Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.
A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H2 SO4 at λem = 364 nm after excitation at λex = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd.


Long-acting nicardipine for elderly hypertensive patients: effect on diurnal variation of blood pressure.
The effect of long-acting nicardipine tablets on diurnal variation of blood pressure was compared with that of standard nicardipine tablets and long-acting nifedipine tablets by 24-hour ambulatory blood pressure monitoring in 35 patients with hypertension. Long-acting nicardipine decreased systolic blood pressure in each age group, and there was no difference in its anti-hypertensive effect when compared with the other two drugs. All three drugs had no effect on the amplitude of daily blood pressure variation, and all three drugs decreased the baseline blood pressure in each age group when compared with untreated patients. In addition, no change was observed in the decrement of baseline blood pressure after switching from the other two drugs to long-acting nicardipine. Long-acting nicardipine had less effect on diurnal blood pressure variation than standard nicardipine tablets, which are administered three times daily. In each age group, long-acting nicardipine also more effectively inhibited the increase in cardiac work resulting from the morning rise phenomenon when compared with standard nicardipine tablets. These findings suggest that long-acting nicardipine may be a more useful preparation for the treatment of essential hypertension, particularly in elderly patients.


[An overview of the management of erectile disorders].
The large successive studies on the treatment of erectile disorders started with local injections of papaverine in 1982, followed by the marketing of intracavernous injections of alprostadil in 1994 and, in 1998, sildenafil, the first type 5 phosphodiesterase inhibitor. An efficient alternative to improve the quality and duration of an erection is presently represented by intra-cavernous injections of alprostadil alfadex when oral treatments are insufficient, inefficient or contraindicated.


Immunogenic and antigenic epitopes of immunoglobulins. II. Antigenic differences between secreted and membrane IgG demonstrated using monoclonal antibodies.
Twenty-three monoclonal antibodies with specificity for epitopes in the Fc fragment of IgG have been used to investigate antigenic differences between secreted and membrane forms of IgG produced by 2 human B lymphoblastoid cell lines (LCL). All of the monoclonals reacted with IgG secreted by the cell lines, as demonstrated by their ability to agglutinate SRBC coated with immunoglobulin isolated from culture supernatants. Membrane IgG expression was studied using direct and indirect rosette assays with antibody-coated ORBC. A surprisingly high number of antibodies, 13 on EB2 and 9 on EB4, did not bind to the cell surface immunoglobulin. These included antibodies with specificities for both C gamma 3 and C gamma 2 domain determinants. Similar results were obtained with an indirect radiobinding assay, indicating that negative results with the rosette test were not due to steric hindrance by the red cell carrier. Their performance in indirect hemagglutination indicated that most of the antibodies that did not bind to membrane IgG were of high avidity. It is concluded that the epitopes for which these antibodies are specific are not available on the cell surface. Possible explanations for the apparent antigenic differences between secreted and membrane forms of IgG are discussed against the background of previous work on the structure and mode of insertion of cell surface immunoglobulin.


Measuring Membrane Lipid Turnover with the pH-sensitive Fluorescent Lipid Analog ND6.
Exo-/endocytosis is a common process mediating the exchange of biomolecules between cells and their environment and among different cells. Specialized cells use this process to execute vital body functions such as insulin secretion from β cells and neurotransmitter release from chemical synapses. Owing to its physiological significance, exo-/endocytosis has been one of the most studied topics in cell biology. Many tools have been developed to study this process at the gene and protein level, because of which much is known about the protein machinery participating in this process. However, very few methods have been developed to measure membrane lipid turnover, which is the physical basis of exo-/endocytosis. This paper introduces a class of new fluorescent lipid analogs exhibiting pH-dependent fluorescence and demonstrates their use to trace lipid recycling between the plasma membrane and the secretory vesicles. Aided by simple pH manipulations, those analogs also allow the quantification of lipid distribution across the surface and the intracellular membrane compartments, as well as the measurement of lipid turnover rate during exo-/endocytosis. These novel lipid reporters will be of great interest to various biological research fields such as cell biology and neuroscience.


Reverse Transcription Polymerase Chain Reaction-based System for Simultaneous Detection of Multiple Lily-infecting Viruses.
A detection system based on a multiplex reverse transcription (RT) polymerase chain reaction (PCR) was developed to simultaneously identify multiple viruses in the lily plant. The most common viruses infecting lily plants are the cucumber mosaic virus (CMV), lily mottle virus (LMoV), lily symptomless virus (LSV). Leaf samples were collected at lily-cultivation facilities located in the Kangwon province of Korea and used to evaluate the detection system. Simplex and multiplex RT-PCR were performed using virus-specific primers to detect single-or mixed viral infections in lily plants. Our results demonstrate the selective detection of 3 different viruses (CMV, LMoV and LSV) by using specific primers as well as the potential of simultaneously detecting 2 or 3 different viruses in lily plants with mixed infections. Three sets of primers for each target virus, and one set of internal control primers were used to evaluate the detection system for efficiency, reliability, and reproducibility.


Recent data on mitral valve prolapse and magnesium deficit.
Idiopathic mitral valve prolapse (IMVP) is a widespread disease. IMVP may be latent, but most patients describe a great variety of symptoms. The clinical pictures of IMVP and of latent tetany are superimposed with regard to Mg deficit. IMVP appears as a late complication of latent tetany due to magnesium deficit (LTMD). The Mg deficit has various causes: insufficient Mg intake (especially during slimming diets), and depletion of Mg provoked by stress, coffee excess, corticosteroids or catecholamine excess. The high prevalence in women is mainly due to the ovarian hormones. Constitutional factors such as the HLA Bw35 antigen and the behavioural type A favour Mg depletion. The HLA-Bw35-positive individuals show a lower level of tissue Mg. In the development of the valvular lesion there are some other associated factors apart from Mg deficit which alter collagen metabolism: ascorbic acid deficit, febrile illnesses, corticosteroid excess. Symptomatology is dominated by the latent tetany syndrome. Palpitations and precordial pain are the most frequent cardiac symptoms. The click and mid-late systolic murmer do not appear in all IMVP cases. In clinical investigation the following tests are indispensable: echocardiogram, electrocardiogram, evaluation of plasma and erythrocyte Mg, calcaemia and calciuria. In particular cases more sophisticated studies are necessary. Therapy based on Mg should be applied consistently and for long periods of time. Mg therapy results in the control of latent tetany as well as in morphologic recovery. The administration of Mg in LT prevents the development of IMVP.


Ex vivo gene therapy using granulocyte-macrophage colony-stimulating factor-transduced tumor vaccines.
There is no standard effective therapy for metastatic renal-cell carcinoma (RCC) or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted to a tumor-associated antigen may be effective. Transduction of the gene encoding granulocyte-macrophage colony-stimulating factor has shown promise in preclinical studies, and clinical trials are in their early stages. Both autologous cancer cells and partially HLA-matched allogenic cells are being studied. No dose-limiting side effects have been observed, and a few patients have had transient objective tumor regressions. Further trials with more frequent and, probably, longer immunization schedules are needed to define efficacy.


Genetic status of p53 in stomach cancer: somatic mutations and polymorphism of codon 72.
The incidence of somatic mutagenesis of p53 oncosuppressor protein in malignant tumors of the stomach and genetic polymorphism of p53 were studied in patients with stomach cancer on DNA samples isolated from tumor tissues obtained during surgery. The incidence of Pro/Pro genotype increased in the patients, while the percentage of Arg/Pro heterozygotes was markedly lower compared to long-living persons without cancer. The incidence of p53 somatic mutations in exons 5, 7, 8 was 70.8%; multiple mutations were detected in half of the examined patients. The relationship between the intensity of p53 mutagenesis and histological structure of the tumor was detected. The contribution of p53 genetic status to the risk of stomach cancer can be more effectively evaluated on DNA samples isolated from not only tumor cells, but also from normal tissues. The effects of epigenetic factors determining the intensity of somatic mutagenesis of p53 in tumors should be taken into account.


Thromboprophylaxis in patients with multiple organ injuries--is there an alternative to low-molecular-weight heparins (LMWH)?
The number of body injuries keeps growing and that is mostly due to increasing number of car accidents. How to prevent thrombosis in such cases is still under discussion with the biggest issue being the proper timing. Most of the input to such discussion usually comes from extrapolating data from other studies, which is hardly of help for treatment of such group of patients. The authors focus on collection and analysis of most recent data and recommendations that are available in literature. They show that low-molecular-weight heparins are by far the most common, if not sole pharmacologic means of thromboembolism prevention in patients with numerous body injuries.


[Expressions of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases 1 in skeletal muscles of aged rats with sarcopenia].
To investigate the changes of skeletal muscle mass and strength and the expressions of matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinases-1 (TIMP-1) and collagen-1 in the skeletal muscle of aged rats with sarcopenia. With 11 young (6-month-old) SD rats as control group, 18 aged (25-month-old) SD rats were divided into two groups (n=9) according to the relative lean mass determined dual X-ray absorptiometry (DXA), namely aged control group and aged sarcopenia group (the relative lean mass was 2SD higher in aged control than in aged sarcopenia group. The forelimb grip strength of the rats was measured using an electronic grip strength meter. The extracellular matrix (ECM) of the rat's gastrocnemius was observed with HE staining and sirius Red staining, and the protein expressions of collagen-1, MMP-1, and TIMP-1 in the muscular tissues were detected with Western blotting. Compared with the young rats, the aged control rats had significantly lower relative grip strength (P < 0.01) and increased expressions of collagen-1 and TIMP-1 (P < 0.05) and ECM content in the skeletal muscles, but the relative lean mass and MMP-1 protein expression were comparable between the two groups (P>0.05). Compared with the aged control rats, the aged sarcopenic rats had significantly lowered relative lean mass (P < 0.01) and MMP-1 expressions of (P < 0.05) and increased expressions of collagen-1 and TIMP-1 proteins and ECM content in the muscular tissues (P < 0.05) without significant changes in the relative grip strength (P>0.05). MMP-1/TIMP-1 imbalance in the skeletal muscle during aging affects ECM metabolism and leads to increased collagen fibers, which in turn affects the skeletal muscle mass and function and contribute to the onset of sarcopenia.


