Blue and green ammonia production: A techno-economic and life cycle assessment perspective.
Blue and green ammonia production have been proposed as low-carbon alternatives to emissions-intensive conventional ammonia production. Although much attention has been given to comparing these alternatives, it is still not clear which process has better environmental and economic performance. We present a techno-economic analysis and full life cycle assessment to compare the economics and environmental impacts of blue and green ammonia production. We address the importance of time horizon in climate change impact comparisons by employing the Technology Warming Potential, showing that methane leakage can exacerbate the climate change impacts of blue ammonia in short time horizons. We represent a constrained renewable electricity availability scenario by comparing the climate change impact mitigation efficiency per kWh of renewable electricity. Our work emphasizes the importance of maintaining low natural gas leakage for sustainability of blue ammonia, and the potential for technological advances to further reduce the environmental impacts of photovoltaics-based green ammonia.


Hiding in plain sight: the F segment and other conserved features of seed plant SKn dehydrins.
An 11-residue amino acid sequence, DRGLFDFLGKK, is highly conserved in a subset of dehydrins found across the full spectrum of seed plants and here given the name F-segment. An 11-residue amino acid sequence, DRGLFDFLGKK, is highly conserved in identity and polarity in 130 non-redundant dehydrin sequences representing conifers and all major angiosperm groups. This newly described motif is here given the name F segment based on the pair of hydrophobic F residues at the core of the sequence. The majority of dehydrins previously classified as SKn dehydrins contain one F segment N terminal to the S and K segments and can accordingly be reclassified as FSKn dehydrins. A cysteine-containing variant, GCGMFDFLKK, occurs in a few rosid and asterid taxa. The S segment in this and other dehydrin types also includes previously overlooked conserved features, including a KLHR prefix and charged or G residues within and following the characteristic string of S residues. Secondary structure prediction models indicate that the F segment and S segment prefix may form amphipathic helices that could be involved in membrane or protein binding.


Pre-mRNA splicing: a complex picture in higher definition.
Intron excision from pre-mRNAs of higher eukaryotes requires a transition from splice-site recognition across short exons to organization of the spliceosome across long introns. Recently, insight into this transition has been provided and, in addition, it has been shown that an alternative splicing factor, the polypyrimidine-tract-binding protein, can exert its control on splice-site choice by blocking this key step in the assembly of the splicing machinery.


Biliary carcinoma. A review of 109 cases.
One hundred nine patients operated on for bile duct carcinoma were reviewed. Herein, we reported 83 proximal duct tumors, 12 mid-duct tumors, and 14 distal third tumors. Resectability was 10 percent, 33 percent, and 100 percent, respectively, with an operative mortality of 0 percent, 25 percent, and 23 percent. The median survival time and 5 year survival rate for these resected groups were 21 months and 25 percent for proximal duct tumors, 8 months and 0 percent for mid-duct tumors, and 16 months and 20 percent for distal third tumors. Eighty-three patients were treated with strictly palliative procedures with an operative mortality of 19 percent, an adjusted median survival rate of 10.9 months, and a 5 year survival rate of 0. The 2 and 5 year survival rates of patients with well-differentiated tumors were 73 percent and 15 percent, respectively, whereas for patients with poorly differentiated lesions, it was 6 percent and 0. Although most patients require palliative decompressive procedures, resection should be attempted whenever possible. It is expected that nonoperative techniques will have an increased role in the treatment of poor-risk patients or those who have unresectable disease.


Clinical pharmacokinetics of carbamazepine.
The relationship between daily dose and plasma levels of carbamazepine is poor. The slope of that relationship varies with the patient population. Children require twice as much of the drug as adults do to achieve a given level. Also, dosage requirements increase in the presence of other drugs that are enzyme inducers. Recent reports suggest that the 10,11-epoxide metabolite of carbamazepine can contribute to the neurotoxicity attributed to carbamazepine. Carbamazepine is a broad-spectrum enzyme inducer. Three reports in the past 2 years show that haloperidol levels are reduced by approximately 50% when carbamazepine is introduced. Those interactions may complicate the interpretation of clinical trials of carbamazepine.


Rules of Engagement: A Guide to Developing Agent-Based Models.
Agent-based models (ABM), also called individual-based models, first appeared several decades ago with the promise of nearly real-time simulations of active, autonomous individuals such as animals or objects. The goal of ABMs is to represent a population of individuals (agents) interacting with one another and their environment. Because of their flexible framework, ABMs have been widely applied to study systems in engineering, economics, ecology, and biology. This chapter is intended to guide the users in the development of an agent-based model by discussing conceptual issues, implementation, and pitfalls of ABMs from first principles. As a case study, we consider an ABM of the multi-scale dynamics of cellular interactions in a microbial community. We develop a lattice-free agent-based model of individual cells whose actions of growth, movement, and division are influenced by both their individual processes (cell cycle) and their contact with other cells (adhesion and contact inhibition).


"The very interesting finding suggests that…": A cognitive frame-based analysis of interest markers by authors' geo-academic location in applied linguistics research articles.
Linguistic expressions of interest instantiated by interesting, intriguing, and fascinating that signal the authorial stance are not uncommon in applied linguistics research articles. Nevertheless, they have received little scholarly attention. This paper, taking a cognitive semantic approach, reports on a study that sought to examine how linguistically expressed interest in applied linguistics research articles is leveraged by researchers' geo-academic location (the Core vs. the Periphery). Drawing on a semantic frame generated for interest markers in academic writing, this study focused on the incidence of the various elements of the Interest frame in the discipline of applied linguistics based on a mixed-methods approach. The corpus-based quantitative analyses found that academic writers' geo-academic location was a robust predictor of authors' overall use of interest markers and some frame elements associated with the Interest frame. Triangulation with the interview data obtained from disciplinary specialists revealed that the observed differences could be attributable to the hierarchical academia featuring periphery-based scholars' unequal access to the knowledge production market and under-representation.


A new therapeutic approach in the medical treatment of Cushing's syndrome: glucocorticoid receptor blockade with mifepristone.
Cushing's syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone. We review the literature regarding mifepristone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential drug interactions, drug initiation and dose titration, and monitoring of drug tolerability are provided. Clinical trial data have shown that mifepristone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports. This article provides a review of the pharmacology and clinical use of mifepristone in Cushing's syndrome, as well as detailed guidance on the management of patients treated with this novel agent.


Maternal autonomy on health in a community as assessed by signing of consent for caesarean section and its sociodemographic correlates.
To assess the level of maternal autonomy in a Nigerian community using maternal preference to sign the consent for caesarean section as the assessment tool and to evaluate the sociodemographic and obstetric correlates. A cross-sectional survey of parturients 2-5 days after caesarean delivery in a tertiary health facility in Benin City, Nigeria using a pretested interviewer administered questionnaire to obtain information on whom they would prefer to sign the consent form for caesarean section. A total of 197 parturients were interviewed. The consent form was signed by 177 (90%) of the respondents. However, 96 (48.7%) preferred their spouses to sign. Maternal attainment of tertiary level education and a higher mean maternal age was significantly associated with maternal preference to sign the consent form. The level of maternal autonomy on reproductive health issues based on this simple survey is less than satisfactory. However, this study has provided baseline data for surveillance and follow-up studies of this important variable.


Disruption of type 5 adenylyl cyclase gene preserves cardiac function against pressure overload.
The sympathetic nervous system is designed to respond to stress. Adenylyl cyclase (AC) is the keystone of sympathetic transmission, yet its role in response to acute overload in the heart or in the pathogenesis of heart failure is controversial. We examined the effects of pressure overload, induced by thoracic aortic banding, in mice in which type 5 AC, a major cardiac AC isoform, was disrupted (AC5-/-). Left ventricular weight/tibial length ratio (LVW/TL) was not different between the WT and AC5-/- at baseline and increased progressively and similarly in both groups at 1 and 3 wk after aortic banding. However, LV ejection fraction (LVEF) fell in WT at 3 wk after banding (from 70 +/- 2.8 to 57 +/- 3.9%, P < 0.05), and this decrease was associated with LV dilatation, indicating incipient cardiac failure. In contrast, AC5-/- mice did not exhibit a fall in LVEF from 74 +/- 2.2%. The number of apoptotic myocytes was similar at baseline, but it increased roughly 4-fold in WT at both 1 and 3 wk after banding, and significantly less, P < 0.05, in AC5-/-. Importantly, the increase in apoptosis occurred before the decline in LVEF in WT. The protective mechanism seems to involve Bcl-2, which was up-regulated significantly more in AC5-/- mice with pressure overload. Our findings suggest that limiting type 5 AC plays a protective role in response to pressure overload and the development of heart failure, potentially through limiting the incidence of myocardial apoptosis.


Endoluminal balloon dilatation for pelvi-ureteric junction obstruction in children: an effective alternative to open pyeloplasty.
Pelvi-ureteric junction obstruction (PUJO) is one of the commonest causes of paediatric urinary tract obstruction. Open pyeloplasty has always been the reference standard treatment with variable results. Recently, attention has turned to minimally invasive procedures. We reviewed our 8-year experience with endoluminal balloon dilatation to ascertain whether this procedure is an effective minimally invasive alternative. The hospital databases, case notes, and radiology records of 14 patients who underwent 15 balloon dilatations for PUJO were examined. Patient demographics, clinical presentation, radiological investigations, operative details, morbidity and follow up were noted. The median age was 10.5 years (range 19 months to 14 years); 33% female and 66% male. Nine primary dilatations, five dilatations following open pyeloplasty, and one re-dilatation were performed. The median stenting time was 44 days (range 1-63 days) and the median in-patient stay was 2 days (range 1-17). There were six minor complications due to blocked stents, misplaced stents, or stents falling out. All patients were followed up at 12 months, and nine had further follow up. The median length of follow up was 44 months (range 22-75). Median diameter of the renal pelvis and MAG3 drainage scores improved from 34 to 16 mm and 4 to 3, respectively, from pre-dilatation to most recent follow up. At the most recent follow up, none of the patients had symptoms attributable to PUJO. Our results suggest that, using specialized techniques and a multidisciplinary surgeon-radiologist approach, balloon dilatation can be an effective alternative to open pyeloplasty.


