Insecticidal Evaluation of essential oils of <Emphasis Type="BoldItalic">Citrus sinensis</Emphasis> L. (Myrtales: Myrtaceae) against housefly, <Emphasis Type="BoldItalic">Musca domestica</Emphasis> L. (Diptera: Muscidae)

The housefly, Musca domestica L., is one of the most common insects, associated with vectoring of various etiological agents. In order to search for effective control agent, the essential oil of sweet orange [Citrus sinensis (L.) Osbeck] was evaluated for its insecticidal activity against the larvae and pupae of housefly using contact toxicity and fumigation bioassays. In the contact toxicity assay, lethal concentration, LC₅₀ of C. sinensis essential oil against housefly larvae, varied between 3.93 and 0.71 μl/cm² for different observation days, while lethal time, LT₅₀, varied between 5.8 to 2.3 days. Mortality of larvae were significant with different concentrations (F = 2.79, df = 4, P < 0.05) and time (F = 6.69, df = 3, P < 0.01). In fumigant assay for housefly larvae, LC₅₀ of 71.2 and 52.6 μl/l was obtained in 24 and 48 h, respectively. Scanning electron microscopy of oil treated larvae revealed extreme dehydration and surface distortion while control larvae were free from any of the above symptoms and presented smooth surface, conforming effect of essential oil on housefly larvae. Percentage inhibition rate of oil against housefly pupae was 27.3–72.7% for contact toxicity and 46.4–100% for fumigation assay. Compositional analysis of C. sinensis essential oil using gas chromatography/mass spectrometry (GC-MS) revealed d-limonene (73.24%), α-pinene (5.86%) and myrcene (4.45%) as major components whereas its vapour profile (solid-phase micro extraction-GC/MS) was dominated by d-limonene at 92.57%. Significant activity of C. sinensis essential oil against larvae and pupae of housefly, pave the way for its use as eco-friendly housefly control measure.     

The c.797 G>A (p.R266K) cystathionine β‐synthase mutation causes homocystinuria by affecting protein stability

Mutations in the cystathionine beta‐synthase (CBS) gene are the cause of classical homocystinuria, the most common inborn error in sulfur metabolism. The c.797 G>A (p.R266K) mutation in CBS was originally described in several Norwegian pyridoxine responsive CBS deficient patients, and heterologous gene expression studies have shown that the protein has near wild‐type levels of enzyme activity. Here, we characterize a transgenic mouse lacking endogenous Cbs and expressing p.R266K human CBS protein from a zinc inducible metallothionein promoter (Tg‐R266K Cbs^‐/‐). Unlike mice expressing other mutant CBS alleles, the Tg‐R266K transgene is unable to efficiently rescue neonatal lethality of Cbs^‐/‐ on a C57BL/6J background. On a C3H/HeJ background, zinc‐induced Tg‐R266K Cbs^‐/‐ mice express CBS mRNA, but have very low levels of CBS protein and enzyme activity, resulting in extreme elevations in serum total homocysteine (tHcy). Treatment with pyridoxine did not have any appreciable effect on tHcy, indicating this allele is not pyridoxine responsive in mice. However, treatment with the proteasome inhibitor bortezomib resulted in an 97% reduction in tHcy and a 2381% increase in liver CBS activity. These studies show that the p.R266K mutation causes increased proteasomal degradation in vivo, and that treatments that stabilize the protein can be used to reverse its effect.     

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system

Abstract

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5?g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.     

A pilot study of neuromuscular ultrasound as a biomarker for amyotrophic lateral sclerosis

Introduction: This study explores the reliability and responsiveness of neuromuscular ultrasound in amyotrophic lateral sclerosis (ALS). Methods: Investigations were conducted with 10 healthy controls, 10 patients with ALS (single point in time), and 10 different patients with ALS (followed over 6 months; 4 completed follow-up). Ultrasound was used to measure the thickness of the geniohyoid, bilateral biceps/brachialis, bilateral tibialis anterior, and bilateral hemidiaphragms (at inspiration and expiration). Interrater and intrarater reliability and change in muscle thickness over 6 months were measured. Results: Interrater correlation coefficients ranged between 0.80 and 0.99 in healthy controls and between 0.78 and 0.97 in patients with ALS. Intrarater correlation coefficients ranged between 0.83 and 0.98 in healthy controls. The mean percentage decline in muscle thickness over 6 months was 20.25%. Discussion: Muscle ultrasound appears to be a reliable technique for measuring important muscles in patients with ALS. Larger studies with age-matched controls should be conducted to assess further the responsiveness of this biomarker in ALS. Muscle Nerve 59 :181–186, 2019     

Factors associated with enrollment in cancer genetics research.

Previous studies have identified low patient accrual in large-scale cancer clinical trials, particularly for underrepresented groups, such as ethnic minorities, females, and patients >65 years. As there have been few studies examining participation in cancer genetics epidemiologic research, our objective was to identify clinical and demographic factors predicting enrollment in these studies. A total of 1,111 patients diagnosed with colorectal cancer presenting to a gastrointestinal oncology clinic were approached to enroll in a study investigating the role of the MSH6 gene in familial colorectal cancer. Patient consent was sought for providing a blood specimen for DNA analysis and review of medical records/tumor specimens and contacting family members to confirm the family history of cancer. Seven predictor variables for enrollment (age, sex, ethnicity, family history of colorectal cancer in a first-degree relative, presence of children, insurance type, and type of visit) were analyzed using logistic regression analysis to determine the effect on decision to enroll. Of 1,111 patients approached, 696 (62.6%) enrolled in the study. Of these approached individuals, 4.2% were of nonwhite ethnicity and 33.5% were age > or =65 years. Patients of white ethnicity [odds ratio (OR), 2.10; P = 0.018], males (OR, 1.47; P = 0.002), those ages < or =65 years (OR, 1.42; P = 0.009), and those with a first-degree relative with colorectal cancer (OR, 1.57; P = 0.005) were significantly more likely to enroll. Fewer than 4% of all participants denied permission for the study researchers to access information from medical records or to be recontacted by researchers to discuss the enrollment of additional family members. Our data suggest that, once subjects decided to enroll, the majority (88%) was comfortable with consenting to all study components, including the creation of cell lines and future recontact. Low participation rates for ethnic minorities, females, and elderly patients are similar for both cancer genetics and clinical trial studies.     