Considerations in the treatment of dyslipidemia associated with chronic kidney failure and renal transplantation.
In comparison to the general population, individuals with chronic kidney failure experience an increased risk for atherosclerotic cardiovascular disease attributed predominantly to pronounced abnormalities in lipid metabolism. The emerging consensus is that patients with chronic kidney failure should be treated aggressively for dyslipidemia. Statins reduce the risk of cardiovascular disease in a range of at-risk patients; this class of lipid-lowering drugs should be considered first-line treatment of dyslipidemia observed in renal disease patients. Although the statins share a common lipid-lowering effect, there are differences within this class of drugs. The statins differ in their pharmacokinetic effects, drug interaction profiles, and risk of myotoxicity. This article characterizes the dyslipidemia observed in the renal failure setting and reviews the therapeutic considerations involved in selecting among the statins. Lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, and rosuvastatin are the available statins in the United States.


ERG findings in three hypothyroid adult dogs with and without levothyroxine treatment.
To evaluate the effects of levothyroxine (LTh) on the electroretinogram (ERG) of adult dogs. Binocular, full field photopic and scotopic ERGs were recorded from an anesthetized Maltese Bichon cross (MB), a Yorkshire Terrier (YT) and a Shetland Sheepdog (SS) affected with hypothyroidism and treated with a daily dose of LTh at 20 microg/kg. The photopic ERGs were evoked to 12 different intensities ranging from 0.81 to -2.19 log cd.s/m(2) and presented under photopic conditions in order to assess (from the derived luminance-response curves) Vmax and b : a amplitude ratio parameters. Photopic flicker ERGs were obtained at 30 Hz. The scotopic ERGs (intensity: -3.09 log cd.s/m(2)) were recorded while the retina was dark-adapting and after 32 min of dark adaptation. This procedure was performed on two separate sessions: following a 3-day interruption of LTh treatment (S1) and following 30 days without interruption of LTh treatment (S2). The mean photopic a-wave peak times were 9.8 ms at S1 and 5.0 ms at S2, respectively. The mean photopic b-wave peak times were 23.3 ms at S1 and 11.5 ms at S2, respectively, and the mean scotopic b-wave peak times (after 32 min of dark adaptation) were 45.2 ms at S1 and 26.0 ms at S2, respectively. No other significant ERG changes were observed. Our results indicate that a dose of 20 microg/kg of LTh given to adult dogs was accompanied by a marked peak time shortening of both photopic and scotopic ERGs, without affecting other ERG parameters.


Etiologic diagnosis of renal calculus disease.
Renal calculus disease is a common cause of morbidity in industrialized societies, accounting for seven to 10 of every 1000 hospital admissions. Recent advances in surgical therapy have made operative therapy much less invasive while maintaining a high level of success. However, the need to reduce the incidence of this disease persists as more than one half of all stone formers will have recurrence. Although the etiology and therapy for several types of renal calculi are established, much remains unknown concerning the mechanisms of formation of the most prevalent form of renal calculi, calcium oxalate. This article reviews recent basic science and clinical research that attempts to identify the etiologies of renal calculus formation.


Analysis of Pediatric Tendon Injuries in the Hand in Comparison with Adults.
The purpose of this study was to identify the epidemiologic characteristics of hand tendon injuries in children and to compare these with those of adults. This retrospective study was conducted on acute traumatic tendon injuries of the hand treated at our institution from 2005 to 2013, based on medical records and X-ray findings. Age, sex, hand injured, mechanism of injury, tendons and zones injured, number of affected digits, and comorbidities and complications were analyzed. Patients were divided into 2 groups: a pediatric group (≤15 years) and an adult group (>15 years). Over the 9-year study period, 533 patients were surgically treated for acute traumatic tendon injuries of the hand. In the pediatric group (n=76), being male, the right hand, the extensor tendon, complete rupture, the middle finger, and glass injury predominated in hand tendon injuries. In the adult group (n=457), results were similar, but injury to the index finger and knife injury were the most common. An accompanying fracture was more common in the adult group and complication rates were non-significantly different. This comparative analysis revealed no significant epidemiologic intergroup differences. The belief that pediatric tendon injuries tend to be less severe is misplaced, and careful physical examination and exploration should be conducted in pediatric cases of hand injury.


Muricauda marina sp. nov., isolated from marine snow of Yellow Sea.
A Gram-staining-negative, long rod-shaped, non-motile, strictly aerobic bacterial strain, designated H19-56T, was isolated from a surface marine snow sample collected from the Yellow Sea near China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that H19-56T represented a member of the genus Muricauda and showed the highest sequence similarity to Muricauda ruestringensis B1T (96.9 %). H19-56T grew optimally at pH 8.0, 32 °C and in the presence of 3 % (w/v) NaCl. The DNA G+C content was 43.6 mol%. H19-56T contained MK-6 as the predominant respiratory quinone and had iso-C15 : 0 and iso-C15 : 1G as the major cellular fatty acids. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and three unidentified lipids. On the basis of the results of the polyphasic analyses, this isolate was considered to represent a novel species of the genus Muricauda, for which the name Muricauda marina sp. nov. is proposed. The type strain is H19-56T (CGMCC 1.15774T=JCM 31456T=MCCC 1K03196T=KCTC 52374T).


Trichorhinophalangeal syndrome with low expression of TRPS1 on epidermal and hair follicle epithelial cells.
Trichorhinophalangeal syndrome (TRPS) is an autosomal-dominant congenital hair loss disease characterized by sparse and slow-growing scalp hair, craniofacial and skeletal abnormalities, pear-shaped nose, thin upper lip, brittle and thin toenails, and bilateral brachydactyly of the big toes. We report a case of TRPS1 exhibiting these clinical features with a novel heterozygous single nucleotide substitution in exon 3 of the TRPS1 gene. By immunohistochemical analysis of a biopsied specimen of the patient's alopecia lesion, we found for the first time that the expression level of TRPS1 was markedly reduced in the epidermis and the outer root sheath of hair follicles as compared to a normal subject. In addition, higher expression of phospho-Stat3 was found consequent to the loss of TRPS1 in the outer root sheath.


Local intramuscular transplantation of autologous mononuclear cells for critical lower limb ischaemia.
Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.


[Clinical and immunological profile of HIV infected patients in Cotonou, Benin].
This study had for aim to identify the clinical status and the level of immuno-deficiency of HIV-infected patients on their first visit. One hundred and thirty-six HIV+ patients were prospectively evaluated from November 1, 2001 to May 31, 2002. One hundred and thirty-four were infected with HIV1 and two with HIV2. The mean age on the first consultation was 37 +/- 2 years. The m/w sex ratio was 0.9. 46.3% were stage C. The main clinical symptoms were: weight loss (88%), fever (80%), cough (71%), diarrhea (51%). BMI was normal in 70% and KI > or =80% in 57% of the cases but immuno-deficiency was severe with CD4 cells count <200 per mm3 in 69%. The main diseases were digestive candidiasis (53%), pneumonia (18%), tuberculosis (12%), non-determined pneumonia (29%), prurigo (20%), zona (16%), cryptosporidiosis (4%), cerebral toxoplasmosis (3%), and Kaposi's sarcoma (1%).


Facial hemangioma, and associated malformations: a case report.
Facial hemangioma can be isolated lesions or associated with a wide variety of systemic findings. We report a 9-month-old girl who shows an extensive facial hemangioma, intracranial and extracranial vascular malformations, a Dandy-Walker malformation and congenital cardiac malformations. This patient serves as an ample reason why children with similar cutaneous lesions should be carefully evaluated for other associated defects.


Self-construction of core-shell and hollow zeolite analcime icositetrahedra: a reversed crystal growth process via oriented aggregation of nanocrystallites and recrystallization from surface to core.
Zeolite analcime with a core-shell and hollow icositetrahedron architecture was prepared by a one-pot hydrothermal route in the presence of ethylamine and Raney Ni. Detailed investigations on samples at different preparation stages revealed that the growth of the complex single crystalline geometrical structure did not follow the classic crystal growth route, i.e., a crystal with a highly symmetric morphology (such as polyhedra) is normally developed by attachment of atoms or ions to a nucleus. A reversed crystal growth process through oriented aggregation of nanocrystallites and surface recrystallization was observed. The whole process can be described by the following four successive steps. (1) Primary analcime nanoplatelets undergo oriented aggregation to yield discus-shaped particles. (2) These disci further assemble into polycrystalline microspheres. (3) The relatively large platelets grow into nanorods by consuming the smaller ones, and meanwhile, the surface of the microspheres recrystallizes into a thin single crystalline icositetrahedral shell via Ostwald ripening. (4) Recrystallization continues from the surface to the core at the expense of the nanorods, and the thickness of the monocrystalline shell keeps on increasing until all the nanorods are consumed, leading to hollow single crystalline analcime icositetrahedra. The present work adds new useful information for the understanding of the principles of zeolite growth.


ETAscape: analyzing protein networks to predict enzymatic function and substrates in Cytoscape.
Most proteins lack experimentally validated functions. To address this problem, we implemented the Evolutionary Trace Annotation (ETA) method in the Cytoscape network visualization environment. The result is the ETAscape plugin, which builds a structural genomics network based on local structural and evolutionary similarities among proteins and then globally diffuses known annotations across the resulting network. The plugin displays these novel functional annotations, their confidence, the molecular basis for individual matches and the set of matches that lead to a prediction. The ETA Network Plugin is available publicly for download at http://mammoth.bcm.tmc.edu/networks/.


Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in Chinese Patients with Advanced IgA Nephropathy.
Treatment of advanced Immunoglobulin A nephropathy (IgAN) patients with estimated glomerular filtration rate (eGFR) below 45 mL/min per 1.73 m2 remains inconsistent. The aim of this study is to compare the effects of corticosteroid and immunosuppressant therapies among these patients. A total of 201 adult patients with advanced IgAN (eGFR < 45 mL/min/1.73 m2 and proteinuria > 1 g/24h at biopsy) grouped into supportive care (SC), steroids alone (CS), and steroids plus immunosuppressant (IT) groups, were investigated between 30th December 2002 and 30th June 2016. The primary endpoint was the combined endpoint of a 50% decline in eGFR and/or end stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m2 or maintenance renal replacement treatment). Responses to therapy included complete remission (CR: urinary protein excretion < 0.5 g/24h, with eGFR decrease less than 10% baseline), partial remission (PR: proteinuria decrease by > 50% baseline, with eGFR decrease less than 10% baseline), no response (NR: proteinuria decrease < 50% baseline, or eGFR decrease > 10% baseline) and ESRD. Kaplan-Meier and Cox proportional hazards analyses were performed. During the follow-up period (37.2 ± 22.7 months), 6.8% patients in SC group, 25.0% in CS group, and 38.0% in IT group achieved CR or PR, while 78.4%, 62.5% and 49.3% patients in these 3 groups reached primary endpoint respectively (p < 0.001). Three-year renal survival rates in SC and combined immunosuppressive treatment groups (CS and IT groups) were 33.8% vs 51.2% (p = 0.02), and 5-year renal survival rates were 12.2% vs 21.3% (p = 0.1) respectively. Multivariate Cox regression analysis showed that hypertension (HR = 2.44, 95% CI 1.51-3.95; p < 0.001), Scr (HR = 1.01, 95% CI 1.00-1.01; p < 0.001), T1-T2 lesion (HR = 1.99, 95% CI 1.35-2.93; p = 0.001) were independent indicators of poor renal outcome. Immunosuppressive treatment (CS and IT therapy) may improve short-term renal outcome compared with supportive treatment in advanced IgAN patients.


Quantitative Human Immunodeficiency Virus (HIV)-1 Antibodies Correlate With Plasma HIV-1 RNA and Cell-associated DNA Levels in Children on Antiretroviral Therapy.
This study measured serial plasma human immunodeficiency virus (HIV)-1-specific antibody (Ab) levels in children who initiated antiretroviral therapy (ART) prior to 2 years of age, and evaluated their relationship to peripheral blood HIV-1 RNA and DNA levels. We studied 46 HIV-1-infected children, stratified by age at ART initiation (<3 mo, early therapy [ET]; >3 mo-2 years, late therapy [LT]) and by virologic response (R) or non-response (NR), before and up to 4 years following ART. We studied 20 HIV-1-uninfected children born to HIV-1-infected mothers (seroreverters [SR]) as controls. Plasma immunoglobulin G (IgG) Ab levels directed against HIV-1 envelope (gp160, gp41), gag (capsid, p24; matrix, p17), reverse transcriptase (p66/51), and integrase (p31) were serially measured using quantitative enzyme-linked immunosorbent assays. HIV-1 Ab rates of decline were estimated over the first 15 months of the study. The HIV-1 Ab rates of decline in the ET-R group were similar to those in the SR group for all Ab specificities, except for p17 (P = .01). Ab decline rates in the LT-R group and the NR group were significantly slower than in the SR group for all tested Ab specificities. After 1 year of age, Ab levels to p31 and p17 were significantly associated with HIV-1 RNA levels (P < .001); Ab levels to gp160 (P < .001) and gp41 (P < .001) were significantly associated with cell-associated HIV-1 DNA levels. Quantitative HIV-1-specific Ab levels may be useful for screening children on ART for viral suppression or for residual, cell-associated HIV-1 DNA levels. NCT00000872.


Does Including Public Health Students on Interprofessional Teams Increase Attainment of Interprofessional Practice Competencies?
Interprofessional education (IPE) creates dynamic experiential learning that can address social determinants of health that influence health outcomes. To examine the effects of including public health students on IPE teams on the interprofessional practice domain constructs (values/ethics, roles/responsibilities, interprofessional communication, and teams and teamwork). This single-case, mixed-methods study was performed using a grounded theory approach. Students from 8 graduate health sciences programs participated in an asynchronous, 6-week, online IPE learning activity. Three of the 4 interprofessional practice domain constructs were examined as outcome variables: participants' biomedical vs biopsychosocial patient approach (values/ethics); reported change in attitudes, beliefs, or values about other health professions (roles/responsibilities); and anticipated changes in future professional behaviors/interactions/approaches (teams and teamwork). Predictor variables were having an MPH participant on the IPE team, participants' enrollment in a clinical or nonclinical program, and student perception of the online format (interprofessional communication). Three hundred nineteen students were included, 261 from clinical and 58 from nonclinical programs. A significant association was found between having an MPH participant on the IPE teams and participants' awareness of the influence of social determinants of health (OR, 2.04; 95% CI, 1.13-3.66; P<.05). Program type was also significantly associated with awareness of the influence of social determinants of health, such that participants in nonclinical programs were significantly more likely to report the importance of social determinants of health in the care plan (OR, 3.68; 95% CI, 1.38-9.84; P<.01). Participants were significantly less likely to report future behavior change if they were in clinical programs (OR, 0.44; 95% CI, 0.23-0.86; P<.05) or if they disliked the online format (OR, 0.25; 95% CI, 0.14-0.42; P<.01). The model fit the data well (χ23=30.80; P<.001). Inclusion of MPH students on IPE teams has the potential to increase clinical participants' awareness of the influence of social determinants of health and interest in incorporating a biopsychosocial approach to health care.


Syringomyelia: a clinical review of 75 cases.
Records of 75 patients with syringomyelia are reviewed. Their clinical course fell into one of three main groups: (1) those with a long history of a steadily progressive disability; (2) those with a long history but little or no progression of their disability; and (3) those with a short, fairly rapid downhill course.On the basis of this study, x-ray therapy seems to be of little value in the treatment of this disease. Surgical treatment on the other hand appears to offer more hope for a selected group of patients who are progressing at the time of examination. In this group surgery is recommended (1) in the presence of a foramen magnum anomaly with signs and symptoms related to this deformity; (2) in the presence of a distended cord with pain and evidence of a spinal fluid block; and (3) when the possibility of an ependymoma exists.


Meta-analysis of the prevalence of physical inactivity among Brazilian adolescents.
A systematic review and meta-analysis were carried out to investigate the prevalence of physical inactivity among adolescents in Brazil. We identified articles that had been published up to August 2010 and the search was conducted using six electronic databases. We did not enforce any search limitations. Forest plot-type graphs were generated using the prevalence of physical inactivity stratified by region and sex. Meta-regression models were fitted to identify possible sources of heterogeneity in the prevalence estimates. Of the 1,496 articles initially identified, 37 were deemed appropriate for the systematic review. Prevalence rates ranged from 2% to 80% for male and from 14% to 91% for female subgroups. The lowest prevalence rates of physical inactivity were found to be for the Southern region, whereas the highest rates were observed in the North-Northeast. The methods employed to evaluate physical inactivity in Brazilian adolescents also differed among the studies. This variation demonstrates the need for standardised and validated methods of measuring physical activity in epidemiological investigation.


Fertility intentions to have a second or third child among the childbearing-age population in Central China under China's three-child policy: A cross-sectional study.
On May 31, 2021, the Chinese authorities announced that couples can have up to three children, aiming to stimulate a rise in fertility levels. However, there is limited research on second and third birth intentions of the childbearing-age population under China's three-child policy, and the existing results are inconsistent. A cross-sectional survey was performed in Central China from June to August 2022. A total of 13 479 respondents aged 20-49 were enrolled in the study through a multi-stage sampling method. Data on the intentions to have a second or third child were collected using anonymized questionnaires. Descriptive statistics were performed to assess fertility intentions. Multivariate logistic regression analyses were used to assess the associations between fertility intentions and the related factors. Among families with a single child, 29.7% (1444 / 4859) of the respondents intended to have a second child, while among two-child families, 10.6% (750 / 7056) respondents intended to have a third child. Overall, participants indicated that the ideal number of children was 1.85 ± 0.52. The age-specific fertility intentions of the one-child families were always higher than those of two-child families; however, based on couples' age groups, the number of ideal children reported by two-child families was always higher than that of one-child families. Fertility intentions were influenced by the respondents' gender, age, residence, marital status, educational level, average working time, childcare support, marital satisfaction, accessibility of educational resources, health condition of both spouses, loan situation, size of living house and the gender of the first child or second child. The general prevalence of the second and third birth intention of the childbearing-age population in Central China is not high. To increase the birth rate, it is necessary to create a favourable fertility context and offer supportive measures.


UPLC-PDA coupled HR-TOF ESI/MS2 -based identification of derivatives produced by whole-cell biotransformation of epothilone A using Nocardia sp. CS692 and a cytochrome P450 overexpressing strain.
Epothilone A, a microtubule-stabilizing agent used as therapeutics for the treatment of cancers, was biotransformed into three metabolites using Nocardia sp. CS692 and recombinant Nocardia overexpressing a cytochrome P450 from Streptomyces venezuelae (PikC). Among three metabolites produced in the biotransformation reaction mixtures, ESI/MS2 analysis predicted two metabolites (M1 and M2) as novel hydroxylated derivatives (M1 is hydroxylated at the C-8 position and M2 is hydroxylated at C-10 position), each with an opened-epoxide ring in their structure. Interestingly, metabolite M3 lacks an epoxide ring and is known as deoxyepothilone A, which is also called epothilone C. Metabolite M1 was produced only in PikC overexpressing strain. The endogenous enzymes of Nocardia sp. catalyzed hydroxylation of epothilone A to produce metabolite M2 and removed epoxide ring to produce metabolite M3. All the metabolites were identified based on UV-vis analysis and rigorous ESI/MS2 fragmentation based on epothilone A standard. The newly produced metabolites are anticipated to display novel cytotoxic effects and could be subjects of further pharmacological studies.


