Segregation analysis in families with Charcot-Marie-Tooth disease allows reclassification of putative disease causing mutations.
The identification of disease causing, or putative disease causing, mutations in index patients with Charcot-Marie-Tooth disease (CMT) allows for genetic testing of family members. Relevant variants identified in index patients are of either definite, likely or uncertain pathogenicity. The main objective of this study was to make an evaluation of the family investigations performed as part of the assessment of genetic variants of unknown clinical significance (VUS). Between 2004 and 2010 molecular genetic family investigations were requested for 87 family members from 41 families harbouring PMP22dup or genetic variants in GJB1, MPZ, MFN2 and NEFL. Relatives were tested for the family mutation and data from the requisitions were evaluated by means of statistical tools. The results within each indication category are presented and discussed in detail. Twenty-two relatives (9 affected) from eight families were included in the segregation analyses, which invoked reclassification of three MFN2 mutations, two of which were de novo substitutions (c.2146_2148dup, c.692C > T). One MFN2 substitution was downgraded due to non-segregation (c.1709 A > G), and a MPZ substitution (c.103 G > A) upgraded due to segregation with the phenotype in the family. The results allow for the evaluation of the patient phenotypes ascertained in families, as opposed to the phenotypic descriptions of index patients. They indicate that de novo MFN2 mutations are regularly found in patients with a classical CMT2 phenotype. They also demonstrate the importance of a precise clinical and neurophysiologic diagnosis of affected family members. This particularly applies for the examination of variants of uncertain clinical significance. Finally, the fact that 14,6% of affected relatives tested for (probable or certain) pathogenic mutations were mutation negative, demonstrates that clinical evaluation alone is not always sufficient in order to determine their diagnosis. We believe that the results will aid in the estimation and planning of resources required for the various aspects of family evaluations in CMT.


Single-molecule mechanics of R403Q cardiac myosin isolated from the mouse model of familial hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy (FHC) is an inherited cardiac disease that can result in sudden death in the absence of any overt symptoms. Many of the cases documented to date have been linked with missense mutations in the beta-myosin heavy chain gene. Here we present data detailing the functional impact of one of the most deadly mutations, R403Q, on myosin motor function. Experiments were performed on whole cardiac myosin purified from a mouse model of FHC to eliminate potential uncertainties associated with protein expression systems. The R403Q mutant myosin demonstrated 2.3-fold higher actin-activated ATPase activity, 2.2-fold greater average force generation, and 1.6-fold faster actin filament sliding in the motility assay. The force- and displacement-generating capacities of both the normal and mutant myosin were also characterized at the single molecule level in the laser trap assay. Both control and mutant generated similar unitary forces ( approximately 1 pN) and displacements ( approximately 7 nm) without any differences in event durations. On the basis of the distribution of mean unitary displacements, this mutation may possibly perturb the mechanical coordination between the 2 heads of cardiac myosin. Any of these observations could, alone or possibly in combination, result in abnormal power output and potentially a stimulus for the hypertrophic response.


Surgical anatomy of the facial nerve relating to facial rejuvenation surgery.
The aim of this review was to familiarize the reader with critical facial nerve anatomy relating to facial rejuvenation surgeries. The temporal branch to the upper orbicularis oculi muscle (OOM): The temporal branch was under the temporoparietal fascia above the zygomatic arch and divided into 2 to 4 branches. The highest level of the twigs that entered the OOM on the x axis and the y axis with the origin of the lateral canthus is +2.51 ± 0.23 cm and +2.70 ± 0.35 cm; and the lowest, 0 cm and +2.68 ± 0.32 cm, respectively. The zygomatic and the buccal branch to the lower OOM: All pretarsal and preseptal OOMs were innervated by 5 to 7 terminal twigs of the zygomatic branches of the facial nerve that approached the muscle at a right angle. The medial portion of the lower OOM was innervated by 1 to 2 terminal twigs of the buccal branch, and the middle portion was innervated with 2 to 3 twigs of the zygomatic branch. The lateral portion was supplied by the uppermost zygomatic branch, which split into 2 to 4 twigs. The temporal branch to the corrugator supercilii muscle: A plexus mainly from the inferior ramus partly from the middle ramus of the temporal branch of the facial nerve enters the corrugator supercilii muscle in the supraorbital area. The temporal branch has as many as 4 to 7 rami, with interconnection among them. The buccal branch to the procerus muscle: The buccal branch crosses the intercanthal line (the nasion to the medial canthus) at approximately one third laterally. The nerve entrance was within a circle with a diameter of 5 mm, and its center was located 9 mm lateral and 10 mm superior from the nasion. It was approximately at the midpoint of the lateral half of the intercanthal line and the lower one third between the intercanthal line and the tangential line of the supraorbital rim. The buccal branch, the buccal fat pad, and the parotid duct: The buccal branches and the parotid duct crossed each other within a semicircle with a 30-mm radius. The base (diameter) was parallel to a horizontal line passing the corner of the mouth and 12 mm above. Its center was located 53 mm lateral to it. The buccal branches of the facial nerve have 2 locations at the buccal fat pad: type I, branches crossing superficial to the buccal fat pad in 14 (73.7%) of 19 specimens, and type II, 2 twigs passing through the buccal extension of the buccal fat pad in 5 (26.3%) of 19 specimens. The buccal branch to the upper orbicularis oris muscle: Approximately 4 branches (4.06 ± 0.83) entering the pars marginalis were found. Most ramifying points (14/17, 82%) were located within a circle with a 5-mm radius, and the center was 12 mm lateral and 26 mm superior to the mouth corner. The mandibular branch according to the neck position: At the one-fourth point, the border-nerve distance decreased (4.32 ± 2.60 mm) with the neck in ipsilateral rotation and the border-nerve distance increased (5.97 ± 2.62 mm) with the neck in contralateral rotation. We hope that this knowledge will aid surgeons in achieving successful outcomes.


Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line.
The role of mechanosensitive (MS) Ca2+-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca2+ entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to glass coverslips within flow chambers that allowed applications of physiological and pathological shear stress. Arterial shear (1002.6 s-1) induced a sustained increase in [Ca2+] i in Meg-01 cells and enhanced the frequency of repetitive Ca2+ transients by 80% in platelets. These Ca2+ increases were abrogated by the MS channel inhibitor Grammostola spatulata mechanotoxin 4 (GsMTx-4) or by chelation of extracellular Ca2+ Thrombus formation was studied on collagen-coated surfaces using DiOC6-stained platelets. In addition, [Ca2+] i and functional responses of washed platelet suspensions were studied with Fura-2 and light transmission aggregometry, respectively. Thrombus size was reduced 50% by GsMTx-4, independently of P2X1 receptors. In contrast, GsMTx-4 had no effect on collagen-induced aggregation or on Ca2+ influx via TRPC6 or Orai1 channels and caused only a minor inhibition of P2X1-dependent Ca2+ entry. The Piezo1 agonist, Yoda1, potentiated shear-dependent platelet Ca2+ transients by 170%. Piezo1 mRNA transcripts and protein were detected with quantitative RT-PCR and Western blotting, respectively, in both platelets and Meg-01 cells. We conclude that platelets and Meg-01 cells express the MS cation channel Piezo1, which may contribute to Ca2+ entry and thrombus formation under arterial shear.


Identification and quantification of amino acids and related compounds based on Differential Mobility Spectrometry.
Amino acids and related compounds constitute a class of biomarkers which is analyzed for early diagnosis of metabolic diseases (MDs). Protocols based on liquid chromatography hyphenated to tandem mass spectrometry (LC-MS/MS) are routinely used for MD diagnosis. Our ultimate objective is to evaluate the analytical performance of differential mobility spectrometry (DMS) hyphenated to MS/MS, in the perspective of using DMS-MS/MS as an alternative or complementary method for the topics of emergency in metabolic diagnosis and newborn rapid screening. The aim of the present study is to evaluate the robustness of a DMS-MS/MS protocol for the separation, identification, and quantification of amino acids and related compounds. Performance in terms of peak capacity and separation of isobaric and isomeric species is compared to those using drift tube type ion mobility spectrometry instruments. High reproducibility of the measurement of the DMS compensation voltage (CV) of metabolites shows that this CV parameter, or the corresponding electric field, could be used for application in metabolite identification. Multiple measurements show that the CV value of each AA or related compound is stable over a large period of time (6 months). Potential effects of matrix or concentration of the analytes on the DMS identifier are found to be negligible. Quantification of a selected set of metabolites in human plasmas has been carried out. The method linearity, intra-assay and inter-assay precision, detection limit, quantification limit and trueness analysis were assessed as adequate for both physiological and pathological conditions. Concentration levels of metabolites derived with our DMS-MS protocols were found to be in good agreement with those obtained with routine LC-MS/MS protocols used for the diagnosis of MDs at the Hospital Robert Debré (Paris).


"No-reflow" phenomenon in acute ischemic stroke.
Acute ischemic stroke (AIS) afflicts millions of individuals worldwide. Despite the advancements in thrombolysis and thrombectomy facilitating proximal large artery recanalization, the resultant distal hypoperfusion, referred to "no-reflow" phenomenon, often impedes the neurological function restoration in patients. Over half a century of scientific inquiry has validated the existence of cerebral "no-reflow" in both animal models and human subjects. Furthermore, the correlation between "no-reflow" and adverse clinical outcomes underscores the necessity to address this phenomenon as a pivotal strategy for enhancing AIS prognoses. The underlying mechanisms of "no-reflow" are multifaceted, encompassing the formation of microemboli, microvascular compression and contraction. Moreover, a myriad of complex mechanisms warrant further investigation. Insights gleaned from mechanistic exploration have prompted advancements in "no-reflow" treatment, including microthrombosis therapy, which has demonstrated clinical efficacy in improving patient prognoses. The stagnation in current "no-reflow" diagnostic methods imposes limitations on the timely application of combined therapy on "no-reflow" post-recanalization. This narrative review will traverse the historical journey of the "no-reflow" phenomenon, delve into its underpinnings in AIS, and elucidate potential therapeutic and diagnostic strategies. Our aim is to equip readers with a swift comprehension of the "no-reflow" phenomenon and highlight critical points for future research endeavors.


