How Does Chinese Outward Foreign Direct Investment Respond to Host Country Cultural Tolerance and Trust?
Based on 2010 to 2019 Chinese outward foreign direct investment (OFDI) panel data from 39 host countries, this paper studies the relationships between host country cultural characteristics and Chinese OFDI. The OLS regression results show that the cultural tolerance and trust in the host countries are significantly positively correlated with Chinese OFDI, which are robust according to the system GMM tests. Further analysis reveals that cultural tolerance is more positively related to Chinese OFDI in host countries with higher legislation and economic freedom, while cultural trust is positively associated with Chinese OFDI in host countries with lower legislation and economic freedom. In addition, higher cultural tolerance and trust promote Chinese OFDI in countries with greater cultural distance. Unlike traditional studies based on cultural distance in international trade, using more representative cultural characteristics, this paper provides references to Chinese OFDI decision-making based on the root characteristics associated with heterogeneous cultural influences.


Optical properties of Cr2+:ZnSe single crystal and film.
To realize an electrically pumped compact mid-IR microlaser, the optical properties of a Cr(2+):ZnSe film deposited by rf magnetron cosputtering were compared with those of a single crystal. The mid-IR room temperature photoluminescence efficiency of the film appears only twice less than the one of the single crystal under direct (1850 nm) and indirect (458 nm) excitations. The smaller Cr(2+) fluorescence lifetime values of the film were attributed to the presence in the film of a large amount of chromium in a valence state different from Cr(2+) and of structural defects in the ZnSe host matrix.


Predictors of shoulder level after spinal fusion in adolescent idiopathic scoliosis.
For patients with adolescent idiopathic scoliosis, shoulder balance influences their treatment satisfaction and psychological well-being. Several parameters are known to affect postoperative shoulder balance, but few prognostic models are as yet available. This study aimed to identify independent predictive factors that can be used to assess preoperatively which patients are at risk of postoperative shoulder elevation, and to build a linear prediction model. N = 102 patients with all Lenke types were reviewed radiographically before surgery and 1 year afterward. The outcome measures were coracoid height difference (CHD), clavicular angle (CA), and clavicle-first rib intersection difference (CiRID). Predictive factors commonly used in the literature were investigated using correlation analysis and statistical testing. Significant contributing factors were included in three multiple linear regression models (for CHD, CA, and CiRID). The mean shoulder level (CHD) significantly changed from a lower left shoulder value of -8.5 mm before surgery to 3.3 mm at the follow-up examination. A high preoperative left shoulder level by CiRID, a large amount of Cobb angle correction of the distal thoracic curve, a low preoperative Cobb angle in the lumbar curve, and a structural proximal thoracic curve proved to be determinants and thus risk factors for left-sided shoulder elevation after surgery. The three models predicting CHD, CA, and CiRID at the follow-up examination included these four risk factors and were significant. Preoperative variables have the strongest influence on shoulder level after spinal instrumentation. Additionally, extensive correction of the distal thoracic curve can cause elevation of the left shoulder.


Diffuse Large B-cell Lymphoma in the elderly: standard treatment and new perspectives.
Diffuse large B-cell lymphoma (DLBCL) is the most common histotype in non Hodgkin lymphoma, with a peak incidence in the sixth decade. The standard treatment for elderly FIT DLBCL patients is Rituximab-CHOP; in unfit and frail patients, chemotherapy at reduced intensity should be considered. Areas covered: In this article, we will review use of standard therapies and new drugs investigated such as immonomudulating agents (IMiDs), Bruton Tyrosine Kinase (BTK), in fit, unfit, frail and very elderly DLCBL patients. Expert commentary: R-CHOP21 in fit DLBCL patients is still the standard of care, while in elderly unfit patients a reduction of doses of cytotoxic drugs or schemes that avoid antracycline should be considered. The Comprensive Geriatric Assesment based in age, comorbidities and functional abilities of daily living is an important tool in elderly, in order to discriminate between fit, unfit or frail patients. Novel drugs represent valid therapeutic options in relapsed/refractory setting so continued participation in clinical trials should be encouraged.


Tamsulosin for ureteral stones--use in a pediatric population?
Urologists are using tamsulosin (Flomax) off-label as an aid for passing ureteral stones. The safety and efficacy of tamsulosin for this condition has been studied extensively in adults; however, studies are lacking in the pediatric population.


A growing divide: Trends in social inequalities in healthy longevity in Australia, 2001-20.
This study examines two decades of change in social inequalities in life and health expectancy among older adults in Australia, one of the few countries that escaped an economic recession during the global financial crisis. We compare adults aged 45+ across three measures of individual socio-economic position-education, occupation, and household wealth-and use multistate life tables to estimate total life expectancy (TLE) and life expectancy free of limiting long-term illness (LLTI-free LE) based on 20 waves of the Household, Income and Labour Dynamics in Australia Survey (2001-20). Our findings highlight substantial social disparities in both TLE and LLTI-free LE in Australia. Grouping individuals by household wealth shows striking differentials in LLTI-free LE. We observe widening social disparities in healthy longevity over time by all three measures of socio-economic position. This diverging trend in healthy longevity is troubling against the backdrop of widening income and wealth inequalities in Australia.


CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer.
CXC-chemokines are involved in the chemotaxis of neutrophils, lymphocytes and monocytes. However, role of these chemokines in tumorigenesis, especially with regard to interaction between tumor and its microenvironment, has not been clearly elucidated. The purpose of this study was to analyze the co-operative role of CXCL8 and CXCL12 in the tumor-stromal interaction in pancreatic cancer (PaCa). Using enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), we initially confirmed the expression of ligands and receptors, respectively, of CXC-chemokines in PaCa and stromal cells. We examined the co-operative role of CXCL8 and CXCL12 in proliferation/invasion of PaCa and human umbilical vein endothelial cells (HUVECs), and in HUVEC tube-formations through tumor-stromal interaction by MTS, Matrigel invasion, and angiogenesis assays, respectively. We detected expression of CXCR4, but not CXCR2, in all PaCa cells and fibroblasts. PaCa cells secreted CXCL8, and fibroblast cells secreted CXCL12. CXCL8 production in PaCa was significantly enhanced by CXCL12, and CXCL12 production in fibroblasts was significantly enhanced by co-culturing with PaCa. CXCL8 enhanced proliferation/invasion of HUVECs but did not promote proliferation/invasion of PaCa. Both recombinant and PaCa-derived CXCL8 enhanced tube formation of HUVECs that were co-cultured with fibroblast cells. CXCL12 enhanced the proliferation/invasion of HUVECs and the invasion of PaCa cells but had no effect on tube formation of HUVEC. We showed that PaCa-derived CXCL8 and fibroblast-derived CXCL12 cooperatively induced angiogenesis in vitro by promoting HUVEC proliferation, invasion, and tube formation. Thus, corresponding receptors CXCR2 and CXCR4 are potential antiangiogenic and antimetastatic therapeutic targets in PaCa.


