Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict the clinical outcome of patients with advanced nonsmall cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors.
Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein classified in the category of human MUC1 mucin. KL-6 has been reported to serve as a sensitive marker for interstitial pneumonia; however, recent studies have suggested that it can also be used as a tumor marker as its origin shows. To further elucidate the clinicopathological significance of circulating KL-6 in lung cancer, we monitored the circulating KL-6 levels in advanced nonsmall cell lung cancer (NSCLC) patients and analyzed the association between these levels and the clinical outcome of EGFR-TKI treatment. The pretreatment levels of circulating KL-6 were found to be significantly higher in progressive disease (PD) patients than disease-controlled (partial response (PR) and stable disease (SD)) patients. Multivariate analyses revealed the circulating KL-6 level to be an independent prognostic factor for overall survival as well as progression-free survival. In addition to these observations, we found that changes in circulating KL-6 levels at 2 weeks after the start of EGFR-TKI treatment from the baseline could quite precisely discriminate PD cases from PR or SD patients and the clinical outcome of EGFR-TKI in NSCLC patients. These results indicate that the monitoring of circulating KL-6 levels in NSCLC patients is effective for both selecting patients to be treated with EGFR-TKI and predicting the clinical outcome of EGFR-TKI. In addition, the findings suggest that the circulating KL-6 level could be used as a clinically relevant biomarker in patients with NSCLC, particularly those who are candidates for EGFR-TKI treatment.


Attachment styles and orthorexia nervosa among Lebanese adolescents: The indirect effect of self-esteem.
Orthorexia nervosa (ON), defined as the pathological obsession for pure foods, remains a novelty in the field of eating disorders. Many studies in the literature have shown that attachment styles correlate with the development of eating disorders. Patients with eating disorders were found to be more avoidant and anxious and less secure than individuals who do not have eating disorders. However, studies on the relationship between attachment styles and ON remain limited, particularly in adolescents. This study assessed the relationship between attachment styles and ON in Lebanese adolescents (15-18 years), along with evaluating the indirect effect of self-esteem on this association. This study used a cross-sectional design and was carried out during May-June 2020 with 555 students (15-18 years) enrolled. The Düsseldorf Orthorexia Scale was utilized to screen for ON tendencies. A linear regression was conducted taking the DOS score as the dependent variable. The PROCESS Macro was used to test the indirect effect of self-esteem between attachment styles and ON. Higher fearful and preoccupied attachment styles, female gender, and more physical activity were significantly associated with more ON tendencies, whereas higher self-esteem was significantly associated with less ON tendencies. When adjusting for all sociodemographic characteristics and other attachment styles, none of the attachment styles remained significantly correlated with ON tendencies. Self-esteem mediated the association between secure attachment style and ON and between dismissive attachment style and ON. The rise in ON warrants further studies and investigations to raise awareness and plan behavioral interventions in order to treat it.


Characterization of angiotensin II receptors in the rat fetus.
The presence of AII receptors during early and late embryonic development was studied by binding of 125I[Sar1, Ile8] AII to whole mouse blastocysts and membrane-rich fractions from rat conceptuses, 7 to 21 days in gestation. In early mouse embryos there was no detectable binding under a variety of experimental conditions. However, in late gestation rat fetuses, specific and high affinity binding was observed, with a concentration of sites similar in membranes from whole and eviscerated fetuses. Using less than 100 micrograms of membrane protein, binding was time and temperature dependent, maintaining equilibrium from 30 to 120 min at 23 degrees C and it was enhanced by addition of Mg+2 up to 5 mM, EGTA 2 mM and dithiothreitol up to 2.5 mM. Scatchard analysis of the binding data indicated Kd values ranging between 0.7 and 0.9 nM. Binding was first detectable at day 10 (14.3 +/- 2.3 fmol/mg), increasing to 104 +/- 16, 2,625 +/- 168, 5,993 +/- 152 and 5,902 +/- 92 by days 12, 15, 18, and 21 of gestational age, respectively. Since the functional significance of these binding sites depends on the availability of the agonist ligand, acid extracts from eviscerated 10-day-old fetuses were analyzed for the presence of AII. Measurement of AII by radioimmunoassay revealed immunoreactive AII-like material (845 pg/g of tissue), with an elution pattern identical to that of AII standard in a Sephadex G-50 column. This material was bioactive, as demonstrated by its ability to displace 125I[Sar1, Ile8]AII from adrenal glomerulosa membranes, an effect which was abolished by pretreatment of the extract with AII antibody.(ABSTRACT TRUNCATED AT 250 WORDS)


Cyclic changes in salivary activity of N-acetyl-beta-d-glucosaminidase; a possible efficient indicator for predicting ovulation and pregnancy.
Salivary activity of N-acetyl-beta-D-glucosaminidase showed a characteristic pattern of changes during the normal menstrual cycle with a distinct peak on Day 13, 14, or 15 before the next menstruation. This peak of enzyme activity occurred withing one day of the nadir of basal body temperature and was absent in women with spontaneous or iatrogenic anovulatory cycles. These results are stongly suggestive that the salivary determination of this activity may be convenient indicatior for determining the day of ovulation.


[Therapeutic experiences with high-dose ARA-C and L-ASP].
Five patients, 4 with ALL, 1 with AML received 8 cycles of HD-ARA-C (Capizzi protocol). One complete remission was achieved, 2 patients died shortly after cycle 1 and could not be evaluated. Two patients responded partially. Toxicity was considerable.


Altered visual perception in long-term ecstasy (MDMA) users.
The present study investigated the long-term consequences of ecstasy use on visual processes thought to reflect serotonergic functions in the occipital lobe. Evidence indicates that the main psychoactive ingredient in ecstasy (methylendioxymethamphetamine) causes long-term changes to the serotonin system in human users. Previous research has found that amphetamine-abstinent ecstasy users have disrupted visual processing in the occipital lobe which relies on serotonin, with researchers concluding that ecstasy broadens orientation tuning bandwidths. However, other processes may have accounted for these results. The aim of the present research was to determine if amphetamine-abstinent ecstasy users have changes in occipital lobe functioning, as revealed by two studies: a masking study that directly measured the width of orientation tuning bandwidths and a contour integration task that measured the strength of long-range connections in the visual cortex of drug users compared to controls. Participants were compared on the width of orientation tuning bandwidths (26 controls, 12 ecstasy users, 10 ecstasy + amphetamine users) and the strength of long-range connections (38 controls, 15 ecstasy user, 12 ecstasy + amphetamine users) in the occipital lobe. Amphetamine-abstinent ecstasy users had significantly broader orientation tuning bandwidths than controls and significantly lower contour detection thresholds (CDTs), indicating worse performance on the task, than both controls and ecstasy + amphetamine users. These results extend on previous research, which is consistent with the proposal that ecstasy may damage the serotonin system, resulting in behavioral changes on tests of visual perception processes which are thought to reflect serotonergic functions in the occipital lobe.


The estimation op physiological variability of some isolates of Fusarium nivale /Fr./ Ces.
The extend of physiological variability of five Isolates of Fusarium nivale /Fr./ Ces. using a tandem - crossed Immunoelectrophoresis was studied. In the homological reaction of antiserum antl-F. nivale fourteen precipiration lines were obtained. The variability of antigens originated from different isolates was found. The studied isolates showed differentiation In pathogenicity to three rye genotypes.


Male breast cancer: a natural history study.
Eighty-seven cases of male breast cancer seen over a 30-year period were reviewed. The overall observed and corrected five-year survival rates of 42% and 53% correspond well with the results in other series. Factors predicting disease-free interval and survival included size of primary lesion, ipsilateral axillary status, and presence of ulceration, which appear to be similar to those observed for female breast cancer. Eighteen patients (21%) had a second primary tumor (seven with cutaneous malignancies) and were of an older age group with a higher incidence of positive family history of breast cancer as well as other tumors. The overall prognosis of breast cancer in males does not appear to be less favorable than that in females.


Towards scanning nanostructure X-ray microscopy.
This article demonstrates spatial mapping of the local and nanoscale structure of thin film objects using spatially resolved pair distribution function (PDF) analysis of synchrotron X-ray diffraction data. This is exemplified in a lab-on-chip combinatorial array of sample spots containing catalytically interesting nanoparticles deposited from liquid precursors using an ink-jet liquid-handling system. A software implementation is presented of the whole protocol, including an approach for automated data acquisition and analysis using the atomic PDF method. The protocol software can handle semi-automated data reduction, normalization and modeling, with user-defined recipes generating a comprehensive collection of metadata and analysis results. By slicing the collection using included functions, it is possible to build images of different contrast features chosen by the user, giving insights into different aspects of the local structure.


Selective effects of acute and chronic stress on slow and alpha-theta cortical functional connectivity and reversal with subanesthetic ketamine.
Anxious, depressive, traumatic, and other stress-related disorders are associated with large scale brain network functional connectivity changes, yet the relationship between acute stress effects and the emergence of persistent large scale network reorganization is unclear. Using male Thy 1-jRGECO1a transgenic mice, we repeatedly sampled mesoscale cortical calcium activity across dorsal neocortex. First, mice were imaged in a homecage control condition, followed by an acute foot-shock stress, a chronic variable stress protocol, an acute on chronic foot-shock stress, and finally treatment with the prototype rapid acting antidepressant ketamine or vehicle. We derived functional connectivity metrics and network efficiency in two activity bands, namely slow cortical activity (0.3-4 Hz) and theta-alpha cortical activity (4-15 Hz). Compared to homecage control, an acute foot-shock stress induced widespread increases in cortical functional connectivity and network efficiency in the 4-15 Hz temporal band before normalizing after 24 h. Conversely, chronic stress produced a selective increase in between-module functional connectivity and network efficiency in the 0.3-4 Hz band, which was reversed after treatment with the rapid acting antidepressant ketamine. The functional connectivity changes induced by acute stress in the 4-15 Hz band were strongly related to those in the slow band after chronic stress, as well as the selective effects of subanesthetic ketamine. Together, this data indicates that stress induces functional connectivity changes with spatiotemporal features that link acute stress, persistent network reorganization after chronic stress, and treatment effects.


