Somatosensory sensitivity in patients with persistent idiopathic orofacial pain is associated with pain relief from hypnosis and relaxation.
In a recent study hypnosis has been found to relieve persistent idiopathic orofacial pain. Quantitative sensory testing (QST) is widely used to evaluate somatosensory sensitivity, which has been suggested as a possible predictor of management outcome. The objectives of this study were to examine: (1) possible associations between clinical pain relief and baseline somatosensory sensitivity and (2) the effect of hypnosis management on QST parameters. Forty-one patients with persistent idiopathic orofacial pain completed this randomized controlled study in 1 of 2 groups: hypnosis (hypnotic analgesia suggestions) or control (relaxation). QST at 2 intraoral (pain region and contralateral mirror image region) and 3 extraoral (hand and both cheeks) sites was performed at baseline and after the hypnosis/control management, together with pressure pain thresholds and pressure pain tolerance thresholds determined bilaterally at the masseter and temporalis muscles, the temporomandibular joints, and the third finger. Degree of pain relief was negatively correlated with a summary statistic of baseline somatosensory sensitivity (summed z-score), that is, high baseline somatosensory sensitivity was associated with low pain relief (r=-0.372, P=0.020). Hypnosis had no major effect on any QST measure compared with relaxation (P>0.063). High pain sensitivity at baseline may predict poor pain management outcome. In addition, despite clear clinical pain relief, hypnosis did not significantly or specifically influence somatosensory sensitivity. Future studies should further explore QST measures as possible predictors of different management response in orofacial pain conditions.


Effects of phenobarbital on stereoselective metabolism of ifosfamide in rats.
Plasma and urinary levels of ifosfamide (IF) enantiomers and their metabolites 2-dechloroethylifosfamide, 3-dechloroethylifosfamide, 4-hydroxyifosfamide, and isophosphoramide mustard were determined for control and phenobarbital-treated male Sprague-Dawley rats by using pseudoracemates and GC/MS and stable-isotope dilution analytical methods. For the control rats, the mean AUC for (S)-IF in plasma was greater than that for (R)-IF (R/S AUC ratio, 0.78) and the mean half-life of 41.8 min for (S)-IF was slightly longer than that of 34.3 min for (R)-IF. Phenobarbital pretreatment significantly decreased the AUC values for (R)-IF and (S)-IF, to 21 and 30% of the control values, respectively, and shortened plasma half-lives for both enantiomers [half-life for (R)-IF, 19.8 min; half-life for (S)-IF, 19.4 min]. The urinary excretion values for (R)-IF and (S)-IF were decreased to 41 and 30% of the control values, respectively. The overall amounts of the metabolites in urine were concomitantly increased. Additionally, there were significant reversals in both the R/S AUC ratio and the urinary excretion of 3-dechloroethylifosfamide. Moreover, the enantioselectivity for the generation of 4-hydroxyifosfamide and isophosphoramide mustard disappeared after phenobarbital treatment. These results strongly suggested that the 4-hydroxylation and dechloroethylation of IF enantiomers were mediated by different P450 isozymes or the same isozyme with different stereochemical selectivities.


Poor Reliability and Poor Adherence to Self-Monitoring of Blood Glucose Are Common in Women With Gestational Diabetes Mellitus and May Be Associated With Poor Pregnancy Outcomes.
To evaluate the compliance with self-monitoring of blood glucose (SMBG) and the reliability of diabetes logbooks in women with gestational diabetes mellitus (GDM), as well as the associated determinants and outcomes. We prospectively selected French-speaking women with newly diagnosed GDM who had been referred to our diabetes management program and understood SMBG principles. At the next follow-up visit, we collected SMBG results from glucose meters and logbooks. We analyzed pregnancy outcomes. Data were analyzed over 13 ± 3 days in 91 women. Only 61.5% had performed ≥80% of the required tests. Poor compliance was associated with a family history of diabetes, social deprivation, and non-European origin. The average time between pre- and postprandial tests was 141 ± 20 min, with 46.5% of women performing ≥80% of postprandial measurements 100-140 min after meals. Inadequate timing was associated with ethnicity and higher HbA1c at baseline. A total of 23.1% of women had <90% matched values in diary and meter memory, and a poor concordance was associated with a family history of diabetes. Poor adherence was associated with more preeclampsia (12.2 vs. 1.9%, P = 0.049), and inadequate postprandial test timing with a higher HbA1c at delivery (5.3 ± 0.4 vs. 5.0 ± 0.3% [34 ± 2 vs. 31 ± 2 mmol/mol], P < 0.01), despite more frequent insulin therapy. Although women with GDM are considered to be highly motivated, SMBG adherence and reliability are of concern and may be associated with poor gestational prognosis, suggesting that caregivers should systematically check the glucose meter memory to improve GDM management.


Analysis of birth weight and gestational age in Taiwan.
Appropriate interpretation of monitored fetal growth throughout pregnancy in individual patients and populations is dependent upon the availability of adequate standards. Previously published standards either were based on small samples, data decades old or were characteristic of foreign subpopulations. We have reviewed the data on a series of 46,575 singleton live births at Chang Gung Memorial Hospital from 1979 to 1989. The ratio of males to females was 1.08. The fetal growth pattern in the third trimester of pregnancy approximates a sigmoid curve. Fetal growth was most rapid from the 32nd to the 37th week of gestation with an average increase of 240 g per week. The birth weight declined beyond 42 weeks' gestation. There were significantly greater weight gains amongst male fetuses as compared to female fetuses from the 34th to the 42nd week of gestation. The mean birth weight recorded at 40 weeks' gestation in male and female newborns was 3,381 g and 3,262 g, respectively. Comparing the birth weight of term pregnancies using our data, with those of a previous, two-decade old report (1945-1967) by Chen, we found that birth weight were slightly higher in this study. The derived fetal growth curves are useful for clinical, public health, and investigational purposes.


Herbal medicines for diabetes control among Indian and Pakistani migrants with diabetes.
Drawing on data collected during a 16-month ethnographic investigation, this paper explores practices around Indians' and Pakistanis' use of herbal medications for diabetes control. The ethnographic study was conducted among Indian and Pakistani migrants in Edinburgh, Scotland and included extended participant observation, six group discussions and 21 semi-structured interviews. Respondents showed great resistance in adhering to medication prescriptions for diabetes control due to their various side effects, especially within the stomach. In order to avoid such side effects, respondents decreased medication dosage and turned to non-allopathic remedies that usually consisted of herbal medications that, according to Indians and Pakistanis, did not cause side effects as medications did and tackled the cause of the disease rather than its symptoms. Such remedies however, were not only combined with allopathic ones but also eventually replaced without the doctor's consultation.


[Clinicopathological features and molecular genetic changes of lung salivary gland-type clear cell carcinoma].
Objective: To investigate the clinicopathological features, immunophenotype, differential diagnosis, molecular genetic changes and prognosis of salivary gland-type clear cell carcinoma (CCC) of the lung. Methods: Eight cases of salivary gland-type CCC of the lung diagnosed at Fudan University Shanghai Cancer Center and Shanghai Pulmonary Hospital, China from March 2017 to December 2020 were retrieved and analyzed. The pathological sections of these cases were studied using immunohistochemical staining, fluorescence in situ hybridization (FISH), and RNA-seq fusion gene detection based on next generation sequencing technique. The patients were followed up and the relevant literature was reviewed. Results: The 8 patients included 3 males and 5 females, with age ranging from 43 to 64 years (average, 58 years). All patients underwent radical lobectomy and lymph node dissection, while only one had lymph node metastases. The eight patients were followed up for 6 to 45 months, and were all recurrence-free. Histopathologically, the tumor was mainly composed of eosinophilic and clear cells arranged in trabecular, ribbon and nest patterns. Hyalinization was often observed in the stroma around the nest. Immunohistochemical staining showed that 8/8 cases were positive for EMA and CK7; 5/8 cases were positive for p63 and p40; 4/8 cases were positive for SOX10; and the cases were all negative for S-100, SMA and calponin. EWSR1 gene fusion was detected in all cases by FISH. RNA-seq fusion gene was detected in 6 cases based on next generation sequencing. The EWSR1-ATF1 gene fusion was detected in 5 cases, among which one case also had the ATF1-SPTLC2 gene fusion. All 5 cases with EWSR1-ATF1 gene fusion showed that EWSR1 exon 12/13 fused with ATF1 exon 3. And EWSR1-CREM gene fusion was detected in one case. Conclusions: Salivary gland-type CCC of the lung is an extremely rare primary lung tumor arising from the bronchial mucosa. The diagnosis and differential diagnosis of this tumor depend on classic histomorphology, especially the auxiliary detection of EWSR1 fusion gene. The primary treatment choice of this tumor is complete surgical resection. Lymph node metastases may occur, but the overall prognosis is good.


Quantitative morphometry of perifoveal capillary networks in the human retina.
To quantify the distribution and morphometric characteristics of capillary networks in the human perifovea. To determine correlations between the location of neuronal subcellular compartments and the morphometric features of regional capillary networks in the layered retina. The perifoveal region, located 2 mm nasal to the fovea, was studied in 17 human donor eyes. Novel micropipette technology was used to cannulate the central retinal artery and label the retinal microcirculation using a phalloidin perfusate. γ-synuclein, Goα, and parvalbumin antibodies were also used to co-localize the nerve fiber layer (NFL), retinal ganglion cell layer (RGCL), inner plexiform layer (IPL), and inner nuclear layer (INL). Confocal scanning laser microscopy was used for capillary imaging. Capillary diameter, capillary density, and capillary loop area measurements were compared between networks. Four capillary networks were identified in the following retinal layers: (1) NFL, (2) RGCL and superficial portion of IPL, (3) deep portion of IPL and superficial portion of INL, and (4) deep portion of INL. Laminar configurations were present in NFL and deep INL networks. Remaining networks demonstrated three-dimensional configurations. Capillary density was greatest in the networks serving the IPL. Capillary loop area was smallest in the two innermost networks. There was no difference in capillary diameter between networks. Capillary networks in the human perifovea are morphometrically heterogeneous. Morphometric features of regional capillary networks in the layered retina may serve a critical role in supporting neuronal homeostasis. Improved knowledge of these features may be important for understanding pathogenic mechanisms underlying retinal vascular diseases.


