Lung Ultrasound for Initial Diagnosis and Subsequent Monitoring of Aspiration Pneumonia in Elderly in Home Medical Care Setting.
The number of aspiration pneumonia cases has increased in recent times. A definitive diagnosis of aspiration pneumonia is difficult in resource-limited settings where radiological equipment is unavailable. We report the initial diagnosis and subsequent monitoring of aspiration pneumonia in a home medical care setting. An 88-year-old Japanese male presented an acute onset of dyspnea, fever, and productive cough. At home, lung ultrasound displayed pleural effusion along with B-lines and subpleural consolidations. Upon admission, tests revealed increased total leucocyte counts with left-shifted neutrophils, elevated C-reactive protein levels, and positive sputum Gram stain. Chest X-ray imaging and computed tomography (CT) showed bibasilar infiltrates and wall thickening in the left S10 bronchi. The patient was diagnosed with aspiration pneumonia and treated with an antibiotic. After a 10-day hospitalization, lung ultrasound showed some remaining B-lines and disappearance of pleural effusion and subpleural consolidation. Chest X-ray image was normal, and CT revealed pleural abnormality and disappearance of bibasilar infiltrates, consistent with the ultrasound findings. Aspiration pneumonia develops with various clinical signs. However, diagnosis using chest X-ray imaging or CT in resource-limited settings is difficult. Ultrasound might allow physicians to make more accurate judgments, particularly while monitoring aspiration pneumonia following initial diagnosis in resource-limited settings.


[Different localization of thrombomodulin].
Thrombomodulin (TM) is the endothelial cofactor of the anticoagulant protein C system. The distribution of TM in the organism was studied in the rabbit using a goat anti TM, affinity-purified antibody and a peroxidase-labelled antigoat immunoglobulin. TM antigen was found on the endothelial surface of all blood vessels: capillaries, arteries and veins. The reaction was specific: connective tissue, smooth and striated muscle bone, cartilage, nerve tissue, secretary epithelia and all parenchyma studied were not strained. Moreover TM antigen was present on the surface of serosa: peritoneum, pericardium and pleura as well as on synovial membranes and on arachnoid, all along the central nervous system. It was absent from pia and dura mater. The antigen was found only after formalin fixation on the vessels and body cavities surface on which it lies. This observation shows that the antigen is easily detached from these surfaces and suggest a possible mobility of this endothelial molecule for which it lies. This observation shows that the antigen is easily detached from these surfaces and suggest a possible mobility of this endothelial molecule for which production and function sites might differ.


Atorvastatin reduces tissue damage in rat ovaries subjected to torsion and detorsion: biochemical and histopathologic evaluation.
The aim of this study was to evaluate the effects of atorvastatin as an antioxidant and tissue protective agent and study the biochemical and histopathological changes in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries. The experiment used 48 adult female rats, and the experimental groups can be summarized as: group I, a sham operation; group II, a sham operation +10 mg/kg atorvastatin; group III, bilateral ovarian ischemia; and groups IV and V, bilateral ovarian ischemia +5 and 10 mg/kg atorvastatin before 30 min of ischemia, respectively (after a 3-h period of ischemia, the bilateral ovaries were surgically removed); group VI, 3-h period of ischemia followed by 3-h reperfusion; groups VII and VIII received 5 and 10 mg/kg atorvastatin, respectively, 2.5 h after the induction of ischemia, and at the end of a 3-h period of ischemia, bilateral vascular clips were removed and 3-h reperfusion continued. After the experiments, superoxide dismutase (SOD) and myeloperoxidase (MPO) activity and levels of glutathione (GSH) and lipid peroxidation (LPO) were determined, and histopathological changes were examined in all rat ovarian tissue. Ischemia and I/R increased the LPO level and MPO activity while decreasing the SOD activity and GSH level significantly in comparison to the sham group. The 5- and 10-mg/kg doses of atorvastatin before ischemia and I/R reversed the trend in LPO level and MPO activity. The levels of SOD and GSH were decreased by ischemia and I/R. The administration of atorvastatin before ischemia and I/R treatments also reversed the trend in the SOD and GSH levels. In the I/R plus atorvastatin groups, although minimal vascular dilation in the ovary stoma and some degenerative cell clusters were seen, most of the cellular structures showed no pathological changes. Administration of atorvastatin is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.


Death from donor-transmitted malignancy despite emergency liver retransplantation.
Transplantation of organs procured from donors with malignancies identified subsequent to implantation presents a significant dilemma regarding the optimal management strategy to simultaneously minimize the risk for cancer transmission and recipient morbidity. In this report, we present a patient who underwent orthotopic liver transplantation for hepatitis B cirrhosis. The donor had no previous history of cancer. On autopsy, enlarged mediastinal lymph nodes led to the discovery of a 1-cm lung tumor. Histological examination showed pulmonary adenocarcinoma with metastatic mediastinal disease. Despite urgent retransplantation within 7 days, the recipient developed metastatic pulmonary adenocarcinoma diagnosed 11 months after transplantation and died soon thereafter. Analysis of short tandem repeat regions of chromosomal DNA from the recipient, the 2 liver donors, and the posttransplantation tumor corroborates that the first donor was the source of the malignancy. This case of donor-transmitted malignancy underscores the need for vigilance by the procuring surgeon in identifying potential malignancy during organ retrieval and use of a full autopsy on selected donors after organ procurement.


Evaluation of Veterans Affairs primary care nurse practitioner residency: Achievement of competencies.
The Institute of Medicine has recommended the establishment of residency programs for advanced practice nursing graduates. Currently, the evidence about program effectiveness is limited. To describe the nurse practitioner (NP) resident outcomes on seven competency domains established by the VA Centers of Excellence in Primary Care Education (VA CoEPCE). We evaluated mean NP resident competency self-ratings and mean mentor ratings over the 12-month program across NP residency programs at five sites. Highest and lowest rated items and differences between NP resident self-ratings and mentor ratings were analyzed. Mean NP resident self-ratings and mean mentor ratings demonstrated statistically significant improvement in all domains (p < .0001). At 12 months, NP residents were rated by their mentors as able to practice without supervision in all competency domains. At 1 and 12 months, clinical, leadership and quality improvement/population management competencies were the lowest scored domains while patient-centered care, interprofessional team collaboration, shared decision-making and sustained relationships competencies were highest. These results provide initial evidence for the effectiveness of VA CoEPCE NP residency programs and also highlight areas of needed improvement.


Nutrition communication - Rhetoric & reality.
Given the context that undernutrition in India co-exists with the problems of overweight/obesity and associated non-communicable diseases as well as micronutrient deficiencies, integrating nutritional concerns in developmental policies and governance is gaining significance. There are many schemes implemented to tackle malnutrition in India, but creating synergy and linking these schemes with each other to achieve a common goal are lacking. Nutrition communication can be an important component to create the synergy required to change malnourished India to malnutrition-free India. Although nutrition education/communication is recognized as a necessary component in various national nutrition programmes, there is not much evidence of distinct evaluation of these components. Only a minor proportion of community nutrition research has been devoted to nutrition education and communication. Although there are scattered efforts in experimenting with newer communication approaches and media for promoting nutrition, there is a dearth of published literature. In this review an attempt was made to critically examine the nutrition education and communication research and practice with special focus on India. This review provides a historical perspective of evolution of nutrition education and communication with an overview of communication approaches, media, methods and technologies used in various research studies and programmes as well as the lessons learnt.


Management of ureteral obstruction in crossed fused renal ectopia: A case report.
Crossed fused renal ectopia is a rare congenital malformation. We describe a case in which a 58-year-old male with left-sided crossed fused renal ectopia presented with urinary bladder outlet obstruction due to metastatic prostate adenocarcinoma. Glomerular filtration rate (GFR) was 13 mL/min, creatinine 4 mg/dL, and blood urea nitrogen (BUN) 58 mg/dL. The patient underwent successful image-guided placement of percutaneous nephrostomy tubes which were later converted to nephroureteral stents. Labs improved to a GFR of 28 mL/min, creatinine of 2.4 mg/dL, and BUN of 41 mg/dL. In this case standard image-guided renal decompression techniques were effective in treating a patient with crossed fused renal ectopia.


Ten reasons why operating department practitioners and theatre nurses might not want to quote or cite from this article.
Academic writing can fill pre- and postregistration students with fear and dread. Students often construct written work around re-worded passages from their sources. This results in poor quality work, low marks and frustration. The aim of this article is to inform students embarking on courses in higher education about what academic writing is and equally importantly what it is not.


Circulatory changes during and after surgical anesthesia in hypertensive patients treated with clonidine, methyldopa and reserpine.
The cardiovascular changes in 27 hypertensive patients belonging to WHO classes I-II and treated with either clonidine, methyldopa or reserpine during thiopentone-N2O-O2-relaxant-analgesic anesthesia were studied. The variations in systolic and diastolic blood pressure and heart rate during induction of anesthesia and surgery did not differ according to the antihypertensive drug with which the patient was treated. Hypokalemia was found to be the most common postoperative complication in all study groups. The results suggest that the selection of antihypertensive drug does not form a risk factor when hypertensive patients are being prepared for anesthesia and surgery.


Community detection algorithms: a comparative analysis.
Uncovering the community structure exhibited by real networks is a crucial step toward an understanding of complex systems that goes beyond the local organization of their constituents. Many algorithms have been proposed so far, but none of them has been subjected to strict tests to evaluate their performance. Most of the sporadic tests performed so far involved small networks with known community structure and/or artificial graphs with a simplified structure, which is very uncommon in real systems. Here we test several methods against a recently introduced class of benchmark graphs, with heterogeneous distributions of degree and community size. The methods are also tested against the benchmark by Girvan and Newman [Proc. Natl. Acad. Sci. U.S.A. 99, 7821 (2002)] and on random graphs. As a result of our analysis, three recent algorithms introduced by Rosvall and Bergstrom [Proc. Natl. Acad. Sci. U.S.A. 104, 7327 (2007); Proc. Natl. Acad. Sci. U.S.A. 105, 1118 (2008)], Blondel [J. Stat. Mech.: Theory Exp. (2008), P10008], and Ronhovde and Nussinov [Phys. Rev. E 80, 016109 (2009)] have an excellent performance, with the additional advantage of low computational complexity, which enables one to analyze large systems.