Routine postoperative intensive care monitoring is not necessary after radical cystectomy.
Patients undergoing radical cystectomy have historically required intensive care monitoring in the perioperative period. We examined the postoperative care of these patients since the institution of a clinical care pathway with special attention to the need for intensive care unit admission. We reviewed the records of 304 consecutive patients who underwent radical cystectomy from December 1995 to July 2000. Variables examined were the location and nature of postoperative care, American Society of Anesthesiologists score, estimated blood loss, transfusion requirement, hospital stay, perioperative minor complications, major complications, the mortality rate and urinary diversion type. Of the 304 patients 20 (6.5%) required intensive care unit monitoring during postoperative recovery and 18 were admitted directly to the intensive care unit postoperatively. Compared with the total population those admitted to the intensive care unit had increased hospital stay (p = 0.002), higher American Society of Anesthesiologists score (p <0.001), higher transfusion requirement (p = 0.001) and shorter operative time (p = 0.02). Patients who received blood transfusion and those with major complications were more likely to need intensive care unit care (p = 0.019 and <0.001, respectively). A single patient died who did not receive intensive care unit care. Our clinical care pathway outlines postoperative care on the regular urology floor for patients who undergo radical cystectomy. This policy has been safe and efficacious. We believe that admission to the intensive care unit should only be done in select cases.


MACULAR THICKNESS BY USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN CHILDREN AND ADOLESCENTS.
To determine the distribution of macular and cube thickness and their normal range in the students aged 9 years to 15 years and to investigate their associated demographic and biometric factors. This study was based on the data of the second phase of the Shahroud School Children Eye Cohort Study, conducted in 2018. After measurements of visual acuity, biometry, and subjective and cycloplegic refraction, retinal examination was performed using the Zeiss Cirrus HD 4000 optical coherence tomography. The data of 5,043 right eyes were analyzed after applying the exclusion criteria. The central macular thickness was 239 ± 19.35 μ m. The mean cube volume and cube thickness were 9.94 ± 0.44 and 278 ± 12.20, respectively. According to multiple linear regression analysis, the central macular thickness was significantly lower in girls (coefficient [β]: -9.18; P < 0.001) and rural students (β: 3.86; P < 0.001) and had a direct association with axial length (β: 5.19; P < 0.001), lens thickness (β: 5.33; P = 0.003), and mean keratometry (β: 2.41; P < 0.001). The cube volume was lower in girls (β: -0.13; P < 0.001) and higher in rural students (β: 0.05; P < 0.001). Macular thickness was slightly higher in Iranian children. Sex, living place, axial length, lens thickness, and mean keratometry were the main associated factors with macular thickness.


Laminotomy/medial facet approach in the excision of thoracic disc herniation.
The author describes a technique of thoracic discectomy that has evolved from the posterolateral transfacet and the transpedicular approaches but that spares the pedicle and most of the facet joint. This approach was used to remove a total of 11 discs (T6-12) in seven patients. The follow-up period ranged from 8 months to 3 years. In four patients with axial and/or girdle pain significant improvement was demonstrated. The paraparesis in one patient with myelopathy improved postoperatively; that in another patient improved but recurred 8 months postoperatively. In one patient who experienced preoperative leg weakness, the weakness was slightly increased postoperatively, but this sequela was only transient. There were no other complications, and there were no deaths. This technique appears safe and effective. It can be adapted to the conventional laminectomy known to spine surgeons and requires no specialized instruments. Further trials appear warranted.


Role of RepB in the replication of plasmid pJB01 isolated from Enterococcus faecium JC1.
The plasmid pJB01 (GenBank Accession No. AY425961) isolated from the pathogenic bacterium, Enterococcus faecium JC1, is 2235 base pairs in length and consists of a putative double-strand origin (dso), a single-strand origin, a counter-transcribed RNA, and three open reading frames. A comparison of a few replication factors and motifs, bind and nic regions, for replication initiation on the nucleotide sequence level revealed that it belongs to the pMV158 family among RC-replicating plasmids. A runoff DNA synthesis assay demonstrated that nicking occurred between G525 and A526, which is located on the internal loop of a putative secondary structure in the dso. Unlike all the other plasmids of the pMV158 family having two or three direct repeats, pJB01 has three non-tandem direct repeats of 5'-CAACAAA-3' separated by four nucleotides, as the RepB-binding site in the dso. Moreover, the nick site on the internal loop is located at 77 nucleotides upstream from the RepB-binding region. Irrespective of the structural difference of direct repeats from other members of the pMV158 family, we think, it is still a new member of this plasmid family. The introduction of mutations in conserved regions of RepB confirmed that RepB N-moiety is important for nicking/nick-closing activity. Within N-moiety, especially all of the motif R-III, the Y100 in R-IV and Y116 in R-V residues, played particularly critical roles in this activity, however, for its binding, both of the N- and C-moieties of RepB were needed.


Analysis of antibiotics by capillary electrophoresis.
This article reviews recent developments in the characterization of antibiotics. Many capillary electrophoretic techniques have been utilized in their analyses, addressing various aspects of quantifying, profiling and monitoring. Sensitive electrochemical and laser-induced fluorescence detection systems have been utilized, demonstrating trace level determinations in clinical settings and in environmental samples. Different sample introduction methods have been explored, enhancing detection sensitivity, or reducing or eliminating sample manipulation prior to injection.


Congenital malignant extrarenal rhabdoid tumor: prenatal ultrasound findings.
Congenital cancer is rare, and metastatic cancer of the infant at birth is even more unusual. Pregnancy management may be altered if fetal tumors are detected by prenatal ultrasound. We present a 29-week gestation with polyhydramnios and a fetus with a congenital malignant extrarenal rhabdoid tumor on the left neck and chest with generalized metastases. Cytogenetic analysis of the tumor cells revealed a trisomy 7. Prenatal ultrasound permits in utero detection of fetal tumors and identification of complications.


Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection.
Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset.


Higher mercury contamination is associated with shorter telomeres in a long-lived seabird - A direct effect or a consequence of among-individual variation in phenotypic quality?
Mercury is a heavy metal, which is pervasive and persistent in the marine environment. It bioaccumulates within organisms and biomagnifies in the marine food chain. Due to its high toxicity, mercury contamination is a major concern for wildlife and human health. Telomere length is a biomarker of aging and health, because it predicts survival, making it a potential tool to investigate sublethal effects of mercury contamination. However, the relationship between telomeres and mercury contamination is unclear. We measured feather mercury concentration in Cory's Shearwaters Calonectris borealis, long-lived seabirds and top predators, between 9 and 35 years of age and related it to telomere length in erythrocytes. Cory's Shearwaters with higher mercury concentrations had shorter telomeres and the effect was sex-dependent, reaching significance in males only. This may be explained by the fact that males have longer telomeres and higher and more variable mercury concentrations than females in this population. The mercury effect on telomere length was stronger on longer telomeres in the genome within individuals. We discuss the hypotheses that the negative correlation could either be a direct effect of mercury on telomere shortening and/or a consequence of variation in phenotypic quality among individuals that results in a covariation between mercury contamination and telomere length.


Variables influencing cadmium concentrations in hair of pre-school children living in different areas of the Federal Republic of Germany.
The influence of several factors on cadmium (Cd) concentrations in the hair of 474 pre-school children was examined. The study was performed in an industrial (Duisburg) and rural area (Westfalen) of the (FRG). Season, sex, hair color, and place of residence were found to be the main factors influencing Cd levels in hair. Concentrations of Cd in samples obtained during summer were on the average nearly twice as high as those sampled during winter (geometric means: 116.1 vs. 63.7 ng/g). Boys had more Cd in their hair than girls (111.5 vs. 74.0 ng/g). Cd levels in hair decreased from red to blond, to brown, and black hair. Children living in Duisburg had more Cd in their hair than those from rural areas (103.9 vs. 77.0 ng/g). Cd content in hair was inversely related to age.


Tailoring genetic information and services to clients' culture, knowledge and language level.
This article discusses approaches to dealing with transcultural care. Patient treatment can be improved by considering various cultural differences, establishing empathy, and focused listening. Scenarios, points for reflection and suggestions for non-judgemental language are provided.


Use of a microsimulation method for assessing dynamics of smoking status and gains in life expectancy after quitting in a longitudinal cohort of US older adults.
Previous studies were unable to estimate the dynamics of smoking status in the US elderly general population, and no study has assessed the benefit of quitting in terms of resultant gains in life expectancy. We proposed a novel method to estimate the per cent of quitting in remaining lifetime, successful quitting and relapse, as well as life expectancy by participants' baseline smoking status. Longitudinal cohort. US community-dwelling population. Respondents from the Medicare Health Outcome Survey Cohort 15 (baseline 2012, follow-up 2014). We included respondents who were aged ≥65 years and alive at the baseline and participated in the baseline survey (n=164 597).Primary and secondary outcome measuresAttempt quitting, successful quitting, relapse rates and life expectancy by smoking status at age 65-95 years. Among daily smokers aged 65 years, 61% would attempt to quit during their remaining lifetime, and 31% would quit successfully. Among some days smokers aged 65 years, 69% would attempt to quit during their remaining lifetime, and 37% would quit successfully. Among recent ex-smokers aged 65 years, 53% would relapse. Life expectancy at age 65 years was 20.0 (SE=0.27), 17.2 (SE=0.30), 16.2 (SE=0.29) and 15.9 (SE=0.29) years for long time non-smokers, recent ex-smokers, some days smokers and daily smokers, respectively. Although recent ex-smokers had a higher 2-year mortality than current smokers, those who quit up to 77 years (77 years for men and 87 years for women) had a significantly longer (p<0.05) life expectancy. Sensitivity analysis demonstrated that the model assumptions had a relatively small impact on estimates with a maximum relative bias within ±7%. This study provides detailed information regarding the dynamics of smoking status in an understudied and growing population and demonstrates the benefit of smoking cessation on life expectancy. Future research should focus on understanding specific predictors of smoking cessation.


Extracellular signals, transcriptional responses and cellular specificity.
The expression of a relatively small set of common primary response genes is frequently induced, in a variety of cellular responses, by growth factors, protein hormones and neurotransmitters. The characterization of these genes and their products may provide clues to the mechanisms by which ligand- and cell-specific responses may be generated.


