Coronary revascularization in women.
Historically, mortality rates have been higher in women than in men for both PCI and CABG. Recent registries and studies have shown that women have mortality rates similar to men after correcting for age and comorbidities. The gender gap is narrowing with respect to outcomes for women with both PCI and CABG. Revascularization with PCI and CABG in women with stable angina (SA), unstable angina (UA), non ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI) will all be reviewed in light of the most recent studies and registries.


Nonoperative treatment for pain sensitization in patients with low back pain: protocol for a systematic review.
Low back pain is a disability that occurs worldwide. It is a heterogeneous disorder that affects patients with dominant nociceptive, neuropathic, and central sensitization pain. An important pathophysiology of low back pain involves pain sensitization. Various nonoperative interventions are available for treatment, but there is inconclusive evidence on the effectiveness of these interventions for pain sensitization, leading to arbitrary nonoperative treatments for low back pain. We will conduct a systematic review of RCTs evaluating the effectiveness and safety of nonoperative treatment for pain sensitization in patients with low back pain. The primary outcomes will be static quantitative sensory testing, dynamic quantitative sensory testing, and pain algometry. The secondary outcome will be adverse events. We will search the PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Library databases. Two independent authors will screen the titles and abstracts, review full texts, extract data, assess the risk of bias, and evaluate the quality of evidence. We will qualitatively and quantitatively synthesize the results using a random effects model for meta-analysis. This systematic review aims to provide evidence regarding which treatment, if any, provides the greatest benefit for pain sensitization and safety among patients with low back pain. Evidence synthesized from this systematic review will inform clinical practice and further research. Since there is still a small amount of research, additional studies might need to be conducted in the future. Submitted to PROSPERO on March 20, 2021, CRD42021244054.


Stability of food insecurity status in paediatric primary care.
The American Academy of Pediatrics recommends screening for food insecurity (FI) at all well-child visits due to well-documented negative effects of experiencing FI in childhood. Before age 3, children have twelve recommended primary care visits at which screening could occur. Little is known regarding the stability of FI status at this frequency of screening. Data derived from electronic health records were used to retrospectively examine the stability of household FI status. Age-stratified (infant v. toddler) analyses accounted for age-based differences in visit frequency. Regression models with time since last screening as the predictor of FI transitions were estimated via generalised estimating equations adjusting for age and race/ethnicity. A paediatric primary care practice in Philadelphia. 3451 distinct patients were identified whose health record documented two or more household FI screens between April 1, 2012 and July 31, 2018 and were aged 0-3 years at first screen. Overall, 9·5 % of patients had a transition in household FI status, with a similar frequency of transitioning from food insecure to secure (5·0 %) and from food secure to insecure (4·5 %). Families of toddlers whose last screen was more than a year ago were more likely to experience a transition to FI compared with those screened 0-6 months prior (OR 1·91 (95 % CI 1·05, 3·47)). Screening more than annually may not contribute substantially to the identification of transitions to FI.


[S100B level and cognitive dysfunction after robotic-assisted laparoscopic radical prostatectomy procedures: a prospective observational study].
The present study investigated the association between Postoperative Cognitive Dysfunction (POCD) and increased serum S100B level after Robotic-Assisted Laparoscopic Radical Prostatectomy (RALRP). The study included 82 consecutive patients who underwent RALRP. Serum S100B levels were determined preoperatively, after anesthesia induction, and at 30 minutes and 24 hours postoperatively. Cognitive function was assessed using neuropsychological testing preoperatively and at 7 days and 3 months postoperatively. Twenty-four patients (29%) exhibited POCD 7 days after surgery, and 9 (11%) at 3 months after surgery. Serum S100B levels were significantly increased at postoperative 30minutes and 24 hours in patients displaying POCD at postoperative 7 days (p = 0.0001 for both) and 3 months (p = 0.001 for both) compared to patients without POCD. Duration of anesthesia was also significantly longer in patients with POCD at 7 days and 3 months after surgery compared with patients without POCD (p = 0.012, p = 0.001, respectively), as was duration of Trendelenburg (p = 0.025, p = 0.002, respectively). Composite Z score in tests performed on day 7 were significantly correlated with duration of Trendelenburg and duration of anesthesia (p = 0.0001 for both). S100B increases after RALRP and this increase is associated with POCD development. Duration of Trendelenburg position and anesthesia contribute to the development of POCD. Clinicaltrials.gov (N° NCT03018522).


The disposition of tert-butyl-D-serine in the rat.
1. Following intravenous administration of 14C-tert-butyl-D-serine to rats, radioactivity was eliminated rapidly via the kidneys. 2. One metabolite was detected in urine and was identified as the N-acetyl derivative of tert-butyl-serine. 3. Elimination was more rapid in female than male rats.


Temporal summation in the achromat.
We investigated temporal summation of the rods in a complete achromat, who lacks cone vision. Critical duration (tc) was estimated both at the achromat's preferred area of fixation and at an area 12 deg laterally in the nasal visual field. Comparable tc determinations were made in a normal trichromat. At background luminances of 0.0 and 0.6 scot. td, where the rods mediate detection, the values of tc were similar for the achromat and the normal. At a luminance of 813 scot. tds, however, where the middle-wavelength sensitive cones mediate detection in the trichromat, the tc for the achromat was much longer than that for the trichromat.


Designing a New Payment Model for Oral Care in Seniors.
With 10,000 baby boomers turning 65 every day, many will be on fixed incomes and will lose dental insurance upon retirement. This article presents why a dental benefit in Medicare might save the US government money, and who would likely benefit. It details an approach to estimating costs of inclusion of a dental benefit in Medicare, and compares the proposed approach to existing proposals. Additionally, the ensuing steps needed to advance the conversation to include oral health in healthcare for the aged will be discussed.


ADHD in adults with recurrent depression.
Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life. In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression. 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication. ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups. Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered.


Systematic Functional Dissection of Common Genetic Variation Affecting Red Blood Cell Traits.
Genome-wide association studies (GWAS) have successfully identified thousands of associations between common genetic variants and human disease phenotypes, but the majority of these variants are non-coding, often requiring genetic fine-mapping, epigenomic profiling, and individual reporter assays to delineate potential causal variants. We employ a massively parallel reporter assay (MPRA) to simultaneously screen 2,756 variants in strong linkage disequilibrium with 75 sentinel variants associated with red blood cell traits. We show that this assay identifies elements with endogenous erythroid regulatory activity. Across 23 sentinel variants, we conservatively identified 32 MPRA functional variants (MFVs). We used targeted genome editing to demonstrate endogenous enhancer activity across 3 MFVs that predominantly affect the transcription of SMIM1, RBM38, and CD164. Functional follow-up of RBM38 delineates a key role for this gene in the alternative splicing program occurring during terminal erythropoiesis. Finally, we provide evidence for how common GWAS-nominated variants can disrupt cell-type-specific transcriptional regulatory pathways.


Formic acid enhanced effective degradation of methyl orange dye in aqueous solutions under UV-Vis irradiation.
Developing efficient technologies to treat recalcitrant organic dye wastewater has long been of great research and practical interest. In this study, a small molecule, formic acid (FA), was applied as a process enhancer for the degradation of methyl orange (MO) dye as a model recalcitrant organic pollutant in aqueous solutions under the condition of UV-Vis light irradiation and air aeration at the ambient temperature of 25 °C. It was found that the decolouration of the dye solutions can be rapidly achieved, reducing the time, for example, from around 17.6 h without FA to mostly about less than 2 h with the presence of FA. The mineralization rate of MO dye reached as high as 81.8% in 1.5 h in the case of initial MO dye concentration at 25 mg L(-1), which is in contrast to nearly no mineralization of the MO dye for a similar system without the FA added. The study revealed that the generation of the H2O2 species in the system was enhanced and the produced OH radicals effectively contributed to the degradation of the MO dye. Process parameters such as the initial concentration of MO dye, FA dosage and solution pH were all found to have some effect on the degradation efficiency under the same condition of UV-Vis light irradiation and air aeration. The MO dye degradation performance was found to follow a first-order reaction rate to the MO dye concentration in most cases and there existed a positive correlation between the reaction rate constant and the initial FA concentration. Compared to the traditional H2O2/UV-Vis oxidation system, the use of FA as a process-enhancing agent can have the advantages of low cost, easy availability, and safe to use. The study hence demonstrates a promising approach to use a readily available small molecule of FA to enhance the degradation of recalcitrant organic pollutants, such as MO dye, especially for their pre-treatment.


Assessment of phytoplankton class abundance using in vivo synchronous fluorescence spectra.
In this study the feasibility of using the in vivo synchronous fluorescence spectra (SFS) of phytoplankton samples for determining the relative abundance of specific classes of phytoplankton was investigated. In total, 405 SFS of nine phytoplankton species cultivated under different conditions were measured and evaluated. First, principal component analysis (PCA) was used to obtain nine representative spectra, and three feature spectrum bands at 200-235, 310-335, and 355-585 nm of SFS were found to have a better discriminatory capability. The nine phytoplankton species were spectrographically sorted into six classes. Second, a relationship between the chlorophyll a (chla) concentration of phytoplankton extracts and the in vivo SFS intensity was found; thus the corresponding phytoplankton class abundance can be expressed by the concentration of standard chla. For this data set, the detection limit ranged 1.02-6.89 microg/L chla for different classes. Finally, qualitative and quantitative analyses of 30 mixtures of phytoplankton were carried out using the nonnegative least square regression (NNLS) method. The dominant phytoplankton classes could be identified while the qualitative recognition correctness rate was 88% and the quantitative standard deviation with fluorometrically determined chla was -0.14-0.04. Hence, it was possible to estimate the abundance of dominant phytoplankton classes.


