Rapid Communication: Dietary selenium improves skeletal muscle mitochondrial biogenesis in young equine athletes.
Exercise is known to promote mitochondrial biogenesis in skeletal muscle as well as enhance mitochondrial function and efficiency in human and rodent models. These adaptations help to decrease exercise-associated production of reactive oxygen species, which can negatively affect health and performance if antioxidant mechanisms are overwhelmed. Little is known about the adaptations of mitochondria in response to exercise training in the growing horse or if supplementation with a dietary antioxidant can improve mitochondrial function. To evaluate the separate and combined effects of selenium (Se) supplementation, training, and an acute strenuous exercise bout on mitochondrial adaptations in young horses, 30 American Quarter Horse yearlings were randomly assigned to an exercise training group or a no-training group and, within each group, received either 0.1 or 0.3 mg Se/kg DM for 14 wk. The study was split into 2 phases (wk 0 to 8 and wk 9 to 14), with half of the trained horses switched to the opposite dietary treatment in Phase 2. At the end of each phase, all horses underwent a 120-min submaximal exercise test (SET; SET 1 and SET 2). Biopsies of the middle gluteal muscle were collected before and after each phase of the study and in response to each SET and analyzed for markers of mitochondrial number and function. At rest, horses receiving 0.3 mg Se/kg DM had higher citrate synthase activity ( = 0.021) than horses receiving 0.1 mg Se/kg DM, indicating higher mitochondrial content. In contrast, cytochrome oxidase (CCO) activity was not affected by dietary Se overall, but horses that were dropped from 0.3 mg Se/kg DM to 0.1 mg Se/kg DM during Phase 2 showed a decrease ( = 0.034) in integrated CCO activity from wk 9 to 14, suggesting impaired mitochondrial function. Mitochondrial enzyme activities were unaffected by an acute, strenuous exercise bout (SET 1 and SET 2). Our relatively low-intensity exercise training protocol did not appear to induce functional mitochondrial adaptations. However, elevated dietary Se may impart beneficial effects on mitochondrial biogenesis during growth and training. A more strenuous exercise training protocol should be investigated to determine the potential benefits of elevated dietary Se for elite equine athletes.


Relative insensitivity of mitochondria in hardened and nonhardened rye coleoptile cells to freezing in situ.
Mitochondria were isolated from excised coleoptiles of hardened and nonhardened winter rye (Secale cereale L. cv. Puma) seedlings which had been frozen extracellularly to different temperatures. No significant differences in the respiratory functions (ADP/O and respiratory control) were observed between mitochondria isolated from nonlethally and lethally frozen cells of both the hardened and nonhardened rye. These results suggest that mitochondria in situ can retain their normal function even after the cell was killed by the dehydrative stresses of extracellular freezing. Presumably, a different level of sensitivity to freezing stresses exists between mitochondrial and other membranous elements in the cell.


Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia.
Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.


Malaria in Wisconsin 1981-1989: a review of cases and update on chemoprophylaxis.
Malaria continues to be a significant cause of travel related morbidity and mortality for US citizens. Yet there have been no previous analyses of malaria cases reported in Wisconsin. To provide timely information to Wisconsin physicians, the authors present a review of reported malaria cases in Wisconsin for the years 1981 through 1989, and an update of current Center for Disease Control malaria chemoprophylaxis.


Biventricular repair of atrioventricular septal defect with common atrioventricular valve and double-outlet right ventricle.
The combination of an atrioventricular septal defect with a common atrioventricular junction guarded by a common valve, and double-outlet right ventricle, is a rare lesion that presents a challenge for surgical repair. This report describes our surgical approach and results in 16 patients undergoing biventricular repair for such a combination of lesions. A retrospective analysis was performed for all patients undergoing biventricular repair of atrioventricular septal defect with common atrioventricular valve and double-outlet right ventricle between 1991 and 2008. Patients with tetralogy of Fallot and common atrioventricular valve were excluded from analysis. Early and actuarial outcomes were evaluated using the chi(2) test for categorical variables and Wilcoxon rank sum for ordinal variables. The median age at operation was 16 months. Heterotaxy syndrome was present in 12 of the 16 patients (9 right isomerism and 3 left isomerism), and 6 had concurrent totally anomalous pulmonary venous connections. Primary repair was achieved in 6 patients, and 10 underwent one or more prior operations (most frequently a shunt, banding of the pulmonary trunk, or repair of the anomalous pulmonary venous connections). Enlargement of the ventricular septal defect by resection of the muscular outlet septum was required in 11 patients, in whom the ventricular septal defect emptied entirely or primarily to the inlet of the right ventricle. A conduit was placed from the right ventricle to the pulmonary arteries in 13. There was 1 death before discharge from hospital, 1 late death, and 2 episodes of heart block. Among survivors, follow-up was complete with a median follow-up of 66 months. No patient had late obstruction of the left ventricular outflow tract. The presence of heterotaxy with totally anomalous pulmonary venous connections was associated with combined mortality and significant morbidity (p = 0.008). Although technically challenging, the surgical repair can be accomplished with acceptable early results. Heterotaxy syndrome, with concurrent anomalous connections of the pulmonary veins, represented the strongest identified risk factor for death or significant complication.


Molecular weights and subunit structure of LamB proteins.
Phage lambda-receptor proteins of Escherichia coli, LamB proteins, form oligomeric aggregates to build transmembrane diffusion pores selective for maltose and maltodextrins. The molecular weights (MW) of functional oligomers as well as dissociated monomers were determined by sedimentation equilibrium analysis in homogeneous non-ionic surfactant and deuterium oxide and in 6 M guanidine-HCl, respectively. The MW of oligomers and monomers appeared as 135 600 and 45 900, respectively. Thus, functional Lamb proteins consisted of three identical subunits.


Vaccination Coverage among Prisoners: A Systematic Review.
Prison inmates are highly susceptible for several infectious diseases, including vaccine-preventable diseases. We conducted a systematic international literature review on vaccination coverage against hepatitis B virus (HBV), hepatitis A virus (HAV), combined HAV/HBV, tetanus-diphtheria, influenza, pneumococcal, and combined measles, mumps, and rubella (MMR) in prison inmates, according to the PRISMA guidelines. The electronic databases were used Web of Science, MEDLINE, Scopus, and Cinhal. No language or time limit were applied to the search. We defined vaccination coverage as the proportion of vaccinated prisoners. There were no limitations in the search strategy regarding time period or language. Of 1079 identified studies, 28 studies were included in the review. In total, 21 reported on HBV vaccine coverage (range between 16-82%); three on HAV (range between 91-96%); two studies on combined HAV/HBV (77% in the second dose and 58% in the third); three studies on influenza vaccine (range between 36-46%), one of pneumococcal vaccine coverage (12%), and one on MMR coverage (74%). We found that data on vaccination coverage in prison inmates are scarce, heterogeneous, and do not include all relevant vaccines for this group. Current published literature indicate that prison inmates are under-immunized, particularly against HBV, influenza, MMR, and pneumococci. Strengthen immunization programs specifically for this population at risk and improvement of data record systems may contribute to better health care in prisoners.


Ultrahigh Sensitivity of a Plasmonic Pressure Sensor with a Compact Size.
This study proposes a compact plasmonic metal-insulator-metal pressure sensor comprising a bus waveguide and a resonator, including one horizontal slot and several stubs. We calculate the transmittance spectrum and the electromagnetic field distribution using the finite element method. When the resonator's top layer undergoes pressure, the resonance wavelength redshifts with increasing deformation, and their relation is nearly linear. The designed pressure sensor possesses the merits of ultrahigh sensitivity, multiple modes, and a simple structure. The maximum sensitivity and resonance wavelength shift can achieve 592.44 nm/MPa and 364 nm, respectively, which are the highest values to our knowledge. The obtained sensitivity shows 23.32 times compared to the highest one reported in the literature. The modeled design paves a promising path for applications in the nanophotonic field.


Mesenchymal stromal cells for ocular surface repair.
Cornea is a transparent, robust tissue that comprises highly organized cells. Disruption of this specialized tissue can lead to scarring and subsequent blindness, making corneal damage a considerable challenge worldwide. At present, the available medical treatments are unable to address the wide range of corneal diseases. Mesenchymal stem cells (MSCs) have increasingly been investigated for their regenerative effect on ocular surface injury due to their unique ability for growth factor production, anti-inflammatory activity, immunomodulatory capacity and differentiation into multiple cell lineages. Within this review, we explore the pathogenesis of corneal disorders in response to injury and disease, and the potential for MSCs to modulate this process as a treatment. Through the review of over 25 animal studies, we investigate the common mechanisms of action by which MSCs have their effect and discuss their potential for treating and/or preventing corneal deterioration Depending on the environmental cues, MSCs can exert a potent effect on corneal wound healing through reducing opacity and vascularization, whilst promoting re-epithelialization. Whilst their mechanism is multifactorial, it seems clear that the anti-inflammatory/immunomodulatory factors they produce in response to damage are key to their control of cellular milieu and improving healing outcomes.


Novel Selenium-based compounds with therapeutic potential for SOD1-linked amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease as well as Lou Gehrig's disease, is a progressive neurological disorder selectively affecting motor neurons with no currently known cure. Around 20% of the familial ALS cases arise from dominant mutations in the sod1 gene encoding superoxide dismutase1 (SOD1) enzyme. Aggregation of mutant SOD1 in familial cases and of wild-type SOD1 in at least some sporadic ALS cases is one of the known causes of the disease. Riluzole, approved in 1995 and edaravone in 2017 remain the only drugs with limited therapeutic benefits. We have utilised the ebselen template to develop novel compounds that redeem stability of mutant SOD1 dimer and prevent aggregation. Binding modes of compounds have been visualised by crystallography. In vitro neuroprotection and toxicity of lead compounds have been performed in mouse neuronal cells and disease onset delay of ebselen has been demonstrated in transgenic ALS mice model. We have developed a number of ebselen-based compounds with improvements in A4V SOD1 stabilisation and in vitro therapeutic effects with significantly better potency than edaravone. Structure-activity relationship of hits has been guided by high resolution structures of ligand-bound A4V SOD1. We also show clear disease onset delay of ebselen in transgenic ALS mice model holding encouraging promise for potential therapeutic compounds. Our finding established the new generation of organo-selenium compounds with better in vitro neuroprotective activity than edaravone. The potential of this class of compounds may offer an alternative therapeutic agent for ALS treatment. The ability of these compounds to target cysteine 111 in SOD may have wider therapeutic applications targeting cysteines of enzymes involved in pathogenic and viral diseases including main protease of SARS-Cov-2 (COVID-19). Project funding was supported by the ALS Association grant (WA1128) and Fostering Joint International Research (19KK0214) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan.