Engineering Induced Pluripotent Stem Cells for Cancer Immunotherapy.
Cell-based immunotherapy, such as chimeric antigen receptor (CAR) T cell therapy, has revolutionized the treatment of hematological malignancies, especially in patients who are refractory to other therapies. However, there are critical obstacles that hinder the widespread clinical applications of current autologous therapies, such as high cost, challenging large-scale manufacturing, and inaccessibility to the therapy for lymphopenia patients. Therefore, it is in great demand to generate the universal off-the-shelf cell products with significant scalability. Human induced pluripotent stem cells (iPSCs) provide an "unlimited supply" for cell therapy because of their unique self-renewal properties and the capacity to be genetically engineered. iPSCs can be differentiated into different immune cells, such as T cells, natural killer (NK) cells, invariant natural killer T (iNKT) cells, gamma delta T (γδ T), mucosal-associated invariant T (MAIT) cells, and macrophages (Mφs). In this review, we describe iPSC-based allogeneic cell therapy, the different culture methods of generating iPSC-derived immune cells (e.g., iPSC-T, iPSC-NK, iPSC-iNKT, iPSC-γδT, iPSC-MAIT and iPSC-Mφ), as well as the recent advances in iPSC-T and iPSC-NK cell therapies, particularly in combinations with CAR-engineering. We also discuss the current challenges and the future perspectives in this field towards the foreseeable applications of iPSC-based immune therapy.


Investigating the neural correlates of continuous speech computation with frequency-tagged neuroelectric responses.
In order to learn an oral language, humans have to discover words from a continuous signal. Streams of artificial monotonous speech can be readily segmented based on the statistical analysis of the syllables' distribution. This parsing is considerably improved when acoustic cues, such as subliminal pauses, are added suggesting that a different mechanism is involved. Here we used a frequency-tagging approach to explore the neural mechanisms underlying word learning while listening to continuous speech. High-density EEG was recorded in adults listening to a concatenation of either random syllables or tri-syllabic artificial words, with or without subliminal pauses added every three syllables. Peaks in the EEG power spectrum at the frequencies of one and three syllables occurrence were used to tag the perception of a monosyllabic or tri-syllabic structure, respectively. Word streams elicited the suppression of a one-syllable frequency peak, steadily present during random streams, suggesting that syllables are no more perceived as isolated segments but bounded to adjacent syllables. Crucially, three-syllable frequency peaks were only observed during word streams with pauses, and were positively correlated to the explicit recall of the detected words. This result shows that pauses facilitate a fast, explicit and successful extraction of words from continuous speech, and that the frequency-tagging approach is a powerful tool to track brain responses to different hierarchical units of the speech structure.


Perceptions of smoking cessation programs in rural Appalachia.
To identify perspectives on smoking cessation programs in Appalachian Kentucky, a region with particularly high smoking rates and poor health outcomes. Insufficient existing research led us to conduct 12 focus groups (smokers and nonsmokers) and 23 key informant interviews. Several findings previously not described in this high-risk population include (1) transition from pro-tobacco culture toward advocacy for tobacco cessation approaches, (2) region-specific challenges to program access, and (3) strong and diverse social influences on cessation. To capitalize on changes from resistance to support for smoking cessation, leaders should incorporate culturally appropriate programs and characteristics identified here.


Egestive feeding responses in Aplysia persist after sectioning of the cerebral-buccal connectives: evidence for multiple sites of control of motor programs.
Ingestive and egestive behaviors in Aplysia are generated by motor neurons and interneurons chiefly located in the buccal ganglion, but cerebral ganglion neurons appear to contribute to both ingestive and egestive motor programs. We investigated if the cerebral ganglion input to the buccal ganglion is necessary for the generation of buccal ingestive and egestive behaviors in free-moving animals. We confirmed a prior study that showed that animals with lesions of the cerebro-buccal connectives (CBCs) do not exhibit rhythmic biting following seaweed stimulation of the lips, but do show swallowing of seaweed inserted into the buccal cavity. We found that CBC-lesioned animals also exhibited rejection of a tube inserted into the buccal cavity and esophagus. The programs for swallowing and rejection behaviors were similar to those observed before lesioning the CBCs, although the rate of swallowing was slower. These results suggest that the cerebral input to the buccal ganglion is necessary for generating biting responses, but is not required for producing swallowing or rejection responses.


Intermediate imperforate anus: clinical and radiographic implications.
Five male infants are described with imperforate anus with external signs of a low lesion but with subsequent evidence of a higher lesion with demonstration of a fistula into the anterior urethra either at surgery or by radiographic studies. The cases should be considered an intermediate form of imperforate anus with external signs of a low lesion but with fistula characteristically to the membranous or bulbous urethra. These infants should be treated surgically as high lesions with initial diverting colostomies.


Three neuroparsin genes from oriental river prawn, Macrobrachium nipponense, involved in ovary maturation.
In this study, we identified three neuroparsin (NP) genes in Macrobrachium nipponense: Mn-NP1, Mn-NP2, and Mn-NP3, encoding 99, 100, and 101 amino acid proteins, respectively. Multiple sequence alignments showed that these genes contained 12 cysteine residues, of which 11 were at conserved positions. The total sequence identity between the genes was 47.5%, and they showed a high degree of sequence identity (> 54% similarity) with other crustacean genes. Phylogenetic tree analysis showed that Mn-NPs were clustered at different branches, indicating that Mn-NPs may have different functions. Tissue distribution data revealed that the three genes were present in males and females during the breeding and nonbreeding season, but their expression patterns differed. Mn-NP1 was highly expressed in the breeding season, in the male testis, and highly expressed in the nonbreeding season, in the female ovary. Mn-NP3 exhibited biased female expression in the breeding and nonbreeding season, with dominant expression in the ovary. All Mn-NPs were detected during embryo development, but with different expression patterns. These data indicated that Mn-NP1 may function during embryonic development, and that Mn-NP2 may be expressed during early embryo cell division, and late larval development. Mn-NP3 expression patterns reflected maternal inheritance, and may be associated with ovarian maturation. These expression data suggested that Mn-NP1 and Mn-NP2 are negatively correlated with ovarian development, with inhibition roles during this development. Mn-NP3 may be involved in vitellogenesis.


Cultural antecedents to community: An evaluation of community experience in the United States, Thailand, and Vietnam.
To what extent does community experience differ between low context and high context societies? Prior literature theorizes that community experience consists of two separate, yet highly related concepts: community attachment, an individual's general rootedness to a place, and community satisfaction, how well an individual's community meets their societal needs. We test this conceptualization of community experience across communities in the US and two Southeast Asian nations: Thailand and Vietnam. We argue that Southeast Asian nations constitute "high context" societies with relatively high social integration and solidarity while the US is more individualized and less socially integrated and thus constitutes a "low context" society. Our results provide empirical evidence that individuals' experience of community varies between low and high context societies. These results demonstrate that cultural context continues to matter in regards to the lived experience of community and researchers need to remain vigilant in accounting for such differences as they seek to examine the concept of community more broadly.


Lower urinary tract symptoms that predict microscopic pyuria.
Urinary dipsticks and culture analyses of a mid-stream urine specimen (MSU) at 105 cfu ml-1 of a known urinary pathogen are considered the gold standard investigations for diagnosing urinary tract infection (UTI). However, the reliability of these tests has been much criticised and they may mislead. It is now widely accepted that pyuria (≥1 WBC μl-1) detected by microscopy of a fresh unspun, unstained specimen of urine is the best biological indicator of UTI available. We aimed to scrutinise the greater potential of symptoms analysis in detecting pyuria and UTI. Lower urinary tract symptom (LUTS) descriptions were collected from patients with chronic lower urinary tract symptoms referred to a tertiary referral unit. The symptoms informed a 39-question inventory, grouped into storage, voiding, stress incontinence and pain symptoms. All questions sought a binary yes or no response. A bespoke software package was developed to collect the data. The study was powered to a sample of at least 1,990 patients, with sufficient power to analyse 39 symptoms in a linear model with an effect size of Cohen's f2 = 0.02, type 1 error probability = 0.05; and power (1-β); 95% where β is the probability of type 2 error). The inventory was administered to 2,050 female patients between August 2004 and November 2011. The data were collated and the following properties assessed: internal consistency, test-retest reliability, inter-observer reliability, internal responsiveness, external responsiveness, construct validity analysis and a comparison with the International Consultation on Incontinence Modular Questionnaire for female lower urinary tract symptoms (ICIQ-FLUTS). The dependent variable used as a surrogate marker of UTI was microscopic pyuria. An MSU sample was sent for routine culture. The symptoms proved reliable predictors of microscopic pyuria. In particular, voiding symptoms correlated well with microscopic pyuria (χ2 = 88, df = 1, p < 0.001). The symptom inventory has significant psychometric characteristics as below: test-retest reliability: Cronbach's alpha was 0.981; inter-observer reliability, Cronbach's alpha was 0.995, internal responsiveness F = 221, p < 0.001, external responsiveness F = 359, df = 5, p < 0.001. The correlation coefficients for the domains of the ICIQ-FLUTS were around R = 0.5, p < 0.001. This symptoms score performed well on the standard, psychometric validation. The score changed in response to treatment and in a direction appropriate to the changes in microscopic pyuria. It correlated with measures of quality of life. It would seem to make a good candidate for monitoring treatment progress in ordinary clinical practice.


A pathway map of glutamate metabolism.
Glutamate metabolism plays a vital role in biosynthesis of nucleic acids and proteins. It is also associated with a number of different stress responses. Deficiency of enzymes involved in glutamate metabolism is associated with various disorders including gyrate atrophy, hyperammonemia, hemolytic anemia, γ-hydoxybutyric aciduria and 5-oxoprolinuria. Here, we present a pathway map of glutamate metabolism representing metabolic intermediates in the pathway, 107 regulator molecules, 9 interactors and 3 types of post-translational modifications. This pathway map provides detailed information about enzyme regulation, protein-enzyme interactions, post-translational modifications of enzymes and disorders due to enzyme deficiency. The information included in the map was based on published experimental evidence reported from mammalian systems.