Cardiac resynchronization therapy with or without defibrillator: experience from a high-volume Belgian implantation centre.
Cardiac resynchronization therapy (CRT) is an important treatment modality for heart failure with reduced ejection fraction and ventricular conduction delay. Considering limited health care budgets in an aging population, adding a defibrillator function to CRT remains a matter of debate. Our aim was to describe the experience of a high-volume Belgian implantation centre with CRT with/without defibrillator (CRT-D/P). Consecutive CRT patients (n = 221), implanted between October 2008 and April 2011 in Ziekenhuis Oost-Limburg (Genk), were reviewed. From 209 primo-implantations, 74 CRT-D and 98 CRT-P patients with complete follow-up inside the centre, were analysed. Despite differences in baseline characteristics, both groups demonstrated similar reverse left ventricular remodelling, improvement in New York Heart Association functional class and maximal aerobic capacity. During mean follow-up of 18 +/- 9 months, 21 patients died and 83 spent a total of 1200 days in hospital. Annual mortality was 8% and equal among the groups. The mode of death differed between CRT-D (predominantly pump failure) and CRT-P patients (pump failure, comorbidity and sudden death). The yearly population attributable risk of malignant ventricular arrhythmia was 8.16% in CRT-D and 1.38% in CRT-P patients. With current guidelines applied to the Belgian reimbursement criteria and at physicians'discretion, patient selection for CRT-D/ CRT-P was appropriate, with similar reverse remodelling, functional capacity improvement and good clinical outcome in both groups. High-risk patients for malignant ventricular arrhythmia were more likely to receive CRT-D, although the yearly attributable risk remained 1.38% in CRT-P patients.


Seeking support through solidarity: female leader's experiences of workplace solidarity in male-dominated professions.
While there is a plethora of research that documents the numerous barriers affecting female leaders in the modern workplace, there is a lack of literature which focuses on strategies or motivating resources that women use to navigate the workplace environment. Despite facing significant barriers in their leadership journeys, there are female leaders who are able to overcome these barriers to achieve leadership positions. These women leaders draw on personal and external motivating factors to assist them in dealing with the challenges associated with being a female leader as a result, research on motivating strategies for women's career progression is a research topic that warrants immediate attention. Female solidarity as a motivating resource has been gaining traction in the field of leadership studies and can be seen as a supportive resource that can be used by current and aspiring female leaders to progress in underrepresented environments. Although female solidarity is but only one of the many strategies that can be implemented to motivate women in leadership positions, the increase of female solidarity in the workplace is expected to alleviate the conditions that reinforce essentialist notions of the "queen bee syndrome" in which women are seen as unsupportive of each other. A qualitative research approach was used for this study, following an interpretive descriptive design. A total of 13 semi-structured interviews were conducted with female leaders in male-dominated professions within South Africa. Data was analysed using thematic content analysis. Results of the study were analyzed in line with three primary content areas, i.e., barriers to female solidarity in the workplace, benefits of female solidarity in the workplace and workplace interventions to increase solidarity. In the context of the study the predominant barriers to female solidarity within male-dominated workplaces were identified as unfair workplace behaviours, generational beliefs, societal expectations, organisational cultures, stereotypes and stigmas. The benefits of female solidarity within male-dominated workplaces were identified as career shaping mentorship, female recognition, female representation and female support. Lastly, the interventions that can be implemented to increase female solidarity within male-dominated workplaces were conceptualised as networking, transforming the company culture, socialisation and mentorship.


[Arteriovenous fistula of splenic vessels after splenectomy].
Arteriovenous fistula of the splenic vessels is a rare complication of splenectomy since only 7 cases (including the case reported herein by the authors) are presently known. Simultaneous ligation of the vessels seems to be an important causative factor; enzymatic necrosis of the vessel walls due to a minute peroperative trauma to the pancreatic tail is also a plausible mechanism. All fistulas have been recognized within two years after splenectomy. Clinical findings consist of various signs among which a continuous left flank murmur is the most constant. Cardiac repercussions are usually lacking. The fistula induces hepatic lesions which never evolve towards hepatic sclerosis or cirrhosis and are reversible after closure of the arteriovenous communication. Portal hypertension is present only when associated hepatic lesions block the portal blood flow. Until recent years, surgical closure of the fistula was performed with satisfying results. Recently, non surgical closure has become possible and seems suitable in poor-risk patients.


The Role of IL-17 in Protection against Mucosal Candida Infections.
Interleukin-17 (IL-17) is a proinflammatory cytokine produced by adaptive CD4+ T helper cells and innate lymphocytes, such as γδ-T cells and TCRβ+ "natural" Th17 cells. IL-17 activates signaling through the IL-17 receptor, which induces other proinflammatory cytokines, antimicrobial peptides and neutrophil chemokines that are important for antifungal activity. The importance of IL-17 in protective antifungal immunity is evident in mice and humans, where various genetic defects related to the IL-17-signaling pathway render them highly susceptible to forms of candidiasis such oropharyngeal candidiasis (OPC) or more broadly chronic mucocutaneous candidiasis (CMC), both caused mainly by the opportunistic fungal pathogen Candida albicans. OPC is common in infants and the elderly, HIV/AIDS and patients receiving chemotherapy and/or radiotherapy for head and neck cancers. This review focuses on the role of IL-17 in protection against candidiasis, and includes a brief discussion of non-Candida albicans fungal infections, as well as how therapeutic interventions blocking IL-17-related components can affect antifungal immunity.


