Triose-phosphate isomerase (TIM) of the psychrophilic bacterium Vibrio marinus. Kinetic and structural properties.
The purification and characterization of triose-phosphate isomerase from the psychrophilic bacterium Vibrio marinus (vTIM) is described. Crystal structures of the vTIM-sulfate complex and the vTIM-2-phosphoglycolate complex (at a 2.7-A resolution) are also presented. The optimal growth temperature of Vibrio marinus is 15 degrees C. Stability studies show that vTIM is an unstable protein with a half-life of only 10 min at 25 degrees C. The vTIM sequence is most closely related to the sequence of Escherichia coli TIM (eTIM) (66% identity), and several unique structural features described for eTIM are also seen in vTIM, but eTIM is considerably more stable. The Td values of vTIM and eTIM, determined by calorimetric studies, are 41 and 54 degrees C, respectively. Amino acid sequence comparison reveals that vTIM has an alanine in loop 8 (at position 238), whereas all other TIM sequences known to date have a serine. The vTIM mutant A238S was produced and characterized. Compared with wild type, the catalytic efficiency of the A238S mutant is somewhat reduced, and its stability is considerably increased.


Comparison of the personality and other psychological factors of students with internet addiction who do and do not have associated social dysfunction.
There is ongoing controversy about whether or not internet addiction should be considered a non-substance behavioral addiction (like gambling disorder) and, if so, what diagnostic criteria should be used to define the condition. Current criteria for internet addiction give equal diagnostic weight to the physiological symptoms and the social consequences of internet addiction. Assess the psychological correlates of social dysfunction among individuals with internet addiction. A total of 133 students who sought treatment at the Guangji Psychiatric Hospital from July 2011 to December 2013 for psychological problems related to excessive internet use and who currently met Young criteria for internet addiction were identified; 31 of the 38 students who meet rigorous criteria for concurrent internet-related social dysfunction and a random sample of 44 of the 95 students without concurrent social dysfunction completed a battery of psychosocial measures: seven supplementary scales of the Minnesota Multiphasic Personality Inventory (MMPI), the Egna Minnen av Barndoms Uppfostran perceived parenting scale, the Perceived Social Support Scale, the Trait Coping Style Questionnaire, and the Symptom Checklist 90. Compared to persons with internet addiction without accompanying social dysfunction, those with social dysfunction had higher levels of interpersonal sensitivity, hostility, and paranoia; lower levels of social responsibility, anxiety, self-control, and family social support; and they were more likely to employ negative coping strategies. There were however, no differences in perceived parenting styles between the two groups. A relatively small proportion of individuals who meet the physiological markers of internet addiction simultaneously report significant internet-related social dysfunction. There are several psychosocial measures that distinguish persons with internet addiction who do or do not have concurrent social dysfunction. Further research is needed to determine whether or not these are two distinct subtypes of internet addiction and whether or not persons with internet addiction without concurrent social dysfunction should be classified as suffering from a 'mental disorder'.


The role of glucocorticoids and corticotropin-releasing hormone regulation on anxiety symptoms and response to treatment.
The stress response has been linked to the expression of anxiety and depression, but the mechanisms for these connections are under continued consideration. The activation and expression of glucocorticoids and CRH are variable and may hold important clues to individual experiences of mood disorders. This paper explores the interactions of glucocorticoids and CRH in the presentation of anxiety and depressive disorders in an effort to better describe their differing roles in each of these clinical presentations. In addition, it focuses on ways in which extra-hypothalamic glucocorticoids and CRH, often overlooked, may play important roles in the presentation of clinical disorders.


Service use and satisfaction among elderly former prisoners of war in South Carolina.
This project was developed to evaluate the use of and satisfaction with Veteran's Affairs (VA) medical services and disability benefits among surviving elderly prisoners of war (POWs) in South Carolina. A single-assessment quantitative survey strategy was implemented to learn more about the service use patterns and satisfaction with care of two groups of male former POWs (N = 87): those who were members of a national POW service organization and those who were not. Data show that the majority of these POWs had used the VA for medical care in the previous year, received disability compensation through the VA, and were satisfied with VA primary care medical services. Furthermore, differences between these two POW groups were minimal. Results provide preliminary evidence that many former POWs rely heavily upon the VA for provision of primary medical and specialty care and disability compensation and that POWs are generally satisfied with the VA services and benefits they receive.


Antiepileptic drugs on calcium currents recorded from cortical and PAG neurons: therapeutic implications for migraine.
Cortex and periaqueductal grey (PAG) play a major role in the pathophysiology of migraine. Some antiepileptic drugs (AEDs) influence the activity of these structures by modulating high-voltage-activated (HVA) Ca(2+) channels and are effective in migraine prevention. The aim of the present study was to investigate the expression of total HVA Ca(2+) channels in cortical and PAG neurons and to study the differential action of AEDs on these channels. Isolated neurons were visually identified based on morphological criteria. HVA currents were recorded by whole-cell patch-clamp technique. The distribution ratio of L-, N-, P-, Q- and R-type HVA Ca(2+) channels was different between cortical and PAG neurons. In particular, we found that P- and Q-type HVA Ca(2+) channels were more expressed in PAG neurons than in cortical cells, whereas L- and R-type HVA Ca(2+) channels showed an opposite distribution. Interestingly, N-type HVA Ca(2+) channels were equally distributed in these two neuronal populations. A differential sensitivity to AEDs of HVA Ca(2+) channels located on cortical and PAG neurons was observed for topiramate (TPM), but not for lamotrigine (LTG) or levetiracetam (LEV). In fact, whereas both LTG and LEV were equally effective and potent in inhibiting HVA Ca(2+) currents in the two neuronal populations, TPM showed a much higher potency and efficacy in blocking these currents in PAG neurons than in cortical pyramidal cells. TPM, in fact, inhibited N-, P- and L-type channels in PAG neurons, whereas in cortical neurons this AED modulated only P- and L-type channels. Unlike the other AEDs investigated, valproic acid did not affect HVA Ca(2+) currents in cortical and PAG neurons. The negative modulation of specific subtypes of HVA Ca(2+) channels by various AEDs can restore normal electrical activity in target brain areas such as cortex and PAG, providing interesting therapeutic approaches in migraine prevention.


Management and treatment of ankylosing spondylitis.
Our purpose is to review the developments in the treatment of ankylosing spondylitis in 2004. Tumor necrosis factor blockers have been shown to have rapid and persistent efficacy with limited additional toxicity up to 4 years with continuing therapy, but cessation of therapy results in relapse in most patients. Therapy is cost-effective. There are some differences between the different tumor necrosis factor blockers currently available. Other biologic therapies are not as promising. Algorithms have been developed to aid in early diagnosis. This may be relevant for future therapeutic strategies. Tumor necrosis factor blockers are effective and safe in active spinal disease, but simple measures such as exercise and nonsteroidal anti-inflammatory drug therapy are still considered the basis of standard therapy. Early disease diagnosis is becoming easier, and is likely to be important for optimal therapeutic responses. Future research will include the effect of tumor necrosis factor blockade on structural disease progression.


Influenza Vaccination in Italian Healthcare Workers (2018-2019 Season): Strengths and Weaknesses. Results of a Cohort Study in Two Large Italian Hospitals.
Annual vaccination is the most effective way to combat influenza. As influenza viruses evolve, seasonal vaccines are updated annually. Within the European project Development of Robust and Innovative Vaccine Effectiveness (DRIVE), a cohort study involving Italian healthcare workers (HCWs) was carried out during the 2018-2019 season. Two aims were defined: to measure influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza cases and to conduct an awareness-raising campaign to increase vaccination coverage. Each subject enrolled was followed up from enrollment to the end of the study. Each HCW who developed ILI was swabbed for laboratory confirmation of influenza. Influenza viruses were identified by molecular assays. A Cox regression analysis, crude and adjusted for confounding variables, was performed to estimate the IVE. Among the 4483 HCWs enrolled, vaccination coverage was 32.5%, and 308 ILI cases were collected: 23.4% were positive for influenza (54.2% A(H1N1) pdm09; 45.8% A(H3N2)). No influenza B viruses were detected. No overall IVE was observed. Analyzing the subtypes of influenza A viruses, the IVE was estimated as 45% (95% CI: -59 to 81) for A(H1N1) pdm09. Vaccination coverage among HCWs increased. Study difficulties and the circulation of drifted variants of A(H3N2) could partly explain the observed IVE.


[Specific dynamic action of food in obese patients].
Certain features of the body hormonal system participation in the realizing of the specific dynamic action of food (SDAF) were studied in 26 patients with exogenous constitutional obesity. The radioimmunoassay was used to estimate the levels of a number of hormones (gastrin, insulin, glucagon, triiodothyronine, thyrotrophin, adrenocorticotrophin and hydrocortisone) in the peripheral blood of the patients on an empty stomach (the basal level) and 1,2 and 4 hours after food protein intake. The control group consisted of 20 normal subjects. It has been shown that SDAF is a complex process of changing from the state of hunger to satiation that involves many regulatory components, both nervous and humoral. The study of the features of the SDAF development in health and disease presents valuable information on the mechanisms of metabolic disorders in the body in varying pathologic states including obesity.


Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases.
Nrf2 is a transcription factor that has emerged as the cell's main defense mechanism against many harmful environmental toxicants and carcinogens. Nrf2 is negatively regulated by Keap1, a substrate adaptor protein for the Cullin3 (Cul3)-containing E3-ligase complex, which targets Nrf2 for ubiquitination and degradation by the ubiquitin proteasome system (UPS). Recent evidence suggests that constitutive activation of Nrf2, due to mutations in Keap1 or Nrf2, is prominent in many cancer types and contributes to chemoresistance. Regulation of Nrf2 by the Cul3-Keap1-E3 ligase provides strong evidence that tight regulation of Cullin-ring ligases (CRLs) is imperative to maintain cellular homeostasis. There are seven known Cullin proteins that form various CRL complexes. They are regulated by neddylation/deneddylation, ubiquitination/deubiquitination, CAND1-assisted complex assembly/disassembly, and subunit dimerization. In this review, we will discuss the regulation of each CRL using the Cul3-Keap1-E3 ligase complex as the primary focus. The substrates of CRLs are involved in many signaling pathways. Therefore, deregulation of CRLs affects several cellular processes, including cell cycle arrest, DNA repair, cell proliferation, senescence, and death, which may lead to many human diseases, including cancer. This makes CRLs a promising target for novel cancer drug therapies.