Malignant tumors of temporal bone in Songklanagarind Hospital: management and results.
To evaluate the clinical course and treatment in patients with carcinoma of temporal bone The authors retrospectively reviewed the patients treated for primary carcinoma of temporal bone in Otolaryngology Head and Neck Surgery department, at Songklanagarind Hospital between 2002 and 2013. Thirty-two patients, including 10 cancer ofpinna and 22 carcinoma of the External Auditory Canal (EAC), were included in this study. The treatment modality was lateral temporal bone resection and postoperative radiotherapy and palliative radiotherapy for advanced stage tumors (T4). Twelve patients were excluded due to difference in modality. Twenty patients remained in the study. Twenty patients had carcinoma of EAC, early stage (T1, T2) 36.4% and late stage (T3, T4) 63.6%. The overall survival of this group was 46.9%. The median survival period was 22 months (0.286-0.769, 95% CI). The complete resection is the treatment of choice in primary cancer of temporal bone. Postoperative radiotherapy for a microscopic residual tumor is highly recommended. The most important thing is early diagnosis.


Microtox solid phase test: Effect of diluent used in toxicity test.
Microtox solid phase test is an acute toxicity test for solid matrices based on inhibition of natural bioluminescence of the marine bacterium Vibrio fischeri. Protocols developed to overcome the effects of confounding factors are proposed in the literature that differs by important practical and methodological issues. This work focused on diluents used for sediment resuspension and dilution. Two artificial seawaters, one natural seawater and two phosphate buffer solutions, were compared. The results showed that toxicity data obtained using different diluents were not comparable and that test sensitivity is highest using 0.1M phosphate buffer solution. The effects of medium on test organism were also investigated, in order to verify the capacity of media to maintain bioluminescence. The results underlined the importance of pH and Eh to explain the observed differences in toxicity.


Arthroscopic repair of anterior glenohumeral instability and rotator interval lesions.
As the techniques and instrumentation for shoulder arthroscopy continue to improve and evolve, its role in the treatment of anterior shoulder instability progresses also. With more surgeons becoming familiar with these advancements and techniques, arthroscopic stabilization results continue to improve and help arthroscopy become the "preferred method" for the treatment of shoulder instability. Adjunct procedures such as closure of the rotator interval also are helping to improve our arthroscopic results and are an important improvement in our understanding of the pathoanatomy of shoulder instability repairs.


Stress, glucocorticoids and structural plasticity of the hippocampus.
Sustained stress can have numerous pathophysiological effects. Adrenal glucocorticoid hormones are principal effectors in the stress response. They have profound effects on mood and behavior and affect neurochemical transmission and neuroendocrine control. We have used the experimental paradigm of chronic psychosocial stress in tree shrews to investigate the impact of aversive social encounters on brain structures. Chronic stress in male tree shrews which is accompanied by constantly elevated levels of glucocorticoids leads to structural changes in hippocampal neurons. Whereas dendritic atrophy of hippocampal pyramidal neurons and impairment of neurogenesis in the dentate gyrus could be demonstrated in chronically stressed tree shrews, a loss of hippocampal neurons was not observed in this animal model. The present review summarizes recent results on the question which structural changes occur during chronic stress in neurons of the brain and whether glucocorticoids might be responsible for such stress effects. The role of transmitter systems in stress-related neuronal plasticity is also discussed.


Ecotoxicity and biodegradability in soil and aqueous media of lubricants used in forestry applications.
The work presented in this article focuses on the environmental impact of hydraulic fluids used in forestry. Migration and biodegradability of three biolubricants and a mineral lubricant were monitored in two forest soils and in a liquid medium. These studies proved that biolubricants were easily degradable products and showed ultimate biodegradability rates significantly higher than those of the fluid of mineral origin, specially in a soil environment. This superiority was even greater when fluid behaviour was observed after 1000h of use. Ecotoxicity test enabled the classification and comparison of biolubricants and showed that toxicity levels of the biolubricants were never high however, even after use, as compared to petroleum-based fluid.


EMG responses evoked by the termination of galvanic (DC) vestibular stimulation: 'off-responses'.
Vestibular responses in soleus electromyography (EMG) evoked by the sudden onset of galvanic (DC) stimulation ('on-responses') have been described in detail previously. The aim of the present study was to describe responses in soleus triggered by the termination of galvanic stimulation ('off-responses'). In 10 healthy human subjects, we studied responses to transmastoid (bilateral) stimuli of 200 ms and 2 s average duration and 3 or 4 mA intensity. We obtained both on- and off-responses using the same raw data. EMG activity was recorded onto tape while current pulses of systematically varying duration were delivered. Averaged on-responses were obtained by triggering from the beginning of the current pulses. Averaged off-responses were obtained by triggering from the termination of the current pulses. Short-latency (SL) and medium latency (ML) off-responses were both obtained in all but one study. The SL and the ML components of the off-responses were present and had similar latencies and amplitudes, but opposite excitability, to the on-responses obtained with the same stimuli. Off-responses to galvanic vestibular stimulation can be recorded from soleus EMG. Our findings imply that vestibular SL and ML reflex responses in the legs are dependent on the change in the rate of vestibular nerve discharge, not its absolute level. Both on- and off-responses have properties appropriate to a role in maintaining body stability.


Alcoholic cardiomyopathy versus chronic myocarditis--immunohistological investigations with LCA, CD3, CD68 and tenascin.
Dilated cardiomyopathy (DCM) is a disorder of unknown aetiology characterized by the left ventricular cavity enlargement and wall thinning associated with reduced left ventricular wall motion. DCM in chronic alcoholics is supposed to be caused by alcohol induced myocardial damage (alcoholic cardiomyopathy). Nevertheless, cardiotropic viruses, such as enteroviruses have long been suspected as causative agents for at least some forms of DCM. In the present study, 13 cases of DCM in chronic alcoholics were investigated with qualification and quantification of infiltrating leucocytes using immunohistological antibodies against leucocyte common antigen (LCA), T-lymphocytes (CD3) and macrophages (CD68). In addition, the expression of tenascin, playing a role in the initiation of fibrotic changes, was examined. All antigens were known to be possibly enhanced in cases of chronic myocarditis. Using these immunohistological techniques, 2 out of 13 cases had evidence for chronic inflammatory myocardial alterations in the sense of lymphocytic infiltrates (>2.0 CD3 T-lymphocytes/visual field at 400 x (HPF); >7 CD3 T-lymphocytes per mm(2)). These cases were diagnosed as having inflammatory cardiomyopathy. The other cases without myocardial inflammation were diagnosed as idiopathic/alcoholic DCM.


Neck and back pain: Differences between patients treated in primary and specialist health care.
To describe and compare patients with neck and back pain treated by physiotherapists in primary healthcare (PHC) and in departments for physical medicine and rehabilitation in specialist healthcare (SHC) in Norway. Cross-sectional study using data from the FYSIOPRIM database in PHC and the Norwegian Neck and Back Registry in SHC. Neck and back pain patients in the period 2014-18 aged ≥ 18 years were included. Demographics, lifestyle and clinical factors were investigated. A total of 8,125 patients were included: 584 in PHC and 7,541 in SHC. Mean age was 47.1 and 45.5 years, respectively, with more females in PHC (72% vs 56%). Low levels of education and physical activity, high workload and receiving social benefits were associated with treatment in SHC. Treatment in SHC was most common from 3 to 12 months' pain duration. Higher pain intensity and lower health-related quality of life were found in patients treated in SHC, no differences were found for psychological distress. This is the first study comparing register data in patients with neck and back pain treated in PHC and SHC. Differences were found in pain and health-related quality of life, but levels of psychological distress were similar between patients treated in PHC and those treated in SHC.


Phosphorylation of the human erythrocyte glucose transporter by protein kinase C: localization of the site of in vivo and in vitro phosphorylation.
1. The human erythrocyte glucose transporter was phosphorylated in vitro by protein kinase C. 2. Tryptic cleavage of phosphorylated native transporter produced two major unphosphorylated membrane-embedded fragments weighing 23 and 19 kDa and released numerous water-soluble peptides. 3. Ion-exchange FPLC of the soluble tryptic peptides resolved the mixture into two phosphopeptide peaks. 4. Tryptic digestion of glucose transporter that was phosphorylated in vivo in response to phorbol esters produced soluble phosphopeptides that eluted at identical salt concentrations. 5. Proteolytic digestion and peptide mapping of the transporter revealed that the site(s) of phosphorylation lie within the large cytoplasmic domain that bisects the molecule.


Reference values for trace essential elements in the whole blood and serum samples of the adult Serbian population: significance of selenium deficiency.
This study was aimed to determine reference values (RVs) for the manganese (Mn), copper (Cu), zinc (Zn), and selenium (Se) in the whole blood (B) and serum (S) samples of the Serbian population. Blood specimens were collected from healthy persons (n = 295; women/men ratio = 149/146; mean age: 42 ± 2 years). The RVs were calculated as lower limit (LL) and upper limit (UL) of the 95% confidence interval (CI) and were expressed as percentiles (P) in the range from P2.5 to P97.5. The influences of sex, age, and smoking habits on element profiles were considered. It was found that the contents of B-Cu and S-Cu were higher in women, while the contents of B-Zn and S-Zn were higher in men. Both trace elements were significantly increased in a group of persons above 40 when compared to a younger persons (≤ 40 years). According to smoking habits, increased content was found only for S-Mn in the nonsmoker's group (p < 0.05). Comparing our results to the results reported in other population groups worldwide, the Serbian population had significantly reduced content of Se in both types of samples. This finding could highlight the deficiency of Se in the investigated Serbian population and could contribute to the better understanding of the molecular basis for the increased incidence of thyroid and other diseases in which selenium plays a key role.