Anti-acetylcholine receptor antibody related idiotypes in myasthenia gravis.
Anti-acetylcholine receptor antibody associated idiotypes were defined by six murine monoclonal antibodies raised against purified receptor antibodies. Four of the monoclonal antibodies bound to idiotopes located within or close to the antigen binding site of the anti-receptor antibodies; the other two monoclonal antibodies were directed against framework determinants. These monoclonal antibodies recognized idiotopes present on immunoglobulins in 14-60% of patients presenting myasthenia gravis, indicating substantial idiotype sharing. These idiotopes were also found in patients with no detectable anti-receptor antibody activity in their serum. In all patients studied, the pattern of idiotypes fluctuated considerably during the course of the disease regardless of clinical symptoms. This suggests continuous modulation of the autoimmune process in myasthenia gravis.


Adeno-associated virus-mediated bone morphogenetic protein-7 gene transfer induces C2C12 cell differentiation into osteoblast lineage cells.
To investigate the effects of bone morphogenetic protein-7 (BMP7)-expressing recombinant adeno-associated virus (AAV) vector on the differentiation of C2C12 cells. AAV-BMP7 was packaged by infecting the stable cell clone BHK-21 (integrated with recombinant AAV vector plasmid pSNAV-BMP7) with recombinant herpes simplex virus type 1, which expresses AAV-2 Rep and Cap and possesses AAV packaging functions. Following infection with AAV-BMP7 at multiplicities of infection of 1 x 10(5) vector genomes per cell and subsequent culture, C2C12 cells were assessed qualitatively for BMP7 production, alkaline phosphatase activity, osteocalcin production and Cbfal and MyoD expression. C2C12 cells transduced with AAV-BMP7 could produce BMP7 protein until d 28. Alkaline phosphatase in the cultured C2C12 cell lysate was elevated. Secreted osteocalcin in the culture medium was detectable at d 12 and Cbfal mRNA expression level was upregulated, coinciding with downregulation of MyoD in a temporal manner. The present in vitro study demonstrated that AAV-BMP7 could infect and efficiently convert C2C12 cells from myoblasts into osteoblast lineage cells.


Genetic association study of APOA1/C3/A4/A5 gene cluster and haplotypes on triglyceride and HDL cholesterol in a community-based population.
Polymorphism of apolipoprotein A1/C3/A4/A5 gene cluster affected lipid profiles in general population. We reported 6 polymorphisms, APOA1 -75G>A, APOA1 83C>T, APOC3 3175C>G, APOC3 3206G>T, APOA4 127A>G, and APOA5 553G>T in APOA1/C3/A4/A5 gene and the haplotype structures on triglyceride and HDL traits among ethnic Chinese. Overall, there were statistically significant differences in the distribution of APOA1 -75G>A and APOA5 +553G>T genotypes comparing cases with control subjects. For the APOA1 -75 SNP, a lower risk of triglyceride/HDL among subjects with A/A genotype compared with those with the G/G genotype (odds ratio, OR=0.39, 95% CI 0.16-0.92, P=0.04). However, the risk magnitude reduced after multivariate adjustments. For continuous traits, we found that only in APOA5 +553 T allele carriers showed a significant higher triglyceride and a significant lower HDL cholesterol level than subjects with APOA5 +553 G/G genotypes. There were significant differences in overall haplotype frequencies between case and control subjects (P<0.001). There is an important role of APOA1/C3/A4/A5 gene polymorphisms and haplotypes in the development of high triglyceride/HDL ratio in Chinese.


Phosphatidylglycerol is involved in protein translocation across Escherichia coli inner membranes.
Newly synthesized proteins to be exported out of the cytoplasm of bacterial cells have to pass across the inner membrane. In Gram-negative bacteria ATP, a membrane potential, the products of the sec genes and leader peptidases (enzymes which cleave the N-terminal signal peptides of the precursor proteins) are required. The mechanism of translocation, however, remains elusive. Important additional roles for membrane lipids have been repeatedly suggested both on theoretical grounds and on the basis of experiments with model systems but no direct evidence had been obtained. We demonstrate here, using mutants of Escherichia coli defective in the synthesis of the major anionic membrane phospholipids, that phosphatidylglycerol is involved in the translocation of newly synthesized outer-membrane proteins across the inner membrane.


Free choice of sickness funds in regulated competition: evidence from Germany and The Netherlands.
Sickness funds became the focal point of health insurance reforms in the 1990s. Policy makers expected funds to become more consumer-oriented and more active in managing the provision of health care. This is especially true for two countries in the heart of Europe that, on first view, have many similar institutional characteristics. Both Germany and The Netherlands have introduced competition between sickness funds in the last decade. We present extensive quantitative, as well qualitative, data with regard to the behaviour of consumers after the introduction of free choice between sickness funds. National data was used with regard to contribution rates and member flows and survey data was used to investigate personal motives for actual change and perception of differences between sickness funds. In Germany, contribution rates between sickness funds differ significantly. Accordingly, these differences are the main reason for consumers to switch funds, which occurs on a considerable scale. However, survey data show that other reasons may be important too. In The Netherlands, premium differences are much lower. The same is true for the degree of change. Survey data show that consumers perceive very small differences between sickness funds and do not see much reason for change. Our findings support the claim that the degree of actual changing depends strongly on economic incentives, especially with regard to the extent of financial risk sickness funds have to bear and to the extent premiums or contribution rates can differ. However, the higher the financial risk of individual sickness funds actually is, the higher the incentives for risk selection.


Patient and graft survival in hepatitis C recipients after adult living donor liver transplantation in the United States.
End stage liver disease from chronic hepatitis C is the leading indication for liver transplantation in the United States. Small studies suggest that recurrent hepatitis C may be more common and occur earlier after living donor liver transplantation compared to deceased donor liver transplantation. The objective of our study was to analyze the United Network for Organ Sharing liver transplant database to compare patient and graft survival in recipients transplanted for chronic hepatitis C who received a living donor organ and deceased donor organ between 1999 and 2002. We identified 279 living donor recipients and 3955 deceased donor recipients. Living donor recipients were less ill at the time of transplant, more likely to be female, and received grafts from younger donors. In the living donor group and deceased donor group, 1-year graft survival was 77% and 82%, respectively, and 2-year graft survival was 72% and 75%, respectively, P =.11. One-year patient survival was 87% in both groups and 2-year patient survival was 83% and 81% in the living donor group and deceased donor group, respectively, P =.68. Short-term patient and graft survival are similar between living donor and deceased donor liver transplant recipients with hepatitis C suggesting that recurrent hepatitis C does not seem to affect short-term outcomes.


Fantastic plastic? Experimental evaluation of polyurethane bone substitutes as proxies for human bone in trauma simulations.
Recent years have seen steady improvements in the recognition and interpretation of violence related injuries in human skeletal remains. Such work has at times benefited from the involvement of biological anthropologists in forensic casework and has often relied upon comparison of documented examples with trauma observed in skeletal remains. In cases where no such example exists investigators must turn to experimentation. The selection of experimental samples is problematic as animal proxies may be too dissimilar to humans and human cadavers may be undesirable for a raft of reasons. The current article examines a third alternative in the form of polyurethane plates and spheres marketed as viable proxies for human bone in ballistic experiments. Through subjecting these samples to a range of impacts from both modern and archaic missile weapons it was established that such material generally responds similarly to bone on a broad, macroscopic scale but when examined in closer detail exhibits a range of dissimilarities that call for caution in extrapolating such results to real bone.


Vitrectomy for Proliferative Diabetic Retinopathy Associated with Klinefelter Syndrome.
We encountered a patient with Klinefelter syndrome (KS) who experienced poor outcomes after vitrectomy for proliferative diabetic retinopathy (PDR). A 44-year-old male with poorly controlled diabetes was diagnosed with KS by chromosome analysis. Ocular findings revealed severe PDR complicated with extensive preretinal hemorrhages and traction retinal detachment in his left eye, and pars plana vitrectomy was subsequently performed for treatment. A clotting hemorrhage developed during surgery and proved difficult to control. Due to postoperative bleeding and redetachment, the vitrectomy was repeated. At the second operation, we performed a silicone oil tamponade; however, the retina was redetached under the silicone oil, and the light perception vision ultimately disappeared. The patient, despite showing increased blood coagulability due to diabetes, presented severe coagulopathy, likely related to KS. In patients with KS and severe PDR, the potential difficulty of vitrectomy should always be kept in mind.


Comments by Microbiologists for Interpreting Antimicrobial Susceptibility Testing and Improving the Appropriateness of Antibiotic Therapy in Community-Acquired Urinary Tract Infections: A Randomized Double-Blind Digital Case-Vignette Controlled Superiority Trial.
In primary care, urinary tract infections (UTIs) account for the majority of antibiotic prescriptions. Comments from microbiologists on interpreting the antimicrobial susceptibility testing (AST) profile for urinalysis were made to improve the prescription of antibiotics. We aimed to explore the added value of these comments on the quality of antibiotic prescribing by a superior double-blind digital randomized case-vignette trial among French general practitioners (GPs). One case vignette with (intervention) or without (control) a 'comment' after AST was randomly assigned to GPs. Among 815 participating GPs, 64.7% were women, at an average age of 37 years. Most (90.1%) used a computerized decision support system for prescribing antibiotics. Empirical antibiotic therapy was appropriate in 71.9% (95% CI, 68.8-75.0) of the cases, without differences between arms. The overall appropriateness of targeted antibiotic therapy (primary outcome) was not significantly increased when providing 'comments': 83.4% vs. 79.9% (OR = 1.26, 95% CI, 0.86-1.85). With the multivariate analysis, the appropriateness was improved by 2-folds (OR = 2.38, 95% CI, 1.02-6.16) among physicians working in healthcare facilities. Among digital-affine young general practitioners, the adjunction of a 'comment' by a microbiologist to interpret urinalysis in community-acquired UTIs did not improve the overall level of appropriateness of the targeted antibiotic.