Changes in antibiotic sensitivity patterns of Gram-negative bacilli in burns.
Sensitivity tests with 12 antibiotics on 1,018 strains of Gram-negative bacilli isolated in a burns unit between 1969 and 1971 showed some important differences from results in similar tests on a series of strains isolated between 1965 and 1967. These changes included the emergence of a large proportion of kanamycin-resistant strains of Klebsiella aerogenes, Proteus mirabilis, and Escherichia coli and of smaller proportions of trimethoprim- and gentamicin-resistant strains; also the complete replacement of Proteus mirabilis with dissociated resistance to ampicillin by strains showing linked resistance to ampicillin and carbenicillin. The probable relationship of these changes to the emergence of an R factor determining resistance to tetracycline, kanamycin, carbenicillin, ampicillin, and cephaloridine in Enterobacteria and Pseudomonas aeruginosa is discussed.


Voltage-dependent slowing of K channel closing kinetics by Rb+.
We have studied the effect of Rb+ on K channel closing kinetics in toadfish pancreatic islet cells. These channels are voltage dependent, activating at voltages positive to -10 mV. The channels also inactivate upon prolonged depolarizations, and the inactivation time course is best fit by the sum of two exponentials. Instantaneous current-voltage relationships show that external Rb+ enters the channel as easily as K+, but carries less current. In the voltage range from -140 to -50 mV, the closing time course of the channels can be fit with a single exponential. When Rb+ is present in the external solution the channels close more slowly. The magnitude of this Rb+ effect is voltage dependent, decreasing at more negative voltages. Similarly, when the internal solution contains Rb+ instead of K+ the closing time constants are increased. The effect of internal Rb+ is also voltage dependent; at voltages positive to -80 mV the closing time constant in internal Rb+ is slower than in K+, whereas at more negative voltages the difference is negligible. With internal Rb+, the relationship between the closing time constant and voltage is best fit with two exponential components, suggesting the presence of two distinct voltage-dependent processes. The results are discussed in terms of a model of the K channel with two internal binding sites, and we conclude that Rb+ produces its effects on channel gating by binding to a site in the pore.


"Effect of COVID-19 Vaccination on Menstrual Cycle Patterns of Reproductive-Age Women: A Multi-centric Observational Study."
The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns and pre- and post-menstrual symptoms in women aged 18-45 years. COVID-19 vaccination was introduced to combat the dreadful impacts of human coronavirus infection. The two indigenously developed COVID-19 vaccines approved for use in India are COVISHILED and COVAXIN. To investigate the effects of COVID-19 vaccination on the menstrual cycle, pre- and post-menstrual symptoms and to establish the correlation with the type of vaccine received. Multi-centric observational study conducted in six institutes of national importance in different states of India over one year. A total of 5709 female participants fulfilling inclusion criteria were enrolled. Data about the impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on the menstrual cycle and its associated symptoms were obtained using all participants' online and offline interviews. Of 5709 participants, 78.2% received COVISHIELD and 21.8% COVAXIN. Of the total 5709 participants, 333(5.8%) developed post-vaccination menstrual disturbances, with 32.7% having frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleeding. A total of 301 participants noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of the menstrual cycle (p=0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to the COVISHIELD (5.3%) group. A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in the COVISHIELD group (p=0.031), with generalized weakness and body pains as the main complaints (p=0.001). No significant difference was observed in the incidence of COVID-19 infection with these vaccines. No significant associations were observed when comparing menstrual abnormalities among those with COVID-19 infection (p>0.05). COVISHILED and COVAXIN vaccines were associated with menstrual cycle disturbances and pre-and post-menstrual symptoms in a small proportion of participants, with 94.7% having no change in the amount of bleeding during menstruation post-vaccination. The menstrual irregularities observed were significantly higher with the COVAXIN vaccine. Others: Further, long-term studies are required to confirm that the impact of COVID-19 vaccination on the menstrual cycle may be short-lasting, with no severe effects on women's menstrual health.


Black tea lowers blood pressure and wave reflections in fasted and postprandial conditions in hypertensive patients: a randomised study.
Hypertension and arterial stiffening are independent predictors of cardiovascular mortality. Flavonoids may exert some vascular protection. We investigated the effects of black tea on blood pressure (BP) and wave reflections before and after fat load in hypertensives. According to a randomized, double-blind, controlled, cross-over design, 19 patients were assigned to consume black tea (129 mg flavonoids) or placebo twice a day for eight days (13 day wash-out period). Digital volume pulse and BP were measured before and 1, 2, 3 and 4 h after tea consumption. Measurements were performed in a fasted state and after a fat load. Compared to placebo, reflection index and stiffness index decreased after tea consumption (p<0.0001). Fat challenge increased wave reflection, which was counteracted by tea consumption (p<0.0001). Black tea decreased systolic and diastolic BP (-3.2 mmHg, p<0.005 and -2.6 mmHg, p<0.0001; respectively) and prevented BP increase after a fat load (p<0.0001). Black tea consumption lowers wave reflections and BP in the fasting state, and during the challenging haemodynamic conditions after a fat load in hypertensives. Considering lipemia-induced impairment of arterial function may occur frequently during the day, our findings suggest regular consumption of black tea may be relevant for cardiovascular protection.


White matter structure in youth with behavioral and emotional dysregulation disorders: a probabilistic tractographic study.
Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes. To determine whether diffusion imaging, a neuroimaging technique examining white matter (WM) structure, can identify neural correlates of emotional dysregulation in a sample of youth with different psychiatric disorders characterized by behavioral and emotional dysregulation. Using global probabilistic tractography, we examined relationships between WM structure in key tracts in emotional regulation circuitry (ie, cingulum, uncinate fasciculus, and forceps minor) and (1) broader diagnostic categories of behavioral and emotional dysregulation disorders (DDs) and (2) symptom dimensions cutting across conventional diagnoses in 120 youth with behavioral and/or emotional DDs, a referred sample of the Longitudinal Assessment of Manic Symptoms (LAM) study. Thirty age- and sex-matched typically developing youth (control participants) were included. Multivariate multiple regression models were used. The study was conducted from July 1, 2010, to February 28, 2014. Fractional anisotropy as well as axial and radial diffusivity were estimated and imported into a well-established statistical package. We hypothesized that (1) youth with emotional DDs and those with both behavioral and emotional DDs would show significantly lower fractional anisotropy compared with youth with behavioral DDs in these WM tracts and (2) that there would be significant inverse relationships between dimensional measures of affective symptom severity and fractional anisotropy in these tracts across all participants. Multivariate multiple regression analyses revealed decreased fractional anisotropy and decreased axial diffusivity within the uncinate fasciculus in youth with emotional DDs vs those with behavioral DDs, those with both DDs, and the controls (F6,160 = 2.4; P = .032; all pairwise comparisons, P < .002). In the same model, greater severity of manic symptoms was positively associated with higher fractional anisotropy across all affected youth (F3,85 = 2.8; P = .044). These findings suggest that abnormal uncinate fasciculus and cingulum WM structure may underlie emotional, but not behavioral, dysregulation in pediatric psychiatric disorders and that a different neural mechanism may exist for comorbid emotional and behavioral DDs.


Performance of emergency mechanical ventilators in response to the covid-19 pandemic: an intercomparison study.
Emergency mechanical ventilators developed during the pandemic were used to meet the high demand in intensive care units to care for COVID-19 patients. An example of such ventilators is Masi, developed in Peru and installed in more than 15 hospitals around the country. This study aimed to compare Masi's performance with other emergency mechanical ventilators manufactured during the covid-19 pandemic such as Neyün, Spiro Wave and a prototype developed by the Faculty of Engineering of the National University of Asuncion (FIUNA). Three configurations of a test lung were used, combining different values of resistance and compliance (C1, C2 and C3). Ventilators were set to volume-controlled ventilation with tidal volume = 400 mL, respiratory rate = 12 breaths/minute, and positive end-expiratory pressure (PEEP) = 8 cm H2O. These parameters were measured in a series of ten two-minute tests which then were evaluated through a two-way analysis of variance, considering the type of ventilator and test lung configuration as the two independent variables. For target values, MASI delivered VT that ranged from 319 to 432 ml (-20 to +8%), respiratory rate of 12 bpm, and PEEP from 8.4 to 9.5 cm H2O (+5 to +20%). In contrast, for instance, Neyün delivered VT that ranged from 199 to 543 ml (-50 to +35%) and PEEP from 7.05 to 9.21 cm H2O (--11 to +15%), with p<0.05. The analysis of variance showed that he differences between preset and delivered parameters were influenced by the type of ventilator and, significantly, by the test lung configuration.Clinical Relevance- This establishes the most advantageous conditions in which three emergency mechanical ventilators work and a quantitative perspective in this topic.


Psychiatric impairment, social contact, and violent behavior: evidence from a study of outpatient-committed persons with severe mental disorder.
The need to better understand and manage risk of violent behavior among people with severe mental illness in community care settings is increasingly being recognized, as public-sector mental health systems face mandates to provide more cost-effective services in less restrictive environments. The potential for serious violence in a small proportion of severely mentally ill (SMI) individuals has emerged as a key factor that increases cost and limits continuity and normalization of community-based services for populations with psychiatric disabilities. A major challenge to developing better strategies for risk assessment and management in community care settings involves specifying complex interactions between psychiatric impairment and the conditions of social life--including the quality and frequency of contact with others at close quarters. This is a study of the determinants of violent behavior in a sample of 331 adults with severe mental disorders in community-based treatment. An interaction between severity of functional impairment and frequency of social contact was found to be significantly associated with risk of violence. Among respondents with Global Assessment of Functioning (GAF) scores in the lowest 20%, more frequent contact with family and friends was linked to a higher probability of violent events. However, among better functioning respondents, frequent social contact was associated with lower risk of violence and greater satisfaction with relationships. These findings suggest that, where violence risk is concerned, the most salient feature of psychiatric impairment is the impairment of social relationships--the ways in which disorders of thought and mood not only distort one's subjective appraisal of experience and threat, but impair the ability to relate meaningfully to others, to resolve conflict and derive necessary support from family and friends. Thus, social contact may be a mixed blessing for SMI individuals. For some, it signals a positive quality of life, but for others--particularly those with extreme psychiatric impairment--frequent contact may add to conflict, stress, and increased potential and opportunity for physical violence. The impact of psychiatric impairment on violent behavior cannot be known in isolation, but must be considered in a social context. Effective community-based strategies to anticipate and prevent violence in the lives of persons with severe mental illness must take into account such interactions between social and clinical variables.