Anxiety symptoms in older Chinese adults in primary care settings: Prevalence and correlates.
Integrating mental health services into primary care is a potentially cost-effective way to decrease the treatment gap for anxiety in older adults but data on the epidemiology of anxiety symptoms in older Chinese adults in primary care settings have been very limited. This study investigated the prevalence and correlates of anxiety symptoms in Chinese older primary care patients. A total of 753 older primary care patients (≥65 years) were consecutively recruited from 13 primary care clinics in Wuhan, China, and interviewed with the validated Chinese version of the short form of the Geriatric Anxiety Inventory (GAI-SF). The prevalence of anxiety symptoms (GAI-SF ≥ 3) in older primary care patients was 21.1%. Statistically significant correlates of anxiety symptoms were female sex (vs. male, OR = 1.85, P = 0.002), poor economic status (vs. good, OR = 2.31, P = 0.013), fair and poor family relationship (vs. good, OR = 1.85, P = 0.006), hypertension (OR = 2.01, P < 0.001), chronic gastric ulcer (OR = 6.82, P < 0.001), and Parkinson's disease (OR = 7.83, P = 0.031). Anxiety symptoms are prevalent among older adults attending primary care clinics. Efforts for preventing or reducing anxiety symptoms in older primary care patients may be more useful to target those who are women, have poor financial status, don't have a good family relationship, suffer from hypertension, have chronic gastric ulcer, and suffer from Parkinson's disease.


Oral mucosal lesions in Indians from Northeast Brazil: cross-sectional study of prevalence and risk indicators.
The aim of this cross-sectional study was to evaluate the prevalence of oral mucosal lesions, and their risk indicators in adult Kiriri Indians from Northeast Brazil. Clinical oral examination was performed on a representative sample of 223 Indians (age ≥ 19 years). A systematic evaluation of lips, labial mucosa and sulcus, commissures, buccal mucosa and sulcus, gingiva and alveolar ridge, tongue, floor of the mouth, and soft and hard palate was performed. Bivariate analysis was conducted to assess associations between mucosal conditions and age, gender, income, educational level, diabetic status, and smoking status. Mucosal lesions were found in 50 participants (22.4%). The most prevalent lesions were fistulae (6.2%) and traumatic ulcers (4.48%). Oral mucosal was associated with higher age (≥ 35 years; odds ratio [OR] = 1.99, 95% confidence interval [CI]: 1.05-3.76, P = 0.03) and lower education level (<9 years; OR = 2.13, 95% CI: 0.96-4.71, P = 0.06). Mucosal conditions are prevalent in Kiriri Indians and the presence of mucosal lesions is associated with advanced age and lower education. A public health program aimed at preventing and treating mucosal lesions and targeted toward the high-risk group is vital to improve the oral health status of this population.


QTL mapping and transcriptomic analysis of fruit length in cucumber.
A total of 151 recombinant inbred lines (RILs) were derived from the cross between 'Cucumis sativus L. hardwickii' (HW) and a cultivated Northern Chinese inbred line 'XinTaiMiCi' (XTMC). We used resequencing to construct the genetic map and analyze the genetic background of RIL population, and combined with the phenotypes of RIL population and the analysis of RNA-seq data, we located the major loci controlling the fruit length of cucumber and related analysis. A genetic map containing 600 bin markers was constructed via re-sequencing. Based on the phenotype data collected in two different seasons (spring 2021 and autumn 2022), the major quantitative trait loci (QTLs) controlling cucumber fruit length were located and their transcriptomic analysis carried out. The results revealed three QTLs (Fl2.1, Fl4.1, and Fl6.1) detected repeatedly in the two seasons, of which Fl4.1 was the dominant QTL. From the functional annotation of corresponding genes there, we discovered the gene Csa4G337340 encoding an auxin efflux carrier family protein. The expression of that gene was significantly lower in XTMC and the long-fruit RIL lines than in HW and the short-fruit RIL lines; hence, we speculated the gene could be negatively correlated with the fruit length of cucumber. Transcriptomic analysis showed that 259 differentially expressed genes (DEGs) were enriched in the plant hormone signal transduction pathway. In addition, among those DEGs, 509 transcription factors were detected, these distributed in several transcription factor gene families, such as bHLH, AP2/ErF -ERF, C2H2, and NAC. Therefore, we concluded that the major gene controlling the fruit length of cucumber is located in the interval of Fl4.1, whose gene Csa4G337340 may be involved in the negative regulation of fruit length. Further, genes related to plant hormone signal transduction and several transcription factors were also found involved in the regulation of cucumber fruit length. Our results provide a reference for the fine mapping of major genes and analyzing the mechanism of cucumber fruit length.


The dosing-time dependent influence of chronic cyclosporin A treatment on daily profiles of plasma glucose and insulin in the Wistar rat.
The dosing-time dependent effects of cyclosporin A (CsA) on glucose and insulin plasma levels were evaluated in the light of possible alterations of their biological rhythms. Male Wistar rats weighing 200-250 g were habituated to a 12:12 h light-dark cycle. At the beginning of the experiments, on day D0 (before any treatment), significant rhythms were obtained for plasma glucose and immunoreactive insulin (IRI). The plasma glucose showed a 12 h periodicity and the plasma IRI a more pronounced rhythm, with both 12 h and 24 h significant components. Plasma glucose and IRI were then determined in drug-treated (20 mg CsA/kg b.wt/day; dosing time point: T01, T07, T13, or T20) and control rats during and after a 21-day treatment period. The CsA-treated rats developed hyperglycemia and a marked enhancement of the amplitude of the daily glucose rhythm. The magnitude of these effects differed among the groups (p < 0.001). Most pronounced alterations were observed on day 21 (D21) in group T07: M = 22.5 +/- 4.0 mmol/l; A = 9.2 +/- 6.0 mmol/l. The mean plasma insulin showed little though significant (p < 0.01) decreases. For instance, on D21 in group T01, M = 28.5 +/- 3.6 microU/ml, and in group T07, M = 28.7 +/- 2.5 microU/ml. In parallel, plasma CsA levels increased during the 21-day period and differed among groups (p < 0.01). The highest levels (4-5 mg/l) were obtained in T07 and T19 on D21. After drug cessation, the levels of plasma glucose were reduced, but stayed higher than control values. Body weights were monitored; the rate of growth was lower (p < 0.01) in CsA-treated rats than in controls (2.93 +/- 0.11 versus 5.1 +/- 0.11 g/day, respectively).


Relationship between autonomic dysfunction and BP variability in subjects with diabetes mellitus.
Autonomic vagal heart rate (HR) control, office BP and ambulatory BP were examined in 54 diabetic subjects, aged 63 +/- 6 years. Sixteen subjects were insulin-dependent. The HR response to deep breathing (the bradypnoea test) was used to evaluate the vagal HR control, and ambulatory BP was determined by the Spacelabs 5200 system (one determination every 15 minutes, for 24 hours). Twenty-seven subjects had normal office BP (SBP < or = 140 mmHg and DBP < or = 90 mmHg), seven had established hypertension (SBP > or = 160 mmHg and DBP > or = 95 mmHg) and 30 were borderline hypertensives. Over the total group, office systolic/diastolic BP (mean +/- SD) was 142 +/- 20/85 +/- 10 mmg. Systolic/diastolic ambulatory BP was 123 +/- 13/77 +/- 10 mmHg and ambulatory HR was 70 +/- 8 beats/min. Because of the small age range of our subjects, the HR score was not correlated with age (r = 0.19, NS). The HR score was not correlated with the levels of office and ambulatory pressures. In contrast, it was significantly correlated with the variability of ambulatory SBP, whether the variability was defined by the pressure standard deviation, or by the ratio SD/mean value (r = 0.40, P = 0.005 and r = 0.33, P < 0.017, respectively). We suggest that an impairment of the autonomic control in diabetics might induce an increase in variability of SBP. BP variability might play a role in the cardiovascular complications observed in diabetics.


Use of a refractive index-coupled diffuser to both generate and measure high-numerical aperture illumination for light microscopy.
While numerical aperture of transillumination at or above 1.25 can be achieved with a substage oiled Abbe condenser, such immersion-capable condensers can be expensive limiting their use in resource poor settings. Also the measurement of numerical aperture generated by illuminators has received relatively little attention in the literature compared to methods for measuring the numerical aperture of acceptance by objectives. In this article, I show how an inexpensive paper diffuser with refractive-index coupling to the sample slide can generate illumination of a numerical aperture of over 1.4 at a small fraction of the cost of oiled dioptric condensers of comparable numerical aperture. In addition, I present two ways in which a diffuser may also be used to measure the numerical aperture generated by an illuminator using either a calibrated index-coupled paper diffuser to implement an interpolative variation of the Horsfall method or a diffuser as a detector screen coupled to a self-built microscope slide-based illumination system apertometer.


The Leaching Behavior of Potassium Extraction from Polyhalite Ore in Water.
The extraction of potassium from polyhalite ore (K2SO4·MgSO4·2CaSO4·2H2O) can help alleviate potassium resource shortages in China. In this study, the leaching behavior of potassium extracted from polyhalite ore in water was investigated using leaching experiments and kinetic analysis. The effects of various factors, such as liquid-to-solid ratio, leaching temperature, leaching time, and polyhalite ore particle size were comprehensively studied. It was found that high temperatures improved the reaction rate and efficiency at the beginning (1-15 min) but reduced the final leaching efficiency of potassium. And this phenomenon is discussed from the aspects of the dissolution-reprecipitation of potassium, newly formed solid products during the leaching process, and leaching thermodynamics. The leaching of potassium followed the Avrami model, with an apparent activation energy of 26.29 kJ/mol. Additionally, it was determined that the mixed controlled step (surface chemical reaction and diffusion) was the controlling step during potassium leaching. This study clarified the leaching mechanism of the polyhalite in water, and the causes of hindering the leaching of potassium were analyzed. The research results can provide theoretical reference and solutions for parameter design for the enhanced leaching process and selection of leaching agents in the future.


Towards Clinical Translation of LED-Based Photoacoustic Imaging: A Review.
Photoacoustic imaging, with the capability to provide simultaneous structural, functional, and molecular information, is one of the fastest growing biomedical imaging modalities of recent times. As a hybrid modality, it not only provides greater penetration depth than the purely optical imaging techniques, but also provides optical contrast of molecular components in the living tissue. Conventionally, photoacoustic imaging systems utilize bulky and expensive class IV lasers, which is one of the key factors hindering the clinical translation of this promising modality. Use of LEDs which are portable and affordable offers a unique opportunity to accelerate the clinical translation of photoacoustics. In this paper, we first review the development history of LED as an illumination source in biomedical photoacoustic imaging. Key developments in this area, from point-source measurements to development of high-power LED arrays, are briefly discussed. Finally, we thoroughly review multiple phantom, ex-vivo, animal in-vivo, human in-vivo, and clinical pilot studies and demonstrate the unprecedented preclinical and clinical potential of LED-based photoacoustic imaging.


