucosa: A Case Report.
Vitiligo significantly affects self-esteem and deteriorates the quality of life of affected persons. Radiotherapy has several early and late effects but it is not known to induce vitiligo. This is a case report of a patient suffering from carcinoma buccal mucosa that had developed vitiligo in the radiotherapy portal. To the best of my knowledge this is a one of the first case reports of its kind as this patient had no history of vitiligo but developed it soon after radiotherapy. Since radiotherapy is an essential component of cancer management, the radiation oncologist must be aware of this toxicity of radiotherapy. Choosing the high energy of photon beam may reduce the risk of such toxicities.


Short communication: Changes in the association between milk yield and age at first calving in holstein cows with herd environment level for milk yield.
The aim of this study was to evaluate the effect of herd environment class on the genetic and phenotypic relationships of mature equivalent milk yield (MY) on age at first calving (AFC). Data analyzed were 248,230 first parity records of Holstein cows, daughters of 588 sires in 3,042 herds in the United States. Heritability for AFC was 0.33 +/- 0.01 and 0.20 +/- 0.01 in high and low environment herds, respectively, and 0.47 +/- 0.01 in the complete data set. The correlation between AFC sires' predicted breeding values of low and high classes was 0.69. Genetic correlations between MY and AFC were -0.52 +/- 0.02 and -0.31 +/- 0.03 in high and low environment herds, respectively, and -0.44 +/- 0.02 in the complete data set representing intermediate environments. If selection is based on the whole data set, expected correlated responses for AFC estimated as a result of 1,000 kg of genetic gain in MY, for high and low herd environment herds were -26.1 and -15.3 d, respectively, and -32.6 for the complete data set; hence the highest reduction in AFC occurs in intermediate environment herds. Different estimates of the heritability of AFC, the correlation between AFC breeding values of low and high classes as well as changes in the genetic correlation between MY and AFC across environments indicate genotype x environment interaction. Caution in interpretation is warranted because genetic relationships are dynamic, especially in populations undergoing selection. Current relationships may differ from those during the time period of the present study (1987-1994). Notwithstanding this possibility, methods and findings from the present study provide insight about the complexity of genetic association and genotype x environment interactions between AFC and MY.


Hand-off communication: a requisite for perioperative patient safety.
Transitions from one care provider to another put patients at increased risk of injuries and errors. A standardized approach to hand-off communication helps minimize these risks. One recognized approach to addressing this concern is the SBAR (ie, situation, background, assessment, recommendation) communication technique. Reference cards with the SBAR communication approach can be used by all staff members during hand offs in the preoperative, intraoperative, and postoperative phases of surgical patient care.


Genome Sequence of Acinetobacter baumannii Strain 5021_13, Isolated from Cerebrospinal Fluid.
We report here the 4.1-Mb draft genome sequence of Acinetobacter baumannii strain 5021_13, a cerebrospinal fluid isolate from northern India. This genome information will help studies toward understanding the epidemiology and pathogenicity of this important nosocomial pathogen.


Closing the loop in practice to assure the desired performance.
A closed loop control process assures that a system performs within control limits. In closed loop control, the system's output feeds back directly to change the system's inputs. We describe an approach to planning and monitoring care that uses closed loop control to assure the desired performance using examples from Vanderbilt University Medical Center's ventilator management initiative. The approach has three components: an explicit end-to-end plan; a record of what is done as it is done; and an instant display of the status of each patient against their plan. The status display provides process control by showing the clinical team where correction is needed while they have time to act prospectively. Plans, displays and performance evolve together iteratively until the desired performance is achieved.


Lutetium 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy.
Prostate-specific membrane antigen (PSMA) is a receptor on the surface of prostate cancer cells that is revolutionising the way we image and treat men with prostate cancer. New small molecule peptides with high-binding affinity for the PSMA receptor have allowed high quality, highly specific PET imaging, in addition to the development of targeted radionuclide therapy for men with prostate cancer. This targeted therapy for prostate cancer has, to date, predominately used Lutetium 177 (Lu) labelled PSMA peptides. Early clinical studies evaluating the safety and efficacy of Lu PSMA therapy have demonstrated promising results with a significant proportion of men with metastatic prostate cancer, who have already failed other therapies, responding clinically to Lu PSMA. This review discusses the practical issues of administering Lu PSMA, and gives an overview of the findings from currently published trials in regards to treatment response rates, expected toxicities and safety.


