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Purpose The importance of nutraceuticals and functional foods has been a topic of interest in nutrition research for many years. This review aims to summarize the findings on the nutritive value and health benefits of chia, as well as its use as a food fortificant. Design/methodology/approach Published literature on the nutritive value and therapeutic properties of chia has been reviewed. Findings Chia, an ancient grain, belongs to the mint family (Lamiaceae) and was cultivated in Mexico and Guatemala by the Mayas and Aztecs of a pre-Columbian era. In addition to being gluten-free, chia seeds are concentrated source of omega-3 fatty acids (mainly α-linolenic acid), fiber (insoluble) and polyphenolic compounds (myricetin, quercetin, kaempferol, chlorogenic and caffeic acids), which were found to be comparatively higher than many other grains, cereals and oily seeds. Chia supplementation has potential to lower incidence of cardiovascular disease, obesity, hypertension, cancer, diabetes, pruritus and celiac disease. Because of its nutraceutical and physiochemical properties, chia has been widely used as a whole seed, flour, seed mucilage, gel and oil for developing various enriched food products, such as bread, pasta, cakes, cookies, chips, cheese, yoghurt, meat, fish and poultry. Originality/value With advancement in nutrition research, chia would have a great future perspective as feed, food and medicine. However, further research is needed to validate the potential therapeutic effect of chia supplementation on human health.

Here, we report on a phase IIa study to determine the intubation rate, survival, viral clearance, and development of endogenous Abs in patients with COVID-19 pneumonia treated with convalescent plasma (CCP) containing high levels of neutralizing anti–SARS-CoV-2 Abs. Radiographic and laboratory evaluation confirmed all 51 treated patients had COVID-19 pneumonia. Fresh or frozen CCP from donors with high titers of neutralizing Abs was administered. The nonmechanically ventilated patients (n = 36) had an intubation rate of 13.9% and a 30-day survival rate of 88.9%, and the overall survival rate for a comparative group based on network data was 72.5% (1625/2241). Patients had negative nasopharyngeal swab rates of 43.8% and 73.0% on days 10 and 30, respectively. Patients mechanically ventilated had a day-30 mortality rate of 46.7%; the mortality rate for a comparative group based on network data was 71.0% (369/520). All evaluable patients were found to have neutralizing Abs on day 3 (n = 47), and all but 1 patient had Abs on days 30 and 60. The only adverse event was a mild rash. In this study on patients with COVID-19 disease, we show therapeutic use of CCP was safe and conferred transfer of Abs, while preserving endogenous immune response., Patients with COVID-19 pneumonia receiving high-titer convalescent plasma showed antibody transfer with preservation of endogenous production, and database survival comparison is promising for the early group.

A survey was conducted to assess socio-economic disparity in the prevalence of anemia among schoolchildren (11-17 years) in few regions of Punjab. Two hundred and ten children from government schools of Punjab were selected and their blood hemoglobin levels were estimated; clinical examination was done for various signs/ symptoms of anemia; and dietary iron intake was analysed and compared with the recommended dietary allowances of ICMR (2010). Analysis of variance followed by Tukey's post-hoc test was applied to assess socio-economic disparity in the prevalence of anemia. Overall, 97% of the children were anemic, out of which 80 vs. 17% were moderately and mildly anemic, respectively. Statistically, no significant difference was found in the mean hemoglobin level of the subjects with respect to family income, parent’s education and religion, whereas, substantial disparity was noted with respect to caste. Scheduled caste subjects had the highest prevalence rate than general category and Backward Class and Other Backward Class subjects. Dietary iron intake of the children was grossly inadequate, ranging from 35 to 41% of the ICMR (2010) recommendations. Therefore, it can be established that anemia prevalence depends more on food habits and dietary behaviour of the children than on socio-economic factors. Dietary diversification should be canvassed at the root level, as anemia is likely the result of predominantly starch-based monotonous poor quality diets with minimal amounts of meat, vegetables and fruits.

