Prevalence and quality of antihypertensive therapy among hypertension patients enrolled in the Ghana National Health Insurance Scheme.
Hypertension is a leading cause of morbidity in Ghana. However, there is insufficient data on the prevalence and quality of antihypertensive therapy. To describe the prevalence of use and quality of antihypertensive therapy. A cross-sectional study design was used to analyze the 2015 Ghana National Health Insurance Scheme (NHIS) electronic claims data. Hypertension diagnosis was defined using ICD-10 codes. The primary outcomes assessed were the prevalence of use and quality of antihypertensive therapy. Quality of antihypertensive therapy was defined as the use of antihypertensive agents recommended for treating hypertension patients with comorbid heart failure, myocardial Infarction/Coronary Artery Disease, diabetes, chronic kidney disease or stroke. We used multivariable logistic regression models to identify predictors of antihypertensive use and quality of therapy. Antihypertensive medication use was very high (86%) among the 161 873 hypertension patients covered under the Ghana NHIS. Only a third (32%) of hypertension patients received guideline-concordant therapy. Angiotensin receptor blockers were consumed at the highest dosages of 120 (Interquartile Range [IQR]: 60, 180) daily defined doses over a year. Males (odds ratio [OR] = 0.60; 95% Confidence Interval [CI]:0.58, 0.61) and those with comorbid stroke (OR = 0.91, 95% CI:0.84, 0.99), diabetes (OR = 0.72; 95% CI:0.69, 0.74) and stroke (OR = 0.74, 95%CI:0.68, 0.80) were less likely to use antihypertensives, all other predictors were associated with higher use. Antihypertensive medication use was very high among hypertension patients covered under the Ghana NHIS. However, there was indication of suboptimal quality of the antihypertensive therapy provided.


Hereditary pancreatitis presenting in childhood: case report with family studies.
A 12-year-old boy presented with recurrent abdominal pain and failure to thrive and was shown to have chronic calcific pancreatitis. Investigations failed to show any of the demonstrable causes of pancreatitis, but on family study four close paternal relatives were found to have had chronic pancreatitis, three with radiological calcification. No definable cause for pancreatitis had been determined in any of these relatives.


Patterns of lumbar myelographic findings in patients with LBP a 5 years retrospective study at Yehuleshet Higher Clinic, Addis Ababa, Ethiopia.
Low back pain (LBP) is usually defined as pain, muscle tension, or stiffness localized below the costal margin and above the inferior gluteal folds, with or without leg pain (sciatica). LBP is a common health problem and the imaging of which need carful clinical diagnostic triage. Most of us will experience at least one episode of LBP during our life. Despite its burden to the health facilities, more than 90% have no identifiable organic cause so their diagnosis is based on exclusion of other specific pathologies. The study asses level of association of LBP and lumbar Myelographic findings in a higher clinic in Addis Ababa and provide baseline information of patterns of lumbar myelographic disease. This is a retrospective record review of patients with LBP for whom lumbar myelography was done at Yehuleshet Higher Clinic. Data were collected from the clinics record, both hard and soft copy records were used a total of 1688 patients who had lumbar myelography study done for a complaint of LBP in the years from 2002-2008 are included in the study. Among the study subjects 895 (53%) were males and 793 (47%) were females. Mean age was 42.41 +/- 13.22. 1073 (63.6%) had abnormal myelographic findings and the rest 615 (36.4%) had normal lumbar myelography. The commonest abnormality is disc prolapse 36.7% with L4-L5 and L5-S1 being the commonest sites. Even if lumbar myelography showed abnormal findings in 63.6% a significant number of the studies (36.4%) were normal indicating lack of optimal clinical triage. Overall in countries like ours, where the recommended primary imaging modality, i.e., MRI is inaccessible and expensive, the value of myelography is unquestionable. But because of the invasive nature of the examination which also uses radiation, a diagnostic clinical triage should be taken first before subjecting patients to Myelographic procedures. Further studies to assess the positive predictive value of myelography with surgical confirmation are recommended.


Surveillance uncovers the smoking gun for resistance emergence.
Today, antibiotic resistance is becoming a major healthcare concern. As global travel increases, more antibiotic-resistant bacteria will be disseminated from one country to another, thereby imposing a problem worldwide. Since the development of resistance is an evolutionary process, constant surveillance is needed to gain insight into the problem and surveillance studies needed to document the spread of antibiotic resistance. The basic objectives of surveillance studies in antimicrobial resistance are: to determine the level of resistance in a particular geographical area; to monitor changes in the level of resistance and make this information available to therapeutic policy-makers, as well as to detect new mechanisms of resistance for use as early warning signs; to study how such resistance develops, persists and spreads, and to monitor interventions. Although, surveillance provides the smoking gun for emergence of antibiotic resistance, improvement of the system is necessary and may be achieved through enhanced information technology and diagnostic tools.


Subcutaneous Corynebacterium parvum in bladder cancer: a controlled study of its immunological effects.
Fourteen out of 26 patients with invasive bladder cancer were randomly assigned to receive weekly subcutaneous injections of Corynebacterium parvum (CP) in addition to standard treatment. Peripheral blood T lymphocyte percentage, K cell activity, mitogen responsiveness, and monocyte and polymorph leucotaxis were measured at intervals over a period of 1 to 2 years. The only consistent difference between the CP-treatment patients and the controls was a slightly higher level of K cell activity in the former, who, however, fared rather worse than the controls in terms of survival.


Myeloma stem cell phenotype. Implications for treatment.
The phenotypic heterogeneity of myeloma cells in fact delineates a differentiation process that appears to be an integral part of the disease process. Immature myeloma cells interact with their microenvironment differently than do the more mature cells. As a result of this interaction, the immature cells display different responses to chemotherapy than do the mature cells. Addressing this issue by tailoring treatment to target immature as well as mature myeloma cells may change dramatically the outcome of treatment. The ability to define the myeloma clone by molecular genetic techniques has markedly increased the ability to detect clonal cells. This technique provides a most sensitive tool for monitoring elimination of tumor cells; however, the role of the early clonal B cells identified through the use of ASO-PCR in the disease process needs to be clarified. Currently, a great deal of effort is directed towards development of treatment protocol that will eliminate all clonal cells, and a method of purging clonal cells from harvested mobilized peripheral stem cells. Understanding the biologic significance of early clonal B cells in myeloma will allow for a more rational approach to curative treatment.


Does race or ethnicity play a role in the origin, pathophysiology, and outcomes of preeclampsia? An expert review of the literature.
The burden of preeclampsia, a substantial contributor to perinatal morbidity and mortality, is not born equally across the population. Although the prevalence of preeclampsia has been reported to be 3% to 5%, racial and ethnic minority groups such as non-Hispanic Black women and American Indian or Alaskan Native women are widely reported to be disproportionately affected by preeclampsia. However, studies that add clarity to the causes of the racial and ethnic differences in preeclampsia are limited. Race is a social construct, is often self-assigned, is variable across settings, and fails to account for subgroups. Studies of the genetic structure of human populations continue to find more variations within racial groups than among them. Efforts to examine the role of race and ethnicity in biomedical research should consider these limitations and not use it as a biological construct. Furthermore, the use of race in decision making in clinical settings may worsen the disparity in health outcomes. Most of the existing data on disparities examine the differences between White and non-Hispanic Black women. Fewer studies have enough sample size to evaluate the outcomes in the Asian, American Indian or Alaskan Native, or mixed-race women. Racial differences are noted in the occurrence, presentation, and short-term and long-term outcomes of preeclampsia. Well-established clinical risk factors for preeclampsia such as obesity, diabetes, and chronic hypertension disproportionately affect non-Hispanic Black, American Indian or Alaskan Native, and Hispanic populations. However, with comparable clinical risk factors for preeclampsia among women of different race or ethnic groups, addressing modifiable risk factors has not been found to have the same protective effect for all women. Abnormalities of placental formation and development, immunologic factors, vascular changes, and inflammation have all been identified as contributing to the pathophysiology of preeclampsia. Few studies have examined race and the pathophysiology of preeclampsia. Despite attempts, a genetic basis for the disease has not been identified. A number of genetic variants, including apolipoprotein L1, have been identified as possible risk modifiers. Few studies have examined race and prevention of preeclampsia. Although low-dose aspirin for the prevention of preeclampsia is recommended by the US Preventive Service Task Force, a population-based study found racial and ethnic differences in preeclampsia recurrence after the implementation of low-dose aspirin supplementation. After implementation, recurrent preeclampsia reduced among Hispanic women (76.4% vs 49.6%; P<.001), but there was no difference in the recurrent preeclampsia in non-Hispanic Black women (13.7 vs 18.1; P=.252). Future research incorporating the National Institute on Minority Health and Health Disparities multilevel framework, specifically examining the role of racism on the burden of the disease, may help in the quest for effective strategies to reduce the disproportionate burden of preeclampsia on a minority population. In this model, a multilevel framework provides a more comprehensive approach and takes into account the influence of behavioral factors, environmental factors, and healthcare systems, not just on the individual.


A rigorous small area modelling-study for the Helicobacter pylori epidemiology.
This paper presents an investigation into spatial risk differences over small distances for the Helicobacter pylori infection in the city of Leipzig, Germany and two rural districts. A model, using Bayesian inference, was developed that adjusts the risk for individual-specific factors, and for spatial or individual over-dispersion, respectively. Additionally, the model takes into account conditional spatial autocorrelation. We found a significant positive association to the H. pylori infection risk for: "more than three children live in the household" (OR=2.4, p=0.001), "more persons live per sq.m than average" (OR=1.4, p=0.03), "home situated at main road" (OR=1.4, p=0.04) and "using well water" (OR=2.3, p=0.05). A protective effect was identified for "travelled to low prevalence region" (OR=0.4, p<0.0001) and "born in Germany" (OR=0.2, p<0.0001). Three administrative areas with significantly increased spatial risk were identified: one in the rural district and two in the city of Leipzig. The model explained 24.9% of the total deviance. Contrary to expectations, the largest part of deviance of the data was not explained by the identified significant risk factors, but by individual-specific heterogeneities. We conclude that further - so far not discussed - factors influence the risk and the spatial variation of the H.pylori infection. Furthermore, from the results we speculate about a possible impact of long-time air pollution and surface water.