Cationic lipids for gene delivery: many players, one goal.
Lipid-based carriers represent the most widely used alternative to viral vectors for gene expression and gene silencing purposes. This class of non-viral vectors is particularly attractive for their ease of synthesis and chemical modifications to endow them with desirable properties. Despite combinatorial approaches have led to the generation of a large number of cationic lipids displaying different supramolecular structures and improved behavior, additional effort is needed towards the development of more and more effective cationic lipids for transfection purposes. With this review, we seek to highlight the great progress made in the design of each and every constituent domain of cationic lipids, that is, the chemical structure of the headgroup, linker and hydrophobic moieties, and on the specific effect on the assembly with nucleic acids. Since the complexity of such systems is known to affect their performances, the role of formulation, stability and phase behavior on the transfection efficiency of such assemblies will be thoroughly discussed. Our objective is to provide a conceptual framework for the development of ever more performing lipid gene delivery vectors.


Retroperitoneal laparoscopy rather than an open procedure for resection of pheochromocytomas could minimize intraoperative blood pressure fluctuations and transfusion events.
We retrospectively reviewed the outcomes after laparoscopy versus an open procedure for the resection of pheochromocytoma. Forty-nine patients were enrolled into the study between June 2004 and December 2008 having been diagnosed with pheochromocytoma. The selection criteria were patients who were diagnosed with pheochromocytoma on admission based on clinical manifestations, imaging examinations and laboratory tests. Twenty-six patients underwent a retroperitoneal laparoscopic resection of their pheochromocytoma (LRP), and another 23 patients underwent an open resection of the pheochromocytoma (ORP). The ORP was similar to the LRP on the incidence of intraoperative blood pressure fluctuation. While compared to ORP, the process of LRP could effectively control the degree of fluctuations in intraoperative blood pressure(P < 0.05). Patients who received LRP had a significantly reduced volume of fluid in their drain on the first postoperative day than those who received ORP(P < 0.05), and due to the drain being removed sooner, they were consequently able to mobilize earlier(P < 0.05). The LRP cohort consisted of four patients with tumors ranging from 6 to 7 cm and three of them were successfully achieved. Intraoperatively or within 24 h postoperatively, 10 out of 23 patients who had undergone ORP received a transfusion, while none of those in the LRP cohort received a transfusion. Retroperitoneal LRP allowed patients to mobilize earlier and minimized the occurrence of intraoperative blood pressure fluctuations and transfusion events. Adequate preoperative preparation and skilled laparoscopic manipulation appeared to guarantee the safety of the procedure, and large tumors did not absolutely contraindicate the use of laparoscopy.


Bacterial ghost cell based bivalent candidate vaccine against Salmonella Typhi and Salmonella Paratyphi A: A prophylactic study in BALB/c mice.
Typhoid and emerging paratyphoid fever are a severe enteric disease worldwide with high morbidity and mortality. Licensed typhoid vaccines are in the market, but no paratyphoid vaccine is currently available. In the present study we developed a bivalent vaccine against Salmonella Typhi and Paratyphi A using a bacterial ghost platform. Bacterial ghost cells (BGs) are bacteria-derived cell membranes without cytoplasmic contents that retain their cellular morphology, including all cell surface features. Furthermore, BGs have inherent adjuvant properties that promote an enhanced humoral and cellular immune reaction to the target antigen. Sodium hydroxide was used to prepare ghost cells of Salmonella Typhi and Paratyphi A. The bacterial ghost cells were characterised using electron microscopy. Then BALB/c mice were immunized three times (0th, 14th and 28th day) with the bivalent typhoidal bacterial ghost cells. Haematological study of adult mice throughout immunization period reflected that the immunogen was safe to administer and does not affect the animals' health. After complete immunization, we found significant serum antibody titter against whole cell lysate, outer membrane protein and lipopolysaccharide of both bacteria, and cell-mediated immunity was observed in an ex-vivo experiment. CD4+, CD8a+ and CD19+ splenic cell populations were increased in immunized animals. Bivalent Typhoidal ghost cell immunized mice showed better survival, less bacterial colonization in systemic organs, and less inflammation and/or destruction of tissue in histopathological analysis than non-immunized control mice.Serum antibodies of immunized animals can significantly inhibit bacterial motility and mucin penetration ability with better killing properties against Salmonella Typhi and Paratyphi A. Furthermore, significant passive protection was observed through the adoptive transfer of serum antibody and lymphocytes of immunized animals to naïve animals after bacterial infection. In summary, Bivalent Typhoidal Bacterial Ghost cells (BTBGs) enhances immunogenic properties and serves as a safe and effective prevention strategy against Salmonella Typhi and Paratyphi A.


Impact of donor kinship on non-T-cell depleted haploidentical stem cell transplantation with post transplantation cyclophosphamide for acute leukemia: From the ALWP of the EBMT.
Non-T-cell depleted haploidentical hematopoietic cell transplantation (Haplo-HCT) is a unique transplantation setting in which several donors are available. We assessed the impact of donor kinship on outcome of Haplo-HCT with post-transplantation cyclophosphamide in a cohort of 717 acute leukemia patients. We compared sibling with parent donors in patients ≤45 years, and child with sibling donors in patients >45 years. Donor kinship was not associated with worse outcomes in multivariate analysis. For patients ≤45 years, the hazard ratio (HR) for leukemia-free survival (LFS), overall survival (OS), relapse incidence (RI), and chronic graft-versus-host disease (cGVHD) was 0.87 (p = 0.75), 1.19 (p = 0.7), 0.52 (p = 0.19), and 0.99 (p = 0.97) for parents versus siblings, respectively, and for patients >45 years the HR was 0.93 (p = 0.8), 0.98 (p = 0.94), 1.3 (p = 0.53), and 0.98 (p = 0.95) for children versus siblings, respectively. Univariate incidence of acute GVHD grade II-IV was significantly higher in patients transplanted from siblings versus children (p = 0.002). Factors associated with inferior outcome were advanced disease and earlier transplant. In patients ≤45 years, acute lymphocytic leukemia and peripheral blood stem cell graft were additional prognostic factors for OS. We did not find a significant impact of donor kinship on transplantation outcome when analyzing by age group (≤45 and >45 years).


Comparative nucleotide sequence analysis of polymorphic variable-number tandem-repeat Loci in Mycobacterium ulcerans.
We analyzed a set of variable-number tandem-repeat (VNTR) loci to assess their nucleotide sequence diversity in isolates of three Mycobacterium ulcerans genotypes. Sequence variants in two loci resulted in intraspecies resolution of Southeast Asian and Asian genotypes in contrast to a homogenous sequence composition among African isolates. Nucleotide sequence polymorphism in repeat units can enhance discrimination of VNTR loci.


Physiological and lifestyle factors contributing to risk and severity of peri-orbital dark circles in the Brazilian population.
Peri-orbital dark circles are a cosmetic concern worldwide, and have been attributed to hyperpigmentation from allergy or atopic dermatitis, blood stasis, structural shadowing effects, and a thin epidermis/dermis under the eye. It is of interest to better understand lifestyle and demographic risk factors and the relative impact of melanin, blood and epidermal/dermal factors on the severity of Peri-orbital dark circles. To compare by non-invasive imaging the impact of biological factors to a visual grading scale for Peri-orbital dark circles, and test the correlation of various demographic factors with Peri-orbital dark circles. Subjects completed a lifestyle and health survey, and Peri-orbital dark circles severity was evaluated using standardized photographs. Hyperspectral image analysis was used to assess the contributions of melanin, blood volume, degree of blood oxygen saturation, and dermal scattering. Family history was the most significant risk factor for Peri-orbital dark circles. The average age of onset was 24 years, and earlier onset correlated with higher severity scores. Asthma was significantly associated with Peri-orbital dark circles scores, but self-reported allergy was not. In this study, sleep was not correlated with Peri-orbital dark circles scores. Hyperspectral imaging indicated that melanin was the dominant correlate for Peri-orbital dark circles severity, while oxygen saturation was secondary. The difference between under-eye and cheek measurements for ΔL*and ΔE* were the most significant instrumental parameters correlated with visual assessment of Peri-orbital dark circles severity. Although typically associated with lack of sleep, risk of Peri-orbital dark circles is primarily hereditary. The main factors contributing to the appearance of Peri-orbital dark circles are melanin and (deoxygenated) blood.


Chitin Pickering Emulsion for Oil Inclusion in Composite Films.
A film containing a stable and well-dispersed hydrophobic phase in a surfactant-free bio-based hydrophilic matrix is proposed. In this study, an aqueous suspension of rod-like chitin nanocrystals (ChiNCs), mixed with paraffin oil, form an oil-in-water Pickering emulsion with a droplet diameter of 3 μm. These emulsions mixed with a 5 wt% starch solution formed homogeneous composite films by solvent casting. Various amounts of emulsion were incorporated, leading to self-supported films with a volume of oil as high as 45 vol%, with less than 1% of ChiNCs. This model inclusion system leads to droplets homogeneously dispersed throughout the composite films, as revealed by microscopy (SEM and CLSM) with mechanical properties controlled by the matrix. Finally, the droplets were easily released from the matrix by enzymatic hydrolysis. This easy-to-implement transparent film proved to be a good candidate when it is desirable to disperse a poor water-soluble component in a hydrophilic edible matrix.


The role of genes affected by human evolution marker GNA13 in schizophrenia.
Numerous variants associated with increased risk for SCZ have undergone positive selection and were associated with human brain development, but which brain regions and developmental stages were influenced by the positive selection for SCZ risk alleles are unclear. We analyzed SCZ using summary statistics from a genome-wide association study (GWAS) from the Psychiatric Genomics Consortium (PGC). Machine-learning scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele has reached fixation) and incomplete selection (loci where a selected allele has not yet reached fixation). Based on the p value of single nucleotide polymorphisms (SNPs) with selection scores in the top 5%, we formed five subgroups: p < 0.0001, 0.001, 0.01, 0.05, or 0.1. We found that 48 and 29 genes (p < 0.0001) in complete and incomplete selection, respectively, were enrichedfor the transcriptionalco-expressionprofilein theprenatal dorsolateral prefrontal cortex (DFC), inferior parietal cortex (IPC), and ventrolateral prefrontal cortex (VFC). Core genes (GNA13, TBC1D19, and ZMYM4) involved in regulating early brain development were identified in these three brain regions. RNA sequencing for primary cortical neurons that were transfected Gna13 overexpressed lentivirus demonstrated that 135 gene expression levels changed in the Gna13 overexpressed groups compared with the controls. Gene-set analysis identified important associations among common variants of these 13 genes, which were associated with neurodevelopment and putamen volume [p = 0.031; family-wise error correction (FWEC)], SCZ (p = 0.022; FWEC). The study indicate that certain SCZ risk alleles were likely to undergo positive selection during human evolution due to their involvement in the development of prenatal DFC, IPC and VFC, and suggest that SCZ is related to abnormal neurodevelopment.