Geometric Brownian motion under stochastic resetting: A stationary yet nonergodic process.
We study the effects of stochastic resetting on geometric Brownian motion with drift (GBM), a canonical stochastic multiplicative process for nonstationary and nonergodic dynamics. Resetting is a sudden interruption of a process, which consecutively renews its dynamics. We show that, although resetting renders GBM stationary, the resulting process remains nonergodic. Quite surprisingly, the effect of resetting is pivotal in manifesting the nonergodic behavior. In particular, we observe three different long-time regimes: a quenched state, an unstable state, and a stable annealed state depending on the resetting strength. Notably, in the last regime, the system is self-averaging and thus the sample average will always mimic ergodic behavior establishing a stand-alone feature for GBM under resetting. Crucially, the above-mentioned regimes are well separated by a self-averaging time period which can be minimized by an optimal resetting rate. Our results can be useful to interpret data emanating from stock market collapse or reconstitution of investment portfolios.


Infidelity in the Time of COVID-19.
Infidelity occurs in approximately 25% of marriages and is associated with various negative consequences for individuals (e.g., depression, anxiety, and post-traumatic stress), the couple relationship (e.g., financial loss, increased conflict, and aggression), and the couple's children (e.g., internalizing and externalizing behaviors). Infidelity is also one of the most frequently cited reasons for divorce. The increased stress brought on by the pandemic may be putting couples at an increased risk for experiencing infidelity, and data collected during the pandemic have shown that people across the United States are engaging in behaviors that are associated with a high likelihood of experiencing infidelity. The negative consequences of infidelity are also likely to be exacerbated for couples during the pandemic due to the intersection with the social, emotional, and financial consequences of COVID-19. Furthermore, couples are likely to experience disruptions and delays to the affair recovery process during the pandemic, which can negatively impact their ability to heal. Therefore, recommendations for navigating affair recovery during the pandemic, including adaptations for therapy, are also discussed.


[Death in a tetany attack].
A case of latent tetany in a 24-year-old woman is reported. She had suffered several attacks of tetany in the last 12 years, mostly triggered by external stimuli. One evening, the woman was found dead in the hall of her flat beside the telephone with the upper limbs in a tetanic convulsive attitude. The attack of tetany was triggered by a telephone conversation. The parathyroid glands were normal. Day-old purulent myocarditis could be demonstrated in the left ventricle under the light microscope. The two possible pathogenetic explanations of the causal chain leading to death are discussed. It was astonishing that a clinical symptom (tetanic convulsion) was fixed in rigor mortis.


[The "forty-nine" and "seventeen" problems].
The single most common age of murderers in Japan is 49. Individuals aged between 45 and 54 are, however, likely to commit not offences but suicides comparing with other generations. One factor behind this phenomenon is the trend toward company downsizing, which is thought to affect the mental attitude of workers. This trend is destroying the Japanese lifetime employment system and undermining worker's loyalty to the company. On the other hand, in the broader category of felony crimes (assault, burglary, arson, murder), offenders aged 17 are the most common in Japan. This is thought to be partly due to the effect of so-called "school collapse" (school system failure) on the mental attitude of students. "School collapse" implies dysfunction of educational practice as a result of chattering, bullying and violence in the classroom. It is the reflection of students' dissatisfaction with the group-oriented school system. Therefore, students are unable to find any purposes in school and exhibit aggressive behaviours. In terms of mental health for both middle-age and teenage generations, it is necessary to devise new strategies whereby people can break away from the pressure of loyalty to the group. For both "normal" and "disabled" workers, rights of recuperations, adequate unemployment benefits policy, and support system for occupational change should be established. Simultaneously, for both "normal" and "disabled" students, reform of the school system under the concepts of diversity of education, rights of selection, and rights of refusal is urgently necessary. With respect to forensic psychiatry, without the provision of social supports, labeling of conduct disorder as well as other disorders should be avoided. In particular, instead of introducing security hospitals, drastic improvements of medical reformatories and medical prisons are necessary to provide adequate medical and social supports for offenders with psychiatric disorders.