"It cannot be boring!": Developing a measure of function for young adults accessing integrated youth services.
In Canada, the prevalence of mental health challenges is highest in young people aged 12-24. Mental health challenges frequently cause marked functional impairment. Despite this, we are unaware of any existing conceptualization and/or measures of function that has been developed from the perspective of young people. The objective of this paper is to develop a conceptual and measurement model, including a preliminary set of items, for an outcome measure of function for young adults accessing mental health services. We conducted this study in three phases. In phase 1, we conducted three focus groups to conceptualize function as a construct from the perspective of young adults. In phase 2, we co-designed a set of items with youth (n = 4) to capture the construct. In phase 3, we invited young people (n = 12) accessing mental health services to complete workbooks and participate in one of two focus groups to evaluate whether items were clear, captured function comprehensively, and were relevant. We transcribed and compiled all data to eliminate, refine and generate new items. In phase 1, a conceptual model of function was developed with three main themes: basic needs, roles and responsibilities, and social connections. In phase 2, 97 candidate items were developed, and in phase 3, a candidate pool of 50 items resulted for psychometric testing. This youth-centred conceptualization of function and preliminary item bank has the potential to advance person-centred care, outcomes, and experiences for youth seeking mental health services.


Placement of intracranial pressure monitors by non-neurosurgeons.
Maintaining adequate cerebral perfusion is important in the treatment of patients with closed head injury. Placement of an intracranial pressure (ICP) monitor is necessary to determine both ICP and the cerebral perfusion pressure and serves as a guide to the contemporary management of traumatic brain injury. Insertion of such monitoring devices historically has been performed by neurosurgeons, but others including general (trauma) surgeons have successfully inserted simple ICP monitors. The purpose of this study was to assess the efficacy of ICP monitor placement and to compare the complication rates for ICP monitor placement by general surgery residents, trauma surgeons, and staff neurosurgeons. We retrospectively reviewed the medical records of trauma patients with cerebral injury who required insertion of parenchymal ICP monitors from January 1994 to January 1999. Monitor placement was performed by staff neurosurgeons, general surgical residents, and trauma surgeons. Surgical residents received appropriate training in the placement of ICP monitors from attending trauma surgeons and neurosurgeons. Records were examined for demographic variables such as age, gender, mechanism of injury, admission Glasgow Coma Score, and Injury Severity Score. Records were also reviewed for duration of ICP monitoring and for complications (i.e., intracranial hemorrhage after monitor placement, monitor-related infection, monitor malfunction, and monitor displacement). One hundred fifty-seven monitors were placed in 146 patients with intracranial injury. Surgical residents placed 87 ICP monitors without neurosurgical or trauma attending surgeons at the bedside and 43 with immediate supervision by general surgeons or neurosurgeons. Neurosurgeons placed 26 monitors without the participation of residents, and an attending trauma surgeon placed one monitor without the involvement of a resident or a neurosurgeon. There were no major technical complications, no episodes of catheter-induced intracranial hemorrhage, and no infectious complications. These data suggest that simple ICP monitors may be inserted by non-neurosurgeons without significant problems or complications. The low complication rate associated with this procedure was similar for neurosurgeons and non-neurosurgeons. We believe that insertion of simple parenchymal ICP monitors should be considered a core skill for trauma surgeons and should be included in surgical residency training. Insertion of ICP monitors by non-neurosurgeons is a potential method of improving the care of patients with brain injury in geographic areas that are underserved by neurosurgeons.


Fibronectin induces macrophage migration through a SFK-FAK/CSF-1R pathway.
Integrins, following binding to proteins of the extracellular matrix (ECM) including collagen, laminin and fibronectin (FN), are able to transduce molecular signals inside the cells and to regulate several biological functions such as migration, proliferation and differentiation. Besides activation of adaptor molecules and kinases, integrins transactivate Receptor Tyrosine Kinases (RTK). In particular, adhesion to the ECM may promote RTK activation in the absence of growth factors. The Colony-Stimulating Factor-1 Receptor (CSF-1R) is a RTK that supports the survival, proliferation, and motility of monocytes/macrophages, which are essential components of innate immunity and cancer development. Macrophage interaction with FN is recognized as an important aspect of host defense and wound repair. The aim of the present study was to investigate on a possible cross-talk between FN-elicited signals and CSF-1R in macrophages. FN induced migration in BAC1.2F5 and J774 murine macrophage cell lines and in human primary macrophages. Adhesion to FN determined phosphorylation of the Focal Adhesion Kinase (FAK) and Src Family Kinases (SFK) and activation of the SFK/FAK complex, as witnessed by paxillin phosphorylation. SFK activity was necessary for FAK activation and macrophage migration. Moreover, FN-induced migration was dependent on FAK in either murine macrophage cell lines or human primary macrophages. FN also induced FAK-dependent/ligand-independent CSF-1R phosphorylation, as well as the interaction between CSF-1R and β1. CSF-1R activity was necessary for FN-induced macrophage migration. Indeed, genetic or pharmacological inhibition of CSF-1R prevented FN-induced macrophage migration. Our results identified a new SFK-FAK/CSF-1R signaling pathway that mediates FN-induced migration of macrophages.


Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A.
The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.


Microalgal blooms: a global issue with negative impact in Chile.
Ecological and health problems posed by microalgal blooms (red tides) occurring in the Southern part of Chile are reviewed. Out of the six human illnesses provoked by microalgal toxins, paralytic shellfish poisoning is the most important, because of its high mortality rate and the high levels of phycotoxins found in contaminated molluscs. Saxitoxin and its analogues bind to a receptor in the voltage-gated sodium channel of neural membranes. The most important toxin-producer microalgae are Alexandrium catenella and Dinophysis acuta. Phycotoxins become concentrated by filter-feeding shellfish, like Mytilus chilensis. Highly sensitive methods available for detection of microalgal toxins are analyzed.


Effects of the in vitro manipulation of stem cells: epigenetic mechanisms as mediators of induced metabolic fluctuations.
The increasing popularity of stem cells in life science research has at least two major causes. On one hand, the study of stem cells may provide insights into one of the major secrets of biology: the mechanisms of cell differentiation. On the other hand, stem cells are potentially promising tools for regenerative therapy. The understanding of how environmental stimuli are translated into phenotypic differentiation through gene expression changes and how the same stimuli at the same time may perturb the normal process of cellular differentiation, growth and maintenance is a central issue for fundamental research but is also essential for the development of efficient and safe procedures for therapeutic use. This article assembles the known facts, as pieces of a puzzle, into a coherent picture around the idea of why stem cells are so sensitive to their culture environment and what practical consequences this implies.


The complete mitochondrial genome of Chalcophora japonica chinensis Schaufuss, 1879 (Coleoptera: Buprestidae).
Chalcophora japonica chinensis Schaufuss, 1879 (Coleoptera: Buprestidae) is a common pine pest in Chongqing, Fujian, Yunnan, and other in China. The mitochondrial genome of C. japonica is 15,759 bp in size. The genome includes 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), and two ribosomal RNA genes (rRNAs). The overall GC content of the mitogenome is 32.0%. The results showed that C. japonica was most related to Chrysochroa fulgidissima, Trachys variolaris, and Agrilus mali. The full mitochondrial genome of C. japonica is now available, allowing researchers to better understand the species' genetic evolution and regulatory strategies.


The effects of exercise on lipid profile and blood glucose levels in people living with HIV: A systematic review of randomized controlled trials.
Exercise is commonly prescribed to improve lipid profile and glucose levels in people living with HIV (PLWH). This systematic review was performed in order to examine the effects of exercise interventions on lipid profile and glucose levels on PLWH. Randomized controlled trials (RCTs) investigating the effects of exercise on blood glucose, triglycerides (TG), total cholesterol (TC), HDL and LDL published up to November 2017 were reviewed. Two reviewers assessed inclusion and exclusion criteria, methodological quality and extracted the data. The PEDro scale was used to assess the quality of the included studies. Nine RCTs involving 638 PLWH met inclusion criteria. The median PEDro scale score was 5 out of 10. Three combined aerobic exercise + resistance exercise studies (AE+RE) showed improvements in blood glucose levels, one study showed improvements in HDL, one showed improvements in TG, and one showed improvements in TC. The AE only study reported improvements in HDL, while the RE only study reported improvements in TG, TC, HDL and LDL. Exercise can be effective for the improvement of some metabolic parameters, especially blood glucose and HDL. However, due to methodological issues, small number of studies and differences in exercise protocols, these findings should be interpreted with caution.


[Expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension].
To investigate the expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension and to discuss their role in the pathogenesis of portal hypertensive vasculopathy. RT-PCR was used to detect the expression of local angiotensinogen mRNA in 28 specimens of splenic artery and vein obtained during operation of elective separation and amputation on 28 portal hypertension (PH) patients, 20 males and 8 females, aged 51.7 +/- 10 (30 - 65), and in 12 specimens of normal vessel from 12 patients undergoing splenectomy due to traumatic rupture of spleen. Chemiluminescent electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappaB in splenic artery and vein. The levels of local angiotensinogen mRNA in the splenic artery and vein of PH group were 0.48 +/- 0.21 and 0.43 +/- 0.16 respectively, both significantly higher than those in the control group (0.23 +/- 0.12 and 0.18 +/- 0.10, both P < 0.05). There was no significant difference between the splenic artery and vein in the expression of local angiotensinogen mRNA in PH group. The activation levels of NF-kappaB in splenic artery and vein of the PH patients were 1.44 +/- 0.23 and 1.38 +/- 0.18 respectively, both significantly higher than those of the control group (0.19 +/- 0.20 and 0.25 +/- 0.16 respectively, both P < 0.05). However, there was no significant difference in the activation levels of NF-kappaB between the splenic artery and vein in the PH patients (P > 0.05). Local angiotensinogen and activation of NF-kappaB maybe one of the factors in the pathogenesis of portal hypertensive vasculopathy, which can cause and advance portal hypertensive vasculopathy.


