A framework for assessing the potential for a double dividend from a policy-induced reduction in alcohol consumption on the economy.

OBJECTIVES: Tax policies targeted at reducing alcohol consumption are typically understood to be associated with economic losses, including in alcohol production and trade sectors. This study sought to determine whether the overall effect of reduced alcohol consumption might be positive once improvements in productivity associated with reduced alcohol-related consumption are considered. STUDY DESIGN: This study used Computable General Equilibrium economic modelling. METHODS: An economic modelling framework was developed for Scotland, which considered the fiscal and economic impacts of alcohol taxation and the economy-wide impacts. Simulation of hypothetical alcohol taxes and improvements in labour productivity calibrated on losses due to absenteeism and presenteeism in Scotland in 2017. RESULTS: The long-run impacts of a five pence increase in taxation alone produce negative economic impacts on jobs and Gross Domestic Product in Scotland (1189 jobs and £71.12 million). These effects are reduced by half - but remain negative - when the revenues from such policy are recycled to the economy through government spending. A small improvement in labour productivity - equivalent to 4.95% of the total productivity gap from absenteeism and presenteeism estimated for Scotland - would be sufficient to turn the economic consequence non-negative. CONCLUSIONS: The overall macroeconomic impact of policies targeted at alcohol consumption should include consideration of the potential productivity effect and that impact studies that do not include such mechanisms are likely to overstate the negative economic impacts of alcohol policies.

Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome.

BACKGROUND AND PURPOSE: Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. MATERIALS AND METHODS: Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. RESULTS: Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. CONCLUSIONS: The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.

Bilateral endogenous panophthalmitis caused by Salmonella typhi: first case report.

Metastatic bilateral endogenous panophthalmitis is a rare but devastating ocular infection. A young male presented with high-grade fever of 4 days duration along with rapidly progressive proptosis and loss of vision in both eyes. Systemic examination revealed bronchopneumonia and the blood culture was positive for Salmonella typhi. Ocular examination revealed bilateral panophthalmitis, which was confirmed on ultrasound B scan and MRI of the orbits. The patient was started on intravenous antibiotics and a core vitrectomy was performed in the right eye along with intravitreal antibiotic injection. Bronchopneumonia, proptosis and periorbital edema resolved with systemic antibiotic therapy but the patient developed bilateral phthisis bulbi. This is the first case report of metastatic, bilateral panophthalmitis caused by Salmonella typhi.

Ovarian steroid cell tumor, not otherwise specified.

Ovarian steroid cell tumours are rare virilizing tumours. They are three types of tumours of ovary which are characterized by steroid cell proliferation : Leydig cell tumour, steroid cell tumour, Not Otherwise Specified (NOS) and stromal luteoma. Here we present a case of 36 year old female, who presented with history of weight loss since last two and half months. There is history of amenorrhoea and hirsuitism. Her CA was 125: 11.4 IU/ml (0-35 U/mL). Blood Testosterone levels was elevated with value of 150 ng/ml (5.71-77 ng/ml). Serum Inhibin A, Inhibin B, FSH, LH and prolactin were within normal limits. The steroid cell tumour, NOS are mostly benign but few of them behave in malignant fashion. Hayes and Scully gave few histopathological features which favour malignant behavior. These tumours should be differentiated from leydig cell tumour by lack of cytoplasmic Reinkes' crystals as well as from other neoplasms like primary clear cell carcinoma, metastatic clear cell renal cell carcinoma and adrenocortical tumour.

Variants in ACTG2 underlie a substantial number of Australasian patients with primary chronic intestinal pseudo-obstruction.

BACKGROUND: Primary chronic intestinal pseudo-obstruction (CIPO) is a rare, potentially life-threatening disorder characterized by severely impaired gastrointestinal motility. The objective of this study was to examine the contribution of ACTG2, LMOD1, MYH11, and MYLK mutations in an Australasian cohort of patients with a diagnosis of primary CIPO associated with visceral myopathy. METHODS: Pediatric and adult patients with primary CIPO and suspected visceral myopathy were recruited from across Australia and New Zealand. Sanger sequencing of the genes encoding enteric gamma-actin (ACTG2) and smooth muscle leiomodin (LMOD1) was performed on DNA from patients, and their relatives, where available. MYH11 and MYLK were screened by next-generation sequencing. KEY RESULTS: We identified heterozygous missense variants in ACTG2 in 7 of 17 families (~41%) diagnosed with CIPO and its associated conditions. We also identified a previously unpublished missense mutation (c.443C>T, p.Arg148Leu) in one family. One case presented with megacystis-microcolon-intestinal hypoperistalsis syndrome in utero with subsequent termination of pregnancy at 28 weeks' gestation. All of the substitutions identified occurred at arginine residues. No likely pathogenic variants in LMOD1, MYH11, or MYLK were identified within our cohort. CONCLUSIONS AND INFERENCES: ACTG2 mutations represent a significant underlying cause of primary CIPO with visceral myopathy and associated phenotypes in Australasian patients. Thus, ACTG2 sequencing should be considered in cases presenting with hypoperistalsis phenotypes with suspected visceral myopathy. It is likely that variants in other genes encoding enteric smooth muscle contractile proteins will contribute further to the genetic heterogeneity of hypoperistalsis phenotypes.