Optimizing Oral Medication Schedules for Inpatient Sleep: A Quality Improvement Intervention.
Hospitalized children experience frequent nighttime awakenings. Oral medications are commonly administered around the clock despite the comparable efficacy of daytime administration schedules, which promote sleep. With this study, we evaluated the effectiveness of a quality improvement initiative to increase the proportion of sleep-friendly antibiotic administration schedules. Interprofessional stakeholders modified computerized provider order entry defaults for 4 oral antibiotic medications, from around the clock to administration occurring exclusively during waking hours. Additionally, care-team members received targeted education. Outcome measures included the proportion of sleep-friendly administration schedules and patient caregiver-reported disruptions to sleep. Pre- and posteducation surveys were used to evaluate education effectiveness. Balancing measures were missed antibiotic doses and related escalations of care. Interrupted time series analysis revealed a 72% increase (interceptpre: 18%; interceptpost: 90%; 95% confidence interval: 65%-79%; P < .001) in intercept for percentage of orders with sleep-friendly administration schedules (orders: n pre = 1014 and n post = 649). Compared with preeducation surveys, care-team members posteducation were more likely to agree that oral medications scheduled around the clock cause sleep disruption (resident: 71% pre, 90% post [P = .01]; nurse: 63% pre, 79% post [P = .03]). Although sleep-friendly orders increased, patient caregivers reported an increase in sleep disruption due to medications (pre 28%, post 46%; P < .001). A simple, low-cost intervention of computerized provider order entry default modifications and education can increase the proportion of sleep-friendly oral antibiotic administration schedules for hospitalized children. Patient perception of sleep is impacted by multiple factors and often does not align with objective data. An increased focus on improving sleep during hospitalization may result in heightened awareness of disruptions.


7Li PGSE diffusion measurements on LiPPh2: a solvent dependence of the structure.
The first application of 7Li pulsed-gradient spin-echo (PGSE) diffusion methods to structural lithium chemistry is reported. The data, which provide quantitative diffusion constants at 155 K, lead to a new method of estimating solvent viscosity at this temperature and clearly show a solvent dependence for the structure of LiPPh2. In THF, LiPPh2 exists as a mononuclear solvated species, whereas in Et2O, a dinuclear structure is found. D values for the model compound PHPh2 in THF have been measured.


Sorafenib inhibited cell growth through the MEK/ERK signaling pathway in acute promyelocytic leukemia cells.
The present study assessed the mechanism underlying the effect of sorafenib on the proliferation and apoptosis of the acute promyelocytic leukemia (APL) cell line NB4. NB4 cells were treated with different concentrations of sorafenib (0, 1.5, 3, 6, and 12 µM) for 24, 48 and 72 h. Cell proliferation, cell cycle, and apoptosis were analyzed using an MTT assay and flow cytometry analysis, respectively. Reverse transcription-semi-quantitative polymerase chain reaction and western blot analysis were performed to assess the expression of caspase-3, caspase-8, myeloid cell leukemia (MCL)1, cyclin D1, mitogen-activated protein kinase (MEK), phosphorylated (P)-MEK, extracellular signal-regulated kinase (ERK) and P-ERK. The results of the MTT assay demonstrated that, compared with untreated cells, the proliferation of sorafenib-treated NB4 cells was inhibited dose- and time-dependently. Furthermore, cell cycle arrest was induced in the G0/G1 phase and cell apoptosis was promoted in a dose-dependent manner in sorafenib-treated NB4 cells compared with untreated cells. In addition, the expression of the proapoptotic molecules caspase-3 and caspase-8 was significantly upregulated, and the expression of the antiapoptotic molecule MCL1 and the cell cycle-associated cyclin D1 was downregulated in sorafenib-treated NB4 cells compared with untreated cells. Furthermore, the phosphorylation of MEK and ERK was inhibited in sorafenib-treated NB4 cells compared with untreated cells. Sorafenib may inhibit proliferation and induce cell cycle arrest and apoptosis in APL cells. The underlying mechanisms of such effects may be associated with alterations to the expression of apoptosis-associated and cell cycle-associated molecules via MEK/ERK signaling pathway inhibition.