A genome-wide linkage scan in Tunisian families identifies a novel locus for non-syndromic posterior microphthalmia to chromosome 2q37.1.
Posterior microphthalmia (PM) is a relatively rare autosomal recessive condition with normal anterior segment and small posterior segment resulting in high hyperopia and retinal folding. It is an uncommon subtype of microphthalmia that has been mostly reported to coexist with several other ophthalmic conditions and to occur in sporadic cases. The membrane-type frizzled-related protein (MFRP) is the only gene so far reported implicated in autosomal recessive, non-syndromic and syndromic forms of PM. Here, we performed a clinical and genetic analysis using six consanguineous families ascertained from different regions of Tunisia and affected with non-syndromic PM that segregates as an autosomal recessive trait. To identify the disease-causing defect in these families, we first analysed MFRP gene, then some candidate genes (CHX10, OPA1, MITF, SOX2, CRYBB1-3 and CRYBA4) and loci (MCOP1, NNO1 and NNO2) previously implicated in different forms of microphthalmia. After exclusion of these genes and loci, we performed a genome-wide scan using a high density single nucleotide polymorphism (SNP) array 50 K in a large consanguineous pedigree. SNP genotyping revealed eight homozygous candidate regions on chromosomes 1, 2, 3, 6, 15, 17 and 21. Linkage analysis with additional microsatellite markers only retained the 2q37.1 region with a maximum LOD score of 8.85 obtained for D2S2344 at theta = 0.00. Further investigations are compatible for linkage of four more families to this region with a refined critical interval of 2.35 Mb. The screening of five candidate genes SAG, PDE6D, CHRND, CHRNG and IRK13 did not reveal any disease-causing mutation.


Cytomegalovirus seroprevalence in organ donors and kidney transplant recipients, Colombia, 2010-2014.
Cytomegalovirus infections have gained high importance for individuals that have received organ transplants given the clinical implications this may have in immunocompromised patients. To describe the seroprevalence of cytomegalovirus in organ donors and recipients of kidney transplants nationwide from the six regions established by the Red Nacional de Donación y Trasplante. We conducted a descriptive retrospective study that included 1,813 organ donors and 3,313 recipients of kidney transplants, and we calculated IgM and IgG seroprevalence for cytomegalovirus. IgG prevalence was stratified according to sex, age group, and region, and the results were analyzed in each donor-recipient pair and classified according to the risk. Statistical packages IBM SPSS®, Statistics 22, and Epi Info 7 were utilized. IgG prevalence for cytomegalivirus was 86.8% in donors and 91.0% in kidney transplant recipients with statistical significance observed for age, geographical location, and between donors and recipients. We analyzed 1,764 pairs of donors and recipients, of which 91.4% were categorized as having intermediate risk. The results of this study showed high cytomegalovirus infection rates in Colombia. Given the risk, categorization of patients undergoing transplants, measures should be adopted by medical teams to minimize risks.


Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors.
Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ~80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets.


A survey of clergy practices associated with premarital financial counseling.
The purpose of this exploratory study was to gain an understanding of the state of clergy-led premarital financial counseling. Clergy respondents (n = 223) indicated that they often include a financial component in their formal premarital counseling. The most frequently discussed financial topics are budgeting, managing debt and credit, and saving. The most frequently cited obstacles to providing premarital financial counseling are lack of time and lack of subject matter expertise.


Robust state estimation for neural networks with discontinuous activations.
Discontinuous dynamical systems, particularly neural networks with discontinuous activation functions, arise in a number of applications and have received considerable research attention in recent years. In this paper, the robust state estimation problem is investigated for uncertain neural networks with discontinuous activations and time-varying delays, where the neuron-dependent nonlinear disturbance on the network outputs are only assumed to satisfy the local Lipschitz condition. Based on the theory of differential inclusions and nonsmooth analysis, several criteria are presented to guarantee the existence of the desired robust state estimator for the discontinuous neural networks. It is shown that the design of the state estimator for such networks can be achieved by solving some linear matrix inequalities, which are dependent on the size of the time derivative of the time-varying delays. Finally, numerical examples are given to illustrate the theoretical results.


[Progress in researches on stem cell therapy for erectile dysfunction].
Erectile dysfunction (ED) commonly results from endothelial dysfunction and erectile nerve damage. Recent researches have focused on the preclinical studies of stem cell-based therapies targeted at repairing penile endothelium and protecting erectile nerves. Early studies showed that stem cell- or gene-modified stem cell-based therapies may have enduring efficacy and eventually lead to a cure for ED. Such stem cells as embryonic, mesenchymal, muscle-derived and adipose-derived ones and endothelial progenitor cells all have differentiation potentials and obvious advantages in protecting and repairing both nervi erigentes and corpus cavernosum vascular endothelial cells. Stem cell-based therapies promise to be an effective approach to human erectile dysfunction.


Toward early detection of Helicobacter pylori-associated gastric cancer.
Gastric cancer is typically diagnosed at a late stage, leading to poor prognoses. Helicobacter pylori is responsible for 70% of gastric cancers globally, and patients with this bacterial infection often present with early stages of the carcinogenic pathway such as inflammation or gastritis. Although many patients continue to progress to advanced-stage disease after antibacterial treatment, there are no follow-up screening protocols for patients with a history of H. pylori. Several biomarkers (Lgr5, CD133, CD44) become upregulated during gastric carcinogenesis. A logistic regression model is developed using clinical data from 59 patients at different stages of the carcinogenic pathway to identify the likelihood of being at an advanced stage of disease for all combinations of age, sex, and marker positivity. Using these likelihood distributions and the observed rate of marker positivity increase, time to high likelihood (probability >0.8) of advanced disease for individual patients is predicted. A strong correlation between marker positivity and disease stage was found for all three markers. Disease stage was accurately classified by the respective regression models for more than 86% of retrospective patients. Highly patient-specific predictions of time to onset of dysplasia were made, allowing the classification of 17 patients initially diagnosed with intestinal metaplasia into high-, intermediate-, or low-risk categories. We present an approach designed to integrate pathology, mathematics, and statistics for detection of the earliest precancerous, treatable lesion. Given the simplicity and robustness of the framework, such technique has the potential to guide personalized screening schedules to minimize the risk of undetected malignant transformation.


The piscine plasma retinol-binding protein. Purification, partial amino acid sequence and interaction with mammalian transthyretin of rainbow trout (Oncorhynchus mykiss) retinol-binding protein.
1. Retinol-binding protein (RBP) has been isolated from the pooled plasma or rainbow trouts (Oncorhinchus mykiss) by gel filtration, hydrophobic interaction chromatography and ion-exchange chromatography. By this procedure two forms of the protein, both with a molecular mass (approximately 20 kDa) similar to that of mammalian RBP, were purified to homogeneity. Five amino acid substitutions have been found in the partial (about 60%) sequences of the two forms of trout RBP, which are presumably acetylated at their N terminus. The apparent participation of six conserved cysteines in the formation of disulphide bridges, as in human RBP, and the similarity (about 60%) of the amino acid sequence of trout and mammalian RBPs, indicate the existence of a similar overall structure organization in evolutionary distant RBPs. 2. Although the two forms of trout RBP are not physiologically involved in the formation of any protein--protein complex in plasma, they are capable of interacting with mammalian transthyretin, albeit with a binding affinity (K'd = 15-40 microM) considerably lower than that of mammalian RBP. Our data indicate that the two forms of trout RBP also possess the region that in mammalian RBP has the functional role of binding transthyretin. It is suggested that transthyretin (or a homologous protein) was modified, during phylogenetic development of the non mammalian vertebrates, to acquire a binding site for such a region of the RBP molecule.


Carbohydrate-binding component of amphibian embryo cell surfaces: restriction to surface regions capable of cell adhesion.
Superficial cells from early amphibian embryos display regional specializations of their cell surfaces. That portion of the plasma membrane facing the perivitelline space (apical surface) is nonadhesive, whereas, in the same cell, the lateral and basal portions of the plasma membrane will adhere to other cells. These adhesive differences are maintained on single cells that have been dissociated from the intact embryo. Extracts of cleavage-stage Rana pipiens embryos are capable of agglutinating formalinized sheep erythrocytes. The hemagglutination activity can be blocked by a yeast mannan and a family of glycoproteins containing high levels of mannose, indicating the presence of a lectin with oligomannosyl specificity. The cell surface location of this carbohydrate-binding component can be demonstrated by the ability of the formalinized sheep erythrocytes to form rosettes with living dissociated embryonic superficial cells. Rosette formation is blocked by the same inhibitors that are effective in blocking the activity of the crude extracts. The formalinized sheep erythrocytes form rosettes only to those cell surface regions of the superficial cells that are capable of adhering to other amphibian embryo cells. Receptors for concanavalin A, a lectin that binds D-mannose and D-glucose residues, have also been shown to be present exclusively over the adhesive regions of the superficial cells. The involvement of a carbohydrate-binding component with oligomannosyl specificity in the adhesive mechanisms of these cells is suggested by this restriction of both the embryonic amphibian lectin and its possible receptors (concanavalin A receptors) to adhesive regions of the cell surface.


