Surgical treatment of differentiated microcarcinomas of the thyroid.
Thyroid microcarcinomas (TMC) are histologically malignant diseases, despite their limited dimensions and non-aggressive behaviour; frequent multifocality of the disease and local recurrence is really possible after conservative resection. Modern therapeutic approaches to thyroid microcarcinoma include both radical surgical treatment, influenced by the frequent locoregional diffusion of TMC, consisting of a total thyroidectomy with an eventual central and/or functional unilateral lymphadenectomy, depending on the clinical evidence of lymh node metastases and conservative treatment based on more limited resections which take into account the slow clinical progression of this type of tumour. The aim of our work is to examine the therapeutic guidelines for surgical treatment of TMC which, in our experience, are closely dependent on clinical presentation type. From 1991 to 2000, more than 400 patients with thyroid disease were referred to the Department of Surgical Science and Applied Medical Technologies "F. Durante". Threehundred-seventythree patients received surgical treatment: in 311 patients a benign disease was diagnosed, while in 62 neoplasia was present. In total we observed 30 TMC, consisting of 28 papillary and 2 follicular microcarcinomas. On the basis of clinical presentation we divided patients in three groups: A--patients with a clinically suspicious neoplastic lesion before surgical treatment; B--patients in whom histological diagnosis of cancer was "incidental" after an operation performed for benign disease; C--patients in whom a neck lymph node metastases were clinically found before diagnosis of an "occult" papillary carcinoma in the thyroid gland. 27 total thyroidectomies and 3 conservative resections, that required successive total exeresis, were performed. In 5 cases a central neck lymph node dissection was carried out and in 5 + 1 cases functional modified lateral neck dissections was deemed necessary. Our data suggest that an evaluation of tumor's malignancy cannot be carried out on the basis of its dimensions alone. Indeed, biological aggressivity, whether local or at a distance, is a prerogative of both large and small tumours. Therefore a microcarcinoma must be considered a full-blown form of thyroid cancer and as such must be treated. Total thyroidectomy may be followed by identification of possible local metastases. "Whole body" scintigraphy allows to identify and treat with radioiodine therapy, possible recurrent lesions. Therefore in conclusion, total resection is not only a useful, but also a necessary treatment for the correct diagnostic and therapeutic follow-up of these patients.


The suicide inactivation of ox liver short-chain acyl-CoA dehydrogenase by propionyl-CoA. Formation of an FAD adduct.
Propionyl-CoA gave an unexpectedly low turnover (0.03 s-1) and high Km (153 microM) as a substrate for ox liver short-chain acyl-CoA dehydrogenase (SCAD). On addition of an excess of propionyl-CoA to SCAD the flavin A448 decreased to about 30% of its original value and the peak at 368 nm was replaced by one at 335 nm. The decrease in A448 exhibited first-order kinetics and correlated with a first-order decrease in the enzyme's catalytic activity to 22% of the initial value. The flavin, released from propionyl-CoA-treated enzyme with trichloroacetic acid, reacted with O2 to form a stable free radical. This suggests that a reduced N-5 flavin adduct is formed on the enzyme and protected from O2. The released adduct was separated from unmodified flavin and excess propionyl-CoA by h.p.l.c., and was shown by 3H-labelling to contain CoA. The incompleteness of the decrease in the enzyme's A448 and specific activity on incubation with propionyl-CoA probably reflects an equilibrium between covalently and non-covalently bound acyl-CoA, since the spectral changes could be reversed. The enzyme was also re-activated by dilution and incubation with a large molar excess of butyryl-CoA. The rate constant, approx. 2 X 10(-3) s-1, for re-activation, taken with the extrapolated rate constant for the opposing inactivation reaction, 8.9 X 10(-3) s-1, explains the 22% residual activity at equilibrium. The results suggest that propionyl-CoA is a suicide inhibitor for SCAD.


[Structure of the inguinal gland in the mountain hare in various states of reproductive activity. I. The sebaceous glands].
Histology and ultrastructure of sebaceous glands of the integumental inguinal gland of the hare were studied during the periods of low and high reproductive activity (in winter and in spring breeding season). It was established that the glands were functioning continually (cells in acini of all the animals used contained numerous secretory granules). The expansion of agranular endoplasmic reticulum and Golgi complex in secretory cells of sexually active animals, especially of males, shows an increased intensity of gland secretory process during the breeding season.


Ammonia acquisition in enteric bacteria: physiological role of the ammonium/methylammonium transport B (AmtB) protein.
Homologues of the amtB gene of enteric bacteria exist in all three domains of life. Although their products are required for transport of the ammonium analogue methylammonium in washed cells, only in Saccharomyces cerevisiae have they been shown to be necessary for growth at low NH4+ concentrations. We now demonstrate that an amtB strain of Escherichia coli also grows slowly at low NH4+ concentrations in batch culture, but only at pH values below 7. In addition, we find that the growth defect of an S. cerevisiae triple-mutant strain lacking the function of three homologues of the ammonium/methylammonium transport B (AmtB) protein [called methylammonium/ammonium permeases (MEP)] that was observed at pH 6.1 is relieved at pH 7.1. These results provide direct evidence that AmtB participates in acquisition of NH4+/NH3 in bacteria as well as eucarya. Because NH3 is the species limiting at low pH for a given total concentration of NH4+ + NH3, results with both organisms indicate that AmtB/MEP proteins function in acquisition of the uncharged form. We confirmed that accumulation of [14C]methylammonium depends on its conversion to gamma-N-methylglutamine, an energy-requiring reaction catalyzed by glutamine synthetase, and found that at pH 7, constitutive expression of AmtB did not relieve the growth defects of a mutant strain of Salmonella typhimurium that appears to require a high internal concentration of NH4+/NH3. Hence, contrary to previous views, we propose that AmtB/MEP proteins increase the rate of equilibration of the uncharged species, NH3, across the cytoplasmic membrane rather than actively transporting-that is, concentrating-the charged species, NH4+.


Inheritance of a Chromosome 3 and 21 Translocation in the Fetuses, with One also Having Trisomy 21, in Three Pregnancies in One Family.
The majority of chromosome rearrangements are balanced reciprocal and Robertsonian translocations. It is now known that such abnormalities cause no phenotypic effect on the carrier but lead to increased risk of producing unbalanced gametes. Here, we report the inheritance of a translocation between chromosomes 3 and 21 in a family with one of two fetuses with Down Syndrome carrying the same translocation and the other also carrying the same translocation without the additional chromosome 21. Chromosomal analysis from fetal amniotic fluid and peripheral blood lymphocytes from the family were performed at the Çukurova University Hospital at Adana, Turkey. We assessed a family in which the translocation between chromosomes 3 and 21 segregates: one of the three progenies carried the 47,XX,+21,t(3;21)(q21;q22) karyotype and presented with Down Syndrome; another of the three progenies carried the 46,XX,t(3;21) (q21;q22) karyotype and the third had the 46,XY karyotype. Their mother is phenotypically normal. Apparently this rearrangement occurred due to an unbalanced chromosome segregation of the mother [t(3;21)(q21;q22)mat]. This family will enable us to explain the behavior of segregation patterns and the mechanism for each type of translocation from carrier to carrier and their effects on reproduction and numerical aberrations. These findings can be used in clinical genetics and may be used as an effective tool for reproductive guidance and genetic counseling.


Northern range expansion of European populations of the wasp spider Argiope bruennichi is associated with global warming-correlated genetic admixture and population-specific temperature adaptations.
Poleward range expansions are observed for an increasing number of species, which may be an effect of global warming during the past decades. However, it is still not clear in how far these expansions reflect simple geographical shifts of species ranges, or whether new genetic adaptations play a role as well. Here, we analyse the expansion of the wasp spider Argiope bruennichi into Northern Europe during the last century. We have used a range-wide sampling of contemporary populations and historical specimens from museums to trace the phylogeography and genetic changes associated with the range shift. Based on the analysis of mitochondrial, microsatellite and SNP markers, we observe a higher level of genetic diversity in the expanding populations, apparently due to admixture of formerly isolated lineages. Using reciprocal transplant experiments for testing overwintering tolerance, as well as temperature preference and tolerance tests in the laboratory, we find that the invading spiders have possibly shifted their temperature niche. This may be a key adaptation for survival in Northern latitudes. The museum samples allow a reconstruction of the invasion's genetic history. A first, small-scale range shift started around 1930, in parallel with the onset of global warming. A more massive invasion of Northern Europe associated with genetic admixture and morphological changes occurred in later decades. We suggest that the latter range expansion into far Northern latitudes may be a consequence of the admixture that provided the genetic material for adaptations to new environmental regimes. Hence, global warming could have facilitated the initial admixture of populations and this resulted in genetic lineages with new habitat preferences.


Land use and transportation issues in environmental control.
Analyses have been made of the effects of environmental controls and planning at regional, subarea, and project levels. The results obtained at the regional level are reviewed for a proposed highway development around Baltimore, Md. The findings for both short-term and long-term effects of alternative transport policies are summarized in respect of population and employment, economic indicators, traffic and travel, air quality, water and solid waste, noise, and environmentally sensitive areas. Problems at subarea and project levels are briefly considered.


Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry as an alternative proteomics platform to ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry for samples of intermediate complexity.
We demonstrate the use of capillary zone electrophoresis with an electrokinetically pumped sheath-flow electrospray interface for the analysis of a tryptic digest of a sample of intermediate protein complexity, the secreted protein fraction of Mycobacterium marinum. For electrophoretic analysis, 11 fractions were generated from the sample using reverse-phase liquid chromatography; each fraction was analyzed by CZE-ESI-MS/MS, and 334 peptides corresponding to 140 proteins were identified in 165 min of mass spectrometer time at 95% confidence (FDR < 0.15%). In comparison, 388 peptides corresponding to 134 proteins were identified in 180 min of mass spectrometer time by triplicate UPLC-ESI-MS/MS analyses, each using 250 ng of the unfractionated peptide mixture, at 95% confidence (FDR < 0.15%). Overall, 62% of peptides identified in CZE-ESI-MS/MS and 67% in UPLC-ESI-MS/MS were unique. CZE-ESI-MS/MS favored basic and hydrophilic peptides with low molecular masses. Combining the two data sets increased the number of unique peptides by 53%. Our approach identified more than twice as many proteins as the previous record for capillary electrophoresis proteome analysis. CE-ESI-MS/MS is a useful tool for the analysis of proteome samples of intermediate complexity.