A Case of an Intraorbital Wooden Chip Foreign Body Diagnosed and Removed Several Months after Injury Despite Repeated Imaging Study.
Intraorbital foreign bodies due to trauma are commonly encountered in clinical practice. However, organic foreign bodies, such as wood chips, can sometimes be difficult to diagnose. Here, we report the case of a patient with a wooden chip located intraorbitally that was not detected until spontaneous discharge, despite repeated diagnostic imaging. A 43-year-old intoxicated woman presented to our hospital with a bruised face and eyelid. The patient was diagnosed with conjunctivitis and iritis, but no foreign body was noted in repeated imaging studies since the first visit. Therefore, the patient was observed and managed conservatively. The patient returned to the hospital 114 days after the injury, with no improvement in her conjunctivitis. Examination revealed exposure of a foreign body in the lower eyelid conjunctiva, which was removed during emergency surgery. There are no clear criteria for imaging diagnosis of organic foreign bodies in the body. However, it may be possible to detect them by changing the imaging conditions and examining the computed tomography values in detail. In addition, in case of persistent clinical symptoms, such as inflammation, the image examination should be reviewed. In eyelid trauma, the medical history is sometimes unknown, so it must be remembered that a detailed examination and, in some cases, clinical symptoms are important in making a diagnosis.


New developments in scleroderma interstitial lung disease.
To review the recent medical literature pertaining to interstitial lung disease found in association with systemic sclerosis remains a major contributor to morbidity and mortality. Significant progress is being made in terms of understanding the pathogenesis, the best approaches to clinical evaluation, and various options for therapy of systemic sclerosis patients whose disease course is complicated by interstitial lung disease. Recent studies highlight the importance of microvascular disease, autoimmunity, and fibroblast differentiation/activation in the pathogenesis of systemic sclerosis-interstitial lung disease, particularly in the early phase of disease. It appears as if the balance between various pro-fibrotic/pro-inflammatory and anti-fibrotic/anti-inflammatory mediators may be central to interstitial lung disease pathogenesis, which presents potential opportunities for therapeutic intervention. The clinical approach to staging of disease activity remains controversial. High resolution computed tomography scans, bronchoalveolar lavage and various serum markers (e.g., surfactant protein D and KL-6) each may provide useful information about the degree of activity of the systemic sclerosis-interstitial lung disease. Currently, treatment recommendations are limited by a scarcity of well designed clinical trials, but the recently completed Scleroderma Lung Study is a model for future studies and is providing useful information about this important complication of systemic sclerosis. Basic and clinical studies of systemic sclerosis patients with interstitial lung disease are yielding promising data that ultimately will be translated in to more effective diagnostic and therapeutic strategies.


Analysis of genetic differentiation and genomic variation to reveal potential regions of importance during maize improvement.
Exploring genetic differentiation and genomic variation is important for both the utilization of heterosis and the dissection of the genetic bases of complex traits. We integrated 1857 diverse maize accessions from America, Africa, Europe and Asia to investigatetheir genetic differentiation, genomic variation using 43,252 high-quality single-nucleotide polymorphisms(SNPs),combing GWAS and linkage analysis strategy to exploring the function of relevant genetic segments. We uncovered many more subpopulations that recently or historically formed during the breeding process. These patterns are represented by the following lines: Mo17, GB, E28, Ye8112, HZS, Shen137, PHG39, B73, 207, A634, Oh43, Reid Yellow Dent, and the Tropical/subtropical (TS) germplasm. A total of 85 highly differentiated regions with a DEST of more than 0.2 were identified between the TS and temperate subpopulations. These regions comprised 79% of the genetic variation, and most were significantly associated with adaptive traits. For example, the region containing the SNP tag PZE.108075114 was highly differentiated, and this region was significantly associated with flowering time (FT)-related traits, as supported by a genome-wide association study (GWAS) within the interval of FT-related quantitative trait loci (QTL). This region was also closely linked to zcn8 and vgt1, which were shown to be involved in maize adaptation. Most importantly, 197 highly differentiated regions between different subpopulation pairs were located within an FT- or plant architecture-related QTL. Here we reported that 700-1000 SNPs were necessary needed to robustly estimate the genetic differentiation of a naturally diverse panel. In addition, 13 subpopulations were observed in maize germplasm, 85 genetic regions with higher differentiation between TS and temperate maize germplasm, 197 highly differentiated regions between different subpopulation pairs, which contained some FT- related QTNs/QTLs/genes supported by GWAS and linkage analysis, and these regions were expected to play important roles in maize adaptation.


Fixed-ratio combination therapy with GLP-1 receptor agonist liraglutide and insulin degludec in people with type 2 diabetes.
A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme 'Dual action of liraglutide and insulin degludec in type 2 diabetes' (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo. Areas covered: Combination therapy with IDegLira reduces HbA1c more than monotherapy with a GLP-1RA (liraglutide) or insulin (degludec or glargine). Combination therapy leads also to weight loss, or a stable body weight, with no increase in hypoglycaemia. Rates of adverse events did not differ between treatment groups; however, gastrointestinal side effects were fewer with IDegLira compared with liraglutide treatment alone. A limitation of the DUAL™ development programme is that patients receiving basal insulin doses in excess of 50 units were excluded from the studies. Expert commentary: In conclusion, IDegLira combines the clinical advantages of basal insulin and GLP-1RA treatment, and is a treatment strategy that could improve the management of patients with T2D.


[Primary epithelioid adrenal angiosarcoma mimicking undifferentiated carcinoma].
The adrenal primary epithelioid angiosarcoma (ASE) is a rare malignant tumor which can be histologically confused with other neoplasms. We report one case in a 79-year-old man who underwent adrenal tumor surgery for a mass fortuitly discovered by imaging for examination of an inflammatory syndrome associated with anemia. The histological diagnosis was difficult because of the undifferentiated and epithelioid appearance of tumor cells, whose immunohistochemical epithelial markers positivity led to frequent confusion with a metastatic carcinoma. Careful research for vascular differentiation at histopathological study and expression of immunohistochimical endothelial markers, are crucial to confirm the diagnosis.


Two-dimensional analysis of interleukin 2-regulated tyrosine kinase activation mediated by the p70-75 beta subunit of the interleukin 2 receptor.
The proliferation of activated T lymphocytes is dependent on the interaction of the polypeptide growth factor interleukin 2 (IL 2) with its heterodimeric receptor, which consists of a p55 alpha subunit and a p70-75 beta subunit. Previously, it was shown that IL 2 stimulates rapid serine phosphorylation of several membrane and cytysolic proteins. Here, using anti-phosphotyrosine antibodies to purify phosphotyrosyl proteins and two-dimensional gel analysis, we show that IL 2 stimulates rapid tyrosine phosphorylation of a variety of cellular proteins, including pp180, pp92, and pp42 in activated human T lymphocytes. In addition, we have examined IL 2-induced tyrosine phosphorylation in the human cell line YT2C2 which expresses mostly the beta subunit of the IL 2 receptor and the gibbon cell line MLA-144 which expresses only the beta subunit. In both of these cell lines, IL 2 induced tyrosine phosphorylation of the same proteins phosphorylated in normal human T lymphocytes in response to IL 2. We conclude that the beta subunit is sufficient to induce tyrosine phosphorylation of the normal cellular target substrates involved in signal transduction.


Smoking and associated factors among adolescents in Tallinn, Helsinki and Moscow: a multilevel analysis.
To investigate variations in smoking and associated factors on individual and aggregate level among adolescents in Tallinn (Estonia), Helsinki (Finland) and Moscow (the Russian Federation). The data was collected in Tallinn (N=1268 in Estonian and N=901 in Russian schools), in Helsinki (N=1396) and in Moscow (N=618) from pupils aged 13-18 by self-administered questionnaire. Multilevel analysis was used to estimate the possible effects of background characteristics, of the proximity of other smokers and the school context on the tobacco use of pupils. The prevalence rate of smoking among girls in Russian schools in Tallinn (34.6%), among girls in Helsinki (39.5%), and in Moscow (32.1%) was higher than that among girls in Estonian schools in Tallinn (17.6%). Smoking was slightly less prevalent among boys in Helsinki (27.5%), compared to boys in Estonian (33.6%) and Russian (35.6%) schools in Tallinn, and to boys in Moscow (32.8%). Smoking increased with age. Multilevel analysis showed that smoking differed by school among pupils. Individual determinants of smoking as study site, grade, friends', siblings' and parental smoking behaved differently depending upon school. Friends and siblings' smoking showed interaction with study site to the smoking among girls. Strategies aimed at influencing smoking behaviour need to be directed not only towards the individual, but also towards the influences within the child's school environment.


Levels of wound calprotectin and other inflammatory biomarkers aid in deciding which patients with a diabetic foot ulcer need antibiotic therapy (INDUCE study).
Deciding if a diabetic foot ulcer is infected in a community setting is challenging without validated point-of-care tests. Four inflammatory biomarkers were investigated to develop a composite algorithm for mildly infected diabetic foot ulcers: venous white cell count, C-reactive protein (CRP) and procalcitonin, and a novel wound exudate calprotectin assay. Calprotectin is a marker of neutrophilic inflammation. In a prospective study, people with uninfected or mildly infected diabetic foot ulcers who had not received oral antibiotics in the preceding 2 weeks were recruited from community podiatry clinics for measurement of inflammatory biomarkers. Antibiotic prescribing decisions were based on clinicians' baseline assessments and participants were reviewed 1 week later; ulcer infection was defined by clinicians' overall impression from their two assessments. Some 363 potential participants were screened, of whom 67 were recruited, 29 with mildly infected diabetic foot ulcers and 38 with no infection. One participant withdrew early in each group. Ulcer area was 1.32 cm2 [interquartile range (IQR) 0.32-3.61 cm2 ] in infected ulcers and 0.22 cm2 (IQR 0.09-1.46 cm2 ) in uninfected ulcers. Baseline CRP for mild infection was 9.00 mg/ml and 6.00 mg/ml for uninfected ulcers; most procalcitonin levels were undetectable. Median calprotectin level in infected diabetic foot ulcers was 1437 ng/ml and 879 ng/ml in uninfected diabetic foot ulcers. Area under the receiver operating characteristic curve for a composite algorithm incorporating calprotectin, CRP, white cell count and ulcer area was 0.68 (95% confidence intervals 0.52-0.82), sensitivity 0.64, specificity 0.81. A composite algorithm including CRP, calprotectin, white cell count and ulcer area may help to distinguish uninfected from mildly infected diabetic foot ulcers. Venous procalcitonin is unhelpful for mild diabetic foot ulcer infection.


