Trend in Age at the Initial Pacemaker Implantation in Patients With Bradyarrhythmia - A 50-Year Analysis (1970-2019) in Japan.
This study investigated whether the age of patients undergoing pacemaker implantation is increasing.Methods and Results: This study retrospectively reviewed the consecutive cases of 3,582 patients who underwent an initial pacemaker implantation at our hospitals because of symptomatic bradyarrhythmias between 1970 and 2019. The exclusion criteria were: patients with AV block due to cardiac surgery or AV junction ablation, and patients aged <20 years. The patients were divided into 5×10-year groups: those treated in the 1970s (1970-1979), 1980s (1980-1989), 1990s (1990-1999), 2000s (2000-2009), and 2010s (2010-2019). A total of 3,395 patients satisfied the study criteria. The average age at which the patients underwent a first pacemaker implantation increased across the 10-year periods: 63.7±13.2 years in the 1970s, 66.2±12.6 years (1980s), 69.1±12.4 years (1990s), 72.0±11.1 years (2000s), and 75.8±10.0 years (2010s) and advanced significantly in the 1990s, 2000s, and 2010s compared to the 1970s (all P<0.001). The ratio of patients aged ≥80 and ≥90 years increased from 10.6% and 0% in the 1970 s to 38.2% (P<0.001) and 5.2% (P= 0.017) in the 2010s, respectively. The average age at initial pacemaker implantation increased by 12.1 years over the last 50 years in Japan. In particular, the ratios of ≥80 and ≥90 years as the patients age increased significantly.


Epigenetic regulation of an IAP retrotransposon in the aging mouse: progressive demethylation and de-silencing of the element by its repetitive induction.
The recent insertion of a murine intracisternal A-particle (IAP) retrotransposon within one of the introns of a housekeeping gene, the circadian m.nocturnin gene, revealed a singular expression profile, both throughout the daytime and the mouse life span. Measurement of the levels of transcripts from this element by quantitative real-time RT-PCR, in organs of 1-24-month-old mice, disclosed that the inserted element--which is part of a large family of otherwise severely repressed mobile elements--becomes active upon aging, specifically in the liver where the m.nocturnin housekeeping gene is expressed in a circadian manner and induces a circadian expression of the IAP sequence. This age-dependent induction is cell-autonomous, as it persists in hepatocytes in primary culture. We further show, using methylation-sensitive enzymes, a correlation between the life-time kinetics of this process and a liver-specific demethylation of the IAP promoter. These results strongly support a model whereby the progressive demethylation and turning on of the IAP sequence is the sole result of the transient, daily activation-throughout the mouse life span--of its promoter. This phenomenon, which develops on a timescale of months to years in the aging mouse, might reveal a general epigenetic--and stochastic--process, which could account for a large series of events associated with cell and animal aging.


Aspirin-induced hepatotoxicity in juvenile rheumatoid arthritis. A prospective study.
Recent reports of and our own experience with biochemical alterations of liver function secondary to salicylate therapy stimulated this prospective study. Thirty-four children with juvenile rheumatoid arthritis, 6 children with acute cartilagenous necrosis of the hipfollowing slipped capital femoral epiphysis, and 2 children with ulcerative colitis and hip disease who were on salicylates were followed over a period of 1-27 months with serial determinations of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, and serum salicylate. Prothrombin time was measured in 14 children. Twenty-two of 34 children with rheumatoid arthritis and none of the 8 controls demonstrated abnormalities of various liver functions at serum salicylate levels between 7.0 and mg%. Three children demonstrated severe abnormalities characterized by marked elevation of SGOT, SGPT, LDH, and AP, prolongation of prothrombin time, and epistaxis. This type of reaction occurred within 5-14 days of initiation of aspirin therapy and occurred at serum salicylate levels between 18 and 43 mg%. Moderate changes in various liver function tests were observed in 19 other children. None of those children who were tested showed prolongation of prothrombin time. The serum salicylate level in this group varied between 7.0 and 38.2 mg%. The abnormal liver function tests returned to normal in 6 children upon withdrawal of aspirin and in 12 others even when salicylates were continued. Therefore, despite the occurrence of biochemical abnormalities following chronic salicylate therapy, it does not appear to be necessary to discontinue their use except in those children who develop bleeding.


[Influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in workers].
Objective: To investigate the influence of occupational aluminum exposure on cognitive function and glutamate receptor protein expression in peripheral blood lymphocytes in workers and the possibility of glutamate receptor being used as a biomarker for cognitive impairment in aluminum workers. Methods: From October to December, 2014, cluster sampling was performed to select 121 workers in aluminum electrolysis workshop as exposure group and 231 workers in thermoelectric workshop and logistics department as control group. Mini-Mental State Examination, clock drawing test, digit span test (DST) , verbal fluency test (VFT) , and Fuld Object-Memory (FOM) Evaluation were used to analyze cognitive function. Graphite furnace atomic absorption spectrophotometry was used to measure plasma aluminum level as an exposure indicator. Enzyme-linked immunosorbent assay was used to measure the content of glutamate receptor proteins in peripheral blood lymphocytes, including the subunits of N-methyl-D-aspartate receptor NR1, NR2A, and NR2B and metabotropic glutamate receptor 1 (mGluR1) . The correlation between cognitive function indices and the content of glutamate receptor proteins was analyzed. Results: There was no significant difference in plasma aluminum level between the control group and the exposure group (132.52±80.40 μg/L vs 182.88±72.32 μg/L, P>0.05) . According to the plasma aluminum level, the study subjects were divided into control group and low-, medium-, and high-level plasma aluminum groups, and there were significant differences in plasma aluminum level between these groups (all P<0.01) . The high-level plasma aluminum group had a significantly lower memory ability score than the control group and the low- and medium-level plasma aluminum groups (all P<0.05) . The high-level plasma aluminum group had lower DST and digital span forward (DSF) scores than the control group and the low-and medium-level plasma aluminum groups. The low-, medium-, and high-level plasma aluminum groups had lower digital span backward (DSB) scores than the control group. The medium-and high-level plasma aluminum groups had lower VFT scores than the control group and the low-level plasma aluminum group. The high-level plasma aluminum group had significantly lower expression of NR1 and NR2A proteins than the control group and the low-and medium-level plasma aluminum groups, and the medium- and high-level plasma aluminum groups had significantly higher expression of mGluR1 protein than the control group and the low-level plasma aluminum group (all P<0.05) . The expression of NR1 and NR2A proteins was negatively correlated with plasma aluminum level (r=-0.475 and -0.692, both P<0.05) , andthe expression of mGluR1 protein was positively correlated with plasma aluminum level (r=0.756, P<0.05) . The expression of NR1 protein was positively correlated with DSF, DSB, DST, and VFT scores (r(s)=0.213, 0.249, 0.271, and 0.228, all P<0.05) , and the expression of NR2A protein was positively correlated with VFT score (r(s)=0.206, P<0.05) . Conclusion: Occupational aluminum exposure may affect workers' memory function, and the expression of NR1 and NR2A in peripheral blood lymphocytes is correlated with cognitive function indices and can be used as biomarkers for cognitive impairment in aluminum workers.


Parasite spillover: indirect effects of invasive Burmese pythons.
Identification of the origin of parasites of nonindigenous species (NIS) can be complex. NIS may introduce parasites from their native range and acquire parasites from within their invaded range. Determination of whether parasites are non-native or native can be complicated when parasite genera occur within both the NIS' native range and its introduced range. We explored potential for spillover and spillback of lung parasites infecting Burmese pythons (Python bivittatus) in their invasive range (Florida). We collected 498 indigenous snakes of 26 species and 805 Burmese pythons during 2004-2016 and examined them for lung parasites. We used morphology to identify three genera of pentastome parasites, Raillietiella, a cosmopolitan form, and Porocephalus and Kiricephalus, both New World forms. We sequenced these parasites at one mitochondrial and one nuclear locus and showed that each genus is represented by a single species, R. orientalis, P. crotali, and K. coarctatus. Pythons are host to R. orientalis and P. crotali, but not K. coarctatus; native snakes are host to all three species. Sequence data show that pythons introduced R. orientalis to North America, where this parasite now infects native snakes. Additionally, our data suggest that pythons are competent hosts to P. crotali, a widespread parasite native to North and South America that was previously hypothesized to infect only viperid snakes. Our results indicate invasive Burmese pythons have affected parasite-host dynamics of native snakes in ways that are consistent with parasite spillover and demonstrate the potential for indirect effects during invasions. Additionally, we show that pythons have acquired a parasite native to their introduced range, which is the initial condition necessary for parasite spillback.


Purtscher's retinopathy: a case of visual impairment associated with multiple trauma.
This case study describes a patient with multiple trauma associated with acute visual impairment. Funduscopic examination revealed scattered and confluent cotton wool exudates bilaterally. This retinopathy was first described by Othmar Purtscher, an Austrian ophthalmologist, in 1910, which he later referred to as "angiopathia retinae traumatica."


Seeking Sanctuary: Violence Against Women in El Salvador, Honduras, and Guatemala.
This article identifies the way spaces of violence operate within gendered hierarchies in El Salvador, Guatemala, and Honduras. As migration accelerates, gender-related differences become evident. Strong push factors underlined by patriarchal power systems and hypermasculine spaces have normalized violence against women. Using data from the United Nations High Commissioner for Refugees (UNHCR), Médecins Sans Frontières (MSF), and local data from the three countries, this article illustrates how gender inequalities sustain the emigration of women. The study also evaluates how the interweaving of female murders has further ostracized women and forced them to flee their home countries in search of sanctuary.


Imagery: a strategic intervention to empower clients. Part I--Review of research literature.
This article is the first of a two-part series on the use of imagery in nursing practice. Imagery, an ancient healing technique, is a cognitive tool that acts as a communication mechanism among perception, emotion, and bodily change. Research has found that imagery can help reduce pain and stress, alter the course of disease, and improve clients' outlook on their illness. Imagery engenders a feeling of control and gives the client an effective tool for self-care. This article presents an overview of the history of imagery in medicine and nursing, discusses different types of imagery, and examines possible uses for imagery in a CNS's practice. Finally, recent research studies of imagery in nursing, psychology, and medicine are examined. The second article will help the nurse learn to use imagery in practice and will include a detailed imagery script.