Regulation of kidney organogenesis: homeobox genes, growth factors, and Wilms tumor.
Factors regulating the temporal and spatial expression of kidney developmental programs are beginning to be identified. Evidence accumulated in the past few years indicates that the Hox and Pax genes, in particular, are important for early kidney development. A number of soluble growth factors were also shown to be essential for nephrogenesis to proceed in vitro. Errors in kidney development include Wilms tumor, a common childhood malignancy, which in many cases seems to be caused by faulty transcriptional regulation.


Septic complications in patients with permanent pacemakers.
Nine patients with implanted pacemakers had the diagnosis of septicaemia to endocarditis. The diagnosis was established on the basis of a repeatedly positive haemoculture. The interval since the first pacemaker implantation to the onset of sepsis to endocarditis was about 5 years. All nine patients had previous reoperation either of the pacemaker or its lead due to decubitus. While, in four patients, the route of infection was a pacemaker lead in its extravascular couse, in 5 patients the source of infection was a lead placed right in the venous system. All patients were treated with ATB according to the antibioticogram. 4 patients had the pacemaker lead extracted. In the remaining five, the pacemaker lead was removed by catheterization. All patients recovered. There is only one way of eliminating infection that caused the sepsis, that is, to remove the foreign body present in the patient - the pacemaker leas in this particular case.


Carbonic Anhydrase Inhibitor with Topical NSAID Therapy to Manage Cystoid Macular Edema in a Case of Gyrate Atrophy.
Gyrate atrophy of the choroid and retina (GACR) is a rare chorioretinal dystrophy characterized by a deficiency of the enzyme ornithine aminotransferase, inherited in an autosomal recessive pattern. We report a case of a 17-year-old girl with GACR, for whom the level of serum ornithine had been reduced by an arginine-restricted diet. The patient was responsive to an association of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and a carbonic anhydrase inhibitor (CAI) to reduce cystoid macular edema (CME). The efficacy of topical NSAIDs and systemic CAI association indicates that the imbalance in the distribution of retinal pigment epithelium membrane-bound carbonic anhydrase could play a major role in CME pathogenesis in GACR. To our knowledge, this is the first case of therapy with CAI treatment for GACR-related CME.


A phosphoproteomic analysis of the ErbB2 receptor tyrosine kinase signaling pathways.
Overexpression of the ErbB2 receptor tyrosine kinase is common in human cancers and is associated with an increased level of metastasis. To better understand the cellular signaling networks activated by ErbB2, a phosphoproteomic analysis of tyrosine-phosphorylated proteins was carried out in ErbB2-overexpressing breast and ovarian cancer cell lines. A total of 153 phosphorylation sites were assigned on 78 proteins. Treatment of cells with Herceptin, a monoclonal antibody that inhibits ErbB2 activity, significantly reduced the number of detectable protein phosphorylation sites, suggesting that many of these proteins participate in ErbB2-driven cell signaling. Of the 71 proteins that were differentially phosphorylated, only 13 were previously reported to directly associate with ErbB2. The differentially phosphorylated proteins included kinases, adaptor/docking proteins, proteins involved in cell proliferation and migration, and several uncharacterized RNA binding proteins. Selective depletion of some of these proteins, including RNA binding proteins SRRM2, SFRS1, SFRS9, and SFRS10, by siRNAs reduced the rate of migration of ErbB2-overexpressing ovarian cancer cells.


An evaluation of the balanced placebo design in alcohol administration research.
Results from a study using the balanced placebo design to assess alcohol's effects on anxiety raise serious doubts about the utility of the design even at moderate blood alcohol concentrations. Despite being informed that they were not drinking alcohol, 44% of the subjects who were administered alcohol reported consuming at least some alcohol. Moreover, subjects' scores on the Marlowe-Crowne Social Desirability Index (MCSD) were associated with deception success, suggesting that individual differences in reporting bias influence the manipulation. In contrast, only 6% of subjects who were told that they had consumed alcohol but were given tonic water were not deceived. Among subjects in this placebo condition, scores on the MCSD were not associated with success of the deception. These data suggest that at a moderate dose of alcohol, drink deception in the antiplacebo condition is much more difficult to execute than in the placebo condition, and that deception in the former condition may be confounded with experimenter demand.


Breather statics and dynamics in Klein-Gordon chains with a bend.
In this paper, we examine a nonlinear model with an impurity emulating a bend. We justify the geometric interpretation of the model and connect it with earlier work on models including geometric effects. We focus on both the bifurcation and stability analysis of the modes that emerge as a function of the strength of the bend angle, but we also examine dynamical effects including the scattering of mobile localized modes (discrete breathers) off of such a geometric structure. The potential outcomes of such numerical experiments (including transmission, trapping within the bend as well as reflection) are highlighted and qualitatively explained. Such models are of interest both theoretically in understanding the interplay of breathers with curvature, but also practically in simple models of photonic crystals or of bent chains of DNA.


Brain region specificity in reactive oxygen species production and maintenance of redox balance.
The brain produces various reactive oxygen species in enzymatic and non-enzymatic reactions as a by-product of metabolism and/or for redox signaling. Effective antioxidant system in the brain cells maintains redox balance. However, neurons and glia from some brain regions are more vulnerable to oxidative stress in ischemia/reperfusion, epilepsy, and neurodegenerative disorders than the rest of the brain. Using fluorescent indicators in live cell imaging and confocal microscopy, we have measured the rate of cytosolic and mitochondrial reactive oxygen species production, lipid peroxidation, and glutathione levels in cortex, hippocampus, midbrain, brain stem and cerebellum in acute slices of rat brain. We have found that the basal rate of ROS production is at its highest in brain stem and cerebellum, and that it is mainly generated by glial cells. Activation of neurons and glia by glutamate and ATP led to maximal rates of ROS production in the midbrain compared to the rest of the brain. Mitochondrial ROS had only minor implication to the total ROS production with maximal values in the cortex and minimal in the midbrain. The basal rate of lipid peroxidation was higher in the midbrain and hippocampus, while the GSH level was similar in most brain regions with the lowest level in the midbrain. Thus, the rate of ROS production, lipid peroxidation and the level of GSH vary across brain regions.


Induction of dendritic cell migration upon Toxoplasma gondii infection potentiates parasite dissemination.
The processes leading to systemic dissemination of the obligate intracellular parasite Toxoplasma gondii remain unelucidated. In vitro studies on human and murine dendritic cells (DC) revealed that active invasion of DC by Toxoplasma induces a state of hypermotility in DC, enabling transmigration of infected DC across endothelial cell monolayers in the absence of chemotactic stimuli. Infected DC exhibited upregulation of maturation markers and co-stimulatory molecules. While modulation of cell adhesion molecules CD11/CD18 was similar for Toxoplasma-infected DC and lipopolysaccharide (LPS)-matured DC, Toxoplasma-infected DC did not exhibit upregulation of CD54/ICAM-1. Induction of host cell migration in vitro required live intracellular parasite(s) and was inhibited by uncoupling the Gi-protein signalling pathway with pertussis toxin, but did not depend on CCR5, CCR7 or Toll/interleukin-1 receptor signalling. When migration of Toxoplasma-infected DC was compared with migration of LPS-stimulated DC in vivo, similar or higher numbers of Toxoplasma-infected DC reached the mesenteric lymph nodes and spleen respectively. Adoptive transfer of Toxoplasma-infected DC resulted in more rapid dissemination of parasites to distant organs and in exacerbation of infection compared with inoculation with free parasites. Altogether, these findings show that Toxoplasma is able to subvert the regulation of host cell motility and likely exploits the host's natural pathways of cellular migration for parasite dissemination.


MicroRNA-Mediated Direct Reprogramming of Human Adult Fibroblasts Toward Cardiac Phenotype.
Modulation of microRNA expression holds the promise to achieve direct reprogramming of fibroblasts into cardiomyocyte-like cells as a new strategy for myocardial regeneration after ischemic heart disease. Previous reports have shown that murine fibroblasts can be directly reprogrammed into induced cardiomyocytes (iCMs) by transient transfection with four microRNA mimics (miR-1, 133, 208, and 499, termed "miRcombo"). Hence, study on the effect of miRcombo transfection on adult human cardiac fibroblasts (AHCFs) deserves attention in the perspective of a future clinical translation of the approach. In this brief report, we studied for the first time whether miRcombo transient transfection of AHCFs by non-viral vectors might trigger direct reprogramming of AHCFs into cardiomyocyte-like cells. Initially, efficient miRNA delivery to cells was demonstrated through the use of a commercially available transfection agent (DharmaFECT1). Transient transfection of AHCFs with miRcombo was found to upregulate early cardiac transcription factors after 7 days post-transfection and cardiomyocyte specific marker cTnT after 15 days post-transfection, and to downregulate the expression of fibroblast markers at 15 days post-transfection. The percentage of cTnT-positive cells after 15 days from miRcombo transfection was ∼11%, as evaluated by flow cytometry. Furthermore, a relevant percentage of miRcombo-transfected AHCFs (∼38%) displayed spontaneous calcium transients at 30 days post-transfection. Results evidenced the role of miRcombo transfection on triggering the trans differentiation of AHCFs into iCMs. Although further investigations are needed to achieve iCM maturation, early findings from this study pave the way toward new advanced therapies for human cardiac regeneration.