Transcriptional plasticity of fibroblasts in heart disease.
Cardiac fibroblasts play an essential role in maintaining the structural framework of the heart. Upon stress, fibroblasts undergo a cell state transition to activated fibroblasts (also referred to as myofibroblasts), a highly synthetic cell type that proliferates, migrates, and secrets both extracellular matrix as well as signaling factors that can modulate cellular crosstalk [J. Clin. Invest. 132, e148554]. Activated fibroblasts are critical regulators of cardiac wound healing after injury, but their excessive and persistent activation promote tissue fibrosis, a hallmark feature of the pathological remodeling of the heart. While much of the previous work in cardiac fibroblast biology has focused on the role of canonical signaling pathways or components of the extracellular matrix, recent efforts have been focused on deciphering the gene regulatory principles governing fibroblast activation. A better understanding of the molecular mechanisms that trigger and sustain the fibrotic process in heart disease has the potential to accelerate the development of therapies that specifically target the cardiac activated fibroblasts, which are at the moment unavailable. This concise review focuses on the mechanisms underlying the chromatin and transcriptional regulation of cardiac fibroblast activation. We discuss recent work from our group and others in this space, highlighting the application of single-cell genomics in the characterization of fibroblast function and diversity, and provide an overview on the prospects of targeting cardiac fibroblasts in heart disease and the associated challenges.


Effect of vaccination with a recombinant fusion protein encoding an astacinlike metalloprotease (MTP-1) secreted by host-stimulated Ancylostoma caninum third-stage infective larvae.
Laboratory dogs were vaccinated intramuscularly with a recombinant fusion protein (expressed and isolated from Escherichia coli) formulated with the Glaxo SmithKline Adjuvant System 02 (AS02). The fusion protein encoded Ac-MTP-1, a developmentally regulated astacinlike metalloprotease secreted by host-stimulated Ancylostoma caninum third-stage larvae (L3). Control dogs were injected intramuscularly with an equivalent amount of AS02 adjuvant alone. The vaccinated and control dogs were then challenged by s.c. injection of 500 L3 of the canine hookworm A. caninum. The vaccinated dogs developed prechallenge immunoglobulin G2 (IgG2) antibody responses specific to anti-Ac-MTP-1-fusion protein with titers ranging between 1:40,000 and 1:364,000, whereas they developed antigen-specific immunoglobulin E antibody responses with titers ranging between 1:500 and 1:1,500. By immunoblotting, canine sera obtained from the vaccinated dogs recognized a protein of the estimated apparent molecular weight of Ac-MTP-1 in activated L3 secretory products. Spearman rank order correlations between the canine intestinal adult hookworm burden and quantitative egg counts at necropsy and anti-Ac-MTP-1 IgG2 antibody titers revealed a statistically significant inverse association (r = -0.89; P = 0.04), suggesting that this molecule offers promise as a recombinant vaccine.


[Study of hypophyseal and gonadal hormones and cases of postmenopausal occurrence of bronchial asthma].
A study was conducted into the hormone profile of women with no previous history of allergy who developed bronchial asthma after menopause in order to discover any differences between these and patients of a similar age with allergic bronchial asthma. The serum levels of the following hypophyseal and gonadal hormones were therefore analysed: luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17 oestradiol (17BE2) in both groups of patients and in a control group of healthy postmenopausal volunteers. The results showed lower FSH and LH and higher 17B7(2) levels in the patients with bronchial asthma but no clinical history of allergy than in either the patients with allergic asthma or the healthy volunteers. When the hormone picture in some of the group 1 patients normalised, the clinical symptoms disappeared. One possible explanation is the following: excess oestrogen in the "non-allergy" patients might have caused an imbalance in the PgF/PgE ratio which is thought to contribute to the regulation of bronchomotor tone. The same phenomena might also have accelerated the release of arachidonic acid and its metabolites.


Comparing study of the effect of nanosized silicon dioxide and microsized silicon dioxide on fibrogenesis in rats.
This study compares the effect of nanosized silicon dioxide (nanosized SiO2) and microsized silicon dioxide (microsized SiO2) particles on fibrogenesis in rats. Wistar rats were instilled intratracheally with saline, 20 mg of nanosized SiO2 or 20 mg of microsized SiO2, and were sacrificed at 1 and 2 months after instillation. The lungs of rats were analysed for the changes of lung/body coefficient and hydroxyproline content. Changes in pathology and fibrotic grade were observed by use of hematoxylin and eosin and Van Gieson dyeing. The expression of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) was observed by use of immunohistochemical technique, and protein expression quantitatively analysed by image analysis. The lung/body coefficient and hydroxyproline content of nanosized SiO2 groups were significantly lower than those of microsized SiO2 groups at both 1 and 2 months after instillation (P<0.05 or P<0.01), but without significant differences from those of saline control groups. At 1 month after instillation, there were mainly cellular nodules (Stage I) in nanosized SiO2 group, while in microsized SiO2 group Stage II, II+ of silicotic nodules were observed. At 2 months after instillation, there were still Stage I of silicotic nodules in nanosized SiO2 group. In microsized SiO2 group mainly Stage II+, III of silicotic nodules were found. Quantity image analysis showed that the expressions of IL-4 and TGF-beta1 in nanosized SiO2 groups were significantly lower than those in microsized SiO2 groups (P<0.01), but without significant difference from those of saline control groups. Our experiment revealed that the effect of fibrogenesis of nanosized SiO2 might be milder than that of microsized SiO2 in rats, potentially resulting from nanoparticals tending to be diffused and easily translocated due to their ultrafine particle size compared to microsized particles.


Voluntary policies on checkout foods and healthfulness of foods displayed at, or near, supermarket checkout areas: a cross-sectional survey.
To determine if voluntary policies on supermarket checkout foods are associated with a difference in the healthfulness of foods displayed at, or near, supermarket checkout areas. Cross-sectional survey of foods at, or near, supermarket checkouts categorised as less healthy or not according to the Food Standards Agency's Nutrient Profiling Model. One city in Eastern England (population about 125 000). All stores in nine supermarket groups open for business in June-July 2017 in the study city. Supermarket checkout food policies were categorised as clear and consistent, vague or inconsistent, or none. In thirty-three stores, 11 434 checkout food exposures were recorded, of which 8010 (70·1 %) were less healthy; and 2558 foods in areas near checkouts, of which 1769 (69·2 %) were less healthy. After adjusting for a marker of store size, the odds of a checkout food exposure being 'less healthy' was lower in stores with vague or inconsistent checkout policies (OR=0·63; 95 % CI 0·49, 0·80) and in stores with clear and consistent checkout policies (OR=0·33; 95 % CI 0·24, 0·45), compared with no policy. There was no difference in the odds of foods near, but not at, checkouts being less healthy according to checkout food policy. Supermarket checkout food policies were associated with lower odds of checkout foods but not foods near, but not at, checkouts being less healthy. Further research is required to explore impacts on purchasing and consumption.


Provisional report on diving-related fatalities in Australian waters 2002.
This report covers a total of 33 deaths, of which 17 were in people using a snorkel (three breath-hold diving), 13 in those using scuba, and three in those using surface-supply (hookah) breathing apparatus. There was a wide range of causes of death among the snorkel users, the most unusual being two cases of 'stroke' due to acute, severe hypertensive responses to box jellyfish envenomation. Cardiovascular factors were implicated in nine cases, including a significant history of cardiac disease in three, and single cases of 'silent' cardiomyopathy, 'stroke' in association with hypertension, and obesity. Two cases occurred during the victims' probable first use of a snorkel. In the scuba group, cardiac factors were implicated in 10 of the 13 fatalities, though other factors were also present. Inexperience was critical in at least two cases, and one died when an unsuspected congenital bronchogenic cyst ruptured during an apparently normal ascent. These reports are based on presently available coronial or published reports.


Induction of in vitro resistance to 4'-epidoxorubicin and cis-dichlorodiammineplatinum in hepatoma cells.
We have developed in vitro resistance to 4'-epidoxorubicin (Epi-A) and cis-dichlorodiammineplatinum (cis-DDP) in one rat (MH1C1) and one human hepatoma cell line (HepG2). When compared to their parental cells, the Epi-A resistant rat cells were 17 times and the resistant human cells 27 times more resistant to Epi-A in terms of GI50 in the cell growth inhibition assay. The cis-DDP resistant rat cells were 20 times and the resistant human cells 12 times more resistant to cis-DDP. Cross-resistance to cis-DDP was observed in the Epi-A resistant rat cells but not in the human cells. The multidrug resistant gene product, GP 170, was markedly expressed in both Epi-A resistant substrains compared with their parent lines, suggesting a role of this protein in the development of resistance to Epi-A. Cadmium-binding proteins of metallothionein (MT) size bound 52% of cytosolic 109cadmium in the cis-DDP resistant human cells compared with 8% in the parental cells. This may indicate that these proteins contribute to the observed cis-DDP resistance.


[Effects of ligustrazine on the mitochondrial structure and functions in the process myocardial hypertrophy].
To explore changes of mitochondrial structure and functions, as well as the protection of ligustrazine in the process of myocardial hypertrophy. Neonatal myocardial cells were isolated and cultured with angiotensin II (Ang II) for 72 or 96 h. The total protein content was detected using BCA method. The cell diameter was measured by inverted microscope, by which to reflect the proliferation situation of cardiomyocytes. The mitochondrial membrane potential (MMP) was measured by fluorescence microscope. The mitochondrial monoamine oxidase (MAO) activity was detected by spectrophotometer. The mitochondrial cytochrome oxidase (COX) activity and the mitochondrial damage percentage were detected by microplate reader, by which to reflect the damage of mitochondrial outer membrane's structure and the membranes' function. Also, cells were treated with ligustrazine and losartan and then the pharmacological effects on the mitochondrial structure and functions in the myocardial cells treated with Ang II were observed. At 72 h and 96 h, when compared with the blank group, cells treated with Ang II had increased total protein content (P < 0.01) and enlarged diameter (P < 0.01). Treated with Ang II, the MAO activity and the outer membrane damage percentage of myocardial cells significantly increased (P < 0.01), and mitochondrial COX activity and the mitochondrial MMP significantly decreased (P < 0.01). Compared with the model group at the same time period, ligustrazine significantly reduced myocardial cells' total protein content and myocardial cell diameter, and significantly decreased myocardial cells' MAO activity, increased mitochondrial COX activity, improved the outer membrane damage percentage and inner membrane MMP at 72 and 96 h, all showing statistical difference (P < 0.01, P < 0.05). During the process of myocardial hypertrophy existed the damage to the mitochondrial structure and functions. Ligustrazine protected the mitochondrial structure and functions of the myocardial cells in reversing Ang II induced myocardial cell hypertrophy.


