A rare homozygous missense GDF2 (BMP9) mutation causing PAH in siblings: Does BMP10 status contribute?
Pulmonary arterial hypertension (PAH) is a disease characterized by pathological remodeling of the pulmonary vasculature causing elevated pulmonary artery pressures and ultimately, right ventricular failure from chronic pressure overload. Heterozygous pathogenic GDF2 (encoding bone morphogenetic protein 9 (BMP9)) variants account for some (>1%) adult PAH cases. Only three pediatric PAH cases, harboring homozygous or compound heterozygous variants, are reported to date. Ultra-rare pathogenic GDF2 variants are reported in hereditary hemorrhagic telangiectasia and overlapping disorders characterized by telangiectasias and arteriovenous malformations (AVMs). Here, we present two siblings with PAH homozygous for a GDF2 mutation that impairs BMP9 proprotein processing and reduces growth factor domain availability. We confirm an absence of measurable plasma BMP9 whereas BMP10 levels are detectable and serum-dependent endothelial BMP activity is evident. This contrasts with the absence of activity which we reported in two children with homozygous pathogenic GDF2 nonsense variants, one with PAH and one with pulmonary AVMs, both with telangiectasias, suggesting loss of BMP10 and endothelial BMP activity in the latter may precipitate telangiectasia development. An absence of phenotype in related heterozygous GDF2 variant carriers suggests incomplete penetrance in PAH and AVM-related diseases, indicating that additional somatic and/or genetic modifiers may be necessary for disease precipitation.


Vitamin E As a Potential Interventional Treatment for Metabolic Syndrome: Evidence from Animal and Human Studies.
A constellation of medical conditions inclusive of central obesity, hyperglycemia, hypertension, and dyslipidemia is known as metabolic syndrome (MetS). The safest option in curtailing the progression of MetS is through maintaining a healthy lifestyle, which by itself, is a long-term commitment entailing much determination. A combination of pharmacological and non-pharmacological approach, as well as lifestyle modification is a more holistic alternative in the management of MetS. Vitamin E has been revealed to possess anti-oxidative, anti-inflammatory, anti-obesity, anti-hyperglycemic, anti-hypertensive and anti-hypercholesterolemic properties. The pathways regulated by vitamin E are critical in the development of MetS and its components. Therefore, we postulate that vitamin E may exert some health benefits on MetS patients. This review intends to summarize the evidence in animal and human studies on the effects of vitamin E and articulate the contrasting potential of tocopherol (TF) and tocotrienol (T3) in preventing the medical conditions associated with MetS. As a conclusion, this review suggests that vitamin E may be a promising agent for attenuating MetS.


The t-PA-encapsulated PLGA nanoparticles shelled with CS or CS-GRGD alter both permeation through and dissolving patterns of blood clots compared with t-PA solution: an in vitro thrombolysis study.
Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 mum, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 mum. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis.


Labeling of participants in high blood pressure screening programs. Implications for blood cholesterol screenings.
Screening programs have expanded to identify the many persons who are unaware of their high blood cholesterol level and thus are at an increased risk for coronary heart disease. These programs bring both potential benefits and potential risks to the participant. One potential risk is that of iatrogenic effects of learning one's risk status, often referred to as the "labeling phenomenon." Research that has addressed the labeling phenomenon in blood pressure screening programs has important implications for blood cholesterol screenings. Detrimental effects on screening participants are possible, but they can be attenuated by careful attention to characteristics of the debriefing and counseling that should be included in screening protocols.


Rearrangement products of 3-methanesulfonyl-N-methyl-N-nitroaniline.
Two isomeric products (C(8)H(10)N(2)O(4)S) of the rearrangement of 3-methanesulfonyl-N-methyl-N-nitroaniline have been investigated, viz. 3-methanesulfonyl-N-methyl-2-nitroaniline, which was the main product of the rearrangement, and 5-methanesulfonyl-N-methyl-2-nitroaniline. In both molecules, the aromatic rings are appreciably deformed towards ortho-quinonoidal geometry by electronic and steric interactions. The crystal structure is stabilized, in both cases, by weak C-H.O hydrogen bonds.


Prevalence Comparison of Past-year Mental Disorders and Suicidal Behaviours in the Canadian Armed Forces and the Canadian General Population.
Military personnel in Canada and elsewhere have been found to have higher rates of certain mental disorders relative to their corresponding general populations. However, published Canadian data have only adjusted for age and sex differences between the populations. Additional differences in the sociodemographic composition, labour force characteristics, and childhood trauma exposure in the populations could be driving these prevalence differences. Our objective is to compare the prevalence of past-year mental disorders and suicidal behaviours in the Canadian Armed Forces Regular Force with the rates in a representative, matched sample of Canadians in the general population (CGP). Data sources were the 2013 Canadian Forces Mental Health Survey and the 2012 Canadian Community Health Survey-Mental Health. CGP sample was restricted to match the age range, employment status, and history of chronic conditions of Regular Force personnel. An iterative proportional fitting method was used to approximate the marginal distribution of sociodemographic and childhood trauma variables in both samples. Relative to the matched CGP, Regular Force personnel had significantly higher rates of past-year major depressive episode, generalized anxiety disorder, and suicide ideation. However, lower rates of alcohol use disorder were seen in Regular Force personnel relative to the matched CGP sample. Factors other than differences in sociodemographic composition and history of childhood trauma account for the excess burden of mental disorders and suicidal behaviours in the Canadian Armed Forces. Explanations to explore in future research include occupational trauma, selection effects, and differences in the context of administration of the 2 surveys.


Dedifferentiated chondrosarcoma: Radiological features, prognostic factors and survival statistics in 23 patients.
Dedifferentiated chondrosarcoma is a rare, highly malignant tumor with a poor survival. There are many confusing issues concerning the imaging feature that can facilitate early diagnosis and the factors that might be related to outcomes. Twenty-three patients with dedifferentiated chondrosarcoma confirmed by pathology were retrospectively reviewed from 2008 to 2015. The patients' clinical information, images from radiographs (n = 17), CT (n = 19), and MRI (n = 17), histological features, treatment and prognosis were analyzed. There were 12 males and 11 females, and the mean age was 50.39 years old. Fourteen cases affected the axial bone (pelvis, spine), and 9 cases involved the appendicular bone. Seven (41.17%), 9 (47.36), and 12 (66.66%) lesions showed a biphasic nature on radiograph, CT and MRI, respectively. Of the lesions, 17.39% (4/23) were accompanied by pathological fractures. Histologically, the cartilage component was considered histological Grade1 in 12 patients and Grade 2 in 11 patients. The dedifferentiated component showed features of osteosarcoma in 8 cases, malignant fibrous histiocytoma in3 cases, myofibroblastic sarcoma in 1 case and spindle cell sarcoma in 11cases. Twenty-two cases were treated with surgical resection, and 17 cases achieved adequate (wide or radical) surgical margin. In 8 cases, surgery was combined with adjuvant chemotherapy. The overall median survival time was nine months; 17.4% of patients survived to five years. Axial bone location, lung metastasis at diagnosis, inadequate surgical margin, incorrect diagnosis before surgery and pathological fractures was related to poorer outcome. Pre- or postoperative chemotherapy had no definitively effect on improved survival.


Electrical stimulation increases phosphorylation of tyrosine hydroxylase in superior cervical ganglion of rat.
Electrical stimulation of the superior cervical ganglion of the rat increased the phosphorylation of tyrosine hydroxylase (tyrosine 3-monooxygenase, EC 22.214.171.124) in this tissue. Ganglia were incubated with [32P]Pi for 90 min and were then electrically stimulated via the preganglionic nerve. Tyrosine hydroxylase was isolated from homogenates of the ganglia by immunoprecipitation followed by polyacrylamide gel electrophoresis. 32P-labeled tyrosine hydroxylase was visualized by radioautography, and the incorporation of 32P into the enzyme was quantitated by densitometry of the radioautograms. Stimulation of ganglia at 20 Hz for 5 min increased the incorporation of 32P into tyrosine hydroxylase to a level 5-fold that found in unstimulated control ganglia. The increase in phosphorylation of tyrosine hydroxylase was dependent on the duration and frequency of stimulation. Preganglionic stimulation did not increase the phosphorylation of tyrosine hydroxylase in a medium that contained low Ca2+ and high Mg2+. Increases in phosphorylation were reversible; within 30 min after the cessation of stimulation, the incorporation of 32P into tyrosine hydroxylase decreased to the level found in unstimulated ganglia. The nicotinic antagonist hexamethonium reduced the increase in 32P incorporation into tyrosine hydroxylase by about 50%, while the muscarinic antagonist atropine had no effect. Thus, preganglionic stimulation appeared to increase the phosphorylation of tyrosine hydroxylase in part by a nicotinic mechanism and in part by a noncholinergic mechanism. Antidromic stimulation of ganglia also increased the phosphorylation of tyrosine hydroxylase. Two-dimensional gel electrophoresis revealed that electrical stimulation also increased the incorporation of 32P into at least six other phosphoproteins in the ganglion.


A Low-Cost Micro-Volume Nephelometric System for Quantitative Immunoagglutination Assays.
Immunoassays have been widely used in scientific research and clinical diagnosis due to their versatile detection capability and high specificity. Immunoagglutination assays are kinds of immunoassay, which can simply and rapidly measure the concentration of analytes. In this work, we developed a low-cost micro-volume nephelometric system for quantitative immunoagglutination assays. We used off-the-shelf components to build the system, and the total cost of key components is only about 20 US dollars. The total detection volume in our system was as low as 3 µL, which could significantly reduce the reagent cost and required sample volume. We further evaluated the system performance via the immunoagglutination assay to measure the concentration of C-reactive protein, a plasma protein with levels rising in response to inflammation. The results demonstrated that our system could measure the concentration of analytes with relatively high sensitivity and precision within four minutes, and has high potential to be applied for clinical diagnostic tests.