Crosstalk between cAMP and pheromone signalling pathways in Ustilago maydis.
In the phytopathogenic basidiomycete Ustilago maydis mating and dikaryon formation are controlled by a pheromone/receptor system and the multiallelic b locus. Recently, a gene encoding a G protein alpha subunit, gpa3, was isolated and has subsequently been implicated in pheromone signal transduction. Mutants deleted for gpa3 are sterile and nonpathogenic, and exhibit a morphology that is similar to that of mutants with defects in the adenylate cyclase gene uac1. We have found that the sterility and mutant morphology of gpa3 deletion strains can be rescued by exogenous cAMP. In these mutants and in the corresponding wild-type strains, exogenous cAMP stimulates pheromone gene expression to a level comparable to that seen in the pheromone-stimulated state. In addition, we demonstrate that uac1 is epistatic to gpa3. We conclude that Gpa3 controls the cAMP signalling pathway in U. maydis and discuss how this pathway feeds into the pheromone response.


Comprehensive Identification of RNA-Binding Proteins by RNA Interactome Capture.
RNA associates with RNA-binding proteins (RBPs) from synthesis to decay, forming dynamic ribonucleoproteins (RNPs). In spite of the preeminent role of RBPs regulating RNA fate, the scope of cellular RBPs has remained largely unknown. We have recently developed a novel and comprehensive method to identify the repertoire of active RBPs of cultured cells, called RNA interactome capture. Using in vivo UV cross-linking on cultured cells, proteins are covalently bound to RNA if the contact between the two is direct ("zero distance"). Protein-RNA complexes are purified by poly(A) tail-dependent oligo(dT) capture and analyzed by quantitative mass spectrometry. Because UV irradiation is applied to living cells and purification is performed using highly stringent washes, RNA interactome capture identifies physiologic and direct protein-RNA interactions. Applied to HeLa cells, this protocol revealed the near-complete repertoire of RBPs, including hundreds of novel RNA binders. Apart from its RBP discovery capacity, quantitative and comparative RNA interactome capture can also be used to study the responses of the RBP repertoire to different physiological cues and processes, including metabolic stress, differentiation, development, or the response to drugs.


Brain FDG-PET correlates of saccadic disorders in early PSP.
New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.


Difficulties experienced by health care professionals who performed home visits to screen for postpartum depression during the COVID-19 pandemic: a qualitative study in Japan.
Postpartum depression is a risk factor for suicide and maltreatment of children, and its early detection and appropriate intervention are issues to be resolved. In Japan, local governments are working to detect postpartum depression early by conducting home visits to families with infants within 4 months postpartum, but home-visit professionals have faced new difficulties due to the coronavirus disease 2019 (COVID-19) pandemic that started in 2020. The purpose of this study was to clarify the difficulties experienced by health care professionals who perform home visits to screen for postpartum depression. Focus-group interviews were conducted during the COVID-19 pandemic with health care professionals (n = 13) who make postpartum home visits to families with infants within 4 months. Data were analyzed using thematic analysis. Four main categories were identified that describe the difficulties experienced by health care professionals: "Lack of support for partners," "Difficulty in talking face-to-face," "Inability to offer family assistance," and "Anxiety about being a source of infection." This study shed light on the difficulties faced by professionals in supporting mothers and children in the community during the COVID-19 pandemic. Although these difficulties were considered to have become apparent during the pandemic, the results may offer an important perspective for postpartum mental health support even after the pandemic ends. Accordingly, it may be necessary for these professionals to receive supported through multidisciplinary collaboration in order to improve postpartum care in the community.


Absence of anti-pendrin auto-antibodies in the sera of Tunisian patients with autoimmune thyroid diseases.
We previously demonstrated that the PDS gene is involved in the genetic susceptibility to autoimmune thyroid diseases (AITD) in Tunisia. In the same population, we now investigated the presence of anti-pendrin auto-antibodies (aAbs) in AITD patients' sera. Thirty seven Tunisian AITD patients and 19 healthy subjects from families previously linked to the PDS gene, 75 unrelated patients and 20 healthy unrelated subjects were included in our study. The detection of anti-pendrin aAbs in patients' sera was performed by ELISA using membrane protein extracts of CHO cells expressing pendrin (CHO-hPDS) and by immunofluorescence using transient COS-7 cells expressing a GFP tagged pendrin. CHO cells transfected with human TPO in the same ELISA conditions were used as positive control. The majority of AITD patients' sera were positive for the presence of anti-TPO aAbs. In contrast, no reactivity was detected with CHO-hPDS membrane protein extracts. Likewise, no significant immunostaining was found on transfected COS-7cells upon exposure to patients' and controls' sera. Our data point to the absence of anti-pendrin aAbs in Tunisian AITD patients' sera.


Soil seed bank distribution and restoration potential in the vegetation of Buska Mountain range, Hamar district, southwestern Ethiopia.
The seed banks are vital components for the reestablishment of degraded lands since they are used to predict the future coverage of vegetation and allow for the implementation of appropriate conservation measures in a particular area. The study was conducted in the Buska Mountains of the Hamar area in south-western Ethiopia and determined the composition, density and vertical distribution of soil seed banks under various land-use systems and soil layers. A total of 96 soil samples were involved in the study; four land-use types (grassland, forest, scrub and bare ground). Three distinct soil layers from each plot (0-3 cm, 3-6 cm, 6-9 cm depths) were sampled. Jaccard's Similarity Coefficient was applied to evaluate the correspondence between different land-use types and soil layers. One-way ANOVA was used to compute species density and composition respectively within land-use systems along with the seed bank and above ground vegetation. Fifty six (56) species within 27 plant families and 50 genera were recorded. Twenty percent of the species was contributed by Asteraceae followed by Poaceae (16%). Herbaceous growth forms were the most dominant in the area, contributing about 78.6%. The total seedling density in the study plots was 8171 seedlings/m2. Jaccard's Similarity Coefficient is relatively higher (0.52) between grassland and scrub, while the forest and bare land had the least amount of similarity (0.22). There was seen a higher similarity of species between the first and second soil layers and a decreasing density with soil depth. A substantial difference between the aboveground species and seed bank was recorded in the area. The lower resemblance between the standing vegetation and the seed bank infers a lower overall restoration potential and suggests other alternative regeneration mechanisms such as seedling plantation of priority indigenous plant species and avoiding anthropogenic disturbances.


The role of galanin in cholinergically-mediated memory processes.
1. Galanin, a 29 amino-acid neuroactive peptide, has been shown to affect diverse processes throughout the nervous system and to coexist with several "classical" neurotransmitters, including norepinephrine, serotonin, and acetylcholine. 2. Galanin coexists with acetylcholine in neurons of the medial septum, diagonal band, and nucleus basalis of Meynert, cells which degenerate during the course of Alzheimer's disease. 3. In the ventral hippocampus, galanin inhibits the release of acetylcholine and inhibits carbachol stimulated phosphatidyl inositol hydrolysis. 4. Galanin impairs choice accuracy in learning and memory paradigms in rats, and is therefore hypothesized to be a contributory factor in the memory and cognitive disabilities found in Alzheimer's patients. 5. Newly developed galanin antagonists, by eliminating putative inhibitory effects of endogenous galanin on cholinergic function, may serve as useful therapies for memory disorders.


Distribution of the two forms of Plasmodium falciparum erythrocyte binding antigen-175 (eba-175) gene in Lao PDR.
The erythrocyte binding antigen 175 (EBA-175) is a 175 kDa antigen of Plasmodium falciparum and plays a major role in erythrocyte recognition by the parasite. The antigen is also supposed to be partly responsible for the invasion of erythrocytes by merozoites. EBA-175 has been sequenced from the FCR-3 and CAMP strains of P. falciparum. The sequences were identical in most parts of the gene. Differences were apparent in a 423 bp segment in the FCR-3 strain, the F-Fragment, that is not found in the CAMP-strain and a 342 bp segment, the C-Fragment, which is present in the CAMP-strain but not in the FCR-3-strain. The aim of this study was to assess the distribution of the two EBA-175-alleles in the Lao PDR. Altogether, 240 blood-samples were collected in two areas of the country: Attapeu in the south and Lung Namtha in the north. Subsequently, the material was scanned for the F-and C-fragments. In the whole study population, 52% carried the F-fragment, and 41% the C-fragment while seven percent of the patients were infected with at least two parasite strains and showed both alleles. Distribution of the alleles showed significant differences between the north and the south province. Reasons for this include possible importation of different parasite strains from neighbouring countries.


Ranibizumab 0.5 mg treat-and-extend regimen for diabetic macular oedema: the RETAIN study.
To demonstrate non-inferiority of ranibizumab treat-and-extend (T&E) with/without laser to ranibizumab pro re nata (PRN) for best-corrected visual acuity (BCVA) in patients with diabetic macular oedema (DMO). A 24-month single-masked study with patients randomised 1:1:1 to T&E+laser (n=121), T&E (n=128) or PRN (control; n=123). All patients received monthly injections until BCVA stabilisation. The investigator decided on re-treatment in the PRN and treatment-interval adaptations in the T&E groups based on loss of BCVA stability due to DMO activity. Likewise, laser treatment was at investigator's discretion. Collectively, these features reflect a real-life scenario. Endpoints included mean average change in BCVA from baseline to months 1-12 (primary), mean BCVA change from baseline to months 12 and 24, treatment exposure and safety profile. Both T&E regimens were non-inferior to PRN based on mean average BCVA change from baseline to months 1-12 (T&E+laser: +5.9 and T&E: +6.1 vs PRN: +6.2 letters; both p<0.0001). Mean BCVA change at month 24 was similar across groups (+8.3, +6.5 and +8.1 letters, respectively). The mean number of injections was 12.4 and 12.8 in the T&E+laser and T&E groups and 10.7 in the PRN group. The T&E regimens showed 46% reduction in the number of clinic visits. Over 70% of patients maintained their BCVA, with treatment intervals of ≥2 months over 24 months. Safety profile was consistent with that described in the product information. T&E is a feasible treatment option for patients with DMO, with a potential to reduce treatment burden. Slightly more injections were required versus PRN, likely due to the specifics of the T&E regimen applied here. NCT01171976.