Aim of the study: To study the cross-sectional area, the maximum thickness of the nerve fascicle and the thickness/width ratio of the sural nerve in patients with diabetes mellitus and non-diabetic subjects using high-resolution ultrasonography and to correlate the results with nerve conduction studies. Material and methods: This prospective study was conducted among 60 patients divided into two groups: A and B. Group A consisted of 30 patients >18 years of age with a history of type 2 diabetes mellitus, and Group B consisted of 30 non-diabetic patients >18 years of age. High-resolution ultrasonography was performed using a linear transducer with the frequency of 5-18 MHz in all the patients in the prone position with the transducer placed in a transverse position at the junction of the middle and lower thirds of the calf. Nerve conduction studies were performed using Aleron 201 (RMS) in all the patients. Results: As compared to the control group, the sural nerve in the diabetic group showed increased cross-sectional area, maximum thickness of the nerve fascicle and thickness/width ratio (p 18 years of age with a history of type 2 diabetes mellitus, and Group B consisted of 30 non-diabetic patients >18 years of age. High-resolution ultrasonography was performed using a linear transducer with the frequency of 5–18 MHz in all the patients in the prone position with the transducer placed in a transverse position at the junction of the middle and lower thirds of the calf. Nerve conduction studies were performed using Aleron 201 (RMS) in all the patients. Results: As compared to the control group, the sural nerve in the diabetic group showed increased cross-sectional area, maximum thickness of the nerve fascicle and thickness/width ratio (p

Tomato (Solanum lycopersicum) is one of the major vegetable plant and a model system for fruit development. Its global importance is due to its lycopene pigment which has anti-oxidative and anti-cancerous properties. Though > 1.5 M biotic stress associated ESTs of tomato are available but cumulative analysis to predict genes is warranted. Availability of whole genome de novo assembly can advantageously be used to map them over different chromosome. Further, available 0.14 M catalogued markers can be used to introgress specific desirable genes in varietal improvement program. We report here 57 novel genes associated with biotic stress of tomato along with 50 genes having physical location over different chromosomes. We also report 52 cis-regulating elements and 69 putative miRNAs which are involved in regulation of these biotic stresses associated genes. These putative candidate genes associated with biotic stress can be used in molecular breeding in the endeavor of tomato productivity along with its sustainable germplasm management.

Objective To determine the prevalence of osteophyte induced lung fibrosis (OIF) and its relationship to osteophyte size, location, and surrounding fat. Methods 94 CT scans of the chest were reviewed, size of the largest osteophyte and the presence of fibrosis were recorded. Results Presence of fibrosis was higher among patient with large (> 10 mm) osteophytes compared to those with small (1–10 mm) osteophytes. Age and presence of periosteophyte fat were significantly associated with presence of fibrosis. Conclusions As the size of an osteophyte increases, there is a greater likelihood of lung fibrosis. Subpleural fat protects the lung from OIF.

As the use of serotonergic agents to treat depression has increased, so too has the incidence of serotonin syndrome. We identify the common agents implicated in serotonin syndrome and the clinical tools to diagnose, manage, and prevent serotonergic toxicity.

Background Chronic kidney disease is increasing in prevalence. The association between low baseline estimated glomerular filtration rate (eGFR) and future myocardial infarction has not been comprehensively assessed. Methods A systematic review and meta-analysis of observational studies evaluating the risk for future myocardial infarction associated with eGFR 2 was completed. Data sources included PubMed, EMBASE, and the Cochrane Library. Included studies were required to have prospectively collected data, followed subjects for at least 6months, and reported baseline eGFR levels and the multivariable-adjusted relative risk for future myocardial infarction. A random effects model was used and subgroup analyses were conducted. Results 26 publications representing 41 observational cohorts were selected. In total, 1,986,850 participants with more than 35,752 documented myocardial infarctions (follow-up range: 9months to ~20years) were evaluated. eGFR 2 was associated with a relative risk of 1.52 (95% confidence interval 1.39–1.67; p 2 was associated with a relative risk of 1.21 (1.09–1.34; p =0.0002) for myocardial infarction. Significant heterogeneity existed among both eGFR groups. Subgroup analysis found a further increase in risk for myocardial infarction as eGFR declined from 30 to 60 to 2 (1.40, 95% confidence interval, 1.21–1.61 vs.1.94, 95% confidence interval, 1.51–2.50; p =0.03). Conclusions Decreased baseline eGFR is independently associated with increased future myocardial infarction, and the risk increases with advanced renal insufficiency. Clinicians should be wary of acute coronary syndromes in patients with CKD.

The potential of cloud computing for overriding the needs for deploying various infrastructures for running a server based services brought up a revolutionary change in the way the traditional demands of the people use to be handled. Cloud computing provides the software’s on pay per use option which make it easier for the people who are not able to meet the economic requirements. Since the whole scenario is beneficial to big industries like facebook, google, orkut etc , various order fields are also getting dependent on cloud computing. Since tons of data is uploading every second to the cloud server does needs to be mined properly for efficient data storage.in this paper we try to integrate the data preprocessing technique with data classification technique to mine big data’s of asthma based patients.