Types of Family Caregiving and Daily Experiences in Midlife and Late Adulthood: The Moderating Influences of Marital Status and Age.
Guided by the life-course perspective, this study contributes to the family caregiving, aging, and disability literature by examining the daily experiences of three types of family caregivers in midlife and late adulthood. A sample of 162 caregivers from the National Survey of Midlife in the United States study completed interviews, questionnaires, and a Daily Diary Study. Multilevel models showed the patterns of daily time use did not differ by caregiver types. Caregivers of sons/daughters with developmental disabilities (DD) experienced more daily stressors than caregivers of parents with health conditions (HC) and caregivers of spouses with HC. Unmarried caregivers of sons/daughters with DD reported spending more time on daily leisure activities and exhibited greater daily stressor exposure than other family caregivers. Age did not moderate the associations between caregiver types and daily experiences. Findings highlight the important consideration of the caregivers' characteristics to better determine the quality of their daily experiences in midlife and late adulthood.


[Classification of skin injuries inflicted by the teeth of the carnivorous animals].
The current approaches to the classification of skin injuries inflicted by the teeth of the carnivores on the human body are discussed. The new morphological classification is proposed taking into consideration the current views of the mechanisms underlying the formation of tooth marks on the integumental tissues of the victims of attacks by carnivorous animals. Morphological characteristics of skin injuries are briefly described in the framework of the new classification.


Axial Tooth Contour Alteration Following Fixed Prosthodontic Treatment.
This study evaluated the effect of crown restoration on the tooth labial axial contour. The pre-treatment and post-treatment models of 13 patients who underwent complex fixed prosthodontic treatment were obtained. All the models were converted to virtual models. Each post-treatment model was overlapped on the corresponding pre-treatment model to evaluate the contour alteration of the clinical crown. The contour of the crowned teeth significantly increased following the crown restoration treatment. The increase of the contour was directly proportional to the distance from the gingival margin. The anterior teeth had a significantly greater contour increase than the posterior teeth.


Analysis of the structure and variability of nucleolar organizer regions of Salmo trutta by C-, Ag-, and restriction endonuclease banding.
Nucleolar organizer regions (NORs) of brown trout were investigated using C-, Ag-, and restriction endonuclease banding. The presence of constitutive heterochromatin was confirmed by C-banding. Giemsa-staining, C-banding, and Ag-banding revealed great variability in the size of the short arm of the NOR-bearing chromosome. This size variation was due in some cases to NOR duplication. Restriction endonuclease digestion induced a specific banding pattern for AluI, DdeI, HaeIII, MboI, and HinfI, indicating some features about the sequence composition of the NOR-associated heterochromatin.


A naturally occurring α(s1)-casein-derived peptide in bovine milk inhibits apoptosis of granulosa cells induced by serum-free conditions.
Several naturally occurring peptides in bovine milk were characterized by tandem mass spectrometry and Edman degradation. Chromatograms of peptide fractions (passed through an ultra-filtration membrane, nominal molecular weight limit 3000) prepared from colostrum (collected immediately after parturition) and transitional milk (collected 5 days postpartum) showed that they were almost identical. In total, six peptides, α(s1)-CN (f16-23) (RPKHPIKH), α(s1)-CN (f16-24) (RPKHPIKHQ), α(s1)-CN (f17-25) (PKHPIKHQG), α(s1)-CN (f46-52) (VFGKEKV), α(s1)-CN (f94-105) (HIQKEDVPSER), and β-CN (f121-128) (HKEMPFPK), were identified. One of the major peptides, the N-terminal fragment of αs1 -casein, varied structurally during early lactation: α(s1)-CN (f17-25) (PKHPIKHQG) and α(s1)-CN (f16-23) (RPKHPIKH)/α(s1)-CN (f16-24) (RPKHPIKHQ) were found in colostrum and transitional milk, respectively. A chemically synthesized peptide, α(s1)-CN (f16-23) (RPKHPIKH), inhibited apoptosis of bovine granulosa cells induced by serum-free conditions in a dose-dependent manner, in consequence of caspase-3 and caspase-9 suppressions. The physiological function of the peptide remains unclear, but it may have potential use as pharmaceutical agent and as an anti-apoptotic agent in cell culture medium.


Concomitant reduction of disease activity and IL-10 secreting peripheral blood mononuclear cells during immunoadsorption in patients with active systenic lupus erythematosus.
In patients with systemic lupus erythematosus (SLE) increased secretion of interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMC) is associated with overproduction of pathogenic autoantibodies. Herein we report the effect of immunoadsorption (IA) on the number of IL-10 secreting PBMC in patients with active SLE. Three courses of IA were performed in 9 patients with active SLE (SLAM 15,9+/-2,9). Each course consisted of 3 treatments on consecutive days. ELISPOT assay using IL-10 specific monoclonal antibodies was used to determine the number of IL- 10 secreting PBMC before and after each treatment. Eleven healthy, age and sex matched volunteers served as controls. Anti-ds-DNA autoantibodies were reduced to 67+/-14% after the treatment period. Before therapy patients showed significantly more spontaneously IL-10 secreting PBMC than controls (p<0.01). After the first course a significant reduction of the IL-10 secreting cells to normal levels was observed which paralleled the development of disease activity (p<0.01). Our results demonstrate a concomitant reduction of disease activity, anti-ds-DNA antibodies and the number of IL-10 secreting PBMC. The production of anti-ds-DNA antibodies and IL-10 are interdependent. Thus we conclude that IA is beneficial in SLE by depletion of these pathogenic antibodies which may lead to a reduced IL-10 secretion in vivo.


Factorials of real negative and imaginary numbers - A new perspective.
Presently, factorials of real negative numbers and imaginary numbers, except for zero and negative integers are interpolated using the Euler's gamma function. In the present paper, the concept of factorials has been generalised as applicable to real and imaginary numbers, and multifactorials. New functions based on Euler's factorial function have been proposed for the factorials of real negative and imaginary numbers. As per the present concept, the factorials of real negative numbers, are complex numbers. The factorials of real negative integers have their imaginary part equal to zero, thus are real numbers. Similarly, the factorials of imaginary numbers are complex numbers. The moduli of the complex factorials of real negative numbers, and imaginary numbers are equal to their respective real positive number factorials. Fractional factorials and multifactorials have been defined in a new perspective. The proposed concept has also been extended to Euler's gamma function for real negative numbers and imaginary numbers, and beta function.


Urinary metabolites of organophosphate flame retardants: temporal variability and correlations with house dust concentrations.
A reduction in the use of polybrominated diphenyl ethers (PBDEs) because of human health concerns may result in an increased use of and human exposure to organophosphate flame retardants (OPFRs). Human exposure and health studies of OPFRs are lacking. We sought to define the degree of temporal variability in urinary OPFR metabolites in order to inform epidemiologic study design, and to explore a potential primary source of exposure by examining the relationship between OPFRs in house dust and their metabolites in urine. Nine repeated urine samples were collected from 7 men over the course of 3 months and analyzed for bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP), metabolites of the OPFRs tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP), respectively. Intraclass correlation coefficients (ICCs) were calculated to characterize temporal reliability. Paired house dust and urine samples were collected from 45 men. BDCPP was detected in 91% of urine samples, and DPP in 96%. Urinary BDCPP showed moderate-to-strong temporal reliability (ICC range, 0.55-0.72). ICCs for DPP were lower, but moderately reliable (range, 0.35-0.51). There was a weak [Spearman r (r(S)) = 0.31] but significant (p = 0.03) correlation between urinary BDCPP and TDCPP concentrations in house dust that strengthened when nondetects (r(S) = 0.47) were excluded. There was no correlation between uncorrected DPP and TPP measured in house dust (r(S) < 0.1). Household dust may be an important source of exposure to TDCPP but not TPP. Urinary concentrations of BDCPP and DPP were moderately to highly reliable within individuals over 3 months.


[Morphometric study of the thyroid gland].
The article surveys the most important morphometric methods used for investigating the thyroid gland. Applicability of various histophysiological criteria for evaluation of the functional state of the organ and investigation of changes in its individual structural components in physiological and pathological processes is discussed. The connection between various quantitative indices and the most rational morphometric techniques based on the methods of planimetry and stereology are considered.


The institutional context of multicultural education: what is your institutional curriculum?
Recently revised accreditation standards require medical schools and residency training programs to integrate multicultural training into their curricula. Most multicultural training models concern the educational outcomes of individual trainees who have received digestible "units" of multicultural education or "cultural competence" training designed for trainees' individual consumption. Few have taken a critical perspective on how an individual trainee must learn, change his or her behavior, and sustain that behavioral change within a specific institutional context. The authors discuss the educational impact of one's institutional learning environment--the institution's ethos, teachers, modeling, policies, and processes--on the multicultural education of physician trainees. A usable conceptual model is offered with which educators can identify those dimensions of one's "institutional curriculum" that may enhance or obstruct trainees' optimal learning and behavior change regarding issues of multiculturalism in medicine. Comparisons are drawn to the recent medical literature concerning professionalism education and the hidden curriculum. Distinctions are drawn between overlapping areas of planned, received, intended, and unintended learning and values, as communicated from faculty, attendings, and residents to students. Ways of maximizing ideal learning and minimizing unintended consequences are discussed. The goal is for medical educators to be able to ask, What is the institutional curriculum of my training program regarding issues of race, difference, etc? What elements of that institutional curriculum can be recaptured and reclaimed as consistent with and supportive of tenets of excellent patient care for all?


An Old Disease Comes Back: Reporting 2 Cases of Neonatal Measles.
We report two cases of neonatal measles (one congenital and one post natal infection) admitted to our neonatal intensive care unit and discuss the management. This report intend to keep alert against measles and point out the risk for susceptible pregnant women and their offspring in countries with reduction of coverage from anti measles vaccine.


The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli.
Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic.