Crystal structure of chicken liver basic fatty acid-binding protein complexed with cholic acid.
Two paralogous groups of liver fatty acid-binding proteins (FABPs) have been described: the mammalian type liver FABPs and the basic type (Lb-FABPs) characterized in several vertebrates but not in mammals. The two groups have similar sequences and share a highly conserved three-dimensional structure, but their specificity and stoichiometry of binding are different. The crystal structure of chicken Lb-FABP complexed with cholic acid and that of the apoprotein refined to 2.0 A resolution are presented in this paper. The two forms of the protein crystallize in different space groups, and significant changes are observed between the two conformations. The holoprotein binds two molecules of cholate in the interior cavity, and the contacts observed between the two ligands can help to explain the reason for this stoichiometry of binding. Most of the amino acids involved in ligand binding are conserved in other members of the Lb-FABP family. Since the amino acid sequence of the Lb-FABPs is more similar to that of the bile acid-binding proteins than to that of the L-FABPs, the possibility that the Lb-FABPs might be more appropriately called liver bile acid-binding proteins (L-BABPs) is suggested.


Ductal carcinoma in situ: size and resection volume predict margin status.
There is strong evidence that breast conservation surgery (BCS) with negative margins for ductal carcinoma in situ (DCIS) is associated with low rates of recurrence. Our goal was to identify factors associated with positive margins in BCS for DCIS. A retrospective database review identified 823 patients diagnosed with DCIS. The current analysis included 546 of those patients treated with BCS from 2000 to 2006 with complete data regarding tumor and lumpectomy dimensions. Variables analyzed included tumor size, lumpectomy volume, estrogen and progesterone receptor status, histologic subtype, grade, and age at diagnosis. χ analysis and t tests were used to identify factors that may predict positive margins. A multivariate regression model was developed to determine independent variables predictive of positive margin status. A total of 33% of specimens had positive margins. Lumpectomy volume, tumor size, nuclear grade (low vs. high), and number of slides positive for DCIS were all significant for positive margin status by bivariate analysis. On multivariate analysis, tumor size (P < 0.001; odds ratio, 2.37; 95% confidence interval, 1.712, 3.296) and resection volume (P = 0.0006; odds ratio, 0.48; 95% confidence interval, 0.318, 0.729) remained significantly associated with positive margin status. Age at diagnosis, histologic subtype, tumor grade, and estrogen and progesterone status all were not associated with margin status. Positive margins after BCS for DCIS are associated with larger lesions and a smaller volume of resection. With 33% of patients having positive margins, these data suggest that a more aggressive initial resection may avoid positive margins and thus lower the risk of recurrence or the need for additional surgery.


Allograft replacement of the trachea. Experimental synchronous revascularization of composite thyrotracheal transplant.
We describe a method for experimental tracheal transplantation that uses synchronous revascularization based on the blood supply of the related thyroid gland. This study compares the structural integrity and histologic features of nonvascularized tracheal transplants, revascularized thyrotracheal composite allografts, with and without immunosuppression. Eighteen adult beagle dogs underwent tracheal transplant operations with one of the preceding methods. Postmortem specimens were studied macroscopically and histologically, 3 to 28 days postoperatively. Proximal, mid, and distal segments of each graft (twelve-ring segments) were examined microscopically. Nonvascularized tracheal transplants necrosed completely as early as 3 days postoperatively. The vascularized composite thyrotracheal allografts survived for up to 28 days. Six dogs did not receive immunosuppressive agents; tracheal cartilage was preserved in this group, but soft tissue necrosis developed. Six dogs received cyclosporine; tracheal cartilages and all soft tissues remained histologically intact. This difference may be due to early tracheal cartilage ischemia in the nonvascularized group, rejection of the soft tissues in the nonimmunosuppressed group, and viability of all structures in the vascularized and immunosuppressed group. Revascularization of the transplanted trachea with the thyroid arteries maintains the vascularity and hence the viability of the trachea. A reliable substitute for long-segment tracheal resections is finally found. We predict that clinical application of this technique will solve a major problem in the surgery of the airways.


Ultrastructural investigations on protective effects of NCX 4016 (nitroaspirin) on macrovascular endothelium in diabetic Wistar rats.
The effect of a nitric oxide-donating aspirin derivative, 2-acetoxy-benzoate 3-(nitroxy-methyl)phenyl ester (NCX 4016), and aspirin on the aortic endothelium of diabetic rats was investigated by using scanning and transmission electron microscopy. Control and streptozotocin-treated rats were used. Metabolic control was assessed by measuring blood and urine metabolites, and 24-h urine volume. The ultrastructural study was performed after 7 weeks of diabetes and 6 weeks of therapy. Streptozotocin treatment induced a persistent hyperglycemia which was not influenced by the pharmacological treatments. Values of blood metabolites were in line with the diabetic status. Both scanning and transmission electron microscopy revealed that aortic endothelium was severely damaged in all diabetic rats except for the NCX 4016 treated ones. Our data document the protective effects of NCX 4016 on the vascular endothelium of diabetic rats. Since aspirin had no protective action, NCX 4016 may have exerted its beneficial action by releasing nitric oxide.


Extreme weather conditions as a gender-specific risk factor for acute myocardial infarction.
Acute coronary syndrome is a disease with high prevalence and high mortality. Exposure to heat or cold increases the risks of myocardial infarction significantly. Gender-specific effects of this have not yet been examined. Our goal was to determine whether extreme weather conditions, which become more and more frequent, are gender-specific risk factors for myocardial infarction, in order to help provide faster diagnosis and revascularization therapy for patients. We analysed the incidence of ST-elevation myocardial infarction (STEMI) in a large urban area over a 65-months period in a cohort study. A day was the unit of analysis. Incidence rate ratios (IRR) with Poisson regression models were calculated. All patients with STEMI on Saturdays and Sundays were included. Gender, high or low perceived temperatures (PT), a function of temperature, wind speed and humidity, and meteorological cold and heat warnings by the Austrian Central Institute for Meteorology and Geodynamics (ZAMG) were considered as risk factors. During the 562 days of the study period, a total of 1109 patients with STEMI (803; 72% men, mean age 61;14 years) were included. The gender difference between men and women was much more pronounced on cold (0 °C) days (85% of patients male; 1.8 per day) than on hot (20 °C) days (71% male; 1.4 per day) or days without extreme temperatures (72% male; 1.4 per day). We found significant interaction between gender and cold days (IRR of the interaction term 2.3 (95% CI 1.2-4.6), p = 0.02). No gender-specific effect was observed on warm days (IRR for interaction 0.9 (95% CI 0.6-1.3), p = 0.3). Low perceived temperature pronouncedly increases the already elevated risk for STEMI in males. Whether this effect is based on gender alone, or on one of the cardiovascular risk factors which are more common in men, is up to further study.


In vivo function of a gammaherpesvirus virion glycoprotein: influence on B-cell infection and mononucleosis.
The human gammaherpesviruses Epstein-Barr virus and Kaposi Sarcoma-associated herpesvirus both contain a glycoprotein (gp350/220 and K8.1, respectively) that mediates binding to target cells and has been studied in great detail in vitro. However, there is no direct information on the role that these glycoproteins play in pathogenesis in vivo. Infection of mice by murid herpesvirus 4 strain 68 (MHV-68) is an established animal model for gammaherpesvirus pathogenesis and expresses an analogous glycoprotein, gp150. To elucidate the in vivo function of gp150, a recombinant MHV-68 deficient in gp150 production was generated (vgp150Delta). The productive viral replication in vitro and in vivo was largely unaffected by mutation of gp150, aside from a partial defect in the release of extracellular virus. Likewise, B-cell latency was established. However, the transient mononucleosis and spike in latently infected cells associated with the spread of MHV-68 to the spleen was significantly reduced in vgp150Delta-infected mice. A soluble, recombinant gp150 was found to bind specifically to B cells but not to epithelial cells in culture. In addition, gp150-deficient MHV-68 derived from mouse lungs bound less well to spleen cells than wild-type virus. Thus, gp150 is highly similar in function in vitro to the Epstein-Barr virus gp350/220. These results suggest a role for these analogous proteins in mononucleosis and have implications for their use as vaccine antigens.


[Papillary adenocarcinomas of the biliary tract].
Papillary adenocarcinomas remain at present some of the rare tumours of the biliary pathways. They raise numerous problems in connection with the diagnosis and with the surgical attitude. The authors present their personal experience acquired in 8 cases of papillary adenocarcinomas of the biliary pathways in which, after removal by curettage external biliary drainage was performed (4 cases, 2 survivals for 3 and 10 months respectively). Cholecystogastrostomy was performed in 2 cases and choledocoduodenostomy in two more patients (survivals of 3 and 20 months respectively).


Inhibition and inactivation of pyruvate phosphate dikinase with Cr(III) complexes of adenosine 5'-triphosphate and inorganic pyrophosphate.
The exchange inert complexes beta,gamma-bidentate Cr(H2O)4ATP and P1,P2-bidentate Cr(H2O)4PP were found to bind to the Bacteriodes symbiosus pyruvate phosphate dikinase ATP and PP binding sites, respectively. The inactivation of the enzyme that was observed with these complexes was shown to involve covalent attachment of the entire complex to the enzyme via insertion of enzyme amino acid side chains into the coordination sphere of the Cr(III). Incubation of Cr(H2O)4ATP with other proteins also resulted in covalent attachment.