Adenoid cystic carcinoma: a rare breast carcinoma.

Adenoid cystic carcinoma is a rare neoplasm accounting for <0.1% of breast carcinomas. The mean age of presentation is fifth to sixth decade of life and it generally presents as a painful breast lump. The histological features are characteristic with cribriform and acinar pattern of basaloid cells. It is triple negative tumor with CD117 and p63 positivity and excellent prognosis.

Temperature affects the results of the glutaraldehyde test in the diagnosis of pulmonary tuberculosis.

SETTING: Subjects attending the District Tuberculosis Clinic and a Teaching Hospital in Jodhpur were studied at the Desert Medicine Research Centre, Jodhpur. OBJECTIVES: To confirm the effect of temperature on the results of the blood glutaraldehyde test (GT) and to examine the sensitivity and specificity of the restandardised test procedure. DESIGN: Blood glutaraldehyde gelification time (BGGT) was compared, in the same blood samples, at 19, 22 and 25 degrees C and after storage at 1) room temperature and at 2) 2-8 degrees C for 3-5 h, using the paired t-test. After restandardisation of the procedure, the GT was carried out on 88 sputum culture-positive cases with pulmonary tuberculosis (PTB) and 182 controls. The technician was blinded to patient information. RESULTS: BGGT significantly varied with the temperature of the water bath and the temperature at which blood samples were stored before testing. When the test was carried out in the water bath at 22 degrees C after storing blood for 3-5 h at 2-8 degrees C, as per the restandardised procedure, the specificity of GT was 96.2% (95 %CI 93.36-98.95) and the sensitivity was 84.1% (95%CI 76.45-91.73). CONCLUSION: Restandardised GT is a reliable, simple, easy, rapid, inexpensive and user-friendly test for diagnosis of PTB which does not require sophisticated laboratory equipment.

Acute Intermittent Porphyria in a Kumhar community of Western Rajasthan.

OBJECTIVE: To know the current magnitude of the occurrence of Acute Intermittent Porphyria in Kumhar community of a part of Western Rajasthan. MATERIAL AND METHODS: This is a cross sectional study of rural community of Kumhars of Bikaner district of Western Rajasthan. The households of kumhar community were approached. Besides recording other information and examination details, their urine samples were subjected to Watson-Schwartz Test. RESULT: 1237 subjects out of a total of 2385 kumhar population distributed among 20 randomly selected villages of Bikaner district could be studied. The prevalence of AIP was estimated to be 1.16%. (CI=0.012 +/- 0.0005), showing higher prevalence than the earlier reported studies. The cases exhibited varied symptomatology. Overall preponderance was in favor of females (2:1) and majority of cases (38.9%) were found in the age group of 20-29 years. Average age of manifestation was 24.5 +/- 4.8 years. A follow up was also done to know the disease consequences, if any. CONCLUSIONS: The study finds higher prevalence of the disease and as such warrants a need for generating awareness among the families of cases in the specific caste group in the study area for early detection and better management of the disease.

Leishman and Giemsa stain: a new reliable staining technique for blood/bone marrow smears.

INTRODUCTION: Peripheral blood and bone marrow smear examination is an important basic tool for the diagnosis of different haematological conditions including haematological malignancies. We created a newer modification of the conventional Leishman and Giemsa stains as Leishman and Giemsa (L&G) stain and compared the efficacy and reliability of this stain with conventional stains. The study was performed to evaluate the staining efficacy, feasibility, time and cost of L&G stain over the conventional Leishman and Giemsa stains. METHODS: A pilot study was carried out in the Department of Haematology of our hospital from October 2013 to December 2013. Hundred selected cases, each with peripheral blood and bone marrow smears were taken, and three sets of the smears were prepared from each sample--one for L&G stain and other two--one each for conventional Leishman and Giemsa stains. This staining is further incorporated in our routine standard operating protocols for staining of all the peripheral blood smears in automated stainer, Sysmex SP10. RESULT: The average grading score from each staining methods from all the three experts was compiled. The average grading score of L&G staining method was noted to be significantly higher than the other two methods (analysis of variance test, P value < 0.05). When modified L&G stain (C) was compared with stain conventional stains (A and B), a P value of <0.001 was noted in all parameters except between Leishman stain and L&G stain in mature RBC and WBC nucleus and RBC inclusions (P value between 0.05 and 0.001). CONCLUSION: L&G staining is a newer staining technique of immense help in high-throughput haematology laboratories by offering a time-saving, cost-effective and better staining option to conventional staining methods. It gives a better nuclear and cytoplasmic differential staining and can also be used in automated blood counters/stainer.