Emergence of chikungunya virus in Indian subcontinent after 32 years: A review.
An outbreak of chikungunya virus is currently ongoing in many countries in Indian Ocean since January 2005. The current outbreak appears to be the most severe and one of the biggest outbreaks caused by this virus. India, where this virus was last reported in 1973, is also amongst affected countries. Chikungunya virus has affected millions of the people in Africa and Southeast Asia, since it was first reported in 1952 in Tanzania. Even then, natural history of this disease is not fully understood. The intra-outbreak studies, point towards recent changes in the viral genome facilitating the rapid spread and enhanced pathogenecity. The available published scientific literature on chikungunya virus was searched to understand the natural history of this disease, reasons for the current outbreak and the causes behind re-emergence of the virus in India. The paucity of the scientific information on various epidemiological aspects of chikungunya virus threatens off an epidemic as control of spread of virus might be difficult in the absence of appropriate knowledge. There is an immediate need of the research on chikungunya virus, for an effective vaccine besides strengthening the existing diagnostic laboratory facilities. The current outbreak can also be taken as a lesson for establishment of a system for continuous surveillance of diseases, considered disappeared from the countries. The re-emergence and epidemics are unpredictable phenomena but the impact of such events can be ameliorated by appropriate knowledge and by being in the right state of preparedness.


Assessing the stable conformations of ibuprofen in solution by means of Residual Dipolar Couplings.
Detailing the conformational equilibria between global and local minimum energy structures of anti-inflammatory α-arylpropionic acids directly in solution is of the utmost importance for a better understanding of the structure-activity relationships, hence providing valuable clues for rational structure-based drug design studies. Here the conformational preferences of the widely used pharmaceutical ibuprofen were investigated in solution by NMR spectroscopy in weakly ordering phases. A thorough theoretical treatment of the anisotropic interactions that are relevant for NMR spectra led to a conformational model characterized by six pairs of symmetry-related conformers, in particular four couples of gauche structures, with a total probability of 93%, and 2 couples of trans structures, counting for the remaining 7%.


MR angiography of the cerebral perforating arteries with magnetization prepared anatomical reference at 7 T: comparison with time-of-flight.
To develop a magnetic resonance imaging (MRI) protocol that visualizes both the perforating arteries and the related anatomy in a single acquisition at 7 T. T(1)-weighted magnetization prepared imaging (MPRAGE) was empirically modified for use as angiography method at 7 T. The resulting sequence depicts the vasculature simultaneously with the surrounding anatomical structures, and is referred to as "magnetization prepared anatomical reference MRA" (MPARE-MRA). The method was compared to time-of-flight (TOF) MRA in seven healthy subjects. The conspicuity of the perforating arteries and the contrast between gray and white matter were evaluated both quantitatively by contrast-to-noise (CNR) measurements, and qualitatively by two radiologists who scored the images. The contrast-to-noise ratio (CNR) between blood and background was 28 +/- 9 for MPARE-MRA and 35 +/- 16 for TOF-MRA, indicating good conspicuity of the vessels. CNR values were: internal capsule (IC) vs. caudate head (CH): 4.2 +/- 0.7; IC vs. putamen: 3.5 +/- 0.6; white matter vs. gray matter: 9.7 +/- 2.5. The benefits of ultra-high-field MRI can transform MPRAGE into a new angiography method to image small vessels and associated parenchyma at the same time. This technique can be used to study the correlation between tissue damage and vascular pathology.


Erythropoietin improves neuronal proliferation in dentate gyrus of hippocampal formation in an animal model of Alzheimer's disease.
Alzheimer's disease (AD) is a prevalent disorder with severe learning and memory defects. Because it has been demonstrated that erythropoietin (EPO) has positive effects on the central nervous system, the aim of this study was to evaluate the effect of EPO on neuronal proliferation in dentate gyrus of hippocampal formation in a well-defined model for AD. A rat model of sporadic dementia of Alzheimer's type was established by a bilateral intracerebroventricular injection of streptozotocin (ICV-STZ). Impairment of learning and memory was confirmed 2 weeks after ICV-STZ injection by passive avoidance learning test and then rats were divided into fourgroups:Control, control-EPO, Alzheimer and Alzheimer-EPO. EPO was injected intraperitoneally every other day with a dose of 5000 IU/kg and, finally, the rats were anesthetized and decapitated for immunohistochemical study and neurogenesis investigation (by Ki67 method) in dentate gyrus of hippocampal formation. The results driven from the histological study showed that EPO significantly increases neuronal proliferation in dentate gyrus of hippocampus in the Alzheimer-EPO group compared with the control, control-EPO and Alzheimer groups; however, there were no differences between the other groups. Our results show that even though EPO in intact animals doesnot change neurogenesis in dentate gyrus, it can nonetheless significantly increase neurogenesis if there is an underlying disorder like neurodegenerative diseases.


Epidemiological characteristics of Vibrio parahaemolyticus outbreaks, Zhejiang, China, 2010-2022.
Vibrio parahaemolyticus is one of the most common foodborne pathogens and poses a significant disease burden. The purpose of the study was to elucidate the epidemiological characteristics of Vibrio parahaemolyticus outbreaks in Zhejiang Province, and provide insights for the targeted prevention and control of foodborne diseases. Descriptive statistical methods were utilized to analyze the data on Vibrio parahaemolyticus outbreaks reported by all Centers for Disease Control and Prevention (CDCs) through Foodborne Disease Outbreaks Surveillance System (FDOSS) in Zhejiang Province from 2010 to 2022. From 2010 to 2022, a total of 383 outbreaks caused by Vibrio parahaemolyticus were reported by 90 CDCs in 11 prefectures of Zhejiang Province, resulting in 4,382 illnesses, 326 hospitalizations and 1 death. The main symptoms of the outbreak-related cases were diarrhea (95.18%), abdominal pain (89.23%), nausea (55.64%), vomiting (50.57%), fever (24.21%), etc. The outbreaks occurring between July and September accounted for 77.54% of all outbreaks (297 out of 383). Outbreaks associated with restaurants accounted for the majority (57.96%, 222/383) of all outbreaks, followed by those linked to staff canteens (15.40%, 59/383) and rural banquets (11.23%, 43/383). 31.85% of all outbreaks were associated with the consumption of aquatic products, while ready-to-eat foods such as Chinese cold dishes and cooked meat products accounted for 12.53% of all outbreaks. Serotype O3:K6 (81.94%, 118/144) was the predominant serotype responsible for outbreaks from 2010 to 2020, while serotype O10:K4 (57.89%, 33/57) was the predominant serotype from 2021 to 2022. In-depth and comprehensive analysis of long-term surveillance data on Vibrio parahaemolyticus outbreaks is essential to gain insight into the epidemiological characteristics, identify long-term patterns and recent trends, and enable governments to prioritize interventions and develop targeted policies to mitigate such outbreaks.


Research on Handwashing Techniques of Peritoneal Dialysis Patients From Yiwu, Southeast China.
The aim of the present study was to evaluate handwashing technique, bacteriology, and factors influencing handwashing technique of 86 stable chronic peritoneal dialysis (PD) patients from Yiwu City in Southeast China. Based on the "Hygienic standard for disinfection in the hospital", we also performed sampling for bacteriology from PD operators after they washed their hands. We compared their clinical features including the pathogenic bacteria of their previous peritonitis episodes and their handwashing evaluation results according to their bacteriologic sampling results. 65% of patients turned off the tap by bare hand, and 74% did not follow the six-step handwashing method. Dialysis duration longer than 6 months (P = 0.04) and lower income (P = 0.05) were independent risk factors for higher handwashing error scores. The overall rate of appropriate handwashing, according to the "hygienic standard for disinfection in the hospital" was 26%. The bacteriologic sampling results showed that the most common pathogenic bacterium was Staphylococcus aureus (92%). PD operators whose hand bacteria culture was qualified contained a lower proportion of participants with advanced age (P = 0.07). Patients with repeated peritonitis occurrence had a significantly higher score on handwashing error (P < 0.01) and were more likely to develop Staphylococcus infection. We found that in Yiwu city patients on dialysis for more than 6 months, were of low income and had multiple prior episodes of PD peritonitis had poor handwashing compliance. Elderly patients had higher rates of positive bacterial culture (Staphylococcus) from their hands.


Mannose-resistant adhesion of motile Aeromonas to INT407 cells and the differences among isolates from humans, food and water.
Aeromonas has been recognized as an important enteropathogen, but factors related to its virulence have not been clarified. For most enteric pathogens, attachment is a prerequisite for infection and for the effective delivery of toxins to the intestinal epithelial cells. We examined a total of 273 strains isolated from stool, food and environmental specimens by an assay for mannose-resistant adhesion to INT407 cells in vitro. Seventeen of the 102 faecal isolates were adhesive strains with more than 10 bacteria adhering per cell, while only 2 of the 118 isolates from foods and river water adhered to the cells (P less than 0.001). It is possible that the adhesion might serve as a marker for discrimination between the pathogenic and nonpathogenic isolates. The 8 highly adhesive strains with more than 20 adhering organisms per cell were scrutinized for the mechanism of adhesion. No correlation was apparent between the adhesion to INT407 cells and hydrophobicity. It was noted that fucose inhibited the adhesion of four strains as well as haemagglutination by them. Electronmicroscopic studies showed the presence of flexible and curvilinear fimbriae in only 2 of the 8 highly adhesive strains.