Atypical SREDA During Wakefulness, NREM and REM Sleep in a Young Teenager: A Diagnostic Challenge.
Subclinical rhythmic electrographic discharges of adult (SREDA) is a rare variant considered to be normal in EEG. It consists of sharp-contoured or sinusoidal waveforms in the theta frequency range (usually 5-7 Hz), occurring in a widespread distribution, often maximal over the parietotemporal regions. SREDA is usually bilateral but could be unilateral (atypical SREDA). Compared with true ictal activities, SREDA has little change in frequency, morphology, and distribution. It has been described in adults and is extremely rare in children/adolescents. There are only 5 cases published in children. We report a case of atypical SREDA in a child that may have occurred in wakefulness, non-rapid eye movement (NREM) sleep, and REM sleep. This finding was initially misdiagnosed as epilepsy. Inpatient video-EEG demonstrated that during periods of SREDA in quiet wakefulness the patient did not have any signs or symptoms with the SREDA pattern; SREDA abated whenever the patient was alerted or if he spontaneously initiated some activities. SREDA with same morphology was noted in NREM and REM sleep. The patient had no true epileptogenic abnormalities and hence antiepileptic medication was discontinued and stopped uneventfully. This case illustrates the importance of recognizing this rare variant, avoiding a misdiagnosis of epilepsy as it occurred in our case.


Long-term study of chronic oral aluminum exposure and spatial working memory in rats.
The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1% aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline.


Conformational changes in orotidine 5'-monophosphate decarboxylase: "remote" residues that stabilize the active conformation.
The structural factors responsible for the extraordinary rate enhancement ( approximately 10(17)) of the reaction catalyzed by orotidine 5'-monophosphate decarboxylase (OMPDC) have not been defined. Catalysis requires a conformational change that closes an active site loop and "clamps" the orotate base proximal to hydrogen-bonded networks that destabilize the substrate and stabilize the intermediate. In the OMPDC from Methanobacter thermoautotrophicus, a "remote" structurally conserved cluster of hydrophobic residues that includes Val 182 in the active site loop is assembled in the closed, catalytically active conformation. Substitution of these residues with Ala decreases k(cat)/K(m) with a minimal effect on k(cat), providing evidence that the cluster stabilizes the closed conformation. The intrinsic binding energies of the 5'-phosphate group of orotidine 5'-monophosphate for the mutant enzymes are similar to that for the wild type, supporting this conclusion.


Ultrathin Porated Elastic Hydrogels As a Biomimetic Basement Membrane for Dual Cell Culture.
The basement membrane is a critical component of cellular bilayers that can vary in stiffness, composition, architecture, and porosity. In vitro studies of endothelial-epithelial bilayers have traditionally relied on permeable support models that enable bilayer culture, but permeable supports are limited in their ability to replicate the diversity of human basement membranes. In contrast, hydrogel models that require chemical synthesis are highly tunable and allow for modifications of both the material stiffness and the biochemical composition via incorporation of biomimetic peptides or proteins. However, traditional hydrogel models are limited in functionality because they lack pores for cell-cell contacts and functional in vitro migration studies. Additionally, due to the thickness of traditional hydrogels, incorporation of pores that span the entire thickness of hydrogels has been challenging. In the present study, we use poly-(ethylene-glycol) (PEG) hydrogels and a novel zinc oxide templating method to address the previous shortcomings of biomimetic hydrogels. As a result, we present an ultrathin, basement membrane-like hydrogel that permits the culture of confluent cellular bilayers on a customizable scaffold with variable pore architectures, mechanical properties, and biochemical composition.


Pain research update from a genetic point of view.
Molecular biology investigates the genetic causes of many diseases. Currently, molecular biology in pain research lags behind the investigations of the molecular basis of mental disorders. A significant challenge in pain genetic research is the fact that pain involves emotional factors. Tools available for pain measurements and interindividual comparisons have been imperfect. Another problem relates to research ethics. Unlike animal studies, there is very limited ability to evoke experimental pain in a group of humans with precisely defined age, sex, medication, and pain experience. Nevertheless, pain investigations at the gene level have commenced. Recent progress in molecular biology has enabled gene expression modulation in animal models using "knockout," "oligo-antisense," and viral vector techniques. These methods enable investigation, at molecular level, as to which of the approximately 30,000 genes of the human genome might be involved in pain mediation, which of these are polymorphic, and which polymorphisms are responsible for interindividual differences in pain perception. Recently, the genetic bases of familial hemiplegic migraine and congenital insensitivity to pain with anhidrosis have been shown. In the last 6 years, genetic pain research has focused on potential gene therapy for patients with chronic pain. Results of these studies are encouraging and potentially applicable to clinical practice in the near future.


Effects of Physical Therapy on a Patient With Lemierre's Syndrome Who Had Atelectasis and Limited Range of Motion in the Neck.
Lemierre's syndrome (LS) is a severe infectious disease that can lead to the formation of neck abscesses and thrombosis. LS may be an indication for surgery; however, there are few reports on the physical therapy approaches used in patients with LS. A male patient in his 20s reported atelectasis and limited range of motion in the neck after resection of a deep neck abscess on the left side of the neck caused by LS. Thrombophlebitis was also observed around the neck lesion, indicating the risk of pulmonary embolism. Physical therapy was initiated with low-load, deep breathing exercises. Additional breathing exercises, such as respiratory assistance and positive pressure loading, were initiated after the administration of anticoagulants. Although the therapeutic intervention was delayed due to the unstable wound with partially resected muscle, it was assumed that the impairment of the range of motion in the neck was unlikely to persist as the patient was young. No critical adverse events were observed, and the range of motion was recovered such that the patient was able to resume playing baseball. The presence of a venous thrombus and inflammation may affect physical therapy; however, careful management of the exercise load could aid in the safe and effective treatment of LS without the incidence of complications, even in the early postoperative period.


Giant Spin Splitting in Chiral Perovskites Based on Local Electrical Field Engineering.
Chiral hybrid organic-inorganic perovskites (chiral HOIPs) present potential spintronic and spin-optoelectronic applications due to their unique spin-related properties. However, the spin physics in chiral HOIPs has rarely been explored by theoretical studies. Here, with first-principles calculations, we investigate the spin characteristics of the Pb-I based chiral HOIPs and propose an effective approach to significantly increase the spin splitting with a halogen-substituted chiral molecule. Compared to the value of 13 meV without halogen substitution, the spin splitting energy can be significantly enhanced to 73, 90, and 105 meV with F, Cl, and Br substitution, respectively. A k·p model Hamiltonian based on a symmetry argument reveals that the halogen substitution enhances the local electric field, inducing distortion of the PbI6 octahedron. Further calculation demonstrates that halogen substitution can strongly modify the electrostatic potential surface of the chiral molecules. This work presents an effective molecular engineering approach to modulate spin splitting of chiral HOIPs, shedding light on the design of spintronic materials.


Life span strategy implementation in verbal learning: size and type of cluster adoption.
Temporal and semantic associative processes during the acquisition of new verbal information undergo various changes across the life span. Temporal order clusters and subjective clusters were monitored during verbal learning trials using the Rey (Auditory Verbal Learning Task) for 1471 participants aged 8-91. Pairs, three-word, and four-word clusters were measured. Subjective clusters were generated at similar frequency across the whole life span. By contrast, a clear inverted-U curve across life span was indicated for temporal clusters. More words were subjectively clustered than clustered by temporal presentation order. The number of words clustered increased across trials, and cluster types showed a different increase profile across trials. The subjective cluster increment was faster and steeper than the temporal cluster increment in most of the age segments. Life span trajectory tendencies in the formation of temporal and semantic associations in recall were interpreted in relation to different frameworks of cognitive life span changes.


High-density lipoprotein induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through sphingosine kinase-2.
High-density lipoprotein (HDL) has a significant cardioprotective effects. HDL induces cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in vascular endothelial cells, which contributes to its anti-atherogenic effects. However, the underlying mechanisms are not fully understood. In the present study, we observed that HDL-stimulated COX-2 expression and PGI-2 production in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. These effects triggered by HDL were inhibited by pertussis toxin (PTX), protein kinase C (PKC) inhibitor GF109203X, and ERK inhibitor PD98059, suggesting that Gαi/Gαo-coupled GPCR, PKC, and ERK pathways are involved in HDL-induced COX-2/PGI-2 activation. More importantly, we found that silencing of sphingosine kinase 2 (SphK-2) also blocked HDL-induced COX-2/PGI-2 activation. In addition, HDL-activated SphK-2 phosphorylation accompanied by increased S1P level in the nucleus. Our ChIP data demonstrated that SphK-2 is associated with CREB at the COX-2 promoter region. Collectively, these results indicate that HDL induces COX-2 expression and PGI-2 release in endothelial cells through activation of PKC, ERK1/2, and SphK-2 pathways. These findings implicate a novel mechanism underlying anti-atherothrombotic effects of HDL.


Association of polymorphic variants of PTPN22, TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads.
Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.


Examining emotional pain among individuals with chronic physical pain: Nomothetic and idiographic approaches.
Emotional pain (i.e., pain affect in response to psychological experiences such as rejection or loss) may be a component of chronic pain syndromes given high co-occurrence with depression and neurobiological overlaps in pain affect resulting from physical and emotional experiences. In the current set of studies, we examined the relationship between emotional and physical pain using both nomothetic (i.e., group-level) and idiographic (i.e., individual-level) approaches. Individuals with chronic pain were recruited from the Washington University Pain Center. First, we assessed the relationship between emotional and physical pain at the group level. Then, three individuals from the group-level study completed ecological momentary assessment four times per day for at least four weeks. We assessed relationships between emotional and physical pain using correlations and dynamic structural equation modeling. Emotional pain severity was significantly positively correlated with physical pain at the group level. However, results from idiographic analyses suggested that one individual did not display a significant correlation between physical and emotional pain, and two individuals displayed correlations larger than expected based on the group-level data. Competing models suggested that emotional and physical pain represented distinct constructs for the individuals studied. These results suggest that emotional pain may be an important component of chronic pain syndromes. However, idiographic models revealed heterogeneity that may have important implications for treatment. Further research is needed to understand whether idiographic relationships between emotional and physical pain can help identify effective treatment targets for individuals with co-occurring emotional and physical symptoms.