Steric and electronic influence on photochromic switching of N,C-chelate four-coordinate organoboron compounds.
A four-coordinate organoboron compound B(ppy)Mes(2) (1, ppy=2-phenylpyridyl, Mes=mesityl) was previously found to undergo reversible photochromic switching through the formation/breaking of a C-C bond, accompanied by a dramatic color change from colorless to dark blue. To understand this unusual phenomenon, a series of new four-coordinate boron compounds based on the ppy-chelate ligand and its derivatives have been synthesized. In addition, new N,C-chelate ligands based on benzo[b]thiophenylpyridine and indolylpyridine have also been synthesized and their boron compounds were investigated. The crystal structures of most of the new compounds were determined by X-ray diffraction analysis. UV/Vis, NMR, and electrochemical methods were used to monitor the photoisomerization process. DFT calculations were performed for all compounds to understand the photophysical and electronic properties of this class of molecules. The results of our study showed that the bulky mesityl group is necessary for photochromic switching. Electron-donating and electron-withdrawing groups on the ppy chelate have a distinct impact on the photoisomerization rate and the photochemical stability of the molecule. Furthermore, we have found that the non-ppy-based N,C-chelate ligands such as benzo[b]thiophenepyridyl can also promote photoisomerization of the boron chromophore in the same manner as the ppy chelate, but the product is thermally unstable.


Blood donors' perceptions, motivators and deterrents in Sub-Saharan Africa - a scoping review of evidence.
Achieving an adequate blood supply in Sub-Saharan Africa (SSA) through donor mobilization and retention is crucial. Factors that motivate or deter blood donors vary according to beliefs and social norms. Understanding the factors that influence blood donation behaviour in SSA is vital to developing effective strategies to address blood donor motivation and retention. This review of 35 studies from 16 SSA countries collates available evidence concerning the perceptions, motivators and deterrents that influence blood donors in SSA. The review revealed a common understanding that blood and blood donation save lives. The main deterrent to blood donation was fear due to lack of knowledge and discouraging spiritual, religious and cultural perceptions of blood donation. The main motivators for blood donation were altruism, donating blood for family and incentives. The findings support the need for targeted, culturally sensitive education, recruitment and retention strategies to improve the blood supply in SSA.


The protective role of vitamin D3 in a murine model of asthma via the suppression of TGF-β/Smad signaling and activation of the Nrf2/HO-1 pathway.
Asthma is a common worldwide health burden, the prevalence of which is increasing. Recently, the biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3, has been reported to have a protective role in murine asthma; however, the molecular mechanisms by which vitamin D3 attenuates asthma‑associated airway injury remain elusive. In the present study, BALB/c mice were sensitized to ovalbumin (OVA) and were administered 100 ng 1,25-dihydroxyvitamin D3 (intraperitoneal injection) 30 min prior to each airway challenge. The inflammatory responses were measured by ELISA, airway damage was analyzed by hematoxylin and eosin staining, airway remodeling was analyzed by Masson staining and periodic acid‑Schiff staining, markers of oxidative stress were measured by commercial kits, and the expression levels of α‑smooth muscle actin (α-SMA) and the activity of the NF‑E2‑related factor 2 (Nrf2)/heme oxygenase‑1 (HO‑1) and the transforming growth factor‑β (TGF‑β)/Smad signaling pathways were measured by immunohistochemistry and western blotting. The results demonstrated that OVA‑induced airway inflammation and immunoglobulin E overexpression were significantly reduced by vitamin D3 treatment. In addition, treatment with vitamin D3 decreased α‑SMA expression, collagen deposition and goblet cell hyperplasia, and inhibited TGF‑β/Smad signaling in the asthmatic airway. The upregulated levels of malondialdehyde, and the reduced activities of superoxide dismutase and glutathione in OVA‑challenged mice were also markedly restored following vitamin D3 treatment. Furthermore, treatment with vitamin D3 enhanced activation of the Nrf2/HO‑1 pathway in the airways of asthmatic mice. In conclusion, these findings suggest that vitamin D3 may protect airways from asthmatic damage via the suppression of TGF‑β/Smad signaling and activation of the Nrf2/HO‑1 pathway; however, these protective effects were shown to be accompanied by hypercalcemia.


Fissurectomy versus lateral internal sphincterotomy in the treatment of chronic anal fissures: no advantages in terms of post-operative incontinence.
The standard treatment for chronic anal fissures that have failed non-operative management is lateral internal sphincterotomy. Surgery can cause de novo incontinence. Fissurectomy has been proposed as a sphincter/saving procedure, especially in the presence of a deep posterior pouch with or without a crypt infection. This study investigated whether fissurectomy offers a benefit in terms of de novo post-operative incontinence. Patients surgically managed with fissurectomy or lateral internal sphincterotomy for chronic anal fissures from 2013 to 2019 have been included. Healing rate, changes in continence and patient satisfaction were investigated at long-term follow-up. One hundred twenty patients (55 females, 65 males) were analysed: 29 patients underwent fissurectomy and 91 lateral internal sphincterotomy. Mean follow-up was 55 months [confidence interval (CI) 5-116 months]. Both techniques showed some rate of de novo post-operative incontinence (> +3 Vaizey score points): 8.9% lateral internal sphincterotomy, 17.8% fissurectomy (p = 0.338). The mean Vaizey score in these patients was 10.37 [standard deviation (sd) 6.3] after lateral internal sphincterotomy (LIS) and 5.4 (sd 2.3) after fissurectomy Healing rate was 97.8% in the lateral internal sphincterotomy group and 75.8% in the fissurectomy group (p = 0.001). In the lateral internal sphincterotomy group, patients with de novo post-op incontinence showed a statistically significant lower satisfaction rate (9.2 ± 1.57 versus 6.13 ± 3; p = 0.023) while no differences were present in the fissurectomy group (8.87 ± 1.69 versus 7.4 ± 1.14; p = 0.077). Lateral internal sphincterotomy is confirmed as the preferred technique in term of healing rate. Fissurectomy did not offer a lower rate of de novo post-operative incontinence, but resulted in lower Vaizey scores in patients in whom this occurred. Satisfaction was lower in patients suffering a de novo post-operative incontinence after lateral internal sphincterotomy.


A model of substitution trajectories in sequence space and long-term protein evolution.
The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution.


Atrial fibrillation and pneumothorax after transthoracic needle lung biopsy.
An obese 65-year-old male smoker with chronic obstructive pulmonary disease developed an iatrogenic pneumothorax with pulmonary haemorrhage during an elective transthoracic needle biopsy of a pulmonary lesion. Successful re-inflation was achieved with a chest drain which was then removed before transfer to the medical ward. He later developed persistent atrial fibrillation with breathlessness and haemoptysis. He was treated empirically for a pulmonary embolus, which was subsequently ruled out with CT pulmonary angiogram. Serial chest radiographs demonstrated recurrence of his pneumothorax and a chest drain was re-inserted. His atrial fibrillation was erroneously managed as supraventricular tachycardia, which was resistant to vagal manoeuvres and adenosine but later responded to intravenous amiodarone before a further relapse. Upon successful management of the pneumothorax, his atrial fibrillation terminated. This case highlighted the persistent and serious nature of complications posttransthoracic needle biopsy.


[Identification of corium stomachium galli by molecular taxonomy].
To establish a convenient and accurate method of DNA molecular marker for the identification of corium stomachium galli. Cytb mtDNA sequences of Gallus gallus domestica and three other species of poultry were downloaded from Genbank. Species-specific PCR primers were designed according to the differential DNA fragments of the cytb genes. PCR tests were performed with the DNAs extracted from G. gallus domestica, three other poultry species and domestic mammal animals. The specific primers of G. gallus domestica could only amplify the cytb mtDNA of G. gallus domestica. The primers are specific to G. gallus domestica mtDNA and can used to discern Corium stomachium from the false medicine.


The "dawn phenomenon"--a common occurrence in both non-insulin-dependent and insulin-dependent diabetes mellitus.
The dawn phenomenon is a condition recently described in patients with insulin-dependent diabetes mellitus (IDDM) that is characterized by abrupt increases in fasting levels of plasma glucose or insulin requirements or both between 5 and 9 a.m., in the absence of antecedent hypoglycemia. To determine its potential clinical relevance, we assessed its frequency and reproducibility in 20 patients with IDDM and in 13 patients with non-insulin-dependent diabetes mellitus (NIDDM) during overnight closed-loop (feedback-controlled) intravenous insulin infusion. After 6 a.m., plasma glucose levels increased similarly in NIDDM (89 +/- 2 mg per deciliter, midnight to 6 a.m., vs. 98 +/- 2 mg per deciliter, 6 to 9 a.m.; P less than 0.01). Insulin requirements increased at least 50 per cent for 1 1/2 hours in 77 per cent of patients with NIDDM and in 75 per cent of patients with IDDM. In five patients with IDDM who were studied on four occasions, the phenomenon occurred during 17 of the 20 observation periods, with insulin requirements after 6 a.m. increasing 225 +/- 34 per cent; coefficients of variation in individual patients ranged from 4 to 25 per cent. Thus, the dawn phenomenon occurs commonly in both NIDDM and IDDM, but its potential variability must be taken into consideration when one is attempting to adjust insulin doses.


