Pattern of lung cancer in Turkey, 1994-1998.
Lung cancer is the most common neoplasm in Turkey, but there is not enough data on the characteristics of this mortal illness in our country. The Turkish Thoracic Society, Lung and Pleural Malignancies Study Group (TTS-LPMSG) conducted a national retrospective hospital-based study to determine the pattern of lung cancer in Turkey. A total of 11,849 lung cancer patients were studied between 1994 and 1998, 90.4% were male and 9.6% were female. The majority of patients were smokers (77.9%) or ex-smokers (10.8%). The mean age at the time of diagnosis was 58.4 years (20-84) and 56.7% of the patients were aged between 46 and 65 years. The most common histological types were squamous cell (45.4%), small cell (SCLC; 20.5%) and adenocarcinoma (20.2%). The majority of patients with non-small-cell lung cancer were diagnosed with metastatic disease (40.4%). Of the patients with SCLC patients, 37.9% had limited stage disease and 62.7% extensive stage disease at diagnosis. The results of the largest data so far collected in Turkey show that the vast majority of patients with lung cancer are male, squamous cell is the most common histological type, and only a small proportion of patients are diagnosed at an early stage.


Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months' follow-up.
To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose. Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with a total dose of 0.6 Gy applied in 6 fractions of 0.1 Gy twice weekly (low dose). In all patients lateral opposing 4- to 6-MV photon beams were used. The results were measured using a visual analogue scale, the Calcaneodynia score, and the SF12 health survey. The fundamental phase of the study ended after 3 months, and the follow-up was continued up to 1 year. Patients with insufficient pain relief after 3 months were offered reirradiation with the standard dosage at any time afterward. Of 66 patients, 4 were excluded because of withdrawal of consent or screening failures. After 3 months the results in the standard arm were highly significantly superior compared with those in the low-dose arm (visual analogue scale, P=.001; Calcaneodynia score, P=.027; SF12, P=.045). The accrual of patients was stopped at this point. Further evaluation after 12 months' follow-up showed the following results: (1) highly significant fewer patients were reirradiated in the standard arm compared with the low-dose arm (P<.001); (2) the results of patients in the low-dose arm who were reirradiated were identical to those in the standard arm not reirradiated (reirradiation as a salvage therapy if the lower dose was ineffective); (3) patients experiencing a favorable result after 3 months showed this even after 12 months, and some results even improved further between 3 and 12 months. This study confirms the superior analgesic effect of radiation therapy with 6-Gy doses on painful heel spur even for a longer time period of at least 1 year.


The incommensurately modulated structures of low-temperature labradorite feldspars: a single-crystal X-ray and neutron diffraction study.
Labradorite feldspars of the plagioclase solid solution series have been known for their complicated subsolidus phase relations and enigmatic incommensurately modulated structures. Characterized by the irrationally indexed e-reflections in the diffraction pattern, e-labradorite shows the largest variation in the incommensurate ordering states among the e-plagioclase structures. The strongly ordered low-temperature e-labradorite is one of the last missing pieces of the e-plagioclase puzzle. Nine plutonic and metamorphic labradorite feldspar samples from Canada, Ukraine, Minnesota (USA), Tanzania and Greenland with compositions ranging from An52.5 to An68 were studied with single-crystal X-ray diffraction. Two crystals from Labrador, Canada, and Duluth, MN, USA, with wide enough twin lamellae were analyzed with single-crystal neutron diffraction. The incommensurately modulated structures of e-plagioclase are refined for the first time with neutron diffraction data, which confirmed that the T-O distance modulation in the low-temperature e-plagioclase results from the Al-Si ordering in the framework. Detailed configurations of the M site are also observed in the structures refined from neutron diffraction data, which were not possible to see with X-ray diffraction data. The relation between the q-vectors and the mole% An composition is revealed for the entire compositional range of e-plagioclase, from An25 to An75. The previously proposed two-trend relation depending on the cooling rate and phase transition path is confirmed. A new classification of e-plagioclase (eα, eβ and eγ) is proposed based on the q-vector of the structure, which makes it an independent character from the presence/absence of density modulation. New parameters are proposed to quantify the ordering states of these complicated aperiodic structures of e-plagioclases, such as the difference between 〈T1o-O〉 and 〈T1m-O〉 at phase t = 0.2 or the normalized intensity of the (071\bar 1) reflection.


Link between domoic acid production and cell physiology after exchange of bacterial communities between toxic Pseudo-nitzschia multiseries and non-toxic Pseudo-nitzschia delicatissima.
Bacteria are known to influence domoic acid (DA) production by Pseudo-nitzschia spp., but the link between DA production and physiology of diatoms requires more investigation. We compared a toxic P. multiseries to a non-toxic P. delicatissima, investigating links between DA production, physiological parameters, and co-occurring bacteria. Bacterial communities in cultures of both species were reduced by antibiotic treatment, and each of the diatoms was inoculated with the bacterial community of the other species. The physiology of P. delicatissima was minimally affected by the absence of bacteria or the presence of alien bacteria, and no DA was detected. P. multiseries grew faster without bacteria, did not produce a significant amount of DA, and exhibited physiological characteristics of healthy cells. When grown with alien bacteria, P. multiseries did not grow and produced more DA; the physiology of these cells was affected, with decreases in chlorophyll content and photosynthetic efficiency, an increase in esterase activity, and almost 50% mortality of the cells. The alien bacterial community had morphological and cellular characteristics very different from the original bacteria, and the number of free-living bacteria per algal cell was much higher, suggesting the involvement of bacteria in DA production.


Feasibility and Acceptability of a Culturally Tailored Website to Increase Fruit and Vegetable Intake and Physical Activity Levels in African American Mother-Child Dyads: Observational Study.
African American youth (aged 8-14 years) do not adhere to national dietary and physical activity guidelines. Nonadherence to these recommendations contributes to disproportionate rates of obesity compared with their white counterparts. Culturally tailored electronic health (eHealth) solutions are needed to communicate nutrition and physical activity messages that resonate with this target population. This study aimed to identify the impact of exposure to a website hosting culturally tailored cartoons to inspire fruit and vegetable uptake and physical activity levels in African American mother-child dyads. Statistical analysis included paired sample t tests to evaluate knowledge gains, self-efficacy, and readiness to change. Adapted items from Prochaska's Stages of Change toward the following 4 behaviors were assessed with pre- and posttest surveys: (1) fruit and vegetable selection on my plate, (2) meal preparation, (3) fruit and vegetable selection outside of home, and (4) physical activity. Open-ended comments on videos from mother-child dyads were used to determine user acceptance. Observations of repeated responses during content analysis informed coding and development of key themes. A final sample size of 93 mother-child dyads completed the study. Mothers reported significant improvement from precontemplation or contemplation stages to preparation or action stages for (1) fruit and vegetable selection on her plate (P=.03), (2) meal preparation for her family (P=.01), (3) fruit and vegetable selection outside the home (P<.001), and (4) physical activity (P<.001). Significant improvements were found in knowledge, stage of change, and self-efficacy for the 4 target behaviors of interest (P<.001). Children's open-ended commentary reported vicarious learning and positive character identification with brown-skinned cartoons exhibiting healthful food and exercise behaviors. Mothers commented on the lack of accessible produce in their neighborhoods not depicted in the cartoon videos. Culturally adapted cartoons that incorporate tailored preferences by African American families, such as race or demography, may help increase adherence to target health behaviors when developing eHealth behavior solutions.


Computerized Cognitive Rehabilitation of Attention and Executive Function in Acquired Brain Injury: A Systematic Review.
Comprehensive review of the use of computerized treatment as a rehabilitation tool for attention and executive function in adults (aged 18 years or older) who suffered an acquired brain injury. Systematic review of empirical research. Two reviewers independently assessed articles using the methodological quality criteria of Cicerone et al. Data extracted included sample size, diagnosis, intervention information, treatment schedule, assessment methods, and outcome measures. A literature review (PubMed, EMBASE, Ovid, Cochrane, PsychINFO, CINAHL) generated a total of 4931 publications. Twenty-eight studies using computerized cognitive interventions targeting attention and executive functions were included in this review. In 23 studies, significant improvements in attention and executive function subsequent to training were reported; in the remaining 5, promising trends were observed. Preliminary evidence suggests improvements in cognitive function following computerized rehabilitation for acquired brain injury populations including traumatic brain injury and stroke. Further studies are needed to address methodological issues (eg, small sample size, inadequate control groups) and to inform development of guidelines and standardized protocols.