The discovery and development of belimumab: the anti-BLyS-lupus connection.
For the first time in more than 50 years, the US Food and Drug Administration has approved a drug specifically for the treatment of systemic lupus erythematosus (SLE). This drug, belimumab (Benlysta), is a human monoclonal antibody that neutralizes the B-cell survival factor, B-lymphocyte stimulator (BLyS). The approval of belimumab combined a pioneering approach to genomics-based gene discovery, an astute appreciation of translational medicine, a disciplined clinical strategy, a willingness to take calculated risks, a devoted cadre of patients and physicians and a healthy dose of serendipity. Collectively, these efforts have provided a model for the development of a new generation of drugs to treat the broad manifestations of SLE. However, as a substantial percentage of SLE patients do not respond to belimumab, further research is needed to better characterize the pathogenetic mechanisms of SLE, identify additional therapeutic targets, and develop effective and nontoxic novel agents against these targets.


Genetic association studies in cancer: good, bad or no longer ugly?
For some time, investigators have appreciated that genetic association studies in cancer are complex because of the multi-stage process of cancer and the daunting challenge of analysing genetic variants in population and family studies. Because of recent technological advances and annotation of common genetic variation in the human genome, it is now possible for investigators to study genetic variation and cancer risk in many different settings. While these studies hold great promise for unravelling multiple genetic risk factors that contribute to the set of complex diseases called cancer, it is also imperative that study design and methods of interpretation be carefully considered. Replication of results in sufficiently large, well-powered studies is critical if genetic variation is to realise the promise of personalised medicine--namely, using genetic data to individualise medical decisions. In this regard, the plausibility of validated genetic variants can only be realised by the study of gene-gene and gene-environment interactions. The genetic association study in cancer has come a long way from the days of restriction fragment length polymorphisms, and now promises to scan an entire genome 'agnostically' in search of genetic markers for a disease or outcome. Moreover, the application and interpretation of these studies should be conducted cautiously.


Mechanical response at peri-implant mandibular bone for variation of pore characteristics of implants: A Finite Element Study.
In this paper, the mechanical response of generic dental implants having calculated porosities with varying pore-sizes has been evaluated. The purpose of this study was to compare the developed stress-strain of designed porous implants (i.e., stress at the implant and strain at the peri-implant bone) with that of the non-porous implant. 3D model of a mandible was prepared from CT scan data and nine generic dental implant models have been designed having 10%, 20%, and 30% porosity with 500, 700, and 900 micron pore size along with a non-porous model for carrying out FE analyses. First, failure analyses of implants, under a biting force of 250 N have been performed. Next, the remaining implants have been further evaluated under average compressive chewing load of 100 N, for mechanical responses at bone-implant interface. Von Mises strain at the peri-implant mandibular bone increases with the increase in percentage porosity of the implant material and maximum implant stress remained much below the yield stress level. Implant stiffness and compressive strength vary as a function of porosity and pore size. Strain obtained on the peri-implant bone is sufficient enough to facilitate better bone growth with the 700 micron pore size and 30% porosity, thus reducing the effect of stress shielding.


Assessment of olfactory and trigeminal function using chemosensory event-related potentials.
To give an overview on the theoretical and practical applications of chemosensory event-related potentials. Chemosensory event-related potentials (ERPs) may be elicited by brief and precisely defined odorous stimuli. Based on the principles of air-dilution olfactometry, a stimulator was developed in the late 1970s, which allows stimulation of the olfactory neuroepithelium and the nasal mucosa with no concomitant mechanical stimulation. Chemosensory ERPs were obtained after stimulation of the olfactory nerve (olfactory ERPs) or the trigeminal nerve (somatosensory or trigeminal ERPs). The characteristics of the stimulator for chemosensory research as well as the variables influencing the responses are discussed in this paper. Implementation and normative data from our department are reported with different clinical examples from otorhinolaryngologic clinic. The bulk of the evoked response consists of a large negative component (often referred to as N1), which occurs between 320 and 450 ms after stimulus onset. This component is followed by a large positive component, often referred to as P2, occurring between 530 and 800 ms after stimulus onset. Absence of olfactory ERPs and presence (even with subtle changes) of somatosensory ERPs is a strong indicator of the presence of an olfactory dysfunction. This review examines and discusses the methods of chemosensory stimulation as well as the electrophysiological correlates elicited by such stimuli. The clinical applications of chemosensory ERPs in neurology and otorhinolaryngology are outlined.


Lewis and ABO-Rh blood group systems in patients with bipolar affective disorder.
In this study Lewis and ABO-Rh blood group systems were investigated in forty patients with bipolar affective disorder and forty healthy control subjects. The results were discussed in view of the literature.


Effect of sulfur particle morphology on the performance of element sulfur-based denitrification packed-bed reactor.
The effect of particle morphology on denitrification performance in element sulfur-based denitrification (ESDeN) packed-bed process is a gap. In this study, three different types of commercial sulfur particles were selected to build the ESDeN reactors. The results showed the reactors filled with rougher sulfur particles took shorter time to reach stable denitrification performance in the start-up stage. The reactors filled with cap-shape sulfur particles received the maximum nitrate removal rate of 849.49 ± 79.29 g N m-3 d-1 at empty bed contact time of 0.50 h, which was 2.34 times higher than that with ball-shape sulfur particles in the steady stage. The superior denitrification performance in the cap-shape particles set linked to its larger effective volumetric surface area (ωe, 1.67 times larger) and to the longer actual hydraulic retention time (AHRT, 1.80 times longer). This study extends the knowledge of the dependency of sulfur particle properties on denitrification performance in ESDeN packed-bed reactor.


Influence of resin cement polymerization shrinkage on stresses in porcelain crowns.
The aim of this study was to analyze the influence of polymerization shrinkage of the cement layer on stresses within feldspathic ceramic crowns, using experimentally validated FEA models for (1) increasing occlusal cement thickness; and, (2) bonded versus non-bonded ceramic-cement interfaces. 2-D axial symmetric models simulated stylized feldspathic crowns (1.5mm occlusal thickness) cemented with resin-cement layers of 50-500μm on dentin preparations, being loaded (500N) or not. Ceramic-cement interface was either bonded or not. Cement was bonded to the dentin in all models. Maximum axial shrinkage of 0%, 1%, 2%, 3%, 4% and 4.65% were simulated. The first principal stresses developing in the cementation surface at the center and at the occluso-axial line-angle of the crown were registered. Polymerization shrinkage of the cement increased tensile stresses in the ceramic, especially in loaded non-bonded crowns for thicker cement layers. Stresses in loaded non-bonded crowns increased as much as 87% when cement shrinkage increased from 0% to 4.65% (100-187MPa), for a 500μm-thick cement. Increasing polymerization shrinkage strain raised the tensile stresses, especially at the internal occlusal-axial line-angle, for bonded crowns. Changes in the polymerization shrinkage strain (from 0% to 4.65%) have little effect on the tensile stresses generated at the cementation surface of the ceramic crowns, when the occlusal cement thickness is thin (approx. 50μm for bonded crowns). However, as the cement becomes thicker stresses within the ceramic become significant.


Redox-stress response resistance (RRR) mediated by hyperoxidation of peroxiredoxin 2 in senescent cells.
Aging is closely related to redox regulation. In our previous work, we proposed a new concept, "redox-stress response capacity (RRC)," and found that the decline in RRC was a dynamic characteristic of aging. However, the mechanism of RRC decline during aging remains unknown. In this study, using the senescent human fibroblast cell model and Caenorhabditis elegans model, we identified that peroxiredoxin 2 (PRDX2), as a hydrogen peroxide (H2O2) sensor, was involved in mediating RRC. PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C. elegans also showed decreased RRC. The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells. Moreover, the level of PRDX2 hyperoxidation also increased in old C. elegans. Simultaneous overexpression of both PRDX2 and sulfiredoxin (SRX) rescued the reduced RRC and delayed senescence. The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity, resulting in the decreased cellular response to H2O2, which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity. Treatment of young cells with a high level of H2O2 to induce a higher level of PRDX2-SO3 resulted in mimicking the RRC decline in senescent cells, which is also similar to a model of insulin resistance induced by high levels of insulin. All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells, we named it redox-stress response resistance, RRR. RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.


Investigation of age-specific behavioral and proteomic changes in an animal model of chronic ethanol exposure.
Alcohol use during adolescence represents a major health concern given that this is a period in which the brain continues to undergo critical developmental changes. Much behavioral research has been conducted in animal models of alcohol exposure, and a vulnerable period in adolescence has been identified that suggests lasting effects of ethanol exposure during adolescence. However, identification of molecular changes underlying the behavioral outcomes observed as a result from exposure to ethanol during adolescence remains a major technical challenge. In this chapter, we describe a method that allows for assessment of the effects of chronic ethanol exposure during adolescence relative to adulthood through global-scale analysis of protein expression as well as evaluation of behavioral responsivity in adolescent and adult rats. Results from this type of analysis can facilitate identification of age-specific molecular markers associated with behavioral changes following treatment with ethanol or in other animal models of drug abuse.


Serum 25-hydroxyvitamin D measurement in a large population survey with statistical harmonization of assay variation to an international standard.
An automated application of Immunodiagnostic Systems Limited (IDS) OCTEIA 25-hydroxyvitamin D [25(OH)D] enzyme immunoassay was developed for analyses of 25(OH)D in more than 7000 participants of the 1958 cohort. Variation between 25(OH)D assays hampers between-study comparisons and the definition of relevant cutoffs for hypovitaminosis D. The objective of the study was to evaluate the importance of assay variation on the estimated prevalence of hypovitaminosis D and assess the use of statistical harmonization to overcome the observed differences. Agreement analyses were performed between two commercial 25(OH)D assays (IDS enzyme immunoassay and Diasorin RIA), with validation using performance data from Vitamin D External Quality Assessment Scheme (DEQAS). The study was conducted in England, Scotland, and Wales. Members of the 1958 British birth cohort participated in the study. 25(OH)D was measured both by IDS and Diasorin RIA in 781 samples. Additional quality control data were obtained through participation in DEQAS (five distributions throughout the survey). Average 25(OH)D concentrations by IDS were -15.7 and -13.7 nmol/liter lower, compared with Diasorin or DEQAS mean, respectively (both P < 0.0001). Graphical examination demonstrated a dose-related bias between IDS with Diasorin and DEQAS mean, but log transformation removed the bias. After using the log difference between the measurements as an adjustment factor, there were no differences in average 25(OH)D concentrations (P >or= 0.21 for comparison of IDS with Diasorin or DEQAS) and estimates for hypovitaminosis D obtained by IDS were similar to Diasorin. Differences between assays have implications for public health messages about hypovitaminosis D. Harmonization of results with DEQAS enabled the use of previously determined cutoffs for hypovitaminosis D.