A preliminary experience with the Russell-Taylor reconstruction nail for complex femoral fractures.
Eleven cases of complex femoral fractures were seen from November 1987 to November 1989; five ipsilateral femoral neck and shaft fractures and six comminuted subtrochanteric fractures. High-energy accidents accounted for most of these injuries. There were numerous associated injuries, many requiring operative procedures. All of the fractures were treated with Russell-Taylor reconstruction nails. All fractures united, but there were two delayed unions. There was no delay in diagnosis of the femoral neck fractures, and all healed without avascular necrosis. Malalignment occurred in one case, shortening of the femur occurred in two cases, and in two cases only one screw could be placed in the femoral head. In three patients technical errors related to nail insertion led to fracture complications. The use of the Russell-Taylor reconstruction nail is technically demanding. However, we conclude that in complex femoral fractures, this device offers superior stabilization over other currently used methods of internal fixation.


[Looking for a new past: strategies and problems of methodologies in historical demography].
"This article presents a state of the art [discussion] on the methodologies of historical demography.... This analysis is oriented to evaluate goals, possibilities and limitations in the methods of historical demography. These methods are introduced in terms of answers to two basic questions in this field: how demographers reconstruct population dynamics of the past and how they explain behaviour of these demographic systems." (SUMMARY IN ENG)


Some aspects of thermoregulation in newborn reindeer calves (Rangifer tarandus tarandus).
At birth reindeer calves often are exposed to sub-zero ambient temperatures (Ta) sometimes even combined with wind and precipitation. The resting metabolism was measured in three different age groups (1, 7 and 14 days old) at Ta's of -20, -5, 10 and 20 degrees C. Resting metabolism in the thermoneutral zone decreased from 5.1 W X kg-1 at day 1 and 7 to 4.8 W X kg-1 at day 14. At day 1 apparent lower critical temperature (Tlc) was 11 degrees C, while at day 7 it was 7.7 degrees C and at day 14 7.3 degrees C, but total body conductance continued to decrease below apparent Tlc. At Ta's of -5 and -20 degrees C total body conductance was: 0.77 and 0.72 W X degrees C-1 at day 1, 0.98 and 0.92 W X degrees C-1 at day 7, 1.08 and 0.91 W X degrees C-1 at day 14, respectively. Thermal conductance of pelt samples from the trunk was determined in vitro at different combinations of windspeed, Ta and wetness. The conductance of dry fur increased from 5.9 to 11.8 W X m-2 X degrees C-1 at a windspeed of 0 and 10 m X s-1, respectively, as compared to 28.7 W X m-2 X degrees C-1 when wetted without wind. Newborn reindeer calves seem to be heavily dependent on non-shivering thermogenesis in brown adipose tissue for their cold defence since deep body temperature in a calf subjected to propranolol infusion when exposed to a Ta of -25 degrees C in combination with a 10 m X s-1 windspeed increased its cooling rate five times.


Effects of tidal volume, ventilatory frequency, and oxygen insufflation flow on the fraction of inspired oxygen in cadaveric horse heads attached to a lung model.
To measure the effects of tidal volume, ventilatory frequency, and oxygen insufflation flow on the fraction of inspired oxygen in cadaveric horse heads attached to a lung model. 8 heads of equine cadavers. Each cadaveric horse head was intubated with a nasotracheal tube that extended into the proximal portion of the trachea. Oxygen was delivered through an oxygen catheter contained within and extending to the tip of the nasotracheal tube. The trachea was connected to the lung model by use of a spiral-wound hose with a sampling adaptor. Eight treatment combinations involving 2 tidal volumes (5 and 8 L), 2 ventilatory frequencies (6 and 12 mechanical breathes/min), and 2 insufflation rates (10 and 15 L/min) were applied to each head. Hand-drawn inspired gas samples were collected and analyzed for oxygen concentrations. The fraction of inspired oxygen (measured at mid trachea) ranged from 26.8% to 39.4%. Fraction of inspired oxygen was significantly higher with a smaller tidal volume, lower ventilatory frequency, and higher insufflation rate. In the study model, measured fraction of inspired oxygen varied with ventilatory pattern as well as oxygen insufflation rate. Clinically, this information could be beneficial for interpretation of data regarding arterial blood gases and hemoglobin saturation and in making appropriate oxygen insufflation decisions for anesthetized horses that are breathing room air.


The Japan Geriatrics Society consensus statement "recommendations for older persons to receive the best medical and long-term care during the COVID-19 outbreak-considering the timing of advance care planning implementation".
Since the end of 2019, a life-threatening infectious disease (coronavirus disease 2019: COVID-19) has spread globally, and numerous victims have been reported. In particular, older persons tend to suffer more severely when infected with a novel coronavirus (SARS-CoV-2) and have higher case mortality rates; additionally, outbreaks frequently occur in hospitals and long-term care facilities where most of the residents are older persons. Unfortunately, it has been stated that the COVID-19 pandemic has caused a medical collapse in some countries, resulting in the depletion of medical resources, such as ventilators, and triage based on chronological age. Furthermore, as some COVID-19 cases show a rapid deterioration of clinical symptoms and accordingly, the medical and long-term care staff cannot always confirm the patient's values and wishes in time, we are very concerned as to whether older patients are receiving the medical and long-term care services that they wish for. It was once again recognized that it is vital to implement advance care planning as early as possible before suffering from COVID-19. To this end, in August 2020, the Japan Geriatrics Society announced ethical recommendations for medical and long-term care for older persons and emphasized the importance of conducting advance care planning at earlier stages. Geriatr Gerontol Int 2020; 20: 1112-1119.


The Metabolism of Hormones during Seed Germination and Dormancy: IV. The Metabolism of (S)-2-C-Abscisic Acid in Ash Seed.
Embryos from dormant and stratified Fraxinus americana seed were incubated with (S)-2-(14)C-abscisic acid (ABA) under a variety of conditions. Both dormant and stratified embryos rapidly metabolize abscisic acid to phaseic acid, dihydrophaseic acid, and an unidentified polar metabolite apparently derived from dihydrophaseic acid. Although the stratified embryos may have an increased capacity to metabolize abscisic acid, our calculations suggest that such an increased capacity would probably not be physiologically significant.Dormant intact seeds also metabolize (S)-2-(14)C-abscisic acid during stratification at 5 C or incubation at 25 C. The metabolites appear to be similar to those observed in excised embryos although by 12 days of stratification a fourth metabolite is observed. More than 90% of the (14)C-abscisic acid was metabolized after 26 days of stratification at 5 C or after 12 days of incubation at 25 C. Stratification at 5 C leads to the breaking of dormancy while incubation at 25 C does not.


Calcitonin gene-related peptide and substance P decrease in the rabbit colon during colitis. A time study.
The sensory neuropeptides, substance P and calcitonin gene-related peptide, have been implicated in inflammatory reactions in several tissues. An immune-complex model of colitis was used in rabbits to determine the colonic content (nmol/g protein) of immunoreactive substance P and calcitonin gene-related peptide at various times after induction of inflammation to assess changes in these neuropeptides during the inflammatory response. Calcitonin gene-related peptide content was decreased by 66% 4 hours after induction of inflammation and reached a maximum of 80% at 48 hours. The substance P content was decreased at 8 hours, with a maximum decrease of 64% at 48 hours. Substance P decrease was detected in the muscle layer. The amounts of substance P in the mucosal/submucosal layer extracts were too low to allow accurate measurements. Calcitonin gene-related peptide decreased both in the muscle and the mucosal-submucosal layers. Immunohistochemical analysis showed that calcitonin gene-related peptide and substance P innervation patterns were comparable in normal and inflamed colon, even though there appeared to be a decrease in density and intensity of the staining, particularly for calcitonin gene-related peptide at 48 hours. The early decrease of calcitonin gene-related peptide and substance P during the time course of colitis might be due to release from nerve terminals of the gut during the inflammatory response. The profound changes in colonic calcitonin gene-related peptide and substance P content during colitis may have important implications during inflammation and subsequent tissue repair and may also lead to disturbances in gut motility.


[Study on the efficacy of quarantine during outbreaks of acute hemorrhagic conjunctivitis outbreaks at schools through the susceptive-infective-quarantine-removal model].
To assess the efficacy of quarantine for acute hemorrhagic conjunctivitis (AHC) outbreaks control in schools, by using the Compartment Model. Through combining the characters of both AHC and compartment model, we built a susceptive-infective-removal (SIR) model suited for AHC outbreaks control in schools, and then quarantine was added into the model to develop a susceptive-infective-quarantine-removal (SIQR) model. An outbreak of AHC in Changsha in 2011 was employed as a sample to assess the effect of quarantine for the prevention and control of AHC. Basic reproduction number (λ0) of the AHC outbreak without intervention was 6.80, thus the transmission speed of the disease became quite fast. If no intervention had been adopted, almost all the students, faculties and staff members would have been infected within 23 days, and the accumulative cases would become 738, with the total attack rate (TAR) as 99.73%. The peak of the outbreak was at Sep. 11th and the number of new cases was 126 on that day. The efficacy would have been different if quarantine forces had been taken at different time and differently. The bigger and earlier the quarantine force had been adopted, the lower morbidity peak and the smaller TAR would have been appeared, with better efficacy of outbreak control. If the quarantine rate had been taken at the level of 90% on the sixth day, the accumulative case would have been reduced to 132 and the TAR had become 17.84% consequently. Quarantine program could be used as a main intervention approach to be employed for ACH outbreak at schools.