Relations between personality measures and physiological reactivity using a perceptual motor challenge.
60 undergraduates participated in research designed to investigate the relations between psychological and physiological measures of personality under stress. Psychological assessments were elicited from responses to the Jenkins Activity Survey. Physiological assessments were elicited during 5 1-min. trials on the pursuit rotor, a perceptual motor task. Pearson correlations and multiple regression analyses were consistent with the notion that psychological and physiological assessments yield contradictory information and that research is needed to develop valid methodologies with which to assess human stress.


[Role of dopamine receptors in the mechanism of action of neuroleptics].
The authors analyze the literature and their own data on the influence of neuroleptics on the cerebral dopamine and adrenoreceptors. It is shown that antipsychotic activity of neuroleptics correlates with their ability to block D2 dopamine receptor whereas their sedative properties are in a better agreement with the blockade of alpha 1-adrenoreceptor. Effects at the molecular level, other than the blockade of the above receptors, may be involved in forming the activity spectrum of each drug.


Solubilization of a functionally active platelet-activating factor receptor from rabbit platelets.
Binding of platelet-activating factor (PAF) to a specific high-affinity membrane receptor has been demonstrated in numerous cell types, but very little is known about the molecular nature of this receptor. The receptor from rabbit platelets was solubilized using CHAPS, digitonin, octyl glucoside, Nonidet P-40 or sodium cholate, either with pre-bound [3H]PAF or in the absence of ligand. We have been able to demonstrate for the first time that the receptor solubilized with CHAPS, in the absence of ligand, could retain its binding activity. It migrated as a high molecular mass complex (greater than 350 kDa) on a Bio-Gel A-0.5 m gel filtration column. Binding to solubilized receptor rapidly reached an equilibrium at room temperature, but was much slower at 0 degrees C. Scatchard plots were used to calculate the number (approx. 100 per cell) and the affinity (Kd 2.5 +/- 1.4 nM) of the solubilized receptors. These values were comparable with those obtained from whole-cell binding experiments. Competition by PAF antagonists also verified that the assay was measuring PAF receptor binding activity. The presence of a protein in the receptor complex was demonstrated by heat and trypsin inactivation of binding activity. Trypsin had no effect on binding of PAF to whole cells, but was able to decrease binding activity in solubilized receptor preparations. Attempts to demonstrate the involvement of a glycoprotein by use of various lectin columns proved unsuccessful. The latter results are consistent with findings suggesting that the binding site of the PAF receptor may not be exposed at the cell surface.


CT sinogram-consistency learning for metal-induced beam hardening correction.
This paper proposes a sinogram-consistency learning method to deal with beam hardening-related artifacts in polychromatic computerized tomography (CT). The presence of highly attenuating materials in the scan field causes an inconsistent sinogram that does not match the range space of the Radon transform. When the mismatched data are entered into the range space during CT reconstruction, streaking and shading artifacts are generated owing to the inherent nature of the inverse Radon transform METHODS: The proposed learning method aims to repair inconsistent sinogram by removing the primary metal-induced beam hardening factors along the metal trace in the sinogram. Taking account of the fundamental difficulty in obtaining sufficient training data in a medical environment, the learning method is designed to use simulated training data and a patient's implant type-specific learning model is used to simplify the learning process. The feasibility of the proposed method is investigated using a dataset, consisting of real CT scans of pelvises containing simulated hip prostheses. The anatomical areas in training and test data are different, in order to demonstrate that the proposed method extracts the beam hardening features, selectively. The results show that our method successfully corrects sinogram inconsistency by extracting beam hardening sources by means of deep learning. This paper proposed a deep learning method of sinogram correction for beam hardening reduction in CT for the first time. Conventional methods for beam hardening reduction are based on regularizations, and have the fundamental drawback of being not easily able to use manifold CT images, while a deep learning approach has the potential to do so.


Clinical outcomes of hepatitis C treatment in a prison setting: feasibility and effectiveness for challenging treatment populations.
More than one-third of people in the United States with hepatic C virus (HCV) infection pass through the correctional system annually. Data are lacking on outcomes of treatment with pegylated interferon plus ribavirin (PEG-RBV) in correctional settings. During 2002-2006, we analyzed patients in the Connecticut Department of Correction who received PEG-RBV. We assessed the rates of sustained virological response, hospitalization, and use of medications to treat psychiatric disorders and anemia. Of 138 treatment-naive patients referred for treatment, 68 (49%) were approved. Overall, sustained virological response occurred in 47.1% of patients (for HCV genotype 1, 43.1%; for HCV genotypes 2 and 3, 58.8%). Only 9 patients (13%) discontinued treatment because of adverse effects. Multiple regression analysis revealed that not achieving a sustained virological response was correlated with HCV genotype 1 infection plus cirrhosis (adjusted odds ratio, 12.9; 95% confidence interval, 1.1-148) and baseline major depression (adjusted odds ratio, 3.4; 95% confidence interval, 1.01-11.6), but not with HIV infection, a baseline HCV RNA level >or=400,000 IU/mL, or black race. Compared with baseline, the rate of prescription of a new mood stabilizer (2.2 vs. 0.8 prescriptions per person-year) or an opioid (1.8 vs. 0.5 prescriptions per person-year) was higher during treatment, whereas there was no change in the rate of prescription of benzodiazepines and antipsychotic medications. These results support the feasibility and clinical effectiveness of PEG-RBV for the treatment of chronic HCV infection in correctional facilities.


Occupancy modeling, maximum contig size probabilities and designing metagenomics experiments.
Mathematical aspects of coverage and gaps in genome assembly have received substantial attention by bioinformaticians. Typical problems under consideration suppose that reads can be experimentally obtained from a single genome and that the number of reads will be set to cover a large percentage of that genome at a desired depth. In metagenomics experiments genomes from multiple species are simultaneously analyzed and obtaining large numbers of reads per genome is unlikely. We propose the probability of obtaining at least one contig of a desired minimum size from each novel genome in the pool without restriction based on depth of coverage as a metric for metagenomic experimental design. We derive an approximation to the distribution of maximum contig size for single genome assemblies using relatively few reads. This approximation is verified in simulation studies and applied to a number of different metagenomic experimental design problems, ranging in difficulty from detecting a single novel genome in a pool of known species to detecting each of a random number of novel genomes collectively sized and with abundances corresponding to given distributions in a single pool.


Alpha1-macroglobulin: a potential obesity-related factor in serum.
The identification of factors related to obesity is very important for an early diagnosis of susceptibility to obesity and, accordingly, its prevention. The objective of the current study was to search for specific obesity-related factors in serum, as they can be measured non-invasively. Male Sprague-Dawley rats were fed a high-fat (HF) diet for eight weeks to generate obesity-prone (OP) and obesity-resistant (OR) rats. After blood sampling, serum proteome analysis was conducted using two-dimensional gel electrophoresis (2-DE) combined with mass spectrometry (MS). Apolipoprotein A-I (apo A-I), beta-actin, and vitamin D-binding protein (DBP) prepeptide were up-regulated in both the OP and OR rats. Two down-regulated haptoglobulins were observed in the OP and OR rats. Alpha1-macroglobulin (alpha1-M) and an unknown protein product were decreased in the OP rats compared with the OR rats. Alpha1-M was nearly undetectable in the OP rats from the 2-DE map and was further confirmed to be down-regulated by ELISA. The syntropic changes in the proteins apo A-I, beta-actin, DBP prepeptide, and haptoglobulin in the OP and OR rats might be a reflection of the HF diet. The unknown protein product should be isolated and identified. Alpha1-M is proved to be a potential serum factor related to obesity proneness and obesity resistance.


Selection for body weight induces differences in exploratory behavior and learning in mice.
Mice that were selected for over 108 generations for body weight at the postnatal (PN) day 21 were examined in the open field (OF) test and in the Lashley maze (LM) for their exploratory behavior and spatial learning. Light (L), heavy (C) and control (K) lines of mice in three age groups: PN-21, PN-56 and PN-90, were tested once in the OF and three times in the LM. During the session in the OF the L mice displayed a steady increase of behavioral activity (sum of locomotion and rearing, climbing, sniffing, and grooming acts), whereas mice C and K habituated in the last stage. During entire session in the OF activity of the L mice was lower than that of the C and K mice. The L mice displayed high defecation/urination scores. In the learning task the L mice performed worse than the C and K mice. In conclusion, behavior of the L line was different from that of the two other lines: they showed higher anxiety and poorer spatial learning.


Pattern of convergence of the receptors of the barnacle's three ocelli onto second-order cells.
The giant barnacle, Balanus nubilus, has three simple eyes, two lateral and one median. We have studied the convergence of the receptors of these ocelli by recording from the second-order cell (I-cell) and from the receptors' terminals. The I-cell's responses to illumination of the median and lateral eyes are similar in shape, dynamic range, and reversal potential, but the response to lateral input has a longer latency, a slower rise time, and a smaller amplitude. These differences primarily reflect the different voltage changes in the terminals of the decrementally conducting median and lateral receptors. Simultaneous recordings from the terminals of median and lateral receptors showed that the responses to light recorded in lateral terminals had a longer latency, a slower rise time, and smaller amplitude than signals in median terminals. The differences in the I-cell's responses to median and lateral input were essentially eliminated by stimulating the median and lateral ocellar nerves with extracellular suction electrodes positioned at equal distances from the receptors' terminals. The similarity of the I-cell's responses to median and lateral input suggests that lateral photoreceptors, like median receptors, contact the I-cell directly. No evidence was found for interaction between median and lateral receptors. Simultaneous fills of median and lateral receptors with cobalt showed minimal overlap between their terminal arbors. No voltage change was detected in the second receptor when the voltage in the first was changed with current pulses or when action potentials were elicited in the presence of tetraethylammonium ions. The absence of a detectable response in the terminals of one eye's receptors when the receptors of the other eye were stimulated with current or light suggests that there is no feedback from the I-cell to the receptors. Simultaneous illumination of the median and lateral eyes produced responses in the I-cell expected from two independent inputs. The first synaptic stage of the visual pathway in the barnacle is thus unusually simple, consisting of a small number of electrically isolated photoreceptors converging upon the same pair of second-order cells with no feedback interaction.