Genotype/phenotype relationship in Gaucher disease patients. Novel mutation in glucocerebrosidase gene.
Objectives Gaucher disease (GD) is the most common inherited lysosomal storage disease, caused by mutations in acid β-glucosidase (GBA) gene. This study aimed to identify mutations in Andalusia patients with GD and their genotype-phenotype correlation. Methods Descriptive observational study. University Hospital Virgen del Rocio patients diagnosed from GD from 1999 to 2019 were included. Demographic and clinical data, β-glucocerebrosidase activity, variants pathogenic in GBA gene and biomarkers for monitoring treatment were collected from digital medical record. Results Twenty-six patients with aged between 1 day and 52 years were studied. A total of six mutations described as pathogenic and one mutation not described above [c.937T>C (p.Tyr313His)] were identified in the GBA gene, four patients were homozygotes and 22 compound heterozygotes. Twenty-four patients were diagnosed in non-neuropathic form (type 1) and two cases presented neurological involvement (type 2 or 3). The most common variant was c.1226A>G (p.Asn409Ser), which was detected in 24 patients, followed by c.1448T>C (p.Leu483Pro) variant, identified in 13 patients. The c.1448T>C (p.Leu483Pro) mutation has been presented in the most severe phenotypes with neurological involvement associated with type 2 and 3 GD, while c.1226A>G (p.Asn409Ser) mutation has not been associated with neurological alterations. Splenomegaly and bone disease were the most frequent clinical manifestations, and thrombocytopenia was the most common hematological disorder. Conclusions The c.1226A>G (p.Asn409Ser) and c.1448T>C (p.Leu483Pro) mutations were the most common. The c.937T>C (p.Tyr313His) was identified as a novel mutation. The c.1448T>C (p.Leu483Pro) mutation was associated with neurological alterations and c.1226A>G (p.Asn409Ser) mutation has not been associated it.


[Biologic characteristics of new Bacillus subtilis isolates].
Characteristics of new Bacillus subtilis isolates from the environment and had high antagonistic activity were studied. Absence of virulence and toxin production allows to regard them as potential probiotic cultures. Growth media for cultivation of B.subtilis were chosen according to the principle of individual adequacy in system, which give the ability to optimize processes of cultivation, obtaining of inhibitory substances and antagonistic activity spectrum determination.


Salicylic Acid Release from Syndiotactic Polystyrene Staple Fibers.
Films and fibers of syndiotactic polystyrene (sPS), being amorphous or exhibiting nanoporous crystalline (NC) or dense crystalline phases, were loaded with salicylic acid (SA), a relevant non-volatile antimicrobial molecule. In the first section of the paper, sPS/SA co-crystalline (CC) δ form is characterized, mainly by wide angle X-ray diffraction (WAXD) patterns and polarized Fourier transform infrared (FTIR) spectra. The formation of sPS/SA δ CC phases allows the preparation of sPS fibers even with a high content of the antibacterial guest, which is also retained after repeated washing procedures at 65 °C. A preparation procedure starting from amorphous fibers is particularly appropriate because involves a direct formation of the CC δ form and a simultaneous axial orientation. The possibility of tuning drug amount and release kinetics, by simply selecting suitable crystalline phases of a commercially available polymer, makes sPS fibers possibly useful for many applications. In particular, fibers with δ CC forms, which retain SA molecules in their crystalline phases, could be useful for antimicrobial textiles and fabrics. Fibers with the dense γ form which easily release SA molecules, because they are only included in their amorphous phases, could be used for promising SA-based preparations for antibacterial purposes in food processing and preservation and public health. Finally, using a cell-based assay system and antibacterial tests, we investigated the cellular activity, toxicity and antimicrobial properties of amorphous, δ CC forms and dense γ form of sPS fibers loaded with different contents of SA.


[Metabolic engineering of terpenoids in plants].
Terpenoids are present in all organisms but are especially abundant in plants, with more than 30,000 compounds. Not only do they play an important role in the life of plant, but also have high commercial values. However, the content of many important terpenoids in plant is very low. Therefore, how to improve the inefficient production of terpenoids is an urgent task. Metabolic engineering has been one of the most potential technologies to improve terpenoids production in recent years, following the study of metabolic pathway and regulation mechanism of terpenoids. Although there are some breakthroughs, metabolic engineering of terpenoids is still full of challenges because of the lack of knowledge on metabolic control of most terpenoids. Functional genomics approaches, including transcriptomics, proteomics and metabolomics, are potential tools for exploring of metabolic engineering. Integrating transcriptomics and metabolomics is an effective way to discover new genes involved in metabolic pathway. In this paper, the representative research outcomes about the metabolic engineering of terpenoids in plant were reviewed concisely and then the application of functional genomics approaches to study metabolic pathway and regulation mechanism of terpenoids and the strategies for metabolic engineering of terpenoids were discussed.


Delayed visual maturation: pupillary responses implicate subcortical and cortical visual systems.
Vision in very early infancy is probably subserved by subcortical pathways, with many cortical processes only fully emerging by 3 months of age. The improvement of vision in delayed visual maturation (DVM) occurs around this time, and this has given rise to the suggestion that the condition may have a subcortical basis that resolves with the appearance of cortical function. To explore further the role of cortical and subcortical visual systems in DVM we studied the visual development in identical twins, one of whom had type 1b DVM. Two non-invasive methods of investigating visual pathway function were employed: the acuity card procedure (a behavioural response) and luminance and grating pupillometry. While the former reflects both subcortical and cortical function and can be detected at birth, pupil responses to gratings reflect cortical activity alone and normally become measurable at 1 month of age. Development of both behavioural and pupillary responses was delayed in DVM, indicating that although the underlying defect is primarily subcortical, secondarily it delays the emergence of cortically mediated responses. The observed rapidity of improvement--over a very few days and within a narrow age range--suggests a discrete rather than a widespread structural abnormality, the improvement of which is closely linked to postmenstrual age.


Effect of routine heparins treatment in acute coronary syndrome on serum pregnancy-associated plasma protein a concentration.
Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful marker of acute coronary syndrome (ACS). Serum PAPP-A concentrations are affected by unfractionated heparin (UFH) in ACS population, and we tried to investigate the time profile of effects of routine heparins treatment on serum PAPP-A concentrations in ACS population thoroughly and give advice to sample collection of related study. Twenty cases were involved in this study: ten patients with acute myocardial infarction received subcutaneous low molecular weight heparin (LMWH) twice a day (group A), and the other ten percutaneous coronary intervention patients with stenting received intravenous UFH (group B). Samples were collected before and after heparin administration and serum PAPP-A concentrations were analyzed in these samples. Serum PAPP-A concentration increased in both group A and B. In group A, PAPP-A concentration elevated gradually (14.5 to 29.4 mIU/L, P<0.05) throughout the observation period and normalized at 48h after drug discontinuation. In group B, there was a rapid and intense increase after intravenous heparin injection (13.1 to 49.3 mIU/L, P<0.05), and a new PAPP-A peak was induced by additional heparin administration. Heparins-induced increase in serum PAPP-A concentration lasted until 48h after drug use was discontinued. We recommend that samples from these patients for PAPP-A measurement should be collected at least 48h after the last administration if its not available before the administration of heparins.


Long-acting β₂ agonists for asthma: a clinical paradox.
This action is the most recent in a long history of concerns and controversies about the safety of these agents. The changes are based on FDA's analyses of studies that demonstrated a worsening of asthma symptoms and resulting in hospitalization or death in asthma patients using the therapies. In addition to the labeling changes, FDA also requires a risk evaluation and mitigation strategy (REMS) to facilitate the safe use of the products. REMS includes a medication guide for patients and a plan to educate health care professionals about the appropriate use of LABAs.


miR-940 upregulation contributes to human cervical cancer progression through p27 and PTEN inhibition.
Cervical cancer is considered as a gynecological malignancy accompanied with high rates of mortality across the world. Effective diagnostic, prognostic markers as well as therapeutic targets are necessary to be explored. The p27 and PTEN are known to modulate tumor cell growth and proliferation. However, the molecular mechanisms modulating these genes have not completely been elucidated. In our study, real-time (RT) quantitative PCR indicated that miR‑940 levels were upregulated in human cervical cancer tissue samples and cell lines. Overexpression of miR‑940 could reduce overall survival in patients. Ectopic miR‑940 accelerated cervical cancer cell growth, proliferation and cell cycle arrest in vitro as well as tumor formation in vivo. p27 and PTEN were evidenced as direct targets for miR‑940 and inhibition of p27 and PTEN recovered the suppressive function of miR‑940-silenced cell towards to proliferation and tumorigenicity in cervical cancer cells. In addition, miR‑940 expression was inversely associated with p27 and PTEN expression levels and actively with cyclin D1 in cervical cancer specimens. The results from our study demonstrated that miR‑940 regulated p27 and PTEN post-transcriptionally and might play a significant role in cervical cancer development and progression. Thus, miR‑940 might provide a potential value as therapeutic target for cervical cancer treatment in future.


Thermal conditions during neonatal anoxia affect the endogenous level of brain-derived neurotrophic factor.
Anoxia during delivery is a complication that can disturb infant brain development leading to various types of neurological disorders. Our studies have shown that increased body temperature of newborn rats of both sexes intensifies the postanoxic oxidative stress and prevents triggering the endogenous adaptive response such as HIF-1α activation. Currently, brain-derived neurotrophic factor-BDNF is considered to be a modulator of neuronal plasticity. In the developing brain, mature BDNF and its precursor exhibit prosurvival action through the TrkB receptor and proapoptotic functions binding to p75NTR , respectively. The aim of our experiments was to check the effects of body temperature on the postanoxic level of BDNF and on the expression of its receptors as well as on the marker of apoptosis-caspase-3 in the rat brain. Two-day-old Wistar Han rats (male/female ratio, 1:1) were exposed to anoxia in 100% nitrogen atmosphere for 10 min in different thermal conditions, which allowed them to regulate their rectal temperature at the following levels: normothermic-33°C; hyperthermic-37°C; and extremely hyperthermic-39°C. Thermal conditions during neonatal anoxia affected the level of proBDNF, BDNF as well as their receptors and caspase-3 in the forebrain. The increased BDNF protein level followed by decreased caspase-3 protein level was probably dependent on body temperature under anoxic conditions and was observed only in rats maintaining decreased body temperature. The positive effect of BDNF was not observed under hyperthermic conditions. Moreover, BDNF level changes correlated with body temperature probably affected the learning and spatial memory in juvenile rats.