Foveal translocation: a comparison of two techniques.
Subfoveal choroidal neovascular membrane is a leading cause of legal blindness. Photocoagulation has been effective, but photocoagulation of the fovea causes a decrease in vision immediately after treatment. Surgical removal of the choroidal neovascular membrane is effective for choroidal neovascular membrane in some cases, but it restores useful vision for reading (20/40 or better) in a small number of cases of choroidal neovascular membrane not due to presumed ocular histoplasmosis syndrome. A new treatment for subfoveal choroidal neovascular membrane, foveal translocation, is an innovative procedure in which the fovea is translocated onto healthier retinal pigment epithelium. Three techniques have been developed to relocate the retina, 2 of which (retinotomy and scleral shortening) we performed in 5 cases each. Preliminary results in these 10 cases indicate that foveal translocation provides improvement of visual acuity in 40% of eyes and final visual acuities useful for reading (better than 20/40) in 20% of eyes undergoing translocation with either technique. Further study is essential to refine the amount of translocation needed and to decrease complications of the 2 techniques, including retinal detachment, proliferative vitreoretinopathy, macular pucker, corneal astigmatism, and constricted visual field.


Regulation of Neuronal Stem Cell Proliferation in the Hippocampus by Endothelial Ceramide.
Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of major depressive disorder and functions as a target of antidepressants. Here, we investigated (i) whether ceramide accumulates in endothelial cells in the neurogenetic zone of the hippocampus after glucocorticosterone-mediated stress, (ii) whether ceramide is released into the extracellular space of the hippocampus and (iii) whether extracellular ceramide inhibits neuronal proliferation. Ceramide was determined in endothelial cell culture supernatants or extracellular hippocampus extracts by a kinase assay. Endothelial ceramide in the hippocampus was analyzed by confocal microscopy of brain sections stained with Cy3-labelled anti-ceramide antibodies and FITC-Isolectin B4. Neuronal proliferation was measured by incubation of pheochromocytoma neuronal cells with culture supernatants and extracellular hippocampus extracts. Treatment of cultured endothelial cells with glucocorticosterone induces a release of ceramide into the supernatant. Likewise, treatment of mice with glucocorticosterone triggers a release of ceramide into the extracellular space of the hippocampus. The release of ceramide is inhibited by concomitant treatment with the antidepressant amitriptyline, which also inhibits the activity of the acid sphingomyelinase. Studies employing confocal microscopy revealed that ceramide is formed and accumulates exclusively in endothelial cells in the hippocampus of stressed mice, a process that was again prevented by co-application of amitriptyline. Ceramide released in the culture supernatant or into the extracellular space of the hippocampus reduced proliferation of neurons in vitro. The data suggest a novel model for the pathogenesis of major depressive disorder, i.e. the release of ceramide-enriched microvesicles from endothelial cells that negatively affect neuronal proliferation in the hippocampus, but may also induce cardiovascular disease and other systemic symptoms of patients with major depressive disorder.


Sparsity-driven synchronization in oscillator networks.
The emergence of synchronized behavior is a direct consequence of networking dynamical systems. Naturally, strict instances of this phenomenon, such as the states of complete synchronization, are favored or even ensured in networks with a high density of connections. Conversely, in sparse networks, the system state-space is often shared by a variety of coexistent solutions. Consequently, the convergence to complete synchronized states is far from being certain. In this scenario, we report the surprising phenomenon in which completely synchronized states are made the sole attractor of sparse networks by removing network links, the sparsity-driven synchronization. This phenomenon is observed numerically for nonlocally coupled Kuramoto networks and verified analytically for locally coupled ones. In addition, we unravel the bifurcation scenario underlying the network transition to completely synchronized behavior. Furthermore, we present a simple procedure, based on the bifurcations in the thermodynamic limit, that determines the minimum number of links to be removed in order to ensure complete synchronization. Finally, we propose an application of the reported phenomenon as a control scheme to drive complete synchronization in high connectivity networks.


Dietary potassium and blood pressure in a population.
A population based study of 685 men and women aged 20 to 79 yr in a predominantly Caucasian community in Southern California found dietary potassium intake estimated from 24-h recall dietary history to be significantly and negatively correlated with age-adjusted systolic pressure in both men and women and with age-adjusted diastolic blood pressure in men. These correlations remained after exclusion of persons taking antihypertension medication or those with categorical hypertension (blood pressure greater than 160/95), and also persisted after adjusting for other dietary variables including alcohol and calcium intake. In women, correlations with blood pressure increased after excluding those taking sex hormones, suggesting that hormonal status may be an important determinant of blood pressure in women and may obscure other relationships. These findings support the etiological relationship of dietary potassium with blood pressure in populations.


[Hospitalization burden of hand, foot and mouth disease in Anhua county of Hunan province, 2013-2016].
Objective: To estimate the serotype and age-specific hospitalization burden associated with hand, foot and mouth disease (HFMD) in Anhua county of Hunan province, between October 2013 and September 2016. Methods: We collected hospitalization records of HFMD patients from 6 virological surveillance hospitals, and reimbursement records through new rural cooperative medical system from 23 township health centers to estimate the age-specific hospitalization burden of HFMD in Anhua. Combined with the results of virological surveillance, the serotype-specific hospitalization burden of HFMD in Anhua, was estimated. Results: During the three years, it was estimated that 3 541 clinical diagnosed HFMD cases, including 3 146 laboratory-confirmed HFMD cases, were hospitalized in Anhua, but only one was diaguosed as being severe. The estimated average hospitalization rate was 723/100 000(95%CI: 699/100 000-747/100 000) for clinical diagnosed HFMD and 642/100 000 (95%CI: 620/100 000-665/100 000) for laboratory-confirmed HFMD between October 2013 and September 2016. The cases caused by Cox A16 (208/100 000) and Cox A6 (202/100 000) had higher hospitalization rates compared with the cases caused by EV71 (130/100 000), Cox A10 (38/100 000) and other enterovirus (64/100 000), and the difference was statistically significant (P<0.001). HFMD-associated hospitalization rates peaked in children aged 1 year (3 845/100 000), and then decreased with age. Compared with the hospitalized HFMD caused by EV71 and Cox A16, Cox A6-associated hospitalizations mainly occurred in younger age groups (P<0.001). Conclusion: Our study revealed a substantial hospitalization burden associated with mild HFMD caused by EV71, Cox A16, Cox A6 and Cox A10, especially in young children, in Anhua.


Developmental dyslexia in different languages: language-specific or universal?
Most of the research on developmental dyslexia comes from English-speaking countries. However, there is accumulating evidence that learning to read English is harder than learning to read other European orthographies (Seymour, Aro, & Erskine, 2003). These findings therefore suggest the need to determine whether the main English findings concerning dyslexia can be generalized to other European orthographies, all of which have less irregular spelling-to-sound correspondences than English. To do this, we conducted a study with German- and English-speaking children (n=149) in which we investigated a number of theoretically important marker effects of the reading process. The results clearly show that the similarities between dyslexic readers using different orthographies are far bigger than their differences. That is, dyslexics in both countries exhibit a reading speed deficit, a nonword reading deficit that is greater than their word reading deficit, and an extremely slow and serial phonological decoding mechanism. These problems were of similar size across orthographies and persisted even with respect to younger readers that were at the same reading level. Both groups showed that they could process larger orthographic units. However, the use of this information to supplement grapheme-phoneme decoding was not fully efficient for the English dyslexics.


Information and Communication Technologies to Support Chronic Disease Self-Management: Preconditions for Enhancing the Partnership in Person-Centered Care.
In order to alleviate the pressure on health care systems exerted by the growing prevalence of chronic diseases, information and communication technologies (ICT) are being introduced to enable self-management of chronic diseases by supporting partnerships between patients and health care professionals. This move towards chronic disease self-management is accompanied by a shift in focus on integrating the patient with his or her perceptions on the chronic disease as a full-fledged partner into the health care system. This new perspective has been described as "person-centered care" (PCC). To date, information and communication technologies only partially build on the principles of PCC. This paper examines the preconditions of ICT to enable a person-centered approach to chronic disease management. Using cancer treatment as a case study for ICT-enabled PCC, we conducted a comparative analysis of thirteen scientific studies on interventions presented as ICT-enabled PCC for cancer treatment, to answer the research question: What are the preconditions of ICT-enabled PCC in chronic disease management? Based on the intended and actual outcomes, we distilled in several analytic steps the preconditions of ICT-enabled PCC for chronic disease self-management. We distinguished four user-related preconditions of ICT-enabled PCC: (shared) decision making, personalized ICT, health-related quality of life, and efficiency. We argue that these four preconditions together can improve people's self-management of chronic diseases by strengthening the partnership between the patient and the healthcare professional. Moreover, the study revealed a discrepancy between intended and reported actual outcomes in terms of realizing person-centered care.


A Review on Electrochemical Sensors and Biosensors Used in Phenylalanine Electroanalysis.
Phenylalanine is an amino acid found in breast milk and in many foods, being an essential nutrient. This amino acid is very important for the human body because it is transformed into tyrosine and, subsequently, into catecholamine neurotransmitters. However, there are individuals who were born with a genetic disorder called phenylketonuria. The accumulation of phenylalanine and of some metabolites in the body is dangerous and may cause convulsions, brain damage and mental retardation. Determining the concentration of phenylalanine in different biologic fluids is very important because it can provide information about the health status of the individuals envisaged. Since such determinations may be made by using electrochemical sensors and biosensors, numerous researchers have developed such sensors for phenylalanine detection and different sensitive materials were used in order to improve the selectivity, sensitivity and detection limit. The present review aims at presenting the design and performance of some electrochemical bio (sensors) traditionally used for phenylalanine detection as reported in a series of relevant scientific papers published in the last decade.


Angiopoietin-like protein 1 decreases blood brain barrier damage and edema following focal cerebral ischemia in mice.
Angiopoietin-like protein (Angptl) 1, a member of the angiopoietin-related protein family, modulates angiogenesis but little else is known of its physiological role. We found that angptl1 was upregulated at the 7th day after focal cerebral ischemia in normal mice. In order to understand the role of angptl1 in cerebral infarction, we induced focal cerebral ischemia in normal and glial fibrillary acidic protein promoter-angptl1 transgenic mice. In the transgenic mice without ischemia, overexpression of angptl1 in the whole brain led to a decrease in cortical microvascular density. Following focal cerebral ischemia, edema, but not infarct size, was less in transgenic mice relative to wild type littermates. This effect might be due to a reduction in the blood brain barrier breakdown, as confirmed by a decrease in Evans Blue leakage in the early post-ischemic phase. We conclude that angptl1 may have a beneficial role in the preservation of vascular integrity following focal cerebral ischemia.