Focused ultrasound combined with radiotherapy for malignant brain tumor: a preclinical and clinical study.
Blood-brain barrier (BBB) remains to be the major obstacle to conquer in treating patients with malignant brain tumors. Radiation therapy (RT), despite being the mainstay adjuvant modality regardless of BBB, the effect of radiation induced cell death is hindered by the hypoxic microenvironment. Focused ultrasound (FUS) combined with systemic microbubbles has been shown not only to open BBB but also potentially increased regional perfusion. However, no clinical study has investigated the combination of RT with FUS-BBB opening (RT-FUS). We aimed to provide preclinical evidence of RT-FUS combination in GBM animal model, and to report an interim analysis of an ongoing single arm, prospective, pilot study (NCT01628406) of combining RT-FUS for recurrent malignant high grade glioma patients, of whom re-RT was considered for disease control. In both preclinical and clinical studies, FUS-BBB opening was conducted within 2 h before RT. Treatment responses were evaluated by objective response rate (ORR) using magnetic resonance imaging, progression free survival, and overall survival, and adverse events (AE) in clinical study. Survival analysis was performed in preclinical study and descriptive analysis was performed in clinical study. In mouse GBM model, the survival analysis showed RT-FUS (2 Gy) group was significantly longer than RT (2 Gy) group and control, but not RT (5 Gy) group. In the pilot clinical trial, an interim analysis of six recurrent malignant high grade glioma patients underwent a total of 24 RT-FUS treatments was presented. Three patients had rapid disease progression at a mean of 33 days after RT-FUS, while another three patients had at least stable disease (mean 323 days) after RT-FUS with or without salvage chemotherapy or target therapy. One patient had partial response after RT-FUS, making the ORR of 16.7%. There was no FUS-related AEs, but one (16.7%) re-RT-related grade three radiation necrosis. Reirradiation is becoming an option after disease recurrence for both primary and secondary malignant brain tumors since systemic therapy significantly prolongs survival in cancer patients. The mechanism behind the synergistic effect of RT-FUS in preclinical model needs further study. The clinical evidence from the interim analysis of an ongoing clinical trial (NCT01628406) showed a combination of RT-FUS was safe (no FUS-related adverse effect). A comprehensive analysis of radiation dosimetry and FUS energy distribution is expected after completing the final recruitment.


Genetic analysis of the chitinase system of Serratia marcescens 2170.
To carry out a genetic analysis of the degradation and utilization of chitin by Serratia marcescens 2170, various Tn5 insertion mutants with characteristic defects in chitinase production were isolated and partially characterized. Prior to the isolation of the mutants, proteins secreted into culture medium in the presence of chitin were analyzed. Four chitinases, A, B, C1, and C2, among other proteins, were detected in the culture supernatant of S. marcescens 2170. All four chitinases and a 21-kDa protein (CBP21) lacking chitinase activity showed chitin binding activity. Cloning and sequencing analysis of the genes encoding chitinases A and B of strain 2170 revealed extensive similarities to those of other strains of S. marcescens described previously. Tn5 insertion mutagenesis of strain 2170 was carried out, and mutants which formed altered clearing zones of colloidal chitin were selected. The obtained mutants were divided into five classes as follows: mutants with (i) no clearing zones, (ii) fuzzy clearing zones, (iii) large clearing zones, (iv) delayed clearing zones, and (v) small clearing zones. Preliminary characterization suggested that some of these mutants have defects in chitinase excretion, a negatively regulating mechanism of chitinase gene expression, an essential factor for chitinase gene expression, and a structural gene for a particular chitinase. These mutants could allow researchers to identify the genes involved in the degradation and utilization of chitin by S. marcescens 2170.


Humoral immune response to vaccines in patients with rheumatoid arthritis treated with tocilizumab: results of a randomised controlled trial (VISARA).
To evaluate the effect of tocilizumab (TCZ), an interleukin 6 receptor inhibitor, on humoral immune responses to immunisations in patients with rheumatoid arthritis (RA). Patients with RA with inadequate response/intolerance to one or more anti-tumour necrosis factor-α agents were randomly assigned (2:1) to TCZ 8 mg/kg intravenously every 4 weeks plus methotrexate (MTX) or MTX alone up until week 8. Serum was collected before vaccination at week 3, antibody titres were evaluated at week 8, and then all patients received TCZ+MTX through week 20. End points included proportion of patients responding to ≥6/12 pneumococcal polysaccharide vaccine (PPV23) serotypes (primary) and proportions responding to tetanus toxoid vaccine (TTV; secondary) at week 8. 91 patients were randomised. At week 8, 60.0% of TCZ+MTX and 70.8% of MTX patients responded to ≥6/12 PPV23 serotypes, with insufficient evidence for any difference in treatments (10.8% (95% CI -33.7 to 12.0)), and 42.0% and 39.1%, respectively, responded to TTV. Two of three TCZ+MTX patients with non-protective baseline TTV antibody titres achieved protective levels by week 8. The safety profile of TCZ was consistent with previous reports. Short-term TCZ treatment does not significantly attenuate humoral responses to PPV23 or TTV. To maximise vaccine response, patients should be up to date with immunisations before starting TCZ treatment. NCT01163747.


High-Power Laser Application for Immediate Implant Placement in Infected Sites: A Systematic Review.
Objective: The purpose of this study was to review the literatures regarding the treatment outcomes of applying laser to the infected sites in immediate implant placement. The review tended to primarily target a question: does applying high-power laser have any positive effect on infected sites in immediate implant placement? Background: Although immediate placement of dental implants has been referred to as a predictable and successful procedure, it is prone to the presence of infection that interferes with the healing process, and triggers the failure of implants. Materials and methods: A thorough electronic database search was conducted on PubMed/Medline, Embase, Web of Science, Google Scholar, and the Cochrane library in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Two writers worked separately on screening the eligible studies, assessing whether there was a risk of bias, and extracting the required data. Results: Five out of the 60 studies nominated by the database search matched the inclusion criteria. The studies were carried out on a total of 192 patients with 296 implants in all. Ultimately, the study focused on 245 implants whose infected bed had been already decontaminated and prepared with the help of the high-intensity laser, used either alone or in combination with other approaches before implantation. With only nine failures, the implants inserted in infected and irradiated areas had a 96.3% overall survival rate. Conclusions: Taking the limitations of the review into account, the authors arrived at the conclusion that high-power laser irradiation can be beneficial for immediate implant placement in infected sites.


Bone microstructure and the evolution of growth patterns in Permo-Triassic therocephalians (Amniota, Therapsida) of South Africa.
Therocephalians were a speciose clade of nonmammalian therapsids whose ecological diversity and survivorship of the end-Permian mass extinction offer the potential to investigate the evolution of growth patterns across the clade and their underlying influences on post-extinction body size reductions, or 'Lilliput effects'. We present a phylogenetic survey of limb bone histology and growth patterns in therocephalians from the Middle Permian through Middle Triassic of the Karoo Basin, South Africa. Histologic sections were prepared from 80 limb bones representing 11 genera of therocephalians. Histologic indicators of skeletal growth, including cortical vascularity (%CV) and mean primary osteon diameters (POD), were evaluated in a phylogenetic framework and assessed for correlations with other biologically significant variables (e.g., size and robusticity). Changes in %CV and POD correlated strongly with evolutionary changes in body size (i.e., smaller-bodied descendants tended to have lower %CV than their larger-bodied ancestors across the tree). Bone wall thickness tended to be high in early therocephalians and lower in the gracile-limbed baurioids, but showed no general correlation with cross-sectional area or degree of vascularity (and, thus, growth). Clade-level patterns, however, deviated from previously studied within-lineage patterns. For example, Moschorhinus, one of few therapsid genera to have survived the extinction boundary, demonstrated higher %CV in the Triassic than in the Permian despite its smaller size in the extinction aftermath. Results support a synergistic model of size reductions for Triassic therocephalians, influenced both by within-lineage heterochronic shifts in survivor taxa (as reported in Moschorhinus and the dicynodont Lystrosaurus) and phylogenetically inferred survival of small-bodied taxa that had evolved short growth durations (e.g., baurioids). These findings mirror the multi-causal Lilliput patterns described in marine faunas, but contrast with skeletochronologic studies that suggest slow, prolonged shell secretion over several years in marine benthos. Applications of phylogenetic comparative methods to new histologic data will continue to improve our understanding of the evolutionary dynamics of growth and body size shifts during mass extinctions and recoveries.


A functional link between polo-like kinase 1 and the mammalian target-of-rapamycin pathway?
Polo like kinase-1 is a key effector of cell division and its overexpression in several cancers is often linked with negative prognostic. We recently described that Plk1 is overexpressed in acute myeloid leukemia, and that its inhibition selectively reduces the proliferation of leukemic cells. Here, we report that Plk1 inhibition or depletion using pharmacological and siRNA approaches decreased the phosphorylation of two mTOR substrates in AML cells. In HCT116 cells, inducible expression of a constitutively active form of Plk1 leads to activation of mTOR, as shown by increased phosphorylation of its 4E-BP1 and RPS6 down-stream targets. In addition, cells overexpressing the active form of Plk1 were characterized by abnormal growth that could be reversed by rapamycin, a specific inhibitor of the TORC1 complex. Altogether these data suggest the existence of a molecular and functional link between the Plk1 mitotic kinase and the mTOR pathway. Given the different established functions of Plk1 and mTOR during the cell cycle, we will discuss the possible meaning of this functional relationship.


