Surgical Outcomes of Inguinal-, Pubic-, and Adductor-Related Chronic Pain in Athletes: A Systematic Review Based on Surgical Technique.
Controversies remain regarding the surgical treatment of inguinal-, pubic-, and adductor-related chronic groin pain (CGP) in athletes. To investigate the outcomes of surgery for CGP in athletes based on surgical technique and anatomic area addressed. Systematic review; Level of evidence, 4. The PubMed and Embase databases were searched for articles reporting surgical treatment of inguinal-, pubic-, or adductor-related CGP in athletes. Inclusion criteria were level 1 to 4 evidence, mean patient age >15 years, and results presented as return-to-sport, pain, or functional outcomes. Quality assessment was performed with the CONSORT (Consolidated Standards of Reporting Trials) statement or MINORS (Methodological Index for Non-randomized Studies) criteria. Techniques were grouped as inguinal, adductor origin, pubic symphysis, combined inguinal and adductor, combined pubic symphysis and adductor, or mixed. Overall, 47 studies published between 1991 and 2020 were included. There were 2737 patients (94% male) with a mean age at surgery of 27.8 years (range, 12-65 years). The mean duration of symptoms was 13.1 months (range, 0.3-144 months). The most frequent sport involved was soccer (71%), followed by rugby (7%), Australian football (5%), and ice hockey (4%). Of the 47 articles reviewed, 44 were classified as level 4 evidence, 1 study was classified as level 3, and 2 randomized controlled trials were classified as level 1b. The quality of the observational studies improved modestly with time, with a mean MINORS score of 6 for articles published between 1991 and 2000, 6.53 for articles published from 2001 to 2010, and 6.9 for articles published from 2011 to 2020. Return to play at preinjury or higher level was observed in 92% (95% CI, 88%-95%) of the athletes after surgery to the inguinal area, 75% (95% CI, 57%-89%) after surgery to the adductor origin, 84% (95% CI, 47%-100%) after surgery to the pubic symphysis, and 89% (95% CI, 70%-99%) after combined surgery in the inguinal and adductor origin. Return to play at preinjury or higher level was more likely after surgery for inguinal-related CGP (92%) versus adductor-related CGP (75%). However, the majority of studies reviewed were methodologically of low quality owing to the lack of comparison groups.


Meta-analysis on the use of hyaluronic acid gel to prevent intrauterine adhesion after intrauterine operations.
Intrauterine adhesion (IUA) is a severe complication that occurs following abortion, and hyaluronic acid gel has been used to prevent IUA following intrauterine operation. The present study aimed to systematically evaluate the efficacy of hyaluronic acid gel in preventing IUA following intrauterine operation. In the current study, a literature search was performed using PubMed, Cochrane Library and EMbase databases for randomized controlled clinical trials that used hyaluronic acid gel as an adjuvant therapy following intrauterine operation. The terms 'hyaluronic acid', 'intrauterine adhesions', 'Asherman's syndrome', 'IUA', 'dilatation and curettage', 'abortion' and 'hysteroscopic' were used to search for articles published online before July 31, 2018. RevMan 5.3 software was used to analyze the indicators of uterine cavity adhesion formation and pregnancy rates following intrauterine operation. A total of seven randomized controlled clinical studies were included, consisting of 952 patients who underwent intrauterine operation. The meta-analysis indicated that the use of hyaluronic acid gel reduced the incidence of IUA [relative risk (RR)=0.42; 95% confidence interval (CI)=0.30-0.57; P<0.001] and the score for IUA after an intrauterine operation (mean difference=-1.29; 95%=-1.73 to -0.84; P<0.001). A subgroup analysis revealed that the preventive effect of hyaluronic acid gel on IUA was not affected by the type of intrauterine operation, namely abortion (RR=0.40; 95% CI=0.26-0.62; P<0.001) and hysteroscopy (RR=0.44; 95% CI=0.28-0.68; P<0.001). The preventive effect of hyaluronic acid gel on IUA was also not affected by primary disorders/diseases including the following: Abortion (RR=0.48; 95% CI=0.29-0.78; P=0.003); IUA (RR=0.38; 95% CI=0.21-0.67; P<0.001) and submucosal myoma of the uterus, endometrial polyps or mediastinum uterus (RR=0.40; 95% CI=0.18-0.90; P=0.03). Hyaluronic acid gel improved pregnancy rates after intrauterine operations (RR=1.94; 95% CI=1.46-2.60; P<0.001). In conclusion, hyaluronic acid gel was indicated to significantly reduce the incidence of IUA following intrauterine operation, regardless of the type of intrauterine operation or the presence of primary diseases. Treatment with hyaluronic acid gel was also revealed to increase pregnancy rates following intrauterine operation.


Down-regulation of transforming growth factor-beta receptors: cooperativity between the types I, II, and III receptors and modulation at the cell surface.
The types I, II, and III receptors (RI, RII, RIII) for transforming growth factor-beta (TGF-beta) become down-regulated in response to ligand, presumably via their internalization from the cell surface. This report examines the down-regulation of full-length RI, RII, and RIII in cells endogenously or transiently expressing these receptors. Down-regulation occurred rapidly (within 2 h after TGF-beta1 treatment at 37 degrees C) and showed a dose response, between 10 and 200 pM TGF-beta1, in cells expressing RI, RII, and RIII (Mv1lu and A549 cells). A comparison between Mv1Lu and mutant cell derivatives R-1B (lacking RI) or DR-26 (lacking RII) indicated that all three receptors were necessary for efficient down-regulation. Down-regulation experiments, utilizing TGF-beta-treated 293 cells transiently expressing different combinations of these receptors indicated that neither RII or RIII were down-regulated when expressed alone and that RI was required for maximal down-regulation of RII. RII and RIII were partially down-regulated when these receptors were coexpressed in the absence of RI (in R-1B and 293 cells). Surprisingly, TGF-beta receptors were partially down-regulated in Mv1Lu, A549, and 293 cells treated with TGF-beta1 at 4 degrees C. Microscopic examination of 293 cells coexpressing RI fused to green fluorescent protein (RI-GFP) and RII indicated that, after treatment with TGF-beta1 at 4 degrees C, RI-GFP formed aggregates at the cell surface at this temperature. RI-GFP was not detected at the surface of these cells after TGF-beta1 treatment at 37 degrees C. Our results suggest a two phase mechanism for TGF-beta1 receptor down-regulation involving receptor modulation (aggregation) at the cell surface and internalization.


Quality of Care for Huntington's Disease in the United States: Findings from a National Survey of Patients and Caregivers.
Little is known about the quality of care for people living with Huntington's disease (HD) in the United States. To document the current HD care experience and identify gaps in care provision in the United States. Web-based surveys for persons self-identifying as being affected by HD (PAHD, which included individuals with, or at risk for HD) or as caregivers/family members, were developed and refined with targeted input from focus groups comprised of caregivers and family members. The surveys were disseminated via social media and patient advocacy partners from April-May 2017. Total valid responses numbered 797, including 585 caregiver/family respondents and 212 PAHD responses. Respondents reported care provision from HD specialty centers, primary care, movement disorder clinics, and other settings. One in five respondents reported that the person with HD was not currently receiving medical or community care. Respondents generally reported a good level of care, with HD specialists providing the highest rated healthcare experience. Caregiver/family respondents reported helping with a range of activities including budget/finances (60.5%), housekeeping (57.1%) and daily help (53.2%). Most respondents (97.9%) reported searching online, including general information about HD (86.4%), using HD social media channels (61.3%) and looking up clinical trials (59.8%). Respondents emphasized a need for support in financial planning and accessing care, and also for more HD education in the medical community. There is need for more support for HD patients and families. People desire more credible, accessible information. Improving resources available to patients and families should be a goal for HD organizations, along with measurement of patient outcomes.


Stimulation of implant fixation by parathyroid hormone (1-34)-A histomorphometric comparison of PMMA cement and stainless steel.
Whereas continuous exposure to PTH results in bone resorption, PTH administration at intermittent doses results in bone formation by increasing osteoblast number and activity. PTH leads to faster fracture repair and better fixation of orthopaedic implants in animal models. The present study evaluates if PTH is able to increase the contact surface between bone and implant and whether the effect of PTH is dependent on implant material characteristics. The implants were made as rods, either of stainless steel or Palacos R bone-cement. The steel rods had a surface roughness of R(a) 0.1 microm and the cement rods R(a) 2.2 microm. In 40 adult male rats, one cement rod was inserted in the left tibia and one steel rod in the right tibia. After implantation, the rats were divided into groups by random. One group was injected three times a week with human PTH (1-34) at a dose of 60 microg/kg BW/injection. The second group was injected with the vehicle only. Both groups were then divided into groups for 2 and 4 weeks time till tibial harvest. The tibial segments around the hole of the rods were then prepared by standard histological techniques. The linear tissue surfaces, that had been in contact with the surface of the rod, were analyzed in a blind fashion. PTH increased the bone contact fraction compared with the vehicle in the steel group from 7.4 (SD 7.6) to 21.1 (SD 10.7) % after 2 weeks and from 9.8 (SD 8.1) to 47.1 (SD 13.3) % after 4 weeks. In the cement group PTH increased the contact index again compared with the vehicle from 7.8 (SD 10.2) to 53.6 (SD 26.3) % already after 2 weeks and from 14.3 (SD 15) to 65.6 (SD 15.7) % after 4 weeks. The bone trabeculae adjacent to the implant had become fewer and thicker after the treatment with PTH (1-34), with an increase of the bone mass in the area next to the bone-implant-interface. The earlier onset of PTH effects in the rougher cement group suggests that intermittent PTH treatment might lead to an increased micro-interlock between implant and bone, and might therefore be considered as a possible drug to enhance incorporation of orthopedic implants.