Plant sterol-enriched margarines and reduction of plasma total- and LDL-cholesterol concentrations in normocholesterolaemic and mildly hypercholesterolaemic subjects.
To compare effects on plasma total-, LDL-, and HDL-cholesterol concentrations of margarines enriched with different vegetable oil sterols or sitostanol-ester. A randomized double-blind placebo-controlled balanced incomplete Latin square design with five treatments and four periods of 3.5 weeks. Margarines enriched with sterols from soybean, sheanut or ricebran oil or with sitostanol-ester were compared to a non-enriched control margarine. Sterol intake was between 1.5-3.3 g/d. Two thirds of the soybean oil sterols were esterified to fatty acids. Unilever Research Laboratory, Vlaardingen, The Netherlands. One hundred healthy non-obese normocholesterolaemic and mildly hypercholesterolaemic volunteers aged 45+/-12.8 y, with plasma total cholesterol levels below 8 mmol/L at entry. Plasma lipid, carotenoid and sterol concentrations, blood clinical chemistry and haematology, fatty acid composition of plasma cholesterylesters and food intake. Ninety-five volunteers completed the study. None of the margarines induced adverse changes in blood clinical chemistry, serum total bile acids or haematology. Plasma total- and LDL-cholesterol concentrations were significantly reduced by 8-13% (0.37-0.44 mmol/L) compared to control for margarines enriched in soybean oil sterol-esters or sitostanol-ester. No effect on HDL-cholesterol concentrations occurred. The LDL- to HDL-cholesterol ratio was reduced by 0.37 and 0.33 units for these margarines, respectively. Effects on blood lipids did not differ between normocholesterolaemic and mildly hypercholesterolaemic subjects. Plasma sitosterol and campesterol levels were significantly higher for the soybean oil sterol margarine and significantly lower for the sitostanol-ester margarine compared to control. Dietary intake was very similar across treatments. The fatty acid composition of plasma cholesterylesters confirmed the good compliance to the treatment. All sterol enriched margarines reduced lipid-standardized plasma alpha- plus beta-carotene levels. Plasma lycopene levels were also reduced but this effect was not significant for all products. A margarine with sterol-esters from soybean oil, mainly esters from sitosterol, campesterol and stigmasterol, is as effective as a margarine with sitostanol-ester in lowering blood total- and LDL-cholesterol levels without affecting HDL-cholesterol concentrations. Incorporation in edible fat containing products of such substances may substantially reduce the risk of cardiovascular disease in the population.


Stroke Survivors' Experiences of Physical Rehabilitation: A Systematic Review of Qualitative Studies.
To report and synthesize the perspectives, experiences, and preferences of stroke survivors undertaking inpatient physical rehabilitation through a systematic review of qualitative studies. MEDLINE, CINAHL, Embase, and PsycINFO were searched from database inception to February 2014. Reference lists of relevant publications were searched. All languages were included. Qualitative studies reporting stroke survivors' experiences of inpatient stroke rehabilitation were selected independently by 2 reviewers. The search yielded 3039 records; 95 full-text publications were assessed for eligibility, and 32 documents (31 studies) were finally included. Comprehensiveness and explicit reporting were assessed independently by 2 reviewers using the consolidated criteria for reporting qualitative research framework. Discrepancies were resolved by consensus. Data regarding characteristics of the included studies were extracted by 1 reviewer, tabled, and checked for accuracy by another reviewer. All text reported in studies' results sections were entered into qualitative data management software for analysis. Extracted texts were inductively coded and analyzed in 3 phases using thematic synthesis. Nine interrelated analytical themes, with descriptive subthemes, were identified that related to issues of importance to stroke survivors: (1) physical activity is valued; (2) bored and alone; (3) patient-centered therapy; (4) recreation is also rehabilitation; (5) dependency and lack of control; (6) fostering autonomy; (7) power of communication and information; (8) motivation needs nurturing; and (9) fatigue can overwhelm. The thematic synthesis provides new insights into stroke survivors' experiences of inpatient rehabilitation. Negative experiences were reported in all studies and include disempowerment, boredom, and frustration. Rehabilitation could be improved by increasing activity within formal therapy and in free time, fostering patients' autonomy through genuinely patient-centered care, and more effective communication and information. Future stroke rehabilitation research should take into account the experiences and preferences of stroke survivors.


Mycoplasma: growth precipitation as a serodiagnostic method.
A serological test is described which is designated the growth precipitation test and is based on the release of diffusible compounds from mycoplasma strains. During growth of mycoplasmas on solid substrates, precipitation lines are formed with antibodies from homologous antisera independent of heat-labile serum factors. The application of the test as a serodiagnostic tool was investigated by performing a complete serological cross-test with 10 mycoplasma strains. The test was compared with the growth inhibition test, the complement fixation test, and the indirect hemagglutination test. It is demonstrated that the growth precipitation test has a good degree of specificity. The species and subspecies used here showed cross-reactions between serologically closely related strains, but these heterologous reactions occurred only after longer incubation than the homologous reactions.


Predicting methicillin resistance and the effect of inadequate empiric therapy on survival in patients with Staphylococcus aureus bacteremia.
The restriction of vancomycin hydrochloride use is recommended as a measure to decrease the emergence of vancomycin resistance in gram-positive organisms; however, vancomycin also is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA) infections. If vancomycin use is restricted to patients with documented infections due to methicillin-resistant organisms, then patients with MRSA infections may not initially receive vancomycin. This study was performed to determine factors that predict MRSA bacteremia and if ineffective empiric antibiotic therapy increased the risk of death in patients with S aureus bacteremia. We conducted a retrospective cohort study of all patients with clinically significant S aureus bacteremia (132 episodes in 128 patients) diagnosed between October 1, 1995, and January 1, 1998, at an urban acute care Veterans Affairs medical center (approximately 200 acute care beds) in Baltimore, Md. During the study period, vancomycin was a restricted antibiotic. Empiric use had to be approved by an attending physician specializing in infectious diseases. Compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly older (70 vs 58 years; P<.01), more likely to have a history of MRSA (47% vs 6%; P<.01) and a nosocomial infection (76% vs 50%; P<.01), and less likely to use injection drugs (8% vs 32%; P<.01). In addition, compared with patients who had methicillin-sensitive S aureus bacteremia, patients with MRSA bacteremia were significantly less likely (45% vs 98%; P<.01) to receive effective antibiotic therapy during the first 48 hours of hospitalization. However, the risk of death due to ineffective empiric therapy was less than 1 (relative risk, 0.82; 95% confidence interval, 0.36-1.88) and did not change significantly when adjusted for age, occurrence of sepsis, or nosocomial infection. The results of this study support the safety of the restriction of vancomycin use in patients with clinically significant S aureus bacteremia. However, patients with a history of MRSA are more likely to have future MRSA infections and should receive empiric therapy using vancomycin for possible S aureus infections, particularly for nosocomial infections.


[Profile on circadian blood pressure and the influencing factors in essential hypertensive patients after treatment].
To explore the circadian blood pressure (BP) profile and its influencing factors in essential hypertensive patients after treatment. Cross-sectional surveillance was carried out in essential hypertensive subjects after treatment whose clinic blood pressure had been under control as 140/90 mm Hg (1 mm Hg = 0.133 kPa) for at least one month. All patients underwent a twenty-four-hour ambulatory blood pressure monitoring device (spacelabs 90207). The nocturnal fall of blood pressure (BP) was calculated from (daytime mean BP-night-time mean BP)/daytime BP, while 'daytime' values were recorded between 6 h and 22 h and 'night-time' values between 22 h and 6 h. Non-dippers were defined as those whose nocturnal decrease in mean systolic BP and/or mean diastolic BP was < 10% of the daytime BP. Binary logistic regression analysis was used to evaluate the correlation between circadian blood pressure profile and factors as gender, age, height, body mass index (BMI), family history of premature cardiovascular disease, women under age 65 or men under age 55, smoking habits, grade of hypertension, and strategy of antihypertensive drugs. 208 treated essential hypertensive patients were enrolled in the study. 79 individuals were dippers and 129 were non-dippers. Data from logistic regression analysis showed that four factors as age, premature family history of cardiovascular disease, overweight or obesity, and strategy of antihypertensive drugs were significantly influencing the circadian blood pressure profile in treated hypertensive patients. The incidence of non-dippers in patients of 70 years of age or older and those between 60 and 69 were 3.3 and 2.3 times of those with less than 60 (P = 0.009 and 0.031, respectively). The prevalence of non-dippers in patients with a premature family history of cardiovascular disease was 3.7 times greater than those in subjects without a premature history of cardiovascular disease (P = 0.029). Similarly, the incidence of non-dippers in patients of overweight (24 </= BMI < 28) and obesity (BMI >/= 28) were 3.0 and 4.8 times of those in subjects of normal weight (P = 0.003 and 0.009, respectively). Compared with patients treated with long-acting calcium channel blockers (CCBs), patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) alone had less prevalence of nondippers (OR = 0.139, P = 0.010). Patients treated with joint antihypertensive scheme including ACE inhibitors or ARBs(but not including diuretics) had the tendency of lower incidence of abnormal circadian blood pressure rhythm (OR = 0.453, P = 0.118). Patients treated with joint antihypertensive scheme including diuretics (not including ACE inhibitors or ARBs) and with joint antihypertensive strategy including diuretics and ACE inhibitors or ARBs had lower incidence of nondippers (OR = 0.378 and 0.273, respectively; P = 0.030 and 0.011, respectively). Approximately 2/3 treated essential hypertensive patients had a non-dipper blood pressure profile. Age, premature family history of cardiovascular disease, overweight/obesity, and antihypertensive drugs strategy were correlated with circadian blood pressure profile. Compared with long-acting CCBs, diuretics, ACE inhibitors or ARBs might be helpful in keeping the circadian blood pressure rhythm at normal range.


Laparotomy versus no laparotomy in the management of early-stage, favorable-prognosis Hodgkin's disease: a decision analysis.
To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging. The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months. These results suggest that a role remains for surgical staging in the management of early-stage HD.