Cement fixation and screw retention: parameters of passive fit. An in vitro study of three-unit implant-supported fixed partial dentures.
It is generally assumed that passively fitting superstructures are a prerequisite for long-lasting implant success. In the study presented, the strain development of three-unit implant fixed partial dentures (FPDs) was evaluated at the bone surrounding the implant and on the superstructure using a strain gauge technique. Six groups of three-unit FPDs representing the commonly used techniques of bridge fabrication were investigated with 10 samples each, in order to quantify the influence of impression technique, mode of fabrication and retention mechanism on superstructure fit. Two ITI implants (Straumann, Waldenburg, Switzerland) were anchored in a measurement model according to a real-life patient situation and strain gauges were fixed mesially and distally adjacent to the implants and on the bridge pontics. The developing strains were recorded during cement setting and screw fixation. For statistical analysis, multivariate two sample tests were performed setting the level of significance at P=0.1. None of the investigated bridges revealed a truly passive fit without strains occurring. About 50% of the measured strains were found to be due to impression taking and model fabrication, whereas the remaining 50% were related to laboratory inaccuracies. The two impression techniques used did not reveal any significant differences in terms of precision. Both modes of fixation--i.e. cement and screw retention--provoked equally high stress levels. In the fabrication of screw-retained FPDs, similar results were obtained from the use of burn-out plastic copings and the technique of casting wax moulds to premachined components. Bonding bridge frames onto gold cylinders directly on the implants significantly reduces strain development.


Reference values for bone density and bone mineral content from 5 to 80 years old in a province of Chile.
The assessment of bone health throughout the life cycle is essential to determine fracture risk. The objectives of the work were (a) compare bone mineral density and content with international references from the United States, (b) determine maximum bone mass, (c) propose references for bone health measurements from ages 5 to 80 years old. Research was carried out on 5,416 subjects. Weight and height were measured. Body Mass Index (BMI) was calculated. The total body was scanned using dual energy X-ray absorptiometry (DXA). Information was extracted from the bone health measures (bone mineral density (BMD) and bone mineral content (BMC)) for both sexes, according to pediatric and adult software. Differences were identified between the mean values of Chilean and American men for BMD (~0.03 to 0.11 g/cm2) and BMC (~0.15 to 0.46 g). Chilean females showed average values for BMD similar to the US references (~-0.01 to 0.02 g/cm2). At the same time, they were relatively higher for BMC (~0.07 to 0.33 g). The cubic polynomial regression model reflected a relationship between BMD and BMC with chronological age in both sexes. For males, R2 was higher (R2 = 0.72 and 0.75) than for females (R2 = 0.59 and 0.66). The estimate of maximum bone mass (MBM) for males emerged at 30 years old (1.45 ± 0.18 g/cm2 of BMD and 3.57 ± 0.60 g of BMC) and for females at age 28 (1.22 ± 0.13 g/cm2 of BMD and 2.57 ± 0.44 g of BMC). The LMS technique was used to generate smoothed percentiles for BMD and BMC by age and sex. Results showed that maximum bone mass occurred in females at age 28 and in males at 30. Reference values obtained from this research may be used to evaluate bone health, diagnose bone fragility and osteoporosis in individuals and regional population groups.


Characterization of few mode fiber components and connected systems.
Methods for measurement of polarization dependent loss and cross talk of individual few mode fiber components and connected systems are presented. A new method for determining the cross talk of the individual components, from the measurements on the connected system is presented and verified through simulations and measurements. The method is based on Fourier analysis of the wavelength dependent interference of the loss of the system.


Integration of plant viruses in electron beam lithography nanostructures.
Tobacco mosaic virus (TMV) is the textbook example of a virus, and also of a self-assembling nanoscale structure. This tubular RNA/protein architecture has also found applications as biotemplate for the synthesis of nanomaterials such as wires, as tubes, or as nanoparticle assemblies. Although TMV is, being a biological structure, quite resilient to environmental conditions (temperature, chemicals), it cannot be processed in electron beam lithography (eBL) fabrication, which is the most important and most versatile method of nanoscale structuring. Here we present adjusted eBL-compatible processes that allow the incorporation of TMV in nanostructures made of positive and negative tone eBL resists. The key steps are covering TMV by polymer resists, which are only heated to 50 °C, and development (selective dissolution) in carefully selected organic solvents. We demonstrate the post-lithography biochemical functionality of TMV by selective immunocoating of the viral particles, and the use of immobilized TMV as direct immunosensor. Our modified eBL process should be applicable to incorporate a wide range of sensitive materials in nanofabrication schemes.


Differences in respiratory arousal threshold in Caucasian and Chinese patients with obstructive sleep apnoea.
Ethnic differences in obstructive sleep apnoea (OSA) phenotype may not be limited to obesity and craniofacial factors. The aims of the study were to (i) compare the proportion of Caucasians and Chinese patients with a low respiratory arousal threshold (ArTH) and (ii) explore the influence of anatomical compromise on ArTH. Interethnic comparison was conducted between cohorts of Caucasian and Chinese patients from specialist sleep disorder clinics. Polysomnography and craniofacial photography were performed. A low respiratory ArTH was determined by an ArTH score of 2 or above (one point for each: apnoea-hypopnoea index (AHI) < 30/h, nadir oxygen saturation (SaO2 ) > 82.5%, fractions of hypopnoeas > 58.3%). Anatomical compromise was stratified according to the photographic face width measurement. A total of 348 subjects (163 Caucasians and 185 Chinese) were analysed. There was a significantly lower proportion of Chinese patients with moderate-severe OSA (AHI ≥ 15) who had a low ArTH (28.4% vs 48.8%, P = 0.004). This difference remained significant among those with severe OSA (AHI ≥ 30) (2.6% vs 17.1%, P = 0.02). The proportion of moderate-severe OSA Caucasians with a low ArTH was significantly less in those with severe anatomical compromise (36.6% vs 61.0%, P = 0.03), whereas there was no difference in Chinese patients (25.5% vs 31.5%, P = 0.49). Compared to Caucasians with severe OSA, a low respiratory ArTh appears to be a less common pathophysiological mechanism in Chinese patients. Caucasians with less severe anatomical compromise exhibit evidence of a lower ArTh, an association which is absent in Chinese patients. Our data suggest that OSA mechanisms may vary across racial groups.


HLA antigen in Chinese patients with hepatocellular carcinomas.
One hundred and fourteen Chinese patients with hepatocellular carcinomas (HCC) were studied for alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), anti-HBsAg, and HLA markers. Younger patients with HCC (less than 60 yr old) were more significantly associated with elevated serum AFP (P less than 0.0001) and serum HBsAg (P less than 0.0001) than were older (greater than or equal to 60 yr old) patients. A strong correlation existed between serum AFP and HBsAg among the patients (P less than 0.0001). Of 27 AFP-negative patients, 15 (55.6%) had HLA-B15 compared to 53 of 238 (22.3%) healthy controls (corrected P less than 0.003, relative risk = 4.4). The frequency of HLA-B15 was even higher in the AFP-negative plus HBsAg-negative subgroup (61%). AFP-negative patients also had a significant lack of blood group A.


Ionization and fragmentation of isomeric van der Waals complexes embedded in helium nanodroplets.
The ionization and charge transfer processes, which occur when a doped helium droplet undergoes electron impact, are studied for droplets doped with van der Waals complexes with various structures and electrostatic moments. The mass spectra of the two isomers of hydrogen cyanide complexed with either cyanoacetylene or acetylene in helium droplets were obtained using optically selected mass spectrometry, and show that the structure of the complex has a large effect on the fragmentation pattern. The resulting fragmentation pattern is consistent with an ionization process in which charge steering strongly influences the site of initial ionization. The observed dissociation products may also be subject to caging by the helium matrix.


Increased number of Langerhans cells in oral lichen planus and oral lichenoid lesions.
The aim of this study was to quantify the presence of Langerhans cells (LC) in oral lichen planus (OLP) and oral lichenoid lesions (OLL), comparing them with normal epithelium. Thirty-six patients with biopsy-proven OLP or OLL were selected for the study, as well as 23 control subjects free of inflammatory conditions. Immunohistochemical reactions were performed using the streptavidin-biotin peroxidase complex method with CD1a and CD83 primary antibodies. Densities were compared between groups and correlated with microscopic findings. Patients with lichenoid conditions (OLP + OLL) presented higher densities of CD1a(+) cells than the control subjects (P = .03). Higher densities of CD1a were associated with a thinner layer of inflammatory cells (P = .02). This study indicates that OLP and OLL are characterized by the recruitment of LC, which may play a significant role on its pathogenesis.


Cancer classification of single-cell gene expression data by neural network.
Cancer classification based on gene expression profiles has provided insight on the causes of cancer and cancer treatment. Recently, machine learning-based approaches have been attempted in downstream cancer analysis to address the large differences in gene expression values, as determined by single-cell RNA sequencing (scRNA-seq). We designed cancer classifiers that can identify 21 types of cancers and normal tissues based on bulk RNA-seq as well as scRNA-seq data. Training was performed with 7398 cancer samples and 640 normal samples from 21 tumors and normal tissues in TCGA based on the 300 most significant genes expressed in each cancer. Then, we compared neural network (NN), support vector machine (SVM), k-nearest neighbors (kNN) and random forest (RF) methods. The NN performed consistently better than other methods. We further applied our approach to scRNA-seq transformed by kNN smoothing and found that our model successfully classified cancer types and normal samples. Cancer classification by neural network. Supplementary data are available at Bioinformatics online.


