Reliability and validity of the Upper Limb Physician's Rating Scale in children with cerebral palsy.
The Upper Limb Physician's Rating Scale (ULPRS) is a tool that assesses movement quality of the upper limbs. It is used as an outcome measure after botulinum toxin type A injection in children with cerebral palsy (CP). This study aimed to investigate the reliability and validity of the ULPRS in children with spastic CP. Thirty children with spastic CP (M:F=17:13) aged 5 to 13 years old were recruited. The ULPRS was scored based on recorded videotapes by four physicians on two separate occasions. The Melbourne Assessment of Unilateral Upper Limb Function (MUUL) was scored by an occupational therapist. Intraclass correlation coefficients (ICCs), 95% confidence intervals and weighted kappa statistics were calculated for the scores of ULPRS to obtain interrater and intrarater reliability. The relationship between ULPRS and MUUL was assessed using Pearson correlation coefficients. The ICCs for the total ULPRS scores were 0.94 between raters and 0.99 to 1.00 within raters. The weighted kappa statistics for subitem scores for the ULPRS ranged from 0.67 to 1.00 within raters and from 0.46 to 0.86 between raters. The relationship between ULPRS and MUUL was strong (Pearson correlation coefficient=0.751; p<0.05). The results demonstrated the high reliability of the total ULPRS score within and between raters. A significant concurrent validity between ULPRS and MUUL also supports the clinical utility of the ULPRS as an outcome measure of spastic upper limb in children with CP.


Phase diagram of poly(methyl-p-tolyl-siloxane): a temperature- and pressure-dependent dielectric spectroscopy investigation.
The dynamics of poly(methyl-p-tolyl-siloxane) (PMpTS) have been studied as a function of temperature (in the range from 143 to 413 K), pressure (0.1-300 MPa), frequency (10(-2)-10(6) Hz), and molecular weight. Independent pressure-volume-temperature (PVT) measurements (for temperatures in the range from 293 to 393 K and for pressures in the range from 10 to 200 MPa) allowed calculation of the relevant thermodynamic parameters. Two dielectrically active channels of relaxation were found, one in the glassy state reflecting a localized motion of the substituted phenyl ring and one at higher temperatures reflecting the usual segmental (alpha) relaxation. In PMpTS, there are two dominant control variables; both density and temperature have a strong influence on the segmental dynamics. The PVT results allowed us to follow distinct thermodynamic (T,P) paths resulting in states bearing the same density. These isodensity states are characterized by an apparent activation energy (Q(V)) that is not very different from the corresponding activation energy under isobaric conditions (Q(V)/Q(P) approximately 0.55) reflecting the importance of thermal effects. At temperatures above the glass temperature (T(g)), strong orientation correlations exist above some critical pressure that depends on temperature. This state extends from T(g) up to 1.08 T(g) and separates a normal liquid at higher temperatures from an oriented liquid at lower temperatures. Using the "phase diagram" we discuss separately the influence of the temperature and density on the PMpTS dynamics.


Remodeling Tumor-Associated Macrophages and Neovascularization Overcomes EGFRT790M -Associated Drug Resistance by PD-L1 Nanobody-Mediated Codelivery.
Precision medicine has made a significant breakthrough in the past decade. The most representative success is the molecular targeting therapy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small-cell lung cancer (NSCLC) with oncogenic drivers, approved by the US Food and Drug Administration (FDA) as first-line therapeutics for substituting chemotherapy. However, the rapidly developed TKI resistance invariably leads to unsustainable treatment. For example, gefitinib is the first choice for advanced NSCLC with EGFR mutation, but most patients would soon develop secondary EGFRT790M mutation and acquire gefitinib resistance. TKI resistance is a severe emergency issue to be solved in NSCLC, but there are a few investigations of nanomedicine reported to address this pressing problem. To overcome EGFRT790M -associated drug resistance, a novel delivery and therapeutic strategy is developed. A PD-L1 nanobody is identified, and first used as a targeting ligand for liposomal codelivery. It is found that simvastatin/gefitinib combination nanomedicine can remodel the tumor microenvironment (e.g., neovascularization regulation, M2-macrophage repolarization, and innate immunity), and display the effectiveness of reversing the gefitinib resistance and enhancing the EGFRT790M -mutated NSCLC treatment outcomes. The novel simvastatin-based nanomedicine provides a clinically translatable strategy for tackling the major problem in NSCLC treatment and demonstrates the promise of an old drug for new application.


A randomized controlled trial of a group acceptance-based intervention for cancer survivors experiencing anxiety at re-entry ('Valued Living'): study protocol.
Anxiety is a common concern of cancer survivors during the transition from active cancer treatment to cancer survivorship (the re-entry phase). This paper presents the study protocol for a novel group-based behavioral intervention to improve mental health, well-being, and medical use outcomes among anxious cancer survivors at re-entry. This two-armed, prospective randomized controlled trial will randomize a minimum of 100 re-entry-phase cancer survivors with moderate to high anxiety to the intervention or a usual care control condition. The intervention is delivered in a group format over 7 weeks; content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based intervention. Participants will be recruited from community cancer care centers and the intervention will be led by the onsite clinical social workers. Participants will be assessed at baseline, mid-intervention, post-intervention, and 3- and 6-month follow-up. ACT participants will complete process measures before the beginning of group sessions 2, 4, and 6; all participants will complete the process measures during the regular assessments. The primary outcome is anxiety symptoms; secondary outcomes include anxiety disorder severity, fear of recurrence, depressive symptoms, cancer-related trauma symptoms, sense of life meaning, vitality/fatigue, and medical utilization. This clinical trial will provide valuable evidence regarding the efficacy of the group ACT intervention in community oncology settings. Clinicaltrials.gov NCT02550925 .


Induction and direction of immune responses by vaccine adjuvants.
Successful vaccination against infectious or neoplastic disease programs the host's immune system, in a multistep process, to generate an efficient defense and memory response. Conditioning of immune responses to nonreplicating, poorly immunogenic antigens generally requires the help of an adjuvant. The present review attempts to classify vaccine adjuvants functionally, according to recently proposed, mutually exclusive concepts of immunity induction. These include the geographical concept of immune reactivity and the theory of depot effect. Both emphasize the importance of antigen delivery and localization to the lymph node in time after immunization. Other concepts stress the importance of key signals, such as "infectious nonself" or "danger," which influence the activation state of the antigen-presenting cell (APC) and, hence, its capacity to prime naïve T cells. The nature of adjuvant-induced immune responses is discussed in relation to each concept.


Current Role and Potential of Polymeric Biomaterials in Clinical Obesity Treatment.
The rise of obesity and associated fatal diseases has taken a massive toll worldwide. Despite the existing pharmaceuticals and bariatric surgeries, these approaches manifest limited efficacy or accompany various side effects. Therefore, researchers seek to facilitate the prolonged and specific delivery of therapeutics. Or else, to mimic the essential part of "gastric bypass" by physically blocking excessive absorption via less invasive methods. To achieve these goals, polymeric biomaterials have gained tremendous interest recently. They are known for synthesizing hydrogels, microneedle patches, mucoadhesive coatings, polymer conjugates, and so forth. In this Review, we provide insights into the current studies of polymeric biomaterials in the prevention and treatment of obesity, inspiring future improvements in this regime of study.


Immune status, and not HIV infection or exposure, drives the development of the oral microbiota.
Even with antiretroviral therapy, children born to HIV-infected (HI) mothers are at a higher risk of early-life infections and morbidities including dental disease. The increased risk of dental caries in HI children suggest immune-mediated changes in oral bacterial communities, however, the impact of perinatal HIV exposure on the oral microbiota remains unclear. We hypothesized that the oral microbiota of HI and perinatally HIV-exposed-but-uninfected (HEU) children will significantly differ from HIV-unexposed-and-uninfected (HUU) children. Saliva samples from 286 child-participants in Nigeria, aged ≤ 6 years, were analyzed using 16S rRNA gene sequencing. Perinatal HIV infection was significantly associated with community composition (HI vs. HUU-p = 0.04; HEU vs. HUU-p = 0.11) however, immune status had stronger impacts on bacterial profiles (p < 0.001). We observed age-stratified associations of perinatal HIV exposure on community composition, with HEU children differing from HUU children in early life but HEU children becoming more similar to HUU children with age. Our findings suggest that, regardless of age, HIV infection or exposure, low CD4 levels persistently alter the oral microbiota during this critical developmental period. Data also indicates that, while HIV infection clearly shapes the developing infant oral microbiome, the effect of perinatal exposure (without infection) appears transient.


[Natural therapy instead of chemistry? Probiotics in gastroenterology].
Probiotics are living microorganisms that upon ingestion exert health benefits. The impact of probiotics on gut flora represents a new and interesting therapeutic approach in a number of diseases of the gastrointestinal tract. According to actual publications and guidelines of medical societies, the clinical relevance of probiotics can be described as follows: (a) In the case of ulcerative colitis, available data demonstrate benefits of probiotic therapy. (b) The available data regarding pouchitis are limited, but the therapeutic effect seems to be excellent. (c) In the case of Crohn's disease, the role of probiotics is not clearly defined, thus the results of new trials have to be awaited before probiotic therapy is recommended. (d) Further indications such as antibiotic-associated diarrhea, acute pancreatitis or irritable bowel syndrome have been reported recently. The results of these clinical trials have been encouraging, but they often included only a small number of patients and therefore a clear-cut assessment seems difficult at the moment.


Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.
There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.


[Changes of glutamate and GABA in cerebrospinal fluid of patients with pneumonia complicated with central nervous system damage].
Glutamate(Glu), gamma-aminobutyric acid(GABA), and malondialdehyde(MDA) in cerebrospinal fluid (CSF) were measured in 18 children with pneumonia complicated with central nervous system(CNS) damage, 14 children with pneumonia without CNS damage, and 7 children with hypocalcemic tetany. The concentration of Glu and MDA and the ratio of Glu/GABA in CSF of pneumonia without CNS damage were significantly higher than the others. The ratio of Glu/GABA in CSF of the children with pneumonia with consciousness obstacle after convulsion was higher than that without consciousness obstacle after convulsion. These results suggest that Glu and free radicals may play a critical role in the CNS damage caused by pneumonia, however GABA may reduce the CNS damage caused by pneumonia.


Bioconversion technologies of crude glycerol to value added industrial products.
Crude glycerol that is produced as the by-product from biodiesel, has to be effectively utilized to contribute to the viability of biodiesel. Crude glycerol in large amounts can pose a threat to the environment. Therefore, there is a need to convert this crude glycerol into valued added products using biotechnological processes, which brings new revenue to biodiesel producers. Crude glycerol can serve as a feedstock for biopolymers, poly unsaturated fatty acids, ethanol, hydrogen and n-butanol production and as a raw material for different value added industrial products. Hence, in this review we have presented different bioconversion technologies of glycerol to value added industrial products.


Using item scores and response times in person-fit assessment.
The use of joint models for item scores and response times is becoming increasingly popular in educational and psychological testing. In this paper, we propose two new person-fit statistics for such models in order to detect aberrant behaviour. The first statistic is computed by combining two existing person-fit statistics: one for the item scores, and one for the item response times. The second statistic is computed directly using the likelihood function of the joint model. Using detailed simulations, we show that the empirical null distributions of the new statistics are very close to the theoretical null distributions, and that the new statistics tend to be more powerful than several existing statistics for item scores and/or response times. A real data example is also provided using data from a licensure examination.


Magnetic field generation in Rayleigh-Taylor unstable inertial confinement fusion plasmas.
Rayleigh-Taylor instabilities (RTI) in inertial confinement fusion implosions are expected to generate magnetic fields. A Hall-MHD model is used to study the field generation by 2D single-mode and multimode RTI in a stratified two-fluid plasma. Self-generated magnetic fields are predicted and these fields grow as the RTI progresses via the ∇n(e)×∇T(e) term in the generalized Ohm's law. Scaling studies are performed to determine the growth of the self-generated magnetic field as a function of density, acceleration, Atwood number, and perturbation wavelength.


Forecasting the Future of Antiphospholipid Syndrome: Prospects and Challenges.
Antiphospholipid syndrome (APS) is an autoimmune condition affecting young patients, primarily women, negatively impacting their quality of life. APS is under-recognized and underdiagnosed and can have devastating results if untreated, mainly due to uncontrolled thrombosis. Research in the past decades has led to several breakthroughs with important implications for clinical practice. Here, we summarize the state of APS diagnosis, treatment, pathophysiology, and research directions that hold promise for advancing diagnosis and treatment.


Transcriptomic Analysis of the Mouse Mammary Gland Reveals New Insights for the Role of Serotonin in Lactation.
Serotonin regulates numerous processes in the mammary gland. Our objective was to discover novel genes, pathways and functions which serotonin modulates during lactation. The rate limiting enzyme in the synthesis of non-neuronal serotonin is tryptophan-hydroxylase (TPH1). Therefore, we used TPH1 deficient dams (KO; serotonin deficient, n = 4) and compared them to wild-type (WT; n = 4) and rescue (RC; KO + 100 mg/kg 5-hydroxytryptophan injected daily, n = 4) dams. Mammary tissues were collected on day 10 of lactation. Total RNA extraction, amplification, library preparation and sequencing were performed following the Illumina mRNA-Seq. Overall, 97 and 204 genes (false discovery rate, FDR ≤ 0.01) exhibited a minimum of a 2-fold expression difference between WT vs. KO and WT vs. RC dams, respectively. Most differentially expressed genes were related to calcium homeostasis, apoptosis regulation, cell cycle, cell differentiation and proliferation, and the immune response. Additionally, gene set enrichment analysis using Gene Ontology and Medical Subject Headings databases revealed the alteration of several biological processes (FDR ≤ 0.01) including fat cell differentiation and lipid metabolism, regulation of extracellular signal-related kinase and mitogen-activated kinase cascades, insulin resistance, nuclear transport, membrane potential regulation, and calcium release from the endoplasmic reticulum into the cytosol. The majority of the biological processes and pathways altered in the KO dams are central for mammary gland homeostasis. Increasing peripheral serotonin in the RC dams affects specific pathways that favor lactation. Our data confirms the importance of serotonin during lactation in the mammary gland.


Synthesis of 4-aryl substituted 3,4-dihydropyrimidinones using silica-chloride under solvent free conditions.
This paper describes an improved procedure for the efficient and facile synthesis of 4-aryl substituted 3, 4-dihydropyrimidinones under mild reaction conditions with excellent yields using inexpensive silica chloride under solvent free conditions.


Inflammatory mediators in nasal lavage among school-age children from urban and rural areas in São Paulo, Brazil.
Some studies have shown that inflammatory processes in the nasal air passages may reflect or affect those in the lower airways. We decided to indirectly assess the inflammatory status of the nasal airways in two groups of children with different sensitization rates to aeroallergens. To compare the inflammatory activity in the nasal airways, through the determination of mediators in nasal lavage fluid in two distinct populations. Cross-sectional study. Two public elementary schools, one in an urban setting and the other in a rural setting of the State of São Paulo, Brazil. Two groups of 40 elementary school children with different sensitization rates to aeroallergens were formed. Samples of nasal lavage fluid were assessed for eosinophil cationic protein (ECP) and tryptase. Non-parametric tests were used for statistical analysis. Significantly higher levels of ECP were observed among students living in the urban area than those in the rural area (p < 0.05). No significant difference in the tryptase levels was observed. Also, the urban children who were sensitized to aeroallergens presented higher levels of ECP in nasal mucosa than the non-sensitized children, while this difference was not observed among the rural children. The lack of mast cell activity and increased eosinophil degranulation revealed a chronic inflammatory state in the nasal air passages. The higher eosinophil activity in the urban area, coinciding with higher sensitization to aeroallergens, suggests that there must be some factors in the urban area that can modulate airway inflammation by influencing the activation of inflammatory cells. Our findings showed that there was no difference in the concentrations of tryptase in nasal lavage fluids between the two studied groups. However, the children from the urban area presented with higher concentrations of eosinophil cationic protein than did those from the rural area. Also, the urban children who were sensitized to aeroallergens presented with greater concentrations of eosinophil cationic protein in nasal mucosa than the non-sensitized children, while this difference was not observed among the rural children.


Anti-Ia-reactive cells in mycosis fungoides: a study of skin biopsies, single epidermal cells and circulating T lymphocytes.
Skin sections, epidermal cells in suspension and circulating T lymphocytes were investigated for the presence of Ia-like antigens in a group of patients with the cutaneous T-cell lymphoma mycosis fungoides (MF) and in healthy controls. Highly purified anti-Ia antibodies were used in indirect immunofluorescence, indirect peroxidase and peroxidase-antiperoxidase techniques. Allogeneic and autologous mixed leukocyte reaction tests with epidermal cells from MF lesions as stimulator cells were also performed. The majority of the dermal lympho-histiocytes and mononuclear cells in the epidermal Pautrier microabscesses expressed Ia-like antigens. So also did a greater proportion of circulating T lymphocytes than in the controls. In some MF patients a high percentage of single epidermal cells of non-lymphoid character also reacted with the antibodies. The possible significance of the present findings for the pathogenesis of MF is discussed.


Restrictions in the response to autologous thyroglobulin in the human.
Fragments of thyroglobulin containing the autoreactive epitopes were prepared by an existing procedure, plus an ion-exchange chromatography step which increased their purity. Before purification, 39% of the fragmental material was bound by rabbit anti-human thyroglobulin whereas only 8% was bound by autoantibody, thus confirming earlier reports of more limited epitopes for human autoantibodies than heterologous antibody. Thyroglobulin autoantibodies in the globulin fractions from six human sera showed between 70 and 100% cross-reaction with one another, indicating that the majority of antibodies are directed against the same epitopes. The data are consistent with an estimated of two distinct major epitopic specificities with occasional sera having antibodies directed against a third site. Chemical modification of tyrosine residues by iodination did not inhibit the binding of thyroglobulin to either human autoantibodies or rabbit anti-human thyroglobulin; thus tyrosine residues do not contribute significantly to the epitopes for either auto- or heteroantibodies.


Epilepsy in an elderly patient caused by Hashimoto's encephalopathy.
Late-onset seizures are frequently caused by cerebrovascular disease, head trauma, degenerative disorders or CNS tumors. In one-third of cases, the etiology remains obscure. In only 60-70% of adult-onset epilepsy is antiepileptic drug treatment successful. Although seizures are a well-known symptom of Hashimoto's encephalopathy, it is rarely taken into consideration as differential diagnosis in epilepsy. We describe a 74-year-old patient with seizures and slowly progressive cognitive deterioration. Previous therapeutic attempts with carbamazepine, lamotrigine and topiramate had not been effective. We suspected Hashimoto's encephalopathy, which was treated with prednisolone 100 mg/d over 6 months. This regimen led to a cessation of the complex partial seizures and cognitive improvement. We conclude that Hashimoto's encephalopathy is a possible differential diagnosis in epilepsy in the elderly. Glucocorticoid treatment should be considered if there are no important contraindications.