Release and uptake of gene transfer agent by Rhodopseudomonas capsulata.
Many strains of Rhodopseudomonas capsulata are capable of exchanging genetic information via a recently discovered gene transfer process involving the release and subsequent uptake from the medium of particles containing genetic information (gene transfer agents, GTAs). No viral activities are observed to be associated with this system. An assay has been developed to quantitate gene transfer in R. capsulata. Conditions are described for which the number of cells acquiring a new genetic trait is direcly proportional to the number of GTAs and independent of the number of receipient cells. These conditions were used for the assay of the uptake and release of GTAs by cells. The maximum fraction of recipients that acquire a given genetic marker is approximately 4 X 10(-4). Free GTA appears in a growing culture in one or two abrupt waves near the time of transition from exponential to stationary phase. During these waves, the titer of GTA for a given marker may reach 2 X 103/ml. A comparison of the frequency of single- and double-marker transfers suggests that most of the cells in early-stationary-phase cultures are active recipients. The ultraviolet inactivation spectrum of GTA resembles that of the small ribonucleic acid phages. The inactivation cross section section beta, for GTA was calculated to be 1.7 X 10(-16) cm2/photon at 265 nm.


[Elements making up the identity of the nurse in descriptions expressed by graduating students].
Identity is usually conceived by choosing a series of characteristics which should be truly considered a person's own; it searches to fulfill needs that other way would stop individuals to build their own destinies. We aimed to apprehend the nurse's identity built by a group of Nursing undergraduate students. It was used a qualitative approach. "Care" was the word mostly used by the students while trying to explain what means to be a nurse. However, few of them could define the meaning of this care. From the students' speeches, we verified that the nurse is very related to the practical work, despite the fact that they affirm it to be an intellectual work. Another point discussed in this article is that the students do not mention the professors influence while building their perception of nurses.


Diversity of Neotropical stalked-puffball: Two new species of Tulostoma with reticulated spores.
Species of the genus Tulostoma are easily recognizable by the presence of a spore sac, with a mouth from which spores are released, attached to a stipe. Tulostoma is a species-diverse genus with a worldwide distribution, and some attempts were made to delimitate species and to evaluate reliable taxonomic-informative characteristics for species identification. However, there is a notable information gap regarding Neotropical species, especially for geographic distribution and DNA data, which hampers further understanding of the infrageneric diversity, evolution, and ecology of this genus. Based on morphological analysis, molecular phylogenetics and geographic distribution, we propose here two new species of Tulostoma with reticulated spores, from the two threatened Brazilian geographical areas, Atlantic Forest and "campos rupestres" (rupestrian grassland), as well as we provide notes on the taxonomic rank of Tulostoma exasperatum var. ridleyi.


An ethanol/ether soluble apoprotein from rat lung surfactant augments liposome uptake by isolated granular pneumocytes.
Ethanol/ether soluble apoproteins, comprising 17% of the total recovered surfactant-associated proteins, were isolated from rat lung surfactant and purified by silicic acid chromatography. The protein that eluted in 4:1 chloroform/methanol accounted for greater than 85% of protein in the ethanol/ether soluble fraction and was termed surfactant apoprotein Et (Apo Et). By sodium dodecyl sulfate polyacrylamide gel electrophoresis, this protein had an apparent molecular weight of approximately 10,500. Apo Et was evaluated for its effect on uptake of synthetic phospholipids in liposomal form by isolated granular pneumocytes (Type II alveolar epithelial cells) in primary culture. Liposomes were prepared to approximate the phospholipid composition of the alveolar surfactant, and uptake was measured by the accumulation of the radioactively labeled dipalmitoyl phosphatidyl choline fraction. The uptake of liposomal phosphatidylcholine by cells incubated for 2 h with Apo Et was increased by 61% over control. Most of the cell-associated phospholipid uptake was resistant to treatment with trypsin, suggesting an increased internalization of liposomal material in the presence of Apo Et. The effect of Apo Et on uptake was concentration and time dependent and was not associated with cell damage, phospholipase activity, or detergent properties of the protein. Apo Et had no significant effect on phosphatidylcholine uptake by granular pneumocytes maintained for 7 d in primary culture. Apo Et augmented the uptake of phospholipids by alveolar macrophages although total uptake by these cells was less than that observed with granular pneumocytes. Because Apo Et increases the rate of uptake of surfactant phospholipids by alveolar cells (granular pneumocytes and alveolar macrophages), this protein may represent a physiologically important regulator for clearance of lung surfactant phospholipids.


Antigen-specific bacterial vaccine combined with anti-PD-L1 rescues dysfunctional endogenous T cells to reject long-established cancer.
Immunogenic tumors grow progressively even when heavily infiltrated by CD8(+) T cells. We investigated how to rescue CD8(+) T cell function in long-established immunogenic melanomas that contained a high percentage of endogenous PD-1(+) tumor-specific CD8(+) T cells that were dysfunctional. Treatment with αPD-L1 and αCTLA-4 blocking antibodies did not prevent tumors from progressing rapidly. We then tested exogenous tumor-specific antigen delivery into tumors using Salmonella Typhimurium A1-R to increase antigen levels and generate a proinflammatory tumor microenvironment. Antigen-producing A1-R rescued the endogenous tumor-specific CD8(+) T cell response: proliferation was induced in the lymphoid organs and effector function was recovered in the tumor. Treatment with antigen-producing A1-R led to improved mouse survival and resulted in 32% rejection of long-established immunogenic melanomas. Following treatment with antigen-producing A1-R, the majority of tumor-specific CD8(+) T cells still expressed a high level of PD-1 in the tumor. Combining antigen-producing A1-R with αPD-L1 blocking antibody enhanced the expansion of tumor-specific CD8(+) T cells and resulted in 80% tumor rejection. Collectively, these data demonstrate a powerful new therapeutic approach to rescue dysfunctional endogenous tumor-specific CD8(+) T cells and eradicate advanced immunogenic tumors.


Laparoscopic tailored Nissen fundoplication.
It is difficult sometimes to determine the suture points for proper Nissen fundoplication under laparoscopy. We introduce a new procedure to define the suture points in Laparoscopic Nissen fundoplication (LNF). After dissection of the hiatus and mobilization of the fundus, the circumference of the esophagus c is measured at a point 2-cm cranial from the esophagogastric junction over the 52-Fr bougie. The inner diameter of the fundoplication is calculated based on the esophageal diameter. To create a 2-cm fundoplication in which the greater curvature of the gastric fundus is moved straight toward the cranial side without any twist, we located points a and b, which correspond to the top of the left and right suture positions on fundoplication, respectively. Approximately 2 cm of floppy Nissen is constructed by suturing caudally with intervals of ~1 cm. A total of 20 patients (3 men, 17 women, mean age, 64.5 years) with gastroesophageal reflux disease and/or hiatal hernia underwent LNF using this procedure. LNF was successful in all 20 patients. There were no complications except for mild dysphagia in two patients, which disappeared within 3 weeks. Improvement of the symptom scores for heartburn, regurgitation, and dysphagia was observed in all patients. The evaluation of the fundoplication by the morphologic scores was quite satisfactory. During a median follow-up period of 30 months, 19 patients exhibited no recurrence, and 1 patient had a mild recurrence but was controlled by PPI on demand. Our new procedure is very safe and effective to create a proper Nissen fundoplication. In addition, our preliminary findings highlight the feasibility of precise localization of suture points without the need to measure the circumference of the esophagus and that LNF could be performed without a bougie.


Significance of neoplastic involvement of margins obtained by endoscopic mucosal resection in Barrett's esophagus.
Although EMR has been used for elimination of neoplasia in BE, the significance of positive carcinoma margins and depth of invasion on endoscopic resection pathology has not been assessed using a valid standard. The aim of this study was to assess the accuracy of tumor staging by EMR using esophagectomy as the standard. Medical records of patients, who underwent endoscopic resection for esophageal carcinoma or high-grade dysplasia in BE followed by esophagectomy, were reviewed. Data were abstracted from a prospectively maintained EMR database. Endosonography and endoscopic resection were performed by a single experienced endoscopist. Two experienced GI pathologists interpreted all histological results. Standard statistical tests were used to compare continuous and categorical variables. Twenty-five patients were included in the study. Three patients had mucosal carcinoma and 16 had submucosal carcinoma following endoscopic resection. Surgical pathology staging was consistent with preoperative EMR staging in all patients. No patient with negative mucosal resection margins had residual tumor at the resection site at esophagectomy. In patients with submucosal carcinoma, 8 had residual carcinoma at the EMR site at surgery and 5 patients had metastatic lymphadenopathy. Tumor staging using EMR pathology is accurate when compared with surgical pathology following esophagectomy. Negative margins on EMR pathology correlate with absence of residual disease at the EMR site at esophagectomy. Submucosal carcinoma on EMR specimens was associated with a high prevalence of residual disease at surgery (50%) and metastatic lymphadenopathy (31%).


A manual and an automatic TERS based virus discrimination.
Rapid techniques for virus identification are more relevant today than ever. Conventional virus detection and identification strategies generally rest upon various microbiological methods and genomic approaches, which are not suited for the analysis of single virus particles. In contrast, the highly sensitive spectroscopic technique tip-enhanced Raman spectroscopy (TERS) allows the characterisation of biological nano-structures like virions on a single-particle level. In this study, the feasibility of TERS in combination with chemometrics to discriminate two pathogenic viruses, Varicella-zoster virus (VZV) and Porcine teschovirus (PTV), was investigated. In a first step, chemometric methods transformed the spectral data in such a way that a rapid visual discrimination of the two examined viruses was enabled. In a further step, these methods were utilised to perform an automatic quality rating of the measured spectra. Spectra that passed this test were eventually used to calculate a classification model, through which a successful discrimination of the two viral species based on TERS spectra of single virus particles was also realised with a classification accuracy of 91%.