The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB).
Liver carnitine palmitoyltransferase I catalyzes the transfer of long-chain fatty acids into mitochondria. L-CPT I is considered the rate-controlling enzyme in fatty acid oxidation. Expression of the L-CPT I gene is induced by starvation in response to glucagon secretion from the pancreas, an effect mediated by cAMP. Here, the molecular mechanisms underlying the induction of L-CPT I gene expression by cAMP were characterized. We demonstrate that the cAMP response unit of the L-CPT I gene is composed of a cAMP-response element motif and a DR1 sequence located 3 kb upstream of the transcription start site. Our data strongly suggest that the coactivator PGC-1 is involved in the regulation of this gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB). Indeed, (i) cotransfection of CREB or HNF4 alpha dominant negative mutants completely abolishes the effect of cAMP on the L-CPT I promoter, and (ii) the cAMP-responsive unit binds HNF4 alpha and CREB through the DR1 and the cAMP-response element sequences, respectively. Moreover, cotransfection of PGC-1 strongly activates the L-CPT I promoter through HNF4 alpha bound at the DR1 element. Finally, we show that the transcriptional induction of the PGC-1 gene by glucagon through cAMP in hepatocytes precedes that of L-CPT-1. In addition to the key role that PGC-1 plays in glucose homeostasis, it may also be critical for lipid homeostasis. Taken together these observations suggest that PGC-1 acts to coordinate the process of metabolic adaptation in the liver.


[Simultaneous correction for blood matrix effect on determination of magnesium, copper and lead concentration in blood samples by ICP-MS using CAIS].
The influence of matrix effect on the determination of magnesium, copper and lead in human blood matrix stimulant and its correction was studied by using both conventional internal reference method & common analyte internal standardization (CAIS). The obtained results indicate that CAIS method is applicable for simultaneous correction of multi-elements in blood matrix. The relative errors between the determined and the true values are 3.05% (by CAIS method), 12.39% (by conventional internal reference correction) and 23.91% (without correction), respectively. Otherwise, the influences of the mass discrepancy and that of the determination intensities between elements are not obvious for the correction of blood matrix. The reliability of CAIS was validated by the determination of both bovine blood and bovine serum standard materials.


Inhibition of growth, production of insulin-like growth factor-II (IGF-II), and expression of IGF-II mRNA of human cancer cell lines by antagonistic analogs of growth hormone-releasing hormone in vitro.
Antagonistic analogs of growth hormone-releasing hormone (GHRH) suppress growth of various tumors in vivo. This effect is exerted in part through inhibition of the GHRH-GH-insulin-like growth factor (IGF)-I axis. Nevertheless, because autocrine/paracrine control of proliferation by IGF-II also is a major factor in many tumors, the interference with this growth-stimulating pathway would offer another approach to tumor control. We thus investigated whether GHRH antagonists MZ-4-71 and MZ-5-156 also act on the tumor cells directly by blocking the production of IGF-II. An increase in the IGF-II concentration in the media during culture was found in 13 of 26 human cancer cell lines tested. Reverse transcription-PCR studies on 8 of these cell lines showed that they also expressed IGF-II mRNA. Antagonists of GHRH significantly inhibited the rate of proliferation of mammary (MDA-MB-468 and ZR-75-1), prostatic (PC-3 and DU-145), and pancreatic (MiaPaCa-2, SW-1990, and Capan-2) cancer cell lines as shown by colorimetric and [3H]thymidine incorporation tests and reduced the expression of IGF-II mRNA in the cells and the concentration of IGF-II secreted into the culture medium. Growth and IGF-II production of lung (H-23 and H-69) and ovarian (OV-1063) cancer cells that express mRNA for IGF-II and excrete large quantities of IGF-II also was marginally suppressed by the antagonists. These findings suggest that antagonistic analogs of GHRH can inhibit growth of certain tumors not only by inhibiting the GHRH-GH-IGF-I axis, but also by reducing the IGF-II production and by interfering with the autocrine regulatory pathway.


Habitat-specific pigmentation in a freshwater isopod: adaptive evolution over a small spatiotemporal scale.
Pigmentation in the freshwater isopod Asellus aquaticus (Crustacea) differed between habitats in two Swedish lakes. In both lakes, isopods had lighter pigmentation in stands of submerged vegetation, consisting of stoneworts (Chara spp.), than in nearby stands of reed (Phragmites australis). Experimental crossings of light and dark isopods in a common environment showed that pigmentation had a genetic basis and that genetic variance was additive. Environmental effects of diet or chromatophore adjustment to the background had minor influence on pigmentation, as shown by laboratory rearing of isopods on stonewort or reed substrates, as well as analyses of stable isotope ratios for isopods collected in the field. In both study lakes, the average phenotype became lighter with time (across generations) in recently established stonewort stands. Taken together, these results indicate that altered phenotype pigmentation result from evolutionary responses to local differences in natural selection. Based on the assumption of two generations per year, the evolutionary rate of change in pigmentation was 0.08 standard deviations per generation (haldanes) over 20 generations in one lake and 0.22 haldanes over two generations in the other lake. This genetic change occurred during an episode of population growth in a novel habitat, a situation known to promote adaptive evolution. In addition, stonewort stands constitute large and persistent patches, characteristics that tend to preserve local adaptations produced by natural selection. Results from studies on selective forces behind the adaptive divergence suggest that selective predation from visually oriented predators is a possible selective agent. We found no indications of phenotype-specific movements between habitats. Mating within stonewort stands was random with respect to pigmentation, but on a whole-lake scale it is likely that mating is assortative, as a result of local differences in phenotype distribution.


Recurrent selection with reduced herbicide rates results in the rapid evolution of herbicide resistance in Lolium rigidum.
There has been much debate regarding the potential for reduced rates of herbicide application to accelerate evolution of herbicide resistance. We report a series of experiments that demonstrate the potential for reduced rates of the acetyl-co enzyme A carboxylase (ACCase)-inhibiting herbicide diclofop-methyl to rapidly select for resistance in a susceptible biotype of Lolium rigidum. Thirty-six percent of individuals from the original VLR1 population survived application of 37.5 g diclofop-methyl ha(-1) (10% of the recommended field application rate). These individuals were grown to maturity and bulk-crossed to produce the VLR1 low dose-selected line VLR1 (0.1). Subsequent comparisons of the dose-response characteristics of the original and low dose-selected VLR1 lines demonstrated increased tolerance of diclofop-methyl in the selected line. Two further rounds of selection produced VLR1 lines that were resistant to field-applied rates of diclofop-methyl. The LD50 (diclofop-methyl dose required to cause 50% mortality) of the most resistant line was 56-fold greater than that of the original unselected VLR1 population, indicating very large increases in mean population survival after three cycles of selection. In vitro ACCase inhibition by diclofop acid confirmed that resistance was not due to an insensitive herbicide target-site. Cross-resistance studies showed increases in resistance to four herbicides: fluazifop-P-butyl, haloxyfop-R-methyl, clethodim and imazethapyr. The potential genetic basis of the observed response and implications of reduced herbicide application rates for management of herbicide resistance are discussed.


Novel Sequence Features of DNA Repair Genes/Proteins from Deinococcus Species Implicated in Protection from Oxidatively Generated Damage.
Deinococcus species display a high degree of resistance to radiation and desiccation due to their ability to protect critical proteome from oxidatively generated damage; however, the underlying mechanisms are not understood. Comparative analysis of DNA repair proteins reported here has identified 22 conserved signature indels (CSIs) in the proteins UvrA1, UvrC, UvrD, UvsE, MutY, MutM, Nth, RecA, RecD, RecG, RecQ, RecR, RuvC, RadA, PolA, DnaE, LigA, GyrA and GyrB, that are uniquely shared by all/most Deinococcus homologs. Of these CSIs, a 30 amino acid surface-exposed insert in the Deinococcus UvrA1, which distinguishes it from all other UvrA homologs, is of much interest. The uvrA1 gene in Deinococcus also exhibits specific genetic linkage (predicted operonic arrangement) to genes for three other proteins including a novel Deinococcus-specific transmembrane protein (designated dCSP-1) and the proteins DsbA and DsbB, playing central roles in protein disulfide bond formation by oxidation-reduction of CXXC (C represents cysteine, X any other amino acid) motifs. The CXXC motifs provide important targets for oxidation damage and they are present in many DNA repair proteins including five in UvrA, which are part of Zinc-finger elements. A conserved insert specific for Deinococcus is also present in the DsbA protein. Additionally, the uvsE gene in Deinococcus also shows specific linkage to the gene for a membrane-associated protein. To account for these novel observations, a model is proposed where specific interaction of the Deinococcus UvrA1 protein with membrane-bound dCSP-1 enables the UvrA1 to receive electrons from DsbA-DsbB oxido-reductase machinery to ameliorate oxidation damage in the UvrA1 protein.


Multiplex spectroscopy: determining the transition moments and absolute concentrations of molecular species.
A procedure is described that uses two spectroscopic techniques, absorption and infrared degenerate four-wave mixing, in tandem (multiplex) to measure the transition dipole moments and absolute concentrations of molecular species in situ. The method is demonstrated by the measurement of the relative transition moments and concentrations of two dissimilar sample gas components, hydrogen chloride and nitrogen dioxide, but is applicable to a wide variety of molecules and, thus, can provide new information for transient molecular species. Further, difficulties in obtaining quantitative information through techniques such as laser-induced fluorescence, coherent anti-Stokes Raman scattering, and degenerate four-wave mixing spectroscopies can be overcome when a multiplex approach is used.