What a neurologist should know about depression in Parkinson's disease.
Depression is a frequent non-motor symptom of Parkinson's disease. Its prevalence varies widely across studies (between 2.7% and 90%); around 35% have clinically significant depressive symptoms. Although depression can have an immense impact on the quality of life of affected patients and their caregivers, depressive symptoms in Parkinson's disease frequently remain unrecognised and, as a result, remain untreated. Here we overview the diagnostic challenges and pitfalls, including the factors contributing to the underdiagnosis of depression. We also discuss current ideas on the underlying pathophysiology. Finally, we offer a treatment approach based on currently available evidence.


Molecular cloning and characterization of a novel beta-adrenergic receptor.
In an attempt to isolate new G protein-coupled receptors from turkey erythrocytes, reverse transcribed polymerase chain reaction was performed on fetal turkey blood RNA using degenerate primers based on conserved sequences present in seven transmembrane receptors. An open reading frame in one of the clones, designated 4C (497 base pairs), displayed approximately 50-60% identity to all of the previously cloned beta-adrenergic receptors (beta-ARs). A lambda-DASH turkey genomic library was screened with a probe generated from the partial 4C cDNA, and the gene encoding this receptor was localized to a 3.5-kilobase pair HindIII fragment. Ribonuclease protection analysis of turkey lung mRNA indicated that the 3' end of the coding sequence of the 4C gene, like beta 3-AR, was interrupted by an intron. To obtain the cDNA sequence of 4C, RNA-polymerase chain reaction was performed using primers complementary to regions identified by ribonuclease protection analysis to be present in 4C mRNA. Comparison of the genomic and cDNA sequences of 4C indicated that the first exon encodes 414 amino acids of the protein, the second exon (68 base pairs) encodes an additional 12 residues followed by a stop codon, and the third exon is composed of 3'-untranslated sequence. The 4C receptor was transiently expressed in COS-1 cells, and the apparent affinities of a series of beta-AR agonists and antagonists were determined using [125I]iodocyanopindolol. As implicated by its amino acid sequence, 4C displayed a pharmacological selectivity that was consistent with that of a beta-AR but distinct from other cloned beta-ARs. Isoproterenol, epinephrine, and norepinephrine stimulated cyclic AMP accumulation in a concentration-dependent manner in mouse L cells stably expressing the 4C receptor. No effect on phospholipase C activity was observed. Ribonuclease protection assays indicated that 4C mRNA exhibits a broad tissue distribution, which suggests that it may play an important role in avian physiology.


Intervention efficacy for eliminating patient misidentification using step-by-step problem-solving procedures to improve patient safety.
This study aimed to evaluate the efficacy of interventions to reduce patient misidentification incidents classified as level 2 and over (adverse events occurred for patients) with the step-by-step problem-solving method. All incidents related to patient misidentification were selected, and relevant information was collected from the original electronic incident reports. We then conducted an eight-step problem-solving process with the aim of reducing patient misclassification and improving patient safety. Step 1: the number of misidentification-related incident reports and the percentage of these reports in the total incident reports increased each year. Step 2: the most frequent misidentification type was sample collection tubes, followed by drug administration and hospital meals. Step 3: we set a target of an 20% decrease in patient misidentification cases classified as level 2 or over compared with the previous year, and established this as a hospital priority. Step 4: we found that discrepancies in patient identification procedures were the most important causes of misidentification. Step 5: we standardized the patient identification process to achieve an 10% reduction in misidentification. Step 6: we disseminated instructional videos to all staff members. Step 7: we confirmed there was an 18% reduction in level 2 and over patient misidentification compared with the previous year. Step 8: we intend to make additional effort to decrease misidentification of patients by a further 10%. Level 2 and over patient misidentification can be reduced by a patient identification policy using a step-by-step problem-solving procedure. This study aimed to evaluate the efficacy of interventions to reduce patient misidentification incidents with step-by-step problem-solving method. Continued seamless efforts to eliminate patient misidentification are mandatory for this activity.


Transabdominal ultrasound accurately identifies a significant iliac vein area-reducing lesion in patients with pelvic venous insufficiency.
In patients with pelvic venous disorders secondary to pelvic venous insufficiency (PVI), the optimal imaging modality is ill-defined. Transabdominal ultrasound (TAU) is widely used to identify the presence of iliac vein stenosis. The purpose of the present investigation is to determine the accuracy of TAU for determining the presence of an iliac vein area-reducing lesion compared with intravascular ultrasound (IVUS). From January to December 2020, a retrospective review of prospectively collected data from 96 patients treated for symptomatic PVI at the Center for Vascular Medicine was performed. All patients had complete history and physical examination findings, demographics, CEAP (clinical, etiologic, anatomic, pathophysiologic), revised venous clinical severity score, and TAU, diagnostic venography, and IVUS measurements recorded in our electronic medical record system. All TAU measurements were performed by the same ultrasound technician with the patient in the supine position. Iliac vein diameters of the common femoral, external iliac, and common iliac veins and the inferior vena cava were obtained. Differences in body habitus were normalized by dividing the minimum diameter measurement of the stenotic vessel with that of the ipsilateral common femoral vein, subtracting this number from 1 and multiplying by 100 (stenosis = [1 - minimal diameter/common femoral diameter] × 100). The normalized stenoses were then compared with the IVUS-derived area reducing measurements. A receiver operating characteristic curve was created, and logistic regression analysis for the probability of predicting an area-reducing lesion of >50% and >60% with TAU was performed. The sensitivity, specificity, and positive and negative predictive values were calculated. The average age of the entire cohort was 49.8 ± 13.5 years, with 69 women and 27 men. The CEAP distribution was as follows: C0, 5%; C1, 5%; C2, 10%; C3, 40%; C4a,b, 30%; C5, 7%; and C6, 3%. The average revised venous clinical severity score was 6.2 ± 2.6. The indications for intervention were leg symptoms alone in 43%, pelvic symptoms alone in 3%, and combined leg and pelvic symptoms in 54%. TAU identified a stenosis of ≥50% in 92 of the 96 patients (96%). For a ≥50% stenosis, a normalized diameter of ≤3 mm demonstrated a sensitivity, specificity, and positive and negative predictive value of 75%, 75%, 98%, and 12%, respectively. Logistic regression analysis indicated that TAU was significant in predicting the presence of a ≥60% area-reducing lesion (odds ratio, 1.03; 95% confidence interval, 1.01-1.05; P = .009). The area under the receiver operating characteristic curve (c-statistic) was 68.6%. The sensitivity, specificity, and positive and negative predictive values were 66.7%, 66.7%, 81.5%, and 47.6%, respectively, for a normalized diameter of ≥4 mm. The ability of TAU to identify an iliac vein stenosis of ≥50% is 96%. The positive predictive value for TAU to identify a ≥60% iliac vein area-reducing lesion is high, with moderate sensitivity and specificity. For patients with symptoms consistent with pelvic venous disorders secondary to PVI, TAU is a good preintervention screening modality for properly trained vascular imaging specialists with findings that correlate well with IVUS measurements.


Increased rate of penicillin non-susceptible strains of N. meningitidis in Naples, Italy.
Neisseria meningitidis is a causative agent of community-acquired sepsis and meningitis in humans. These diseases are associated with high mortality and morbidity if treatment is not started promptly. The empiric antibiotic treatment depends on patient factors and local epidemiology. In the past years, an increased number meningococcal strain with reduced susceptibility to penicillin has also been described. We analysed the susceptibility pattern of 11 N. meningitidis strains isolated between 2013 and 2016. Only three (27%) strains were fully susceptible to penicillin, suggesting that a third-generation cephalosporin, instead of penicillin, as empiric therapy is more reliable when an invasive meningococcal disease is suspected.


Evaluation of the Novel PET Tracer [11C]HACH242 for Imaging the GluN2B NMDA Receptor in Non-Human Primates.
There are currently no positron emission tomography (PET) radiotracers for the GluN2B (NR2B) binding sites of brain N-methyl-D-aspartate (NMDA) receptors. In rats, the GluN2B antagonist Ro25-6981 reduced the binding of N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamin ([11C]HACH242). This paper reports the evaluation of [11C]HACH242 PET in non-human primates at baseline and following administration of the GluN2B negative allosteric modulator radiprodil. Eight 90-min dynamic [11C]HACH242 PET scans were acquired in three male anaesthetised rhesus monkeys, including a retest session of subject 1, at baseline and 10 min after intravenous 10 mg/kg radiprodil. Standardised uptake values (SUV) were calculated for 9 brain regions. Arterial blood samples were taken at six timepoints to characterise pharmacokinetics in blood and plasma. Reliable input functions for kinetic modelling could not be generated due to variability in the whole-blood radioactivity measurements. [11C]HACH242 entered the brain and displayed fairly uniform uptake. The mean (± standard deviation, SD) Tmax was 17 ± 7 min in baseline scans and 24 ± 15 min in radiprodil scans. The rate of radioligand metabolism in plasma (primarily to polar metabolites) was high, with mean parent fractions of 26 ± 10 % at 20 min and 8 ± 5 % at 85 min. Radiprodil increased [11C]HACH242 whole-brain SUV in the last PET frame by 25 %, 1 %, 3 and 17 % for subjects 1, 2, 3 and retest of subject 1, respectively. The mean brain to plasma ratio was 5.4 ± 2.6, and increased by 39 to 110 % in the radiprodil condition, partly due to lower parent plasma radioactivity of -11 to -56 %. The present results show that [11C]HACH242 has a suitable kinetic profile in the brain and low accumulation of lipophilic radiometabolites. Radiprodil did not consistently change [11C]HACH242 brain uptake. These findings may be explained by variations in cerebral blood flow, a low fraction of specifically bound tracer, or interactions with endogenous NMDA receptor ligands at the binding site. Further experiments of ligand interactions are necessary to facilitate the development of radiotracers for in vivo imaging of the ionotropic NMDA receptor.