Diurnal efficacy of alpha-lipoic acid/nifedipine/glimepiride combination mitigates diabetic neuropathies in rats.
Time-dependent effects of alpha-lipoic acid/nifedipine/glimepiride combination on diabetic neuropathies were investigated in rats. 7 groups (n=9) of rats were used. First and second groups were apparently normal and diabetic rats respectively, and were administered 1mL/kg distilled water. The rest of the groups were diabetic and administered 10mg/kg glimepiride at night-time (8:00 pm). Groups 4-7 were administered additional 20mg/kg nifedipine at morning-time (8:00 am), while groups 5-7 were also administered 100mg/kg alpha-lipoic acid (ALA) in the morning, afternoon and night-time respectively (8:00 am, 2:00 pm and 8:00 pm). During the 28 days of oral treatment, paw pressure, tail immersion and motor coordination tests were conducted. The rats were euthanized on the 29th day after a charcoal meal. The small intestines were excised to determine intestinal transit while the brain was collected, homogenised and used to determine levels of oxidative stress. Data show that treatment with ALA at 8:00 am or 2:00 pm significantly (P≤0.01) produced a delay in the onset and improved prognosis of neuropathies. Treatment with ALA at 8:00 pm prevented manifestation of neuropathies throughout the study with positive antioxidant effects. Time-dependent ALA treatment in combination with nifedipine and glimepiride should be studied in humans with an approximately similar circadian timing. This may provide additional clinical therapeutic options for diabetic neuropathies.


Current trend of acute myocardial infarction in Korea (from the Korea Acute Myocardial Infarction Registry from 2006 to 2013).
Although the incidence of acute myocardial infarction (AMI) in Korea has been rapidly changed because of westernization of diet, lifestyle, and aging of the population, the recent trend of the myocardial infarction have not been reported by classification. We investigated recent trends in the incidence and mortality associated with the 2 major types of AMI. We reviewed 39,978 patients registered in the Korea Acute Myocardial Infarction Registry for either ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment elevation acute myocardial infarction (NSTEMI) from 2006 to 2013. When the rate for AMI were investigated according to each year, the incidence rates of STEMI decreased markedly from 60.5% in 2006 to 48.1% in 2013 (p <0.001). In contrast, a gradual increase in the incidence rates of NSTEMI was observed from 39.5% in 2006 to 51.9% in 2013 (p <0.001). As risk factors, hypertension, diabetes mellitus, and dyslipidemia were much more common in patients with NSTEMI than STEMI. Among medical treatments, the use of β blockers, angiotensin receptor blocker, and statin were increased from 2006 to 2013 in patients with STEMI and NSTEMI. Patients with STEMI and NSTEMI were more inclined to be increasingly treated by invasive treatments with percutaneous coronary intervention. In conclusion, this study demonstrated that the trend of myocardial infarction has been changed rapidly in the aspect of risk factors, ratio of STEMI versus NSTEMI, and therapeutic strategies during the recent 8 years in Korea.


[Oral protozoans and diabetes: study in 117 patients].
A study on the presence of oral Entamoeba gingivalis and Trichomonas tenax has been carried out on calculus or dental plaque from 117 diabetic subjects. Statistical analysis of results shows no correlation between diabetes and protozoa. The same frequency was found between diabetic and normal subjects. Nevertheless, a significant relation has been found between the diabetes and the yeasts.


Genetic analysis of mitomycin C-induced interchange in Drosophila melanogaster females.
A genetic analysis of an array of mitomycin-induced rearrangements in immature Drosophila oocytes is reported. Induced aberrations were recovered representing detachments of the compound-X chromosome, Y chromosome fragments, X chromosome loss and mosaicism. The spectrum of rearrangements induced by mitomycin C was very similar to that induced by X-ray treatment of immature oocytes. This work suggests that mitomycin C has two models of action. The drug is radiomimetic for it induces the types of aberrations recovered after X-irradiation. Mitomycin C also seems to have a delayed effect which is reflected in the relatively high recovery of mosaics.


Parathyroid Hormone and Parathyroid Hormone-Related Protein Analogs in Osteoporosis Therapy.
The purpose is to review the efficacy and optimal use of parathyroid hormone and parathyroid hormone-related protein analogs in osteoporosis treatment. The parathyroid hormone analog teriparatide, a potent stimulator of bone remodeling, increases hip and spine bone mineral density and reduces the risk of vertebral and non-vertebral fractures in postmenopausal osteoporotic women. The parathyroid hormone-related protein analog, abaloparatide, also reduces fracture incidence but has pharmacological effects that differ from teriparatide, particularly in cortical bone. These analogs provide maximal benefit when their use is followed by a potent antiresorptive medication. Moreover, studies have shown that the combination of teriparatide and the RANK-ligand inhibitor, denosumab, increase bone density and estimated strength more than monotherapy and more than any currently available regimen. Parathyroid hormone and parathyroid hormone-related protein analogs, whether as monotherapy, in combination with antiresorptive agents or in sequence with antiresorptive agents, will likely play an expanding role in osteoporosis management.


Simultaneous high-performance liquid chromatographic determination of antazoline phosphate and tetrahydrozoline hydrochloride in ophthalmic solution.
A method for the determination of 2-[(N-phenyl)benzylaminomethyl]-2-imidazoline X H3PO4 (antazoline phosphate) and 2-(1,2,3,4-tetrahydro-1-naphthyl)-2-imidazoline X HCl (tetrahydrozoline hydrochloride) in ophthalmic solution is described. The pharmaceutical preparation is analysed directly by reversed-phase ion-pair high-performance liquid chromatography and the method is very rapid, selective and simple.


Genistein inhibits chondrogenic differentiation and mineralization of ATDC5 cells.
Isoflavones are phytoestrogens abundant in leguminous crops and are used to prevent a variety of hormonal disorders. In the present study, the effects of genistein and daidzein on the chondrogenic differentiation of ATDC5 cells were investigated. Genistein (10 μM) treatment markedly reduced production of sulfated proteoglycans and collagen fibers in the ATDC5 cells. Genistein suppressed the expression of genes involved in chondrocyte differentiation such as Sox9, Col2a1, Col10a1, Acan, and Tgfb1. Additionally, genistein significantly decreased calcium deposition in ATDC5 cells during chondrogenic differentiation; however, it increased calcification under non-chondrogenic mineralizing conditions. Daidzein exhibited a similar effect of suppressing chondrogenesis in ATDC5 cells, although its efficacy was 10-times lower than that of genistein. These findings suggest that a high concentration of genistein inhibits chondrogenesis and chondrogenic mineralization, whereas it enhances non-chondrogenic mineralization.


Novel characterization method for fibrous materials using non-contact acoustics: material properties revealed by ultrasonic perturbations.
Fibrous materials are unique hierarchical complex structures exhibiting a range of mechanical, thermal, optical and electrical properties. The inherent discontinuity at micro and macro levels, heterogeneity and multi-scale porosity differentiates fibrous materials from other engineering materials that are typically continuum in nature. These structural complexities greatly influence the techniques and modalities that can be applied to characterize fibrous materials. Typically, the material response to an applied external force is measured and used as a characteristic number of the specimen. In general, a range of equipment is in use to obtain these numbers to signify the material properties. Nevertheless, obtaining these numbers for materials like fiber ensembles is often time consuming, destructive, and requires multiple modalities. It is hypothesized that the material response to an applied acoustic frequency would provide a robust alternative characterization mode for rapid and non-destructive material analysis. This research proposes applying air-coupled ultrasonic acoustics to characterize fibrous materials. Ultrasonic frequency waves transmitted through fibrous assemblies were feature extracted to understand the correlation between the applied frequency and the material properties. Mechanical and thermal characteristics were analyzed using ultrasonic features such as time of flight, signal velocity, power and the rate of attenuation of signal amplitude. Subsequently, these temporal and spectral characteristics were mapped with the standard low-stress mechanical and thermal properties via an empirical artificial intelligence engine. A high correlation of >0.92 (S.D. 0.06) was observed between the ultrasonic features and the standard measurements. The proposed ultrasonic technique can be used toward rapid characterization of dynamic behavior of flexible fibrous assemblies.


A comparison of reversible versus irreversible protein glutathionylation.
Glutathionylation is generally a reversible posttranslational modification that occurs to cysteine residues that have been exposed to reactive oxygen species (P-SSG). This cyclical process can regulate various clusters of proteins, including those involved in critical cellular signaling functions. However, certain conditions can favor the formation of dehydroamino acids, such as 2,3-didehydroalanine (2,3-dehydroalanine, DHA) and 2,3-didehydrobutyrine (2,3-dehydrobutyrine), which can act as Michael acceptors. In turn, these can form Michael adducts with glutathione (GSH), resulting in the formation of a stable thioether conjugate, an irreversible process referred to as nonreducible glutathionylation. This is predicted to be prevalent in nature, particularly in more slowly turning over proteins. Such nonreducible glutathionylation can be distinguished from the more facile cycling signaling processes and is predicted to be of gerontological, toxicological, pharmacological, and oncological relevance. Here, we compare reversible and irreversible glutathionylation.


Bis(2-carboxybenzo-ato-κO)bis-[1-cyclo-propyl-6-fluoro-4-oxo-7-(piperazin-4-ium-1-yl)-1,4-dihydro-quinoline-3-carboxyl-ato-κO,O]manganese(II) dihydrate.
The title compound, [Mn(C(17)H(18)FN(3)O(3))(2)(C(8)H(5)O(4))(2)]·2H(2)O or [Mn(cfH)(2)(1,2-Hbdc)(2)]·2H(2)O (cfH = ciprofloxacin = 1-cyclo-propyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazin-yl)-3-quinoline carb-oxy-lic acid, 1,2-bdc = benzene-1,2-dicarboxyl-ate), has been prepared under hydro-thermal conditions. The Mn(2+) atom, located on an inversion centre, exhibits a distorted octa-hedral geometry, coordinated by four O atoms from two symmetry-related zwitterionic ciprofloxacin ligands in the equatorial positions and two O atoms of two 1,2-Hbdc ligands in the axial positions. The complex mol-ecules are linked into a two-dimensional network through N-H⋯O and OW-H⋯O hydrogen bonds. A strong intramolecular hydrogen bond between the carboxyl/carboxylate groups of the 1,2-Hbdc anion is also present. The layers are further extended through off-set aromatic π-π stacking inter-actions of cfH groups [centroid-centroid distance of 3.657 (2) Å] into the final three-dimensional supra-molecular arrays.