Different Metabolites in the Roots, Seeds, and Leaves of Acanthopanax senticosus and Their Role in Alleviating Oxidative Stress.
In this study, we examined the metabolites from different parts of Acanthopanax senticosus and their role in alleviating damage caused by oxidative stress. We used UHPLC-QTOF-MS to analyze the chemical components in the root, seed, and leaf extracts of A. senticosus. Two multivariate statistical analysis methods-namely, principal component analysis and partial least square discriminant analysis-were used to distinguish the samples obtained from different parts of the plant. Using univariate statistics, 130 different metabolites were screened out. Among these, the relative content of flavonoids and terpenoids was found to be highest in the leaves, the lignin and phenolic acid content was highest in the roots, and the amino acid and phenolic acid levels were highest in seeds. An MTT assay was used to test the anti-H2O2 oxidative damage to PC12 cells in different parts of the sample. Lastly, using Pearson's correlation analysis, various metabolites from different parts of A. senticosus were correlated with their antioxidant effects from the corresponding parts. Fifty-two related different metabolites were found, of which 20 metabolites that were positively correlated to oxidative stress were present at a relatively higher level in the roots, whereas 32 metabolites that were negatively correlated were present at relatively higher levels in the seeds and leaves. The results of this study reveal the distribution characteristics and the antioxidant activity of different metabolites of A. senticosus and provide a reference for the rational development of its medicinal parts.


Acupuncture effect and central autonomic regulation.
Acupuncture is a therapeutic technique and part of traditional Chinese medicine (TCM). Acupuncture has clinical efficacy on various autonomic nerve-related disorders, such as cardiovascular diseases, epilepsy, anxiety and nervousness, circadian rhythm disorders, polycystic ovary syndrome (PCOS) and subfertility. An increasing number of studies have demonstrated that acupuncture can control autonomic nerve system (ANS) functions including blood pressure, pupil size, skin conductance, skin temperature, muscle sympathetic nerve activities, heart rate and/or pulse rate, and heart rate variability. Emerging evidence indicates that acupuncture treatment not only activates distinct brain regions in different kinds of diseases caused by imbalance between the sympathetic and parasympathetic activities, but also modulates adaptive neurotransmitter in related brain regions to alleviate autonomic response. This review focused on the central mechanism of acupuncture in modulating various autonomic responses, which might provide neurobiological foundations for acupuncture effects.


Noosa, 2 years later… a critical analysis of recent literature.
Since the second World Congress on the Abdominal Compartment Syndrome (WCACS) in Noosa 2 years ago, interest and publications on intra-abdominal hypertension (IAH) and ACS have increased exponentially. This paper aimed to critically review recent publications and put this new data into the context of already acquired knowledge concerning IAH/ACS. A Medline and PubMed search was performed from January 2005 up to now using "intra-abdominal pressure (IAP)", "intra-abdominal hypertension (IAH)", "abdominal compartment syndrome (ACS)" and "decompressive laparotomy" as search items. Although consensus definitions of IAH/ACS have been formulated recently, data on awareness are still disconcerting. Several groups refined current IAP measurement techniques and tested new direct IAP measurement devices for use in selected subpopulations. A series of recent publications identified specific patient subpopulations in IAH/ACS, like patients with burns or severe acute pancreatitis, with their specific pathophysiology and therapy. Although many studies already assessed the effect of elevated IAP on regional and micro-circulatory organ perfusion, a number of new publications attempted to unravel the link between elevated IAP and more "downstream" organ function or histology. Finally, therapy for IAH/ACS still reveals more questions than it answers. Global resuscitation does not necessarily equate with organ resuscitation. In fact, fluid-resuscitation may even induce IAH/ACS. After publication of consensus guidelines on IAH/ACS, there is an urgent need for human intervention studies and, in parallel, clinically relevant animal models. Given moderately low incidence of ACS and the complex and interrelated pathologies of the critically ill patient with IAH/ACS, large animal models of pathology-induced IAH/ACS might create the opportunity to gain clinically relevant knowledge on the treatment of IAH/ACS.


In Vivo RNAi Screening Identifies MDA5 as a Significant Contributor to the Cellular Defense against Influenza A Virus.
Responding to an influenza A virus (IAV) infection demands an effective intrinsic cellular defense strategy to slow replication. To identify contributing host factors to this defense, we exploited the host microRNA pathway to perform an in vivo RNAi screen. To this end, IAV, lacking a functional NS1 antagonist, was engineered to encode individual siRNAs against antiviral host genes in an effort to rescue attenuation. This screening platform resulted in the enrichment of strains targeting virus-activated transcription factors, specific antiviral effectors, and intracellular pattern recognition receptors (PRRs). Interestingly, in addition to RIG-I, the PRR for IAV, a virus with the capacity to silence MDA5 also emerged as a dominant strain in wild-type, but not in MDA5-deficient mice. Transcriptional profiling of infected knockout cells confirmed RIG-I to be the primary PRR for IAV but implicated MDA5 as a significant contributor to the cellular defense against influenza A virus.


Are patients' preferences for information and participation in medical decision-making being met? Interview study with lung cancer patients.
We examined the degree to which newly diagnosed patients with advanced lung cancer wanted to be informed and involved in medical decision-making, and whether the patients felt their preferences were met. Patients from 13 hospitals in Flanders were interviewed with a standard questionnaire. A total of 128 patients (68%) participated. Of the patients who wanted to be informed about life expectancy, half (53%) reported they were informed, and of those who wanted to be informed about palliative care and end-of-life decisions, 25% and 31% said they were informed, respectively. With regard to participation in medical decision-making (in general, about treatment, transfer or end-of-life), patients who preferred the doctor to make decisions or those who preferred to make the decision themselves often achieved this (in their perception), while patients who wanted an in-between position with some involvement, often did not. To conclude, preferences of patients with lung cancer for information concerning delicate topics and for shared decision-making with the physician were not well met.


Registries of cleft lip/palate cases between 2004 and 2010 in Denizli, Turkey.
Oral clefts are one of the most common birth defects in humans. However, few population-based studies of these defects have been carried out in Turkey. Our objective was to determine the registries of cases of cleft lip and palate. All cases of cleft lip and palate referred to central state hospitals in Denizli between January 2000 and May 2010 were investigated retrospectively. Anomalies were determined and classified according to the ICD-10 coding system. A total of 194 cases were identified consisting of 92 females (47.4%), 100 males (51.6%), and 2 subjects of undetermined gender (1%) with an age range of 1 to 65 years. Among the 194 cases, 127 subjects (65.5%) had isolated cleft palate, including 63 females and 64 males; 42 (21.6%) subjects had cleft lip, including 17 females and 25 males; and 25 subjects (12.9%) had cleft lip and palate, including 12 females and 13 males. Studies of oral cleft prevalence are insufficient in Turkey owing to the incompleteness of registries, and the chromosome analysis rate has reached a reasonable level only in recent years.


Combined use of conventional smear and liquid-based preparation versus conventional smear for thyroid fine-needle aspiration.
The purpose of the study was to compare the diagnostic utility of the combined conventional smear (CS) and liquid-based preparation (LBP) compared to CS with respect to the non-diagnostic rate, the atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) rate, and the diagnostic performances for malignancy. This retrospective study was approved by the Institutional Review Board, and the need to obtain informed consent was waived. In our institution, thyroid FNAs were processed with CS before October 2012, and LBP has been used in combination with CS after October 2012. On-site evaluation for the adequacy of CS was not performed. This study included nodules 5 mm or larger with FNAs performed by faculties: 811 nodules in 773 patients for CS, and 926 nodules in 894 patients for combined CS and LBP. Nodules with surgery or either benign or malignancy cytology on initial or repeat FNA were regarded to have the reference standards needed to calculate diagnostic performances. The proportion of Bethesda categories and diagnostic performances were compared between the two groups with z test. The non-diagnostic rate, the AUS or FLUS rate, and the diagnostic performances for malignancy were similar (All P > 0.05). The follicular neoplasm (FN) or suspicious for FN rate decreased from 1.2 to 0.3 % (P = 0.034). The benign rate increased from 51.4 to 57.0 % (P = 0.019). Combined CS and LBP decreased FN or suspicious for FN diagnoses, and increased benign diagnoses compared to CS with comparable non-diagnostic rates and AUS or FLUS rates, and comparable diagnostic performances.


The breadth of memory search.
The recall of previously studied items is widely believed to incorporate a search of a markedly constrained set of possibilities, and the present study examines whether this set of items typically includes unstudied semantic associates of the study items. In an episodic task, participants recalled a previously studied list of eight exemplars drawn from a small or large category, and, in a semantic task, participants generated exemplars from these categories. Category size affected the time course of recall in the semantic task but not in the episodic task. This empirical dissociation between episodic and semantic memory is consistent with the view that episodic memory search efficiently excludes unstudied semantic associates of the study items and is instead constrained to those items sharing the temporal and spatial attributes of the episode.


