Clinical role of lung ultrasound for diagnosis and monitoring of COVID-19 pneumonia in pregnant women.

Lung ultrasound has been suggested recently by the Chinese Critical Care Ultrasound Study Group and Italian Academy of Thoracic Ultrasound as an accurate tool to detect lung involvement in COVID-19. Although chest computed tomography (CT) represents the gold standard to assess lung involvement, with a specificity superior even to that of the nasopharyngeal swab for diagnosis, lung ultrasound examination can be a valid alternative to CT scan, with certain advantages, particularly for pregnant women. Ultrasound can be performed directly at the bed-side by a single operator, reducing the risk of spreading the disease among health professionals. Furthermore, it is a radiation-free exam, making it safer and easier to monitor those patients who require a series of exams. We report on four cases of pregnant women affected by COVID-19 who were monitored with lung ultrasound examination. All patients showed sonographic features indicative of COVID-19 pneumonia at admission: irregular pleural lines and vertical artifacts (B-lines) were observed in all four cases, and patchy areas of white lung were observed in two. Lung ultrasound was more sensitive than was chest X-ray in detecting COVID-19. In three patients, we observed almost complete resolution of lung pathology on ultrasound within 96 h of admission. Two pregnancies were ongoing at the time of writing, and two had undergone Cesarean delivery with no fetal complications. Reverse transcription polymerase chain reaction analysis of cord blood and newborn swabs was negative in both of these cases. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Complementemia in pregnancies with antiphospholipid syndrome.

Prognosis of pregnancies in women with antiphospholipid syndrome has dramatically improved over the past two decades using conventional treatment with low molecular weight heparin and low-dose aspirin. However, despite this regimen, 10-15% of antiphospholipid syndrome patients experience pregnancy losses. Several studies have been performed in order to identify risk factors predictive of complications. Thrombosis has been generally accepted as the key pathogenetic mechanism underlying pregnancy morbidity. However, the thrombogenic state alone is not able to explain all the different mechanisms leading to pregnancy failure. In fact, emerging evidence shows that complement pathway could play an important role in mediating clinical events in antiphospholipid syndrome. However, the exact mechanism through which complement mediates antiphospholipid syndrome complications remains unknown. Low complement levels (C3 and C4) are associated with poor pregnancy outcome in women with antiphospholipid syndrome in different studies. Hypocomplementemia could be indicated as an early predictor of adverse pregnancy outcome, available at the beginning of pregnancy for starting, if necessary, additional treatment to conventional therapy. However, future studies need to better understand the impact of low complement level on antiphospholipid syndrome pregnancy outcome.

Sustainable bioenergy for climate mitigation: developing drought-tolerant trees and grasses.

BACKGROUND AND AIMS: Bioenergy crops are central to climate mitigation strategies that utilize biogenic carbon, such as BECCS (bioenergy with carbon capture and storage), alongside the use of biomass for heat, power, liquid fuels and, in the future, biorefining to chemicals. Several promising lignocellulosic crops are emerging that have no food role - fast-growing trees and grasses - but are well suited as bioenergy feedstocks, including Populus, Salix, Arundo, Miscanthus, Panicum and Sorghum. SCOPE: These promising crops remain largely undomesticated and, until recently, have had limited germplasm resources. In order to avoid competition with food crops for land and nature conservation, it is likely that future bioenergy crops will be grown on marginal land that is not needed for food production and is of poor quality and subject to drought stress. Thus, here we define an ideotype for drought tolerance that will enable biomass production to be maintained in the face of moderate drought stress. This includes traits that can readily be measured in wide populations of several hundred unique genotypes for genome-wide association studies, alongside traits that are informative but can only easily be assessed in limited numbers or training populations that may be more suitable for genomic selection. Phenotyping, not genotyping, is now the major bottleneck for progress, since in all lignocellulosic crops studied extensive use has been made of next-generation sequencing such that several thousand markers are now available and populations are emerging that will enable rapid progress for drought-tolerance breeding. The emergence of novel technologies for targeted genotyping by sequencing are particularly welcome. Genome editing has already been demonstrated for Populus and offers significant potential for rapid deployment of drought-tolerant crops through manipulation of ABA receptors, as demonstrated in Arabidopsis, with other gene targets yet to be tested. CONCLUSIONS: Bioenergy is predicted to be the fastest-developing renewable energy over the coming decade and significant investment over the past decade has been made in developing genomic resources and in collecting wild germplasm from within the natural ranges of several tree and grass crops. Harnessing these resources for climate-resilient crops for the future remains a challenge but one that is likely to be successful.