OCT-Angiography for Detection of Choroidal Neovascularization: A Retrospective Real-Life Study.
The purpose of the study was to assess OCT-angiography (OCT-A) contribution for choroidal neovascularization (CNV) detection, with respect to multimodal imaging (MMI) modality (including OCT, fluorescein angiography (FFA), and indocyanine green angiography [ICG]), in a real-life consultation practice. Data of all consecutive patients undergoing OCT-A examination for CNV suspicion were collected between September 2017 and September 2019 at Strasbourg University Hospital, France. Only eyes which had anti-VEGF injection in the last 3 months were excluded. All types of neovascularization were included. For all patients, data from OCT, OCT-A, FFA, and ICG were interpreted by residents and retinal specialists, independently. Final diagnosis of CNV was based on decision to treat. Sensibility, specificity, and predictive values were computed for OCT-A alone and for MMI (OCT combined to angiography). They were computed for each group. OCT-A was also assessed as "contributory" (i.e., assessing without doubt the presence or absence of CNV) or not, with respect to MMI. In total, 161 eyes of 145 patients were included. MMI sensibility was better than OCT-A sensibility (93.8 vs. 65.6%). OCT-A specificity was better than MMI specificity (96.9 vs. 89.5%). OCT-A was essential for diagnosis in 16.9% of cases. Sensibility and specificity values for all exams were better when interpreted by retinal specialists than residents. OCT-A was judged "contributory" in 57.4% of eyes. OCT-A was significantly less contributory when artefacts were present (32.9% of eyes with artefacts vs. 63.5% without, p < 0.001). OCT-A showed to be essential in diagnosing CNV in >16% of cases. However, it often failed to conclude for the absence of CNV, which obliged to perform more exams such as angiography. OCT-A must be part of diagnostic procedure for CNV detection but does not discard angiography in everyday life practice.


Diagnosis and treatment of unconsummated marriage in an Iranian couple.
Unconsummated marriage is a problem among couples who would not be able to perform natural sexual intercourse and vaginal penetration. This disorder is more common in developing countries and sometimes couples would come up with non-technical and non-scientific methods to overcome their problem. Multi-dimensional approach and narrative exposure therapy used in this case. This study would report a case of unconsummated marriage between a couple after 6 years. The main problem of this couple was vaginismus and post-traumatic stress. Treatment with multi-dimensional approach for this couple included methods like narrative exposure therapy, educating the anatomy of female and male reproductive system, correcting misconceptions, educating foreplay, educating body exploring and non-sexual and sexual massage and penetrating the vagina first by women finger and then men's after relaxation. The entire stages of the treatment lasted for four sessions and at the one-month follow-up couple's satisfaction was desirable. Unconsummated marriage is one of the main sexual problems; it is more common in developing countries than developed countries and cultural factors are effective on intensifying this disorder. The use of multi-dimensional approach in this study led to expedite diagnosis and treatment of vaginismus.


Genome-wide effect of tetracycline, doxycycline and 4-epidoxycycline on gene expression in Saccharomyces cerevisiae.
Tetracycline (Tet) and derivative chemicals (e.g., doxycycline or Dox) have gained widespread recognition for their antibiotic properties since their introduction in the late 1970s, but recent work with these chemicals in the lab has shifted to include multiple techniques in all genetic model systems for the precise control of gene expression. The most widely used Tet-modulated methodology is the Tet-On/Tet-Off gene expression system. Tet is generally considered to have effects specific to bacteria; therefore, it should have few off-target effects when used in eukaryotic systems, and a previous study in the yeast Saccharomyces cerevisiae found that Dox had no effect on genome-wide gene expression as measured by microarray. In contrast, another study found that the use of Dox in common cell lines and several model organisms led to mitonuclear protein imbalance, suggesting an inhibitory role of Dox in eukaryotic mitochondria. Recently, a new Dox derivative, 4-epidoxycycline (4-ED) was developed that was shown to have less off-target consequences on mitochondrial health. To determine the best tetracycline family chemical to use for gene expression control in S. cerevisiae, we performed RNA sequencing (RNA-seq) on yeast grown on standard medium compared with growth on media supplemented with Tet, Dox or 4-ED. We found each caused dozens of genes to change expression, with Dox eliciting the greatest expression responses, suggesting that the specific tetracycline used in experiments should be tailored to the specific gene(s) of interest when using the Tet-On/Tet-Off system to reduce the consequences of confounding off-target responses.


Therapeutic potential of short-chain fatty acid production by gut microbiota in neurodegenerative disorders.
Dietary fibers are a major source of short-chain fatty acids (SCFAs) in the body, and the fermentation products of SCFAs induced by intestinal microbiota affect energy metabolism. Apart from serving as an energy source in the intestines, SCFAs also inhibit autophagy, nucleotide-binding oligomerization domain-containing protein, LRR, and pyrin domain-containing protein 3 inflammasome. SCFAs provide numerous therapeutic benefits through their influence on cognitive functioning and neurodegenerative diseases (NDD) pathophysiology. Additionally, NDDs are associated with abnormalities in the gut microbiota, including an increased load of pathogens and opportunistic microbes. SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of NDD and cognitive decline by regulating inflammation and oxidative stress. Basically, SCFAs function as cofactors for the host's mitochondrial enzymes and are being studied for their ability to reverse the alteration in the gut microbiota seen in many NDDs and cardiac diseases. In the present review, the focus is on the detrimental and beneficial roles of SCFAs in NDD, emphasizing the effects of SCFA on following phenomenon: (1) alteration in gut microbiota profile associated with NDD, (2) the molecular mechanism of metabolic regulation by SCFA's, and its co-relation with NDD, (3) use of mitochondrial antioxidants as a strategy for maintaining microbiota diversity in the gut, and (4) the future direction of metabolism and neurodegeneration in the gut-brain axis. In addition, the interplay between gut microbiota, SCFAs, epithelial barrier, and neuroimmune signaling in neurodegeneration has been reviewed.


[Extrophy of the bladder].
Between 1970 and 1980 we operated on 10 patients with congenital extrophy of the bladder and attempted staged anatomical and functional closure in all cases. Currently two patients have a functioning closed bladder, four are in different stages of treatment, and four have undergone urinary diversion. The importance of functional bladder reconstruction is stressed. Though it requires long hospitalization, and complication may result, the procedure can be justified because the anomaly is so grotesque.


Complement inhibition with eculizumab for thrombotic microangiopathy rescues a living-donor kidney transplant in a patient with antiphospholipid antibody syndrome.
Antiphospholipid antibody syndrome (APS) is an enigmatic heterogeneous disorder despite several revelations in its pathobiology. Renal transplantation in patients with APS has been notoriously difficult due to the high risk of development of thrombotic microangiopathy (TMA), which is often refractory to conventional treatment modalities such as aggressive anticoagulation and plasmapheresis. We describe a case of a 58-year-old male with secondary APS undergoing living unrelated renal transplantation for end-stage renal disease from lupus nephritis. Shortly after transplantation, he developed graft dysfunction from APS related TMA that was refractory to systemic anticoagulation and plasmapheresis. After becoming hemodialysis dependent, the patient was started on eculizumab, a humanized monoclonal antibody against complement factor 5, as salvage therapy. We show that this intervention successfully rescued his renal allograft and that the patient has remained dialysis free for over 20 months. Our experience adds to the limited body of literature suggesting the role of complement inhibition in facilitating renal transplantation in patients with APS spectrum of disorders, thus adding a new tool to the therapeutic armamentarium for this difficult disease. The optimal treatment schedule and long term safety data for eculizumab in complement mediated TMA is still unclear. The search for an optimal biomarker to help guide treatment duration is an area of active research.


Hyperpnoeic response independent of limb movements at exercise onset in mice.
We have shown that constant-load treadmill exercise in mice produces an abrupt ventilatory increase to a maximal level at exercise onset. We examined what caused this abrupt response. We measured ventilation during 30-min constant-load exercise on a treadmill, below the lactate threshold, in conscious mice. Video analysis showed that hyperpnoea started before locomotion began. Incremental changes in speed did not further increase ventilation during the early phase of exercise. Next, we measured ventilatory responses to a sudden movement of the treadmill belt on which the mice were kept in a stationary position by a mesh cover. Hyperpnoea started concurrently with the sudden belt movement. In the absence of locomotion, ventilation increased to the extent reached during exercise hyperpnoea. Finally, the abrupt response showed plasticity but was attenuated by experience. The present study shows the importance of factors independent of limb movements in the hyperpnoeic response during the early phase of treadmill exercise in mice.


Guillain-Barre syndrome in colorectal cancer.
Guillain-Barré syndrome has been reported in the setting of different malignancies. To the best of our knowledge, the association of Guillain-Barré syndrome and colorectal cancer has been reported in only two cases. As Guillain-Barré syndrome is potentially life threatening, it should be considered in the differential diagnosis of patients with colorectal cancer with neurological findings. Here we report two cases of Guillain-Barré syndrome in the setting of metastatic colorectal cancer.


[Cytologic analysis of the secretory epithelium of submaxillary salivary glands hypertrophied by repeated amputation of the lower incisors in rats].
Repeated amputation of the lower incisor in August line rats induced hypertrophy of the submandibular and sublingual salivary glands. This was true hypertrophy accompanied by hypertrophy of the structural units (acini, cells, nuclei). Cell hypertrophy depended on the hypertrophy of the organellae and the accumulation of secretory materials in the cells. Hypertrophy of the nuclei of acinar cells was conditioned by polyploidisation. Polyploidisation and the changes in the cell ulctrastructure in the submandibular salivary glands pointed to the increase in the functional activity of the organ.


Discovery of a novel class of heteroaryl-pyrrolidinones as positive allosteric modulators of the muscarinic acetylcholine receptor M1.
This Letter describes the synthesis and optimization of a series of heteroaryl-pyrrolidinone positive allosteric modulators (PAMs) of the muscarinic acetylcholine receptor M1 (mAChR M1). Through the continued optimization of M1 PAM tool compound VU0453595, with a focus on replacement of the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one with a wide variety of alternative 4,5-dihydropyrrolo-fused heteroaromatics, the generation of M1 PAMs with structurally novel chemotypes is disclosed. Two compounds from these subseries, 8b (VU6005610) and 20a (VU6005852), show robust selectivity for the M1 mAChR, and no M1 agonism. Both compounds have favorable preliminary PK profiles in vitro;8b additionally demonstrates high brain exposure in a rodent IV cassette model.