CD4-expressing cells are early mediators of the innate immune system during sepsis.
It is well established that the immune response to sepsis is mediated by leukocytes associated with the innate immune system. However, there is an emerging view that T lymphocytes can also mediate this response. Here, we observed a significant depletion of both CD4 and CD8 T cells in human patients after blunt trauma. To determine what effect the loss of these cells may have during a subsequent infection, we obtained CD4- and CD8-deficient mice and subjected them to cecal ligation and puncture (CLP). We observed that CD4 knockout (KO) mice showed increased CLP-induced mortality compared with CD8-deficient and wild-type (WT) mice especially within the first 30 h of injury. CD4 KO mice also exhibited significantly increased IL-6 concentrations after the CLP. The CD4 KO mice had an increased concentration of bacteremia as compared with WT mice. Antibiotic treatment decreased mortality in the CD4 KO mice as compared with no changes in the wild mice after CLP. Neutrophils isolated from septic CD4 KO mice showed decreased spontaneous oxidative burst compared with neutrophils taken from septic controls. We examined the role of IFN-gamma by using mice deficient in this cytokine and found these mice to have significantly higher mortality as compared with WT mice. Finally, we detected a 2-fold increase in CD11b+ cells that exhibited intracellular IFN-gamma staining in the peritoneum of WT mice after CLP. The data suggest that CD4+ cells may facilitate the early clearance of bacteria by regulating neutrophils function possibly through an IFN-gamma-dependent mechanism.


Subcapsular Hematoma Causing Anuria After Renal Graft Trauma.
A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.


"Maybe They Don't Even Know That I Exist": Challenges Faced by Family Members and Friends of Patients with Advanced Kidney Disease.
Family members and friends of patients with advanced chronic illness are increasingly called on to assist with ever more complex medical care and treatment decisions arising late in the course of illness. Our goal was to learn about the experiences of family members and friends of patients with advanced kidney disease. As part of a study intended to identify opportunities to enhance advance care planning, we conducted semistructured interviews at the Veterans Affairs Puget Sound Health Care System with 17 family members and friends of patients with advanced kidney disease. Interviews were conducted between April of 2014 and May of 2016 and were audiotaped, transcribed, and analyzed inductively using grounded theory to identify emergent themes. The following three themes emerged from interviews with patients' family members and friends: (1) their roles in care and planning were fluid over the course of the patient's illness, shaped by the patients' changing needs and their readiness to involve those close to them; (2) their involvement in patients' care was strongly shaped by health care system needs. Family and friends described filling gaps left by the health care system and how their involvement in care and decision-making was at times constrained and at other times expected by providers, depending on system needs; and (3) they described multiple sources of tension and conflict in their interactions with patients and the health care system, including instances of being pitted against the patient. Interviews with family members and friends of patients with advanced kidney disease provide a window on the complex dynamics shaping their engagement in patients' care, and highlight the potential value of offering opportunities for engagement throughout the course of illness.


Allonursing in tufted capuchin monkeys (Cebus nigritus): milk or pacifier?
Allonursing, the behaviour of females nursing offspring that are not their own, is relatively frequent in capuchin monkeys. Using focal-animal sampling and ad libitum observations we describe the pattern of allonursing in a wild group of tufted capuchins, Cebus nigritus (4 cohorts, 22 infants), at Iguazú National Park, north-eastern Argentina, and test several hypotheses on the adaptive value of allonursing. During 2,351 contact hours with the group (including 4,207 focal-animal samples totalizing 329 h focused on infants) we observed 39 allonursing bouts. Infants were not allonursed more frequently by close kin than by more distant allomothers. Offspring of dominant females were allonursed more frequently than those of low-ranking females. Nursing bouts were longer than allonursing bouts. Our results suggest that allonursing in tufted capuchins has a social function and is not mainly aimed at providing milk to infants.


Characterization of the functional response in the human spinal cord: Impulse-response function and linearity.
Functional magnetic resonance imaging (fMRI) has emerged during the last decade as the main non-invasive technique for the investigation of human brain function. More recently, fMRI was also proposed for functional studies of the human spinal cord, but with controversial results. In fact, the functional contrast is not well-characterized, and even its origin has been challenged. In the present work, we characterized the temporal features of the functional signal evoked in the human spinal cord by a motor task, studied with an approach based on time-locked averaging of functional time series of different durations. Based on the results here reported, we defined an impulse-response function (irf) able to explain the functional response for motor tasks in the interval of 15-42 s of duration, thus suggesting the linearity of the phenomenon in this interval. Conversely, with stimulation durations ranging between 3 and 9 s, the functional signal was not detectable, and was under the level predicted by a linear behavior, suggesting deviation from linearity during short stimulations. The impulse-response function appeared slower than in the brain, peaking at about 9 s after its beginning. The observed contrast was generally larger than in the brain, on the order of about 5.4% of baseline signal at 1.5 T. The findings further suggested that the physiological origin of T(2) weighted functional imaging is similar in the spinal cord and in the brain.


Osteogenesis imperfecta and campomelic dysplasia: difficulties in prenatal diagnosis.
The classic features of osteogenesis imperfecta and campomelic dysplasia typically are so specific that these two forms of skeletal dysplasia are among the few that can be diagnosed in the second trimester of pregnancy. We report a series of seven examples of osteogenesis imperfecta and one example of campomelic dwarfism to illustrate the difficulty of differentiating these two disorders in utero. The prenatal sonographic findings in three of the osteogenesis imperfecta cases mimicked campomelic dwarfism, whereas the case of campomelic dwarfism was antenatally diagnosed as osteogenesis imperfecta.


Complications of laparoscopic radical cystectomy during the initial experience.
Radical cystectomy is the standard of care for patients with muscle invasive bladder cancer. While open radical cystectomy is now a standard procedure, laparoscopic radical cystectomy is still in its infancy. We performed this surgery laparoscopically in 11 patients and review the procedure specific complications. Beginning in February 1999, 11 patients underwent laparoscopic radical cystectomy at the Department of Urology, All India Institute of Medical Sciences, New Dehli. Urinary diversion was performed by an open-hand sewn ileal conduit. There were three intraoperative complications specifically related to the laparoscopic radical cystectomy. These included injury to the external iliac vein in one patient and a small rectal tear in two. All were repaired with laparoscopic free hand suturing with normal postoperative recovery. Other laparoscopy-related complications were subcutaneous emphysema in one patient and hypercarbia necessitating conversion to open surgery in a patient who, four weeks after surgery, died of multiple organ failure. One patient had margins positive and received cisplatinum-based chemotherapy. All patients had normal renal function and preserved upper tracts with no evidence of metastasis at a mean of 18.4 months follow up (range 1-48 months). Though there were three complications specific to the laparoscopic radical cystectomy, none necessitated a conversion to open surgery or hampered the overall outcome. Absence of local recurrence or metastatic disease at four years of follow up suggests that the procedure is oncologically valid. Laparoscopic radical cystectomy is a new procedure and it is important to critically analyze the complications in order to reduce their occurrence and allow the development of a better technique.


Clinical risk in rehabilitation: an exploratory investigation in Campania region.
Clinical risk management is a comprehensive programme that encompasses all the measures implemented to improve the quality of the healthcare service and ensure patient safety, which is based on learning through error. This process is intended to bring about ongoing improvements in clinical practice, starting with risk identification, before moving on to risk assessment and analysis, in order to reduce risks where possible. When clinical risk management is applied in rehabilitation, the first step involves identifying errors by assessing adverse events, which are considered to indicate the existing risk. Our work aims to explore the characteristics of the clinical risk in rehabilitation so as to learn more about its extent, its components, and its implications for the user. Our study involved numerous workers operating in four different branches of rehabilitation - speech therapy, physiotherapy, psychomotor education and occupational therapy - at forty-nine private rehabilitation centres in the province of Naples, an area that has not been studied before. A questionnaire was drafted regarding the main errors committed in the rehabilitation sector. It was then distributed and collected in again, after which the results were analysed and outcomes measured. Out of a total of 556 questionnaires distributed, 493 were returned (88.6% response rate.). The study revealed that for all the rehabilitation branches considered, the macro-category of errors linked to technical and professional aspects accounted for the highest percentage of the total errors (39%). In this study, the most frequent errors linked to technical and professional aspects were: wrong dose errors, treatment planning errors and functional assessment errors. There is an evident need to take action in order to manage the clinical risk in rehabilitation: to promote a concept of errors as opportunities for learning and improvement; to maintain the focus on both individual responsibility and on any systemic failings; to share fundamental values such as transparency, collaboration between workers, communication with patients, and a commitment to ongoing improvements in healthcare quality.