Methicillin-resistant Staphylococcus aureus bacteremia in children.
We reviewed the records of 20 patients with bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) and 49 patients with methicillin-susceptible S. aureus (MSSA) bacteremia occurring during a 39-month period. Sixteen of the MRSA bacteremias were clinically significant, as were 42 of the MSSA bacteremias. MRSA bacteremia was almost always nosocomial and occurred mainly in very young patients who were often prematurely born and severely compromised by underlying diseases. In contrast patients with MSSA bacteremia were frequently older children who had no underlying disease and acquired their bacteremic illness in the community. The seven patients with nosocomial MSSA bacteremia had characteristics similar to those of the patients with MRSA bacteremia. Fatality rates for patients with clinically significant bacteremia were 50% for MRSA and 2% for MSSA. Treatment of MRSA bacteremia with vancomycin was effective, provided it was begun early. At hospitals with endemic MRSA it may be necessary to use vacomycin in the initial treatment of nosocomial bacteremia in high risk patients until the identity and antimicrobial susceptibility of the bloodstream pathogen can be determined.


Dietary flavonoid intake and incident coronary heart disease: the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Flavonoids are dietary polyphenolic compounds with a variety of proposed beneficial cardiovascular effects, but rigorous prospective studies that examine the association between flavonoid intake and incident coronary heart disease (CHD) in geographically and racially diverse US samples are limited. With the use of the new, expanded USDA flavonoid database, we assessed the association between total flavonoid and flavonoid subclass intakes with incident CHD in a biracial and geographically diverse cohort, as well as effect modification by age, sex, race, and region of residence. Participants were 16,678 black and white men and women enrolled in the REGARDS (REasons for Geographic and Racial Differences in Stroke) study, a national prospective cohort study. All participants were without CHD at baseline, and all completed a Block98 food-frequency questionnaire. Flavonoid intakes were estimated from USDA flavonoid databases, which were recently improved to address missing values for cooked foods and to adjust for flavonoid losses due to processing. Incident CHD events were participant reported and adjudicated by experts. Quintiles of flavonoid intake were examined as predictors of incident CHD by using Cox proportional hazards regression to obtain HRs. Tests for trend used the quintile medians. Over a mean ± SD follow-up of 6.0 ± 1.9 y, 589 CHD events occurred. High flavonoid intake was associated with self-identified white race, exercise, not smoking, more education, and higher income. In models that adjusted for sociodemographic, health behavior, and dietary factors, there was an inverse association between anthocyanidin and proanthocyanidin intakes and incident CHD (HRs for quintile 5 compared with quintile 1-anthocyanidins: 0.71; 95% CI: 0.52, 0.98; P-trend = 0.04; proanthocyanidins: 0.63; 95% CI: 0.47, 0.84; P-trend = 0.02). There was no association between total flavonoid or other flavonoid subclass intakes and incident CHD. Reported anthocyanidin and proanthocyanidin intakes were inversely associated with incident CHD. There was no significant effect modification by age, sex, race, or region of residence.


Relationship between terminal ileal pressure waves and propagating proximal colonic pressure waves.
The relationship between propagating distal ileal and proximal colonic motor patterns has not been systematically examined in humans. Our aim was to define the relationships, if any, between prolonged propagating contractions or discrete clustered contractions and cecal propagating sequences using multiple manometric recording sites spanning the distal ileum and unprepared colon. In 14 healthy volunteers, a 17-lumen-perfused silicon catheter was positioned pernasally such that at least three recording sites lay in the ileum and the remainder in the colon. Intersidehole distance was 7.5 cm. In 271 h of recording, 30% of the terminal ileal propagating events was temporally associated with cecal propagating sequences. Significantly more prolonged propagating contractions (11 of 24, 46%; P = 0.02) were associated with cecal propagating sequences than were associated with ileal discrete clustered contractions (4 of 26, 15%). This trend was more pronounced at night. Of 159 cecal propagating sequences, 15 (9%) were preceded by an ileal propagating event. The remaining 91% was preceded by increased nonpropagating activity commencing 2 min before the cecal propagating sequence (P = 0.0002). We conclude that distal ileal propagating motor patterns are one stimulus for cecal propagating sequences, with the association being stronger for prolonged propagating contractions than for discrete clustered contractions.


Respiratory syncytial virus infection: mechanisms of redox control and novel therapeutic opportunities.
Respiratory syncytial virus (RSV) is one of the most important causes of upper and lower respiratory tract infections in infants and young children, for which no effective treatment is currently available. Although the mechanisms of RSV-induced airway disease remain incompletely defined, the lung inflammatory response is thought to play a central pathogenetic role. In the past few years, we and others have provided increasing evidence of a role of reactive oxygen species (ROS) as important regulators of RSV-induced cellular signaling leading to the expression of key proinflammatory mediators, such as cytokines and chemokines. In addition, RSV-induced oxidative stress, which results from an imbalance between ROS production and airway antioxidant defenses, due to a widespread inhibition of antioxidant enzyme expression, is likely to play a fundamental role in the pathogenesis of RSV-associated lung inflammatory disease, as demonstrated by a significant increase in markers of oxidative injury, which correlate with the severity of clinical illness, in children with RSV infection. Modulation of ROS production and oxidative stress therefore represents a potential novel pharmacological approach to ameliorate RSV-induced lung inflammation and its long-term consequences.


A messy reality: an analysis of New Zealand's elective surgery scoring system via media sources, 2000-2006.
Waiting lists for elective procedures are a characteristic feature of tax-funded universal health systems. New Zealand has gained a reputation for its 'booking system' for waiting list management, introduced in the early-1990s. The New Zealand system uses criteria to 'score' and then 'book' qualifying patients for surgery. This article aims to (i) describe key issues focused on by the media, (ii) identify local strategies and (iii) present evidence of variation. Newspaper sources were searched (2000-2006). A total of 1199 booking system stories were identified. Findings demonstrate, from a national system perspective, the extraordinarily difficult nature of maintaining overall control and coordination. Equity and national consistency are affected when hospitals respond to local pressure by reducing access to elective treatment. Findings suggest that central government probably needs to be closely involved in local-level management and policy adjustments; that through the study period, the New Zealand system appears to have been largely out of the control of government; and that governments elsewhere may need to be cautious when considering developing similar systems. Developing and implementing scoring and booking systems may always be a 'messy reality' with unintended consequences and throwing regional differences in service management and access into stark relief.


Myocardial infarction after carotid stenting and endarterectomy: results from the carotid revascularization endarterectomy versus stenting trial.
The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) found a higher risk of stroke after carotid artery stenting and a higher risk of myocardial infarction (MI) after carotid endarterectomy. Cardiac biomarkers and ECGs were performed before and 6 to 8 hours after either procedure and if there was clinical evidence of ischemia. In CREST, MI was defined as biomarker elevation plus either chest pain or ECG evidence of ischemia. An additional category of biomarker elevation with neither chest pain nor ECG abnormality was prespecified (biomarker+ only). Crude mortality and risk-adjusted mortality for MI and biomarker+ only were assessed during follow-up. Among 2502 patients, 14 MIs occurred in carotid artery stenting and 28 MIs in carotid endarterectomy (hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.032) with a median biomarker ratio of 40 times the upper limit of normal. An additional 8 carotid artery stenting and 12 carotid endarterectomy patients had biomarker+ only (hazard ratio, 0.66; 95% confidence interval, 0.27 to 1.61; P=0.36), and their median biomarker ratio was 14 times the upper limit of normal. Compared with patients without biomarker elevation, mortality was higher over 4 years for those with MI (hazard ratio, 3.40; 95% confidence interval, 1.67 to 6.92) or biomarker+ only (hazard ratio, 3.57; 95% confidence interval, 1.46 to 8.68). After adjustment for baseline risk factors, both MI and biomarker+ only remained independently associated with increased mortality. In patients randomized to carotid endarterectomy versus carotid artery stenting, both MI and biomarker+ only were more common with carotid endarterectomy. Although the levels of biomarker elevation were modest, both events were independently associated with increased future mortality and remain an important consideration in choosing the mode of carotid revascularization or medical therapy. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00004732.


Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: a longitudinal, multilevel, mediated moderation analysis.
This study was designed to examine the prospective relations of life stress and genetic status with increases in drug use. African Americans (N = 399) in rural Georgia (Wave 1 mean age = 17 years) provided three waves of data across 27.5 months and a saliva sample from which the dopamine receptor D4 (DRD4) gene was genotyped. Multilevel growth curve modeling analysis indicated that emerging adults manifested the highest escalations in drug use when they reported high life stress and carried an allele of DRD4 with 7 or more repeats (7 + R allele). In addition, emerging adults who reported high life stress and carried the 7 + R allele evinced the largest increases in two proximal risk factors for drug use: affiliations with drug-using companions and drug use vulnerability cognitions. Furthermore, when the Gene × Environment interaction effects on the increases in affiliations with drug-using companions and vulnerability cognitions were entered into the model forecasting drug use, the Life Stress × DRD4 Status interaction on drug use became nonsignificant in the presence of the risk mechanisms. This finding provides an example of "second generation" Gene × Environment interaction research in which the interaction's effects on proximal risk mechanisms account for its effects on outcomes.