An Evaluation of the Mechanical Properties of a Hybrid Composite Containing Hydroxyapatite.
There is currently a lack of scientific reports on the use of composites based on UDMA resin containing HAp in conservative dentistry. The aim of this study was therefore to determine the effect of hydroxyapatite content on the properties of a hybrid composite used in conservative dentistry. This paper compares a commercial hybrid composite with experimental composites treated with 2% by weight (b/w), 5% b/w, and 8% b/w hydroxyapatite. The composites were subjected to bending strength, compression, and diametrical compression tests, as well as those for impact strength, hardness, and tribological wear. The obtained results were subjected to statistical analysis. Increased hydroxyapatite was found to weaken the mechanical properties; however, 2% b/w and 5% b/w hydroxyapatite powder was found to achieve acceptable results. The statistical analysis showed no significant differences. HAp is an effective treatment for composites when applied at a low concentration. Further research is needed to identify an appropriate size of HAp particles that can be introduced into a composite to adequately activate the surface and modification its composition.


Lymphocyte subsets in lung cancer.
Altered cellular immune function has been demonstrated in patients with lung cancer, including decreased numbers of circulating lymphocytes and changes in the percentage of lymphocytes in various functional subsets. We quantitated lymphocyte subsets in 54 patients with lung cancer including patients with limited (stages 1 and 2) nonsmall cell lung cancer (NSCLC, n = 23), advanced (stage 3) NSCLC (n = 16), and small cell cancer (SCLC, n = 15). Serum albumin was decreased in 15 lung cancer patients, and lymphocyte subsets were separately evaluated in these patients. Lymphocyte populations in cancer patients were compared to those of nonsmokers and a smoking patient population. No difference from smokers was noted in patients with limited NSCLC. Patients with SCLC and advanced NSCLC had significantly decreased numbers of T-helper and T-suppressor cells (p less than 0.05). Patients with lung cancer and hypoalbuminemia had the greatest decrease in number of circulating T-helper cells (p less than 0.001). B-lymphocytes were also decreased in patients with advanced NSCLC and patients with hypoalbuminemia (p less than 0.05). A decrease in population of T-lymphocytes subsets is frequent in patients with SCLC, advanced NSCLC, and lung cancer patients with hypoalbuminemia.


Monitoring bypassing agent therapy - a prospective crossover study comparing thromboelastometry and thrombin generation assay.
The aim of this study was to evaluate the capability of thromboelastometry (ROTEM) and thrombin generation assay (TGA) to monitor the treatment response of bypassing agent (BPA) therapy and to study whether one method is superior to another. In a prospective crossover study haemophilia A patients with high titre inhibitors were included to receive a dose of 75 U kg(-1) activated prothrombin complex concentrates (aPCC) intravenously. Blood sampling was performed at baseline, 15, 30 min, 1, 2, 3 and 4 h post-infusion for TGA and ROTEM analysis. After a washout period of 14 days the subjects received recombinant FVIIa (rFVIIa) at a dose of 90 μg kg(-1) and similar blood sampling was performed. Healthy subjects were used as controls. Six haemophilia A patients with inhibitors were included. We found that TGA parameters endogenous thrombin potential (ETP) and peak thrombin increased 2-3 folds from baseline 15-30 min after infusion. ROTEM parameters MaxVel and maximum clot firmness increased to a level comparable to that of healthy controls. An individual difference in response was observed for different parameters among participants. ETP and peak thrombin were almost two-fold greater following aPCC infusion compared to rFVIIa, whereas ROTEM parameters showed no difference in response between the two products. The study showed that ROTEM and TGA have a great potential to evaluate the effect of BPA in haemophilia patients with inhibitors. TGA seemed to be more sensitive than ROTEM in reflecting the difference in treatment response between aPCC and rFVIIa. Additional prospective clinical studies are needed to clarify which assay and what parameters are clinically predictive.


Impact of Telemedicine on Mortality, Length of Stay, and Cost Among Patients in Progressive Care Units: Experience From a Large Healthcare System.
To determine whether Telemedicine intervention can affect hospital mortality, length of stay, and direct costs for progressive care unit patients. Retrospective observational. Large healthcare system in Florida. Adult patients admitted to progressive care unit (PCU) as their primary admission between December 2011 and August 2016 (n = 16,091). Progressive care unit patients with telemedicine intervention (telemedicine PCU [TPCU]; n = 8091) and without telemedicine control (nontelemedicine PCU [NTPCU]; n = 8000) were compared concurrently during study period. Primary outcome was progressive care unit and hospital mortality. Secondary outcomes were hospital length of stay, progressive care unit length of stay, and mean direct costs. The mean age NTPCU and TPCU patients were 63.4 years (95% CI, 62.9-63.8 yr) and 71.1 years (95% CI, 70.7-71.4 yr), respectively. All Patient Refined-Diagnosis Related Group Disease Severity (p < 0.0001) and All Patient Refined-Diagnosis Related Group patient Risk of Mortality (p < 0.0001) scores were significantly higher among TPCU versus NTPCU. After adjusting for age, sex, race, disease severity, risk of mortality, hospital entity, and organ systems, TPCU survival benefit was 20%. Mean progressive care unit length of stay was lower among TPCU compared with NTPCU (2.6 vs 3.2 d; p < 0.0001). Postprogressive care unit hospital length of stay was longer for TPCU patients, compared with NTPCU (7.3 vs 6.8 d; p < 0.0001). The overall mean direct cost was higher for TPCU ($13,180), compared with NTPCU ($12,301; p < 0.0001). Although there are many studies about the effects of telemedicine in ICU, currently there are no studies on the effects of telemedicine in progressive care unit settings. Our study showed that TPCU intervention significantly decreased mortality in progressive care unit and hospital and progressive care unit length of stay despite the fact patients in TPCU were older and had higher disease severity, and risk of mortality. Increased postprogressive care unit hospital length of stay and total mean direct costs inclusive of telemedicine costs coincided with improved survival rates. Telemedicine intervention decreased overall mortality and length of stay within progressive care units without substantial cost incurrences.


Rare cases of bowel obstruction: internal hernias.
Internal hernias are a rare form of dislocation of the abdominal viscera, usually in the small intestine, in the peritoneal sacs or cavities, resulting from the defective coalescence of the peritoneal flaps due to abnormal rotation of the medium intestine in the second stage of embryogenesis. In this paper the authors describe three cases observed during the last twelve months: two cases were ascribable to left paraduodenal hernia and one to a transepiploic hernia. Special attention needs to be paid to knowledge of the rotation process of the primitive medium intestine and to understanding whether an internal hernia underlies the clinical picture, when occlusive patients have not previously undergone surgery and show no signs of external hernias. In the surgical treatment of paraduodenal hernias, special attention must be paid to incarcerated loops, in order to prevent severe vascular complications caused by potential lesions to the mesenteric vessels.


Homologous Recombination-Enzymes and Pathways.
Homologous recombination is an ubiquitous process that shapes genomes and repairs DNA damage. The reaction is classically divided into three phases: presynaptic, synaptic, and postsynaptic. In Escherichia coli, the presynaptic phase involves either RecBCD or RecFOR proteins, which act on DNA double-stranded ends and DNA single-stranded gaps, respectively; the central synaptic steps are catalyzed by the ubiquitous DNA-binding protein RecA; and the postsynaptic phase involves either RuvABC or RecG proteins, which catalyze branch-migration and, in the case of RuvABC, the cleavage of Holliday junctions. Here, we review the biochemical properties of these molecular machines and analyze how, in light of these properties, the phenotypes of null mutants allow us to define their biological function(s). The consequences of point mutations on the biochemical properties of recombination enzymes and on cell phenotypes help refine the molecular mechanisms of action and the biological roles of recombination proteins. Given the high level of conservation of key proteins like RecA and the conservation of the principles of action of all recombination proteins, the deep knowledge acquired during decades of studies of homologous recombination in bacteria is the foundation of our present understanding of the processes that govern genome stability and evolution in all living organisms.


[Low molecular weight heparins. Implications in anesthesia and resuscitation].
Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).


Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma.
Des-gamma-carboxy prothrombin is an abnormal prothrombin which increases in the plasma of patients with hepatocellular carcinoma. To clarify the process of des-gamma-carboxy prothrombin synthesis, immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K (phylloquinone and menaquinone) concentrations were determined in human liver tissue, including hepatocellular carcinoma. In the patients with elevated plasma des-gamma-carboxy prothrombin levels, both immunoreactive prothrombin and des-gamma-carboxy prothrombin significantly increased in hepatoma tissues compared with non-cancerous liver tissue. On the other hand, no significant difference was observed in the endogenous vitamin K (K1, MK-4, MK7) concentrations between hepatoma and noncancerous portions, in either the cases with or without increase of plasma des-gamma-carboxy prothrombin. These data strongly suggested that in the patients with an increase of plasma des-gamma-carboxy prothrombin, overproduction of prothrombin in hepatoma plays in important role in the synthesis of des-gamma-carboxy prothrombin.


Human microRNAs target a functionally distinct population of genes with AT-rich 3' UTRs.
While investigating microRNA targets, we have found that human genes divide into two roughly equal populations, based on the fraction of A plus T bases in their 3' UTRs. Using the Gene Ontology database, we find significant functional differences between the two gene populations, with AT-rich genes implicated in transcription and translation processes, and GC-rich genes implicated in signal transduction and posttranslational protein modification. Better understanding of the background distribution of nucleotides in 3' UTRs may allow improved prediction of microRNA-targeted genes in humans. We predict at least 1,200 KnownGene transcripts to be regulated by microRNAs. The large majority of these microRNA targets are in the AT-rich 3' UTR population. However, notwithstanding this preference for AT-rich targets, microRNA targets are found preferentially to be regulatory genes themselves, including both transcription factors and posttranslational modifiers. These results suggest that some processes involving mRNA, of which microRNA regulation may be just one, require AT-richness of 3' UTRs for functionality. A relationship, not simply one-to-one, between these 3' UTR populations and large-scale genomic isochores is described.


