Teratogenic effects of radiofrequency electromagnetic radiation on the embryonic development of chick: A study on morphology and hatchability.

The present study was aimed at studying the effects of RF-EMR in causing teratogenic changes in the embryonic development of organisms using chick embryo as a model. The fertilized eggs of the hen were incubated in a digital humidified incubator and exposed to RF-EMR from 2G and 4G mobile phones by ringing at regular time intervals. The dose of RF-EMR was varied by increasing the call duration and number of calls per day, with the lower dose being a call duration of 50 min/day and the higher dose being 90 min/day. The phone kept had a range of radiofrequency between 900 and 1800 MHz and SAR (Specific Absorption Rate) 1.355 (2G) and 1.12 (4G) watts/ kg respectively. The batch of eggs incubated without any exposure to RF-EMR was taken as control. The hatchability of 2G and 4G experimental groups were respectively, 65% and 75% at lower radiation exposure and 40% and 55% at higher radiation exposure. The teratogenic effects of RF-EMR on the morphology of chick embryos manifested as the cross beak, non-retracted yolk sac, macrocephaly, malformed legs and toes, disability in standing and balancing the body and variations in body weight, body length and beak length. The results indicate that the RF-EMR poses potential threats to the developing stages of organisms.

Consensus exercise identifying priorities for research in the field of general surgery of childhood in the UK.

BACKGROUND: The evidence base underlying clinical practice in children's general surgery is poor and high-quality collaborative clinical research is required to address current treatment uncertainties. The aim of this study was, through a consensus process, to identify research priorities for clinical research in this field amongst surgeons who treat children. METHODS: Questions were invited in a scoping survey amongst general surgeons and specialist paediatric surgeons. These were refined by the study team and subsequently prioritized in a two-stage modified Delphi process. RESULTS: In the scoping survey, a total of 226 questions covering a broad scope of children's elective and emergency general surgery were submitted by 76 different clinicians. These were refined to 71 research questions for prioritization. A total of 168 clinicians took part in stage one of the prioritization process, and 157 in stage two. A 'top 10' list of priority research questions was generated for both elective and emergency general surgery of childhood. These cover a range of conditions and concepts, including inguinal hernia, undescended testis, appendicitis, abdominal trauma and enhanced recovery pathways. CONCLUSION: Through consensus amongst surgeons who treat children, 10 priority research questions for each of the elective and emergency fields have been identified. These should provide a basis for the development of high-quality multicentre research projects to address these questions, and ultimately improve outcomes for children requiring surgical care.

Perineal closure following extralevator abdominoperineal excision for cancer of the rectum.

AIM: Extralevator abdominoperineal resection (ELAPE) may be complicated by perineal wound healing problems and herniation. We report a consecutive series of 38 such patients with selective use of a fasciocutaneous V-Y buttock advancement flap (BAF). METHOD: Data were collected on a series of patients undergoing ELAPE for rectal malignancy between August 2011 and July 2017. Demographics, management and outcomes were recorded prospectively. Perineal wound problems were considered as 'major' if they required packing; otherwise, they were classed as 'minor'. RESULTS: Thirty-eight patients [eight female and 30 male; median age 63 (range: 35-89) years] underwent ELAPE. Thirty-seven had an adenocarcinoma of the rectum and one had a malignant melanoma. The median tumour height (from the anal verge) was 30 (range: 0-80) mm. Sixteen patients had a BAF. The median length of stay was 10 (range: 6-25) days. Primary perineal healing occurred in 18 (47%) patients. Major wound breakdown occurred in three (10%) patients and minor wound breakdown in 17 (45%). Two of the 16 patients having a BAF had major wound breakdown: one wound took 9 weeks to heal completely and the other took 9 months. Of the 22 patients who did not have a BAF, one had a major wound breakdown which closed by 3 months. There were no perineal fistulae or chronic sinuses. There were two perineal herniae that were successfully repaired by perineal insertion of biological mesh (Permacol™; Covidien, Dublin, Ireland). CONCLUSIONS: Selective use of a BAF for perineal closure can give good results in terms of healing and an acceptably low early perineal herniation rate.

Retention of laryngoscopy skills in medical students: a randomised, cross-over study of the Macintosh, A.P. Advance(™) , C-MAC(®) and Airtraq(®) laryngoscopes.