Patterns of hearing loss resulting from cis-platinum therapy.
The purpose of this study was to provide a clinically useful classification of the hearing loss that occurs with chemotherapy using cis-diamminedichloroplatinum (cis-platinum). Serial audiometric testing was performed on 66 patients who underwent cis-platinum chemotherapy (2 to 6 courses, 100 mg/m2). Subsequent hearing losses were classified according to (1) whether hearing loss occurred after the first or second course of chemotherapy, (2) the magnitude of loss, and (3) the frequencies affected. Of 39 patients who could be classified, 21 (54%) had no loss or mild loss, 14 (36%) had early loss, and 4 (10%) had late loss. Different patterns of hearing loss were observed. The observation that different patterns of hearing loss occur implies that different mechanisms of hearing loss exist. Some mechanisms must be more important in different patients. Our data are important with regard to continuation of chemotherapy treatment after hearing loss occurs. Most significant hearing loss (90%) occurred early or not at all. If early hearing loss occurred and treatment was continued, the speech frequencies were eventually affected in 71% of patients. Recognition of the patterns of hearing loss are important considerations when discontinuation of therapy is being considered.


Beta-adrenergic relaxation of mouse urinary bladder smooth muscle in the absence of large-conductance Ca2+-activated K+ channel.
In urinary bladder smooth muscle (UBSM), stimulation of beta-adrenergic receptors (beta-ARs) leads to activation of the large-conductance Ca2+-activated K+ (BK) channel currents (Petkov GV and Nelson MT. Am J Physiol Cell Physiol 288: C1255-C1263, 2005). In this study we tested the hypothesis that the BK channel mediates UBSM relaxation in response to beta-AR stimulation using the highly specific BK channel inhibitor iberiotoxin (IBTX) and a BK channel knockout (BK-KO) mouse model in which the gene for the pore-forming subunit was deleted. UBSM strips isolated from wild-type (WT) and BK-KO mice were stimulated with 20 mM K+ or 1 microM carbachol to induce phasic and tonic contractions. BK-KO and WT UBSM strips pretreated with IBTX had increased overall contractility, and UBSM BK-KO cells were depolarized with approximately 12 mV. Isoproterenol, a nonspecific beta-AR agonist, and forskolin, an adenylate cyclase activator, decreased phasic and tonic contractions of WT UBSM strips in a concentration-dependent manner. In the presence of IBTX, the concentration-response curves to isoproterenol and forskolin were shifted to the right in WT UBSM strips. Isoproterenol- and forskolin-mediated relaxations were enhanced in BK-KO UBSM strips, and a leftward shift in the concentration-response curves was observed. The leftward shift was eliminated upon PKA inhibition with H-89, suggesting upregulation of the beta-AR-cAMP pathway in BK-KO mice. These results indicate that the BK channel is a key modulator in beta-AR-mediated relaxation of UBSM and further suggest that alterations in BK channel expression or function could contribute to some pathophysiological conditions such as overactive bladder and urinary incontinence.


Intrapatient comparison of 308-nm monochromatic excimer light and localized narrow-band UVB phototherapy in the treatment of vitiligo: a randomized controlled trial.
Limited data are available about the use of 308-nm monochromatic excimer light (MEL) and localized 311-nm narrow-band ultraviolet B (NB-UVB) in the treatment of vitiligo. The aim of this study was to evaluate the efficacy of 308-nm MEL versus localized 311-nm NB-UVB in vitiligo patients. Eleven patients participated in this prospective intrapatient placebo-controlled randomized trial. In each patient, 3 lesions were selected and treated with NB-UVB, MEL and placebo during 24 sessions, respectively. Repigmentation was evaluated clinically and by objective surface measurement. Twenty percent of the lesions treated with NB-UVB achieved repigmentation scores above 50%. None of the lesions treated with MEL achieved a repigmentation higher than 50% after 24 sessions. Localized 311-nm NB-UVB is effective in the treatment of vitiligo. It should be considered for localized vitiligo as it is easily accessible. In this study the efficacy of localized 311-nm NB-UVB was superior to 308-nm MEL.


RNA today. Molecular Evolution of Introns and Other RNA Elements: a Keystone Symposium, Taos, NM, USA, February 2-8, 1991.
RNA research is alive and well. The joyride for those studying the biochemistry and molecular biology of RNA continues, although perhaps not at the thrill-a-month pace of recent years. The Keystone Symposium provided an opportunity to gain deeper insight into RNA-based biological phenomena by attempting to place current research in an evolutionary context. In this sense the meeting was an unqualified success. The meeting participants, having been warmed by the New Mexico sun and the chile-laden cuisine, now return to their laboratories determined to pursue not only the details of RNA biochemistry and molecular biology, but also the evolutionary implications of their work.


Update of the mortality experience of employees with occupational exposure to 1,2-dibromo-3-chloropropane (DBCP).
DBCP (1,2-dibromo-3-chloropropane), a nematocide, was used in the United States from the mid-1950s until 1977. The U.S. Environmental Protection Agency (EPA) restricted and eventually banned its use after the 1977 discovery of DBCP-induced sterility in production workers. The present study is an update of the mortality (1957-1989) experience of a cohort of 548 male employees who had potential for exposure in the production and formulation of DBCP. While adjusting for age, calendar-year, and pay status of all other Midland-area Dow Chemical male employees, there were 68 total observed deaths in the cohort compared to 72.1 expected (Mantel Haenszel Relative Risk 0.9, 95% Confidence Interval 0.7-1.2) and 19 deaths from all malignancies compared to 19.0 expected (RR 1.0, 95% CI 0.6-1.6). Of the a priori anatomic cancer sites of interest, there were no deaths from stomach, liver, kidney, testes, or nasal cavity cancers. Altogether, there were 7 deaths from lung cancer compared to 6.6 expected (RR 1.1, 95% CI 0.5-2.3). Among the 81 employees with exposure categorized as direct for 1 or more years, there were 3 observed lung cancer deaths compared to 0.9 expected (RR 3.3, 95% CI 1.1-9.6). Smoking was a confounding factor in the interpretation of this observation. Although the present analysis nearly doubled the number of person-years from the original study, the conclusions remain limited by the cohort's size and duration of follow-up.


Milia-like idiopathic calcinosis cutis in a child with Down syndrome.
Idiopathic calcinosis cutis refers to progressive deposition of crystals of calcium phosphate in the skin and other areas of the body, in the absence of any inciting factor. Idiopathic calcinosis cutis may sometimes take the form of small, milia-like lesions. Most commonly, such milia like lesions are seen in the setting of Down syndrome. Herein, we report a 5-year-old girl with multiple asymptomatic discrete milia-like firm papules distributed over the face and extremities. A diagnosis of milia-like idiopathic calcinosis cutis associated with Down Syndrome was provisionally made and was confirmed by histopathology and karyotyping.


Depression genetic risk score is associated with anhedonia-related markers across units of analysis.
Investigations of pathophysiological mechanisms implicated in vulnerability to depression have been negatively impacted by the significant heterogeneity characteristic of psychiatric syndromes. Such challenges are also reflected in numerous null findings emerging from genome-wide association studies (GWAS) of depression. Bolstered by increasing sample sizes, recent GWAS studies have identified genetics variants linked to MDD. Among them, Okbay and colleagues (Nat. Genet. 2016 Jun;48(6):624-33) identified genetic variants associated with three well-validated depression-related phenotypes: subjective well-being, depressive symptoms, and neuroticism. Despite this progress, little is known about psychopathological and neurobiological mechanisms underlying such risk. To fill this gap, a genetic risk score (GRS) was computed from the Okbay's study for a sample of 88 psychiatrically healthy females. Across two sessions, participants underwent two well-validated psychosocial stressors, and performed two separate tasks probing reward learning both before and after stress. Analyses tested whether GRS scores predicted anhedonia-related phenotypes across three units of analyses: self-report (Snaith Hamilton Pleasure Scale), behavior (stress-induced changes in reward learning), and circuits (stress-induced changes in striatal reward prediction error; striatal volume). GRS scores were negatively associated with anhedonia-related phenotypes across all units of analyses but only circuit-level variables were significant. In addition, the amount of explained variance was systematically larger as variables were putatively closer to the effects of genes (self-report < behavior < neural circuitry). Collectively, findings implicate anhedonia-related phenotypes and neurobiological mechanisms in increased depression vulnerability, and highlight the value of focusing on fundamental dimensions of functioning across different units of analyses.


Mineral Levels in Thalassaemia Major Patients Using Different Iron Chelators.
The goal of the present study was to determine the levels of minerals in chronically transfused thalassaemic patients living in Antalya, Turkey and to determine mineral levels in groups using different iron chelators. Three iron chelators deferoxamine, deferiprone and deferasirox have been used to remove iron from patients' tissues. There were contradictory results in the literature about minerals including selenium, zinc, copper, and magnesium in thalassaemia major patients. Blood samples from the 60 thalassaemia major patients (the deferoxamine group, n = 19; the deferiprone group, n = 20 and the deferasirox group, n = 21) and the controls (n = 20) were collected. Levels of selenium, zinc, copper, magnesium, and iron were measured, and all of them except iron showed no significant difference between the controls and the patients regardless of chelator type. Serum copper levels in the deferasirox group were lower than those in the control and deferoxamine groups, and serum magnesium levels in the deferasirox group were higher than those in the control, deferoxamine and deferiprone groups. Iron levels in the patient groups were higher than those in the control group, and iron levels showed a significant correlation with selenium and magnesium levels. Different values of minerals in thalassaemia major patients may be the result of different dietary intake, chelator type, or regional differences in where patients live. That is why minerals may be measured in thalassaemia major patients at intervals, and deficient minerals should be replaced. Being careful about levels of copper and magnesium in thalassaemia major patients using deferasirox seems to be beneficial.


Systematic review of the different aspects of primary snoring.
Primary snoring, also known as simple or non-apnoeic snoring, is regarded as the first stage of sleep disordered breathing without severe medical consequences for the snorer and co-sleeper. Although it is a highly prevalent phenomenon in the general population, our knowledge is limited because of the lack of a consensus on terminology. This systematic review of the aspects used in the definitions of simple/primary snoring was conducted to obtain an inventory of current practices and compare these definitions with the conceptual definition of the American Academy of Sleep Medicine. PubMed and Web of Science were searched from July 2016 onwards without any language limitations, and 362 references were obtained. After selection based on titles, 39 remained, among which 29 contained a definition or reference to a definition. In 69% of the studies, a cut-off <5 apnoea/Hypopnoea events per hour of sleep on the Apnoea-Hypopnoea Index was used. Despite this tendency, the cut-offs ranged from 0 to <15/h. Unfortunately, the cut-off and occasional requirements did not match the conceptual definition of the American Academy of Sleep Medicine. A consensus must be reached on an operational and clinically relevant definition based on the clear conceptual definition.