Safety of ultrasound-guided small-bore chest tube insertion in patients on clopidogrel.
The safety of small-bore chest tubes insertion with ultrasound (US) guidance has been well demonstrated in patients not receiving antiplatelet therapy. Given the current widespread use of these agents, pulmonologists frequently encounter patients on this therapy and requiring drainage of the pleural space. The use of these agents clearly increases the risk of bleeding, but it is not always possible to stop this therapy before the procedure, especially in patients requiring urgent drainage and those with coronary stents. The purpose of this study is to report our experience on the safety of US-guided small-bore chest tube placement in patients receiving clopidogrel. This was a retrospective review of the charts of adult patients who underwent small-bore chest tube insertion by the pulmonary service while on clopidogrel. Data collected included patient's and effusion characteristics, indication for clopidogrel and for the procedure, and any significant bleeding complication defined as hemothorax, chest wall hematoma, a reduction in hemoglobin of >2 g/dL, or any bleeding requiring blood transfusion, surgery, or chest tube insertion. US of the chest was performed before insertion but did not include Doppler study of intercostal arteries. Lateral insertion at or anterior to the posterior axillary line was the preferred choice when possible. Forty-three procedures were performed in 30 patients. Seventy percent were male with a mean age of 71 years. The indications for clopidogrel were coronary stents (50%), acute coronary syndrome (27%), prevention of graft occlusion after coronary artery bypass graft (CABG) (13%), femoral stent or endarterectomy (7%), and carotid endarterectomy (3%). The etiology of the effusions was post-CABG (43%), heart failure (17%), end-stage renal disease (13%), pneumothorax (10%), and others (17%). The procedures were therapeutic in 41 cases and diagnostic in 2. The indications for the procedure were respiratory distress (65%), respiratory failure (23%), and pneumothorax (7%). Fifteen procedures (35%) were performed in 10 patients in the ICU and 6 of them were mechanically ventilated. Nine patients were obese based on body mass index. Neither significant bleeding nor other minor complications were seen. OH 44195: The insertion of small-bore chest tube in patients receiving clopidogrel can be safe if performed by experienced operators and by using US guidance along with lateral insertion site, which has the lowest risk of lacerating the intercostal arteries.


Catecholamine and thyroid hormone metabolism in a case of anorexia nervosa.
Alterations in catecholamine (CA) and thyroid hormone metabolism were examined in a 12-year-old girl with anorexia nervosa during 3 months of treatment. According to her body weight change, the observation period was divided into 3 stages: initial emaciation (stage 1), stable maintenance of the -30% level of the previous weight (stage 2) and convalescent stage (stage 3). Stage 1 was characterized by relatively high urinary norepinephrine (NE) and epinephrine (E) but low dopamine (DA) excretion, elevated plasma DA-beta-hydroxylase (DBH) activity and reduced serum thyroid hormones, especially the triiodothyronine (T3) level. In stage 2, urinary CAs were markedly suppressed, while serum thyroid hormones gradually increase. In stage 3, a great increase in DA excretion, a fall in plasma DBH activity and normalization of thyroid hormones were observed. In the low T3 state below 60 ng/dl, urinary NE + E/DA ratios were elevated and widely fluctuated (0.58 +/- 0.30, SD), but were gradually decreased and completely stabilized in the normal T3 state (0.07 +/- 0.02, P less than 0.001). These results indicate that (1) although total CA production was depressed in anorexia nervosa, a change from an adrenergic-dominant to a dopaminergic-dominant state occurs in accordance with body weight gain, and (2) this shift in the CA profile is associated with concomitant recovery of reduced thyroid hormone concentrations. Thus, as for the energy expenditure, compensatory changes were observed in CAs and thyroid hormones in relation to caloric restriction.


Post-Caesarean Drain Placement - Minor Procedure Leading to Major Complication.
Intra abdominal drain insertion in doubtful cases has been practised since many years. It may be associated with certain minor as well as major complications like drain site haemorrhage, infection, intestinal perforation and even visceral herniation from the site. Herein, we report a case of 28-year-old unbooked G2P1L1 at 33 weeks gestation with previous caesarean, who underwent Lower Segment Caesarean Section (LSCS) in view of breech presentation in labour. On sixth postoperative day, tubular structure herniation through the drain site was observed. She was undertaken for laparotomy and fallopian tube herniation through the drain site was confirmed. Ipsilateral salpingectomy was done. Thus, drain placement lead to prolonged hospital stay and maternal morbidity.


In vitro drug sensitivity predicts response and survival after individualized sensitivity-directed chemotherapy in metastatic melanoma: a multicenter phase II trial of the Dermatologic Cooperative Oncology Group.
In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome. The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay. Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041). In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.


Avulsion and storage media.
Avulsion of a tooth caused by trauma, and its successful treatment is a challenging situation that a dentist encounters in clinical practice. There is a definitive treatment for the avulsed tooth, which depends on many factors. The immediate replacement and replantation of the avulsed tooth is necessary, but it cannot always be accomplished for a number of reasons. Thus, the tooth should be transported in a suitable medium to maintain the cell viability. The storage medium is one of the important factors that will help the dentist in rendering successful treatment for the avulsed tooth. There is a continuing search for an ideal storage medium. This review paper focuses on the various storage media, with special reference to coconut water.


Genetic characterization of three novel chicken parvovirus strains based on analysis of their coding sequences.
Chicken parvovirus (ChPV) is one of the causative agents of viral enteritis. Recently, the genome of the ABU-P1 strain of ChPV was fully sequenced and determined to have a distinct genomic composition compared with that of vertebrate parvoviruses. However, no comparative sequence analysis of coding regions of ChPVs was possible because of the lack of other sequence information. In this study, we obtained the nucleotide sequences of all genomic coding regions of three ChPVs by polymerase chain reaction using 13 primer sets, and deduced the amino acid sequences from the nucleotide sequences. The non-structural protein 1 (NS1) gene of the three ChPVs showed 95.0 to 95.5% nucleotide sequence identity and 96.5 to 98.1% amino acid sequence identity to those of NS1 from the ABU-P1 strain, respectively, and even higher nucleotide and amino acid similarities to one another. The viral proteins (VP) gene was more divergent between the three ChPV Korean strains and ABU-P1, with 88.1 to 88.3% nucleotide identity and 93.0% amino acid identity. Analysis of the putative tertiary structure of the ChPV VP2 protein showed that variable regions with less than 80% nucleotide similarity between the three Korean strains and ABU-P1 occurred in large loops of the VP2 protein believed to be involved in antigenicity, pathogenicity, and tissue tropism in other parvoviruses. Based on our analysis of full-length coding sequences, we discovered greater variation in ChPV strains than reported previously, especially in partial regions of the VP2 protein.


Cisterna magna reconstruction with arachnoid suturing in brainstem surgery.
We present an effective and easily applied technique for cisterna magna reconstruction with arachnoid suturing in brainstem surgery. Suturing with 10-0 monofilament was done in a patient with a medulla oblongata hemangioblastoma (diagnosed von Hippel-Lindau disease). Seven years later, follow-up imaging revealed a new lesion close to the previous one and the patient underwent reoperation. The craniotomy and dural incision were repeated, and the intact arachnoid was visualized with no meningocerebral adhesions. This technique preserves normal anatomic landmarks and facilitates and shortens dissection in reoperations, almost like a virgin case. We propose this technique for every lower brainstem and fourth ventricle procedure. The video can be found here: https://youtu.be/RKMcSoK6ycY.


Intratumoral IL15 Improves Efficacy of Near-Infrared Photoimmunotherapy.
IL15 is a potent inducer of differentiation and proliferation of CD8+ T and natural killer (NK) cells, making it a promising candidate for cancer immunotherapy. However, limited efficacy of systemic monotherapy utilizing intravenous IL15 suggests the needs for alternative routes of administration or combination treatment with other therapies. Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective anticancer treatment that elicits a massive release of tumor antigens and immunogenic signals. Here, we investigated whether intratumoral IL15 can enhance the effectiveness of cancer cell-targeted NIR-PIT using syngeneic murine tumor models. Intratumoral injection of IL15 was more effective than intraperitoneal IL15 in vivo in suppressing tumor growth and inducing intratumoral immune responses. When the efficacy of CD44-targeted NIR-PIT was compared in vivo between IL15-secreting MC38 (hIL15-MC38) and parental MC38 tumors, the hIL15-MC38/NIR-PIT group showed the best tumor growth inhibition and survival. In addition, the hIL15-MC38/NIR-PIT group showed significant dendritic cell maturation and significant increases in the number and Granzyme B expression of tumor-infiltrating CD8+ T, NK, and natural killer T cells compared with the treated parental line. Furthermore, intratumoral IL15 injection combined with CD44-targeted NIR-PIT showed significant tumor control in MC38 and Pan02-luc tumor models. In bilateral tumor models, CD44-targeted NIR-PIT in hIL15-MC38 tumors significantly suppressed the growth of untreated MC38 tumors, suggesting abscopal effects. Mice that achieved complete response after the combination therapy completely rejected later tumor rechallenge. In conclusion, local IL15 administration synergistically improves the efficacy of cancer cell-targeted NIR-PIT probably by inducing stronger anticancer immunity, indicating its potential as an anticancer treatment strategy.