Patient with a 22q11.2 deletion with no overlap of the minimal DiGeorge syndrome critical region (MDGCR).

The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.

The predictive value of first-trimester embryonic heart rates in infertility patients.

OBJECTIVE: To analyze whether first-trimester embryonic (fetal) heart rates (FHR) are useful in predicting pregnancy outcome for infertility patients. METHODS: Patients in a university-based reproductive endocrinology and infertility practice were studied prospectively. Infertile women who achieved clinical pregnancy underwent first-trimester transvaginal sonographic evaluation, and FHR in patients achieving viable pregnancies were compared with those experiencing fetal loss. RESULTS: Overall, 99 pregnancies reached viability and 17 resulted in fetal loss before 20 weeks' gestation. Patient age, methods of conception, and number of previous fetal losses did not differ significantly between the two groups. A significant correlation (r = .70, P < .001) was found between increasing FHR levels and advancing gestational age in patients with viable pregnancies and, although to a weaker extent, patients who miscarried (r= .52, P < .05). A significantly higher number of viable pregnancies, compared with fetal losses, had FHR falling within one (70.7% compared with 41.2%, P < .025) and two (99.0% compared with 64.7%, P < .001) standard deviations of the mean for viable pregnancies at corresponding gestational ages. The majority of FHR of failing pregnancies fell below the individual reference ranges. CONCLUSION: First-trimester FHR can help predict pregnancy outcome for infertility patients. Women with FHR outside the reference range from the mean for viable pregnancies at corresponding gestational ages may be at risk for eventual pregnancy loss.

Elevated first-trimester serum relaxin concentrations in pregnant women following ovarian stimulation predict prematurity risk and preterm delivery.

OBJECTIVE: To determine whether ovarian stimulation would result in higher circulating relaxin concentrations and whether this hyperrelaxinemia would be associated with prematurity. METHODS: Two groups of women were studied: 1) women achieving pregnancy after ovarian stimulation (n = 114) and 2) women achieving pregnancy without treatment (n = 37). Serum was obtained at 6-12 weeks' gestational age; fetal number was determined by transvaginal ultrasound. Prematurity risk or preterm delivery was determined from the obstetric record. A specific human relaxin enzyme-linked immunosorbent assay was used to measure serum relaxin concentrations. Hyperrelaxinemia was defined as levels greater than 3 standard deviations above the weighted mean of levels in normal unstimulated singleton pregnancies at 6-12 weeks' gestation. RESULTS: An association was found between prematurity risk or premature delivery and peripheral relaxin concentrations during weeks 6-12 of pregnancy in women having ovarian stimulation and in women having multiple gestations. Circulating relaxin concentrations greater than 16 ng/mL in women having ovarian stimulation and levels greater than 7 ng/mL in women who had multiple gestations predicted prematurity risk or premature delivery in 50% of the women. CONCLUSIONS: These data demonstrate that after ovarian stimulation, some women have highly elevated circulating first-trimester relaxin concentrations. First-trimester hyperrelaxinemia identifies a group of women at risk for prematurity who can be monitored aggressively.

Hydroxyethyl starch macromolecules reduce myocardial reperfusion injury.

We assessed the value of a fraction of hydroxyethyl starch (HES Pz) in reducing the myocardial reperfusion injury in a canine open-chest model in which 1 hour of left anterior descending coronary artery occlusion was followed by 24 hours of reperfusion. Three treatment infusions (5% of blood volume) were compared: Ringer's lactate, serum albumin, and HES Pz (70% of the macromolecules between 100,000 and 1,000,000 d). When compared with Ringer's lactate and albumin, HES Pz significantly reduced the ratio of 24-hour infarct size to pretreatment area at risk (3% vs 19% and 16%, respectively) and myocardial water content (0.5% vs 3% and 1%). Potassium content differences between injured and normal myocardium were significantly less in the infarct regions of animals receiving HES Pz. In the canine model, HES Pz reduced 1-hour myocardial ischemia reperfusion injury significantly.

Bursting properties of units in cat globus pallidus and entopeduncular nucleus: the effect of excitotoxic striatal lesions.