CYP2E1*5B, CYP2E1*6, CYP2E1*7B, CYP2E1*2, and CYP2E1*3 allele frequencies in iranian populations.
CYP2E1 encodes an enzyme which is mainly involved in bioactivation of potential carcinogens such as N-nitrosamines. Polymorphisms in the gene have been reported to be associated with cancer. The aim of this study was to evaluate genotype distributions and allele frequencies of five CYP2E1 polymorphisms in Iran. Two hundred healthy individuals of an Iranian population from the southwest were included in this study. PCR-restriction fragment length polymorphism and Tetra-ARMS PCR methods were applied for CYP2E1 genotyping. The allele frequencies for *5B, *6, *7B, *2, and *3 were calculated to be 1.5%, 16%, 28.5%, 0%, and 2.75% respectively. Results of this study showed that no significant differences in genotype and allele frequencies of five single nucleotide polymorphisms with respect to the gender and tribes. The chi-square test showed that the genotype frequencies of CYP2E1*5B were similar to Caucasians, but the distribution of CYP2E1*6 genotypes was similar to Asians. The frequencies of CYP2E1*2 (0%) and CYP2E1*3 (2.75%) alleles were within the range for Caucasians and Orientals. In the case of CYP2E1*7B, the data werelimited. Accordingly, the results were only compared with Europeans and the comparison showed significant differences. In conclusion, ethnic and geographic differences may explain discrepancies in the prevalence of CYP2E1 polymorphisms.


The Epidemiology of Low Back Pain and Injury in Dance: A Systematic Review.
Dance is a physical pursuit that involves loading the spine through repetitive dynamic movements and lifting tasks. As such, low back pain (LBP) and low back injury (LBI) have been identified as common health problems in contemporary and classical ballet dancers. However, clarity regarding the experience of LBP and LBI in dance is lacking. To systematically review and synthesize the epidemiology of LBP and LBI in dance populations. A comprehensive search of 6 electronic databases, back catalogs of dance science-specific journals, and reference lists of relevant articles and a forward citation search were performed. Fifty full-text articles were included in the final systematic review. There was considerable methodological heterogeneity among the included studies. The median (range) point, yearly, and lifetime prevalence of LBP was 27% (17%-39%), 73% (41%-82%), and 50% (17%-88%), respectively. The lower back contributed to 11% (4%-22%) of time loss and 11% (5%-23%) of medical-attention injuries. Dancers are vulnerable to LBP and LBI. The use of definitions that are sensitive to the complexity of LBP and LBI would facilitate improved understanding of the problem within dance, inform health care strategies, and allow for monitoring LBP-specific intervention outcomes. J Orthop Sports Phys Ther 2019;49(4):239-252. Epub 18 Jan 2019. doi:10.2519/jospt.2019.8609.


Analysis of enzymopathies in the human red blood cells by constraint-based stoichiometric modeling approaches.
The human red blood cell (RBC) metabolism is investigated by calculating steady state fluxes using constraint-based stoichiometric modeling approaches. For the normal RBC metabolism, flux balance analysis (FBA) is performed via optimization of various alternative objective functions, and the maximization of production of ATP and NADPH is found to be the primary objective of the RBC metabolism. FBA and two novel approaches, minimization of metabolic adjustment (MOMA) and regulatory on-off minimization (ROOM), which can describe the behavior of the metabolic networks in case of enzymopathies, are applied to observe the relative changes in the flux distribution of the deficient network. The deficiencies in several enzymes in RBC metabolism are investigated and the flux distributions are compared with the non-deficient FBA distribution to elucidate the metabolic changes in response to enzymopathies. It is found that the metabolism is mostly affected by the glucose-6-phosphate dehydrogenase (G6PDH) and phosphoglycerate kinase (PGK) enzymopathies, whereas the effects of the deficiency in DPGM on the metabolism are negligible. These stoichiometric modeling results are found to be in accordance with the experimental findings in the literature related to metabolic behavior of the human red blood cells, showing that human RBC metabolism can be modeled stoichiometrically.


Octadentate Oxine-Armed Bispidine Ligand for Radiopharmaceutical Chemistry.
In this study, we present the synthesis and characterization of the octadentate bispidine ligand, H2bispox2 and its complexes with medicinally useful radiometal nuclides (111In3+ and 177Lu3+), including their X-ray diffraction single crystal structures with the stable isotopes. 111InCl3 radiolabels the ligand quantitatively at ambient conditions ([L] = 10-5 M, room temperature, pH 7 and 15 min) and the in vitro human serum stability assays demonstrated high stability of the [111In(bispox2)]+ complex over 5 days. Moreover, the β - emitter 177Lu radiolabels the ligand at 37 °C in 30 min (pH 8). These initial investigations reveal the potential of the octadentate bispidine ligand H2bispox2 as a useful chelator for 111In and 177Lu-based radiopharmaceuticals.


Dispersive Solid-Phase Extraction Using Microporous Sorbent UiO-66 Coupled to Gas Chromatography-Tandem Mass Spectrometry: A QuEChERS-Type Method for the Determination of Organophosphorus Pesticide Residues in Edible Vegetable Oils without Matrix Interference.
A QuEChERS-type method without matrix interference was designed and developed to determine organophosphorus pesticide residues in edible vegetable oils, based on dispersive solid-phase extraction with cleanup using UiO-66 as sorbent. Microporous UiO-66 directly and selectively adsorbed organophosphorus pesticides and excluded interfering compounds. Clean analytes were obtained by elution and analyzed using gas chromatography-tandem mass spectrometry. The dispersive solid-phase extraction conditions (amount of adsorbent, extraction time, desorption solvent volume, and elution time) were optimized. The limits of detection of the pesticides in vegetable oils were 0.16-1.56 ng/g. Under optimized conditions, the average pesticide recoveries were 81.1-113.5%. The intraday and interday relative standard deviations for analyte recovery were <8.2 and <13.9%, respectively. Thus, the method is reliable and could detect organophosphorus pesticide residues in edible vegetable oils. Furthermore, UiO-66 can be easily recycled and reused at least 10 times, reducing the cost of analysis.


Primary hyperparathyroidism and pancreatitis.
Frequently a causal relationship between hyperparathyroidism (HPT) and pancreatitis has been defended. Bess et al. queried the existence of any causality. A series of 686 patients with surgically confirmed primary hyperparathyroidism (PHPT) was analysed with a coincidence of pancreatitis of 1.5% (n = 10). Three patients had an attack immediately after exploration of the neck, which is more than one would expect after a non-related operation. Although these data are not conclusive, a causal relationship cannot be excluded. It is uncertain whether a parathyrotoxic crisis due to surgical manipulation plays a part. In 27 patients a partial or total thyroidectomy was performed at the time of the parathyroidectomy. None of these patients had a postoperative pancreatitis, which means that in this series the recently postulated protective role of calcitonin cannot be confirmed.


Instructive Role of the Microenvironment in Preventing Renal Fibrosis.
Accumulation of myofibroblasts is a hallmark of renal fibrosis. A significant proportion of myofibroblasts has been reported to originate via endothelial-mesenchymal transition. We initially hypothesized that exposing myofibroblasts to the extract of endothelial progenitor cells (EPCs) could reverse this transition. Indeed, in vitro treatment of transforming growth factor-β1 (TGF-β1)-activated fibroblasts with EPC extract prevented expression of α-smooth muscle actin (α-SMA); however, it did not enhance expression of endothelial markers. In two distinct models of renal fibrosis-unilateral ureteral obstruction and chronic phase of folic acid-induced nephropathy-subcapsular injection of EPC extract to the kidney prevented and reversed accumulation of α-SMA-positive myofibroblasts and reduced fibrosis. Screening the composition of EPC extract for cytokines revealed that it is enriched in leukemia inhibitory factor (LIF) and vascular endothelial growth factor. Only LIF was capable of reducing fibroblast-to-myofibroblast transition of TGF-β1-activated fibroblasts. In vivo subcapsular administration of LIF reduced the number of myofibroblasts and improved the density of peritubular capillaries; however, it did not reduce the degree of fibrosis. A receptor-independent ligand for the gp130/STAT3 pathway, hyper-interleukin-6 (hyper-IL-6), not only induced a robust downstream increase in pluripotency factors Nanog and c-Myc but also exhibited a powerful antifibrotic effect. In conclusion, EPC extract prevented and reversed fibroblast-to-myofibroblast transition and renal fibrosis. The component of EPC extract, LIF, was capable of preventing development of the contractile phenotype of activated fibroblasts but did not eliminate TGF-β1-induced collagen synthesis in cultured fibroblasts and models of renal fibrosis, whereas a receptor-independent gp130/STAT3 agonist, hyper-IL-6, prevented fibrosis. In summary, these studies, through the evolution from EPC extract to LIF and then to hyper-IL-6, demonstrate the instructive role of microenvironmental cues and may provide in the future a facile strategy to prevent and reverse renal fibrosis. Stem Cells Translational Medicine 2017;6:992-1005.


Single-centre experience with autosomal recessive limb-girdle muscular dystrophy: case series and literature review.
Limb-girdle muscular dystrophy (LGMD) is a group of myopathies that lead to progressive muscle weakness, predominantly involving the shoulder and pelvic girdles; it has a heterogeneous genetic etiology, with variation in the prevalence of subtypes according to the ethnic backgrounds and geographic origins of the populations. The aim of the present study was to analyze a series of patients with autosomal recessive LGMD (LGMD-R) to contribute to a better characterization of the disease and to find the relative proportion of the different subtypes in a Southern Brazil cohort. The sample population consisted of 36 patients with LGMD-R. A 9-gene targeted next-generation sequencing panel revealed variants in 23 patients with LGMD (64%), and it identified calpainopathy (LGMD-R1) in 26%, dysferlinopathy (LGMD-R2) in 26%, sarcoglycanopathies (LGMD-R3-R5) in 13%, telethoninopathy (LGMD-R7) in 18%, dystroglicanopathy (LGMD-R9) in 13%, and anoctaminopathy (LGMD-R12) in 4% of the patients. In these 23 patients with LGMD, there were 27 different disease-related variants in the ANO5, CAPN3, DYSF, FKRP, SGCA, SGCB, SGCG, and TCAP genes. There were different causal variants in different exons of these genes, except for the TCAP gene, for which all patients carried the p.Gln53* variant, and the FKRP gene, which showed recurrence of the p.Leu276Ile variant. We analyzed the phenotypic, genotypic and muscle immunohistochemical features of this Southern Brazilian cohort.