3D analysis of thermal and stress evolution during laser cladding of bioactive glass coatings.
Thermal and strain-stress transient fields during laser cladding of bioactive glass coatings on the Ti6Al4V alloy basement were numerically calculated and analysed. Conditions leading to micro-cracking susceptibility of the coating have been investigated using the finite element based modelling supported by experimental results of microscopic investigation of the sample coatings. Consecutive temperature and stress peaks are developed within the cladded material as a result of the laser beam moving along the complex trajectory, which can lead to micro-cracking. The preheated to 500°C base plate allowed for decrease of the laser power and lowering of the cooling speed between the consecutive temperature peaks contributing in such way to achievement of lower cracking susceptibility. The cooling rate during cladding of the second and the third layer was lower than during cladding of the first one, in such way, contributing towards improvement of cracking resistance of the subsequent layers due to progressive accumulation of heat over the process.


Comparative efficacy of one versus two doses of praziquantel on cure rate of Schistosoma mansoni infection and re-infection in Mayuge District, Uganda.
The current recommended control strategy for schistosomiasis is annual treatment using 40 mg/kg of praziquantel. However, praziquantel is only effective on adult worms and giving a second dose may increase its efficacy. We assessed the effect of one versus two doses of praziquantel on cure rate and re-infection with Schistosoma mansoni in a high endemic community along Lake Victoria, Uganda. To investigate the effect of the two regimens, 395 infected people were randomised into two groups; one received a single standard dose of praziquantel (Distocide® 600 mg, Shin Poong Pharmaceuticals, Seoul, Republic of Korea), 40mg/kg body weight, while the other group received a second dose 2 weeks later. Cure rate and infection intensity were assessed 9 weeks after the first treatment using standard parasitological procedures. Re-infection levels were monitored 8 and 24 months after treatment. Those who received two doses were more likely to be cured (69.7%) compared to those who received a single dose (47.9%) (χ(2) = 18.5, p < 0.001). Geometric mean intensity (GMI) of infection at 9 weeks (eggs per gram of faeces [epg]) was 12.0 epg (CI95: 8.9-16.1) for individuals who received 2 doses and 22.1 epg (CI95: 16.9-28.8) for those in the single dose arm. Eight months after treatment, prevalence of re-infection for individuals in the double dose arm (61.6%, CI95: 50.2-73.1) was not significantly different from that of those in a single dose arm (68.3%, CI95: 59.9-76.8). The difference in GMI of re-infection for individuals in the single dose arm (33.8 epg, CI95: 23.2-49.3) and those in the double dose arm (34.5 epg, CI95: 24.7-48.1) was not significant. Twenty four months after treatment, prevalence of re-infection was not significantly different. The difference in GMI of re-infection for those in the single dose arm (57.5 epg, CI95: 33.9-97.5) and those in the double dose arm (42.2 epg, CI95: 29.9-59.6) was also insignificant. Our results suggest that a second dose of praziquantel given 2 weeks after the first dose improves cure rate and reduces S. mansoni infection intensity. However, there is no added advantage on reduction of S. mansoni re-infection by administering two doses of praziquantel. CLINICAL TRIALS.GOV IDENTIFIER: NCT00215267.


Fluid dynamic design for mitigating undesired cell effects and its application to testis cell response testing to endocrine disruptors.
Microfluidic devices have emerged as powerful tools for cell-based experiments, offering a controlled microenvironment that mimic the conditions within the body. Numerous cell experiment studies have successfully utilized microfluidic channels to achieve various new scientific discoveries. However, it has been often overlooked that undesired and unnoticed propagation of cellular molecules in such bio-microfluidic channel systems can have a negative impact on the experimental results. Thus, more careful designing is required to minimize such unwanted issues through deeper understanding and careful control of chemically and physically predominant factors at the microscopic scale. In this paper, we introduce a new approach to improve microfluidic channel design, specifically targeting the mitigation of the aforementioned challenges. To minimize the occurrence of undesired cell positioning upstream from the main test section where a concentration gradient field locates, an additional narrow port structure was devised between the microfluidic upstream channel and each inlet reservoir. This port also functioned as a passive lock that hold the flow at rest via fluid-air surface tension, which facilitated manual movement of the device even when cell attachment was not achieved completely. To demonstrate the practicability of the system, we conducted experiments and diffusion simulations on the effect of endocrine disruptors on germ cells. To this end, a bisphenol-A (BPA) concentration gradient was generated in the main channel of the system at BPA concentrations ranging from 120.8 μM to 79.3 μM, and the proliferation of GC-1 cells in the BPA gradient environment was quantitatively evaluated. The features and concepts of the introduced design is to minimize unexpected and ignored error sources, which will be one of the issues to be considered in the development of microfluidic systems to explore extremely delicate cellular phenomena.


Incidental low grade mucinous neoplasm of appendix in pregnancy: A case report & literature review.
Mucinous neoplasms of appendix account for 0.2-0.4% of all the appendix specimens. The occurrence of this neoplasm in pregnancy is extremely rare. We describe a case of a pregnant lady who was diagnosed as acute appendicitis and found to have Low-Grade Mucinous neoplasm on histopathology. In the existent literature, there are only a few such cases reported and none from our Middle East region. 42-year-old pregnant lady at 24 weeks of gestation presented with classical symptoms of acute appendicitis. She had leukocytosis but the Ultrasound was equivocal. She underwent laparoscopic appendectomy and found to have an inflamed appendix. Postoperative recovery was satisfactory and was discharged home. The histopathology report showed low-grade mucinous neoplasm of the appendix and she was detailed about it on follow up. The incidence of appendiceal neoplasm is rare in routine appendectomy and carcinoid is the most common tumor of the appendix. Low-Grade mucinous neoplasm is a rare entity and its presence in pregnancy is further rarer. Since this neoplasm does not manifest with a characteristic clinical profile it is difficult to diagnose, even with extensive preoperative evaluation. Although surgical treatment is straight forward, the management of the appendiceal neoplasm during pregnancy necessitates full knowledge of the natural history of the disease to attain equilibrium of concern for maternal survival and fetal health.


Performance Management in Healthcare Organizations: Concept and Practicum.
Organizational performance can create and sustain competitive advantages for corporations and even improve their sustainability and future prospects. Health care organizations present a sector where performance management is structured by multiple dimensions. The scope of this study is to analyze the issue of performance management in healthcare organizations and specifically the implementation of the Balanced Scorecard (BSC) methodology on organizations providing health services. The study provides a discussion on the BSC development process, the steps that management has to take in order to prepare the implementation of the BSC and finally discusses a practical example of a scorecard with specific strategic goals and performance indicators. Managers of healthcare organizations and specifically those providing services to the elderly and the general population could use the propositions of the study as a roadmap for processing, analyzing, evaluating and implementing the balanced scorecard approach in their organizations' daily operations. BSC methodology can give an advantage in terms of enhanced stakeholder management and preservation within a highly volatile and competitive economic environment.


Real-time estimation and prediction of the mortality caused due to COVID-19 using particle swarm optimization and finding the most influential parameter.
On March 11, 2020, the World Health Organization has declared the outbreak of COVID-19 as Pandemic, which is the massive challenges faced globally. Previous studies have indicated that the meteorological parameters can play a vital role in transmissibility and Mortality. In the present work, the influence of Comorbidity and meteorological parameters are investigated for Mortality caused due to COVID. For this, the most affected city by COVID-19 is considered, i.e., Mumbai, India, as a case study. It was found that Comorbidity is the most influential parameter on the Mortality of COVID-19. The Spearman correlation coefficient for meteorological parameters lies between 0.386 and 0.553, whereas for Comorbidity was found as 0.964. A regression model is developed using particle swarm optimization to predict the mortality cases for Mumbai, India. Further, the developed model is validated for the COVID-19 cases of Delhi, India, to emphasize the utility of the developed model for other cities. The measured and predicted curve shows a good fit with a mean percentage error of 0.00957% and a coefficient of determination of 0.9828. Thus, particle swarm optimization techniques demonstrate very high potential for the prediction of Mortality caused due to COVID-19. It is insisted that by providing constant health monitoring and adequate care for the comorbidity patients, the Mortality can be suppressed drastically. The present work can serve as an input to the policymakers to overcome the COVID-19 pandemic in India as well as other parts of the world.


The significance of exercise-induced Q waves.
The significance of transient exercise-induced Q waves present during treadmill testing was prospectively evaluated and correlated with the findings at cardiac catheterization. Exercise-induced Q waves were present in 14 of 560 patients (2.5 per cent) undergoing treadmill exercise testing. Thirteen patients had Q waves in leads V1 through V3 and one patient had Q waves in leads II, III and aVF. Ten patients underwent cardiac catheterization; six did not have coronary artery disease as determined by angiography. Two patients had a documented anterior myocardial infarction and did not undergo cardiac catheterization. Exercise myocardial perfusion imaging was performed in 10 patients. Six patients without coronary artery disease had no evidence of exercise perfusion defects. In the four patients with coronary artery disease, three patients had an abnormal resting perfusion study without change with exercise and one patient had a new exercise myocardial perfusion defect. We conclude that exercise-induced transient Q waves are not diagnostic of underlying coronary disease. In patients without coronary artery disease the mechanism of exercise-induced Q waves is as yet unclear. In patients with coronary artery disease, the mechanism may also be undefined or secondary to myocardial ischemia.


Spatial and temporal dynamics of DNA replication sites in mammalian cells.
Fluorescence microscopic analysis of newly replicated DNA has revealed discrete granular sites of replication (RS). The average size and number of replication sites from early to mid S-phase suggest that each RS contains numerous replicons clustered together. We are using fluorescence laser scanning confocal microscopy in conjunction with multidimensional image analysis to gain more precise information about RS and their spatial-temporal dynamics. Using a newly improved imaging segmentation program, we report an average of approximately 1,100 RS after a 5-min pulse labeling of 3T3 mouse fibroblast cells in early S-phase. Pulse-chase-pulse double labeling experiments reveal that RS take approximately 45 min to complete replication. Appropriate calculations suggest that each RS contains an average of 1 mbp of DNA or approximately 6 average-sized replicons. Double pulse-double chase experiments demonstrate that the DNA sequences replicated at individual RS are precisely maintained temporally and spatially as the cell progresses through the cell cycle and into subsequent generations. By labeling replicated DNA at the G1/S borders for two consecutive cell generations, we show that the DNA synthesized at early S-phase is replicated at the same time and sites in the next round of replication.