Regulatory Efficacy of the Polyunsaturated Fatty Acids from Microalgae Spirulina platensis on Lipid Metabolism and Gut Microbiota in High-Fat Diet Rats.
Ultra-high performance liquid chromatography coupled with photo-diode array detector and electrospray ionization-mass spectrometry was employed to analyze the major fatty acids in Spirulina platensis 95% ethanol extract (SPL95). The effects of SPL95 on hepatoprotection were evaluated, including liver tissue histopathology, liver, and serum biochemical analysis. The active principle of SPL95 revealed a hypolipidemic effect, as indicated by down-regulating the mRNA and protein levels of sterol regulatory element-binding transcription factor-1c, 3-hydroxy-3-methyl glutaryl coenzyme A reductase, acetyl CoA carboxylase pathway, and upregulating adenosine 5'-monophosphate-activated protein kinase-α in liver. SPL95 enriched the beneficial bacteria, including Prevotella, Alloprevotella, Porphyromonadaceae, Barnesiella, and Paraprevotella. Treatment with SPL95 led to a decrease in microbes, such as Turicibacter, Romboutsia, Phascolarctobacterium, Olsenella, and Clostridium XVIII, which were positively correlated with serum triglyceride, total cholesterol, and low-density-lipoprotein cholesterol levels, but negatively correlated with the serum high-density-lipoprotein cholesterol levels. These results provide evidence that the fatty acid from SPL95 may be used as a novel adjuvant therapy and functional food to regulate gut microbiota in obese and diabetic individuals.


Chondrosarcoma of the bone with nodal metastasis: the first case report with review of literature.
Primary bone sarcomas are rarely known to metastasize to lymph nodes. This is attributed to paucity of lymphatic channels in the bone. Even though some bone sarcomas like osteosarcoma are known to have nodal metastasis, such affections have not been reported with primary osseous chondrosarcoma. We describe a case of primary chondrosarcoma of proximal humerus with axillary nodal metastasis. The patient underwent a forequarter amputation with axillary nodal clearance. The histopathological examination revealed metastasis of chondrosarcoma in lymph nodes. We also have reviewed the related literature and discussed the possible mechanism of this nodal metastasis.


Chorea-Ballismus Associated with Hyperglycemia.
Chorea-ballismus which is a rare complication of nonketotic hyperglycemia may be the first symptom of type 2 diabetes mellitus. In this paper, we present two patients, who had involuntary movements and were diagnosed as having ballismus-chorea associated with nonketotic hyperglycemia. While one of the patients was not diagnosed with diabetes mellitus, the other one did not administer insulin therapy for a long time which was prescribed. The patients were investigated by cranial imaging and biochemical tests. The symptoms improved in one of them within hours, however, it took days to improve for the other one. This clinical situation, which is thought to be caused by hyperglycemia, cerebral ischemia and failure of gamma-aminobutyric acid (GABA) and which probably improves with regulation of blood glucose levels, should be kept in mind by emergency physicians, because it can be the first presentation of type 2 diabetes mellitus.


[Long-term survival of a patient with extrahepatic cholangiocarcinoma treated with adjuvant radiotherapy for positive ductal margins after surgical resection].
A 57-year-old man with abdominal discomfort visited our hospital. Abdominal computed tomography (CT) revealed no tumorous lesions. Endoscopic retrograde cholangiography (ERC) revealed a tumorous lesion in the middle bile duct. Peroral cholangioscopy-assisted biopsy was performed, and the lesion was diagnosed as a papillary adenocarcinoma. Extra bile duct resection and regional lymph node dissection were performed; however, residual carcinoma in situ was detected at the ductal margins by intraoperative frozen section analysis. Therefore, external radiation therapy at a dose 50.4 Gy/28 Fr was administered after the operation. No complication due to radiotherapy occurred. The patient remains alive and recurrence -free for more than 7 years after the operation. We report the long-term disease-free survival of a patient with extrahepatic cholangiocarcinoma who was treated with external radiation therapy for positive ductal margins after surgical resection.


Parasitic infections in sickle cell crisis: Nigerian experience.
Data collected on 150 sickle cell patients in Nigeria were analyzed to determine the frequency of parasitic infections in clinical and hematologic crisis. Fifty-three adult and 97 pediatric patients (mean age: 27.6 years and 9.7 years, respectively) were studied. Of these patients, 82 were males and 68 females. One hundred thirty-nine had the SS and 11 the SC genotype. Blood samples collected from patients on admission for sickle cell-related illnesses were examined microscopically for evidence of Plasmodium sp, and stool samples were analyzed for presence of any helminth. A total of 102 parasitic infections associated with clinical cases of sickle cell crisis were recorded (malaria, 36[35.3%]; helminths, 49 ([48%]; and malaria and helminths together, 17 [16.7%]). Of the 49 helminthic infections, 26 (53.1%) were due to Ascaris lumbricoides, 15 (30.6%) were due to hookworms, 7 (14.3%) were due to Trichuris trichiura, and 1 (2%) was due to Strongyloides stercoralis. The mean hemoglobin levels during clinical crisis were 7.1 g/dL for helminths, 6.4 g/dL for malaria, and 6.1 g/dL for malaria and helminths together. Reticulocyte counts were 1.4% for helminths, 1.5% for malaria, and 1.2% for both malaria and helminths together. Severity and duration of the clinical crisis were longer for events associated with a single parasitic organism infection than for those with multiple organisms. Routine blood smear examination for malaria and stool analysis should be included in the laboratory evaluation of individuals with sickle cell anemia in developing countries as these infestations could play an important role in precipitating a crisis.


Epithelial genes in chronic rhinosinusitis with and without nasal polyps.
Genetic studies on chronic inflammatory diseases have resulted in an emphasis on the epithelial interface with the environment and the genes that influence this interaction. This study examines the expression of key epithelial genes implicated in the pathogenesis of other inflammatory disorders for their role in chronic rhinosinusitis (CRS). Epithelial cells were collected from the inferior turbinate, middle turbinate, and/or uncinate from 62 subjects undergoing sinonasal surgery. Patient groups included 21 CRS patients with nasal polyposis, 23 CRS patients without nasal polyposis, and 18 controls. Samples were analyzed for S100A7, S100A8, S100A9, SLC9A3R1, G-protein-coupled receptor for asthma, and serine protease inhibitor kazal type 5 (SPINK5) by quantitative real-time polymerase chain reaction. Immunohistochemistry (IHC) was performed to analyze expression of SPINK5 lympho epithelial kazal-type inhibitor (LEKTI) in sinonasal samples. Expression of S100A7 and S100A8 was significantly decreased in CRS with and without nasal polyps when compared with controls. S100A9 expression was significantly decreased in CRS without nasal polyps, and SPINK5 expression was significantly decreased in CRS with nasal polyps. SPINK5 (LEKTI) protein was detected in sinonasal tissue and was significantly decreased in polyp samples using IHC. This study shows marked reductions in the level of expression of several genes involved in epithelial barrier maintenance and repair in the inflammatory state of CRS.


