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Eculizumab is an effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). However, considering the risk of life-threatening meningococcal disease, life-long duration and costs, there are strict criteria for initiation of therapy. To evaluate the application and real-world effectiveness of eculizumab in the Netherlands, a multicenter retrospective cohort study was conducted: indications and treatment outcomes were collected for 105 Dutch PNH patients. In all patients, eculizumab was initiated conforming to indications as formulated in the Dutch PNH guideline. According to recently published response criteria, 23.4% of the patients had reached a complete hematological response, 53.2% a good or partial response, and 23.4% a minor response after 12 months of therapy. In the majority of patients the response remained stable during long-term follow-up. The degree and relevance of extravascular hemolysis significantly differed between response groups (p = 0.002). Improvements of EORTC-QLQc30 and FACIT-fatigue scores were observed, however patients reported lower scores than the general population. A detailed evaluation of 18 pregnancies during eculizumab showed no maternal or fetal deaths, and no thromboembolic events during pregnancy. This study demonstrates that the majority of patients benefit from eculizumab when adhering to the indications as formulated in the Dutch PNH guideline. However, novel therapies are needed to further improve real-world outcomes, such as hematological responses and quality of life. | Hemoglobinuria, Paroxysmal |
Buprenorphine is a partial agonist at the micro -opioid receptor with long duration of action and also exhibits delayed antagonist activity. Buprenorphine is finding increasing use as a treatment agent for opioid abuse, though its low efficacy is not well tolerated by all addicts. There is interest in developing a higher efficacy version of buprenorphine and in this mini-review some of the ligands recently discovered, that share with buprenorphine a profile of agonism followed by delayed antagonism, are discussed. | Etorphine |
OBJECTIVE: Reflect on the essence of care in health vulnerability from the phenomenological perspective of Martin Heidegger. METHOD: Theoretical-reflexive study, anchored in three essential parts: 1) Care in Heidegger; 2) The essence of care in health vulnerability; And 3) Nursing care actions on health vulnerability. RESULTS: Vulnerability must be recognized as an indelible trait of the human condition and has its constituents in the human being, co-presence and care. Caring is an interactive process that reveals itself in the relationship with the other. Respecting the integrity of the Being in vulnerability must be a priority in nursing care, through behaviors that privilege the Being. CONCLUSION: Understanding ontological care and its relation to vulnerability under Heidegger's phenomenological view allowed us to uncover the facets of care in health vulnerability by adding to the nursing knowledge body a comprehensive and reflective perspective. OBJETIVO: Refletir sobre a essencia do cuidado na vulnerabilidade em saude sob a perspectiva fenomenologica de Martin Heidegger. METODO: Estudo teorico-reflexivo, ancorado em tres partes essenciais: 1) O cuidado em Heidegger; 2) A essencia do cuidado na vulnerabilidade em saude; e 3) As acoes do cuidar em enfermagem na vulnerabilidade em saude. RESULTADOS: A vulnerabilidade deve ser reconhecida como traco indelevel da condicao humana e tem seus constituintes na pessoa humana, co-presencas e cuidado. O cuidar e um processo interativo que se desvela na relacao com o outro. Respeitar a integridade do Ser em vulnerabilidade deve ser prioridade no cuidar em enfermagem, por meio de comportamentos que privilegiem o Ser. CONCLUSAO: Compreender ontologicamente o cuidado e a sua relacao com a vulnerabilidade sob o olhar fenomenologico de Heidegger permitiu desvelar as facetas do cuidado na vulnerabilidade em saude, agregando ao corpo de conhecimento da Enfermagem uma perspectiva compreensiva e reflexiva. | Nursing Care |
Regrouping is a common management practice on commercial dairy farms. The objectives of this study were to examine the effects of regrouping on feeding behavior, social behavior, and milk production. Eleven mid-lactation Holstein cows were individually introduced into previously established social groups. Behavior and milk production were monitored from 3 d before until 3 d after regrouping. Cows were fed a total mixed ration ad libitum twice daily. Time-lapse video was used to quantify feeding and social behavior. Cows spent approximately 15 min less time eating in the first hour following regrouping compared with the 3 d before regrouping. Cows were displaced from the feeding area on average 10 times/d before regrouping, but this value increased to more than 25 times ( +/- 2.6) on the day of mixing and gradually declined on the days following. The number of lying bouts declined from 12.2 +/- 0.9 to 10.5 +/- 0.9 on the day of regrouping; lying time showed a similar tendency. Cows initiated, on average, 7.5 +/- 1.3 allogrooming events/d over the 3 d before regrouping but this declined to 1.3 +/- 1.3 events on the day of mixing and remained lower than baseline for the following 3 d. Milk production declined from 43.4 +/- 1.5 kg/d to 39.7 +/- 1.5 kg/d on the day of regrouping, but did not differ from premixing levels on subsequent days. This study shows that regrouping can disrupt behavior and production in the hours and days following regrouping and suggests the need for future research to identify management changes that reduce these effects. | Lactation |
Black-headed grosbeaks (Pheucticus melanocephalus) and rose-breasted grosbeaks (Pheucticus ludovicianus) are passerine bird species known to hybridize in the Great Plains of North America. Both extrinsic (environmental) and intrinsic factors (pre- and postzygotic reproductive isolation) have been credited for the generation and maintenance of the grosbeak hybrid zone, but little is known about the genetic characteristics of this hybrid zone. To investigate the stability and extent of the grosbeak hybrid zone, we constructed clines from both molecular sequence data (mtDNA, three autosomal intron loci, and one Z-linked locus) and morphological data (morphometric analyses and hybrid index scores) to determined zone centre and width. Hybrid zone centre and width were also determined for samples collected across the zone 40 years ago from morphological data. The present and past clines were compared and provided support for stability in hybrid zone location and width, and the evolutionary implications of this are discussed. Three models of hybrid zone maintenance were investigated to consider the influence of intrinsic and extrinsic factors on this zone. Our results suggest low hybrid frequencies, a stable zone location and narrow width, and reduced hybrid fitness over the past 40 years best categorize the grosbeak hybrid zone as a tension zone. | DNA, Z-Form |
PURPOSE: After radiation therapy (RT), various radiation-induced toxicities can develop in about one-fourth of patients. An international interest in using morbidity and mortality rates to monitor the quality of care and integrate morbidity and mortality review (MMR) meetings into organizations' governance processes has arisen. We report the first results of patients included in our MMR procedure that included biological assays for individual intrinsic radiosensitivity (IIRS). METHODS AND MATERIALS: Twenty-three patients were prospectively included in the MMR database. Twenty-two were evaluable for IIRS. Prostate (n=10) and breast (n=8) cancers were the most frequent disease types. The total dose delivered, determined according to the type of disease, ranged from 30 to 74 Gy. Our MMR procedure requires strict criteria: patients with unresolved toxicity of grade 3 or higher with availability of clinical (photographic) data, IIRS results obtained from skin biopsy assays, treatment modalities, and follow-up data. The RT technique and dosimetry were reviewed. RESULTS: Our prospective registration of toxicities showed mainly rectitis, occurring in 7 cases, and skin toxicities, occurring in 9. Of the 7 patients with rectitis, 5 received 66 Gy of post-prostatectomy RT with V50 (rectum volume receiving 50 Gy) ranging from 45% to 75% and a mean maximal dose of 66.5 Gy. For dermatitis and cystitis, the mean maximal doses were in the range of classical constraints without any overdosage or dose heterogeneity. No errors were found in the review of treatment planning and positioning. Conversely, all the patients were considered biologically as radiosensitive with genomic instability and ATM (ataxia telangiectasia mutated)-dependent DNA double-strand break repair impairments. CONCLUSIONS: The MMR review of files allowed clear answers for patients on the relationship between clinical events and their IIRS. Our procedure has allowed education of all our staff to monitor, identify, and document clinical, physical, and biological aspects of radiation-induced toxicities. Thus we recommend the introduction of the MMR procedure in RT departments. | Acute Radiation Syndrome |
Xylulose kinase is an important enzyme involved in xylose metabolism, which is considered as essential biocatalyst for sustainable lignocellulosic-derived pentose utilization. Bacillus coagulans IPE22 is an ideal bacterium for refinery due to its strong ability to ferment xylose at high temperature. However, the B. coagulans xylose utilization mechanism remains unclear and the related promising enzymes need to be developed. In the present study, the gene coding for xylulose kinase from B. coagulans IPE22 (Bc-XK) was expressed in Escherichia coli BL21 (DE3). Bc-XK has a 1536 bp open reading frame, encoding a protein of 511 amino acids (56.15 kDa). Multiple sequence alignments were performed and a phylogenetic tree was built to evaluate differences among Bc-XK and other bacteria homologs. Bc-XK showed a broad adaptability to high temperature and the enzyme displayed its best performance at pH 8.0 and 60 degrees C. Bc-XK was activated by Mg(2+) , Mn(2+) , and Co(2+) . Meanwhile, the enzyme could keep activity at 60 degrees C for at least 180 min. K(M) values of Bc-XK for xylulose and ATP were 1.29 mM and 0.76 mM, respectively. The high temperature stability of Bc-XK implied that it was an attractive candidate for industrial application. | Bacillus coagulans |
The neural cell adhesion molecule (NCAM) regulates differentiation and functioning of neurons by accumulating at the cell surface where it mediates the interactions of neurons with the extracellular environment. NCAM also induces a number of intracellular signaling cascades, which coordinate interactions at the cell surface with intracellular processes including changes in gene expression, transport and cytoskeleton remodeling. Since NCAM functions at the cell surface, its transport and delivery to the cell surface play a critical role. Here, we review recent advances in our understanding of the molecular mechanisms of the intracellular transport and cell surface delivery of NCAM. We also discuss the data suggesting a possibility of cross talk between activation of NCAM at the cell surface and the intracellular transport and cell surface delivery of NCAM." | Neural Cell Adhesion Molecules |
Mycotoxins are secondary metabolites produced by fungi contaminating the food chain that are toxic to animals and humans. Children up to 12 years old are recognized as a potentially vulnerable subgroup with respect to consumption of these contaminants. Apart from having a higher exposure per kg body weight, they have a different physiology from that of adults. Therefore they may be more sensitive to neurotoxic, endocrine and immunological effects. For these reasons, a specific and up-to-date risk analysis for this category is of great interest. In this review, an accurate analysis of the main mycotoxins occurring in food intended for children (deoxynivalenol, aflatoxins, ochratoxins, patulin and fumonisins) is presented. In particular, known mechanisms of toxicity and levels of exposure and bioaccessibility in children are shown. In addition, recent discoveries about the strategies of mycotoxins managing are discussed. | Infant Food |
This review of vasopressin in septic shock differs from previous reviews by providing more information on the physiology and pathophysiology of vasopressin and vasopressin receptors, particularly because of recent interest in more specific AVPR1a agonists and new information from the Vasopressin and Septic Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists was reviewed and synthesized. Vasopressin, a key stress hormone in response to hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin receptors and purinergic receptors. Rationales for use of vasopressin in septic shock are as follows: first, a deficiency of vasopressin in septic shock; second, low-dose vasopressin infusion improves blood pressure, decreases requirements for norepinephrine and improves renal function; and third, a recent randomized, controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests low-dose vasopressin may decrease mortality of less severe septic shock. Previous clinical studies of vasopressin in septic shock were small or not controlled. There was no difference in 28-day mortality between vasopressin-treated versus norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There was potential benefit in the prospectively defined stratum of patients with less severe septic shock (5 to 14 mug/minute norepinephrine at randomization): vasopressin may have lowered mortality compared with norepinephrine (26% versus 36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin also decreased mortality (compared with norepinephrine) if less severe septic shock was defined by the lowest quartile of arterial lactate or by use of one (versus more than one) vasopressor at baseline. Other investigators found greater hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also unique adverse effects (elevated liver enzymes and serum bilirubin). Use of higher dose vasopressin requires further evaluation of efficacy and safety. There are very few studies of interactions of therapies in critical care--or septic shock--and effects on mortality. Therefore, the interaction of vasopressin infusion, corticosteroid treatment and mortality of septic shock was evaluated in VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased 28-day mortality compared with corticosteroids plus norepinephrine (44% versus 35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective randomized controlled trials would be necessary to confirm this interesting interaction. In conclusion, low-dose vasopressin may be effective in patients who have less severe septic shock already receiving norepinephrine (such as patients with modest norepinephrine infusion (5 to 15 mug/minute) or low serum lactate levels). The interaction of vasopressin infusion and corticosteroid treatment in septic shock requires further study. | Vasopressins |
This paper reviews some of the questions that have been asked by experts and others as to why nuclear power plants are not located or placed underground. While the safeguards and present designs make such installations unnecessary, there are some definite advantages that warrant the additional cost involved. First of all, such an arrangement does satisfy the psychological concern of a number of people and, in so doing, might gain the acceptance of the public so that such plants could be constructed in urban areas of load centers. The results of these studies are presented and some of the requirements necessary for underground installations described, including rock conditions, depth of facilities, and economics. | Nuclear Reactors |