Enhanced retrieval of DNA from human fecal samples results in improved performance of colorectal cancer screening test

Colorectal cancer accounts for more than 10% of all cancer deaths but is curable, if detected early. We reported previously on a stool-based screening test in which DNA from stool samples is subjected to genome analysis; sensitivity of the test has been limited in part by inefficiency of retrieving DNA from stool. Our aim was to test the impact of a new purification method that would increase the yield of human DNA from stool. DNA from 86 cancer and 100 non-cancer subjects (diagnosed by colonoscopy) were purified from stool with a new method for DNA recovery based on sequence-specific capture with acrylamide gel immobilized capture probes as well as with a previously developed magnetic bead-capture procedure. The new purification method gives an average 5.4-fold increase in the quantity of human DNA that can routinely be retrieved from fecal samples. The increased recovery of DNA corresponds with an increase in assay sensitivity from 53% (CI: 42 to 64%) to 70% (CI: 59 to 79%); P = 0.0005 (by McNemar's test), with no change in specificity. The newly developed sample preparation method mitigates a major problem in detecting rare cancer-associated genetic changes in heterogeneous clinical samples such as stool.     

Percutaneous radiofrequency ablation of pulmonary malignancies: combined treatment with brachytherapy

OBJECTIVE: The purpose of this article is to report the clinical experience and technical feasibility of percutaneous radiofrequency ablation in conjunction with brachytherapy, a novel approach in the treatment of lung neoplasms. Data from three patients with lung malignancies illustrate the expanding therapeutic indications of this minimally invasive intervention. CONCLUSION: Percutaneous radiofrequency ablation in conjunction with brachytherapy is a promising minimally invasive combination modality. It may be a treatment option for patients with primary, recurrent, or metastatic malignancies of the lung that are not amenable to surgery or further external beam radiation therapy.     

Antisaccade performance is abnormal in schizophrenia patients but not in their biological relatives

Numerous studies have replicated the finding that schizophrenia patients make an increased number of errors on an antisaccade task. Some studies have reported that relatives of schizophrenia patients also make an increased number of antisaccade errors, a finding that has been interpreted to support the usefulness of compromised antisaccade performance as an index of genetic liability for schizophrenia. We examined performance on an antisaccade task in schizophrenia patients, nonpsychiatric controls, first-degree relatives of schizophrenia patients and first-degree relatives of nonpsychiatric controls. Schizophrenia patients made significantly more errors than did nonpsychiatric controls, but relatives of schizophrenia patients did not differ from relatives of controls or from all controls. Increased antisaccade errors on the standard version of the antisaccade task are associated with schizophrenia, but do not seem to be a co-familial trait for schizophrenia.     

Multimodal Imaging in Masquerade Syndromes

Masquerade syndromes present to uveitis clinics due to the appearance of inflammatory signs and chronic symptoms that are not responsive to conventional treatment. They are frequently misdiagnosed and treated as refractory inflammatory conditions, which delays appropriate diagnosis and management. This review of literature focuses on the commonly encountered masquerade syndromes and discusses the role of multimodal imaging in addressing these complex clinical presentations. We review the conventional imaging techniques for these patients and discuss emerging technological advances that may help in establishing a diagnosis. We present cases highlighting the utility of multimodal imaging in identifying the etiology.     

Dietary intake of S-(α-carboxybutyl)-dl-homocysteine induces hyperhomocysteinemia in rats

Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to homocysteine (Hcy), forming dimethylglycine and methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal injection of S-(α-carboxybutyl)-dl-homocysteine (CBHcy) results in hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine whether it could be absorbed and cause hyperhomocysteinemia as observed in the intraperitoneal administration of the compound in mice. We hypothesized that dietary administered CBHcy will be absorbed and will result in the inhibition of BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an l-amino acid–defined diet either containing or devoid of CBHcy (5 mg per meal) for 3 days. The treatment decreased liver BHMT activity by 90% and had no effect on methionine synthase, methylenetetrahydrofolate reductase, phosphatidylethanolamine N-methyltransferase, and CTP:phosphocholine cytidylyltransferase activities. In contrast, cystathionine β-synthase activity and immunodetectable protein decreased (56% and 26%, respectively) and glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats, and S-adenosylhomocysteine levels did not change. Furthermore, plasma choline decreased (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment had no effect on global DNA and CpG island methylation, liver histology, and plasma markers of liver damage. We conclude that CBHcy-mediated BHMT inhibition causes an elevation in total plasma Hcy that is not normalized by the folate-dependent conversion of Hcy to methionine. Furthermore, metabolic changes caused by BHMT inhibition affect cystathionine β-synthase and glycine N-methyltransferase activities, which further deteriorate plasma Hcy levels.