In addition to being effective and easy to learn how to use, the ideal laryngoscope should be associated with minimal reduction in skill performance during gaps in practice over time. We compared the time taken to intubate the trachea of a manikin by novice medical students immediately after training, and then after 1 month, with no intervening practice. We designed a two-period, four-group, randomised, cross-over trial to compare the Macintosh, Venner(™) A.P. Advance(™) with difficult airway blade, C-MAC(®) with D-Blade and Airtraq(®) with wireless video-viewer. A bougie was used to aid intubation with the Macintosh and the C-MAC. After training, there was no significant difference in median (IQR [range]) intubation time using the videolaryngoscopes compared with the Macintosh, which took 30 (26.5-35 [12-118])s. One month later, the intubation time was longer using the C-MAC (41 (29.5-52 [20-119])s; p = 0.002) and A.P. Advance (40 (28.5-57.5 [21-107])s; p = 0.0003)m compared with the Macintosh (27 (21-29 [16-90])s); there was no difference using the Airtraq (27 (20.5-32.5 [15-94])s; p = 0.258) compared with the Macintosh. While skill acquisition after a brief period of learning and practice was equal for each laryngoscope, performance levels differed after 1 month without practice. In particular, the consistency of performance using the C-MAC and A.P. Advance was worse compared with the Macintosh and the Airtraq. While the clinical significance of this is doubtful, we believe that reliable and consistent performance at laryngoscopy is desirable; for the devices that we tested, this requires regular practice.

Cadaveric study of movement of an unstable atlanto-axial (C1/C2) cervical segment during laryngoscopy and intubation using the Airtraq(®) , Macintosh and McCoy laryngoscopes.

Concern that laryngoscopy and intubation might create or exacerbate a spinal cord injury has generated extensive research into cervical spinal movement during laryngoscopy. We performed a randomised trial on six cadavers, using three different laryngoscopes, before and after creating a type-2 odontoid peg fracture. Our primary outcome measure was the change in the space available for the spinal cord at the C1/2 segment measured by cinefluoroscopy. Tracheal intubation was performed using a minimal view of the glottis, a bougie, and manual in-line stabilisation. In a cadaveric model of type-2 odontoid fracture, the space available for the cord was preserved in maximum flexion and extension, and changed little on laryngoscopy and intubation.

Mediterranean diet and depressive symptoms among older adults over time.

OBJECTIVE: To examine whether adherence to a Mediterranean-based dietary pattern is predictive of depressive symptoms among older adults. DESIGN: Generalized estimating equation models were used to test the association between a Mediterranean-based dietary pattern and depressive symptoms over time. Models were adjusted for age, sex, race, education, income, widowhood, antidepressant use, total calorie intake, body mass index, smoking, alcohol consumption, number of self-reported medical conditions, cognitive function, and physical disability. SETTING: Chicago, Illinois. PARTICIPANTS: Community-dwelling participants (n=3502) of the Chicago Health and Aging Project aged 65+ years (59% African American) who had no evidence of depression at the baseline. MEASUREMENTS: Adherence to a Mediterranean-based dietary pattern was assessed by the MedDietScore. Dietary evaluation was performed with a food frequency questionnaire at baseline and related to incident depression as measured by the presence of four or more depressive symptoms from the 10-item version of the Center for Epidemiologic Studies Depression scale. RESULTS: Over an average follow-up of 7.2 years, greater adherence to a Mediterranean-based diet was associated with a reduced number of newly occurring depressive symptoms (parameter estimate = -0.002, standard error = 0.001; p = 0.04). The annual rate of developing depressive symptoms was 98.6% lower among persons in the highest tertile of a Mediterranean-based dietary pattern compared with persons in the lowest tertile group. CONCLUSION: Our results support the hypothesis that adherence to a diet comprised of vegetables, fruits, whole grains, fish, and legumes may protect against the development of depressive symptoms in older age.

Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination.

OBJECTIVE: To investigate the interrelations of serum vitamin B12 markers with brain volumes, cerebral infarcts, and performance in different cognitive domains in a biracial population sample cross-sectionally. METHODS: In 121 community-dwelling participants of the Chicago Health and Aging Project, serum markers of vitamin B12 status were related to summary measures of neuropsychological tests of 5 cognitive domains and brain MRI measures obtained on average 4.6 years later among 121 older adults. RESULTS: Concentrations of all vitamin B12-related markers, but not serum vitamin B12 itself, were associated with global cognitive function and with total brain volume. Methylmalonate levels were associated with poorer episodic memory and perceptual speed, and cystathionine and 2-methylcitrate with poorer episodic and semantic memory. Homocysteine concentrations were associated with decreased total brain volume. The homocysteine-global cognition effect was modified and no longer statistically significant with adjustment for white matter volume or cerebral infarcts. The methylmalonate-global cognition effect was modified and no longer significant with adjustment for total brain volume. CONCLUSIONS: Methylmalonate, a specific marker of B12 deficiency, may affect cognition by reducing total brain volume whereas the effect of homocysteine (nonspecific to vitamin B12 deficiency) on cognitive performance may be mediated through increased white matter hyperintensity and cerebral infarcts. Vitamin B12 status may affect the brain through multiple mechanisms.

Change in body mass index and risk of incident Alzheimer disease.