Five new naturally occurring natural products, including two atisine-type diterpene alkaloids (1 and 2), two atisane-type diterpenes (3 and 4), and a new natural product spiramine C2 (5), along with nine known ones (6-14), were isolated from the ethanolic extracts of the whole plant of Spiraea japonica var. acuminata Franch. Their structures were elucidated by extensive spectroscopic analysis. The anti-tobacco mosaic virus (TMV) activities of all the compounds were evaluated by the conventional half-leaf method. Six compounds (2, 3, 6, 7, 11, and 12) exhibited moderate activities at 100 mug/mL with inhibition rates in the range of 69.4-92.9%, which were higher than that of the positive control, ningnanmycin. Their preliminary structure-activity relationships were also discussed. | Spiraea |
BACKGROUND: Protection offered by coronavirus disease 2019 (COVID-19) vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking. METHODS: We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals (n = 55) who were either primed with Ad26.COV2.S only (n = 13) or were boosted with a homologous (Ad26.COV2.S, n = 28) or heterologous (BNT162b2, n = 14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n = 16) or double (n = 44) dose of BNT162b2. FINDINGS: We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals. In contrast, the impact of the homologous boost was quantitatively minimal in Ad26.COV2.S-vaccinated individuals, and Spike-specific antibodies and T cells were narrowly focused to the S1 region. CONCLUSIONS: Despite the small sample size of the study and the lack of well-defined correlates of protection against COVID-19, the immunological features detected support the utilization of a heterologous vaccine boost in individuals who received Ad26.COV2.S vaccination. FUNDING: This study is partially supported by the Singapore Ministry of Health's National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001, and COVID19RF-008), The Medical College St. Bartholomew's Hospital Trustees - Pump Priming Fund for SMD COVID-19 Research. | ChAdOx1 nCoV-19 |
CONCLUSION: This study observed a much higher percentage of unilateral sinus pathology than reported in the literature. Comprehensive evaluations of patient age, presenting symptoms, nasoendoscopy examination, and computed tomography (CT) findings help in the diagnosis of unilateral sinus disease. Nevertheless, histological confirmation remains obligatory for diagnosis. OBJECTIVES: To evaluate the clinical features, diagnosis, pathology, and CT findings in patients who had undergone sinus surgery for unilateral sinus diseases. PATIENTS AND METHODS: Among 524 patients who had undergone sinus surgery, patients with unilateral sinus opacification on the preoperative CT scans were selected. Data were collected from the medical records and CT findings were evaluated. RESULTS: Unilateral sinus opacification was identified in 121 (23.1%) patients. Male gender was predominant and the greatest number of patients had chronic rhinosinusitis. The mean age was oldest for fungus ball and youngest for antrochoanal polyp. Purulent discharge and foul odor were the common presenting symptoms under inflammatory conditions, while frequent epistaxis and cheek swelling were the main symptoms in neoplastic diseases. Calcifications were observed only in patients with fungus ball, while bony destruction was detected in both benign and malignant tumors. Punch biopsy performed in the office offered accurate histopathologic diagnosis in 94.3% of the patients. | Paranasal Sinus Diseases |
Bursera microphylla (BM), one of the common elephant trees, is widely distributed in the Sonoran desert in Mexico. The Seri ethnic group in the Sonoran desert uses BM as an anti-inflammatory and painkiller drug for the treatment of sore throat, herpes labialis, abscessed tooth, and wound healing. Dried stems and leaves of BM are used in a tea to relieve painful urination and to stimulate bronchial secretion. Furthermore, BM is used for fighting venereal diseases. To investigate the effects of the hexane fraction of resin methanol extract (BM-H) on cell growth, the acute myeloid cell line (OCI-AML3) was treated with 250, 25, or 2.5 microg/mL of BM-H. The first 2 concentrations were able to significantly decrease OCI-AML3 cell number. This reduced cell number was associated with decreased S-phase, blockade of G(2)/M phase of the cell cycle, and increased cell death. Similar results were obtained on all tested tumor cell lines of different origins. We found that blockade of the cell cycle was a result of upregulation of p21 protein in a p53-independent way. Increase of p21 was possibly a result of upstream upregulation of p-ERK (which stabilizes p21 protein) and downregulation of p-38 (which promotes its degradation). Regarding cell death, activation of caspase-3, but not of caspase-8 or -9, was detectable after BM-H treatment. In conclusion, these data suggest that BM-H inhibited proliferation of cell lines mainly by a p21-dependent, p53-independent mechanism and promoted apoptosis through activation of caspase-3 but not caspase-8 or -9. | Cell Line, Tumor |
A deteriorating neurologic state in a child with an acute brain insult is a life-threatening situation, and the decisions made during the first few minutes of management will frequently determine the outcome. Often, the family physician is the first person contacted by the parents to evaluate the sudden change in a child. Attention must be first directed toward ensuring an airway and maintaining adequate circulation. Computed tomographic study, toxicology screen and determination of acid-base status should follow. Possible causes of acute coma in children include trauma, child abuse, intracerebral hemorrhage, tumor, meningitis and poisoning. | Coma |
Pancreatic islet transplantation has become an established approach to beta-cell replacement therapy for the treatment of insulin-deficient diabetes. Recent progress in techniques for islet isolation, islet culture, and peritransplant management of the islet transplant recipient has resulted in substantial improvements in metabolic and safety outcomes for patients. For patients requiring total or subtotal pancreatectomy for benign disease of the pancreas, isolation of islets from the diseased pancreas with intrahepatic transplantation of autologous islets can prevent or ameliorate postsurgical diabetes, and for patients previously experiencing painful recurrent acute or chronic pancreatitis, quality of life is substantially improved. For patients with type 1 diabetes or insulin-deficient forms of pancreatogenic (type 3c) diabetes, isolation of islets from a deceased donor pancreas with intrahepatic transplantation of allogeneic islets can ameliorate problematic hypoglycemia, stabilize glycemic lability, and maintain on-target glycemic control, consequently with improved quality of life, and often without the requirement for insulin therapy. Because the metabolic benefits are dependent on the numbers of islets transplanted that survive engraftment, recipients of autoislets are limited to receive the number of islets isolated from their own pancreas, whereas recipients of alloislets may receive islets isolated from more than one donor pancreas. The development of alternative sources of islet cells for transplantation, whether from autologous, allogeneic, or xenogeneic tissues, is an active area of investigation that promises to expand access and indications for islet transplantation in the future treatment of diabetes." | Islets of Langerhans Transplantation |
BACKGROUND: As the coverage rate of the measles vaccine increases, not all patients present the typical symptoms of measles after exposure to the measles virus (MV). The virus loads in clinical specimens from patients with vaccine-modified non-typical measles are expected to be low compared with those of primary MV infection. A rapid and sensitive laboratory procedure is required for diagnosis of measles. METHODS: SYBR Green (TaKaRa) and TaqMan (ABI) real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were developed to detect MV-RNA. For the real-time RT-PCR, primer sets were designed from a region of the MV H gene of the Edmonston strain (genotype A). A TaqMan probe specific for the H gene of genotype D MV was used. The minimum detectable level of MV-RNA in the SYBR Green and TaqMan real-time RT-PCR assays was evaluated using synthetic MV-RNA. The sensitivity of real-time RT-PCR was compared with that of nested RT-PCR and the virus isolation method using throat swabs and peripheral blood samples from patients with measles. RESULTS: The minimum detectable level of RNA was 10 and 10(2) copies for SYBR Green RT-PCR and TaqMan RT-PCR, respectively. Ten-10(6) copies of standard RNA were linearly detected on SYBR Green RT-PCR. The sensitivity of SYBR Green RT-PCR was equal to that of nested RT-PCR. MV-RNA was detected in virus isolation-negative throat swabs on SYBR Green RT-PCR. CONCLUSION: SYBR Green RT-PCR is a highly sensitive, rapid, and useful diagnostic procedure for the detection of MV. | Measles virus |
An insect cell line, IAL-PID2, was exposed to UV and analyzed for its ability to incorporate [3H]-thymidine and to elongate replicon-sized DNA fragments. After exposure to 5 or 10 J/m2 UV, the cells exhibited a rapid and prolonged depression in the rate of thymidine incorporation. Photoreactivation reduced this depression but did not entirely reverse it. For exposures of 5 J/m2 or above, full recovery did not occur until 18 h after exposure. The blockage of fork progression after UV exposure was fluence-dependent, with replication segments after exposure to 20 J/m2 being shorter than those observed after exposure to 10 J/m2. Immediately after exposure to either 10 or 20 J/m2, photoreactivation reversed blockage of fork progression, indicating that the (5-6) cyclobutyl pyrimidine dimer is responsible for blockage. This also indicates that blockage of fork progression may not be the only factor responsible for the prolonged depression seen in thymidine incorporation. Three hours after exposure to either 10 or 20 J/m2, replication segments were still significantly shorter than control segments. Photoreactivation completely reversed blockage after exposure to 10 J/m2, but did not completely reverse blockage after exposure to 20 J/m2, indicating that at such fluences, other lesions may play a role in UV-induced blockage of fork progression. | Thymidine |
Out of 207 cases died of trauma, diaphragmatic rupture takes part in 18 (8.7%). The authors tested how often closed diaphragmatic rupture takes part with correlation of neighboring anatomic injury. Because of these rare incidence, a surgeon with injury of the next organs to the diaphragm needs always to think of it's rupture. | Diaphragm |
Progress in the knowledge of the pathophysiology of portal hypertension has opened the door to pharmacological treatments, resulting in a dramatic change in the therapeutic approach to portal hypertension. This review summarizes pharmacological agents that have been shown to effectively decrease portal pressure, paying special attention to its mechanisms of action. In addition, the way to monitor response and clinical efficacy of pharmacological agents is reviewed. | Liver Circulation |
In crisis situations, time is of the essence. Effective messaging to individuals at risk is critical to mitigating the most severe outcomes. Extant crisis communication literature has focused on differentiating crisis types based on perceived blame, particularly in cases of for-profit company malfeasance, but less work has been done to understand how the public makes these types of attributions. This quantitative systematic review investigates the relationship between severity of a large-scale crisis outcome and attributions of blame toward relevant entities. Moderators of interest include the attribution term used with participants (e.g., blame, responsibility), the type of crisis event, and the entity presented as at fault. Overall, a small but significant positive relationship is identified in the majority of studies between severity of a large-scale crisis outcome and attributions of blame. Results suggest that while crisis type and entity to blame are moderators, the attribution term(s) used with participants plays a less significant role. Implications and future directions are considered. | Social Perception |
BACKGROUND AND AIM: Furazolidone-based regimens for the eradication of Helicobacter pylori are low cost and effective although less tolerable. Our aim was to compare the efficacy and compliance of 1-week furazolidone-based quadruple therapy (furazolidone, amoxicillin, bismuth subcitrate, omeprazole; FABO) with 2-week quadruple therapy using the same drugs. METHODS: One hundred and fifty-six consecutive patients with H. pylori related diseases were enrolled in our study. The patients were randomized into two groups of FABO1 and FABO2 groups receiving, 1 or 2 weeks' quadruple H. pylori eradication therapies, respectively, as follows: furazolidone (200 mg twice daily), amoxicillin (1 g twice daily), bismuth (240 mg twice daily) and omeprazole (20 mg twice daily). The chi(2) test was used to compare the efficacy of the therapies. RESULTS: The per-protocol eradication rate in FABO1 and FABO2 groups were 56/66 (84.8%) and 57/69 (82.6%), respectively. The intention-to-treat eradication rate was 56/78 (71.8%) in FABO1 group and 57/78 (73.1%) in FABO2 group. There was not any significant statistical difference between two groups. A significant decrease in compliance in FABO2 group was seen. CONCLUSION: This is an encouraging report showing a therapy with possible success in decreasing the duration of H. pylori infection as well as reaching the eradication rate of 80%. | Furazolidone |
Among the congenital malformations of the lower limb, hemimelia of the fibula is particularly important because of its frequency and the large number of anatomic forms which have been observed. Attempts at various therapeutic approaches have ranged from external prostheses to amputations and finally major skeletal lengthening. Based on a statistical study of 17 patients, we examined the different steps in the treatment of such cases with the aim of preserving the limb. Modalities for lengthening procedures and complications were studied in a comparison with results obtained with classical treatments. | Ectromelia |
Rhinomanometry can still be considered as the standard technique for the objective assessment of the ventilatory function of the nose. Reliable technical requirements are given by fast digital sensors and modern information technology. However, the xyimaging of the pressure-flow relation typically shows loops as a sign of hysteresis, with the need for resolution of the breath in four phases. The three pillars of 4-phase rhinomanometry (4PR) are the replacement of estimations by measurements, the introduction of parameters related to the subjective sensing of obstruction, and the graphical information regarding the disturbed function of the nasal valve. In a meta-analysis of 36,563 clinical measurements, we analyze the errors of the classic" parameters (flow in 150 Pa) and reject the further use of these parameters as obsolete, because they correspond to an inaccurate estimation rather than proper measurement. In a pre-study of 1580 measurements, the logarithmic effective resistance (Reff) was found to have the highest correlation with values obtained from a visual analog scale. Next, we classify the inspiratory effective resistance in 20,069 measurements without treatment and 16,494 measurements after decongestion with xylometazoline 0.1 % spray in 20 % percentiles. The gradation of obstruction delivers not only "normal" values but also indications for the severity of the obstruction in adult Caucasian noses. Adoption of the distribution for the growing nose and analysis of the total nasal resistance is addressed, and typical findings of nasal valve phenomena are outlined." | Rhinomanometry |