Escherichiacoli Nissle 1917 as a Novel Microrobot for Tumor-Targeted Imaging and Therapy.
Highly efficient drug delivery systems with excellent tumor selectivity and minimal toxicity to normal tissues remain challenging for tumor treatment. Although great effort has been made to prolong the blood circulation and improve the delivery efficiency to tumor sites, nanomedicines are rarely approved for clinical application. Bacteria have the inherent properties of homing to solid tumors, presenting themselves as promising drug delivery systems. Escherichia coli Nissle 1917 (EcN) is a commonly used probiotic in clinical practice. Its facultative anaerobic property drives it to selectively colonize in the hypoxic area of the tumor for survival and reproduction. EcN can be engineered as a bacteria-based microrobot for molecular imaging, drug delivery, and gene delivery. This review summarizes the progress in EcN-mediated tumor imaging and therapy and discusses the prospects and challenges for its clinical application. EcN provides a new idea as a delivery vehicle and will be a powerful weapon against cancer.


International Comparison of Causative Bacteria and Antimicrobial Susceptibilities of Urinary Tract Infections between Kobe, Japan, and Surabaya, Indonesia.
Variation by country in urinary tract infection (UTI)-causative bacteria is partly due to the differences in the use of antibiotics. We compared their frequencies and antibiotic susceptibilities in the treatment of patients with UTI from 2 cities, Kobe, Japan, and Surabaya, Indonesia. We retrospectively analyzed 1,804 urine samples collected from patients with UTI in 2014 (1,251 collected in 11 months at Kobe University Hospital in Kobe and 544 collected in 2 months at Dr. Soetomo Hospital in Surabaya). Surabaya data were divided into adult and pediatric patients because a substantial number of specimens from pediatric-patients had been collected. The results indicated that Escherichia coli was the most common uropathogen (24.1% in Kobe and 39.3% in Surabaya) and was significantly resistant to ampicillin and substantially to first- and third-generation cephalosporins in Surabaya adults but not in Kobe adults (p < 0.01). Enterococcus faecalis was often isolated in Kobe (14.0%), but not in Surabaya (5.3%). Klebsiella spp. were isolated at a higher rate in Surabaya pediatric patients (20.3%) than in Surabaya adults (13.6%) and Kobe adults (6.6%). The antibiotic susceptibilities of the isolates form Surabaya isolates tended to be lower than the ones from Kobe. Extended-spectrum β-lactamase-producing Gram-negative bacteria were detected at a significantly higher rate in Surabaya than in Kobe (p < 0.001). These results showed that the antimicrobial resistance patterns of UTI-causative bacteria are highly variable among 2 countries, and the continuous surveillance of trends in antibiotic resistance patterns of uropathogens is necessary for the future revision of antibiotic use.


Quality of life in children with pityriasis rosea: a prospective case control study.
Our aim was to investigate the effects on quality of life of pityriasis rosea (PR) in children and the concerns of their parents. We recruited all children ages 5-16 years with a diagnosis of PR in a primary care setting over a period of 30 months. Controls were the next child of the same sex and comparable age consulting for atopic dermatitis or for conditions unrelated to the skin. Information on parental concerns was also gathered. Ten children with PR and 20 control subjects were recruited. Total Children's Dermatology Life Quality Index (CDLQI) scores of children with PR (mean 3.50; 95% confidence interval [CI] 2.66-4.34) were significantly lower than those of children with atopic dermatitis (mean 7.70; 95% CI 5.59-9.81). Children with PR had significantly lower scores for symptoms and feelings, personal relationships, and sleep. Total CDLQI scores of children with PR were significantly higher than those of children with no active skin problem (mean 0.30; 95% CI -0.18 to 0.78). Significantly more parents of children with PR had concerns regarding the etiology, infectivity, relapse, and complications or dangers of the disease. We concluded that quality of life (QOL) of children with PR is significantly less affected than that of children with atopic dermatitis and significantly more affected than in children with no active skin problem. The major concerns of parents of children with PR are the etiology, infectivity, relapse, and complications or dangers. These results have important implications on whether active intervention is worthwhile for this disease.


Spectral lineshapes in nonlinear electronic spectroscopy.
We outline a computational approach for nonlinear electronic spectra, which accounts for the electronic energy fluctuations due to nuclear degrees of freedom and explicitly incorporates the fluctuations of higher excited states, induced by the dynamics in the photoactive state(s). This approach is based on mixed quantum-classical dynamics simulations. Tedious averaging over multiple trajectories is avoided by employing the linearly displaced Brownian harmonic oscillator to model the correlation functions. The present strategy couples accurate computations of the high-lying excited state manifold with dynamics simulations. The application is made to the two-dimensional electronic spectra of pyrene, a polycyclic aromatic hydrocarbon characterized by an ultrafast (few tens of femtoseconds) decay from the bright S2 state to the dark S1 state. The spectra for waiting times t2 = 0 and t2 = 1 ps demonstrate the ability of this approach to model electronic state fluctuations and realistic lineshapes. Comparison with experimental spectra [Krebs et al., New Journal of Physics, 2013, 15, 085016] shows excellent agreement and allows us to unambiguously assign the excited state absorption features.


Population density and basic reproductive number of COVID-19 across United States counties.
The basic reproductive number (R0) is a function of contact rates among individuals, transmission probability, and duration of infectiousness. We sought to determine the association between population density and R0 of SARS-CoV-2 across U.S. counties, and whether population density could be used as a proxy for contact rates. We conducted a cross-sectional analysis using linear mixed models with random intercept and fixed slopes to assess the association of population density and R0. We also assessed whether this association was differential across county-level main mode of transportation-to-work percentage. Counties with greater population density have greater rates of transmission of SARS-CoV-2, likely due to increased contact rates in areas with greater density. The effect of population density and R0 was not modified by private transportation use. Differential R0 by population density can assist in more accurate predictions of the rate of spread of SARS-CoV-2 in areas that do not yet have active cases.


Three-dimensional photoprecipitation of oriented LiNbO3-like crystals in silica-based glass with femtosecond laser irradiation.
We demonstrate crystals (LiNbO(3)-like) that were space-selectively nucleated and grown in the bulk of silica-based glass by femtosecond laser irradiation at a high repetition rate (typ. 300 kHz). Oriented crystals with their polar axis mostly aligned with or perpendicular to the laser scanning direction have been fabricated by manipulation of the temperature gradient in adjusting the laser parameters. The mechanism for the orientation of femtosecond laser-induced crystallization is briefly discussed.


Prevalence of oro-dental anomalies among schoolchildren in Sana'a city, Yemen.
Practitioners and policy-makers need information about the relative frequency of dental anomalies among children in their region. This study investigated the prevalence of different oral anomalies among schoolchildren in Sana'a city, Yemen. A sample of 1000 private and public schoolchildren aged 4-12 years were examined by the same examiner using disposable tongue blades. The total prevalence of oral anomalies was 15.1%, most commonly in boys (male:female ratio 3.2:1) aged 7-12 years. The most prevalent dental anomaly related to hard tissues was tooth hypoplasia (2.8%), followed by hypocalcification (2.6%), then microdontia (0.5%), macrodontia (0.4%), hypodontia (0.4%), supernumerary teeth (0.3%), tooth transposition (0.3%), dental fusion (0.2%) and gemination (0.2%). The most prevalent soft tissues anomaly was fissured tongue (4.0%), followed by ankyloglossia (1.8%), geographic tongue (0.9%), macroglossia (0.4%) and hairy tongue (0.3%). Appropriate measures need to be taken early to mitigate the negative impact and later costs of treatment of anomalies.


Hierarchical classification of snowmelt episodes in the Pyrenees using seismic data.
In recent years the analysis of the variations of seismic background signal recorded in temporal deployments of seismic stations near river channels has proved to be a useful tool to monitor river flow, even for modest discharges. The objective of this work is to apply seismic methods to the characterization of the snowmelt process in the Pyrenees, by developing an innovative approach based on the hierarchical classification of the daily spectrograms. The CANF seismic broad-band station, part of the Geodyn facility in the Laboratorio Subterráneo de Canfranc (LSC), is located in an underground tunnel in the Central Pyrenees, at about 400 m of the Aragón River channel, hence providing an excellent opportunity to explore the possibilities of the seismic monitoring of hydrological events at long term scale. We focus here on the identification and analysis of seismic signals generated by variations in river discharge due to snow melting during a period of six years (2011-2016). During snowmelt episodes, the temporal variations of the discharge at the drainage river result in seismic signals with specific characteristics allowing their discrimination from other sources of background vibrations. We have developed a methodology that use seismic data to monitor the time occurrence and properties of the thawing stages. The proposed method is based on the use of hierarchical clustering techniques to classify the daily seismic spectra according to their similarity. This allows us to discriminate up to four different types of episodes, evidencing changes in the duration and intensity of the melting process which in turn depends on variations in the meteorological and hydrological conditions. The analysis of six years of continuous seismic data from this innovative procedure shows that seismic data can be used to monitor snowmelt on long-term time scale and hence contribute to climate change studies.


O-(2-[18F]-Fluoroethyl)-L-Tyrosine (FET) in Neurooncology: A Review of Experimental Results.
In recent years, PET using radiolabelled amino acids has gained considerable interest as an additional tool besides MRI to improve the diagnosis of cerebral gliomas and brain metastases. A very successful tracer in this field is O-(2-[18F]fluoroethyl)-L-tyrosine (FET) which in recent years has replaced short-lived tracers such as [11C]-methyl-L-methionine in many neuro-oncological centers in Western Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2- [18F]fluoro-2-deoxy-D-glucose. Many clinical studies have demonstrated that FET PET provides important diagnostic information regarding the delineation of cerebral gliomas for therapy planning, an improved differentiation of tumor recurrence from treatment-related changes and sensitive treatment monitoring. In parallel, a considerable number of experimental studies have investigated the uptake mechanisms of FET on the cellular level and the behavior of the tracer in various benign lesions in order to clarify the specificity of FET uptake for tumor tissue. Further studies have explored the effects of treatment related tissue alterations on tracer uptake such as surgery, radiation and drug therapy. Finally, the role of blood-brain barrier integrity for FET uptake which presents an important aspect for PET tracers targeting neoplastic lesions in the brain has been investigated in several studies. Based on a literature research regarding experimental FET studies and corresponding clinical applications this article summarizes the knowledge on the uptake behavior of FET, which has been collected in more than 30 experimental studies during the last two decades and discusses the role of these results in the clinical context.