Renal lesions in rats infected with Rattus serotype hantavirus (SR-11 strain).
Hemorrhagic fever with renal syndrome (HFRS) virus, strain SR-11 (SR) was inoculated intraperitoneally into specific-pathogen-free (SPF) newborn rats, from which the kidney lesions were examined pathologically. The infected rats revealed proteinuria on and after 16 days postinoculation (PI). Histologically, the epithelial cells of the renal tubules showed mild vacuolar and granular degeneration with cytoplasmic inclusion bodies (CIB) on and after 16 days PI. Ultrastructurally, a decrease in number of mitochondria and endocytic vesicles was recognized in the epithelial cells of the proximal renal tubules. Occasionally, both the proximal and distal renal tubular cells had CIB near well-developed Golgi apparatus on and after 13 days PI. Immunohistochemically, CIB were positive for anti-SR nucleocapsid antibody, but negative for anti-SR envelope protein antibody. From the results obtained here, it was concluded that the proteinuria in rats infected with HFRS virus resulted from an insufficiency of reabsorption in the proximal renal tubules, and that CIB consisted of the viral nucleocapsid protein.


The relation between ApoB/ApoA-1 ratio and the severity of coronary artery disease in patients with acute coronary syndrome.
Apolipoprotein B is considered the primary protein constituent of low-density lipoprotein. LDL contains variable quantities of cholesterol, but each lipoprotein contains a single ApoB protein. Thus, ApoB is a better index for the LDL circulation if compared to LDL cholesterol. On the contrary, apolipoprotein A-1 is a main structural protein of high-density lipoprotein. It has a major role in reversing cholesterol flow and cellular cholesterol homeostasis once detected. The aim of the study is to measure apo B/apo A-1 ratio in patients with acute coronary syndrome and assess its relationship with the severity of CAD. A total of 90 patients were enrolled in the study and subdivided into 3 groups: 30 patients of STEMI, 30 patients of NSTEMI, and 30 patients presented with unstable angina. Serum levels of apolipoprotein A-1 and apolipoprotein B were properly measured upon admission, and apo B/apo A-1 ratio was calculated. Both of Apo B and Apo B/Apo A1 ratio correlated significantly with Gensini scores (P value <0.001). High Gensini score patients had significantly high Apo B/Apo A1 ratio with the best cutoff value of 0.8 with sensitivity of 90% and specificity of 70%. Apo B is an independent risk predictor for the severity of CAD in patients with acute coronary syndromes. Moreover, the Apo B/Apo A1 ratio remains highly significant in patients with high Gensini score.


[A case of Cushing's disease: hallucinatory paranoid state preceding physical symptoms].
A 39-year old woman presented with hallucinatory paranoid state, particularly with erotomania, around September, 1988 (at the age of 39), and was hospitalized in a mental hospital for 9 days from May 1, 1989, to receive major tranquilizer therapy. At admission, the leukocyte count was 10,400/mm3 showing a mild leukocytosis, and there was temporary adynamia in the upper extremities. Thereafter, mild leukocytosis persisted intermittently. On May 12, 1989, the patient visited the Department of Neuropsychiatry, Kansai Medical University, and clinical examinations revealed mental symptoms including insomnia and erotomania, delusion of reference and auditory hallucination without persecutory taint. She showed clear consciousness and well understanding. Characteristically, her expression and behavior were smooth and emotional communication was available. There were neither alterations in her basic mood, nor flaccid association of idea. No abnormalities were seen in the hair and skin, and buffalo hump was not observed. Blood examination revealed a leukocyte count of 10,700/mm3, suggesting a mild leukocytosis. According to the patient, the menses have been regular. Although major tranquilizer therapy has been maintained, she gradually developed emotional instability, and tended to show fatigue and regressive changes in her personality. She was hospitalized in a mental hospital from October 25, 1989 to July 24, 1991. Since 1990, when she was in the hospital, she gradually developed obesity, hypertension, acne, and diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)


The efficacy of suppressive antibiotic treatment in patients managed non-operatively for periprosthetic joint infection and a draining sinus.
Objectives: Patients with prosthetic joint infections (PJIs) not suitable for curative surgery may benefit from suppressive antibiotic therapy (SAT). However, the usefulness of SAT in cases with a draining sinus has never been investigated. Methods: A multicentre, retrospective observational cohort study was performed in which patients with a PJI and a sinus tract were eligible for inclusion if managed conservatively and if sufficient follow-up data were available (i.e. at least 2 years). SAT was defined as a period of > 6 months of oral antibiotic therapy. Results: SAT was initiated in 63 of 72 (87.5 %) included patients. Implant retention during follow-up was the same in patients receiving SAT vs. no SAT (79.4 % vs. 88.9 %; p = 0 .68). In total, 27 % of patients using SAT experienced side effects. In addition, the occurrence of prosthetic loosening in initially fixed implants, the need for surgical debridement, or the occurrence of bacteremia during follow-up could not be fully prevented with the use of SAT, which still occurred in 42 %, 6.3 %, and 3.2 % of cases, respectively. However, the sinus tract tended to close more often (42 % vs. 13 %; p = 0 .14), and a higher resolution of pain was observed (35 % vs. 14 %; p = 0 .22) in patients receiving SAT. Conclusions: SAT is not able to fully prevent complications in patients with a draining sinus. However, it may be beneficial in a subset of patients, particularly in those with pain or the hindrance of a draining sinus. A future prospective study, including a higher number of patients not receiving SAT, is needed.