Comparison of culture-dependent and independent techniques for characterisation of the microflora of peroxyacetic acid treated, vacuum-packaged beef.
The diversity of microflora associated with peroxyacetic acid (POAA) treated and untreated beef was investigated by 16S rDNA gene cloning, DGGE analysis and conventional bacterial cultivation. Following vacuum packaging, POAA treated and untreated meat samples were stored for up to 18 weeks at -1.5 degrees C. Each culture independent method showed Carnobacterium spp. to predominate on both POAA treated and untreated meat. However, 16S rDNA gene analysis also detected the presence of psychrotolerant Clostridium spp. in the POAA-treated beef. Culture-dependent analysis did not distinguish Carnobacterium spp. from Lactobacilli. Although culture-dependent analysis showed an increase in the ratio of Enterobacteriaceae to lactic acid bacteria from weeks 6-18 in the POAA treated compared with the untreated meat, the numbers of Enterobacteriaceae were significantly less on POAA treated than on untreated meat. The combination of data collected by culture-dependent and independent techniques provided the most robust approach for elucidating the efficacy of chemical sanitization of chilled vacuum-packaged beef. If conventional cultivation is used for monitoring bacterial spoilage of vacuum-packaged chilled meats it is recommended that culture methods specific for Carnobacterium and Clostridium spp. should be included in order to provide a more complete indication of microbial diversity.


[Experience with rituximab in the treatment of systemic erythematosus lupus].
To assess the short-term effectiveness and tolerance of rituximab in patients with systemic lupus erythematous and distinct clinical manifestations. Thirteen patients were studied. Rituximab (RTX) was indicated for refractory nephritis in 6 patients, severe thrombocytopenia in 5, aplastic anemia in 1 and peritoneal vasculitis associated with nephritis in 1. All patients received 4 weekly doses of 375 mg/m(2) of RTX. The mean length of follow-up was 12±8.5 months. Response was favorable in 9 patients: 3 with nephritis, 5 with thrombocytopenia and 1 with peritoneal vasculitis and nephritis. The mean SLE disease activity index decreased from 11 to 6.5 points. Thrombocytopenia recurred in 2 patients, who responded well to retreatment. The present study demonstrates that RTX is safe and effective as short-term therapy for distinct clinical manifestations associated with SLE.


The effect of acetyl-salicylic-acid pretreatment on re-formed aqueous humor. A study of intracapsular lens extraction in the human eye.
Aqueous humor (a.h.) was sampled in 67 patients operated on for cataract by intracapsular lens extraction at the start and finish of surgery. Twenty eight of these patients received pretreatment with acetyl-salicylic acid (ASA), to a total of 2.5 g, beginning 18 hours prior to surgery. A serum sample was drawn immediately following the operation from 55 patients. Using radial immunodiffusion, albumin and IgG were measured in primary and secondary a.h. and in serum. The group pretreated with ASA showed a significantly smaller relative increase of IgG (P < 0.05). The increase of the proteins, however, showed no dependence on their serum-level and the only side-effect of the treatment was an unexplained rise in serum-albumin. The possible clinical application of patients with a high risk of postoperative complications is briefly summarized.


The management of renal angiomyolipomas in a patient with tuberous sclerosis.
A 17-year-old girl, who was diagnosed with tuberous sclerosis in infancy, presented with multiple bilateral renal masses, the largest of which was 6.0 cm in diameter on the left side. History and physical examination, ultrasonography, MRI, CT, magnetic resonance angiography, and measurement of serial creatinine levels. Bilateral angiomyolipomas.Management Observation, serial imaging, embolization and infarction.


Sexual selection and sperm quantity: meta-analyses of strategic ejaculation.
Multiple mating or group spawning leads to post-copulatory sexual selection, which generally favours ejaculates that are more competitive under sperm competition. In four meta-analyses we quantify the evidence that sperm competition (SC) favours greater sperm number using data from studies of strategic ejaculation. Differential investment into each ejaculate emerges at the individual level if males exhibit phenotypic plasticity in ejaculate properties in response to the likely risk and/or intensity of sperm competition after a given mating. Over the last twenty years, a series of theoretical models have been developed that predict how ejaculate size will be strategically adjusted in relation to: (a) the number of immediate rival males, with a distinction made between 0 versus 1 rival ('risk' of SC) and 1 versus several rivals ('intensity' of SC); (b) female mating status (virgin or previously mated); and (c) female phenotypic quality (e.g. female size or condition). Some well-known studies have reported large adjustments in ejaculate size depending on the relevant social context and this has led to widespread acceptance of the claim that strategic sperm allocation occurs in response to each of these factors. It is necessary, however, to test each claim separately because it is easy to overlook studies with weak or negative findings. Compiling information on the variation in outcomes among species is potentially informative about the relevance of these assumptions in different taxa or mating systems. We found strong evidence that, on average, males transfer larger ejaculates to higher quality females. The effect of female mating status was less straightforward and depended on how ejaculate size was measured (i.e. use of proxy or direct measure). There is strong evidence that ejaculate size increased when males were exposed to a single rival, which is often described as a response to the risk of SC. There is, however, no evidence for the general prediction that ejaculate size decreases as the number of rivals increases from one to several males (i.e. in response to a higher intensity of SC which lowers the rate of return per sperm released). Our results highlight how meta-analysis can reveal unintentional biases in narrative literature reviews. We note that several assumptions of theoretical models can alter an outcome's predicted direction in a given species (e.g. the effect of female mating status depends on whether there is first- or last-male sperm priority). Many studies do not provide this background information and fail to make strong a priori predictions about the expected response of ejaculate size to manipulation of the mating context. Researchers should be explicit about which model they are testing to ensure that future meta-analyses can better partition studies into different categories, or control for continuous moderator variables.


Application of lateral supraclavicular incision in unilateral thyroid papillary carcinoma surgery.
The standard approach to thyroidectomy is a collar incision via the anterior neck, and the neck scar has always been a source of worry for patients. Acceptable wound cosmetology has become a focus for thyroid surgeons. To verify the effectiveness and cosmetic results of thyroidectomy through a lateral supraclavicular incision. 180 patients were randomly divided into two groups: a lateral supraclavicular approach and a conventional transcervical approach. The main outcomes included incision length, intraoperative blood loss, operative time, total drainage volume, hospitalization expense, early postoperative pain measured by visual analog scale, infection, and perceived cosmetic outcome. There were no statistical significances between the two groups in terms of age, gender, nodule size, intraoperative blood loss, operative time, total drainage volume, hospital expense and postoperative complications, whereas there were significant differences in terms of incision length (5.2±1.04cm vs. 6.9±1.14cm, p<0.05). The lateral supraclavicular incision is a safe and feasible approach for thyroidectomy. Compared with conventional approach, it provides a better cosmetic result.


Bacteremia in critically ill immunocompromised patients with acute hypoxic respiratory failure: A post-hoc analysis of a prospective multicenter multinational cohort.
The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF). We performed a secondary analysis of a prospective cohort of immunocompromised patients with ARF (EFRAIM study). After exclusion of blood cultures positive for coagulase negative Staphylococci, we compared patients with (n = 236) and without (n = 1127) bacteremia. The incidence of bacteremia was 17%. Bacterial pneumonia and extra-pulmonary ARDS were the main causes of ARF in bacteremic patients. Bacteremia involved gram negative rods (48%), gram positive cocci (40%) or were polymicrobial (10%). Bacteremic patients had more hematological malignancy, higher SOFA scores and increased organ support within 7 days. Bacteremia was associated with higher crude ICU mortality (40% versus 32%, p = 0.02), but neither hospital (49% versus 44%, p = 0.17) nor 90-day mortality (60% versus 56%, p = 0.25) were different from non-bacteremic patients. After propensity score matching based on baseline characteristics, the difference in ICU mortality lost statistical significance (p = 0.06), including in a sensitivity analysis restricted to patients with pneumonia. We analyzed a large population of immunocompromised patients with ARF and an incidence of bacteremia of 17%. We could not demonstrate an impact of bacteremia on mortality after adjusting for baseline characteristics.


Impact of tobacco use on corneal thickness and endothelial health: a systematic review with meta-analyses.
To investigate the impact of tobacco use on corneal thickness and corneal endothelial health. We searched the PubMed/MEDLINE, EMBASE, the Cochrane Central and all affiliated databases of the Web of Science on 20 July 2020. Two authors reviewed the studies and extracted the data in an independent fashion. Studies were reviewed qualitatively in the text, and central corneal thickness (CCT) and corneal endothelial characteristics (endothelial cell density, endothelial cell variability, average of endothelial cell size and endothelial cell hexagonality) were introduced for quantitative analyses. Eighteen studies (2077 were smokers and 6429 non-smokers) were identified, of which 17 studies provided data eligible for one or more of the quantitative analyses. When compared to non-smokers, smokers had a higher CCT (+3.3 μm, 95% CI: +0.9 to +5.7 μm, p = 0.007) and a lower endothelial cell density (-140 cells/mm2 , 95% CI: -30 to -250 cells/mm2 , p = 0.01). Other corneal endothelial measures did not differ significantly. Tobacco use is associated with a higher CCT and lower corneal endothelium cell density, but the clinical impact of these findings is small. Further studies are warranted on patients with a priori poor corneal health, where smoking may constitute an important risk of further progression, for example upon anterior segment surgery.


Multiple endocrine cell types in thyroid medullary carcinoma. Evidence for calcitonin, somatostatin, ACTH, 5HT and small granule cells.
10 cases of thyroid medullary carcinoma (TMC) have been studied ultrastructurally and histochemically. Well differentiated calcitonin-producing C cells were present in all tumours, being prevalent in 9 cases. 5-Hydroxytryptamine (5HT) storing cells were found in two cases, somatostatin immunoreactive cells in at least 5 cases and ACTH-immunoreactive cells in 4 cases. Ultrastructurally, at least 3 types of apparently non-C cells were observed. Type 1 cells with large, poorly osmiophilic granules resembling those of gastroenteropancreatic D cells, were present in 6 cases; they appeared to correlate well with somatostatin immunoreactive cells. Type 2 cells with large osmiophilic granules were found in 5 cases; they resembled ACTH-MSH cells of the human pituitary and may correspond to the ACTH-immunoreactive cells of light microscopy. Type 3 cells with small granules and an unknown function were found in 6 cases, always in scarce number. It is concluded that TMC, although mainly made up of C cells, usually contains large proportions of other endocrine cell types.