Even though cultivated rice is highly sensitive to salinity, significant variability exists in the primary and secondary gene-pool of rice with respect to traits of salinity tolerance. Breeding salinity tolerance rice varieties is imperative due to climate change and increasing rice demand for global population. A meta-analysis of plethora of genomic data and published literature available on various genes/factors associated with response to rice salinity and tolerance can be used to enlist selected candidates genes affecting salinity. Such genes can be utilized to identify potential candidate salinity resistance genes from donor rice genotypes and facilitate their transfer to high yielding varieties of rice through marker-assisted breeding. This approach has tremendous advantage over transgenic approach as no bio-safety or regulatory issues are involved in exploiting the variability. Meta-analyses were performed on three datasets viz., rice microarray data of 166 series comprising of 2586 samples, 1228 published research literature in the last one and half decades and RNA-Seq data of 454 and Illumina from Sequence Retrieval Archive (SRA) at NCBI. Among microarray dataset, six salinity related series were finally selected and multi experiment analysis revealed 2289 differentially expressed genes belonging to 44 gene families. Out of these, 13 families viz., AP2-EREBP, AUX/IAA, bZIP, C2H2, bHLH, C3H, HB, HSF, MYB, MYB-related, NAC, Tify and WRKY were selected. Applying various parameters on the published literature data, 13 genes were selected, of which five were common to the different microarray datasets. From RNA-Seq data, total of 751 differentially expressed genes were obtained from 21 gene families, out of which 11 genes were common with those obtained from microarray data and five genes, viz., AP2-EREBP/DREB, MYB, HSF, bZIP and NAC were common to all the three data sets. Based on the results obtained, a total of 31 meta-analyzed genes have been selected and recommended for use in genetic improvement programs aimed at salinity resistance in rice. The meta-analysis of microarray, RNA-Seq and published literature has been successfully used to select 31 best salinity tolerance associated genes which can be exploited by candidate gene approach for targeted introgression through marker assisted breeding. This approach has multi-fold advantages, as it obviates statutory and ecological issues. Such endeavors are more warranted for combating the key abiotic stresses like salinity, whose effects are increasing due to a changing climate.

The study of the seed storage behavior and cryopreservation of embryonic axes was attempted in Citrus jambhiri genotypes using air desiccation-freezing, vitrification, and encapsulation-dehydration methods. Seeds of this species revealed nonorthodox seed storage behavior with moderate seed longevity and sensitivity to desiccation and freezing. Successful cryopreservation was achieved with all three methods using embryonic axes; however, the recovery growth percentage significantly differed among these methods. Cryopreservation was efficient for the embryonic axes desiccated to 13%-15% moisture content. Freezing of embryonic axes at this moisture content in liquid nitrogen showed a good recovery rate of 40%-50%. In the vitrification method, embryonic axes subjected to PVS2 treatment for 40 min had the highest recovery rate of 25% after cryopreservation. In the encapsulation-dehydration method, encapsulated axes precultured on 0.5 M sucrose medium followed by 6 h of desiccation had the highest recovery growth of 30%-60% after cryopreservation. Out of the three methods employed, the encapsulation-dehydration method gave the best recovery values for embryonic axes. High regeneration values of embryos in comparison to embryonic axes prompted us to undertake large-scale cryobanking of C. jambhiri using embryos (seeds without seed coats) and more than 100 accessions of C. jambhiri have been cryostored in the national cryobank. This would further serve the purpose of conserving nucellar embryos with zygotic embryos.