Renal transplantation in light chain nephropathy: case report and review of the literature.
A successful cadaveric transplantation in a patient with irreversible renal insufficiency due to light chain nephropathy is reported. Remission of the monoclonal gammopathy was induced with melphalan and prednisone and after 4.5 years of hemodialysis a cadaveric kidney transplantation was performed, which resulted in excellent renal function up to 3.5 years after transplantation. Along with 8 previously reported patients in the literature this case demonstrates that renal transplantation can no longer be withheld from this category of patients, when they are in remission and no other major complications of their monoclonal gammopathy are present.


Online hydrogen-deuterium exchange and a tandem-quadrupole time-of-flight mass spectrometer coupled with liquid chromatography for metabolite identification in drug metabolism.
A method for metabolite identification in drug discovery and development utilizing online hydrogen-deuterium (H-D) exchange and a tandem-quadrupole time-of-flight mass spectrometer coupled with liquid chromatography has been developed for the first time. For purposes of evaluating this method, nimodipine is incubated with rat, dog, monkey, and human hepatic microsomes over a 60-min period. This procedure involves the replacement of H(2)O with D(2)O in the mobile phase. The equilibration time required to change (switch) from H(2)O in the mobile phase into D(2)O is approximately 10 min. There is no significant difference between the retention times in H(2)O or D(2)O mobile phase. The results show that the separations of nimodipine and its metabolites and the subsequent H-D exchanges were achieved online. This leads to the identification of nimodipine metabolites formed in vitro. Five metabolites of nimodipine are identified and characterized. These metabolites are formed by dehydrogenation, demethylation of methoxy group, cleavage of the ester groups by hydrolysis or oxidation, and hydroxylation of methyl groups. The combination of the H-D exchange process and the assay system is found to be a powerful tool for the study of metabolite identification. The method appears to be highly desirable for identification of metabolites produced by dehydrogenation, oxidation, and dealkylation, which are discussed herein. This method also greatly enhances throughput, which in turn facilitates the ability to rapidly provide metabolite elucidation.


[Epidemiological aspects of leprosy: a spatial approach].
The objective of this study was to identify spatial patterns in the occurrence of leprosy in Duque de Caxias, a municipality (county) with high endemicity for the disease in the State of Rio de Janeiro, Brazil. The authors selected all new leprosy cases reported to the Brazilian National Database on Diseases of Notification (SINAN) from 1998 to 2006. The analysis was performed according to three-year periods, followed by spatial analysis according to the local empirical Bayesian method and calculation of global (Moran) and local (LISA) spatial autocorrelation. The analysis showed marked improvement in the epidemiological situation associated with earlier diagnosis. There was a reduction in the proportion of cases with grade II leprosy, from 13.6% to 8.6% (p = 0.04), and increased detection of cases with the indeterminate form, from 10.3% to 18% (p = 0.00). Spatial analysis identified a cluster in the South-Northwest of the municipality, not directly related to the actions or decentralization campaign, proving to be an important tool for identifying critical areas for the endemic and assessing the impact of strategic measures to combat the disease.


Protocol for a randomized, double blind, placebo controlled, crossover trial of Melatonin for treatment of Nocturia in adults with Multiple Sclerosis (MeNiMS).
Nocturia (the symptom of needing to wake up to pass urine) is common in progressive Multiple Sclerosis (MS) patients. Moderate-to-severe nocturia affects quality of life, can exacerbate fatigue and may affect capacity to carry out daily activities. Melatonin is a natural hormone regulating circadian cycles, released by the pineal gland at night-time, and secretion is impaired in MS. Melatonin levels can be supplemented by administration in tablet form at bedtime. The aim of this study is to evaluate the effect of melatonin on mean number of nocturia episodes per night in MS patients. Secondary outcome measures will assess impact upon quality of life, urinated volumes, lower urinary tract symptoms (LUTS), cognition, sleep quality and sleep disturbance of partners. A randomized, double blind, placebo controlled, crossover trial consisting of two, six week treatment phases (active drug melatonin 2 mg or placebo), with a 1 month wash-out period in between. The primary outcome (change in nocturia episodes per night) in this two arm, two treatment, two period crossover design, will be objectively measured using frequency volume charts (FVC) at baseline and following both treatment phases. Questionnaires will be used to assess quality of life, sleep quality, safety and urinary tract symptoms. Qualitative interviews of participants and partners will explore issues including quality of life, mechanisms of sleep disturbance and impact of nocturia on partners. This study will evaluate whether melatonin reduces the frequency of nocturia episodes in MS patients, and therefore whether 'Circadin' has the potential to reduce LUTS and fatigue, and improve cognition and overall quality of life. (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869.


Endodontic-periodontal microsurgery for combined endodontic-periodontal lesions: An overview.
Endodontic and periodontal microsurgery has surpassed the success rates for traditional endodontic and periodontal surgical procedures. Excellent healing results are being attributed to both the techniques, when employed, for isolated endodontic or periodontal defects. Combined endodontic-periodontal lesions have been referred to as a true challenge, requiring not only endodontic microsurgical management but also concurrent bone grafting and membrane barriers techniques. The prevention of epithelial downgrowth and regeneration of periodontal cementum, fiber, and bone seals the fate of these cases. Achieving primary closure with submergence of grafts has a positive effect on GTR outcome. New techniques of periodontal microsurgery, such as minimally invasive papilla preserving flaps with passive internal mattress suturing, have managed to obtain 90% primary flap closure over grafted sites. Root surface treatment and conditioning has also shown to be beneficial for GTR. Endodontic microsurgery for the combined lesion has not integrated these advances yet. These advances, along with a recently suggested treatment strategy, are ushering in the level next in management of the combined lesions. This article offers an overview of the combined lesion, the disease, its classification, treatment strategy, regenerative tools, microsurgical recommendations, and outcome studies.


Patient Safety Culture and Associated Factors Among Health-Care Providers in the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.
Patient safety is an issue of global concern; however, health-care organizations have lately observed to pay more attention to the importance of establishing a culture of safety. The study aimed to assess the level of patient safety culture and associated factors among health-care providers at the University of Gondar comprehensive specialized hospital, Northwest Ethiopia, 2020. A cross-sectional study design supported by the qualitative approach was conducted from March 15 to May 15/2020. A stratified simple sampling technique was used to select 575 study participants. The standardized tool, which measures 12 safety culture dimensions, was used for data collection. Bivariate and multivariable linear regression analyses performed using SPSS version 23. The significance level was obtained at 95% CI and p-value <0.05. For the qualitative part, a semi-structured interview guide with probing was used. Data were analyzed thematically using open code software version 4.02. The overall level of positive patient safety culture was 45.3% (95% CI: 44.7, 45.9) with a response rate of 92.2%. Factor analysis indicated that female, masters, participation in patient safety program, adverse event report, hospital management encourage reporting event and resource were positively associated with the patient safety culture. Whereas divorced/widowed, midwives, anesthetist, medicine, pediatrics, emergency, outpatient, pharmacy, direct contact with patients, and hospital management blame when medical errors happened were negatively associated. The in-depth interview revealed that teamwork, health-care professionals' attitude toward patient safety and patient involvement as important factors that influence patient safety culture. The overall level of positive patient safety culture was low. All variables except age, training, working hour, and working experience were factors significantly associated with the patient safety culture. Health-care policy-makers and managers should consider patient safety culture a top priority, and also create a blame-free environment that promotes event reporting.


Liver Transplantation for Intrahepatic Cholangiocarcinoma: What Are New Insights and What Should We Follow?
Intrahepatic cholangiocarcinoma (iCCA) is a complex malignancy carrying poor prognosis. Liver transplantation (LT) was historically contraindicated for iCCA, due to poor outcomes after LT. However, an increasing number of studies have challenged this premise, because LT alone or combined with neoadjuvant chemotherapy has achieved relatively satisfactory transplant outcomes in well selected iCCA cases. This current review based on existing clinical researches, evinced that LT might serve as a viable option in iCCA cases as follows: ① unresectable tumor restricted to 2 cm, along with context of chronic liver diseases; and ② unresectable tumor locally advanced within the liver (without extrahepatic metastasis or vascular invasion) but responses to tumor down-staging treatments (namely, systemic neoadjuvant therapy and/or locoregional therapy). On the contrary, it is recommended as contraindications in iCCA cases as follows: ① patients with tumor progression while waiting for a transplant (increase of diameter, macrovascular invasion, new nodules, escalation of carbohydrate antigen 19-9, or extrahepatic spread); ② patients with iCCA recurrence. Conclusively, tumor burden, tumor biology, and response to down-staging strategies should be taken into consideration before LT. Whereas, the concept of "locally advanced stage" remains to be defined in the future, especially the optimized combination of "maximum size of largest lesion", "number of lesions", with/without "tumor differentiation", just like the Milan criteria which is widely used for hepatocellular carcinoma. Given the scarcity of donor organ, and also the debate about LT in iCCA, accurate consensus about LT for iCCA patients is still urgently warranted.


Legionnaires' disease at autopsy.
Sporadic deaths from Legionnaires' disease may escape detection at autopsy. Known epidemiological and clinical features of the disease should arouse suspicion and prompt appropriate bacteriological studies. The pathological findings in Legionnaires' disease are almost entirely confined to the lungs and are not distinct from any other severe bacterial bronchopneumonia. The causative organism, Legionella pneumophila, is difficult to identify on a Gram stain but will stain nonspecifically with the Giemsa, Warthin-Starry, and Dieterle techniques. The direct fluorescent antibody method allows specific identification of Legionella in paraffin-embedded tissue sections.