Suppression of lipopolysaccharide-induced fulminant hepatitis and tumor necrosis factor production by bisbenzylisoquinoline alkaloids in bacillus Calmette-Guerin-treated mice.
The bisbenzylisoquinoline (BBI) alkaloids chondocurine, cycleanine, tetrandrine and berbamine were tested for their capacity to suppress hepatic injury and production of tumor necrosis factor (TNF) induced by lipopolysaccharide (LPS) in mice primed with bacillus Calmette-Guerin (BCG). When administered for three consecutive days before LPS injection, chondocurine, cycleanine and tetrandrine (10 mg/kg/day) strongly suppressed serum alanine aminotransferase (EC 18.104.22.168.) and aspartate aminotransferase (EC 184.108.40.206.); however, berbamine gave only slight protection. Chondocurine, cycleanine and tetrandrine but not berbamine significantly reduced the level of TNF which peaked 2 hr after LPS injection. This study shows that BBI alkaloids prevent BCG/LPS-induced hepatitis at least in part by suppressing TNF production.


Proteomic analysis of chlorosome-depleted membranes of the green sulfur bacterium Chlorobium tepidum.
Green sulfur bacteria are obligate anaerobic phototrophs, which in addition to outer and plasma membranes contain chlorosomes. The analysis of the membrane proteome of Chlorobium tepidum from chlorosome-depleted membranes is described in this study. The membranes were purified by sucrose density centrifugation and characterized by 1-DE and 2-DE coupled with MS, absorption spectroscopy, and electron microscopy. 1-DE and 2-DE were employed to analyze the membrane proteins and to characterize the capabilities of the methods. Solubilization of the membrane proteins prior to 2-DE was improved by using a series of zwitterionic detergents. Based on the resolved spots after 2-DE, the combination of amidosulfobetaine 14 with Triton X-100 is more efficient than the combination of CHAPS, N-decyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, and Triton X-100. From the application of 1-DE and 2-DE, 167 and 202 unique proteins were identified, respectively, using PMF by MALDI-TOF MS. Both methods resulted in the detection of 291 different proteins of which only 88 were predicted membrane proteins, indicating the limitation of membrane protein detection after separation with electrophoresis methods. In addition, 53 of these proteins were identified as outer membrane proteins.


Influence of collection and storage materials on glycol ether concentrations in urine and blood.
Glycol ethers, such as propylene glycol monomethyl ether (PGME) and propylene glycol monobuthyl ether (PGBE) are solvents found in many professional and domestic products. In biomonitoring studies, the type of materials used to collect, store, and transport these samples can greatly influence the analytical results because materials can adsorb the analyte. Plastic tubes generally have a hydrophobic internal surface that can reduce the concentration of certain chemicals and result in an underestimation of workers' exposures. The aim of this study was to assess whether the storage of PGME and PGBE spiked blood and urine samples led to different PGME and PGBE concentrations in vials made of glass and common plastics (polypropylene (PP), polyethylene (PE) or polystyrene (PS)). Glycol ether concentrations were quantified with headspace gas chromatography equipped with a flame ionization detector. Our results show stable urinary PGME and PGBE concentrations in PP, while up to 15% variations in urinary PGME for PE and PS. For PGME and PGBE in blood, we observed no statistically significant losses in glass, while losses were recorded for all types of plastic tested (PS, PP and PE). We conclude that biomonitoring samples should be collected in glass for blood and PP for urine.


Detection of antibodies to Toxoplasma gondii among owned dogs in Cambodia.
Toxoplasma gondii is a protozoan parasite belonging to the phylum Apicomplexa, which has a two-host life cycle and an extensive global distribution. The presence of antibodies to T. gondii was examined in owned dogs in Cambodia. In total, 103 dog serum samples from 37 households in northern Cambodia were collected and examined for evidence of T. gondii infection using an indirect immunofluorescent antibody test. In total, 52 of 103 (50.5%) samples were serologically positive for T. gondii in this study. No significant risk factor associated with T. gondii infection was found. To the best of our knowledge, this is the first report of the seroprevalence of T. gondii in dogs from Cambodia, which revealed a considerable risk of infection for humans. Therefore, consuming undercooked dog meat or contacting feces with contaminated cat feces should be restricted to avoid the possibility of zoonosis. Further studies are needed to determine the epidemiology of T. gondii in populations of larger dogs and other animals to improve our understanding of the situation of the pathogen in this country.


Neurocysticercosis in Western Europe: a re-emerging disease?
The objective of the study was to estimate the magnitude of neurocysticercosis in Western Europe and to determine the pattern of disease expression in the region. Review of patients with neurocysticercosis diagnosed in Western Europe from 1970 to 2011. Abstracted data included: demographic profile, clinical manifestations, form of neurocysticercosis, and whether the disease occurred in immigrants, European international travelers, or Europeans who had never been abroad. A total of 779 patients were found. Of these, only 28 were diagnosed before 1985. Countries with more reported patients were Portugal (n = 384), Spain (n = 228), France (n = 80), The United Kingdom (n = 26), and Italy (n = 21). Information on citizenship status, clinical manifestations, and forms of the disease was available in only 30-40% of patients. Immigrants accounted for 53% of cases, European travelers for 8%, and non-traveler Europeans for 39%. Immigrants/European travelers were most often diagnosed during the new Millennium, presented most often with seizures, and had less frequently inactive (calcified) neurocysticercosis than non-traveler Europeans. The prevalence of neurocysticercosis in Western Europe may be on the rise. The pattern of disease expression is different among immigrants/European travelers than among non-traveler Europeans. It is possible that some patients had acquired the disease as the result of contact with Taenia solium carriers coming from endemic countries. Much remains to be learned on the prevalence of neurocysticercosis in this region.


[The success and complications of antenatal corticosteroid treatment to improve pulmonary maturity: a question of the dosage? (author's transl)].
From January 1978 to December 1979 cortico-steroids to improve prenatal pulmonary maturity were administered to 174 patients. Patients with additional factors to accelerate pulmonary maturity or patients with additional factors to pre-dispose to pulmonary asphyxia during labor were not evaluated. 43 patients who delivered 47 children were studied. The cortico-steroid treatment and delay of delivery for over 48 hours improved the survival chances of the pre-mature infants. Following the administration of 4 times 2 mg beta-methasone-phosphate 26.7% of the infants had respiratory distress syndrome whereas no respiratory distress syndrome was found after 4 times 4 mg of beta-methasone-phosphate.


'Ready Mixed', improved nucleic acid amplification assays for the detection of Escherichia coli DNA and RNA.
The selective amplification of E. coli nucleic acid sequences could be used for the early warning of faecal contamination in environmental samples. Modified assays for E. coli DNA and RNA markers are presented with improved integrity and performance over existing methods, and demonstrated using 'ready mixed', preserved reagent mixtures.


The phagokinetic tracks of 3T3 cells.
This paper describes a technique of visualizing tracks of cultured cells moving on a glass substrate covered with gold particles. It leads to the following observations: -If the tracks of many cells are examined, cell line characteristic track patterns become apparent. -In several cases, second or third generation descendents of 3T3 cells were observed to repeat track patterns of their ancestor cell. -If a 3T3 cell collides with another 3T3 cell or a nonmigrating BSC-1 cell, it forms an outgoing track from the impact area as if the cell was elastically reflected at the target.


Traffic safety analysis of powered two-wheelers (PTWs) in Slovenia.
Due to the 2006 European research report on powered two-wheelers (PTWs) riders' traffic safety, Slovenia represents the highest risk for PTW riders in the European Union. Namely, in Slovenia we have the largest number of PTW riders' deaths per billion travelled kilometers in 2006. Since then the traffic safety situation in the field of PTW riders in Slovenia has been improving and we will discuss that phenomenon in the present paper. The paper identifies and analyzes the causes that led to such a critical situation. Further, the evaluation of activities that were carried out to improve the road safety for powered two-wheeler riders in Slovenia in the last past years are discussed. In conclusion a selection of measures and actions is presented that already has been and also should be carried out in the future.


Patterns of mating call preferences in túngara frogs, Physalaemus pustulosus.
We examine acoustic mating preferences of a focal population at four different scales of divergence: within the population, between populations in the same genetic group, between populations in different genetic groups and between different species. At all scales there is substantial genetic divergence, variation in mating signals and preferences are influenced by signal variation. There is, however, no support for the hypothesis that mating preferences accumulate predictably with genetic distance. Females preferred the local conspecific call to the foreign conspecific call in about one-third of the experiments, and preferred the local call to all of the heterospecific calls tested. But there was no significant relationship between the variation in the strength of preference and genetic distance either among conspecific populations, or among heterospecific species. Thus, in this study macroevolutionary patterns are not apparent at the microevolutionary scale.


Comparison of light-microscopic methods for visualizing horseradish peroxidase granules in stained and unstained tissue.
This study was directed toward a comparison of the effectiveness of three different light-microscopical methods for identifying and studying the features of cells that contain horseradish peroxidase (HRP) granules. The cells studied were located in the trigeminal ganglia and were labeled after the injection of HRP solutions into single, maxillary, canine teeth. The tissue was examined with light field, dark field, and differential interference optical systems. The results indicated that differential interference optics were especially useful in revealing the presence of intracellular HRP granules in both unstained and stained tissue, particularly when cells only contained small amounts of HRP. It was also noted that a wide variety of quantitative analyses could be performed with differential interference optics, even when using unstained tissue.