A prognostic and immunotherapeutic predictive model based on the cell-originated characterization of tumor microenvironment in lung adenocarcinoma.
Tumor microenvironment (TME) plays a crucial role in predicting prognosis and response to therapy in lung cancer. Our study established a prognostic and immunotherapeutic predictive model, the tumor immune cell score (TICS), by differentiating cell origins in lung adenocarcinoma (LUAD) based on the transcriptomic data of 2,510 patients in 14 independent cohorts, including 12 public datasets and two in-house cohorts. The high TICS was associated with prolonged overall survival (OS), especially in the early-stage LUAD. For the advanced-stage LUAD, high TICS predicted a superior OS in patients who were treated with immunotherapy instead of chemotherapy or TKI. The result suggested that TICS could serve as an indicator for the prognostic stratification management of patients in the early-stage LUAD, and as a potential guide for therapeutic decision-marking in the advanced-stage LUAD. Our findings provided an insight into prognosis stratification and potential guidance for treatment strategy selection.


Ultrasound of the nerves - An appropriate addition to nerve conduction studies to differentiate paraproteinemic neuropathies.
To investigate the use of peripheral nerve ultrasound (PNUS) in addition to nerve conduction studies (NCS) in the diagnosis of paraproteinemic neuropathies (PN). PNUS/NCS of predefined peripheral nerves and the 5th/6th cervical roots were performed in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) (+/-paraprotein), patients with anti-MAG neuropathy, and patients with neuropathy and multiple myeloma or monoclonal gammopathy of uncertain significance (MGUS) - summarized as M-protein associated neuropathies (MPAN) and compared to controls (+/-paraprotein). 39 patients and 27 age-matched controls were included. Nerve enlargement was most marked in patients with CIDP, while in anti-MAG neuropathies enlargement was significant in the legs. In MPAN, no nerve enlargement is found regularly. However, in two cases, the diagnostic steps were influenced by the finding of multiple enlarged nerves and finally immunotherapy response was successfully initiated. By the use of the ultrasound pattern sum score (UPSS), differentiation of PN can be simplified. Due to the heterogeneous findings in NCS, correct diagnosis of PN, and straightforward therapeutic decisions often may be controversial. Particularly in cases of M-protein related neuropathy, the finding of multiple nerve enlargements facilitates the decision for therapeutic approaches or nerve biopsy. The UPSS enables the distinction of different PN from each other. The use of an ultrasound quantification tool in addition to NCS facilitates a differentiation of PN.


Is the perceived risk of fire-related injury and trust in local authorities affected by rescue services' actual ability?
Rescue services are one of the most crucial actors in providing fire-related societal protection, particularly in terms of response times. To achieve this, considerable funding and/or full-time organisations are required - something that is not always feasible and leads to differences in rescue service related protection in different municipalities. In turn, the question is how such variations affect the perceived risk of being injured in a residential fire and levels of general institutional trust in the municipality. By utilising a dataset on risk perception and trust, combined with data on the ability and structure of municipal rescue services, this study can show that a municipal's average perception of the risk of attaining a fire-related injury closely follows response times - indicating that individuals living in areas with less societal protection are aware of this fact. However, the results also indicate that general institutional trust and perception of risk on a municipal level seems to relate to each other in such a way that municipal types (with similar sociodemographic characteristics and rescue service ability) congregate around similar levels of perceived risk and trust. In turn, this study therefore indicates that perceived risk and trust differs in different municipalities and that efficiency measurements not necessarily encompass all these differences.


Genotyping and drug resistance patterns of Mycobacterium tuberculosis strains observed in a tuberculosis high-burden municipality in Northeast, Brazil.
This study has used a combination of clinical information, spoligotyping, and georeferencing system to elucidate the genetic diversity of the Mycobacterium tuberculosis isolates circulating in a TB-prevalent municipality of Northeast Brazil. A total of 115 M. tuberculosis strains were isolated from pulmonary tuberculosis patients from January 2007 to March 2008 in Fortaleza. Drug susceptibility and spoligotyping assays were performed and place of residence of the patients were georeferenced. Of the M. tuberculosis strains studied, 51 (44.3%) isolates were resistant to at least one drug (R-TB) and 64 (55.7%) were sensitive to all the drugs tested (S-TB). A high frequency of resistance was found in previously treated cases (84%) and among new cases (16%; p<0.001). A total of 74 (64%) isolates were grouped into 22 spoligotyped lineages, while 41 (36%) isolates were identified as new. Among the predominant genotypes, 33% were Latim American Mediterranean (LAM), 12% Haarlem (H), and 5% U. There was no association of geographic distribution of RT-TB patients as compared to the controls and also the geographic location to the spoligotype patterns. The geospatial analysis revealed that 24 (23%) patients (hot spot zones) either shared the same residence or lived in a close neighborhood of a case. Among these concentration zones, the patients lived in the same residence and shared a common genotype pattern and resistance pattern. It was observed that the spoligopatterns family distribution was similar to that reported for South America, prevailing the LAM and H lineages. A high rate-case among the resistant TB group occurs as a result of transmitted and acquired resistance. A more effective surveillance program is needed in order to succeed in reducing tuberculosis in Northeast Brazil.


Neurophysiological study on possible protective and therapeutic effects of Sidr (Zizyphus spina-christi L.) leaf extract in male albino rats treated with pentylenetetrazol.
In this study, anti-convulsant effect of Sidr leaf extract was examined by using pentylenetetrazol (PTZ) model on male albino rat by evaluating the changes in norepinephrine (NE), dopamine (DA) and serotonin (5-HT) contents in different brain regions (cerebellum, brainstem, striatum, cerebral cortex, hypothalamus and hippocampus). The administration of subconvulsive dose of PTZ (40 mg/kg i.p.) every other day for 9 days caused a significant decrease in monoamine content in different brain areas, this is may be due to the increase in nitric oxide levels, although antagonized the GABAA receptors which led to neurotransmitter release so the content is decreased. Administration of PTZ after treatment with Sidr (50 mg/kg i.p.) leaf extract for 3 weeks as a protective group and administration of Sidr leaf extract for 3 weeks after treatment of PTZ as a therapeutic group caused significant increase in NE, DA, and 5-HT contents in all tested brain regions at most of the time intervals studied. This may be due to the presence of peptide and cyclopeptide alkaloids in the extract which inhibit neurotransmitter activity which led to the inhibition of neurotransmitter release. From these results, we can say that the Sidr leaf extract has neuroprotective and therapeutic roles against pentylenetetrazol convulsant effect.


Dual use of cigarettes and smokeless tobacco among South African adolescents.
To determine factors associated with dual use of tobacco products in a population of black South African adolescents. Data were obtained from a self-administered questionnaire completed by a representative sample of grade 8 students from 21 randomly selected secondary state schools in the Limpopo Province, South Africa (n=1878). Of the respondents, 11.4% used smokeless tobacco (SLT), and 55.2% of SLT users also smoked cigarettes (dual users). Dual users were more likely to be vulnerable to depression, engage in binge drinking, smoke cannabis, and attend schools without rules against smoking. Dual tobacco use forms part of multiple-risk-taking behavior.


Heterogeneous distribution of serum prolactin values in apparently healthy young women, and the effects of oral contraceptive medication.
Controversy over effects of oral contraceptives (OCs) on serum prolactin (PRL) levels from retrospective studies suggested performing a prospective study. Statistical analyses of PRL levels in 552 reproductive-age, nonmedicated women indicated a provisionally lognormal distribution of values less than 15 ng/ml, contaminated by a small number of abnormally high values less than or equal to 90 mg/ml. Truncated samples were used to estimate a "normal range" of PRL levels for three subsets of the study sample, classified according to number of weeks after pregnancy. Fifty-microgram estrogen-containing OCs doubled basal PRL levels at 5 to 8 weeks in those whose initial control values fell below 15 ng/ml, but the PRL elevation was no longer evident at 6 months of drug use. These OCs induced a small but significant lowering of PRL at 5 to 8 weeks in those with control levels of 15 ng/ml or higher. Thirty-five-microgram estrogen-containing OCs failed to alter PRL levels at 5 to 8 weeks in those with control values less than 15 ng/ml.


Put them out to pasture? What are old granule cells good for, anyway...?
In this issue, Alme and colleagues propose a novel hypothesis that young adult-born neurons represent the functional population of the dentate gyrus, and that old granule cells "retire" from relevance. Here, we present several implications of this interesting theory for the function of both neurogenesis and the dentate gyrus.


Intraocular miR-211 exacerbates pressure-induced cell death in retinal ganglion cells via direct repression of FRS2 signaling.
MicroRNAs (miRNAs) are emerging as important regulators of neurodegenerative diseases. However, research into ocular intracellular miRNAs, though possessing great potential to uncover novel and valuable therapeutic targets for glaucoma, is only at an early stage. Here we show that expression levels of miR-211 were significantly induced in aqueous humor (AH) samples from patients with glaucoma when compared to normal AH samples. Notably, oxidative stress-elicited miR-211 potentiated high pressure-induced retinal ganglion cells (RGCs) death by impairing ERK activation but enhancing P38 activation, an effect mediated by direct downregulation of fibroblast growth factor receptor substrate 2 (Frs2) signaling pathway in a sequence complementarity-dependent fashion. In support of the concept of a fundamental connection between miR-211 upregulation and augmented pressure-induced cell death in RGCs, we showed that ectopic expression of the exogenous FRS2 was sufficient to neutralize the miR-211-induced decrease in the cell viability and significantly improved miR-211-inhibited cell survival, in high pressure-challenged RGC-5 cells. Together, our findings show that miR-211 negatively modulates cell survival programs upon high pressure challenge by regulating Frs2 signaling, and they define roles for miR-211/Frs2 cascade in a regulatory feedback loop that mediates the pathogenesis of glaucoma.