Poor results of anterior cruciate ligament repair in adolescence.
Eight adolescents were followed 3-8 years after primary suture of a substance rupture of the anterior cruciate ligament. Only 3 patients had good function, and 5 were unstable. We conclude that the Palmer-Marshall technique should not be used in children and adolescents.


[Biological properties of tick-borne encephalitis strains isolated in different parts of its geographic range].
A comparative study of over 200 tick-borne encephalitis (TBE) virus strains isolated from patients and ticks in different regions varying in the proportion of severe clinical forms of TBE was carried out. The strains were tested for their pathogenicity for white mice, cytopathic and plaque-forming properties as well as for the interferon-inducing capacity in SPEV cells. All the strains were found to be highly neurovirulent for mice, to produce plaques with diameters varying form less than 1 to 10 mm, and to induce interferon production in SPEV cell. Among the TBE virus strains isolated in the Baltic republics and Vologda region there occurred strains causing complete destruction of SPEV cells at later intervals than the prototype strains. No association of the examined properties of TBE virus strains with the region of isolation or with the clinical forms of human disease was established.


Bright-Yellow-Emissive N-Doped Carbon Dots: Preparation, Cellular Imaging, and Bifunctional Sensing.
Fluorescent carbon dots (CDs) have attracted much attention in recent years because of their superior optical and chemical properties, thus demonstrating many potential applications. However, the previously reported CDs mostly show strong emission only in the blue-light region, and the long-wavelength (i.e., yellow- to red-light) emissions are usually very weak. Such a drawback restricts their further applications, particularly in the biology-relevant fields. Herein, a rare example of N-doped CDs that emit bright-yellow fluorescence (i.e., y-CDs) is reported using 1,2,4-triaminobenzene as carbon precursor. The as-prepared y-CDs exhibit not only respectable emission quantum yield and highly optical stabilities but superior biocompatibility and biolabeling potentials. In addition, the y-CDs are found to show an interesting "ON-OFF-ON" three-state emission with the stepwise addition of Ag(+) and cysteine (Cys), indicating potential applications as a bifunctional sensing platform. Thanks to the highly intense emission of y-CDs, the gradual quenching and restoration of their fluorescence with the addition of Ag(+) and further Cys could also be observed with the naked eye. More importantly, the ensemble of the y-CDs and Ag(+) demonstrates practicability for the highly selective and sensitive detection of Cys in human plasma samples with satisfactory results.


Local production of proteins in normal human bronchial secretion.
Concentrations of albumin, IgG, IgA, IgM, alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, transferrin, haptoglobin, and coeruloplasmin were determined by radial immunodiffusion in the blood sera and bronchial washings of 8 patients without clinical, radiologic or bronchoscopic evidence of lung diseases. The local production of the proteins was calculated with a formula used by Deuschl and Johansson for the estimation of local synthesis of bronchial immunoglobulins. The formula was completed by a reduction factor established by the authors, based on their previous investigations. The calculations indicated that the individual proteins were secreted locally in various percentages of the total amount found in the secretion, as follows: IgG, 37%; IgA, 84.5%; transferrin, 44.5%, alpha 1-antitrypsin, 15.2%; coeruloplasmin, 11.3%. Local synthesis of IgM was found only in 3 patients. The alpha 1-acid glycoprotein and the haptoglobin do not seem to be secreted locally by the normal bronchial mucosa; they reach the mucus from blood only, through ultrafiltration.


Possible regulatory roles of promoter g-quadruplexes in cardiac function-related genes - human TnIc as a model.
G-quadruplexes (G4s) are four-stranded DNA secondary structures, which are involved in a diverse range of biological processes. Although the anti-cancer potential of G4s in oncogene promoters has been thoroughly investigated, the functions of promoter G4s in non-cancer-related genes are not well understood. We have explored the possible regulatory roles of promoter G4s in cardiac function-related genes using both computational and a wide range of experimental approaches. According to our bioinformatics results, it was found that potential G4-forming sequences are particularly enriched in the transcription regulatory regions (TRRs) of cardiac function-related genes. Subsequently, the promoter of human cardiac troponin I (TnIc) was chosen as a model, and G4s found in this region were subjected to biophysical characterisations. The chromosome 19 specific minisatellite G4 sequence (MNSG4) and near transcription start site (TSS) G4 sequence (-80 G4) adopt anti-parallel and parallel structures respectively in 100 mM KCl, with stabilities comparable to those of oncogene G4s. It was also found that TnIc G4s act cooperatively as enhancers in gene expression regulation in HEK293 cells, when stabilised by a synthetic G4-binding ligand. This study provides the first evidence of the biological significance of promoter G4s in cardiac function-related genes. The feasibility of using a single ligand to target multiple G4s in a particular gene has also been discussed.


Regulation of lipid disorders by ethanol extracts from Zingiber zerumbet in high-fat diet-induced rats.
The aim of this study was to investigate the antihyperlipidaemic effects of the ethanol extract of Zingiber zerumbet (L) Smith (EEZZ). After being fed a high-fat diet (HFD) for 2weeks, rats were dosed orally with EEZZ (100, 200 or 300mg/kg) or fenofibrate (100mg/kg) once daily for 8weeks. EEZZ (300mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights and plasma lipid levels. EEZZ caused reductions in hepatic triglyceride and cholesterol content, and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes. HFD-induced reductions in the hepatic proteins of peroxisome proliferator-activated receptor (PPAR) α, acyl-CoA oxidase (ACO) and cytochrome P450 isoform 4A1 (CYP4A1) were reversed by EEZZ. These results suggest that EEZZ reduced the accumulation of visceral fat and improved hyperlipidaemia in HFD-fed rats by increasing fatty acid oxidation, an effect which is likely to be mediated via up-regulation of hepatic PPARα.


Warm humidified CO2 insufflation improves pericardial integrity for cardiac surgery: a randomized control study.
Flooding the surgical field with dry cold CO<inf>2</inf> during open-chamber cardiac surgery has been used to mitigate air entrainment into the systemic circulation. However, exposing epithelial surfaces to cold, dry gas causes tissue desiccation. This randomized controlled study was designed to investigate whether the use of humidified warm CO<inf>2</inf> insufflation into the cardiac cavity could reduce pericardial tissue damage and the incidence of micro-emboli when compared to dry cold CO<inf>2</inf> insufflation. Forty adult patients requiring elective open-chamber cardiac surgery were randomized to have either dry cold CO<inf>2</inf> insufflation via a standard catheter or humidified warm CO<inf>2</inf> insufflation via the HumiGard device (Fisher & Paykel Healthcare, Panmure, Auckland, New Zealand). The primary endpoint was biopsied pericardial tissue damage, assessed using electron microscopy. We assessed the percentage of microvilli and mesothelial damage, using a damage severity score (DSS) system. We compared the proportion of patients who had less damage, defined as DSS<2. Secondary endpoints included the severity of micro-emboli, by visual assessment of bubble load on transesophageal echocardiogram; lowest near infrared spectroscopy; total de-airing time; highest cardio-pulmonary bypass sweep speed; hospital length of stay and complications. A higher proportion of patients in the humidified warm CO<inf>2</inf> group displayed conserved microvilli (47% vs. 11%, P=0.03) and preserved mesothelium (42% vs. 5%, P=0.02) compared to the control group. There were no differences in the secondary outcomes. Humidified warm CO<inf>2</inf> insufflation significantly reduced pericardial epithelial damage when compared to dry cold CO<inf>2</inf> insufflation in open-chamber cardiac surgery. Further studies are warranted to investigate its potential clinical benefits.


Complete development of Caryospora bigenetica (Apicomplexa: Eimeriidae) in vitro.
The development of Caryospora bigenetica in vitro is described by light microscopy. Sporozoites from snake-derived oocysts were purified and inoculated onto cultures of primary testicle cells of the cotton rat, cotton rat kidney cells, and human fetal lung cells. Intracellular sporozoites were observed one and two days postinoculation (DPI). Motile, extracellular first-generation merozoites were present 3 DPI, and second-generation merozoites were present 5 DPI. Mature gamonts were observed 9 DPI and developed into unsporulated oocysts by 10 DPI. Oocystes sporulated in vitro, and excystation was observed. Cells that were penetrated by in vitro-produced sporozoites formed caryocysts by 16 DPI. To test infectivity of in vitro-derived stages, merozoites were removed from cultured cells 5 DPI and inoculated intraperitoneally into a mouse; infection resulted. Sporulated oocysts removed from cell cultures 12 DPI produced facial swelling in an orally inoculated cotton rat.


Effects of home parenteral nutrition on resting metabolic rate: a case study.
Resting metabolic rate (RMR) measurement by indirect calorimetry is often used in acute care; however, indirect calorimetry is rarely performed on patients treated at home with complex therapies such as home parenteral nutrition (HPN). A new hand-held indirect calorimeter is now available to measure RMR and oxygen consumption (VO2). This is a case study of a 35-year-old female who had her RMR and VO2 measured at rest while receiving cyclic HPN and while off of HPN over a period of 8 days. Results indicate that her RMR was higher while receiving HPN. Measuring RMR in patients receiving HPN may be very beneficial to avoid underfeeding and overfeeding. It will be important for the clinician to note if the patient is receiving HPN at the time of the measurement because RMR may be affected by HPN infusion.


