Increased superoxide dismutase and Down's syndrome.
The enzyme superoxide dismutase (SOD) is a constitutive enzyme coded by a gene located in Chromosome 21 (21q22.1). Thus, the tissues from patients with trisomy 21 contain 50% more SOD activity. It is often suggested that the increased SOD content in the cells of Down's syndrome patients is responsible for many of the neurological symptoms of this disease. This hypothesis is not supported by most of the available data. In this paper we discuss why the increased SOD activity should not influence neuronal function and propose, instead, that the main problem may be an overexpression of other genes also located in chromosome 21 such as the beta amyloid precursor, as well as oncogenes and other Down's syndrome-related genes. We also propose that the increased SOD may be, instead, responsible for the increased incidence of Down's syndrome in children of older women. The augmented antioxidant protection resulting from an extra copy of chromosome 21 may, with time, selectively protect human oocytes from apoptosis, increasing their proportion with age, explaining the higher incidence of this disease.


An evaluation of inter and intra population structure of Uttar Pradesh, inferred from 24 autosomal STRs.
The present study was designed to explore the STR diversity and genomic history of the inhabitants of the most populous subdivision of the country. A set of 24 hypervariable autosomal STRs was used to estimate the genetic diversity within the studied population. A panel of 15 autosomal STRs, which is most common in the previously reported data sets, was used to estimate the genetic diversity between the studied population, and obtained unique relations were reported here. The genetic diversity and polymorphism among 636 individuals of different ethnic groups, residing in Bareilly, Pilibhit, Shahjahanpur, Gorakhpur, Jhansi, and Varanasi regions of Uttar Pradesh, India, was investigated. This investigation was carried out via 24 autosomal STRs. The 24 loci studied showed the highest value of combined power of discrimination (CPD = 1), combined power of exclusion (CPE = 0.99999999985), combined paternity index (CPI = 6.10 × 109) and lowest combined matching probability (CPM = 7.90 × 10-31). The studied population showed genetic closeness with the population of Uttarakhand, the Jats of Delhi,the Jat Sikh (Punjab), and the population of Rajasthan. Among the tested loci, SE33 and Penta E were found to be most useful in terms of the highest discrimination power, lowest matching probability, the highest power of exclusion, and highest polymorphism information content for the Uttar Pradesh population .


Positive end-expiratory pressure for resuscitation of newborn infants at birth.
Effective ventilation is the key to successful neonatal resuscitation. Positive pressure ventilation is initiated with manual ventilation devices which may or not deliver positive end-expiratory pressure (PEEP). PEEP is known to have beneficial effects in preterm animal models and its use is ubiquitous in mechanical ventilation in neonatal intensive care. To determine whether the use of PEEP during positive pressure ventilation at neonatal resuscitation reduces mortality or morbidity. The standard search strategy of the Cochrane Neonatal Review Group was used. Pub Med (1966 to May 2004) was searched using the MeSH headings Infant, Newborn, Resuscitation, Positive Pressure Respiration and the text words Positive End-Expiratory Pressure or PEEP. The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2004) was searched using text words Newborn and Resuscitation. No language restrictions were applied. The abstracts of the Society for Pediatric Research and the European Society for Pediatric Research, were searched from 1995-May 2004. Abstracts were also searched in Anaesthesiology, Canadian Journal of Anaesthesia, British Journal of Anaesthesia, Anaesthesia and Intensive Care and Anaesthesia and Analgesia. Randomised and quasi-randomised controlled trials comparing ventilation devices providing PEEP with those not providing PEEP in the resuscitation of infants at birth. Assessment of methodology regarding blinding of randomisation, intervention and outcome measurements as well as completeness of follow-up was planned. We planned to evaluate the treatment effect using a fixed effects model using relative risk (RR), relative risk reduction, risk difference (RD) and number needed to treat (NNT) for categorical data and using mean, standard deviation and weighted mean difference (WMD) for continuous data. We planned an evaluation of heterogeneity to help determine the suitability of pooling results. No studies were found meeting the criteria for inclusion in this review. There is insufficient evidence to determine the efficacy and safety of PEEP during positive pressure ventilation at neonatal resuscitation. Randomised clinical trials comparing positive pressure ventilation with and without PEEP at neonatal resuscitation are warranted.


Clinical profile and determinants of short-term outcome of acute kidney injury: A hospital-based prospective study from Northeastern India.
Acute kidney injury (AKI) is an outcome of multiple etiologies and is mostly reversible. Data on its incidence and outcome, particularly from India, are limited. To study the etiology, clinical profile, and short-term prognosis in AKI. A hospital-based prospective observational study on AKI. Seventy-five AKI patients diagnosed by Acute Kidney Injury network criteria were selected. Patients with preexisting chronic kidney disease were excluded. Data were compiled using the Statistical Package for the Social Sciences version 17. Regression analysis was done for determining the association of various variables for mortality. P < 0.05 was considered statistically significant. The mean age of patients was 41.09 ± 16.17 years with a male:female ratio of 1.42:1. Comorbidities were present in 37.3%, with diabetes mellitus (10.6%) and chronic liver disease (10.6%) being the most common. Fever was the most common (40%) presenting symptom, followed by oliguria (25.8%). Infection was the most common cause of AKI (56%), with sepsis in 26.7% followed by acute gastroenteritis in 17.3%. Pneumonia was the primary focus in 50% of cases with sepsis. Mean serum creatinine and urea at admission were 2.37 ± 0.90 and 92.44 ± 39.67 mg/dl, respectively. Serum creatinine rose progressively to 2.96 ± 1.18 and 3.26 ± 1.56 mg/dl at 24 and 48 h, respectively, since hospitalization. Majority of the cases (73.3%) were nonoliguric. Hemodialysis was necessary in 24% of cases. Mean hospital stay was 8.16 days. In-hospital mortality was 24%. Among survivors, 92.9% had complete renal recovery on discharge. Sepsis, need for hemodialysis, urea >100 mg/dl, and peak serum creatinine >3 mg/dl were contributors to mortality (P < 0.01). Infections, especially sepsis, were the most common cause of AKI. Hemodialysis was required in one-quarter of the patients. Sepsis, need for hemodialysis, and high creatinine were associated with a significantly higher mortality.


Activity-dependent slowing of conduction velocity provides a method for identifying different functional classes of C-fibre in the rat saphenous nerve.
Repetitive firing of nerve fibres results in the slowing of their conduction velocity. The extent of conduction velocity slowing throughout a standard electrical stimulus (20 s, 20 Hz, 2 x electrical threshold) was examined in identified C-fibres dissected from the saphenous nerve of anaesthetized rats. The aim of this study was to establish whether the different functional classes of C-fibre could be identified on the basis of their activity-dependent slowing of conduction velocity. Following 20 s of stimulation at 20 Hz, nociceptive C-fibres showed a significantly greater slowing of conduction velocity (mean +/- S.E.; polymodal and heat nociceptors = 29.2% +/- 0.7, n = 53; mechanical nociceptors = 27.7% +/- 1.7, n =13) than cold thermoreceptive fibres (10.8% +/- 0.6, n = 10), mechanoreceptors (14.4% +/- 0.8, n = 17) and spontaneously active sympathetic efferent units (14.9% +/- 0.8, n = 24). The degree of conduction velocity slowing shown by a unit was not correlated with its resting conduction velocity. There was little overlap of the degree of conduction velocity slowing between the nociceptive and non-nociceptive fibres. Also, there was little overlap of conduction velocity slowing between the mechanoreceptors and the cold units, particularly after just 6 s of stimulation at 20 Hz. Units for which no receptive field to mechanical or thermal stimuli could be found showed a bimodal distribution of conduction velocity slowing. In the saphenous nerve, such inexcitable units will be of three main types--sympathetic efferent units, "sleeping" or "silent" nociceptors and non-cutaneous afferent fibres. Those inexcitable units slowing in conduction velocity by greater than 20% showed a similar distribution to the polymodal nociceptors and those inexcitable units slowing by less than 20% showed a similar distribution to the spontaneously active sympathetic units. Twenty-three of the 61 units without mechanical or thermal receptive fields were investigated using electrical skin stimulation and topical application of 5 or 10% mustard oil. Afferent fields could not be found for any of the nine units that slowed in conduction velocity by less than 20%. Afferent fields were detected for 11 of the remaining 14 insensitive units, which all showed a greater than 20% slowing from resting conduction velocity. Therefore, one can distinguish nociceptive and non-nociceptive afferent fibres simply by looking at the axonal property of activity-dependent slowing of conduction velocity. Moreover, it is possible to use this axonal property to separate the two classes of non-nociceptive afferent C-fibre (i.e. mechanoreceptors and cold thermoreceptors). In addition, one can also use this parameter to differentiate between the afferent and non-afferent populations of inexcitable C-fibres. The ability to identify a particular fibre type on the basis of an axonal property provides a useful tool for the functional classification of fibres in experiments where axons are separated from their terminals.


Dual-modulation laser line-locking scheme.
Dual modulation laser line locking, useful for long-term trace species monitoring, achieves wavelength stability <0.1 ppm and rejects baseline drift in the measured absorbance3000-fold.


ROBUST AUTOCALIBRATED LORAKS FOR EPI GHOST CORRECTION.
Nyquist ghosts are a longstanding problem in a variety of fast MRI experiments that use echo-planar imaging (EPI). Recently, several structured low-rank matrix modeling approaches have been proposed that achieve state-of-the-art ghost-elimination, although the performance of these approaches is still inadequate in several important scenarios. We present a new structured low-rank matrix recovery ghost correction method that we call Robust Autocalibrated LORAKS (RAC-LORAKS). RAC-LORAKS incorporates constraints from autocalibration data to avoid ill-posedness, but allows adaptation of these constraints to gain robustness against possible autocalibration imperfections. RAC-LORAKS is tested in two challenging scenarios: highly-undersampled multi-channel EPI of the brain, and cardiac EPI with a double-oblique slice orientation. Results show that RAC-LORAKS can provide substantial improvements over existing ghost correction methods, and potentially enables new imaging applications that were previously confounded by ghost artifacts.