Genome-Wide Analysis of ROS Antioxidant Genes in Resurrection Species Suggest an Involvement of Distinct ROS Detoxification Systems during Desiccation.
Abiotic stress is one of the major threats to plant crop yield and productivity. When plants are exposed to stress, production of reactive oxygen species (ROS) increases, which could lead to extensive cellular damage and hence crop loss. During evolution, plants have acquired antioxidant defense systems which can not only detoxify ROS but also adjust ROS levels required for proper cell signaling. Ascorbate peroxidase (APX), glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) are crucial enzymes involved in ROS detoxification. In this study, 40 putative APX, 28 GPX, 16 CAT, and 41 SOD genes were identified from genomes of the resurrection species Boea hygrometrica, Selaginella lepidophylla, Xerophyta viscosa, and Oropetium thomaeum, and the mesophile Selaginella moellendorffii. Phylogenetic analyses classified the APX, GPX, and SOD proteins into five clades each, and CAT proteins into three clades. Using co-expression network analysis, various regulatory modules were discovered, mainly involving glutathione, that likely work together to maintain ROS homeostasis upon desiccation stress in resurrection species. These regulatory modules also support the existence of species-specific ROS detoxification systems. The results suggest molecular pathways that regulate ROS in resurrection species and the role of APX, GPX, CAT and SOD genes in resurrection species during stress.


Rice Immature Pollen 1 (RIP1) is a regulator of late pollen development.
We isolated a pollen-preferential gene, RICE IMMATURE POLLEN 1 (RIP1), from a T-DNA insertional population of japonica rice that was trapped by a promoterless beta-glucuronidase (GUS) gene. Semi-quantitative reverse transcription-PCR (RT-PCR) analyses confirmed that the RIP1 transcript was abundant at the late stages of pollen development. Transgenic plants carrying a T-DNA insertion in the RIP1 gene displayed the phenotype of segregation distortion of the mutated rip1 gene. Moreover, rip1/rip1 homozygous progeny were not present. Reciprocal crosses between Rip1/rip1 heterozygous plants and the wild type showed that the rip1 allele could not be transmitted through the male. Microscopic analysis demonstrated that development in the rip1 pollen was delayed, starting at the early vacuolated stage. Close examination of that pollen by transmission electron microscopy also showed delayed formation of starch granules and the intine layer. In addition, development of the mitochondria, Golgi apparatus, lipid bodies, plastids and endoplasmic reticulum was deferred in the mutant pollen. Under in vitro conditions, germination of this mutant pollen did not occur, whereas the rate for wild-type pollen was >90%. These results indicate that RIP1 is necessary for pollen maturation and germination. This gene encodes a protein that shares significant homology with a group of proteins containing five WD40 repeat sequences. The green fluorescent protein (GFP)-RIP1 fusion protein is localized to the nucleus. Therefore, RIP1 is probably a nuclear protein that may form a functional complex with other proteins and carry out essential cellular and developmental roles during the late stage of pollen formation.


Post-void residual urine under 150 ml does not exclude voiding dysfunction in women.
It has been claimed that post-void residual urine (PVR) below 150 ml rules out voiding dysfunction in women with stress urinary incontinence (SUI) and provides license to perform sling surgery. The cut-off of 150 ml seems arbitrary, not evidence-based, and so we sought to investigate the ability of PVR < 150 ml to exclude voiding dysfunction. We retrospectively reviewed the charts of all patients who underwent invasive urodynamics from 1 January 2013 to 31 December 2013. Voiding dysfunction was diagnosed if both the invasive urodynamic and the free flow showed abnormal results. We registered the PVR in patients with voiding dysfunction and divided them into groups with PVR < 150 ml and PVR ≥ 150 ml. Patients were then analyzed for bladder outlet obstruction and detrusor underactivity. Of the 205 patients undergoing invasive urodynamics in 2013, a total of 20 had voiding dysfunction, 2 with PVR ≥ 150 ml. Eighteen patients had PVR < 150 ml (range 0-50 ml); 9 had bladder outlet obstruction while 7 had detrusor underactivity. Two patients were uncategorized. Out of the 20 patients, 7 had no symptoms or complaints indicating voiding dysfunction. Patients with voiding dysfunction often have normal PVR and so PVR < 150 ml cannot exclude voiding dysfunction. All patients should be evaluated using free flow measurements along with PVR to obtain a reliable, objective measurement of their voiding pattern, before anti-incontinence surgery.


When size and shape matter: morphometric characterization of two sympatric dragonflies of the genus Perithemis (Odonata: Libellulidae).
Perithemis mooma, Kirby, 1889 and Perithemis icteroptera (Selys in Sagra, 1857) live in sympatry from southern Brazil to central Argentina. The taxonomy of the genus Perithemis Hagen, 1861 has been hampered by the use of characters that are highly variable or show slight differences among species. Our objective was to assess the efficiency of traditional morphometrics (TM) and geometric morphometrics (GM) to discriminate between these species using wing size and shape and vulvar lamina contour, and to analyze the presence of sexual dimorphism in wing size and shape in both species. The TM and landmark-GM methods were applied on the fore and hind wings, while the outline-based GM method was applied on the vulvar lamina. GM allowed species delimitation using shape variables of either wing. The wing and vulvar lamina shapes were confirmed to be good diagnostic characters to separate these species and appear to be promising tools for distinguishing among other species of this genus. Centroid size failed to achieve species separation. Both species exhibited sexual size dimorphism (SSD). In contrast to what would be expected for Perithemis whose males are strongly territorial, P. icteroptera and P. mooma showed female-biased SSD suggesting a common pattern in Perithemis.


Using stochastic simulation modelling to study occupancy levels of decentralised admission avoidance units in Norway.
Identifying alternatives to acute hospital admission is a priority for many countries. Over 200 decentralised municipal acute units (MAUs) were established in Norway to divert low-acuity patients away from hospitals. MAUs have faced criticism for low mean occupancy and not relieving pressures on hospitals. We developed a discrete time simulation model of admissions and discharges to MAUs to test scenarios for increasing absolute mean occupancy. We also used the model to estimate the number of patients turned away as historical data was unavailable. Our experiments suggest that mergers alone are unlikely to substantially increase MAU absolute mean occupancy as unmet demand is generally low. However, merging MAUs offers scope for up to 20% reduction in bed capacity, without affecting service provision. Our work has relevance for other admissions avoidance units and provides a method for estimating unconstrained demand for beds in the absence of historical data.


Ultraviolet B irradiation modulates the immune system of fish (Rutilus rutilus, Cyprinidae). I. Phagocytes.
Roach (Rutilus rutilus) were irradiated with a single dose of ultraviolet B (UVB) radiation (0.4 J/cm2) in order to study the effects of UVB on the nonspecific immune defense mechanisms of fish. Neutrophils and macrophages were isolated from the head kidney of fish on days 1-14 postirradiation. Both random and directed migration of neutrophils, studied by migration under agarose assay, were suppressed on day 1 after UVB irradiation. The respiratory burst of phorbol 12-myristate 13-acetate-stimulated neutrophils and macrophages was also suppressed at days 1 and 2 after UVB irradiation. The suppression of migration and respiratory burst were restored or the responses were even enhanced later, but on the other hand spontaneous cytotoxicity of neutrophils toward 51chromium-labeled K562 target cells stayed suppressed throughout the 14 day follow-up. This study indicates that UVB radiation has the potential to suppress the functioning of phagocytes and to compromise the immune system of fish.


Nonparametric Joint Shape and Feature Priors for Image Segmentation.
In many image segmentation problems involving limited and low-quality data, employing statistical prior information about the shapes of the objects to be segmented can significantly improve the segmentation result. However, defining probability densities in the space of shapes is an open and challenging problem, especially if the object to be segmented comes from a shape density involving multiple modes (classes). Existing techniques in the literature estimate the underlying shape distribution by extending Parzen density estimator to the space of shapes. In these methods, the evolving curve may converge to a shape from a wrong mode of the posterior density when the observed intensities provide very little information about the object boundaries. In such scenarios, employing both shape- and class-dependent discriminative feature priors can aid the segmentation process. Such features may involve, e.g., intensity-based, textural, or geometric information about the objects to be segmented. In this paper, we propose a segmentation algorithm that uses nonparametric joint shape and feature priors constructed by Parzen density estimation. We incorporate the learned joint shape and feature prior distribution into a maximum a posteriori estimation framework for segmentation. The resulting optimization problem is solved using active contours. We present experimental results on a variety of synthetic and real data sets from several fields involving multimodal shape densities. Experimental results demonstrate the potential of the proposed method.


Telomere Length among Chinese Aged 75+ Years.
Telomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong. Participants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried's criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia. Among 555 participants (mean age 83.6 ± 3.8 years, 41.3% females), the mean T/S ratio was 1.01 ± 0.20. Males had a lower T/S ratio (0.97 ± 0.20) compared with females (1.07 ± 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia. Among Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.