Phospholipid Bicelles Improve the Conformational Stability of Rhodopsin Mutants Associated with Retinitis Pigmentosa.
Mutations in the visual photoreceptor rhodopsin are the cause of the retinal degenerative disease retinitis pigmentosa. Some naturally occurring mutations can lead to protein conformational instability. Two such mutations, N55K and G90V, in the first and second transmembrane helices of the receptor, have been associated with sector and classical retinitis pigmentosa, respectively, and showed enhanced thermal sensitivity. We have carefully analyzed the effect of phospholipid bicelles on the stability and ligand binding properties of these two mutants and compared it with those of the detergent-solubilized samples. We have used a phospholipid bilayer consisting of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). We find that DMPC/DHPC bicelles dramatically increase the thermal stability of the rhodopsin mutants G90V and N55K. The chromophore stability and regeneration of the mutants were also increased in bicelles when compared to their behavior in a dodecyl maltoside detergent solution. The retinal release process was slowed in bicelles, and chromophore entry, after illumination, was improved for the G90V mutant but not for N55K. Furthermore, fluorescence spectroscopy measurements showed that bicelles allowed more exogenous retinal binding to the photoactivated G90V mutant than in a detergent solution. In contrast, N55K could not reposition any chromophore either in the detergent or in bicelles. The results demonstrate that DMPC/DHPC bicelles can counteract the destabilizing effect of the disease-causing mutations and can modulate the structural changes in the ensuing receptor photoactivation in a distinct specific manner for different retinitis pigmentosa mutant phenotypes.


Assessing the Relationship Between Drive for Thinness and Taste-Shape Correspondences.
Eating disorder tendencies are psychological characteristics that are prevalent in healthy young females and are known to be among the risk factors for eating disorders such as anorexia and bulimia nervosa. People with greater eating disorder tendencies strongly associate sweet and fatty foods with weight gain and strictly avoid consuming such foods. However, little is known about how eating disorder tendencies influence the association between taste and body shape impression. Research on crossmodal correspondences suggests that people preferentially associate sweet tastes with round shapes, and individual differences affect the degree of such associations. This study investigates how the degree of taste-shape matching is related to eating disorder tendencies with a preliminary investigation of what mediates this relationship. Two experiments were conducted: in Experiment 1, healthy participants rated the degree of association between basic taste words (sweet/sour/salty/bitter) and roundness of shape and subsequently completed questionnaires addressing eating disorder tendencies. In Experiment 2, participants answered additional questionnaires addressing obsessiveness, dichotomous thinking, and self-esteem. The results of Experiment 1 indicated a positive correlation between drive for thinness, which is one indicator of an eating disorder tendency, and the degree of matching sweetness to round shape. Experiment 2 replicated the results of Experiment 1 and revealed the mediating effect of obsessiveness. These findings suggest a relationship between individual differences in taste-shape matching and eating disorder tendency and the preliminary mediating role of obsessiveness. The present study provides new insight into the role of sweet-round matching in eating disorder tendencies and the associated psychological mechanisms.


The Reliability and Validity of the Korean Version of the Autism-Spectrum Quotient.
This study was conducted to investigate the reliability and validity of the Korean version of Autism-Spectrum Quotient (AQ). 20 participants with high-functioning autism (HFA) and 99 normal participants were recruited. All participants were completed the AQ and Empathy Quotient (EQ), and parents of the HFA group completed the parent-report AQ. For testing the reliability, we examined Cronbach's alpha, performed item analysis, and compared self versus parent report score of HFA participants. For testing the validity, we compared the difference of the score of AQ among HFA and control group using independent t-tests, and performed correlation analysis between AQ and EQ. The receiver operation characteristic curve analysis was performed to determine a cut-off. The Korean version of the AQ exhibited adequate internal consistency, and in most items, the HFA group scored higher in comparison to the control group. It was demonstrated that AQ has good discriminant validity through the confirmation of the significant difference in the AQ score between two groups. The concurrent validity was established through the significant correlation between AQ and EQ in the HFA group. The best estimate cut-off score of AQ for screening was 23. The Korean version of the AQ was determined as a reliable and valid instrument to assess HFA in Korean population.


Enhanced cardiac differentiation of mouse embryonic stem cells by use of the slow-turning, lateral vessel (STLV) bioreactor.
Embryoid body (EB) formation is a common intermediate during in vitro differentiation of pluripotent stem cells into specialized cell types. We have optimized the slow-turning, lateral vessel (STLV) for large scale and homogenous EB production from mouse embryonic stem cells. The effects of inoculating different cell numbers, time of EB adherence to gelatin-coated dishes, and rotation speed for optimal EB formation and cardiac differentiation were investigated. Using 3 × 10(5) cells/ml, 10 rpm rotary speed and plating of EBs onto gelatin-coated surfaces three days after culture, were the best parameters for optimal size and EB quality on consequent cardiac differentiation. These optimized parameters enrich cardiac differentiation in ES cells when using the STLV method.


Selective thoracic fusion of King II scoliosis with segmental spinal instrumentation.
Segmental spinal instrumentation with Harrington rod secured to the spine by sublaminar wires was a popular method of scoliosis correction in 1980's. It was gradually replaced by newer rod-hook systems due to concern about neurological complications. However, correction of type II and III curves by selectively fusing the thoracic curves with these new instruments has resulted in poor results in some cases. The aim of this study is to review the result of selective thoracic fusion treated by segmental spinal instrumentation. Between January 1989 to October 1994, 31 patients with King II scoliosis were treated operatively in our unit. These consisted of 29 girls and 2 boys. The mean age of these patients were 11.3 years. The study population consisted of 21 Chinese, 5 Malays and 5 Indians. In one patient, the thoracic curve was convex to the left whilst the thoracic curves in the majority were to the right. The surgery was performed by three surgeons using harrington rods and posterior fusion with autograft. Anterior releases were also required in eight patients to increase flexibility. The curve correction obtained was an improvement from a average preoperative cobb's angle of 71.5 degrees to 39.5 degrees postoperatively. After an average follow-up period of 77.9 months, the correction deteriorated by 22% in the thoracic curve and 59% in the lumbar spine without disturbance to truncal balance. Only one sublaminar wire broke. However, no implant failure or removal has to be performed as yet. This technique appears useful in our institution with minimal morbidity.


Dry eye disease in the young: A narrative review.
Dry eye disease (DED), a multifactorial ocular disease that significantly impacts quality of life, is most commonly reported in adults. This review describes the prevalence, risk factors, diagnosis and management of DED in children. A literature search, conducted from January 2000-December 2022, identified 54 relevant publications. Using similar diagnostic criteria to those reported in adults, namely standardized questionnaires and evaluation of tear film homeostatic signs, the prevalence of DED in children ranged from 5.5% to 23.1 %. There was limited evidence for the influence of ethnicity in children, however some studies reported an effect of sex in older children. Factors independently associated with DED included digital device use, duration of digital device use, outdoor time and urban living, Rates of DED were higher in children with ocular allergy and underlying systemic diseases. Compared with similar studies in adults, the prevalence of a prior DED diagnosis or a diagnosis based on signs and symptoms was lower in children, but symptoms were commonly reported. Treatment options were similar to those in adults, including lifestyle modifications, blinking, management of lid disease and unpreserved lubricants in mild disease with escalating treatment with severity. Management requires careful exploration of symptoms, medical history and the diagnosis and management of ocular comorbidities such as allergy and anterior blepharitis. Appropriately powered population-based studies are required to understand the prevalence of and risk factors for DED in children. Development of age-appropriate thresholds for signs and symptoms of DED would support better diagnosis of disease and understanding of natural history.


Linac mechanic QA using a cylindrical phantom.
Precise mechanical operation of a linear accelerator (linac) is critical for accurate radiation therapy dose delivery. Quantitative procedures for linac mechanical quality assurance (QA) used in the standard of care are time consuming and therefore conducted on a relatively infrequent basis. We present a method for evaluating the mechanical performance of a linac based on a series of projection portal images of a prototype cylindrical phantom with embedded radiopaque fiducial markers. The marker autodetection process included modeling imager response to the radiation beam where the projected cylinder attenuation yielded a non-uniform image background. The linac mechanical characteristics were estimated based on nonlinear multi-objective optimization of the projected marker locations. The estimated geometry parameters for the tested commercial model were gantry angle deviation 0.075 +/- 0.076 degrees (1 SD), gantry sag 0.026 +/- 0.02 degrees , source-to-axis distance SAD 998.3 +/- 1.7 mm, source-to-detector distance SDD 1493 +/- 5.0 mm, couch vertical motion 0.6 +/- 0.45 mm, couch rotation 0.154 +/- 0.1 degrees and average linac rotation center (1.02, -0.27, -0.37) +/- (0.36,0.333,1.20) mm relative to the laser intersection. The imager shift was [-0.44, 2.6] +/- [0.20, 1.1] mm and the imager orientation was in-plane rotation 0.05 +/- 0.03 degrees , roll -0.14 +/- 0.09 degrees and pitch -0.9 +/- 0.604 degrees . The performance of this procedure concerning marker detection and optimization was examined by comparing the detected set of marker coordinates to its back-calculated counterpart for three subgroups of markers: central, wall and intermediate relative to the center of the phantom. The maximum difference was less than 0.25 mm with a mean of 0.146 mm and a standard deviation of 0.07 mm. The clinical use of this automated procedure will allow more efficient, more thorough, and more frequent mechanical linac QA.


A realistic model for the analysis of heart magnetic stimulation.
The aim of the paper is the development of an accurate numerical model to compute the current density flowing through the heart of a virtual human body, and induced by an external electric or magnetic excitation. The model has been experimentally validated and then applied to investigate the main characteristics of the heart magnetic stimulation. This has been carried out by comparing the current density induced in the cardiac region by an external magnetic pulse with the corresponding quantity due to the more traditional electric source. Magnetic stimulation is studied because it offers some advantages: in fact, compared with the electrical stimulation, this technique is contactless and might allow the stimulation of a dressed patient. The design constraint of the whole system is represented by the current density, whose waveform and intensity are a compromise between the strength of the magnetic induction field and the pulse rise time.