[Treatment of tracheobronchomegaly with an Ultraflex prosthesis. A case report].
Tracheobronchomegaly is defined as a dilatation of the trachea and the large bronchi. It may occur as a familial condition or in association with a connective tissue disease, e.g. Ehlers-Danlos syndrome. Tracheobronchomegaly occurs late in adults. The predominant symptoms are bronchial irritation and recurrent bronchopulmonary infections (because of ineffective cough). Diagnosis is provided by thoracic imaging, particularly computed tomography that enables measuring the precise diameter of the trachea. We report the case of one patient with tracheobronchomegaly who was greatly improved after implantation of Ultraflex tracheobronchial prostheses.


Neonatal listeriosis followed by nosocomial infection.
Neonatal listeriosis is widely reported, but this is the first case reported in Serbia. A newborn developed respiratory distress syndrome 2 hours after delivery and was admitted to the neonatal intensive care unit. Initial empirical therapy was inappropriate. Consequently, on the second day, the patient developed meningitis. Listeria monocytogenes was isolated from the tracheal aspirate, blood, periumbilical swab, and cerebrospinal fluid. After bacteriology results, the therapy was changed to ampicillin and meropenem. On day 11 of hospitalization, the patient developed nosocomial infection due to multidrug-resistant Stenotrophomonas maltophilia. Since therapeutic options were limited, the patient was treated with ciprofloxacin. After 26 days of hospitalization the patient showed complete recovery and was discharged with no apparent sequelae. This case showed the importance of bacteriological examination in cases of infections caused by uncommon organisms. Pediatricians should be aware of the neonatal infection caused by Stenotrophomonas maltophilia.


Regulation of C/EBPdelta-dependent transactivation by histone deacetylases in intestinal epithelial cells.
The C/EBPdelta transcription factor is involved in the positive regulation of the intestinal epithelial cell acute phase response. C/EBPdelta regulation by histone deacetylases (HDACs) during the course of inflammation remains to be determined. Our aim was to examine the effect of HDACs on C/EBPdelta-dependent regulation of haptoglobin, an acute phase protein induced in intestinal epithelial cells in response to pro-inflammatory cytokines. HDAC1, HDAC3, and HDAC4 were expressed in intestinal epithelial cells, as determined by Western blot. GST pull-down assays showed specific HDAC1 interactions with the transcriptional activation and the b-ZIP C/EBPdelta domains, while the co-repressor mSin3A interacts with the C-terminal domain. Immunoprecipitation assays confirmed the interaction between HDAC1 and the N-terminal C/EBPdelta amino acid 36-164 domain. HDAC1 overexpression decreased C/EBPdelta transcriptional activity of the haptoglobin promoter, as assessed by transient transfection and luciferase assays. Chromatin immunoprecipitation analysis showed a displacement of HDAC1 from the haptoglobin promoter in response to inflammatory stimuli and an increased acetylation of histone H3 and H4. HDAC1 silencing by shRNA expression increased both basal and IL-1beta-induced haptoglobin mRNA levels in epithelial intestinal cells. Our results suggest that interactions between C/EBPs and HDAC1 negatively regulate C/EBPdelta-dependent haptoglobin expression in intestinal epithelial cells.


Cloning, chromosomal assignment, and regulation of the rat thyrotropin receptor: expression of the gene is regulated by thyrotropin, agents that increase cAMP levels, and thyroid autoantibodies.
A rat thyrotropin (thyroid-stimulating hormone, TSH) receptor cDNA was isolated that encoded a protein of 764 amino acids, Mr 86,528. Transfection of the cDNA caused COS-7 cells to develop a TSH-sensitive adenylate cyclase response and the ability to bind 125I-labeled TSH; both activities were similar to those of rat FRTL-5 thyroid cells and not duplicated by lutropin. The gene represented by the cDNA was assigned to mouse chromosome 12 and human chromosome 14. Northern analyses identified two species of mRNA, 5.6 and 3.3 kilobases, in FRTL-5 thyroid cells; the transcripts appeared to differ only in the extent of their 3' noncoding sequences. There were minimal amounts of the two mRNAs in rat ovary, and neither was detected in RNA preparations from rat testis, liver, lung, brain, spleen, and FRT thyroid cells, which do not have a functional TSH receptor. TSH decreased both mRNA species 3- to 4-fold within 8 hr in FRTL-5 thyroid cells; down-regulation was dependent on TSH concentration and duplicated by forskolin, cholera toxin, or 8-bromo-cAMP but not by a phorbol ester. Down-regulation was also duplicated by thyroid-stimulating autoantibodies, which increased cAMP levels, but not by thyrotropin binding-inhibiting auto-antibodies, which actually increased TSH receptor mRNA levels.


A wearable robotic orthosis with a spring-assist actuator.
This paper introduces a wearable robotic orthosis with spring-assist actuators, which is designed to assist people who have difficulty in walking. The spring-assist actuator consists of an electrical motor and a spring, which are attached to a rotational axis in parallel to each other. The spring-assist actuator is developed based on the analysis on the stiffness of the knee and hip joints during walking. "COWALK-Mobile," which is a wearable robotic orthosis, is developed using the spring-assist actuators to reduce the required motor torque during walking. The COWALK-Mobile has active hip and knee joints and passive ankle joints to provide assistive torque to the wearer. The required joint torque is generated by the spring as well as the electrical motor, which results in a decrease of maximum required torque for the motor. In order to evaluate the performance of the spring-assist actuator, experiments are carried out. The experiments show that the spring-assist actuators reduced the required motor torque during walking.


Modeling the Distribution of Medically Important Tick Species in Florida.
The lone star (Amblyomma americanum), black-legged (Ixodes scapularis) and American dog ticks (Dermacentor variabilis) are species of great public health importance as they are competent vectors of several notable pathogens. While the regional distributions of these species are well characterized, more localized distribution estimates are sparse. We used records of field collected ticks and an ensemble modeling approach to predict habitat suitability for each of these species in Florida. Environmental variables capturing climatic extremes were common contributors to habitat suitability. Most frequently, annual precipitation (Bio12), mean temperature of the driest quarter (Bio9), minimum temperature of the coldest month (Bio6), and mean Normalized Difference Vegetation Index (NDVI) were included in the final models for each species. Agreement between the modeling algorithms used in this study was high and indicated the distribution of suitable habitat for all three species was reduced at lower latitudes. These findings are important for raising awareness of the potential for tick-borne pathogens in Florida.


Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure.
To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.