In this article we develop the concept that the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop. Activation of the loop begins when the hippocampus detects newly arrived information that is not already stored in its long-term memory. The resulting novelty signal is conveyed through the subiculum, accumbens, and ventral pallidum to the VTA where it contributes (along with salience and goal information) to the novelty-dependent firing of these cells. In the upward arm of the loop, dopamine (DA) is released within the hippocampus; this produces an enhancement of LTP and learning. These findings support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory. | Ventral Tegmental Area |
Since its initial discovery in 2010 in the Gaoligong Mountains on the Sino-Myanmar border, there remains no direct information on the feeding habits of the black snub-nosed monkey (Rhinopithecus strykeri). This species is on the verge of extinction, with an estimated remaining population of < 400 individuals. Due to difficulties in following these monkeys across steep mountainous terrain, during 203 observation days (September 2015-January 2017) we recorded 80 h of behavioral records of a wild population (Luoma group). Our preliminary results identified 14 plant species and four lichen species consumed by the monkeys. In addition, we provided the only two captive individuals of this species with a cafeteria diet composed of > 600 wild-collected plant species that were gathered from known R. strykeri habitats to determine which plant species and food items were considered palatable. Our results indicate that the captive monkeys freely consumed young and mature leaves, fruits/seeds, buds, flowers, twigs, and bark from 170 different species of trees, bushes, and herbs representing 76 genera and 41 plant families, as well as 15 species of lichen. All foods consumed by the wild monkeys were also consumed by the captive individuals. Food plants consumed by R. strykeri were found principally in intact subtropical evergreen broadleaf forests and hemlock-broadleaf mixed forests at an altitude of 2200-3000 m. Strict enforcement of habitat protection and access to resources across this elevation zone appear to be essential for the conservation and survivorship of this critically endangered primate. | Colobinae |
Boron is a naturally occurring material and is used in industrial and domestic products. Its major release into the environment is through weathering processes and wastewater discharge. Boron is an essential nutrient for plants, but can above certain concentrations be toxic to aquatic and terrestrial organisms. This paper assesses the ecotoxicology and environmental safety of boron. It draws together the data for toxicological effects of boron and compares these with environmental concentrations of boron, measured in Europe and the U.S.A. Generally, environmental concentrations of boron found in surface water are below levels identified as toxic to aquatic organisms. Concentrations high enough to produce toxic effects in laboratory tests are found in areas where weathering of boron-rich formations and deposits occurs, such as in the southwestern United States. However, reproducing populations of the most sensitive species, rainbow trout, have been observed in surface waters in these regions, indicating no cause for concern. The prime concern for effects on terrestrial plants centers on the use of irrigation water with elevated levels of boron. At present, there is no evidence of widespread damage to crops resulting from this practice. In some areas, wastewater is used for irrigation and crops grown under these conditions are generally confined to those relatively insensitive to boron toxicity. Good irrigation practices will be necessary, however, in arid regions with high evapotranspiration rates and care will be needed when using wastewater, particularly in areas with naturally high boron levels. It is not anticipated that there will be any significant increase in the discharge of boron to the environment in the foreseeable future. The use of boron-containing products is expected to increase, but glass will remain the dominant market and the use of boron in detergents in Europe is expected to decrease due to the introduction of bleach activators and liquid detergents. There is a possibility that perborate may be used in detergents in the U.S.A.; however, the estimated increase in boron concentrations is likely to be environmentally insignificant. | Boron |
BACKGROUND: Epidural steroid injection (ESI) is a common practice for pain treatment since 1953. In 2014, the FDA issued a warning about ESI. Studies have focused on the effect of the particle size and their ability to generate harmful aggregates. Although steroid aggregates provide longer times for reabsorption, therefore a longer anti-inflammatory effect, they are potentially harmful to the central nervous system via embolic mechanisms.Previous studies have established that steroidal aggregates with asizes over 100 mu m are potentially able to occlude blood vessels. Studies by Tiso et al and Benzon et al addressed the role of steroids on CNS adverse events, with similar outcomes. The main difference was on the role of aggregates with a size over 100 mu m, which Benzon et al. attributed to the ability of certain steroid preparations to rapidly precipitate and form large aggregates. OBJECTIVES: Studying the effect of the time elapsed between mixing the steroid preparation and injection on the number and size of aggregates with sizes above 100 mu m. STUDY DESIGN: Original study in basic science. SETTING: Basic scienceMETHODS: Steroids evaluated are commonly used in Spain for ESI: betamethasone, triamcinolone, and dexamethasone. The size and number of the aggregates was determined for undiluted commercial steroid preparations in the usual amount for a single and double dosage used for ESI.Samples were examined with a Leica TCS-SP2 microscope at the first, the fifth and the 30th minute after shaking the preparations. Aggregates observed in the different preparations were manually counted and grouped in the following size range: 0-20, 20-50, 50-100, 100-300, 300-500 and > 500 mu m.Statistical analysis was carried out using the R software. Nonparametric techniques were used in the comparison of aggregate size. Global comparison of the groups using the Kruskal-Wallis test and post-hoc comparisons using the Wilcoxon test, adjusting P-values by the Holm method for multiple comparisonsRESULTS: Aggregates present in triamcinolone and betamethasone samples were statistically larger than in dexamethasone samples. Triamcinolone suspensions produced significantly larger aggregates than betamethasone five minutes after mixing. Triamcinolone preparations produced greater particle aggregates (> 500 mu m), which were not present in dexamethasone and betamethasone preparations. LIMITATIONS: Study how the human internal factors like blood elements and spinal fluid could interact with steroids and influence the size of the aggregates formed. CONCLUSIONS: This study demonstrates that the size of the particles injected depends on the type of steroid and the time allowed between mixing and injecting. The results demonstrate that waiting longer than 5 minutes between mixing and injecting can predispose the formation of potentially harmful aggregates in triamcinolone and betamethasone samples. The presence of greater particle aggregates (> 500 mu m) may occlude some important vessels and arteries with serious adverse results. Vigorous shaking of the injectable could prevent such events. KEY WORDS: Epidural steroid injection, triamcinolone, betamethasone, dexamethasone, steroid aggregates. | Steroids, Fluorinated |
The objective of this study is to determine the three dimensional kinematics of the human pelvis including both sacroiliac joints following a simulated open book injury induced on cadavers by applying anterior-posterior compressive loads to the pelvis. An electromagnetic digitizing and motion tracking system was utilized to measure the morphology of the pelvis and the relative movements of its bones during this simulated open book fracture. The screw displacement axis method was used to describe the relative motion between the sacrum and each hipbone. Morphologically, it was found that the articular surfaces forming the sacroiliac joints could be approximated with planar surfaces directed from proximal and lateral to distal and medial and from posteromedial to anterolateral. The kinematic data obtained from this study indicate that there is a direct correlation between the opening of the symphysis pubis and the opening of the sacroiliac joint (SIJ) during open book injury. This suggests that the extent of injury of the SIJ maybe estimated from the degree of opening of the symphysis pubis as demonstrated on anteroposterior (A-P) x-rays. The results obtained from this study also indicate that the motion of the hipbone with respect to the sacrum on the side of the sacroiliac joint opening is almost a pure rotation, which translates clinically on the A-P x-rays as pure opening of the SIJ without vertical displacement. The average axis of rotation was found to be almost parallel to the SIJ planar articular surface. Furthermore, the pubic bone on the side of SIJ opening was found to displace inferiorly and posteriorly. One can thus conclude that in open book pelvic injuries, the pubic bone on the side of injury displaces inferiorly on the outlet projection x-rays with no vertical displacement of the SIJ. This is important since the initial assessment of the open book injury in the emergency room includes outlet projection x-rays. From this study, the relative vertical positions of the pubic bones on these x-rays can help the surgeon in differentiating open book fracture injury from other pelvic injuries. | Pubic Symphysis |
The advent of computed tomography screening for lung cancer will increase the incidence of ground-glass opacity (GGO) nodules detected and referred for diagnostic evaluation and management. GGO nodules remain a diagnostic challenge; therefore, a more systematic approach is necessary to ensure correct diagnosis and optimal management. Here we present the latest advances in the radiologic imaging and pathology of GGO nodules, demonstrating that radiologic features are increasingly predictive of the pathology of GGO nodules. We review the current guidelines from the Fleischner Society, the National Comprehensive Cancer Network, and the British Thoracic Society. In addition, we discuss the management and follow-up of GGO nodules in the light of experience from screening trials. Minimally invasive tissue biopsies and the marking of GGO nodules for surgery are new and rapidly developing fields that will yield improvements in both diagnosis and treatment. The standard-of-care surgical treatment of early lung cancer is still minimally invasive lobectomy with systematic lymph node dissection. However, recent research has shown that some GGO lesions may be treated with sublobar resections; these findings may expand the surgical treatment options available in the future. | Multiple Pulmonary Nodules |
During infection with positive-strand RNA viruses, viral RNA synthesis associates with modified intracellular membranes that form unique and captivating structures in the cytoplasm of the infected cell. These viral replication organelles (ROs) play a key role in the replicative cycle of important human pathogens like coronaviruses, enteroviruses, or flaviviruses. From their discovery to date, progress in our understanding of viral ROs has closely followed new developments in electron microscopy (EM). This review gives a chronological account of this progress and an introduction to the different EM techniques that enabled it. With an ample repertoire of imaging modalities, EM is nowadays a versatile technique that provides structural and functional information at a wide range of scales. Together with well-established approaches like electron tomography or labeling methods, we examine more recent developments, such as volume scanning electron microscopy (SEM) and in situ cryotomography, which are only beginning to be applied to the study of viral ROs. We also highlight the first cryotomography analyses of viral ROs, which have led to the discovery of macromolecular complexes that may serve as RO channels that control the export of newly-made viral RNA. These studies are key first steps towards elucidating the macromolecular complexity of viral ROs." | Viral Replication Compartments |
Clinical studies of aztreonam were undertaken by 220 investigators in 86 university and general hospitals in Japan. A total of 1,447 patients were treated by investigators in various fields. Satisfactory clinical responses were achieved in 67% of all patients. Efficacy rates by field of specialty were: internal medicine, 67%; urology, 61%; general surgery, 73%; and surgical patients in other fields (obstetrics-gynecology, otorhinolaryngology, and ophthalmology), 78%. Among 364 patients with complicated urinary tract infections, the efficacy rate was 60%. Seventy-four percent of 1,122 gram-negative aerobic organisms were eradicated after treatment with aztreonam. Adverse reactions occurred in 2.1% of patients; none were serious. Mild elevations of serum aminotransferases were observed in approximately 4% of patients for whom test results were reported. In conclusion, aztreonam demonstrated remarkable effectiveness in the treatment of gram-negative infections in hospitalized patients. | Monobactams |
The inner ear of fishes contains three paired otolithic end organs, the saccule, lagena and utricle, which function as biological accelerometers. The saccule is the largest otolith in most fishes and much of our current understanding on auditory function in this diverse group of vertebrates is derived from anatomical and neurophysiological studies on this end organ. In contrast, less is known about how the utricle contributes to auditory functions. In this study, chronically implanted electrodes were used, along with neural telemetry or tethers to record primary afferent responses from the utricular nerve in free-ranging and naturally behaving oyster toadfish Opsanus tau Linnaeus. The hypothesis was that the utricle plays a role in detecting underwater sounds, including conspecific vocalizations, and exhibits directional sensitivity. Utricular afferents responded best to low frequency (80-200 Hz) pure tones and to playbacks of conspecific boatwhistles and grunts (80-180 Hz fundamental frequency), with the majority of the units ( approximately 75%) displaying a clear, directional response, which may allow the utricle to contribute to sound detection and localization during social interactions. Responses were well within the sound intensity levels of toadfish vocalization (approximately 140 SPL dBrms re. 1 microPa with fibers sensitive to thresholds of approximately 120 SPL dBrms re. 1 microPa). Neurons were also stimulated by self-generated body movements such as opercular movements and swimming. This study is the first to investigate underwater sound-evoked response properties of primary afferents from the utricle of an unrestrained/unanesthetized free-swimming teleost fish. These data provide experimental evidence that the utricle has an auditory function, and can contribute to directional hearing to facilitate sound localization. | Saccule and Utricle |
OBJECTIVE: We investigated adolescent's knowledge of the consequences of sun exposure in order to determine what preventive measures would be effective. MATERIAL AND METHODS: A questionnaire was given to 241 adolescents (111 girls and 130 boys) aged 13 to 15 years whose background included all social occupational categories. The questionnaire included 21 open response items. We also interviewed 100 adolescents 3 months after an information session with a 1-hour slide presentation. RESULTS: Eighty-five percent of the girls and 62 p. 100 of the boys said they exposed themselves to sun regularly. For 50 p. 100 of the adolescents, sun exposure occurred between 12 noon and 4 p.m. Less than 9 p. 100 knew that this period corresponds to maximal sunlight intensity and that maximal photoprotection is necessary. Only 47 p. 100 of the girls and 25 p. 100 of the boys regularly used protective skin lotions. Twenty-five percent of the girls used a lotion adapted to their phototype and 8 p. 100 of the boys. Twenty percent of the adolescents questioned were aware that applications should be repeated every 2 hours or after bathing. The cost of skin lotions was never cited as a limiting factor for their use. More than 90 p. 100 of the adolescents gave correct responses at the second test. DISCUSSION: Our study demonstrated that the risk of sun exposure is largely unrecognized by adolescents and that they have very incomplete information concerning protective measures. An adapted information program would be useful for this risk population. | Sunburn |