Aim The present study aimed to explore the ameliorative role of alpha7 (α7) neuronal nicotinic acetylcholine receptor (nAChR) modulation in epilepsy and associated comorbidities in postpentylenetetrazole (PTZ)-kindled mice. Material and methods The subconvulsive dose of PTZ (35 mg/kg, i.p.) was used to induce kindling-associated epileptogenesis in mice. After successful kindling, animals were treated intraperitoneally with saline, phenytoin (35 mg/kg), valproate (300 mg/kg), choline chloride (α7 agonist; 400 mg/kg and 800 mg/kg), and methyllycaconitine citrate (α7 antagonist; 3.5 mg/kg and 7.0 mg/kg) for 10 days. All the groups except naive were exposed to PTZ injections on day 3, 6, and 9 of treatment to assess seizure severity score. Epilepsy-associated comorbid depression was evaluated by tail suspension test, sucrose preference test, and plasma corticosterone levels, whereas epilepsy-associated memory deficit condition was assessed by step-through paradigm, Morris water maze, and nitrite levels. Neurochemical perturbations related to epilepsy and associated depression and memory deficit were measured by high-performance liquid chromatography (HPLC). Results Post-PTZ-kindled mice displayed significant depressive behavior and memory impairment as compared with naive mice as evidenced by corresponding behavioral and biochemical observations. Methyllycaconitine citrate treatment was unable to produce any ameliorative effect in diseased condition. Choline administration dose dependently ameliorated depression, memory impairment, and seizure severity in post-PTZ-kindled mice. The behavioral findings of the study were concurred with neurochemical and biochemical findings. Conclusion In conclusion, the present study demonstrated the amelioration of epilepsy, comorbid depression, and memory deficit by α7 nAChR agonist choline chloride in PTZ-kindled mice model.

Statin-induced necrotising autoimmune myopathy (SINAM) is a rare disease characterised by proximal muscle weakness and elevated creatine kinase levels that is usually in the thousands. Anti-3-hydroxy-3-methyl glutaryl co-enzyme A reductase (HMGCR) antibodies are associated with SINAM. Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that is usually of unknown aetiology but can also be associated with concurrent extrahepatic autoimmune disorders. We are reporting a case of biopsy proven AIH associated with SINAM in a patient presenting with oropharyngeal dysphagia. The patient had elevated anti-HMGCR antibodies and anti-smooth muscle antibodies. SINAM and AIH were confirmed by muscle biopsy and liver biopsy, respectively. The patient had complete resolution of his symptoms and complete normalisation of his liver function tests after 6 months of the treatment.

The main objective of animal genomics is to comprehend the genetic and molecular basis of all biological processes in animal. By understanding that, animals can be utilized as biological resources in the development of new breeds with improved quality and minimized costs. Animals with stress-resistant quality along with yield traits and reproductive traits are of major interest. This data, along with suitable technology, may help in designing predictive procedures for animal health and may also become part of future breeding decision management systems. Existing technologies generate a large amount of genomic data that requires proper processing, storage, and distribution. This data include sequence information as well as information on various markers, maps, functional discoveries, etc. In this chapter, we provide an insight on how different approaches, tools, and databases can be fruitfully utilized for the various animal breeding and genetics programs. Important objectives for animal bioinformatics comprises to encourage the submission of all sequence data into the public domain via various repositories; to make accessible the annotation of genes, proteins, and phenotypes; and to illustrate the relationships within the animal data and also between animal and other organisms.

In the present era, genomics represent a crucial role in the field of life sciences. Advancements in genomics and the development of high-throughput techniques facilitate the characterization of a wide range of genes according to their functions such as regulation of genes, metabolic pathways, and their reconstruction. In the era of genomics we face the challenge of storage and analysis of a huge amount of important data. Even in this early stage of the era there are many commercial techniques and tools/software available to analyze next-generation sequencing (NGS) data. All of these programs can be used for many uses such as sequence alignments, polymorphism detection, and functional and structural comparative genomics. In this chapter, we focus on advances in bioinformatics and also computational biology in genome sequencing and NGS data analysis and on the potential applications for the efficient collection, storage, and analysis of the huge amount of genomic data generated by researchers and the information retrieved from different sources and web browsers in relation to NGS analysis.

Objectives: The objective of this study was to evaluate the clinical efficacy of epidural steroid injections through different approaches using pain relief and improvement in functional capacity as outcome measures. Materials and Methods: Sixty patients with low backache and unilateral radiculopathy were randomly assigned to three groups of twenty patients each, for undergoing lumbar epidural steroid injection (LESI) through midline, transforaminal, and paramedian approaches under fluoroscopic guidance. All the patients were assessed at 1 week, 1 month and 3 months postintervention using visual analog scale (VAS) score, Quebec disability score, and depression score. Results: The primary and secondary outcome measured in terms of improvement of VAS showed statistically significant reduction (P < 0.05) when compared to preprocedure baseline readings on both intragroup analysis (Groups I, II and III) at 1-week, 1-month, and 3-month follow-up. However, on intergroup comparison, the difference in improvement of VAS score noted was statistically insignificant with P value of 0.07 (Group I/II), 0.19 (Group II/III), 0.85 (Group I/III) at final 3rd month follow-up. In addition, intergroup comparison for secondary outcome showed statistically insignificant improvement (P value for Quebec score 0.73 [Group I/II], 0.34 [Group II/III], 0.79 [Group I/III] and depression score 0.78 [Group I/II], 0.67 [Group II/III], 0.98 [Group I/III]) at final 3rd month follow-up. Conclusions: All three LESI approaches proved highly effective individually in terms of short-term pain relief, improvement in the quality of life, and depression; however, none proved to be better than the other.