Percutaneous Intradermal Purse-String closure for Correction of Male Tuberous Nipple-Areola Complex Deformity.
Male tuberous breast is an exceedingly rare condition that not fit properly into the majority of existing classifications of gynecomastia. This deformity has been categorized by Cordova and Moschella as gynecomastia grade III; however, they do not make any reference to the isolated tuberous deformity of the nipple-areola complex (NAC). Considering that the areolar area is the main ''esthetic unit'' in the male chest, surgical correction of the isolated tuberous NAC deformity can be challenging. There is a belief that this deformity is unsuccessfully corrected when approached through a limited periareolar incision at the lower pole. A complete periareolar incision, with a concentric excision of excess areolar skin, is usually required leaving an unnatural-looking round periareolar scar on the male thorax. We describe a variation of a surgical technique for the correction of a male tuberous NAC deformity in a teenager who rejected a conspicuous round periareolar scar after surgery. This modification combines a conventional lower hemiareolar approach with a percutaneous intradermal purse-string suture in the superior areolar margin to reduce the areolar diameter, avoiding an evident circumareolar scar. At the six-month follow-up, areolar widening or tuberous deformity relapse was not observed. The patient felt satisfied with the outcome. The use of percutaneous intradermal purse-string periareolar suture for correction of this rare deformity is a simple and reproducible surgical technique that could help to obtain a better cosmetic result by restoring the contour of the male chest while minimizing the visibility of the residual scar. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Theoretical and phantom based investigation of the impact of sound speed and backscatter variations on attenuation slope estimation.
Quantitative ultrasound features such as the attenuation slope, sound speed and scatterer size, have been utilized to evaluate pathological variations in soft tissues such as the liver and breast. However, the impact of variations in the sound speed and backscatter due to underlying fat content or fibrotic changes, on the attenuation slope has not been addressed. Both numerical and acoustically uniform tissue-mimicking experimental phantoms are used to demonstrate the impact of sound speed variations on attenuation slope using clinical real-time ultrasound scanners equipped with linear array transducers. Radiofrequency data at center frequencies of 4 and 5 MHz are acquired for the experimental and numerical phantoms respectively. Numerical phantom sound speeds between 1480 and 1600 m/s in increments of 20 m/s for attenuation coefficients of 0.3, 0.4, 0.5, 0.6, and 0.7 dB/cm/MHz are simulated. Variations in the attenuation slope when the backscatter intensity of the sample is equal, 3 dB higher, and 3 dB lower than the reference is also evaluated. The sound speed for the experimental tissue-mimicking phantoms were 1500, 1540, 1560 and 1580 m/s respectively, with an attenuation coefficient of 0.5 dB/cm/MHz. Radiofrequency data is processed using three different attenuation estimation algorithms, i.e. the reference phantom, centroid downshift, and a hybrid method. In both numerical and experimental phantoms our results indicate a bias in attenuation slope estimates when the reference phantom sound speed is higher (overestimation) or lower (underestimation) than that of the sample. This bias is introduced via a small spectral shift in the normalized power spectra of the reference and sample with different sound speeds. The hybrid method provides the best estimation performance, especially for sample attenuation coefficient values lower than that of the reference phantom. The performance of all the methods deteriorates when the attenuation coefficient of the reference phantom is lower than that of the sample. In addition, the hybrid method is the least sensitive to sample backscatter intensity variations.


Levels and patterns of polycyclic aromatic hydrocarbons (PAHs) in soils after forest fires in South Korea.
To investigate the influence of biomass burning on the levels of polycyclic aromatic hydrocarbons (PAHs) in soils, temporal trends and profiles of 16 US Environmental Protection Agency priority PAHs were studied in soil and ash samples collected 1, 5, and 9 months after forest fires in South Korea. The levels of PAHs in the burnt soils 1 month after the forest fires (mean, 1,200 ng/g dry weight) were comparable with those of contaminated urban soils. However, 5 and 9 months after the forest fires, these levels decreased considerably to those of general forest soils (206 and 302 ng/g, respectively). The burnt soils and ash were characterized by higher levels of light PAHs with two to four rings, reflecting direct emissions from biomass burning. Five and 9 months after the forest fires, the presence of naphthalene decreased considerably, which indicates that light PAHs were rapidly volatilized or degraded from the burnt soils. The temporal trend and pattern of PAHs clearly suggests that soils in the forest-fire region can be contaminated by PAHs directly emitted from biomass burning. However, the fire-affected soils can return to the pre-fire conditions over time through the washout and wind dissipation of the ash with high content of PAHs as well as vaporization or degradation of light PAHs.


Diagnosis of pervasive developmental disorders: when and how? An area-based study about health care providers.
Pervasive developmental disorders (PDDs) can be very difficult to diagnose in children and to communicate such a diagnosis to their parents. Families of children with PDD learn of their child's diagnosis long after the first symptoms are noted in the child's behavior. An area-based survey was conducted to assess all social and health care providers taking care of patients with PDDs in the Veneto Region (North-East Italy). Only 28% of health care providers arrived at a definite diagnosis when the child was in his/her first year of age, 51% when the child was 2-3 years old and 21% from age of 4 years and up. On average, the latency between the time of the diagnosis and its communication to the family was 6.9 months. However, a number of families did not ever have a diagnosis communicated to them. Sometimes, 68% of the providers did not communicate a PDDs diagnosis to patient's families, and 4% of them quite commonly. The well-known delay in making a diagnosis of PDDs has two distinct components: one relating to the difficulty of confirming a diagnosis of PDDs, the other, hitherto unrecognized, relating to the family being notified.


Sensitive identification of silibinin as anticancer drug in human plasma samples using poly (β-CD)-AgNPs: A new platform towards efficient clinical pharmacotherapy.
Silibinin is effective in significantly inhibiting the growth of cancer cells which shown significant anti-neoplastic effects in a variety of in vitro and in vivo cancer models, including skin, breast, lung, colon, bladder, prostate and kidney carcinomas. So, development of a new method to its biomedical analysis in clinical samples in highly demanded. In this study, an innovative electroanalysis method for the accurate, sensitive and rapid recognition of silibinin in human plasma samples was proposed and validated. The sensing platform was designed using silver nanoparticles (AgNPs) dispersed on the polymeric layer of β-cyclodextrin (β-CD). AgNPs with cubic shape providing a large effective surface area for β-CD electropolymerization. So, a layer with high electron conductivity boosting the detection electrochemical signals. Also, poly(β-CD) providing an efficient substrate with cavities to interact with silibinin and its oxidation. Differential pulse voltammetry technique was conducted to measure silibinin concentration in human real samples. Under optimized conditions, proposed sensor indicated linear relationship between the anodic peak current and concentration of silibinin in the range of 0.0103-10.3 µM on the standard and human plasma samples. Based on obtained results, proposed sensor is an efficient platform to efficient therapy of cancer based on recognition of silibinin in clinical samples.


Proportion of Ophthalmic Self-Medication and Associated Factors among Adult Ophthalmic Patients Attending Borumeda Hospital, Dessie, Northeast Ethiopia.
The aim of this study was to determine the proportion of ophthalmic self-medication and associated factors among adult ophthalmic patients attending Borumeda Hospital, Northeast Ethiopia, 2019. An institution-based cross-sectional study design was conducted on 402 participants at Borumeda Hospital from April 29 to May 24, 2019. Systematic random sampling technique was used to get study participants. Data were collected with a face-to-face interview by using a semistructured questionnaire. Data were entered into Epi Info 7 and analyzed by SPSS 20. Descriptive statistics and binary logistic regression analysis were employed. P values of less than 0.05 were considered statistically significant. The proportion of ophthalmic self-medication was 28.6% (95% CI; 24.6-33.3). Age-group 29-42 years (AOR: 2.19, 95% CI: 1.06-4.52), absence of health insurance (AOR: 4.29; 2.35-7.84), more than 10 kilometer traveling distance to get eye services (AOR: 3.11; 1.58-6.12), previous experience of ocular illness (AOR: 2.62, 95% CI: 1.53-4.48), family or friend experience of ocular illness (AOR: 2.65, 95%CI: 1.43-4.92), availability of ophthalmic medicine bottle/tube at home (AOR: 4.59, 95% CI: 2.36-8.92), and poor knowledge about hazards of self-medication (AOR: 6.22; 3.26-11.85) were significantly associated with ophthalmic self-medication. Conclusion and Recommendations. The proportion of ophthalmic self-medication was high, which needs stakeholders' attention. The policymakers and regulatory body better to scale-up health insurance coverage, nearby accessible eye care services, improve knowledge of patients regarding the effect of ophthalmic self-medication, and proper disposal of leftover eye medication from the house. It is better to take regulatory actions on those who dispense ophthalmic medications without prescription.


The Parkinson-Associated Toxin Paraquat Shifts Physiological α-Synuclein Tetramers toward Monomers That Can Be Calpain-Truncated and Form Oligomers.
Abnormal aggregation of α-synuclein (αS) is thought to initiate neuronal dysfunction and death in Parkinson disease (PD). In addition to higher-molecular-weight, oligomeric, and polymeric forms of αS associated with neurotoxicity and disease, recent findings indicate the occurrence of physiological tetrameric assemblies in healthy neurons in culture and in brain. Herein, the PD-associated neurotoxin paraquat reduced physiological tetramers and led to calpain-truncated monomers and an approximately 70-kDa apparent oligomer different in size from physiological αS multimers. These truncated and oligomeric forms could also be generated by calpain cleavage of pure, recombinant human αS in vitro. Moreover, they were detected in the brains of tetramer-abrogating, E46K-amplified (3K) mice that model PD. These results indicate that paraquat triggers membrane damage and aberrant calpain activity that can induce a pathologic shift of tetramers toward an excess of full-length and truncated monomers, the accumulation of αS oligomers, and insoluble cytoplasmic αS puncta. The findings suggest that an environmental precipitant of PD can alter αS tetramer/monomer equilibrium, as already shown for several genetically caused forms of PD.


Dose proportionality of transdermal nitroglycerin.
The FDA Cooperative Efficacy Study of transdermal nitroglycerin utilized a combination of marketed products over a wide dose range. Unfortunately, plasma nitroglycerin concentrations were not determined. The current study was conducted to assess plasma nitrate concentrations after transdermal doses of 15, 30, 60, and 105 mg/24 hr employing the FDA Cooperative Study design. Plasma concentrations of nitroglycerin, 1,3-glyceryl dinitrate, and 1,2-glyceryl dinitrate were determined during the 24 hr of application and for 1 hr after transdermal system removal. Dose proportionality was assessed after normalizing the data by theoretical dose. For nitroglycerin, dose-normalized AUC(0-infinity) and Cmax were higher for the 105 mg/24 hr dose than for the other doses. For the metabolites, 1,3-glyceryl dinitrate and 1,2-glyceryl dinitrate, there were no differences in dose-normalized AUC(0-infinity) and dose-normalized Cmax between the dose levels. No differences were seen in Tmax between the dose levels for all three species. Based on the dinitrate metabolites, dose proportionality was seen over the 15 to 105 mg/24 hr dose range. Nitroglycerin, however, was found to be linear only between 15 and 60 mg/24 hr.