Esophageal motility disorders are diseases in which there are malfunctions of the act of swallowing due to a change in neuromuscular structures. The main symptom is therefore dysphagia for solid and/or liquid foods, often accompanied by symptoms such as chest pain, regurgitation, heartburn, and weight loss. Esophageal manometry is the gold standard in diagnostics. Endoscopy and radiology serve to exclude inflammatory or malignant changes. With the introduction of high-resolution esophageal manometry (HRM), the diagnosis of esophageal motility disorders has improved and led to a new classification with the Chicago Classification, which has been modified several times in the last decade, most recently in 2020 with the Chicago Classification v4.0. Compared to the previous version 3.0, there are some important changes that are presented based on the most important esophageal motility disorders in everyday clinical practice. | Deglutition Disorders |
Cell-to-cell-junctions of endothelial cells are specialized and differentiated areas of the plasma membrane. The main functions include the separation of the intravascular and extravascular compartments, the mechanical connection of the cells, and the maintenance of the cell polarity. Although a wide heterogeneity of endothelial cell-to-cell junctions exists in situ, they should be considered in general as adherens type junctions in which gap and tight junctions are morphologically inserted. Under certain pathological conditions, such as wound healing, angiogenesis and many types of inflammation, the interendothelial junctions have to be dissociated and reorganized in which proteins of the junctions are crucially involved. These important mechanisms predict a sophisticated regulation of junctional proteins. The present paper describes the organization and functional aspects of the occludin/ZO-1 complex typically found in tight junctions, the cadherin/catenin complex of the adherens junctions and the connection of these protein complexes to the dense peripheral band via actin filaments. In addition, special attention has been drawn on the function of junction-associated proteins with respect to their role under fluid shear stress and interendothelial gap formation during inflammation." | Platelet Endothelial Cell Adhesion Molecule-1 |
Previously we have shown that both factor XI and factor XIa are bound specifically to distinct, high-affinity sites on the surface of activated platelets in the presence of high Mr kininogen. To determine the functional significance of factor XIa binding to platelets, bound factor XIa has now been compared with the unbound enzyme. Platelets incubated with thrombin, high Mr kininogen, and 125I-labeled factor XIa bound 130 to 500 molecules of factor XIa per platelet. Scatchard analysis of binding data give a dissociation constant (Kd) of 822 pmol/L +/- 140 (SEM). Rates of factor IX activation, assayed by release of trichloroacetic acid-soluble 3H-labeled activation peptide from purified [3H]-factor IX, were similar when factor XIa was bound to platelets and when it was free in solution. The platelet-bound factor XIa was isolated by centrifugation through 20% sucrose and was functionally characterized both in a factor XIa coagulation assay and in the factor IX activation peptide release assay in comparison with unbound factor XIa in the presence of treated platelets. The functional activity of platelet-bound factor XIa as a factor IX activator as well as its structural integrity were shown to be fully retained on the platelet surface. Since platelets bind factor XI and promote its proteolytic activation to factor XIa, factor XIa binding to platelets may serve to localize factor IX activation to the hemostatic plug, where factor XIa is protected from inactivation by plasma protease inhibitors and where acceleration of subsequent coagulation reactions can occur. | Factor XIa |
Ambulatory esophageal pH monitoring is an essential method in patients exhibiting signs of non-erosive reflux disease (NERD) to make an objective diagnosis. Intra-esophageal pH monitoring is important in patients who are non-responsive to medications and in those with extraesophageal symptoms, particularly in NERD, before surgical interventions. With the help of the wireless capsule pH monitoring, measurements can be made under more physiological conditions as well as longer recordings can be performed because the investigation can be better tolerated by patients. Ambulatory esophageal pH monitoring can be detected within normal limits in 17%-31.4% of the patients with endoscopic esophagitis; therefore, normal pH monitoring cannot exclude the diagnosis of gastroesophageal reflux disease (GERD). Multi-channel intraluminal impedance pH (MII-pH) technology have been developed and currently the most sensitive tool to evaluate patients with both typical and atypical reflux symptoms. The sensitivity of a pH catheter test is 58% for the detection of acid reflux compared with MII-pH monitoring; further, its sensitivity is 28% for the detection of weak acid reflux compared with MII-pH monitoring. By adding impedance to pH catheter in patients with reflux symptoms, particularly in those receiving PPIs, it has been demonstrated that higher rates of diagnoses and symptom analyses can be obtained than those using only pH catheter. Esophageal manometry is used in the evaluation of patients with functional dysphagia and unexplained noncardiac chest pain and prior to antireflux surgery. The use of esophageal manometry is suitable for the detection of esophageal motor patterns and extreme motor abnormalities (e.g., achalasia and extreme hypomotility). Esophageal manometry and ambulatory pH monitoring are often used in assessments prior to laparoscopic antireflux surgery and in patients with reflux symptoms refractory to medical treatment. Although the esophageal motility is predominantly normal in patients with non-acid reflux, ineffective esophageal motility is often monitored in patients with acid reflux. In the literature, there are contradictory and an insufficient number of studies regarding radiological methods for the diagnosis of GERD. There are inconsistent values for sensitivity and specificity among the barium studies. There are inadequate studies in the literature involving scintigraphic examinations in the diagnosis of GERD, and a majority of existing studies have been conducted in the pediatric group. The results of a few studies do not provide sufficient contribution toward the implementation in clinical practice. | Esophageal pH Monitoring |
Uranium may pose a hazard to ecosystems and human health due to its chemotoxic and radiotoxic properties. The long half-life of many U isotopes and their ability to migrate raise concerns over disposal of radioactive wastes. This work examines the long-term U bioavailability in aerobic soils following direct deposition or transport to the surface and addresses two questions: (i) to what extent do soil properties control the kinetics of U speciation changes in soils and (ii) over what experimental timescales must U reaction kinetics be measured to reliably predict long-term of impact in the terrestrial environment? Soil microcosms spiked with soluble uranyl were incubated for 1.7 years. Changes in U(VI) fractionation were periodically monitored by soil extractions and isotopic dilution techniques, shedding light on the binding strength of uranyl onto the solid phase. Uranyl sorption was rapid and strongly buffered by soil Fe oxides, but U(VI) remained reversibly held and geochemically reactive. The pool of uranyl species able to replenish the soil solution through several equilibrium reactions is substantially larger than might be anticipated from typical chemical extractions and remarkably similar across different soils despite contrasting soil properties. Modelled kinetic parameters indicate that labile U(VI) declines very slowly, suggesting that the processes and transformations transferring uranyl to an intractable sink progress at a slow rate regardless of soil characteristics. This is of relevance in the context of radioecological assessments, given that soil solution is the key reservoir for plant uptake. | Soil Pollutants, Radioactive |
The purpose of the study was to evaluate the influence of beta-blockers and ivabradine on long-term prognosis of patients with stable angina. 90 patients with stable angina that have been involved in present study along with nitrates, antiplatelet agents and statins received bisoprolol (Group I), carvedilol (Group II) and ivabradine (Group III). We analyzed the following indicators: patient adherence to treatment, cases of myocardial infarction and circulatory decompensation, which resulted in necessity of patient's hospitalization during the year of observation, calculating the probability of achieving a key prognostic endpoint by patient using the concept of the odds ratio and determination of important components in the progression of the disease. We concluded that in compared patients groups developed cardiovascular death and unstable angina with almost equal frequency. As for cases of myocardial infarction and the need for revascularization, their number was smaller in patients who in addition to standard treatment received ivabradine. Prognosis of patients with stable angina after 12 months of treatment primarily depends on their adherence to treatment, age, heart rate, presence of harmful habits, and markers of endothelial dysfunction, including endothelin-1 and homocysteine. | Angina, Stable |
Hexose-6-phosphate dehydrogenase (H6PD) is a luminal enzyme of the endoplasmic reticulum that is distinguished from cytosolic glucose-6-phosphate dehydrogenase by several features. H6PD converts glucose-6-phosphate and NADP(+) to 6-phosphogluconate and NADPH, thereby catalyzing the first two reactions of the pentose-phosphate pathway. Because the endoplasmic reticulum has a separate pyridine nucleotide pool, H6PD provides NADPH for luminal reductases. One of these enzymes, 11beta-hydroxysteroid dehydrogenase type 1 responsible for prereceptorial activation of glucocorticoids, has been the focus of much attention as a probable factor in the pathomechanism of several human diseases including insulin resistance and the metabolic syndrome. This review summarizes recent advances related to the functions of H6PD." | 11-beta-Hydroxysteroid Dehydrogenase Type 1 |
IgG4-related sclerosing mesenteritis is a rare disease of mesentery of an unknown etiology which shows a constellation of histopathologic findings of lymphoplasmacytic inflammation with IgG4-positive plasma cells and marked fibrosis. This chronic inflammatory condition of mesentery forming an abdominal cocoon has never been described before to the best of our knowledge. Here, we report a patient with a history of subacute small bowel obstruction who was found to have an intra-abdominal encapsulating mass in the right iliac fossa and was finally diagnosed as IgG4-related sclerosing encapsulating peritonitis (abdominal cocoon) based on peroperative findings, histology and immunohistochemistry. | Panniculitis, Peritoneal |
No detectable induction of mutation to streptomycin resistance could be used in wild-type Micrococcus radiodurans and its radiation-sensitive and super-resistant mutants by ionizing or UV-radiation. N-methyl-N'-nito-N-nitrosoguanidine (NTG) was mutagenically active. The results suggest that repair of radiation-damaged DNA in Micrococcus radiodurans is mutation-proof. | Nitrosoguanidines |
BACKGROUND: Cervical spine fractures in the elderly are relatively common. The management of such injuries may be complicated by underlying medical debility and osteopenia as well as reduced tolerance to halo immobilization. METHODS: Over a 1-year period, 43 cervical spine fractures were treated at our institution. Ten (23%) were in persons 70 years of age or older. This retrospective analysis describe the clinical features, treatment, and outcome of these 10 elderly patients. All fractures in this patient population involved the atlantoaxial complex, including five combination C1-C2 fractures. Six patients were treated with early halo immobilization and three were initially managed with a rigid cervical collar. Three patients required posterior cervical fusion. RESULTS: Of the six patients undergoing halo immobilization, five progressed to osseous union. Three patients were immobilized in a Philadelphia collar resulting in one osseous union, one nonunion, and one death. Three patients underwent posterior cervical fusion with subsequent osseous union in all three. CONCLUSIONS: Although external immobilization with a halo device is our treatment of choice for most C1 and C2 fractures in elderly patients, a Philadelphia collar is useful in select cases when halo immobilization or early surgical fusion is contraindicated. Posterior cervical fusion can be safely and effectively performed in elderly patients and should be strongly considered for initial therapy in the elderly with fracture types unlikely to progress to osseous union with external immobilization alone. | Spinal Fractures |
There are now more than seven hundred accountable care organizations (ACOs) in the United States. This article describes some of their most salient characteristics including the number and types of contracts involved, organizational structures, the scope of services offered, care management capabilities, and the development of a three-category taxonomy that can be used to target technical assistance efforts and to examine performance. The current evidence on the performance of ACOs is reviewed. Since California has the largest number of ACOs (N=67) and a history of providing care under risk-bearing contracts, some additional assessments of quality and patient experience are made between California ACOs and non-ACO provider organizations. Six key issues likely to affect future ACO growth and development are discussed, and some potential diagnostic" indicators for assessing the likelihood of potential antitrust violations are presented." | Risk Sharing, Financial |
Two new steroidal saponins (1 and 2), along with four known ones (3 approximately 6) were obtained from the roots and rhizomes of Maianthemum henryi, their structures were determined to be spirost-5, 25(27)-diene-lbeta, 3beta-diol 1-O-alpha-L-rhamnopyranosyl-(1 --> 2)-4-O-acetyl-beta-D-fucopyranoside (1), (23S, 24S)-spirost-5, 25(27)-diene-lbeta, 3beta, 23, 24-tetrol 1-O-alpha-L-rhamnopyranosyl-(1 --> 2)-4-O-acetyl-beta-D-fucopyranoside (2), spirost-5, 25(27)-diene-lbeta, 3beta-diol 1-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-fucopyranoside (3), spirost-5, 25(27)-diene-lbeta, 3beta-diol 1-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-xylopyranoside (4), Henryioside A (5)ãÂÂHenryioside B (6), by physicochemical properties and spectroscopic methods. In addition, their cytotoxic activity against human HepG2 tumor cells was evaluated by MTT method and all of the compounds exhibited cytotoxicity with the cells. | Maianthemum |