Genome-wide transcript and protein analysis highlights the role of protein homeostasis in the aging mouse heart.
Investigation of the molecular mechanisms of aging in the human heart is challenging because of confounding factors, such as diet and medications, as well as limited access to tissues from healthy aging individuals. The laboratory mouse provides an ideal model to study aging in healthy individuals in a controlled environment. However, previous mouse studies have examined only a narrow range of the genetic variation that shapes individual differences during aging. Here, we analyze transcriptome and proteome data from 185 genetically diverse male and female mice at ages 6, 12, and 18 mo to characterize molecular changes that occur in the aging heart. Transcripts and proteins reveal activation of pathways related to exocytosis and cellular transport with age, whereas processes involved in protein folding decrease with age. Additional changes are apparent only in the protein data including reduced fatty acid oxidation and increased autophagy. For proteins that form complexes, we see a decline in correlation between their component subunits with age, suggesting age-related loss of stoichiometry. The most affected complexes are themselves involved in protein homeostasis, which potentially contributes to a cycle of progressive breakdown in protein quality control with age. Our findings highlight the important role of post-transcriptional regulation in aging. In addition, we identify genetic loci that modulate age-related changes in protein homeostasis, suggesting that genetic variation can alter the molecular aging process.


Human CRSP interacts with RNA polymerase II CTD and adopts a specific CTD-bound conformation.
Activation of gene transcription in mammalian cells requires several classes of coactivators that participate in different steps of the activation cascade. Using conventional and affinity chromatography, we have isolated a human coactivator complex that interacts directly with the C-terminal domain (CTD) of RNA polymerase II (Pol II). The CTD-binding complex is structurally and functionally indistinguishable from our previously isolated CRSP coactivator complex. The closely related, but transcriptionally inactive, ARC-L complex failed to interact with the CTD, indicating a significant biochemical difference between CRSP and ARC-L that may, in part, explain their functional divergence. Electron microscopy and three-dimensional single-particle reconstruction reveals a conformation for CTD-CRSP that is structurally distinct from unliganded CRSP or CRSP bound to SREBP-1a, but highly similar to CRSP bound to the VP16 activator. Together, our findings suggest that the human CRSP coactivator functions, at least in part, by mediating activator-dependent recruitment of RNA Pol II via the CTD.


Research Diagnostic Criteria Axis II in screening and as a part of biopsychosocial subtyping of Finnish patients with temporomandibular disorder pain.
To assess Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) Axis II variables in an initial psychosocial screening and as a part of biopsychosocial subtyping of Finnish referral patients with TMD pain for adjunct multidisciplinary assessment. Consecutive Finnish referral patients with TMD pain (n = 135) participated in this questionnaire-based survey. Psychosocial screening was based on Graded Chronic Pain Scale (GCPS) and culturally adjusted Symptom Checklist 90-revised (SCL-90R) depression scale scores and subtyping on GCPS pain-related interference in accordance with previous treatment tailoring studies. Biopsychosocial subtyping variables included symptoms of depression and somatization, general health, pain-related worry, sleep dysfunction, and coping ability. Subtype comparisons were analyzed with Bonferroni adjusted P values and multivariable logistic regression (SAS 9.3). Based on psychosocial screening, 44% of the patients were psychosocially uncompromised (TMD subtype 1), 33% moderately, and 23% severely compromised (TMD subtypes 2 and 3). Compared to TMD subtype 1, TMD subtype 2 patients reported intermediate scores, and the most vulnerable TMD subtype 3 had the poorest general health, most elevated depression, somatization, worry and sleep dysfunction, and poor coping ability (P < .05). According to multivariable logistic regression, depression and worry levels were significantly higher in TMD subtype 3 compared to TMD subtype 1, whilst patients in TMD subtypes 1 and 2 reported significantly better coping ability compared to TMD subtype 3 (P < .05). The Finnish RDC/TMD Axis II was found reliable in initial TMD pain patient screening and with further biopsychosocial assessment identified three main TMD subtypes, two with compromised psychosocial profiles for adjunct multidisciplinary assessment.


Results of Four-Stented Biological Aortic Valves and How They Compare to PARTNER-3.
According to our nationwide registry, total numbers of surgical aortic valve implantation (sAVR) are constantly declining, while transcathether aortic valve implantation (TAVI) indications are widened toward intermediate- and low-risk patients. So, is there still room for conventionally implanted valves? Can results compete with TAVI or will sAVR be marginalized in the near future? Between 2011 and 2019, 1,034 patients (67.1% male, mean = 72.2 years) were enrolled receiving stented biological valves with or without concomitant coronary artery bypass grafting (CABG), atrial ablation, or wrapping of the ascending aorta. Odds ratios for the early and late mortality were calculated regarding comorbidities as potential risk factors. Statistical analysis was performed using SPSS. Overall, early mortality (EM) was 6.1%, 1-year mortality was 11.2%, and 5-year mortality was 19.9%. In low-risk patients (EuroSCORE II <4%), it was 1.0, 2.7, and 9.3%. Incidence of EM was significantly increased following decompensation, prosthetic valve, pacemaker carrier, dialysis, and pulmonary hypertension. Postoperative complications, such as systemic inflammatory response syndrome (SIRS), sepsis, multiorgan failure, hepatic failure, dialysis, gastrointestinal bleeding, and ileus, also increased EM. Late mortality was significantly increased by dialysis, hepatic cirrhosis, infected port system, aortic valve endocarditis, prosthetic valve carrier, and chronic hemodialysis. Conventionally implanted aortic valves do well early and late. The fate of the patient is dependent on individual risk-factors. Particularly, in low-risk patients, sAVR can compete with TAVI showing overall good early, as well as late results being even superior in some important aspects such as pacemaker implantation rate. Thus, the time is yet not ripe for TAVI to take over primary indications for AVR in low-risk patient.


Current options in the treatment of mitochondrial diseases.
Mitochondrial diseases (MD) are disorders caused by an impairment of the mitochondrial respiratory chain function. They are usually progressive, isolated or multi-system diseases and have variable times of onset. Because mitochondria have their own DNA (mtDNA), MD can be caused by mutations in both mtDNA and nuclear DNA (nDNA). The complexity of genetic control of mitochondrial function is in part responsible for the intra- and inter-familiar clinical heterogeneity of this class of diseases. Despite the remarkable progress in understanding of the molecular bases of these disorders, therapy of MD is quite inadequate. Present options of treatment mainly include physical, pharmacological and gene therapy approaches. Aerobic exercise and physical therapy is useful to prevent or correct deconditioning and may improve exercise tolerance. Pharmacological approach is based on removing noxious metabolites, using reactive oxygen species scavengers and administrating vitamins and cofactors which is especially important in case of primary deficiencies of specific compounds such as Coenzyme Q10. Gene therapy is fascinating but it is difficult to apply because of polyplasmy and heteroplasmy. Experimental methods include gene shifting, allotopic expression, mitochondrial transfection or correcting mtDNA mutations with specific restriction endonucleases. Here, we discussed some recent patents. Progresses in each of these fields may open interesting perspectives for the future.


Pre-ischemic renal lavage protects against renal ischemia-reperfusion injury by attenuation of local and systemic inflammatory responses.
Postischemic acute kidney injury (AKI) is a common clinical complication and often fatal, with no effective treatment available. Little is known about the role of leukocytes trapped in renal vessels during ischemia-reperfusion injury (IRI) in the postischemic AKI. We designed a new animal model in rats with preforming renal artery lavage prior to IRI to investigate the effect of diminishing the residual circulating leukocytes on kidney damage and inflammation. Moreover, the functional changes of macrophages in hypoxia reoxygenation condition were also analyzed. We found pre-ischemic renal lavage significantly decreased the serum creatinine and blood urea nitrogen levels, and downregulated the mRNA and protein expressions in kidneys and urinary secretion of kidney injury molecule-1 of rats after IRI. The renal pathological damage caused by IRI was also ameliorated by pre-ischemic renal lavage, as evidenced by fewer cast formation, diminished morphological signs of AKI in the tissue at 24 hours after IRI. Pre-ischemic renal lavage reduced the numbers of infiltrating CD68+ macrophages and MPO+ neutrophils. The mRNA expression of pro-inflammatory mediator in IRI kidneys and the levels of pro-inflammatory cytokines in circulatory system and urine were also reduced due to pre-ischemic lavage. Compared with nontreated rats with IRI, pre-ischemic renal lavage significantly reduced the phosphorylation levels of ERK and p65 subunit of NF-κB in the kidney after IRI. In addition, we found hypoxia/reoxygenation could promote the expression of pro-inflammatory mediators and inhibit the expression of anti-inflammatory factors by regulating ERK/NF-κB signaling pathway. Thus, pre-ischemic renal lavage could clearly reduce the renal damage after IRI by attenuating inflammation, and macrophages trapped in renal vessels during IRI could be important pathogenic factors driving tissue injury.


Perturbations of language network connectivity in primary progressive aphasia.
Aphasias are caused by disruption in structural integrity and interconnectivity within a large-scale distributed language network. We investigated the distribution and behavioral consequences of altered functional connectivity in three variants of primary progressive aphasia (PPA). The goal was to clarify relationships among atrophy, resting connectivity, and the resulting behavioral changes in 73 PPA and 33 control participants. Three core regions of the left perisylvian language network: the inferior frontal gyrus (IFG), middle temporal gyrus (MTG), and anterior temporal lobe (ATL) were evaluated in agrammatic (PPA-G), logopenic (PPA-L), and semantic (PPA-S) PPA variants. All PPA groups showed decreased connectivity between IFG and MTG. The PPA-S group also showed additional loss of connectivity strength between ATL and the other language regions. Decreased connectivity between the IFG and MTG nodes in PPA-G remained significant even when controlled for the effect of atrophy. In the PPA group as a whole, IFG-MTG connectivity strength correlated with repetition and grammar scores, whereas MTG-ATL connectivity correlated with picture naming and single-word comprehension. There was no significant change in the connectivity of homologous regions in the right hemisphere. These results show that language impairments in PPA are associated with perturbations of functional connectivity within behaviorally concordant components of the language network. Altered connectivity in PPA may reflect not only the irreversible loss of cortical components indexed by atrophy, but also the dysfunction of remaining neurons.