Congenital dyserythropoietic anaemia type II (HEMPAS): characterization of aberrant intracellular organelles by immunogold electron microscopy.
Erythrocytes are reticulocytes obtained from peripheral blood of a congenital dyserythropoietic anaemia type II patient were examined by immunoelectron microscopy using anti-band 3 and anti-glycophorin A antibodies. Vacuoles which have membranous structures inside were stained heavily by these antibodies, indicating the presence of band 3 and glycophorin A in these vacuoles. Empty vacuoles which open to the cell surface and those present in cytoplasm were also stained by these antibodies at the inside of the wall. These observations suggest that the vacuoles are functioning for trapping and discarding the defective plasma membranes. On the other hand, small vesicles and ferritin-loaded vacuoles were not stained by these antibodies. In these experiments, peripheral cisternae and most of the intracellular membranous structures at blebs and clefts were not stained by the antibodies. Therefore, they are probably part of the endoplasmic reticulum or are derived from intracellular organelles but not from the plasma membranes.


Infertility in advanced reproductive age. Results of in vitro fertilization and embryo transfer according to the woman's age.
The Authors discuss the phenomenon of the gradual decline of a woman's fecundability with the passing of time and particularly the potential causes of infertility in advanced reproductive age and the most efficient therapeutic management. They conclude that more advanced aided conception techniques such as IVF/ET, GIFT, ZIFT and IPI should be preferred to surgery for women over a certain age, especially where the infertility problem is of more than five years standing, and discuss the effect of the subject's age on the various stimulation techniques available. The Authors then report their experience with IVF/ET in 806 induction cycles using five different stimulation protocols at the Foundation for Studies on Human Reproduction in Palermo.


Apolipoprotein E genotypes are associated with lipid-lowering responses to statin treatment in diabetes: a Go-DARTS study.
Apolipoprotein E (APOE) genotypes have been associated with variations in plasma-lipid levels and with response to statins, although the influence of APOE on the response to statins remains controversial, especially in patients with diabetes. We sought to evaluate the association of the APOE genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to statins, in a large population-based cohort of patients with diabetes. A total of 1383 patients, commencing statins between 1990 and 2006, were identified from the Genetics of Diabetes Audit and Research in Tayside Scotland database. Statin response was determined both by the minimum LDLc achieved, and by the failure of the patients to reach a clinical target LDLc (< or =2 mmol/l). APOE genotype and potential confounding covariates were entered into the linear and logistic regression models. We found an association of APOE genotypes with both baseline and treatment responses. E2 homozygotes achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10). Minimum LDLc was associated by a linear trend with genotype. This relationship remained statistically significant after adjustment for baseline LDLc, adherence, duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10). This study demonstrates the potential clinical value of the APOE genotype as a robust marker for LDLc responses to statin drugs, which might contribute to the identification of a particularly drug-resistant subgroup of patients. This marker provides information over and above baseline lipid levels.


Pharmacoeconomic Appraisal of Treating Head and Neck Cancer with Various Chemotherapy and Chemoirradiation Regimens Using Branded and Jan-aushadhi Drugs in India.
According to recent studies, head and neck cancers (HNC) make up a substantial proportion of all cancers in India and are proportionately high in the lower socioeconomic people practising tobacco and alcohol. Chemotherapy is a crucial component of treating HNC, and this study was carried out to determine the Cost Minimization Analysis (CMA) by comparing the price of the high and least expensive branded drugs marketed in India. This study was performed to understand the cost difference (CD), Cost ratio (CR) and percentage of cost variation (PCV) of both individual drugs and the standard anticancer regimens. The Current Index of Medical Stores was used to determine the costs of the most and least expensive branded medications and analysed. The results indicated that Paclitaxel-Cisplatin-5 Fluoruracil chemotherapy regimen exhibited the greatest variance in cost, with the Jan Aushadhi brand of medicine costing 8.1 times and 4.3 times less than the most expensive and cheapest branded drugs, respectively. The cost of the concurrent cisplatin regimen with Jan Aushadi Medicine was Rs 1764, Rs 3489.64 with the lowest branded drug, and Rs 8477 with the most expensive branded drug. Also when compared to Jan Aushadhi medication, the cost of Ciplatin was 4.8 times higher with the most expensive branded drug and 2 times higher with the least expensive branded drug. As far as the authors are aware of this is the first study that addresses the pharmacoeconomic appraisal of treating HNC with various chemotherapy and chemoirradiation regimens. This study will help oncologists, pharmacists, and healthcare workers comprehend the financial advantages of treating breast cancer with less expensive chemotherapeutic agents instead of brand-name medications.


Insertion and substitution chemistry at the boron fourth position in charge-neutral zwitterionic tripodal tris(methimazolyl)borate ligands.
A number of new charge-neutral zwitterionic tris(methimazolyl)borate ligands have been synthesized, either by substitution of the dimethylamine group in the adduct (dimethylamine)tris(methimazolyl)borane (1) or by insertion into its B-N(dimethylamine) bond by an unsaturated Lewis base. Two new anionic ligands, (thiocyanato)tris(methimazolyl)borate and (cyano)tris(methimazolyl)borate, have also been accessed by this method.


Lasers in pediatric surgery.
During the last few years the laser has become a very interesting instrument in pediatric surgery. This is the result of the wide variation in tissue interactions and the possibility of specific applications. The CO2 laser is a highly precise cutting instrument whereas the argon laser has its great advantage in the treatment of superficial vascular anomalies. The most important laser in pediatric surgery is the Nd:YAG laser, on the one hand because its radiation can be transmitted by fibres, on the other because with the relationship between interaction time and power density, and the choice of application, it is possible to change the tissue interaction from precise cutting to specific coagulation and homogeneous coagulation. As a result, indications for lasers in pediatric surgery range from the treatment of superficial haemangiomas to typical endoscopic procedures and the resection of parenchymatous organs and tumours.


Cancer incidence in the Agricultural Health Study after 20 years of follow-up.
To evaluate cancer incidence in the Agricultural Health Study (AHS), a cohort of private pesticide applicators, their spouses, and commercial applicators, based on 12,420 cancers, adding 5,989 cancers, and 9 years of follow-up since last evaluation. We calculated age, year, sex, and race-adjusted standardized incidence ratios (SIR) and 95% confidence intervals (CI) for cancer sites in the AHS relative to the general population. Overall AHS cancer incidence was lower than the general population (SIRprivate = 0.91, CI 0.89-0.93; SIRspouse = 0.89, CI 0.86-0.92; SIRcommercial = 0.83, CI 0.76-0.92), with notable deficits across applicators and spouses for oral cavity, pancreas, and lung cancers. Cancer excesses included prostate cancer, lip cancer, certain B-cell lymphomas (e.g., multiple myeloma), acute myeloid leukemia (AML), thyroid cancer, testicular cancer, and peritoneal cancer. The lung cancer deficit was strongest among applicators reporting potential exposure to endotoxin at study enrollment (tasks such as raising animals and handling stored grain). Although an overall deficit in cancer was observed, there were notable exceptions, including newly observed excesses for AML, thyroid, testicular, and peritoneal cancers. Furthermore, endotoxin exposure may, in part, account for observed lung cancer incidence deficits. Cancer incidence patterns in the AHS suggest farm exposures' relevance to cancer etiology.


A New Self-Powered Sensor Using the Radial Field Piezoelectric Diaphragm in d33 Mode for Detecting Underwater Disturbances.
This paper presents a new sensor based on a radial field bulk piezoelectric diaphragm to provide energy-efficient and high-performance situational sensing for autonomous underwater vehicles (AUVs). This sensor is self-powered, does not need an external power supply, and works efficiently in d33 mode by using inter-circulating electrodes to release the radial in-plane poling. Finite element analysis was conducted to estimate the sensor behavior. Sensor prototypes were fabricated by microfabrication technology. The dynamic behaviors of the piezoelectric diaphragm were examined by the impedance spectrum. By imitating the underwater disturbance and generating the oscillatory flow velocities with a vibrating sphere, the performance of the sensor in detecting the oscillatory flow was tested. Experimental results show that the sensitivity of the sensor is up to 1.16 mV/(mm/s), and the detectable oscillatory flow velocity is as low as 4 mm/s. Further, this sensor can work well under a disturbance with low frequency. The present work provides a good application prospect for the underwater sensing of AUVs.


Flicker sensitivity measured with intermittent stimuli: II. Comparison between temporal gradient detection and the "De Lange" curves.
The threshold gradient for perception of a linear change in luminance with time has been measured as a function of the stimulus duration. These data are compared with the "De Lange" curves representing the flicker sensitivity measured with intermittent presentation of the stimulus as a function of the stimulus duration. For this purpose it is necessary to take into account the fact that a linear luminance gradient, being a relatively low-frequency signal, is affected less by the low-pass filter supposedly situated in the visual system than by a sinusoidal signal (flicker) of the same duration.


Obesity: thermodynamic principles in perspective.
The energy balance equation applicable to all living organisms was used as a framework on which to construct a critical review of some of the more controversial aspects of the obesity problem. The equation matches energy intake against all the known forms of work that the body does in utilizing that energy, including external and internal work and the work of adipose tissue synthesis (stored energy). Equations representing everyday living conditions, resting, fasting and basal conditions were constructed. The equation applicable to everyday living (working, non-fasting) was used to develop a set of model paradigms to illustrate some of the devices that can be invoked to decrease expenditure and conserve energy. These served as models of how obesity can arise in the absence of calorie overconsumption. The same equation was then used to create a set of opposite paradigms showing how obesity can be prevented by increasing expenditure to waste energy and stabilize body weight when challenged by hyperphagia. In order to see caloric intake and the various work terms in their proper quantitative relationships it was necessary to assign numerical values to the equation. These were selected from published reports of caloric values representative of a non-obese adult of average size engaged in a typical white collar occupation. It was then easy to adjust these assigned values commensurate with the objectives described in the preceding paragraph. Since obesity research is hampered by a confusing array of metabolic interactions it was essential to alter only one of the energy terms at a time, excluding all metabolic interactions except for those unavoidable ones dictated by the laws of thermodynamics. Only in this way could we see the body's multiple energy forms in clear perspective with regard to their real quantitative significance in the energy balance sheet and their potential impact on body weight. Creating these models gave us the added advantage of enabling us better to evaluate the scientific literature because the data we generated, although theoretical, served as excellent standards against which to compare the real data that have emanated from research laboratories.(ABSTRACT TRUNCATED AT 400 WORDS)


mTOR signaling controls VGLUT2 expression to maintain pain hypersensitivity after tissue injury.
Mammalian target of rapamycin (mTOR) is a serine-threonine protein kinase that controls protein synthesis in the nervous system. Here, we characterized the role of protein synthesis regulation due to mTOR signaling in rat dorsal root ganglion (DRG) following plantar incision. The number of phosphorylated mTOR (p-mTOR)-positive neurons was increased 2-4days after the incision. Rapamycin inhibited p-mTOR expression in the DRG and thermal hypersensitivity 3days but not 1day after the incision. Vesicular glutamate transporter 2 (VGLUT2) expression was increased after the plantar incision, which was inhibited by rapamycin. These results demonstrated that tissue injury induces phosphorylation of mTOR and increased protein level of VGLUT2 in the DRG neurons. mTOR phosphorylation involves in maintenance of injury-induced thermal hypersensitivity.