Fatty acid DSF binds and allosterically activates histidine kinase RpfC of phytopathogenic bacterium Xanthomonas campestris pv. campestris to regulate quorum-sensing and virulence.
As well as their importance to nutrition, fatty acids (FA) represent a unique group of quorum sensing chemicals that modulate the behavior of bacterial population in virulence. However, the way in which full-length, membrane-bound receptors biochemically detect FA remains unclear. Here, we provide genetic, enzymological and biophysical evidences to demonstrate that in the phytopathogenic bacterium Xanthomonas campestris pv. campestris, a medium-chain FA diffusible signal factor (DSF) binds directly to the N-terminal, 22 amino acid-length sensor region of a receptor histidine kinase (HK), RpfC. The binding event remarkably activates RpfC autokinase activity by causing an allosteric change associated with the dimerization and histidine phosphotransfer (DHp) and catalytic ATP-binding (CA) domains. Six residues were found essential for sensing DSF, especially those located in the region adjoining to the inner membrane of cells. Disrupting direct DSF-RpfC interaction caused deficiency in bacterial virulence and biofilm development. In addition, two amino acids within the juxtamembrane domain of RpfC, Leu172 and Ala178, are involved in the autoinhibition of the RpfC kinase activity. Replacements of them caused constitutive activation of RpfC-mediated signaling regardless of DSF stimulation. Therefore, our results revealed a biochemical mechanism whereby FA activates bacterial HK in an allosteric manner, which will assist in future studies on the specificity of FA-HK recognition during bacterial virulence regulation and cell-cell communication.


Preliminary screening method for the determination of inorganic arsenic in urine.
A simple and rapid method was developed for the routine determination and classification of inorganic arsenic based on its clinical and forensic properties. Inorganic arsenic was isolated from urine by using copper granules, which was then made to react with ammonium molybdate in order to detect its presence with the naked eye. Based on studies of extraction and reaction conditions, e.g., reaction temperature and time, a colorimetric screening method was established. The reaction mixture was measured by a spectrophotometer, and there was linearity from 0.05 to 2.0microg/ml and the correlation coefficients of the calibration curves were greater than 0.99. The coefficients of intra-day variation at 0.2 and 2.0microg/ml of inorganic arsenic in urine were 9.6 and 4.2%, respectively (n=5). The minimum detectable level in urine is 0.03microg/ml, and it is possible to detect the lowest level of poisoning according to the published reports. The proposed method was applied to a poisoning case wherein the patient ingested NEOARSEN BLACK with alcohol, which contained 45% of arsenic trioxide. This method produced positive results in all the urine samples tested, and this method is useful for the screening of inorganic arsenic based on its clinical properties because it enables the detection of inorganic arsenic in urine without expensive equipment.


Coping and defence mechanisms: What are we assessing?
The present research study addresses the disparity between theoretical considerations and empirical evidence regarding the relationships between coping strategies and defence mechanisms. Self-reported measures of coping and defences were administered to a Romanian adult sample (N = 542; 74.53% female, mean age = 31.28). Using structural equation modelling, models that assumed independence between coping and defences were compared with models that assumed the existence of relationships between the two concepts. Findings identified strong relationships between coping and defences, indicating large common variance between the two concepts. Furthermore, results suggested that coping and defences can be classified into two independent types of adaptation processes. Results of this research study suggested that coping and defences are facets of common adaptation processes.


Making the case for the nurse as the leader of care coordination.
Care coordination has emerged as an effective model of care that contributes to healthcare reform's triple aim of decreasing costs, understanding the needs of individuals, and improving outcomes. This paper provides an argument that nurses should be the leaders of care coordination. Relationships among care coordination, nursing education, and professional values are made to show a common thread that ties the foundations of each. Benefits to outcomes and improved costs by nurses are also presented as defense for this claim. Rebuttals to arguments against this claim attempt to repudiate their worth and continue to show nursing's strategic position to assume this role.


Relationships between diaphragmatic hiatus and infra-diaphragmatic esophagus: a combined X-ray and manometry study.
The relationship between the diaphragmatic hiatus, the infra-diaphragmatic esophagus and a manometric tube were examined in 10 patients not suffering from hiatal hernia or gastroesophageal reflux. During surgery, two metal markers were attached to the diaphragmatic hiatus and two others were fixed at the vertex of the angle of His. X-ray examinations were taken during manometric recordings of the high pressure zone (HPZ) both at rest and during relaxation. Comparison between the radiographs showed that during swallowing the manometric tube did not move with respect to the vertebral bodies; contraction of the esophagus caused complete disappearance of the infra-diaphragmatic esophagus. It was also observed that during pressure drop in the HPZ (so-called lower esophageal sphincter relaxation), the manometric recording site is located below the vertex of the angle of His, i.e. in the gastric cavity. These findings provide the basis for a hypothesis to explain the passage of a solid bolus through the lower esophagus into the stomach.


Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide-poisoned individuals.
The purpose of this study was to evaluate a new pharmacological strategy using a first-generation succinate prodrug, NV118, in peripheral blood mononuclear cells (PBMCs) obtained from subjects with carbon monoxide (CO) poisoning and healthy controls. We obtained human blood cells from subjects with CO poisoning and healthy control subjects. Intact PBMCs from subjects in the CO and Control group were analyzed with high-resolution respirometry measured in pmol O2 per second per 10-6 PBMCs. In addition to obtaining baseline respiration, NV118 (100 μM) was injected, and the same parameters of respiration were obtained for comparison in PBMCs. We measured mitochondrial dynamics with microscopy with the same conditions. We enrolled 37 patients (17 in the CO group and 20 in the Control group for comparison) in the study. PMBCs obtained from subjects in the CO group had overall significantly lower respiration compared with the Control group (P < 0.0001). There was a significant increase in respiration with NV118, specifically with an increase in maximum respiration and respiration from complex II and complex IV (P < 0.0001). The mitochondria in PBMCs demonstrated an overall increase in net movement compared with the Control group. Our results of this study suggest that the therapeutic compound, NV118, increases respiration at complex II and IV as well as restoration of mitochondrial movement in PBMCs obtained from subjects with CO poisoning. Mitochondrial-directed therapy offers a potential future strategy with further exploration in vivo.


Deriving electricity from dye processing wastewater using single chamber microbial fuel cell with carbon brush anode and platinum nano coated air cathode.
Single chamber air cathode microbial fuel cell (MFC) is a promising and sustainable technology to generate electricity. In the present study, the potential of air cathode MFC treating dye processing wastewater was investigated at various organic loads with interest focused on power densities, organic removal and coulombic efficiencies. The highest power density of about 515 mW/m2 (6.03 W/m3) with 56% of coulombic efficiency was procured at 1.0 (g COD/L) organic load. The high potency of TCOD (total chemical oxygen demand), SCOD (soluble chemical oxygen demand) and TSS (Total Suspended Solids) removal of about 85%, 73% and 68% respectively was achieved at the organic load of 1.0 (g COD/L). The bacterial strains in anode region at the initial stage of MFC operation were reported to be responsible for potential organic removal. The bacterial strains in air cathode MFC were identified as Paenibacillus sp. strain JRA1 (MH27077), Pseudomonas sp. strain JRA2 (MH27078), Ochrobactrum sp. strain JRA3 (MH27079), Sphingobacterium sp. strain JRA4 (MH27080), Stenotrophomonas sp. strain JRA5 (MH27081), Bacillus sp. strain JRA6 (MH27082) and Clostridium sp. strain JRA7 (MH27083) using phylogenetic analysis. After 60 days of air cathode MFC operation, the bacterial community in biofilm samples was dominated by Bacillus, Ochrobactrum and Pseudomonas (20-22%). The biofilm sample collected from the carbon brush consisted of Bacillus (33%), Ochrobactrum (30%), Pseudomonas (28%), Clostridium (6%) and Stenotrophomonas (3%). The present study revealed the treatment efficiency of dye processing wastewater along with power generation in single chambered air cathode MFC.


[Concept of the Pain Management in the Convalescent Rehabilitation].
Convalescent rehabilitation is a treatment designed to facilitate the process of recovery from disease or injury to as normal a condition as possible. The effective rehabilitation is required to improve functions to bring about the highest possible level of independence, physically, psychologically, socially and economically within a limited hospitalization period. Pain often inhibits the effective rehabilitation, and the pain management in the convalescent rehabilitation ward is important. In particular, it is important to evaluate the pain promptly and accurately, and to treat it by a multidisciplinary team approach, preventing a shift to chronic pain. In this article, we describe the role of each member in the convalescent rehabilitation team and the characteristic pains caused by representative diseases.


A simple method for assessing severity of common root rot on barley.
Common root rot caused by Cochliobolus sativus is a serious disease of barley. A simple and reliable method for assessing this disease would enhance our capacity in identifying resistance sources and developing resistant barley cultivars. In searching for such a method, a conidial suspension of C. sativus was dropped onto sterilized elongated subcrown internodes and incubated in sandwich filter paper using polyethylene transparent envelopes. Initial disease symptoms were easily detected after 48h of inoculation. Highly significant correlation coefficients were found in each experiment (A, B and C) between sandwich filter paper and seedling assays, indicating that this testing procedure was reliable. The method presented facilitates a rapid pre-selection under uniform conditions which is of importance from a breeder's point of view.


Building Bridges in Palliative Rehabilitation: An Evidence-Based Toolkit to Promote Collaboration.
Background: Palliative care and rehabilitation professionals caring for seriously ill people and their families face barriers to effective, timely collaboration. Barriers such as ineffective communication processes, role misunderstanding across professions, and resource limitations can lead to underutilization of rehabilitation services for this vulnerable population. Objectives: To create practical connections between palliative care and rehabilitation professionals and to provide tools and strategies for teams to develop the core competencies (role clarity, communication, teamwork, and shared values) necessary to provide coordinated, timely, effective care to people living with serious illness. Design: With Interprofessional Education Collaborative (IPEC) Core Competencies1 as a framework for interprofessional collaborative practice, a quality improvement project was conducted at a large academic medical center. The 5-phase project included literature review, expert interviews, identification of barriers and facilitators, development of strategies to mitigate barriers, and pilot testing of select strategies. Results: The PalRehab Toolkit consists of strategies to enhance interprofessional collaborative practice and infuse rehabilitation into palliative care in the acute care setting. Preliminary evaluation of piloted strategies suggests increased communication across professions, improved role clarity, and an increased likelihood of collaboration. Conclusion: Providing educational offerings, establishing efficient communication channels, and infusing rehabilitation concepts into palliative care practices, as outlined in the PalRehab Toolkit, may positively impact interprofessional collaborative practice and improve care delivery for people with serious illness and their families.