The iron content of human 5-lipoxygenase has been determined by a colorimetric assay using the chromogenic ligand FerroZine. The highly active enzyme was obtained from a baculovirus expression system and purified using an ATP-agarose chromatography column (Denis, D., Falgueyret, J.-P., Riendeau, D., and Abramovitz, M. (1991) J. Biol. Chem. 266, 5072-5079). A linear correlation was observed between the enzyme's specific activity and iron content in six different preparations. Enzyme with the highest specific activity (24 mumol of 5-hydroperoxyeicosatetraenoic acid/mg of protein) contained 1.1 mol of iron/mol of enzyme, whereas inactive enzyme contained no detectable iron. The iron is tightly bound to the enzyme and could only be released after inactivation of the enzyme by exposure to oxygen. | Arachidonate Lipoxygenases |
Branchio-oto-renal syndrome is an autosomal dominant disorder characterized by branchial anomalies, hearing loss, and renal urinary tract malformations. We herein report a 32-year-old Japanese man with a right preauricular pit, bilateral mixed hearing loss, and malposition of the right kidney who presented with proteinuria. The findings of a left kidney biopsy were compatible with a perihilar variant of secondary focal segmental glomerular sclerosis. A trio exome analysis conducted among the patient and his parents failed to identify the causal gene variant, despite a sporadic pattern. His kidney function remained stable for 11 years with an angiotensin II receptor blocker. | Branchio-Oto-Renal Syndrome |
The severe side effects of chemosynthetic anti-diarrhea drugs have created an interest in low-toxic alternative plant-derived compounds. FengLiao consists of Polygonum hydropiper Linn. and Daphniphyllum calycinum Bench., and is widely used in China to treat diarrhea due to low levels of toxicity. In this study, the effects of FengLiao were analyzed in a castor oil-induced diarrhea model, using the anti-diarrhea drug, loperamide, as the positive control. The effects were evaluated using stool characteristics and the expression levels of various diarrhea-related factors in the jejunum and liver, as well as changes in the microbiota of the jejunum. The symptoms of diarrhea and stool consistency were improved through FengLiao and loperamide treatment. Furthermore, FengLiao down-regulated alpha 1-acid glycoprotein (AGP) and C-reactive protein (CRP) levels, and up-regulated transferrin (TRF) mRNA levels in the liver, and down-regulated Aquaporin 3 (AQP3) and Na+/H+ exchanger isoform 8 (NHE8) expression in the epithelial cells of the jejunum. It also increased the relative abundance of Bifidobacterium, Aerococcus, Corynebacterium_1 and Pseudomonas, and lowered the Firmicutes/Bacteroidetes (F/B) ratio, which maintained the balance between immunity and intestinal health. Taken together, FengLiao alleviated castor oil-induced diarrhea by altering gut microbiota, and levels of jejunum epithelial transport proteins and acute phase proteins. | Saxifragales |
Facial blushing is one of the cardinal symptoms of social phobia and has a strong negative impact on the quality of life. Traditional therapeutic options are psychotherapy and pharmacological treatment. The results of these treatments on facial blushing are poorly documented. To investigate whether endoscopic bilateral transection of the upper thoracic sympathetic chain is efficient in the treatment of facial blushing, 244 consecutive patients were treated with bilateral endoscopic transthoracic sympathicotomy (ETS). The results were evaluated by questionnaire and symptoms assessed with visual analogue scales (0-10). There was no mortality nor conversion to open surgery. No Horner's syndrome occurred. Two patients with postoperative pneumothorax were treated with intercostal drainage and one small pulmonary embolus was detected. The questionnaire was answered by 219 patients (90%) a mean (+/- SEM) of 8 months (+/- 9 days) after surgery. Facial blushing (mean +/- SEM) was reduced from 8.7 +/- 0.1 to 2.2 +/- 0.2, P < 0.0001, by the operation. Heart palpitations in stressful situations were also reduced (3.7 +/- 0.3 to 1.3 +/- 0.1, P < 0.0001). The quality of life was substantially improved. The main side-effect was redistribution of sweating from the upper to the lower part of the body. Increased sweating of the trunk occurred in 75% of the patients. Overall, 85% of the patients were satisfied with the result and 15% were to some degree dissatisfied, mainly due to insufficient effect, but only four patients (2%) regretted the operation. As this is an open study, the results must be viewed with caution. ETS, however, appears to be an efficient, safe and minimally invasive surgical method for the treatment of facial blushing. | Blushing |
It has become apparent that major sources of reactive oxygen species (ROS) in mammalian cells are the NADPH oxidases. These multimeric enzymes are composed of membrane bound catalytic subunits, or Nox enzymes and a small docking subunit termed p22phox. Depending on the Nox isoform, cytosolic regulatory subunits also play a role in their activation. There are 7 Nox isoforms. The first identified was Nox2, also termed gp91(phox), which is present in phagocytic cells and is responsible for the oxidative burst. Unlike Nox2, the other Nox enzymes exhibit sustained production of ROS at somewhat lower levels. Their modes of activation differ, as do their cellular distribution. Nox 1-4 are expressed in vascular cells in rodents. Nox 5 has been identified in atherosclerotic lesions of humans but is not expressed in rodents. Stimulation of cells with angiotensin II, cytokines, catecholamines, high glucose, or mechanical stretch promote NADPH oxidase activation, in large part due to recruitment of cytosolic subunits to the membrane subunit, leading to formation of the functional enzyme complex that can transfer electrons molecular oxygen and formation of superoxide (O(2) (.-)). Superoxide serves as a progenitor for other ROS, including hydrogen peroxide (H(2)O(2)), peroxynitrite (OONO(-)), and hypochlorous acid (HOCl(-)). Enhanced activity the NADPH oxidases and increased expression of its subunits occur in many pathological conditions including hypertension, diabetes, atherosclerosis, cardiac hypertrophy and heart failure. Studies of genetically altered mice have shown that deletion of various NADPH oxidase subunits protect against these diseases, while their overexpression promotes pathology.(-) | NADH, NADPH Oxidoreductases |
Promoter shutoff is a general method for analyzing essential genes, but in the fungus Aspergillus oryzae, no tightly repressed promoters have been reported. To overcome the current limitations of conditional promoters, we examined sorbitol- and galactose-responsive genes using microarrays to identify regulatable genes with only minor physiological and genetic effects. We identified two sorbitol-induced genes (designated as sorA and sorB), cloned their promoters, and built a regulated egfp and brlA expression system. Growth medium-dependent enhanced green fluorescence protein (EGFP) fluorescence and conidiation were confirmed for egfp and brlA under the control of their respective promoters. We also used this shutoff system to regulate the essential rhoA, which demonstrated the expected growth inhibition under repressed growth conditions. Our new sorbitol promoter shutoff system developed can serve as a valuable new tool for essential gene analyses of filamentous fungi. | Aspergillus oryzae |
PURPOSE: A prototype 256-slice cone beam computed tomography (CT) provides complete volumetric data within a single gantry rotation (1 s/rotation) with 0.5 mm slice-thickness. MATERIALS AND METHODS: Calcified phantoms (200-400 HU) were attached to the balloon of a pulsating phantom and moved at a rate of 5-90/min. Acquisition was performed during one to-and-fro motion at each pulsation rate without electrocardiogram (ECG)-gating. Each period was divided into 10 phases, and compared to conventional multislice CT scanning without ECG-gating. RESULTS: At 5-20/min, the configuration of calcified phantoms continued to the through-plane without gaps. At 60/min, duplicated calcified phantoms at end-systole and end-diastole were observed without motion. At 90/min, motion could be observed without gaps but was more blurred, and total calcified volume, Agatston scores, mean and max CT values of three phantoms were almost equal compared with those at static state. However, at 60/min, total calcified volume, scores, mean and max CT values of three phantoms were decreased to 64%, 37%, 80% and 56%, respectively, compared with those at static state. In multislice CT, even at lower rates, there were gaps in the through-plane. At 60/min, total calcified volume, scores, mean and max CT values of three phantoms were decreased to only 8%, 3%, 79% and 53%, respectively, compared with static state. CONCLUSION: This new prototype's unique character (synchrony) enables the acquisition of pulsating objects. These can be acquired without gaps in the through-plane even in the absence of ECG-gating. However, its present temporal resolution only permits accurate quantitative evaluation of calcium up to 20/min. | Tomography, Spiral Computed |
ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC. (B. chinense) is the dried root of B. chinense, belonging to the Umbelliferae family. B. chinense has been reported since ancient times for its effect of soothing the liver and relieving depression. Additionally, its important role in treating depression, depressed mood disorders and anti-inflammation has been proven in previous studies. However, its specific mechanism of action remains unknown. AIM OF THE STUDY: The key targets and metabolites of the antidepressant effect of B. chinense were investigated based on the cAMP signalling pathway. The study examined the mechanism for the antidepressant effect of B. chinense by target prediction, analysis of related metabolites and potential metabolic pathways. MATERIALS AND METHODS: A network pharmacology approach was used to predict the antidepressant targets and pathways of B. chinense. A depression rat model was established through the CUMS (chronic unpredictable mild stress) procedure. The depression model was assessed by body weight, sugar-water preference, water maze and enzyme-linked immunosorbent assay (ELISA) indicators (5hydroxytryptamine, etc.). The key metabolic pathways were screened by correlations between metabolites and key targets. Finally, a quantitative analysis of key targets and metabolites was experimentally validated. RESULTS: B. chinense significantly ameliorated the reduction in body weight, sugar-water preference rate and cognitive performance in the water maze experiment in rats with depression induced by CUMS. ELISA, Western blotting (WB) and reverse transcription-polymerase chain reaction (RT-PCR) assays showed that B. chinense significantly improves the expression of protein kinase cyclic adenylic acid (cAMP)-activated catalytic subunit alpha (PRKACA), cAMP-response element-binding protein (CREB) and cAMP activation in the rat brain induced by CUMS. According to metabolic pathway analysis, B. chinense shows an antidepressant effect primarily by regulating the cAMP metabolic pathway. CONCLUSION: B. chinense upregulated PRKACA and CREB expression and the level of the key metabolite cAMP in the cAMP/PKA/CREB pathway while reducing the inflammatory response to depression treatment. These new findings support future research on the antidepressant effects of B. chinense." | Cyclic AMP-Dependent Protein Kinase Catalytic Subunits |
We have cloned a novel cDNA from human brain which encodes a non-voltage-dependent Na+ channel (BNC1). BNC1 has some sequence similarity (24-28%) with a new channel family that includes subunits of the mammalian epithelial Na+ channel, the Caenorhabditis elegans degenerins, and the Helix aspersa FMRF-amide-gated Na+ channel. Like other family members it is inhibited by amiloride. However, its predicted structure differs from other family members, its discrimination between Na+ and Li+ is different, and in contrast to other mammalian family members, coexpression with other cloned subunits of the family does not increase current. BNC1 has a unique pattern of expression with transcripts detected only in adult human brain and in spinal cord. Thus, BNC1 is the first cloned member of a new subfamily of mammalian Na+ channels. The function of BNC1 as a non-voltage-gated Na+ channel in human brain suggests it may play a novel role in neurotransmission. | Degenerin Sodium Channels |
Although the symptoms associated with trigeminal neuralgia have been well documented, the root cause of this disease initially eluded most surgeons. Although early remedies were haphazard because of a lack of understanding about the condition, near the 20th century both medical and procedural therapies were established for the treatment of trigeminal neuralgia. These treatments include a variety of medications, chemoneurolysis, radiofrequency lesioning, percutaneous ablative procedures, stereotactic radiosurgery, and open rhizotomy and microvascular decompression. This report recounts the history of trigeminal neuralgia, from its earliest descriptions to the historical evolution of nonsurgical and surgical therapies." | Microvascular Decompression Surgery |
Activity concentrations of (134)Cs and (137)Cs have been determined in 23 species of mushrooms of the genus Cortinarius (59 individual samples) collected from the Reggio Emilia in Italy 1992-1999 and in 4 species (16 composite samples and 413 individuals) from the Pomerania region in Poland from 1996 to 2015. Across all the Cortinarius species from the Reggio Emilia, the activity concentrations were relatively high in Cortinarius alboviolaceus, Cortinarius duracinus, Cortinarius orellanus, Cortinarius rapaceus, and Cortinarius subannulatus, in which (137)Cs was at 10,000 ~ 100,000 Bq kg(-1) dry biomass (db) in 1994. Smaller activity concentrations were found in Cortinarius bivelus, Cortinarius bulliardii, Cortinarius cotoneus, Cortinarius largus, Cortinarius lividoviolaceus, Cortinarius purpureus, Cortinarius rufo-olivaceus, Cortinarius torvus, and Cortinarius venetus with levels at 1000 ~ 6000 Bq kg(-1) db from 1992 to 1994, and further in Cortinarius anserinus, Cortinarius auroturbinatus, C. largus, Cortinarius praestans, Cortinarius purpurascens, Cortinarius scaurus, Cortinarius sebaceous, Cortinarius talus, and Cortinarius variecolor with activity concentrations at 100 ~ 600 Bq kg(-1) db in 1994. All the data were calculated for dehydrated fungal material corrected back to the exact date samples of collection. The greatest activity concentrations of (137)Cs both in Italy (1992-1999) and Poland (1996-2010) were found in the popular Cortinarius caperatus, confirming its very high capacity of radiocaesium accumulation. Besides (137)Cs, the isotope (134)Cs was detected in some species from the Reggio Emilia. An average calculated ratio of activities of (134)Cs to (137)Cs referenced to 1986 was equal to 0.38 in mushrooms from the Reggio Emilia, and this value slightly differ from that specific for Chernobyl fallout, which was 0.54. It was calculated that (137)Cs originating from Chernobyl accident constituted about 68 % of the total activity concentration of the isotope in Reggio Emilia in 1986, while as much as 32 % of (137)Cs in mushrooms were from the global fallout from nuclear bomb testing. | Cortinarius |
The ascomycete fungus, Fusarium graminearum (teleomorph Gibberella zeae), is the most common causal agent of Fusarium head blight (FHB), a devastating disease for cereal crops worldwide. F. graminearum produces ascospores (sexual spores) and conidia (asexual spores), which can serve as disease inocula of FHB. Meanwhile, Fusarium-infected grains are often contaminated with mycotoxins such as trichothecenes (TRIs), fumonisins, and zearalenones, among which TRIs are related to the pathogenicity of F. graminearum, and these toxins are hazardous to humans and livestock. In recent years, with the complete genome sequencing of F. graminearum, an increasing number of functional genes involved in the production of secondary metabolites, hyphal differentiation, sexual and asexual reproduction, virulence and pathogenicity have been identified from F. graminearum. In this review, the secondary metabolite synthesis, hyphal development and pathogenicity related genes in F. graminearum were thoroughly summarized, and the genes associated with secondary metabolites, sexual reproduction, energy metabolism, and pathogenicity were highlighted. | Gibberella |