The role of the socket in the periodontal healing of replanted dogs' teeth stored in ViaSpan for extended periods.
In a previous study on the extended storage of extracted dogs' teeth, it was hypothesized that changes in the socket environment might play a role in the periodontal healing of these teeth. The purpose of this study was to evaluate the role of the socket in the periodontal healing of replanted dogs' teeth. Extracted endodontically treated dogs' teeth were stored in ViaSpan for 6 hours and replanted into sockets after 6, 48 or 96 hours. Controls included teeth extracted and replanted immediately, 48-hour stored teeth replanted into 48-hour sockets and 96-hour stored teeth replanted into 96-hour sockets. After 6 months the dogs were killed and the teeth prepared for histologic evaluation according to Andreasen. Overall healing for the groups and healing for teeth within the groups were evaluated and compared. The best results were obtained when the teeth were replanted immediately. For the teeth stored in ViaSpan for 6 hours, complete healing decreased significantly as the age of the socket increased. In addition, the rate of replacement resorption increased significantly with increasing socket age for the 6-hour stored teeth. Forty-eight-hour stored teeth replanted into 48-hour sockets had the lowest healing rate with levels of inflammatory resorption not seen in the other groups. According to the results of this study, the socket environment plays an important role in the healing of replanted teeth in dogs.


Analysis of clinical studies related to apexification techniques.
The aim of this study was to gather all the clinical studies regarding apexification and artificial apical barrier techniques, point out the possible differences of the clinical procedures and investigate how these are changing over time. An electronic search was carried out in PubMed, covering the period from March 1968 to July 2015. More articles were retrieved by hand-searching or by the reference section of the included articles. Specific criteria were set in order to determine the relevance of each study. One hundred and thirty eight articles were included, 53% of them concerned apexification with MTA plug. Long term apexification studies demonstrated 13% for a single change of the intracanal medicament and 85% for two or more. In 13% of the studies concerning artificial apical plug, the procedure included a single visit. Calcium hydroxide was left in the root canal for 3-12 months in 59% of the long term apexification studies, for 12-24 in 42% and for 24 months or more in 10%. Both techniques can lead to favourable clinical outcomes. There is a tendency for the artificial apical barrier apexification over the years, which usually includes the use of intracanal medicament for a short time.


Pregnancy outcomes of antibody negative and untreated subclinical hypothyroidism.
Subclinical hypothyroidism is thought to be associated with adverse pregnancy outcomes but the data is conflicting and generally depends on antibody positivity and treatment. We evaluated the pregnancy outcomes in Turkish population with untreated, antibody negative subclinical hypothyroidism for the first time. We searched for 30 015 patients between January 2016 and May 2017 retrospectively. Finally, a total of 930 pregnant women with untreated, antibody negative subclinical hypothyroidism and 7986 controls were included. Demographic characteristics, laboratory findings and pregnancy outcomes, including pregnancy loss, impaired glucose tolerance, gestational diabetes, hypertensive disorders of pregnancy, preterm birth, neonatal intensive care unit admission, placenta previa and abruption, cesarean delivery, low birthweight, Apgar score <7 and premature rupture of membranes were recorded. Demographic and laboratory characteristics were similar between two groups except thyroid stimulating hormone levels and previous uterine surgery rates. Subclinical hypothyroidism group had an increased risk of pregnancy loss (odds ratio [OR] 2.583; 95% confidence interval [CI] 1.982-3.365; P < 0.001), impaired glucose tolerance (OR 1.952; 95% CI 1.450-2.627; P < 0.001), hypertensive disorders of pregnancy (OR 1.476; 95% CI 1.113-1.923; P = 0.004), neonatal intensive care unit admission (OR 1.620; 95% CI 1.084-2.420; P = 0.019), placenta previa (OR 12.581; 95% CI 5.046-31.363; P < 0.001) and cesarean delivery (OR 1.263; 95% CI 1.091-1.462; P = 0.002). Subclinical hypothyroidism has worse pregnancy outcomes as compared to euthyroid pregnant women even in antibody negativity. Therefore, we suggest that all pregnant women should routinely be screened in their first antenatal visits for thyroid functions.


Short-term effect of atorvastatin on ischaemic threshold in hypercholesterolaemic patients with stable ischaemic heart disease.
Hypercholesterolaemia is associated with a loss of endothelium-dependent vasodilation, which may facilitate the occurrence of myocardial ischaemia in patients with coronary artery disease (CAD). The improvement of endothelial dilator function after 4 to 6 weeks of oral lipid-lowering therapy has been documented. Whether this early restoration of endothelial function by statins translates into anti-ischaemic effects is unknown. This study was designed to determine the effect of 4 weeks' treatment with 80 mg atorvastatin daily on exercise-induced ischaemia in patients with stable ischaemic heart disease (IHD) receiving standard anti-anginal drug therapy. A total of 41 patients with documented CAD, exercise-induced ischaemia and LDL-cholesterol > 130 mg/dl underwent exercise ECG, angina score and lipid level assessment at baseline, after 4 weeks of placebo treatment, and after 4 weeks of therapy with atorvastatin 80 mg. Primary endpoint was the change in time to 1 mm ST-segment depression (= ischaemic threshold) between placebo and treatment period. Atorvastatin treatment resulted in a 55% reduction of low-density lipoprotein (LDL) cholesterol (from mean of 162 (SD 32) to 72 (20) mg/dl). For a comparable rate-pressure product, the average time to 1 mm ST-segment depression was 295 (112) s at baseline, 314 (149) s after placebo and 301 (131) s after atorvastatin, indicating that the ischaemic threshold was not significantly modulated after 4 weeks of atorvastatin treatment. There was also no significant change in global angina score or in time to maximal ST-segment depression. High-dose atorvastatin treatment for 4 weeks drastically reduced LDL-cholesterol. However, the present study did not demonstrate a significant effect on the ischaemic threshold in patients with stable IHD already under treatment with anti-ischaemic agents.