[Conclusion: probable and possible futures. MRI with ultra high magnetic field].
MR neuroimaging does not interfere with brain function. Because it is safe, it can be used to study the brains of both patients and healthy volunteers. The tasks performed by neurons depend largely on their precise location, and high-field magnets have the potential to provide a 5- to 10-fold increase in spatiotemporal resolution. This should allow brain function to be studied on a scale of only a few thousand neurons, possibly at the intermediate scale of the "neural code". NeuroSpin, a new CEA research center, is dedicated to neuro-MRI at high magnetic field stengths. As a forum for dialogue between those developing and those using these instruments, it brings together researchers and engineers, technicians and medical doctors. NeuroSpin is one of the few institutions in Europe, if not the world, where these experts can come together in one place to design, construct and use machines equipped with ultrastrong magnets. The strongest "routine" MR device currently operates at 3 Tesla (60 000 times the earth's magnetic field), whereas a first French system operating at 7 Tesla (140 000 times the earth's field) is now available for human studies, and another system operating at 11.7 Tesla (world record) should be delivered in 2011. Preclinical studies are also being conducted with magnets operating at 7 Tesla and, soon, 17.6 Tesla.


Application and implications of Mental Health Act 2007 (NSW) certificate use in acute generalist settings.
Objective This retrospective study aimed to explore the appropriate application and implications of Mental Health Act 2007 (NSW) (MHA) certificate use in a metropolitan generalist hospital in New South Wales. Methods A de-identified MHA certificate review was undertaken within acute generalist medical and surgical specialties between June 2012 and May 2013. To assess differences, data were separated into two categories according to whether certificates were completed by psychiatry trainees or generalist medical officers. Analysis of indications for detention was also undertaken and qualitatively matched against legislative criteria. Results A total of 43 MHA certificates were included in the review, which highlighted missing elements in most certificates. Differences were found when professional consensus by the researchers was used to match documentation to legislative criteria. The researchers disagreed with nine of the 16 indications (mental illness/mental disorder) by the generalist medical officers and only one indication by a psychiatry trainee. Six of the certificates appeared to be related to lack of capacity and need for treatment of medical conditions, thus more related to Guardianship Act 1987 (NSW) applications. Conclusion This study highlights inconsistencies in legislative knowledge and requirements between professional groups. Education and training opportunities have been identified to ensure greater consistency in application of the MHA, preservation of patient rights and avoidance of stigma. MHA use in this setting should be exercised with caution and by appropriately trained individuals. What is known about the topic? The MHA and its state and territory counterparts provide for the treatment, care and support of people who have a mental illness and the protection of a person's rights therein. Despite not being intended for application in generalist facilities, mental health legislation is widely used in generalist facilities and certificates are completed by generalist health professionals with limited training in this area of practice. What does this paper add? This study adds to the limited body of knowledge in relation to MHA detention in acute generalist facilities. Disparate preparation of medical officers in the use of this legislation has been identified, which has potential wider implications for patients beyond immediate care. What are the implications for practitioners? Inadequate attention to correct completion of MHA certificates and associated documentation could potentially invalidate detention, leaving healthcare professionals and institutions open to litigious claims that restrictive or coercive practices subsequent to the certificate's completion were technically unlawful. Further, detention under the MHA, albeit temporarily, has potential human rights issues attached and wrongful detention could lead to longstanding issues relating to stigma.


Predictors of mortality in alcoholic men: a 20-year follow-up study.
This study investigates the predictors of mortality in 156 male alcoholics who were psychiatrically hospitalized between 1967 and 1968 and followed for > 20 years. The findings showed that an older age, liver cirrhosis, and separation or divorce at intake were all associated with a shorter time to death. These results corroborate those of other follow-up studies that have identified age, health, and social support as independent correlates of mortality in alcoholics. From a therapeutic standpoint, the most alterable predictor is social support. Thus, the establishment of a salutary social network and social support system should be an integral part of the alcoholic's treatment plan.


Characterization of gonadal transcriptomes from Nile tilapia (Oreochromis niloticus) reveals differentially expressed genes.
Four pairs of XX and XY gonads from Nile tilapia were sequenced at four developmental stages, 5, 30, 90, and 180 days after hatching (dah) using Illumina Hiseq(TM) technology. This produced 28 Gb sequences, which were mapped to 21,334 genes. Of these, 259 genes were found to be specifically expressed in XY gonads, and 69 were found to be specific to XX gonads. Totally, 187 XX- and 1,358 XY-enhanced genes were identified, and 2,978 genes were found to be co-expressed in XX and XY gonads. Almost all steroidogenic enzymes, including cyp19a1a, were up-regulated in XX gonads at 5 dah; but in XY gonads these enzymes, including cyp11b2, were significantly up-regulated at 90 dah, indicating that, at a time critical to sex determination, the XX fish produced estrogen and the XY fish did not produce androgens. The most pronounced expression of steroidogenic enzyme genes was observed at 30 and 90 dah for XX and XY gonads, corresponding to the initiation of germ cell meiosis in the female and male gonads, respectively. Both estrogen and androgen receptors were found to be expressed in XX gonads, but only estrogen receptors were expressed in XY gonads at 5 dah. This could explain why exogenous steroid treatment induced XX and XY sex reversal. The XX-enhanced expression of cyp19a1a and cyp19a1b at all stages suggests an important role for estrogen in female sex determination and maintenance of phenotypic sex. This work is the largest collection of gonadal transcriptome data in tilapia and lays the foundation for future studies into the molecular mechanisms of sex determination and maintenance of phenotypic sex in non-model teleosts.


Orphan G-protein-coupled receptors : strategies for identifying ligands and potential for use in eating disorders.
G-protein-coupled receptors (GPCRs) are key regulators of intercellular interactions, participating in almost every physiological response. They exert their effects by being activated by a variety of endogenous ligands. Traditionally, these ligands were identified first, providing tools to characterise the receptors. However, since the late 1980s, homology screening approaches have allowed the GPCRs to be found first, and in turn used as orphan targets to identify their ligands. Over the last decade this method has led to the identification of 12 novel neuropeptide families. Interestingly, four of these deorphanised GPCR systems, melanin-concentrating hormone, ghrelin, orexin and neuropeptide B/neuropeptide W, have been found to play a role in the control of energy balance. This article reviews the role of these GPCR systems in the control of food intake and energy expenditure, and discusses their potential use in therapies directed at eating disorders. As obesity has reached epidemic proportions across the developed world, pharmacotherapy has focused on this condition. However, difficulties in weight control also characterise disorders of binge eating such as bulimia and binge-eating disorder. Consequently, hypophagic treatments may be of potential benefit in normal, overweight or obese individuals displaying aberrant (out of control) eating behaviour.


Do Expectations of Divorce Predict Union Formation in the Transition to Adulthood?
This study describes the association between explicit expectations to divorce and subsequent first union formation over the transition to adulthood (ages 18-28). Expectations for marriage in young adulthood predict union formation. Even before marrying, young adults may express a perceived risk of eventual divorce, and expectations of divorce may also have implications for union formation over the transition to adulthood. Data from the 2005-2015 years of the Panel Study of Income Dynamics Transition to Adulthood Supplement (n = 2052) were used to estimate the association between expectations to divorce and entry into first premarital cohabitation and first marriage using discrete-time logistic and multinomial logistic survival models. As hypothesized, greater expectations for divorce predicted slower entrance into first marriage, even controlling for expectations for marriage and various sociodemographic characteristics, and predicted a greater likelihood of both remaining single and being first observed cohabiting instead of marrying in young adulthood for both men and women. Despite desiring to marry, young adults may delay marriage if they are concerned about their risk of future divorce.


Animal models of spontaneous intracerebral hemorrhage.
Intracerebral hemorrhage (ICH) is a type of stroke that results in significant mortality and morbidity. Currently there is no definitive treatment for this disease. The paucity of animal models that reflect the heterogeneity of this spontaneous human disease could be the reason. In this review, we searched the literature for animal models of spontaneous ICH and found eight relevant papers. Two were related to hypertension and six were related to cerebral amyloid angiopathy (CAA). One model used double transgenic mice overexpressing human renin and angiotensinogen which caused the mice to be hypertensive. Induction of ICH, however required addition of a high salt diet and nitric oxide synthase inhibition. Another mouse model of hypertension employed subcutaneous angiotensin II infusion and nitric oxide synthase inhibition plus acute injections of angiotensin to further elevate blood pressure. Five CAA models were in transgenic mice overexpressing amyloid precursor protein. One relied on the natural development of CAA in squirrel monkeys. While all of the spontaneous ICH models have some advantages, the disadvantages include the sporadic time of onset of ICH and variability in size and location of ICH. Since there are no known efficacious treatments for ICH, it is not known if findings in the animal models will find treatments that are effective in humans.


Role of Guided Ultrasound in the Treatment of De Quervain Tenosynovitis by Local Steroid Infiltration.
Ultrasound guidance for steroid injection in de Quervain disease is useful in identifying the presence of subcompartments and effectively injecting the drug into tendon sheath. We prospectively studied 50 patients with features of de Quervain disease to determine the effectiveness of ultrasound in positioning of needle for steroid injection and effectiveness of single versus multiple injections in the presence of subcompartments. Scalp vein set was inserted into the tendon sheath under ultrasound guidance and sterile conditions. Mixture containing 1 mL of methylprednisolone 40 mg with 1 mL of 2% lignocaine was injected and the patient followed for 6 months. In patients having subcompartments, improvement was better when two separate injections into each subcompartment were given compared with single. Ultrasound guidance is helpful in identifying the existence of subcompartment and injecting the subcompartments separately. Scalp vein set may be very effective in ultrasound-guided injection. This is a level III study.


Skeletal Health Part 2: Development of a Nurse Practitioner Bone Support Clinic for Urologic Patients.
Part 1 of this article highlighted the potential negative effects of cancer on the skeleton and provided an overview of available treatment options. Part 2 presents a nurse practitioner-led Bone Support Clinic, which was developed for patients with cancer-induced bone disease and cancer therapy-induced bone loss. This clinic, started in 2011 in a university medical center urology/oncology outpatient center in London, England, United Kingdom, has been a collaborative effort among a multidisciplinary team of doctors, nurse practitioners and nurses. Patients have responded positively to the improved continuity of care, and we have been able to assess and treat impending skeletal-related events in a more timely manner The needs of our patient population and problems with the existing service are reviewed, and the importance of a multidisciplinary approach to these problems is discussed. Initiation of a nurse practitioner-led Bone Support Clinic and the impact of timely response to the effects of cancer and cancer therapies on the skeletal system are outlined and offered as a model.