Molecular epidemiology of extended-spectrum beta-lactamase-producing extra-intestinal pathogenic Escherichia coli strains over a 2-year period (2017-2019) from Zimbabwe.
This study was designed to characterize extended-spectrum beta-lactamase (ESBL)-producing extra-intestinal pathogenic Escherichia coli (E.coli) (ExPEC) associated with urinary tract infections in nine different geographic regions of Zimbabwe over a 2-year period (2017-2019). A total of 48 ESBL-positive isolates from urine specimen were selected for whole-genome sequencing from 1246 Escherichia coli isolates biobanked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Programme to provide representation of different geographical regions and year of isolation. The majority of ESBL E. coli isolates produced cefotaximase-Munich (CTX-M)-15, CTX-M-27, and CTX-M-14. In this study, sequence types (ST) 131 and ST410 were the most predominant antimicrobial-resistant clones and responsible for the increase in ESBL-producing E. coli strains since 2017. Novel ST131 complex strains were recorded during the period 2017 to 2018, thus showing the establishment and evolution of this antimicrobial-resistant ESBL clone in Zimbabwe posing an important public health threat. Incompatibility group F plasmids were predominant among ST131 and ST410 isolates with the following replicons recorded most frequently: F1:A2:B20 (9/19, 47%), F2:A1: B (5/19, 26%), and F1:A1:B49 (8/13, 62%). The results indicate the need for continuous tracking of different ESBL ExPEC clones on a global scale, while targeting specific STs (e.g. ST131 and ST410) through control programs will substantially decrease the spread of ESBLs among ExPEC.


Transcription Factor Id1 Plays an Essential Role in Th9 Cell Differentiation by Inhibiting Tcf3 and Tcf4.
T helper type 9 (Th9) cells play important roles in immune responses by producing interleukin-9 (IL-9). Several transcription factors are responsible for Th9 cell differentiation; however, transcriptional regulation of Th9 cells is not fully understood. Here, it is shown that Id1 is an essential transcriptional regulator of Th9 cell differentiation. Id1 is induced by IL-4 and TGF-β. Id1-deficient naïve CD4 T cells fail to differentiate into Th9 cells, and overexpression of Id1 induce expression of IL-9. Mass spectrometry analysis reveals that Id1 interacts with Tcf3 and Tcf4 in Th9 cells. In addition, RNA-sequencing, chromatin immunoprecipitation, and transient reporter assay reveal that Tcf3 and Tcf4 bind to the promoter region of the Il9 gene to suppress its expression, and that Id1 inhibits their function, leading to Th9 differentiation. Finally, Id1-deficient Th9 cells ameliorate airway inflammation in an animal model of asthma. Thus, Id1 is a transcription factor that plays an essential role in Th9 cell differentiation by inhibiting Tcf3 and Tcf4.


Multiomic Strategies Reveal Diversity and Important Functional Aspects of Human Gut Microbiome.
It is well accepted that dysbiosis of microbiota is associated with disease; however, the biological mechanisms that promote susceptibility or resilience to disease remain elusive. One of the major limitations of previous microbiome studies has been the lack of complementary metatranscriptomic (functional) data to complement the interpretation of metagenomics (bacterial abundance). The purpose of this study was twofold, first to evaluate the bacterial diversity and differential gene expression of gut microbiota using complementary shotgun metagenomics (MG) and metatranscriptomics (MT) from same fecal sample. Second, to compare sequence data using different Illumina platforms and with different sequencing parameters as new sequencers are introduced, and to determine if the data are comparable on different platforms. In this study, we perform ultradeep metatranscriptomic shotgun sequencing for a sample that we previously analyzed with metagenomics shotgun sequencing. We performed sequencing analysis using different Illumina platforms, with different sequencing and analysis parameters. Our results suggest that use of different Illumina platform did not lead to detectable bias in the sequencing data. The analysis of the sample using MG and MT approach shows that some species genes are highly represented in the MT than in the MG, indicating that some species are highly metabolically active. Our analysis also shows that ~52% of the genes in the metagenome are in the metatranscriptome and therefore are robustly expressed. The functions of the low and rare abundance bacterial species remain poorly understood. Our observations indicate that among the low abundant species analyzed in this study some were found to be more metabolically active compared to others, and can contribute distinct profiles of biological functions that may modulate the host-microbiota and bacteria-bacteria interactions.


Fatalism or destiny? A qualitative study and interpretative framework on Dominican women's breast cancer beliefs.
A growing literature on Latino's beliefs about cancer focuses on the concept of fatalismo (fatalism), despite numerous conceptual ambiguities concerning its meaning, definition, and measurement. This study explored Latina women's views on breast cancer and screening within a cultural framework of destino ("destiny"), or the notion that both personal agency and external forces can influence health and life events. Semi-structured interviews were conducted with 25 Latinas from the Dominican Republic aged 40 or over. Respondents reported complex notions of health locus of control that encompassed both internal (e.g., individual action) and external (e.g., the will of God) forces shaping breast cancer prevention efforts. Furthermore, women actively participated in screening because they believed that cancer could become a death sentence if diagnosed late or left untreated. In contrast to simplistic notions of "fatalism", our analysis suggests complex strategies and beliefs regarding breast cancer and cancer screening that speak of resiliency rather than hopelessness.


Problematic use of social networking sites among urban school going teenagers.
Social networking sites like Facebook, Orkut and Twitter are virtual communities where users can create individual public profiles, interact with real-life friends and meet other people based on shared interests. An exponential rise in usage of Social Networking Sites have been seen within the last few years. Their ease of use and immediate gratification effect on users has changed the way people in general and students in particular spend their time. Young adults, particularly teenagers tended to be unaware of just how much time they really spent on social networking sites. Negative correlates of Social Networking Sites usage include the decrease in real life social community participation and academic achievement, as well as relationship problems, each of which may be indicative of potential addiction. the aim of the study was to find out whether teenagers, specially those living in cities spend too much time on social networking websites. 200 subjects, both boys and girls were included in the cross sectional study who were given a 20 item Young's internet addiction test modified for social networking sites. The responses were analyzed using chi square test and Fisher's exact test. 24.74% of the students were having occasional or 'frequency' problems while 2.02% of them were experiencing severe problems due to excessive time spent using social networking sites. With the ever increasing popularity of social media, teenagers are devoting significant time to social networking on websites and are prone to get 'addicted' to such form of online social interaction.


Interactions With Robots: The Truths We Reveal About Ourselves.
In movies, robots are often extremely humanlike. Although these robots are not yet reality, robots are currently being used in healthcare, education, and business. Robots provide benefits such as relieving loneliness and enabling communication. Engineers are trying to build robots that look and behave like humans and thus need comprehensive knowledge not only of technology but also of human cognition, emotion, and behavior. This need is driving engineers to study human behavior toward other humans and toward robots, leading to greater understanding of how humans think, feel, and behave in these contexts, including our tendencies for mindless social behaviors, anthropomorphism, uncanny feelings toward robots, and the formation of emotional attachments. However, in considering the increased use of robots, many people have concerns about deception, privacy, job loss, safety, and the loss of human relationships. Human-robot interaction is a fascinating field and one in which psychologists have much to contribute, both to the development of robots and to the study of human behavior.


Dihydrofolate reductase amplification and sensitization to methotrexate of methotrexate-resistant colon cancer cells.
Gene amplification is one of the most frequent manifestations of genomic instability in human tumors and plays an important role in tumor progression and acquisition of drug resistance. To better understand the factors involved in acquired resistance to cytotoxic drugs via gene amplification, we have analyzed the structure and dynamics of dihydrofolate reductase (DHFR) gene amplification in HT29 cells treated with methotrexate (MTX). Analysis of the DHFR gene amplification process shows that the amplicon exhibits a complex structure that is consistently reproduced in independent treatments. The cytogenetic manifestation of the amplification in advanced stages of the treatment may be in the form of double minutes or as a homogeneously stained region. To get insights into the mechanisms of resistance, we have also investigated the sensitization to MTX of MTX-resistant cells after drug withdrawal and reexposure to MTX. Passive loss of the DHFR amplicon by withdrawal of the drug results in MTX-sensitive cells exhibiting a substantial reduction of their capacity or even an incapacity to generate resistance when submitted to a second cycle of MTX treatment. On a second round of drug administration, the resistant cells generate a different amplicon structure, suggesting that the formation of the amplicon as in the first cycle of treatment is not feasible. These results indicate that DHFR gene amplification is a "wear and tear" process in HT29 cells and that MTX-resistant cells may become responsive to a second round of treatment if left untreated during a sufficient period of time.


Cytochrome P450 for environmental remediation: catalytic mechanism, engineering strategies and future prospects.
Environmental pollution is a global concern. Various organic compounds are released into the environment through wastewater, waste gas, and waste residue, ultimately accumulating in the environment and the food chain. This poses a significant threat to both human health and ecology. Currently, a growing body of research has demonstrated that microorganisms employ their Cytochrome P450 (CYP450) system for biodegradation, offering a crucial approach for eliminating these pollutants in environmental remediation. CYP450, a ubiquitous catalyst in nature, includes a vast array of family members distributed widely across various organisms, including bacteria, fungi, and mammals. These enzymes participate in the metabolism of diverse organic compounds. Furthermore, the rapid advancements in enzyme and protein engineering have led to increased utilization of engineered CYP450s in environmental remediation, enhancing their efficiency in pollutant removal. This article presents an overview of the current understanding of various members of the CYP450 superfamily involved in transforming organic pollutants and the engineering of biodegrading CYP450s. Additionally, it explores the catalytic mechanisms, current practical applications of CYP450-based systems, their potential applications, and the prospects in bioremediation.


The use of high-pressure liquid chromatography with electrochemical detection for the assay of nantradol and its application to delta 9- tetrahydrocannabinol.
High-pressure liquid chromatography with electrochemical detection permits sensitive, selective and quantitative analysis of biological and pharmaceutical compounds containing electroactive functional groups. In support of pharmacological and clinical studies with nantradol, a potent, nonopioid analgetic, a specific HPLC/electrochemical assay for nantradol and related compounds in plasma was recently developed. In preliminary studies we have now extended this technique to the detection of delta 9- and 11-OH-delta 9- tetrahydrocannabinol. Results are presented which indicate that HPLC coupled to an electrochemical detector provides sensitivity for these compounds in plasma in the low ng/ml range.