New approach for particulate exposure monitoring: determination of inhaled particulate mass by 24 h real-time personal exposure monitoring.
The objectives of this study were to measure particulate pollution (PM(10), PM(2.5), and PM(1.0)) continuously (24 h/day for 7 day) using real-time exposure monitoring and to estimate total inhalation mass using breathing rate and time-activity. Breathing rates were calculated from measured heart rates. Participants were asked to record a time-activity diary every 15 min. Five microenvironments were defined based on the time-activity diary: home, workplace/school, other indoor, outdoor, and transportation. The average masses of inhaled PM(10) were 530, 316, and 280 μg/day for two office workers, a housewife, and three students, respectively; those of PM(2.5) were 316, 279, and 210 μg/day; and those of PM(1.0) were 251, 264, and 187 μg/day, respectively. We found that home and office/school microenvironments were the main contributors of PM(10), PM(2.5), and PM(1.0) inhaled mass during weekdays and weekends because dwelling time was a determinant factor for inhaled mass. Considering microenvironmental concentration, breathing rate, and dwelling time in each microenvironment, indoor home microenvironments were the largest source of particulate inhalation, followed in order by workplace, transportation, other indoor, and outdoor microenvironments. 34.6% and 69.6% of PM(10) inhalation mass were accumulated in home microenvironments during weekdays and weekends, respectively. The inhaled mass of particulate <1.0 μm (PM(1.0)) in size occupied largest, followed in order by particulate 10-2.5 μm (coarse particle) and 2.5-1.0 μm in size for all occupations.


Recommendations for the optimal management of peritoneal metastases in patients with colorectal cancer: a TTD and GECOP-SEOQ expert consensus statement.
Peritoneal metastases (PM) occur when cancer cells spread inside the abdominal cavity and entail an advanced stage of colorectal cancer (CRC). Prognosis, which is poor, correlates highly with tumour burden, as measured by the peritoneal cancer index (PCI). Cytoreductive surgery (CRS) in specialized centres should be offered especially to patients with a low to moderate PCI when complete resection is expected. The presence of resectable metastatic disease in other organs is not a contraindication in well-selected patients. Although several retrospective and small prospective studies have suggested a survival benefit of adding hyperthermic intraperitoneal chemotherapy (HIPEC) to CRS, the recently published phase III studies PRODIGE-7 in CRC patients with PM, and COLOPEC and PROPHYLOCHIP in resected CRC with high-risk of PM, failed to show any survival advantage of this strategy using oxaliplatin in a 30-min perfusion. Final results from ongoing randomized phase III trials testing CRS plus HIPEC based on mitomycin C (MMC) are awaited with interest. In this article, a group of experts selected by the Spanish Group for the Treatment of Digestive Tumours (TTD) and the Spanish Group of Peritoneal Oncologic Surgery (GECOP), which is part of the Spanish Society of Surgical Oncology (SEOQ), reviewed the role of HIPEC plus CRS in CRC patients with PM. As a result, a series of recommendations to optimize the management of these patients is proposed.


Fine-needle aspiration of the liver: out of the ivory tower and into the community.
This study of 160 consecutive fine-needle aspirates of localized hepatic masses analyzed the efficacy of the technique when extended into a multicenter setting. The aspirates were processed and interpreted by a single cytology service, but they were performed, under radiographic imaging, in eight different hospitals by at least 20 radiologists, few of whom had had the opportunity to acquire long-term experience. Of 108 malignancies, 101 were correctly sampled (sensitivity, 93.5%), including 30 primary hepatocellular carcinomas, 70 metastatic tumors, and 1 lymphoma. Specific benign pathologic lesions in 12 cases were amenable to cytodiagnosis. The problem of the remaining 47 samples, which contained exclusively blood, necrotic material, or normal and reactive hepatic constituents, was addressed at length. These were considered "nondiagnostic" samples in the context of aspirating focal masses. The majority had benign lesions on further study, but tumors were found in seven, all of which had been sampling errors, resulting in a negative predictive value of 82.5%. Fine-needle sampling of localized lesions, particularly neoplasms, can thus perform well in transition from single-center studies to more widespread usage in daily practice. Confident reliance on the procedure can be maintained if appropriate radiologic and cytologic facilities exist, provided that the limitations of nonneoplastic aspirates are fully understood.


Recovery of immune complexes from serum-based samples is dependent on the concentration of reactants: heat-inactivated and unheated samples compared by nephelometric assay.
We examined heat-treated and untreated samples for immune complexes (IC) with a nephelometric type Clq binding assay. Curves of absorbance vs. concentration derived from aggregated gamma-globulin in serum samples showed curvilinear behavior, while curves obtained from aqueous samples were highly linear. Curves from heat-treated sera bent upward, while those from unheated sera tended to level off, causing the curves to cross. Heated sera showed greater recovery of IC in the high range and unheated sera greater recovery of IC in the low. Recovery from serum-based samples varied as the concentrations of both Clq and IC in the reaction mixture changed when aqueous curves were used as calibrators. This behavior in serum-based samples seems to be caused by endogenous binders of IC, and may be an important reason for inter-laboratory variation in results from similar samples.


Synthesis and biological properties of C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives as cyclin-dependent kinase inhibitors. Part II.
In this study, C-2, C-8, N-9 substituted 6-(3-chloroanilino)purine derivatives were synthesized and their inhibitory effects on cyclin-dependent kinases (CDK2, 4) as well as their cytotoxicities were evaluated. The effects of substituents at the C-2, C-8, and N-9 positions of the substituted purine were investigated. Among the compounds tested, [6-(3-chloroanilino)-2-(2-hydroxymethyl-4-hydroxypyrrolidyl)-9- isopropylpurine] (4h) was the most active inhibitor of CDK2 with IC50 of 0.3 microM, i.e. a two-fold increased inhibitory activity as compared to roscovitine. Results from structure-activity relationship studies should allow the design of more potent and selective CDK2 inhibitors, which may provide an effective therapy for cancer or other CDK-dependant diseases.


[Association between gene mutation of cytochrome P450 1A1 in exon 7 A4889G locus and susceptibility to endometriosis].
To assess the possible association between gene mutation of cytochrome P450 1A1(CYP1A1) in exon 7 A4889G locus and the susceptibility to endometriosis (EM). Allele specific-polymerase chain reaction method was used to analyze gene mutation in exon 7 A4889G locus of CYP1A1 in 76 patients with endometriosis and 80 healthy controls. The frequency of allele G on A4889G locus of CYP1A1 gene showed a significant difference between the study cohort and the control group (Chi2=7.498, P<0.01), with an odds ratio of 1.957. Statistically significant difference in the frequencies of genotypes AA, AG and GG was observed between the two groups (Chi2=6.915, P<0.05). Individuals with homozygotes for G allele were at higher risk of suffering from EM when compared against those with homozygotes for A allele, the odds ratio being 3.437 (Chi2=5.430, P<0.05). The above results suggest that gene mutation of CYP1A1 in exon 7 A4889G locus might be a genetic susceptible factor of endometriosis. The mutation allele of CYP1A1 gene appears to increase the risk of endometriosis.


Involvement of protein kinase C in platelet-activating factor-stimulated diacylglycerol accumulation in murine peritoneal macrophages.
Incubation of murine peritoneal macrophages with platelet-activating factor (PAF; 1-O-alkyl(C16 + C18)-2-acetyl-sn-glycerol-3-phosphorylcholine) results in the rapid accumulation of [3H]inositol phosphates and sn-1,2-diacylglycerol (DAG) and mobilization of intracellular calcium (Prpic, V., Uhing, R. J., Weiel, J. E., Jakoi, L., Gawdi, G., Herman, B., and Adams, D. O. (1988) J. Cell Biol. 107, 363-372). We have further investigated the relationship of phosphoinositide metabolism to accumulation of DAG and the possible involvement of protein kinase C in the accumulation of DAG in response to PAF. DAG accumulation proceeds at a slower rate than the accumulation of either [3H] inositol 1,4,5-trisphosphate or total [3H]inositol phosphates. Accumulation of DAG from additional precursors is suggested from both an estimation of the mass of total inositol phosphates produced and the accumulation of [3H]choline in response in PAF. Down-regulation of protein kinase C by prolonged pretreatment with phorbol ester or inhibition of the enzyme with sphingosine inhibited the PAF-generated accumulation of DAG at 10 min by approximately 80%. Under the same conditions, no inhibition of PAF-stimulated generation of [3H]inositol 1,4,5-trisphosphate was observed. Similar inhibition was observed when 10 microM ionomycin or 0.1 microM phorbol 12-myristate 13-acetate were used to stimulate accumulation of DAG. The results suggest that PAF stimulates the accumulation of DAG from source other than phosphatidylinositol metabolism in peritoneal macrophages and that this occurs subsequent to the activation of protein kinase C.


Roentgenological investigations of the urethra in the dianosis of prostatic cancer.
The reliability of roentgenological demonstration of the urethra in prostatic cancer has been examined and the advantages of double contrast retrograde urethrocystography and resistance miction-cystourethrography are accentuated. These investigations are indicated in preparation for radiotherapy, operative therapy, transurethral resection and after reduced uroflow.