Association between infant feeding patterns and diarrhoeal and respiratory illness: a cohort study in Chittagong, Bangladesh.
In developing countries, infectious diseases such as diarrhoea and acute respiratory infections are the main cause of mortality and morbidity in infants aged less than one year. The importance of exclusive breastfeeding in the prevention of infectious diseases during infancy is well known. Although breastfeeding is almost universal in Bangladesh, the rates of exclusive breastfeeding remain low. This cohort study was designed to compare the prevalence of diarrhoea and acute respiratory infection (ARI) in infants according to their breastfeeding status in a prospective cohort of infants from birth to six months of age. A total of 351 pregnant women were recruited in the Anowara subdistrict of Chittagong. Breastfeeding practices and the 7-day prevalence of diarrhoea and ARI were recorded at monthly home visits. Prevalences were compared using chi-squared tests and logistic regression. A total of 272 mother-infant pairs completed the study to six months. Infants who were exclusively breastfed for six months had a significantly lower 7-day prevalence of diarrhoea [AOR for lack of EBF = 2.50 (95%CI 1.10, 5.69), p = 0.03] and a significantly lower 7-day prevalence of ARI [AOR for lack of EBF = 2.31 (95%CI 1.33, 4.00), p < 0.01] than infants who were not exclusively breastfed. However, when the association between patterns of infant feeding (exclusive, predominant and partial breastfeeding) and illness was investigated in more detail, there was no significant difference in the prevalence of diarrhoea between exclusively [6.6% (95% CI 2.8, 10.4)] and predominantly breastfed infants [3.7% (95% CI 0.09, 18.3), (p = 0.56)]. Partially breastfed infants had a higher prevalence of diarrhoea than the others [19.2% (95% CI 10.4, 27.9), (p = 0.01)]. Similarly, although there was a large difference in prevalence in acute respiratory illness between exclusively [54.2% (95%CI 46.6, 61.8)] and predominantly breastfed infants [70.4% (95%CI 53.2, 87.6)] there was no significant difference in the prevalence (p = 0.17). The findings suggest that exclusive or predominant breastfeeding can reduce rates of morbidity significantly in this region of rural Bangladesh.


Indocyanine green mediated photothrombosis for the management of predominantly classic choroidal neovascularisation caused by age related macular degeneration.
To study the effectiveness of indocyanine green mediated photothrombosis in the management of predominantly classic subfoveal choroidal neovascularisation associated with age related macular degeneration. Prospective, non-comparative, interventional case series of nine patients with predominantly classic subfoveal choroidal neovascularisation secondary to age related macular degeneration who declined photocoagulation or verteporfin photodynamic therapy. Patients were submitted to one or more treatments with an intravenous injection of a small volume of high concentration indocyanine green solution followed by low irradiance, large spot 810 nm continuous laser application via a transpupillary approach. Main outcome measures were change in best corrected visual acuity and macular exudative manifestations. After 12 months of follow up, the final best corrected visual acuity was the same (plus or minus two ETDRS lines) in five eyes (55%), improved more than two ETDRS lines in three eyes (33%), and worsened by more than two lines in the remaining eye. The improved vision was probably related to partial or complete restoration of the macular architecture as a result of fluid resolution, whereas the worsened vision was primarily the result of treatment failure in achieving substantial choroidal neovascular occlusion. There were no complications related to the procedure. Indocyanine green mediated photothrombosis may be an effective alternative treatment for predominantly classic subfoveal choroidal neovascularisation caused by age related macular degeneration.


Isolation and characterization of a maintenance DNA-methyltransferase gene from peach (Prunus persica [L.] Batsch): transcript localization in vegetative and reproductive meristems of triple buds.
A cDNA coding for a DNA (cytosine-5)-methyltransferase (METase) was isolated from peach (Prunus persica [L.] Batsch) and the corresponding gene designated as PpMETI. The latter encoded a predicted polypeptide of 1564 amino acid residues and harboured all the functional domains conserved in the maintenance METases group type I. PpMETI was a single copy in the cultivar Chiripa which was used as a model in the present study. Expression analyses revealed that PpMETI transcripts were more abundant in tissues with actively proliferating cells such as apical tips, uncurled leaves, elongating herbaceous stems, and small immature fruits. Peach plants bear bud clusters (triads or triple buds), consisting of two lateral and one central bud with floral and vegetative fates, respectively. PpMETI in situ hybridization was performed in triple buds during their entire developmental cycle. High and low levels of PpMETI transcript were related to burst and quiescence of vegetative growth, respectively. Message localization distinguished lateral from central buds during the meristem switch to the floral phase. In fact, the PpMETI message was abundant in the L1 layer of protruding domes, a morphological trait marking the beginning of floral transition. The PpMETI transcript was also monitored during organ flower formation. Altogether, these data suggest a relationship between DNA replication and PpMETI gene expression.


Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases.
The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. To characterize the RANK/RANKL/OPG pathway in patients affected with NET. Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.


Using porcine small intestinal submucosa in intestinal regeneration.
Small intestinal submucosa (SIS) is an unusual tissue that promotes constructive tissue remodeling when applied as a xenogeneic material. The aim of our experimental study was to assess its effectiveness in intestinal regeneration. Twenty white New Zealand rabbits were anesthetized and underwent celiotomy. A 6-cm antimesenteric incision was created at the jejunal segment. An elliptical SIS graft measuring 6 cm long and 2 cm wide was sutured to the jejunal defect as a patch graft. Thirteen living rabbits were divided into groups of three and the grafts were harvested at postoperative weeks 2, 4, and 6. The obtained specimens were evaluated for gross and histologic appearance. In morphometric examination, in the 2, 4, and 6 weeks groups, the diameters of grafted intestines were larger than preoperatively by 50%, 25%, and 25% respectively; also the grafts had contracted to 0%, 25%, and 50% of their original sizes respectively. At the end of 2 weeks, the grafts were intact without evidence of epithelial regeneration. By 4 weeks, intestinal tissue regeneration was started, and epithelial coverage of the grafts was detected. The grafts were covered with a complete intestinal mucosa at 6 weeks. Remarkable regeneration marked fibroplasia, angiogenesis, and mild mononuclear cell infiltration had also occurred throughout the grafts at 6 weeks. Porcine SIS appeared an effective biodegradable scaffold, facilitating regeneration of intestinal tissue. These results suggest that SIS may be useful to increase the mucosal surface of intestine and may provide a new substance for short gut syndrome in the future.


Stiff-person syndrome: insights into a complex autoimmune disorder.
Stiff-person syndrome (SPS) is characterised by progressive rigidity and muscle spasms affecting the axial and limb muscles. Since its initial description in 1956, marked progress has been made in the clinical characterisation, understanding of pathogenesis and therapy of this disorder. SPS can be classified according to the clinical presentation into classic SPS and SPS variants: focal or segmental-SPS, jerking-SPS and progressive encephalomyelitis with rigidity and myoclonus. Most patients with SPS have antibodies directed against the glutamic acid decarboxylase, the rate-limiting enzyme for the production of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Antibodies directed against GABA(A) receptor-associated protein, and the glycine-α1 receptor can also be observed. Paraneoplastic SPS is commonly associated with antiamphiphysin antibodies and breast cancer. Treatment of SPS with drugs that increase the GABAergic tone combined with immunotherapy can improve the neurological manifestations of these patients. The prognosis, however, is unpredictable and spontaneous remissions are unlikely.


Synthesis of labeled BCX-4208, a potent inhibitor of purine nucleoside phosphorylase.
BCX-4208, a novel inhibitor of the enzyme purine nucleoside phosphorylase, mimics the charged ribosyl oxocarbenium ion formed during the transition state of the enzyme-catalyzed C-N bond cleavage of nucleosides. A slow-onset, tight-binding inhibitor with a Ki(*) of 16 +/- 1.4 pM, BCX-4208 is one of the most potent inhibitors known for the enzyme. In support of our BCX-4208 clinical program, a mass spectrometric assay has been developed that required labeled BCX-4208 as an internal standard. The synthesis of [(2)H](2)-BCX-4208 and [(13)C]-BCX-4208 is described in this report.


Grip force safety margin in rock climbers.
When holding an object, grip force (Gf) is larger than the smallest force needed to prevent slipping (Gmin). The unnecessary grip force is termed safety margin (SM = Gf - Gmin). Because some hand injuries in rock climbing are largely encouraged by excessive grip force, safety margin was examined in a set of expert climbers, and compared to a set of non-climbers. Subjects were asked to hold a heavy or a light object during either a short or a long duration. We focused on the relative safety margin (RSM = 100 x SM/Gmin) adopted at the initiation of each trial. With the heavy object, climbers and non-climbers had similar RSMs (155 versus 148 %). With the light object, higher RSMs were reached, albeit smaller in climbers as compared to non-climbers (232 versus 386 %). Surprisingly, all subjects exhibited larger RSMs at the initiation of a long trial (246 versus 215 %). We conclude that expertise in rock climbing is not accompanied by key changes in RSMs that increase the likelihood of hand injuries. On the other hand, the fact that grip force is so crudely optimized at large load, especially when planning to sustain a hold, does promote the risk of hand injury in climbers.


Discovery of an ectopic activation site on the M(1) muscarinic receptor.
Receptors have well-conserved regions that are recognized and activated by hormones and neurotransmitters. Most drugs bind to these sites and mimic or block the action of the native ligands. Using a high-throughput functional screen, we identified a potent and selective M(1) muscarinic receptor agonist from a novel structural class. Using a series of chimeric receptors, we demonstrated that this ligand activates the receptor through a region that is not conserved among receptor subtypes, explaining its unprecedented selectivity. This region of the receptor is distinct from the conserved region that is recognized by traditional ligands. The finding that receptors for small-molecule transmitters can have multiple, structurally distinct activation sites has broad implications for the study of receptor structure/function and the potential for the discovery of novel ligands with high selectivity.