Association between false-positive TORCH and antiphospholipid antibodies in healthy pregnant women.

The present study investigated: (a) the presence of antiphospholipid antibodies and (b) the obstetric outcome in healthy pregnant women showing false-positive TORCH-Toxoplasmosis, Other: syphilis, varicella-zoster, Rubella, Cytomegalovirus (CMV), and Herpes infections-results. Data from 23 singleton healthy pregnancies with false-positive TORCH results were collected. Each woman was systematically screened for TORCH IgG and IgM during the pre-conception assessment and/or at the beginning of pregnancy. In the presence of IgM positivity, when indicated (CMV, toxoplasmosis, rubella, herpes simplex virus), IgG avidity was evaluated and, if possible, polymerase chain reaction was performed on an amniotic fluid sample in order to distinguish between primary infection or false positivity. The antiphospholipid antibodies tests were: lupus anticoagulant, anticardiolipin antibodies IgG, IgM, and anti-ß2glicoprotein I IgG, IgM. The antiphospholipid antibodies tests, if positive, were repeated after 12 weeks to confirm the results. In pregnant women with false-positive TORCH, the overall prevalence of positive antiphospholipid antibodies for one or more tests was 52.2%. To clarify the correlation of false-positive TORCH results with clinical practice, obstetric outcome was analyzed in terms of live births, week of delivery, neonatal birth weight, and neonatal birth weight percentile. A statistically significant lower neonatal birth weight and neonatal birth weight percentile were observed in women with false-positive TORCH associated with antiphospholipid antibodies positivity (Group A) in comparison with those in women with false-positive TORCH without antiphospholipid antibodies positivity (Group B). No statistically significant difference was found for the week of delivery between the two groups. It is hoped that future studies will verify the life-long persistence of antiphospholipid antibodies positivity by follow-up of these women and identify who will develop a classical antiphospholipid syndrome or other autoimmune disorders.

Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: a multi-institution correlative biomarker study.

BACKGROUND: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. METHODS: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data. We evaluated associations between plasma AR and overall survival (OS) and progression-free survival (PFS) in 73 chemotherapy-naïve and 98 post-docetaxel CRPC patients treated with enzalutamide or abiraterone (Primary cohort) and 94 chemotherapy-naïve patients treated with enzalutamide (Secondary cohort; PREMIERE trial). RESULTS: In the primary cohort, AR gain was observed in 10 (14%) chemotherapy-naïve and 33 (34%) post-docetaxel patients and associated with worse OS [hazard ratio (HR), 3.98; 95% CI 1.74-9.10; P < 0.001 and HR 3.81; 95% CI 2.28-6.37; P < 0.001, respectively], PFS (HR 2.18; 95% CI 1.08-4.39; P = 0.03, and HR 1.95; 95% CI 1.23-3.11; P = 0.01, respectively) and rate of PSA decline ≥50% [odds ratio (OR), 4.7; 95% CI 1.17-19.17; P = 0.035 and OR, 5.0; 95% CI 1.70-14.91; P = 0.003, respectively]. AR mutations [2105T>A (p.L702H) and 2632A>G (p.T878A)] were observed in eight (11%) post-docetaxel but no chemotherapy-naïve abiraterone-treated patients and were also associated with worse OS (HR 3.26; 95% CI 1.47-not reached; P = 0.004). There was no interaction between AR and docetaxel status (P = 0.83 for OS, P = 0.99 for PFS). In the PREMIERE trial, 11 patients (12%) with AR gain had worse PSA-PFS (sPFS) (HR 4.33; 95% CI 1.94-9.68; P < 0.001), radiographic-PFS (rPFS) (HR 8.06; 95% CI 3.26-19.93; P < 0.001) and OS (HR 11.08; 95% CI 2.16-56.95; P = 0.004). Plasma AR was an independent predictor of outcome on multivariable analyses in both cohorts. CONCLUSION: Plasma AR status assessment using ddPCR identifies CRPC with worse outcome to enzalutamide or abiraterone. Prospective evaluation of treatment decisions based on plasma AR is now required. CLINICAL TRIAL NUMBER: NCT02288936 (PREMIERE trial).