Self-reported side-effects of antihypertensive drugs: an epidemiological study on prevalence and impact on health-state utility.
The aim in this study was to assess the frequency and type of self-reported side-effects among hypertensives in a general population, and to estimate the relationship between drug use and side-effects and health utility using the Rating Scale (RS) method. The study is based on a postal questionnaire that was sent to a random sample of 8000 inhabitants aged 20-84 years (response rate 68%) in Uppsala County, Sweden, in 1995. The results showed that nearly 20% of the users of antihypertensive drugs reported side-effects. Men and women reported side-effects to nearly the same extent. In the linear regression analyses, those with hypertension, with or without medication, rated lower health utilities (-6.0 and -7.1 respectively) than did normotensives after controlling for age and sex. The lowest value, -8.7, was found among drug users who experienced side-effects. Side-effects causing impotence and emotional distress, i.e. insomnia, tiredness and depression had the strongest negative impact on health utility. To conclude, the study showed that side-effects among hypertensives are common. Both the disease and the drug treatment adversely affect the patient's well-being. However, drug treatment was of less importance than that found in prior studies. The findings here stress that side-effects should be taken into greater consideration when evaluating drug treatment.


Attentional orienting towards smoking-related stimuli.
According to incentive salience theory, conditioned stimuli (CS+) associated with drug reinforcement acquire the capacity to elicit a conditioned attentional orienting response, which controls drug-seeking and drug-taking behaviour. We sought evidence for this proposal by measuring visual attentional orienting towards smoking pictures presented briefly in the periphery of the visual field, versus control pictures likewise presented, in smokers versus non-smokers. In each trial, smokers and non-smokers responded manually to a dot probe stimulus that appeared in a location previously occupied by either a smoking picture or a control picture. Attentional bias scores were calculated by subtracting the median reaction time (RT) in the former condition from the median RT in the latter condition. In two experiments, light-smokers (smokers of fewer than 20 cigarettes/day) produced a mean bias score that was significantly greater than that of heavy-smokers (smokers of 20 or more cigarettes/day) and non-smokers. In addition, when smokers from the two experiments were pooled, a significant quadratic relationship was found between cigarettes/day and the attentional bias for the smoking stimuli. These findings are consistent with incentive salience theories and dual-process theories of addiction.


Right Heart Failure in Different Left Ventricular Assist Devices: Single-Center Experience.
Background: Right heart failure (RHF) following left ventricular assist device (LVAD) implantation increases morbidity and mortality for those who develop this complication. The purpose of this study was to assess the differences in incidence of RHF and outcomes between 2 types of continuous-flow LVADs at a single center. Methods: From January 2012 through June 2016, 184 patients were implanted with a continuous-flow LVAD (161 patients with the HeartMate II and 23 patients with the HeartWare device) either as a bridge to transplant or as destination therapy. Preoperative demographics, medical history, laboratory values, hemodynamics, and device type were analyzed to determine the variables associated with RHF and mortality. Results: Preoperative variables between the 2 groups were homogeneous. Most patients were Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (92%) and New York Heart Association class IV (81%). More patients in the HeartMate II group had the indication of destination therapy (54% vs 30%), while more patients in the HeartWare group were implanted as bridge to transplant (70% vs 46%). RHF occurred in 57% of HeartWare patients compared to 16% of patients who received the HeartMate II (P=0.0001). After propensity score analysis, patients receiving the HeartWare device had increased odds for RHF (P=0.0013) and renal failure requiring dialysis (P=0.0135). The HeartMate II patient survival rate exceeded the HeartWare patient survival rate at 1 year (82.1% vs 67.2%) and at 2 years (74.6% vs 61.7%), but this difference did not achieve statistical significance (log-rank P=0.087). Conclusion: These results indicate that device type may affect RHF incidence and mortality. Studies at other centers are needed to replicate these findings.


Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence, clinical settings, and visual acuity outcomes after treatment.
To report the incidence, clinical settings, and visual acuity outcomes of acute-onset endophthalmitis after cataract surgery. Retrospective, observational case series. Annual cataract surgery statistics were determined by review of electronic surgical records. The clinical and microbiologic records were reviewed of all patients with clinically diagnosed endophthalmitis within 6 weeks after cataract surgery at a single university-affiliated hospital between January 2000 and November 2004. main outcome measures: Operative technique, intraoperative complications, and visual acuity. The incidence of acute-onset endophthalmitis after cataract surgery was 0.04% (7/15,920) for cataract surgeries of all methods, 0.05% (6/11,462) for cataract surgery by clear cornea phacoemulsification, and 0.02% (1/4,458) for cataract surgery by methods other than clear cornea phacoemulsification (P = .681, Fisher's exact test). Six of seven (86%) cases occurred in the right eye, and all cases were performed by right-handed surgeons through temporal incisions. Five of seven (71%) patients had relative immune compromise. Four of seven (57%) patients had an intraoperative complication: vitreous loss in three patients and iris prolapse in one patient. Two patients had topical placement of lidocaine 2% gel before povidone-iodine preparation. The visual acuity at final follow up was 20/25 or better in four patients and count fingers or worse in three patients. The incidence of acute-onset endophthalmitis after temporal clear cornea incision phacoemulsification is low (0.05%). Potential risk factors for endophthalmitis may include intraoperative complications, relative immune compromise, application of lidocaine 2% gel before povidone-iodine preparation, and inferior incision location.


In case of obesity, longevity-related mechanisms lead to anti-inflammation.
The exact mechanisms which contribute to longevity have not been figured out yet. Our aim was to find out a common way for prompting longevity by bringing together the well-known applications such as food restriction, exercise, and probiotic supplementing in an experimental obesity model. Experimental obesity was promoted in a total of 32 young (2 months old) and 32 aged (16 months old) male Wistar albino rats through 8-week cafeteria diet (salami, chocolate, chips, and biscuits). Old and young animals were divided into groups each consisting of eight animals and also divided into four subgroups as obese control, obese food restriction, obese probiotic-fed and obese exercise groups. Probiotic group diet contained 0.05 %w/total diet inactive and lyophilized Lactobacillus casei str. Shirota. The exercise group was subjected to treadmill running 1 h/day, at 21 m/min and at an uphill incline of 15 % for 5 days a week. Food restriction group was formed by giving 40 % less food than the others. The control group was fed regular pellet feed ad libitum. This program was continued for 16 weeks. Blood samples from all the groups were analyzed for fasting glucose, insulin, IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3), interleukin (IL)-6, IL-12, malondialdehyde (MDA), fT3, TT3, fT4, TT4, and liver tissue MDA levels were measured. All applications showed anti-inflammatory effects through the observed changes in the levels of IGFBP-3, IL-6, and IL-12 in the young and old obese rats. While the interventions normally contribute to longevity by recruiting different action mechanisms, anti-inflammatory effect is the only mode of action for all the applications in the obesity model.


The Role of Bioactive Compounds from Dietary Spices in the Management of Metabolic Syndrome: An Overview.
Metabolic syndrome (MetS) is a combination of physiologically dysregulated parameters that can include elevated fasting blood glucose, high blood pressure, central obesity, increased triglyceride levels, insulin resistance, diabetes, elevated low density lipoprotein levels, and reduced high density lipoprotein levels in the blood. Effective clinical management of MetS is critical as it is strongly associated with long lasting and fatal complications in patients. Alongside standard care of lifestyle changes and medication, dietary supplements derived from herbal resources could be an alternative therapeutic strategy that is safe, efficient, culturally acceptable, and has few side effects. Of the dietary supplements, spicy foods have always been considered a great source of functional bioactive compounds. Herbal therapy is broadly used in many countries as a treatment or as a preventive measure in the management of MetS risk factors, including blood glucose, blood pressure, and blood lipid levels. Herein, an attempt is made to evaluate the recent studies in the management of MetS with herbal alternatives, and to explore the possibility of their use as therapeutic treatments or supplements.


Activation of the Listeria monocytogenes Virulence Program by a Reducing Environment.
Upon entry into the host cell cytosol, the facultative intracellular pathogen Listeria monocytogenes coordinates the expression of numerous essential virulence factors by allosteric binding of glutathione (GSH) to the Crp-Fnr family transcriptional regulator PrfA. Here, we report that robust virulence gene expression can be recapitulated by growing bacteria in a synthetic medium containing GSH or other chemical reducing agents. Bacteria grown under these conditions were 45-fold more virulent in an acute murine infection model and conferred greater immunity to a subsequent lethal challenge than bacteria grown in conventional media. During cultivation in vitro, PrfA activation was completely dependent on the intracellular levels of GSH, as a glutathione synthase mutant (ΔgshF) was activated by exogenous GSH but not reducing agents. PrfA activation was repressed in a synthetic medium supplemented with oligopeptides, but the repression was relieved by stimulation of the stringent response. These data suggest that cytosolic L. monocytogenes interprets a combination of metabolic and redox cues as a signal to initiate robust virulence gene expression in vivoIMPORTANCE Intracellular pathogens are responsible for much of the worldwide morbidity and mortality from infectious diseases. These pathogens have evolved various strategies to proliferate within individual cells of the host and avoid the host immune response. Through cellular invasion or the use of specialized secretion machinery, all intracellular pathogens must access the host cell cytosol to establish their replicative niches. Determining how these pathogens sense and respond to the intracellular compartment to establish a successful infection is critical to our basic understanding of the pathogenesis of each organism and for the rational design of therapeutic interventions. Listeria monocytogenes is a model intracellular pathogen with robust in vitro and in vivo infection models. Studies of the host-sensing and downstream signaling mechanisms evolved by L. monocytogenes often describe themes of pathogenesis that are broadly applicable to less tractable pathogens. Here, we describe how bacteria use external redox states as a cue to activate virulence.


Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells.
Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.