Cross-sectional survey on complementary and alternative medicine awareness among health care professionals and students using CHBQ questionnaire in a Balkan country.
To conduct a study on attitudes, knowledge, and use of complementary and alternative medicine (CAM) therapies in Serbia. Available data about CAM therapies in the region are scarce, opinions lacking from health sector. Balkan region countries had a delay in issuing national policies on CAM therapies. The questionnaire used was based on previously validated CAM Health Belief Questionnaire (CHBQ), formulated as 5-item Likert type scale, adjusted for local environment. Health care students and professionals were evaluated. The questionnaire comprehended 10 closed questions on attitudes, knowledge and use of CAM therapies. This survey was conducted in eight cities of Serbia, January 2010-July 2011. A total of 797 participants was included. The second group of participants was 145 healthcare professionals (50 academic staff, 64 clinical staff, 19 pharmacists, 6 other clinical branch specialists and 6 nurses). Data were collected by an interview. Examinees could acquire maximum of 70 points, 35 representing neutral attitude. Students of dentistry (54.65±6.07) were better informed on CAM therapies than medicine students (50.26±7.92). Pharmacy students (51.16±7.10) accepted low-scientific CAM. Pharmacists scored better than university professors (55.12±6.55 vs. 50.29±9.50). Primary health care professionals had better awareness than pharmacists in dispensing pharmacies. Both groups of participants preferred use of vitamins over any other CAM therapy. These pioneering efforts in the region exposed weaknesses in CAM attitudes of current and future health care professionals. Nevertheless, awareness on alternative medicine treatment choices is growing among Balkan prescribers. Supportive legal framework would facilitate dissemination of CAM medical practices.


Gut microbes may facilitate insect herbivory of chemically defended plants.
The majority of insect species consume plants, many of which produce chemical toxins that defend their tissues from attack. How then are herbivorous insects able to develop on a potentially poisonous diet? While numerous studies have focused on the biochemical counter-adaptations to plant toxins rooted in the insect genome, a separate body of research has recently emphasized the role of microbial symbionts, particularly those inhabiting the gut, in plant-insect interactions. Here we outline the "gut microbial facilitation hypothesis," which proposes that variation among herbivores in their ability to consume chemically defended plants can be due, in part, to variation in their associated microbial communities. More specifically, different microbes may be differentially able to detoxify compounds toxic to the insect, or be differentially resistant to the potential antimicrobial effects of some compounds. Studies directly addressing this hypothesis are relatively few, but microbe-plant allelochemical interactions have been frequently documented from non-insect systems-such as soil and the human gut-and thus illustrate their potential importance for insect herbivory. We discuss the implications of this hypothesis for insect diversification and coevolution with plants; for example, evolutionary transitions to host plant groups with novel allelochemicals could be initiated by heritable changes to the insect microbiome. Furthermore, the ecological implications extend beyond the plant and insect herbivore to higher trophic levels. Although the hidden nature of microbes and plant allelochemicals make their interactions difficult to detect, recent molecular and experimental techniques should enable research on this neglected, but likely important, aspect of insect-plant biology.


Accumulation of heterocyclic amines across low-temperature sausage processing stages as revealed by UPLC-MS/MS.
The accumulation of heterocyclic amines (HAs) in low-temperature sausages in each processing stage was investigated using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). The maximum total levels for free HAs, protein-bound HAs, and all HAs were respectively 1.91 ng/g, 162.91 ng/g and 164.82 ng/g. Harman, norharman, Glu-P-1, and PhIP accumulated from raw sausages and reached maximum of 50.88 ng/g, 84.59 ng/g, 9.60 ng/g, and 4.69 ng/g after steaming. The highest level of IQ[4,5-b] was 0.36 ng/g found in raw sausages. AαC, MeAαC, DMIP, and 1,5,6-TMIP were all produced after drying and reached maximum after steaming: 3.25 ng/g, 6.52 ng/g, 0.15 ng/g, and 2.78 ng/g. Additionally, Phe-P-1 reached a maximum of only 0.02 ng/g after drying. MeIQ was generated only after steaming, reaching a maximum of 2.11 ng/g. These results may provide some basis for the inhibition of HAs in meat products through target processing stages.


High sensitivity method for fluorofore detection in gradient polyacrylamide slab gels through excitation by laser light: application to glycoproteins stained with concanavalin A-fluorescein isothiocyanate.
An easy-to-assemble apparatus for the laser-light excitation of fluorofores in polyacrylamide gels is described. The assemblage is made up of a continuous-wave ion-argon laser with adjustable power output, a beam diffuser, appropriate filters to block excitation light, and a photographic camera. With this setup a minimum 20-fold increase of sensitivity was obtained for fluorofore detection in polyacrylamide gels as compared to the more conventional uv-light excitation using a commercial preparation of Con A-FITC (concanavalin A-fluorescein isothiocyanate) as reference molecule in the gel. The same apparatus, used to analyze the Con A-positive glycoproteins contained in serum Cohn fraction IV separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, showed a number of fluorescent components in a wide range of relative intensities while uv-light excitation showed none. Acrylamide concentration in the gel is critical, since a working limit of between 10 and 12% has been found, above which the diffusion of Con A-FITC in the gel, necessary to label glycoprotein bands, is hampered. The system described here also permits the optimization of detection of minor components not otherwise observable by conventional light excitation, because light power, angle of incidence, and beam divergence can be adapted to analyze specific areas of the sample gel.


Protein-Protein Interaction Modelling with the Fragment Molecular Orbital Method.
Fragment molecular orbital (FMO) method enables ab initio quantum-chemical calculations for biomolecular systems with high accuracy and moderate computational cost. Through this analysis we can evaluate the inter-fragment interaction energies (IFIEs) that provide useful measures for effective interactions between the fragments representing amino-acid residues and ligand molecules. Here I describe how to prepare the input structures and perform the FMO calculations for protein-protein complex system. In addition to the pre-processing, some useful tools for the post-processing analysis are also illustrated.


The rapid identification of group A beta-hemolytic streptococci in the upper respiratory tract. Current status.
Rapid detection of group A beta-hemolytic streptococcal antigen on throat swabs has become more popular in the management of patients with pharyngitis. Although the specificity of these commercially available kits usually has been satisfactory, the sensitivity has varied considerably. Currently most physicians accept a positive rapid test result but frequently require culture confirmation of a negative rapid antigen detection test on a throat swab.


Purification and assembly of bacterial tubulin BtubA/B and constructs bearing eukaryotic tubulin sequences.
Bacterial tubulin BtubA/B is a close structural homolog of eukaryotic αβ-tubulin, thought to have originated by transfer of ancestral tubulin genes from a primitive eukaryotic cell to a bacterium, followed by divergent evolution. BtubA and BtubB are easily expressed homogeneous polypeptides that fold spontaneously without eukaryotic chaperone requirements, associate into weak BtubA/B heterodimers and assemble forming tubulin-like protofilaments. These protofilaments coalesce into pairs and bundles, or form five-protofilament tubules proposed to share the architecture of microtubules. Bacterial tubulin is an attractive framework for tubulin engineering. Potential applications include humanizing different sections of bacterial tubulin with the aims of creating recombinant binding sites for antitumor drugs, obtaining well-defined substrates for the enzymes responsible for tubulin posttranslational modification, or bacterial microtubule-like polymeric trails for motor proteins. Several divergent sequences from the surface loops of bacterial tubulin have already been replaced by the corresponding eukaryotic sequences, yielding soluble folded chimeras. We describe the purification protocol of untagged bacterial tubulin BtubA/B by means of ion exchange, size exclusion chromatography, and an assembly-disassembly cycle. This is followed by methods and examples to characterize its assembly, employing light scattering, sedimentation, and electron microscopy.


[Capillary hemangioma of the left ventricle. A case report and review of the literature].
The authors report a case of isolated left ventricular capillary haemangioma, diagnosed after chest X-ray during a routine medical check-up showed a deformation of the left heart border. Echocardiography showed a solid well circumscribed tumour. Its vascular origin was confirmed at coronary angiography. Myocardial biopsy performed after left thoracotomy confirmed the histological diagnosis. The authors review the medical literature of this condition in the light of this rare finding.


Compression distance can discriminate animals by genetic profile, build relationship matrices and estimate breeding values.
Genetic relatedness is currently estimated by a combination of traditional pedigree-based approaches (i.e. numerator relationship matrices, NRM) and, given the recent availability of molecular information, using marker genotypes (via genomic relationship matrices, GRM). To date, GRM are computed by genome-wide pair-wise SNP (single nucleotide polymorphism) correlations. We describe a new estimate of genetic relatedness using the concept of normalised compression distance (NCD) that is borrowed from Information Theory. Analogous to GRM, the resultant compression relationship matrix (CRM) exploits numerical patterns in genome-wide allele order and proportion, which are known to vary systematically with relatedness. We explored properties of the CRM in two industry cattle datasets by analysing the genetic basis of yearling weight, a phenotype of moderate heritability. In both Brahman (Bos indicus) and Tropical Composite (Bos taurus by Bos indicus) populations, the clustering inferred by NCD was comparable to that based on SNP correlations using standard principal component analysis approaches. One of the versions of the CRM modestly increased the amount of explained genetic variance, slightly reduced the 'missing heritability' and tended to improve the prediction accuracy of breeding values in both populations when compared to both NRM and GRM. Finally, a sliding window-based application of the compression approach on these populations identified genomic regions influenced by introgression of taurine haplotypes. For these two bovine populations, CRM reduced the missing heritability and increased the amount of explained genetic variation for a moderately heritable complex trait. Given that NCD can sensitively discriminate closely related individuals, we foresee CRM having possible value for estimating breeding values in highly inbred populations.