Comparison of pre- and post-surgical images of reusable and single use flexible ureteroscopes: a qualitative analysis.
Given the fragility of reusable ureterorenoscopes, many single use instruments have appeared on the market. Unfortunately, reuse of these scopes occurs in undeveloped countries in order to cut costs. This raises safety concerns for the patient.The aim of this article was to macroscopically evaluate the changes that single use flexible ureterorenoscopes (su-fURS) suffer after a retrograde intrarenal surgery (RIRS), and to compare them to reusable fURS. Pre and post-operative images of the instruments used in 23 RIRS were obtained. All the cases had renal calculi of the inferior calix between 10-15 mm, and all of them were treated with Holmium laser. The ureterorenoscopes used were: Storz® Flex X2, Storz® Flex XC, Pusen® 3022, OTU® Wiscope, AnQIng® Innovex and Boston Scientific® LithoVue. Qualitative comparisons of these were made. After su-fURS usage, significant damage was observed, especially on the distal tip. Deflection was not compromised. Reusable fURS did not sustain any damage after their use. fURS are delicate equipment, especially if they are of single use. The considerable damage sustained by single use scopes could mean that reuse of these instruments is dangerous and should be avoided.


The zoonotic, fish-borne liver flukes Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini.
Clonorchis sinensis, Opisthorchis felineus and Opisthorchis viverrini are the three most important liver flukes involved in human health, infecting more than 45 million people worldwide. Both C. sinensis and O. viverrini, and possibly O. felineus, can induce human cholangiocarcinoma as well as inducing other hepatobiliary pathology. Although the life cycles of all three species are similar, only that of O. felineus in Europe remains predominantly zoonotic, while O. felineus in Asia and C. sinensis have a stronger mixture of zoonotic and anthroponotic components in their life cycles. Opisthorchis viverrini from the Mekong area of southeastern Asia is predominantly anthroponotic. Here we discuss the comparative epidemiology of these three taxa comparing in detail the use of first, second and final animal hosts, and consider the potential role of humans in spreading these pathogens. In addition we discuss the genetic structure of all three species in relation to potentially cryptic species complexes.


Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin.
Campylobacter jejuni is one of the most important bacterial pathogens causing food-borne illness worldwide. Crossing the intestinal epithelial barrier and host cell entry by C. jejuni is considered the primary reason of damage to the intestinal tissue, but the molecular mechanisms as well as major bacterial and host cell factors involved in this process are still widely unclear. In the present study, we characterized the serine protease HtrA (high-temperature requirement A) of C. jejuni as a secreted virulence factor with important proteolytic functions. Infection studies and in vitro cleavage assays showed that C. jejuni's HtrA triggers shedding of the extracellular E-cadherin NTF domain (90 kDa) of non-polarised INT-407 and polarized MKN-28 epithelial cells, but fibronectin was not cleaved as seen for H. pylori's HtrA. Deletion of the htrA gene in C. jejuni or expression of a protease-deficient S197A point mutant did not lead to loss of flagella or reduced bacterial motility, but led to severe defects in E-cadherin cleavage and transmigration of the bacteria across polarized MKN-28 cell layers. Unlike other highly invasive pathogens, transmigration across polarized cells by wild-type C. jejuni is highly efficient and is achieved within a few minutes of infection. Interestingly, E-cadherin cleavage by C. jejuni occurs in a limited fashion and transmigration required the intact flagella as well as HtrA protease activity, but does not reduce transepithelial electrical resistance (TER) as seen with Salmonella, Shigella, Listeria or Neisseria. These results suggest that HtrA-mediated E-cadherin cleavage is involved in rapid crossing of the epithelial barrier by C. jejuni via a very specific mechanism using the paracellular route to reach basolateral surfaces, but does not cleave the fibronectin receptor which is necessary for cell entry.


What primary microcephaly can tell us about brain growth.
Autosomal recessive primary microcephaly (MCPH) is a neuro-developmental disorder that causes a great reduction in brain growth in utero. MCPH is hypothesized to be a primary disorder of neurogenic mitosis, leading to reduced neuron number. Hence, MCPH proteins are likely to be important components of cellular pathways regulating human brain size. At least six genes can cause this disorder and four of these have recently been identified: autosomal recessive primary microcephaly 1 (MCPH1), abnormal spindle-like, microcephaly associated (ASPM), cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) and centromere protein J (CENPJ). Whereas aberration of ASPM is the most common cause of MCPH, MCPH1 patients can be more readily diagnosed by the finding of increased numbers of "prophase-like cells" on routine cytogenetic investigation. Three MCPH proteins are centrosomal components but have apparently diverse roles that affect mitosis. There is accumulating evidence that evolutionary changes to the MCPH genes have contributed to the large brain size seen in primates, particularly humans. The aim of this article is to review what has been learnt about the rare condition primary microcephaly and the information this provides about normal brain growth.


Sense of coherence and social support as predictors of mental health during COVID-19 pandemic.
to verify the role of sense of coherence, sense of national coherence, social support and trust in institutions to predict mental health in Brazilians during the COVID-19 pandemic. a cross-sectional study, carried out from November, 2020 to January, 2021 via an online survey. Standardized instruments were used. The sample consisted of 1,630 Brazilians. Pearson's correlation and linear regression were performed in data analysis. sense of coherence was the only predictor of anxiety [β= -0.61; p<0.001], explaining 38% of the variance in its scores, while sense of coherence [β= 0.52; p<0.001], sense of national coherence [β= 0.16; p<0.001], and social support [β= 0.15; p<0.001] predicted positive mental health and together explained 51% of its variance. the findings suggest that sense of coherence, sense of national coherence and social support represent important predictors for mental health and that strengthening these resources, could potentially promote Brazilians' mental health.


Integrative approach to elucidate the embryological effects of caffeine in Cyprinus carpio: Bioconcentration and alteration of oxidative stress-related gene expression patterns.
Caffeine (CAF) is an alkaloid, which acts as a central nervous system (CNS) stimulant drug. In recent years, CAF has been recurrently detected in water bodies, generating deleterious effects in aquatic organisms. The information on the toxic effects of CAF in the environment is still limited. Thus, the objective of this work was to determine whether CAF at environmentally relevant concentrations (CAF concentrations were selected based on studies on the worldwide occurrence of this compound and on the toxicity of CAF in aquatic species) is capable of inducing alterations to embryonic development and alteration of oxidative stress-related gene expression patterns in Cyprinus carpio. For this purpose, common carp embryos (2 hpf) were exposed to realistic concentrations of CAF until 96 hpf. Alterations to embryonic development and teratogenic effects were evaluated at 12, 24, 48, 72 and 96 hpf. In addition, oxidative stress in carp embryos at 72 and 96 hpf was evaluated by cellular oxidation biomarkers (lipoperoxidation level, hydroperoxide content and carbonyl protein content) and antioxidant enzymes activities (superoxide dismutase and catalase). Oxidative stress-related gene expression (sod, cat and gpx1) was also evaluated. Our results showed that CAF concentrations above 500 ng/L are capable of producing teratogenic effects. Furthermore, CAF was able to induce alterations such cardiac malformations, somite alterations, pericardial edema and chorda malformations. Concerning oxidative stress, the results demonstrated that CAF induce oxidative damage on the embryos of C. carpio. Our outcomes also showed up-regulations in genes related to antioxidant activity sod, cat and gpx by CAF exposure. In conclusion CAF at environmentally relevant concentrations is able to alter the embryonic development of common carp by the oxidative stress pathway. Based on the above evidence, it can be inferred that acute exposure to CAF can lead to a toxic response that significantly harms fish's health, adversely affecting their essential organs' functioning.


Vaginal removal of prolapsed pedunculated submucous myoma: a short, simple, and definitive procedure with minimal morbidity.
Our objective was to evaluate the outcome of vaginal removal of prolapsed pedunculated submucous myomas over a 10-year period. Retrospective observational study. Fifty-two patients were admitted with the diagnosis of prolapsed pedunculated submucous myoma. Six patients were excluded because of an a priori decision for abdominal hysterectomy. In 46 patients an attempt for vaginal myomectomy under general anesthesia was done. Vaginal myomectomy was successful in 44 patients (95.6%). There were no immediate complications. Histological diagnosis of leiomyoma was confirmed in 34 cases (73.9%) and in the remainders intrauterine pathology was endometrial polyp. Total abdominal hysterectomy was performed in additional 6 patients (13.7%) 3 months to 5 years following vaginal myomectomy. Vaginal myomectomy is the treatment of choice for prolapsed pedunculated submucous myoma. The associated morbidity is minimal.