Treatment of canine mast cell tumours with prednisolone and radiotherapy.
This retrospective study describes 35 dogs with non-resectable, grade I-III mast cell tumours on the head or limb treated with prednisolone (40 mg m(-2) daily) for 10-14 days prior to radiotherapy (4 x 800 cGy fractions at 7-day intervals) from a 4 MV linear accelerator. Prednisolone was continued at a reduced dose rate (20 mg m(-2)) during radiotherapy and for 2 months or longer afterwards. Eighteen of 24 tumours (75%) decreased in size in response to prednisolone treatment. By 6-8 weeks following radiotherapy, 12 dogs had achieved a complete remission and 19 a partial response. Two tumours remained static and two progressed during the course of treatment. The overall response rate was 88.5%. With long-term follow-up, 11 dogs experienced local recurrence (n = 4), metastasis (n = 5) or both (n = 2). The median progression-free interval was 1031 days (95% CI 277.44-1784.56, Kaplan-Meier), with 1- and 2-year progression-free rates of 60 and 52%, respectively. Tumour grade did not predict the prognosis for this group of dogs, but tumour location did affect the outcome. Dogs with tumours located on the limb survived longer than those with tumours on the head. The combination of prednisolone with radiotherapy appears to have a useful role in the management of measurable mast cell tumours sited on the head and distal extremities.


Epithelial mesenchymal interrelations at the skin level. A quantitative study.
Epithelial mesenchymal interrelations at the skin level were quantitatively studied by analysing the modifications of fibrocytes in the framework of total connective cells and capillaries of the dermic mesenchyme and of the number of mitoses in the epidermis. A normal group of guinea pigs was compared with a massaged one (II) and a massaged one using ointment (III). There were found significant differences between the elements of the first and those of the second and third groups, and no significant differences between the 2nd and the 3rd ones. There were established and compared the ratio of dermal fibrocytes to other connective cells, to dermal capillaries and to epidermal mitoses: the ratio remained similar in all groups. These results lead to the conclusion that dermis (expressed by its cells and capillaries) and epidermis (reflected in mitoses) have a correlated response to the mechanical action exerted in physiological limits, and that the epithelial mesenchymal dependence at the skin level is determined by the strong interrelations which are not easily modifiable.


Clonal chromosomal abnormalities in desmoid tumors. Implications for histopathogenesis.
Desmoid tumors (aggressive fibromatosis) are regarded as lesions of uncertain histopathogenesis. Cytogenetic analyses of 26 desmoid tumor specimens from abdominal or extraabdominal sites of 22 patients with or without Gardner's syndrome (GS) showed clonal karyotypic abnormalities in 7 cases, random abnormalities in 14 cases, and striking telomeric fusion in 5 cases. Loss of chromosome Y, a reported feature of fibromatosis in penile and palmar locations, was detected as a clonal aberration in two patients. Additionally, involvement of 5q was observed in six patients, two of whom had GS. Clonal interstitial deletions of 5q were observed in three patients, one with and two without GS. These findings confirm a clonal and probable neoplastic origin for desmoid tumor and suggest that abnormalities of the Y chromosome and 5q may be important in the genesis of this neoplasm.


Reconstructive Trends After Tissue-Expander Loss in Breast Reconstruction.
Tissue-expander breast reconstruction (TEBR) is a common method of reconstruction after mastectomy but may result in complications that may necessitate removal. Although complications in TEBR have been well studied, there is a paucity of data regarding outcomes after tissue-expander loss. In this study, we examine the eventual reconstructive pathways and associated factors of patients who required tissue-expander removal after infection. This retrospective study examines patients undergoing breast reconstruction at a single institution. Patients included underwent mastectomy, immediate TEBR, and subsequent tissue-expander loss. Patients who underwent autologous reconstruction after mastectomy or had successful TEBR were excluded. Patients were followed for an average of 7 years, with a minimum of 2 years and a maximum of 13 years. A total of 674 TEBR patients were initially screened, of which 60 patients (8.9%) required tissue-expander removal because of infection or skin necrosis. Thirty-one of these patients (group 1) did not complete reconstruction after initial tissue-expander loss, whereas the remaining 29 patients (group 2) underwent either TEBR or autologous reconstruction after tissue-expander loss. Group 1 had a significantly higher mean body mass index than group 2 (32.61 ± 8.88 vs 28.69 ± 5.84; P = 0.049) and also lived further away from our institution than group 2 (P = 0.052), which trended toward significance. There were otherwise no significant differences in demographics between the 2 groups.Among the 29 patients in group 2, 18 patients underwent a second TEBR (group 2a), and 11 patients underwent autologous reconstruction (group 2b). Patients in group 2b had a significantly greater mean number of complication related admissions (1.11 ± 0.323 vs 1.55 ± 0.688; P = 0.029) and also had higher occurrence of postmastectomy radiation therapy (16.7% vs 45.5%; P = 0.092), although this was not significant. There were otherwise no differences between the 2 groups. Our data demonstrate the trends in breast reconstruction decision making after initial tissue-expander loss. This study elucidates the factors associated with patients who undergo different reconstructive options. Further work is needed to delineate the specific reasons between the decision to pursue different reconstructive pathways among a larger cohort of patients.


Studies on the Energy-coupling Sites of Photophosphorylation: V. Phosphorylation Efficiencies (P/e(2)) Associated with Aerobic Photooxidation of Artificial Electron Donors.
The rate of Hill reaction can be measured accurately as O(2) uptake (the Mehler reaction) if a rapidly autoxidizable electron acceptor (e.g., methylviologen) is used. However, when an artificial electron donor-ascorbate couple (or ascorbate alone) replaces the natural donor, water, the rate of O(2) consumption is no longer a reliable measure of the electron flux, because superoxide radical reactions contribute to O(2) uptake. Such radical reactions, however, can be suppressed by adding enough superoxide dismutase to the reaction mixture. Indeed in all of the photosystem I- and photosystem II-donor reactions tested (except with benzidine which was tested without ascorbate added), the O(2) uptake was inhibited by 30 to 50% by the addition of superoxide dismutase. The rate of phosphorylation was totally unaffected by the enzyme. The reasessment of the phosphorylation efficiencies thus made by the use of superoxide dismutase led us to the following conclusions. The phosphorylation efficiency associated with the transfer of electrons from a donor to methlylviologen (than to O(2)) through both photosystems II and I is practically independent of the donor used-catechol, benzidine, p-aminophenol, dicyanohydroquinone, or water. The P/e(2) ratio is 1.0 +/- 0.1. Only ascorbate gives a slightly lower value (P/e(2) = 0.9). (NH(2)OH-treated, non-water-splitting chloroplasts were used for reactions with these artificial donors.) The phosphorylation efficiency associated with DCMU-insensitive, photosystem I-mediated transfer of electrons from a donor to methylviologen (then to O(2)) is again largely independent of the donor used, such as diaminodurene, diaminotoluene, and reduced 2,6-dichlorphenol-indophenol. The P/e(2) ratio is 0.6 +/- 0.08.


Emission of volatile sulfur compounds from spruce trees.
Spruce (Picea Abies L.) trees from the same clone were supplied with different, but low, amounts of plant available sulfate in the soil (9.7-18.1 milligrams per 100 grams of soil). Branches attached to the trees were enclosed in a dynamic gas exchange cuvette and analyzed for the emission of volatile sulfur compounds. Independent of the sulfate supply in the soil, H(2)S was the predominant reduced sulfur compound continuously emitted from the branches with high rates during the day and low rates in the night. In the light, as well as in the dark, the rates of H(2)S emission increased exponentially with increasing water vapor flux from the needles. Approximately 1 nanomole of H(2)S was found to be emitted per mole of water. When stomata were closed completely, only minute emission of H(2)S was observed. Apparently, H(2)S emission from the needles is highly dependent on stromatal aperture, and permeation through the cuticle is negligible. In several experiments, small amounts of dimethylsulfide and carbonylsulfide were also detected in a portion of the samples. However, SO(2) was the only sulfur compound consistently emitted from branches of spruce trees in addition to H(2)S. Emission of SO(2) mainly proceeded via an outburst starting before the beginning of the light period. The total amount of SO(2) emitted from the needles during this outburst was correlated with the plant available sulfate in the soil. The diurnal changes in sulfur metabolism that may result in an outburst of SO(2) are discussed.


Current Pretreatment/Cell Disruption and Extraction Methods Used to Improve Intracellular Lipid Recovery from Oleaginous Yeasts.
The production of lipids from oleaginous yeasts involves several stages starting from cultivation and lipid accumulation, biomass harvesting and finally lipids extraction. However, the complex and relatively resistant cell wall of yeasts limits the full recovery of intracellular lipids and usually solvent extraction is not sufficient to effectively extract the lipid bodies. A pretreatment or cell disruption method is hence a prerequisite prior to solvent extraction. In general, there are no recovery methods that are equally efficient for different species of oleaginous yeasts. Each method adopts different mechanisms to disrupt cells and extract the lipids, thus a systematic evaluation is essential before choosing a particular method. In this review, mechanical (bead mill, ultrasonication, homogenization and microwave) and nonmechanical (enzyme, acid, base digestions and osmotic shock) methods that are currently used for the disruption or permeabilization of oleaginous yeasts are discussed based on their principle, application and feasibility, including their effects on the lipid yield. The attempts of using conventional and "green" solvents to selectively extract lipids are compared. Other emerging methods such as automated pressurized liquid extraction, supercritical fluid extraction and simultaneous in situ lipid recovery using capturing agents are also reviewed to facilitate the choice of more effective lipid recovery methods.


Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.
Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life. Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment. Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)). We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.