Evaluation of selective screening of donors for antibody to Trypanosoma cruzi: seroprevalence of donors who answer "no" to risk questions.
Selective testing of donors for Trypanosoma cruzi infection relies on identification of at-risk donors with screening questions. Using risk modeling and a seroprevalence study, we evaluated the risk of questions failing to identify T. cruzi antibody-positive donors. The rate of donors with unreported risk was estimated by a telephone survey of 2677 donors who answered "no" to risk questions. The number of T. cruzi antibody-positive donors missed by risk questions was estimated from the product of this rate and the selective testing T. cruzi antibody-positive rate. The 95% confidence interval (CI) was estimated by Monte Carlo simulation. To test the model, 60,132 donors were tested for T. cruzi antibody (26% of donors in selected regions, Phase I). In Winnipeg, Manitoba, the highest-risk region, 26,915 donors were tested (92.5% of donors, Phase II). In the telephone survey, 21 (0.8%) donors reported risk factors that would have identified them for selective testing. Seven were born in Mexico or Central or South America, five had travel risk, and nine had mother or maternal grandmother risk. The 95% CI for predicted number of T. cruzi antibody-positive donors answering "no" to risk questions was 0.71 to 4.38. In Phase I, one Winnipeg donor confirmed positive but had answered risk questions correctly. No other positive donations were identified. The estimated risk of T. cruzi-positive donors who answer "no" to risk questions is low and is confirmed by the seroprevalence among these donors.


Lipopolysaccharide-induced persistent inflammation ameliorates fat accumulation by promoting adipose browning in vitro and in vivo.
This work aimed to explore whether the persistent inflammation induced by lipopolysaccharide (LPS) ameliorates fat accumulation by promoting adipose browning in vitro and in vivo. LPS over 1 ng/mL reduced lipid accumulation while increasing the expressions of specific genes involved in inflammation, mitochondrial biogenesis, and adipose browning in 3T3-L1 adipocytes. Moreover, LPS in intraperitoneal injection decreased white adipose tissue weight and elevated interscapular brown adipose tissue weight in mice. According to RT-PCR and western blot analysis results, the expressions of genes and proteins related to inflammation, mitochondrial biogenesis, lipolysis, and brown or beige markers in different tissues were elevated after LPS intervention. Cumulatively, LPS-induced persistent inflammation may potentially ameliorate fat accumulation by facilitating adipose browning in 3T3-L1 adipocytes and mice. These results offer new perspectives into the effect of persistent inflammation induced by LPS on regulating fat metabolism, thereby reducing fat accumulation by boosting adipose browning procedure.


Spotlight on the impact of viral infections on Hematopoietic Stem Cells (HSCs) with a focus on COVID-19 effects.
Hematopoietic stem cells (HSCs) are known for their significant capability to reconstitute and preserve a functional hematopoietic system in long-term periods after transplantation into conditioned hosts. HSCs are thus crucial cellular targets for the continual repair of inherited hematologic, metabolic, and immunologic disorders. In addition, HSCs can undergo various fates, such as apoptosis, quiescence, migration, differentiation, and self-renewal. Viruses continuously pose a remarkable health risk and request an appropriate, balanced reaction from our immune system, which as well as affects the bone marrow (BM). Therefore, disruption of the hematopoietic system due to viral infection is essential. In addition, patients for whom the risk-to-benefit ratio of HSC transplantation (HSCT) is acceptable have seen an increase in the use of HSCT in recent years. Hematopoietic suppression, BM failure, and HSC exhaustion are all linked to chronic viral infections. Virus infections continue to be a leading cause of morbidity and mortality in HSCT recipients, despite recent advancements in the field. Furthermore, whereas COVID-19 manifests initially as an infection of the respiratory tract, it is now understood to be a systemic illness that significantly impacts the hematological system. Patients with advanced COVID-19 often have thrombocytopenia and blood hypercoagulability. In the era of COVID-19, Hematological manifestations of COVID-19 (i.e., thrombocytopenia and lymphopenia), the immune response, and HSCT may all be affected by the SARS-CoV-2 virus in various ways. Therefore, it is important to determine whether exposure to viral infections may affect HSCs used for HSCT, as this, in turn, may affect engraftment efficiency. In this article, we reviewed the features of HSCs, and the effects of viral infections on HSCs and HSCT, such as SARS-CoV-2, HIV, cytomegalovirus, Epstein-Barr virus, HIV, etc. Video Abstract.


Some ultrastructural effects of testosterone and insulin on the ventral prostate of rats in organ culture.
The fine structure of the secretory epithelial cells of rat's ventral prostate has been studied following organ culture. Culturing with either testosterone or insulin alone, and with the two hormones combined, were carried out to investigate how insulin modifies the action of testosterone on the maintenance of cellular integrity. After 4 days in hormone-free culture, the secretory epithelial cells showed signs of cellular atrophy and regression, involving loss of the apical microvilli, absence of the apical secretory vacuoles, atrophy of the Golgi apparatus, decrease in rough endoplasmic reticulum and the appearance of autophagic vacuoles. The presence in the medium of either testosterone or insulin alone, or combined, prevented cellular atrophy and regression. The best maintenance of cellular integrity was obtained in a culture containing both hormones. The effects of insulin was approximately equivalent to those of testosterone in the maintenance of cellular integrity.


Venlafaxine versus mirtazapine in the treatment of undifferentiated somatoform disorder: a 12-week prospective, open-label, randomized, parallel-group trial.
We set out to compare the efficacy and tolerability of mirtazapine versus venlafaxine in patients with undifferentiated somatoform disorder (USD) using the Patient Health Questionnaire-15 (PHQ-15). This was a 12-week prospective, open-label, randomized, parallel-group trial. The trial consisted of six visits that included baseline and weeks 1, 2, 4, 8 and 12. The primary effectiveness measure was the mean change in PHQ-15 total score from baseline to the end of treatment. Secondary effectiveness measures included the mean changes in total scores on the Beck Depression Inventory (BDI) and the 12-item General Health Questionnaire (GHQ) from baseline to the end of treatment. Ninety-five subjects were randomized to either mirtazapine (n = 50) or venlafaxine (n = 45); 71 subjects completed the study (mirtazapine: n = 39/50 [78%]; venlafaxine: n = 32/45 [71%]). The mean total score on the PHQ-15 decreased by 34.7% (-8.4, p < 0.0001) from baseline to endpoint in the mirtazapine group and by 26.6% (-6.1, p < 0.0001) in the venlafaxine group. A marginally significant between-group difference was observed for the mean change in total score on the PHQ-15 from baseline to endpoint (F = 4.126, p = 0.046). The mean total scores on the GHQ-12 and BDI from baseline to endpoint decreased by -4.9 (29.4%, p < 0.0001) and -13.5 (55.9%, p < 0.0001), respectively, in the mirtazapine group, and by -4.3 (26.2%, p = 0.001) and -9.02 (46.0%, p < 0.0001), respectively, in the venlafaxine group. No between-group difference was observed for the mean changes in total scores on the secondary effectiveness measures from baseline to endpoint. Both treatments were well tolerated. Our findings suggest that both mirtazapine and venlafaxine may be effective and well tolerated in the treatment of patients with USD. Double-blind, placebo-controlled and/or head-to-head comparison studies are required to allow definite conclusions to be drawn.


Studies on the neuromuscular junction with a special preference to nicotinic receptors in normal delivering cows and cows suffering from parturient paresis.
Acetylcholine synthesizing (ACh-s) activity, and binding of 3H-alpha-bungarotoxin (3H-Btx) and 3H-d-tubocurarine (3H-TC) were analysed in gluteus media muscle from normal cows and from cows suffering from parturient paresis, both at parturition and 3 months later. At parturition, the ACh-s activity was 50% lower in the muscle of paretic cows than in non-paretic cows. No difference was found in the number of 3H-Btx and 3H-TC binding sites at parturition, while 3 months after parturition the numbers of 3H-TC and 3H-Btx binding sites were significantly higher in normal than in paretic cows. These significant differences in the number of receptors and a possible underlying receptor regulation defect might be a plausible etiological factor for the disease parturient paresis.


Reconstructive surgical treatment of isolated deep intrabony defects with guided tissue regeneration using entire papilla preservation technique: A prospective case series.
The aim of this prospective study is to evaluate the clinical applicability of the entire papilla preservation (EPP) technique in the regenerative treatment of isolated deep intrabony defects using native collagen membrane and bone grafting materials. Fifteen healthy and non-smoker patients (nine males and six females; mean age: 47.73 ± 12.18; range 21 to 63 years) with one isolated deep intrabony defect each (baseline probing depth (PD): 9.03 ± 1.62 mm; clinical attachment level (CAL): 11.16 ± 1.81 mm) were treated with guided tissue regeneration. Surgical access to the defect was provided by a single buccal vertical incision with an interdental tunneling flap. Following the granulation tissue removal, intrabony defect was filled with bone substitutes. A collagen barrier was trimmed and placed under the intact defect-associated papilla with palatal positioning suture. Microsurgical sutures were used for primary closure. At 1 week, healing of the 15 sites was uneventful. During the study, all sites showed 100% primary closure rate. At 1-year follow-up, an average CAL gain of 5.86 ± 1.28 mm (P < 0.0001), PD reduction of 6.1 ± 1.47 mm (P < 0.0001), and minimal increase in gingival recession of 0.23 ± 0.62 mm (P = 0.168) were observed. This novel surgical technique, that keeps the interdental papilla intact, seems promising to provide optimal biomaterial protection and healing conditions, even when a collagen barrier and bone substitutes are applied.


Evaluation of the toxicity of di-iso-pentyl-phthalate (DiPeP) using the fish Danio rerio as an experimental model.
The presence of phthalates constitutes a risk to the health of aquatic environments and organisms. This work aimed to evaluate the toxic effects of di-iso-pentyl-phthalate (DiPeP) at environmentally relevant concentrations of 5, 25, and 125 µg/L in Danio rerio after subchronic exposure for 14 days. DiPeP altered the antioxidant system in the liver (125 μg/L), intestine (25 μg/L), brain, and gills in all concentrations tested. In animals exposed to 125 μg/L, DNA damage was identified in the gills. In addition, loss of cell boundary of hepatocytes, vascular congestion, necrosis in the liver, and presence of immune cells in the intestinal lumen were observed. Erythrocytic nuclear alterations in the blood occurred in animals exposed to 25 μg/L. DiPeP was quantified in muscle tissue at all exposure concentrations, appearing in a concentration-dependent manner. Contaminants such as DiPeP will still be used for a long time, mainly by industries, being a challenge for industry versus environmental health.