A 70-year-old woman with lung metastases from a breast cancer presented with worsening cough and dyspnoea. She recently had a pleurodesis for a malignant pleural effusion. Chest CT scans demonstrated various radiological changes leading to diagnostic challenges. Differential diagnoses included empyema, pleural disease progression, pulmonary oedema, pneumonitis, lymphangitis and atypical infections. She deteriorated despite a multimodality treatment strategy. Postmortem examination confirmed that lung changes were consistent with a bronchoalveolar carcinoma unrelated to the known metastatic breast cancer. The eventual knowledge of this diagnosis was reassuring to the treating medical team and a comfort to the relatives who witnessed the lack of response to standard treatment.

Classification of tumor into its subtypes is a critical issue these days in tumor diagnosis and treatment. The correct classification of tumor into its subtypes leads to the appropriate treatment. Traditional methods classify cancers based on morphological appearance that leads to misclassification because of the similar appearance of sub-types of cancer. To overcome this problem of misclassification, gene expression profiles of genes are used. Gene expression profiling of genes using DNA microarray data plays an important role in classification of tumor. But microarray data consists of genes expressions of thousands of genes so a method is required to reduce the dimensionality of data. In this paper, t-test scoring method is used for selecting important genes and artificial neural network is applied for the classification process. Resilient backpropagation is used as training algorithm. The experimental method employed in this paper shows that the proposed method classifies the data with more accuracy using eight genes only. So it has low computational complexity because of elimination of irrelevant features and high accuracy.

This paper describes a medical condition of liver called steatosis in which healthy liver cells are replaced by triglyceride fat. It impairs the normal functioning of the liver. A classification method is implemented that can quantitatively sort the ultrasound liver images into normal or fatty liver by studying the pathological modification caused at tissue level. The novelty of the method is that it uses a combination of seven different texture analysis models for extracting features. Then, two-fold feature selection methods (Fisher's Discrimination Ratio and Pearsons Correlation Coefficient) remove the redundancy and highly correlated features. This further reduced the dataset into only five features. Naive Bayes classifier is trained using only these five features and provides an overall accuracy of 92.3% with 100% sensitivity.

Conflicting data exists on the role of exercise interventions in patients with prostate cancer (PCa) regarding quality of life (QOL) endpoints.To evaluate the effects of exercise interventions on fatigue, QOL, depression, and anxiety in PCa patients.We searched seven major databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science, and Scopus) for randomized control trials (RCTs) of supervised exercise interventions for men with PCa from database inception to October 2015. For meta-analyses, studies required standardized fatigue, QOL, or mood-related scales with standard-care control groups. The effect size was measured in terms of mean difference (MD) with 95% confidence interval (CI) for continuous outcomes using a random-effects model. Statistical heterogeneity between studies was assessed using the Cochrane Q test and IWe selected 13 RCTs enrolling 1057 PCa patients (mean age 69.4±2.1 yr) undergoing exercise interventions, of which eight studies involving 675 patients qualified for meta-analyses. The study duration varied from 4 wk to 6 mo. A 12-16-wk exercise intervention significantly improved fatigue symptoms (MD 4.83, 95% CI 3.24-6.43; p0.00001) as assessed according to the Functional Assessment of Cancer Therapy (FACT)-Fatigue scale. Fatigue remained improved at 6 mo (MD 3.60, 95% CI 2.80-5.12; p0.00001). Furthermore, exercise interventions improved QOL measured using the FACT-General (MD 3.93, 95% CI 1.37-5.92; p = 0.003) and FACT-Prostate (MD 3.85, 95% CI 1.25-6.46; p=0.04) scales. The pooled data did not reveal a significant improvement in depression or anxiety.Combined evidence from RCTs shows improvement in QOL and fatigue according to FACT scales. No significant differences in depression or anxiety were observed.Exercise improves fatigue and quality-of-life outcomes in patients with prostate cancer. Further studies are necessary to identify patient-specific exercise regimens to optimize these benefits.