Regulation of breast cancer resistant protein by peroxisome proliferator-activated receptor α in human brain microvessel endothelial cells.
Breast cancer resistance protein (BCRP/ABCG2), an ATP-binding cassette (ABC) membrane-associated drug efflux transporter, is known to localize at the blood-brain barrier (BBB) and can significantly restrict xenobiotic permeability in the brain. The objective of this study is to investigate the regulation of BCRP functional expression by peroxisome proliferator-activated receptor alpha (PPARα), a ligand-activated transcription factor primarily involved in lipid metabolism, in a cerebral microvascular endothelial cell culture system (hCMEC/D3), representative of human BBB. We demonstrate that PPARα-selective ligands (i.e., clofibrate, GW7647) significantly induce BCRP mRNA and protein expression in a time- and concentration-dependent manner, whereas pharmacological inhibitors (i.e., MK886, GW6471) prevent this induction. Using [(3)H]mitoxantrone, an established BCRP substrate, we observe a significant reduction in its cellular accumulation by monolayer cells treated with clofibrate, suggesting increased BCRP efflux activity. In addition, we show a significant decrease in BCRP protein expression and function when PPARα is down-regulated by small interfering RNA. Applying chromatin immunoprecipitation and quantitative real-time polymerase chain reaction, we observe that clofibrate treatment increases PPARα binding to the peroxisome proliferator response element within the ABCG2 gene promoter. This study provides the first evidence of direct BCRP regulation by PPARα in a human in vitro BBB model and suggests new targeting strategies for either improving drug brain bioavailability or increasing neuroprotection.


[Diabetes insipidus following the rupture of cerebral aneurysms--with special reference to preoperative cases].
The authors reported 4 cases with preoperative diabetes insipidus (DI) following the rupture of cerebral aneurysms. In addition, the incidence of preoperative DI and the mechanisms as the cause of DI in cases with the ruptured cerebral aneurysms were also discussed. In the 114 cases underwent clipping of the ruptured cerebral aneurysms more than 14 days after the bleed, only 4 cases (3.5%) developed DI preoperatively. The time period between last subarachnoid hemorrhage and the onset of DI ranged from 23 to 35 days. This delayed onset of DI after subarachnoid hemorrhage was different from previous reports. A few of mechanisms had been suggested through which DI could be brought about in cases with cerebral aneurysm. That is; direct compression to the hypothalamo-hypophysial system by a giant aneurysm. compression and destruction of the hypothalamus by a hematoma or hemorrhage, ischemic changes in the hypothalamo-hypophysial system caused by vasospasm. In the present 4 cases, no had giant aneurysms. Although CT scan revealed subarachnoid clot in all cases, it did not show apparent hypothalamic lesion except case 1 who had small hematoma in the region of the basal frontal interhemispheric fissure. Symptomatic vasospasm was recognized in 3 cases. However, one of them had mild vasospasm restricting in M1 portion and case 3 was free of any vasospasm. Furthermore, the time period from the identification of vasospasm until the onset of DI ranged from 2 to 3 weeks. These results suggest that another mechanism in addition to a hemorrhage, hematoma and/or vasospasm may exist.(ABSTRACT TRUNCATED AT 250 WORDS)


A compact torsional reference device for easy, accurate and traceable AFM piconewton calibration.
The invention of the atomic force microscope led directly to the possibility of carrying out nanomechanical tests with forces below the nanonewton and the ability to test nanomaterials and single molecules. As a result there is a pressing need for accurate and traceable force calibration of AFM measurements that is not satisfactorily met by existing calibration methods. Here we present a force reference device that makes it possible to calibrate the normal stiffness of typical AFM microcantilevers down to 90 pN nm(-1) with very high accuracy and repeatability and describe how it can be calibrated traceably to the International System of Units via the ampere and the metre, avoiding in that way the difficulties associated with traceability to the SI kilogram. We estimate the total uncertainty associated with cantilever calibration including traceability to be better than 3.5%, thus still offering room for future improvement.


Improvement of neurological recovery in the insomnia rats by Warming Yang Strategy through targeting SIRT4 by inhibiting inflammation and apoptosis.
The incidence rate of insomnia is increasing, but the mechanism of it remains unclear. Warming Yang Strategy (WY) is a kind of Traditional Chinese Medicine, and it is proved to be effective in treating insomnia patients. The insomnia animal was established with chlorophenylalanine (PCPA). Morris water maze and open field test were performed to evaluate the influence of WY on the neurological recovery of insomnia rats. TUNEL staining and flow cytometry were used to measure apoptosis level. WY promoted the neurological recovery in the insomnia rats through Morris water maze and open field test evaluation. The increase of γ-aminobutyric acid, dopamine, 5-hydroxytryptamine, and norepinephrine caused by WY was suppressed by siSIRT4. The decrease of apoptosis and inflammation factors expression induced by WY was promoted by siRNA-SIRT4 (siSIRT4). WY improve neurological recovery in the insomnia rats through SIRT4 by inhibiting inflammation and apoptosis. This research might provide a novel insight for the prevention and treatment of insomnia through targeting SIRT4.


Effects of a Worksite-Based Self-Management Program in Traditional Retail Market Workers: Longitudinal Associations with Metabolic Parameters.
(1) Background: This study explored the effects of a worksite-based self-management program on metabolic parameters in traditional retail market workers during a 3-year period. (2) Methods: Seventy traditional retail market workers who completed 3 years of follow-up were included in this study. The worksite-based self-management program was developed to help traditional retail market workers manage metabolic parameters themselves based on the following content: (I) using a metabolic syndrome action checklist, (II) counseling, (III) creating improvement action plans, and (IV) evaluating implemented improvements. (3) Results: The rates of implemented improvements showed success. Fasting blood sugar and triglycerides showed yearly reductions from baseline for 3 years, which eventually led to a decreased metabolic syndrome score and maintenance of metabolic parameters in the normal range for 3 years. (4) Conclusions: A worksite-based self-management program on metabolic parameters in traditional retail market workers was effective. It improved their intention to self-assess and cope their health problems and eventually decreased their metabolic syndrome score. It should be considered for the primary prevention of metabolic syndrome among traditional retail market workers.


Angiotensin-converting enzyme insertion/deletion polymorphism associated with allergic rhinitis susceptibility: evidence from 1410 subjects.
Whether the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene increases susceptibility to allergic rhinitis (AR) is still undetermined. Therefore, this meta-analysis was performed to systematically assess the possible association between them. The OVID, Medline, Embase, Web of Science, CNKI and Wangfang databases were searched to identify the eligible studies focusing on the association between ACE I/D polymorphism and susceptibility to AR. A total of 1410 subjects from six studies were subjected to meta-analysis. In the overall analysis, ACE I/D polymorphism had a statistically significant association with increased AR risk under all genetic models (p<0.05). In the subgroup analysis by ethnicity, significant elevated AR risks were associated with ACE I/D polymorphism in Asians under all genetic models (p<0.05) and in Caucasians under under allele contrast, homozygous comparison and recessive models (p<0.05). In the subgroup analysis by age, ACE I/D polymorphism was associated with significant elevated risks of AR in adults (p<0.05) but not in children (p>0.05) under all genetic models. The ACE I/D polymorphism may be a risk factor for AR and studies with large sample size and representative population are warranted to verify this finding.


Timing of neurodegeneration and beta-amyloid (Abeta) peptide deposition in the brain of aging kokanee salmon.
Brains of kokanee salmon (Oncorhynchus nerka kennerlyi) in one of four reproductive stages (sexually immature, maturing, sexually mature, and spawning) were stained with cresyl violet and silver stain to visualize neurodegeneration. These reproductive stages correlate with increasing somatic aging of kokanee salmon, which die after spawning. Twenty-four regions of each brain were examined. Brains of sexually immature fish exhibited low levels of neurodegeneration, whereas neurodegeneration was more marked in maturing fish and greatest in spawning fish. Neurodegeneration was present in specific regions of the telencephalon, diencephalon, mesencephalon, and rhombencephalon. Pyknotic neurons were observed in all regions previously reported to be immunopositive for A beta. Regions that did not exhibit neurodegeneration during aging included the magnocellular vestibular nucleus, the nucleus lateralis tuberis of the hypothalamus, and Purkinje cells of the cerebellum, all of which also lack A beta; perhaps these regions are neuroprotected. In 14 of 16 brain areas for which data were available on both the increase in A beta deposition and pyknosis, neurodegeneration preceded or appeared more or less simultaneously with A beta production, whereas in only two regions did A beta deposition precede neurodegeneration. This information supports the hypothesis that A beta deposition is a downstream product of neurodegeneration in most brain regions. Other conclusions are that the degree of neurodegeneration varies among brain regions, neurodegeneration begins in maturing fish and peaks in spawning fish, the timing of neurodegeneration varies among brain regions, and some regions do not exhibit accelerated neurodegeneration during aging.


[Clinical analysis of 70 cases of polycythemia vera].
To analyze the clinical characteristics and laboratory data, treatment and prognosis of polycythemia vera (PV) and provide evidence for screening of high-risk population and looking for measures to reduce complecations. A retrospective study was performed among 70 patients with PV from May 2005 to May 2014, 43 males and 27 females, aged (56.6±13.1) to collect the data about characteristics, laboratory data, myelogram chromosome, karyotypes, BCR/ABL and JAK2 V617F genes, as well as lactate dehydrogenase (LDH) and so on. At diagnosis, there were 42 cases (60.00%) had symptoms, 25 cases (35.71%) had thrombosis and embolism. Hemorrhage occurred in 3 cases (4.29%), splenomegaly in 48 cases (68.57%), hepatomegaly in 7 cases (10.00%). The average hemoglobin at diagnosis was 195.17 g/L, the white blood cells count was 10.12×10(9)/L, the platelet count was 295×10(9)//L. The chromosome karyotypes were all normal. The positive percentage of JAK2 V617F mutation was 87.69% (57/65). The disease outcomes were myelofibrosis for 3 paitents, death from ineffective treatment after transforming to myelofibrosis and then biphenotype acute leukemia for 1 patient, and death from cardiorespiratory failure for 2 patients. The level of erythropoietin in JAK2 V617F mutated group were significantly lower than those in wild-type JAK2 V617F group (P<0.05). The level of hemoglobin and platelet counts in JAK2 V617F mutated group were significantly higher than those in wild-type JAK2 V617F group (both P<0.05). PV is one of meyloproliferation neoplasm, characterized by abnormally increasing blood cells, thrombosis and transforming to other myeloproliferative neoplasms.