Spatial and temporal population genetic variation and structure of Nothotsuga longibracteata (Pinaceae), a relic conifer species endemic to subtropical China.
Nothotsuga longibracteata, a relic and endangered conifer species endemic to subtropical China, was studied for examining the spatial-temporal population genetic variation and structure to understand the historical biogeographical processes underlying the present geographical distribution. Ten populations were sampled over the entire natural range of the species for spatial analysis, while three key populations with large population sizes and varied age structure were selected for temporal analyses using both nuclear microsatellites (nSSR) and chloroplast microsatellites (cpSSR). A recent bottleneck was detected in the natural populations of N. longibracteata. The spatial genetic analysis showed significant population genetic differentiation across its total geographical range. Notwithstanding, the temporal genetic analysis revealed that the level of genetic diversity between different age class subpopulations remained constant over time. Eleven refugia of the Last Glacial Maximum were identified, which deserve particular attention for conservation management.


Lung cancer.
This synthesis of the literature on radiotherapy for lung cancer is based on 80 scientific articles, including 2 meta-analyses, 29 randomized studies, 19 prospective studies, and 21 retrospective studies. These studies involve 28172 patients. Basic treatment for limited-stage small cell lung cancer (SCLC), is chemotherapy. Addition of radiotherapy to the primary tumor and mediastinum reduces local recurrence, prolongs long-term survival, and is often indicated. Current, and future, studies can be expected to show successive improvements in results for SCLC by optimizing the combination of radiotherapy and chemotherapy. Should these treatments be given simultaneously or sequentially, and in which order? Which fractionation is best? Probably, no change in resource requirements for radiotherapy will be necessary, with the possible exception of changes in fractionation. Surgery constitutes primary treatment for nonsmall cell lung cancer (NSCLC) stages I and II. Radiotherapy may provide an alternative for patients who are inoperable for medical reasons. The value of radiotherapy following radical surgery for NSCLC remains to be shown. It is not indicated based on current knowledge. For NSCLC stage III, radiotherapy shrinks tumors and prolongs survival at 2 and 3 years. Whether it influences long-term survival after 5 years has not been shown. Considering the side effects of treatment, one must question whether limited improvements in survival motivate routine radiotherapy in these patients. Earlier attempts to add chemotherapy to radiotherapy to improve treatment results of NSCLC have not yielded convincing results. Several studies are currently on-going. Prophylactic cranial irradiation (PCI) greatly reduces the risk for brain metastases from SCLC. However, it has little influence on survival. Many treatment centers give PCI to SCLC patients who have achieved complete remission. This practice may be questioned since PCI is associated with serious complications. PCI is not indicated in patients with NSCLC. In SCLC, where the disease is extensive, only palliative radiotherapy is appropriate. Radiotherapy is an important treatment alternative in special palliative situations involving severe cough, severe bleeding, pain, pulmonary obstructions, and vena cava superior syndrome. In these situations, good results may be achieved with few fractions.


Factors associated with ureteral burn injury from an electrified guidewire.
During ureteroscopic procedures, electrocautery is often utilized in the presence of an intra-ureteral guidewire. Inadvertent electrification of the guidewire may occur if the active electrode comes into contact with the guidewire, potentially resulting in a ureteral burn injury. This study investigates under what conditions electrification of a ureteral guidewire would result in ureteral burn injury. Porcine kidney/ureter units were tested in a saline bath using a guidewire within the ureter. The collecting system was filled with either saline or water and the guidewire was electrified with varying power and mode settings. The contact area between the wire and ureter was adjusted to 1/2 or 1/4 of the total ureteral length. The ureters were then inspected for evidence of burn injury microscopically by a pathologist in a blinded fashion. Ten kidney/ureter units were tested. Four units were filled with saline and none of these demonstrated any burn injury. Six kidney/ureter units were filled with water prior to electrification of the wire. Small amounts of burned tissue were noted in those with the full length of the ureter exposed. Moderate to severe burning was present in those with 1/2 of the ureter exposed. Ureters exposed to 120-W cutting current had more injury than those exposed to 80-W coagulation current. Inadvertent electrification of a ureteral guidewire does not necessarily result in ureteral burn injury. The presence and extent of ureteral injury depends primarily on the irrigating fluid used, as well as the amount of ureter exposed to the electrified guidewire.


A novel method for preclinical detection of PrPSc in blood.
In this study, we demonstrate that a moderate amount of protein misfolding cyclic amplification (PMCA) coupled to a novel surround optical fibre immunoassay (SOFIA) detection scheme can be used to detect the disease-associated form of the prion protein (PrP(Sc)) in protease-untreated plasma from preclinical and clinical scrapie sheep, and white-tailed deer with chronic wasting disease, following natural and experimental infection. PrP(Sc), resulting from a conformational change of the normal (cellular) form of prion protein (PrP(C)), is considered central to neuropathogenesis and serves as the only reliable molecular marker for prion disease diagnosis. While the highest levels of PrP(Sc) are present in the central nervous system, the development of a reasonable diagnostic assay requires the use of body fluids that characteristically contain exceedingly low levels of PrP(Sc). PrP(Sc) has been detected in the blood of sick animals by means of PMCA technology. However, repeated cycling over several days, which is necessary for PMCA of blood material, has been reported to result in decreased specificity (false positives). To generate an assay for PrP(Sc) in blood that is both highly sensitive and specific, we have utilized limited serial PMCA (sPMCA) with SOFIA. We did not find any enhancement of sPMCA with the addition of polyadenylic acid nor was it necessary to match the genotypes of the PrP(C) and PrP(Sc) sources for efficient amplification.


Assessment of peripheral arterial occlusive disease: comparison of multislice-CT angiography (MS-CTA) and intraarterial digital subtraction angiography (IA-DSA).
The aim of the study was to assess the arterial vascular system of the lower extremities in patients with peripheral arterial occlusive disease using Multislice-CT angiography (MS-CTA) and to compare the results with the standard of reference, intraarterial digital subtraction angiography (IA-DSA). MS-CTA and IA-DSA of the lower extremities were carried out on 23 patients with peripheral arterial occlusive disease (Fontain Stage IIb: 18, III: 3, IV: 2). MS-CTA comprised a 4 x 2.5 mm collimation, 15 mm table feed/rotation, 0.5 sec rotation time and 3 mm slice thickness (1.5 mm reconstruction increment). Delay time was determined by bolus tracking. 150 ml of contrast media were injected intravenously at a flow rate of 3 ml/sec. Maximum intensity projection (MIP) reformations were performed using a semi-automatic vessel tracking program. MS-CTA (axial and MIP-reformatted images) and IA-DSA were reviewed by two radiologists. The grade of vascular stenosis as well as occlusion were rated on a scale of 0 to 3 (0=0-50% stenosis, 1 = 51-75% stenosis, 2 = 76-99% stenosis, 3 = occlusion). For MS-CTA, the mean delay time was 30.2 s (23-40 s), mean scan time was 37.4 (33-42 s). Data analysis was based upon a total of 1136 vascular segments for both methods (568 each). A comparison of all the evaluated segments in both techniques revealed a MS-CTA / IA-DSA 86.3% match. Out of 442 segments proximal the trifurcation, 386 were correctly assessed in MS-CTA (87.3%) and distal the trifurcation, 101 out of 126 segments were rated correctly (80.2%). In MS-CTA, an overall confidence interval of 95% can be achieved in 83.2% to 89.0% for correctly rated stenosis grading. In patients with peripheral arterial occlusive disease, MS-CTA of the lower extremity is a promising minimal-invasive method for detection of relevant arterial stenoses. However, the technique was limited to routine diagnostic purposes due to severe calcifications and time consuming reconstruction procedures.


[Effect of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury].
To explore the role of mitochondrial apoptosis on pulmonary fibrosis in rats with severe scald injury. According to the random digital table, a total number of 32 Wistar rats were divided into 4 groups: sham burn (group A), burn group (group B), 12-week post burn recovery group (group C), and 12-week post burn recovery plus a second burn injury group (group D). In group A and group B, lung tissues were harvested on post burn day 4. After received first burn injury 12 weeks, the group C and group D received separately a second sham burn injury and burn injury. Lung tissues were harvested on post burn day 4 after the second burn injury. All tissues were examined for cells apoptosis by Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL). Pulmonary fibrosis was assessed by Masson trichrome staining and Sirius red staining. The protein expression levels of cleaved Caspase-3, Bax and Bcl-2 were assessed by Western blot. Both Masson trichrome staining and Sirius red staining showed obvious pulmonary fibrosis in group C and group D. The apoptosis rates of group B, C and D were significantly higher than that in group A ((15.50±3.30)%, (7.88±3.10)%, (15.88±3.23)% vs (2.10±1.07)%, all P<0.05). Compared to group A, cleaved Caspase-3 levels were significantly higher in group B, C and D ((0.59±0.11), (0.33±0.08), (0.73±0.13) vs (0.16±0.05), all P<0.05). The ratio of Bax/Bcl-2 in group B, C and D also increased significantly ((2.08±0.30), (0.83±0.09), (1.54±0.12) vs (0.64±0.05), all P<0.05). Severe burn injury can induce pulmonary fibrosis and mitochondrial apoptosis may play an important role in the development of pulmonary fibrosis.


A unique case of Fusobacterium nucleatum spondylodiscitis communicating with a pleural empyema through a fistula.
Species (spp.) belonging to the genus Fusobacterium are anaerobic commensals colonizing the upper respiratory tract, the gastrointestinal tract, and the genitals. Infections with Fusobacterium spp. have been reported at many anatomical sites, including pneumonias and pleural empyemas; however, there are very few published cases of Fusobacterium spp. causing spondylodiscitis or fistulas. Bone infections with Fusobacterium can spread directly to surrounding muscular tissue or by hematogenous transmission to any other tissue including pleurae and lungs. Similarly, pleural infections can spread Fusobacterium spp. to any other tissue including fistulas and bone. Concomitant pleural empyema and spondylodiscitis are rare; however, there are a few published cases with concomitant disease, although none caused by Fusobacterium spp. A 77-year-old female patient was assessed using computed tomography (CT) scanning of the thorax and abdomen, as well as analyses of fluid drained from the region affected by the pleural empyema. A diagnosis of Fusobacterium empyema, fistula, bacteremia, and spondylodiscitis was made, and the patient's condition improved significantly after drainage of the pleural empyema and relevant long-term antibiotic treatment. We describe the first confirmed case with concomitant infection with Fusobacterium nucleatum as spondylodiscitis and pleural empyema connected by a fistula.