Vascularized Pericranial Flap as a Method to Prevent Persistent Skull Defects After Craniectomy for Sagittal Synostosis.
Some cranial defects resulting from sagittal craniectomy for craniosynostosis never completely close and require cranioplasty. This study evaluates the results of 2 methods to minimize such defects: (1) trapezoidal craniectomy that is narrower posteriorly (2) vascularized pericranial flap that is sewn to the dura under a rectangular craniectomy.Children who underwent primary open sagittal craniectomy with biparietal morcellation (with/without frontal cranioplasty) for single-suture nonsyndromic sagittal synostosis from 2013 through 2018 were included. Children were excluded if there was a dural tear, if they had no 1-year follow-up, or if they had unmeasured and/or uncounted skull defects. Surgeries were divided into (1) standard craniectomy, (2) trapezoidal craniectomy, or (3) craniectomy with pericranial flap. Differences in percentage of children with defects and mean total defect area 1 year postsurgery were compared between the 3 groups.We reviewed 148 cases. After exclusions, 34 of 53 children (64%) who underwent standard craniectomy, 6 of 17 children (35%) who had pericranial flaps, and 5 of 11 children (46%) who underwent trapezoidal craniectomy had defects 1 year postsurgery. The percentage of children with defects (P = 0.0364) but not the defect area was significantly higher in the standard craniectomy than in the pericranial flap group. The percentage of subjects with defects was not significantly different between the standard and the trapezoidal craniectomy groups.Sewing a vascularized pericranial flap to the dura at the craniectomy site may protect against persistent bony defects after sagittal craniectomy for craniosynostosis. Longer follow-up is needed to determine if this technique leads to lower rates of cranioplasty.


Monoclonal anti-deoxyribonucleic antibodies. I. Isotype and specificity studies.
Ten monoclonal anti-DNA antibodies generated in three separate fusion experiments performed using nonimmunized B/W spleen cells were studied. Their antigenic specificities were demonstrated to be identical and directed against a conformational determinant of the B helical form of double-stranded DNA (dsDNA). These data suggest that autoantibodies to dsDNA in B/W mice could constitute a homogeneous population.


Role of RpoS in fine-tuning the synthesis of Vi capsular polysaccharide in Salmonella enterica serotype Typhi.
Regulation of the synthesis of Vi polysaccharide, a major virulence determinant in Salmonella enterica serotype Typhi, is under the control of two regulatory systems, ompR-envZ and rscB-rscC, which respond to changes in osmolarity. Some serotype Typhi strains exhibit overexpression of Vi polysaccharide, which masks clinical detection of lipopolysaccharide O antigen. This variation in Vi polysaccharide and O antigen display (VW variation) has been observed since the initial studies of serotype Typhi. In this study, we report that rpoS plays a role in this increased expression in Vi polysaccharide. We constructed a variety of isogenic serotype Typhi mutants that differed in their expression levels of RpoS and examined the role of the rpoS product in synthesis of Vi polysaccharide under different osmolarity conditions. Vi polysaccharide synthesis was also examined in serotype Typhi mutants in which the native promoter of the rpoS was replaced by an araCP(BAD) cassette, so that the expression of rpoS was arabinose dependent. The RpoS(-) strains showed increased syntheses of Vi polysaccharide, which at low and medium osmolarities masked O antigen detection. In contrast, RpoS(+) strains showed lower syntheses of Vi polysaccharide, and an increased detection of O antigen was observed. During exponential growth, when rpoS is unstable or present at low levels, serotype Typhi RpoS(+) strains overexpress the Vi polysaccharide at levels comparable to those for RpoS(-) strains. Our results show that RpoS is another regulator of Vi polysaccharide synthesis and contributes to VW variation in serotype Typhi, which has implications for the development of recombinant attenuated Salmonella vaccines in humans.


Phenotypic expression of recurrent disease after liver transplantation.
Recurrence of the primary disease has become a major focus for transplant hepatologists both when investigating graft dysfunction and when tailoring immunosuppression to maximize graft survival. However, disease recurrence varies in penetrance, can be predictable or random, and does not always conform to the expected pattern of disease. The cholestatic hepatitis syndromes associated with hepatitis B and C are the most dramatic examples of phenotypic change. Being on immunosuppressive drugs may intensify the progression of infectious and malignant diseases, but this effect is not predictable. A significant minority of patients with each of the autoimmune diseases, counter-intuitively, get recurrent disease despite immunosuppression of a potency that is adequate to prevent rejection of the liver graft. Disease patterns emerge after liver transplantation for cryptogenic cirrhosis that shed light on the cause of the native liver disease, for example, nonalcohol-related fatty liver disease and autoimmune hepatitis. The phenotypic expression of disease recurrence can be modified by specific drugs used for immunosuppression and by HLA-antigen matching profiles. Understanding and modifying the phenotypic expression of recurrent disease after liver transplantation is a fertile area for research and continued refinement of clinical care.


Aqueous-Phase Reactions of Anthropogenic Emissions Lead to the High Chemodiversity of Atmospheric Nitrogen-Containing Compounds during the Haze Event.
Nitrogen-containing organic compounds (NOCs), a type of important reactive-nitrogen species, are abundant in organic aerosols in haze events observed in Northern China. However, due to the complex nature of NOCs, the sources, formation, and influencing factors are still ambiguous. Here, the molecular composition of organic matters (OMs) in hourly PM2.5 samples collected during a haze event in Northern China was characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). We found that CHON compounds (formulas containing C, H, O, and N atoms) dominated the OM fractions during the haze and showed high chemodiversity and transformability. Relying on the newly developed revised-workflow and oxidation-hydrolyzation knowledge for CHON compounds, 64% of the major aromatic CHON compounds (>80%) could be derived from the oxidization or hydrolyzation processes. Results from FT-ICR MS data analysis further showed that the aerosol liquid water (ALW)-involved aqueous-phase reactions are important for the molecular distribution of aromatic-CHON compounds besides the coal combustion, and the ALW-involved aromatic-CHON compound formation during daytime and nighttime was different. Our results improve the understanding of molecular composition, sources, and potential formation of CHON compounds, which can help to advance the understanding for the formation, evolution, and control of haze.


Regorafenib for gastrointestinal malignancies : from preclinical data to clinical results of a novel multi-target inhibitor.
Intracellular signals for cancer cell growth, proliferation, migration, and survival are frequently triggered by protein tyrosine kinases (TKs). The possibility of disrupting core disease pathways has led to development and widespread clinical use of specific TK inhibitors that in the past decade have markedly changed treatment strategies and impacted on overall outcomes. However, intrinsic resistance may limit the benefit of these drugs, and multiple escape routes compensate for the inhibited signaling. The disruption of several points of the same pathway and the simultaneous interference with different intracellular oncogenic processes have both been recognized as valuable strategies to maximize the therapeutic potential of this class of agents. In this scenario, regorafenib has emerged as a novel, orally active, multitarget compound with potent activity against a number of angiogenic and stromal TKs, including vascular endothelial growth factor receptor 2 (VEGFR-2), tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE-2), fibroblast growth factor receptor 1 (FGFR-1), and platelet-derived growth factor receptor (PDGFR). Moreover, the drug has the capability of blocking KIT, RET and V600 mutant BRAF. Starting from interesting preclinical results, this review describes the clinical development of regorafenib in gastrointestinal malignancies, focusing on data derived from cutting edge clinical trials that have provided evidence of efficacy in pretreated patients with advanced colorectal cancer or gastrointestinal stromal tumors.


Ab Initio Benchmark Study of Nonadiabatic S1-S2 Photodynamics of cis- and trans-Hexatriene.
The dynamics of the nonadiabatically coupled lowest singlet excited states of cis- and trans-hexatriene are studied theoretically, in a comprehensive electronic structure and quantum dynamical investigation. At the ground state equilibrium geometry the relevant S2 and S1 states carry the A1 (Ag) and B2 (Bu) symmetry labels, for the cis (trans) isomer. Various high-level electronic structure methods are used, including the recently reparametrized DFT/MRCI method, and the results are critically compared. Key parameters of interest are the vertical energy gap and the strength of vibronic coupling between the interacting electronic states. To estimate their influence, suitable comparison calculations are performed. The results are used as the basis for quantum dynamical calculations on the UV absorption spectrum and electronic population transfer involving the S1 and S2 states. Up to nine nonseparable degrees of freedom are included in the calculations. The experimental UV absorption spectrum in the 5-5.2 eV energy range can be very well reproduced. The time-dependent wavepacket propagations reveal a population transfer on the order of 30-50 fs, which becomes increasingly complete with more degrees of freedom included in the calculation. The results are briefly compared with analogous data for the s-trans-butadiene system treated by some of us recently.


The C. elegans CDK8 Mediator module regulates axon guidance decisions in the ventral nerve cord and during dorsal axon navigation.
Receptors expressed on the growth cone of outgrowing axons detect cues required for proper navigation. The pathway choices available to an axon are in part defined by the set of guidance receptors present on the growth cone. Regulated expression of receptors and genes controlling the localization and activity of receptors ensures that axons respond only to guidance cues relevant for reaching their targets. In genetic screens for axon guidance mutants, we isolated an allele of let-19/mdt-13, a component of the Mediator, a large ~30 subunit protein complex essential for gene transcription by RNA polymerase II. LET-19/MDT-13 is part of the CDK8 module of the Mediator. By testing other Mediator components, we found that all subunits of the CDK8 module as well as some other Mediator components are required for specific axon navigation decisions in a subset of neurons. Expression profiling demonstrated that let-19/mdt-13 regulates the expression of a large number of genes in interneurons. A mutation in the sax-3 gene, encoding a receptor for the repulsive guidance cue SLT-1, suppresses the commissure navigation defects found in cdk-8 mutants. This suggests that the CDK8 module specifically represses the SAX-3/ROBO pathway to ensure proper commissure navigation.