SARS-CoV-2 associated pathogenesis, immune dysfunction and involvement of host factors: a comprehensive review.
Infectious diseases, especially viral infections, have emerged as a major concern for public health in recent years. Recently emerged COVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has been declared a pandemic by World Health Organization since March 2020. It was first identified in Wuhan, China, in December 2019 and has since claimed more than a million lives. Complicated symptoms are associated with rising incidence and fatality rates, while many of the vaccine candidates are in the final stages of clinical trials. This review encompasses a summary of existing literature on COVID-19, including the basics of the disease such as the causative agent's genome characterization, modes of transmission of the virus, pathogenesis, and clinical presentations like associated immune responses, neurological manifestations, the variety of host genetic factors influencing the disease and the vulnerability of different groups being affected by COVID-19.


Friedelin and Glutinol induce neuroprotection against ethanol induced neurotoxicity in pup's brain through reduction of TNF-α, NF-kB, caspase-3 and PARP-1.
Ethanol administration triggers an inflammatory response that leads to a complex series of immune responses including the release of an excessive amount of inflammatory mediators particularly tumor necrosis factor (TNF-α) and nuclear factor-kB (NF-KB) which produce a large amount of reactive oxygen species. The inflammatory-induced cytotoxicity is increased when the PI3-kinase/Akt pathway is inhibited. Some studies have also shown that ethanol suppresses the PI3-kinase signaling pathway induced by receptor activation. Friedelin and Glutinol belong to pentacyclic triterpenoid class and are known for their anti-inflammatory and antioxidant properties. The present study was aimed to elucidate the effects of these phytoconstituents on one of the key ethanol-induced neuronal damage pathways. The pups having (5-7 g average body weight) were used and randomly divided into groups. The control and ethanol treated pups were administered 0.9% normal saline while treated pups received glutinol and friedelin (30 mg/kg subcutaneously) respectively. After four hours all the experimental animals were sacrificed and their brains were collected carefully for protein expression analysis of p-Akt, TNF-α, NF-KB, caspase-3 and PARP-1 employing immunoblotting technique. Hemolytic, DNA protection, chelating power and β-carotene assays results revealed that freidelin and glutinol are safe for parenteral administration. Glutinol administration with ethanol significantly abridged the ethanol induced over expression of TNF-α, caspase-3 and PARP-1 in pup's brain. Similarly, freidelin attenuated the neurodegeneration by inhibiting the ethanol induced p-JNK and NF-kB expression in pups' brain. This protection may be attributed to the revival of p-Akt signaling for cell survival. It is concluded that the present study demonstrates the neuro-protective effects of friedelin and glutinol via modulating the capase-3 and PARP-1 expression and modulating the neuronal apoptotic pathways.


Intrauterine adhesions: current diagnostic and therapeutic trends.
In the period January 1981-December 1984, 31 cases of intrauterine adhesions (8 severe, 10 moderate and 13 minimal) were diagnosed at the First Department of Obstetrics and Gynecology, University of Milan. This pathology had altered the menstrual function in 21 subjects and reproductive capacity in 27. Synecholysis was performed at hysteroscopy, followed by application of an IUD in 7 patients and sequential treatment with estrogens and progestins in 22. After treatment 67.7% of the women had normal menstruation, and 40.7% of those wanting a child achieved pregnancy with live birth. Repeat hysterography and hysteroscopy after several months showed complete normalization of the uterine cavity in 62.5% of the women, and persistence of minimal and moderate adhesions in 25% and 12.5% respectively. Dissection with miniature scissors under visual control, followed by application of an IUD and sequential administration of estrogens and progestins seems at present the most effective therapeutic regimen for intrauterine adhesions.


Bexmarilimab-induced macrophage activation leads to treatment benefit in solid tumors: The phase I/II first-in-human MATINS trial.
Macrophage Clever-1 contributes to impaired antigen presentation and suppression of anti-tumor immunity. This first-in-human trial investigates the safety and tolerability of Clever-1 blockade with bexmarilimab in patients with treatment-refractory solid tumors and assesses preliminary anti-tumor efficacy, pharmacodynamics, and immunologic correlates. Bexmarilimab shows no dose-limiting toxicities in part I (n = 30) and no additional safety signals in part II (n = 108). Disease control (DC) rates of 25%-40% are observed in cutaneous melanoma, gastric, hepatocellular, estrogen receptor-positive breast, and biliary tract cancers. DC associates with improved survival in a landmark analysis and correlates with high pre-treatment intratumoral Clever-1 positivity and increasing on-treatment serum interferon γ (IFNγ) levels. Spatial transcriptomics profiling of DC and non-DC tumors demonstrates bexmarilimab-induced macrophage activation and stimulation of IFNγ and T cell receptor signaling selectively in DC patients. These data suggest that bexmarilimab therapy is well tolerated and show that macrophage targeting can promote immune activation and tumor control in late-stage cancer.


Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates.
Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the first example of allenoate activation by using chiral isochalcogenoureas (IChU) for formal (4+2) cycloaddition reactions. Compared to established phosphine and amine catalysis, the use of these easily available Lewis bases enables new stereoselective reaction pathways proceeding with high enantioselectivities, diastereoselectivities, and in good yields. In addition, the factors governing enantioselectivity and the origin of the observed differences compared to other commonly used Lewis bases are explained.


A general method to correct PET data for tissue metabolites using a dual-scan approach.
This article presents and analyses a general method of correcting for the presence of radiolabeled metabolites from a parent radiotracer in tissue during PET scanning. The method is based on a dual-scan approach, i.e., parent scan together with an independent supplementary scan in which the radiolabeled metabolite of interest itself is administered. The method corrects for the presence of systemically derived radiolabeled metabolite delivered to the tissues of interest through the blood. Data from the supplementary scan are analyzed to obtain the tissue impulse response function for the metabolite. The time course of the radiolabeled metabolite in plasma in the parent scan is convolved with its tissue impulse response function to derive a correction term. This is not a simple subtraction technique but 1 that takes account of the different time-activity curves of the radiolabeled metabolite in the 2 scans. The method, its implications, and its limitations are discussed with respect to [11C]thymidine and its principal metabolite 11CO2. The general method, based on a dual-scan approach, can be used to correct for radiolabeled metabolites in tissues of interest during PET scanning. The correction accounts for radiolabeled metabolites that are derived systemically and delivered to the tissues of interest through the blood.


Secure Messaging Intervention in Patients Starting New Antidepressant to Promote Adherence: Pilot Randomized Controlled Trial.
There are a range of effective pharmacological and behavioral treatments for depression. However, approximately one-third of patients discontinue antidepressants within the first month of treatment and 44% discontinue them by the third month of treatment. The major reasons reported for discontinuation were side effect burden, patients experiencing that the medications were not working, and patients wanting to resolve their depression without using medication. This study tested the acceptability, feasibility, and preliminary effectiveness of an SMS messaging intervention designed to improve antidepressant adherence and depression outcomes in veterans. The intervention specifically targeted the key reasons for antidepressant discontinuation. For example, the secure message included reminders that it can take up to 6 weeks for an antidepressant to work, or prompts to call their provider should the side effect burden become significant. This pilot was a 3-armed randomized controlled trial of 53 veterans undergoing depression treatment at the Iowa City Veterans Affairs Health Care System. Veterans starting a new antidepressant were randomized to secure messaging only (SM-Only), secure messaging with coaching (SM+Coach), or attention control (AC) groups. The intervention lasted 12 weeks with follow-up assessments of key outcomes at 6 and 12-weeks. This included a measure of antidepressant adherence, depressive symptom severity, and side effect burden. The 2 active interventions (SM-Only and SM+Coach) demonstrated small to moderate effect sizes (ESs) in improving antidepressant adherence and reducing side effect burden. They did not appear to reduce the depressive symptom burden any more than in the AC arm. Veteran participants in the SM arms demonstrated improved medication adherence from baseline to 12 weeks on the Medication Adherence Rating Scale compared with those in the AC arm, who had a decline in adherence (SM-Only: ES=0.09; P=.19; SM+Coach: ES=0.85; P=.002). Depression scores on the 9-Item Patient Health Questionnaire decreased for all 3 treatment arms, although the decline was slightly larger for the SM-Only (ES=0.32) and the SM+Coach (ES=0.24) arms when compared with the AC arm. The 2 intervention arms indicated a decrease in side effects on the Frequency, Intensity, and Burden of Side Effects Ratings, whereas the side effect burden for the AC arm increased. These differences indicated moderate ES (SM-Only vs AC: ES=0.40; P=.07; SM+Coach: ES=0.54; P=.07). A secure messaging program targeting specific reasons for antidepressant discontinuation had small-to-moderate ES in improving medication adherence. Consistent with prior research, the intervention that included brief synchronic meetings with a coach appeared to have a greater benefit than the SMS-alone intervention. Veterans consistently engaged with the SMS messaging in both treatment arms throughout the study period. They additionally provided feedback on which texts were most helpful, tending to prefer messages providing overall encouragement rather than specific wellness recommendations. ClinicalTrials.gov NCT03930849; https://clinicaltrials.gov/study/NCT03930849.


Emerging role of gasotransmitters in renal transplantation.
Once patients with kidney disease progress to end-stage renal failure, transplantation is the preferred option of treatment resulting in improved quality of life and reduced mortality compared to dialysis. Although 1-year survival has improved considerably, graft and patient survival in the long term have not been concurrent, and therefore new tools to improve long-term graft and patient survival are warranted. Over the past decades, the gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have emerged as potent cytoprotective mediators in various diseases. All three gasotransmitters are endogenously produced messenger molecules that possess vasodilatory, anti-apoptotic, anti-inflammatory and anti-oxidant properties by influencing an array of intracellular signaling processes. Although many regulatory functions of gasotransmitters have overlapping actions, differences have also been reported. In addition, crosstalk between NO, CO and H2S results in synergistic regulatory effects. Endogenous and exogenous manipulation of gasotransmitter levels modulates several processes involved in renal transplantation. This review focuses on mechanisms of gas-mediated cytoprotection and complex interactions between gasotransmitters in renal transplantation.