AMXT-1501, a novel polyamine transport inhibitor, synergizes with DFMO in inhibiting neuroblastoma cell proliferation by targeting both ornithine decarboxylase and polyamine transport.
Neuroblastoma (NB) is associated with MYCN oncogene amplification occurring in approximately 30% of NBs and is associated with poor prognosis. MYCN is linked to a number of genes including ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. ODC expression is elevated in many forms of cancer including NB. Alpha-difluoromethylornithine (DFMO), an ODC inhibitor, is currently being used in a Phase I clinical trial for treatment of NB. However, cancer cells treated with DFMO may overcome their polyamine depletion by the uptake of polyamines from extracellular sources. A novel polyamine transport inhibitor, AMXT-1501, has not yet been tested in NB. We propose that inhibiting ODC with DFMO, coupled with polyamine transport inhibition by AMXT-1501 will result in enhanced NB growth inhibition. Single and combination drug treatments were conducted on three NB cell lines. DFMO IC50 values ranged from 20.76 to 33.3 mM, and AMXT-1501 IC50 values ranged from 14.13 to 17.72 µM in NB. The combination treatment resulted in hypophosphorylation of retinoblastoma protein (Rb), suggesting growth inhibition via G1 cell cycle arrest. Increased expression of cleaved PARP and cleaved caspase 3 in combination-treated cells starting at 48 hr suggested apoptosis. The combination treatment depleted intracellular polyamine pools and decreased intracellular ATP, further verifying growth inhibition. Given the current lack of effective therapies for patients with relapsed/refractory NB and the preclinical effectiveness of DFMO with AMXT-1501, this combination treatment provides promising preclinical results. DFMO and AMXT-1501 may be a potential new therapy for children with NB.


Betweenness centrality of teams in social networks.
Betweenness centrality (BC) was proposed as an indicator of the extent of an individual's influence in a social network. It is measured by counting how many times a vertex (i.e., an individual) appears on all the shortest paths between pairs of vertices. A question naturally arises as to how the influence of a team or group in a social network can be measured. Here, we propose a method of measuring this influence on a bipartite graph comprising vertices (individuals) and hyperedges (teams). When the hyperedge size varies, the number of shortest paths between two vertices in a hypergraph can be larger than that in a binary graph. Thus, the power-law behavior of the team BC distribution breaks down in scale-free hypergraphs. However, when the weight of each hyperedge, for example, the performance per team member, is counted, the team BC distribution is found to exhibit power-law behavior. We find that a team with a widely connected member is highly influential.


Effects of strength and neuromuscular training on functional performance in athletes after partial medial meniscectomy.
The aims of this study were to determine an effective knee function rehabilitation program for athletes undergoing partial medial meniscectomy. Participants were randomly assigned to neuromuscular training (NT) or strength training (ST) group and subjected to functional assessments before surgery and again at 4, and 8 weeks post hoc. Functional knee assessment, such as Lysholm knee scoring, star excursion balance, and BTE PrimusRS isokinetic performance tests were evaluated in each group. All postoperational symptoms were significantly improved after 4 and 8 weeks of NT and ST. Both NT and ST programs showed effective knee function recovery seen as an increase in muscular strength and endurance. However, the NT program showed the most significant functional improvement of dynamic balance and coordination.


Histamine determination in human urine using sub-2 μm C18 column with fluorescence and mass spectrometric detection.
A fast, sensitive, and selective method for the determination of histamine in human urine samples by ultrahigh pressure liquid chromatography (LC) with fluorescence and mass spectrometry (MS) detection is investigated. A fluorescent reagent, 4-(1-pyrene) butyric acid N-hydroxysuccinimide ester was conjugated to the primary and secondary amino moieties of histamine. The structure of dipyrene-labeled histamine in human urine was determined by quadrupole time-of-flight MS with electospray ionization interface. The determination of the dipyrene derivative of histamine in urine samples was achieved within 3.9 min on an ultrahigh pressure LC Eclipse Zorbax XDB-C(18) column with 1.8 μm particle diameter. In this work, histamine separation was achieved significantly faster (3.9 min) with improved detection limit (signal-to-noise = 3) of 0.04 nM than 19.5 min with a detection limit of 0.183 nM as reported in a previous method.