Role of portable sleep studies for diagnosis of obstructive sleep apnea.
There is growing awareness of the significance of obstructive sleep apnea in the general population and in the medical community and, as a result, there is a growing demand for diagnosis and treatment. Attended, in-laboratory polysomnography is resource intensive and not readily available in some communities. Alternate diagnostic strategies have been proposed including the use of home sleep studies. Although these portable systems have been in use for many years, only in the past few years have a significant number of studies been performed to evaluate these systems in the home setting. The use of actigraphy and peripheral arterial tonometry for diagnostic purposes has also recently been investigated. In the laboratory setting, measurements of sleep-disordered breathing with specific portable sleep systems correspond well with measurements provided by standard polysomnography. In the home setting, portable systems demonstrate several important limitations including lost or inadequate data collection, logistic concerns, and mildly reduced diagnostic accuracy. Data regarding the potential cost benefit of home studies is inconclusive. Home polysomnography is a viable option for evaluating patients with moderate or high clinical suspicion for sleep-disordered breathing. However, patients with failed or equivocal home studies and those with negative studies but persistent symptoms should undergo standard polysomnography. Further investigations are needed to compare long-term outcomes in patients evaluated using portable devices versus standard polysomnography.


Measuring Frailty Using Patient-Reported Outcomes (PRO) Data: A Feasibility Study in Patients with Multiple Myeloma.
The objective of this retrospective study was to determine the feasibility of measuring frailty using patient responses to relevant EORTC QLQ-C30 items as proxy criteria for the Fried Frailty Phenotype, in a cohort of patients with Relapsed/Refractory Multiple Myeloma (RRMM). Data were pooled from nine Phase III randomized clinical trials submitted to the FDA for regulatory review between 2010 and 2021, for the treatment of RRMM. Baseline EORTC QLQ-C30 responses were used to derive a patient-reported frailty phenotype (PRFP), based on the Fried definition of frailty. PRFP was assessed for internal consistency reliability, structural validity, and known groups validity. This study demonstrated the feasibility of adapting patient responses to relevant EORTC QLQ-C30 items to serve as proxy Fried frailty criteria. Selected items were well correlated with one another and PRFP as a whole demonstrated adequate internal consistency reliability and structural validity. Known groups analysis demonstrated that PRFP could be used to detect distinct comorbidity levels and distinguish between different functional profiles, with frail patients reporting more difficulty in walking about, washing/dressing, and doing usual activities, as compared to their pre-frail and fit counterparts. Among the 4928 patients included in this study, PRFP classified 2729 (55.4%) patients as fit, 1209 (24.5%) as pre-frail, and 990 (20.1%) as frail. Constructing a frailty scale from existing PRO items commonly collected in cancer trials may be a patient-centric and practical approach to measuring frailty. Additional psychometric evaluation and research is warranted to further explore the utility of such an approach.


Generating arbitrary photoacoustic fields with a spatial light modulator.
Ultrasound fields have broad applications in imaging, sensing, medical therapy, etc. In these applications, it is of great importance to generate desired ultrasound fields. The generation of arbitrary ultrasound fields is challenging using phased array transducers or a monolithic acoustic hologram. In this work, by taking advantage of the photoacoustic effect and spatial light modulating technique, we demonstrate that dynamic and high-resolution arbitrary acoustic fields in liquid can be realized. We clearly show ultrasonic vortex and arbitrary 2D/3D ultrasonic fields in our photoacoustic system. All the measured pressure fields agree well with the desired ones. We anticipate these rapidly tunable photoacoustic fields will find applications in dynamic acoustic tweezers and ultrasonic imaging.


Hemoglobin A1c and fructosamine correlate in a patient with sickle cell disease and diabetes on chronic transfusion therapy.
In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A1c (HbA1c ) is unreliable and the American Diabetes Association recommends monitoring long-term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA1c . We present a case of a patient with SCD and cystic fibrosis-related diabetes on monthly chronic transfusions therapy (CTT) who had well-correlated "steady state" HbA1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long-term glycemic control in patients with SCD on CTT programs.


Changes of plasma membrane AtPase activity, membrane potential and transmembrane proton gradient in Kandelia candel and Avicennia marina seedlings with various salinities.
The salt-secreting mangrove, Avicennia marina, and non-salt-secreting mangrove, Kandelia candel were cultivated in sand with various salinities(0 per thousand, 10 per thousand, 20 per thousand, 30 per thousand, 40 per thousand) for 60 d. Plasma membrane vesicles of high-purity in leaves and roots of A. marina and K. candel seedlings were obtained by two-phase partitioning. The function of the plasma membranes, the activity of ATPase, membrane potential and transmembrane proton gradient, at various salinities were investigated. The results showed that within a certain range of salinity (A. marina and roots of K. candel: 0-30 per thousand; leaves of K. candel: 0-20 per thousand), the activity of ATPase increased with increasing salinity, while high salinity (above 30 per thousand or 20 per thousand) inhibited ATPase activity. In comparison with A. marina, K. candel appeared to be more sensitive to salinity. The dynamics of membrane potential and transmembrane proton gradient in leaves and roots of A. marina and K. candel seedlings were similar to that of ATPase. When treated directly by NaCl all the indexes were inhibited markedly: there was a little increase within 0-10 per thousand (K. candel) or 0-20 per thousand (A. marina) followed by sharp declining. It indicated that the structure and function of plasma membrane was damaged severely.


Keratoconus corneal architecture after riboflavin/ultraviolet A cross-linking: ultrastructural studies.
Study to investigate the effects of collagen cross-linking on the ultrastructural organization of the corneal stroma in the human keratoconus cornea (KC). Three normal, three keratoconus (KC1, KC2, KC3), and three cross-linked keratoconus (CXL1, CXL2, CXL3) corneas were analyzed. The KC corneas were treated with a riboflavin-ultraviolet A (UVA) treatment (CXL) method described by Wollensak et al. Penetrating keratoplasty (PKP) was performed 6 months after treatment. All samples were processed for electron microscopy. The riboflavin-UVA-treated CXL corneal stroma showed interlacing lamellae in the anterior stroma followed by well-organized parallel running lamellae. The lamellae contained uniformly distributed collagen fibrils (CFs) decorated with normal proteoglycans (PGs). The CF diameter and interfibrillar spacing in the CXL cornea were significantly increased compared to those in the KC cornea. The PG area in the CXL corneas were significantly smaller than the PGs in the KC cornea. The epithelium and Bowman's layer were also normal. On rare occasions, a thick basement membrane and collagenous pannus were also observed. Corneal cross-linking leads to modifications of the cornea stroma. The KC corneal structure showed a modification in the CF diameter, interfibrillar spacing, and PG area. This resulted in a more uniform distribution of collagen fibrils, a key feature for corneal transparency.


Inhibition of Shigella flexneri by the normal intestinal flora. I. Mechanisms of inhibition by Klebsiella.
Growth curves were plotted for Shigella flexneri and Klebsiella (Aerobacter aerogenes) multiplying in pure and mixed culture. In mixed culture, Klebsiella inhibited Shigella. Exponential growth was interrupted and Shigella entered into a logarithmic death phase. An analysis of cultures at the time inhibition occurred revealed that formic and acetic acids produced by Klebsiella were responsible for the inhibition of Shigella. Klebsiella strongly reduced the culture medium. The volatile fatty acids, operating under reduced conditions, exerted a bactericidal effect on Shigella. Results are discussed with reference to the possible role of volatile fatty acids as factors responsible for Shigella inhibition in vivo.


Design, Synthesis, and Evaluation of Orally Available Clioquinol-Moracin M Hybrids as Multitarget-Directed Ligands for Cognitive Improvement in a Rat Model of Neurodegeneration in Alzheimer's Disease.
A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against Alzheimer's disease were evaluated. Biological activity results demonstrated that these hybrids possessed significant inhibitory activities against phosphodiesterase 4D (PDE4D) and Aβ aggregation as well as remarkable antioxidant effects and excellent blood-brain barrier permeability. The optimal compound, 18d (WBQ5187), exhibited excellent PDE4D inhibitory potency (IC50 = 0.32 μM), significant antioxidant effects, appropriate biometal chelating functions, and interesting properties that modulated self- and metal-induced Aβ aggregation. Two-dimensional NMR studies revealed that 18d had significant interactions with Aβ1-42 at the R5, H6, H14, Q15, and F20 residues. Furthermore, this typical hybrid possessed preeminent neuroprotective effects against inflammation in microglial cells. Most importantly, oral administration of 18d·HCl demonstrated marked improvements in cognitive and spatial memory in a rat model of Alzheimer's disease and protected hippocampal neurons from necrosis.


Excellent optical and interfacial performance of a PEDOT-b-PEG block copolymer counter electrode for polymer electrolyte-based solid-state dye-sensitized solar cells.
A poly(3,4-ethylenedioxythiophene)-b-poly(ethylene glycol) (PEDOT-b-PEG) block copolymer doped with perchlorate on FTO shows excellent optical and interfacial performance as a counter electrode (CE), such as low charge transfer resistance and low reflectivity for polymer electrolyte-based solid-state dye-sensitized solar cells (DSCs), resulting in 8.45% energy conversion efficiency, greater than the common Pt CE, via a facile room-temperature process.