Randomized controlled trial of mammographic screening from age 40 ('Age' trial): patterns of screening attendance.
The Age trial was a randomized controlled trial to study the effect on breast cancer mortality of invitation to annual mammography from age 40 to 41. Uptake of invitation to screening mammography in UK women aged below 50 is of interest, particularly in the light of the recent announcement that the national breast screening programme will begin inviting women from age 47. The trial took place in 23 National Health Service breast screening units in England, Wales and Scotland between 1991 and 2004. Data on invitation and attendance during 13 years of trial fieldwork were analysed. The participants were 53,884 women in the intervention arm of the Age trial who were randomized to receive annual invitation to mammography from age 40 or 41 up to age 48. The trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151. Uptake of invitation to routine screening was 68% at first round and 69% at subsequent rounds. A total of 43,709 women in the intervention arm (81%) attended at least one routine screen and 23,262 (43%) attended at least seven screens; 31,392 women attended 75% or more of all routine invitations they were offered. Previous trial attendance was a predictor of subsequent uptake; attendance was inversely related to Townsend deprivation score. Uptake in this trial was comparable with that in the UK screening programme for women aged over 50. There was an inverse relationship between deprivation level and the number of screens attended.


A mutation-centric approach to identifying pharmacogenomic relations in text.
To explore the notion of mutation-centric pharmacogenomic relation extraction and to evaluate our approach against reference pharmacogenomic relations. From a corpus of MEDLINE abstracts relevant to genetic variation, we identify co-occurrences between drug mentions extracted using MetaMap and RxNorm, and genetic variants extracted by EMU. The recall of our approach is evaluated against reference relations curated manually in PharmGKB. We also reviewed a random sample of 180 relations in order to evaluate its precision. One crucial aspect of our strategy is the use of biological knowledge for identifying specific genetic variants in text, not simply gene mentions. On the 104 reference abstracts from PharmGKB, the recall of our mutation-centric approach is 33-46%. Applied to 282,000 abstracts from MEDLINE, our approach identifies pharmacogenomic relations in 4534 abstracts, with a precision of 65%. Compared to a relation-centric approach, our mutation-centric approach shows similar recall, but slightly lower precision. We show that both approaches have limited overlap in their results, but are complementary and can be used in combination. Rather than a solution for the automatic curation of pharmacogenomic knowledge, we see these high-throughput approaches as tools to assist biocurators in the identification of pharmacogenomic relations of interest from the published literature. This investigation also identified three challenging aspects of the extraction of pharmacogenomic relations, namely processing full-text articles, sequence validation of DNA variants and resolution of genetic variants to reference databases, such as dbSNP.


Knowledge of Biomedical Waste Management Amidst the Clinical Students of Dental College, Tamilnadu State, India - A Cross Sectional Observational Study.
The objective of study was to assess the knowledge and awareness of the management of biological waste (BMW) among undergraduate students of Dental College, Tamilnadu state. Among the students of Dental College in Tamilnadu state, India, a cross-sectional observational research was conducted. A pre-designed questionnaire was distributed to the students. Their expertise and awareness of managing biomedical waste were the variables that were investigated. One hundred and eighty students were participated. The male to female ratio was 1:2, and the average age of responders was 19.76 ± 1.03 years. When it comes to information concerning the management of biomedical waste, an average of 60.33% were correct and 39.57% were incorrect. For their knowledge of the same, 81.35% were correct and 18.65% were incorrect. The findings indicated that students had a high degree of knowledge and understanding regarding the management of biomedical waste.


Immunohistochemical investigation of epidermal growth factor receptor expression in ameloblastomas.
Immunohistochemical analysis was performed to determine the localization of epidermal growth factor receptor (EGFR) in ameloblastomas. Ameloblastoma samples were classified into follicular, plexiform, and basal cell types. The number of cases in each category was 17, 19 and 3, respectively. Ameloblastomas, disregarding their histological type, consist of two cell forms: peripheral columnar cells and central stellate cells. The frequency of EGFR expression was much higher in the latter than in the former (P < 0.005). On analysis with respect to histological types, the frequency of EGFR expression in columnar cells was not significantly different between the follicular and the plexiform types, but was observed more frequently in the stellate cells in the follicular than in the plexiform ameloblastomas (P < 0.05). This pattern of EGFR expression was not consistent with the PCNA staining pattern, but was similar to that of keratin expression which we have reported previously. The present study suggests that EGFR expression in ameloblastomas is closely associated with tumour differentiation, and squamous differentiation in particular.


Reverse taxonomy: an approach towards determining the diversity of meiobenthic organisms based on ribosomal RNA signature sequences.
Organisms living in or on the sediment layer of water bodies constitute the benthos fauna, which is known to harbour a large number of species of diverse taxonomic groups. The benthos plays a significant role in the nutrient cycle and it is, therefore, of high ecological relevance. Here, we have explored a DNA-taxonomic approach to access the meiobenthic organismic diversity, by focusing on obtaining signature sequences from a part of the large ribosomal subunit rRNA (28S), the D3-D5 region. To obtain a broad representation of taxa, benthos samples were taken from 12 lakes in Germany, representing different ecological conditions. In a first approach, we have extracted whole DNA from these samples, amplified the respective fragment by PCR, cloned the fragments and sequenced individual clones. However, we found a relatively large number of recombinant clones that must be considered PCR artefacts. In a second approach we have, therefore, directly sequenced PCR fragments that were obtained from DNA extracts of randomly picked individual organisms. In total, we have obtained 264 new unique sequences, which can be readily placed into taxon groups, based on phylogenetic comparison with currently available database sequences. The group with the highest taxon abundance were nematodes and protozoa, followed by chironomids. However, we find also that we have by far not exhausted the diversity of organisms in the samples. Still, our data provide a framework within which a meiobenthos DNA signature sequence database can be constructed, that will allow to develop the necessary techniques for studying taxon diversity in the context of ecological analysis. Since many taxa in our analysis are initially only identified via their signature sequences, but not yet their morphology, we propose to call this approach 'reverse taxonomy'.


Associations between reproductive and menstrual factors and postmenopausal androgen concentrations.
Reproductive and menstrual characteristics, as well as high circulating estrogen and androgen concentrations, are associated with the risk of breast and ovarian cancer in postmenopausal women. To explore possible etiological relationships between menstrual and reproductive characteristics and cancer risk, we examined associations between menstrual and reproductive factors and serum concentrations of total testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S). This study was conducted in 167 postmenopausal women, using data from the pre-randomization visit of an exercise clinical trial. Participants were sedentary, overweight/ obese, and not on hormone therapy. DHEA-S concentrations were 42% higher, total testosterone concentrations were 35% lower, and free testosterone concentrations were 23% lower in women with both ovaries removed compared with those with both remaining (p = 0.01, p = 0.01, and p = 0.03, respectively). Women who had used herbal therapy in the past had, on average, 25% higher concentrations of total and free testosterone than women who had never used these herbal therapies (p = 0.03 and p = 0.004, respectively). No other significant associations were detected. Overall, this study does not support the hypothesis that reproductive or menstrual factors, with the exception of oophorectomy status, are associated with postmenopausal androgen concentrations.


[Structural rearrangements of the plasmid R68,45 in cells of Brucella suis].
The mobilizing activity of the plasmid R68,45 in Escherichia coli and Brucella abortus has been studied. The plasmid R68,45 has been found to lose its ability to mobilize the chromosome in Brucella suis cells. The experiments on the conjugational transfer of R68,45 were confirmed by restriction analysis of the plasmid DNA. R68,45 has been shown to lose Cma in brucella cells via deletion. The molecular mechanisms of deletion process in brucella and other bacteria are discussed.


Informal caregiving in head and neck cancer: caregiving activities and psychological well-being.
The purpose of this study was to quantify the general cancer support activities that long-term carers of head and neck cancer (HNC) survivors engage in; and the relationships between these care activities and psychological well-being. Respondents answered a survey detailing their caring activities, the amount of time that they spent on those activities and how comfortable they felt engaging in them. Psychological well-being was assessed by the Depression Anxiety Stress Scales-21. A total of 197 carers took part in the study. The majority (76%) were women, mean age 57.4. Mean time since diagnosis was 6.2 years. In the past month, 45% of carers did not spend any extra time per week helping their relative/friend with general caring activities such as cleaning the house; 31% spent 1-19 hr/week and 23% spent 20 or more hours/week doing so. Most carers were comfortable assisting their relative/friend, though more carers felt uncomfortable assisting with HNC-specific support tasks (31% uncomfortable helping with medication) compared with general support tasks (7% uncomfortable helping with appointments). Feeling uncomfortable with head and neck-specific care tasks was a significant predictor of experiencing depression and anxiety.


Tuina Manipulation to Reduce Inflammation and Cartilage Loss in Knee Osteoarthritis Rats.
Clinical trials suggest that Tuina manipulation is effective in treating knee osteoarthritis (KOA), while further studies are required to discover its mechanism. Therefore, the manipulation of animal models of knee osteoarthritis is critical. This protocol provides a standard process for Tuina manipulation on KOA rats and a preliminary exploration of the mechanism of Tuina for KOA. The press and kneading manipulation method (a kind of Tuina manipulation that refers to pressing and kneading the specific area of the body surface) is applied on 5 acupoints around the knee joint of rats. The force and frequency of the manipulation were standardized by finger pressure recordings, and the position of the rat during manipulation is described in detail in the protocol. The effect of manipulation can be measured by pain behavior tests and microscopic findings in synovial and cartilage. KOA rats showed significant improvement in pain behavior. The synovial tissue inflammatory infiltration was reduced in the Tuina group, and the expression of tumor necrosis factor (TNF)-α was significantly lower. Compared to the control group, chondrocyte apoptosis was less in the Tuina group. This study provides a standardized protocol for Tuina manipulation on KOA rats and preliminary proof that the therapeutic effects of Tuina may be related to reducing synovial inflammation and delayed chondrocyte apoptosis.