Coronary heart disease mortality and adjuvant tamoxifen therapy.
Data from randomized clinical trials in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease. In view of these findings, we examined mortality from coronary heart disease among patients with early stage breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy. Deaths occurring among women who were randomly assigned to 5 years of either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to determine the cause. Three categories of heart disease-related death were defined: 1) death from a definite fatal myocardial infarction, 2) death from definite fatal coronary heart disease/possible myocardial infarction, and 3) death from possible fatal coronary heart disease. Comparisons of the findings by treatment group were made on the basis of average annual hazard (i.e., death) rates and the corresponding relative hazard of death. The average annual death rate from coronary heart disease was lower for patients who received tamoxifen than for patients who received placebo, but the difference was not statistically significant. There were eight definite heart-related deaths (i.e., definite fatal myocardial infarction or definite fatal coronary heart disease/possible myocardial infarction) among the patients who received tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were 12 definite heart-related deaths among the patients who received placebo, yielding an average annual rate of 0.94 per 1000. The corresponding relative hazard of death from definite fatal heart disease (tamoxifen versus placebo) was 0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group and 10 deaths in the placebo group were classified as possible cases of fatal coronary heart disease. When these cases and the definite cases were considered together, the average annual death rate for the patients who received tamoxifen was 1.48 per 1000, and the rate for the patients who received placebo was 1.73 per 1000. The corresponding relative hazard of death was 0.85 (95% confidence interval = 0.46-1.58). The findings from the B-14 trial are consistent with the findings from the Scottish and the Swedish trials, suggesting that tamoxifen treatment reduces coronary heart disease among patients with breast cancer. Continued follow-up of the patients in these trials and in ongoing prevention trials is needed to accumulate enough data so that reliable conclusions can be drawn about the benefits of tamoxifen in preventing heart disease.


Surgical Outcome of Patients With Supratentorial Meningiomas Aged 80 Years or Older-Retrospective International Multicenter Study.
Demographic changes will lead to an increase in old patients, a population with significant risk of postoperative morbidity and mortality, requiring neurosurgery for meningiomas. This multicenter study aims to report neurofunctional status after resection of patients with supratentorial meningioma aged 80 years or older, to identify factors associated with outcome, and to validate a previously proposed decision support tool. Neurofunctional status was assessed by the Karnofsky Performance Scale (KPS). Patients were categorized in poor (KPS ≤40), intermediate (KPS 50-70), and good (KPS ≥80) preoperative subgroups. Volumetric analyses of tumor and peritumoral brain edema (PTBE) were performed; volumes were scored as small (<10 cm3), medium (10-50 cm3), and large (>50 cm3). The study population consisted of 262 patients, and the median age at surgery was 83.0 years. The median preoperative KPS was 70; 117 (44.7%) patients were allotted to the good, 113 (43.1%) to the intermediate, and 32 (12.2%) to the poor subgroup. The median tumor and PTBE volumes were 30.2 cm3 and 27.3 cm3; large PTBE volume correlated with poor preoperative KPS status (P = .008). The 90-day and 1-year mortality rates were 9.0% and 13.2%, respectively. Within the first postoperative year, 101 (38.5%) patients improved, 87 (33.2%) were unchanged, and 74 (28.2%) were functionally worse (including deaths). Each year increase of age associated with 44% (23%-70%) increased risk of 90-day and 1-year mortality. In total, 111 (42.4%) patients suffered from surgery-associated complications. Maximum tumor diameter ≥5 cm (odds ratio 1.87 [1.12-3.13]) and large tumor volume (odds ratio 2.35 [1.01-5.50]) associated with increased risk of complications. Among patients with poor preoperative status and large PTBE, most (58.3%) benefited from surgery. Patients with poor preoperative neurofunctional status and large PTBE most often showed postoperative improvements. The decision support tool may be of help in identifying cases that most likely benefit from surgery.


Morphometrics of domestic Panstrongylus rufotuberculatus in Bolivia.
The trend to domesticity in Triatominae may represent a transitionary phase, towards increasing vectorial importance in the transmission of Chagas disease to humans, and requires sustained entomological surveillance. Although generally considered a sylvatic species, Panstrongylus rufotuberculatus has been recently captured inside human dwellings in the provinces of Nor Yungas and Muñecas in the Department of La Paz, Bolivia, providing evidence of this species' ability to colonise domestic habitats. The results of previous research on domestic and sylvatic specimens of other species of Triatominae indicate that morphometrics could be used to monitor this adaptive process. The most likely cause of differences seen in the size and shape of bugs from domestic colonies of P. rufotuberculatus from two neighbouring villages in Bolivia is probably genetic drift rather than environmental influences. Comparison with allopatric sylvatic specimens, including the holotype of P. rufatuberculatus, showed a general reduction in size from sylvatic to domestic specimens.


Sources and transport of contaminants of emerging concern: A two-year study of occurrence and spatiotemporal variation in a mixed land use watershed.
The occurrence and spatiotemporal variation of 26 contaminants of emerging concern (CECs) were evaluated in 68 water samples in 2011-2012 in the Zumbro River watershed, Minnesota, U.S.A. Samples were collected across a range of seasonal/hydrological conditions from four stream sites that varied in associated land use and presence of an upstream wastewater treatment plant (WWTP). Selected CECs included human/veterinary pharmaceuticals, personal care products, pesticides, phytoestrogens, and commercial/industrial compounds. Detection frequencies and concentrations varied, with atrazine, metolachlor, acetaminophen, caffeine, DEET, and trimethoprim detected in more than 70% of samples, acetochlor, mecoprop, carbamazepine, and daidzein detected in 30%-50% of samples, and 4-nonylphenol, cotinine, sulfamethoxazole, erythromycin, tylosin, and carbaryl detected in 10%-30% of samples. The remaining target CECs were not detected in water samples. Three land use-associated trends were observed for the detected CECs. Carbamazepine, 4-nonylphenol, erythromycin, sulfamethoxazole, tylosin, and carbaryl profiles were WWTP-dominated, as demonstrated by more consistent loading and significantly greater concentrations downstream of the WWTP and during low-flow seasons. In contrast, acetaminophen, trimethoprim, DEET, caffeine, cotinine, and mecoprop patterns demonstrated both seasonally-variable non-WWTP-associated and continual WWTP-associated influences. Surface water studies of CECs often target areas near WWTPs. This study suggests that several CECs often characterized as effluent-associated have additional important sources such as septic systems or land-applied biosolids. Finally, agricultural herbicide (atrazine, acetochlor, and metolachlor) profiles were strongly influenced by agricultural land use and seasonal application-runoff, evident by significantly greater concentrations and loadings at upstream sites and in early summer when application and precipitation rates are greatest. Our results indicate that CEC monitoring studies should consider a range of land uses, seasonality, and transport pathways in relation to concentrations and loadings. This knowledge can augment CEC monitoring programs to result in more accurate source, occurrence, and ecological risk characterizations, more precisely targeted mitigation initiatives, and ultimately, enhanced environmental decision-making.


Suicidal adverse events in pediatric randomized, controlled clinical trials of antidepressant drugs are associated with active drug treatment: a meta-analysis.
The aim of this study was to compare the incidence of suicidal ideation and behaviors observed with antidepressant drug treatment to the incidence with placebo, in randomized, controlled pediatric clinical trials. Manufacturers of nine antidepressant drugs identified suicidal adverse events in randomized, placebo-controlled, pediatric clinical trials that they had sponsored. Events were found with an electronic search for adverse event descriptions, including key words suggesting suicidal ideation or self-injury, along with a manual review of all adverse events meeting the standard regulatory definition for seriousness. Incidence rate data for these events supplied by the manufacturers were combined across trials to yield Mantel-Haenszel combined risk estimates. Data from 22 randomized, short-term, placebo-controlled, pediatric trials in various indications, involving nine different antidepressant drugs, were available for analysis. A total of 2298 pediatric subjects were exposed to active drug, and 1952 to placebo. Seventy eight (78) serious suicidal adverse events occurred in these trials (54 with active drug and 24 with placebo); there were no completed suicides. The combined incidence rate ratio across all trials for serious suicidal adverse events was 1.89 (95% Confidence Interval, 1.18-3.04). In short-term, placebo-controlled, pediatric studies of antidepressants, active drug treatment was associated with a rate of serious suicidal events almost twice that of placebo.