An overview of practical issues in the diagnosis of gastroenteropancreatic neuroendocrine pathology.
Although somewhat uncommon, neuroendocrine tumors of the gastrointestinal tract and pancreas have come under scrutiny in recent times. With advances in imaging techniques, more of these tumors are being removed and sent for pathologic evaluation. It is important for the diagnostic pathologist to be aware of recent developments in this field. This overview focuses on nomenclature/terminology, classification, practical issues related to recent developments in immunohistochemical markers that aid diagnosis and may relate to prognosis, and molecular advances. Currently available literature and personal experience in the field of neuroendocrine pathology. The preferred terminology is neuroendocrine/tumor/carcinoma and it is recommended that the World Health Organization classification be used, taking note of the site variations that may occur. A large number of immunohistochemical markers are available but a core panel that is relevant to the site should be used. Cytokeratin 19 positivity is an independent marker of aggressive behavior in pancreatic neuroendocrine tumors. Gastrointestinal neuroendocrine tumors arise via the CpG island methylator phenotype pathway, whereas their pancreatic counterparts arise as a result of chromosomal instability. The MEN1 gene is implicated in both syndromic and sporadic forms of these tumors.


Bisphosphonates: bone, muscle and joint pain.
1) Comparative trials and reports by healthcare professionals show that severe and sometimes incapacitating muscle, joint and bone pain can occur days, months or years after beginning long-term oral bisphosphonate therapy. Patients treated for osteoporosis are particularly at risk; 2) This type of pain affects between 2% and 5% of patients, especially those taking an oral bisphosphonate once a week; 3) The role of a bisphosphonate should be considered when a patient presents with musculoskeletal pain. Discontinuation of bisphosphonate therapy can be tried and may represent a better option than escalation of analgesic therapy.


[Influence of some topical antibiotics and FGF2, EGF and rhGH on the biological characteristics of fibroblasts in vitro].
To investigate the influence of some topically used antibiotics (amikacin, gentamicin, chloromycetin and sulfamylon), basic fibroblast growth factor (FGF2) , epithelial growth factor (EGF) and recombinant human growth hormone (rhGH) on the growth of fibroblasts in vitro. Fibroblasts were cultured and passaged. The cultured cells were then divided into control (routine culture of fibroblasts), amikacin (amikacin in respective dose of 0.021, 0.210, 2.100 mg/L), gentamicin (in respective dose of 5, 50, 500 mg/L) , chloromycetin (in respective dose of 0.01, 0.10, 1.00 mg/L), sulfamylon (in respective dose of 5, 10 g/L), FGF2 (2400 U/ml), EGF (2000 U/ml) and rhGH (0.016, 0.160, 1.600 g/L) groups. After the above agents were added to the culture medium respectively, the proliferation of the cultured fibroblasts was determined with MTT method, and the result was expressed as A (absorption) value. The cell cycle was determined with flow cytometry and the morphology of the cells was observed with inverted microscope. (1) MTT method: The A value of fibroblasts cultured with amikacin, gentamicin, chloromycetin and sulfamylon in various doses was obviously lower than that in control group (0.4553 +/- 0.0217, P < 0.05 or 0.01) , and the A value of sulfamylon group was the lowest in two doses (0.1013 +/- 0.0011 for 5 g/L and 0.0950 +/- 0.0041 for 10 g/L, P < 0.01). On the other hand,the A value in FGF2 and rhGH group(0.016 g/L) was much higher than that in the control (P < 0.05). However,theA value in EGF (both doses) and rhGH groups (0.160, 1.600 g/L) was close to that in control (P > 0.05). (2) Cell cycle determination: The proliferation index (PI) of fibroblasts cultured with amikacin in dose of 0.210 mg/L showed no difference compared to that in control (9.63 +/- 0.45)%, (P > 0.05). But the PI of fibroblasts cultured with FGF2, EGF and rhGF in dose of 0.016 g/L was increased significantly (46.76 +/- 2.33)%, (42.30 +/- 1.41)%, and (13.29 +/- 0.47)%, respectively, (P < 0.05 or 0.01). (3) Histological examination of the cells: The number of fibroblasts in elongated or spindle shape was larger, showing a blur contour but high transparency in control as well as in EGF and rhGH groups (both 0.160 and 1.600 g/L doses groups). The number of cells was lower in amikacin, gentamicin, chloromycetin and sulfamylon groups with sharp but irregular contour and lower transparency, and more granule-like materials and vacuoles in the cytoplasm. The cells in the FGF2 and rhGH (in dose of 0.016 g/L) groups exhibited dense with even distribution and slender or spindle shape and with more mitotic figures but blur contour and high transparency. Different kinds of the topically used therapeutic agents for burn wounds exert different influence on the biological characteristics of fibroblasts in vitro. The topically used agents for burn wounds should be carefully selected so that wound healing will be promoted and scar formation inhibited.


Atmospheric Methyl Bromide (CH3Br) from Agricultural Soil Fumigations.
The treatment of agricultural soils with CH(3)Br (MeBr) has been suggested to be a significant source of atmospheric MeBr which is involved in stratospheric ozone loss. A field fumigation experiment showed that, after 7 days, 34 percent of the applied MeBr had escaped into the atmosphere. The remaining 66 percent should have caused an increase in bromide in the soil; soil bromide increased by an amount equal to 70 percent of the applied MeBr, consistent with the flux measurements to within 4 percent. Comparison with an earlier experiment in which the escape of MeBr to the atmosphere was greater showed that higher soil pH, organic content and soil moisture, and deeper, more uniform injection of MeBr may in combination reduce the escape of MeBr.


Allelic loss at chromosome 11q13 alters FGF3 gene expression in a human breast cancer progression model.
Identification of markers with the potential to predict tumorigenic behavior is important in breast cancer, due to the variability in clinical disease progression. Genetic alterations during neoplastic progression may appear as changes in total DNA content, single genes, or gene expression. Oncogenic alterations are thought to be prognostic indices for patients with breast cancer. Breast cancer deregulation can occur in the normal cellular process and can be measured by microsatellite instability (MSI)/loss of heterozygosity (LOH). Chromosome 11 is unique in this respect, as three regions of MSI/LOH have been identified (11p15-p15.5, 11q13-q13.3 and 11q23-q24). There are many important families of genes, such as FGF, CCND1, FADD, BAD and GAD2, that are located on chromosome 11 and these play a crucial role in breast cancer progression. Among them, different members of the fibroblast growth factor (FGF) family of genes are clustered around human chromosome 11q13 amplicon, which are constantly altering during breast cancer progression. Therefore, in this study, locus 11q13 and FGF3 gene (11q13) function were investigated in a radiation and estrogen breast cancer model induced by high-LET (α-particle) radiation and estrogen exposure. To assess the effect of ionizing radiation and estrogen at chromosome 11q13 loci and the subsequent role of FGF3 gene expression, various microsatellite markers were chosen in this region, and allelic loses (~20-45%) were identified by PCR-SSCP analysis. Results showed an increase in FGF3 protein expression and a 6- to 8-fold change in gene expression of FGF3 and associated genes. These deregulations could be utilized as an appropriate target for therapeutic intervention in breast cancer.


Estimation of the transport and carboxylation components of the intracellular limitation to leaf photosynthesis.
A model is presented which enables gas exchange data to be used to partition the intracellular resistance to leaf photosynthesis into carboxylation and transport components. A basic assumption is that the over-all kinetics of the carboxylation reaction fit the Michaelis-Menten equation.The model was tested for cotton (Gossypium hirsutum L., var. Deltapine Smoothleaf), where photorespiration was suppressed by using gas mixtures containing less than 1.5% oxygen. It was concluded that the transport resistance formed the major component of the intracellular resistance for the plants studied. However, in some cases the major intracellular factor limiting photosynthesis, at an ambient CO(2) concentration of 600 ng cm(-3), was the carboxylation system, which was close to saturation.


Anatomic study of full facial and scalp allografts without cutaneous facial scars.
Conventional reconstructive procedures for face and scalp reconstruction fall short of aesthetic and functional goals because of the unique quality and quantity of facial and scalp soft tissue. The purpose of this cadaver study was to demonstrate the feasibility of a flap design for full face and scalp composite tissue allotransplantation, without cutaneous facial scars. Six fresh human cadavers were dissected with sagittal scalp and mucosal incisions for full face and scalp harvest without cutaneous facial incisions. Sub-galeal and sub-SMAS dissection allowed for inclusion of the external carotid and internal jugular systems. Time of facial-scalp flap harvesting, length of the arterial and venous pedicles, length of sensory nerves (that were included in the facial flaps) and approximate surface area of the flaps were measured. Three of six flaps were transferred to recipient cadavers and the time of transfer was recorded. As a proof of concept, the external carotid arteries of one of six cadavers was flushed to remove clots and perfused with a radio-opaque latex polymer, Microfil (Flow Tech Inc.), to study flap perfusion by X-ray imaging. In the donor cadaver, the mean harvesting time of the total facial-scalp flap was 105 ± 19 minutes. The mean length of the supraorbital, infraorbital, mental and great auricular nerves were 1.3 ± 0.2, 1.3 ± 0.1, 1.3 ± 0.1, and 4.8 ± 0.6 cm, respectively. The mean length of the external carotid artery and external jugular vein were 8.7 ± 0.3 and 9.2 ± 0.4 cm, respectively. The approximate area of the harvested flap was 1063 ± 60 cm(2). In preparation for full face and scalp allotransplantation in humans, this study has demonstrated the feasibility of a full face and scalp flap without visible facial incisions.


Multiple-dose pharmacokinetics and in vitro antimalarial activity of dapsone plus pyrimethamine (Maloprim) in man.
1. The multiple-dose kinetics of dapsone (DDS), its major metabolite monoacetyldapsone (MADDS) and pyrimethamine (PYR) were studied in six healthy adult male volunteers following weekly administration of Maloprim (100 mg DDS plus 12.5 mg PYR). 2. After the last maintenance dose of Maloprim, the following kinetic parameters (mean values) were determined for DDS and PYR, respectively: maximum plasma concentration (Cmax) = 1,134 and 116 ng ml-1; elimination half-life (t1/2) = 23 and 105 h; plasma clearance (CL) = 37.6 and 15.9 ml h-1 kg-1 and apparent volume of distribution (Vss) = 1.20 and 2.29 l kg-1. The mean t1/2 of MADDS was 22 h. 3. The mean whole blood to plasma (B/P) and erythrocyte to plasma (E/P) concentration ratios for DDS were 1.04 and 1.09, respectively. MADDS had a B/P ratio of 0.69 and an E/P ratio of 0.33. The B/P and E/P ratios for PYR were 0.98 and 0.54, respectively. 4. The drug combination was assessed in vitro by measuring inhibition of re-invasion of two Plasmodium falciparum isolates grown in the presence of volunteers' sera. The chloroquine (CQ)- and PYR-sensitive FC-27 isolate was completely inhibited by the sera but the drug combination was ineffective against the CQ- and PYR-resistant K1 strain. The in vitro findings suggest that Maloprim may not be effective against strains of P. falciparum with a high level of resistance to pyrimethamine.