Prognostic value of preoperative NLR, dNLR, PLR and CRP in surgical renal cell carcinoma patients.
Emerging evidences indicate that inflammation plays a crucial role in carcinogenesis and tumor progression. Inflammatory response biomarkers are recognized as promising prognostic factors for improving predictive accuracy in renal cell carcinoma (RCC). We aimed to evaluate the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR) and serum C-reactive protein (CRP) in RCC. 484 surgical RCC patients were enrolled from 2006 to 2010 in this study. Receiver operating curve (ROC) was applied to assess the optimal cutoff levels for four biomarkers, and the prognostic values were determined by Kaplan-Meier curve, univariate and multivariate COX regression models. The predictive accuracy was evaluated by concordance index (c-index). The median follow-up duration after surgical resection was 36 months. The optimal cutoff levels were 2.78 for NLR, 2.05 for dNLR, 185 for PLR and 5.1 for CRP by ROC curves analysis. Elevated NLR, dNLR, PLR and CRP were significantly correlated with worse overall survival (OS). Multivariate analysis showed that elevated NLR was an independent risk factor for OS, and NLR was superior to dNLR, PLR and CRP based on hazard ratio (HR 2.10, 95 % CI 1.21-3.64, P = 0.008). Additionally, the nomogram could more effectively work in predicting OS (c-index: 0.749) in surgical RCC patients. Pre-operation NLR can be considered as a potential prognostic biomarker in patients with RCC who underwent surgical resection.


Differential liquid phase proteomic analysis of the effect of selenium supplementation in LNCaP cells.
The effect of 100 nM sodium selenite supplementation was studied on LNCaP cells by a proteomic approach, on ProteomeLab PF 2D platform. Proteins were separated by liquid phase bi-dimensional chromatography and analyzed by pair-wise alignment of peaks to detect those differentially expressed. Differential expression threshold was set at a twice difference level and proteins matching this criterion were identified by MALDI-TOF and confirmed by ESI-ion trap MS/MS. Not all differentially expressed proteins found by PF 2D could be identified by MS analysis, the sensitivity of which emerging as the limiting factor. Thus, only the most abundant proteins, differently expressed following selenium supplementation, were identified. We positively showed an increase of expression of thioredoxin reductase 1, enolase 1, phosphoglycerate mutase 1, glyceraldehyde-3-phosphate dehydrogenase, heterogeneous nuclear ribonucleoprotein A2/B1, isoform A2, Ras-GTPase-activating protein SH3-domain-binding protein and Keratin 18 and a decrease of expression of peroxiredoxin 1 and heat shock protein 70, protein 8, isoform 1. Results are consistent, at least in part, with the less oxidant environment brought about by the synthesis of Se-dependent peroxidases, keeping low the steady-state concentration of hydrogen peroxide.


Adenocarcinoma of the appendix.
Thirty-two patients with primary adenocarcinoma of the appendix were studied in this collective review. Immediate operation was performed in 21 patients with a diagnosis of acute appendicitis. At operation, tumor of the appendix was only identified in 50 percent of the 32 patients studied. Survival was unrelated to the histologic tumor type, but significantly correlated with the extent of tumor spread. Right hemicolectomy led to a significant increase in survival compared with appendectomy alone and to a significant decrease in risk of recurrence. In Dukes' B2 and C patients, differences in the survival curves were in favor of right hemicolectomy. Long-term survival was obtained by repeat laparotomy with resection of mucinous material in patients with pseudomyxoma peritonei.


Characterization of the physicochemical changes and volatile compound fingerprinting during the chicken sugar-smoking process.
Sugar-smoking contributes to improving flavor attributes of meat products. However, there is rather limited information concerning the relationship between sugar-smoking process parameters and volatile compound (VC) fingerprinting as well as related quality attributes of sugar-smoked chicken. In this work, the changes in VC across the whole sugar-smoking process were determined and analyzed and physicochemical properties, free fatty acid, thiobarbituric acid reactive substances values, and E-nose were also performed to characterize the quality properties of sugar-smoked chicken breast (CB) and chicken skin (CS). Results suggested that a higher amount (P < 0.05) of total VC was observed in CS compared with CB during the whole processing, which may be correlated with higher thiobarbituric acid reactive substances values, and higher polyunsaturated fatty acid/saturated fatty acid ratio. According to E-nose analysis, the volatile flavor is clearly separated in the sugar-smoking stage. Volatile fingerprinting results revealed that heterocycles were the characteristic flavor formed during sugar-smoking process and hexanal, nonanal, furfural, 5-methyl-2-furancarboxaldehyde, and 2-acetyl-5-methylfuran were the major volatiles of the CS, which was closely related to lipid oxidation and caramelization reaction. Above all, the flavor of sugar-smoked chicken was mainly derived from CS and sugar-smoked process improved the flavor of CS. This study could provide theoretical guidance for regulation of the color and flavor of sugar-smoked chicken and further promote the development of the industry.


Formation of (FexMn(2-x))O3 solid solution and high sulfur capacity properties of Mn-based/M41 sorbents for hot coal gas desulfurization.
Several MCM-41 materials were synthesized at different conditions by hydrothermal procedure using cheap and easily available industrial water glass as silica source. Fe doped manganese-based oxide/MCM-41 sorbents were prepared by a sol-gel method. The effects of loadings of metal oxide, Fe/Mn molar ratios over MCM-41 and reaction temperature on the performance of sorbent for hot coal gas desulfurization were investigated. Various techniques such as BET, XRD, XPS, LRS and HRTEM were used to characterize the sorbents. The result indicated Fe(3+) ions could occupy a position of Mn(3+) in cubic lattice of Mn2O3 and the (FexMn2-x)O3 solid solution is mainly active phase of sorbent. Moreover, the result of nine successive sulfurization-regeneration cycles of sorbent showed high sulfur adsorption capacity and endurable stability of FeMn4Ox/MCM-41 for H2S removal.


Proteome dynamics during postnatal mouse corpus callosum development.
Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled amino acids in mammals (SILAM). The analyzed corpus callosi had distinct proteomic profiles depending on age, indicating rapid progression of specific molecular events during this period. The proteomic profiles were then segregated into five separate clusters, each with distinct trajectories relevant to their intended developmental functions. Our analysis both confirms many previously-identified proteins in aspects of corpus callosum development, and identifies new candidates in understudied areas of development including callosal axon refinement. We present a valuable resource for identifying new proteins integral to corpus callosum development that will provide new insights into the development and diseases afflicting this structure.


TiO₂-KH550 Nanoparticle-Reinforced PVA/xylan Composite Films with Multifunctional Properties.
In order to improve the strength of polyvinyl alcohol (PVA)/xylan composite films and endow them with ultraviolet (UV) shielding ability, TiO₂-KH550 nanoparticles was synthesized and added into the PVA/xylan matrix. The TiO₂-KH550 nanoparticle dispersed well in the 0.04% sodium hexametaphosphate (SHMP) solution under ultrasonic and stirring treatments. Investigations on the properties of the films showed that TiO₂-KH550 had the positive impact on improving the strength, moisture, and oxygen barrier properties of the composite films. The maximum tensile strength (27.3 MPa), the minimum water vapor permeability (2.75 × 10-11 g·m-1·s-1·Pa-1), and oxygen permeability (4.013 cm³·m-2·24 h-1·0.1MPa-1) were obtained under the addition of 1.5% TiO₂-KH550. The tensile strength of TiO₂-KH550 reinforced composite film was increased by 70% than that of the pure PVA/xylan composite film, and the water vapor and oxygen permeability were decreased by 31% and 41%, respectively. Moreover, the UV transmittance of the film at the wavelength of 400 nm was almost zero when adding ≈1.5~2.5% (weight ratio, based on the total weight of PVA and xylan) of TiO₂-KH550, which indicated the PVA/xylan composite films were endowed with an excellent UV light shielding ability.


Progressive Structural Complexity in Ferroelectric 1,2,4-Triazolium Hexabromoantimonate(III): Interplay of "Order-Disorder" and "Displacive" Contributions to the Structural Phase Transitions.
Halobismuthates(III) and haloantimonates(III) with the R3MX6 chemical composition create a new and broadly unexplored class of ferroelectric compounds. In this paper, we report the haloantimonate(III) ferroelectric comprising an aromatic (1,2,4-triazolium) cation, i.e., (C2N3H4)3[SbBr6] (TBA). Temperature-resolved structural and spectroscopic studies indicate that TBA undergoes two solid-solid phase transitions between tetragonal [P42/m (I)] and monoclinic [P21/n (II) and P21 (III)] phases. TBA experiences a paraelectric-ferroelectric phase transition at 271/268 K (II-III) driven by "order-disorder" and "displacive" molecular mechanisms. The ferroelectric properties of phase III have been confirmed by hysteresis loop measurement, and additionally, the acentric order has been further supported by second-harmonic generation measurements. Insight into the molecular origins of the ferroelectric polarization was provided by periodic ab initio calculations using the Berry phase approach at the density functional theory (DFT-D3) method level employed for calculations of spontaneous polarization.


Two-dimensional spectrophotometry with high spatial and temporal resolution by digital video techniques and powerful computers.
A two-dimensional spectrophotometer having a spatial raster resolution of 512 X 512 picture elements with 256 grey levels and a time resolution of 30 images per min is assembled by combination of digital video techniques and a powerful computer system. The instrument is applied to the analysis of pattern formation processes in cytoplasmic media.