Association of Short Interpregnancy Interval With Pregnancy Outcomes According to Maternal Age.
Interpregnancy intervals shorter than 18 months are associated with higher risks of adverse pregnancy outcomes. It is currently unknown whether short intervals are associated with increased risks among older women to the same extent as among younger women. To evaluate whether the association between short interpregnancy (delivery to conception) interval and adverse pregnancy outcomes is modified by maternal age. A population-based cohort study conducted in British Columbia, Canada, evaluated women with 2 or more singleton pregnancies from 2004 to 2014 with the first (index) pregnancy resulting in a live birth. Data analysis was performed from January 1 to July 20, 2018. Risks of maternal mortality or severe morbidity (eg, mechanical ventilation, blood transfusion >3 U, intensive care unit admission, organ failure, death), small-for-gestational age (<10th birthweight percentile for gestational age and sex), fetal and infant composite outcome (stillbirth, infant death, <third birthweight percentile for gestational age and sex, delivery <28 weeks), and spontaneous and indicated preterm delivery. Risks of each outcome for 3- to 24-month interpregnancy intervals were estimated, according to maternal age at index birth (20-34 and ≥35 years). Adjusted risk ratios (aRRs) comparing predicted risks at 3-, 6-, 9-, and 12-month intervals with risks at 18-month intervals for each age group were calculated. The potential role of other factors explaining any differences (unmeasured confounding) was examined in several sensitivity analyses. Among 148 544 pregnancies, maternal mortality or severe morbidity risks were increased at 6-month compared with 18-month interpregnancy intervals for women aged 35 years or older (0.62% at 6 months vs 0.26% at 18 months; aRR, 2.39; 95% CI, 2.03-2.80), but not for women aged 20 to 34 years (0.23% at 6 months vs 0.25% at 18 months; aRR, 0.92; 95% CI, 0.83-1.02). Increased adverse fetal and infant outcome risks were more pronounced for women aged 20 to 34 years (2.0% at 6 months vs 1.4% at 18 months; aRR, 1.42; 95% CI, 1.36-1.47) than women 35 years or older (2.1% at 6 months vs 1.8% at 18 months; aRR, 1.15; 95% CI, 1.01-1.31). Risks of spontaneous preterm delivery at 6-month interpregnancy intervals were increased for women 20 to 34 years old (5.3% at 6 months vs 3.2% at 18 months; aRR, 1.65; 95% CI, 1.62-1.68) and to a lesser extent for women 35 years or older (5.0% at 6 months vs 3.6% at 18 months; aRR, 1.40; 95% CI, 1.31-1.49). Modest increases in risks of small-for-gestational age and indicated preterm delivery at short intervals did not vary meaningfully by maternal age. Sensitivity analyses suggested that observed associations were not fully explained by unmeasured confounding. The findings of this study suggest that short interpregnancy intervals are associated with increased risks for adverse pregnancy outcomes for women of all ages.


A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.
Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.


The continued evaluation of the effects of chemotherapy in patients with advanced carcinoma of the prostate.
The response and duration of survival were evaluated for patients with stage D relapsing prostatic cancer who were randomized to cyclophosphamide (cytoxan), 5-fluorouracil (5-FU) or standard therapy, or to subsequent chemotherapies. The chemotherapies on initial randomization were superior to the standard therapy in the number of responders and duration of response. Survival was longer for responders (stable or partial regression) on chemotherapy by comparison to responders (stable only) on standard therapy. The survival for patients receiving initial and crossover chemotherapy was significantly improved for patients who responded to therapy. Chemotherapy of advanced relapsing stage D prostatic cancer is more beneficially treated by specific chemotherapy as shown in this randomized study.


Alprazolam treatment for panic disorders.
Office records of 27 private patients who were treated with alprazolam for panic disorders were evaluated by a second psychiatrist. Alprazolam treatment led to a complete remission of panic attacks in 85% of the patients; panics ceased within an average of 6 days, at a mean dose of 2.2 mg/day. In addition, alprazolam was found to bring about a complete absence of phobic avoidance behavior in 21 of the 23 agoraphobic patients in the group. This is the first study to demonstrate the efficacy of medication alone as a treatment for agoraphobia.


Research progress of intra-aortic balloon counterpulsation in the treatment of acute myocardial infarction with cardiogenic shock: A review.
The mortality rate of patients with acute myocardial infarction complicated with cardiogenic shock is very high, and in recent years, intra-aortic balloon counterpulsation has been used more and more. It plays a very important role in improving left ventricular ejection, increasing coronary artery perfusion pressure and reducing myocardial oxygen consumption. This article reviews the development of intra-aortic balloon counterpulsation in the treatment of acute myocardial infarction with cardiogenic shock in recent years.


Phonological disorders I: a diagnostic classification system.
Data are presented to support the validity and utility of a diagnostic classification system for persons with phonological disorders. Rationale for the classification system is developed from current reviews of issues and concepts in phonology and classification systems. The system proceeds from a worksheet for reduction of phonological and other assessment data, through five hierarchical levels of classification entries. The system will accommodate lower-level elaboration of etiological subgrouping, pending appropriate research. A retrospective classification study of 43 children with delayed speech is described. Procedural details relating classification procedures to two companion papers (Shriberg & Kwiatkowski, 1982a, 1982b) are provided.


Metabolic and antiproliferative consequences of activated polyamine catabolism in LNCaP prostate carcinoma cells.
Depletion of intracellular polyamine pools invariably inhibits cell growth. Although this is usually accomplished by inhibiting polyamine biosynthesis, we reasoned that this might be more effectively achieved by activation of polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase (SSAT); a strategy first validated in MCF-7 breast carcinoma cells. We now examine the possibility that, due to unique aspects of polyamine homeostasis in the prostate gland, tumor cells derived from it may be particularly sensitive to activated polyamine catabolism. Thus, SSAT was conditionally overexpressed in LNCaP prostate carcinoma cells via a tetracycline-regulatable (Tet-off) system. Tetracycline removal resulted in a rapid approximately 10-fold increase in SSAT mRNA and an increase of approximately 20-fold in enzyme activity. SSAT products N(1)-acetylspermidine, N(1)-acetylspermine, and N(1),N(12)-diacetylspermine accumulated intracellularly and extracellularly. SSAT induction also led to a growth inhibition that was not accompanied by polyamine pool depletion as it was in MCF-7 cells. Rather, intracellular spermidine and spermine pools were maintained at or above control levels by a robust compensatory increase in ornithine decarboxylase and S-adenosylmethionine decarboxylase activities. This, in turn, gave rise to a high rate of metabolic flux through both the biosynthetic and catabolic arms of polyamine metabolism. Treatment with the biosynthesis inhibitor alpha-difluoromethylornithine during tetracycline removal interrupted flux and prevented growth inhibition. Thus, flux-induced growth inhibition appears to derive from overaccumulation of metabolic products and/or from depletion of metabolic precursors. Metabolic effects that were not excluded as possible contributing factors include high levels of putrescine and acetylated polyamines, a 50% reduction in S-adenosylmethionine, and a 45% decline in the SSAT cofactor acetyl-CoA. Overall, the study demonstrates that activation of polyamine catabolism in LNCaP cells elicits a compensatory increase in polyamine biosynthesis and downstream metabolic events that culminate in growth inhibition.


A 3D Resolution Measure for Optical Microscopy.
An information-theoretic three-dimensional (3D) resolution measure for the optical microscope is introduced. Based on the Cramer-Rao inequality, this resolution measure specifies a lower bound on the accuracy with which a given distance separating two objects in 3D space can be estimated from the acquired image. Useful in many applications, accurate determination of the distance of separation can, for example, help to characterize the interaction that occurs between two closely spaced biomolecules in a biological cell. In addition to presenting the underlying theory, we show that the resolution measure predicts that, by detecting a sufficient number of photons from an object pair, arbitrarily small distances of separation can be estimated with prespecified accuracy. Furthermore, we illustrate its dependence on properties such as the object pair's 3D spatial orientation. With estimations on simulated images, we show that the maximum likelihood estimator is capable of attaining the accuracy predicted by the resolution measure.


Mechanism of interleukin-1β induced-increase in mouse intestinal permeability in vivo.
Interleukin-1β (IL-1β) has been shown to play an essential role in mediating intestinal inflammation of Crohn's disease and other inflammatory conditions of the gut. Previous studies from our laboratory have shown that IL-1β causes an increase in intestinal tight-junction permeability in Caco-2 monolayers in vitro. However, the IL-1β effect on the intestinal epithelial barrier in vivo remains unclear. the major aims of this study were to examine the effect of IL-1β on mouse intestinal epithelial barrier in vivo and to delineate the mechanisms involved using an in vivo model system consisting of a recycling perfusion of mouse small intestine. Intraperitonial injection of IL-1β at varying doses (0-10 μg) caused a concentration-dependent increase in mouse intestinal permeability to the paracellular marker dextran (10 KD), and the maximal increase in dextran flux occurred at IL-1β dose of 5 μg. IL-1β treatment caused an increase in myosin light-chain kinase (MLCK) mRNA and protein expression in the small intestinal tissue starting at 24 h, which continued up to 72 h. Additionally, IL-1β did not cause an increase in intestinal permeability in MLCK-deficient mice (C57BL/6 MLCK(-/-)). MLCK inhibitor ML-7 (2 mg/kg body weight) also inhibited the IL-1β-induced increase in small intestinal permeability. The IL-1β-induced increase in mouse intestinal permeability was associated with an increase in NF-κB activation. The intestinal tissue-specific silencing of NF-κB p65 inhibited the IL-1β-induced increase in intestinal permeability and increase in MLCK expression. These data show for the first time that IL-1β causes an increase in mouse intestinal permeability in vivo. These data suggested that the mechanism of IL-1β-induced increase in mouse intestinal permeability in vivo involved NF-κB p65-induced activation of the mouse enterocyte MLCK gene.