Perinatal outcome in pregnant women with cancer: are there any effects of chemotherapy?

Cancer is the leading cause of death in women of reproductive age. During the last decades and especially in developed countries, the incidence of cancer is increasing dramatically, with an incidence of 1 in 1,000 pregnancies. This is mostly related to delay of pregnancy into the late reproductive years. The aim of this study was to investigate the outcome of pregnancy in women with diagnosis of cancer; in particular, neonatal morbidity and mortality, after in utero exposure to chemotherapy, were evaluated. A total of 59 singletons and one twin pregnancy complicated by cancer were followed at our tertiary centre over the last 15 years. A different treatment, based on surgery and/or chemotherapy in pregnancy or delayed to the postpartum period, was employed. There were 59 live births (97%), one foetal loss and one stillbirth at 28 weeks. The congenital malformation rate was 5% (n = 3). The rate of preterm birth was 83%. The mean birthweight and mean birthweight percentile were 2,098 g (740-3930) and 46 (7-93), respectively; 32% of neonates were small for gestational age (SGA). Dividing the population into treated or untreated with chemotherapy, the rate of SGA was not statistically significant different between the two groups. Our results showed that chemotherapy administered during the second trimester or later did not influence intrauterine foetal growth, but the high prevalence of SGA neonates in the two groups, exposed or not exposed to chemotherapy, suggests an influence of maternal cancer per se on foetal growth.

The prognostic value of stromal and epithelial periostin expression in human breast cancer: correlation with clinical pathological features and mortality outcome.

BACKGROUND: PN is a secreted cell adhesion protein critical for carcinogenesis. In breast cancer, it is overexpressed compared to normal breast, and a few reports suggest that it has a potential role as a prognostic marker. METHODS: Tumour samples obtained at the time of mastectomy from 200 women followed for a median time of 18.7 years (range 0.5-29.5 years) were investigated through IHC with a polyclonal anti-PN antibody using tissue microarrays. Epithelial and stromal PN expression were scored independently according to the percentage of coloured cells; the 60th percentile of PN epithelial expression, corresponding to 1%, and the median value of PN stromal expression, corresponding to 90%, were used as arbitrary cut-offs. The relationships between epithelial and stromal PN expression and clinical-pathological features, tumour phenotype and the risk of mortality following surgery were analysed. Appropriate statistics, including the Fine and Gray competing risk proportional hazard regression model, were used. RESULTS: The expression of PN in tumour epithelial cells was significantly lower than that which was observed in stromal cells (p < 0.000). No specific association between epithelial or stromal PN expression and any of the clinical-pathological parameters analysed was found as it was observed in respect to mortality when these variables were analysed individually. However, when both variables were considered as a function of the other one, the expression of PN in the stromal cells maintained a statistically significant predictive value with respect to both all causes and cancer-specific mortality only in the presence of high epithelial expression levels. No significant differences in either all causes or BCa-specific mortality rates were shown according to epithelial expression for tumours displaying higher stromal PN expression rates. However, the trends were opposite for the higher stromal values and the patients with high epithelial expression levels denoted the group with the worst prognosis, while higher epithelial values in patients with lower stromal expression levels denoted the group with the best prognosis, suggesting that PN epithelial/stromal interactions play a crucial role in breast carcinogenesis, most likely due to functional cross-talk between the two compartments. On the basis of PN expression in both compartments, we defined 4 subgroups of patients with different mortality rates with the group of patients characterized by positive epithelial and low stromal PN expression cells showing the lowest mortality risk as opposed to the groups of patients identified by a high PN expression in both cell compartments or those identified by a low or absent PN expression in both cell compartments showing the worst mortality rates. The differences were highly statistically significant and were also retained after multiparametric analysis. Competing risk analysis demonstrated that PN expression patterns characterizing each of previous groups are specifically associated with cancer-specific mortality. CONCLUSIONS: Although they require further validation through larger studies, our findings suggest that the patterns of expression of PN in both compartments can allow for the development of IHC "signatures" that maintain a strong independent predictive value of both all causes and, namely, of cancer-specific mortality.

Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Epidermal growth factor-like domain 7 promotes migration and invasion of human trophoblast cells through activation of MAPK, PI3K and NOTCH signaling pathways.

Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.

Self-injection of dermal filler: an underdiagnosed entity?

Dermal fillers are increasingly used by clinicians (and nonclinicians) in patients requiring facial rejuvenation, as well as for other aesthetic uses such as treatment of age-related wrinkles, skin folds and depressed scars. We report the case of a patient who injected herself with dermal filler purchased over the internet and who required intervention for the undesired effect. We would like to highlight the ease with which these devices can be purchased over the internet, the risks they pose and the necessity of regulating their administration.

Cerebral sinovenous thrombosis in neonatal antiphospholipid syndrome: a new entity?

Neonatal antiphospholipid syndrome (neonatal APS) seems to be exceedingly rare, as the antiphospholipid antibodies (aPL) related thrombosis in the neonatal period. The pathogenesis of perinatal aPL related thrombosis may be explained both by the transplacental passage of the maternal antibodies and by the production of de novo antibodies by the neonate. However, few cases of neonatal APS are reported in the literature, especially regarding arterial thrombotic events. In particular, only two cases of neonatal aPL related isolated cerebral sinovenous thrombosis (CSVT) are described in the literature. Despite its frequency, CSVT results in significant mortality and morbidity, probably also due to the difficulty in early diagnosis and then in correct managing in the neonatal period. A diagnosis of neonatal APS should be considered in the evaluation of neonates with CSVT, as well as in any case of neonatal thrombosis, to correctly manage the affected neonates and counsel the mother for future pregnancies.

Reference values for peak expiratory flow in Indian adult population using a European Union scale peak flow meter.

BACKGROUND: Reference values of peak expiratory flow (PEF) in Indian adults have to date been derived locally, using an old (Wright) scale peak flow meter. There are thus no reliable reference values for PEF for Indians and this formed the aim of the study. MATERIALS AND METHODS: A European Union (EU) scale peak flow meter (PFM) was used for the study. A respiratory health and demographic questionnaire was administered to 1000 male and female adults from randomly selected locations in the country in this multi centric study. The locations represented different geographic, ethnic, and socioeconomic backgrounds. Patients were stratified according to height and age. The PEF values were measured using the Breathometer™ (Cipla Ltd., India) with EU scale. Reference equations were derived from multiple regression analysis. RESULTS: A total of 3608 participants were excluded. In 80% of the remaining 6138 healthy adults (M: 3720; F: 2418), the predicted regression equations were derived. Gender, age, and height were the significant determinants of PEF. The equations in L/minute are: Females: PEF = -1.454 (Age) + 2.368 (Height) Males: PEF = -1.807 (Age) + 3.206 (Height). The derived equation was validated by comparing the predicted PEF values with the measured values in the remaining sample of 20% (Mean ΔPEF: M = 1.85 L/minute, CI = -2.76, 6.47; F = 1.64, CI = -2.89, 6.18). An Indian adult with average height and age was found to have approximately 30% lower PEF compared to the corresponding European adult using the Nunn and Gregg equation. CONCLUSION: We derived reference values of PEF for Indian adults using a validated EU scale peak flow meter.

Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

The relationship between TORCH complex false positivity and obstetric outcome in patients with antiphospholipid syndrome.

OBJECTIVE: The presence of TORCH IgM positivity is not a specific indicator of primary infection; the assessment of IgG avidity index has been shown to be useful in identifying or excluding primary infection in pregnant women with no pre-gestational TORCH serology. TORCH is an acronym for Toxoplasmosis, Others (HBV, syphilis, Varicella-Zoster virus, Epstein Barr virus, Coxsackie virus and Parvovirus), Rubella, Cytomegalovirus (CMV) and Herpes Simplex. PATIENTS AND METHODS: Data from 54 pregnancies in women with antiphospholipid syndrome (APS) were assessed in comparison with data from 222 healthy pregnant women as controls. Each woman in both groups was systematically screened for TORCH IgG and IgM during pre-conceptional evaluation and/or at the beginning of pregnancy. The assessment of IgG avidity was also evaluated in order to identify primary infection or false positivity. RESULTS: A significant increase of CMV IgM false positivity in APS in comparison with controls was detected. A worse pregnancy outcome was observed among APS patients having CMV IgM false positivity in comparison with APS patients without false positivity; in particular a statistically significant lower neonatal birth weight and a lower neonatal birth weight percentile were observed. CONCLUSION: Our data suggest that the presence of CMV IgM false positivity could represent a novel prognostic factor for poor pregnancy outcome in APS patients.

Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome.

OBJECTIVE: To investigate the predictive value of serum C3 and C4 complement component levels in relation to pregnancy outcome in patients with antiphospholipid syndrome (APS). MATERIALS AND METHODS: A prospective study of 47 pregnancies associated with APS was performed. Pregnancy outcome was analyzed in terms of: fetal loss, preterm delivery (≤34 gestational weeks), fetal intrauterine growth restriction (IUGR), birth weight <2500 g and preeclampsia. Week at delivery, neonatal birth weight and neonatal birth weight percentile were also investigated. Hypocomplementemia, positivity for anti-dsDNA and triple positivity for antiphospholipid antibodies (aPL) were related to pregnancy outcome. RESULTS: Forty-three pregnancies ended in live births with a fetal loss rate of 8.5%. Fetal death, preterm delivery and birth weight <2500 g were associated with hypocomplementemia (p = 0.019, p = 0.0002, p < 0.0001 respectively). Lower neonatal birth weight, lower neonatal birth weight percentile and lower week at delivery were associated with hypocomplementemia (p < 0.0001, p = 0.0003, p < 0.0001 respectively) and with triple aPL positivity (p = 0.008, p = 0.014, p = 0.03 respectively). A poor pregnancy outcome was confirmed among primary APS (PAPS) pregnancies with hypocomplementemia. Multivariate analysis confirmed that hypocomplementemia was an independent predictor of lower neonatal birth weight (p = 0.0001) and lower week at delivery (p = 0.002). CONCLUSION: Hypocomplementemia could be considered a novel prognostic factor for pregnancy outcome in APS patients.

Household air pollution and COPD: cause and effect or confounding by other aspects of poverty?

SETTING: Household air pollution (HAP) and chronic obstructive pulmonary disease (COPD) are both major public health problems, reported to cause around 4 million and 3 million deaths every year, respectively. The great majority of these deaths, as well as the burden of disease during life is felt by people in low- and middle-income countries (LMICs).OBJECTIVE and DESIGN: The extent to which HAP causes COPD is controversial; we therefore undertook this review to offer a viewpoint on this from the Global Initiative for COPD (GOLD).RESULTS: We find that while COPD is well-defined in many studies on COPD and HAP, there are major limitations to the definition and measurement of HAP. It is thus difficult to disentangle HAP from other features of poverty that are themselves associated with COPD. We identify other limitations to primary research studies, including the use of cross-sectional designs that limit causal inference.CONCLUSION: There is substantial preventable morbidity and mortality associated with HAP, COPD and poverty, separately and together. Although it may not be possible to define clear causal links between HAP and COPD, there is a clear urgency to reduce the avoidable burden of disease these inflict on the world´s poor.