Use of porous polyethylene for correcting defects of temporal region following transposition of temporalis myofascial flap.
Transposition of the temporalis myofascial flap results in permanent aesthetic stigma in the donor site. Reconstruction of this deformity is desirable. The Authors present personal experience in the use of a porous polyethylene prosthesis to camouflage the temporal defects following transposition of the temporalis myofascial flap. From 2002 to 2005, 12 patients (5 male, 7 female, age range 36-84 years, mean 60), following the transposition of the temporalis myofascial flap, underwent reconstruction of the temporal region defect using porous high-density polyethylene temporal implants. The majority of the neoplasms removed proved to be squamous cell carcinomas of the alveolar crest or of the sinusal antrum. The standard surgical technique was used, namely, hemicoronal access and placement of 12 porous high-density polyethylene prostheses (5 left, 7 right). The size of the implants to be used (small, medium, large) was decided during the surgical operation. Of the 12 patients, 2 underwent post-operative radiotherapy, 6 weeks after the implantation of the prosthesis, without adopting any particular precautions to protect the area directly involved in the prosthesis implant. All patients are alive and free from disease, and implant placement appears to be free from post-operative complications. During the period of radiotherapy no complications. directly or indirectly related to the prosthetic implant, arose. Placement of the high-density polyethylene prosthesis fulfilled its filling effect on the deficit with a cosmetic success rate of 90%, as it was well integrated with no evident discontinuity between the edges of the prosthesis and the surrounding tissue or any alteration in the physiological convexity of the treated region. There were no incidents of pain or dysaesthesia of the skin covering the prosthesis. In conclusion, reconstruction of the temporal defect after temporalis myofascial flap transposition with the use of high-density polyethylene implants is an easy and safe method, with excellent functional and aesthetic results.


Is nuclear factor-kappaB a good treatment target in brain ischemia/reperfusion injury?
Nuclear factor-kappaB (NF-kappaB) is a transcription factor which resides in its unactivated form in the cytoplasm. Following activation subsequent to cerebral ischemia and reperfusion injury, NF-kappaB acts on genes for cytokines, adhesion molecules, nitric oxide synthase, cyclooxygenase-2, metalloproteinase-9, and perhaps apoptotic genes. These genes have a variety of positive and negative influences on the outcome of brain injury. The effect of manipulation of NF-kappaB needs to be examined critically, as it pertains to these reactive genes.


Thrombophilic screening in Turner syndrome.
The aim of this study was to determine, in patients with Turner syndrome (TS), the prevalence of thrombophilic disorders correlating with a higher risk of venous thromboembolism (VTE), to evaluate if thrombophilia is associated with the genetic features of these patients and whether screening before hormone replacement therapy (HRT) is advisable. We examined 82 TS patients. In all patients we analyzed activated factor VIII:C, fibrinogen, antithrombin (AT), protein C (PC), protein S (PS), activated PC resistance, and homocysteine. For every patient, an investigation for mutations in prothrombin G20210A, factor V R506Q, methylenetetrahydropholate reductase (MTHFR) C 677T and A1298C was conducted. Low values of PC in 3 patients (3.70%), low values of PS in 12 (14.81%), and hyperhomocysteinemia in 4 (4.87%) were found; 52 girls (64.2%) presented hyperfibrinogenemia. Three patients were heterozygous for the prothrombin G20210A allele mutation (3.66%) and the factor V mutation was present in 4 patients (4.88%). No TS patient had a homozygous mutation. Mutations in the MTHFR gene were present in 62 girls, in 17 patients (20.7%) they were homozygous and in 45 patients (54.88%) heterozygous. Considering the increased risks with the association between VTE and the higher prevalence of PC and PS deficiencies, TT genotype mutations and high level of fibrinogen, it is advisable to perform a complete thrombophilia screening in TS patients before starting HRT.


Complete thoracoscopic lobectomy versus hybrid video-assisted thoracoscopic lobectomy for non-small cell lung cancer.
Video-assisted thoracoscopic surgery (VATS) is the standard approach to lobectomy for early-stage non-small cell lung cancer (NSCLC). However, there are many different types. One of its approaches is complete thoracoscopic surgery (CTS), which may be less invasive because of low chest wall stress. This study compared the treatment outcomes of CTS and hybrid VATS lobectomy for NSCLC. In total, 442 eligible patients with clinical N0 NSCLC underwent lobectomy between 2007 and 2016. Patients were classified into a group of patients who underwent CTS and a group of those who underwent hybrid VATS. Propensity score matching was performed between the two groups. There were 175 patients after matching. The median follow-up period in the CTS and hybrid VATS groups was 60 and 63 months, respectively. The CTS group showed less blood loss (CTS, 50 mL vs. 100 mL, p = 0.005), fewer complications (CTS, 25.7% vs. 36.6%, p = 0.037), and shorter postoperative hospital stays (CTS, 8 days vs. 12 days, p < 0.001). There was no significant difference in the postoperative 30-day mortality rates. Between the patients who underwent CTS and hybrid VATS groups, the 5-year overall survival rates were 85.4% and 86.0% (p = 0.701), the relapse-free survival rates were 76.5% and 74.9% (p = 0.435), and the lung cancer-specific survival rates were 91.5% and 91.7% (p = 0.90), respectively. CTS is less invasive and has superior short-term outcomes as an approach to lobectomy for early-stage NSCLC.


Lung-gut cross-talk: evidence, mechanisms and implications for the mucosal inflammatory diseases.
The mucosal immune system (including airway, intestinal, oral and cervical epithelium) is an integrated network of tissues, cells and effector molecules that protect the host from environmental insults and infections at mucous membrane surfaces. Dysregulation of immunity at mucosal surfaces is thought to be responsible for the alarming global increase in mucosal inflammatory diseases such as those affecting the gastrointestinal (Crohn's disease, ulcerative colitis and irritable bowel syndrome) and respiratory (asthma, allergy and chronic obstructive pulmonary disorder) system. Although immune regulation has been well-studied in isolated mucosal sites, the extent of the immune interaction between anatomically distant mucosal sites has been mostly circumstantial and the focus of much debate. With novel technology and more precise tools to examine histological and functional changes in tissues, today there is increased appreciation of the 'common mucosal immunological system' originally proposed by Bienenstock nearly 40 years ago. Evidence is amounting which shows that stimulation of one mucosal compartment can directly and significantly impact distant mucosal site, however the mechanisms are unknown. Today, we are only beginning to understand the complexity of relationships and communications that exist between different mucosal compartments. A holistic approach to studying the mucosal immune system as an integrated global organ is imperative for future advances in understanding mucosal immunology and for future treatment of chronic diseases. In this review, we particularly focus on the latest evidence and the mechanisms operational in driving the lung-gut cross-talk.


Control of haemolytic disease of the newborn.
The decline in the stillbirth and death rates from haemolytic disease of the newborn in England and Wales between 1961 and 1973 is examined. The possible causes for this decline are identified and data related to each are assembled. The effects of intrauterine transfusions, changes in the abortion law, and changes in the racial mix as well as changes in the incidence of toxaemia of pregnancy and caesarean section can probably be disregarded for this purpose. Two major factors are the change in the birth rank distribution of births in England and Wales and general improvements in the quality of perinatal and obstetric care. When the above factors are excluded the effects of the specific control programmes upon stillbirths are not easy to measure or even detect. They probably accounted for less than one-fifth of the total decline in stillbirths from haemolytic disease of the newborn, although probably a larger proportion of the decline in neonatal deaths. During the period concerned, the most effective component in reducing losses was probably in the care of affected live-born infants and the primary preventive programme played only a minor part. Nevertheless, its effects are now discernible and it is likely to play a larger part in subsequent years. The quantification and monitoring of the part played by the preventive programme may require more developed information systems than are at present avilable.


Verticillium transcription activator of adhesion Vta2 suppresses microsclerotia formation and is required for systemic infection of plant roots.
Six transcription regulatory genes of the Verticillium plant pathogen, which reprogrammed nonadherent budding yeasts for adhesion, were isolated by a genetic screen to identify control elements for early plant infection. Verticillium transcription activator of adhesion Vta2 is highly conserved in filamentous fungi but not present in yeasts. The Magnaporthe grisea ortholog conidiation regulator Con7 controls the formation of appressoria which are absent in Verticillium species. Vta2 was analyzed by using genetics, cell biology, transcriptomics, secretome proteomics and plant pathogenicity assays. Nuclear Vta2 activates the expression of the adhesin-encoding yeast flocculin genes FLO1 and FLO11. Vta2 is required for fungal growth of Verticillium where it is a positive regulator of conidiation. Vta2 is mandatory for accurate timing and suppression of microsclerotia as resting structures. Vta2 controls expression of 270 transcripts, including 10 putative genes for adhesins and 57 for secreted proteins. Vta2 controls the level of 125 secreted proteins, including putative adhesins or effector molecules and a secreted catalase-peroxidase. Vta2 is a major regulator of fungal pathogenesis, and controls host-plant root infection and H2 O2 detoxification. Verticillium impaired in Vta2 is unable to colonize plants and induce disease symptoms. Vta2 represents an interesting target for controlling the growth and development of these vascular pathogens.


Third Trimester Estrogens and Maternal Breast Cancer: Prospective Evidence.
Full-term pregnancy is associated with a transient increase and life-time decrease in maternal breast cancer risk. Estrone (E1), estradiol (E2), and estriol (E3) are in high concentration during the third trimester. E1 and E2 metabolism produces carcinogenic intermediaries, and E3 metabolism does not. We tested the hypothesis that higher E3 in pregnancy is protective while higher E1 plus E2 increases risk. Prospective case-cohort study (n = 620; 204 cases) nested in a 38-year follow-up of 15,528 pregnant women in the Child Health and Development Studies. We measured E1, E2, and E3 in archived third trimester serum and estimated associations with breast cancer. Northern California Kaiser members receiving obstetric care from 1959 to 1967. Breast cancer diagnosed through 1997. Doubling of E1+E2 was associated with greater risk [hazard ratio (HR), 1.7; 95% confidence interval (CI), 1.2 to 2.4]. In contrast, doubling of E3 or the E3/E1+E2 ratio was associated with protection (HR, 0.7; 95% CI, 0.5 to 1.0; HR, 0.6; 95% CI, 0.4 to 0.8, respectively). Associations were stronger for diagnoses within 15 years after delivery compared with 16 to 38 years (Pinteraction = 0.0002) for gravidas >27 years at delivery vs ≤27 (Pinteraction = 0.01) and for primiparas vs multiparas (Pinteraction = 0.02). Relatively high third trimester E3 levels might protect parous women from breast cancer and E1 and E2 might enhance the risk. If findings are confirmed, third trimester pregnancy estrogens could help explain how parity affects breast cancer.