The multiplex bead array approach to identifying serum biomarkers associated with breast cancer.
Breast cancer is the most common type of cancer seen in women in western countries. Thus, diagnostic modalities sensitive to early-stage breast cancer are needed. Antibody-based array platforms of a data-driven type, which are expected to facilitate more rapid and sensitive detection of novel biomarkers, have emerged as a direct, rapid means for profiling cancer-specific signatures using small samples. In line with this concept, our group constructed an antibody bead array panel for 35 analytes that were selected during the discovery step. This study was aimed at testing the performance of this 35-plex array panel in profiling signatures specific for primary non-metastatic breast cancer and validating its diagnostic utility in this independent population. Thirty-five analytes were selected from more than 50 markers through screening steps using a serum bank consisting of 4,500 samples from various types of cancer. An antibody-bead array of 35 markers was constructed using the Luminex bead array platform. A study population consisting of 98 breast cancer patients and 96 normal subjects was analysed using this panel. Multivariate classification algorithms were used to find discriminating biomarkers and validated with another independent population of 90 breast cancer and 79 healthy controls. Serum concentrations of epidermal growth factor, soluble CD40-ligand and proapolipoprotein A1 were increased in breast cancer patients. High-molecular-weight-kininogen, apolipoprotein A1, soluble vascular cell adhesion molecule-1, plasminogen activator inhibitor-1, vitamin-D binding protein and vitronectin were decreased in the cancer group. Multivariate classification algorithms distinguished breast cancer patients from the normal population with high accuracy (91.8% with random forest, 91.5% with support vector machine, 87.6% with linear discriminant analysis). Combinatorial markers also detected breast cancer at an early stage with greater sensitivity. The current study demonstrated the usefulness of the antibody-bead array approach in finding signatures specific for primary non-metastatic breast cancer and illustrated the potential for early, high sensitivity detection of breast cancer. Further validation is required before array-based technology is used routinely for early detection of breast cancer.


Doxycycline ameliorates ischemic and border-zone remodeling and endothelial dysfunction after myocardial infarction in rats.
Although matrix metalloproteinase (MMP) activity increases, endothelial function decreases after myocardial infarction (MI). The antibiotic doxycycline inhibits MMP activity in vitro. The role of doxycycline-mediated MMP inhibition in endothelial function is unclear. Doxycycline ameliorates endothelial dysfunction, in part, by inhibiting MMP activity. We subjected Sprague-Dawley male rats to MI by ligating the left anterior descending arteries. We subjected another group of rats to sham surgery. We administered doxycycline in drinking water (0.67 mg/ml) to both groups 2 days before surgery: the sham group underwent sham surgery and received doxycycline therapy, and the MI group underwent MI and received doxycycline therapy (n = 6 in each group). After 4 weeks, we anesthetized rats and prepared left ventricular rings from infarcted-ischemic (I), non-infarcted near-infarcted (NI), and sham surgery hearts with and without doxycycline treatment. The MMP-2 activity increased significantly in I and NI hearts, and we observed a selective increase in MMP-9 activity only in I hearts, when compared with other groups (p < 0.05), measured by zymography. Cardiac inhibitor of metalloproteinase decreased only in I hearts (p < 0.05 vs other groups), measured by Western analysis, and doxycycline treatment reversed this decrease. Contractile response of rings to acetylcholine was attenuated in the I group, suggesting nitric oxide-mediated dysfunction, and was reversed by doxycycline. The response to nitroprusside was attenuated in I hearts and ameliorated by doxycycline, suggesting cardiomyocyte dysfunction. Bradykinin induced relaxation in rings from sham surgery hearts and from NI hearts, but induced paradoxic contraction in rings from I hearts. Treatment with doxycycline reversed the paradoxic contraction. Results suggest a protective action of doxycycline in the ischemic heart, possibly because of additional pharmacologic actions such as metalloproteinase inhibition.


An immunocytochemical study of cutaneous innervation and the distribution of neuropeptides and protein gene product 9.5 in man and commonly employed laboratory animals.
The cutaneous nerves of rat, cat, guinea pig, pig, and man were studied by immunocytochemistry to compare the staining potency of general neural markers and to investigate the density of nerves containing peptides. Antiserum to protein gene product 9.5 (PGP 9.5) stained more nerves than antisera to neurofilaments, neuron-specific enolase (NSE), and synaptophysin or histochemistry for acetylcholinesterase (AChE). Peptidergic axons showed species variation in density of distribution and were most abundant in pig and fewest in man. However, the specific peptides in nerves innervating the various structures were consistent between species. Nerve fibers immunoreactive for calcitonin gene-related peptide (CGRP) and/or vasoactive intestinal polypeptide (VIP) predominated in all the species; those immunoreactive to tachykinins (substance P and neurokinin A [NKA]) and neuropeptide tyrosine (NPY) were less abundant. Neonatal capsaicin, at the doses employed in this study, destroyed approximately 70% of CGRP- and tachykinin-immunoreactive sensory axons; whereas 6-hydroxydopamine (6-OHDA) at the doses employed resulted in a complete loss of NPY and tyrosine hydroxylase (TH) immunoreactivity without affecting VIP, CGRP, and tachykinins. Thus, this study confirms that antiserum to PGP 9.5 is the most suitable and practical marker for the demonstration of cutaneous nerves. Species differences exist in the density of peptidergic innervation, but apparently not for specific peptides. Not all sensory axons immunoreactive for CGRP and substance P/NKA are capsaicin-sensitive. However, all sympathetic TH- and NPY-immunoreactive axons are totally responsive to 6-OHDA; but no change was seen in VIP-immunoreactive axons, suggesting some demarcation of cutaneous adrenergic and cholinergic sympathetic fibers.


Differential Expression of SWI/SNF Chromatin Remodeler Subunits Brahma and Brahma-Related Gene During Drug-Induced Liver Injury and Regeneration in Mouse Model.
The chromatin remodeling activity of mammalian SWI/SNF complex is carried out by either Brahma (BRM) or Brahma-related gene (BRG-1). The BRG-1 regulates genes involved in cell proliferation, whereas BRM is associated with cell differentiation, and arrest of cell growth. Global modifications of histones and expression of genes of chromatin-remodeling subunits have not been studied in in vivo model systems. In the present study, we investigate epigenetic modifications of histones and the expression of genes in thioacetamide (TAA)-induced liver injury and regeneration in a mouse model. In the present study, we report that hepatocyte proliferation and H3S10 phosphorylation occur during 60 to 72 h post TAA treatment in mice. Furthermore, there was change in the H3K9 acetylation and H3K9 trimethylation pattern with respect to liver injury and regeneration phase. Looking into the expression pattern of Brg-1 and Brm, it is evident that they contribute substantially to the process of liver regeneration. The SWI/SNF remodeler might contain BRG-1 as its ATPase subunit during injury phase. Whereas, BRM-associated SWI/SNF remodeler might probably be predominant during decline of injury phase and initiation of regeneration phase. Furthermore, during the regeneration phase, BRG-1-containing remodeler again predominates. Considering all these observations, the present study depicts an interplay between chromatin interacting machineries in different phases of thioacetamide-induced liver injury and regeneration.


[Effects of sildenafil on erectile dysfunction in the aged men with diabetes].
To evaluate the efficacy and safety of sildenafil on erectile dysfunction in the aged men with diabetes. One hundred and ten patients aged 55 years old above with type I or II diabetes and a minimum 3-month history of ED were studied. Patients were instructed to take one dose of their treatment orally at any time before anticipated sexual activity. Changes from baseline in mean scores on the erectile function domain of the International index of Erectile Function and changes from baseline in the proportion of "yes" responses to question 2, and 3, of the Sexual Encounter Profile were coprimary outcome measures. Treatment with sildenafil significantly improved all primary efficacy variables. Sildenafil therapy significantly enhanced erectile function and was well tolerated by men with diabetes and ED.


[Renal lesions in a case of tuberous sclerosis: association of angiomyolipoma, bilateral polycystic kidney and renal clear-cell carcinoma].
Association cases of tuberous sclerosis (ST) and renal displasia-tumors are infrequently seen in literature. These tumors are bilateral renal cystic displasia (RP) rare hamartomas, p.e. angiomyolipomas, and malignant neoplasms, p.e. renal clear cell carcinomas. There therefor as to the frequency of those pathological associations with ST, AML are frequently seen (50-80%). Reports of polycystic renal disease with ST are rare, whereas occasional associations of renal cell carcinomas with ST are founded out. By extensive literature examination of it's evident that the synchronous association of these pathological lesions is exceptional. This report describes one case of AML, RP and renal clear cell carcinoma in a female, 22 years old, with ST; the pathological, clinical and pathogenetic features are discussed.


Law No. 27 of 1988, 9 February 1988.
This Law amends Iraq Law Number 77 of 1983 relating to the rights of a divorcee with respect to a "dwelling" to provide that a divorcee has the same rights in the dwelling stipulated in Law Number 77, even if the husband "has endowed the owned house or apartment to . . . others prior to . . . divorce."


A computer program to calculate and design oligonucleotide primers from amino acid sequences.
A computer program to generate oligonucleotide sequences from peptide data is presented. The program, PrimerGen, reverse-translates a peptide string into its corresponding degenerate deoxyribonucleotide counterpart, and generates sequences of oligonucleotide molecules which can be synthesized and either used as probes for hybridizations or as primers in polymerase chain reactions.