MALE DIMORPHISMS IN BEETLES AND EARWIGS AND THE QUESTION OF DEVELOPMENTAL CONSTRAINTS.
Analysis of 17 species from six families indicates that male dimorphisms in weapon design may be common, at least in homed beetles. This flexibility in developmental programs constitutes evidence against the idea that the forms of these animals' weapons are the result of developmental constraints.


Incidence and variation of interpretably bone (os incae) in northeastern Thailand.
The squamous segment of occipital bone consists of cartilaginous and membranous origin. The cartilaginous part develops to supra-occipital bone. The membranous part has three primary ossification centers on each side. The first pair ossification center lies above the cartilaginous part between the superior nuchal line and the highest nuchal line and fuse with the cartilaginous part to form a supra-occipital segment of occipital bone. The second and third pairs have two nuclei each forming lateral and medial plates. All of these ossification centers fuse to form squamous segments of occipital bone. The fusion failure between ossification centers of second and third pair nuclei with each other or supra-occipital segment causes separated bone(s) called interparietal bone(s) or os incae. The interparietal bone should be differentiated from Wormian (intrasutural) bone. The incidence from various studies ranges from 0.37% to 9.50% of the population. To study the incidence and variation of interparietal bone in Northeastern Thailand as compared with other studies. A total of 400 Thai native skulls (276 male and 124 female) from the collection of Anatomical Museum of the Faculty of Medicine Khon Kaen University aged from 16 to 93 years old were examined by naked eye and photographed. Wormian bone was excluded by shape and site. The statistical method used was percentage of relative frequency. The incidence of interparietal bone in Northeastern Thailand is 7.25% (29 from 400). Males have a two times higher incidence rate than females, (8.33% versus 4.84%). Eleven patterns of interparietal bone were found. Fusion failure of a third pair ossification center is more common than second pair Knowledge of interparietal bone is useful for neurosurgeons and radiologists to avoid missed diagnosis of skull fracture. Presented interparietal bone may cause difficulty in surgery of occipital and parietal bone. Forensic scientist can use interparietal bone for personal identification.


Effects of encainide and its metabolites on energy requirements for defibrillation.
Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs' effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Soft Cold EI - approaching molecular ion only with electron ionization.
Cold EI is defined as electron ionization of cold molecules in supersonic molecular beams (SMB). Gas chromatography/mass spectrometry (GC/MS) with Cold EI provides informative mass spectra, which combine the usual library-searchable EI fragment ions with enhanced molecular ions for improved library-based identification probabilities. However, in some cases, such as in the analysis of complex petrochemical matrices, a soft ionization method that provides only molecular ions is desirable. GC/MS with Cold EI was used with a fly-through ion source at selected electron energies, including at low electron energies, in an attempt to observe molecular ions alone. We explored low electron energy Cold EI and found that once the sample compound is cooled by the supersonic expansion it can be reheated via reflected scattered helium atoms near the skimmer. Furthermore, once a labile molecular ion is formed it can undergo undesirable collision-induced dissociation (CID) in the same way as in tandem mass spectrometry (MS/MS), and the magnitude of such CID can be significant for labile molecular ions such as those of hydrocarbons. In order to reduce these adverse effects we reduced the helium pressure at the ion source and MS vacuum chamber by increasing the nozzle-skimmer distance. Cold EI at low electron energies was explored with a squalane isomer (C30 H62 ) and with n-C24 H50 . It was found that an increased nozzle-skimmer distance resulted in a noticeable increase in the abundance ratio of molecular ions to low mass fragment ions. Consequently, Cold EI at low electron energies and a large nozzle-skimmer distance converts EI into Soft Cold EI while further approaching the ideal of a molecular ion only ionization method.


Enhancement of susceptibility to Fas-mediated apoptosis in HL-60 cells through down-regulation of cellular FLICE-inhibitory protein by phosphatidylinositol 3-kinase inhibitors.
Promyelocytic leukemia HL-60 cells are resistant to Fas-mediated apoptosis. The signaling pathway for Fas-mediated apoptosis in various cells, including HL-60 cells, is currently unknown. Here, we studied the role of survival/apoptosis associated phosphatidylinositol 3-kinase (PI 3-K)/Akt in this process. We found that both PI 3-K inhibitors, wortmannin and LY294002, markedly suppressed phosphorylation of Akt and Bad in HL-60 cells. PI 3-K inhibitors significantly accelerated not only spontaneous apoptosis, but also Fas-induced apoptosis in HL-60 cells. The pro-apoptotic effect of PI 3-K inhibitors favored Fas-mediated apoptosis rather than spontaneous apoptosis in HL-60 cells. The caspase-3 or -8 inhibitor reduced the pro-apoptotic effect of the PI 3-K inhibitors for Fas-mediated apoptosis in HL-60 cells, but the caspase-9 inhibitor did not. Although PI 3-K inhibitors did not affect Fas expression in HL-60 cells, cellular FLICE-inhibitory protein (c-FLIP) levels were markedly reduced by PI 3-K inhibitor treatment. Furthermore, antisense oligonucleotide of c-FLIP confirmed that down-regulation of c-FLIP enhanced sensitization to Fas-mediated apoptosis in HL-60 cells. These results suggest that the PI 3-K/Akt signaling pathway may, in part, regulate Fas-mediated apoptosis in HL-60 cells through c-FLIP expression.


Low peak bone mass and attenuated anabolic response to parathyroid hormone in mice with an osteoblast-specific deletion of connexin43.
Connexin43 (Cx43) is involved in bone development, but its role in adult bone homeostasis remains unknown. To overcome the postnatal lethality of Cx43 null mutation, we generated mice with selective osteoblast ablation of Cx43, obtained using a Cx43fl allele and a 2.3-kb fragment of the alpha1(I) collagen promoter to drive Cre in osteoblasts (ColCre). Conditionally osteoblast-deleted ColCre;Cx43-/fl mice show no malformations at birth, but develop low peak bone mass and remain osteopenic with age, exhibiting reduced bone formation and defective osteoblast function. By both radiodensitometry and histology, bone mineral content increased rapidly and progressively in adult Cx43+/fl mice after subcutaneous injection of parathyroid hormone (PTH), an effect significantly attenuated in ColCre;Cx43-/fl mice, with Cx43-/fl exhibiting an intermediate response. Attenuation of PTH anabolic action was associated with failure to increase mineral apposition rate in response to PTH in ColCre;Cx43-/fl, despite an increased osteoblast number, suggesting a functional defect in Cx43-deficient bone-forming cells. In conclusion, lack of Cx43 in osteoblasts leads to suboptimal acquisition of peak bone mass, and hinders the bone anabolic effect of PTH. Cx43 represents a potential target for modulation of bone anabolism.


Mitotherapy for Fatty Liver by Intravenous Administration of Exogenous Mitochondria in Male Mice.
Mitochondrial dysfunction is a major and common mechanism in developing non-alcoholic fatty liver disease (NAFLD). Replacement of dysfunctional mitochondria by functional exogenous mitochondria may attenuate intrahepatic excessive lipid and recover hepatocyte function. However, no data shows that mitochondria can be systemically administrated to animals to date. Here we suggest that mitochondria isolated from hepatoma cells are used as a mitotherapy agent to treat mouse fatty liver induced by high-fat diets. When the mitochondria were intravenously injected into the mice, serum aminotransferase activity and cholesterol level decreased in a dose-dependent manner. Also, the mitotherapy reduced lipid accumulation and oxidation injury of the fatty liver mice, improved energy production, and consequently restored hepatocyte function. The mitotherapy strategy offers a new potential therapeutic approach for treating NAFLD.


Lateral laxity in flexion increases the postoperative flexion angle in cruciate-retaining total knee arthroplasty.
Thirty-eight patients diagnosed with osteoarthritis underwent 41 cruciate-retaining total knee arthroplasties. In varus and valgus tests at flexion, subjects were seated on a table at 80° of knee flexion; 50 N was applied perpendicular to the lower leg. The factors affecting the postoperative flexion angle were investigated in a multiregression analysis. The mean joint angles of the flexion-valgus and flexion-varus tests were 3.4° ± 1.4° and 6.2° ± 2.5°, respectively. The flexion-varus angle was correlated with the postoperative flexion angle (P < .01). The mean postoperative flexion angles were 110.8° ± 9.6° and 118.1° ± 8.0° in the groups with the flexion-varus angle of 6° or less and more than 6°, respectively (P = .02). Slack lateral laxity in flexion had a significant effect during knee flexion in cruciate-retaining total knee arthroplasty.


National SAFE KIDS Campaign releases 10-year report.
Unintentional injury is the leading cause of death and disability in children 14 years and under. The National SAFE KIDS Campaign, a nationwide organization aimed at education and prevention of unintentional injury, recently released its 10-year report that describes areas of success, areas in need of improvement, and goals for the future. The full 61-page report is worthy of reading and referencing for all those involved with children and their health care. Highlights of the report are summarized below.


Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells.
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes. Lentiviral vectors (LV) pseudotyped with vesicular stomatitis virus glycoprotein were superior to gammaretroviral and alpharetroviral vectors and other envelopes tested. The elongation factor 1α short (EFS) promoter mediated the most robust expression, whereas expression levels were lower from the potent but more silencing-prone spleen focus forming virus (SFFV) promoter. Both full-length (A2UCOE) and minimal (CBX3) UCOE juxtaposed to two physiological and one viral promoter reduced transgene silencing with equal efficiency. However, a promoter-specific decline in expression levels was not entirely prevented. Upon differentiation of transgene-positive iPSC into endothelial cells, A2UCOE.EFS and CBX3.EFS vectors maintained highest transgene expression in a larger fraction of cells as compared with all other constructs tested here. The function of UCOE diminished, but did not fully counteract, vector silencing and possibilities for improvements remain. Nevertheless, the CBX3.EFS in a LV background exhibited the most promising promoter and vector configuration for both high titer production and long-term genetic modification of human iPSC and their progeny.