The bursting properties of units recorded in globus pallidus and entopeduncular nucleus were studied in awake cats sitting quietly before and after ipsilateral excitotoxic striatal lesions. A computerized statistical procedure was used to identify and evaluate bursts in the recorded spike trains. Bursts were assigned a quantitative statistical measure of burst 'strength' (or improbability) - the surprise value. Before the lesion, 34% of units in the globus pallidus and 60% of units in the entopeduncular nucleus exhibited bursts. Burst units had a significantly slower discharge rate and a significantly greater variability of discharge than non-burst units. The mean length of the interspike intervals immediately preceding the bursts was significantly longer than the overall median intervals in burst units. After the lesion, 21% of units in the globus pallidus and 11% of the units in the entopeduncular nucleus exhibited bursts. Burst units had significantly higher discharge rates and lower discharge variability after the lesion. In contrast, the lesion had no significant effect on the rate or variability of non-burst units. The differences between bursting and non-bursting units in discharge rate and variability disappeared after the lesion. In globus pallidus, the lesion resulted in a significant reduction in the mean number of bursts per unit, surprise value per burst, mean length of bursts, and number of spikes per burst, and a significant increase in the mean discharge rate of burst units. In entopeduncular nucleus, the small number of bursts recorded after the lesion precluded a useful statistical comparison of the effect of striatal lesions on the properties of the bursts. This study demonstrates that removing striatal projections to globus pallidus and entopeduncular nucleus decreases bursting in these nuclei, indicating that intact striatal projections are necessary for the normal production of bursts in these regions.

Effects of excitotoxic striatal lesions on single unit activity in globus pallidus and entopeduncular nucleus of the cat.

Striatal projections to the globus pallidus and entopeduncular nucleus are thought to be GABAergic and inhibitory. Thus, striatal lesions might be expected to increase the spontaneous discharge rate of neurons in these nuclei. To test this prediction, we recorded spontaneous single unit activity from awake cats sitting quietly before and 7-160 days after striatal lesions. Striatal lesions were produced by injecting ibotenic acid into the caudate nucleus and putamen. Median, standard deviation, mean, and coefficient of variation of the interspike intervals were calculated for each unit. In globus pallidus the striatal lesion resulted in a significant decrease in median interval length, i.e. an increase in the discharge rate. The prelesion median of 36 ms (S.E.M. = 2.3) decreased 11% to a postlesion value of 32 ms (S.E.M. = 2.1). The lesion also resulted in a significant decrease in the variability of interspike intervals. The coefficient of variation, 1.31 (S.E.M. = 0.08) before the lesion, decreased 25% to 0.97 (S.E.M. = 0.06) after the lesion. In entopeduncular nucleus, the lesion had no statistically significant effect on the rate of activity, but a significant decrease in the variability of activity occurred. The median interval was 33 ms (S.E.M. = 3.3) before the lesion and decreased 2% to 32 ms (S.E.M. = 2.4). The coefficient of variation decreased 48% from 1.44 (S.E.M. = 0.1) to 0.73 (S.E.M. = 0.03). These observations support the hypothesis that loss of GABAergic inputs to the globus pallidus results in disinhibition. The discharge rate in entopeduncular nucleus was not affected by the striatal lesion, suggesting that striatal substance P or subthalamic excitatory inputs may have a role in regulating discharge rate in the entopeduncular nucleus.

Transnasal correction of choanal atresia.

A simple life-saving modification of the transnasal approach, which does not require endotracheal anesthesia or preoperative tracheostomy, is described. The use of polyethylene tubes, flanged at the distal end and split at the proximal end, is the most significant feature of this technique. In 14 of the 16 cases of choanal atresia presented, this was the definitive corrective procedure, and further revisions or a later transpalatal approach were not required. The advantages of this technique are that it is simple, it may be used in the first 24 hours of life or at any age, the patient may be released from the hospital in 1 to 2 weeks, and minimal postoperative care is required.

Preovulatory follicle number predicts corpora lutea number in early pregnancy.

A moderately strong correlation was coefficient was obtained between the relationship of mature follicle number versus CL number by use of vaginal US. This suggests an accurate prediction of CL number, especially between 1 and 4 mature follicle number as determined by the LOWESS curve.

Detrimental effect of hydrosalpinx fluid on the development and blastulation of mouse embryos in vitro.

OBJECTIVE: To study the effects of human hydrosalpinx fluid on mouse embryo blastulation rate. DESIGN: Comparison of mouse embryo blastulation rate in media containing increasing concentrations of hydrosalpinx fluid. SETTING: Tertiary care center. PATIENT(S): Women undergoing laparoscopic evaluation or treatment for infertility noted to have hydrosalpinx or paratubal cyst. INTERVENTION(S): Exposure of mouse embryos to hydrosalpinx or paratubal cyst fluid collected during laparoscopy. MAIN OUTCOME MEASURE(S): Blastulation rate of mouse embryos. RESULT(S): Culture of mouse embryos at 0% (controls), 0.3%, 0.6%, and 0.9% hydrosalpinx fluid concentrations demonstrated significantly lower blastulation rate at each level compared with the controls. CONCLUSION(S): Hydrosalpinx fluid is highly embryotoxic.