Serum pyruvate kinase in carriers of Duchenne muscular dystrophy.
Five out of 17 carriers of the gene for Duchenne muscular dystrophy had an increased level of serum pyruvate kinase activity, whilst 11, including the same 5, showed an increase in serum creatine kinase.


Vascular burden and genetic risk in association with cognitive performance and dementia in a population-based study.
Vascular risk factors may influence cognitive function and thus represent possible targets for preventive approaches against dementia. Yet it remains unknown, if they associate with cognition independently of the individual genetic risk for dementia. In a population-based study of 1172 community-dwelling individuals aged ≥65 years in Greece, we constructed a vascular burden score (VBS; based on presence of hypertension, diabetes, hyperlipidemia, heart disease, and cerebrovascular disease, range 0-5) and a polygenic risk score (PRS) for clinically-diagnosed Alzheimer's disease (AD) based on 23 genetic variants. We then explored in joint models the associations of the PRS for AD and VBS with global cognitive performance, cognitive performance across multiple cognitive domains, and odds of dementia. The mean age of study participants was 73.9 ± 5.2 years (57.1% females). Both the PRS for AD and VBS were associated with worse global cognitive performance (beta per-SD-increment in PRS: -0.06, 95%CI: -0.10 to -0.02, beta per-point-increment in VBS: -0.05, 95%CI: -0.09 to -0.02), worse performance across individual cognitive domains (memory, executive function, attention, language, visuospatial ability), and higher odds of dementia (OR per-SD increment in PRS: 1.56, 95%CI: 1.17-2.09, OR per-point increment in VBS: 1.38, 95%CI: 1.05-1.81). There was no evidence of an interaction between the two scores. Higher VBS was associated with worse cognitive performance equally across tertiles of the PRS for AD, even among individuals at the highest tertile. Both genetic risk and vascular burden are independently and additively associated with worse cognitive performance and higher odds of dementia.


A novel application of pulmonary transit time to differentiate between benign and malignant pulmonary nodules using myocardial contrast echocardiography.
Malignant pulmonary nodules (PNs) are often accompanied by vascular dilatation and structural abnormalities. Pulmonary transit time (PTT) measurement by contrast echocardiograghy has used to assess the cardiopulmonary function and pulmonary vascular status, such as hepatopulmonary syndrome and pulmonary arteriovenous fistula, but has not yet been attempted in the diagnosis and differential diagnosis of PNs. The aim of this work was to evaluate the feasibility and performance of myocardial contrast echocardiography (MCE) for differentiating malignant PNs from benign ones. The study population consisted of 201 participant: 66 healthy participants, 65 patients with benign PNs and 70 patients with malignant PNs. Their clinical and conventional echocardiographic characteristics were collected. MCE with measurements of PTT were performed. There was no difference in age, sex, heart rate, blood pressure, smoking rate, background lung disease, pulmonary function, ECG, myocardial enzymes, cardiac size and function among the healthy participant, patients with benign and malignant PNs (P > 0.05). PTT did not differ significantly in patients with PNs of different sizes, nor did they differ in patients with PNs of different enhancement patterns (P > 0.05). However, the PTT were far shorter (about one half) in patients with malignant PNs than in patients with benign ones (1.88 ± 0.37 vs. 3.73 ± 0.35, P < 0.001). There was no significantly different between patients with benign PNs and healthy participant (3.73 ± 0.35 vs.3.89 ± 0.36, P > 0.05). The area under the receiver operating characteristics curve (AUC) of PTT was 0.99(0.978-1.009) in discriminating between benign and malignant PNs. The optimal cutoff value was 2.78 s, with a sensitivity of 98.52%, a specificity of 97.34%, and a accuracy of 97.69%. MCE had a powerful performance in differentiating between benign and malignant PNs, and a pulmonary circulation time of < 2.78 s indicated malignant PNs.


Environmental and modifiable risk factors in renal cell carcinoma.
Prevention of disease requires a firm understanding of the relevant environmental and modifiable risk factors. We present a comprehensive review of these factors in renal cell carcinoma. A literature search of the PubMed database was performed to identify clinical studies examining the relationship between environmental and modifiable factors in the development of renal cell carcinoma (terms utilized: kidney cancer; renal cell carcinoma; risk factors; environment; obesity; hypertension; trichloroethylene). An emphasis was placed on more recent studies. Case control and large cohort studies have examined the relationship of numerous environmental and modifiable factors and the risk of renal cell carcinoma. Of particular note are dose-dependent increases in smokers, the obese, and hypertensive patients. Environmental and modifiable risk factors contribute significantly to the risk of sporadic renal cell carcinoma. Emphasis should be placed on smoking cessation and hypertension control. Emerging evidence would suggest that dietary intake and quality impact renal cell carcinoma risk.


COMPARISON OF THREE SHORT-TERM IMMOBILIZATION REGIMES IN WILD VERREAUX'S SIFAKAS (PROPITHECUS VERREAUXI): KETAMINE-XYLAZINE, KETAMINE-XYLAZINE-ATROPINE, AND TILETAMINE-ZOLAZEPAM.
Although research on lemurid primates in Madagascar has been ongoing for several decades, reports on different drug regimes to immobilize wild lemurs are limited. This study compares the efficacy, reliability, and side effects of ketamine-xylazine, ketamine-xylazine-atropine, and tiletamine-zolazepam immobilization in wild Verreaux's sifakas (Propithecus verreauxi). In the course of a long-term study in Kirindy Forest, western Madagascar, eight animals each received a mixture of ketamine (5.32±1.71 mg/kg) and xylazine (0.56±0.19 mg/kg) (KX; 7 males, 1 female) and ketamine (6.58±1.36 mg/kg), xylazine (1.28±0.28 mg/kg), and atropine (0.013±0.003 mg/kg) (KXA; 5 males, 3 females), respectively, and 14 individuals received tiletamine-zolazepam (7.73±1.37 mg/kg) (TZ; 9 males, 5 females). Induction was smooth in all protocols, but showed considerable variation in duration when animals had received KXA. Immobilization as well as recovery lasted significantly longer with TZ than with KX (P<0.05). Occurrence of side effects was not significantly different between the protocols; however, excessive salivation, involuntary muscular contractions, and vocalization only occurred in animals immobilized with TZ. Heart rate measurement at 10 min after onset of complete immobilization yielded significantly higher values if the animals had been immobilized with TZ compared to KX (P<0.05). Heart rate decreased from the first to the second measurement for the KX- and KXA-immobilized animals, whereas immobilization with TZ resulted in an increase in heart rate. The results suggest that KX produces good, but short, immobilization in Verreaux's sifakas at approximately 5 mg/kg ketamine and 0.5 mg/kg xylazine and a smoother and shorter recovery phase than 5 to 10 mg/kg TZ, whereas adding atropine to KX did not provide any benefits.


Catheter ablation for atrial fibrillation results in greater improvement in cardiac function in patients with low versus normal left ventricular ejection fraction.
It is still unknown whether left ventricular ejection fraction (LVEF) might affect the magnitude of improvement after atrial fibrillation (AF) ablation on cardiac function in persistent or longstanding persistent AF (CAF) patients. We performed echocardiography in 35 patients with CAF before and after catheter ablation (CA). Patients were stratified by LVEF into two groups prior to CA-normal LVEF (≥50 % LVEF, N group, n = 24) and a low LVEF group (<50 % LVEF, L group, n = 11). Patients were followed at 1 month, 3 months, 6 months, 1 year, and 2 years after ablation. After 15.8 ± 7.4 months follow-up, the L group showed greater improvement in LVEF and left atrial ejection fraction (LAEF; N group vs L group: LVEF difference (%), 5 ±8 vs 20± 13, p < 0.01; LAEF difference (%), 11 ± 12 vs 21 ± 10, p < 0.05). LA maximal volume and E/e' showed the same tendency after ablation, although the extent of improvement was not statistically significant. Both groups showed almost the same time course of improvement up to 2 years, although the L group showed earlier recovery in LVEF. The greater improvement in several cardiac functions was seen in patients with greater LV dysfunction, after the CA for CAF.


Participation in a Longitudinal Seminar Series Increases Medical Student Engagement with the COVID-19 Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic required a multifaceted response by healthcare professionals. Medical students played only a limited role in the early response, resulting in feelings of disengagement. The authors developed a discussion-based elective course reviewing the COVID-19 response to address this gap in medical student education. Preclinical medical students enrolled in this elective participated in weekly virtual interactive seminars led by expert faculty members. Students completed a final survey quantifying their understanding of the overall COVID-19 response, knowledge of its individual facets, and their feelings of personal engagement on a Likert scale from 1 to 5, with 5 representing the most understanding or engagement. The differences in mean scores on "precourse" and "postcourse" surveys were compared. A total of 65 students enrolled in the elective. Students demonstrated significant improvement in perceived holistic understanding of the response of the medical field to the COVID-19 pandemic (P < 0.001) and in feelings of personal engagement with the pandemic (P < 0.001). In addition, students reported a significantly increased understanding of each facet of the pandemic response covered in the course (8 questions; all P < 0.001). Preclinical medical student participation in a discussion-based seminar course reviewing the COVID-19 pandemic significantly increased feelings of engagement with and understanding of the response of the medical field to the pandemic.


On the use of statistics for representing the knowledge acquired from experts in a medical consulting system.
For making medical consulting systems, it is important and significant to select and devise the method for representing the knowledge acquired from professional experts. As quantities of data required for consultation are increasing according to the progress of medical science, we have to introduce some new kinds of statistics into a medical consultation system. From another point of view, since the process of diagnosis of experts is considered to be a kind of effective model for compressing (or condensing) data quantitatively and qualitatively, we discuss the use of statistics for representing the knowledge acquired from experts from the standpoint of data compression.