Development of beta-amyloid-induced neurodegeneration in Alzheimer's disease and novel neuroprotective strategies.
Alzheimer's disease (AD) is a form of dementia in which people develop rapid neurodegeneration, complete loss of cognitive abilities, and are likely to die prematurely. At present, no treatment for AD is known. One of the hallmarks in the development of AD is the aggregation of amyloid protein fragments in the brain, and much evidence points towards beta-amyloid fragments being one of the main causes of the neurodegenerative processes. This review summarises the present concepts and theories on how AD develops, and lists the evidence that supports them. A cascade of biochemical events is initiated that ultimately leads to neuronal death involving an imbalance of intracellular calcium homeostasis via activation of calcium channels, intracellular calcium stores, and subsequent production of free radicals by calcium-sensitive enzymes. Secondary processes include inflammatory responses that produce more free radicals and the induction of apoptosis. Recently, several new strategies have been proposed to try to ameliorate the neurodegenerative developments associated with AD. These include the activation of neuronal growth factor receptors and insulin-like receptors, both of which have neuroprotective properties. Furthermore, the role of cholesterol and potential protective properties of cholesterol-lowering drugs are under intense investigation. Other promising strategies include the inhibition of beta- and gamma-secretases which produce beta-amyloid, activation of proteases that degrade beta-amyloid, glutamate receptor selective drugs, antioxidants, and metal chelating agents, all of which prevent formation of plaques. Novel drugs that act at different levels of the neurodegenerative processes show great promise to reduce neurodegeneration. They could help to prolong the time of unimpaired cognitive abilities of people who develop AD, allowing them to lead an independent life.


Selective Accumulation to Tumor Cells with Coacervate Droplets Formed from a Water-Insoluble Acrylate Polymer.
Selective targeting of specific cells without the use of biological ligands has not been achieved. In the present study, we revealed that the coacervate droplets formed from poly(2-methoxyethyl acrylate) (PMEA) and its derivatives selectively accumulated to tumor cells. PMEA derivatives, which are insoluble acrylate polymers, induced coacervation in water to form polymer-dense droplets via hydrophobic interaction. Interestingly, the accumulation of coacervate droplets to tumor cells was involved in the bound water content of PMEA derivatives. Coacervate droplets with a high bound water content accumulated and internalized up to 36.6-fold higher in HeLa cervical tumor cells than in normal human fibroblasts (NHDF). Moreover, the interactions between coacervate droplets and plasma membrane components such as CD44 played a key role in this accumulation process. Therefore, coacervate droplets formed from PMEA derivatives have great clinical potential in tumor cell detection, development of alternative tumor-targeting ligands, and optimization of drug delivery carriers.


Congenital upper eyelids ectropion in Down's syndrome.
Congenital bilateral ectropion of the upper eyelids is a rare, benign condition reported in ophthalmic literature. It is more frequently associated with Down's syndrome, ichthyosis, and sporadic cases in newborns from black population. We report three cases of congenital bilateral upper eyelid ectropion associated with Down's syndrome. Management of these patients usually requires medial and lateral canthoplasties, full-thickness pentagonal resection of the upper eyelids and placement of skin grafts. We present herein the evolution of one of these patients and we will discuss the mechanism of the eyelid ectropion and its treatment.


CT after reconstructive repair of the sternum and chest wall.
Acute mediastinitis and sternal infection after sternotomy are potentially devastating complications, but considerable advances in treatment have been made during the past decade. Sternectomy followed by reconstruction with use of either an omental transposition or a muscle flap has markedly decreased mortality and morbidity. After extensive rib resection, various reconstructive repairs, including the use of polytetrafluoroethylene mesh, have proved successful. The authors retrospectively reviewed 27 postoperative computed tomographic (CT) scans obtained in 19 patients. Twelve of these patients had sternal wounds repaired with either omental or muscle flap procedures. Seven patients had chest wall reconstructions with polytetrafluoroethylene patches, muscle transpositions, or both. The authors found no cases of unexpected or unexplained fluid collections on CT scans obtained beyond the 1st month. Any persistent or recurrent collection is suggestive of infection. If clinical and imaging findings are at odds, imaging-directed needle aspiration can help determine whether a fluid collection is infected and in need of further treatment.


Computed Tomography Staging of Middle Ear Cholesteatoma.
To establish computed tomography (CT) staging of middle ear cholesteatoma and assess its impact on the selection of the surgical procedure. Prospective study was conducted on 61 consecutive patients (mean age 26.8 years) with middle ear cholesteatoma. CT scan of the temporal bone and surgery were performed in all patients. CT staging classified cholesteatoma according to its location in the tympanic cavity (T); extension into the mastoid (M); and associated complications (C). Cholesteatoma was staged as stage I (T1, T2), stage II (T3, M1, M2, C1), and stage III (C2). The overall sensitivity of CT staging of cholesteatoma compared to surgery was 88% with excellent agreement and correlation between CT findings and intra-operative findings (K=0.863, r=0.86, P=0.001). There was excellent agreement and correlation of CT staging with surgical findings for T location (K=0.811, r=0.89, P=0.001), good for M extension (K=0.734, r=0.88, P=0.001), and excellent for associated C complications (K=1.00, r=1.0, P=0.001). Atticotympanotomy was carried out in stage I (n=14), intact canal wall surgery was performed in stage II (n=38), and canal wall down surgery was done in stage III (n=5) and stage II (n=4). We established CT staging of middle ear cholesteatoma that helps surgeons to select an appropriate surgery.


Tournament Structure and Success of Players Based on Location in Men's Professional Tennis.
This article discusses the relationship between success of professional male tennis players according to the country and world region from which they originate and the professional tournament structure in men's tennis in that world region and country. The success of a country or world region was defined by the number of players in the top 300 ATP rankings and was calculated for seven time periods between 1975 and 2008. The results showed the correlations between the total number of top 300 ranked players, the total number of tournaments, and the annual tournament prize money of the specific country. The correlations were nearly perfect in the 1975-1990 period (r = 0.93-0.95; p < 0.01) but only high in the 2005-2008 period (r = 0.60-0.64; p < 0.01), suggesting that the association between the number of top 300 ranked tennis players and professional tournaments, while still significant, is in decline. These data should inform the policy and investment decisions of regional and national federations, particularly as they relate to domestic professional tennis tournament structures and to explore opportunities to include professional tournaments of neighbour countries in their player's development programs. Key PointsThis paper observes relation changes between the total number of players, total number of ATP tournaments and total annual prize money in particular continents from 1975 to 2008.The correlation between the tennis success, total number of tournaments and total annual prize money in tournaments was highest from 1975 to 1989 and was gradually decreasing from 1990 to 2008.The leading tennis countries organise over 20 ATP tournaments and entry professional tournaments per year. Tennis less developed countries very often is using the competition systems of the most successful tennis countries.Indications are that tennis will continue to become increasingly global and that this trend may be unlikely to reverse.


[Curative resection for bulky gastrointestinal stromal tumor with conversion therapy by imatinib].
Imatinib is a standard treatment for unresectable gastrointestinal stromal tumor (GIST). We described the case of a 66- year-old woman with bulky GIST of which a diameter was 25 cm. Therefore, we decided the tumor was unresectable. After 2-year administration of imatinib, the diameter of tumor was reduced to 6 cm. After 3-year administration of imatinib, the diameter of tumor was increased to 8 cm. The patient did not have any distant metastasis. He underwent a resection of the tumor. The historical examination showed that c-kit and CD34 were positive. The number of mitosis was 12/50 HPF. Conversion chemotherapy for bulky GIST may contribute to a curative resection.


Henoch-Schonlein nephritis associated with subacute thyroiditis.
We present a 12-year-old boy who developed subacute thyroiditis during the course of rapidly progressive glomerulonephritis due to Henoch-Schonlein purpura (HSP) proven by clinical findings and percutaneous renal needle biopsy. The thyroid gland of the patient suddenly enlarged with mild tenderness while he was on steroid and dipyridamole therapy. Thyroid hormone levels revealed T3 0.31 ng/ml (nl: 0.52-1.75 ng ml), T4 2.53 ug/dl (nl: 4.8-12.8 ug/dl), free T3 0.80 pg/ml (nl: 2.14-5.34 pg/ml), free T4 0.2 ng/dl (nl: 0.73-1.95 ng/dl) and TSH 1.02 U/ml (nl: 0.36-3.25 U/ml). Antimicrosomal antibody was negative while antithyroglobulin antibody was slightly positive (1/80+). Hypoactivity with a spotty pattern was demonstrated by thyroid scanning. Serologically proven mumps infection was detected and may have been a triggering factor in the development of both HSP and subacute thyroiditis.


PCR quantitation of fetal cells in maternal blood in normal and aneuploid pregnancies.
Fetal cells in maternal blood are a noninvasive source of fetal genetic material for prenatal diagnosis. We determined the number of fetal-cell DNA equivalents present in maternal whole-blood samples to deduce whether this number is affected by fetal karyotype. Peripheral blood samples were obtained from 199 women carrying chromosomally normal fetuses and from 31 women with male aneuploid fetuses. Male fetal-cell DNA-equivalent quantitation was determined by PCR amplification of a Y chromosome-specific sequence and was compared with PCR product amplified from known concentrations of male DNA run simultaneously. The mean number of male fetal-cell DNA equivalents detected in 16-ml blood samples from 90 women bearing a 46,XY fetus was 19 (range 0-91). The mean number of male fetal-cell DNA equivalents detected in 109 women bearing a 46,XX fetus was 2 (range 0-24). The mean number of male fetal-cell DNA equivalents detected when the fetus was male compared with when the fetus was female was highly significant (P = .0001). More fetal cells were detected in maternal blood when the fetus was aneuploid. The mean number of male fetal-cell DNA equivalents detected when the fetal karyotype was 47,XY,+21 was 110 (range 0.1-650), which was significantly higher than the number of male fetal-cell DNA equivalents detected in 46,XY fetuses (P = .0001). Feto-maternal transfusion of nucleated cells appears to be influenced by fetal karyotype. The sixfold elevation of fetal cells observed in maternal blood when the fetus had trisomy 21 indicates that noninvasive cytogenetic diagnosis of trisomy 21 should be feasible.