OBJECTIVE: To examine the association of change in body mass index (BMI) with risk of Alzheimer disease (AD). METHODS: Nine hundred eighteen older Catholic clergy participating in the Religious Orders Study without dementia at baseline were studied. Outcome measures were the clinical diagnosis of AD and change in cognitive function. RESULTS: During a mean follow-up of 5.5 years, 151 persons developed AD. BMI averaged 27.4 at baseline and declined in about half the participants. In a proportional hazards model adjusted for age, sex, and education, each 1-unit less of BMI at baseline was associated with about a 5% increase in the risk of AD (hazard ratio = 0.944; 95% CI = 0.908 to 0.981), and each 1-unit annual decline in BMI (about the 10th percentile) was associated with about a 35% increase in the risk of AD compared with a person experiencing no change in BMI (about the 50th percentile) (hazard ratio = 0.730; 95% CI = 0.625 to 0.852). The results were similar after controlling for chronic diseases and excluding persons who developed AD during the first 4 years of observation. Random effects models showed that the rate of cognitive decline increased by about 8% for each 1-unit less of BMI at baseline and declined an additional 40%/year in persons losing 1 unit of BMI/year compared with those with no change in BMI. CONCLUSION: Declining body mass index (BMI) is associated with increased risk of incident Alzheimer disease (AD). Loss of BMI may reflect pathologic processes that contribute to the subsequent development of AD.

An aldol-based approach to the asymmetric synthesis of L-callipeltose, the deoxyamino sugar of L-callipeltoside A.

[reaction: see text] The L-callipeltose subunit of L-callipeltoside A has been synthesized in 10 steps and 13% overall yield from D-threonine. The key steps are a highly diastereoselective Felkin anti aldol addition to a methyl ketone and a selective methylation of a secondary alcohol in the presence of a secondary carbamate.

Experience with a one-stop colorectal clinic.

BACKGROUND AND OBJECTIVE: Colorectal services have traditionally been arranged for the convenience of hospitals rather than patients. This model is not ideal, particularly for minor interventions and diagnostic procedures. In order to address this a one-stop colorectal clinic was set up. PATIENTS AND METHODS: Weekly clinics ran from 6.00 to 9.30 p.m. on Wednesdays for a period of 6 months. Patients with rectal bleeding, altered bowel habit, anorectal symptoms and those requesting screening advice were seen by a consultant or specialist registrar. Patients were asked to fill in a questionnaire at the end of their clinic attendance. RESULTS: 197 patients were seen in 17 clinics; 134 underwent proctoscopy, 72 had a rigid sigmoidoscopy and 85 had a flexible sigmoidoscopy carried out. Twenty-four patients subsequently had a barium enema and 3 were listed for colonoscopy. The main diagnosis was haemorrhoids (n = 104); 14 colorectal neoplasms were discovered (5 cancers and 9 polyps). During the study period the number of patients waiting for lower gastrointestinal endoscopy fell from 119 to 63; 2 months after ending the pilot scheme, the number had risen to 108. CONCLUSION: The clinic was found to have significantly improved patient care. The majority of patients were satisfied with an evening clinic. Flexible sigmoidoscopy without sedation was well tolerated and the ability to perform this at initial assessment had a marked effect on the number of patients awaiting lower gastrointestinal endoscopy.

MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity.

P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications. It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake. Individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy. To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele. The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively). The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin.

Multiple roles of the Dcdc42 GTPase during wing development in Drosophila melanogaster.

The Rho sub-family of GTPases, comprising Rho, Rac and Cdc42. regulates many biological processes, including morphogenesis, cell polarity, migration, the cell cycle and gene expression. It is important to develop genetic approaches to allow the dissection, in vivo, of the mechanisms of GTPase regulation and signal transmission, and their biological consequences. In this regard, wing development in Drosophila melanogaster is an excellent model system. To investigate the functions of the Drosophila Cdc42 GTPase (Dcdc42), we generated phenotypes during wing development, by expression of the dominant-negative N17 and L89 mutants of Dcdc42. We have identified roles for Dcdc42 in wing growth, and in cell fate choice during the development of the wing veins and the peripheral nervous system. Reduction of Dcdc42 signalling following over-expression of Dcdc42N17 resulted in a broader but more diffuse domain characterised by wing-margin sensory bristles. This was correlated with a broadened stripe of wingless expression along the dorsal-ventral boundary of third-instar wing imaginal discs. Together with genetic interactions with loss- and gain-of-function Notch alleles, these data support a role for wild-type Dcdc42 as a negative regulator of Notch signalling.

Molecular misreading in non-neuronal cells.