[An outbreak of Heliotrope food poisoning, Tadjikistan, November 1992-March 1993].
The seeds and roots of Heliotropium lasocarpium, contain a pyrrolizidine alkaloid which causes toxic liver injury and veno-occlusive disease (VOD), characterised by an occlusive lesion of the centrolobular veins of the liver, when consumed by humans. The Farkhar region of Southern Tadjikistan, was blockaded from May to November 1992. This led to a famine and a delay of two months in the wheat harvest. Heliotropium lasocarpium had time to grow in the fields and their seeds were therefore collected with the wheat. The contaminated wheat was distributed to the population, who milled it and made bread. The first case of liver toxicity was six weeks after the first consumption of the contaminated bread. By March 1993, 3,906 cases had been recorded (attack rate = 4%). The attack rate were 0.4%, 5.4%, 4.0%, 2.8% and 1.5% for the less than 1 year, 1-14 years, 15-30 years, 31-50 years and over 50 years age groups respectively. The overall case fatality ratio (CFR) was 1.3% and increased with age from 0 to 5.9% in the same age groups. Two of the ten collective farms represented 83.3% of the cases attack rate of 16.9% and 23.6%. Four stages of illness were defined. Stage I corresponds to abdominal pain, nausea or vomiting, and asthenia. All stage I patients (55.5%) recovered rapidly. Stage II is an association of Stage I and hepatomegalia (29.9%). Stage III includes ascites in addition to these symptoms (13.7%) and stage IV alteration of consciousness (0.9%). The last case was reported on March 4th 1993.(ABSTRACT TRUNCATED AT 250 WORDS)


Haematinic and Hepatoprotective Properties of Telfairia occidentalis Fruit Mesocarp on Phenylhydrazine-Induced Anaemia in Experimental Rats.
The level and potential of iron contained in fluted pumpkin (Telfairia occidentalis) has been exploited as a blood tonic; however, the potentials of some other parts of the plant are unknown. The effect of T. occidentalis fruit mesocarp (aqueous extract) on phenylhydrazine (PHZ)-induced anaemia in experimental rats was investigated in a bid to determine its curative properties and potential in reversing haemolytic anaemia and protection of liver health. The LD50 of the fruit extract was determined using Lorke's method for the determination of acute toxicity. The study involved oral administration of varying doses of the extract to different groups of rats which were monitored for 24 hours. The test sample did not show any signs of toxicity at doses of 5000 mg/kg b.wt, which is the highest possible recommended dose for toxicity testing. For the evaluation of the effects of the fruit extract on haematological indices and biochemical enzyme markers in anaemic rats, 30 matured albino Wistar rats were used. The rats were divided into five groups of six rats each. Group 1 consisted of normal rats (control group), Group 2 consisted of anaemic untreated rats, and Group 3 consisted of anaemic rats treated with the standard drug Astymin, while Groups 4 and 5 were made up of anaemic rats given the extract at doses of 600 mg/kg b.wt and 1000 mg/kg b.wt, respectively. The fruit extract failed to show any significant effect in improving the haemoglobin (Hb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels in anaemic rats but rather may have contributed to a reduction in Hb levels and an unhealthy increase in serum enzyme levels. This is indicative of the apparent inability of the aqueous extract of the T. occidentalis fruit mesocarp to reverse PHZ-induced haemolytic anaemia and may suggest a possible detrimental effect of high doses of the extract over a prolonged period.


Fingerprinting of diverse genomes using PCR with universal rice primers generated from repetitive sequence of Korean weedy rice.
Twenty primers of 20 mer referred to universal rice primer (URP) were developed from a repetitive sequence of rice genome. URP-PCR protocol employed stringent PCR with high annealing temperature throughout the thermo-cycling reaction, giving high reproducibility. Under the PCR condition, each single URP primer produced characteristic fingerprints from diverse genomes containing 14 plants, 7 animals and 6 microbes, indicating its universal applicability. The generality of URP-PCR was demonstrated by applying it to 15 cultivars from five rice species, 23 isolates in four Alternaria species producing host-specific toxins on different host plants and 12 bacterial strains including Escherichia coli, Salmonella spp., and Blucella abortus. PCR approach using URP primers will be useful for studying DNA diversity of most eukaryotic or prokaryotic genomes, especially at inter- and intraspecies levels.


A clue to the diffuse structure in ultraviolet spectra of the GeCl2 A-X transition.
Geometries, harmonic vibrational frequencies, and relative electronic energies of the two low-lying electronic states of the GeCl(2) dimer have been calculated at the CIS(D) method with a cc-pVTZ basis set. Minima corresponding to three isomers on the ground-state potential energy surface have been characterized. The most stable dimer has a dissociation energy of 0.74 eV and has a trans-(GeCl(2))(2) structure. There is also a related, less stable, cis minimum. A third, C(i) symmetry, isomer has a binding energy of 0.31 eV. It is found that this C(i) isomer has substantial dipole transition strength to the first excited singlet state of the dimer with a vertical excitation energy of 3.33 eV. The transition energy (T(0)) between this C(i) isomer and the van der Waals complex on the singlet excited state is predicted to be 4.007 eV, or a 1104 cm(-1) blueshift with respect to that of the GeCl(2) A-X transition. This finding may explain the diffuse structure which has been observed in the ultraviolet laser-induced fluorescence spectra of GeCl(2).


Initial experience with silver-impregnated polyurethane ventricular catheter for shunting of cerebrospinal fluid in patients with infected hydrocephalus.
Infection is a major complication and risk factor of cerebrospinal fluid (CSF) shunting procedures. Recently, antibiotic-impregnated shunt systems have been developed in an attempt to prevent or reduce the CSF infection. The aim of this study was to determine the efficacy of silver-impregnated polyurethane ventricular catheter for shunting of CSF in patients with infected hydrocephalus. Seven patients who had hydrocephalus with high protein level and positive CSF culture underwent implantation of ventriculoperitoneal shunt with silver-impregnated polyurethane ventricular catheter. All of them experienced shunt failure previously due to infection. The Silverline ventricular catheter, which was connected to the Miethke gravity-assisted valve system and peritoneal catheter, was used in all patients. The mean follow-up period after operation was 14 months. Cerebrospinal fluid samples from the reservoir of the shunts were obtained at the end of the third month after operation in all patients. The CSF protein level of the patients was reduced significantly, and the CSF culture became negative after shunt placement with silver-impregnated polyurethane ventricular catheters. The mean CSF silver (Ag) level was 0.51 ng/ml [parts per billion (ppb)], and blood Ag level was 3.65 ng/ml (ppb) at the first month after operation. No shunt obstruction or infection was observed in the follow-up period. Silver-impregnated polyurethane ventricular catheters appear to be safe and well tolerated in patients who sustained infected hydrocephalus. Preliminary results suggest a complete improvement of infection. Longer follow-up and large number of patients are needed to more accurately assess the efficacy of these catheters.


Air Sampling and Analysis of Aeroallergens: Current and Future Approaches.
To review current air sampling instruments and analysis methods and to describe new approaches being developed. Spore trap sampling with analysis by microscopy remains the most widely used methods for aeroallergen determination even though there are often long delays from sample acquisition to data availability, as well as a need for specially-trained staff for sample analysis. The use of immunoassays and molecular biology to analyze outdoor or indoor samples has expanded in recent years and has provided valuable data on allergen exposure. New automated sampling devices capture pollen, analyze, and identify pollen grains by light scattering, laser-induced fluorescence, microscopy, or holography using signal or image processing to classify the pollen in real time or near real time. Air sampling data from current methods provide valuable information on aeroallergen exposure. The automated devices in use and under development show great potential but are not ready to replace existing aeroallergen networks.


Fast screening of analytes for chemical reactions by reactive low-temperature plasma ionization mass spectrometry.
Approaches for analyte screening have been used to aid in the fine-tuning of chemical reactions. Herein, we present a simple and straightforward analyte screening method for chemical reactions via reactive low-temperature plasma ionization mass spectrometry (reactive LTP-MS). Solution-phase reagents deposited on sample substrates were desorbed into the vapor phase by action of the LTP and by thermal desorption. Treated with LTP, both reagents reacted through a vapor phase ion/molecule reaction to generate the product. Finally, protonated reagents and products were identified by LTP-MS. Reaction products from imine formation reaction, Eschweiler-Clarke methylation and the Eberlin reaction were detected via reactive LTP-MS. Products from the imine formation reaction with reagents substituted with different functional groups (26 out of 28 trials) were successfully screened in a time of 30 s each. Besides, two short-lived reactive intermediates of Eschweiler-Clarke methylation were also detected. LTP in this study serves both as an ambient ionization source for analyte identification (including reagents, intermediates and products) and as a means to produce reagent ions to assist gas-phase ion/molecule reactions. The present reactive LTP-MS method enables fast screening for several analytes from several chemical reactions, which possesses good reagent compatibility and the potential to perform high-throughput analyte screening. In addition, with the detection of various reactive intermediates (intermediates I and II of Eschweiler-Clarke methylation), the present method would also contribute to revealing and elucidating reaction mechanisms.


The anti-diabetic drug glibenclamide is an agonist of the transient receptor potential Ankyrin 1 (TRPA1) ion channel.
The anti-diabetic drug glibenclamide inhibits K(ATP) channels in pancreatic β-cells and stimulates insulin release. It also causes adverse effects, among which are abdominal pain, gastrointestinal disturbances and nocturia. We report that glibenclamide activates human TRPA1 in a concentration range that is commonly used to induce inhibition of K(ATP) channels in vitro. Glibenclamide generates calcium transients in HEK293t cells transiently transfected with human TRPA1, which are inhibited by the selective TRPA1 antagonist HC030031 and also evokes outwardly rectifying currents mediated by recombinant TRPA1. Glibenclamide activates a subpopulation of mouse primary sensory neurons, most of which are also sensitive to the selective TRPA1 agonist mustard oil. This glibenclamide sensitivity is completely abolished by genetic ablation of TRPA1. Taken together, our data demonstrate that glibenclamide is an agonist of human TRPA1, which may explain some of the adverse effects of the drug.