How do adolescents with short sleep duration spend their extra waking hours? A device-based analysis of physical activity and sedentary behaviour in a Brazilian sample.
To compare sedentary behaviour and physical activity between short sleepers and adequate sleepers in a sample of Brazilian adolescents. 688 adolescents wore accelerometers on the non-dominant wrist for seven days. Sleep duration, sedentary behaviour, light (LPA), moderate (MPA), and vigorous physical activity (VPA) were estimated. Participants were classified as short (<8h/night) or adequate sleepers (≥8h/night). The minutes and the percentage of time spent in each waking behaviour was compared between short and adequate sleepers. Participants were 16.3 years old, 50.4% were female, and 67.7% were short sleepers. Adequate sleepers engaged in less (min/day) sedentary behaviour (-53.46), LPA (-25.44), MPA (-4.27), and VPA (-0.63) compared to short sleepers. However, no differences were observed for the proportion of time (68% in sedentary behaviour, 28% in LPA, 3% in MPA, and <0.4% in VPA). Patterns of waking behaviours are similar between short and adequate sleepers.


Resting state functional atlas and cerebral networks in mouse lemur primates at 11.7 Tesla.
Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Characterizing neuronal networks in animals is complementary to studies in humans to understand how evolution has modelled network architecture. The mouse lemur (Microcebus murinus) is one of the smallest and more phylogenetically distant primates as compared to humans. Characterizing the functional organization of its brain is critical for scientists studying this primate as well as to add a link for comparative animal studies. Here, we created the first functional atlas of mouse lemur brain and describe for the first time its cerebral networks. They were classified as two primary cortical networks (somato-motor and visual), two high-level cortical networks (fronto-parietal and fronto-temporal) and two limbic networks (sensory-limbic and evaluative-limbic). Comparison of mouse lemur and human networks revealed similarities between mouse lemur high-level cortical networks and human networks as the dorsal attentional (DAN), executive control (ECN), and default-mode networks (DMN). These networks were however not homologous, possibly reflecting differential organization of high-level networks. Finally, cerebral hubs were evaluated. They were grouped along an antero-posterior axis in lemurs while they were split into parietal and frontal clusters in humans.


Chemoimmunotherapy of advanced breast cancer: prolongation of remission and survival with BCG.
Forty-five patients with disseminated breast cancer were given a trial of combination chemotherapy consisting of fluorouracil, adriamycin, and cyclophosphamide (FAC) and immunotherapy with BCG given by scarification. The results were compared with those in a comparable group of 44 patients treated with FAC alone immediately before the chemoimmunotherapy study. The remission rates (73% and 76% for FAC and FAC-BCG respectively) were similar in both studies. The durations of remission for patients on FAC-BCG (medium 12 months) were longer than remissions achieved for patients given FAC alone (median 8 months) (P = 0.068). The most notable effect of BCG was on survival. Thus 21 out of 34 patients achieving remission on FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 11 out of 32 patients achieving remission on FAC (median 15 months) (P = 0.01). Twenty-six of the 45 patients given FAC-BCG were alive at the time of the last follow-up examination (median over 22 months) compared with 12 of the 44 patients given FAC (median 15 months) (P = 0.005). Although the apparent benefit of BCG could be explained by a maldistribution of some prognostic factors, the data suggest that further trial of chemoimmunotherapy of breast cancer should be carried out.


[Manual intrauterine aspiration om the treatment of molar pregnancy].
Thirty six cases of molar pregnancy treated by Manual Vacuum Aspiration (MVA) were reviewed in the Instituto Nacional de Perinatología from January 1st to october 31, 1997. Molar pregnancy rate was 2.3 per 1000 pregnancies. Sixty percent of the cases occurred in women aged 20-30 years old. Previous molar pregnancy was the most frequent risk factor found, it was present in 44.5% of the cases. The mean gestational age was 12.6 weeks. Peridural blocking was used for anesthesia de 86.1% of the cases, in the remainder general anesthesia was used. MVA was performed by different surgeons, following the technique that has been previously reported. Twelve women received sharp curettage immediately after MVA. There were tree women with bleeding complications (1000 cc or more), one case needed blood transfusion. In two cases the evacuation was incomplete. Seven cases became persistent trophoblastic disease. The histopathologic report was consistent with complete molar pregnancy la more than 90% of the cases. Oral contraceptives were selected by 66.7% of the women after the evacuation. It was concluded that MVA is a safe and effective method for the evacuation of molar pregnancy.


Sutureless circumcision using 2-Octyl cyanoacrylate results in more rapid and less painful procedures with excellent cosmetic satisfaction.
Circumcision is the most common surgical procedure in male children in the world and is performed because of cultural, religious or medical reasons. Traditionally, interrupted sutures are used to close the wound, but 2-Octyl cyanoacrylate (2-OCA) tissue glue can be used as an alternative method to close the circumcision wound. To compare the use of 2-OCA with absorbable sutures in circumcision wound closure in prepubescent patients in terms of operative time, complication rate, postoperative pain and cosmetic results. We retrospectively evaluated 662 circumcision procedures using sutures and 609 procedures using 2-OCA for wound closure in prepubescent boys. All circumcision procedures were performed by 2 surgeons in a single centre. Operative time was collected from the hospital surgical software system. 62% of the patients in the suture group and 59% of the patients in the 2-OCA group presented for a postoperative check-up 6 weeks after the circumcision. Data regarding postoperative pain, need for analgesia, cosmetic satisfaction and the ease of wound care were collected through questionnaires completed by 25% of the boy's parents in the suture group and 53% of the parents in the 2-OCA group. Mean operative time was significantly shorter in the 2-OCA group (13 min) than in the suture group (17 min). Complications were comparable and mostly minor. Reintervention was only required in 3 cases. According to the parents, the degree of postoperative pain and the postoperative need for analgesics was significantly lower in the 2-OCA group. Wounds closed with 2-OCA were easier to care for. The cosmetic results after 1 day, after 1 week and after 1 month in the 2-OCA group were significantly superior than in the suture group, according to the parents' evaluation. The use of 2-OCA in circumcision wound closure has been reported before. Previous studies with mainly limited patient numbers report less pain, shorter procedure times and a higher surgeon satisfaction in terms of cosmetic results. This study is the largest study comparing the use of 2-OCA and interrupted sutures in circumcision wound closure. The retrospective character of the study, the lack of a validated questionnaire tool for the cosmetic evaluation and the use of the parent's evaluation are the limitations of this study. The use of 2-OCA in circumcision wound closure results in a shorter operative time, in less postoperative pain, in easy postoperative wound care and in excellent cosmesis when compared to interrupted absorbable sutures. 2-OCA is our current technique of choice in circumcision wound closure.


Bionomics and ecology of Anopheles merus along the East and Southern Africa coast.
Malaria transmission persists despite the scale-up of interventions such as long-lasting insecticide-treated nets (LLINs) and indoor residual spraying (IRS). Understanding the entomological drivers of transmission is key for the design of effective and sustainable tools to address the challenge. Recent research findings indicate a shift in vector populations from the notorious Anopheles gambiae (s.s.) as a dominant vector to other species as one of the factors contributing to the persistence of malaria transmission. However, there are gaps in the literature regarding the minor vector species which are increasingly taking a lead role in malaria transmission. Currently, minor malaria vectors have behavioural plasticity, which allows their evasion of vector control tools currently in use. To address this, we have reviewed the role of Anopheles merus, a saltwater mosquito species that is becoming an important vector of malaria transmission along the East and Southern African coast. We performed a literature review from PubMed and Google Scholar and reviewed over 50 publications relating to An. merus's bionomics, taxonomy, spatial-temporal distribution and role in malaria transmission. We found that An. merus is an important vector of malaria and that it contributes to residual malaria transmission because of its exophilic tendencies, insecticide resistance and densities that peak during the dry seasons as the freshwater mosquitoes decline. Spatial and temporal studies have also shown that this species has increased its geographical range, densities and vectorial capacity over time. In this review, we highlight the resting behaviour and breeding habitats of this mosquito, which could be targeted for surveillance studies and control interventions.


[Evaluation of the quality of the process of stoma demarcation and late complications in ostomized patients].
Following the characterization of adults with an intestinal stoma who were registered in the Program of Education and Support to Stomized Patients, the authors developed a descriptive study in order to evaluate the results of the process of intestinal stoma demarcation as well as to analyze late complications. The sample was formed by 50 subjects, 76% of whom had colostomies and 34% had ileostomies. Regarding the stoma location, 12% did not demonstrate the scientific specifications indicated for the distance from the waist line, 2% for the iliac crest and 2% for the surgery scar. Late complications appeared in 44% of the cases, such as: 28% of peristomal hernias, 16% of stoma prolapses and 4% of skin hyperemias.