Adiabatic RF pulse design for Bloch-Siegert B1+ mapping.
The Bloch-Siegert (B-S) B1+ mapping method has been shown to be fast and accurate, yet it suffers from high Specific Absorption Rate (SAR) and moderately long echo time. An adiabatic RF pulse design is introduced here for optimizing the off-resonant B-S RF pulse to achieve more B-S B1+ measurement sensitivity for a given pulse width. The extra sensitivity can be used for higher angle-to-noise ratio B1+ maps or traded off for faster scans. Using numerical simulations and phantom experiments, it is shown that a numerically optimized 2-ms adiabatic B-S pulse is 2.5 times more efficient than a conventional 6-ms Fermi-shaped B-S pulse. The adiabatic B-S pulse performance is validated in a phantom, and in vivo brain B1+ mapping at 3T and 7T are shown.


Visual stability with goal-directed eye and arm movements toward a target displaced during saccadic suppression.
This experiment tested whether the perceived stability of the environment is altered when there is a combination of eye and visually open-loop hand movements toward a target displaced during the eye movements, i.e., during saccadic suppression. Visual-target eccentricity randomly decreased or increased during eye movements and subjects reported whether they perceived a target displacement or not, and if so, the direction of the displacement. Three experimental conditions, involving different combinations of eye and arm movements, were tested: (a) eye movements only; (b) simultaneous eye and rapid arm movements toward the target; and (c) simultaneous eye and arm movements with a restraint blocking the arm as soon as the hand left the starting position. The perceptual threshold of target displacements resulting in an increased target eccentricity was greater when subjects combined eye and arm movements toward the target object, specially for the no-restraint condition. Subjects corrected most of their arm trajectory toward the displaced target despite the short movement times (average MT = 189 ms). After the movements, the null error feedback of the hand's final position presumably overlapped the retino-oculomotor signal error and could be responsible for the deficient perception of target displacements. Thus, subjects interpreted the terminal hand positions as being within the range of the endpoint variability associated with the production of rapid arm movements rather than as a change of the environment. These results suggest that a natural strategy adopted for processing spatial information, especially in a competing situation, could favour a constancy tendency avoiding systematic perception of a change of environment for any noise or variability at the central or peripheral levels.


Accelerated gastric emptying but no carbohydrate malabsorption 1 year after gastric bypass surgery (GBP).
Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption. Seven morbidly obese subjects (BMI = 44.5 ± 2.8 kg/m(2)) were studied before and 1 year after GBP with a D: -xylose test. After ingestion of 25 g of D: -xylose in 200 mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of D: -xylose) and carbohydrate absorption using standard criteria. One year after GBP, subjects lost 45.0 ± 9.7 kg and had a BMI of 27.1 ± 4.7 kg/m(2). Gastric emptying was more rapid after GBP. The mean time to appearance of D: -xylose in serum decreased from 18.6 ± 6.9 min prior to GBP to 7.9 ± 2.7 min after GBP (p = 0.006). There was no significant difference in absorption before (serum D: -xylose concentrations = 35.6 ± 12.6 mg/dL at 60 min and 33.9 ± 9.1 mg/dL at 180 min) or 1 year after GBP (serum D: -xylose = 31.5 ± 18.1 mg/dL at 60 min and 27.2 ± 11.9 mg/dL at 180 min). These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1 year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis.


Chlorpromazine stimulatory effect on iron uptake by rat brain synaptosomes.
Clinical long-term neuroleptic administration induces extrapyramidal motor side-effects, of which tardive dyskinesia is the most important. Experimentally, dopamine D2 supersensitivity is observed after phenothiazine and butyrophenone treatment. Neuroleptic-induced tardive dyskinesia and D2 modulation have been linked to impaired iron homeostasis in the central nervous system. Increased nonheme iron levels found in the basal ganglia of patients with extrapyramidal symptomology support the connection between iron and neuronal dopaminergic modulation. We now report the effect of chlorpromazine on iron uptake by synaptosomes of rat brain from two different iron donors: [55Fe]citrate and [55Fe]transferrin. Iron uptake from both donors by cortical synaptosomes was stimulated by Ca2+ and enhanced by chlorpromazine in a saturable fashion. Synaptosomes from the striatum also showed increased (60%) iron uptake from [55Fe]citrate in the presence of chlorpromazine. Chlorpromazine stimulated iron uptake by cortical synaptosomes more efficiently than Ca2+, at physiological levels, from both [55Fe]transferrin (50%) and [55Fe]citrate (68%). Calcium potentiated the effect of chloropromazine upon cortical synaptosomal iron uptake from [55Fe]citrate, but had no apparent effect on the uptake from [55Fe]transferrin. Chlorpromazine-stimulated iron uptake from the latter was observed without addition of Ca2+. Moreover, fluorescence measurement of Ca2+ uptake by cortical synaptosomes showed intensified uptake in the presence of 50 microM chlorpromazine (42%). Visible spectral studies of chlorpromazine in the presence of Fe(3+)-citrate and diferric-transferrin did not reveal iron displacement by chlorpromazine from either of the two donors. These data suggest that chlorpromazine may increase iron uptake by neurons, and may be involved in the development of tardive dyskinesia and other extrapyramidal disorders.


Cryptic specialized metabolites drive Streptomyces exploration and provide a competitive advantage during growth with other microbes.
Streptomyces bacteria have a complex life cycle that is intricately linked with their remarkable metabolic capabilities. Exploration is a recently discovered developmental innovation of these bacteria, that involves the rapid expansion of a structured colony on solid surfaces. Nutrient availability impacts exploration dynamics, and we have found that glycerol can dramatically increase exploration rates and alter the metabolic output of exploring colonies. We show here that glycerol-mediated growth acceleration is accompanied by distinct transcriptional signatures and by the activation of otherwise cryptic metabolites including the orange-pigmented coproporphyrin, the antibiotic chloramphenicol, and the uncommon, alternative siderophore foroxymithine. Exploring cultures are also known to produce the well-characterized desferrioxamine siderophore. Mutational studies of single and double siderophore mutants revealed functional redundancy when strains were cultured on their own; however, loss of the alternative foroxymithine siderophore imposed a more profound fitness penalty than loss of desferrioxamine during coculture with the yeast Saccharomyces cerevisiae. Notably, the two siderophores displayed distinct localization patterns, with desferrioxamine being confined within the colony area, and foroxymithine diffusing well beyond the colony boundary. The relative fitness advantage conferred by the alternative foroxymithine siderophore was abolished when the siderophore piracy capabilities of S. cerevisiae were eliminated (S. cerevisiae encodes a ferrioxamine-specific transporter). Our work suggests that exploring Streptomyces colonies can engage in nutrient-targeted metabolic arms races, deploying alternative siderophores that allow them to successfully outcompete other microbes for the limited bioavailable iron during coculture.


Long-term immobilization of soil metalloids under simulated aging: Experimental and modeling approach.
Aging is an inevitable natural process, leading to faded performances of soil amendments. Understanding long-term aging features is crucial for the risk management of contaminated soil. In this study, a novel quantitative aging method, namely, the "soil coin" method, was developed, which can simulate the effects of natural aging on metal(loid) immobilization performances. To better depict the aging features, two models on the basis of conditional probability-induced failure were developed. To effectively immobilize soil arsenic (As) and antimony (Sb), magnesium (Mg) and iron (Fe) oxides were simultaneously introduced to either fresh or pre-oxidized biochar via a facile method. Although post-application aging is harmful, pre-aging (i.e., pre-oxidation using H2O2) in turn served as an effective means to introduce more metal oxides, thereby rendering better short-term and long-term effectiveness for metalloid immobilization. Experimental and modeling approaches suggested that precipitation accounted for long-term immobilization, while a constant aging rate is the key feature for a promising soil amendment. It is suggested that to further calibrate this method and better understand the immobilization performances in the long run, more evidence from the field is needed.


Application of the Care Bundle in Perioperative Nursing Care of the Type A Aortic Dissection.
To investigate the effect of the care bundle in the nursing care of the type A aortic dissection (TAAD). A total of 161 patients with TAAD were included in the study. They were divided into control group (n=79) and care bundle group (n=82). The patients in the control group received routine nursing, while the patients in the care bundle group received routine nursing and care bundle. IL-2, IL-6 and IL-10 levels in the three periods of T0 (before anesthesia), T1 (before anesthesia to 6 h after surgery) and T2 (6-24 h after surgery), intraoperative blood loss, postoperative recovery, ICU stay time, intraoperative pressure ulcer rate, postoperative delirium rate, bloodstream infection rate and doctor satisfaction. The postoperative T and pH levels in two groups were all in the normal range. The levels of IL-2, IL-6 and IL-10 in the care bundle group at different periods were also significantly different. The levels of IL-2 and IL-10 showed an increased trend, while that of IL-6 showed a downward trend. The intraoperative blood loss, postoperative recovery and ICU stay time, intraoperative pressure sore rate, postoperative delirium rate, and bloodstream infection rate were lower, whereas doctor satisfaction was all significantly higher in care bundle group. Care bundle increased the safety of the operation, and it was beneficial to the postoperative rehabilitation for TAAD patients. Patients with TAAD who underwent operation need higher quality care during the entire operation. Cluster nursing is the kind of the nursing model that can better meet the requirements of the intraoperative nursing quality. The intervention methods in this study include 5 core nursing measures. These measures are implemented together in a synergistic manner to effectively improve the quality of nursing care in operating room and the health outcomes of patients with TAAD. Care bundle is worthy of clinical application.


Examining components of community psychosocial stroke interventions using concept mapping.
Stroke impacts psychosocial well-being and engagement in occupation. Psychosocial interventions reduce depression and anxiety but may not impact occupation. Knowledge of key processes and components of community psychosocial stroke interventions can inform future intervention development. To determine the essential elements common to three psychosocial interventions for stroke survivors. Concept maps were created for three community psychosocial stroke interventions based on published literature and communication with researchers who tested the intervention with stroke survivors. The concept maps were then compared to identify common elements. Ongoing communication with researchers ensured accurate representation of each respective intervention. Similarities in intervention processes and components included support for autonomy; individualized information exchange; coping, life skill development and adaptation support; competence development; and the incorporation of goals. Differences included intervention delivery (individual versus group), and the avenues in which psychosocial needs are addressed (occupation versus dialogue). Concept mapping identified similarities among the three interventions that can be best understood using self-determination theory. Clinicians may utilize findings revealed in the process to inform evidence-based psychosocial stroke interventions. Knowledge of key 'active ingredients' for psychosocial community stroke interventions, can be used to guide clinical reasoning and inform development of interventions.