A "turn off-on" fluorescent nanoprobe consisting of CuInS2 quantum dots for determination of the activity of β-glucosidase and for inhibitor screening.
A fluorescent "turn off-on" nanoprobe is described for highly sensitive and selective determination of the activity of the enzyme β-glucosidase (β-Glu). Firstly, cysteine modified CuInS2 quantum dots (Cys-CuInS2 QDs) were prepared from indium(III) and copper(II) salts and the presence of thiourea. The red fluorescence of the Cys-CuInS2 QDs, with excitation/emission maxima at 590/656 nm, is quenched by Cu(II). However, in the presence of β-Glu and the cyanogenic glycoside, enzymatic hydrolysis leads to the formation of cyanide. The latter competitively binds to Cu(II) owing to its high affinity for cyanide. This restores the fluorescence of the Cys-CuInS2 QDs. Under the optimum conditions, fluorescence increases linearly in the 0.5-700 U·L-1 β-Glu activity range. The detection limit is 0.2 U·L-1. The nanoprobe was applied to analyze spiked soil samples, and satisfactory results were obtained. The average recoveries of β-Glu were in the range of 96-103%, and the RSD was lower than 4.0%. The fluorescent probe can also be used to screen for β-Glu inhibitors as demonstrated for castanospermine as an example. Graphical abstractSchematic representation of the fluorescent nanoprobe for β-glucosidase activity detection and inhibitor screening by taking advantage of the fluorescence (FL) "turn-off" and "turn-on" feature of cysteine capped CuInS2 quantum dots (Cys-CuInS2 QDs).


Single-Incision Anatomic Repair Technique for Distal Biceps Tendon Rupture Using Tunneling Device.
Distal biceps tendon ruptures are uncommon and generally occur in men aged 30 to 50 years in their dominant arm as a result of a strong eccentric load. Numerous surgical exposures and methods of fixation exist for repair of a ruptured distal biceps tendon. The goal of surgical management is to restore the anatomic footprint of the biceps tendon on the radial tuberosity to maximize flexion strength, supination strength, and muscle endurance. When compared with 2-incision repair techniques, single-incision repairs historically may not have restored the anatomic footprint of the distal biceps. Single-incision repair with the ArthroTunneler is a safe and effective technique that provides the anatomic restoration of a 2-incision approach with the decreased complication profile of a single-incision approach and does not require suture anchors, buttons, screws, or other implants.


Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide.
Groups of F344 rats of each sex were exposed to either ethylene oxide (ETO) vapor (concentrations of 100, 33 or 10 ppm) or to room air for 6 hours daily, 5 days per week, for up to 2 years. Three representative sections of the brain from each rat were evaluated. Twenty-three primary brain tumors were found, two of which were in control animals. Increased numbers of brain tumors were seen in 100 ppm and 33 ppm ETO exposed male and female rats. Significant trend analyses were found for both males and females, indicating that, under the conditions of this study, ETO exposure above 10 ppm was related to the development of these brain tumors.


Impact of preoperative chronic lung disease on survival after surgical aortic valve replacement.
An increasing number of patients requiring surgical aortic valve replacement (SAVR) present with chronic pulmonary obstructive disease (COPD). The purpose of this study was to compare patients who had a range of COPD from normal to severe and were undergoing SAVR. Retrospective review of 2,379 patients undergoing SAVR ± coronary artery bypass grafting (CABG) from January 2002 to April 2012 at a US academic institution was performed. COPD was defined according to the Society of Thoracic Surgeons (STS) adult cardiac database: normal (forced expiratory volume [FEV] > 75% predicted), mild (FEV in 1 second [FEV1] 60%-75%), moderate (FEV1 50%-59%), and severe (FEV1 < 50%). Multivariable logistic and Cox regression methods were used to determine independent association between COPD and short- and long-term outcomes. Selection bias adjustment was achieved using the STS predicted risk of mortality (PROM). Adjusted odds ratios (AORs) and adjusted hazard ratios (AHR) were calculated using the normal lung function group as the reference. Kaplan-Meier curves were created to estimate long-term survival. One thousand five hundred seventeen of 2,379 patients (63.8%) had isolated SAVR, whereas 862 of 2,379 (36.2%) patients underwent SAVR + CABG. Preoperative COPD was common among patients (21.9%) undergoing SAVR ± CABG and included 332 (14.0%) patients with mild COPD, 89 (3.7%) patients with moderate COPD, and 101 (4.2%) patients with severe COPD. Unadjusted in-hospital mortality rose significantly with COPD class, from 3.9% for those with no COPD to 9.6% to patients with severe COPD. After adjustment, in-hospital mortality was not statistically different in normal patients and in those with COPD. In contrast, when compared with normal patients, adjusted long-term survival was worse across levels of COPD: mild (AHR, 1.70; p < 0.001), moderate (AHR, 2.25; p < 0.001), and severe (AHR, 2.28; p < 0.001). Preoperative COPD is common in the SAVR population and is associated with diminished long-term but not short-term survival.


Decrease in Ca-ATPase activity in aged synaptosomal membranes is not associated with changes in fatty acyl chain dynamics.
We have examined lipid peroxidation (LPO) and fatty acid acyl chain dynamics in synaptosomal membranes isolated from aged rat (Fischer 344 x Brown Norway F1 hybrids) brains, correlating these results with measurements of enzymatic activity of the synaptic plasma membrane Ca2(+)-ATPase (PMCA). Calcium-dependent ATPase activity in these membranes exhibits progressive decreases with a maximal loss of activity with age of approximately 35%. The sensitivity of this membrane-bound ion transporter to the lipid composition of the surrounding membrane, as well as the high abundance of oxidatively sensitive polyunsaturated fatty acyl chains in synaptosomal membranes, suggests that this age-related loss in catalytic turnover may result from LPO-mediated protein modification and/or changes in the physical structure of the bilayer. However, high-performance liquid chromatography analysis of 2,4-dinitrophenylhydrazone derivatives reveals no significant age-related increases in the content of reactive aldehydes (malondialdehyde, formaldehyde, acetaldehyde or acetone) which comprise breakdown products of lipid peroxidation. Electron paramagnetic resonance measurements employing 5- and 12-stearic acid spin labels with the nitroxide reporter groups at two depths in the bilayer were used to assess the fatty acyl chain dynamics (fluidity) of synaptosomal membranes. The resulting spectra demonstrate anisotropic lipid dynamics of two populations of lipids, i.e. lipids in direct association with membrane proteins (boundary lipids) and bulk lipids that do not directly associate with proteins. The nanosecond dynamics of both lipid populations is unaltered with age indicating that any compositional changes occurring with age are insufficient to result in alterations in bilayer fluidity relevant to PMCA activity. Thus, the observed age-related decline in PMCA activity may be explained by direct modification of membrane protein.


Association of baseline Life's Essential 8 score and trajectories with carotid intima-media thickness.
We aimed to examine the association between the baseline Life's Essential 8 (LE8) score and LE8 score trajectories with the continuous carotid intima-media thickness (cIMT) as well as the risk of high cIMT. The Kailuan study has been an ongoing prospective cohort study since 2006. A total of 12,980 participants who completed the first physical examination and cIMT detection at follow-up without a history of CVD and missing data on the component of LE8 metrics in or before 2006 were finally included in the analysis. The LE8 score trajectories were developed from 2006 to 2010 using trajectory modeling of the SAS procedure Proc Traj. The measurement and result review of the cIMT were performed by specialized sonographers using standardized methods. According to quintiles of baseline LE8 score, participants were categorized into five groups: Q1, Q2, Q3, Q4, and Q5. Similarly, based on their LE8 score trajectories, they were classified into four groups: very low-stable group, low-stable group, median-stable group, and high-stable group. In addition to continuous cIMT measurement, we determined the high cIMT based on the age (by 5 years) and sex-specific 90th percentile cut point. To address aims 1 and 2, the association between baseline/trajectory groups and continuous cIMT/high cIMT was assessed by using SAS proc genmod to calculate β, relative risk (RR), and 95% confidence intervals (CI). A total of 12,980 participants were finally included in aim 1, and 8,758 participants met aim 2 of the association between LE8 trajectories and cIMT/high cIMT. Compared with the Q1 group, the continuous cIMT for Q2, Q3, Q4, and Q5 groups were thinner; the other groups had a lower risk of high cIMT. For aim 2, the results indicated that compared with a very low-stable group, the cIMT for the low-stable group, the median-stable group, and the high-stable group were thinner (-0.07 mm [95% CI -0.10~0.04 mm], -0.10 mm [95% CI -0.13~-0.07 mm], -0.12 mm [95% CI -0.16~-0.09 mm]) and had a lower risk of high cIMT. The RR (95% CI) for high cIMT was 0.84 (0.75~0.93) in the low-stable group, 0.63 (0.57~0.70) in the median-stable group, 0.52 (0.45~0.59) in the high-stable group. In summary, our study revealed that high baseline LE8 scores and LE8 score trajectories were associated with lower continuous cIMT and attenuated risk of high cIMT.


The subjectivist interpretation of probability and the problem of individualisation in forensic science.
This paper presents and discusses further aspects of the subjectivist interpretation of probability (also known as the 'personalist' view of probabilities) as initiated in earlier forensic and legal literature. It shows that operational devices to elicit subjective probabilities - in particular the so-called scoring rules - provide additional arguments in support of the standpoint according to which categorical claims of forensic individualisation do not follow from a formal analysis under that view of probability theory.


Anatomical variations in the articular masses of the seventh cervical vertebra simulating fracture.
The articular masses of the seventh cervical vertebra are variable in that about 87% of patients the superior and inferior facets are not parallel. IN ADDITION, THE INFERIOR FACETS ARE OFTEN POSTERIORLY PLACED IN RELATION TO THE SUPERIOR FACETS. These factors contribute to a notched undulating articular mass seen bilaterally on the lateral and oblique projections simulating fracture. The difference in inclination of the superior and inferior facets may cause either the superior or inferior facets to be obscured on the AP VIEW ANGLED CAUDAD--THE POSTERIOR ARCH VIEW. Since these anomalies are bilateral and fractures are almost always unilateral, the differentiation is most easily made on this posterior arch view.