Pyrazolyl-functionalized 2-methylimidazolium-based ionic liquids and their palladium(II) complexes as recyclable catalysts.
A series of pyrazolyl- and 3,5-dimethylpyrazolyl-functionalized 2-methylimidazolium-based salts have been prepared through neat reactions of 1-pyrazolylmethylene-2-methylimidazole and 1-(3,5-dimethylpyrazolylmethylene)-2-methylimidazole with alkyl or polyfluoroalkyl iodides or 1-bromohexane, followed by anion exchange with LiN(SO2CF3)2 or KPF6. Their thermal properties were determined by DSC and TGA. Most of the bis(trifluoromethanesulfonyl)amide salts are room temperature ionic liquids. The influence of anions and of the structural variation in the 2-methylimidazolium-based cations on the physicochemical properties is discussed. These salts reacted easily with palladium(II) chloride to generate mononuclear palladium ionic liquid complexes. The catalytic activity and recyclability of the palladium complexes in the corresponding ionic liquids were preliminarily examined using Heck, Suzuki and Sonogashira cross-coupling reactions in the absence of phosphine ligands.


Isolation and characterization of a novel Pseudomonas sp., strain YG1, capable of degrading pyrrolidine under denitrifying conditions.
A denitrifying bacterium, strain YG1, capable of degrading pyrrolidine under denitrifying conditions, was isolated. On the basis of phenotypic and phylogenetic characteristics, it was identified as a member of the genus Pseudomonas. During the anaerobic degradation of pyrrolidine, YG1 reduced a stoichiometric amount of nitrate to nitrogen gas, demonstrating that the degradation of pyrrolidine is coupled with respiratory nitrate reduction. YG1 also degraded pyrrolidine with a higher degradation rate under aerobic conditions than under denitrifying conditions.


Evaluation of condensed molasses fermentation solubles as a nonprotein nitrogen source for ruminants.
Condensed molasses fermentation solubles (CMS), an effluent from the production of lysine, was evaluated as a nonprotein nitrogen supplement for ruminants by measuring the availability of its nitrogen to rumen microorganisms grown in batch cultures and by comparing CMS to urea as a source of supplemental nitrogen for growing cattle. In vitro dry matter digestion studies showed that, with 1 ml or less of rumen inoculum, microbial digestion was enhanced more (P less than .05) by the addition of CMS than by the addition of urea to 100 mg of cellulose. These stimulatory effects of CMS were absent when either the amount of inoculum (5.0 ml) or cellulose (250 mg) was increased and when wheat straw or alfalfa replaced cellulose as the substrate. Growth rate and feed intake for cattle fed a high-cob/cracked-corn diet containing 2.5 or 5.0% CMS were lower (P less than .05) than for cattle fed the control diet containing urea. Digestibility of dry matter, crude protein, neutral detergent fiber and acid detergent fiber were reduced (P less than .05) by the addition of CMS. Addition of CMS also decreased feed utilization, although the differences were not statistically significant. In conclusion, the nitrogen in CMS was available to rumen microorganisms growth in batch culture; however, CMS was not satisfactory as a substitute for all the urea in a diet for growing cattle containing over 45% of dietary N from the supplemental N source.


Evolution of the Cinnamyl/Sinapyl Alcohol Dehydrogenase (CAD/SAD) gene family: the emergence of real lignin is associated with the origin of Bona Fide CAD.
Lignin plays a vital role in plant adaptation to terrestrial environments. The cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and might have contributed to the lignin diversity in plants. To investigate the evolutionary history and functional differentiation of the CAD gene family, we made a comprehensive evolutionary analysis of this gene family from 52 species, including bacteria, early eukaryotes and green plants. The phylogenetic analysis, together with gene structure and function, indicates that all members of land plants, except two of moss, could be divided into three classes. Members of Class I (bona fide CAD), generally accepted as the primary genes involved in the monolignol biosynthesis, are all from vascular plants, and form a robustly supported monophyletic group with the lycophyte CADs at the basal position. This class is also conserved in the predicted three-dimensional structure and the residues constituting the substrate-binding pocket of the proteins. Given that Selaginella has real lignin, the above evidence strongly suggests that the earliest occurrence of the bona fide CAD in the lycophyte could be directly correlated with the origin of lignin. Class II comprises members more similar to the aspen sinapyl alcohol dehydrogenase gene, and includes three groups corresponding to lycophyte, gymnosperm, and angiosperm. Class III is conserved in land plants. The three classes differ in patterns of evolution and expression, implying that functional divergence has occurred among them. Our study also supports the hypothesis of convergent evolution of lignin biosynthesis between red algae and vascular plants.


Cocktail of chemical compounds robustly promoting cell reprogramming protects liver against acute injury.
Tissue damage induces cells into reprogramming-like cellular state, which contributes to tissue regeneration. However, whether factors promoting the cell reprogramming favor tissue regeneration remains elusive. Here we identified combination of small chemical compounds including drug cocktails robustly promoting in vitro cell reprogramming. We then administrated the drug cocktails to mice with acute liver injuries induced by partial hepatectomy or toxic treatment. Our results demonstrated that the drug cocktails which promoted cell reprogramming in vitro improved liver regeneration and hepatic function in vivo after acute injuries. The underlying mechanism could be that expression of pluripotent genes activated after injury is further upregulated by drug cocktails. Thus our study offers proof-of-concept evidence that cocktail of clinical compounds improving cell reprogramming favors tissue recovery after acute damages, which is an attractive strategy for regenerative purpose.


Effect of obesity on cardiac function in children and adolescents: a review.
Increases in cardiac mass, ventricular dimensions, and stroke volume are typically observed in obese adults, accompanied by evidence of diminished ventricular systolic and diastolic function. Given sufficient severity and duration of excessive body fat, signs of overt congestive heart failure may ensue (cardiomyopathy of obesity). This review of cardiac findings in obese children and adolescents indicates similar anatomic features as well as early subclinical findings of ventricular dysfunction. However, cardiac functional reserve (cardiovascular fitness) appears to be preserved even in those with morbid levels of obesity. Key pointsExcessive body fat increases the work output of the heart.Longstanding increases in heart work result in abnormalities of heart function.Early findings of such changes can be observed in adolescents with severe obesity.


Neurogenesis in the subventricular zone following transcranial magnetic field stimulation and nigrostriatal lesions.
Neurogenesis continues at least in two regions of the mammalian adult brain, the subventricular zone (SVZ) and the subgranular zone in hippocampal dentate gyrus. Neurogenesis in these regions is subjected to physiological regulation and can be modified by pharmacological and pathological events. Here we report the induction of neurogenesis in the SVZ and the differentiation after nigrostriatal pathway lesion along with transcranial magnetic field stimulation (TMFS) in adult rats. Significant numbers of proliferating cells demonstrated by bromodeoxyuridine-positive reaction colocalized with the neuronal marker NeuN were detected bilaterally in the SVZ, and several of these cells also expressed tyrosine hydroxylase. Transplanted chromaffin cells into lesioned animals also induced bilateral appearance of subependymal cells. These results show for the first time that unilateral lesion, transplant, and/or TMFS induce neurogenesis in the SVZ of rats and also that TMFS prevents the motor alterations induced by the lesion.


Relative validity and reproducibility of a 14-item semi-quantitative food frequency questionnaire for cardiovascular prevention.
Dietary habits play a major role in cardiovascular disease risk but few simple nutrition assessment tools are available for clinical practice. We developed a 14-item food frequency questionnaire to evaluate dietary patterns in relation with coronary risk in a French population. This food frequency questionnaire gave different scores of intake: saturated fatty acids (six questions), mono-unsaturated fatty acids, Omega-3 and Omega-6/Omega-3 polyunsaturated fatty acids (five questions), and fruits and vegetables (three questions). Validity was assessed against a 7-day dietary history (n = 49 subjects) and against biomarkers (n = 181). The food frequency questionnaire was also administered twice with an interval of 15 days to evaluate its reproducibility (n = 20). Validity against dietary history was assessed with Spearman correlation coefficients which ranged from 0.47 (fruits and vegetables) to 0.63 (polyunsaturated fatty acids/saturated fatty acids) (all P < 0.05), with a mean value of 0.54. On average, 39% of the subjects were classified in the same quartile with the food frequency questionnaire and the dietary history and 84% in the same or adjacent quartile. Biomarker-based validity using Spearman correlation coefficients varied from 0.21 (saturated fatty acids) to 0.53 (Omega-3 polyunsaturated fatty acids) (all P < 0.05), with a mean value of 0.35. On average, 37% of the participants were classified in the same quartile with the food frequency questionnaire and the corresponding biomarkers and 73% in the same or adjacent quartile. Reproducibility assessed by the intraclass correlation coefficient ranged from 0.71 (mono-unsaturated fatty acids) to 0.93 (global score), with a mean value of 0.81. We validated a short food frequency questionnaire for dietary pattern assessment in coronary prevention.


Helicobacter pylori in Barrett's esophagus and in normal or inflamed esophageal mucosa: a retrospective study.
To investigate on the presence and significance of Helicobacter pylori (Hp) in Barrett's mucosa, esophageal biopsy specimens from 34 patients with columnar-lined epithelium were retrospectively examined. The incidence of colonization was compared with that observed in a control group of 76 subjects with normal esophageal mucosa or moderate esophagitis. Three of the 34 Barrett's specimens were Hp-positive and only 1 of these showed evidence of inflamed mucosa (p = NS). We do not find in this study any evidence to support the existence of association between Hp and Barrett's esophagus or esophageal inflammation. The presence of Hp in antral mucosa of all positive cases suggest the possibility that esophageal colonisation might merely be a consequence of reflux from the gastric antrum.