Dopamine modulates the neural representation of subjective value of food in hungry subjects.
Although there is a rich literature on the role of dopamine in value learning, much less is known about its role in using established value estimations to shape decision-making. Here we investigated the effect of dopaminergic modulation on value-based decision-making for food items in fasted healthy human participants. The Becker-deGroot-Marschak auction, which assesses subjective value, was examined in conjunction with pharmacological fMRI using a dopaminergic agonist and an antagonist. We found that dopamine enhanced the neural response to value in the inferior parietal gyrus/intraparietal sulcus, and that this effect predominated toward the end of the valuation process when an action was needed to record the value. Our results suggest that dopamine is involved in acting upon the decision, providing additional insight to the mechanisms underlying impaired decision-making in healthy individuals and clinical populations with reduced dopamine levels.


NMR and DFT analysis of [Re(2)H(2)(CO)(9)]: evidence of an eta(2)-H(2) intermediate in a new type of fast mutual exchange between terminal and bridging hydrides.
Protonation of the anion [Re(2)H(CO)(9)](-) (1) with a strong acid at 193 K affords the neutral complex [Re(2)H(2)(CO)(9)] (2), that in THF above 253 K irreversibly loses H(2) to give [Re(2)(CO)(9)(THF)], previously obtained by room-temperature protonation of 1. Treatment of 2 with NEt(4)OH restores the starting anion 1. Variable temperature (1)H and (13)C NMR spectra as well as T(1) measurements agree with the formulation of 2 as a classical [Re(2)H(mu-H)(CO)(9)] complex, in which two dynamic processes takes place. The "windshield-wiper motion" observed in several related complexes equalizes the two carbonyls trans to the hydrides (E(a) = 44(1) kJ mol(-)(1)), while another much faster process equalizes bridging and terminal hydrides already at 172 K. The variable temperature behavior of the (1)H transverse relaxation times revealed also proton exchange between 2, water, and the parent anion 1 (due to the acidity of 2), but such a process is too slow to account for the fast hydrides exchange in 2. The nature of the latter process has been investigated both experimentally and theoretically. Kinetic data, obtained by the analysis of the variable temperature (1)H spectra (E(a) = 24.5(5) kJ mol(-1)), revealed a small normal kinetic isotope effect (ca. 1.5). The (2)H chemical shift of the fully deuterated isotopomer 2-d(2) was found isochronous with 2, thus ruling out the presence of a significant concentration of a nonclassical [Re(2)(eta(2)-H(2))(CO)(9)] tautomer, in fast exchange with the classical dihydride. Density functional theory (DFT) calculations, carried out at the B3LYP level, confirmed the formulation of [Re(2)H(2)(CO)(9)] as a classical complex. However, when DFT was used to obtain a detailed description of the dynamic behavior of 2 in solution, a new type of hydride fast exchange emerged, involving the nonclassical tautomer as a relatively high energy (12.7 kJ mol(-1)) intermediate. Isotopic perturbation of the equilibrium by partial deuteration of 2 indicated the preference of deuterium for the bridging sites, with Delta H degrees = -475(4) J mol(-1) and Delta S degrees = -0.80(2) J K(-1) mol(-1). The same preference was observed in the anion [Re(2)H(mu-H)Cl(CO)(8)](-).


Protracted treatment of C57B1 mice with Zn-DTPA after 241Am injection reduces the long-term radiation effects.
Repeated intraperitoneal injections of ZnNa3-diethylenetriaminepenta-acetate (ZnDTPA), once a week, during 8 successive weeks, and starting 4 days after injection of 58 and 373 kBq 241Am/kg to C57B1 mice, were an effective protection against long-term radiation damage. At both dose levels of 241Am, Zn-DTPA reduced the 241Am concentration in bones by between 33% and 45%, and in the liver by 97%. Mean survival with 241Am was shortened in Zn-DTPA-treated mice, by 17% at the lower dose level and by 70% at the higher dose level. After treatment with DTPA at the lower 241Am level, survival became equal to that of control mice without 241Am, while at the higher level life span was still shortened. After the lower 241Am dose the incidence of bone tumours, liver carcinomas and the total number of all malignant tumours were significantly reduced by chelation therapy. The decrease in bone tumour incidence was proportional to the decrease in 241Am concentration and reduction in cumulative radiation dose in bone after chelation therapy. The incidence of liver carcinomas was reduced to that in non-241Am-injected mice and the reduction was thus proportional to the 97% reduction in 241Am concentration of the liver at the end of chelation therapy. After the higher 241Am dose no tumours showed up in sham-treated mice, probably due to the overkill effect on the cells at risk. In the corresponding Zn-DTPA-treated mice, bone tumours and a few other malignant tumours were observed.


Tropical Storm Allison rapid needs assessment--Houston, Texas, June 2001.
On June 5, 2001, Tropical Storm Allison made landfall on Galveston Island, Texas. During the next 2 days, the system soaked much of southeast Texas and south-central Louisiana with more than 10 inches of rain as it moved slowly northward. On June 7, the storm made a clockwise loop back to the southwest, bringing even more rain to already drenched areas. The record rainfall caused billions of dollars in flood-related damage and approximately 25 deaths and led to a presidential disaster, declaration covering 31 Texas counties (Figure 1) and 28 Louisiana parishes. Harris County, Texas (2000 population: 3,400,578), center of the Houston metropolitan area, was among the hardest hit with some areas receiving up to 37 inches of rain in 24 hours (Figure 2). To evaluate the community's immediate public health needs, the City of Houston Department of Health and Human Services (HDHHS) conducted a rapid needs assessment in the areas most affected by flooding. This report summarizes assessment results, which identified increased illness in persons living in flooded homes, suggesting a need for rapid resolution of flood-related damage and the possibility that residents should seek temporary housing during clean-up and repair. The findings underscore the usefulness of rapid needs assessment as a tool to minimize misinformation, identify actual health threats, and ensure delivery of resources to those with the greatest and most immediate need.


The enhanced extended phenomenological kinetics method to deal with timescale disparity problem among different reaction pathways.
Kinetic Monte Carlo method can provide valuable mechanistic insights for catalytic systems. Nonetheless, it suffers from the notorious problem of timescale disparity due to the existence of the complex catalytic network that consists of fast events and slow events. Previously, we have proposed the extended phenomenological kinetics (XPK) method that effectively deals with the timescale disparity problem between diffusion and reaction. However, it remains a great challenge to simulate systems with timescale disparity among different reaction pathways, which is important when selectivity is the major concern. In this study, we implement the enhanced XPK method to address this problem. The new algorithm works by identifying states connected through fast transitions and compressing them into a "superstate" when the chosen states satisfy a local steadystate condition. This state compression algorithm simplifies the reaction network by concealing the fast transitions. The accuracy and efficiency of the algorithm are demonstrated by two model systems: selective catalytic hydrogenation and selective catalytic decomposition. The enhanced XPK method is expected to be beneficial to the kinetic simulations of catalytic systems, especially those with complex reaction networks.


3D bioprinting of an electroactive and self-healing polysaccharide hydrogels.
Polysaccharide hydrogels including alginate, agarose, hyaluronic acid, and chitosan have been widely used as scaffolds in 3D bio-printing field. Konjac glucomannan (KGM) exhibits excellent properties of water solubility, biocompatibility, and biodegradability. Herein composite hydrogels were prepared via Schiff-base reaction between the aldehyde group of oxidized konjac glucomannan (OKGM) and the amino group of branched polyethyleneimine (PEI). The OKGM/PEI composite hydrogel displayed self-healing ability and pH sensitivity and showed shear thinning capability, which is suitable for 3D bio-printing technology. Furthermore, the OKGM/PEI electroactive composite hydrogel was obtained by adding carbon nanotubes (CNTs). Then the rheological behavior and morphology of OKGM/PEI electroactive hydrogels were thoroughly characterized. The conductivities of OKGM/PEI electroactive composite hydrogels increased with increasing the content of CNTs. The rheological behavior and 3D bio-printability of OKGM/PEI electroactive hydrogels were also tested. It was found that CNTs can also improve the bio-printability of OKGM/PEI electroactive hydrogels. Thus, the OKGM/PEI electroactive hydrogels could be employed as scaffolds for muscle and cardiac nerve tissue regeneration.


Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors.
Hepatitis C virus (HCV) replication is dependent on a liver-specific microRNA (miRNA), miR-122. A recent clinical trial reported that transient inhibition of miR-122 reduced viral titres in HCV-infected patients. Here we set out to better understand how miR-122 inhibition influences HCV replication over time. Unexpectedly, we observed the emergence of an HCV variant that is resistant to miR-122 knockdown. Next-generation sequencing revealed that this was due to a single nucleotide change at position 28 (G28A) of the HCV genome, which falls between the two miR-122 seed-binding sites. Naturally occurring HCV isolates encoding G28A are similarly resistant to miR-122 inhibition, indicating that subtle differences in viral sequence, even outside the seed-binding site, greatly influence HCV's miR-122 concentration requirement. In addition, we found that HCV itself reduces miR-122's activity in the cell, possibly through binding and sequestering miR-122. Our study provides insight into the interaction between miR-122 and HCV, including viral adaptation to reduced miR-122 bioavailability, and has implications for the development of anti-miR-122-based HCV drugs.