Safety, efficacy and bronchodilator-sparing effects of nebulized cromolyn sodium solution in the treatment of asthma in children.
In a 12-week study 20 children, ages two to seven years, with moderate to severe asthma received 20 mg cromolyn sodium via a power-driven nebulizer four times daily. Entry criteria required that each patient be maintained on at least one bronchodilator on a daily basis prior to the study. By the conclusion of the trial asthmatic symptoms had declined significantly (p less than 0.01), both as scored by the patients and by the physician. These was a 73% reduction in theophylline dosage over-all. No significant adverse reactions occurred, and there were no meaningful changes in clinical chemistry tests hematology or urinalyses.


Stigmatization of Ebola virus disease survivors in 2022: A cross-sectional study of survivors in Sierra Leone.
Evidence has demonstrated a high proportion of Ebola virus disease (EVD) survivors experienced stigma due to the disease. This study sought to understand the longer-term effects of stigma encountered by survivors of the 2014-2016 EVD epidemic living in Sierra Leone. This was a cross-sectional study of 595 EVD survivors and 403 close contacts (n = 998) from Sierra Leone. Assessments were conducted using a three-part survey between November 2021 to March 2022. We explored the socio-demographic factors associated with stigma experienced by EVD survivors. 50·6 % (n = 301) of EVD survivors reported that they continued to experience at least one aspect of stigma. Females were disproportionately affected by stigma, with 45·2 % of females reporting isolation from friends and family compared to 33·9 % of men (p = 0·005). Multivariable logistic regression models revealed those aged 40-44, living rurally, and reporting an acute infection longer than seven days was associated with EVD-related stigma at the time of survey. This study demonstrates stigma is still prevalent among people who survived EVD in 2022. It also identified socio-demographic factors associated with stigma that can be used for targeting interventions. Importantly, this highlights the continued need for EVD survivors to access mental healthcare and social support systems well after disease recovery. This study was funded by the Canadian Institutes for Health Research (Grant no. PJT-175098. JK is funded by a Tier 2 Canada Research Chair in the Molecular Pathogenesis of Emerging and Re-Emerging Viruses. SS is funded by a Tier 2 Canada Research Chair in Program Science and Global Public Health.


American Association for Cancer Research: dendritic cells: strategies and vaccines. April 1-5, 2000, San Francisco, CA, USA.
Several major sessions on dendritic cells (DCs) reflected the importance of these members of the immune system within cancer research. Technical hurdles to their routine propagation were largely overcome within the past decade, so the study of precursors, as well as the numerous types of dendritic cells, is the focus of intense research. In vitro studies were presented that described further refinements in dendritic cells are collected and culture. Cytokines and other growth factors have been analysed to assess their contribution to the ability of dendritic cells to intake, process and present antigen. In some instances, the dendritic cells themselves are genetically altered to improve their natural biological activity. Many studies have advanced from in vitro work and demonstrated utility in various animal models. Ultimately, there is the hopeful, steady progress into the increasing numbers of experimental immunotherapies against human cancer.


Comparison of laparoscopic Toupet and laparoscopic Nissen fundoplications in neurologically normal children.
We compared laparoscopic Toupet fundoplication (LTF) and laparoscopic Nissen fundoplication (LNF) in neurologically normal children. Forty neurologically normal children who were followed up for more than 3 years after LTF (n = 22) or LNF (n = 18) were reviewed retrospectively. LTF and LNF were performed between 2006 and 2012. There were no significant differences in gender (LTF, 15 male and 7 female patients; LNF:, 12 male and 6 female patients), mean age at surgery (LTF vs LNF: 2.5 vs 2.3 years), mean weight at surgery (LTF vs LNF: 9.6 vs 8.9 kg), preoperative symptoms, preoperative pH monitoring (pH <4) (LTF vs LNF: 26.7% vs 21.8%), mean operative time (LTF vs LNF: 117 vs 126 min), postoperative recommencement of enteral feeding (LTF vs LNF: 3.7 vs 3.8 days), or duration of hospitalization (LTF vs LNF: 5.5 vs 6.3 days). Intraoperative complications were esophageal trauma (LTF; n = 1; 4.5%) and liver trauma (LNF; n = 1; 5.6%) (P = 0.70). Post-LTF complications were wrap stenosis (n = 1; 4.5%), and post-LNF complications were wrap stenosis (n = 1; 5.5%) and gastric outlet obstruction (n = 1; 5.5%) (P = 0.43); all were managed conservatively. No case required conversion to open repair. There was no recurrence after LTF, but there were three cases (16.7%) after LNF (P = 0.08). Reoperation was performed at 4, 11, and 13 months, respectively. Despite LTF and LNF appearing to be equally effective, three LNF cases required reoperation.


Targeted development of informative microsatellite (SSR) markers.
We describe a novel approach, selectively amplified microsatellite (SAM) analysis, for the targeted development of informative simple sequence repeat (SSR) markers. A modified selectively amplified microsatellite polymorphic loci assay is used to generate multi-locus SSR fingerprints that provide a source of polymorphic DNA markers (SAMs) for use in genetic studies. These polymorphisms capture the repeat length variation associated with SSRs and allow their chromosomal location to be determined prior to the expense of isolating and characterising individual loci. SAMs can then be converted to locus-specific SSR markers with the design and synthesis of a single primer specific to the conserved region flanking the repeat. This approach offers a cost-efficient and rapid method for developing SSR markers for predetermined chromosomal locations and of potential informativeness. The high recovery rate of useful SSR markers makes this strategy a valuable tool for population and genetic mapping studies. The utility of SAM analysis was demonstrated by the development of SSR markers in bread wheat.


[Infectious endocarditis in intravenous drug abusers].
Clinical course of infectious endocarditis (IE) was analysed for 43 intravenous drug abusers. 42 of them had primary IE, one patient--secondary. Acute course and high activity of the disease were registered in 86% of the patients. IE was provoked by Staphylococcus aureus (50%), Staphylococcus epidermidis 920%), Staphylococcus haemolyticus (11%), E. coli (8%), Pseudomonas aeruginosa (2%), Candida albicans (2%), mixed microflora (7%). Vegetations were detected on the tricuspid, mitral and aortic valves (52, 23 and 19%, respectively), on more than one valve (6%). Pneumonia, pleuricy, hydrothorax, enlargement of the liver, spleen, nephritis and anemia were found in 76, 44, 9, 100, 75, 70 and 88% of the patients, respectively. Cardiac failure aggravated the disease in half of the patients, lethality was 18%. Thus, IE in intravenous drug abusers is characterized by a primary form, acute active course, prevalent damage to the tricuspid valve, polyorganic involvement, high lethality. IE cure in such patients is feasible only in adequate antibacterial therapy, timely surgical correction and giving up drug abuse.


Greater omentum in reconstruction of refractory wounds.
To evaluate the clinical efficacy of greater omentum in reconstruction of refractory wounds. From August 1988 to May 2001, 20 patients with refractory wound underwent pedicle or microvascular free transfer of the greater omentum. Indications of surgery were electrical injury of the wrist and hand in 9 patients, electrical injury of the scalp and cranial bones in 3, avulsion injury of the scalp in 2, radiation-related ulcer of the chest wall in 2, ulcer and osteomyelitis following resection of the sternum sarcoma in 1, electrical injury of the abdomen in 1, bone and soft tissue defects following compound fracture of the leg in 1, and extensive scar and ulcer of the leg and footdrop following trauma in 1. Severe infection and extensive tissue necrosis were present prior to surgical operation in 12 patients. Eleven patients were treated with pedicled omental flaps, and 9 patients with free omental flaps. The size of the omental flaps ranged from 20 cm x 12 cm to 38 cm x 23 cm. All the omental flaps survived. Healing at the first intention of the wounds was achieved in 17 cases. The on-top skin grafts resulted in partial necrosis of lipid liquefaction developed in the omentum and healed with dressing change in 2 cases. A sinus tract of osteomyelitis occurred in one case and healed after delayed excision of the necrosed bone. Follow-up study of all cases from 3 to 24 months showed no recurrent wounds and post-operative abdominal complication. Recovery with acceptable appearance and restoration of function was satisfactory. Greater omentum provides a well-vascularized tissue with lymphatic ducts for wound coverage. It has strong resistance against infection. It is very malleable and can be molded easily. Therefore it is an ideal tissue in filling cavities and repairing defects, especially in covering large and irregular defects that can not be treated with skin or muscle flaps.


Chronic infection of human umbilical vein endothelial cells by human herpesvirus-6.
Human herpesvirus-6 (HHV-6) exhibits a predominant tropism for CD4+ T-lymphocytes, but can infect other components of the blood as well as surrounding tissue and organs. To understand the role of the endothelium in the transmission and haematogenous spread of this virus, human umbilical vein endothelial cells (HUVEC) were infected with HHV-6 and monitored for viral gene expression. The presence of both early and late viral antigens was demonstrated by indirect immunofluorescence in 37.6 and 6.5%, respectively, of HUVEC. However, attempts to detect the release of infectious virus were not successful, indicating infection is semipermissive in nature. Upon continued passage of infected HUVEC monolayers, HHV-6 antigen-positive cells persisted up to 27 days post-infection. Furthermore, the virus could be recovered from HUVEC monolayers that contained fewer than 1% antigen-positive cells by co-cultivation with peripheral blood mononuclear cells. Together, these findings suggest that endothelial cells may serve as a reservoir for harbouring HHV-6.