ERASM, a pharmacoepidemiologic survey on management of intermittent allergic rhinitis in every day general medical practice in France.
The actual management of intermittent allergic rhinitis is still little known about, despite the disease being very prevalent. We used a cross-sectional survey to address this issue in everyday general medical practice in France. A total of 1321 general practitioners enrolled 3026 patients consulting for a spring exacerbation of allergic rhinitis. Both doctors and patients filled out a specific questionnaire on allergic rhinitis. These patients consulted their doctor two-and-a-half weeks, on average, after the onset of their symptoms. They were bothered for an average of six days per week (5.9 +/- 1.7 days) and for two months per year (8.7 +/- 7.7 weeks) by symptoms which largely exceed the ENT (ear, nose and throat) field, with ocular symptoms (51.7%), pharyngeal irritation (39.0%), cough (30.8%), or respiratory discomfort (17.9%). Of these patients 79.2% had some impairment of their professional life and 91.8% of their daily life. Fifty percent of patients knew to what allergens they were allergic; only 11.1% had additional laboratory tests and 10.3% had subsequent specialist consultation (for most this was with an allergologist). Prescribed drugs were oral antihistamines (92.4%) and nasal glucocorticosteroids (45.2%). Prescriptions were written for a duration of six weeks on average. Seventy-nine percent of patients considered that the information they had received was adequate and easy to understand, but 58.2% of patients would have liked more advice. Furthermore, only 54.7% followed their doctor's prescription scrupulously, and 44% used frequent self-medication. Intermittent allergic rhinitis is a real health problem because of its increasing prevalence, the induction of impaired quality of life and loss of performance, especially at work. General practitioners play a major role in this disorder; they make the diagnosis, start the treatment, give the relevant information, and monitor most of the patients.


Enhancement of skin grafts in the mouse. The combined used of specific and nonspecific immunosuppression.
Enhancement of skin grafts in mice by passively administered alloantiserum was examined in conjunction with the simultaneous use of other immunosuppressive regimens. It could be clearly shown that when a "weak" antilymphocyte serum (ALS) was used, a significant further prolongation of graft survival occurred over that obtained with the enhancing antiserum alone, and these two separate effects were synergistic. When a "strong" ALS was used, no synergistic effects were apparent unless the enhancing alloantiserum was given almost continuously. A similar, but less impressive synergism was seen when the enhancing alloantiserum and azathioprine were used together. Azathioprine, like ALS, presumably acts on T cells, whereas drugs directed against B cells, such as cyclophosphamide and prednisolone, failed to show any synergistic effect.


Research Advances on Molecular Mechanism of Salt Tolerance in Suaeda.
Plant growth and development are inevitably affected by various environmental factors. High salinity is the main factor leading to the reduction of cultivated land area, which seriously affects the growth and yield of plants. The genus Suaeda is a kind of euhalophyte herb, with seedlings that grow rapidly in moderately saline environments and can even survive in conditions of extreme salinity. Its fresh branches can be used as vegetables and the seed oil is rich in unsaturated fatty acids, which has important economic value and usually grows in a saline environment. This paper reviews the progress of research in recent years into the salt tolerance of several Suaeda species (for example, S. salsa, S. japonica, S. glauca, S. corniculata), focusing on ion regulation and compartmentation, osmotic regulation of organic solutes, antioxidant regulation, plant hormones, photosynthetic systems, and omics (transcriptomics, proteomics, and metabolomics). It helps us to understand the salt tolerance mechanism of the genus Suaeda, and provides a theoretical foundation for effectively improving crop resistance to salt stress environments.


Brief Report Treatment of infertility and menopause in a patient with multiple sclerosis affecting the pituitary stalk: a case report.
Multiple Sclerosis (MS) is an immune-mediated inflammatory disease characterized by demyelination of the CNS that affects women in their child-bearing years. There has been no absolute data to suggest infertility in this population; however, women with MS may exhibit decreased fertility due to various etiologies. Furthermore, their transition into menopause presents unique aspects in patient care. We report a case of a 38 year-old female with a diagnosis of MS with subsequent secondary amenorrhea and primary infertility. Multidisciplinary work-up with was consistent with hypothalamic hypogonadism secondary to MS affecting the pituitary stalk. She was treated for infertility in our clinic as well as management of her menopausal symptoms. The patient conceived triplets after 2 cycles of ovarian stimulation with injectable gonadotropins and intrauterine insemination. She underwent fetal reduction to twins. After completion of childbearing, she was treated for menopausal symptoms with various hormonal therapies and ultimately remained on oral conjugated estrogens with no symptoms. To our knowledge, this is the first report of infertility caused by suspected MS involvement of the pituitary stalk. In this patient population, infertility treatment can be successful with gonadotropins and alleviation of menopausal symptoms can be achieved with hormone replacement.


Two-photon laser spectroscopy of antiprotonic helium and the antiproton-to-electron mass ratio.
Physical laws are believed to be invariant under the combined transformations of charge, parity and time reversal (CPT symmetry). This implies that an antimatter particle has exactly the same mass and absolute value of charge as its particle counterpart. Metastable antiprotonic helium (pHe(+)) is a three-body atom consisting of a normal helium nucleus, an electron in its ground state and an antiproton (p) occupying a Rydberg state with high principal and angular momentum quantum numbers, respectively n and l, such that n ≈ l + 1 ≈ 38. These atoms are amenable to precision laser spectroscopy, the results of which can in principle be used to determine the antiproton-to-electron mass ratio and to constrain the equality between the antiproton and proton charges and masses. Here we report two-photon spectroscopy of antiprotonic helium, in which p(3)He(+) and p(4)He(+) isotopes are irradiated by two counter-propagating laser beams. This excites nonlinear, two-photon transitions of the antiproton of the type (n, l) → (n - 2, l - 2) at deep-ultraviolet wavelengths (λ = 139.8, 193.0 and 197.0 nm), which partly cancel the Doppler broadening of the laser resonance caused by the thermal motion of the atoms. The resulting narrow spectral lines allowed us to measure three transition frequencies with fractional precisions of 2.3-5 parts in 10(9). By comparing the results with three-body quantum electrodynamics calculations, we derived an antiproton-to-electron mass ratio of 1,836.1526736(23), where the parenthetical error represents one standard deviation. This agrees with the proton-to-electron value known to a similar precision.


RP11-79H23.3 Inhibits the Proliferation and Metastasis of Non-small-cell Lung Cancer Through Promoting miR-29c.
Evidences indicate that long non-coding RNAs (lncRNAs) are closely involved and contributed to tumorigenesis and cancer progression. As a novel lncRNA, RP11-79H23.3 was found to be an anti-oncogene in bladder cancer. However, the essential roles and functions of RP11-79H23.3 in non-small-cell lung cancer (NSCLC) remains to be elucidated. Here, loss of functional assay was applied to gain insights into the functions of RP11-79H23.3 on the proliferation and metastasis capabilities of A549 and H1299 cells. Meantime, Real-time PCR was utilized to measure RP11-79H23.3 and miR-29c expression in NSCLC tissues. Dual-luciferase reporter assay, CCK8, colony formation assay, transwell and Western blot were performed to illustrate the potential molecular basis of RP11-79H23.3 in NSCLC. RP11-79H23.3 downregulation facilitated cell proliferation, migration, and invasion of NSCLC. The result of dual-luciferase reporter assay represented a direct interaction of RP11-79H23.3 with miR-29c, which suppressed miR-29c expression that showed inversely correlation in NSCLC. Moreover, RP11-79H23.3 siRNA facilitated the progression of NSCLC partially via regulating the expression of miR-29c and the activation of Wnt/β-catenin signaling pathway. Our findings highlighted that RP11-79H23.3, served as an anti-oncogene, accelerated NSCLC progression through sequestering miR-29c, providing a promising therapeutic target for NSCLC.


Iron deficiency does not impair the outcome after elective coronary artery bypass and aortic valve procedures.
BACKGROUND AND AIM OF THE STUDY: Iron deficiency (ID), a common malnutrition, has been linked to impaired prognosis in patients with congestive heart failure. It remains unclear whether ID also affects the outcome after elective cardiac surgery. A total of 378 consecutive patients undergoing either coronary artery bypass grafting (CABG) or surgical aortic valve replacement (SAVR) were prospectively enrolled, and blood samples were taken before surgery for analysis of iron metabolism. Incidence of major adverse cardiovascular and cerebrovascular events (MACCE) was defined as the primary endpoint of the study. ID (ferritin < 100 ng/ml or ferritin = 100-299 ng/ml and transferrin saturation < 20%) was common in cardiac surgery patients (ID, n = 265, 70%) and related to significant decreased preoperative hemoglobin values (ID: 13.6 ± 1.6 g/dl, Non-ID: 14.3 ± 1.5 g/dl, p < 0.01). We did not observe any differences in the postoperative outcome of the two groups. The incidence of MACCE was 4.9% in patients with ID and 8.8% in Non-ID (p = 0.16). In-hospital mortality (ID: 1.9%, Non-ID: 4.4%, p = 0.17) and stroke (ID: 1.1%, Non-ID: 1.8%, p = 0.64) were also not altered by ID. In addition, intensive care unit and hospital stay, perioperative blood transfusions as well as perioperative morbidities, such as acute kidney injury, low cardiac output syndrome, major bleeding complication, and sternal wound infections were comparable in patients with and without ID. The majority of patients undergoing elective CABG or SAVR suffer from ID; however, we found no significant differences in regard to MACCE and postoperative morbidity between ID and non-ID patients.


Overamplification of macronuclear linear DNA molecules during prolonged vegetative growth of Oxytricha nova.
During prolonged vegetative growth of a clonal line of Oxytricha nova, several macronuclear linear DNA molecules increased greatly in copy number over the rest of the approx. 24,000 kinds of molecules comprising the macronuclear genome. One of the amplified sequences was the linear DNA molecule encoding rRNA (rDNA). We have cloned and sequenced the other, smaller, amplified molecules and found that they comprise a gene family, with different allelic versions of one of the family members being amplified. Thus, increased replication is a general property of the molecules comprising this gene family. To date, no function has been assigned to these genes; thus, whether the amplification of these sequences has functional significance is unknown. The rDNA molecule and the two small amplified sequences increased 11-, 24- and 107-fold, respectively, during clonal growth of this line, eventually comprising up to 15% of the macronuclear DNA molecules. Seven other macronuclear DNA molecules did not vary substantially in copy number at different times during the clonal growth of this strain. Analysis of cell-to-cell differences in copy numbers in this clonally aged strain indicated more extensive variation than is evident when large populations from different times are compared.