Between 1954 and 1996 a total of 16 International Congresses of Clinical Chemistry were held. Their main features are reviewed: their size and location; organisation and costs; the awards made to eminent clinical chemists; the publication of congress proceedings; the scientific content of congresses; and the role of industry. These have all changed over this period in a way which reflects the development of clinical chemistry. Although these congresses are becoming increasingly expensive, and cannot satisfy the needs of everyone, they are unique in providing a comprehensive and up-to-date overview of the subject and enabling clinical chemists from different countries to meet and exchange ideas and experiences. | Congresses as Topic |
Melatonin is well-documented to have the ability of reducing nerve inflammation and scavenging free radicals. However, the therapeutic effect of melatonin on spinal cord injury has not been fully described. In this study, we assessed the effect of melatonin on T9 spinal cord injury established by Allen method in rats. Melatonin deficiency significantly delayed the recovery of sensory and motor functions in SCI rats. Treatment with melatonin significantly alleviated neuronal apoptosis and accelerated the recovery of spinal cord function. These results suggest that melatonin is effective to ameliorate spinal cord injury through inhibition of neuronal apoptosis and promotion of neuronal repair. | Nissl Bodies |
HIV-associated nephropathy (HIVAN) is the leading cause of end-stage renal failure in HIV-1 seropositive patients. The pathologic findings include collapsing focal segmental glomerulosclerosis with proliferation of epithelial cells in Bowman's space. Anatomically, these cells correspond to podocytes and exhibit a unique phenotype with loss of many differentiation markers including synaptopodin and dysregulation of the cell cycle markers consistent with proliferation. Podocyte dysfunction appears to be a direct result of HIV-1 protein expression, specifically Nef and Vpr as well as specific host factors that have yet to be elucidated. The mechanism by which Nef induces podocyte proliferation and dedifferentiation has been traced to its ability to activate several signaling pathways including Src-Stat3 and ras-raf-MAPK1, 2. Activation of the cAMP/PKA pathway with all-trans-retinoic acid appears to modulate these changes and returns podocytes to a differentiated, nonproliferating phenotype. | AIDS-Associated Nephropathy |
PURPOSE: Some studies have demonstrated that vascular endothelial growth factor (VEGF) plays a critical role in the pathogenesis of otitis media with effusion (OME) in animal models. However, the levels of VEGF and its receptors in adult OME have not been clarified. Our study was designed to detect the levels of VEGF and its receptors in adult OME and explore their relationship with effusion types, duration and prognosis of OME. METHODS: 61 patients with secretory otitis media were enrolled including 21 males and 40 females, with an average age of 54.7 +/- 17.5 years. The middle-ear effusions were collected by tympanocentesis or myringotomy. The protein concentrations were determined by enzyme-linked immunosorbent assay and messenger RNA by real-time quantitative PCR. RESULTS: VEGF level was higher in AOME group, but not correlated with the recurrence of OME. VEGFR1 and VEGFR2 levels were lower in recurrent group compared with non-recurrent group. VEGFR2 level was higher in serous effusions than mucoid effusions. VEGF messenger RNA was positively correlated both with HIF-1alpha and MUC5B. CONCLUSIONS: VEGF and its receptors function to induce the production of middle-ear effusions (MEEs) at acute stage of OME rather than chronic or recurrent stage, which is mainly mediated by HIF-1alpha pathway. The formation of mucoid effusions is associated with MUC5B and VEGFR2, but not with duration and recurrence of OME. | Tympanocentesis |
Combined heart and lung transplantation has been shown to provide successful therapy for patients with end-stage heart and lung disease. The improved success of lung transplantation has resulted in increasing number of potential recipients and longer waiting times. Maximal utilization of all three thoracic organs is no longer a casual goal but of utmost necessity. We devised a new technique that improves operative visualization, decreases dissection time, and ensures excellent preservation of all three thoracic organs. Bench dissection after extraction of this heart-lung block allows the thoracic and cardiac surgeons to agree on precise dissection of the left atrium and adequate pulmonary venous and atrial cuff. This technique has been used in 48 of our last 50 harvests with excellent results. Utilization of heart and lungs has been 93% and 74%, respectively. | Heart-Lung Transplantation |
This study examines the lexical-grammatical relation within and across in preschool Latino dual language learners (DLLs) with and without specific language impairment (SLI) using language-specific vocabulary and conceptual lexical-semantic skills. The participants were sixty-one typically developing (TD) Spanish-English speaking DLLs and seventy-four DLLs with SLI from low-income households. Standardized and researcher developed assessment tools were used to measure vocabulary, semantics, and grammar in both Spanish and English. Cross-sectional data were analyzed using hierarchical linear regressions to determine the nature of the lexical-grammatical association within and across languages. The study found significant within-language relations between measures of vocabulary and grammar for both groups. Conceptual vocabulary was a significant predictor for English grammar in both groups. For the SLI group only, both English and Spanish vocabulary scores significantly predicted English grammar and bilingual semantics scores predicted Spanish grammar. These findings underscore the role of language-specific vocabulary on grammatical development and suggest the presence of bilingual bootstrapping in DLLs. However, the degree and nature of cross-linguistic associations vary by language ability and language proficiency. The role of age and nonverbal cognition and clinical implications are also discussed. | Specific Language Disorder |
BACKGROUND: Paragonimiasis is a food-borne trematode infection acquired by eating raw or undercooked crustaceans. It is a major public health problem in the far East, but it also occurs in South Asia, Africa, and in the Americas. Paragonimus worms cause chronic lung disease with cough, fever and hemoptysis that can be confused with tuberculosis or other non-parasitic diseases. Treatment is straightforward, but diagnosis is often delayed due to a lack of reliable parasitological or serodiagnostic tests. Hence, the purpose of this study was to use a systems biology approach to identify key parasite proteins that may be useful for development of improved diagnostic tests. METHODOLOGY/PRINCIPAL FINDINGS: The transcriptome of adult Paragonimus kellicotti was sequenced with Illumina technology. Raw reads were pre-processed and assembled into 78,674 unique transcripts derived from 54,622 genetic loci, and 77,123 unique protein translations were predicted. A total of 2,555 predicted proteins (from 1,863 genetic loci) were verified by mass spectrometric analysis of total worm homogenate, including 63 proteins lacking homology to previously characterized sequences. Parasite proteins encoded by 321 transcripts (227 genetic loci) were reactive with antibodies from infected patients, as demonstrated by immunoaffinity purification and high-resolution liquid chromatography-mass spectrometry. Serodiagnostic candidates were prioritized based on several criteria, especially low conservation with proteins in other trematodes. Cysteine proteases, MFP6 proteins and myoglobins were abundant among the immunoreactive proteins, and these warrant further study as diagnostic candidates. CONCLUSIONS: The transcriptome, proteome and immunolome of adult P. kellicotti represent a major advance in the study of Paragonimus species. These data provide a powerful foundation for translational research to develop improved diagnostic tests. Similar integrated approaches may be useful for identifying novel targets for drugs and vaccines in the future. | Paragonimus |
Molecular pharmacognosy is a science of classification and identification, cultivation and protection, and production of active ingredients of graduated drugs at the molecular level. The proposal of molecular pharmacognosy allows the research of crude drugs to advance from the microscopic level to the genetic level. Pueraria lobata root, as a medicinal and edible plant, has high application value and economic value. There are many varieties that are easy to cause confusion, and it is not easy to distinguish and identify according to traditional identification methods. Moreover, the research of P. lobate root at the genetic level is still relatively shallow. the study received extensive attention of scholars. This article reviews recent research on molecular identification of P. lobate, transcriptome sequencing, cloning and synthesis of functional genes of P. lobate root in recent years in order to provide references for further promoting the development and utilization of P. lobate root and its active ingredients. | Pueraria |
In 1976, 163 patients were approved by the Department of Health and Social Security for transfer from the Special Hospitals to the open wards of the National Health Service. By autumn 1978, a quarter were still waiting for admission. Patients meeting most difficulty were the severely handicapped non-offenders, who were usually refused unseen on the ground that local subnormality hospitals were full. The role of the DHSS and of the Regional and Area Authorities was in general restricted to bewailing problems they could not help to solve. Some two years after their transfer, enquiries were made in the NHS about the 105 transferred patients. Removal back to the Special Hospital had been requested for seven, and another three had been removed by the police and prosecuted. | Transfer Agreement |
A prompt rise in circulating immunoreactive N- and C-terminal lipotrophin (LPH) accompanied the increase in ACTH when 100 micrograms CRF-41 was given to 6 normal male subjects. Chromatography of the basal and peak 15-min values showed that there was an equimolar increase in beta-LPH and beta-endorphin, to cause parallel release of ACTH, beta-endorphin and beta-LPH from the pro-opiocortin precursor. | beta-Lipotropin |
Two-dimensional difference gel electrophoresis (2-D DIGE) coupled with mass spectrometry (MS) was used to investigate tumor-specific changes in the proteome of human colorectal cancers and adjacent normal mucosa. For each of six patients with different stages of colon cancer, Cy5-labeled proteins isolated from tumor tissue were combined with Cy3-labeled proteins isolated from neighboring normal mucosa and separated on the same 2-D gel along with a Cy2-labeled mixture of all 12 normal/tumor samples as an internal standard. Over 1500 protein spot-features were analyzed in each paired normal/tumor comparison, and using DIGE technology with the mixed-sample internal standard, statistically significant quantitative comparisons of each protein abundance change could be made across multiple samples simultaneously without interference due to gel-to-gel variation. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and tandem (TOF/TOF) MS provided sensitive and accurate mass spectral data for database interrogation, resulting in the identification of 52 unique proteins (including redundancies due to proteolysis and post-translationally modified isoforms) that were changing in abundance across the cohort. Without the benefit of the Cy2-labeled 12 sample mixture internal standard, 42 of these proteins would have been overlooked due to the large degree of variation inherent between normal and tumor samples. | Keratin-3 |
Pemphigus and bullous pemphigoid are autoantibody-mediated blistering skin diseases. In pemphigus, keratinocytes in epidermis and mucous membranes lose cell-cell adhesion, and in pemphigoid, the basal keratinocytes lose adhesion to the basement membrane. Pemphigus lesions are mediated directly by the autoantibodies, whereas the autoantibodies in pemphigoid fix complement and mediate inflammation. In both diseases, the autoantigens have been cloned and characterized; pemphigus antigens are desmogleins (cell adhesion molecules in desmosomes), and pemphigoid antigens are found in hemidesmosomes (which mediate adhesion to the basement membrane). This knowledge has enabled diagnostic testing for these diseases by enzyme-linked immunosorbent assays and dissection of various pathophysiological mechanisms, including direct inhibition of cell adhesion, antibody-induced internalization of antigen, and cell signaling. Understanding these mechanisms of disease has led to rational targeted therapeutic strategies. | Pemphigoid, Bullous |
The orientational order parameters of monofluoropalmitic acids biosynthetically incorporated into membranes of Acholeplasma laidlawii B in the presence of a large excess of a variety of structurally diverse fatty acids have been determined via 19F nuclear magnetic resonance (19F NMR) spectroscopy. It is demonstrated that these monofluoropalmitic acids are relatively nonperturbing membrane probes based upon physical (differential scanning calorimetry), biochemical (membrane lipid analysis), and biological (growth studies) criteria. 19F NMR is shown to convey the same qualitative and quantitative picture of membrane lipid order provided by 2H-NMR techniques and to be sensitive to the structural characteristics of the membrane fatty acyl chains, as well as to the lipid phase transition. Representatives of each naturally occurring class of fatty acyl chain structures, including straight-chain saturated, methyl-branched, monounsaturated, and alicyclic-ring-substituted fatty acids, were studied and the 19F-NMR order parameters were correlated with the lipid phase transitions (determined calorimetrically). The lipid phase transition was the prime determinant of overall orientational order regardless of fatty acid structure. Effects upon orientational order attributable to specific structural substituents were discernible, but were secondary to the effects of the lipid phase transition. In the gel state, relative overall order was directly proportional to the temperature of the particular lipid phase transition. Not only the overall order, but also the order profile across the membrane was sensitive to the presence of particular structural substituents. In particular, in the gel state specific fatty acyl structures demonstrated a characteristic disordering effect in the membrane order profile. These various observations can be merged to provide a unified picture of the manner in which fatty acyl chain chemistry modulates the physical state of membrane lipids. | Acholeplasma laidlawii |
We explore the consequences of letting the incremental and integrative nature of language processing inform the design of competence grammar. What emerges is a view of grammar as a system of local monotonic constraints that provide a direct characterization of the signs (the form-meaning correspondences) of a given language. This sign-based" conception of grammar has provided precise solutions to the key problems long thought to motivate movement-based analyses, has supported three decades of computational research developing large-scale grammar implementations, and is now beginning to play a role in computational psycholinguistics research that explores the use of underspecification in the incremental computation of partial meanings." | Language |