A histologic study of fractured human vertebral bodies.
Twenty-seven fractured human vertebral bodies and 24 unfractured human vertebrae from adjacent levels were studied postmortem using histologic and high-resolution radiographic techniques. The findings were compared with those in the vertebral bodies of individuals without spinal fracture. Forty-six human thoracolumbar spines were obtained from individuals at autopsy. Standard radiographs were made of all specimens. Twelve of the 46 individuals had a total of 27 fractured vertebral bodies by plain radiographic criteria. Attention was focused on these fractured vertebrae as well as on 24 unfractured vertebral bodies that were harvested from a level immediately adjacent to the fractured vertebral bodies. Twelve vertebral bodies from four individuals with no evidence of fracture or inflammatory spondyloarthropathy were also studied for comparison. The vertebral bodies were graded by their mineral density as measured by dual-energy x-ray absorptiometry and sectioned into 3-mm sagittal cuts. High-resolution contact radiographs were prepared for each section prior to decalcification and tissue sectioning on a large format microtome. Mid-and parasagittal tissue sections of each vertebra were prepared for standard hematoxylin and eosin stains. A total of 126 sections were studied. The histologic characteristics of the fractured vertebrae (n = 27) were compared with those of adjacent unfractured levels (n = 24) and with vertebrae from individuals without fracture (n = 12). Vertebral bodies with fractures secondary to osteoporosis were consistently characterized histologically by focal areas of endochondral new bone formation adjacent to avascular necrotic bone and unreactive marrow. Such ongoing new bone and new vessel formation adjacent to nonhealing areas were also documented in radiographically unfractured vertebral bodies from individuals with osteoporotic fractures at adjacent levels. No areas of endochondral new bone formation or areas of focal necrosis were found in vertebral bodies from individuals without radiographic evidence of osteoporosis. A vascular necrosis of the vertebral body is a common histologic finding in individuals with osteoporosis. Indeed, our histologic observations suggest subclinical fractures and microfractures of the vertebral body may be the underlying pathologic process leading to avascular necrosis in individuals with osteoporosis. Microtrabecular fractures and endplate fractures were commonly seen in osteoporotic vertebral bodies, often in vertebrae that appeared to be uninvolved on specimen radiographs.


Broadband, wide-angle and tunable terahertz absorber based on cross-shaped graphene arrays.
Tunable terahertz absorbers composed of periodically cross-shaped graphene arrays with the ability to achieve near-unity absorbance are proposed and studied. Our results demonstrate that the bandwidth of absorption rate above 90% can reach up to 1.13 terahertz by use of a single layer of cross-shaped graphene arrays. By simply stacking the double layer cross-shaped graphene with careful design, the working bandwidth can be broadened compared with the single-layer graphene-based absorber. The proposed absorbers have the properties of being polarization insensitive and having large angle tolerance, and the tunability of the Fermi level in graphene allows us to realize tunable terahertz absorbers with potential interest in integrated terahertz optoelectronic devices.


Micro-electrolysis technology for industrial wastewater treatment.
Experiments were conducted to study the role of micro-electrolysis in removing chromaticity and COD and improving the biodegradability of wastewater from pharmaceutical, dye-printing and papermaking plants. Results showed that the use of micro-electrolysis technology could remove more than 90% of chromaticity and more than 50% of COD and greatly improved the biodegradability of pharmaceutical wastewater. Lower initial pH could be advantageous to the removal of chromaticity. A retention time of 30 minutes was recommended for the process design of micro-electrolysis. For the use of micro-electrolysis in treatment of dye-printing wastewater, the removal rates of both chromaticity and COD were increased from neutral condition to acid condition for disperse blue wastewater; more than 90% of chromaticity and more than 50% of COD could be removed in neutral condition for vital red wastewater.


Procyanidins and sensory nutrition; Do procyanidins modulate homeostasis via astringent taste receptors?
Long-term intake of procyanidins has been suggested to reduce the risk of cardiovascular disease, dementia, and sensory function decline associated with aging. However, most of the ingested procyanidins are not absorbed and are excreted in the feces, so the mechanism of their beneficial impact is unknown. Procyanidins are the components of astringency in plant foods and their stimulation appears to be directly transmitted to the central nervous system via sensory nerves. Recent attention has been focused on the taste receptors expressed in the extra-oral gastrointestinal tract may regulate homeostasis via the neuroendocrine system. In this paper, we have reviewed recent findings on the relationship between the astringency of procyanidins and their bioregulatory effects.


CD44 and RHAMM expression patterns in the human developing lung.
The hyaluronan (HA) receptors CD44 and RHAMM (CD168) are involved in cellular proliferation, differentiation, and motility. As previously investigated, HA and RHAMM expression in human neonatal lungs correlates to gestational age (GA) and air content. CD44 immunofluorescence was analyzed in postmortem lung samples from infants (n = 93; 22-41 GA) by digital image analysis together with clinical data, including RHAMM expression, lung air, and HA content by hierarchical clustering. Five groups were defined according to RHAMM/CD44 expression, GA, and postnatal age (PNA): extremely to very preterm (EVP; 22-31 GA; Groups 1-2), moderately preterm to term (MPT; 31-41 GA; Groups 3-4), and mixed preterm to term (27-40 GA; Group 5). CD44 correlated linearly with RHAMM in MPT (r = 0.600; p < 0.004). In EVP, high CD44 and low RHAMM corresponded with high PNA and lung air content independently of HA and GA (Group 1 vs 2; p < 0.05). In MPT, high and low CD44 corresponded with low and high RHAMM independently of GA, HA, and lung air content (Group 3 vs 4; p < 0.001). No correlation between CD44 and GA/PNA at death was observed. A linear correlation between CD44 and RHAMM expression occurs during the late saccular phase of lung development at birth, whereas postnatal influences on CD44 and RHAMM expression in extremely to very preterm infants cannot be excluded. The interplay between CD44 and RHAMM, two receptors of hyaluronic acid, can be dependent on the lung developmental stage at birth. This is the second study that analyzes the distribution pattern of CD44 in the human lung during development and the first study performed with quantitative analysis of CD44 expression together with RHAMM expression in the human lung. Our results suggest a relationship in a subset of infants between CD44 and RHAMM expression, which appears at birth during the late saccular stage but not during the earlier stages of lung development.


[Detailed neurologic findings in speech-disordered school children].
We report upon school-children with speech disorders who were examined by a standardized neurological examination. Compared with normal school-children the speech disturbed children show a higher degree of minor nervous dysfunction. The results can be interpreted as a focal disturbance resp. as a developmental deficit of the CNS. Our findings are congruent with those known in literature. We propose to use the discriminating neurological subtests of the mentioned examination as a screening for speech and motor disturbances even in preschool-age.


Characteristics of tree nut challenges in tree nut allergic and tree nut sensitized individuals.
Characteristics and outcomes of tree nut (TN) oral food challenges (OFCs) in patients with TN allergy or sensitization alone are poorly studied. To determine the relation between TN sensitization levels and OFC outcomes. Open TN OFCs performed from 2007 through 2015 at a referral center were analyzed to compare outcome based on skin prick test (SPT) wheal size, food-specific immunoglobulin E (sIgE), peanut co-allergy, and TN sensitization only vs TN allergy with sensitization to other TNs. Delayed OFC was defined as longer than 12 months from the time of an sIgE level lower than 2 kUA/L. Overall passage rate was 86% for 156 TN OFCs in 109 patients (54 almond, 28 cashew, 27 walnut, 18 hazelnut, 14 pecan, 13 pistachio, and 2 Brazil nut). Passage rates were 76% (n = 67) in patients with a history of TN allergy who were challenged to another TN to which they were sensitized and 91% (n = 65) in those with TN sensitization only (mean sIgE 1.53 kUA/L; range 0.35-9.14). Passage rates were 89% (n = 110 of 124) for a TN sIgE level lower than 2 kUA/L and 69% (11 of 16) for a TN sIgE level of at least 2 kUA/L. In 44 challenges in patients with peanut allergy and TN co-sensitization, the TN OFC passage rate was 96%. In 41 TN OFCs with a TN SPT wheal size of at least 3 mm, 61% passed, with a mean wheal size of 4.8 mm (range 3-11) in those passing vs 9 mm (range 3-20) in those failing. TN challenges are frequently passed in patients with TN sensitization with or without a history of TN reactivity despite a TN SPT wheal of at least 3 mm or a TN sIgE level of at least 2 kUA/L. Nearly all patients with peanut allergy and TN co-sensitization passed the TN challenge, questioning the clinical relevance of "co-allergy."


A patient-centered approach to counseling patients with head and neck cancer undergoing human papillomavirus testing: a clinician's guide.
The International Agency for Research on Cancer and the National Cancer Institute have acknowledged human papillomavirus (HPV)-16 as an independent risk factor for oropharyngeal cancer (OPC). HPV-positive oropharyngeal cancer (HPVOPC) is a sexually transmitted entity that is on the rise; within the next 10 years, the annual number of HPV-associated OPC cases is projected to exceed the annual number of cervical cancer cases in the United States. Recognition of HPV status in OPC has broad implications beyond the traditional oncological concerns of timely diagnosis, accurate staging, and appropriate treatment of cancer patients. The National Comprehensive Cancer Network recommends testing the tumor site for HPV-status during OPC management; it is likely this will become a standard component of care for patients with high-probability tumors of the oropharynx. As the practice of HPV testing becomes more common, it behooves providers to be able to adequately address the concerns of patients with HPVOPC. Although there are currently few relevant studies focusing on this population, existing literature on HPV-infected women and patients with cervical cancer strongly supports the concept that patients with HPVOPC need education to optimally address concerns such as self-blame, guilt, intimacy, and interpersonal relationships. When HPV testing is done, it should be accompanied by evidence-driven and patient-centered counseling to best minimize negative psychosocial outcomes and ensure optimum health promotion. Based on the current state of the literature, this article is intended to be a reference for physicians to effectively manage psychosocial outcomes when diagnosing patients with HPV-associated OPC.


Elobixibat, the first-in-class Ileal Bile Acid Transporter inhibitor, for the treatment of Chronic Idiopathic Constipation.
Elobixibat is the first in class ileal bile acid transporter (IBAT) inhibitor. IBAT inhibitors block ileal absorption of bile acids by: (1) interrupting the enterohepatic circulation of bile resulting in a fall in serum cholesterol and (2) increasing the delivery of bile acids into the colon. Increasing colonic bile acids causes mucosal fluid secretion and enhances colonic motor activity. Changes in colonic physiology may be useful in treating constipation. Areas covered: In this review, the author reviews the prevalence and medical cost of Chronic Idiopathic Constipation (CIC) and the heterogeneity of the CIC patient population as a complicating factor in drug development and clinical care. He also reviews the history of Bile Acid cathartics and the complex pharmacophysiology of bile therapy with fluid and electrolyte shifts, colonic motor function changes and mucosal immunologic activation. Finally, the author reviews elobixabat development and the clinical trials that demonstrate improvement in constipation. Expert opinion: The early phases of elobixibat development provide confirmation of high IBAT binding affinity which translates into the expected inhibition of enterohepatic bile acid circulation and enhanced delivery of ileal bile acids to the colon associated with expected physiological changes. Elobixibat as a treatment of CIC appears promising.