Comparison of the effects of Korean ginseng and heat-processed Korean ginseng on diabetic oxidative stress.
To investigate the effects of Korean ginseng (KG, Panax ginseng C.A. Meyer) and heat-processed Korean ginseng (H-KG) on diabetic renal damage, we used the streptozotocin-induced diabetic rat model in this study. The diabetes-induced physiological abnormalities at early-stage were attenuated by KG or H-KG administration through reducing the blood glucose level and improving renal function. The oxidative stress-induced increases in serum and renal thiobarbituric acid-reactive substance levels were significantly reduced by KG and H-KG administrations. Moreover, the protein expressions related to oxidative stress and advanced glycation endproducts were significantly reduced in diabetic rats and/or not significantly increased compared to normal rats by KG or H-KG administration. All of these beneficial effects of H-KG in diabetic rats were stronger than those of KG. Therefore, KG and H-KG may improve diabetic pathological conditions and prevent renal damage associated with diabetic nephropathy, and these protective effects of KG can be improved by heat-processing. This study provides scientific evidence that H-KG may be a potential therapeutic agent for pathological conditions associated with diabetic complications including diabetic nephropathy.


Transcriptomic and metabolomic data integration.
Many studies now produce parallel data sets from different omics technologies; however, the task of interpreting the acquired data in an integrated fashion is not trivial. This review covers those methods that have been used over the past decade to statistically integrate and interpret metabolomics and transcriptomic data sets. It defines four categories of approaches, correlation-based integration, concatenation-based integration, multivariate-based integration and pathway-based integration, into which all existing statistical methods fit. It also explores the choices in study design for generating samples for analysis by these omics technologies and the impact that these technical decisions have on the subsequent data analysis options.


A magnesium-induced triplex pre-organizes the SAM-II riboswitch.
Our 13C- and 1H-chemical exchange saturation transfer (CEST) experiments previously revealed a dynamic exchange between partially closed and open conformations of the SAM-II riboswitch in the absence of ligand. Here, all-atom structure-based molecular simulations, with the electrostatic effects of Manning counter-ion condensation and explicit magnesium ions are employed to calculate the folding free energy landscape of the SAM-II riboswitch. We use this analysis to predict that magnesium ions remodel the landscape, shifting the equilibrium away from the extended, partially unfolded state towards a compact, pre-organized conformation that resembles the ligand-bound state. Our CEST and SAXS experiments, at different magnesium ion concentrations, quantitatively confirm our simulation results, demonstrating that magnesium ions induce collapse and pre-organization. Agreement between theory and experiment bolsters microscopic interpretation of our simulations, which shows that triplex formation between helix P2b and loop L1 is highly sensitive to magnesium and plays a key role in pre-organization. Pre-organization of the SAM-II riboswitch allows rapid detection of ligand with high selectivity, which is important for biological function.


Tunable orbital angular momentum generation in optical fibers.
We present a method in this Letter to generate optical vortices with tunable orbital angular momentum (OAM) in optical fibers. The tunable OAM optical vortex is produced by combining different vector modes HE2,meven (HE2,modd) and TE0,m (TM0,m) when l=1 or combining HEl+1,meven (HEl+1,modd) and EHl-1,modd (EHl-1,meven) when l>1 with a π/2 phase shift. The vortex can be regarded as a result of overlapping two orthogonal optical vortex beams of equal helicity but opposite chirality with a π/2 phase shift. We have experimentally demonstrated the smooth variation of OAM from l=-1 to l=+1 by adjusting a polarizer at the output end of the fiber.


Not So Similar: Different Ways of Nb(V) and Ta(V) Catecholate Complexation.
The reactions between catechol (H2cat) and niobium(V) or tantalum(V) precursors in basic aqueous solutions lead to the formation of catecholate complexes of different natures. The following complexes were isolated and characterized by single-crystal X-ray diffraction (SCXRD): (1) (NH4)3[NbO(cat)3]∙4H2O; (2) K2[Nb(cat)3(Hcat)]·2H2cat·2H2O; (3) Cs3[NbO(cat)3]·H2O; (4) (NH4)4[Ta2O(cat)6]·3H2O; (5) Cs2[Ta(cat)3(Hcat)]·H2cat; (6) Cs4[Ta2O(cat)6]·7H2O. The isolated crystalline products were characterized by elemental analysis, X-ray powder diffraction (XRPD), FTIR, and TGA. The structural features of these complexes, such as {Ta2O} unit geometry, Cs-π interactions, and crystal packing effects, are discussed.


Reconsidering betaine as a natural anti-heat stress agent in poultry industry: a review.
Betaine is found ubiquitously in plants, animals, microorganisms, and rich dietary sources including seafood, spinach, and wheat bran. The chief physiological role of betaine is to function as a methyl donor and an osmolyte. Betaine also acts as an osmolyte, to maintain the avian's cellular water and ion balance to improve the avian's capacity against heat stress via preventing dehydration and osmotic inactivation. It helps in maintaining the protective osmolytic activity, especially in heat-stressed birds. Betaine may promote various intestinal microbes against osmotic variations and thus improve microbial fermentation activity. Previous studies showed that dietary supplementation of betaine in poultry diets could positively affect nutrients' digestibility, reduce abdominal fat weight, and increase breast meat yield. In addition, betaine has been reported to protect internal organs and boost their performance. Its inclusion in poultry diet is sparing essential amino acids like choline and methionine. In addition, it may play an important role in lean meat production by positively affecting the lipid metabolism with increased fatty acids catabolism and thus reducing carcass fat deposition. The aim of this review article was to broaden the knowledge regarding betaine and its importance in the poultry industry to cope with the heat stress problem. Moreover, it should be added to the diet as a natural anti-stressor through different routes (water/feed) to overcome the heat stress problem. However, further studies need to be conducted at the genetic and molecular basis to elucidate the mechanism behind the betaine as a natural anti-heat agent to decrease the heat stress problem in the poultry industry.


Prenatal and early postnatal lead exposure in mice: neuroimaging findings.
Childhood lead exposure has been linked to adult gray matter loss accompanied by changes in myelination and neurochemistry noninvasively revealed by magnetic resonance imaging (MRI) methods. However, the extent, duration and timing of lead exposure required to produce such imaging changes in humans are difficult to ascertain. To determine if such changes are related to early exposure to low levels of lead, we treated mouse dams with 0, 3, or 30 ppm of lead acetate in drinking water for 2 months prior to mating through gestation until weaning of the offspring at post-natal day 21. Two male and two female pups from each litter were imaged at post-natal day 60. Volumetric, diffusion tensor imaging and magnetic resonance spectroscopy (MRS) measurements were obtained using a seven Tesla Bruker animal MRI scanner. Postnatal blood lead levels were identical between groups at the time of imaging. No effects of lead exposure were detected in the volumetric or MRS data. Mean diffusivity in the hippocampus showed significant effects of lead exposure and gender. These data suggest that low-level, gestational lead exposure in a mouse model produces minimal changes observed by MRI.


cAMP/PKA Pathways and S56 Phosphorylation Are Involved in AA/PGE2-Induced Increases in rNaV1.4 Current.
Arachidonic acid (AA) and its metabolites are important second messengers for ion channel modulation. The effects of extracellular application of AA and its non-metabolized analogue on muscle rNaV1.4 Na+ current has been studied, but little is known about the effects of intracellular application of AA on this channel isoform. Here, we report that intracellular application of AA significantly augmented the rNaV1.4 current peak without modulating the steady-state activation and inactivation properties of the rNaV1.4 channel. These results differed from the effects of extracellular application of AA on rNaV1.4 current. The effects of intracellular AA were mimicked by prostaglandin E2 but not eicosatetraynoic acid (ETYA), the non-metabolized analogue of AA, and were eliminated by treatment with cyclooxygenase inhibitors, flufenamic acid, or indomethacin. AA/PGE2-induced activation of rNaV1.4 channels was mimicked by a cAMP analogue (db-cAMP) and eliminated by a PKA inhibitor, PKAi. Furthermore, inhibition of EP2 and EP4 (PGE2 receptors) with AH6809 and AH23848 reduced the intracellular AA/PGE2-induced increase of rNaV1.4 current. Two mutated channels, rNaV1.4S56A and rNaV1.4T21A, were designed to investigate the role of predicted phosphorylation sites in the AA/PGE2-mediated regulation of rNaV1.4 currents. In rNaV1.4S56A, the effects of intracellular db-cAMP, AA, and PGE2 were significantly reduced. The results of the present study suggest that intracellular AA augments rNaV1.4 current by PGE2/EP receptor-mediated activation of the cAMP/PKA pathway, and that the S56 residue on the channel protein is important for this process.


Brief report: sedatives for mothers of stillborn infants: views from a national survey of obstetricians.
Although no guidelines support the use of benzodiazepines in bereavement care, clinicians continue to use this medication for surviving family members. An anonymous survey about perinatal death was sent to 1500 United States obstetricians. One question assessed beliefs about prescribing sedatives to bereaved mothers. Almost half (49%) of 804 obstetricians endorsed the use of sedatives, such as benzodiazepines, for acute bereavement. Grieving families may experience mental and physical anguish after a death; however, benzodiazepines are not part of recommended care for bereavement. The surprisingly high support from physicians for the use of sedatives in the case of maternal grief raises important questions about how physicians can best support bereaved mothers and what effect benzodiazepines may have in the grieving process.


Expression of Nox genes in rat organs, mouse oocytes, and sea urchin eggs.
Degenerate primers were designed to isolate new homologs of Nox family genes in rat organs and sea urchin eggs. The primers were capable of amplifying Nox1, Nox2, Nox3, Nox4, Duox1 and Duox2 but not Nox5, and failed to isolate novel homologs in rat. However, a novel homolog (named as Nox-U1) was identified in sea urchin eggs. In the most conserved region (amino acid 336--417 in human Nox2) Nox-U1 has the highest identity with Nox2, which appears to be abundant in mouse oocytes. However, phylogenetic analysis of the entire sequence has revealed that Nox-U1 is closer to Nox4 or Nox5 than Nox2 or Nox3. Histidine residues assumed to be responsible for heme ligation, motifs for FAD- and NADPH-binding, and two asparagine-linked glycosylation sites are conserved.