Whereas thousands of new neurons are generated daily during adult life, only a fraction of them survive and become part of neural circuits; the rest die, and their corpses are presumably cleared by resident phagocytes. How the dying neurons are removed and how such clearance influences neurogenesis are not well understood. Here, we identify an unexpected phagocytic role for the doublecortin (DCX)-positive neuronal progenitor cells during adult neurogenesis. Our in vivo and ex vivo studies demonstrate that DCX(+) cells comprise a significant phagocytic population within the neurogenic zones. Intracellular engulfment protein ELMO1, which promotes Rac activation downstream of phagocytic receptors, was required for phagocytosis by DCX(+) cells. Disruption of engulfment in vivo genetically (in Elmo1-null mice) or pharmacologically (in wild-type mice) led to reduced uptake by DCX(+) cells, accumulation of apoptotic nuclei in the neurogenic niches and impaired neurogenesis. Collectively, these findings indicate a paradigm wherein DCX(+) neuronal precursors also serve as phagocytes, and that their phagocytic activity critically contributes to neurogenesis in the adult brain. | Doublecortin Domain Proteins |
A thermophilic, Gram-positive, endospore-forming, sulfate-reducing bacterium was isolated from an underground mine in a geothermally active area in Japan. Cells of this strain, designated RL50JIIIT, were rod-shaped and motile. The temperature range for growth was 50-72 degrees C (optimum growth at 61-66 degrees C) and the pH range was 6.4-7.8 (optimum at pH 7.2-7.4). Strain RL50JIIIT tolerated up to 1.5% NaCl, but optimum growth occurred in the presence of 0-1% NaCl. Electron acceptors utilized were sulfate, sulfite, thiosulfate and elemental sulfur. Electron donors utilized were H2 in the presence of CO2, alanine, various carboxylic acids and alcohols. Fermentative growth occurred on lactate and pyruvate. The cell wall contained mesodiaminopimelic acid and the major respiratory isoprenoid quinone was menaquinone 7 (MK-7). Major whole-cell fatty acids were iso-C15:0, iso-C17:0 DMA (dimethyl acetal), iso-C15:0 DMA and iso-C17:0. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed 98.7% similarity with Desulfotomaculum solfataricum DSM 14956T. However, DNA-DNA hybridization experiments with Desulfotomaculum kuznetsovii, Desulfotomaculum luciae and D. solfataricum and the G+C content of the DNA (54.4 mol%) allowed the differentiation of strain RL50JIIIT from the recognized species of the genus Desulfotomaculum. Strain RL50JIIIT therefore represents a novel species, for which the name Desulfotomaculum thermosubterraneum sp. nov. is proposed. The type strain is RL50JIIIT (=DSM 16057T=JCM 13837T). | Desulfotomaculum |
The fatty acid compositions of plasma lipids and cell membranes of certain tissues are modified by dietary fatty acid composition. Furthermore, many other factors (age, sex, ethnicity, health status, genes, and gene x diet interactions) affect the fatty acid composition of cell membranes or plasma lipid compartments. Therefore, it is of great importance to understand the complexity of mechanisms that may modify fatty acid compositions of plasma or tissues. We carried out an extensive literature survey of gene x diet interaction in the regulation of fatty acid compositions. Most of the related studies have been observational studies, but there are also a few intervention trials that tend to confirm that true interactions exist. Most of the studies deal with the desaturase enzyme cluster (FADS1, FADS2) in chromosome 11 and elongase enzymes. We expect that new genetic variants are being found that are linked with the genetic regulation of plasma or tissue fatty acid composition. This information is of great help to understanding the contribution of dietary fatty acids and their endogenic metabolism to the development of some chronic diseases. | Delta-5 Fatty Acid Desaturase |
The term dilated cardiomyopathy (DCM) defines a heterogeneous group of cardiac disorders, which are characterized by left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. In approximately one third of cases, DCM is familial with a genetic pathogenesis and various patterns of inheritance. Although the electrocardiogram (ECG) has been considered traditionally non-specific in DCM, the recently acquired knowledge of the genotype-phenotype correlations provides novel opportunities to identify patterns and abnormalities that may point toward specific DCM subtypes. A learned ECG interpretation in combination with an appropriate use of other ECG-based techniques including ambulatory ECG monitoring, exercise tolerance test and imaging modalities, such as echocardiography and cardiovascular magnetic resonance, may allow the early identification of specific genetic or acquired forms of DCM. Furthermore, ECG abnormalities may reflect the severity of the disease and provide a useful tool in risk stratification and management. In the present review, we discuss the current role of the ECG in the diagnosis and management of DCM. We describe various clinical settings where the appropriate use and interpretation of the ECG can provide invaluable clues, contributing to the important role of this basic tool as cardiovascular medicine evolves. | Laminopathies |
It is not unanimous among scientists if there is beauty in science. Some deny it. Mental clarity of conclusions when captured in simple looking equations is mathematical beauty. This we also find in the Euclidian geometry when performing the Golden Section and by deriving the Golden or Devine Number in golden rectangles, spirals and the Golden Angle. The Golden Section is considered as most beautiful and used in architecture and art. It is found everywhere in nature, e.g. in the pentagram of flowers, in the spirals of the shells of snails and Nautilus and even in galaxies of space. The Golden Angle in plants is realized in the phyllotaxis of spirals of leaf rosettes, in fruit stands and in the cones of conifers and cycads. It optimizes packing of modules such as seeds and fruits as well as the capture of light by leaves for photosynthesis and the fitness of productivity. Although we can mathematically deduce it and scientifically explain its role in organization and formation of patterns of structure and function, we cannot explain why we find it beautiful. In a methodological dualism esthetics and beauty are transcendental categories besides science. Or are the pleasant sensations of the Golden Section elicited by different stimuli to which our brain is adapted? Perhaps the Golden Section found everywhere in the entire universe is a link between natural science and the transcendental dimension, while a flower of a rose remains both a complex scientific system and an object of overwhelming beauty. | Beauty |
Evidence has documented the tumor-promoting properties of long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in many cancers. However, little is known about its role in gallbladder cancer. Here, we aimed to characterize the functional relevance of lncRNA FOXD2-AS1 in gallbladder cancer and the possible mechanisms associated with methylation of MutL homolog-1 (MLH1). Initially, microarray-based gene expression profiling of gallbladder cancer was employed to identify differentially expressed lncRNAs. Next, the expression of lncRNA FOXD2-AS1 was examined, and the cell line presenting with the highest lncRNA FOXD2-AS1 expression was selected for subsequent experimentation. Then, the interaction between lncRNA FOXD2-AS1 and MLH1 was identified. The effect of lncRNA FOXD2-AS1 on proliferation, migration, invasion, and apoptosis as well as tumorigenicity of transfected GBC-SD cells was examined with gain- and loss-of-function experiments. We found that lncRNA FOXD2-AS1 was highly expressed, while MLH1 was poorly expressed in gallbladder cancer cells. Besides, lncRNA FOXD2-AS1 could promote MLH1 methylation by recruiting DNMT1 to the MLH1 promoter, and consequently inhibit MLH1 transcription. Silencing of lncRNA FOXD2-AS1 or overexpression of MLH1 inhibited gallbladder cancer cell proliferation, invasion, and migration, while facilitating cell apoptosis in vitro as well as retarding tumor growth in vivo. Thus, silencing of lncRNA FOXD2-AS1 suppressed the progression of gallbladder cancer via upregulation of MLH1 by inhibiting MLH1 promoter methylation. These findings present lncRNA FOXD2-AS1 knockdown as a potential candidate for the treatment of gallbladder cancer. | MutL Protein Homolog 1 |
Researchers have investigated several therapeutic approaches to treat non-union fractures. Among these, bioactive glasses and glass ceramics have been widely used as grafts. This class of biomaterial has the ability to integrate with living bone. Nevertheless, bioglass and bioactive materials have been used mainly as powder and blocks, compromising the filling of irregular bone defects. Considering this matter, our research group has developed a new bioactive glass composition that can originate malleable fibers, which can offer a more suitable material to be used as bone graft substitutes. Thus, the aim of this study was to assess the morphological structure (via scanning electron microscope) of these fibers upon incubation in phosphate buffered saline (PBS) after 1, 7 and 14 days and, also, evaluate the in vivo tissue response to the new biomaterial using implantation in rat tibial defects. The histopathological, immunohistochemistry and biomechanical analyzes after 15, 30 and 60 days of implantation were performed to investigate the effects of the material on bone repair. The PBS incubation indicated that the fibers of the glassy scaffold degraded over time. The histological analysis revealed a progressive degradation of the material with increasing implantation time and also its substitution by granulation tissue and woven bone. Histomorphometry showed a higher amount of newly formed bone area in the control group (CG) compared to the biomaterial group (BG) 15 days post-surgery. After 30 and 60 days, CG and BG showed a similar amount of newly formed bone. The novel biomaterial enhanced the expression of RUNX-2 and RANK-L, and also improved the mechanical properties of the tibial callus at day 15 after surgery. These results indicated a promising use of the new biomaterial for bone engineering. However, further long-term studies should be carried out to provide additional information concerning the material degradation in the later stages and the bone regeneration induced by the fibrous material. | Bone Substitutes |
As they are now, defined, the DRGs form a manageable, clinically coherent set of patient classes that relate a hospital's case mix to the resource demands and associated costs experienced by the hospital. DRGs are defined based on the principal diagnosis, secondary diagnoses, surgical procedures, age and discharge status of the patients treated. Through DRGs, hospitals can gain an understanding of the patients being treated, the costs incurred and within reasonable limits, the services expected to be required. The classification of patients into DRGs is a constantly evolving process. As coding schemes change, as more comprehensive data is collected or as medical technology or practice changes, the DRG definitions will need to be reviewed and revised. | Prospective Payment System |
INTRODUCTION: Morbidity and mortality of Herpes simplex virus encephalitis (HSE) remain high. Relapses of neurological signs may occur after initial clinical improvement under acyclovir treatment. METHODS: We report here a case of post-HSE anti-N-methyl-d-aspartate receptor-mediated encephalitis in an adult and perform a systematic search on PubMed to identify other cases in adults. RESULTS: We identified 11 previously published cases, to discuss diagnostic and therapeutic management. Symptoms in adults are often inappropriate behaviors, confusion and agitation. Diagnosis of anti-NMDA-R encephalitis after HSE is often delayed. Treatment consists in steroids, plasma exchange, and rituximab. Prognosis is often favorable. CONCLUSION: Anti-NMDA-R antibodies should be searched in cerebrospinal fluid of patients with unexpected evolution of HSE. This emerging entity reopens the hot debate about steroids in HSE." | Anti-N-Methyl-D-Aspartate Receptor Encephalitis |
A pathologic entity, the gingival fenestration, has been described. The lesion is seen infrequently in clinical practice, probably due to the short time span of its existence and the lack of acute symptoms. It is possible that it occurs with greater frequency than generally realized. A hypothesis is presented as to the method of formation of the gingival fenestration and it is suggested that the area should be treated as gingival recession extending to the apical border of the fenestration. | Gingival Pocket |
Pax4-deficient mice have a severe gastrointestinal endocrine deficiency: they lack most pancreatic cells that produce insulin or somatostatin and various duodenal endocrine cell types. Remarkably, Pax4-deficient mice also have an overabundance of ghrelin-expressing cells in the pancreas and duodenum. Detailed analysis of the Pax4 nullizygous pancreas determined that the mutant islets are largely composed of a distinctive endocrine cell type that expresses ghrelin, glucagon, islet amyloid polypeptide (IAPP), and low levels of Pdx1. Lineage-tracing analysis revealed that most of these unique endocrine cells directly arose from Pax4-deficient progenitors. Previous in vitro work reported that Pax4 is a transcriptional repressor of islet amyloid polypeptide (IAPP) and glucagon. In this study, we expanded those results by showing that Pax4 is also a repressor of gherlin. Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract." | Paired Box Transcription Factors |
The results of a 1998 national survey of pharmaceutical services in hospitals throughout Australia are reported. A self-administered questionnaire was sent to all directors of hospital pharmacy services and senior hospital pharmacy managers to determine the extent of clinical and nonclinical pharmacy services provided by hospitals in Australia. Respondents chose the services their departments provide from a list of 26 commonly provided services. The response rate was 58.5%. Respondents were fairly evenly divided between teaching and nonteaching hospitals, but most of the respondents were from public (versus nongovernment) hospitals. The five most commonly provided services were imprest (a wordstock of frequently used medications that are regularly restocked by the pharmacy department), informal drug education for hospital staff, review of medication charts, control of drug purchasing, and inpatient dispensing. Review of medication charts and provision of drug education for the hospital staff were the most widely provided clinical pharmacy services. The most common services available from hospital pharmacies throughout Australia were imprest, informal drug education for hospital staff, review of medication charts, control of drug purchasing for the hospital, and inpatient dispensing. | Pharmacy Service, Hospital |
BHMT (betaine-homocysteine methyltransferase) remethylates homocysteine to form methionine. SAM (S-adenosylmethionine) inhibits BHMT activity, but whether SAM modulates BHMT gene expression is unknown. Transcriptional regulation of the human BHMT is also unknown. The present study examined regulation of the human BHMT gene by SAM and its metabolite, MTA (5'-methylthioadenosine). To facilitate these studies, we cloned the 2.7 kb 5'-flanking region of the human BHMT gene (GenBank accession number AY325901). Both SAM and MTA treatment of HepG2 cells resulted in a dose- and time-dependent decrease in BHMT mRNA levels, which paralleled their effects on the BHMT promoter activity. Maximal suppression was observed with the BHMT promoter construct -347/+33, which contains a number of NF-kappaB (nuclear factor kappaB) binding sites. SAM and MTA treatment increased NF-kappaB nuclear binding and NF-kappaB-driven luciferase activities, and increased nuclear binding activity of multiple histone deacetylase co-repressors to the NF-kappaB sites. Overexpression of p50 and p65 decreased BHMT promoter activity, while blocking NF-kappaB activation increased BHMT expression and promoter activity, and prevented SAM but not MTA's ability to inhibit BHMT expression. The NF-kappaB binding site at -301 is responsible, at least in part, for this effect. Lower BHMT expression can impair homocysteine metabolism, which can induce ER (endoplasmic reticulum) stress. Indeed, MTA treatment resulted in increased expression ER stress markers. In conclusion, SAM and MTA down-regulate BHMT expression in HepG2 cells in part by inducing NF-kappaB, which acts as a repressor for the human BHMT gene. While SAM's mechanism is NF-kappaB-dependent, MTA has both NF-kappaB-dependent and -independent mechanisms." | Betaine-Homocysteine S-Methyltransferase |