Teleconsultation Services in Pediatric Primary Care in Austria: Upgrading Clinical Decision Support in Primary Health Care Settings.
Introduction: The general practitioners' increasing comprehensive pediatric health care provision in Austria faces great challenges in ensuring high-quality health care in the future as the shortage of pediatricians continues to grow. Tele-expertise services provide an excellent opportunity to facilitate and strengthen interdisciplinary collaboration and access medical expertise of uncertainties in diagnosis and treatment plans. The purpose of this study was to investigate and evaluate the usability, applicability, and clinical advantages of an Austrian tele-expertise platform for doctors, emphasizing its value to strengthen collaborative efforts to extend and ensure quality care in infant, child, and adolescent health while focusing on diagnostic acceleration, verification, and potential modification of a treatment plan. Materials and Methods: A mixed-method approach included the retrospective evaluation of data provided via Intercom to elicit professional and geographical distribution and analysis of four hypotheses (H1: geographic distribution of initial enquires; H2: pediatric expertise level of the requester; H3: teleconsultations will result in changes in diagnosis and therapeutic decisions; and H4: teleconsultations stimulate cooperation and collaboration between physicians of all specialties). The study was based on survey questionnaires and qualitative semi-structured interviews. Discussion: Benefits were the most apparent in shorter diagnosis times, a potential quality increase in care, and cooperative stimulation. Intended therapy plans were found to be more sensitive to modification. Nevertheless, an overall positive attitude toward the teleconsultation chat became obvious. Moreover, the potential regarding quality improvements in pediatric primary care, shorter diagnosis time, and improved treatment options was found. Conclusions: Outcomes are urging Austrian health authorities to establish political and legal structures for appropriate monetary compensation and broad application of an expert consultation system. The article further highlights the importance of teleconsultations in critical situations, such as pandemic times.


Effects of hypercapnea and of hypercapnea in combination with hypoxia on midbrain-induced cardiac dysrhythmias.
Stimulation of the midbrain during acute combined arterial hypoxia and hypercapnea produces serious cardiac dysrhythmias which are not evoked when stimulation is elicited either with normal arterial blood gas tensions or with isolated mild hypercapnea. The cardiac dysrhythmias are mediated by both enhanced sympathetic and parasympathetic efferent discharge. The results support the concept that increased autonomic activity in combination with acute arterial hypoxia and hypercapnea contribute significantly to the exhibition of serious cardiac rhythm disturbances. Acute hypoxia appears to be the major determinant of such dysrhythmias.


Plastic ingestion in giant tortoises: An example of a novel anthropogenic impact for Galapagos wildlife.
The human population of Galapagos has rapidly increased in the last decades accelerating the anthropogenic pressures on the archipelago's natural resources. The growing human footprint, including inadequate management of garbage, may lead to conservation conflicts. Here, we assessed the ingestion of debris by Western Santa Cruz giant tortoises (Chelonoidis porteri) within human-modified and protected areas. Additionally, we characterized environmental debris and quantified tortoise abundance together with tortoise fecal samples. We processed a total of 6629 fecal samples along a gradient of anthropogenic disturbance based on human debris presence. We found 590 pieces of debris in samples within human-modified areas (mean of 3.97 items/kg of feces) and only two pieces in the protected area (mean of 0.08 items/kg of feces). Plastic waste was the predominant category in feces within the anthropic area (86.3%; n = 511), followed by cloth, metal, paper, synthetic rubber, construction materials, and glass. On average, the proportion of plastic was higher in feces (84%) than it was in environmental debris (67%), denoting that plastics are more readily ingested than other types of debris. We also found that green, white, and light blue plastics were consumed more often than their prevalence in the environment, suggesting color discrimination. Tortoise abundance was higher in the protected area when compared to the human-modified area; however, recapture rates were higher in anthropized landscapes which increases tortoise exposure to plastics and other human associated threats. Our results indicate that plastics are frequently consumed by tortoises in the polluted anthropic areas of western Santa Cruz, but scarce in protected areas. More research is needed to understand the negative impacts associated with plastics for Galapagos terrestrial species. We encourage local stakeholders to implement current policies limiting expansion of urban areas, plastic use, and improving waste management systems to minimize threats to human and animal health.


The Degree of Diabetic Retinopathy in Patients with Type 2 Diabetes Correlates with the Presence and Severity of Coronary Heart Disease.
Both diabetic retinopathy (DR) and coronary heart disease (CHD) are clinically significant in diabetic patients. We investigated the correlation between the severity of DR and the presence and severity of CHD among type 2 diabetic patients. A total of 175 patients who were examined at the DR clinic and underwent dual-source computed tomography (DSCT) angiography within 6 months were included. The degree of DR was graded as no DR, nonproliferative DR (NPDR), and proliferative DR (PDR). The severity of CHD and the numbers of significant stenotic coronary artery on DSCT angiography according to DR grade were assessed. The mean Agatston Calcium Score (ACS) in patients with PDR was significantly higher than other groups (P < 0.001). The overall odds of an ACS increase were about 4.7-fold higher in PDR group than in no DR group (P < 0.001). In PDR group, in comparison with in no DR, the odds of having 1 or 2 arterial involvement were 3-fold higher (P = 0.044), and those of having 3 were 17-fold higher (P = 0.011). The c-index, one of the predictability values in regression analysis model, was not significantly increased when PDR was added to classical CHD risk factors (0.671 to 0.706, P = 0.111). Conclusively, patients with PDR develop a greater likelihood of not only having CHD, but being more severe nature. PDR has no additional effect to classical CHD risk factors for predicting CHD.


Application of evidence-based teaching in maternal and child health in remote Vietnam.
To develop, implement, and evaluate an evidence-based multidisciplinary teaching program to improve maternal and infant health in remote Vietnam. Needs assessments identified prevention of infection, neonatal resuscitation, and prevention of postpartum hemorrhage as primary targets. A 3-day workshop based on the small group, interactive, skills-based SCORPIO method was developed. Participants underwent formative written and performance-based assessments. Qualitative and quantitative evaluation of course content and teaching method was conducted. Two annual workshops were conducted for 58 health professionals, all of whom demonstrated skills acquisition to an adequate standard on completion. The workshops were rated as good or excellent overall by 100% of the participants, who reported that the content would help with their clinical work and that the teaching method was acceptable and easy to understand. We demonstrated the SCORPIO method can be adapted to teach knowledge and clinical skills in remote Vietnam. Further work is needed to demonstrate an effect on health outcomes.


Integration of Nine Steps into One Membrane Reactor To Produce Synthesis Gases for Ammonia and Liquid Fuel.
The synthesis of ammonia and liquid fuel are two important chemical processes in which most of the energy is consumed in the production of H2 /N2 and H2 /CO synthesis gases from natural gas (methane). Here, we report a membrane reactor with a mixed ionic-electronic conducting membrane, in which the nine steps for the production of the two types of synthesis gases are shortened to one step by using water, air, and methane as feeds. In the membrane reactor, there is no direct CO2 emission and no CO or H2 S present in the ammonia synthesis gas. The energy consumption for the production of the two synthesis gases can be reduced by 63 % by using this membrane reactor. This promising membrane reactor process has been successfully demonstrated by experiment.


Use of botulinum toxin in the treatment of achalasia.
Achalasia is a chronic esophageal motor disorder characterized by failure of the lower esophageal sphincter (LES) to relax during swallowing, aperistalsis of the esophageal body, and, often, an elevated resting LES pressure. Pneumatic dilation and Heller cardiomyotomy have been the time-honored, accepted treatments, but each may carry significant morbidity. Recently, intrasphincteric injection of botulinum toxin has been shown to be an effective treatment for achalasia, probably by reducing the excitatory cholinergic tone of the LES. Subjective and objective improvement have been reported in many patients with few reported adverse reactions. Clinical improvement generally lasts 2-6 months with patients often requiring repeat treatment. Although studies directly comparing botulinum toxin injection with pneumatic dilation and surgical myotomy are needed, botulinum toxin injection has rapidly become another therapeutic option in the treatment of achalasia.


An overview of obesity: its significance to nursing: definition, prevalence, etiologic concerns, and treatment strategies.
This article has presented an overview of obesity. It has explored the significance of obesity to nursing today. The definition of obesity vis-à-vis overweight has been delineated. The psychological, physiologic and socioenvironmental causes of obesity were discussed. Finally, some of the important treatment strategies, past and current, were discussed, concluding that a combination of strategies are needed to treat this complex health problem caused by the interaction of several factors--environmental, physiologic in the form of predisposition, and psychological. The following articles provide the reader with an understanding of obese people and the specific nursing interventions associated with caring for these individuals. Whether the obese patient has a postoperative bypass or is a child in a school system within the community, the nurse's role must be based on an understanding of obesity, its causes, and current treatments.


Antagonistic interaction between Ezh2 and Arid1a coordinates root patterning and development via Cdkn2a in mouse molars.
Patterning is a critical step during organogenesis and is closely associated with the physiological function of organs. Tooth root shapes are finely tuned to provide precise occlusal support to facilitate the function of each tooth type. However, the mechanism regulating tooth root patterning and development is largely unknown. In this study, we provide the first in vivo evidence demonstrating that Ezh2 in the dental mesenchyme determines patterning and furcation formation during dental root development in mouse molars. Mechanistically, an antagonistic interaction between epigenetic regulators Ezh2 and Arid1a controls Cdkn2a expression in the dental mesenchyme to regulate dental root patterning and development. These findings indicate the importance of balanced epigenetic regulation in determining the tooth root pattern and the integration of roots with the jaw bones to achieve physiological function. Collectively, our study provides important clues about the regulation of organogenesis and has general implications for tooth regeneration in the future.


Epigenetic balance of gene expression by Polycomb and COMPASS families.
Epigenetic regulation of gene expression in metazoans is central for establishing cellular diversity, and its deregulation can result in pathological conditions. Although transcription factors are essential for implementing gene expression programs, they do not function in isolation and require the recruitment of various chromatin-modifying and -remodeling machineries. A classic example of developmental chromatin regulation is the balanced activities of the Polycomb group (PcG) proteins within the PRC1 and PRC2 complexes, and the Trithorax group (TrxG) proteins within the COMPASS family, which are highly mutated in a large number of human diseases. In this review, we will discuss the latest findings regarding the properties of the PcG and COMPASS families and the insight they provide into the epigenetic control of transcription under physiological and pathological settings.