+1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin-B(+1) have been identified in the neuropathological hallmarks of Alzheimer's disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs of messenger RNA encoded by genes that have maintained the unchanged wild-type DNA sequence. This process is termed 'molecular misreading'. A key question is whether this process is confined to neurons or whether it could also occur in non-neuronal cells. A transgenic mouse line (MV-B) carrying multiple copies of a rat vasopressin minigene as a reporter driven by the MMTV-LTR promotor was used to screen non-neuronal tissues for molecular misreading by means of detection of the rat vasopressin(+1) protein and mutated mRNA. Molecular misreading was demonstrated to occur in several organs (e.g., epididymis and the parotid gland) where transgenic vasopressin expression is abundant, but its penetrance is variable both between and within tissues. This implies that non-neural tissues too, could be affected by cellular derangements caused by molecular misreading.

Processing of frameshifted vasopressin precursors.

Biosynthesis of the vasopressin (VP) prohormone in magnocellular neurones of the hypothalamo-neurohypophysial system comprises endoplasmic reticulum (ER) transit, sorting into the regulated secretory pathway and subsequent processing in the individual proteins VP, neurophysin and a glycoprotein. These processes are severely disrupted in the homozygous diabetes insipidus (di/di) Brattleboro rat, which expresses a mutant VP precursor due to a single nucleotide deletion in the neurophysin region of the VP gene resulting in VP deficiency. Previous studies have shown the presence of additional frameshift mutations in VP transcripts, in solitary magnocellular neurones of the di/di rat due to a GA dinucleotide deletion resulting in two different mutant VP precursors with partly restored reading frame. Frameshifted VP precursors are also expressed in several magnocellular neurones in wild-type rats. In this study, we determined if the +1 frameshifted precursors from di/di and wild-type rats can lead to biosynthesis of the hormone VP. Therefore, eukaryotic expression plasmids containing the frameshifted VP cDNAs were transiently expressed in peptidergic tumour cell lines, and cells were analysed by reversed phase high-performance liquid chromatography and specific radioimmunoassays, and by immunofluoresence. Neuro2A neuroblastoma cells expressing the +1 frameshifted precursors of di/di rats retained products in the cell body. Only precursor or insignificant quantities of neurophysin-immunoreactive products were detected. In contrast, in AtT20 cells, frameshifted VP precursors were at least partly processed to yield the VP peptide, indicating that they have access to the regulated secretory pathway. Comparison between the two cell lines showed a very slow ER transit of the wild-type prohormone combined with inefficient processing in Neuro2A cells. The results show that mutant precursors can reach the regulated secretory pathway if ER transport is sufficiently rapid as in the case of AtT20 cells. This suggests that the di/di rat may regain the capacity to biosynthesize authentic VP through these +1 frameshifted precursors in magnocellular neurones.

Immunomodulatory and antitumour properties of Psoralea corylifolia seeds.

Psoralea corylifolia seed extract has been found to stimulate the immune system in mice. Administration of the extract was found to inhibit EAC ascitic tumour growth and stimulate natural killer cell activity, antibody-dependent cellular cytotoxicity, antibody-forming cells and the antibody complement-mediated cytotoxicity during tumour development.

Characterization of a human glutathione S-transferase mu cluster containing a duplicated GSTM1 gene that causes ultrarapid enzyme activity.

The mu class glutathione S-transferase gene GSTM1 is polymorphic in humans, with approximately half of the Caucasian population being homozygous deleted for this gene. GSTM1 enzyme deficiency has been suggested to predispose people to lung and bladder cancer. Some people in a Saudi Arabian population, however, have been described previously with ultrarapid GSTM1 enzyme activity. Here we have evaluated the molecular genetic basis for this observation. Genomic DNA from two Saudi Arabian subjects exhibiting ultrarapid enzyme activity and from 13 Swedish subjects having null, one, or two GSTM1 genes were subjected to restriction fragment length polymorphism analysis using the restriction enzymes EcoRI, EcoRV, and HindIII and combinations thereof. Hybridization was carried out using a full-length GSTM1 cDNA or the 5' and 3' parts of the cDNA. The restriction mapping data revealed the presence of a GST mu cluster with two GSTM1 genes in tandem situated between the GSTM2 and GSTM5 genes. A quantitative multiplex polymerase chain reaction method, which simultaneously amplified a fragment of the GSTM1 gene and the beta-globin gene, was developed, and the genomic GSTM1 copy number was determined from the GSTM1/beta-globin ratio. This method clearly separated GSTM1 +/- subjects (ratios between 0.4 and 0.7) from GSTM1 +/+ subjects (ratios between 0.8 and 1.2). The two Saudi Arabians with ultrarapid GSTM1 activities had ratios of approximately 1.5, indicating that they carried three GSTM1 genes. These results demonstrate the existence of a novel mu class GST cluster containing a duplicated active GSTM1 gene causing ultrarapid enzyme activity.