[Development of a stress scale for Korean nursing students].
The purpose of this study was to develop a stress measurement scale for Korean nursing students. Sixty preliminary items were selected by classifying 229 basic items extracted via literature review and Q-sorting method. In order to verify the reliability and validity of the preliminary instrument, data were collected from 617 nursing students in 2 colleges of nursing in Korea. As a result of the item analysis, 58 items were selected. They consisted of 2 types of stress which were college-based stress (38 items) and clinical-based stress (20 items). Ten factors in college-based stress and four factors in clinical-based stress were extracted by factor analysis, and each had a total variance of 63.01%, and 64.93%. Cronbach's Alpha of those 58 items were .937 in college-based stress and .922 in clinical-based stress, which was high. This paper is meaningful in a way that it has developed a tool capable of measuring stress for nursing students, which reflects the characteristics of our country. It is recommended for further study to re-verify the relevance and stability of this measurement.


Help-seeking experiences of men diagnosed with colorectal cancer: a qualitative study.
Advanced-stage diagnosis of colorectal cancer (CRC) leads to poor prognosis and reduced survival rates. The current study seeks to explore the reasons for diagnostic delays in a sample of Australian men with CRC. Semi-structured interviews were conducted in a purposive sample of 20 male CRC patients. Data collection ceased when no new data emerged. Interviews were audiotaped, transcribed and thematically analysed using Andersen's Model of Total Patient Delay as the theoretical framework. Most participants (18/20) had experienced lower bowel symptoms prior to diagnosis. Patient-related delays were more common than delays attributable to the health-care system. Data regarding patient delays fit within the first four stages of Andersen's model. The barriers to seeking timely medical advice were mainly attributed to misinterpretation of symptoms, fear of cancer diagnosis, reticence to discuss the symptoms or consulting a general practitioner. Treatment delays were a minor cause for delayed diagnosis. Delay in referral and scheduling for colonoscopy were among the system-delay factors. In many instances, delays resulted from men's failure to attribute their symptoms to cancer and, subsequently, delay in diagnosis.


Toxocara nematodes in stray cats from shiraz, southern iran: intensity of infection and molecular identification of the isolates.
Toxocara is a common nematode of cats in different parts of Iran. Despite the close association of cats with human, no attempt has been done so far for molecular identification of this nematode in the country. Therefore, current study was performed on identification of some isolates of Toxocara from stray cats in Shiraz, Fars Province, Southern Iran, based on morphological and molecular approaches, and also determination of intensity of infection. This cross-sectional study was carried out on 30 stray cats trapped from different geographical areas of Shiraz in 2011. Adult male and female worms were recovered from digestive tract after dissection of cats. Morphological features using existing keys and PCR-sequencing of ITS-rDNA region and pcox1 mitochondrial l gene were applied for the delineating the species of the parasites. Eight out of 30 cats (26.7%) were found infected with Toxocara nematodes. All the isolates were confirmed as Toxocara cati based on morphological features and the sequence of ribosomal and mitochondrial targets. Intensity of infection ranged from one to a maximum of 39 worms per cat, with a mean of 10.25±12.36, and higher abundance of female nematodes. The most prevalent ascaridoid nematode of stray cats in the study area was T. cati and female nematodes were more abundant than that of males. This issue has important role in spreading of eggs in the environment and impact on human toxocariasis.


[A study of immunologic reactions using biophysical methods].
Chemiluminescent characteristics of the antigen-antibody reaction, effects of gamma-globulin, iodine, hydrogen peroxide, and temperature on the type of the fluorescence of the complex were examined with the use of biomedical chemiluminometer and fluorescent spectrophotometer (Japan). The findings evidence that fluorescence is connected mainly with the tryptophan amino acid residues and with conformational restructuring of protein molecules. Changes in the intensity of chemiluminescence during the formation of a complex may be used for the detection of antibodies in the examinee's body.


Clinical and Immunological Outcomes of HIV-Exposed Uninfected and HIV-Unexposed Uninfected Children in the First 24 Months of Life in Western Kenya.
Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers with HIV received combination antiretroviral therapy. HEU children received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. HEU and HUU children had similar growth curves. HEU children had lower rates of malaria and respiratory illness. Trajectories of plasma cytokines and vaccine-specific antibodies were similar in HEU and HUU children. There were subtle differences in antimalarial antibody dynamics, in which HEU children had overall lower antibody levels against five of the 14 malaria antigens tested. HEU children born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to HUU children. HEU children had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.