Growth and maturation of testes in young coturnix and modification by exogenous FSH, LH, and testosterone--a stereologic evaluation.
Groups of coturnix males kept on continuous light from hatch were used in a study of testicular development. Testes were sampled from birds 4, 11, 18, 25, 32 days, and 4 months of age. Exogenous FSH at 1 and 2 mg., and LH and testosterone at 0.5 and 1.0 mg., were given daily for 3 days before the birds were killed for study at 4, 18, and 32 days of age. The following parameters were recorded: testes weights and volume, seminiferous tubular length and the ratio of length per mm.3 volume, supporting or Sertoli cell nuclear volume, volume of gonocytes, pre-leptotene spermatogonia, primary spermatocytes, and total intratubular volume. The stimulatory effect of exogenous LH and FSH on testes weight and volume, length/unit volume ratio of seminiferous tubules, and total intratubular component of the testes was most apparent at 4 days of age. The inhibitory effect of testosterone was significant at 18 and 32 days in all of these parameters. At 4 days, the 0.5-mg. level reduced the volume of the Sertoli cells and the gonial cell group. Full spermatozoa production was observed when the total length of the seminiferous tubules reached 30 m. It may be concluded from this study that young coturnix are similar to the chick in response to exogenous LH and FSH at 4 days of age. This response was observed even though the coturnix were on continuous light.


Miokamycin and leukocyte activity in man.
The effects of miokamycin on the immune system were studied in healthy volunteers by means of the following assays: phagocytosis, intracellular killing and natural killer activity. The tests were performed before, 2 and 6 h after oral administration of 600 mg of miokamycin. The findings suggest that miokamycin stimulates phagocytosis and intracellular killing. These effects could be clearly shown 2 h after drug intake and disappeared at the 6th hour. On the contrary, the natural killer activity was not significantly stimulated by miokamycin.


Do Anti-tuberculosis Drugs Reach Their Target?─High-Resolution Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Provides Information on Drug Penetration into Necrotic Granulomas.
Tuberculosis (TB) is characterized by mycobacteria-harboring centrally necrotizing granulomas. The efficacy of anti-TB drugs depends on their ability to reach the bacteria in the center of these lesions. Therefore, we developed a mass spectrometry (MS) imaging workflow to evaluate drug penetration in tissue. We employed a specific mouse model that─in contrast to regular inbred mice─strongly resembles human TB pathology. Mycobacterium tuberculosis was inactivated in lung sections of these mice by γ-irradiation using a protocol that was optimized to be compatible with high spatial resolution MS imaging. Different distributions in necrotic granulomas could be observed for the anti-TB drugs clofazimine, pyrazinamide, and rifampicin at a pixel size of 30 μm. Clofazimine, imaged here for the first time in necrotic granulomas of mice, showed higher intensities in the surrounding tissue than in necrotic granulomas, confirming data observed in TB patients. Using high spatial resolution drug and lipid imaging (5 μm pixel size) in combination with a newly developed data analysis tool, we found that clofazimine does penetrate to some extent into necrotic granulomas and accumulates in the macrophages inside the granulomas. These results demonstrate that our imaging platform improves the predictive power of preclinical animal models. Our workflow is currently being applied in preclinical studies for novel anti-TB drugs within the German Center for Infection Research (DZIF). It can also be extended to other applications in drug development and beyond. In particular, our data analysis approach can be used to investigate diffusion processes by MS imaging in general.


Eigenanalysis of dichroic, birefringent, and degenerate polarization elements: a Jones-calculus study.
A theoretical analysis of eigenpolarizations and eigenvalues pertaining to the Jones matrices of dichroic, birefringent, and degenerate polarization elements is presented. The analysis is carried out employing a general model of a polarization element. Expressions for the corresponding polarization elements are derived and analyzed. It is shown that, despite the presence of birefringence, a polarization element can, in a general case, demonstrate a totally dichroic behavior. Moreover, it is proved that birefringence necessarily accompanies dichroic elements with orthogonal eigenpolarizations. A transition between degenerate, dichroic, and birefringent eigenvalues is studied, and examples of synthesis of polarization elements are given.


Synthesis, crystal structure, and biological activities of two chiral mononuclear Mn((III)) complexes.
Two new chiral mononuclear Mn((III)) complexes, [MnL((R)) Cl (C2 H5 OH)]•C2 H5 OH () and [MnL((S)) (CH3 OH)2 ]Cl•CH3 OH (), {H2 L = (R,R)-or (S,S)-N,N'-bis-(2-hydroxy-1-naphthalidehydene)-cyclohexanediamine} were synthesized and characterized by various physicochemical techniques. Bond valence sum (BVS) calculations and the Jahn-Teller effect indicate that the Mn centers are in a +3 oxidation state. The statuses of the two complexes in the solution were confirmed as a pair of enantiomers by electrospray ionization, mass spectrometry (ESI-MS) spectrum. The binding ability of the complexes with calf thymus CT-DNA was investigated by spectroscopic and viscosity measurements. Both of the complexes could interact with CT-DNA via an intercalative mode with the order of (R-enantiomer) > (S-enantiomer). Under the physiological conditions, the two compounds exhibit efficient DNA cleavage activities without any external agent, which also follows the order of R-enantiomer > S-enantiomer. Interestingly, the concentration-dependent DNA cleavage experiments indicate an optimal concentration of 17.5 μM. In addition, the interaction of the compounds with bovine serum albumin (BSA) was also investigated, which indicated that the complexes could quench the intrinsic fluorescence of BSA by a static quenching mechanism.


Image scanning microscopy: an overview.
For almost a century, the resolution of optical microscopy was thought to be limited by Abbé's law describing the diffraction limit of light. At the turn of the millennium, aided by new technologies and fluorophores, the field of optical microscopy finally surpassed the diffraction barrier: a milestone achievement that has been recognized by the 2014 Nobel Prize in Chemistry. Many super-resolution methods rely on the unique photophysical properties of the fluorophores to improve resolution, posing significant limitations on biological imaging, such as multicoloured staining, live-cell imaging and imaging thick specimens. Structured Illumination Microscopy (SIM) is one branch of super-resolution microscopy that requires no such special properties of the applied fluorophores, making it more versatile than other techniques. Since its introduction in biological imaging, SIM has proven to be a popular tool in the biologist's arsenal for following biological interaction and probing structures of nanometre scale. SIM continues to see much advancement in design and implementation, including the development of Image Scanning Microscopy (ISM), which uses patterned excitation via either predefined arrays or raster-scanned single point-spread functions (PSF). This review aims to give a brief overview of the SIM and ISM processes and subsequent developments in the image reconstruction process. Drawing from this, and incorporating more recent achievements in light shaping (i.e. pattern scanning and super-resolution beam shaping), this study also intends to suggest potential future directions for this ever-expanding field.


Incidence in Tanzania of CF antibody to Coxiella burneti in sera from man, cattle, sheep, goats and game.
A total of 3735 sera were examined for the presence of CF antibody to Coxiella burneti. Of the samples tested 724 sera were from humans, 1507 from cattle, 525 from sheep, 575 from goats and 404 from game collected in the Serengeti National Park or Selous Game Reserve. It has been demonstrated that Q fever is well established in the above mentioned species in Tanzania (humans 3-9 per cent, cattle 13-3 per cent, sheep 17-1 per cent, goats 13-6 per cent and in game mainly in ruminants). Possible transmission links in the maintenance cycle of the disease are discussed.


Job dissatisfaction and substance use among employed high school students: the moderating influence of active and avoidant coping styles.
This study extends prior stress-coping-substance use research among adolescents by examining the employment context. Specifically, this study examines the relation of job dissatisfaction to substance use and the potential moderating influence of active and avoidant coping styles. Data were obtained from 446 employed high school students. Ordered-probit regression analyses reveal that job dissatisfaction is positively related to cigarette and alcohol use, but not to illicit drug use. Coping styles do not moderate the relation between job dissatisfaction and substance use. Nonetheless, coping styles have significant main-effect relations to substance use. Active coping is negatively related and avoidant coping is positively related to both cigarette and alcohol use. Neither coping style is related to illicit drug use.


Lateral Ankle Instability after Rotational Injury: A Case Report.
One of the most common orthopedic injury injuries seen in patients at the emergency department is that of the ankle. There are some efficient protocols for their treatment, but more often the clinician is fo-cused in finding and treating possible fractures and disregards ligamentous lesions that lead to instabil-ity, if they become chronic. A patient that suffered an ankle sprain was improperly handled, developed lateral instability of the ankle, and was treated surgically using an autologous semitendinosus graft. A 42-year year-old Caucasian male that after an ankle sprain was examined in various primary health -care centers, four times within six 6 months, with persistent symptoms of his left ankle. After all these months, he was eventually diagnosed with post-traumatic lateral instability of the ankle that was resistant to con-servative treatment. In stress view X-rays, the talar tilt angle was 21°ο and the anterior drawer was measured at 13 mm. The patient was treated surgically with reconstruction of the anterior talofibular and the calcaneofibular ligament using an autologous semitendinosus graft from the left knee. The graft was pinned in the anatomical insertion sites of the ligaments with absorbable screws. A post-surgical physiotherapy regimen was applied for two 2 months. In the post-surgical dynamic stress view X-rays, the talar tilt angle and the anterior drawer were markedly improved, measured at 3°ο and 4 mm, respec-tively. In 11 months post-surgical follow-up, the patient's American Foot and Ankle Score was 85, from the 60 evaluated before treatment. The use of guidelines, regular follow-ups, and functional rehabilitation are key factors to treating ankle injuries. The reconstruction of lateral collateral ligament complex with a semitendinosus graft is one of the surgical options for restoring lateral ankle instability.