Discovering symptom patterns of COVID-19 patients using association rule mining.
The COVID-19 pandemic is a significant public health crisis that is hitting hard on people's health, well-being, and freedom of movement, and affecting the global economy. Scientists worldwide are competing to develop therapeutics and vaccines; currently, three drugs and two vaccine candidates have been given emergency authorization use. However, there are still questions of efficacy with regard to specific subgroups of patients and the vaccine's scalability to the general public. Under such circumstances, understanding COVID-19 symptoms is vital in initial triage; it is crucial to distinguish the severity of cases for effective management and treatment. This study aimed to discover symptom patterns and overall symptom rules, including rules disaggregated by age, sex, chronic condition, and mortality status, among COVID-19 patients. This study was a retrospective analysis of COVID-19 patient data made available online by the Wolfram Data Repository through May 27, 2020. We applied a widely used rule-based machine learning technique called association rule mining to identify frequent symptoms and define patterns in the rules discovered. In total, 1,560 patients with COVID-19 were included in the study, with a median age of 52 years. The most frequently occurring symptom was fever (67%), followed by cough (37%), malaise/body soreness (11%), pneumonia (11%), and sore throat (8%). Myocardial infarction, heart failure, and renal disease were present in less than 1% of patients. The top ten significant symptom rules (out of 71 generated) showed cough, septic shock, and respiratory distress syndrome as frequent consequents. If a patient had a breathing problem and sputum production, then, there was higher confidence of that patient having a cough; if cardiac disease, renal disease, or pneumonia was present, then there was a higher confidence of septic shock or respiratory distress syndrome. Symptom rules differed between younger and older patients and between male and female patients. Patients who had chronic conditions or died of COVID-19 had more severe symptom rules than those patients who did not have chronic conditions or survived of COVID-19. Concerning chronic condition rules among 147 patients, if a patient had diabetes, prerenal azotemia, and coronary bypass surgery, there was a certainty of hypertension. The most frequently reported symptoms in patients with COVID-19 were fever, cough, pneumonia, and sore throat; while 1% had severe symptoms, such as septic shock, respiratory distress syndrome, and respiratory failure. Symptom rules differed by age and sex. Patients with chronic disease and patients who died of COVID-19 had severe symptom rules more specifically, cardiovascular-related symptoms accompanied by pneumonia, fever, and cough as consequents.


[Ruptured thoracic aorta aneurysm: endovascular treatment].
In 1991, a technique to exclude aortic aneurysms from circulation inserting an endoluminal graft through the femoral artery, was described. This procedure, usually used for elective abdominal aneurysms, can also be used in the thoracic aorta. We report a 41 years old male with a Marfan syndrome, presenting with a descending aorta aneurysm that ruptured to the mediastinum and pleural cavity. He was compensated hemodynamically and an endovascular stent-graft was deployed at the ruptured zone, through the femoral artery. The postoperative evolution of the patient was uneventful. This technique will allow a less invasive treatment of ruptured aortic aneurysms.


An information-theoretic approach to estimating the composite genetic effects contributing to variation among generation means: Moving beyond the joint-scaling test for line cross analysis.
The pace and direction of evolution in response to selection, drift, and mutation are governed by the genetic architecture that underlies trait variation. Consequently, much of evolutionary theory is predicated on assumptions about whether genes can be considered to act in isolation, or in the context of their genetic background. Evolutionary biologists have disagreed, sometimes heatedly, over which assumptions best describe evolution in nature. Methods for estimating genetic architectures that favor simpler (i.e., additive) models contribute to this debate. Here we address one important source of bias, model selection in line cross analysis (LCA). LCA estimates genetic parameters conditional on the best model chosen from a vast model space using relatively few line means. Current LCA approaches often favor simple models and ignore uncertainty in model choice. To address these issues we introduce Software for Analysis of Genetic Architecture (SAGA), which comprehensively assesses the potential model space, quantifies model selection uncertainty, and uses model weighted averaging to accurately estimate composite genetic effects. Using simulated data and previously published LCA studies, we demonstrate the utility of SAGA to more accurately define the components of complex genetic architectures, and show that traditional approaches have underestimated the importance of epistasis.


Concentrated cultures of Leuconostoc citrovorum.
Two single-strain cultures of Leuconostoc citrovorum were grown in a broth medium with automatic pH control. Culture concentrates were prepared by centrifugally harvesting the cells and resuspending them in 1/50th the original volume in 10% nonfat milk solids. The concentrates were stored in liquid nitrogen until analyzed. The maximum population attainable was approximately equal when cultures were grown at pH 6.0, 6.5, or 7.0 with sodium hydroxide or ammonium hydroxide as the neutralizer. Citrate was required in the growth medium for the cultures to be able to produce diacetyl subsequently in milk. At pH 6.0, the cells reached maximum population and ability to produce diacetyl. Organoleptic analysis by an experienced flavor panel showed a preference for cottage cheese creamed with a creaming mixture prepared with a culture concentrate rather than a normal culture. The culture concentrates maintained their viability and ability to produce diacetyl for at least 30 days when stored in liquid nitrogen.


Alcohol use disorders, consumption patterns, and health-related quality of life of primary care patients.
This study examined the association of alcohol use disorders and consumption patterns with various dimensions of Health-Related Quality of Life (HRQOL) in primary care patients, as measured by the SF-36 Health Survey. A probability sample of 1333 primary care patients completed the Alcohol Use Disorder and Associated Disabilities Interview Schedule to determine the presence of alcohol abuse or dependence disorders, and answered questions about patterns of alcohol consumption. Physical and Mental Health Component Summaries and primary scales of the SF-36 were used as measures of HRQOL. Patients meeting criteria for alcohol dependence scored lower (poorer HRQOL) on the Mental Health Component Summary and each primary scale of the SF-36, whereas no differences were observed for alcohol abusers compared with patients not meeting criteria for a disorder. The association of alcohol dependence with diminished mental health functioning was mediated by its co-occurrence with mood and anxiety disorders. Patients who drank in a Frequent, Low-Quantity pattern generally had better overall HRQOL than patients from other consumption groups. Binge drinkers and Frequent, High-Quantity Drinkers showed markedly lower scores in the areas of Role Functioning and Mental Health. In contrast to recent studies of mental health problems in primary care, alcohol use disorders and consumption patterns seem to have a modest impact on patients' HRQOL. These effects, though, vary by dimension of functioning, the presence of alcohol dependence rather than abuse, and pattern of alcohol consumption. Global measures of HRQOL such as the SF-36 Health Survey may provide important indicators of treatment effectiveness in primary care intervention studies for patients with drinking problems.


Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high-grade B-cell lymphoma (HGBL) and diffuse large B-cell lymphoma (DLBCL): Can we identify different prognostic subgroups?
High-grade B-cell lymphoma (HGBL)/diffuse large B-cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC-R and BCL2-R and/or BCL6-R-samples with MYC-R and BCL2-R (+/- BCL6-R); n = 21, and HGBL/DLBCL with MYC-R and BCL6-R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called "alternative HGBL/DLBCL"-samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) "No alterations" (n = 55). Patients with HGBL/DLBCL-MYC/BCL2 and "alternative" HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the "no alterations" group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC-R and BCL6-R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL-MYC/BCL2. According to immunohistochemistry, "double/triple" expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups.


Genomic Features of Parthenogenetic Animals.
Evolution without sex is predicted to impact genomes in numerous ways. Case studies of individual parthenogenetic animals have reported peculiar genomic features that were suggested to be caused by their mode of reproduction, including high heterozygosity, a high abundance of horizontally acquired genes, a low transposable element load, or the presence of palindromes. We systematically characterized these genomic features in published genomes of 26 parthenogenetic animals representing at least 18 independent transitions to asexuality. Surprisingly, not a single feature was systematically replicated across a majority of these transitions, suggesting that previously reported patterns were lineage-specific rather than illustrating the general consequences of parthenogenesis. We found that only parthenogens of hybrid origin were characterized by high heterozygosity levels. Parthenogens that were not of hybrid origin appeared to be largely homozygous, independent of the cellular mechanism underlying parthenogenesis. Overall, despite the importance of recombination rate variation for the evolution of sexual animal genomes, the genome-wide absence of recombination does not appear to have had the dramatic effects which are expected from classical theoretical models. The reasons for this are probably a combination of lineage-specific patterns, the impact of the origin of parthenogenesis, and a survivorship bias of parthenogenetic lineages.


N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation after electrical cardioversion: a prospective randomized study.
The purpose of the present prospective randomized study was to evaluate the effects of n-3 polyunsaturated fatty acids on recurrence rates of atrial fibrillation (AF) and inflammation after electrical cardioversion. Calculation of the number of patients needed was based on the assumption of 20% and 65% chance of maintaining sinus rhythm with amiodarone and with polyunsaturated fatty acids, respectively. To observe a significant difference with an alpha level of 0.05 and a power of 0.80 it was necessary to include 22 patients in each group. A total of 47 patients were randomized to amiodarone (n=24) and amiodarone plus n-3 polyunsaturated fatty acids (n=23) groups before scheduled electrical cardioversion. The end-point was the recurrence of AF during 12-month follow-up. Effect of n-3 polyunsaturated fatty acids on inflammation was evaluated with high sensitivity C-reactive protein level measurements. Statistical analysis was performed using unpaired Student' t, Mann Whitney U and Chi-square tests. We analyzed the recurrence of AF using the Cox proportional hazards regression model to control for potentially confounding factors. Nine patients in the amiodarone group (37.5%), and 9 patients in the amiodarone plus n-3 polyunsaturated fatty acids group (39.1%) had recurrence of AF during follow-up (p=1). With the Cox proportional model, risk factors for the recurrence of AF were previous electrical cardioversion (HR 10.33, 95% CI 1.74 to 61.10, p=0.01) and high sensitivity C-reactive protein levels (HR 1.07, 95% CI 1.02 to 1.38, p=0.007). High sensitivity C-reactive protein levels at baseline, at day 15 and during AF recurrence were similar between two groups (p > 0.05 for all). N-3 polyunsaturated fatty acids administration does not reduce the recurrence rates of atrial fibrillation and inflammation.