The major surface antigens of Trypanosoma brucei are the VSG (variant surface glycoprotein) at the bloodstream stage, and procyclin at the procyclic stage. Variation in the VSG allows the parasite to escape the antibody response of its mammalian host. This occurs through either DNA rearrangement in the telomeric VSG gene expression site, or alternate activation, without DNA rearrangement, of different telomeric expression sites. The VSG and procyclin genes each belong to large, polycistronic transcription units. Although the promoters of these units are both active at the two main stages of the parasite life cycle, stage-specific controls operating at the level of RNA elongation and processing lead to strictly differential expression of the end products of the two units. Despite their mutually exclusive control of expression, the VSG and procyclin transcription units share common characteristics. Both contain a similar gene, and both are transcribed by the same type of RNA polymerase, unusually resistant to alpha-amanitin. Among the eight genes present in the VSG transcription unit, two may be involved in the synthesis of cyclic AMP. The function of the other genes is unknown. | Antigenic Variation |
In any history of flight nursing or aeromedical evacuation, one usually sees reference to Lauretta Schimmoler and the Aerial Nurse Corps of America. A pioneer aviatrix with the foresight to see that one day there would be a need for military evacuation of wounded troops by air, Schimmoler spent nearly 15 years developing a paramilitary nursing organization that proved that such a thing could be successfully accomplished. This paper will survey the career of this remarkable woman, examine the structure and function of her organization, and discuss why it never gained official recognition by the military or the Red Cross. | Red Cross |
Muscle samples were obtained from the gastrocnemius of 17 female and 23 male track athletes, 10 untrained women, and 11 untrained men. Portions of the specimen were analyzed for total phosphorylase, lactic dehydrogenase (LDH), and succinate dehydrogenase (SDH) activities. Sections of the muscle were stained for myosin adenosine triphosphatase, NADH2 tetrazolium reductase, and alpha-glycerophosphate dehydrogenase. Maximal oxygen uptake (VO2max) was measured on a treadmill for 23 of the volunteers (6 female athletes, 11 male athletes, 10 untrained women, and 6 untrained men). These measurements confirm earlier reports which suggest that the athlete's preference for strength, speed, and/or endurance events is in part a matter of genetic endowment. Aside from differences in fiber composition and enzymes among middle-distance runners, the only distinction between the sexes was the larger fiber areas of the male athletes. SDH activity was found to correlate 0.79 with VO2max, while muscle LDH appeared to be a function of muscle fiber composition. While sprint- and endurance-trained athletes are characterized by distinct fiber compositions and enzyme activities, participants in strength events (e.g., shot-put) have relatively low muscle enzyme activities and a variety of fiber compositions. | NADH Tetrazolium Reductase |
To address whether St John's wort is useful for the treatment of depression we attempted to retrieve all English-language articles with data on the efficacy, safety, and availability of St John's wort. Randomized, controlled, double-blind trials were selected and assessed for methodological quality using a standardized checklist, and data on pharmacology, cost, regulation, and safety were extracted. Eight studies were identified, found to be of generally good methodological quality, and determined to provide a modest amount of data to suggest that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The absolute increased response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, but ranged from 6% to 18% lower compared with tricyclic antidepressants. More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Rates of side effects were low. As a dietary supplement, St John's wort is currently largely unregulated, but the Food and Drug Administration is reviewing plans to tighten its regulatory oversight. | Clusiaceae |
Genetic causes can be directly responsible for various clinical conditions of male infertility and spermatogenic impairment. With the increased use of assisted reproduction technologies our understanding of genetic basis of male infertility has large implications not only for understanding the causes of infertility but also in determining the prognosis and management of such couples. For these reasons, the genetic investigations represent today an essential and useful tool in the treatment of male infertility. Several evidences are available for the clinical practice regarding the diagnosis; however, there are less information relative to the treatment of the genetic causes of male infertility. Focus of this review is to discuss the main and more common genetic causes of male infertility to better direct the genetics investigation in the treatment of spermatogenic impairment. | Infertility, Male |
This consensus statement presents updated recommendations on diagnosis and treatment of myocarditis in childhood. | Myocarditis |
OBJECTIVE: Access to viral load measurements is constrained in resource-limited settings. A lateral flow urine tenofovir (TFV) rapid assay (UTRA) for patients whose regimens include TFV offers an affordable approach to frequent adherence monitoring. DESIGN: We conducted a cross-sectional study of patients to assess the utility of UTRA to predict virologic failure, defined as a viral load greater than 400 copies/ml. METHODS: We assessed urine TFV among 113 participants at increased risk of viral failure (who had previous viral failure on this regimen or had previously been >/=30 days out of care), comparing low genetic-barrier efavirenz (EFV) regimens (n = 60) to dolutegravir (DTG)-boosted or ritonavir-boosted protease inhibitor (PI/r)-based high genetic-barrier regimens (n = 53). Dried blood spots (DBS) for TFV-diphosphate and plasma for TFV concentrations were collected, with drug resistance assessed if viral failure present. RESULTS: Among 113 participants, 17 of 53 received DTG or PI/r had viral failure at the cross-sectional visit, with 11 (64.7%) demonstrating an undetectable urine TFV; the negative-predictive value (NPV) of undetectable UTRA for viral failure was 85% (34/40); none of the 16 sequenced had dual class drug resistance. In those treated with EFV regimens the sensitivity was lower, as only 1 (4.8%) of 21 with viral failure had an undetectable UTRA (P < 0.001). CONCLUSIONS: Urine tenofovir-testing had a high negative-predictive value for viral failure in patients treated with DTG or ritonavir-boosted protease inhibitor regimens, where viral failure was largely explained by poor drug adherence. Frequent monitoring with inexpensive lateral flow urine TFV testing should be investigated prospectively in between viral load visits to improve viral load suppression on DTG-based first-line therapy in resource-limited settings. | Viremia |
The purpose was the develop a questionnaire to identify the specific listening difficulties of second language (L2) learners. Based on previous research, a questionnaire containing 31 items was developed and administered to 1,056 college freshmen. The whole sample was split randomly into two subsamples, each containing 528 cases. Exploratory factor analysis was performed to analyse the first subsample, and six factors were extracted, explaining a total of 57.1% of variance. To test the factor model, confirmatory factor analysis was conducted with the second subsample. Various fit indices were examined. The best fitting model for the data was a 23-item, six-factor model representing text, input channel and surroundings, relevance, listener, speaker, and task. Apart from the listener factor, all components are external ones and deemed to be uncontrollable by listeners. L2 learners must take an active role in listening practice to overcome L2 listening difficulties. | Psycholinguistics |
Philophthalmus aweerensis, a new eye fluke species, was discovered in the conjunctival cavities of a rhea in the UAE. This fluke was described and differentiated from other eye flukes that had been found in birds in the Middle East such as Philophthalmus palpebrarum, Philophthalmus nocturnus, Philophthalmus gralli, Philophthalmus lucipetus, Philophthalmus distomatosa, and Philophthalmus hegeneri. The new species lacks spination and is characterized by a long cirrus pouch extending behind the caudal margin of the acetabulum, long vitellaria of tubular type reaching the midbody, and a genital opening situated anteriorly to the bifurcation of the caeca. | Rheiformes |
Primate species exhibit considerable variation in behavior and outcomes during intergroup encounters (IGEs). Social group characteristics, like group size, and individual traits, such as sex, rank, and reproductive status, within those groups can influence both IGE engagement and outcomes. To better understand the impact of group heterogeneity on IGEs, we must examine individual strategies to elucidate individual costs and benefits of engaging in these interactions. Here, we present a descriptive study of the IGEs between two small social groups of ring-tailed lemurs (Lemur catta) on St. Catherines Island, GA, USA. We distinguish between dyadic and multiple-individual interactions between groups to compare collective and individual agonistic engagement. All encounters occurred when the East Road group (N = 7 individuals) traveled from the center of their home range to the boundary with Windmill group's (N = 5 individuals) home range, indicating that East Road might have been actively testing this boundary for access to food resources, sleeping trees, and mating opportunities. We also found notable individual variation in participation during IGEs. The daughters of the highest-ranking females were the most-engaged in dyadic intergroup and intragroup aggression, had high win" rates during intergroup dyadic encounters, and engaged in intergroup multiple-individual interactions at high levels. These findings indicate that they might value their home range more as "potential alphas" compared to other group members. Dominant females were the most engaged in multiple-individual interactions, suggesting that they contribute heavily to collective action that might result in a gain or loss of access to resources. Finally, these two small groups might be equally matched despite the two-individual group size disparity due to individual free-riding strategies. Future research should focus on individual strategies during IGEs to characterize the complex decisions and trade-offs that influence participation." | Lemuridae |
Streptococcus pneumoniae (pneumococcus) is a pathogen that causes severe local and life-threatening invasive diseases, which are associated with high mortality rates. Pneumococci have evolved several strategies to evade the host immune system, including complement to disseminate and to survive in various host niches. Thus, pneumococci bind complement inhibitors such as C4b-binding protein (C4BP) and factor H via pneumococcal surface protein C, thereby inhibiting the classical and alternative complement pathways. In this study, we identified the pneumococcal glycolytic enzyme enolase, a nonclassical cell surface and plasminogen-binding protein, as an additional pneumococcal C4BP-binding protein. Furthermore, we demonstrated that human, but not mouse, C4BP bound pneumococci. Recombinant enolase bound in a dose-dependent manner C4BP purified from plasma, and the interaction was reduced by increasing ionic strength. Enolase recruited C4BP and plasminogen, but not factor H, from human serum. Moreover, C4BP and plasminogen bound to different domains of enolase as they did not compete for the interaction with enolase. In direct binding assays with recombinant C4BP mutants lacking individual domains, two binding sites for enolase were identified on the complement control protein (CCP) domain 1/CCP2 and CCP8 of the C4BP alpha-chains. C4BP bound to the enolase retained its cofactor activity as determined by C4b degradation. Furthermore, in the presence of exogenously added enolase, an increased C4BP binding to and subsequently decreased C3b deposition on pneumococci was observed. Taken together, pneumococci specifically interact with human C4BP via enolase, which represents an additional mechanism of human complement control by this versatile pathogen." | Complement C4b-Binding Protein |
This article compares sterilized and non-sterilized women in relation to socio-demographic characteristics, reproductive history, and cohabitation status. Women from 30 to 49 years of age and residing in Campinas, Sao Paulo State, Brazil, were interviewed with a pre-tested and structured questionnaire: 236 women sterilized at least five years before the interview and 236 non-sterilized women. The sterilized women were significantly more likely to be married or cohabiting, to be younger when they began cohabiting, and to have been in the union longer than the non-sterilized women. They also began childbearing at an earlier age and had a history of more pregnancies and more live births than non-sterilized women. Factors associated with a history of 3 or more live births at the time of the interview were surgical sterilization, younger age at first childbirth, older age at the interview, recognition of fewer contraceptive methods, and lower per capita income. The article concludes that sterilization generally appears to be the consequence of higher fertility in a group of women who initiate childbearing early in life, although its role in preventing these women from having even larger families may also have a demographic impact. | Reproductive History |
A sulfated tricarboxylic acid fungal metabolite is an inhibitor of human farnesyl-protein transferase (FPTase). The compound, designated as oreganic acid, has a molecular weight of 494, an empirical formula of C22H38O10S and inhibits FPTase with an IC50 value of 14 nM. Oreganic acid is a selective inhibitor of FPTase because it does not inhibit human geranylgeranyl-protein transferase type I (GGPTase-I). It is not a time-dependent inhibitor, reversibly inhibits FPTase, is competitive with respect to farnesyl diphosphate and non-competitive with respect to the Ras acceptor peptide. The structure of oreganic acid resembles that of farnesyl diphosphate and most likely inhibits FPTase by mimicking farnesyl diphosphate at the active site of the enzyme. | Oncogene Protein p21(ras) |
Tet repressor mutants with a shifted effector specificity, preference for a mutant operator sequence or reversion of activity were combined to construct variants bearing two or three phenotypic alterations. TetR alleles with combinations of altered operator and effector specificities can be created by merging the respective residues in a single polypeptide. The mutations giving rise to revTetR, on the other hand, show drastic influences on the ligand binding phenotypes when combined with respective alterations. One TetR variant displays all three phenotypic alterations and thus demonstrates the general possibility of implementing them in one protein. | Operator Regions, Genetic |
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