The interactive effect of pre-pregnancy overweight and obesity and hypertensive disorders of pregnancy on the weight status in infancy.
We aimed to assess whether hypertensive disorders of pregnancy (HDP) could modify the effect of pre-pregnancy overweight or obesity (OWO) on the risk of offspring high body mass index (BMI) in infancy. A total of 3,765 mother-child pairs were recruited from two Chinese birth cohorts. BMI ≥ 85th percentile, based on World Health Organization criteria, was defined as a high BMI for the risk of developing severe obesity in later life. Logistic regression analysis was used to assess the combined effects and multiplicative interactions of pre-pregnancy OWO + HDP on offspring high BMI. Relative excess risk due to interaction (RERI) or attributable proportion (AP) was used to estimate additive interactions. RERI > 0 or AP > 0 indicates a significant additive interaction. Compared with the non-OWO and normal blood pressure group, the combination of OWO + HDP was positively associated with offspring high BMI at 12 months of age [OR 3.10 (95%CI 1.59, 6.04)], with 51% of the effects attributed to an additive interaction [AP 0.51 (95%CI 0.13, 0.89)]. An interactive effect was found between the pre-pregnancy OWO + HDP and offspring high BMI in infancy. Interventions to control pre-pregnancy OWO and HDP are important to prevent obesity and associated adverse outcomes in offspring.


In vivo genotoxicity of nitrates and nitrites in germ cells of male mice. II. Unscheduled DNA synthesis and sperm abnormality after treatment of spermatids.
Effects of both sodium nitrate (doses of 600 and 1200 mg/kg/day for 3 days) and sodium nitrite (doses of 60 and 120 mg/kg/day for 3 days) on spermatids of mice were investigated by measuring unscheduled DNA synthesis (UDS) 17 days after the end of treatment, and sperm-head abnormality 11 and 17 days after the end of treatment. Neither chemical induced the UDS response in early to mid spermatids (17 days). The only positive result in the sperm-head abnormality test was obtained for the dose of 120 mg/kg/day of sodium nitrite both at 11 and 17 days after treatment. The results presented are in accordance with those of our earlier experiments with the same chemicals, suggesting their nonmutagenic action on the tested germ-cell stages of male mice.


Hypertriglyceridemia and waist circumference predict cardiovascular risk among HIV patients: a cross-sectional study.
Although half of HIV-infected patients develop lipodystrophy and metabolic complications, there exists no simple clinical screening tool to discern the high from the low-risk HIV-infected patient. Thus, we evaluated the associations between waist circumference (WC) combined with triglyceride (TG) levels and the severity of lipodystrophy and cardiovascular risk among HIV-infected men and women. 1481 HIV-infected men and 841 HIV-infected women were recruited between 2005 and 2009 at the metabolic clinic of the University of Modena and Reggio Emilia in Italy. Within each gender, patients were categorized into 4 groups according to WC and TG levels. Total and regional fat and fat-free mass were assessed by duel-energy x-ray absorptiometry, and visceral adipose tissue (VAT) and abdominal subcutaneous AT (SAT) were quantified by computed tomography. Various cardiovascular risk factors were assessed in clinic after an overnight fast. The high TG/high WC men had the most VAT (208.0 ± 94.4 cm(2)), as well as the highest prevalence of metabolic syndrome (42.2%) and type-2 diabetes (16.2%), and the highest Framingham risk score (10.3 ± 6.5) in comparison to other groups (p<0.05 for all). High TG/high WC women also had elevated VAT (150.0 ± 97.9 cm(2)) and a higher prevalence of metabolic syndrome (53.3%), hypertension (30.5%) and type-2 diabetes (12.0%), and Framingham risk score(2.9 ± 2.8) by comparison to low TG/low WC women (p<0.05 for all). A simple tool combining WC and TG levels can discriminate high- from low-risk HIV-infected patients.


Immunoprophylaxis of experimental Mycoplasma pneumoniae disease: effect of aerosol particle size and site of deposition of M. pneumoniae on the pattern of respiratory infection, disease, and immunity in hamsters.
The distribution of Mycoplasma pneumoniae infection in the respiratory tract and the extent of pulmonary pathology were determined by the site of deposition and the number of organisms administered to hamsters. Infection of the upper and lower areas of the respiratory tract occurred when organisms were introduced into both areas by small-particle aerosol (2.3 micrometer) or by intranasal (i.n.) instillation of a 200-microliter inoculum. In contrast, when organisms were delivered primarily to the upper respiratory tract by large-particle aerosol (8 micrometer) or by i.n. instillation of a small volume of inoculum (2 or 20 microliter), infection remained limited to this area in most or all instances. When the lungs became infected after i.n. administration of a 200-microliter inoculum, the most extensive pulmonary lesions were seen in the animals given the largest number of organisms. Each of the modes of administration of M. pneumoniae initiated an infection which conferred measurable resistance to a subsequent challenge capable of inducing extensive pulmonary disease. The most effective resistance was induced by the two modes of administration which produced an infection involving the entire respiratory tract, i.e., small-particle aerosol or i.n. instillation of a 200-microliter inoculum.


Assessment of ST2 and Reg3a levels in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Graft-versus-host disease (GVHD) is a crucial complication leading to significant morbidity and mortality allogeneic hematopoietic stem cell transplantation which occurs in approximately half of the transplant recipients. Suppression of tumorigenicity 2 (ST2) and regenerating islet-derived 3-alpha(Reg3a) might be important biomarkers to predict acute GVHD. In the present study, blood samples were collected from 17 patients with acute GVHD and 12 control patients after allogeneic stem cell transplantation. ST2 and Reg3a were measured in plasma samples compared in patients with acute GVHD and the controls. Median age of the study population was 42 years (range 19–49). When compared to controls, the mean ST2 levels was significant higher in acute GVHD (9794 ng/dL vs. 2646 ng/dL, P = 0.008). Mean Reg3a level did not show significant difference between control and acute GVHD group (8848 ng/dL vs. 5632 ng/dL, respectively, P = 0.190). The ST2 level might be used as a significant biomarker for predicting acute GVHD.


Prevalence of erythromycin-resistant emm92-type invasive group A streptococcal infections among injection drug users in West Virginia, United States, 2021-23.
Increasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and the USA over the past several years. Coupled with this are observations of higher rates of resistance to erythromycin and clindamycin. To characterize iGAS and pharyngitis isolates from West Virginia (WV), a US state outside of the national Active Bacteria Core surveillance purview, where risk factors associated with iGAS infections are prevalent. Seventy-seven invasive group A Streptococcus isolates were collected from 67 unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021 to 2023. Invasive isolates and 20 unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibility in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm subtype and detection of MLSB resistance determinants. Twenty-six (39%) isolates were of a single emm92 type. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported IV drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, 51 (76%) of the 67 iGAS isolates were determined to carry MLSB resistance. Isolates of emm92 type (clonal subtype emm92.0) were associated with iGAS infections in adult IV drug users, but not with paediatric pharyngitis, and were uniformly resistant to erythromycin and clindamycin.


Screening of the SOD1, FUS, TARDBP, ANG, and OPTN mutations in Korean patients with familial and sporadic ALS.
About 5% of amyotrophic lateral sclerosis (ALS) cases are known to be familial (fALS) and mutations in SOD1 and other genes are found in more than 20% of fALS patients and in 2%-4% of apparently sporadic ALS (sALS) cases. However, there are few reports on the proportion of fALS and the frequency of mutations in Korean patients with ALS. We screened mutations in the SOD1, FUS, TARDBP, ANG, and OPTN genes in 258 consecutively enrolled Korean patients with ALS from October 2006 to November 2010. The frequency of fALS was estimated to be 3.5% (9/258), and mutations were identified in 88.9% (8/9) of fALS patients but only in 2.8% (7/249) of sALS patients. Seven fALS and 3 sALS patients had mutations in SOD1 gene while all the others had FUS gene. The proportion of fALS was lower than that reported in Caucasian populations but the frequency of SOD1 gene mutations in Korean fALS patients (77.8%, 7/9) was much higher than that reported in other ethnic groups. These findings might suggest that there is an ethnic difference in the proportion of fALS and the genetic background of ALS.


Synthesis and biological evaluation in vitro and in silico of N-propionyl-N'-benzeneacylhydrazone derivatives as cruzain inhibitors of Trypanosoma cruzi.
An N-acylhydrazone scaffold has been used to develop new drugs with diverse biological activities, including trypanocidal activity against different strains of Trypanosoma cruzi. However, their mechanism of action is not clear, although in T. cruzi it has been suggested that the enzyme cruzain is involved. The aim in this work was to obtain new N-propionyl-N'-benzeneacylhydrazone derivatives as potential anti-T. cruzi agents and elucidate their potential mechanism of action by a molecular docking analysis and effects on the expression of the cruzain gene. Compounds 9 and 12 were the most active agents against epimastigotes and compound 5 showed better activity than benznidazole in T. cruzi blood trypomastigotes. Additionally, compounds 9 and 12 significantly increase the expression of the cruzain gene. In summary, the in silico and in vitro data presented herein suggest that compound 9 is a cruzain inhibitor.


Expression of a murine B16 melanoma-associated antigen analyzed by flow cytometry.
Understanding factors regulating expression of tumor antigens is vital to the design of rational immunotherapeutic strategies. A murine monoclonal antibody (MM2-3C6) that recognizes a B16 murine melanoma-associated membrane antigen was used to study antigen expression in relation to cell cycle, clonal heterogeneity, and growth density. Dual-parameter flow cytometric measurements of DNA content and membrane antigen demonstrated that antigen-positive cells were found throughout the cell cycle. However, some antigen-negative cells were observed and were restricted to the G0/G1 phase demonstrating the antigenic heterogeneity of this tumor line. Three sublines of B16, F1, F10, and F1r with variable metastatic potential, and 50 B16 F1 clones all expressed the antigen with a mean antigen density above background of 8.84 +/- 2.52 [( mean cell fluorescence/cell size] X 10(-3] ranging from 3.68 to 16.57. Further studies of three sublines and five clones showed antigen density fluctuated over an 8-day growth period in culture with daily changes of medium. During log growth from Day 1 (1.2 +/- 0.08 X 10(4) cells/cm2) to Day 4 (20.4 +/- 3.01 X 10(4) cells/cm2), antigen density increased from 4.09 +/- 0.29 to 6.86 +/- 0.29. By Day 8 (26.5 +/- 2.86 X 10(4) cells/cm2) when the cells had been confluent for 3 days, antigen density decreased to 2.54 +/- 0.26 which was significantly lower than other days measured (P less than 0.05). It is concluded that tumor cell proliferation and cell density can modulate antigen expression in this system and, therefore, this may be a useful model to study tumor cell escape from immunotherapy.