Effect of nizatidine on olanzapine-associated weight gain in schizophrenic patients in Korea: a pilot study.
A pilot study was conducted to evaluate the effect of nizatidine on olanzapine-associated weight gain (OAWG) in ten patients with schizophrenia and schizophreniform disorder in Korea. Psychometric ratings with positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) were measured at baseline, week 4 and week 8; as were weight and body mass index (BMI). A combination of nizatidine for 8 weeks resulted in significant reversal of weight gain without worsening the psychopathology (weight: 3.5% and BMI: 3.7%). In line with studies of Western populations, an add-on therapy of nizatidine could be an effective option for the control of weight gain in olanzapine-treated patients in Korea. Our findings call for further evaluation of the effect of this drug on OAWG, with randomized placebo-controlled studies, in Asian populations.


Risks and diagnosis of coronary artery disease in Hodgkin lymphoma survivors.
Higher mortality rates are reported because of cardiovascular diseases in individuals living in industrialized areas of the World. In cancer patients, cardiotoxic chemotherapeutic agents and/or mediastinal radiotherapy are additional risk factors for the development of coronary artery disease. An improved survival rate for patients with Hodgkin lymphoma was reported in recent decades. Determining and handling the long-term effects of cancer treatment have become more important nowadays, parallel to the good results reached in survival rates. Mediastinal radiotherapy and cardiotoxic chemotherapeutic agents are routinely used to treat Hodgkin lymphoma but are commonly associated with a variety of cardiovascular complications. Drugs used in cancer treatment and radiotherapy may cause deleterious effects on contractile capacity and conduction system of the heart. Approximately ten years after the completion of all therapies, the cardiovascular disease risk peaks in patients who survived from Hodgkin lymphoma. The value of coronary computed tomography angiography as a diagnostic tool in determining coronary artery disease as early as possible is underlined in this review, in patients who are in remission and carry the risk of coronary artery disease probably because of chemo/radiotherapy used in their treatment. Survivors of Hodgkin lymphoma especially treated with combined chemoradiotherapy at younger ages are candidates for coronary computed tomography angiography.


Andalusian Registry for familial adenomatous polyposis. Analysis of patients included.
To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p < 0.05). The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic-genotypic correlation with statistical significance.


[Nucleotide sequence of the replicative region of the plasmid ColA-CA31].
ColA-CA31 plasmid DNA region, responsible for the autonomous replication, has been sequenced. The replicative regions of plasmids ColA and ColE1 share the high homology demonstrated in the paper. DNA nucleotide sequences necessary for initiation of RNA I and primer RNA transcription were localized on the ColA genome. RNA I and preprimer RNA of ColA and ColE1 have the similar secondary structure including three palindromes. The absence of homology in ColA and ColE1 hair-pin loops suggests the compatibility of these two plasmids.


Glutamine supplementation to prevent morbidity and mortality in preterm infants.
Glutamine endogenous biosynthesis may be insufficient for tissue needs in states of metabolic stress. Trials in adults have suggested that glutamine supplementation improves clinical outcomes in critically ill adults. It has been suggested that glutamine supplementation may benefit preterm infants, particularly very low birth weight infants. To determine the effects of glutamine supplementation on mortality and morbidity in preterm infants. The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1966 - July 2007), EMBASE (1980 - July 2007), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials that compared glutamine supplementation versus no glutamine supplementation in preterm infants at any time from birth to discharge from hospital. The standard methods of the Cochrane Neonatal Review Group were used, with separate evaluation of trial quality and data extraction by two authors. Data were synthesised using a fixed effects model and reported using typical relative risk, typical risk difference and weighted mean difference. 2365 preterm infants have participated in seven randomised controlled trials. All of the participating infants were of very low birth weight. Three trials assessed enteral glutamine supplementation and four trials assessed parenteral glutamine supplementation. The trials were generally of good methodological quality with adequate allocation concealment, blinding of caregivers and assessors to the intervention, and complete or near-complete follow-up of recruited infants. Glutamine supplementation does not have a statistically significant effect on mortality: typical relative risk 0.98 (95% confidence interval 0.80 to 1.20); typical risk difference 0.00 (95% confidence interval -0.03 to 0.02). The only trial that assessed long-term outcomes did not find any statistically significant differences in various assessments of neurodevelopment at 18 months corrected age. Glutamine supplementation does not have a statistically significant effect on other neonatal morbidities including invasive infection, necrotising enterocolitis, time to achieve full enteral nutrition, or duration of hospital stay. The available data from good quality randomised controlled trials indicate that glutamine supplementation does not confer benefits for preterm infants. The narrow confidence intervals for the effect size estimates suggest that a further trial of this intervention is not a research priority.


Insufficient evidence to conclude whether or not Transcendental Meditation decreases blood pressure: results of a systematic review of randomized clinical trials.
To carry out an independent, systematic review of randomized clinical trials of Transcendental Meditation (TM) for cumulative effects on blood pressure. Searches were made of electronic databases and the collected papers and official web sites of the TM organization. We included only randomized clinical trials, without confounding co-interventions, which measured the cumulative effects of TM on blood pressure. Six trials met the inclusion criteria but one, reported only in abstract form, could not be evaluated. Procedures for establishing baseline blood pressure were adequate in only one trial. Only one of the trials included a follow-on assessment and only one of the evaluable trials tested the effect of TM in hypertensive individuals. Three of the five evaluable trials reported statistically significant differences between intervention groups favouring TM and two found no significant differences between intervention groups. None of the five studies was conducted by independent authors without any affiliation to the TM organization. All the randomized clinical trials of TM for the control of blood pressure published to date have important methodological weaknesses and are potentially biased by the affiliation of authors to the TM organization. There is at present insufficient good-quality evidence to conclude whether or not TM has a cumulative positive effect on blood pressure.


Effect of short-term equal-volume resistance training with different workout frequency on muscle mass and strength in untrained men and women.
Changes in muscle mass and strength will vary, depending on the volume and frequency of training. The purpose of this study was to determine the effect of short-term equal-volume resistance training with different workout frequency on lean tissue mass and muscle strength. Twenty-nine untrained volunteers (27-58 years; 23 women, 6 men) were assigned randomly to 1 of 2 groups: group 1 (n = 15; 12 women, 3 men) trained 2 times per week and performed 3 sets of 10 repetitions to fatigue for 9 exercises, group 2 (n = 14; 11 women, 3 men) trained 3 times per week and performed 2 sets of 10 repetitions to fatigue for 9 exercises. Prior to and following training, whole-body lean tissue mass (dual energy x-ray absorptiometry) and strength (1 repetition maximum squat and bench press) were measured. Both groups increased lean tissue mass (2.2%), squat strength (28%), and bench press strength (22-30%) with training (p < 0.05), with no other differences. These results suggest that the volume of resistance training may be more important than frequency in developing muscle mass and strength in men and women initiating a resistance training program.


A macrophage-specific fluorescent probe for intraoperative lymph node staging.
Successful identification of nodal metastases in patients with cancer is crucial to prescribe suitable treatment regimens that can improve recurrence-free survival. Although some new imaging technologies for nodal staging have been developed, such as nanoparticle-enhanced MRI and quantum-dot-based fluorescence imaging, sound technologies for intraoperative differentiation of metastatic and inflamed lymph nodes remain lacking. In this study, we illustrate the feasibility of using a macrophage-specific fluorescent probe (MFP) to visualize sentinel lymph nodes during surgery, highlighting abnormalities related to inflammation and tumor infiltration with signal enhancement and reduction methods using this technology. MFP was identified by high-throughput screening of fluorescent small-molecule libraries synthesized with a diversity-oriented approach. It selectively visualized monocyte and macrophage cell populations in vitro, by live-cell imaging and flow cytometry, as well as in vivo, for imaging-guided surgery. Collectively, this study provides preclinical proof of concept for an intraoperative imaging platform to accurately assess lymph node status, eliminating the need for invasive nodal dissections that can contribute to complications of cancer therapy.


Expression of alpha-smooth muscle actin in murine bone marrow stromal cells.
Human fibrotic bone marrow (BM) stroma has been shown to contain alpha-smooth muscle actin (alpha-SMA)-positive cells. These closely resemble myofibroblasts that were described in other fibrotic tissues. We studied the expression of alpha-SMA in a series of murine BM-derived stromal cell lines to investigate the cellular origin and functional significance of myofibroblast-like cells in hematopoietic tissues. Although these cell lines differed in their biologic properties, most of them expressed alpha-SMA under certain conditions. Cells expressing alpha-SMA constituted a minor population in post-confluent, growth-arrested cultures. However, the incidence of cells expressing alpha-SMA increased significantly when cultures were transferred to nonconfluent conditions. A similar increase in alpha-SMA-positive cells occurred after a strip of cells was scraped away from the confluent cell layer; the cells of the affected area acquired alpha-SMA-positive contractile phenotype. The relationship between alpha-SMA expression and hematopoietic activity was studied using a cloned cell line of BM origin (14F1.1). The ability of these endothelial-adipocyte cells to support hematopoiesis in vitro was maximal under confluent conditions, whereas their expression of alpha-SMA under such conditions was residual. Moreover, in long-term BM cultures supported by confluent 14F1.1 cells, stromal areas associated with proliferating hematopoietic precursors, known as "cobblestone areas," were devoid of alpha-SMA-positive cells. These observations suggest that the expression of alpha-SMA is reversible and inversely related to hematopoietic activity.


[Estimation of risk areas for hepatitis A].
This study estimated hepatitis A risk areas in a region of Duque de Caxias, Rio de Janeiro State, Brazil. A cross-sectional study consisting of a hepatitis A serological survey and a household survey were conducted in 19 census tracts. Of these, 11 tracts were selected and 1,298 children from one to ten years of age were included in the study. Geostatistical techniques allowed modeling the spatial continuity of hepatitis A, non-use of filtered drinking water, time since installation of running water, and number of water taps per household and their spatial estimation through ordinary and indicator kriging. Adjusted models for the outcome and socioeconomic variables were isotropic; risk maps were constructed; cross-validation of the four models was satisfactory. Spatial estimation using the kriging method detected areas with increased risk of hepatitis A, independently of the urban administrative area in which the census tracts were located.