Understanding the post-surgical bariatric experiences of patients two or more years after surgery.
In Canada, one year after bariatric surgery follow-up appointments become less frequent and surgical recipients must cope with weight management more independently. Up to 50% of patients experience weight regain by two years post-surgery. Understanding the lived experiences of those who have gone through the bariatric process may shed light on what is needed to support others moving forward. Therefore, the purpose of the study was to gain an understanding of the physical, psychological, social, and clinic-related experiences of individuals who have undergone bariatric surgery at least two years prior. The purpose of the study was to gain an understanding of the physical, psychological, social, and clinic-related experiences of individuals who have undergone bariatric surgery at least two years prior. In-depth, individual semi-structured interviews lasting approximately 60 min were conducted. Interviews were transcribed verbatim and inductive content analysis was used to identify emerging themes. Methods were employed throughout to support data trustworthiness. Participants (n = 28; 21 female) were primarily middle-aged (mean: 49.7 ± 12.7 years old), Caucasian (71%), and completed bariatric surgery more than three years. The data fell naturally into four primary themes, namely physical changes and challenges, psychological experiences, social functioning and support, and clinic-related experiences and reflections. Generally, participants described positive improvements in their physical, psychological, and social state since surgery. However, concerns pertaining to several unanticipated outcomes of the surgery were underscored and informed the recommendations for other patients to be prepared to relearn about ones' body, utilize the support services available, and be aware that social relationships may change and/or require tending. Participants' insights can be used to help others meet with long-term success post-bariatric surgery.


Pharmacokinetics of clonazepam in the dog.
After i.v. administration of 0.2 mg/kg clonazepam to dogs, plasma concentrations followed partly a biexponential and partly a monoexponential decline, the terminal elimination half-life (t0.5 beta or t0.5) being 1.4 +/- 0.3 hr. Over the dose range from 0.1 to 0.5 mg/kg the elimination rate was dose-dependent. At the highest dose level, one dog showed signs of a saturation kinetics. After oral administration absorption was rapid, but bioavailability poor and highly variable (20-60%). In spite of the high elimination rate in the single dose studies, clonazepam plasma concentrations in the range known as "therapeutic" in man could be maintained in subacute studies (1 week) by dosing 0.5 mg/kg b.i.d. or t.i.d. This is most likely explained by a saturation of metabolic inactivation and makes the dog a useful model for man when the drug is given continuously. Protein binding averaged 82% and is thus similar to man. Clonazepam passed the blood/CSF barrier rapidly (P = 0.217 min-1) so that steady state conditions were reached within 10-20 min.


Suppressive effects of tenofovir disoproxil fumarate, an antiretroviral prodrug, on mineralization and type II and type III sodium-dependent phosphate transporters expression in primary human osteoblasts.
Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug commonly used for the management of Human Immunodeficiency Virus (HIV) in highly active antiretroviral therapy (HAART) and of chronic Hepatitis B Virus (HBV) infections. Long-term TDF-treated subjects present decrease of bone mineral density and rarely severe osteomalacia. Although these adverse effects have been attributed to the impaired proximal tubule function, a possible direct involvement of TDF on osteoblasts should be taken into account. The aim of this study was to evaluate whether sodium phosphate transporters NPT2A (sodium-dependent phosphate transport protein 2A), NPT2C (sodium-dependent phosphate transport protein 2C), PIT1 (sodium-dependent phosphate transporter 1), and PIT2 (sodium-dependent phosphate transporter 2) were expressed in primary human osteoblasts (HOBs), whether their expression was related to HOBs differentiation and whether TDF could affect mineralization and gene expression. PIT1 and PIT2 were expressed under proliferating conditions and increased after induction of mineralization, while NPT2A and NPT2C were almost undetectable. In HOBs TDF exposure induced a significant dose-dependent decrease in mineralization. Moreover, TDF caused a reduction of COL1A1 and of ATF4 expression in differentiated HOBs. In summary, HOBs do not express NPT2A and NPT2C and do express PIT1 and PIT2, suggesting a role of these two latter in human osteoblast mineralization. TDF impairs osteoblast mineralization, confirming a direct negative effect on bone. Therefore, in clinical practice, bone damage must be suspected and evaluated also in patients receiving TDF without kidney function alterations.


Formation of a stable complex between the human immunodeficiency virus integrase protein and viral DNA.
The integrase (IN) protein of the human immunodeficiency virus (HIV) mediates two distinct reactions: (i) specific removal of two nucleotides from the 3' ends of the viral DNA and (ii) integration of the viral DNA into target DNA. Although IN discriminates between specific (viral) DNA and nonspecific DNA in physical in vitro assays, a sequence-specific DNA-binding domain could not be identified in the protein. A nonspecific DNA-binding domain, however, was found at the C terminus of the protein. We examined the DNA-binding characteristics of HIV-1 IN, and found that a stable complex of IN and viral DNA is formed in the presence of Mn2+. The IN-viral DNA complex is resistant to challenge by an excess of competitor DNA. Stable binding of IN to the viral DNA requires that the protein contains an intact N-terminal domain and active site (in the central region of the protein), in addition to the C-terminal DNA-binding domain.


[Geriatric medicine].
In 2016, consequences, contributing factors, and prevention of inappropriate drug prescribing were investigated. Two studies lift the veil on unexplained falls and syncope. A meta-analysis questions the need to adapting transfusion's threshold to comorbidities, and another one the performance of screening for swallowing disorders. The Framingham Heart Study reports the declining of the incidence of vascular dementia. The role played by microbleeds in cognitive deterioration was investigated and aducanumab showed encouraging effect in Alzheimer's disease. When vaccination against influenza for health workers in nursing home was challenged by a meta-analysis this recommendation must be followed. Vaccines against shingles are effective and safe, and a study confirms the efficacy of the HZ7su among 70+.


Perceptual similarity between piano notes: Simulations with a template-based perception model.
In this paper, the auditory model developed by Dau, Kollmeier, and Kohlrausch [(1997). J. Acoust. Soc. Am. 102, 2892-2905] was used to simulate the perceptual similarity between complex sounds. As complex sounds, a set of piano recordings was used, whose perceptual similarity has recently been measured by Osses, Kohlrausch, and Chaigne [(2019). J. Acoust. Soc. Am. 146, 1024-1035] using a three-alternative forced-choice discrimination task in noise. To simulate this discrimination task, the auditory model required a new back-end stage, the central processor, which is preceded by several processing stages that are to a greater or lesser extent inspired by physiological aspects of the normal-hearing system. Therefore, a comprehensive review of the model parameters as used in the literature is given, indicating the fixed set of parameter values that is used in all simulations. Due to the perceptual relevance of the piano note onsets, this review includes an in-depth description of the auditory adaptation stage, the adaptation loops. A moderate to high correlation was found between the simulation results and existing experimental data.


Recent advances in biology: intercellular communication and quorum sensing in micro-organisms.
N-acyl-L-homoserine lactones are involved as intercellular signalling agents controlling a wide range of physiological responses in Gram-negative bacteria. They function especially in vibrios, pseudomonads and erwinias as well as in Rhizobium and Agrobacterium spp, particularly where the bacteria are in symbiotic or parasitic relationships with higher organisms. Several Gram-negatives, such as Escherichia coli, do not, however, appear to produce or respond to AHLs and they may have other intercellular signalling molecules. The present review reports that several stress related responses in E. coli can be induced by supernatant fluids from cultures which have already induced the response. In some cases at least, the active agents in the supernatant fluids are proteins rather than AHLs.


How Automatically Do Readers Infer Fictional Characters' Emotional States?
We propose that reading stories, such as a narrative about a character who takes money from a store where his best friend works and who later learns that his best friend has been fired, stimulates readers to activate the knowledge of how the character feels when he finds out that his best friend has been fired from a job for something he did. In other words, we propose that readers infer fictional character's emotional states. In this article, we first review two series of laboratory experiments (Gernsbacher, Goldsmith, & Robertson, 1992; Gernsbacher & Robertson, 1992) that empirically tested this hypothesis by measuring participants' reading times to target sentences that contained emotion words that matched (e.g., guilt) or mismatched (e.g., pride) the implied emotional state. We then present a third series of laboratory experiments that tested how automatically such knowledge is activated by using a divided-attention task (tone-identification, per-sentence memory load, or cumulative memory load) and by comparing target-sentence reading time when the emotional state is explicitly mentioned versus only implicit.


Recruiting faith- and non-faith-based schools, adolescents and parents to a cluster randomised sexual-health trial: experiences, challenges and lessons from the mixed-methods Jack Feasibility Trial.
The move toward evidence-based education has led to increasing numbers of randomised trials in schools. However, the literature on recruitment to non-clinical trials is relatively underdeveloped, when compared to that of clinical trials. Recruitment to school-based randomised trials is, however, challenging, even more so when the focus of the study is a sensitive issue such as sexual health. This article reflects on the challenges of recruiting post-primary schools, adolescent pupils and parents to a cluster randomised feasibility trial of a sexual-health intervention, and the strategies employed to address them. The Jack Trial was funded by the UK National Institute for Health Research. It comprised a feasibility study of an interactive film-based sexual-health intervention entitled If I Were Jack, recruiting over 800 adolescents from eight socio-demographically diverse post-primary schools in Northern Ireland. It aimed to determine the facilitators and barriers to recruitment and retention to a school-based sexual-health trial and identify optimal multi-level strategies for an effectiveness study. As part of an embedded process evaluation, we conducted semi-structured interviews and focus groups with principals, vice-principals, teachers, pupils and parents recruited to the study as well as classroom observations and a parents' survey. With reference to social learning theory, we identified a number of individual-, behavioural- and environmental-level factors that influenced recruitment. Commonly identified facilitators included perceptions of the relevance and potential benefit of the intervention to adolescents, the credibility of the organisation and individuals running the study, support offered by trial staff, and financial incentives. Key barriers were prior commitment to other research, lack of time and resources, and perceptions that the intervention was incompatible with pupil or parent needs or the school ethos. Reflecting on the methodological challenges of recruiting to a school-based sexual-health feasibility trial, this study highlights pertinent general and trial-specific facilitators and barriers to recruitment, which will prove useful for future trials with schools, adolescent pupils and parents. ISRCTN 11632300 . Registered on 19 December 2014.