Qualitative diagnosis of hepatocellular carcinoma by contrast enhanced ultrasonography using Coded Harmonic Angio with Levovist.
We attempted to evaluate diagnosis and characterization and to access therapeutic effects in cases of hepatocellular carcinoma (HCC) by contrast enhanced ultrasound (CEUS) using Coded Harmonic Angio (CHA) with Levovist, an intravenous ultrasound contrast agent. Fifty-seven HCC foci in 39 patients, including 37 HCC foci in 28 patients before and after transcatheter arterial chemoembolization or radio frequency ablation, were examined by CEUS using the CHA mode, which is under development. This mode uses digitally encoded pulse sequences that identify and suppress nonmoving tissue signals and enhance contrast signals from Levovist in a gray-scale format. In all cases, abundant tortuous intratumoral blood flow was visualized in the early vascular phase by continuous transmission, while tumor stain was recognized by consecutive 1-to-2 second intermittent transmission. Residual tumor area after treatment was also clearly depicted by intratumoral blood flow and partial enhancement. CEUS using CHA with Levovist is likely to become important in the qualitative diagnosis of hepatic tumor and to improve the efficacy of treatment for HCC.


A novel anti-Alzheimer's disease drug, ladostigil neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor.
The novel therapeutic strategy in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate]. Ladostigil combines neuroprotective effects with monoamine oxidase-A and -B and cholinesterase inhibitory activities in a single molecule, presently in a Phase IIb clinical trial and intended for the treatment of Alzheimer's disease, and dementia comorbid with extrapyramidal disorders and depression. This chapter will discuss the preclinical scientific evidence for the therapeutic potential use of ladostigil in the clinic and molecular signaling pathways that are considered to be involved in the molecular activities of the drug.


A screen for conserved sequences with biased base composition identifies noncoding RNAs in the A-T rich genome of Plasmodium falciparum.
Noncoding RNAs (ncRNAs) such as snRNAs, snoRNAs and microRNAs play important roles in transcription and translation control. These ncRNAs have yet to be discovered in the malarial parasite Plasmodium falciparum, an organism in which these basic biological processes are poorly understood. Inspired by a report by Klein et al., we initiated a bioinformatics screen to uncover several candidate ncRNAs from the parasite genome using two simple criteria: first, elevated GC content in the highly A-T rich intergenic regions of the P. falciparum genome and second, conservation of sequence homology between malaria parasite species. We show that all the annotated tRNAs can be successfully identified in our screen as well as several new candidates that show homology to snRNAs and snoRNAs, and ten candidate ncRNAs of unknown function. Three of the candidate snRNAs, a predicted selenocysteine tRNA and two candidates of unknown function are expressed in asexual stage parasites, further validating the screen. With these results, the biological processes underlying RNA-mediated regulation of transcription, translation and splicing can be studied in an important human pathogen.


Pain among older adults with gastrointestinal malignancies- results from the cancer and aging resilience evaluation (CARE) Registry.
The impact of pain on functional status and mental health among older adults with cancer is a relevant, yet understudied. We sought to identify the prevalence of pain at diagnosis in older adults with gastrointestinal (GI) malignancies and evaluate the association of pain with functional status limitations, cognition, and mental health. This prospective cross-sectional study included older adults (age ≥ 60) with GI cancers enrolled in the CARE Registry. Pain measured in numeric rating scale from 0 to 10. We utilized the literature based cutoff for moderate-severe as ≥ 4. Logistic regression used to assess differences in functional status, falls, cognitive complaints, and depression/anxiety associated with moderate/severe pain, adjusted for sex, race, education, ethnicity, marital status, cancer type/stage, and treatment phase. Our cohort included 714 older adults with an average mean age of 70 years and 59% male. Common diagnoses included colorectal (27.9%) and pancreatic (18%). A total of 43.3% reported moderate/severe pain. After multivariate adjusting for covariates, participants with self-reported moderate/severe pain were more likely to report limitations in instrumental activities of daily living (adjusted odds ratio [aOR] 4.3 95% confidence interval [CI] 3.1-6.1, p < .001), limitation in activities of daily living (aOR 3.2 95% CI 2.0-5.1, p < .001), cognitive complaints (aOR 2.9 95% CI 1.4-6.0, p < .004), anxiety (aOR 2.2 95% CI 1.4-3.4, p < 0.01), and depression (aOR 3.7 95% CI 2.2-6.5, p < .001). Pain is common among older adults with GI cancers and is associated with functional status limitations, cognitive complaints, and depression/anxiety. Strategies to reduce pain and minimize its potential impact on function and mental health warrant future research.


First record of Neolindus Scheerpeltz from French Guiana (Coleoptera, Staphylinidae, Paederinae), with a key to males.
The genus Neolindus Scheerpeltz, 1933, of the tribe Cylindroxystina Bierig, 1943, is recorded from French Guiana for the first time. Two new species, Neolindus irmlerisp. n. and Neolindus hermanisp. n., are described and illustrated. A key to males of Neolindus is provided.


Influence of dual-task on sit-to-stand-to-sit postural control in Parkinson's disease.
Postural control deficits are the most disabling aspects of Parkinson's disease (PD), resulting in decreased mobility and functional independence. The aim of this study was to assess the postural control stability, revealed by variables based on the centre of pressure (CoP), in individuals with PD while performing a sit-to-stand-to-sit sequence under single- and dual-task conditions. An observational, analytical and cross-sectional study was performed. The sample consisted of 9 individuals with PD and 9 healthy controls. A force platform was used to measure the CoP displacement and velocity during the sit-to-stand-to-sit sequence. The results were statistically analysed. Individuals with PD required greater durations for the sit-to-stand-to-sit sequence than the controls (p < 0.05). The anteroposterior and mediolateral CoP displacement were higher in the individuals with PD (p < 0.05). However, only the anteroposterior CoP velocity in the stand-to-sit phase (p = 0.006) was lower in the same individuals. Comparing the single- and dual-task conditions in both groups, the duration, the anteroposterior CoP displacement and velocity were higher in the dual-task condition (p < 0.05). The individuals with PD presented reduced postural control stability during the sit-to-stand-to-sit sequence, especially when under the dual-task condition. These individuals have deficits not only in motor performance, but also in cognitive performance when performing the sit-to-stand-to-sit sequence in their daily life tasks. Moreover, both deficits tend to be intensified when two tasks are performed simultaneously.


Comparison of embryo implantation in Wistar rats that underwent ovarian stimulation using exogenous gonadotropins associated with cetrorelix acetate or leuprolide acetate.
To compare embryo implantation in Wistar rats submitted to ovarian stimulation using recombinant FSH (rFSH) with cetrorelix acetate or leuprolide acetate. Experimental study. Faculty of medicine animal facility. Fifty-six female Wistar rats with normal estrus cycles and 30 male. Ovarian stimulation and laparotomy (by the day 13 of gestation). Embryo implantation. The female rats were subdivided into four groups: group 1, medicated with rFSH, hCG, and cetrorelix acetate; group 2, medicated with rFSH, hCG, and leuprolide acetate; group 3, medicated with rFSH and hCG; and group 4, in which only saline solution was administered. The female rats were mated with fertile male rats on the day of hCG administration with copulation confirmed through cytologic vaginal analysis. The females were killed on the 13th day of gestation. After laparotomy, comparison and identification was done regarding the numbers of corpora lutea and embryo implantations and gestation rates. Group 1 presented lower numbers of corpora lutea and embryo implantations in comparison to the other groups (P<.05). A difference was not found in the gestation rates between the groups. The number of embryo implantations in Wistar rats medicated with rFSH and cetrorelix acetate is lower than that of rats medicated with rFSH and leuprolide acetate.


The effects of attenuation of frequency segments on binaural localization of sound.
Perceived location of tonal stimuli d and narrow noise bands presented in two-dimensional space varies in an orderly manner with changes in stimulus frequency. Hence, frequency has a referent in space that is most apparent during monaural listening. The assumption underlying the present study is that maximum sound pressure level measured at the ear canal entrance for the various frequencies serves as a prominent spectral cue for their spatial referents. Even in binaural localization, location judgments in the vertical plane are strongly influenced by spatial referents. We measured sound pressure levels at the left ear canal entrance for 1.0-kHz-wide noise bands, centered from 4.0 kHz through 10.0 kHz, presented at locations from 60 degrees through -45 degrees in the vertical plane; the horizontal plane coordinate was fixed at -90 degrees. On the basis of these measurements, we fabricated three different bandstop stimuli in which differently centered 2.0-kHz-wide frequency segments were filtered from a broadband noise. Unfiltered broadband noise served as the remaining stimulus. Localization accuracy differed significantly among stimulus conditions (p < .01). Where in the vertical plane most errors were made depended on which frequency segment was filtered from the broadband noise.


Demonstration of membrane-associated phospholipase A2 in cultivated heart muscle cells by immunogold-technique in surface replicas.
Recently we produced mAb's to phospholipase A2 (PIA2) from bee venom for different purposes (allergen-identification and -standardization). Obviously one of these monoclonal antibodies "5D5" binds to a conserved (cross reactive) epitope of membrane PIA2 of intact cells. In this study we demonstrate binding of 5D5 to membrane associated phospholipase A2 of rat heart muscle cells by means of two-step immunogold technique in combination with replica technique.


[Concepts to support dynamic updating processes of guidelines and their practical implementation-Systematic literature review].
Clinical practice guidelines (CPG), which are crucial for evidence-based healthcare, should be kept up to date, especially on topics where emerging evidence could modify one of the recommendations with implications for the healthcare service; however, an updating process, which is practicable for guideline developers as well as users represents a challenge. This article provides an overview of the currently discussed methodological approaches for the dynamic updating of guidelines and systematic reviews. As part of a scoping review, a literature search was conducted in the databases MEDLINE, EMBASE (via Ovid), Scopus, Epistemonikos, medRxiv, as well as in study and guideline registers. Concepts on the dynamic updating of guidelines and systematic reviews or dynamically updated guidelines and systematic reviews or their protocols published in English or German were included. The publications included most frequently described the following main processes that must be adapted in dynamic updating processes 1) the establishment of continuously working guideline groups, 2) networking between guidelines, 3) the formulation and application of prioritization criteria, 4) the adaptation of the systematic literature search and 5) the use of software tools for increased efficiency and digitalization of the guidelines. The transformation to living guidelines requires a change in the needs for temporal, personnel and structural resources. The digitalization of guidelines and the use of software to increase efficiency are necessary instruments, but alone do not guarantee the realization of living guidelines. A process in which dissemination and implementation must also be integrated is necessary. Standardized best practice recommendations on the updating process are still lacking.