Using the deadly mu-conotoxins as probes of voltage-gated sodium channels.
Mu-Conotoxins (mu-CTX) are potent Na channel inhibitory peptides isolated from the venom of the predatory marine snail Conus geographus. Mu-CTXs exert their biological action by physically occluding the ion-conducting pore of voltage-gated Na (Na(v)) channels with a 1:1 stoichiometry in an all-or-none fashion. This article reviews our current knowledge of the mechanism of mu-CTX and the associated structural and functional insights into its molecular target--Na(v) channels.


Serratia marcescens bacteremia traced to an infused narcotic.
From June 30, 1998, through March 21, 1999, several patients in the surgical intensive care unit of a hospital acquired Serratia marcescens bacteremia. We investigated this outbreak. A case was defined as the occurrence of S. marcescens bacteremia in any patient in the surgical intensive care unit during the period of the epidemic. To identify risk factors, we compared patients with S. marcescens bacteremia with randomly selected controls. Isolates from patients and from medications were evaluated by pulsed-field gel electrophoresis. The hair of one employee was tested for fentanyl. Twenty-six patients with S. marcescens bacteremia were identified; eight (31 percent) had polymicrobial bacteremia, and seven of these had Enterobacter cloacae and S. marcescens in the same culture. According to univariate analysis, patients with S. marcescens bacteremia stayed in the surgical intensive care unit longer than controls (13.5 vs. 4.0 days, P<0.001), were more likely to have received fentanyl in the surgical intensive care unit (odds ratio, 31; P<0.001), and were more likely to have been exposed to two particular respiratory therapists (odds ratios, 13.1 and 5.1; P<0.001 for both comparisons). In a multivariate analysis, receipt of fentanyl and exposure to the two respiratory therapists (adjusted odds ratio for one therapist, 6.7; P=0.002; adjusted odds ratio for the other therapist, 9.5; P=0.02) remained significant. One respiratory therapist had been reported for tampering with fentanyl; his hair sample tested positive for fentanyl. Cultures of fentanyl infusions from two case patients yielded S. marcescens and E. cloacae. The isolates from the case patients and from the fentanyl infusions had similar patterns on pulsed-field gel electrophoresis. After removal of the implicated respiratory therapist, no further cases occurred. An outbreak of S. marcescens and E. cloacae bacteremia in a surgical intensive care unit was traced to extrinsic contamination of the parenteral narcotic fentanyl by a health care worker. Our findings underscore the risk of complications in patients that is associated with illicit narcotic use by health care workers.


Caregivers' perspectives and experiences of withdrawing acetylcholinesterase inhibitors and memantine in advanced dementia: a qualitative analysis of an online discussion forum.
There is considerable uncertainty surrounding the medications used to delay the progression of dementia, especially their long-term efficacy and when to withdraw treatment with these agents. Current research regarding the optimal use of antidementia medication is limited, contributing to variability in practice guidelines and in clinicians' prescribing practices. Little is currently known about the experiences encountered by caregivers of people with dementia after antidementia medication is withdrawn. To investigate the experiences and perspectives of carers and family members when antidementia medications (cholinesterase inhibitors and/or memantine) are stopped, by analysing archived threads and posts of an online discussion forum for people affected by dementia. Archived discussions from Talking Point, an online discussion forum hosted by the Alzheimer's Society UK, were searched for threads discussing antidementia medication withdrawal and relevant threads were analysed thematically using the Framework method. Participant demographics were not established due to usernames which ensured anonymity. Four key themes emerged: (1) expectations about withdrawal, (2) method of withdrawal, (3) clinical condition on withdrawal, and (4) the effect of withdrawal on caregivers. Online discussion forums such as Talking Point provide dementia carers with an outlet to seek help, offer advice and share experiences with other members. The study findings highlight the complexity surrounding optimising dementia pharmacotherapy and antidementia medication withdrawal, highlighting the need for treatment to be person-centred and highly individualised.


Postcollapse dynamics of self-gravitating Brownian particles and bacterial populations.
We address the postcollapse dynamics of a self-gravitating gas of Brownian particles in D dimensions in both canonical and microcanonical ensembles. In the canonical ensemble, the postcollapse evolution is marked by the formation of a Dirac peak with increasing mass. The density profile outside the peak evolves self-similarly with decreasing central density and increasing core radius. In the microcanonical ensemble, the postcollapse regime is marked by the formation of a "binarylike" structure surrounded by an almost uniform halo with high temperature. These results are consistent with thermodynamical predictions in astrophysics. We also show that the Smoluchowski-Poisson system describing the collapse of self-gravitating Brownian particles in a strong-friction limit is isomorphic to a simplified version of the Keller-Segel equations describing the chemotactic aggregation of bacterial populations. Therefore, our study has direct applications in this biological context.


Nuclear estradiol and cytosol progestin receptor concentrations in the brain and the pituitary gland and sexual behavior in ovariectomized estradiol-treated middle-aged rats.
We wished to determine whether the altered nuclear estradiol (E2) receptor concentrations in middle-aged rats can explain the diminished responsiveness to E2 observed in aging rats. Therefore, we measured receptor concentrations in various brain areas and the pituitary gland of young and middle-aged ovariectomized rats 2 and 4 days after implantation of Silastic capsules containing E2. To determine whether any observable changes had physiological consequences, we correlated age-dependent changes in E2 nuclear receptor concentrations with two E2-dependent parameters: cytosol progestin receptor levels in equivalent brain areas and pituitary gland and progesterone-facilitated reproductive behaviors. Young (3-4 months old) and middle-aged (10-12 months old) Sprague-Dawley rats were ovariectomized and received Silastic capsules containing E2 dissolved in oil 1 week later (day 0). Groups of rats were killed at 1200 h on either day 2 or day 4. Nuclear E2 and cytosol progestin receptor concentrations were assessed in a nuclear and cytoplasmic extract from the medial basal hypothalamus, preoptic area, amygdala, and pituitary gland. To test steroid-induced mating behavior, ovariectomized young and middle-aged rats were treated with E2-containing capsules for 2 or 4 days. At 0900 h progesterone (0.2 mg/kg BW) was injected sc and receptive and proceptive behaviors were observed when experienced males were introduced 4-6 h later. Two days after implantation of E2 capsules, middle-aged rats exhibited lower nuclear E2 receptor concentrations in the medial basal hypothalamus and preoptic area than young rats. By day 4, there were no significant age-related differences in any brain area or in the pituitary gland. Parallel age-related differences were observed in cytosol progestin receptor concentrations on day 2 but they were not evident by day 4. Similarly, middle-aged rats exhibited deficits in proceptive behavior, lordosis quotient, and lordosis quality score on day 2, but there were no differences compared to young rats on day 4. These data demonstrate that E2-induced nuclear E2 receptor concentrations are lower in selected areas of the brain of middle-aged rats. Such changes appear to be physiologically important because they are correlated with changes in E2-induced cytosol progestin receptor concentrations and steroid-induced behaviors. Furthermore, they may partially account for age-related differences in E2-induced LH surges on day 2.(ABSTRACT TRUNCATED AT 400 WORDS)


A comparison of avian and mammalian cell cultures for the propagation of avian reovirus WVU 2937.
Two avian and seven mammalian cell lines were evaluated for their application in propagating avian reovirus WVU 2937. Cultures were compared for monolayer-formation time, support of viral replication, passages and postinfection time required for expression of cytopathic effect (CPE), type of CPE, and virus yield. CPE was observed on the first passage with infected egg yolk in primary chicken embryo kidney cells, primary through tertiary chicken embryo liver (CEL) cells, and African green monkey kidney (VERO) cells; on the third blind passage of infected supernatant in Georgia bovine kidney cells, Crandall feline kidney cells, and baby hamster cells; on the fifth blind passage in rabbit kidney cells; and on the tenth blind passage in porcine kidney cells. CPE was not observed after 10 viral passages in rabbit bone-marrow cells. Monolayer formation time and postinfection time for CPE expression occurred sooner, and virus yield was greater, with CEL and VERO cells than with other cell lines.


Clinical value of scrotal ultrasound in the investigation of scrotal pathology.
The investigation of scrotal swelling has been aided by the advent of scrotal ultrasound. We have reviewed 100 patients in whom 112 scans were performed. One quarter of this group presented with scrotal pain without swelling. Of these patients, 33% were shown to have normal testes on scan; the remainder all had benign disease. A similar number presented with scrotal pain and swelling and the majority were diagnosed on scan as having epididymitis. Nineteen patients were thought on clinical grounds to have tumours; 6 were proven at operation and all were correctly identified pre-operatively by scanning. Scrotal ultrasound is a useful investigation in the management of both painless and painful scrotal swellings.


Phylogenetic analysis of two Chinese orf virus isolates based on sequences of B2L and VIR genes.
Orf virus (ORFV) is an enveloped virus with a double-stranded DNA genome, causing a contagious pustular dermatitis, mainly in goats and sheep. In this study, two strains of ORFV were isolated from sheep and goat samples in Xinjiang and Shaanxi, China. The B2L and virus interferon resistance (VIR) genes of these two isolates were sequenced and analyzed after PCR amplification. Phylogenetic analysis showed that the two isolates clustered with other ORFV strains but were separated into different subgroups. The Xinjiang strain shared the highest homology with the Gansu strain, whereas the Shaanxi strain shared higher homology with the Taiwan and Hubei strains. This is the first report of the molecular characterization of ORFV in Northwest China, and it provides new information on the genotyping of the causative agents responsible for contagious ecthyma dermatitis outbreaks in China.