Cache-Based Privacy Preserving Solution for Location and Content Protection in Location-Based Services.
Location-Based Services (LBSs) are playing an increasingly important role in people's daily activities nowadays. While enjoying the convenience provided by LBSs, users may lose privacy since they report their personal information to the untrusted LBS server. Although many approaches have been proposed to preserve users' privacy, most of them just focus on the user's location privacy, but do not consider the query privacy. Moreover, many existing approaches rely heavily on a trusted third-party (TTP) server, which may suffer from a single point of failure. To solve the problems above, in this paper we propose a Cache-Based Privacy-Preserving (CBPP) solution for users in LBSs. Different from the previous approaches, the proposed CBPP solution protects location privacy and query privacy simultaneously, while avoiding the problem of TTP server by having users collaborating with each other in a mobile peer-to-peer (P2P) environment. In the CBPP solution, each user keeps a buffer in his mobile device (e.g., smartphone) to record service data and acts as a micro TTP server. When a user needs LBSs, he sends a query to his neighbors first to seek for an answer. The user only contacts the LBS server when he cannot obtain the required service data from his neighbors. In this way, the user reduces the number of queries sent to the LBS server. We argue that the fewer queries are submitted to the LBS server, the less the user's privacy is exposed. To users who have to send live queries to the LBS server, we employ the l-diversity, a powerful privacy protection definition that can guarantee the user's privacy against attackers using background knowledge, to further protect their privacy. Evaluation results show that the proposed CBPP solution can effectively protect users' location and query privacy with a lower communication cost and better quality of service.


Establishing funding rates for colonoscopy and gastroscopy procedures in Ontario.
This paper describes the funding rates established in Ontario to reflect best practices in hospital-based care delivery for these endoscopic procedures: colonoscopy, colonoscopy biopsy, gastroscopy, gastroscopy biopsy, and colonoscopy combined with gastroscopy. The funding rates are based on direct costs and were established using a micro-costing approach after receipt of inputs from 3 working groups and a review of the administrative data and literature, where applicable. The first group advised on nursing activities, time, and staffing ratios along the patient pathway for each of the procedures. The second group provided recommendations about the duration for each procedure, and the third group provided information about supplies and equipment, their use, and costs. The resulting funding rates are $161.18 for colonoscopy and $151.08 for gastroscopy (without accompanying interventions), $16.06 for colonoscopy biopsy and $8.22 for gastroscopy biopsy (added to the respective procedures), and $207.26 for combined colonoscopy and gastroscopy. Detailed costs for each component embedded in the rates are also provided. The rates came into effect in April 2018. The process and outcomes described here allowed for a transparent pricing mechanism in which funding follows the patient, clinical expert consensus is the basis for practice, and providers and payers both understand the components.


Challenges and Best Practices in Ethical Review of Human and Organizational Factors Studies in Health Technology: a Synthesis of Testimonies.
Human and Organizational Factors (HOF) studies in health technology involve human beings and thus require Institutional Review Board (IRB) approval. Yet HOF studies have specific constraints and methods that may not fit standard regulations and IRB practices. Gaining IRB approval may pose difficulties for HOF researchers. This paper aims to provide a first overview of HOF study challenges to get IRB review by exploring differences and best practices across different countries. HOF researchers were contacted by email to provide a testimony about their experience with IRB review and approval. Testimonies were thematically analyzed and synthesized to identify and discuss shared themes. Researchers from seven European countries, Argentina, Canada, Australia, and the United States answered the call. Four themes emerged that indicate shared challenges in legislation, IRB inefficiencies and inconsistencies, general regulation and costs, and lack of HOF study knowledge by IRB members. We propose a model for IRB review of HOF studies based on best practices. International criteria are needed that define low and high-risk HOF studies, to allow identification of studies that can undergo an expedited (or exempted) process from those that need full IRB review. Enhancing IRB processes in such a way would be beneficial to the conduct of HOF studies. Greater knowledge and promotion of HOF methods and evidence-based HOF study designs may support the evolving discipline. Based on these insights, training and guidance to IRB members may be developed to support them in ensuring that appropriate ethical issues for HOF studies are considered.


Malaria control at the district level in Africa: the case of the muheza district in northeastern Tanzania.
An assessment was done in Tanzania to determine the extent to which the primary health care services have contributed to reducing the burden of malaria since the system was initiated in the 1980s. Seven descriptive processes and outcome indicators of effectiveness were used: changes of malaria transmission and incidence over time; use of facility-based care services for malaria; patients' access to professional advice; the trend of treatment failure over time of sulfadoxine-pyrimethamine and chloroquine; survival rates of severe cases at the district hospital; a district malaria control strategy; number of malaria specific training for care providers; and the number of activities carried out on mosquito control measures. The data were collected from 1996 to 2003 in the Muheza district northeastern Tanzania. It covered household interviews with a stratified sample of 1,250 respondents, and in-depth interviews with all 175 health care providers in the 35 health facilities within the district. All six members of the district health management team were also interviewed. Additional data came from dispensary and hospital records, and published literature. The results show an unchanged malaria disease burden. The average number of clinical malaria episodes per child less than five years of age remained between 3 and 3.5 episodes per year in the district since the 1960s. The comparison of cases expected in the population less than five years old with those seen in the district health facilities shows a coverage rate of 33%. Furthermore, between 1990 and 2003, little training on malaria was provided to health staff. The findings imply a limited effectiveness of district health services on malaria control, suggesting a weak process of translating national malaria goals to activities at the district level.


Identification of potential biomarkers associated with immune infiltration in the esophageal carcinoma tumor microenvironment.
Tumor immune cell infiltration was significantly correlated with the progression and the effect of immunotherapy in cancers including esophageal carcinoma (ESCA). However, no biomarkers were identified which were associated with immune infiltration in ESCA. In the present study, a total of 128 common differentially expressed genes (DEGs) were identified between esophageal squamous cell carcinomas (ESCC) and esophageal adenocarcinomas (EAC). The results of gene ontology (GO) enrichment and Reactome pathway analysis displayed that the up-regulated DEGs were mainly involved in the regulation of extracellular matrix (ECM), while the down-regulated DEGs were mainly involved in the regulation of cornification and keratinocyte differentiation. The most significant module of up-regulated DEGs was selected by Molecular Complex Detection (MCODE). Top ten similar genes of COL1A2 were explored, then validation and the prognostic analysis of these genes displayed that COL1A2, COL1A1, COL3A1, ZNF469 and Periostin (POSTN) had the prognostic value which were up-regulated in ESCA. The expressions of COL1A2 and its four similar genes were mainly correlated with infiltrating levels of macrophages and dendritic cells (DCs) and showed strong correlations with diverse immune marker sets in ESCA. To summarize, COL1A2 and its four similar genes were identified as the potential biomarkers associated with immune infiltration in ESCA. These genes might be applied to immunotherapy for ESCA.


NaV1.1 and NaV1.6 selective compounds reduce the behavior phenotype and epileptiform activity in a novel zebrafish model for Dravet Syndrome.
Dravet syndrome is caused by dominant loss-of-function mutations in SCN1A which cause reduced activity of Nav1.1 leading to lack of neuronal inhibition. On the other hand, gain-of-function mutations in SCN8A can lead to a severe epileptic encephalopathy subtype by over activating NaV1.6 channels. These observations suggest that Nav1.1 and Nav1.6 represent two opposing sides of the neuronal balance between inhibition and activation. Here, we hypothesize that Dravet syndrome may be treated by either enhancing Nav1.1 or reducing Nav1.6 activity. To test this hypothesis we generated and characterized a novel DS zebrafish model and tested new compounds that selectively activate or inhibit the human NaV1.1 or NaV1.6 channel respectively. We used CRISPR/Cas9 to generate two separate Scn1Lab knockout lines as an alternative to previous zebrafish models generated by random mutagenesis or morpholino oligomers. Using an optimized locomotor assay, spontaneous burst movements were detected that were unique to Scn1Lab knockouts and disappear when introducing human SCN1A mRNA. Besides the behavioral phenotype, Scn1Lab knockouts show sudden, electrical discharges in the brain that indicate epileptic seizures in zebrafish. Scn1Lab knockouts showed increased sensitivity to the GABA antagonist pentylenetetrazole and a reduction in whole organism GABA levels. Drug screenings further validated a Dravet syndrome phenotype. We tested the NaV1.1 activator AA43279 and two novel NaV1.6 inhibitors MV1369 and MV1312 in the Scn1Lab knockouts. Both type of compounds significantly reduced the number of spontaneous burst movements and seizure activity. Our results show that selective inhibition of NaV1.6 could be just as efficient as selective activation of NaV1.1 and these approaches could prove to be novel potential treatment strategies for Dravet syndrome and other (genetic) epilepsies. Compounds tested in zebrafish however, should always be further validated in other model systems for efficacy in mammals and to screen for potential side effects.


[Hypotony maculopathy diagnosed by optical coherence tomography].
A 40 year-old man with advanced pigmentary glaucoma in the left eye underwent trabeculectomy. In the immediate postoperative period, visual acuity decreased with no alterations noted on examination of the fundus or on angiofluoresceingraphy. Through optical coherence tomography, we were able to make a diagnosis of hypotonic maculopathy and treatment was immediately started. Hypotony maculopathy is one of the most feared complications of filtering eye surgery. In some cases, optical coherence tomography can be useful to confirm its diagnosis non invasively.


[Blastomogenic activity of sulfotrinaphthylene furan].
The biological (including carcinogenic) effect of an anthraquinone dye sulfoderivative--sulfotrinaphthylenfuran--was studied. The agent displayed low toxicity and cumulation in different species of experimental animals and germ cultures. However, a long-term intoxication by the agent led to tumor formation in the lungs of albino mice, following the pattern of focal reticulosis. The blastogenic effect of sulfotrinaphthylenfuran is suggested.


Overall Survival After Whole-Brain Radiation Therapy for Intracerebral Metastases from Testicular Cancer.
To identify predictors and develop a score for overall survival of patients with intracerebral metastasis from testicular cancer. Whole-brain radiation therapy program, age, Karnofsky performance score (KPS), number of intracerebral metastases, number of other metastatic sites and time between testicular cancer diagnosis and radiation therapy were analyzed for their association with overall survival in eight patients. KPS of 80-90% was significantly associated with better overall survival (p=0.006), one or no other metastatic sites showed a trend for a better outcome (p=0.10). The following scores were assigned: KPS 60-70%=0 points, KPS 80-90%=1 point, ≥2 other metastatic sites=0 points, 0-1 other metastatic sites=1 point. Two groups, with 0 and with 1-2 points, were formed. Overall survival rates were 33% vs. 100% at 6 months and 0% vs. 100% at 12 months (p=0.006), respectively. A simple instrument enabling physicians to judge the overall survival of patients with intracerebral metastasis from testicular cancer is provided.