Determinants of the glomerular filtration of proteins.
We showed previously that a theoretical model treating the glomerular capillary wall as a membrane with uniformly distributed fixed negative charges can account for the observed filtration rates of charged derivatives of dextran in the rat. Using measurements of electrophoretic mobility to estimate effective molecular charge, a necessary input parameter, we present evidence that this model is also consistent with reported filtration rates of several proteins in the rat. Apparent fixed-charge concentrations calculated for serum albumin and three forms of horseradish peroxidase are in the range of 100-130 meq/liter, comparable to the 120-170 meq/liter obtained for charged dextrans. Theoretical effects of hemodynamic changes on filtration of charged macromolecules are considered. With increases in glomerular plasma flow rate (QA) or transcapillary hydraulic pressure difference (delta P), the filtrate-to-plasma concentration ratio (theta) is generally predicted to decrease for neutral or anionic macromolecules but to increase for cationic substances. The more highly charged the macromolecule (cationic or anionic), the more sensitive theta is to such hemodynamic perturbations. For serum albumin, absolute filtration rates are predicted to increase as much as twofold for moderate decreases in QA combined with increases in delta P. Alterations in protein molecular charge offer an attractive explanation for changes in protein filtration during acidosis or alkalosis.


The removal of cusps from galaxy centres by stellar feedback in the early Universe.
The standard cosmological model, now strongly constrained by direct observations of the Universe at early epochs, is very successful in describing the evolution of structure on large and intermediate scales. Unfortunately, serious contradictions remain on smaller, galactic scales. Among the main small-scale problems is a significant and persistent discrepancy between observations of nearby galaxies, which imply that galactic dark matter haloes have a density profile with a flat core, and the cosmological model, which predicts that the haloes should have divergent density (a cusp) at the centre. Here we report numerical simulations that show that random bulk motions of gas in small primordial galaxies, of the magnitude expected in these systems, will result in a flattening of the central dark matter cusp on relatively short timescales (approximately 10(8) years). Gas bulk motions in early galaxies are driven by supernova explosions that result from ongoing star formation. Our mechanism is general, and would have operated in all star-forming galaxies at redshifts z > or = 10. Once removed, the cusp cannot be reintroduced during the subsequent mergers involved in the build-up of larger galaxies. As a consequence, in the present Universe both small and large galaxies would have flat dark matter core density profiles, in agreement with observations.


Learning, not adaptation, characterizes stroke motor recovery: evidence from kinematic changes induced by robot-assisted therapy in trained and untrained task in the same workspace.
Both the American Heart Association and the VA/DoD endorse upper-extremity robot-mediated rehabilitation therapy for stroke care. However, we do not know yet how to optimize therapy for a particular patient's needs. Here, we explore whether we must train patients for each functional task that they must perform during their activities of daily living or alternatively capacitate patients to perform a class of tasks and have therapists assist them later in translating the observed gains into activities of daily living. The former implies that motor adaptation is a better model for motor recovery. The latter implies that motor learning (which allows for generalization) is a better model for motor recovery. We quantified trained and untrained movements performed by 158 recovering stroke patients via 13 metrics, including movement smoothness and submovements. Improvements were observed both in trained and untrained movements suggesting that generalization occurred. Our findings suggest that, as motor recovery progresses, an internal representation of the task is rebuilt by the brain in a process that better resembles motor learning than motor adaptation. Our findings highlight possible improvements for therapeutic algorithms design, suggesting sparse-activity-set training should suffice over exhaustive sets of task specific training.


Sensitivity of chest fluoroscopy compared with chest CT and chest radiography for diagnosing hydropneumothorax in association with percutaneous nephrostolithotomy.
Hydropneumothorax (HPTX) is recognized as a potential complication of percutaneous nephrostolithotomy (PCNL), particularly with supracostal access. Postoperative chest radiography (CXR) is routinely used to evaluate the chest after PCNL. We prospectively compared the sensitivity of intraoperative chest fluoroscopy with immediate postoperative portable CXR and postoperative day 1 chest computed tomography (CT) for the detection of pleural fluid. A total of 89 consecutive patients (mean age 47.9 +/- 13.3 years; 100 renal units) undergoing PCNL were prospectively evaluated with intraoperative fluoroscopy at the conclusion of the procedure and then with anteroposterior CXR in the postanesthesia care unit and postoperative day 1 noncontrast, thin-cut CT of the kidneys and lung bases. CT imaging of the lung bases comprised the reference standard for detecting pleural fluid. A total of 104 percutaneous renal accesses in 100 renal units, 60 above and 44 below the 12th rib, were used. In 16 cases (16%), a second-stage procedure was performed to clear residual stone fragments detected on post-PCNL CT. HPTX was detected in 1, 8, and 38 cases by initial fluoroscopy, immediate postoperative CXR, and CT scan, respectively. Intervention was necessary in 7 patients. In 2 patients with fluoroscopic evidence of pleural fluid (1 at the initial PCNL and 1 during second-look flexible nephroscopy), intraoperative pleural drainage was performed percutaneously. In the other 5 patients, intervention was determined by the size of the HPTX on chest CT scan (n = 1) or the presence of symptoms (n = 4). In no case was intervention performed on the basis of the immediate postoperative CXR findings when intraoperative chest fluoroscopy was negative. Intraoperative chest fluoroscopy during PCNL is sufficient to detect clinically significant HPTXs, and, therefore, routine postoperative CXRs are not necessary. However, a high index of suspicion based on clinical symptoms postoperatively should prompt chest imaging.


Implication of the nutritional and nonnutritional factors in the context of preservation of cognitive performance in patients with dementia/depression and Alzheimer disease.
It has been postulated that Alzheimer disease (AD) is a systemic process, which involves multiple pathophysiological factors. A combination of pharmacotherapy and nonpharmacological interventions has been proposed to treat AD and other dementia. The nonpharmacological interventions include but are not limited to increasing sensory input through physical and mental activities, in order to modify cerebral blood flow and implementing nutritional interventions such as diet modification and vitamins and nutraceuticals therapy to vitalize brain functioning. This article highlights the recent research findings regarding novel treatment strategies aimed at modifying natural course of the disease and delaying cognitive decline through simultaneous implementation of pharmacological and nonpharmacological modulators as standardized treatment protocols.


Mouse Models of Bariatric Surgery.
Morbid obesity is linked to increased incidence of glucose intolerance, Type 2 diabetes mellitus, cardiovascular diseases, various forms of liver disease, and specific forms of cancer. Treatment of obesity by lifestyle modifications (i.e., changes in diet and exercise) and drug therapy is generally ineffective. Bariatric surgery is currently the most effective means of treating obesity and related disorders. We as well as others have developed surgical procedures for application to genetic mouse models that mimic an array of human bariatric surgical procedures used in the treatment of obesity. The application of bariatric surgery to genetic mouse models will broaden our understanding of the role of the gut in metabolic disease. Models that have been developed include gastric banding, sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB) with a complete exclusion of the stomach, duodenal-jejunal bypass (DJB), and biliopancreatic diversion (BPD). The detailed methods of these procedures are provided. Curr. Protoc. Mouse Biol. 2:295-306 © 2012 by John Wiley & Sons, Inc.


[Emergent Thoracic Endovascular Aortic Repair and Subxiphoid Pericardiotomy for Retrograde Type A Acute Aortic Dissection with Cardiac Tamponade;Report of a Case].
Type A acute aortic dissection has a high rate of mortality. Emergent surgical repair is the gold standard treatment, but some patients cannot tolerate the open surgery. Here, we report an 82-year-old patient with a history of cerebral infarction and cerebral bleeding who presented with a depressed level of consciousness and who was in a state of shock. A computed tomography (CT) scan showed cardiac tamponade associated with retrograde type A aortic dissection(RAAD), with a primary entry tear at a distal site of the left subclavian artery. We therefore performed emergent primary entry closure with stent grafting using the Conformable Gore Tag device and emergent drainage of the cardiac tamponade with subxiphoid pericardiotomy. Postoperative CT scan showed complete closure of the primary entry tear and a completely thrombosed false lumen. Primary entry closure with stent grafting could be an effective option for RAAD that meets anatomical criteria.


Matrix attachment regions and structural colinearity in the genomes of two grass species.
In order to gain insights into the relationship between spatial organization of the genome and genome function we have initiated studies of the co-linear Sh2/A1- homologous regions of rice (30 kb) and sorghum (50 kb). We have identified the locations of matrix attachment regions (MARs) in these homologous chromosome segments, which could serve as anchors for individual structural units or loops. Despite the fact that the nucleotide sequences serving as MARs were not detectably conserved, the general organizational patterns of MARs relative to the neighboring genes were preserved. All identified genes were placed in individual loops that were of comparable size for homologous genes. Hence, gene composition, gene orientation, gene order and the placement of genes into structural units has been evolutionarily conserved in this region. Our analysis demonstrated that the occurrence of various 'MAR motifs' is not indicative of MAR location. However, most of the MARs discovered in the two genomic regions were found to co-localize with miniature inverted repeat transposable elements (MITEs), suggesting that MITEs preferentially insert near MARs and/or that they can serve as MARs.


Role of heparanase in pulmonary hypertension.
Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right heart dysfunction and even death, especially in critically ill patients. Although drug interventions have shown some efficacy in improving the hemodynamics of PH patients, the mortality rate remains high. Hence, the identification of new targets and treatment strategies for PH is imperative. Heparanase (HPA) is an enzyme that specifically cleaves the heparan sulfate (HS) side chains in the extracellular matrix, playing critical roles in inflammation and tumorigenesis. Recent studies have indicated a close association between HPA and PH, suggesting HPA as a potential therapeutic target. This review examines the involvement of HPA in PH pathogenesis, including its effects on endothelial cells, inflammation, and coagulation. Furthermore, HPA may serve as a biomarker for diagnosing PH, and the development of HPA inhibitors holds promise as a targeted therapy for PH treatment.