Use of genomic prediction to screen sorghum B-lines in hybrid testcrosses.
Use of trifluoromethanesulfonamide (TFMSA), a male gametocide, increases the opportunities to identify promising B-lines because large quantities of F1 seed can be generated prior to the laborious task of B-line sterilization. Combining TFMSA technology with genomic selection could efficiently evaluate sorghum B-lines in hybrid combination to maximize the rates of genetic gain of the crop. This study used two recombinant inbred B-line populations, consisting of 217 lines, which were testcrossed to two R-lines to produce 434 hybrids. Each population of testcross hybrids were evaluated across five environments. Population-based genomic prediction models were assessed across environments using three different cross-validation (CV) schemes, each with 70% training and 30% validation sets. The validation schemes were as follows: CV1-hybrids chosen randomly for validation; CV2-B-lines were randomly chosen, and each chosen B-line had one of the two corresponding testcross hybrids randomly chosen for the validation; and CV3-B-lines were randomly chosen, and each chosen B-line had both corresponding testcross hybrids chosen for the validation. CV1 and CV2 presented the highest prediction accuracies; nonetheless, the prediction accuracies of the CV schemes were not statistically different in many environments. We determined that combining the B-line populations could improve prediction accuracies, and the genomic prediction models were able to effectively rank the poorest 70% of hybrids even when genomic prediction accuracies themselves were low. Results indicate that combining genomic prediction models and TFMSA technology can effectively aid breeders in predicting B-line hybrid performance in early generations prior to the laborious task of generating A/B-line pairs.


Whole Genome Sequence and Phylogenetic Analysis Show Helicobacter pylori Strains from Latin America Have Followed a Unique Evolution Pathway.
Helicobacter pylori (HP) genetics may determine its clinical outcomes. Despite high prevalence of HP infection in Latin America (LA), there have been no phylogenetic studies in the region. We aimed to understand the structure of HP populations in LA mestizo individuals, where gastric cancer incidence remains high. The genome of 107 HP strains from Mexico, Nicaragua and Colombia were analyzed with 59 publicly available worldwide genomes. To study bacterial relationship on whole genome level we propose a virtual hybridization technique using thousands of high-entropy 13 bp DNA probes to generate fingerprints. Phylogenetic virtual genome fingerprint (VGF) was compared with Multi Locus Sequence Analysis (MLST) and with phylogenetic analyses of cagPAI virulence island sequences. With MLST some Nicaraguan and Mexican strains clustered close to Africa isolates, whereas European isolates were spread without clustering and intermingled with LA isolates. VGF analysis resulted in increased resolution of populations, separating European from LA strains. Furthermore, clusters with exclusively Colombian, Mexican, or Nicaraguan strains were observed, where the Colombian cluster separated from Europe, Asia, and Africa, while Nicaraguan and Mexican clades grouped close to Africa. In addition, a mixed large LA cluster including Mexican, Colombian, Nicaraguan, Peruvian, and Salvadorian strains was observed; all LA clusters separated from the Amerind clade. With cagPAI sequence analyses LA clades clearly separated from Europe, Asia and Amerind, and Colombian strains formed a single cluster. A NeighborNet analyses suggested frequent and recent recombination events particularly among LA strains. Results suggests that in the new world, H. pylori has evolved to fit mestizo LA populations, already 500 years after the Spanish colonization. This co-adaption may account for regional variability in gastric cancer risk.


Evidence for rapid weathering response to climatic warming during the Toarcian Oceanic Anoxic Event.
Chemical weathering consumes atmospheric carbon dioxide through the breakdown of silicate minerals and is thought to stabilize Earth's long-term climate. However, the potential influence of silicate weathering on atmospheric pCO2 levels on geologically short timescales (103-105 years) remains poorly constrained. Here we focus on the record of a transient interval of severe climatic warming across the Toarcian Oceanic Anoxic Event or T-OAE from an open ocean sedimentary succession from western North America. Paired osmium isotope data and numerical modelling results suggest that weathering rates may have increased by 215% and potentially up to 530% compared to the pre-event baseline, which would have resulted in the sequestration of significant amounts of atmospheric CO2. This process would have also led to increased delivery of nutrients to the oceans and lakes stimulating bioproductivity and leading to the subsequent development of shallow-water anoxia, the hallmark of the T-OAE. This enhanced bioproductivity and anoxia would have resulted in elevated rates of organic matter burial that would have acted as an additional negative feedback on atmospheric pCO2 levels. Therefore, the enhanced weathering modulated by initially increased pCO2 levels would have operated as both a direct and indirect negative feedback to end the T-OAE.


A new frequency based automatic sleep analysis - description of the healthy sleep.
A new system for complete automated sleep analysis has been developed (Somnoscript2000). Eighteen healthy young volunteers (ages 21-28 years, 9 females and 9 males) underwent a complete polysomnographic (PSG) registration. EEG from 17 electrode positions was recorded simultaneously with the polygraphic parameters (CATEEM(R)). The characterization of the recorded bioelectrical signals is based on the spectral frequency analysis by Fast Fourier Transformation (FFT). A new sleep-staging algorithm was developed, which allows for an objective presentation of the sleep phenomena. This system is characterized by a high reproducibility of the individual polysomnographic data throughout the recording with no significant difference between different all-night recordings of the subject. The sleep architecture shows considerable intersubject variability leading to differentiation of two main subpopulations: "good" and "poor sleepers".


Finger and toenail onycholysis.
Onycholysis - the separation of the nail plate from the nail bed occurs in fingers and toenails. It is diagnosed by the whitish appearance of the separated nail plate from the nail bed. In fingers, the majority is caused by trauma, manicuring, occupational or self-induced behavior. The most common disease producing fingernail onycholysis is psoriasis and pustular psoriasis. Phototoxic dermatitis, due to drugs can also produce finger onycholysis. Once the separation occurs, the environmental flora sets up temporary colonization in the available space. Finger onycholysis is most common in women. Candida albicans is often recovered from the onycholytic space. Many reports, want to associate the yeast as cause and effect, but the data are lacking and the treatment of the candida does not improve finger onycholysis. A reasonable explanation for the frequent isolation of Candida and Pseudomonas in fingernail onycholysis in women, is the close proximity the fingers have to the vaginal and gastrointestinal tract. Fifty per cent of humans harbour C. albicans in the GI tract and it is frequently carried to the vagina during hygienic practices. Finger onycholysis is best treated by drying the nail 'lytic' area with a hair blower, since all colonizing biota are moisture loving and perish in a dry environment. Toenail onycholysis has a very different etiology. It is mechanical, the result of pressure on the toes from the closed shoes, while walking, because of the ubiquitous uneven flat feet producing an asymmetric gait with more pressure on the foot with the flatter sole.


Effect of new and known 1,4-dihydropyridine derivatives on blood glucose levels in normal and streptozotocin-induced diabetic rats.
Analysis of the effect of several 1,4-DHP Ca(2+) channel antagonists on experimental and clinical diabetes shows that structurally similar Ca(2+) channel antagonists can exert opposite effects on Ca(2+) influx, glucose homeostasis and insulin secretion. The influence of the Ca(2+) channel antagonists on pancreatic beta cell functions is dependent on lipophilicity, interactions with the cell membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle membranes, with intracellular receptors, bioavailability and time of elimination from several organs and the bloodstream. In the present work we studied the effect at several doses of new compounds synthesized in the Latvian Institute of Organic Synthesis on blood glucose levels in normal and STZ-induced diabetic rats. The compounds tested were: 1,4-DHP derivatives cerebrocrast (1), etaftoron (2), OSI-1190 (3), OSI-3802 (4), OSI-2954 (5) and known 1,4-DHP derivatives: niludipine (6), nimodipine (7) and nicardipine (8) which possess different lipophilicities. Analysis of the structure-function relationships of the effect of 1,4-DHP derivatives on glucose metabolism showed that cerebrocrast could evoke qualitative differences in activity. Insertion of an OCHF(2) group in position 2 of the 4-phenylsubstituent and propoxyethylgroup R in ester moieties in positions 3 and 5 of the DHP structure, as well as an increase in the number of carbon atoms in the ester moiety, significantly modified the properties of the compound. Thereby cerebrocrast acquired high lipophilicity and membranotropic properties. Cerebrocrast, in a single administration at low doses (0.05 and 0.5 mg x kg(-1), p.o.), significantly decreased the plasma level of glucose in normal rats and in STZ-induced diabetic rats returned plasma glucose to basal levels. This effect was characterized by a slow onset and a powerful long-lasting influence on glucose metabolism, especially in STZ-induced diabetic rats.


The winter peak in the occurrence of acute aortic dissection is independent of climate.
We recently reported the existence of a higher risk of acute aortic dissection (AAD) during the winter months. However, it is not known whether this winter peak is affected by climate. To address this issue, we evaluated data from 969 AAD patients who were enrolled at various sites around the globe and who were participating in the International Registry of Acute Aortic Dissection (IRAD). We found a significant (p = 0.001; chi2 test) difference in the number of AAD events occurring during the different seasons of the year, with highest incidence in winter (28.4%) and lowest incidence in summer (19.9%). Furthermore, the winter peak was evident in both cold and temperate climate settings, suggesting that the relative change in temperature, rather than absolute temperature, and/or endogenous annual rhythms are critical mechanistic factors.


Diagnostic accuracy of ultrasonography versus fine-needle-aspiration cytology for predicting benign thyroid lesions.
Thyroid nodules (TNs) are abnormal growths of thyroid cells that form masses within the thyroid gland. TNs are common, and the importance lies in need to exclude thyroid cancer. This study was intended to evaluate the diagnostic accuracy of ultrasonography for differentiating benign from malignant thyroid lesions in comparison with fine-needle aspiration cytology (FNA cytology). This study involved 133 patients with thyroid lesions. All patients underwent thyroid ultrasonography and ultrasound (US)-guided-FNA cytology and results were compared. Out of 133 patients included in this study, the mean age was 41.2±15 years, and 113 (85%) were female. Thyroid lesions were benign in 126 cases (94.7%) and malignant in nine cases (5.3%). Among 124 patients with thyroid lesions diagnosed as benign with US, 122 (98.38%) were confirmed to be benign with FNA cytology, and only 2 (1.6%) were proved to be malignant. Among nine patients with thyroid lesions diagnosed as malignant by US, 5 (55.6%) were confirmed to be malignant by FNA cytology, and 4 (44.4%) were proved to be benign. The US diagnosed benign thyroid lesions with a sensitivity, specificity, positive predictive value, and negative predictive value of 98.38%, 71.42%, 98.38%, and 55.55%, respectively. The results revealed strong compatibility between diagnosis of benign thyroid lesions by the US and proved diagnosis by FNA cytology (p<0.001). B-mode ultrasonography is a valuable tool in differentiating benign from malignant thyroid lesions. It can almost always predict the benign nature of thyroid lesions with excellent diagnostic accuracy.