Plant-RRBS, a bisulfite and next-generation sequencing-based methylome profiling method enriching for coverage of cytosine positions.
Cytosine methylation in plant genomes is important for the regulation of gene transcription and transposon activity. Genome-wide methylomes are studied upon mutation of the DNA methyltransferases, adaptation to environmental stresses or during development. However, from basic biology to breeding programs, there is a need to monitor multiple samples to determine transgenerational methylation inheritance or differential cytosine methylation. Methylome data obtained by sodium hydrogen sulfite (bisulfite)-conversion and next-generation sequencing (NGS) provide genome-wide information on cytosine methylation. However, a profiling method that detects cytosine methylation state dispersed over the genome would allow high-throughput analysis of multiple plant samples with distinct epigenetic signatures. We use specific restriction endonucleases to enrich for cytosine coverage in a bisulfite and NGS-based profiling method, which was compared to whole-genome bisulfite sequencing of the same plant material. We established an effective methylome profiling method in plants, termed plant-reduced representation bisulfite sequencing (plant-RRBS), using optimized double restriction endonuclease digestion, fragment end repair, adapter ligation, followed by bisulfite conversion, PCR amplification and NGS. We report a performant laboratory protocol and a straightforward bioinformatics data analysis pipeline for plant-RRBS, applicable for any reference-sequenced plant species. As a proof of concept, methylome profiling was performed using an Oryza sativa ssp. indica pure breeding line and a derived epigenetically altered line (epiline). Plant-RRBS detects methylation levels at tens of millions of cytosine positions deduced from bisulfite conversion in multiple samples. To evaluate the method, the coverage of cytosine positions, the intra-line similarity and the differential cytosine methylation levels between the pure breeding line and the epiline were determined. Plant-RRBS reproducibly covers commonly up to one fourth of the cytosine positions in the rice genome when using MspI-DpnII within a group of five biological replicates of a line. The method predominantly detects cytosine methylation in putative promoter regions and not-annotated regions in rice. Plant-RRBS offers high-throughput and broad, genome-dispersed methylation detection by effective read number generation obtained from reproducibly covered genome fractions using optimized endonuclease combinations, facilitating comparative analyses of multi-sample studies for cytosine methylation and transgenerational stability in experimental material and plant breeding populations.


Cross-sectional anatomic images by gamma ray transmission scanning.
60Co gamma-ray transmission data were measured along linear scan paths at a number of angular orientations with respect to the patient and submitted to a computer software program. Reconstructed images are displayed as digital density printouts and as isodensity contours on an x-y plotter or oscilloscope screen. Image resolution is limited primarily by factors such as collimation and the amount of transmission data collected; with the rather rudimentary apparatus at disposal, a spatial resolution better than 5 mm has been achieved.


Direct in vivo imaging of essential bioinorganics in Caenorhabditis elegans.
Metals are essential in biochemistry, with highly regulated localisation and concentration. To continue elucidating the impact of inorganic physiology on cellular process in health and disease requires development of suitable eukaryotic models and experimental approaches. The multicellular organism Caenorhabditis elegans has been widely adopted as a model system and proved to be highly valuable in biomedical research, and here we record the distribution of physiologically important 4th row elements throughout anesthetised, hydrated adult C. elegans without the need for chemical fixation or mechanical sectioning. Probing the partitioning of elements between intact anatomical structures at subcellular length scales allowed the impact of preparation techniques commonly in use for analytical microanalysis to be assessed. In addition, taking advantage of C. elegans as a research tool, these studies were carried out across a cohort of genetically homogenous individuals with specific expression of green fluorescent protein within intestinal cells. These studies allowed direct visualisation of elemental co-localisation with anatomical structures and facilitated analysis of inter-animal variability in biometal abundance and localisation. These data reflect stochastic metabolic activity and confirm C. elegans as a sensitive system in which to explore the effects of altered metal homeostasis.


Structural characterization of a 4-hydroxy-2-alkenal-derived fluorophore that contributes to lipoperoxidation-dependent protein cross-linking in aging and degenerative disease.
Modification of proteins by products of lipid peroxidation results in various fluorescent adducts associated with oxidative stress pathophysiology in degenerative disease. Using n-butylamine as a model for the lysine side chain, the structure of the probable major ex/em 360/430-nm fluorophore that arises from cross-linking of two protein-based lysines by one 4-hydroxy-2-alkenal is shown to be a 2-alkyl-2-hydroxy-1,2-dihydropyrrol-3-one iminium. That this fluorophore can be independently generated in higher yield from either 4-oxo-2-alkenals or 3,4-dioxoalkanals supports a proposed mechanistic pathway that involves two 2e oxidations following initial Schiff base formation.


Lameness detection challenges in automated milking systems addressed with partial least squares discriminant analysis.
Lameness causes decreased animal welfare and leads to higher production costs. This study explored data from an automatic milking system (AMS) to model on-farm gait scoring from a commercial farm. A total of 88 cows were gait scored once per week, for 2 5-wk periods. Eighty variables retrieved from AMS were summarized week-wise and used to predict 2 defined classes: nonlame and clinically lame cows. Variables were represented with 2 transformations of the week summarized variables, using 2-wk data blocks before gait scoring, totaling 320 variables (2 × 2 × 80). The reference gait scoring error was estimated in the first week of the study and was, on average, 15%. Two partial least squares discriminant analysis models were fitted to parity 1 and parity 2 groups, respectively, to assign the lameness class according to the predicted probability of being lame (score 3 or 4/4) or not lame (score 1/4). Both models achieved sensitivity and specificity values around 80%, both in calibration and cross-validation. At the optimum values in the receiver operating characteristic curve, the false-positive rate was 28% in the parity 1 model, whereas in the parity 2 model it was about half (16%), which makes it more suitable for practical application; the model error rates were, 23 and 19%, respectively. Based on data registered automatically from one AMS farm, we were able to discriminate nonlame and lame cows, where partial least squares discriminant analysis achieved similar performance to the reference method.


Effect of oral pre-emptive analgesia on pain management after total knee arthroplasty: a protocol for systematic review and meta-analysis.
Total knee arthroplasty (TKA) is currently regarded as an effective treatment for knee osteoarthritis, relieving patients' pain and significantly enhancing their quality of life and activity levels, allowing them to return to work and daily life after surgery. However, some TKA patients suffer from varying degrees of postoperative residual pain and opioid abuse, which negatively impacts their recovery and quality of life. It has been reported that preoperative treatment with multimodal analgesics improves postoperative pain and reduces opioid consumption. However, there is no conclusive evidence that pre-emptive analgesia provides the same benefits in TKA. In order to inform future research, this protocol focuses on the efficacy and safety of oral analgesics used in TKA pre-emptive analgesia. We will search the literature on the involvement of pre-emptive analgesia in the management of pain in TKA from the PubMed, EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, from their inception to 1 February 2023. Additionally, clinical registry platforms will be investigated to collect data for ongoing studies. Using the Cochrane Risk of Bias Tool, the quality assessment will be conducted. RevMan V.5.4 will be used for the meta-analysis. The statistic I 2 will be used to measure the percentage of total variability due to heterogeneity between studies. Where appropriate, subgroup and sensitivity analyses, assessment of evidence quality and publication bias will be conducted. No ethical approval and consent is required for this systematic review. Moreover, the results of this systematic review will be disseminated through peer-reviewed publications and conference presentations. CRD42022380782.


[Prognostic evolution of Graves' disease treated by synthetic antithyroid (author's transl)].
A follow-up of at least 4 years after withdrawal of a medical treatment of 77 patients with Graves' disease is presented. The treatment consisted in Carbimazole (15-30 mg/d), LT3 (75 ug/d), Propranolol (30-60 mg/d), Hydroxyzine (75 mg/d). A normal thyroid suppressibility (20 mm 99m Tc uptake test) is obtained in patients without goiter faster than in those with goiter. A normal early uptake at the sixth month therapy is a good index for cure. Despite this result the authors recommend a treatment of 12 to 18 months duration because of the probable immunodepressive effect of the antithyroid drugs.


Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.
Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.


Involuntary community treatment of people who are violent and mentally ill: a legal analysis.
Three major legal mechanisms exist for providing involuntary community treatment to people who are violent and mentally disabled: outpatient commitment, preventive commitment, and conditional release from a hospital. In most states, predicted deterioration is either the explicit or the de facto criterion for involuntary community treatment. However, the constitutionality of this standard has been the subject of considerable debate, centering on whether involuntary treatment in the community requires a showing of imminent dangerousness and an overt act of dangerousness and whether a person who is not dangerous solely because of treatment may be committed. The author suggests that the predicted deterioration standard is constitutional, but only if it is accompanied by limitations on the duration of commitment and proof that involuntary treatment is necessary to prevent danger to self or others. The author also discusses whether a person committed under the predicted deterioration standard has the right to refuse treatment and whether persons hospitalized after being committed to involuntary community treatment should receive a hearing.


Adolescent suicide: character traits of high-risk teenagers.
Adolescent suicide rates are increasing and are currently higher than ever recorded. Thus, it has become essential for health professionals, counselors, and parents to become familiar with characteristics of the high-risk teenager. This article examines personality traits and life circumstances which place an adolescent at higher risk for suicide. Among the variables examined are: depression, acute suicidal behavior, poor family relationships, alcohol and drug use, recent loss, failure in school, and other characteristics. As adolescents pass through difficult life stages successfully, teenage suicides will decrease. Professional helpers and parents must be able to recognize the signs which are discussed and take an active role in prevention and/or intervention.


Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.
Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations. We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups. Of 42 555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean±sd age was 51±11 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had ≥4 comorbidities. Age >70 years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having ≥4 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70 years: 0.514, 95% CI 0.458-0.571; ≤70 years: 0.636, 95% CI 0.572-0.696; p=0.004). Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.