Novel imaging enhancements in capsule endoscopy.
Video capsule endoscopy that was launched 10 years ago has become a first-line procedure for examining the small bowel. The most common indications for capsule endoscopy are obscure gastrointestinal bleeding, Crohn's disease, polyposis syndromes, and evaluation of patients with complicated celiac disease. The ideal capsule should improve the quality of the image and have a faster frame rate than the currently available one. There should be a therapeutic capsule capable of performing a biopsy, aspirating fluid, delivering drugs, and measuring the motility of the small bowel wall. Another major leap forward would be the capability of remote control of capsule's movement in order to navigate it to reach designated anatomical areas for carrying out a variety of therapeutic options. Technology for improving the capability of the future generation capsules almost within grasp and it would not be surprising to witness the realization of these giant steps within the coming decade. In this review we will focus on the current clinical applications of capsule endoscopy for imaging of the small bowel and colon and will additionally give an outlook on future concepts and developments of capsule endoscopy.


Computed tomography standardization.
Since the body of literature on computed tomography is growing rapidly, some universally acceptable expression for attenuation values should be adopted. In addition, there is controversy as to the manner of viewing CT scans of the torso: some prefer viewing from below, in the same orientation as conventional radiographs, while the authors prefer viewing from above, consistent with most cross-section anatomy texts and current cranial and body CT displays.


Asymmetric Lewis acid catalysis directed by octahedral rhodium centrochirality.
A rhodium-based asymmetric catalyst is introduced which derives its optical activity from octahedral centrochirality. Besides providing the exclusive source of chirality, the rhodium center serves as a Lewis acid by activating 2-acyl imidazoles through two point binding and enabling a very effective asymmetric induction mediated by the propeller-like C2-symmetrical ligand sphere. Applications to asymmetric Michael additions (electrophile activation) as well as asymmetric α-aminations (nucleophile activation) are disclosed, for which the rhodium catalyst is found to be overall superior to its iridium congener. Due to its straightforward proline-mediated synthesis, high catalytic activity (catalyst loadings down to 0.1 mol%), and tolerance towards moisture and air, this novel class of chiral-at-rhodium catalysts will likely to become of widespread use as chiral Lewis acid catalysts for a large variety of asymmetric transformations.


Morphological changes in spleen, bone marrow and blood of rats after continuous gamma irradiation and indomethacin treatment.
A possibility of modifying the radiation damage of haematopoiesis by indomethacin administered during continuous irradiation was followed. Indomethacin was given in drinking water (average dose of 740.7 micrograms/kg per day) within 7-days continuous irradiation with gamma rays (a daily dose rate of 2.055 Gy, total accumulated dose of 14.385 Gy). Under the given conditions no marked protective effect of indomethacin on haematopoiesis was found with the exception of mild stimulation of myelopoiesis and an increased release of developmentally younger cells of myeloid and erythroid series to the peripheral blood as well.


Sampling survey of disability in 0-6 year-old children in China.
To investigate the current status of disabled children and prevalence of disabilities in children aged 0-6 years and their risk factors, and to provide scientific evidence for making relevant policies for disabled children. In a community-based cross-sectional study, multi-phase, stratified, unequal proportional and cluster sampling was adopted to survey 60 124 children aged 0-6 years. All the investigated children were screened for disabilities, and those with positive screening tests were further diagnosed by various specialties. A total of 819 children were diagnosed as disabled with an overall prevalence of 1.362%, 0.155% for hearing disability, 0.160% for visual disability, 0.931% for intelligent disability, 0.424% for limb disability, and 0.101% for mental disability. Prevalence of disability in children was higher in rural areas, and in families with two or more children, low educational level or in divorced families. The prevalence of disability can be reduced by economic development, improvement of health care and quality of population, as well as harmonious familial relationship, early prevention of disability, and preschool education for disabled children.


Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents.
Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.


Evaluation of an enzyme immunoassay based on sonicate supernatant antigens of Mycobacterium w for immunodiagnosis of leprosy.
An enzyme immunoassay (EIA) based on sonicate supernatant antigens of a cultivable, atypical bacterium, Mycobacterium w (M. w), for immunodiagnosis of leprosy is described. M. w was selected after screening of sonicate supernatant antigens of seven cultivable mycobacteria in EIA. The results of the assay were compared with that of EIA using phenolic glycolipid-I (PGL-I). The M. w assay was more sensitive than PGL-I based EIA, for detection of leprosy patients of all categories, including long term treated patients with low bacterial load. The M. w assay was highly sensitive (93.49%) for detection of active LL patients, and the difference in the positivity of the two assays for LL patients was statistically significant (p 0.05). The combined positivity of the assays with M. w and PGL-I for LL was higher than that with either antigen alone. M. w assay, in addition, was also highly sensitive for detection of patients with active pulmonary tuberculosis.


[Serodiagnosis of the infection caused by the influenza C virus using immunoenzyme analysis].
Serological studies employing enzyme immunoassay and HI tests suggest that influenza C viruses not only play an etiological role in respiratory diseases but can also take part in exacerbation of a number of chronic diseases predominantly affecting children.


[Mechanism of acquiring drug-resistance genes in pathogenic bacteria].
Pathogenic bacteria acquire resistance to chemotherapeutic agents by mutational events in the intrinsic genes or by incorporating foreign resistance genes. The resistance genes to various drugs were transferred among bacteria by transformation with free DNA, phage-mediated transduction, or cell to cell conjugation. Plasmids are capable of self-replication and self-transfer by conjugation. Drug-resistance genes are incorporated into plasmids by transposable elements, transposons. Several kinds of transposons carrying resistance genes to various drugs, or some transposons carrying multiresistance genes, are mobile among genetic elements and confer multiresistance on pathogenic bacteria. There is a specific element, integron, on transposons or plasmids. The integron has the gene and the site for incorporating resistance genes as cassettes and allows expression of the genes.


Sleep quality and associated factors amongst Brazilian physiotherapists during the COVID-19 pandemic.
To investigate the prevalence of sleep problems and associated factors among Brazilian physiotherapists during the Coronavirus Disease 2019 (COVID-19) pandemic. Cross-sectional online survey of physiotherapists in Brazil. Sociodemographic data, sleep quality (Pittsburgh Sleep Quality Index - PSQI) and symptoms of anxiety, depression and stress (21-item Depression, Anxiety and Stress Scale - DASS-21) were assessed. 342 physiotherapists responded the survey (18% male, median age 31 [27-38] years, 78% frontline workers). The three biggest fears reported by frontline physiotherapists were fear of being infected (48%), shortage of personal protective equipment (24%) and the severity of the disease (16%). The overall prevalence of poor sleep quality was 86%. Frontline physiotherapists showed worse scores on all PSQI components but sleep latency, disturbances and daytime dysfunction (p ≤ 0.037). Symptoms of anxiety and stress were highest in frontline workers (p ≤ 0.032). Being a frontline worker was independently associated with a poor sleep quality (odds ratio [95% CI] 1.99 [1.01 to 3.93]). Poor sleep quality was highly prevalent among Brazilian physiotherapists during the COVID-19 outbreak. Frontline physiotherapists showed worse sleep quality and more symptoms of anxiety and stress than non-frontline physiotherapists. Being at the frontline was associated with a higher chance of poor sleep quality.


Immunologic detection of condylomata acuminata-specific antigens.
A rabbit serum fraction was prepared which contained antibody specific for unique antigen(s) found in human condylomata acuminata tissue but not in other human papillomatous or normal tissues. Indirect immunofluorescent staining of cryostat sections of human tissues demonstrated an intense nuclear fluorescence in cells of the prickle cell layer of condylomata acuminata sections. Nuclear fluorescence was not apparent in cells in the basal or dermal layers. The serum fraction did not elicit nuclear fluorescence in epithelial cells of tissue from human vulva, human foreskin, juvenile hand wart, plantar wart, or squamous cell papilloma of the cervix. This demonstration of antigens unique to epithelial cells of condylomata acuminata may prove useful in the often difficult diagnosis of cervical condylomata.


Approximation of continuous fermentation by semicontinuous cultures.
Semicontinuous fermentations, in which a fraction of a culture is replaced with fresh media at regular intervals, have been previously used as a means of approximating continuous growth. In most cases deviations from continuous operation were erroneously estimated using Fencl's model, which is only valid when the specific growth rate is independent of the substrate concentration. An approach to modeling Semicontinuous growth that incorporates the same kinetics followed in batch and continuous growth was developed and tested for Monod's expression for the specific growth rate. A dimensionless form of the model was used to simulate Semicontinuous fermentations for comparison to continuous growth. Differences between Semicontinuous and continuous growth were found to depend on three dimensionless variables: feed concentration, replacement rate, and time between replacements. For given values of the dimensionless feed concentration and time between replacements, a range of dimensionless replacement rates can be determined over which semi-continuous cultures are approximately continuous.


Bosutinib: a second-generation tyrosine kinase inhibitor for chronic myelogenous leukemia.
To review clinical trials and main characteristics of bosutinib, a second-generation tyrosine kinase inhibitor (TKI) for treatment of chronic myelogenous leukemia (CML). Pertinent data were identified through a search of PubMed (January 1990-April 2013) using the primary search terms SKI-606, bosutinib, and CML. Additionally, preliminary reports published in abstract form by the American Society of Clinical Oncology and American Society of Hematology (January 1990-April 2013) were screened for inclusion. Clinical Phase 1, 2, and 3 studies reported in English evaluating the safety and efficacy of bosutinib in patients with CML were reviewed. Bosutinib is a TKI of the breakpoint cluster region/Abelson murine leukemia (BCR-ABL) gene approved by the Food and Drug Administration on September 4, 2012, for second-line treatment of chronic phase, accelerated phase, and blast phase CML. In the second-line setting, bosutinib is effective in some patients with CML resistant or intolerant to imatinib, dasatinib, and/or nilotinib, but it is not effective in patients whose disease expresses the T315I point mutation in BCR-ABL. Bosutinib also has been compared with imatinib, the standard first-line treatment, in 502 patients with newly diagnosed chronic phase CML in a Phase 3 trial. Complete cytogenetic response at 12 months, the primary efficacy end point, is similar between bosutinib and imatinib (p = 0.601); therefore, bosutinib is not indicated in the first-line setting. Common adverse events associated with bosutinib include diarrhea, nausea, and vomiting. Grade 3 and 4 adverse events reported in at least 5% of bosutinib-treated patients include elevated serum lipase and liver aminotransferases, anemia, thrombocytopenia, neutropenia, and diarrhea. Currently available clinical trials suggest that bosutinib is generally a safe and effective treatment option for patients with CML who have failed first-line TKIs and who do not express the T315I mutation; however, tolerability may be problematic for some patients.