Factors associated with reasons incontinent midlife women report for not seeking urinary incontinence treatment over 9 years across the menopausal transition.
We explored factors associated with reasons that women with urinary incontinence (UI) reported for not seeking treatment for their UI from a healthcare professional and whether reasons differed by race/ethnicity, socioeconomic status, or education. We analyzed questionnaire data collected from 1995 to 2005 in the Study of Women's Health Across the Nation. In visits 7 to 9, we elicited reasons that women with UI reported for not seeking treatment and condensed them into: UI not bad enough, beliefs about UI causes (UI is a normal consequence of aging or childbirth), and motivational barriers (such as feeling too embarrassed). We used Generalized Estimating Equations and ordinal logistic regression to evaluate factors associated with these reported reasons and number of reasons. Of the 1,339 women reporting UI, 814 (61.0%) reported they did not seek treatment for UI. The most frequently reported reasons were as follows: "UI not bad enough" (73%), "UI is a normal part of aging" (53%), and "healthcare provider never asked" (55%). Women reporting daily UI had higher odds of reporting beliefs about UI causes (adjusted odds ratio UI 3.16, 95% CI 1.64-6.11) or motivational barriers (adjusted odds ratio UI 2.36, 95% CI 1.21-4.63) compared with women reporting less than monthly UI. We found no interactions by race/ethnicity, socioeconomic status, or education and UI characteristics in reasons that women reported for not seeking UI treatment. Over half of women who did not seek treatment for their UI reported reasons that could be addressed by public health and clinical efforts to make UI a discussion point during midlife well-women visits.


Suppression of silent information regulator 1 activity in noncancerous tissues of hepatocellular carcinoma: Possible association with non-B non-C hepatitis pathogenesis.
Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD(+) )-dependent protein deacetylase. In mice, mSirt1 deficiency causes the onset of fatty liver via regulation of the hepatic nutrient metabolism pathway. In this study, we demonstrate SIRT1 expression, activity and NAD(+) regulation using noncancerous liver tissue specimens from hepatocellular carcinoma patients with non-B non-C (NBNC) hepatitis. SIRT1 expression levels were higher in NBNC patients than in healthy donors, while SIRT1 histone H3K9 deacetylation activity was suppressed in NBNC patients. In the liver of hepatitis patients, decreased NAD(+) amounts and its regulatory enzyme nicotinamide phosphoribosyltransferase expression levels were observed, and this led to inhibition of SIRT1 activity. SIRT1 expression was associated with HIF1 protein accumulation in both the NBNC liver and liver cancer cell lines. These results may indicate that the NBNC hepatitis liver is exposed to hypoxic conditions. In HepG2 cells, hypoxia induced inflammatory chemokines, such as CXCL10 and MCP-1. These inductions were suppressed in rich NAD(+) condition, and by SIRT1 activator treatment. In conclusion, hepatic SIRT1 activity was repressed in NBNC patients, and normalization of NAD(+) amounts and activation of SIRT1 could improve the inflammatory condition in the liver of NBNC hepatitis patients.


[The functional state of the cardiovascular system and the level of physical performance in 7-8-year-old children under conditions of aerotechnogenic pollution].
The aim of the study was to investigate the functional state of the cardiovascular system and the level of physical performance in 7-8-year-old children living in the urban area where air pollution caused by heavy vehicle traffic is high. The cardiovascular system and physical performance were evaluated using the conventional methods in 7-8-year-old 1097 children: a control group included 652 children (363 boys and 289 girls) and a comparison group consisted of 445 persons (239 boys and 206 girls). Under aerotechnogenic pollution, diastolic and mean blood pressures were found to be higher in both groups; the maximum oxygen consumption was lower in the boys and the girls had a decreased heart rate following 4-minute exercise.


Potassium ion transport ATPase in insect epithelia.
K+ transport by the epithelia of midgut, salivary glands, Malpighian tubules, sensory sensilla, possibly rectum, and other organs of certain insects appears to use a unique K+ ATPase. Ouabain inhibition of transport-related events has not been demonstrated in these epithelia. The K+ pump is unlike the Na-K;ump but resembles the H;ump of phosphorylating membranes in its transport orientation, efficient thermodynamics, speculated two K+ per one MgATP2- stoichiometry, electrogenicity, and structure. Older electrochemical, tracer flux, and conductance evidence suggested that the K+ pump was on the apical plasma membrane of transporting cells in these epithelia. New X-ray microanalytical studies (XMA), reveal that the K+ concentration in all cells is more than 100 mM. Together with new microelectrode data these XMA results confirm the apical K+ pump location, resolve the K+ transport sport route, and suggest that the goblet cell cavity facilitates the generation of a large apical PD which may be used in nutrient absorption and pH regulation. K+ portasomes, which resemble F1-Fo ATPase particles, stud these K+ transporting apical membranes and are though to be the unit of active K+ transport. We have suggested a K+ transport mechanism in which two cations (2K+) are abandoned in an isolated domain of the portasomes during ATP2-hydrolysis and are repelled to the opposite membrane side via a K+ channel. Small peptides hydrolysed from the delta-endotoxin of Bacillus thuringiensis inhibit the K+ transport and may be useful as K+ pump inhibitors, apical membrane probes and insecticides. Goblet cell apical membrane fragments (GCAM) as well as fragments from columnar cell apical membrane (CCAM), lateral membrane (LM) and basal membranes (BM) were isolated as clean fractions using ultrasound, aspiration, and both differential and density gradient centrifugation; purification was monitored by electron microscopy. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) reveals that GCAM, CCAM, LM and BM have very different protein compositions. Preliminary enzymology is consistent with the K+ ATPase being on the apical plasma membrane of the goblet cells of midgut and enveloping cells of sensilla.


Strain-dependent variation in collateral circulatory function in mouse hindlimb.
The extent (density and diameter) of the native (preexisting) collateral circulation in healthy tissues and the capacity of collaterals to enlarge/remodel in obstructive arterial disease are important determinants of ischemic injury. Evidence suggests that these parameters vary widely from yet-to-be-identified genetic and environmental factors. Recently, a locus on chromosome 7 was linked to less recovery of perfusion after femoral artery ligation in BALB/c and A/J versus C57BL/6 mouse strains. Moreover, evidence suggested that BALB/c and A/J share an allele(s) at this locus that is different from C57BL/6 mice. Here we tested the hypothesis that differences in collateral extent and/or remodeling underlie these findings. Compared with C57BL/6, BALB/c and A/J strains have fewer native collaterals in hindlimb (also confirmed in brain)-associated with greater reduction in perfusion immediately after femoral ligation, slower recovery of perfusion, greater hindlimb use impairment, and worse ischemia. However, A/J also differed from BALB/c in a number of these parameters, including having more robust collateral remodeling. Analysis of A/J --> C57BL/6 chromosome substitution strains confirmed that a difference in an allele(s) on chromosome 7 conferred most, but not all, of the magnitude of the differences in collateral function. Additional studies of C57BL/6 x BALB/c F1 mice demonstrated that alleles of the C57BL/6 strain exert dominance for collateral traits. Finally, negative results were obtained from studies examining a previously identified candidate gene potentially responsible for these differences-Bcl2-associated athanogene-3. These findings emphasize the major contribution of genetic background to variation in the collateral circulation and its capacity to lessen ischemia in obstructive disease.


Predicting the disease of Alzheimer with SNP biomarkers and clinical data using data mining classification approach: decision tree.
Single Nucleotide Polymorphisms (SNPs) are the most common genomic variations where only a single nucleotide differs between individuals. Individual SNPs and SNP profiles associated with diseases can be utilized as biological markers. But there is a need to determine the SNP subsets and patients' clinical data which is informative for the diagnosis. Data mining approaches have the highest potential for extracting the knowledge from genomic datasets and selecting the representative SNPs as well as most effective and informative clinical features for the clinical diagnosis of the diseases. In this study, we have applied one of the widely used data mining classification methodology: "decision tree" for associating the SNP biomarkers and significant clinical data with the Alzheimer's disease (AD), which is the most common form of "dementia". Different tree construction parameters have been compared for the optimization, and the most accurate tree for predicting the AD is presented.


Neuropsychotoxic and neuroprotective potentials of dextromethorphan and its analogs.
Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.


A search for intermediates in the bacterial biosynthesis of PQQ.
Studies on the biosynthesis of pyrroloquinoline quinone (PQQ) were performed with Acinetobacter calcoaceticus PQQ- -mutants belonging to genetically different complementation groups. All mutants were unable to grow on L-arabinose, the conversion of this substrate by the organism only occurring via membrane-bound quinoprotein (PQQ-containing) glucose dehydrogenase. In general, the same observation and conclusion applied to shikimate and quinate, requiring active quinoprotein quinate dehydrogenase (EC 1.1.99.--), although some mutants appeared to be leaky with respect to PQQ biosynthesis under this condition. A number of mutants were unable to grow on anthranilate and accumulated this compound when the growth medium was supplemented with L-kynurenine. Combined with other observations, it strongly suggests that these are deletion mutants, missing a gene for synthesis of anthranilate hydroxylase (EC 188.8.131.52) as well as nearby located genes for the biosynthesis of PQQ. Supplementation of the growth media with amino acids did not result in stimulation of PQQ biosynthesis. Also cross-feeding experiments, using normal and permeabilized cells with extensive variation in combination and conditions, resulted in neither stimulation nor reconstitution of PQQ synthesis. Under conditions optimal for PQQ production in the wild-type strain, as well as under stress conditions using a limiting amount of added cofactor, excretion of intermediates by PQQ- -mutants could not be detected. Similar results were obtained with PQQ- -mutants from Methylobacterium organophilum and Pseudomonas aureofaciens. A tentative explanation, accounting for the absence of detectable intermediates in the biosynthetic route, is given.