Scrub typhus may be a very a familiar reason for an acute undifferentiated fever. Although there has been an improvement in the diagnostics as well as an increased awareness regarding this disease, it still remains belatedly diagnosed and eventually turns fatal. We present a male patient who was brought to us with jaundice, tender hepatomegaly and distinctly no history fever who turned out to have a Scrub typhus infection and was salvaged owing to a diverse empirical antibiotic coverage. This represents an atypical clinical presentation of a very familiar infection: Tropical rickettsioses infection presenting with afebrile jaundice in an immunocompetent patient. It also brings into perspective the wavered nature of its disease presentation, the significant merit of procuring a good patient history and a change in empirical antibiotic policies especially in areas endemic for scrub typhus

TRAF2 is a component of TNF superfamily signalling complexes and plays an essential role in the regulation and homeostasis of immune cells. TRAF2 deficient mice die around birth, therefore its role in adult tissues is not well-explored. Furthermore, the role of the TRAF2 RING is controversial. It has been claimed that the atypical TRAF2 RING cannot function as a ubiquitin E3 ligase but counterclaimed that TRAF2 RING requires a co-factor, sphingosine-1-phosphate, that is generated by the enzyme sphingosine kinase 1, to function as an E3 ligase. Keratinocyte-specific deletion of Traf2, but not Sphk1 deficiency, disrupted TNF mediated NF-kappa B and MAP kinase signalling and caused epidermal hyperplasia and psoriatic skin inflammation. This inflammation was driven by TNF, cell death, non-canonical NF-kB and the adaptive immune system, and might therefore represent a clinically relevant model of psoriasis. TRAF2 therefore has essential tissue specific functions that do not overlap with those of Sphk1. Refereed/Peer-reviewed

West Nile Virus (WNV) first arrived in Ontario, Canada in 2001 and has since spread throughout most of the province, causing disease in humans. The provincial government established a province-wide surveillance program to monitor WNV transmission throughout the 36 regional health units. Here we have acquired records of WNV human and mosquito surveillance from 2002 to 2013 to describe seasonal and geographic trends in WNV activity in southern Ontario. Additionally, we obtained climate data from seven municipalities to investigate how temperature and precipitation affect WNV transmission dynamics. We identified a strong quadratic relationship between the number of confirmed human cases and positive Culex mosquito pools recorded at the end of each year (R2 = 0.9783, p < 0.001). Using Spearman rank correlation tests, we identified that the minimum infection rate of Culex pipiens/restuans pools are the strongest predictor of human cases at a 1 week lag period. We also identified positive correlations between minimum infection rates, temperature, vector abundance, and cumulative precipitation. Global Moran's I index indicates strong positive autocorrelation and clustering of positive Culex pool counts in southern Ontario. Local indicators of spatial association tests revealed a total of 44 high-high and 1 high-low trap locations (n = 680). In the current work we have identified when and where hot spots of WNV activity have occurred in southern Ontario. The municipalities surrounding the western shore of the Lake Ontario and Windsor-Essex County have the largest records of positive mosquitoes and human cases. We identified that positive mosquitoes are a strong indicator of human cases to follow in the coming weeks. An epidemic action threshold of cumulative positive Culex pools was established, allowing Ontario public health officials to predict an epidemic at epidemiological week 34 (rho = 0.90, p < 0.001). These data have the potential to contribute to more efficient larvicide programs and awareness campaigns for the public.

The questions posed by Dr. Rose reflect critical issues primary care physicians encounter when prescribing medications for patients who are taking serotonergic agents. “Switching strategies” have been described for starting or discontinuing serotonergic antidepressants.[1][1] Options range from

Mutations in Bloom helicase (BLM) lead to Bloom Syndrome (BS). BS is characterized by multiple clinical manifestations including predisposition to a wide spectrum of cancers. Studies have revealed the mechanism of BLM recruitment after stalled replication and its role during the repair of DNA damage. We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates. Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges. Consequently lack of Thr182 phosphorylation leads to multiple manifestations of chromosomal instability including increased levels of DNA damage, lagging chromatin, micronuclei formation, breaks and quadriradials. Hence Thr182 phosphorylation on BLM has two functions-it regulates BLM turnover during mitosis and also helps to maintain the chromosomal stability.