Quality assessment of clinical practice guidelines for the prevention and treatment of childhood overweight and obesity.
The prevalence of childhood overweight and obesity is increasing at dramatic rates in children and adolescents worldwide. Clinical practice guidelines (CPGs) are "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances." Their objective is to provide explicit recommendations for clinical practice based on current evidence for best practice in the management of diseases. The aim of this study was to identify and assess the quality of CPGs for the prevention and treatment of obesity and overweight in childhood. We developed a search to identify CPGs published between January 1998 and August 2007. We considered for inclusion documents that provided recommendations for clinical practice referring to children and adolescents. Three independent appraisers assessed the quality of the1 CPGs using the AGREE (Appraisal of Guidelines Research and Evaluation) instrument. We identified 376 references and selected 22 for further assessment. The overall agreement among reviewers using the intraclass correlation coefficient was 0.856 (95% confidence interval [CI] 0.731-0.932). Six of the 22 initial guidelines were recommended and a further eight were recommended with conditions or provisos. We concluded that the number of documents with recommendations on the prevention and treatment of childhood obesity published during the 10-year study period was considerable, but only a few of them could be considered as high quality. CPGs were deficient in areas such as applicability, editorial independence and rigor in development. Due to the increasing burden of obesity among children and the potential for long-term comorbidities, clinicians need to be critical in assessing the rigor of how these are developed and their appropriateness for use in the clinician's own practice. There is a need to improve the methodology and the quality of CPGs on childhood obesity to help clinicians and other decision-makers to tackle this disease.


Comparison of Outcomes after Reperfusion Therapy between In-Hospital and Out-of-Hospital Stroke Patients.
Patients may experience stroke while being admitted to the hospital (in-hospital stroke (IHS)) and they may be important candidates for reperfusion therapy. IHS patients may have various comorbidities and show worse outcomes compared with patients with an out-of-hospital stroke (OHS). On the other hand, the time from onset to treatment may be shorter in IHS patients than OHS patients. Most outcome studies of reperfusion therapy have been based on findings in OHS patients, and little information is currently available regarding outcomes of IHS, whether the outcomes differ between patients with IHS and those with OHS who receive reperfusion therapy. This is a retrospective observational study using prospectively registered data. Consecutive patients who underwent the reperfusion therapy (intravenous (IV), intra-arterial (IA), or combined IV and IA) between July 2002 and June 2014 in a university hospital were included for this study. We compared the demographics, time interval from symptom onset to treatment, and outcomes between IHS and OHS patients and analyzed the factors associated with in-hospital mortality. A total of 686 patients received the reperfusion therapy during the study period. Of them, 256 (37.3%) patients received the IV tissue plasminogen activator (t-PA) therapy only, 243 (35.4%) patients received the IA therapy only, and 187 (27.3%) patients received the combined IV and IA therapy. Among these, 104 (15.2%) were IHS patients. The time intervals from symptom onset to IV t-PA administration (87.5 ± 48.4 vs. 113.4 ± 38.3 min, p < 0.001) and IA puncture (221.8 ± 195.0 vs. 343.6 ± 155.4 min, p < 0.001) were shorter for IHS than OHS. The rates of successful recanalization and symptomatic intracerebral hemorrhage, and the favorable functional outcome at 3 months were similar between the groups. In-hospital all-cause mortality was higher in IHS than OHS (16.3 vs. 8.4%, p = 0.019), but after adjustment, IHS was not an independent factor. The stroke mortality did not differ between the groups (9.6 vs. 6.9%, p = 0.432). Although IHS patients more frequently had comorbid diseases and higher overall in-hospital mortality, the standard outcomes of the reperfusion therapy were similar between IHS and OHS patients, which might be, in part, ascribed to the shorter interval from symptom onset to treatment in IHS. Considering a substantial portion of IHS patients, we should pay more attention to these patients.


MicroRNAs in pediatric central nervous system embryonal neoplasms: the known unknown.
MicroRNAs (miRNAs) are endogenous short non-coding RNAs that repress post-transcriptional regulation of gene expression, while embryonal central nervous system tumors are the foremost cause of mortality in children suffering from a neoplasm. MiRNAs and their regulatory mechanisms are new to understand, while pediatric CNS tumors are difficult to comprehend. Therefore, identification of the link between them composes a major scientific challenge. The present study, reviewed the current knowledge on the role of miRNA in pediatric CNS embryonal tumors, attempting to collect the existing information in one piece of work that could ideally be used as a guide for future reference and research.


High prevalence of mixed genotype infections in hepatitis B virus infected intravenous drug users.
The clinical relevance of hepatitis B virus (HBV) genotypes has been documented; however, the prevalence of mixed HBV genotype infections in at-risk groups remains controversial. The HBV genotypes were determined in 325 HBV-infected intravenous drug users (IVDU) who were at a greater risk of multiple exposures to different HBV genotypes by using a newly developed line probe assay. The distribution of HBV genotype was as follows: genotype A alone in 2 (0.6%); genotype B alone in 256 (78.8%); genotype C alone in 10 (3.1%); mixed genotype A and B in 18 (5.5%); genotype B and C in 30 (9.2%); genotype B and D in 1 (0.3%); genotype A and C in 1 (0.3%); and mixed infections of genotype A, B, and C in 3 (0.9%). Clonal analysis confirmed further the existence of mixed genotype infection and recombination between different genotypes. Compared with our previous data, the line probe assay seemed more sensitive than polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in identifying HBV genotype (98.8% vs. 65.0%) and detecting mixed genotype infections (16.3% vs. 0%). In conclusion, the prevalence of mixed HBV infections is substantially higher in IVDU in endemic areas, and the line probe assay is a useful method for rapid genotyping of HBV, with particular reference to the detection of mixed genotype infections.


Acebutolol, atenolol, and propranolol and metabolic responses to acute hypoglycaemia in diabetics.
In a double-blind crossover study the symptomatic and metabolic effects of propranolol, acebutolol, and atenolol were studied during insulin-induced hypoglycaemia in diabetics treated with diet or hypoglycaemic tablets. All the drugs prevented tachycardia, but did not affect the other symptoms of hypoglycaemia. Propranolol delayed the recovery of the blood glucose concentration and impaired the secondary rise in the concentrations of blood lactate and non-esterified fatty acids in diet-treated diabetics. Acebutolol potentiated the hypoglycaemic effect of insulin in tablet-treated diabetics (mean difference of blood glucose concentration 0.7 mmol/l (12.6 mg/100 ml)) and this difference was maintained during the recovery phase4 the blood lactate response was also impaired. Atenolol did not differ perceptibly from placebo in its effect on the metabolic responses to acute hypoglycaemia. The results may be explained by differences in the known pharmacological actions of these drugs. They support the hypothesis that beta-adrenoreceptor blocking drugs that are highly beta1 specific and without membrane-stabilising activity should be safer than the non-selective drugs when used in diabetic patients at risk from hypoglycaemia.


Multiple mechanisms contribute to osmotic inducibility of proU operon expression in Escherichia coli: demonstration of two osmoresponsive promoters and of a negative regulatory element within the first structural gene.
Transcription of the proU operon in Escherichia coli is induced several hundredfold upon growth of cells in media of elevated osmolarity. A low-copy-number promoter-cloning plasmid vector, with lacZ as the reporter gene, was used for assaying the osmoresponsive promoter activity of each of various lengths of proU DNA, generated by cloning of discrete restriction fragments and by an exonuclease III-mediated deletion approach. The results indicate that expression of proU in E. coli is directed from two promoters, one (P2) characterized earlier by other workers with the start site of transcription 60 nucleotides upstream of the initiation codon of the first structural gene (proV), and the other (P1) situated 250 nucleotides upstream of proV. Furthermore, a region of DNA within proV was shown to be involved in negative regulation of proU transcription; phage Mu dII1681-generated lac fusions in the early region of proV also exhibited partial derepression of proU regulation, in comparison with fusions further downstream in the operon. Sequences around promoter P1, sequences around P2, and the promoter-downstream negative regulatory element, respectively, conferred approximately 5-, 8-, and 25-fold osmoresponsivity on proU expression. Within the region genetically defined to encode the negative regulatory element, there is a 116-nucleotide stretch that is absolutely conserved between the proU operons of E. coli and Salmonella typhimurium and has the capability of exhibiting alternative secondary structure. Insertion of this region of DNA into each of two different plasmid vectors was associated with a marked reduction in the mean topological linking number in plasmid molecules isolated from cultures grown in high-osmolarity medium. We propose that this region of DNA undergoes reversible transition to an underwound DNA conformation under high-osmolarity growth conditions and that this transition mediates its regulatory effect on proU expression.


Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells.
Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2',5'-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targeting p204, cGas or Sting Notably, the VACV70-triggered innate immune responses affected steroidogenesis in vivo and in vitro The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.


Sequences of the Epstein-Barr Virus (EBV) large internal repeat form the center of a 16-kilobase-pair palindrome of EBV (P3HR-1) heterogeneous DNA.
We have previously characterized several genomic rearrangements of Epstein-Barr virus (EBV) DNA contained in one of the defective EBV genomes harbored by the P3HR-1 (HR-1) line (H. B. Jenson, M. S. Rabson, and G. Miller, J. Virol. 58:475-486, 1986). One recombinant clone of heterogeneous DNA (het DNA) from this defective genome is an EcoRI fragment of 16 kilobase pairs (kbp) which is a palindrome. DNA digestion fragments specific for the center of this palindrome were present in cells which contained het DNA but not in cells which lacked het DNA. Thus, the palindrome was not an artifact of DNA cloning. The organization of the center of this palindrome was studied by DNA sequencing. The comparable region of the parental HR-1 genome was also studied by DNA sequencing. The central 3,495 base pairs (bp) of the palindrome were composed of sequences derived exclusively from internal repeat 1 of EBV, represented by BamHI W fragment. At each end of the central 3,495 hp was a symmetrical recombination with sequences of BamHI-Z, located more than 50 kbp away on the standard EBV genome. The central 3,495 bp were composed of an unduplicated 341 bp flanked by two perfect palindromic repeats of 1,577 bp. The 341-bp unique region was a portion of a 387-bp region of standard HR-1 BamHI-W which was identical to the central 387 bp of the palindrome. This central 387-bp region contained numerous stretches of dyad symmetry capable of forming a large stem-and-loop structure. The palindromic rearrangement had created two novel open reading frames in het DNA derived from standard HR-1 BamHI-W sequences. These two het DNA open reading frames had different amino termini but identical carboxy termini derived from the large open reading frame in standard HR-1 BamHI-W (HR-1 BWRF1). The BamHI-W sequences found in het DNA did not include either the TATA box of standard HR-1 BamHI-W or the exons which are present in the potentially polycistronic latent mRNAs encoding EBV nuclear antigens. These marked alterations in genomic structure may relate to the unique biologic properties of virus stocks containing het DNA by creation of new polypeptides or by formation or deletion of regulatory or functional signals.