Recognition of Patient Groups with Sleep Related Disorders using Bio-signal Processing and Deep Learning.
Accurately diagnosing sleep disorders is essential for clinical assessments and treatments. Polysomnography (PSG) has long been used for detection of various sleep disorders. In this research, electrocardiography (ECG) and electromayography (EMG) have been used for recognition of breathing and movement-related sleep disorders. Bio-signal processing has been performed by extracting EMG features exploiting entropy and statistical moments, in addition to developing an iterative pulse peak detection algorithm using synchrosqueezed wavelet transform (SSWT) for reliable extraction of heart rate and breathing-related features from ECG. A deep learning framework has been designed to incorporate EMG and ECG features. The framework has been used to classify four groups: healthy subjects, patients with obstructive sleep apnea (OSA), patients with restless leg syndrome (RLS) and patients with both OSA and RLS. The proposed deep learning framework produced a mean accuracy of 72% and weighted F1 score of 0.57 across subjects for our formulated four-class problem.


Development of dietary soluble fibres by enzymatic synthesis and assessment of their digestibility in in vitro, animal and randomised clinical trial models.
The aim was to develop novel fibres by enzymatic synthesis, to determine their total dietary fibre by AOAC method 2009.01 and to estimate their potential digestibility and assess their digestibility in vivo using glycaemic and insulinaemic responses as markers in mice and randomised clinical trial models. We found that fibre candidates to which α-(1,2) branching was added were resistant to digestion in the mouse model, depending on the amount of branching. These results show that in vivo models are needed to reliably assess the digestibility of α-glycosidic-linked oligomeric dietary fibre candidates, possibly due to absence of brush border α-glucosidase activity in the current in vitro assessment. α-(1,3)-linked and α-(1,6)-linked glucose oligomers were completely digested in humans and mice. In conclusion, it is possible to develop dietary soluble fibres by enzymatic synthesis. Adding α-(1,2) branching increases their resistance to digestion in vivo and can thus improve their suitability as potential fibre candidates. Clinical Trial Registry: ClinicalTrials.gov, NCT02701270.


RNAPol-ChIP: a novel application of chromatin immunoprecipitation to the analysis of real-time gene transcription.
We describe a procedure, RNAPol-ChIP, to measure actual transcriptional rate. It consists of the detection, by chromatin immunoprecipitation (ChIP), of RNA polymerase II within the coding region of genes. To do this, the DNA immunoprecipitated with polymerase antibodies is analysed by PCR, using an amplicon well within the coding region of the desired genes to avoid interferences with polymerase paused at the promoter. To validate RNAPol-ChIP, we compare our results to those obtained by classical methods in several genes induced during either liver regeneration or acute pancreatitis. When short half-life mRNA genes are studied (e.g. c-fos and egr1), RNAPol-ChIP gives results similar to those of other procedures. However, in genes whose mRNA is more stable (e.g. the hemopexin, hpx, gene) RNAPol-ChIP informs on real-time transcription with results comparable to those of methods such as nuclear run-on or run-off, which require the isolation of highly purified nuclei. Moreover, RNAPol-ChIP advantageously compares with methods based on the analysis of steady-state mRNA (northern blot or RT-PCR). Additional advantages of RNAPol-ChIP, such as the possibility of combining it with classical ChIP analysis to study transcription-associated changes in chromatin are discussed.


Low-cost screening for microbial contaminants in aerosols generated in a dental office.
It has been reported that aerosols and droplets generated by high-speed dental drills and cavitrons are contaminated with blood and bacteria and represent a potential route for transmitting disease. Bacterial cells possess a negative electrical charge, while the cathode ray tubes (CRT) that are used in computer monitors generate positively charged static electric fields. Consequently, bacteria dispersed within these aerosols could be attracted to the screens on CRT monitors. In this study, pathogenic strains of Staphylococcus aureus were found on CRT screens in different locations within the Louisiana State University School of Dentistry facility. The results suggest that surveying CRT screens is a simple method for evaluating the airborne microbial contaminants present within a dental office.