Efficacy and Safety of Endoscopic Resection Followed by Chemoradiotherapy for Superficial Esophageal Squamous Cell Carcinoma: A Retrospective Study.
The reported 1- and 3-year overall survival rates after esophagectomy for stage I superficial esophageal squamous cell carcinoma (SESCC) are 95-97% and 86%, and those after definitive chemoradiotherapy (CRT) are 98% and 89%, respectively. This study was performed to elucidate the efficacy and safety of another treatment option for SESCC: endoscopic resection (ER) followed by CRT. We retrospectively reviewed the overall survival, recurrence, and grade ≥3 adverse events of consecutive patients who refused esophagectomy and underwent ER followed by CRT for SESCC from 1 January 2006 to 31 December 2012. In total, 66 patients with SESCC underwent ER followed by CRT during the study period, and complete follow-up data were available for all patients. The median age was 67 (range, 45-82) years, and the median observation period was 51 (range, 7-103) months. Local and metastatic recurrences occurred in 2 (3%) and 6 (9%) patients, respectively, and 17 (26%) patients died. The 1-, 3-, and 5-year overall survival rates were 98%, 87%, and 75%, respectively. One of the 23 patients with mucosal cancer and 5 of 43 with submucosal cancer developed metastatic recurrences (P=0.65). Five of the 61 patients with negative vertical resection margin and 1 of 5 with positive vertical resection margin developed metastatic recurrences (P=0.39). None of the 30 patients without lymphovascular involvement developed metastatic recurrences; however, 6 of 36 patients with lymphovascular involvement developed metastatic recurrences (P=0.0098). Grade ≥3 adverse events occurred in 21 (32%) patients and all adverse events were associated with CRT, hematological adverse events in 13 (20%), and non-hematological adverse events in 9 (14%). ER followed by CRT provides survival comparable with that of esophagectomy or definitive CRT and has a low local recurrence rate. A particularly favorable outcome is expected for cancers without lymphovascular involvement.


The use of the paediatric tuberculosis score chart in an HIV-endemic area.
Diagnosing tuberculosis (TB) in a human immunodeficiency virus (HIV)-endemic area is extremely difficult, as the clinical symptoms of HIV-seropositive children can be easily confounded with TB. The paediatric tuberculosis score chart (TSC) was developed for resource-poor countries and its use continues to be promoted despite the fact that this scoring system has not been evaluated in countries with a high HIV prevalence. To assess the utility of the TSC in an HIV-endemic area. A prospective cohort study conducted between January and December 1999 at St Theresa's Mission Hospital, Copperbelt Province, Zambia. Results of the TSC (TB score) were compared with the results of a diagnostic algorithm, incorporating sputum smear microscopy, culture and polymerase chain reaction of Mycobacterium tuberculosis, tuberculin skin test, chest X-ray and histology eventually. A total of 147 children were enrolled in the study. On the basis of HIV-serology and clinical findings they were divided into four groups: children with TB (23 HIV-seropositive; 52 HIV-seronegative), 21 HIV-infected children without TB and 51 HIV-seronegative children without TB. The differences in TB scores between the groups were not significant. The sensitivity of the TSC to diagnose TB in this study was 88%; but the specificity was only 25%. The TSC should not be used as a diagnostic tool in countries with a high HIV prevalence. The low specificity of this scoring system leads to overdiagnosis of TB and unnecessary use of costly, antituberculous drugs. New tools for TB diagnosis in children in HIV-endemic areas are urgently needed.


Beneficial Effects of Leucine Supplementation on Criteria for Sarcopenia: A Systematic Review.
Treating sarcopenia remains a challenge, and nutritional interventions present promising approaches. We summarize the effects of leucine supplementation in treating older individuals with sarcopenia associated with aging or to specific disorders, and we focus on the effect of leucine supplementation on various sarcopenia criteria, e.g., muscular strength, lean mass, and physical performance. A literature search for articles related to this topic was performed on the relevant databases, e.g., the PubMed/Medline, Embase, EBSCO, Cochrane, Lilacs, and Dialnet. The identified articles were reviewed according to Preferred Reporting Items for Systematic reviews and meta-analyses (PRISMA) guidelines. Of the 163 articles we consulted, 23 met our inclusion criteria, analysing the effect of leucine or leucine-enriched protein in the treatment of sarcopenia, and 13 of these studies were based on randomized and placebo-controlled trials (RCTs). In overall terms, the published results show that administration of leucine or leucine-enriched proteins (range 1.2-6 g leucine/day) is well-tolerated and significantly improves sarcopenia in elderly individuals, mainly by improving lean muscle-mass content and in this case most protocols also include vitamin D co-administration. The effect of muscular strength showed mix results, and the effect on physical performance has seldom been studied. For sarcopenia-associated with specific disorders, the most promising effects of leucine supplementation are reported for the rehabilitation of post-stroke patients and in those with liver cirrhosis. Further placebo-controlled trials will be necessary to determine the effects of leucine and to evaluate sarcopenia with the criteria recommended by official Working Groups, thereby limiting the variability of methodological issues for sarcopenia measurement across studies.


Spontaneous corneal perforation in ocular rosacea.
Rosacea is a dermatologic condition that affects the midfacial region. Ocular rosacea is most frequently diagnosed when cutaneous signs and symptoms are also present. Ocular manifestations are essentially confined to the eyelids and ocular surface. Ocular involvement ranges from minor irritation, dryness, and blurry vision to potentially severe ocular surface disruption including corneal ulcers, vascularization and rarely perforation. We present a 49-year-old Saudi Arabian female with the diagnosis of rosacea who presented with a peripheral corneal performation. The perforation was successfully managed by surgical repair, oral doxycycline and topical steroid. The final best corrected visual acuity was 20/30 after treatment. Early referral to an ophthalmologist and careful long-term follow-up are recommended.


Epidemiology and outcome of osteomyelitis in the era of sequential intravenous-oral therapy.
There has been little recent information on the epidemiology and outcome of childhood osteomyelitis since the era of sequential intravenous-oral antibiotic therapy. Retrospective chart review. To review the recent experience and outcome of osteomyelitis in children. Between 1984 and 1996 we identified 146 patients with osteomyelitis. Decreased limb use and fever were the most common presenting symptoms, and tenderness was the most common sign. Staphylococcus aureus was the most common causative organism, and Haemophilus influenzae was not identified after 1990. Bone biopsies or aspirates were superior (83%) to blood cultures (32%) in yielding organisms. 99mTc bone scan was the most sensitive imaging test (94%). Lack of use of anti-teichoic acid titers and serum bactericidal titers did not adversely affect outcome. The median duration of intravenous antibiotic therapy was 11 days, with a median duration of total antibiotics of 38 days. Complications occurred in 6.6% of patients. S. aureus remains the most important cause of osteomyelitis. Despite inconsistent use of tests for diagnosis and management and use of sequential intravenous-oral therapy, the overall outcome remains excellent.


The Use of Prostate Specific Antigen Screening in Purchased versus Direct Care Settings: Data from the TRICARE® Military Database.
Fee for service reimbursement incentives may affect care. We compared the odds of prostate specific antigen screening among former and active duty United States military service members based on receipt of primary care from integrated military health facilities vs community providers reimbursed via fee for service. We retrospectively studied the records of all active duty and retired male service members 40 to 64 years old who were covered by the TRICARE® military health benefit in 2010. Beneficiaries may receive primary care at military run facilities via the direct care system or with private physicians via the purchased care system. We compared rates of prostate specific antigen screening between propensity score weighted cohorts of 219,290 men who received primary care in the direct care system and 177,748 who received it in the purchased care system. The screening rate was 35% in the direct care system vs 26% in the purchased care system. After propensity score weighting the former men were significantly more likely to undergo prostate specific antigen screening than men who received primary care in the purchased care system (adjusted OR 1.76, 95% CI 1.729-1.781). Age older than 52 years, rank and black race were associated with increased odds of prostate specific antigen screening in each cohort. These results suggest that salaried primary care providers employed at integrated military facilities are more likely to order prostate specific antigen screening compared to those reimbursed in a fee for service fashion by military insurance. Growing understanding of how fee for service incentives impact prostate specific antigen screening by primary care providers may enable advocates and policy makers to leverage reimbursement systems as a tool to change prostate cancer screening.


Conservative treatment with spontaneous stabilization of Grade II isthmic spondylolisthesis L5/S1 in a forty-four-year old woman, with a six-year follow-up: a case report.
Spondylolisthesis is a pathological condition caused by the slipping of a vertebral body, compared to the underlying structure, following structural and/or degenerative changes to the spine. Studies have attempted evidence to the connection between the natural history of spondylolisthesis, the degree and progression of the slip factor, as well as the pain and disability. Studies have reported a high level of heterogeneity of these factors in different patients as well as difficulty in predicting behaviour. It has been suggested that vertebral instability, independent of the slip factor, could be considered the most important factor to be treated conservatively or surgically. Furthermore, it appears that some patients may manifest complete disk degeneration over time, with vertebral bodies shifting closer and spontaneous stabilisation. This case study reports a forty-four-year old woman, with isthmic spondylolisthesis, where the spine surgeon recommended physiotherapy for conservative treatment, with a prognosis of possible spontaneous stabilization. The case was followed for six years, both clinically and radiologically. Treatment was based on a specific stabilising training program (motor control), immediately aimed to improve the disability and pain factors while waiting for a possible spontaneous stabilisation, that the latest radiological exams revealed with an attempt of arthrodesis. The Oswestry Disability Index (ODI) and the Roland Morris Disability Questionnaire (RMDQ) to measure disability, and the Numeric Rating Scale (NRS) to measure pain, were carried out at the beginning, during and at the end of treatment. They were compared with the radiographic material documenting the evolution of the spondylolisthesis over time. This case study appears to confirm that the hypothesis that a specific aimed approach of rehabilitation may improve the disability and pain levels without compromising the process of spontaneous arthrodesis. The evolution was documented radiographically and clinically over a six-year period.


Common Stress Transcriptome Analysis Reveals Functional and Genomic Architecture Differences Between Early and Delayed Response Genes.
To identify the similarities among responses to diverse environmental stresses, we analyzed the transcriptome response of rice roots to three rhizotoxic perturbations (chromium, ferulic acid and mercury) and identified common early-transient, early-constant and delayed gene inductions. Common early response genes were mostly associated with signal transduction and hormones, and delayed response genes with lipid metabolism. Network component analysis revealed complicated interactions among common genes, the most highly connected signaling hubs being PP2C68, MPK5, LRR-RLK and NPR1. Gene architecture studies revealed different conserved promoter motifs and a different ratio of CpG island distribution between early and delayed genes. In addition, early-transient genes had more exons and a shorter first exon. IMEter was used to calculate the transcription regulation effects of introns, with greater effects for the first introns of early-transient than delayed genes. The higher Ka/Ks (non-synonymous/synonymous mutation) ratio of early-constant genes than early-transient, delayed and the genome median demonstrates the rapid evolution of early-constant genes. Our results suggest that finely tuned transcriptional control in response to environmental stress in rice depends on genomic architecture and signal intensity and duration.