Lower Ilium Evolution in Apes and Hominins.
Elucidating the pelvic morphology of the Pan-Homo last common ancestor (LCA) is crucial for understanding ape and human evolution. The pelvis of Ardipithecus ramidus has been the basis of controversial interpretations of the LCA pelvis. In particular, it was proposed that the lower ilium became elongate independently in the orangutan and chimpanzee clades, making these taxa poor analogues for the pelvis of the LCA. This study examines the variation in relative lower ilium height between and within living and fossil hominoid species (and other anthropoids), and models its evolution using available fossil hominoids as calibration points. We find nuanced differences in relative lower ilium height among living hominoids, particularly in regards to gorillas, which do not have elongate lower ilia (because they are likely to represent the plesiomorphic hominoid condition for this trait). We also show that differences in relative lower ilium height among hominoid taxa are not readily explained by differences in size between species. Our maximum likelihood ancestral state reconstructions support inferences that chimpanzees (Pan troglodytes in particular) and orangutans evolved their elongate lower ilia independently. We also find that the predicted lower ilium height of the Pan-Homo LCA is shorter than all great apes except gorillas. This study adds to a growing body of evidence that finds different regions of the body show different evolutionary histories in different hominoids, and underscores that the unique combinations of morphologies of each modern and fossil hominoid species should be considered when reconstructing the mosaic nature of the Pan-Homo LCA. Anat Rec, 300:828-844, 2017. © 2017 Wiley Periodicals, Inc.


Numbers needed to hospitalize-risks and benefits of admission in the new decade.
While hospitals are central to western style health care systems it is unclear which patients benefit from hospitalization and who might be put at risk. The high cost means that reasons for hospitalization will need to be reviewed in the current economic climate. Accepted grounds for hospitalization include life threatening illness, diagnostic uncertainty with the threat of deteriorating health, the need for specialist expertise or experience or the need for nursing care, including the care of the dying. Some of the traditional surveillance functions of the hospital can now be taken over by technology or alternative settings. These changes will lead to a blurring of margins between Outpatient, Inpatient and Critical Care. Beyond the care of the critically ill patient it is unlikely that all patients currently admitted to hospital benefit from this process and would be admitted in future. A generally accepted system for risk assessment of medial inpatients is urgently needed to allow researchers to examine the effectiveness of health care systems involving hospitalization and the circumstances under which hospitalization is cost effective and improves mortality, morbidity and patient reported outcomes.


Clinical Impact of Baseline Right Bundle Branch Block in Patients Undergoing Transcatheter Aortic Valve Replacement.
This study sought to assess the influence of baseline right bundle branch block (RBBB) on all-cause and cardiovascular mortality as well as sudden cardiac death (SCD) among patients undergoing transcatheter aortic valve replacement (TAVR). Few data exist regarding the late clinical impact of pre-existing RBBB in TAVR recipients. A total of 3,527 patients (mean age 82 ± 8 years, 50.1% men) were evaluated according to the presence of RBBB on baseline electrocardiography. Intraventricular conduction abnormalities were classified according to the American Heart Association, American College of Cardiology Foundation, and Heart Rhythm Society recommendations for standardization and interpretation of the electrocardiogram. TAVR complications and causes of death were defined according to Valve Academic Research Consortium 2 definitions. RBBB was present on baseline electrocardiography in 362 patients (10.3%) and associated with higher 30-day rates of permanent pacemaker implantation (PPI) (40.1% vs. 13.5%; p < 0.001) and death (10.2% vs. 6.9%; p = 0.024). At a mean follow-up of 20 ± 18 months, pre-existing RBBB was independently associated with all-cause mortality (hazard ratio [HR]: 1.31; 95% confidence interval [CI]: 1.06 to 1.63; p = 0.014) and cardiovascular mortality (HR: 1.45; 95% CI: 1.11 to 1.89; p = 0.006) but not with SCD (HR: 0.71; 95% CI: 0.22 to 2.32; p = 0.57). Patients with pre-existing RBBB and without PPI at discharge from the index hospitalization had the highest 2-year risk for cardiovascular death (27.8%; 95% CI: 20.9% to 36.1%; log-rank p = 0.007). In a subanalysis of 1,245 patients without PPI at discharge from the index hospitalization and with complete follow-up regarding the need for PPI, pre-existing RBBB was independently associated with the composite of SCD and PPI (HR: 2.68; 95% CI: 1.16 to 6.17; p = 0.023). Pre-existing RBBB was found in 10% of TAVR recipients and was associated with poorer clinical outcomes. Patients with baseline RBBB without permanent pacemakers at hospital discharge may be at especially high risk for high-degree atrioventricular block and/or SCD during follow-up. Future studies should evaluate strategies aimed at the early detection of patients at risk for late development of high-degree atrioventricular block.


Constraints associated with captivity alter craniomandibular integration in wild boar.
The domestication process is associated with substantial phenotypic changes through time. However, although morphological integration between biological structures is purported to have a major influence on the evolution of new morphologies, little attention has been paid to the influence of domestication on the magnitude of integration. Here, we assessed the influence of constraints associated with captivity, considered as one of the crucial first steps in the domestication process, on the integration of cranial and mandibular structures. We investigated the craniomandibular integration in Western European Sus scrofa using three-dimensional (3D) landmark-based geometric morphometrics. Our results suggest that captivity is associated with a lower level of integration between the cranium and the mandible. Plastic responses to captivity can thus affect the magnitude of integration of key functional structures. These findings underline the critical need to develop integration studies in the context of animal domestication to better understand the processes accountable for the set-up of domestic phenotypes through time.


Li5Sn, the Most Lithium-Rich Binary Stannide: A Combined Experimental and Computational Study.
From reaction of excess lithium with tin, we isolate well-crystallized Li5Sn and solve the crystal structure from single-crystal X-ray diffraction data. The orthorhombic structure (space group Cmcm) features the same coordination polyhedra around tin and lithium as previously predicted by electronic structure calculations for this composition, however differently arranged. An extensive ab initio analysis, including thermodynamic integration using Langevin dynamics in combination with a machine-learning potential (moment tensor potential), is conducted to understand the thermodynamic stability of this Cmcm Li5Sn structure observed in our experiments. Among the 108 Li5Sn structures systematically derived using the structure enumeration algorithm, including the experimental Cmcm structure and those obtained in previous ab initio studies, another new structure with the space group Immm is found to be energetically most stable at 0 K. This computationally discovered Immm structure is also found to be thermodynamically more stable than the Cmcm structure at finite temperatures, indicating that the Cmcm Li5Sn structure observed in our experiments is favored likely due to kinetic reasons rather than thermodynamics.


Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease.
A variety of anatomic and functional neuroimaging findings are associated with Alzheimer's disease (AD). One of the strongest imaging associations identified is between AD and hippocampal atrophy. The epsilon4 allele of the apolipoprotein E (ApoE) gene increases the risk of developing AD and lowers the mean age of onset of the disease. The purpose of this study was to assess the association between hippocampal volume and ApoE polymorphisms in elderly control subjects and in patients with probable AD. We performed magnetic resonance imaging-based volume measurements of the hippocampus in 125 cognitively normal elderly controls and 62 patients with probable AD. ApoE genotyping was performed by using standard methods. Hippocampal volumes were significantly smaller in AD cases than in control subjects. Hippocampal volumes did not differ significantly within either clinical group on the basis of ApoE genotype. Both the epsilon4 allele of ApoE and hippocampal atrophy were significantly but independently associated with AD.


The determinants of self-medication: Evidence from urban Vietnam.
This study examines the primary determinants of self-medications among urban citizens in Ho Chi Minh City, Vietnam using survey data. Employing logistic models, the article finds that the probability of self-medication is positively associated with the respondents' high school degree or vocational certificate, married status, and income while it is negatively related to employed status, the number of children, the geographical distance from home to the nearest hospital, doing exercise, and living in a central region. Meanwhile, using Poisson models the article finds that the frequency of self-medication is positively associated with the respondents' high school and vocational, married, income, and chronic disease while the frequency of self-medication is adversely related to male, employed, children number, distance, being close to health professional and central areas.


[Hormonal and immunological changes in breast cancers with different growth rates].
Thirty-four breast carcinomas revealed unequal growth rates their doubling time ranging 12-150 days. Steroid hormone levels and immunologic vigor were found to significantly differ in patients with different growth rates. Higher rates were associated with more pronounced systemic disorders.


Self-care predictors of metabolic control in NIDDM patients.
The objective of this study was to evaluate whether the relationship between self-care behavior and metabolic control is comparable in patients with non-insulin-dependent diabetes mellitus (NIDDM) on insulin and not on insulin. We studied 84 NIDDM patients hospitalized for an elective admission in Washington University's Model Demonstration Unit. At admission, patients reported the frequency of exercise, blood glucose monitoring, and meal skipping for the previous 2 wk. Metabolic control over the previous 8-12 wk was determined from glycosylated hemoglobin assays. In cross-sectional analysis controlling for patient sociodemographic and health characteristics, glycosylated hemoglobin levels were positively related to meal skipping (P = 0.0008) and negatively related to the frequency of blood glucose monitoring (P = 0.0025). Self-care behaviors explained 26% of the variance in glycosylated hemoglobin levels in NIDDM patients. Multivariate modeling demonstrated no significant interaction effects between insulin treatment and self-care on metabolic control. In conclusion, these findings support the clinical significance of self-care activities for metabolic control in NIDDM patients, particularly meal skipping and blood glucose monitoring.