The lung biological activity of American attapulgite.
Attapulgite is a fibrous mineral industrially consumed at the rate of over a million tons per year but the biological activity of the material is not fully known. To evaluate the in vivo toxicity of the fibrous material, we exposed the tracheal lobe of 16 sheep to a single exposure of either 100 ml saline, 100 mg UICC asbestos fibers in 100 ml saline, 100 mg short asbestos fibers in 100 ml saline, or 100 mg attapulgite in 100 ml saline. The animals were studied by bronchoalveolar lavage (BAL) at Days 2, 12, 24, 40, and 60 and by autopsy at Day 60. In the saline-exposed sheep, BAL and lung histology did not change. In the UICC asbestos-exposed animals, we reproduced the BAL changes previously reported (R. Bégin, M. Rola-Pleszczynski, S. Massé, Y. Berthiaume, and G. Drapeau, 1985, Environ. Res. 36, 389-404). In the short asbestos-exposed sheep, there were no significant BAL changes. In the attapulgite sheep, we found significant and sustained increases in total BAL cells (X2, P less than 0.05), macrophages (X2, P less than 0.05), neutrophils (X5, P less than 0.01), fibronectin (X2-3, P less than 0.05), lactate dehydrogenase (X2, P less than 0.05), beta-glucuronidase (X2, P less than 0.05), but BAL cellularity returned to control levels by Day 60 whereas in the UICC asbestos-exposed sheep, it remained significantly above control. Lung histology demonstrated the characteristic peribronchiolar fibrosing alveolitis in the UICC asbestos-exposed sheep, whereas macrophagic alveolitis with minimal airway distortion was seen in the short asbestos-exposed sheep and in all of the attapulgite-exposed sheep but three which had typical peribronchiolar alveolitis quite similar to that observed in UICC-exposed sheep, but of lower intensity. In conclusion, the study documents that attapulgite is not an inert material for lung tissue; it does produce a macrophagic and neutrophilic alveolitis in the early inflammatory phase of lung reaction with peribronchiolar involvement in some sheep. Whether or not this initial attapulgite induced alveolitis leads to lung fibrosis remains to be evaluated in a longer follow-up study of attapulgite-exposed animals.


Chemically induced mammary gland adenomyoepitheliomas and myoepithelial carcinomas of mice. Immunohistochemical and ultrastructural features.
Myoepithelial cell tumors of the mammary gland have been observed in several mammalian species and are composed of a single cell type (myoepithelium) or, more often, present as a biphasic process including neoplastic ductal epithelial cells. In dogs, these are common tumors, but in humans they are rare neoplasms of the breast, and little is yet known of their pathogenesis, particularly with respect to myoepithelial origin. The present report describes bicellular mammary gland tumors arising from the duct epithelium that were induced in (C57BL/6NCr X DBA/2NCr)F1 (B6D2F1) mice by four weekly oral applications of 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) starting at 8 weeks of age. Mammary tumors developed 7 to 8 months later in 14 of 57 mice, and most showed great morphologic resemblance to human adenomyoepitheliomas and myoepithelial carcinomas. Ultrastructurally, the induced tumors were composed of cuboidal epithelium with a microvillous border originating from the lining duct epithelium and plump oval or highly elongated cells that were identified as myoepithelial in origin. These spindle cells contained abundant microfilaments in parallel orientation, some with focal densities and intermediate filaments that frequently formed loose bundles or compact tonofibrils. The myoepithelial cells possessed well-developed desmosomes and plasma membrane caveolae and were regularly bordered by single or reduplicated basement membranes. By immunohistochemistry, strong immunoreactivity was observed for actin in the myoepithelial tumor component only, whereas cytokeratin was variably present in both duct epithelium and myoepithelium. Neoplastic myoepithelial cells stained purple with phosphotungstic acid hematoxylin (PTAH) and brilliant red with Masson's trichrome. It is suggested that DMBA-induced mouse mammary gland adenomyoepitheliomas and myoepithelial carcinomas may serve as very useful animal models to study myoepithelial tumorigenesis.


Small plot trials documenting effective mating disruption of oriental fruit moth by using high densities of wax-drop pheromone dispensers.
In 2004 field experiments, we compared the effectiveness of various deployment densities of 0.1-ml paraffin wax drops containing 5% pheromone versus Isomate M-Rosso "rope" dispensers for disruption of Grapholita molesta (Busck). Treatments were evaluated in 0.05-ha (12-tree) plots of 'Delicious' apples receiving regular maintenance according to growers' standards, but not sprayed with insecticides. The application densities of 0.1-ml wax drops were 3 per tree (820/ha), 10 per tree (2,700/ha), 30 per tree (8,200/ha), and 100 per tree (27,300/ha). Wax drops were compared with 3-ml dispensers of pheromone-containing paraffin wax or Isomate M-Rosso ropes at 1.8 per tree (500/ha) and untreated control plots. Treatments were applied before the start of each of three moth generations. Orientational disruption, as measured by inhibition of moth captures in pheromone-baited delta traps, was greatest in plots that received 100 drops per tree (99.2%) and 30 drops per tree (99.4%). More than 55% of tethered, virgin females were mated in control plots after one night of deployment. However, no mating was recorded at the two highest application densities of wax drops where orientational disruption of traps exceeded 99%. Mating ranged from 7 to 20% among the other treatments, including Isomate rope dispensers. G. molesta males were observed closely approaching pheromone dispensers in plots containing ropes and wax drops, documenting competitive attraction between synthetic pheromone sources and feral females. The majority of observed G. molesta males approached within 60 cm of wax drops or pheromone ropes and departed within 20 s by flying upwind. Thirty wax drops per tree yielded higher mating disruption of G. molesta than did Isomate M-Rosso dispensers deployed at the recommended rate of 500/ha (1.8 per tree). Measurement of release rates confirmed behavioral data indicating that paraffin wax dispensers would need to be applied once per G. molesta generation in Michigan. Paraffin wax drops are a promising technology for moth mating disruption. They are cheaper and easier to produce, require less total pheromone per annual application, and produce better mating disruption at appropriate deployment densities compared with Isomate M-Rosso dispensers under high G. molesta population densities. The cost-effectiveness of this approach will require an appropriate mechanized applicator for wax drops.