Effect of reading passage length on quantitative acoustic speech assessment in Czech-speaking individuals with Parkinson's disease treated with subthalamic nucleus deep brain stimulation.
Little is known about the minimum sample length required for the stable acoustic assessment of speech in Parkinson's disease (PD). This study aimed to investigate the effect of the duration of the reading passage on the determination of reliable acoustic patterns in individuals with PD treated with subthalamic nucleus deep brain stimulation. A phonetically balanced reading text of 313 words was collected from 32 Czech persons with PD, and 32 age- and sex-matched healthy controls. The reading passage was segmented to produce ten sub-texts of increasing length ranging from a one- to a ten-segment-long sub-text. An error rate analysis was used to estimate the required stabilization value by evaluating the differences between the sub-texts and the entire text across seven hypokinetic dysarthria features. The minimum length of a reading passage equal to 128 words was found to be necessary for acoustic assessment, with similar lengths being required for the controls (120 words) and the two PD subgroups, including Parkinsonian individuals with a mild (126 words) and moderate (128 words) dysarthria severity. The current study provides important guidelines for the necessary sample length for future expert instrumental dysarthria assessments and assists in decreasing the time required for clinical speech evaluations.


Mitotic and labelling activity in normal human epidermis in vivo.
Labelling and mitotic indices were studied in the epidermis of twenty-eight young men. A mean labelling index of 5.5% was found from the whole study and a mean mitotic index of 0.06%. Mitotic index particularly was extremely variable; indices between 0.002 and 0.438% were found in individual biopsies. In the first two of three experiments in which mitotic index at 09.00 hours was compared with that at 15.00 hours, significant differences were found (15.00 hours greater than 09.00 hours by a factor of 2.6, P less than 0.001). However, in the third such experiment no such difference was found, suggesting that the timing and occurrence of diurnal rhythms of mitotic activity may not be consistent in normal human epidermis. In the one experiment in which it was investigated, a significantly higher mitotic index was found at 21.00 hours compared to 09.00 and 15.00 hours. Labelling index did not vary significantly at 09.00, 15.00 or 21.00 hours. However, labelling index did show a significant pattern of change over a 12-month period in two groups of subjects; peaks of labelling were seen in July and troughs in January. Very high ratios of labelled: mitotic cells were found, the median ratio for the whole study being ninety-eight labelled: one mitotic cell. This finding supports the possibility that not all labelled cells subsequently go on to divide in normal human epidermis.


[Characteristic and dynamic of HIV-1 subtype distribution in men who have sex with men in Guangzhou, 2008-2015].
Objective: To understand the characteristics and dynamic of HIV-1 subtype distribution in men who have sex with men (MSM) in Guangzhou between 2008 and 2015. Methods: HIV-1 RNAs were extracted from serum samples of the individuals newly diagnosed with HIV-1 infection among MSM living in Guangzhou between 2008 and 2015. The pol gene segments of HIV-1 genome from these RNA samples were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and were sequenced. Subsequently, the phylogenetic tree was reconstructed using pol sequences of samples and references together and the subtype of HIV-1 was determined. The distributions of HIV-1 subtypes detected in MSM with different demographic characteristics in different years were compared. Results: A total of 2 210 pol gene segments were successfully obtained from 2 473 serum samples of the MSM. The average age of 2 210 MSM was 30.19 years with standard deviation of 8.22 years, the unmarried MSM and those in Han ethnic group accounted for 73.39% and 90.81%, respectively. The proportion of subtype CRF07_BC (38.10%) was highest, followed by CRF01_AE (34.84%), CRF55_01B (14.62%), B (6.06%), URFs (3.58%), CRF59_01B (2.17%) and other subtypes (0.63%). The annual proportions of subtype B (P=0.000, 99%CI:0.000-0.000), CRF07_BC (χ(2)=14.965, P=0.036), CRF55_01B (χ(2)=18.161, P=0.011) and URFs (P=0.001, 99% CI: 0.000-0.001) were significantly different. The proportion of subtype B showed a gradual decrease from 14.08% to 4.33% (P=0.000, 99%CI: 0.000-0.000), while the proportion of URFs rapidly increased from 0% to 6.40% (P=0.000, 99% CI: 0.000-0.000). The rate of URFs was significantly higher in farmers and migrant workers than in other groups (P=0.017, 99%CI: 0.014- 0.020) and the rate of URFs was higher in individuals who had multi sexual partners (χ(2)=5.733, P=0.017). Conclusions: CRF07_BC and CRF01_AE were the predominant HIV-1 subtypes and multiple subtypes co-circulated among MSM in Guangzhou between 2008 and 2015. The recombinations of HIV-1 continue to occur in MSM. Strengthening behavioral intervention for farmers, migrant workers and individuals who have multi sexual partners has the important epidemiological significance against the emerging and circulating of the novel recombinant virus among MSM in Guangzhou.


Tumour markers - new aspects of an old discussion?
The knowledge about the molecular genetic features of cancer has been vastly increased within the last few years. Tumor markers used so far for diagnosis, monitoring, and follow-up of cancer patients are tumor-associated rather than tumor-specific. Therefore, the development of more sensitive and specific tumor markers is urgently needed. In this review, the possibilities of using molecular genetic characteristics of cancer as specific and sensitive tumor markers are discussed.


Actinomycosis imitating an adrenal tumor.
Abdominal actinomycosis is a rare condition that may mimic malignant disease. The authors report a case of adrenal actinomycosis discovered incidentally by computed tomography scan of the abdomen. Frozen sections and culture of the mass were consistent with actinomycosis. The diagnosis and management of actinomycosis is discussed in detail.


Impact of Insect-Resistant Transgenic Maize 2A-7 on Diversity and Dynamics of Bacterial Communities in Rhizosphere Soil.
Artificial modification of Bacillus thuringiensis (Bt) proteins can effectively improve their resistance to target pests, but the effect of such modification on the diversity of rhizosphere microorganisms remains unclear. Transgenic maize 2A-7 contains two artificially modified Bt proteins, mCry1Ab and mCry2Ab. These proteins can enter soil and pose a potential threat to soil microbial diversity. To assess their impacts on rhizosphere bacteria communities, the contents of the two Bt proteins and changes in bacterial community diversity in the rhizosphere soils of transgenic maize 2A-7 and its control variety were analyzed at different growth stages in 2020. The results showed that the two Bt proteins were detected at low levels in the rhizosphere soils of 2A-7 plants. No significant differences in soil bacterial diversity were detected between 2A-7 and its control variety at any of the growth stages. Bioinformatics analysis indicated that the growth stage, rather than the cultivar, was the main factor causing changes in bacterial communities. This research provides valuable data for understanding the impact of Bt crops on the soil microbiome, and establishes a theoretical basis for evaluation of their safety.


The Role of Breast MRI in Detecting Asymptomatic Recurrence After Therapeutic Mastectomy.
OBJECTIVE. MRI is not routinely used to screen for cancer recurrence after therapeutic mastectomy; however, data on this topic are sparse. We performed this study to determine the utility of breast MRI in detecting asymptomatic locoregional recurrence after therapeutic mastectomy. MATERIALS AND METHODS. A retrospective record review identified all breast MRI studies performed in women who had undergone unilateral therapeutic mastectomy over a 6-year period (January 1, 2010, to January 1, 2016). A total of 402 studies were performed in 191 women between the ages of 26 and 78 years old, none of whom were experiencing symptoms on the mastectomy side. BI-RADS assessments for the mastectomy side were extracted from the radiology reports, and the electronic medical records were reviewed for surgical and oncologic history, clinical and imaging follow-up, and pathologic results. Malignancy was determined by pathologic results. Benignity was confirmed by at least one of the following: pathologic results, at least 12 months of documented disease-free clinical follow-up, or at least 12 months of documented disease-free imaging follow-up. Descriptive statistical and 2 × 2 contingency table analyses were performed. RESULTS. In all, 395 MR images (98.3%) were assessed as showing benign findings on the mastectomy side. Seven (1.7%) were interpreted as showing positive findings on the mastectomy side (BI-RADS category 4, suspicious for malignancy). Biopsy was performed in four of the seven positive interpretations. All four biopsies yielded malignancy for a positive predictive value of biopsy of 100%. The three remaining positive cases did not include biopsy; however, in each case, follow-up imaging showed improvement or resolution of the finding, yielding a positive predictive value of an abnormal examination of 57.1%. Two MRI studies were false-negative, with local recurrence within 12 months after MRI deemed to show benign findings, yielding a negative predictive value of 99.5%. Sensitivity and specificity were 66.7% and 99.2%, respectively. The cancer detection rate in the asymptomatic mastectomy side for all MRI examinations was 10 cancers per 1000 examinations. CONCLUSION. Our findings support inclusion of the mastectomy side in MRI examinations of the contralateral breast to screen for cancer recurrence after therapeutic mastectomy.


Extracts of Tripterygium wilfordii Hook F in the Treatment of Rheumatoid Arthritis: A Systemic Review and Meta-Analysis of Randomised Controlled Trials.
Clinical trials have reported the effects of Tripterygium wilfordii Hook F (TwHF) extracts (TEs) in the treatment of rheumatoid arthritis (RA); however, the results have been inconsistent. This meta-analysis is aimed to assess the safety of TEs and their effects on the treatment of RA. Randomised controlled trials (RCTs) comparing the effects of TEs and placebo (PBO) or disease-modifying antirheumatic drugs (DMARDs) in patients with RA were included. Weighted mean differences (MDs) were calculated for net changes by employing fixed-effect or random-effects models. After filtering, ten RCTs (involving 733 participants) were included in this study. The methodological quality of these studies was generally low. Compared with DMARDs, TEs alone produced a mild increase in grip strength (GS) (P = 0.02; standard mean difference (SMD) = 0.81; 95% confidence interval (CI): 0.14 to 1.48). The most common adverse effects (AEs) of TEs were gastrointestinal discomfort, menstruation disorders, and amenorrhea. In conclusion, TEs, as a sort of "herbal DMARD," could be as effective as synthetic DMARDs in the treatment of RA. However, the efficacy of TEs in treating RA should be further estimated with better designed, fully powered, confirmatory RCTs that apply the American College of Rheumatology (ACR) improvement criteria to evaluate their outcomes.