Properties of the muscle proteins--a comparative approach.
The differences in performance that exist between skeletal muscles are in part determined by the presence of different forms of most of the contractile and regulatory proteins of the myofibril - isoforms. These isoforms have common properties but their amino acid sequences are not identical and they exhibit slight differences in biological activities, such as ATPase, affinity for calcium, etc., that are appropriate for the physiological properties of the muscle in which they are present. With the exception of actin, all the major proteins present in the I and A filaments of skeletal muscle have been shown to exist in two or more isoforms. Whereas proteins such as troponin I and troponin C are present as a single isoform in each fibre type in normal muscle, others such as myosin and tropomyosin are present as two or more isoforms, usually in relative amounts characteristic for the fibre type. Type I and type II muscle fibres possess the capacity of synthesizing all the skeletal muscle isoforms of the myofibrillar proteins. The complement of isoforms present in a muscle fibre, however, depends on a number of factors such as the stage of development or regeneration, type of innervation, hormonal effects, etc. Complex mechanisms involving the coordinated control of gene expression must operate to ensure that the set of isoforms of the myofibrillar proteins present is characteristic for the cell type.


Hepatitis E in Nepal.
Hepatitis E is an acute disease caused by hepatitis E virus that usually manifest as acute jaundice. The hallmark of the disease is its high incidence in young adults, and high mortality in pregnant women from acute hepatic failure. It is a waterborne infection and occurs sporadically or as epidemic outbreaks. Kathmandu valley is a hyper-endemic area for hepatitis E, where during last 30 years three large epidemics and many focal outbreaks have occurred. About 50% of the sporadic cases of acute hepatitis in Kathmandu valley are caused by hepatitis E. This paper describes the epidemiology hepatitis E in Nepal, and its clinical features and management.


Specific interaction between DNA polymerase II (PolD) and RadB, a Rad51/Dmc1 homolog, in Pyrococcus furiosus.
Pyrococcus furiosus has an operon containing the DNA polymerase II (PolD) gene and three other genes. Using a two-hybrid screening to examine the interactions of the proteins encoded by the operon, we identified a specific interaction between the second subunit of PolD (DP1) and a Rad51/Dmc1 homologous protein (RadB). To ensure the specific interaction between these two proteins, each gene in the operon was expressed in Escherichia coli or insect cells separately and the products were purified. The in vitro analyses using the purified proteins also showed the interaction between DP1 and RadB. The deletion mutant analysis of DP1 revealed that a region important for binding with RadB is located in the central part of the sequence (amino acid residues 206-498). This region has an overlap to the C-terminal half (amino acids 334-613), which is highly conserved among euryarchaeal DP1s and is essential for the activity of PolD. Our results suggest that, although RadB does not noticeably affect the primer extension ability of PolD in vitro, PolD may utilize the RadB protein in DNA synthesis under certain conditions.


Delay in recognition of pulmonary arterial hypertension: factors identified from the REVEAL Registry.
Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder. Despite the emergence of effective therapy, PAH is commonly at an advanced stage when recognized. Factors associated with a prolonged symptomatic period before the recognition of PAH have not been fully evaluated. The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) enrolled 2,967 US adult patients with PAH from March 2006 to September 2007. Patients were considered to have delayed disease recognition if > 2 years elapsed between symptom onset and the patient receiving a PAH diagnosis, starting on PAH-specific therapy, or receiving a diagnosis by right-sided heart catheterization. In 21.1% of patients, symptoms were experienced for > 2 years before PAH was recognized. Patients with onset of PAH symptoms before age 36 years showed the highest likelihood of delayed disease recognition (OR, 3.07; 95% CI, 2.03-4.66). History of obstructive airways disease (OR, 1.93; 95% CI, 1.5-2.47) and sleep apnea (OR, 1.72; 95% CI, 1.33-2.22) were independently associated with delayed PAH recognition. Six-minute walk distance < 250 m (OR, 1.91; 95% CI, 1.16-3.13), right atrial pressure < 10 mm Hg (OR, 1.77; 95% CI, 1.26-2.48), and pulmonary vascular resistance < 10 Wood units (OR, 1.28; 95% CI, 1.02-1.60) were also associated with delayed disease recognition, but sex, race/ethnicity, and geographic region showed no association. One in five patients in the REVEAL Registry who were diagnosed with PAH reported symptoms for > 2 years before their disease was recognized. Younger individuals and patients with histories of common respiratory disorders were most likely to experience delayed PAH recognition. ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.


Systems and synthetic biology to elucidate secondary metabolite biosynthetic gene clusters encoded in Streptomyces genomes.
Covering: 2010 to 2020 Over the last few decades, Streptomyces have been extensively investigated for their ability to produce diverse bioactive secondary metabolites. Recent advances in Streptomyces research have been largely supported by improvements in high-throughput technology 'omics'. From genomics, numerous secondary metabolite biosynthetic gene clusters were predicted, increasing their genomic potential for novel bioactive compound discovery. Additional omics, including transcriptomics, translatomics, interactomics, proteomics and metabolomics, have been applied to obtain a system-level understanding spanning entire bioprocesses of Streptomyces, revealing highly interconnected and multi-layered regulatory networks for secondary metabolism. The comprehensive understanding derived from this systematic information accelerates the rational engineering of Streptomyces to enhance secondary metabolite production, integrated with the exploitation of the highly efficient 'Design-Build-Test-Learn' cycle in synthetic biology. In this review, we describe the current status of omics applications in Streptomyces research to better understand the organism and exploit its genetic potential for higher production of valuable secondary metabolites and novel secondary metabolite discovery.


Basiliximab in pediatric liver transplantation: a pharmacokinetic-derived dosing algorithm.
The pharmacokinetics and immunodynamics of basiliximab were assessed in 37 pediatric de novo liver allograft recipients to rationally design a dose regimen for this age-group. In part one of the study, patients were given 12 mg/m2 basiliximab by bolus intravenous injection after organ perfusion and on day 4 after transplant. An interim pharmacokinetic evaluation supported a fixed-dose approach for part two of the study in which infants and children received two 10-mg doses of basiliximab and adolescents received two 20-mg doses. Blood samples were collected over a 12-week period for screening for anti-idiotype antibodies and analysis of basiliximab and soluble interleukin-2 receptor (IL-2R) concentrations. Basiliximab clearance in infants and children < 9 yr of age (n = 30) was reduced by approximately 50% compared with adults from a previous study and was independent of age to 9 yr, weight to 30 kg, and body surface area to 1.0 m2. Clearance in children and adolescents 9-14 yr of age (n = 7) approached or reached adult values. An average of 15% of the dose was eliminated via drained ascites fluid, and drug clearance via this route averaged 29% of total body clearance. Patients with > 5 L of ascites fluid drainage tended to have lower systemic exposure to basiliximab. CD25-saturating basiliximab concentrations were maintained for 27 +/- 9 days in part one of the study (mg/m2 dosing) with infants exhibiting the lowest durations. CD25 saturation lasted 37 +/- 11 days in part two of the study, based on the fixed-dose regimen (p = 0.004 vs. mg/mg2 dosing), but did not show the age-related bias observed in part one of the study. Anti-idiotype antibodies were detected in four patients, but this did not influence the clearance of basiliximab or duration of CD25 saturation. All 40 enrolled patients were included in the intent-to-treat clinical analysis. Episodes of acute rejection occurred in 22 patients (55%) during the first 12 months post-transplant. Three patients experienced loss of their graft as a result of technical complications, and six patients died during the 12-month study. Basiliximab was well tolerated by intravenous bolus injection, with no cytokine-release syndrome or other infusion-related adverse events. Hence, basiliximab was safe and well tolerated in pediatric patients undergoing orthotopic liver transplantation. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients < 35 kg in weight should receive two 10-mg doses and those > or = 35 kg should receive two 20-mg doses of basiliximab by intravenous infusion or bolus injection. The first dose should be given within 6 h after organ perfusion and the second on day 4 after transplantation. A supplemental dose may be considered for patients with a large volume of drained ascites fluid relative to body size.


Backscattering of light from a dielectric layer on a reflecting substrate.
Scattering of light from rough dielectric films is studied experimentally. It is shown that the interference pattern of the scattered field depends critically on the power spectrum of the roughness, especially on its long-scale component. When the height of roughness is small compared with the wavelength, the backscattering peak (if it exists) is due to the interference of the singly scattered fields; hence the properties of the backscattered peak are rather unusual. In particular, the width of the peak is determined by the thickness of the film and is independent of the parameters of disorder. The intensity of the peak increases with an increase of the rms height of the surface roughness and becomes independent of the rms when the roughness is of the order of the wavelength.


Recovery from cyclophosphamide-induced lymphopenia results in expansion of immature dendritic cells which can mediate enhanced prime-boost vaccination antitumor responses in vivo when stimulated with the TLR3 agonist poly(I:C).
Recent preclinical studies suggest that vaccination following adoptive transfer of CD8(+) T cells into a lymphopenic host can augment the therapeutic antitumor responses of the transferred cells. However, the mechanism by which the lymphopenic microenvironment benefits Ag-specific CD8(+) T cell responses remains elusive. We show herein that induction of lymphodepletion by a single 4 mg cyclophosphamide (CTX) treatment induces a marked expansion of immature dendritic cells (DCs) in the peripheral blood on days 8-16 post-CTX (termed restoration phase). In vitro, these DCs were functional, because they showed normal phagocytosis and effective Ag presentation capability upon activation. In vivo, administration of the TLR3 agonist poly(I:C) at the peak of DC expansion (day 12 postlymphopenia) induced inflammatory cytokine production and increases in the number of activated DCs in lymph nodes. Importantly, boosting with gp100(25-33) melanoma peptide combined with poly(I:C) 12 days after an initial priming with the same regimen significantly increased the expansion and the antitumor efficacy of adoptively transferred pmel-1 CD8(+) T cells. These responses were abrogated after depletion of activated DCs during Ag boosting. In conclusion, our data show that CTX treatment induces, during the restoration phase, expansion of immature DCs, which are functional and can be exploited in vivo to foster more effective antitumor adoptive immunotherapy strategies.