The effect of glyoxylate on photosynthesis and photorespiration by isolated soybean mesophyll cells.
Incubating isolated soybean leaf mesophyll cells with glyoxylate increased the rates of CO(2) fixation by as much as 150%. In order to cause this stimulation, the glyoxylate must be presented to the cells before the NaHCO(3). Significant stimulation was observed 15 seconds after beginning the glyoxylate treatment. The glyoxylate-dependent stimulation was increased by high O(2) concentrations and decreased by high CO(2) concentrations. Glyoxylate treatment resulted in a 71% inhibition in the rate of CO(2) incorporation into glycolate and glycine. Glyoxylate may be stimulating net photosynthesis solely by decreasing photorespiration or it may be increasing the amount of CO(2) fixed by both decreasing photorespiration and increasing gross photosynthesis. Ribulose bisphosphate carboxylase, when preactivated and assayed in situ, was unaffected by the glyoxylate treatment.


Import Vector Domain Description: A Kernel Logistic One-Class Learning Algorithm.
Recognizing the samples belonging to one class in a heterogeneous data set is a very interesting but tough machine learning task. Some samples of the data set can be actual outliers or members of other classes for which training examples are lacking. In contrast to other kernel approaches present in the literature, in this work, the problem is faced defining a one-class kernel machine that delivers the probability for a sample to belong to the support of the distribution and that can be efficiently trained by a hybrid sequential minimal optimization-expectation maximization algorithm. Due to the analogy to the import vector machine and to the one-class approach, we named the method import vector domain description (IVDD). IVDD was tested on a toy 2-D data set in order to characterize its behavior on a set of widely used benchmarking UCI data sets and, lastly, challenged against a real world outlier detection data set. All the results were compared against state-of-the-art closely related methods such as one-class-SVM and Support Vector Domain Description, proving that the algorithm is equally accurate with the additional advantage of delivering the probability estimate for each sample. Finally, a few variants aimed at providing memory savings and/or computational speed-up in the light of big data analysis are briefly sketched.


The effect of probiotic LSP 122 on the control of post-weaning diarrhoea syndrome of piglets.
Post-weaning diarrhoea syndrome (PWDS) of piglets is caused mainly by enterotoxigenic Escherichia coli (ETEC) strains. A new in-feed probiotic, LSP 122 (Alpharma), containing viable spores of Bacillus licheniformis was tested for its efficacy to control PWDS in piglets in a low health-status farm, using four groups with a total of 256 weaned piglets for a 28-day period. One group (negative control) was offered antimicrobial-free and probiotics-free fed, one group was offered feed supplemented with 10(6)viable spores of Bacillus toyoi (Toyocerin(R)) per gram of feed and two groups were offered feed supplemented with 10(6)and 10(7)viable spores of B. licheniformis per gram of feed, respectively, and were compared with regard to the appearance of clinical signs, mortality, weight gain and feed conversion. The results showed that all groups supplemented with probiotics exhibited a reduced incidence and severity of diarrhoea. Mortality in all probiotic supplemented pigs was significantly lower compared with the negative control group (P<0.05). The evaluation of the weight gain data, as well as feed conversion ratio, indicated that the three treated groups performed remarkably better than the negative control group (P<0.05) and the group receiving the high inclusion of LSP 122 performed better than the two other groups receiving probiotics (P<0.05). No ETEC strains were detected on day 22 in the high inclusion of LSP 122 and Toyocerin groups as compared with the untreated control. It was concluded that the high dosage schedule of LSP 122, providing 10(7)viable spores of B. licheniformis per g of feed, is a very useful agent for the control of PWDS due to ETEC.


Immunocytochemical localization and distribution of human albumin in Wuchereria bancrofti adult worms.
To determine whether albumin is present on adult worms of Wuchereria bancrofti, thin sections of resin-embedded parasites were incubated with a specific antiserum to human albumin. With the exception of the epicuticle, all layers of the cuticle and the hypodermis were intensely labeled. Concentration of gold particles was observed within infoldings of the hypodermal membrane. Moderate labeling of the thin basement membrane that lines the pseudocelomic cavity and the gonoduct was also observed. Within the uterus, ovular membranes labeled intensely; groups of organized particles were seen below ovular membranes and also within invaginations of microfilarial embryos. In contrast, few gold particles were seen on the surface of mature intrauterine microfilariae. No labeling was observed in control sections incubated with antiserum preadsorbed with purified human albumin. The findings suggest that human albumin may be essential for the nutrition and development of W bancrofti microfilariae.


Indonesia: population distribution and redistribution.
The author describes "the broad pattern of contemporary population distribution in Indonesia and the major changes which have occurred in this pattern between the 1930, 1961 and 1971 census enumerations and the 1976 intercensal survey." In the final section, he outlines some of the major demographic, social, economic, political, and geographic factors associated with these patterns of distribution and redistribution.


Maternal Temperature, Corticosterone, and Body Condition as Mediators of Maternal Effects in Jacky Dragons (Amphibolurus muricatus).
AbstractTemperature is a crucial environmental component that imposes physiological constraints and ultimately produces variation in life-history traits. Temperatures experienced by mothers can influence offspring phenotypes, including growth and sex ratios, especially in ectothermic species. However, mechanisms by which thermal information can be passed onto offspring have been underexplored. Here, we investigated corticosterone as a potential mediator of thermal maternal effects. We held female jacky dragons (Amphibolurus muricatus) in two different thermal regimes (short [7 h] or long [11 h] basking treatments), then quantified plasma corticosterone levels and tested for correlations between the resulting corticosterone levels and reproductive outputs. Lizards in the long-bask treatment had significantly higher corticosterone levels than those in the short-bask treatment. Maternal corticosterone, in turn, had sex-dependent effects on offspring hatching size but was not associated with maternal reproductive effort or offspring sex or growth. In contrast, maternal body condition was strongly positively related to both reproductive output (including clutch size and total number of eggs) and offspring size at hatching but had no effect on offspring growth. Basking treatment also interacted with condition and corticosterone to affect egg mass and hatchling snout-vent length, respectively. When we tested for relationships between corticosterone levels and body condition, we found corticosterone to be negatively related to condition in long-bask lizards but only in the postbreeding season. These findings indicate that thermal opportunity alters physiology, with potential consequences for fitness. Moreover, the results suggest interactive influences of temperature, corticosterone, and condition as mediators of maternal effects.


Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis.
Although the carbonic anhydrase inhibitors have been used in the treatment of the primary periodic paralyses (PPs), their efficacy has not been demonstrated in double-blind, placebo-controlled trials. Therefore, we tested the efficacy of dichlorphenamide (DCP; Daranide), a potent carbonic anhydrase inhibitor, in the treatment of episodic weakness in the primary PPs. We performed two multicenter, randomized, double-blind, placebo-controlled crossover trials, one involving 42 subjects with hypokalemic periodic paralysis (HypoPP) and the other involving 31 subjects with potassium-sensitive periodic paralysis (PSPP). In each trial, two 8-week treatment periods were separated by an active washout period of at least 9 weeks. The primary outcome variable in the HypoPP trial was the occurrence of an intolerable increase in attack severity or frequency (end point). The primary outcome variable in the PSPP trial was the number of attacks per week. In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.


Cranial neuralgias.
After a description of the anatomical-functional organization of the human trigeminal system, this chapter discusses the diagnostic and therapeutic options for trigeminal neuralgia (TN). In about 15% of patients who present with the clinical picture of typical TN, this is secondary to a major neurological disease, i.e., benign tumors of the cerebellopontine angle or multiple sclerosis. Some clinical criteria that were used to distinguish between classic and symptomatic TN, such as age at onset, involvement of the ophthalmic division, and responsiveness to medical treatment, are no longer considered reliable. It is recommended that all patients undergo magnetic resonance imaging (MRI) or trigeminal reflex recording. Carbamazepine (CBZ) and oxcarbazepine (OXC) are the first-choice medical treatments. Although other drugs may be effective, these are indicated when the patient cannot reach the therapeutic dosage of CBZ/OXC because of adverse events. Patients unresponsive to CBZ/OXC should be made aware of the available surgical interventions. Surgical procedures (including percutaneous lesions to the ganglion/root, microvascular decompression (MVD) in the posterior fossa, and gamma knife radiosurgery) are extremely efficacious with relatively few complications: each procedure has some advantage and disadvantage with respect to the other. Only MVD is a non-destructive procedure. This chapter also describes management of glossopharyngeal neuralgia, which is often misdiagnosed, and some other chronic pain conditions mediated by the trigeminal system, such as ophthalmic postherpetic neuralgia (PHN).


Antipsychotic polypharmacy: a survey of discharge prescriptions from a tertiary care psychiatric institution.
To perform a retrospective survey of discharge medications at a tertiary care psychiatric facility and to assess the incidence of antipsychotic polypharmacy. This is a retrospective survey that used the Department of Pharmacy's computer database to obtain relevant discharge information on all nongeriatric patients with schizophrenia discharged from Riverview Hospital between November 1, 1996 and October 31, 1998. From a total of 492 eligible patients, 229 met the inclusion criteria and formed the database for the survey. The main finding of the survey was that 27.5% of our discharged patients diagnosed with schizophrenia left our facility on an antipsychotic polypharmacy regimen. Compared with patients discharged on a single antipsychotic, the pooled data revealed a significantly greater use of anticholinergic agents in those patients prescribed an antipsychotic polypharmacy regimen. Further, of the atypical agents, only risperidone showed a statistically significant reduction in dosage when coprescribed with a second antipsychotic. Although antipsychotic polypharmacy persists today, as it has over the past 30 years, evidence-based data to support this controversial treatment strategy is lacking. As a result clinicians are relying on their clinical experience, and perhaps intuition, to design antipsychotic polypharmacy treatment protocols. Efforts should be made to replace subjective clinical impression with a more rational approach to antipsychotic polypharmacy--one that is based on pharmacodynamic and pharmacokinetic understanding of drug action.