Prinzmetal's variant angina.
Although the prevalence of variant angina pectoris is unknown, it appears to be substantially less common than typical, exertional angina and unstable angina at rest. The patient with variant angina typically complains of a pressure-like, squeezing retrosternal chest discomfort of several minutes duration. The diagnosis is secured by the occurrence of transient ST-segment elevation in association with chest pain, both of which resolve spontaneously or with nitroglycerin. After the diagnosis is made, the patient usually becomes symptom-free on calcium-channel blockers with or without long-acting nitrates. Although the long-term survival of these patients is excellent, an occasional individual with variant angina sustains a complication, most often myocardial infarction, a life-threatening arrhythmia, or sudden cardiac death.


Modeling the Kinetics of the Permeation of Antibacterial Agents into Growing Bacteria and Its Interplay with Efflux.
A mathematical model of the passive permeation of a novel solute into bacteria that explicitly accounts for intracellular dilution through growth was developed. A bacterial cell envelope permeability coefficient of approximately >10-8 cm2 · s-1 is predicted to ensure passive permeation into rapidly replicating bacterial cells. The relative importance of the permeability coefficients of the cytoplasmic and outer membranes of Gram-negative bacteria in determining the overall envelope permeability coefficient was analyzed quantitatively. A mathematical description of the balance between passive influx and active efflux was also developed and shows that bacterial expansion through growth can usually be neglected for compounds likely to be prepared in antibacterial drug discovery programs and the balance between passive inward permeation and active outwardly directed efflux predominates. A new parameter, efflux efficiency (η, where η is equal to k/P, in which k is the rate coefficient for the efflux pump and P is the permeability coefficient for the membrane across which the pump acts), is introduced, and the consequences for the efficiency of efflux pumping by a single pump, two pumps in parallel across either the cytoplasmic or the outer membrane, and two pumps in series, one across the cytoplasmic membrane and one across the outer membrane of Gram-negative bacteria, are explored. The results, showing additive efficiency for two pumps acting across a single membrane and multiplicative efficiency for two pumps acting in series across the cytoplasmic and outer membranes, can be quantitatively related to the ratios between MICs measured against pump-sufficient and pump deletion strains and agree with those of previous experimental and theoretical studies.


Differences in Opioid-Related Deaths in the Appalachian Region in 2018-2021 by State and Rural-Urban County Classification.
Introduction The rapid increase in opioid-related deaths since the early 2000s is a major US public health concern. This crisis has transitioned from pharmaceuticals to illicit synthetic opioids and street mixtures. This epidemic has significantly impacted the Appalachian region. This study investigated opioid-related death rates among the Appalachian states, focusing on death rates among urban, suburban, and rural counties. Methods Opioid-related death data from 2018-2021 for the 13 states that make up the Appalachian region were collected using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. Opioid analgesic overdose deaths were defined using ICD-10 codes X40-X44, X60-X64, and Y10-Y14, where an opioid analgesic was also coded (T40.2-T40.4). US census data was used to calculate opioid-related death rates by population. Counties were classified as urban, suburban, and rural using the 2013 Rural-Urban Continuum Codes from the US Department of Agriculture. The data were descriptively broken down and reported as either percentages or means. Results Of the opioid-related deaths between 2018 and 2021, 498 counties were identified in the 13 Appalachian states as having reported at least 10 opioid-related deaths per year. Among these counties, 337 (67.7%) were classified as urban/metropolitan, 138 (27.7%) as suburban, and 23 (4.62%) as rural. Overall, mean opioid-related deaths by populations per 1000 among all counties were 0.24 in 2018, 0.24 in 2019, 0.33 in 2020, and 0.38 in 2021. For urban/metropolitan counties, opioid-related deaths per 1000 gradually increased from 0.23 in 2018 to 0.35 in 2021. For suburban counties, the mean opioid-related deaths per 1000 increased from 0.25 in 2018 to 0.43 in 2021. For rural counties, the mean opioid-related deaths per 1000 increased from 0.43 in 2018 to 0.62 in 2021. Conclusion Opioid-related deaths, on average and by population, have risen steadily in the Appalachian region from 2018-2021 across all geographic areas (urban/metropolitan, suburban, rural). Rural counties consistently showed the highest opioid-related deaths per population compared to urban/metropolitan and suburban areas. Addressing social determinants of health such as income level, education level, healthcare access, and community-based interventions is crucial in combating this issue. Community and health system interventions must be implemented to combat the disproportionately high rate of opioid prescribing in the Appalachian region.


Simulation of dynamic monitoring for intracerebral hemorrhage based on magnetic induction phase shift technology.
Intracerebral hemorrhage (ICH) is a common and severe brain disease associated with high mortality and morbidity. Accurate measurement of the ICH area is an essential indicator for doctors to determine whether a surgical operation is necessary. However, although currently used clinical detection methods, such as computed tomography (CT) and magnetic resonance imaging (MRI), provide high-quality images, they may have limitations such as high costs, large equipment size, and radiation exposure to the human body in the case of CT. It makes long-term bedside monitoring infeasible. This paper presents a dynamic monitoring method for ICH areas based on magnetic induction. This study investigates the influence of the bleeding area and the position of ICH on the phase difference at the detection point near the area to be measured. The study applies a neural network algorithm to predict the bleeding area using the phase difference data received by the detection coil as the network input and the bleeding area as the network output. The relative error between the predicted and actual values of the neural network is calculated, and the error of each group of data is less than 4%, which confirms the feasibility of this method for detecting and even trend monitoring of the ICH area.


Skeletal abnormalities in Refsum's disease (heredopathia atactica polyneuritiformis).
Refsum's disease is a rare inborn error of phytanic acid metabolism in which skeletal abnormalities are part of the clinical syndrome. The reported incidence of bone changes in patients with Refsum's disease varies widely and reflects the small series published to date. An analysis of the skeletal abnormalities of the largest series of patients in the world is presented.


Antisense depletion of death-associated protein kinase promotes apoptosis.
Death-associated protein kinases (DAPK) are serine/threonine protein kinases that have an important role in regulating cell death. In this study two antisense approaches were employed to down-regulate expression of the endogenous DAPK-alpha and DAPK-beta proteins. Transient expression of an antisense DAPK cDNA or antisense morpholino oligonucleotides in HeLa, 3T3, or primary human vascular smooth muscle cells demonstrate that decreased DAPK expression promotes a spontaneous, caspase-mediated apoptosis as evidenced by increased activities of caspases-3 and -9. Clonal HeLa cell lines with attenuated levels of DAPK expression, obtained following selection in the presence of antisense DAPK cDNA, are more sensitive to tumor necrosis factor-induced caspase-mediated apoptosis, and their sensitivity is inversely related to DAPK expression. In contrast, HeLa cells with reduced DAPK expression are moderately resistant to cell death induced by interferon-gamma. This finding is consistent with previous studies showing that DAPK has a role in promoting caspase-independent cell death. Together, these studies demonstrate that the cellular activities of DAPK are critical for antagonizing caspase-dependent apoptosis to promote cell survival under normal cell growth conditions.


P-wave morphology is unaffected by training-induced biatrial dilatation: a prospective, longitudinal study in healthy athletes.
Biatrial enlargement is common in athletes with a further increase occurring after training. P-wave morphology seems to be unaffected by atrial size, however longitudinal data are not available. This study aimed to prospectively investigate whether exercise-induced increase in biatrial size corresponds to electrical changes on 12-lead ECG. Thirty-five athletes were evaluated at the beginning of the training and after 6 months by ECG and standard and speckle-tracking echocardiography. Twenty-three sedentary subjects served as controls. Athletes had greater left atrial (LA) and right atrial (RA) size compared with controls (20.7 ± 4.7 vs. 27.1 ± 6.6 and 17.3 ± 3.8 vs. 23.4 ± 6.3 mL/m2, respectively, p < 0.0001). After 6 months, a further increase in LA and RA size was observed (p < 0.0001 and p = 0.002, respectively). Neither athletes nor controls fulfilled the ECG criteria for RA enlargement and no differences were found for LA enlargement criteria between athletes and controls (2/35, 6% vs. 0/23, 0%, p = 0.23). This percentage remained unchanged after training. Biatrial stiffness remained normal in athletes also after training. Training causes an increase in biatrial volumes, with normal filling pressures and normal stiffness. These changes in atrial morphology are not associated with respective electrical changes, suggesting that P-wave morphology is unaffected by training-induced biatrial dilatation in young healthy athletes.


Microarray experimental design: power and sample size considerations.
Gene expression analysis using high-throughput microarray technology has become a powerful approach to study systems biology. The exponential growth in microarray experiments has spawned a number of investigations into the reliability and reproducibility of this type of data. However, the sample size requirements necessary to obtain statistically significant results has not had as much attention. We report here statistical methods for the determination of the sufficient number of subjects necessary to minimize the false discovery rate while maintaining high power to detect differentially expressed genes. Two experimental designs were considered: 1) a comparison between two groups at a single time point, and 2) a comparison of two experimental groups with sequential time points. Computer programs are available for the methods discussed in this paper and are adaptable to more complicated situations.