Comparison of safety and healthcare utilization following sleeve gastrectomy or gastric bypass among medicare beneficiaries using sex as a biologic variable.
Bariatric surgery is a common operation, but differences in outcomes between males and females are unknown. To compare the risk of mortality, complications, reintervention, and healthcare utilization after sleeve gastrectomy or gastric bypass using sex as a biologic variable. United States. Retrospective cohort study of adults undergoing sleeve gastrectomy or gastric bypass from January 1, 2012 to December 31, 2018 using Medicare claims data. We performed a heterogeneity of treatment effect analysis to determine the impact of sleeve gastrectomy versus gastric bypass comparing males to females. The primary outcome was safety (mortality, complications, and reinterventions) up to 5 years after surgery. The secondary outcome was healthcare utilization (hospitalization and emergency department use). Among 95,405 patients the majority (n = 71,348; 74.8%) were female and most (n = 57,008; 59.8%) underwent sleeve gastrectomy. For all patients, compared to gastric bypass, sleeve gastrectomy was associated with a lower risk of complications and reintervention but a higher risk of revision. Compared to gastric bypass, sleeve gastrectomy was associated with a lower risk of mortality for females (adjusted hazard ratio .86, 95% CI .75-.96) but not males. We found no difference in procedure treatment effect by sex for mortality, hospitalization, emergency department use, or overall reintervention when comparing sleeve to gastric bypass. Females and males have similar outcomes following bariatric surgery. Females have a lower risk of complications but a higher risk of reintervention. Decisions surrounding treatment for this common procedure should be tailored to include a discussion of sex-specific differences in treatment outcome.


DUSP10 alleviates ischemic stroke-induced neuronal damage by restricting p38/JNK pathway.
Neuronal apoptosis is considered one of the hallmarks of ischemic stroke. Dual specificity phosphatase 10 (DUSP10), a member of the dual-specificity phosphatase family, which is involved in the regulation of apoptosis process. This study aimed to investigate the effect of on apoptosis in primary cortical neurons exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) and mice suffered from transient middle cerebral artery occlusion and reperfusion (MCAO/R). The results showed that DUSP10 overexpression improved survival and reduced apoptosis in neurons subjected to OGD/R, which was manifested by decreased apoptotic proteins (cleaved caspase 3 and bax) and TUNEL+ cells, as well as increased the anti-apoptotic protein (bcl-2). DUSP10 overexpression inhibited the p38/JNK signaling pathway after OGD/R treatment, whilst DUSP10 knockdown had opposite effects. In addition, the p38 inhibitor SB203580 or JNK inhibitor SP600125 attenuated the increased apoptosis of OGD/R-stimulated neurons treated with DUSP10 silencing. Consistently, DUSP10 knockdown exacerbated infarct volume in MCAO/R injury. The data of Nissl staining and TUNEL-NeuN double staining revealed that DUSP10 interference aggravated neuronal damage in the ischemic penumbra of mice. Furthermore, DUSP10 inhibition activated the p38/JNK axis accompanied by enhanced phosphorylation of p38 and JNK in vivo. In summary, DUSP10 is a neuroprotective agent against ischemic stroke-induced neuronal damage via suppressing the p38/JNK signaling pathway.


Receptors for vasoactive intestinal peptide on murine lymphocytes turn over rapidly.
The interaction of the neuropeptide vasoactive intestinal peptide (VIP) with its receptors on murine mesenteric lymph node lymphocytes (MLN) has been re-examined in detail. Intact MLN actively internalize surface bound VIP. The rate constants associated with the insertion of receptors at the MLN surface, the internalization of VIP occupied and unoccupied receptors and the elimination of the peptide were determined. At 37 degrees C, MLN insert approximately 140 VIP receptors cell-1 min-1 at their surface, and the rate of internalization of occupied receptors (0.23 min-1) was much greater than that of the unoccupied receptors (0.02 min-1). Exposure of MLN to non-saturating concentrations of VIP markedly altered the expression of VIP receptors at the lymphocyte surface. The rapid turnover of VIP receptors combined with the differential clearance of occupied and unoccupied receptors from the cell surface provides a mechanism by which homologous regulation of VIP receptor expression can occur on these lymphocytes.


Performance evaluation of anti-fixed Leishmania infantum promastigotes immunoglobulin G (IgG) detected by flow cytometry as a diagnostic tool for visceral Leishmaniasis.
Visceral Leishmaniasis (VL) is a severe disease, caused by the protozoans Leishmania infantum and L. donovani that is widely diagnosed using serological tools. These, however, have limitations in performance that limit their use for the correct identification of the cases. This study aimed to evaluate the performance of flow cytometry with fixed parasites for VL diagnosis, comparing it with four other serological tests. Samples from two endemic VL regions in Brazil, diagnosed by direct examination (DG1) and by at least two or one standard serological test (DG2 and DG3, respectively), as well as patients with chronic Chagas' disease (CG1) and healthy controls (CG2) were used in this study. The flow cytometry results were expressed as levels of IgG reactivity, based on the percentage of positive fluorescent parasites (PPFP). Using a 1:4096 serum dilution, a ROC curve analysis of the serum titration on flow cytometry has indicated a PPFP of 2% as the cutoff point to segregate positive and negative results. In the present study, flow cytometry had the best performance for DG1 (sensitivity of 96%) while rK39 (imunocromagraphic rapid test) and DAT (Direct agglutination test) were also associated with high sensitivity and specificity. The substantial agreement and kappa indexes observed suggested similar performances between these two tests and flow cytometry. IFAT (Immunofluorescent antibody test) and ELISA (Enzyme-linked immunosorbent assay) had lower performances and the lower values of agreement with flow cytometry. Together, these findings suggest that although adjustments are needed in order to reduce cross reactivity with other trypanosomatids, flow cytometry has the potential to be a safe serological alternative for the diagnosis of VL.


Unpacking racism during COVID-19: narratives from racialized Canadian gay, bisexual, and queer men.
Epidemics impact individuals unevenly across race, gender, and sexuality. In addition to being more vulnerable to COVID-19 infection, evidence suggests racialized gender and sexual minorities experienced disproportionate levels of discrimination and stigma during the COVID-19 epidemic. Drawing on Critical Race Theory (CRT), we examined the experiences of gay, bisexual, queer, and other men who have sex with men (GBQM) of colour facing discrimination during COVID-19. Engage-COVID-19 is a mixed methods study examining the impact of COVID-19 on GBQM living in Vancouver, Toronto, and Montréal, Canada. We conducted two rounds of qualitative interviews (November 2020 to February 2021, and June to October 2021) with 93 GBQM to explore the evolving impact of COVID-19 on their lives. Transcripts were coded using inductive thematic analysis. Data analysis was conducted using Nvivo software. Fifty-nine participants identified as Black, Indigenous, and/or a Person of Colour (BIPOC). These GBQM of colour described multiple experiences of discrimination during COVID-19. Although participants did not report experiences of discrimination based on their sexual identity during COVID-19, we found that experiences of racism affected how they were treated within their sexual networks. Experiences of racism were most often reported by East Asian and Black GBQM. These participants faced racism in public and online spaces, primarily in the form of verbal harassment. Several participants were also harassed because they wore face masks. Verbal abuse against GBQM of colour was largely prompted by racist discourses related to COVID-19. Racism remains a pernicious threat to the well-being of GBQM of colour. CRT highlights the importance of assessing how sexualized and gendered discourses about race shape the experiences of GBQM of colour navigating multiple epidemics like COVID-19 and HIV. These pervasive discourses unevenly affect racial and sexual minorities across multiple epidemics, and negatively impact health outcomes for these populations.


Sleep and "sundowning" in nursing home patients with dementia.
"Sundowning," a term that is sometimes equated with sleep disturbance or nocturnal delirium in dementia, is a poorly understood psychiatric phenomenon. In this study, we performed systematic, temporally specific, behavioral observations of nine profoundly demented nursing home patients 4 times an hour over a 12-hour period (1300 to 0100h) to determine whether their agitation was more likely to occur at a particular time of day. Results indicated only equivocal evidence that agitation was any worse nocturnally or during the time near sunset, thus raising the possibility that at least some components of sundowning may reflect disruptive behaviors occurring with identical frequency throughout the day but with differential impact upon nursing staff. Additional data indicated that awakening from sleep during darkness was also associated with agitation. A final result was a trend indicating the apparent worsening of agitation seasonally (greater agitation during winter), which may suggest involvement of the circadian timing system.


Xiphoidectomy.
Complex surgical procedures in the upper abdomen required ear exposure. To improve exposure xiphoidectomy is indicated; however, in the past there was an extensive time commitment and unpredictable bleeding. We describe a rapid and bloodless approach to xiphoidectomy, utilizing a self-retaining retractor, controlled osteotomy, and complete removal to the xiphisternal junction. The xiphoid bone is dissected with high-voltage electrosurgery, denatured, and resected completely. Bleeding points are easily controlled with electrocoagulation. This procedure allows optimal exposure to the most superior aspect of the abdominal cavity.


Pressure-driven mesofluidic platform integrating automated on-chip renewable micro-solid-phase extraction for ultrasensitive determination of waterborne inorganic mercury.
A dedicated pressure-driven mesofluidic platform incorporating on-chip sample clean-up and analyte preconcentration is herein reported for expedient determination of trace level concentrations of waterborne inorganic mercury. Capitalizing upon the Lab-on-a-Valve (LOV) concept, the mesofluidic device integrates on-chip micro-solid phase extraction (μSPE) in automatic disposable mode followed by chemical vapor generation and gas-liquid separation prior to in-line atomic fluorescence spectrometric detection. In contrast to prevailing chelating sorbents for Hg(II), bare poly(divinylbenzene-N-vinylpyrrolidone) copolymer sorptive beads were resorted to efficient uptake of Hg(II) in hydrochloric acid milieu (pH=2.3) without the need for metal derivatization nor pH adjustment of prior acidified water samples for preservation to near-neutral conditions. Experimental variables influencing the sorptive uptake and retrieval of target species and the evolvement of elemental mercury within the miniaturized integrated reaction chamber/gas-liquid separator were investigated in detail. Using merely <10 mg of sorbent, the limits of detection and quantification at the 3s(blank) and 10s(blank) levels, respectively, for a sample volume of 3 mL were 12 and 42 ng L(-1) Hg(II) with a dynamic range extending up to 5.0 μg L(-1). The proposed mesofluidic platform copes with the requirements of regulatory bodies (US-EPA, WHO, EU-Commission) for drinking water quality and surface waters that endorse maximum allowed concentrations of mercury spanning from 0.07 to 6.0 μg L(-1). Demonstrated with the analysis of aqueous samples of varying matrix complexity, the LOV approach afforded reliable results with relative recoveries of 86-107% and intermediate precision down to 9% in the renewable μSPE format.