[Clinical Research and Biostatistics].
We discuss the important role of biostatisticians in clinical research. In addition, the biases that occur in a study, especially "confounding" in an observational study, are discussed using a real example. Finally, the manuscript provides an overview of propensity score matching, a method to eliminate confounding.


The shoaling behavior of two cyprinid species in conspecific and heterospecific groups.
Mixed-species shoals of fish are frequently found in the field; however, little is known about individual-level interactions within these groups. We examined the collective motion of two cyprinid species (Chinese bream, Parabramis pekinensis, and qingbo, Spinibarbus sinensis) that occupy partially overlapping habitats but differ in social behavior (high vs low aggressiveness) and preferred flow regime (slow vs fast water velocity). We extracted measures of collective motion from video recordings of eight replicate groups of four individuals of either Chinese bream or qingbo (conspecific group) or two Chinese bream plus two qingbo (heterospecific group). Chinese bream in conspecific groups showed lower percent time moving and mean swimming speed but a similar speed while moving as compared to the qingbo conspecific groups. However, the difference in mean swimming speed and percent time moving vanished in the heterospecific group as Chinese bream elevated their swimming activity to coordinate with qingbo. This finding suggests that the two species may share similar interaction rules regarding shoaling behavior. The conspecific groups of qingbo exhibited a greater distance between group members than Chinese bream, suggesting a difference in cohesion. However, the inter-individual distances of all fish were similar in the heterospecific group. Qingbo in the heterospecific group swam more frequently at the front compared to Chinese bream, possibly due to their higher activity level. We also measured the startle response to an artificial stimulus and found that there was no significant difference among groups. In conclusion, the present study demonstrated that in the heterospecific groups, Chinese bream elevated their percent time moving while qingbo decreased their inter-individual distance to achieve consistent collective movement; thus, the two species showed similar behavior in the mixed-species group.


First Ornithomimid (Theropoda, Ornithomimosauria) from the Upper Cretaceous Djadokhta Formation of Tögrögiin Shiree, Mongolia.
The Upper Cretaceous Djadokhta Formation has been intensively surveyed for its fossil vertebrate fauna for nearly a century. Amongst other theropods, dromaeosaurids and parvicursorines are common in the formation, but ornithomimosaurs are extremely rare. A new ornithomimosaur material was discovered from the Djadokhta Formation, represented by eolian deposits, of the Tögrögiin Shiree locality, Mongolia. This is only the third ornithomimosaur specimen reported from this formation, and includes the astragalus, the calcaneum, the third distal tarsal, and a complete pes. The new material is clearly belonged to Ornithomimidae by its arctometatarsalian foot condition and has the following unique characters; unevenly developed pair of concavities of the third distal tarsal, curved contacts between the proximal ends of second and fourth metatarsals, the elongate fourth digit, and a laterally inclined medial condyle on phalanx IV-1. These diagnostic characters of the Djadokhtan ornithomimosaur indicate that this is a new taxon. Our phylogenetic analysis supports three clades within derived ornithomimosaurs, and the new taxon is placed a member of the derived ornithomimosaurs. The present specimen is the first ornithomimid record from eolian Tögrögiin Shiree locality, and is indicative of their capability to adapt to arid environments.


Advanced Thermoelectric Design: From Materials and Structures to Devices.
The long-standing popularity of thermoelectric materials has contributed to the creation of various thermoelectric devices and stimulated the development of strategies to improve their thermoelectric performance. In this review, we aim to comprehensively summarize the state-of-the-art strategies for the realization of high-performance thermoelectric materials and devices by establishing the links between synthesis, structural characteristics, properties, underlying chemistry and physics, including structural design (point defects, dislocations, interfaces, inclusions, and pores), multidimensional design (quantum dots/wires, nanoparticles, nanowires, nano- or microbelts, few-layered nanosheets, nano- or microplates, thin films, single crystals, and polycrystalline bulks), and advanced device design (thermoelectric modules, miniature generators and coolers, and flexible thermoelectric generators). The outline of each strategy starts with a concise presentation of their fundamentals and carefully selected examples. In the end, we point out the controversies, challenges, and outlooks toward the future development of thermoelectric materials and devices. Overall, this review will serve to help materials scientists, chemists, and physicists, particularly students and young researchers, in selecting suitable strategies for the improvement of thermoelectrics and potentially other relevant energy conversion technologies.