[Molecular genetic markers of predisposition to thrombosis in adolescents with essential hypertension ].
To estimate the spread and distribution of genotypes and alleles of thrombosis predisposition gene polymorphisms in adolescents with essential hypertension (EH). One hundred and thirty-seven 14- to 17-year-old adolescents were examined. There were 3 examined groups: 1) 37 EH patients with prothrombotic changes (PTC); 2) 60 EH patients without PTC; 3) 40 healthy adolescents. Prothrombin time, activated partial thromboplastin time, and the levels of fibrinogen and soluble fibrin monomer complexes were determined. The adolescents were assigned to a PTC group if they had changes by one or several above indicators. Polymerase chain reaction assay was used to type coagulation factor II (FII) and factor V (FV), plasminogen activator inhibitor type 1 (PAI-7), 5,10-methylenetetrahydrofolate reductase (MTHFR), and methionine syntase reductase (MTRR) gene polymorphisms. Group differences were determined by qualitative signs, by using.the χ2test and Yates' correction for continuity and Fisher's exact test if one of the groups had at least 5 individuals. All differences were considered statistically significant at p < 0.05. FV R506Q, FII G20210A, PAI1-675 4G/5G, MTHFR A1298C, and MTRR A66G polymorphisms have not been found to affect the hemostatic system in adolescents with EH. MTHFR C677T may act as a risk factor of PTC in adolescents with EH, by increasing the risk of thrombotic events at an old age. It is recommended that the determination of molecular genetic markers for predisposition to thrombosis be actively used in adolescents with EA to form a risk group for thrombotic events and to implement preventive measures..


[Pathological Diagnoses and Whole-genome Sequence Analyses of the Jaagsiekte Sheep Retrovirus in Xinjiang, China].
To carry out pathologic diagnoses and whole-genome sequence analyses of the Jaagsiekte sheep retrovirus (JSRV) in Xinjiang, China, we first observed sheep suspected to have the JSRV. Then, the extracted virus suspension was observed by transmission electron microscopy (TEM). Total RNAs from lungs of JSRV-infected sheep were extracted and reverse-transcribed using a cDNA synthesis kit. Six pairs of primers were designed according to the exogenous reference virus strain (AF105220). Reverse transcription-polymerase chain reaction was carried out from JSRV-infected tissue, and the whole genome of the JSRV sequenced. Our results showed: flow of nasal fluid ("wheelbarrow test"); different sizes of adenoma lesions in the lungs; papillary hyperplasia of alveolar epithelial cells; alveolar cavity filled with macrophages; dissolute nuclei in central lesions. TEM revealed JSRV particles with a diameter of 88 nm to 125. 4 nm. The full-length of the viral genome sequence was 7456 bp. BLAST analyses showed nucleotide homology of 96% and 95% compared with that of the representative strain from the USA (AF105220) and UK (AF357971). Nucleotide homology was 89.8% and 89.9% compared with the endogenous Jaagsiekte sheep retrovirus, Inner Mongolia strain (DQ838493) and USA strain (EF680300). The specific pathogenic amino-acid sequence "YXXM" was found in the TM district, similar to the exogenous JSRV: this gene has been reported to be oncogenic. This is the first report of the complete genomic sequence of the exogenous JSRV from Xinjiang, and could lay the foundation for study of the biological characteristics and pathogenic mechanisms of the pulmonary adenomatosis virus in sheep.


Phospholipid and triacylglycerol fatty acid content and pattern in the cardiac endothelium of rats depleted in long-chain polyunsaturated omega 3 fatty acids.
Rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3-depleted rats) display several features of the metabolic syndrome including hypertension and cardiac hypertrophy. This coincides with alteration of the cardiac muscle phospholipid and triacylglycerol fatty acid content and/or pattern. In the present study, the latter variables were measured in the cardiac endothelium of normal and omega3-depleted rats. Samples derived from four rats each were obtained from 16 female normal fed rats and three groups of 36-40 female fed omega3-depleted rats each aged 8-9, 15-16 and 22-23 weeks. At comparable mean age, the ratio between the square root of the total fatty acid content of phospholipids and cubic root of the total fatty acid content of triacylglycerols was lower in omega3-depleted rats than in control animals. The total fatty acid content of triacylglycerols was inversely related to their relative content in C20:4omega6. Other differences between omega3-depleted rats and control animals consisted in a lower content of long-chain polyunsaturated omega3 fatty acids in both phospholipids and triacylglycerols, higher content of long-chain polyunsaturated omega6 fatty acids in phospholipids, higher activity of delta9-desaturase (C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios) and elongase [(C16:0 + C16:1omega7)/(C18:0 + C18:1omega9) and C20:4omega6/C22:4omega6 ratios], but impaired generation of C22:6omega3 from C22:5omega3 in the former rats. These findings support the view that cardiovascular perturbations previously documented in the omega3-depleted rats may involve impaired heart endothelial function.


A multicenter evaluation of levobunolol (Vistagan) in Germany.
We evaluated the efficacy and safety of 0.5% levobunolol HC1 (Vistagan) in 2,041 glaucoma patients at 143 sites in the Federal Republic of Germany. This study was a 3-month, open-label, noncomparative trial of levobunolol administered twice daily. Eighty-five percent of the patients completed the study period with well-controlled intraocular pressure (IOP). Treatment was discontinued in the remaining 15%: 7% for adverse reactions, 1% for lack of drug efficacy, and 7% for reasons unrelated to the study treatment. Efficacy, ocular drug tolerance, and systemic safety were judged as good to very good in approximately 80% of the patients. This large, postapproval study confirms previous findings of several well-controlled clinical trials indicating that levobunolol is an effective drug for the treatment of elevated IOP and is safe and comfortable for most patients.


Use of Allevyn heel in the management of heel ulcers.
This small uncontrolled study examined the effectiveness of Allevyn Heel. Twenty-two patients were recruited: 13 with heel pressure ulcers, four with diabetic heel ulcers, four with arterial heel ulcers and one 'other'. Ulcers were assessed before treatment and after the start of the dressing regimen at weeks two and four and at the end of the study. Patients were treated with Allevyn Heel for a mean of 47.2 days, and dressings were left in place for an average of 2.2 days before being changed. By the end of treatment, 32% of the ulcers had completely or almost healed, and a further 27% were showing evidence of granulation. Application was considered easy in 98% of instances, and 91% of the patients reported that Allevyn Heel was comfortable to wear. Allevyn Heel was found to be effective and easy to use. This extends the range of wounds that are suitable for management with Allevyn, although a larger-scale study is needed to confirm the utility of Allevyn Heel for these type of heel wounds. This study was supported by Smith and Nephew, Germany.


Tight adhesions after spinal cord stimulation observed during dorsal root entry zone lesioning for pain after spinal root avulsion: illustrative cases.
Patients often experience strong shooting pains after spinal root avulsion. The efficacy of spinal cord stimulation (SCS) for this type of pain is inconsistent; however, dorsal root entry zone (DREZ) lesioning (DREZ-lesion) has often proven to be an effective treatment modality. The authors report two cases in which DREZ-lesion was performed to treat pain after spinal root avulsion after implantation of SCS, but the operations were challenging due to strong adhesions. The authors present two cases of patients with pain after spinal root avulsion in whom SCS implantation was only temporarily effective. Patients complained of persistent and paroxysmal shooting pains in the upper extremities. SCS removal and DREZ-lesion were performed, but adhesions in the epidural and subdural space contacting the leads were strong, making it difficult to expose the DREZ. Although adhesions around the spinal cord can be caused by trauma, the authors believe that in these cases, the adhesions could have been caused by the SCS leads. There are few previous reports confirming the efficacy of SCS in treating pain after spinal root avulsion; therefore, caution is required when considering SCS implantation.


Current techniques and outcomes in hysteroscopic sterilization: current evidence, considerations, and complications with hysteroscopic sterilization micro inserts.
To describe the current data regarding effectiveness, complications, postoperative evaluation, and surgical interventions associated with Essure hysteroscopic sterilization. Hysteroscopic sterilization is a commonly performed procedure that is offered as a well tolerated, effective, outpatient method of permanent sterilization. Over the past several years, concerns have been raised regarding correct placement and postoperative complications. This has led to statements by both the Food and Drug Administration (FDA) in October, 2016 and American Association of Gynecologic Laparoscopists in February, 2017, as a significant portion of women seek removal of these devices. A current black-box warning issued by the FDA in 2016 recommends discussion of 'the probabilities of rates or events' of adverse outcomes associated with Essure placement. Although hysteroscopic sterilization is usually a safe, effective option for permanent contraception, new evidence regarding complications has emphasized the need for proper education and counseling. Appropriate patient selection and knowledge of potential complications is paramount to ensuring patients, and medical providers are well informed and have realistic expectations regarding potential placement and postoperative issues.


Levothyroxine before conception in women with thyroid antibodies: a step forward in the management of thyroid disease in pregnancy.
Studies suggesting an association between thyroid autoimmunity and pregnancy-related adverse outcomes, particularly miscarriage and preterm delivery, date to nineties. The postulated causes for these associations were attributed to a direct or indirect effect of autoimmunity and/or to a mild thyroid impairment. Since then, small trials and several meta-analyses confirmed a detrimental effect of thyroid autoimmunity and suggested that patients with thyroid autoimmunity who wish to conceive or are pregnant might benefit from levothyroxine treatment to decrease the rate of miscarriage and preterm delivery. A recently published large trial investigated the hypothesis that the administration of levothyroxine in euthyroid antibody-positive women seeking pregnancy might increase the live birth rate. Women who were trying to conceive and had a history of miscarriage or infertility were tested for TSH and thyroperoxidase antibodies. Euthyroid antibody positive women were randomized to receive 50 μg/day of levothyroxine or placebo and were tested for thyroid function throughout pregnancy. In patients with thyroid function test results outside of assay-specific reference limits, the trial agent was discontinued. 56.6% in the LT4 group and 58.3% in the placebo group became pregnant and the live birth rates were similar in the two groups (37.4% vs 37.9%, respectively). There was also no difference in pre-term delivery rate and other maternal and neonatal outcomes between the two groups. The present commentary discusses the main findings of the trial and implications for clinical practice.


Low HIV incidence among women following sexually transmitted infection does not support national pre-exposure prophylaxis recommendations.
: Current United States guidelines recommend that clinicians offer HIV pre-exposure prophylaxis (PrEP) to women with gonorrhea or syphilis. We estimated HIV incidence among women following a syphilis, gonorrhea, or chlamydia diagnosis among women in King County, WA using surveillance data from 2008 to 2018. Among women with diagnosed with gonorrhea and among women diagnosed with chlamydia the estimated HIV incidence rates were 0.06 and 0.02 per 100 person years, respectively. No women reported with syphilis were diagnosed with HIV.