Deciphering the genetic determinism of bud phenology in apple progenies: a new insight into chilling and heat requirement effects on flowering dates and positional candidate genes.

The present study investigates the genetic determinism of bud phenological traits using two segregating F(1) apple (Malus × domestica) progenies. Phenological trait variability was dissected into genetic and climatic components using mixed linear modeling, and estimated best linear unbiased predictors were used for quantitative trait locus (QTL) detection. For flowering dates, year effects were decomposed into chilling and heat requirements based on a previously developed model. QTL analysis permitted the identification of two major and population-specific genomic regions on LG08 and LG09. Both 'chilling requirement' and 'heat requirement' periods influenced flowering dates, although their relative impact was dependent on the genetic background. Using the apple genome sequence data, putative candidate genes underlying one major QTL were investigated. Numerous key genes involved in cell cycle control were identified in clusters within the confidence interval of the major QTL on LG09. Our results contribute towards a better understanding of the interaction between QTLs and climatic conditions, and provide a basis for the identification of genes involved in bud growth resumption.

Effect of Pranayama on stress and cardiovascular autonomic function.

The stress either physical or mental, leads to cardiovascular morbidity. Newly admitted medical students are likely to be exposed to various stresses like change of environment, demanding medical education and different teaching protocol in a medical college. Pranayama is known since ancient times to relieve stress and stabilize autonomic function of the body. Therefore it was decided to study effect of Pranayama on stress and cardiovascular autonomic function. The subjects were first M.B.B.S students and the sample size was 59 consisting of 27 males and 32 females. The group of students thus selected was briefed about the study. After the orientation session, informed written consent was taken, stress questionnaire was put and the autonomic function tests were done. This was followed by practice of Pranayama for 2 months, 1 hour/day for 5 days/week and again stress questionnaire was put and the autonomic function tests were performed on the study group. The above tests were done before and after the practice of Pranayama. The results obtained were analyzed using SPSS software. The stress level has reduced after 2 months of practicing various pranayama as evident by decrease in total stress score which is highly significant. VLF and LF in n.u have reduced significantly after practice of pranayama signifying reduction in sympathetic drive to heart. HF in n.u has increased significantly after practice of pranayama for 2 months showing the increase in parasympathetic output to the heart. LF/ HF ratio reduced significantly after 2 months of practice of pranayama indicating a better sympatho vagal balance with resting balance tilting toward better parasympathetic control.

Assessment of asthma control in users of oral anti-asthma medications.

BACKGROUND: Despite guidelines recommending inhalation therapy as the preferred choice, oral therapy is still widely used in the treatment of asthma in India. However, data about the level of asthma control and healthcare use in patients on oral anti-asthma medications are scarce.METHODS: A retrospective study was conducted to assess the level of asthma control and healthcare use in patients taking oral anti-asthma medications.RESULTS: The study population consisted of 381 adults randomly selected from health screening programmes. All subjects were already receiving oral anti-asthma medications; however, up to 72% had not been diagnosed with asthma by their treating doctors prior to the screening programmes. The cohort had a mean age of 48.26 ± 13.83 years (70% males) and mean peak expiratory flow of 245 ± 78.93 mL/sec. The mean Asthma Control Questionnaire 5 (ACQ-5) score was 2.53 ± 1.15, with respectively 33%, 49.3% and 32.6% reporting at least one episode of breathlessness, one emergency doctor visit and one hospitalisation due to asthma or its symptoms in the past year.CONCLUSION: Underdiagnosis and inappropriate management, as indicated by the poor asthma control and increased hospitalisations seen in this study, is probably a key contributor to the increased burden of the disease in India.