Depression, anxiety, and stress and adverse pregnancy outcomes in pregnant women with history of recurrent pregnancy loss in Nigeria.
The primary purpose of this study was to examine whether pregnant women with a history of recurrent pregnancy loss (RPL) are more likely to experience moderate-to-severe depression, anxiety, or stress symptoms than pregnant women without a history of RPL. The secondary purpose was to determine whether women with prior RPL experienced more unfavorable pregnancy outcomes if they had depression, anxiety, or stress. A prospective case-control study was conducted that included 47 pregnant women with a history of RPL and 94 pregnant women without prior RPL. Participants 20 weeks of gestation or earlier were included. Both groups completed the Depression, Anxiety, and Stress Scale (DASS-21), and were followed up until delivery to determine the pregnancy outcomes. Multivariate logistic regression was used to compare adverse pregnancy outcomes. Among the 47 women with prior RPL, 10 had primary RPL (two or more miscarriages without a successful pregnancy) and 37 secondary RPL (two or more miscarriages with a history of successful pregnancy). RPL was significantly associated with moderate-to-severe levels of depression (P < .001), anxiety (P < .001), and stress (P < .001). Among the RPL group, high stress level was significantly associated with repeat miscarriage (adjusted odds ratio (AOR) = 5.28, 95%CI = 1.25-100.0, P = .03) and preterm labor (AOR = 6.07, 95%CI = 1.61-100.0, P = .04). Depression and anxiety were not associated with adverse pregnancy outcomes. Pregnant women with a history of RPL had considerably higher rates of moderate-to-severe depression, anxiety, and stress. Repeat miscarriage and preterm labor were considerably higher among pregnant women with RPL who were experiencing high stress levels at baseline.


Strength Development and Elemental Distribution of Dolomite/Fly Ash Geopolymer Composite under Elevated Temperature.
A geopolymer has been reckoned as a rising technology with huge potential for application across the globe. Dolomite refers to a material that can be used raw in producing geopolymers. Nevertheless, dolomite has slow strength development due to its low reactivity as a geopolymer. In this study, dolomite/fly ash (DFA) geopolymer composites were produced with dolomite, fly ash, sodium hydroxide, and liquid sodium silicate. A compression test was carried out on DFA geopolymers to determine the strength of the composite, while a synchrotron Micro-Xray Fluorescence (Micro-XRF) test was performed to assess the elemental distribution in the geopolymer composite. The temperature applied in this study generated promising properties of DFA geopolymers, especially in strength, which displayed increments up to 74.48 MPa as the optimum value. Heat seemed to enhance the strength development of DFA geopolymer composites. The elemental distribution analysis revealed exceptional outcomes for the composites, particularly exposure up to 400 °C, which signified the homogeneity of the DFA composites. Temperatures exceeding 400 °C accelerated the strength development, thus increasing the strength of the DFA composites. This appears to be unique because the strength of ordinary Portland Cement (OPC) and other geopolymers composed of other raw materials is typically either maintained or decreases due to increased heat.


Does the Presence of Anxiety and ADHD Symptoms Add to Social Impairment in Children with Autism Spectrum Disorder?
Children with autism spectrum disorder (ASD) experience internalizing and externalizing problems at higher rates than typically developing children, which could worsen social impairment. The present study compared impairment scores (social responsiveness scale, 2nd edition; SRS-2 scores) in 57 children (3-17 years, 82.5% male) with ASD, either with or without heightened levels of anxiety or ADHD symptoms, all per parent report. Children with heightened anxiety problems showed higher scores on four SRS-2 subscales (Social Cognition, Social Communication, Social Motivation, and Restricted Interests and Repetitive Behavior). Children with heightened ADHD traits showed higher scores on two subscales (Social Communication and Social Awareness). These findings suggest similarities and differences in how social deficits in ASD may worsen with anxiety or ADHD symptoms.


Functional outcome after traumatic cervical spinal cord injury is superior in adolescents compared to adults.
Determining differences in neurological and functional outcome between adolescents and adults after acute traumatic spinal cord injury (SCI). Retrospective, multi-center case-control study. 100 cases of patients under 18 years at accident with acute traumatic cervical SCI admitted to SCI centers participating in the European Multi-center study about SCI (EMSCI) between January 2005 and April 2016 were reviewed. According to their age at accident, age 13 to 17, patients were selected for the adolescent group. After applying in- and exclusion criteria 32 adolescents were included. Each adolescent patient was matched with two adult SCI patients for analysis. ASIA Impairment scale (AIS) grade, neurological, sensory, motor level, total motor score, and Spinal Cord Independence Measure (SCIM III) total score. Mean AIS conversion, neurological, motor and sensory levels as well as total motor score showed no significantly statistical difference in adolescents compared to the adult control group after follow up of 6 months. Significantly higher final SCIM scores (p < 0.05) in the adolescent group compared to adults as well as a strong trend for a higher gain in SCIM score (p < 0.061) between first and last follow up was found. Neurological outcome after traumatic cervical SCI is not superior in adolescents compared to adults in this cohort. Significantly higher SCIM scores indicate more functional gain for the adolescent patients after traumatic cervical SCI. Juvenile age appears to be an independent predictor for a better functional outcome.


Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. 1984.
Twenty-five patients with central serous pigment epitheliopathy (CSP), also known as central serous chorioretinopathy, have been observed to have inferior hemispheric retinal pigment epithelial atrophic tracts, presumptive of antecedent retinal detachments. Five of these patients were noted to have clinically discernible, dependent peripheral retinal detachments. The clinical and fluorescein angiographic features of these patients are reviewed. Alterations in the retina, the retinal pigment epithelium (RPE) and the choroid are also described. They include the commonly associated manifestations of CSP such as RPE leaks and macular detachment as well as some newly recognized disturbances such as retinal capillary dilatation (telangiectasia), retinal capillary leakage, retinal lipid deposition, cystoid macular edema, choriocapillaris atrophy, choroidal neovascularization and disciform scarring.


Transfer of care and overstay in the management of cellulitis in the emergency short stay unit: A retrospective cohort study.
This study aimed to quantify the rate of transfer of care or overstay from cellulitis management in the emergency short stay unit (ESSU) and to identify risk factors during initial assessment associated with transfer of care or overstay. A retrospective cohort study was conducted including cellulitis patients diagnosed with and admitted to the ESSU at a metropolitan adult tertiary referral centre. Data abstracted included patient demographics, comorbidities, initial investigations and initial vital signs. Transfer of care or overstay were defined as inpatient admission or a stay in ESSU >28 h, respectively. Of the 451 included patients, 157 (34.8%) met the criteria for transfer of care or overstay. These criteria included admission to hospital inpatient units (115 patients, 73.2%) and patients who overstayed the ESSU time period (42 patients, 26.8%). Variables independently associated with transfer of care or overstay were obesity (adjusted odds ratio [OR] 4.33; 95% confidence interval [CI] 1.38-15.59), i.v. drug use (adjusted OR 2.15; 95% CI 1.03-4.51), white blood cell count (adjusted OR 1.09; 95% CI 1.02-1.16 per 1 × 109 /L increase) and C-reactive protein (adjusted OR 1.004; 95% CI 1.00-1.01 per 1 mg/L increase). Transfer of care or overstay after admission to ESSU was high among patients with cellulitis. Variables independently associated with transfer of care or overstay were obesity, i.v. drug use, elevated white blood cell count and elevated C-reactive protein. Awareness of these variables can inform appropriate guidelines for ESSU admission, potentially improving patient flow and reducing length of stay in the ED and hospital.


Short communication: Lipids and cardiovascular risk after switching HIV-1 patients on nevirapine and emtricitabine/tenofovir-DF to rilpivirine/emtricitabine/tenofovir-DF.
Antiretroviral therapy-related dyslipidemia increases the risk of cardiovascular disease (CVD) and is less frequently observed with nevirapine. Whether substituting rilpivirine for nevirapine has dyslipidemic consequences and alters CVD risk is unknown. The aim of this prospective open-label clinical trial was to evaluate serum lipids, cardiovascular risks, and lipid treatment goals over 48 weeks after switching from nevirapine to rilpivirine. Fifty HIV-1-suppressed patients on stable once-daily nevirapine plus emtricitabine/tenofovir-DF were switched to single-tablet rilpivirine/emtricitabine/tenofovir-DF. Lifestyle, weight, systolic blood pressure (SBP), ≥6 h overnight fasting lipids, 10-year Framingham risk scores (FRS), and Adult Treatment Panel III (ATP-III) lipid goals were evaluated over 48 weeks. Patients were 82% males, were a median of 45 years of age, and were on nevirapine for a median of 66 months. Diets, exercise levels, body mass index, and smoking status did not change during follow-up. At week 24, significant changes (p<0.001) were seen in mean [95% confidence interval (CI)] total cholesterol (-0.67 mmol/liter, CI: -0.50 to -0.83), low-density lipoprotein cholesterol (-0.36, CI: -0.21 to -0.51), and high-density lipoprotein cholesterol (-0.28, CI: -0.20 to -0.35). The total cholesterol/high-density lipoprotein cholesterol ratio increased 0.20 (CI: 0.02 to 0.37; p=0.029). Triglycerides did not change and the SBP decreased 6 mmHg (CI: -1.7 to -10.3; p=0.007). Week 48 lipid profiles and SBP were similar to week 24. The median FRS did not change during follow-up (-0.7%, p=0.119). More patients achieved ATP-III low-density lipoprotein cholesterol (+14.9%; p=0.016) and total cholesterol goals (+25.5%; p<0.001). The lipid profile changes after substituting rilpivirine for nevirapine did not significantly influence FRS, although SBP and the ATP-III low-density lipoprotein and total cholesterol goals improved.