Erratum: figure correction. A gut feeling to cure diabetes: potential mechanisms of diabetes remission after bariatric surgery.
[This corrects the article on p. 406 in vol. 38, PMID: 25541603.].


Adolescents and sexual risk-taking: The interplay of constraining relationship beliefs, healthy sex attitudes, and romantic attachment insecurity.
Although sexual exploration during adolescence may be perceived as normative, many adolescents who are sexually active are likely to engage in risky sexual behaviors detrimental to their well-being. The present study examined the influence of insecure attachment (anxious and avoidant dimensions), healthy sex attitudes, and constraining relationship beliefs on the following sexual risk indicators: age at first sex, number of sexual partners, condom use, length of time knowing sexual partners, seriousness of relationship, and frequency of sex. Cross-sectional data from two cohorts recruited one year apart for a five-year project were analyzed. Adolescents were public high school students from a Southern state in the USA (cohort 1: N = 878, 51.1% females, M = 16.50 years old; cohort 2: N = 759, 46.9% females, M = 15.78 years old). Across both cohorts, healthy sex attitudes were related to having sex for the first time at an older age, having less sexual partners in a lifetime, and knowing one's sexual partner longer. High scores on the avoidant attachment dimension were related to less commitment to the relationship. This dimension also was related to holding lower scores on healthy sex attitudes, which in turn was related to having more sexual partners and knowing one's sexual partner for a shorter time. Although not replicated, higher endorsement of constraining relationship beliefs was associated with inconsistent condom use and greater sex frequency. Findings suggests that attachment insecurity, healthy sex attitudes, and constraining relationship beliefs work together to influence adolescent sexual risks.


3a,11b-Dihy-droxy-3a,11b-dihydro-1H-imidazo[4,5-f][1,10]phenanthroline-2(3H)-thione.
The title compound, C(13)H(10)N(4)O(2)S, was prepared through a cyclization reaction of 1,10-phenanthroline-5,6-dione and thio-urea. The dihedral angle between the pyridine rings is 8.22 (2)°. In the crystal, mol-ecules are connected by N-H⋯O, O-H⋯N, N-H⋯S and O-H⋯S hydrogen bonds, forming a three-dimensional network.


Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis.
Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases. To evaluate whether TKIs can be discontinued in these selected patients with mRCC. A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs. Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day. Response according to Response Evaluation Criteria in Solid Tumours (RECIST). We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design. Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.


Using ultrasound to estimate brain size in the cephalopod Octopus vulgaris cuvier in vivo.
Ultrasound imaging was applied, for the first time, in the examination of the central nervous system of the cephalopod mollusc Octopus vulgaris, an invertebrate. Goals of this study were: i. to reveal and measure the cerebral masses in vivo, in their anatomical position; ii. to evaluate and compare the dimensions of the different parts of the octopus brain in vivo and postmortem, and iii. to test the reproducibility of the ultrasound method both in reaching a given sonographic plane in the same individual at two different times and in evaluating potential changes in brain size due to animal growth. Our results show that ultrasonography is a reliable method to measure the various parts of the octopus brain. Sonographic measurements of the brain masses in vivo were correlated with those determined postmortem. In addition, brain size estimation is reproducible via ultrasound: no significant difference resulted when measurements of the same brain were taken over consecutive days. Furthermore, when the time lapse between the two sonographic examinations was long enough (30 days), we were able to detect changes in brain dimensions in the same octopus.


Solar one-way photoisomerisation of 5',8-cyclo-2'-deoxyadenosine.
Under sunlight irradiation (5'S)-5',8-cyclo-2'-deoxyadenosine 2 photoisomerises to the (5'R) isomer 1, which is the more easily repaired damage when these cyclopurine lesions are formed in DNA.


Oscillatory links of Fgf signaling and Hes7 in the segmentation clock.
Somitogenesis is controlled by the segmentation clock, where the oscillatory expression of cyclic genes such as Hes7 leads to the periodic expression of Mesp2, a master gene for somite formation. Fgf signaling induces the oscillatory expression of Hes7 while Hes7 drives coupled oscillations in Fgf and Notch signaling, which inhibits and activates Mesp2 expression, respectively. Because of different oscillatory dynamics, oscillation in Fgf signaling dissociates from oscillation in Notch signaling in S-1, a prospective somite region, where Notch signaling induces Mesp2 expression when Fgf signaling becomes off. Thus, oscillation in Fgf signaling regulates the timing of Mesp2 expression and the pace of somitogenesis. In addition, Fgf signaling was found to be a primary target for hypoxia, which causes phenotypic variations of heterozygous mutations in Hes7 or Mesp2, suggesting gene-environment interaction through this signaling.


Quality of life in children with tuberous sclerosis complex: A pediatric cohort study.
To evaluate the quality-of-life (QOL) impairment and identify the possible risk factors in patients with tuberous sclerosis complex (TSC) in China. The parent proxy-report PedsQL 4.0 Generic Core Scales were administered to 124 caregivers of children with TSC (aged 2-18 years). For comparison, the survey was also conducted in a demographically group-matched sample of healthy controls (HCs) (aged 2-18 years). A total of 124 children with TSC and 206 HCs were recruited. The mean parent proxy-report total scale score, physical health summary score, and psychosocial health summary score for children with TSC were 65.0 (SD 19.7), 77.6 (SD 22.9), and 58.0 (SD 21.3), respectively, compared with the HC values of 83.6 (SD 14.3), 87.2 (SD 16.9), and 82.8 (SD 15.9). There were statistically significant differences between the two groups (P < .0001). TSC2 mutation (P = .033), epilepsy (P = .011), seizure before 2 years old (P = .001), course of epilepsy (more than 2 years) (P = .001), high reported seizure frequency (more than once a month) (HRSF) (P = .007), multiple antiepileptic drugs (≥2) (P = .002), intellectual disability (ID) (mild and moderate ID, P < .0001, and severe and profound ID, P < .0001), and TANDs (P < .0001) (ADHD, P = .004; agoraphobia, P = .007; and social anxiety disorder, P < .0001) were closely related to lower QOL scores. This study is the first large cohort study on QOL in children with TSC in China. The results of the PedsQL 4.0 indicated that the QOL of children with TSC is significantly lower than that of HCs. TSC2 mutation, epilepsy, early onset, long disease course and HRSF, ID, and TANDs are risk factors for poor QOL.


Reconfigurable Liquid Whispering Gallery Mode Microlasers.
Engineering photonic devices from liquid has been emerging as a fascinating research avenue. Reconfigurably tuning liquid optical micro-devices are highly desirable but remain extremely challenging because of the fluidic nature. In this article we demonstrate an all-liquid tunable whispering gallery mode microlaser floating on a liquid surface fabricated by using inkjet print technique. We show that the cavity resonance of such liquid lasers could be reconfigurably manipulated by surface tension alteration originated from the tiny concentration change of the surfactant in the supporting liquid. As such, remarkable sensing of water-soluble organic compounds with a sensitivity of free spectral range as high as 19.85 THz / (mol · mL(-1)) and the detectivity limit around 5.56 × 10(-3) mol · mL(-1) is achieved. Our work provides not only a novel approach to effectively tuning a laser resonator but also new insight into potential applications in biological, chemical and environmental sensing.


Abnormal Eating Patterns Cause Circadian Disruption and Promote Alcohol-Associated Colon Carcinogenesis.
Alcohol intake with circadian rhythm disruption (CRD) increases colon cancer risk. We hypothesized that eating during or around physiologic rest time, a common habit in modern society, causes CRD and investigated the mechanisms by which it promotes alcohol-associated colon carcinogenesis. The effect of feeding time on CRD was assessed using B6 mice expressing a fusion protein of PERIOD2 and LUCIFERASE (PER2::LUC) were used to model colon polyposis and to assess the effects of feeding schedules, alcohol consumption, and prebiotic treatment on microbiota composition, short-chain fatty acid levels, colon inflammation, and cancer risk. The relationship between butyrate signaling and a proinflammatory profile was assessed by inactivating the butyrate receptor GPR109A. Eating at rest (wrong-time eating [WTE]) shifted the phase of the colon rhythm in PER2::LUC mice. In TS4Cre × APClox468 mice, a combination of WTE and alcohol exposure (WTE + alcohol) decreased the levels of short-chain fatty acid-producing bacteria and of butyrate, reduced colonic densities of regulatory T cells, induced a proinflammatory profile characterized by hyperpermeability and an increased mucosal T-helper cell 17/regulatory T cell ratio, and promoted colorectal cancer. Prebiotic treatment improved the mucosal inflammatory profile and attenuated inflammation and cancer. WTE + alcohol-induced polyposis was associated with increased signal transducer and activator of transcription 3 expression. Decreased butyrate signaling activated the epithelial signal transducer and activator of transcription 3 in vitro. The relationship between butyrate signaling and a proinflammatory profile was confirmed in human colorectal cancers using The Cancer Genome Atlas. Abnormal timing of food intake caused CRD and interacts with alcohol consumption to promote colon carcinogenesis by inducing a protumorigenic inflammatory profile driven by changes in the colon microbiota and butyrate signaling. Accession number of repository for microbiota sequence data: raw FASTQ data were deposited in the NCBI Sequence Read Archive under project PRJNA523141.


The pancreas and immunoglobulins. I. Immunoglobulin levels in pancreatic secretion of patients with normal function: preliminary studies.
Immunoglobulin levels of pancreatic juice following secretin administrations were determined in 35 normal patients. The variation of levels was high. The means and standard errors were as follows: Ig-A--7.2 +/- 7.0; Ig-M--1.5 +/- 0.97; Ig-g--21.44 +/- 16.10.