Chalcogenide optomemristors for multi-factor neuromorphic computation.
Neuromorphic hardware that emulates biological computations is a key driver of progress in AI. For example, memristive technologies, including chalcogenide-based in-memory computing concepts, have been employed to dramatically accelerate and increase the efficiency of basic neural operations. However, powerful mechanisms such as reinforcement learning and dendritic computation require more advanced device operations involving multiple interacting signals. Here we show that nano-scaled films of chalcogenide semiconductors can perform such multi-factor in-memory computation where their tunable electronic and optical properties are jointly exploited. We demonstrate that ultrathin photoactive cavities of Ge-doped Selenide can emulate synapses with three-factor neo-Hebbian plasticity and dendrites with shunting inhibition. We apply these properties to solve a maze game through on-device reinforcement learning, as well as to provide a single-neuron solution to linearly inseparable XOR implementation.


[Obesity, insulin resistance and skeletal muscle characteristics].
Insulin resistance seems to be a metabolic aberration associated with obesity. Impaired insulin action is also central to a cluster of diseases including non-insulin dependent diabetes, hypertension, dyslipidemias and atherosclerosis. Body fat distribution, especially upper body segment obesity is related to insulin-resistance. Glucose uptake is insulin dependent in skeletal muscle and adipose tissue. From a quantitative standpoint, skeletal muscle has the greater impact on whole body glucose economy, therefore the cause of altered insulin sensitivity has been looked for in this tissue. The skeletal muscle is composed of different types of fibers with specific metabolic and circulatory characteristics; type IIB fibers are less insulin-sensitive and their proportion has been related to obesity and insulin resistance. The different factors that may impair insulin action and alter glucose uptake in skeletal muscle are: lower blood flow to muscle, produced by either decreased vasodilation or by increased sympathetic nerve activity; augmented diffusion distance from capillaries to muscle due to a decrease in capillary number or to enlarged muscle cells; decrease of insulin receptors; change in the fatty acid profile of major membrane structural phospholipids; decrease in glucose transporters (GLUT 4) and/or hexokinase; impairment in metabolic routes of glucose in muscle as reduction in glycogen synthase. Also, the high rate of lipolysis present in obesity and in insulin resistance could lead to an impaired glucose oxidation in muscle.


Influence of age on surgical treatment and postoperative outcomes of patients with colorectal cancer in Denmark and Yorkshire, England.
Denmark and Yorkshire are demographically similar and both have undergone changes in their management of colorectal cancer to improve outcomes. The differential provision of surgical treatment, especially in the older age groups, may contribute to the magnitude of improved survival rates. This study aimed to identify differences in the management of colorectal cancer surgery and postoperative outcomes according to patient age between Denmark and Yorkshire. This was a retrospective population-based study of colorectal cancer patients diagnosed in Denmark and Yorkshire between 2005 and 2016. Proportions of patients undergoing major surgical resection, postoperative mortality and relative survival were compared between Denmark and Yorkshire across several age groups (18-59, 60-69, 70-79 and ≥80 years) and over time. The use of major surgical resection was higher in Denmark than in Yorkshire, especially for patients aged ≥80 years (70.5% versus 50.5% for colon cancer, 49.3% versus 38.1% for rectal cancer). Thirty-day postoperative mortality for Danish patients aged ≥80 years was significantly higher than that for Yorkshire patients with colonic cancer [OR (95% CI) = 1.22 (1.07, 1.38)] but not for rectal cancer or for 1-year postoperative mortality. Relative survival significantly increased in all patients aged ≥80 years except for Yorkshire patients with colonic cancer. This study suggests that there are major differences between the management of elderly patients with colorectal cancer between the two populations. Improved selection for surgery and better peri- and postoperative care in these patients appears to improve long-term outcomes, but may come at the cost of a higher 30-day mortality.


Fractionation of castor bean allergens (CB-1A). Isolation of RC-13, a homogeneous allergenic fraction.
Allergens from castor beans (CB-1A) were fractionated by ion-exchange chromatography both on CM- and SP-Sephadex, employing pH gradient. SP-Sephadex showed better results and fractionated the allergens into 7 components, eluted in a narrow pH range (5.0 - 6.6). An attempt to isolate the major acidic fraction of the group involved successive chromatographic steps on the same gel. RC-13, the isolated fraction, proved homogeneous by rechromatography on SP-Sephadex and isolectric focusing with pH range 3.0 - 10.0 polyacrylamide gel. The pl of RC-13 determined by the latter is approximately 4.2 and allergenic activity was demonstrated by heterologous passive cutaneous anaphylaxis in mice using anti-CB-1A rabbit serum.


[Determination of the steno-occlusive degree using non-invasive methods in diabetic patients with peripheral arterial insufficiency].
58 diabetic patients with peripheric arteriopathy are studied by means of segmentary pressure and oscillometry. Best results for proximal levels were those obtained with segmentary pressure index, whereas oscillometry was better for distal level (ankle and foot). The application of these criteria would facilitate the detection of arterial occlusions without need arteriography.


Inguinal hernia repair: an experimental model in the rat to evaluate technical factors.
An experimental model in the rat has been developed that we believe simulates the situation in inguinal hernia. Using this model, the bursting strength of wounds made by approximating uninjured fascia were compared with wounds made by apposing either incised fascia or the raw edges left after excising fascia. The strongest healing resulted when raw edges were apposed and when continuous sutures were used. We believe that these studies give support the use of Shouldice's hernia repair.


Deep brain stimulation telemedicine programming during the COVID-19 pandemic: treatment of patients with psychiatric disorders.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has considerably affected the delivery of postoperative care to patients who have undergone deep brain stimulation (DBS) surgery. DBS teleprogramming technology was developed and deployed in China before the COVID-19 outbreak. In this report, the authors share their experiences with telemedical DBS treatment of patients with psychiatric disorders during the COVID-19 outbreak. Four patients (2 with obsessive-compulsive disorder, 1 with major depressive disorder, and 1 with anorexia nervosa) underwent DBS surgery at Ruijin Hospital and received continuous postoperative DBS telemedicine case management from January 2020 to July 2020. DBS teleprogramming, individualized psychological support, and medical consultations were provided via the authors' DBS telemedicine platform, which also incorporated a synchronous real-time video communication system. Forty-five DBS telemedicine sessions were conducted; there was no unexpected loss of network connection during the sessions. Of these, 28 sessions involved DBS teleprogramming. Adjustments were made to the stimulation voltage, frequency, pulse width, and contact site in 21, 12, 9, and 9 sessions, respectively. Psychological support and troubleshooting were provided during the remaining telemedicine sessions. Modest to substantial clinical improvements after DBS surgery were observed in some but not all patients, whereas stimulation-related side effects were reported by 2 patients and included reversible sleep and mood problems, headache, and a sensation of heat. DBS telemedicine seems to offer a feasible, safe, and efficient strategy for maintaining the delivery of medical care to psychiatric patients during the COVID-19 outbreak. The authors propose that implementation of a comprehensive DBS telemedicine system, which combines DBS teleprogramming with psychological counseling, medical consultations, and medication prescriptions and delivery, could be an efficient and effective approach to manage the mental health and quality of life of patients with psychiatric disorders during future local or global public health crises.


Congenital adrenal hyperplasia due to 11-hydroxylase deficiency: functional characterization of two novel point mutations and a three-base pair deletion in the CYP11B1 gene.
Congenital adrenal hyperplasia is a group of autosomal recessive disorders second most often caused by deficiency of steroid 11-hydroxylase (CYP11B1) due to mutations in the CYP11B1 gene. We studied the functional and structural consequences of two novel missense mutations (W116C, L299P) and an in-frame 3-bp deletion (DeltaF438) in the CYP11B gene, detected in three unrelated families. All patients are suffering from classical CYP11B1 deficiency. In vitro expression studies in COS-7 cells revealed a decreased CYP11B1 activity in the W116C mutant to 2.9 +/- 0.9% (sd) for the conversion of 11-deoxycortisol to cortisol. The L299P mutant reduced the enzymatic activity to 1.2 +/- 0.9%, whereas the DeltaF438 mutation resulted in no measurable residual CYP11B1 activity. Introduction of these mutations in a three-dimensional model structure of the CYP11B1 protein provides a possible explanation for the in vitro measured effects. We hypothesize that the W116C mutation influences the conformational change of the 11-hydroxylase protein necessary for substrate access and product release. The L299P mutation causes a change in the position of the I helix relative to the heme group, whereas the DeltaF438 mutation results in a steric disarrangement of the heme group relative to the enzyme. Studying the enzyme function in vitro helps to understand the phenotypical expression and disease severity of 11-hydroxylase deficiency, which is the basis for accurate genetic counseling, prenatal diagnosis, and treatment. Moreover, the combination of in vitro enzyme function and molecular modeling provides new insights in cytochrome P450 structural-functional relationships.


Consensus Regularized Multi-View Outlier Detection.
Identifying different types of data outliers with abnormal behaviors in multi-view data setting is challenging due to the complicated data distributions across different views. Conventional approaches achieve this by learning a new latent feature representation with the pairwise constraint on different view data. In this paper, we argue that the existing methods are expensive in generalizing their models from two-view data to three-view (or more) data, in terms of the number of introduced variables and detection performance. To address this, we propose a novel multi-view outlier detection method with consensus regularization on the latent representations. Specifically, we explicitly characterize each kind of outliers by the intrinsic cluster assignment labels and sample-specific errors. Moreover, we make a thorough discussion about the proposed consensus-regularization and the pairwise-regularization. Correspondingly, an optimization solution based on augmented Lagrangian multiplier method is proposed and derived in details. In the experiments, we evaluate our method on five well-known machine learning data sets with different outlier settings. Further, to show its effectiveness in real-world computer vision scenario, we tailor our proposed model to saliency detection and face reconstruction applications. The extensive results of both standard multi-view outlier detection task and the extended computer vision tasks demonstrate the effectiveness of our proposed method.