Use of living donor liver transplantation varies with the availability of deceased donor liver transplantation.
The demographics of patients in the United States who undergo living donor liver transplantation (LDLT) versus patients who undergo deceased donor liver transplantation (DDLT) are interesting with respect to the demographics of the donor service areas (DSAs). We examined adult recipients of primary, non-status 1 liver-only transplants from 2003 to 2009. The likelihood of undergoing LDLT was compared to the likelihood of undergoing DDLT by multivariate logistic regression. We examined the adjusted odds ratio (OR) for undergoing LDLT versus DDLT for patients with the same diagnosis and blood type after we stratified the DSAs into quintiles by the median match Model for End-Stage Liver Disease (MELD) scores. LDLT was performed for 1497 of 32,927 liver transplants (4.5%). LDLT decreased in frequency by approximately 30% from 2003 to 2009. In comparison with DDLT recipients, LDLT recipients were younger and had higher albumin levels, lower body mass indices, and lower match MELD scores. Females had increased odds of LDLT in comparison with males (OR = 1.74, P < 0.001). Patients with MELD exception scores were less likely to undergo LDLT (OR = 0.22, P < 0.001). Patients with cholestatic liver disease (adjusted OR = 2.04, P < 0.001) or malignant neoplasms other than hepatocellular carcinoma (adjusted OR = 3.33, P < 0.001) were more likely than patients with hepatitis C virus to undergo LDLT. Other characteristics associated with decreased odds of LDLT were black race (adjusted OR = 0.41, P < 0.001) and government insurance (adjusted OR = 0.51, P < 0.001). LDLT was more frequent in DSAs with high median MELD scores; the adjusted OR for LDLT was 38 for the DSAs in the highest quintile (P < 0.001). In conclusion, there are significant differences associated with race, insurance, sex, MELD exceptions, and DSA MELD scores between patients who undergo LDLT and patients who undergo DDLT. These differences can be hypothesized to be driven in part by the relative availability of LDLT versus DDLT at both the patient level and the DSA level.


Is hunting still healthy? Understanding the interrelationships between indigenous participation in land-based practices and human-environmental health.
Indigenous participation in land-based practices such as hunting, fishing, ceremony, and land care has a long history. In recent years, researchers and policy makers have advocated the benefits of these practices for both Indigenous people and the places they live. However, there have also been documented risks associated with participation in these activities. Environmental change brought about by shifts in land use, climate changes, and the accumulation of contaminants in the food chain sit alongside equally rapid shifts in social, economic and cultural circumstances, preferences and practices. To date, the literature has not offered a wide-ranging review of the available cross-disciplinary or cross-ecozone evidence for these intersecting benefits and risks, for both human and environmental health and wellbeing. By utilising hunting as a case study, this paper seeks to fill part of that gap through a transdisciplinary meta-analysis of the international literature exploring the ways in which Indigenous participation in land-based practices and human-environmental health have been studied, where the current gaps are, and how these findings could be used to inform research and policy. The result is an intriguing summary of disparate research that highlights the patchwork of contradictory understandings, and uneven regional emphasis, that have been documented. A new model was subsequently developed that facilitates a more in-depth consideration of these complex issues within local-global scale considerations. These findings challenge the bounded disciplinary and geographic spaces in which much of this work has occurred to date, and opens a dialogue to consider the importance of approaching these issues holistically.


Adrenal dysfunction in critically ill children.
Cortisol is the major glucocorticoid synthesized by the adrenal cortex and its secretion is under the control of hypothalamic-pituitary axis. There is an increase in corticotrophin-releasing hormone and corticotrophin secretion and a decrease in the negative-feedback effect during critical illness. Adrenal insufficiency (AI) in children with critical illness is defined as an inadequate glucocorticoid response, measured by the peak cortisol or the increment in the cortisol level following exogenous ACTH (corticotrophin) administration. Clinically apparent AI is uncommon in critically ill patients. The incidence of AI in critically ill children varies with the underlying disease, its severity and duration, and multiple different definitions for the diagnosis of AI. Most of the pediatric studies for evaluation of AI during critical illness focused on patients with sepsis or septic shock. In patients with sepsis or septic shock, decreased synthesis or release of corticotrophin-releasing hormone, corticotrophin, and cortisol by cytokines and other circulating mediators released during sepsis are the most likely mechanism of AI. Recent studies in critically ill children reported that the prevalence of AI was not significantly different between septic and nonseptic patients, but it was noteworthy that AI appeared to be common both in septic and nonseptic critically ill children. A multidisplinary approach is necessary to manage to AI in critically ill children. However, no concensus exists among pediatric intensivist and endocrinologysts on diagnosis or treatment of AI in pediatric critical illness.


Pentoxifylline in preterm neonates: a systematic review.
Sepsis, necrotizing enterocolitis (NEC), and chronic lung disease (CLD) in preterm neonates are associated with significant mortality and morbidity, including long-term neurodevelopmental impairment and socioeconomic burden. Safe and effective drugs for the prevention and treatment of these conditions are urgently needed. Pentoxifylline, a synthetic theobromine derivative, is a non-steroidal immunomodulating agent with unique hemorrheologic effects which has been used in a range of infectious, vascular, and inflammatory conditions in adults and children. The unique properties of pentoxifylline explain its potential benefits in preterm neonates with sepsis, NEC, and CLD, conditions characterized by activation of the inflammatory cytokine cascade, free radical toxicity, and impaired microcirculation. Pentoxifylline has anti-inflammatory properties resulting from inhibition of erythrocyte phosphodiesterase. It lowers blood viscosity and improves microcirculation and tissue perfusion. As a phosphodiesterase inhibitor, pentoxifylline downregulates pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-6, and interferon-gamma. Methylxanthines, including caffeine, theophylline, and theobromine are relatively non-toxic drugs; of these, theobromine is the least toxic. Pentoxifylline-related significant adverse events are thus very rare. Unlike other methylxanthines, pentoxifylline does not have significant cardiac and bronchodilating effects at therapeutic doses. Although it is contraindicated in adults with recent cerebral hemorrhage due to its effect on platelets, red blood cells, and plasma fibrinogen levels, no significant adverse effects including thrombocytopenia and bleeding have been reported in critically ill preterm neonates with sepsis or NEC after treatment with pentoxifylline. Based on data from pilot randomized trials and observational studies, our systematic review suggests that pentoxifylline may reduce mortality and/or morbidity in preterm neonates with sepsis, NEC, and CLD. Results of experimental studies also indicate that pentoxifylline may potentially be beneficial in meconium aspiration syndrome and hypoxic ischemic encephalopathy. Given the substantial burden of sepsis, NEC, and CLD in high-risk preterm neonates, and the findings of this systematic review, pentoxifylline needs to be evaluated urgently as a preventative and therapeutic agent for these conditions in randomized controlled trials that can detect minimal clinically significant effect sizes. Further clinical and experimental studies are also necessary to evaluate whether pentoxifylline is safe and effective in meconium aspiration syndrome and hypoxic ischemic encephalopathy.


Cancer of the hypopharynx. Analysis of treatment and results in 162 patients.
Between 1962 and 1972, 190 patients with squamous cell carcinoma of the hypopharynx were seen; 162 received primary treatment at our clinic. Of the 162 lesions, 117 (72%) originated in the pyriform sinus. The most frequent symptom was pain in the throat (87 patients, 54%). One hundred twenty six patients (78%) had tumors extending beyond the hypopharynx (T3 lesions), and 108 patients (67%) had cervical metastasis (stage III or IV). Treatment modalities included surgical excision in 82 patients, radiation in 39, planned combination of preoperative radiation followed by surgery in 18, radiation plus neck dissection in 15, and surgery plus postoperative radiation in eight. Sixty-nine patients (43%) had recurrent tumor. Recurrences were equally frequent in the primary site and the neck. Comparison of treatment modalities showed no differences in overall recurrence. Surgery alone or in combination with radiation reduced the incidence of local recurrence; however, when recurrences were analyzed in relation to stage of lesion, preoperative or postoperative radiation and surgery offered no advantage over surgery alone in reducing local or neck recurrence or in overall survival rate. Treatment by radiation alone was associated with a poorer survival. For the entire group, three-year survival was 52% and five-year survival was 47%.


Mucocele of the appendix presenting as an exacerbated chronic tubo-ovarian abscess: A case report and comprehensive review of the literature.
Appendiceal mucocele is a rare entity of mucinous cystic dilatation of the appendix. It has no typical clinical presentation and is considered a potentially premalignant condition. We present a case of accidental intraoperative finding of an appendiceal mucocele in a 54-year old woman that clinically presented with an exacerbated chronic tubo-ovarian abscess. Trans-vaginal ultrasonography showed an encapsulated, oval, unilocular mass above the uterus with a heteroechogenic structure, homogeneous fluid content, and smooth regular walls without inner proliferation. The histopathologic diagnosis was consistent with an appendiceal cystadenoma. The patient underwent a simple appendectomy. There were no clinical, biochemical or imaging signs of the disease recurrence at 6 months follow up. To our knowledge, this is the only well-documented case of appendiceal mucocele mimicking exacerbated chronic tubo-ovarian abscess reported in the literature. Awareness of a rare entity such as an appendiceal mucocele, which is frequently misdiagnosed as a potential cause of acute abdomen, is necessary for the appropriate management strategy in order to prevent complications.


Evaluating hospital performance based on excess cause-specific incidence.
Formal evaluation of hospital performance in specific types of care is becoming an indispensable tool for quality assurance in the health care system. When the prime concern lies in reducing the risk of a cause-specific event, we propose to evaluate performance in terms of an average excess cumulative incidence, referring to the center's observed patient mix. Its intuitive interpretation helps give meaning to the evaluation results and facilitates the determination of important benchmarks for hospital performance. We apply it to the evaluation of cerebrovascular deaths after stroke in Swedish stroke centers, using data from Riksstroke, the Swedish stroke registry.