Patient satisfaction and treatment adherence of stable human immunodeficiency virus-positive patients in antiretroviral adherence clubs and clinics.
South Africa has experienced a substantial increase in access to antiretroviral treatment (ART) in recent years. Effective strategies to manage access to treatment need to be incorporated into and implemented in ART programmes. Antiretroviral treatment adherence clubs are a new strategy that is being implemented in various parts of South Africa. The aim of the study was to investigate treatment adherence and patient satisfaction of stable human immunodeficiency virus (HIV) patients on ART in ART adherence clubs and clinics. The study was conducted in the Eden district of the Western Cape, South Africa. A cross-sectional analytical study was conducted to examine the relationships between patient satisfaction and treatment adherence in ART adherence clubs and clinics in the Eden district, Western Cape province, South Africa. Validated questionnaires were used to measure patient satisfaction and self-reported treatment adherence. The study included 320 participants (98 club and 222 clinic) from 13 primary health care clinics. The analyses showed that higher levels of satisfaction could be predicted with club participants compared to clinic participants (p = 0.05). There was no significant difference between clinic and club participants with regards to treatment adherence. However, being adherent was more likely in participants who were satisfied (odds ratio = 3.18, 95% confidence interval [1.14-7.11], p < 0.01). Antiretroviral treatment adherence clubs provide a service that patients are more satisfied with although they are not more adherent to treatment. This strategy may be effective for the delivery of long-term care for patients on ART.


Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/β-catenin signaling-associated mechanism.
Growing evidence has demonstrated that pulsed electromagnetic field (PEMF), as an alternative noninvasive method, could promote remarkable in vivo and in vitro osteogenesis. However, the exact mechanism of PEMF on osteopenia/osteoporosis is still poorly understood, which further limits the extensive clinical application of PEMF. In the present study, the efficiency of PEMF on osteoporotic bone microarchitecture and bone quality together with its associated signaling pathway mechanisms was systematically investigated in ovariectomized (OVX) rats. Thirty rats were equally assigned to the Control, OVX and OVX+PEMF groups. The OVX+PEMF group was subjected to daily 8-hour PEMF exposure with 15 Hz, 2.4 mT (peak value). After 10 weeks, the OVX+PEMF group exhibited significantly improved bone mass and bone architecture, evidenced by increased BMD, Tb.N, Tb.Th and BV/TV, and suppressed Tb.Sp and SMI levels in the MicroCT analysis. Three-point bending test suggests that PEMF attenuated the biomechanical strength deterioration of the OVX rat femora, evidenced by increased maximum load and elastic modulus. RT-PCR analysis demonstrated that PEMF exposure significantly promoted the overall gene expressions of Wnt1, LRP5 and β-catenin in the canonical Wnt signaling, but did not exhibit obvious impact on either RANKL or RANK gene expressions. Together, our present findings highlight that PEMF attenuated OVX-induced deterioration of bone microarchitecture and strength in rats by promoting the activation of Wnt/LRP5/β-catenin signaling rather than by inhibiting RANKL-RANK signaling. This study enriches our basic knowledge to the osteogenetic activity of PEMF, and may lead to more efficient and scientific clinical application of PEMF in inhibiting osteopenia/osteoporosis.


Factors Affecting Sexual Activity in Midlife Women: Results from the Midlife Health Study.
The objective of this study was to identify (1) the importance of a number of potential factors affecting the likelihood of sexual activity in perimenopausal women and (2) the likelihood of a number of barriers to sexual activity. A cohort of 780 women undergoing menopausal transition was surveyed annually for up to 7 years. Data were collected on sexual activity and, if not sexually active, reasons for no sexual activity, as well as a number of potential risk factors. Height and weight were measured at an annual clinic visit; serum hormone concentrations were assayed using blood samples donated annually. Data were examined with logistic regression models using the individual as a random effect, with subset analysis of nonsexually active women to determine the likelihood of each barrier. All factors with univariate associations of p < 0.1 were considered in multivariate model building with stepwise addition. A total of 2440 woman-years were included in the analysis of sexual activity. The likelihood of sexual activity increased for women living with a partner, with perceived quality of life, and with less frequent hot flashes. Among 513 woman-years reporting no sexual activity, women living with a partner and women reporting frequent fatigue were less likely to lack a sexual partner, but were more likely to have sexual difficulties. Women with more physical work than average and women with higher serum estradiol levels were less likely to have sexual difficulties. The factors associated with sexual activity in menopausal women are complex, indicating that an individualized approach to improving sexual activity is required.


The distribution of human coronavirus strain 229E on the surface of human diploid cells.
The distribution of human coronavirus strain 229E (HCV 229E) particles on the surface of human diploid (MRCc) cells was examined. Virus particles showed a totally random distribution on fixed cells and on cells to which virus had been adsorbed in the cold. A marked redistribution of virus particles was observed on warming virus-cell preparations to 33 degrees C for 20 min, the peripheral areas of the cell becoming relatively devoid of virus particles while the majority of particles were now located some distance from the edge of the cell. Redistribution did not occur in the presence of metabolic inhibitors.


Calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance in colorectal cancer xenografts.
CPT-11 (irinotecan), the first-line chemotherapy for advanced stage colorectal cancer, remains inactive in about half of patients (primary chemoresistance) and almost all initial responders develop secondary resistance after several courses of treatment (8 months on average). Nude mice bearing HT-29 colon cancer xenografts were treated with CPT-11 and/or an NF-κB inhibitor for two courses. We confirm that NF-κB inhibition potentiated CPT-11 anti-tumoural effect after the first course of treatment. However, tumours grew again at the end of the second course of treatment, generating resistant tumours. We observed an increase in the basal NF-κB activation in resistant tumours and in two resistant sublines, either obtained from resistant HT-29 tumours (HT-29R cells) or generated in vitro (RSN cells). The decrease of NF-κB activation in HT-29R and RSN cells by stable transfections with the super-repressor form of IκBα augmented their sensitivity to CPT-11. Comparing gene expression profiles of HT-29 and HT-29R cells, we identified the S100A10/Annexin A2 complex and calpain 2 as over-expressed potential NF-κB inducers. SiRNA silencing of calpain 2 but not of S100A10 and/or annexin A2, resulted in a decrease in NF-κB activation, an increase in cellular levels of IκBα and a partial restoration of the CPT-11 sensitivity in both HT-29R and RSN cells, suggesting that calpain 2-dependent IκBα degradation mediates CPT-11 secondary resistance. Thus, targeted therapies directed against calpain 2 may represent a novel strategy to enhance the anti-cancer efficacy of CPT-11.


IL-4 is a critical determinant in the generation of allergic inflammation initiated by a constitutively active Stat6.
IL-4 is required for the pathogenesis of atopic diseases and immune regulation. Stat6 is critical for IL-4-induced gene expression and Th cell differentiation. Recently, we have generated mice expressing a mutant Stat6 (Stat6VT) under control of the CD2 locus control region that is transcriptionally active independent of IL-4 stimulation. To determine whether active Stat6 in T cells is sufficient to alter immune regulation in vivo, we mated Stat6VT transgenic mice to IL-4-deficient mice. Stat6VT expression in IL-4-deficient lymphocytes was sufficient to alter lymphocyte homeostasis and promote Th2 differentiation in vitro. HyperTh2 levels in Stat6 transgenic mice correlated with an atopic phenotype that manifested as blepharitis and pulmonary inflammation with a high level of eosinophilic infiltration. In the absence of endogenous IL-4, Stat6VT transgenic mice were protected from allergic inflammation. Thus, in mice with hyperTh2 immune responses in vivo, IL-4 is a critical effector cytokine.


Detection of poliovirus, hepatitis A virus and rotavirus from sewage and water samples.
A modified adsorption-elution technique for concentration of enteric viruses from sewage and water samples was developed. The viruses in water were concentrated by negatively charged membrane filtration, eluted with 2.9% tryptose phosphate broth containing 6% glycine pH 9.0, and reconcentrated using centrifugation by a speedVac concentrator. The presence of poliovirus, hepatitis A virus (HAV) RNA, and rotavirus antigen was determined by cell culture isolation, nested polymerase chain reaction (nested PCR), and enzyme-linked immunosorbent assay (ELISA), respectively. A total of 100 sewage and water samples were collected from various sources in congested communities in Bangkok, concentrated and examined for those enteric viruses. Of 20 surface water samples from canals which located near sewage drains, 15% were positive for HAV RNA by nested PCR. Of 48 domestic sewage samples from man-holes of underground sewers, 8% were positive for rotavirus antigen by ELISA. Even though the samples were concentrated 256-2,000 fold, poliovirus was not found by isolation in cell culture.


Frequently asked questions: iodinated contrast agents.
Although iodinated contrast agents are safe and widely used, adverse events occur and questions remain about their use, safety, and interactions. Some questions are easily answered and others still require extensive investigation. For one frequent question--is informed consent necessary before all contrast media injections--the simple answer is no. Another question concerns use of contrast media in patients with prior reactions or allergies. Contrast agents can be safely used in such patients, but special care must be taken to be aware of what the previous reaction was and to be ready to treat any reaction. The protective role of pre-treatment with steroids is well established for minor reactions, but they may not prevent major reactions. It is important to realize that even life-threatening, anaphylactoid reactions are not the result of a true allergy to contrast media. Many questions arise about contrast agent-induced nephropathy. Baseline serum creatinine values should be obtained in patients who are at risk, not all patients. The incidence and natural history of contrast agent-induced nephropathy remain unclear. It occurs only in patients with compromised renal function before contrast agent injection, but even patients with normal serum creatinine levels can have renal dysfunction. Calculated creatinine clearance is a better way to determine risk and to follow this complication. The outcome in almost all patients is benign, with progression to end-stage renal disease being rare. The major risk factors, in addition to renal dysfunction, are long-standing diabetes mellitus, dehydration, and use of other nephrotoxic medications. Recent work in preventing and ameliorating contrast agent-induced nephropathy with N-acetyl cysteine, substitution of an isosmolal nonionic contrast agent, and various hydration regimens has been promising. Another common concern is use of iodinated contrast agents in pregnant or breast-feeding women. In both cases, there is no evidence of harm to the fetus or infant, but it is prudent to weigh the theoretical risks and benefits and avoid contrast agent administration unless it is truly necessary.