Implementation of the Better Jobs Better Care demonstration: lessons for long-term care workforce initiatives.
Better Jobs Better Care (BJBC) was a long-term care workforce demonstration that sought to improve recruitment and retention of direct care workers by changing public policy and management practice. The purpose of this article is to document and assess BJBC's implementation, analyze factors affecting implementation, and draw lessons from it for other long-term care workforce initiatives. We analyzed qualitative data from project work plans and progress reports, and notes from telephone and in-person interviews with project staff, coalition stakeholders, and state policy experts. We abstracted the data, categorized it, and summarized it by state in matrices for analysis. The five BJBC projects did implement their demonstration plans. Factors that affected project implementation included having demonstration resources; strong, stable leadership; strong coalitions that included key stakeholders; a neutral lead agency; clear goals; effective process; and a favorable state history and context. BJBC demonstrated that recruitment and retention is a long-term care industry problem, not just a nursing home problem. Future initiatives should: recognize that workforce policy and management practice change is difficult and takes time, obtain funding, develop strategies specific to the state history and context, engage key stakeholders, and develop relationships among stakeholders.


Mortality patterns during a war in Guinea-Bissau 1998-99: changes in risk factors?
The crude mortality rate of the whole population and the mortality of children <5 years of age are the common indicators of the severity of a complex emergency situation. However, these indicators rarely take account of differences in socioeconomic conditions and vulnerability. We followed a population in Guinea-Bissau, which fled when fighting took place in the capital during the war in 1998-99. The population stayed close to the area of conflict and returned as soon as a cease-fire was negotiated. A peace treaty was signed after half-a-year. The following 6 months was a period of returning and re-settlement, even though two outbreaks of fighting occurred. In the first half-year the mortality rate was 78% [mortality ratio (MR) = 1.78; 95% CI 1.61-1.97] increased and mortality for children <5 years of age doubled (MR = 2.07; 95% CI 1.79-2.38). In the last 6 months of the war, mortality was slightly increased for children and not at all for the total population. In the first half-year, households living in better houses and having members with schooling were less affected. In the 're-settlement' period two inequalities emerged; the largest ethnic group, Pepel, continued to have high mortality when the mortality of other groups declined; likewise girls continued to have an elevated mortality whereas mortality of boys declined. Whereas specific 'free' interventions reduced social inequalities for the groups affected, for the total population health-inequalities were slightly amplified during the war. Once the population returned to their urban homes, mortality fell to pre-war levels even though some fighting continued, limited humanitarian aid was available and the pre-war infra-structure had not been re-established.


A serological comparison of complement fixation reactions using Brucella abortus and B. melitensis antigens in B. abortus infected cattle.
Brucella abortus and B. melitensis antigens were used in parallel on the National Standard Brucella abortus antiserum and on field sera coming from cattle where practically exclusively B. abortus biotypes 1 and 2 have been isolated over the last 11 years. With the National Standard serum the titres to B. melitensis were consistently lower than those to B. abortus antigen. Most were 1 dilution (twofold) lower. Although a similar trend was seen with the field sera, there were 7/346 sera which had twofold or higher titres to B. melitensis antigen. Although this may be due to the vagaries of the test it also warrants closer investigation of the animals concerned to see whether M-antigen predominant Brucella biotypes are possibly present. The use of the dual antigens could identify herds which are infected only with A-antigen predominant brucellae but would not be reliable for classifying individual animals.


Avoiding inappropriate spine surgery in a patient with major cardiac comorbidities.
We as spine surgeons increasingly need to carefully screen our own patients for major medical/cardiac comorbidities to determine if they are candidates for spine surgery. Our medical/cardiac colleagues rarely understand how long anti-platelet aggregates and non-steroidal anti-inflammatories (NSAIDs) have to be stopped prior to spine operaeitons, and when it is safe for them to be reinstated. A patient over 65 years of age, presented with 6 months of increased bilateral lower extremity sciatica, and 2-block neurogenic claudication. The MR scan showed moderate to severe lumbar stenosis L2-S1 with grade I L4-L5 spondylolisthesis, and multiple bilateral synovial cysts. Nevertheless, his neurological examination was normal. Further, he had > 5 stents placed within the last five years, and had undergone cardiac surgery two years ago requiring placement of a bovine aortic valve, and resection of a left ventricular wall aneurysm. He was also still on full dose Aspirin (325 mg/day), and Clopidogrel (75 mg po bid). Notably, 3 prior spinal surgeons (neurosurgery/orthopedics) had recommended multilevel lumbar laminectomy with instrumented fusions (e.g. including multilevel transforaminal lumbar interbody fusions (TLIF)). Despite multilevel L2-S1 stenosis, Grade I L4-L5 spondylolisthesis, and multilevel bilateral synovial cysts, the patient's normal neurological examination and multiple cardiac comorbidities (i.e. requiring continued full-dose ASA/Clopidogrel) precluded, in my opinion, offering surgical intervention. Rather, I referred the patient to neurology for conservative management. What would you have done?


[Cell-mediated immunity and delayed hypersensitivity study in splenectomy patients: a comparative evaluation between IFN-gamma and skin tests].
The authors of this paper attempt to indicate a feasible, easy-to-use and inexpensive instrument for daily assessing and monitoring of splenectomized subjects to see if they are immunocompromised. Skin tests which are considered easy and inexpensive, may be useful for immunological investigation if their effectiveness is considered equal to that of more difficult and expensive methods. They have also assessed the effectiveness of ST in the study of specific cell-mediated immunity in general and also in cases of delayed hypersensibility, comparatively to serum IFN gamma dosage. The latter is produced by Th1 lymphocytes and Natural Killer cells and is considered a reasonable indicator of cell-mediated immunity and Th1-related delayed hypersensibility. The results of this study confirm that ST is effective in 100% of all splenectomized patients compared to positivity of 60% for the compromise of the immunocompetent system revealed by serum IFN gamma dosage in the same sample of patients. In addition, the fundamental role of other cytokines was confirmed. These include IL-2 which is produced by Th1 lymphocytes and whose lack of results in splenectomized patients are immunocompromised. This is revealed not only by IFN gamma dosage but also by ST.


Upper airway patency and nocturnal desaturation in habitual snoring and obstructive sleep apnea: pathogenesis of sleep-related breathing disorders.
Sixty patients, 53 men and 7 women, referred for excessive snoring or suspected sleep apnea syndrome were analyzed by polysomnography, Mueller maneuver, cephalometric roentgenography, and pulmonary function testing, to evaluate the contribution of static and dynamic upper airway obstruction in the pathogenesis of sleep-related breathing disorders and OSAS. Desaturation index and maximal desaturation were used in the analysis as indicators of severity of sleep-related breathing disorders. Body Mass Index, increased collapsibility at the base of the tongue by the Mueller maneuver, increased distance between hyoid and mandibular plane, and increased soft palate diameters by cephalometry as well as a decreased peak inspiratory flow by pulmonary function testing were found to be related to increased oxygen desaturation parameters. In a multivariate analysis the significant obstruction parameters could explain only 37% of the variability of maximum desaturation and 31% of the variability of desaturation index, 63 and 69%, respectively, must therefore be explained by other mechanisms. We conclude that instability of respiratory and muscular control, possibly enhanced by sleep-phase-related changes, is more important in the pathogenesis of sleep-related breathing disorders than pure anatomic narrowing of the airway.


Strength tracking using the OMNI resistance exercise scale in older men and women.
Strength tracking uses ratings of perceived exertion (RPE) as a reference value to determine changes in strength as a function of a resistance training program. The purpose of this investigation was to determine if the OMNI Resistance Exercise Scale (OMNI-RES) could be used to track training-induced strength changes in older adults. Twenty-two men (64.3 + 3.2 years) and 27 women (63.8 + 2.8 years) volunteered to participate. Subjects underwent a maximal lifting test, during which they estimated perceived exertion before and following 12 weeks of resistance exercise training. Leg press (LP), latissimus dorsi pull-down (LA), chest press (CP), leg extension (LE), leg curl (LC), arm extension (AE), and arm curl (AC) were performed. Paired samples t-tests were used to compare resistance lifted pre- and post-training at each criterion RPE (4, 6, and 8). One repetition maximum increased from pretraining to post-training (p < 0.05) for all exercises. The resistance lifted at each criterion RPE also increased (p < 0.05) during the 12-week training session for every exercise. Older adults lifted more weight at 3 criterion RPEs as their strength increased, providing an RPE-based procedure to track strength training changes using the OMNI-RES. As such, it seems that RPE from the OMNI-RES can be used to track strength in older adults.


miR-34 modulates apoptotic gene expression in Ingenol mebutate treated keloid fibroblasts.
Keloids are benign skin tumors that develop in individuals who have a positive family history of keloid disorders. Keloids are characterized by a deregulated wound‑healing process, atypical fibroblasts with extreme deposition of extracellular matrix components, particularly collagen, increased cell proliferation and associated failure of apoptosis. Recently ingenol‑mebutate has been used as a novel agent with anti‑proliferative activity on human keloids as an alternative treatment option in patients, once conventional therapies have failed. We hypothesized that microRNAs (miR/miRNA) may be involved in the balance between lesion formation and repair. A comprehensive understanding of the molecular mechanism underlying the Ingenol‑mebutate response in keloid fibroblast following Ingenol‑mebutate exposure has been established previously. Therefore, the present study analyzed changes in miRNAs and apoptotic gene regulation in Ingenol‑mebutate treated keloid fibroblast, by reverse transcription‑quantitative polymerase chain reaction and a DNA fragmentation assay. The range of upregulated miRNAs and downregulated genes encoding cell death appeared to be associated with the degree of the morphological alterations in Ingenol‑mebutate treated keloids. In particular, the upregulation of miR‑34a was detected in keloid fibroblasts during and following Ingenol‑mebutate exposure. Keloid fibroblasts that overexpressed miR‑34a showed differential expression of genes involved in the apoptotic signaling pathway such as p53. In conclusion, the Ingenol‑mebutate treatment used here was effective in reducing keloid fibroblast growth in cell culture experiments and the expression of particular miRNAs modulated the pro‑apoptotic gene expression following Ingenol-mebutate treatment.