During day and night: Childhood psychotic experiences and objective and subjective sleep problems.
Psychotic experiences comprise auditory and visual perceptive phenomena, such as hearing or seeing things that are not there, in the absence of a psychotic disorder. Psychotic experiences commonly occur in the general pediatric population. Although the majority of psychotic experiences are transient, they are predictive of future psychotic and non-psychotic disorders. They have been associated with sleep problems, but studies with objective sleep measures are lacking. This study assessed whether psychotic experiences were associated with actigraphic sleep measures, symptoms of dyssomnia, nightmares, or other parasomnias. This cross-sectional population-based study comprises 4149 children from the Generation R Study. At age 10 years, psychotic experiences including hallucinatory phenomena were assessed by self-report; dyssomnia and parasomnia symptoms were assessed by mother- and child-report. Additionally, at age 11 years, objective sleep parameters were measured using a tri-axial wrist accelerometer in N = 814 children, who wore the accelerometer for five consecutive school days. Psychotic experiences were not associated with objective sleep duration, sleep efficiency, arousal, or social jetlag. However, psychotic experiences were associated with self-reported dyssomnia (B = 2.45, 95%CI: 2.13-2.77, p < 0.001) and mother-reported parasomnia, specifically nightmares (ORadjusted = 3.59, 95%CI 2.66-4.83, p < 0.001). Similar results were found when analyses were restricted to hallucinatory phenomena. Childhood psychotic experiences were not associated with objective sleep measures. In contrast, psychotic experiences were associated with nightmares, which are a known risk indicator of psychopathology in pre-adolescence. More research is needed to shed light on the potential etiologic or diagnostic role of nightmares in the development of psychotic phenomena.


The origin variability of the iliolumbar artery and iatrogenic sciatica.
The iliolumbar artery (ILA) is a standard branch from the posterior trunk of the internal iliac artery. It is the only pelvic artery ascending from pelvic cavity. Current study comprises 171 cadavers dissection to assess the origin variability of ILA. The present study identified the incidence of the ILA origin variability in Caucasian population which also clarified the iliolumbar variability in males and females. The current study shows that the ILA arises from the common iliac artery in 2%, from the external iliac artery in 0.3% and from the internal iliac artery in 13.8% either from its dorsal or dorsomedial aspects in 1 and 12.8%, respectively. The common, external and internal iliac arteries are defined as a high (early) origin and occurred in 16.1%. The posterior trunk of the internal iliac artery is the most common origin of the ILA found to be in 77.9%. Occasionally, it also arose from the superior gluteal artery (0.7%) and the sciatic artery (0.3%). Furthermore, the ILA arises from the anterior trunk indirectly as from the inferior gluteal artery in 0.3%. The ILA arising from the superior or inferior gluteal artery or from the sciatic artery is defined as a low (delayed) origin and occurred in 1.3%. In contrast, the ILA was 4.7%. Consequently, variability of the ILA leads to vascular variability of the lumbosacral trunk of the sciatic nerve. Clinicians have to be aware of these variations to avoid unnecessary ligation to prevent sciatic neuropathy.


The capacity of animals to acquire language: do species differences have anything to say to us?
Following the Gardners' discovery that an ape named Washoe could learn to produce and combine a number of hand movements similar to those used by deaf human beings, a variety of 'ape-language projects' sprang up. Some projects used different symbol systems, others used different training techniques, and others used different species of apes. While debate still rages regarding the appropriate way to interpret the symbolic productions of apes, three species of great apes (gorilla, orangutan, and chimpanzee) have now been credited with this capacity while no lesser apes or monkeys have been reported, at present, to have acquired such communicative skills. Among all of the claims made for the various animal species, the philosophers have entered the fray attempting to define the essence of what it is about language that makes it 'human'. This paper will compare and contrast the above positions to arrive at behavioural definitions of symbolic usage that can be applied across species. It will then present new data on a fourth ape species Pan paniscus which is proving to be the first non-human species to acquire symbolic skills in a spontaneous manner.


Systemic Photoprotection in Melanoma and Non-Melanoma Skin Cancer.
Non-melanoma skin cancers (NMSCs), which include basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and actinic keratosis (AK), are the most common cancer diseases in the Caucasian race. If diagnosed late and improperly treated, BCC and SCC can become locally advanced and metastasize. Malignant melanoma (MM) is less frequent but more lethal than NMSC. Given the individual and social burdens of skin cancers, performing an adequate prevention is needed. Ultraviolet (UV) ray exposure is one of the main risk factors for skin cancer. Thus, the first-choice prevention strategy is represented by photoprotection that can be both topical and systemic. The latter consists of the oral administration of molecules which protect human skin against the damaging effects of UV rays, acting through antioxidant, anti-inflammatory, or immunomodulator mechanisms. Although several compounds are commonly used for photoprotection, only a few molecules have demonstrated their effectiveness in clinical trials and have been included in international guidelines for NMSC prevention (i.e., nicotinamide and retinoids). Moreover, none of them have been demonstrated as able to prevent MM. Clinical and preclinical data regarding the most common compounds used for systemic photoprotection are reported in this review, with a focus on the main mechanisms involved in their photoprotective properties.


Large-scale analysis of human alternative protein isoforms: pattern classification and correlation with subcellular localization signals.
We investigated human alternative protein isoforms of >2600 genes based on full-length cDNA clones and SwissProt. We classified the isoforms and examined their co-occurrence for each gene. Further, we investigated potential relationships between these changes and differential subcellular localization. The two most abundant patterns were the one with different C-terminal regions and the one with an internal insertion, which together account for 43% of the total. Although changes of the N-terminal region are less common than those of the C-terminal region, extension of the C-terminal region is much less common than that of the N-terminal region, probably because of the difficulty of removing stop codons in one isoform. We also found that there are some frequently used combinations of co-occurrence in alternative isoforms. We interpret this as evidence that there is some structural relationship which produces a repertoire of isoformal patterns. Finally, many terminal changes are predicted to cause differential subcellular localization, especially in targeting either peroxisomes or mitochondria. Our study sheds new light on the enrichment of the human proteome through alternative splicing and related events. Our database of alternative protein isoforms is available through the internet.


Closed-loop stimulation as a physiological rate-modulated pacing approach based on intracardiac impedance to lower the atrial tachyarrhythmia burden in patients with sinus node dysfunction and atrial fibrillation.
The effectiveness of rate-modulated pacing for the suppression of atrial fibrillation (AF) is controversial. Closed-loop stimulation (CLS) is a heart rate modulation technique based on the contractility of the right ventricle estimated by sensing myocardial impedance, and CLS can still adapt to the heart rate in conditions where there are no significant changes in acceleration or ventilation, such as emotional stress. We elucidated the association between CLS and atrial tachyarrhythmia (AT) burden in patients with sinus node dysfunction and paroxysmal AF history before pacemaker implantation. We retrospectively reviewed all consecutive patients who underwent pacemaker implantation for sinus node dysfunction with an AF history before implantation. Overall, 146 patients were analyzed, with fixed-rate pacing (FP) in 82, CLS in 31, and non-CLS rate modulation in 33 patients. The AF/AT episodes were detected in 98 patients during a 12-month period. The median AF/AT burden was 1.6% (interquartile: 0.0%, 11.0%) in FP; 0% (0.0%, 2.5%) in CLS, and 1.0% (0.1%, 9.3%) in non-CLS. The AF/AT burden was significantly lower for CLS than for FP and non-CLS rate modulation (P < .01 and P = .04, respectively). CLS was associated with lower risks of AF/AT occurrence (hazard ratio [HR], 0.31; P = .02) and AF/AT burden more than 5% (HR, 0.28; P = .05), even after adjusting for potential confounders. This association was independent of the percentage of atrial pacing. CLS was associated with lower AF/AT burden after pacemaker implantation in patients with sinus node dysfunction and AF history.


Genetic instability associated with insertion of IS6100 into one end of the Streptomyces lividans chromosome.
Analysis of 548 recombinant strains of Streptomyces lividans carrying chromosomal insertions of IS6100 revealed that six mutants contained DNA amplifications. The amplifications differed in size but included IS6100 sequences. Hybridization with representative cosmid clones containing sequences from the unstable regions of the chromosome indicated that, in each mutant, DNA rearrangements affected just one of the chromosome ends. The amplifications were derived either from a region immediately proximal to the terminal inverted repeat (TIR) or further distal, from a previously characterized type I amplifiable unit of DNA. There was no evidence for extensive deletions accompanying the amplifications and chromosome linearity was maintained with, at least in five mutants, clear evidence for no loss of either TIR. The nature of the rearrangements provides evidence that insertions affecting the integrity of a chromosome end can contribute to genetic instability in Streptomyces.


Capsaicin-induced release of substance P increases cochlear blood flow in the guinea pig.
Physiological evidence from several studies suggests that endogenous vasoactive peptides, such as substance P (SP), and their respective receptor populations may participate in the mechanisms that govern the autoregulatory capacity of the cochlear vascular system. However, these studies do not provide evidence regarding the origin or mechanism of action of SP. Capsaicin sensitivity has been used as a marker for sensory neurons, and the release of SP following capsaicin treatment suggests a sensory transmitter role for SP. The present investigation examines the relationship between the capsaicin-sensitive sensory neurons and SP in the regulation of cochlear blood flow (CBF). In 75 pigmented guinea pigs, the cochlea was surgically exposed and a laser Doppler flowmeter probe placed on the bony surface of the first turn to monitor CBF. Capsaicin solutions (2 microliters, 0.01%, 0.001% and 0.0001%) applied to the round-window membrane (RWM) resulted in a dose-related CBF increase, without change in the systemic blood pressure. This effect could be inhibited by application of a specific SP receptor antagonist, [D-Pro2,D-Trp7,9]-SP, after which none of the capsaicin concentrations used induced a change in CBF. Moreover, after RWM application of 50 nmol/2 microliters of SP there was a significant increase in CBF. No CBF change was observed with the lower concentrations of 10 nmol SP or 100 pmol SP. These results indicate a role of SP in CBF regulation and give indirect evidence that SP is released from capsaicin-sensitive primary sensory neurons.