Cardiovascular magnetic resonance in children with suspected myocarditis: current practice and applicability of adult protocols.
Cardiovascular magnetic resonance serves as a useful tool in diagnosing myocarditis. Current adult protocols are yet to be validated for children; thus, it remains unclear if the methods used can be applied with sufficient image quality in children. This study assesses the use of cardiovascular magnetic resonance in children with suspected myocarditis. Image data from clinical cardiovascular magnetic resonance studies performed in children enrolled in Mykke between June 2014 and April 2019 were collected and analysed. The quality of the data sets was evaluated using a four-point quality scale (4: excellent, 3: good, 2: moderate, 1: non-diagnostic). A total of 102 patients from 9 centres were included with a median age (interquartile range) of 15.4(10.7-16.6) years, 137 cardiovascular magnetic resonance studies were analysed. Diagnostic image quality was found in 95%. Examination protocols were consistent with the original Lake Louise criteria in 58% and with the revised criteria in 35%. Older patients presented with better image quality, with the best picture quality in the oldest age group (13-18 years). Sedation showed a negative impact on image quality in late gadolinium enhancement and oedema sequences. No such correlation was seen in cardiac function assessment sequences. In contrast to initial scans, in follow-up examinations, the use of parametric mapping increased while late gadolinium enhancement and oedema sequences decreased. Cardiovascular magnetic resonance protocols for the assessment of adult myocarditis can be applied to children without significant constraints in image quality. Given the lack of specific recommendations for children, cardiovascular magnetic resonance protocols should follow recent recommendations for adult cardiovascular magnetic resonance.


Flow field-flow fractionation: a pre-analytical method for proteomics.
Proteome analysis requires a comprehensive approach including high-performance separation methods, mass spectrometric analysis, and bioinformatics. While recent advances in mass spectrometry (MS) have led to remarkable improvements in the ability to characterize complex mixtures of biomolecules in proteomics, a proper pre-MS separation step of proteins/peptides is still required. The need of high-performance separation and/or isolation/purification techniques of proteins is increasing, due to the importance of proteins expressed at extremely low levels in proteome samples. In this review, flow field-flow fractionation (F4) is introduced as a complementary pre-analytical separation method for protein separation/isolation, which can be effectively utilized for proteomic research. F4 is a set of elution-based techniques that are capable of separating macromolecules by differences in diffusion coefficient and, therefore, in hydrodynamic size. F4 provides protein separation without surface interaction of the analyte with packing or gel media. Separation is carried out in an open channel structure by a flow stream of a mobile phase of any composition, and it is solely based on the interaction of the analytes with a perpendicularly-applied, secondary flow of the fluid. Therefore, biological analytes such as proteins can be kept under a bio-friendly environment without losing their original structural configuration. Moreover, proteins fractionated on a size/shape basis can be readily collected for further characterization or proteomic analysis by MS using, for instance, either on-line or off-line methods based on electrospray ionization (ESI) or matrix-assisted laser desorption-ionization (MALDI). This review focuses on the advantages of F4 compared to most-assessed separation/isolation techniques for proteomics, and on selected applications based on size-dependent proteome separation. New method developments based on the hyphenation of F4 with on-line or off-line MS, and with other separation methods such as capillary isoelectric focusing (CIEF) are also described.


Comparative analysis of diagnostic methods and risk factors for Aelurostrongylus abstrusus infection in brazilian cats.
This study aimed to prospectively evaluate the risk factors of infection by Aelurostrongylus abstrusus in Brazilian cats with cough and/or radiographic changes, using as diagnostic tools the Baermann method (BM), polymerase chain reaction (PCR) of feces, bronchoalveolar lavage fluid (BALF), and cytology. Forty-three cats that were presented with cough or lung radiographic abnormalities compatible with bronchoalveolar disease were included in the study. After clinical evaluation, feces samples were collected to investigate lungworm parasitism through BM and PCR. BALF was performed to provide samples for cytology, bacteriology, and fungal culture. Stool PCR was considered the gold standard for diagnosis tests, and the other methods were evaluated by their agreement. PCR presented 74% (32/43) of positivity for A. abstrusus, while in the BM, 41% (18/43) were positive. BM showed sensitivity of 56.25% and specificity of 100% when compared with PCR. No larva was found in the cytological evaluation of 21 BALF samples. Lungworm is an important cause of bronchopulmonary disease in domestic cats in Brazil and should be included as a differential diagnosis when a cat is presented with cough or radiographic abnormalities. BM is a sensitive, non-invasive, and cheap technique to diagnose the disease, but it is not as sensitive as PCR.


Five Years of Accurate PM2.5 Measurements Demonstrate the Value of Low-Cost PurpleAir Monitors in Areas Affected by Woodsmoke.
Low-cost optical sensors are used in many countries to monitor fine particulate (PM2.5) air pollution, especially in cities and towns with large spatial and temporal variation due to woodsmoke pollution. Previous peer-reviewed research derived calibration equations for PurpleAir (PA) sensors by co-locating PA units at a government regulatory air pollution monitoring site in Armidale, NSW, Australia, a town where woodsmoke is the main source of PM2.5 pollution. The calibrations enabled the PA sensors to provide accurate estimates of PM2.5 that were almost identical to those from the NSW Government reference equipment and allowed the high levels of wintertime PM2.5 pollution and the substantial spatial and temporal variation from wood heaters to be quantified, as well as the estimated costs of premature mortality exceeding $10,000 per wood heater per year. This follow-up study evaluates eight PA sensors co-located at the same government site to check their accuracy over the following four years, using either the original calibrations, the default woodsmoke equation on the PA website for uncalibrated sensors, or the ALT-34 conversion equation (see text). Minimal calibration drift was observed, with year-round correlations, r = 0.98 ± 0.01, and root mean square error (RMSE) = 2.0 μg/m3 for daily average PA PM2.5 vs. reference equipment. The utitilty of the PA sensors without prior calibration at locations affected by woodsmoke was also demonstrated by the year-round correlations of 0.94 and low RMSE between PA (woodsmoke and ALT-34 conversions) and reference PM2.5 at the NSW Government monitoring sites in Orange and Gunnedah. To ensure the reliability of the PA data, basic quality checks are recommended, including the agreement of the two laser sensors in each PA unit and removing any transient spikes affecting only one sensor. In Armidale, from 2019 to 2022, the continuing high spatial variation in the PM2.5 levels observed during the colder months was many times higher than any discrepancies between the PA and reference measurements. Particularly unhealthy PM2.5 levels were noted in southern and eastern central Armidale. The measurements inside two older weatherboard houses in Armidale showed that high outdoor pollution resulted in high pollution inside the houses within 1-2 h. Daily average PM2.5 concentrations available on the PA website allow air pollution at different sites across regions (and countries) to be compared. Such comparisons revealed major elevations in PA PM2.5 at Gunnedah, Orange, Monash (Australian Capital Territory), and Christchurch (New Zealand) during the wood heating season. The data for Gunnedah and Muswellbrook suggest a slight underestimation of PM2.5 at other times of the year when there are proportionately more dust and other larger particles. A network of appropriately calibrated PA sensors can provide valuable information on the spatial and temporal variation in the air pollution that can be used to identify pollution hotspots, improve estimates of population exposure and health costs, and inform public policy.


Identification of a Cytopathogenic Toxin from Sneathia amnii.
Sneathia amnii is a poorly characterized emerging pathogen that has been implicated in amnionitis and urethritis. We found that S. amnii damages fetal membranes, and we identified and purified a cytotoxic exotoxin that lyses human red blood cells and damages cells from fetal membranes. The gene appears to be cotranscribed with a second gene that encodes a protein with identity to two-partner system transporters, suggesting that it is the "A," or secreted component of a type Vb system. The toxin is 1,881 amino acids with a molecular weight of approximately 200 kDa. It binds to red blood cell membranes and forms pores with a diameter of 2.0 to 3.0 nm, resulting in osmolysis. Because it appears to be the "A" or passenger component of a two-partner system, we propose to name this novel cytotoxin/hemolysin CptA for cytopathogenic toxin component A.IMPORTANCESneathia amnii is a very poorly characterized emerging pathogen that can affect pregnancy outcome and cause urethritis and other infections. To date, nothing is known about its virulence factors or pathogenesis. We have identified and isolated a cytotoxin, named CptA for cytopathogenic toxin, component A, that is produced by S. amnii CptA is capable of permeabilizing chorionic trophoblasts and lysing human red blood cells and, thus, may play a role in virulence. Except for small domains conserved among two-partner secretion system passenger proteins, the cytotoxin exhibits little amino acid sequence homology to known toxins. In this study, we demonstrate the pore-forming activity of this novel toxin.


Spectrum of renal lesions in HIV patients.
A variety of renal lesions have been reported in HIV positive patients from western world however there is paucity of Indian data. Over a four year period, all hospitalised HIV positive patients were screened for renal involvement. Screening was done with urinalysis. Those with abnormality in urine examination underwent further assessment with clinical, biochemical, immunological profile and renal biopsy. Renal histology was studied by light and electron microscopy. Twenty-five (17.6%) of the 142 patients screened, had proteinuria/abnormal urinary sediment however none of the patient had proteinuria in nephrotic range. Fourteen of these 25 patients were asymptomatic while others had AIDS. Renal biopsy was studied by light microscopy in all and by electron microscopy in 11 cases. On histology mesangioproliferative GN was encountered in eight, focal segmental glomerulosclerosis in four and collapsing GN in one patient. In two cases cryptococcal infiltration and in one lymphomatous deposits were seen in glomerulus and interstitium. In one patient interstitium showed granulomas and in other three mononuclear cell infiltration. Histology was normal in 8 (32%) patients. On EM visceral cell hyperplasia and vacuolisation was seen in all, two had collapse of glomerular basement membrane and in three cases tubuloreticular structures were seen. There was no co-relation of renal histology with duration or severity of the disease (p > 0.05). No deterioration of renal function was seen over a short follow up period of 4.2 months (1-20 months). This study highlights that HIV patients exhibiting abnormal urinary sediment usually have underlying renal lesion and at times unexpected opportunistic infections may be present.