Arsenic trioxide-induced apoptosis of human malignant lymphoma cell lines and its mechanisms.
To investigate the responses of human Burkitt lymphoma cells to arsenic trioxide (As2O3) and the possible mechanisms. Epstein-Barr virus (EBV)-positive human B-lymphoma Raji cell line and EBV-negative human B-lymphoma BJAB cell line were used as in vitro models to assess the cell apoptosis by morphology and DNA agarose gel electrophoresis. Protein expression was analyzed using Western blotting. After 24-hour treatment with the 2, 5 and 10 micromol/L As2O3, the concentrations of As2O3 achievable in vivo, cell apoptosis was induced in human Burkitt lymphoma BJAB cells at the rates of 47.6%+/-4.8% (Mean+/-SD, n=3), 66.4%+/-5.1%, 87.0%+/-7.3% and at 35.5%+/-3.8%, 51.5%+/-6.2%, 62.2%+/-7.9% respectively in Raji cells, corresponding to the concentration of As2O3. EBV-infected Raji cell line was less sensitive to As2O3 than EBV-negative BJAB cell line (P<0.05). As2O3-induced apoptosis was accompanied by down-regulation of Bcl-xL protein expression and activation of apoptosis protein caspase-3, as identified by Western blotting. As2O3 exerts apoptosis-inducing effects on human Burkitt lymphoma cells through down-regulation of Bcl-xL protein expression and activation of apoptosis protein caspase-3, and may serve as a candidate therapeutic agent against malignant lymphoma for both systemic and local therapies.


Advances in Silicon-Based Integrated Lidar.
Silicon-based Lidar is an ideal way to reduce the volume of the Lidar and realize monolithic integration. It removes the moving parts in the conventional device and realizes solid-state beam steering. The advantages of low cost, small size, and high beam steering speed have attracted the attention of many researchers. In order to facilitate researchers to quickly understand the research progress and direction, this paper mainly describes the research progress of silicon-based integrated Lidar, including silicon-based optical phased array Lidar, silicon-based optical switch array Lidar, and continuous frequency-modulated wave Lidar. In addition, we also introduced the scanning modes and working principles of other kinds of Lidar, such as the Micro-Electro-Mechanical System, mechanical Lidar, etc., and analyzed the characteristics of the Lidars above. Finally, we summarized this paper and put forward the future expectations of silicon-based integrated Lidar.


Great vessel transposition for antegrade delivery of the TAG endoprosthesis in the proximal aortic arch.
To report a technique for antegrade delivery of the TAG stent-graft during repair of lesions in the proximal aortic arch. Via an 8-cm median sternotomy, a bifurcated graft, usually 14 or 16 mm in diameter, is anastomosed to the ascending aorta with 4-0 Prolene suture; a 10-mm straight graft is cut obliquely and anastomosed to the heel of the bifurcated graft for delivery of the endograft antegrade across the aortic arch. The great vessels in turn are clamped, transected at the arch, and sutured to the bypass graft. A 9-F sheath is secured in the conduit, and a 250-cm angled hydrophilic guidewire is passed to the desired iliac artery and exteriorized through the femoral sheath. The conduit is clamped, and the TAG's delivery sheath is substituted for the 9-F sheath. A marker is placed on the conduit to assure that the stent-graft is deployed just beyond the limb origins of the bifurcated graft. The conduit is introduced across the aortic arch, followed by the endograft, which is positioned at the marker as the sheath is withdrawn into the conduit. After completion angiography, the delivery sheath is removed, and the conduit is transected and oversewn. Heparinization is reversed, and the incision is closed, with one mediastinal drainage tube in place. This technique allows precise delivery of the endoluminal graft at the proximal aortic arch, thus avoiding problems with retrograde delivery.


Therapeutic significance of peroxisome proliferator-activated receptor modulators in diabetes.
Peroxisome proliferator-activated receptors (PPARs) are a group of three nuclear receptor isoforms, identified and encoded by different genes: PPARalpha, PPARdelta and PPARgamma. Each subtype of PPAR appears to be differently expressed in a tissue-specific manner due to its binding to a specific consensus DNA sequence of peroxisome proliferator response elements (PPREs). PPARalpha plays a significant role in the regulation of nutrient metabolism, including fatty acid oxidation, gluconeogenesis and amino acid metabolism. PPARdelta is expressed ubiquitously and has been found to be effective in controlling dyslipidemia and cardiovascular diseases, while PPARgamma isotype is mainly expressed in adipose tissue where it stimulates adipogenesis and lipogenesis. Thus PPARs have emerged as potential molecular targets for the design and synthesis of a different class of compounds, considering the conformation of receptors for the treatment of human metabolic disorders. This review concerns the therapeutic importance of PPARs in diabetes drug development.


Rickettsioses in the central hills of Sri Lanka: serological evidence of increasing burden of spotted fever group.
To study the epidemiology, clinical features, and changing pattern of rickettsial infections on the western slopes of the hilly Central Province of Sri Lanka over 6 years. All patients with rickettsial infections who presented to the Teaching Hospital, Peradeniya were studied prospectively from January 2002 to December 2007. An immunofluorescent antibody assay (IFA) was used to confirm the diagnosis. Of the 371 clinical cases of rickettsial infection, 122 underwent IFA to confirm the diagnosis. Species-specific IgG antibodies were positive in 105/122 (86.1%) cases: 43/105 (40.9%) to Rickettsia conorii and 6/105 (5.7%) to Orientia tsutsugamushi, with mixed antibody reactivity to more than one antigen in 56/105 (53.3%) cases, including Rickettsia typhi in 27/105 (25.7%). Among those with mixed IgG reactivity, IgM assays were used to detect pathogens responsible for acute infections. Finally, a total of 55 spotted fever group (SFG) infections, seven scrub typhus infections, and one case of murine typhus were identified. Of the 105 positive cases, 53 (50.5%) were male and 52 (49.5%) were female, and the mean age was 40 years (range 11-83 years). In the SFG patients, 13/55 (24%) had severe vasculitis with fern leaf type skin necrosis and 17/55 (31%) had arthritis. Three patients (5%) had an altered level of consciousness. A patient with scrub typhus had transient deafness. None of the 105 patients had an eschar. It appears that SFG rickettsioses are on the rise in the hilly Central Province of Sri Lanka, whilst murine typhus and scrub typhus are present at a lower rate.


Can Lactobacillus fermentum LF10 and Lactobacillus acidophilus LA02 in a slow-release vaginal product be useful for prevention of recurrent vulvovaginal candidiasis?: A clinical study.
To assess the effectiveness of the association of 2 specific strains, Lactobacillus fermentum LF10 (DSM 19187) and Lactobacillus acidophilus LA02 (DSM 21717), specifically formulated in slow-release effervescent tablets, in patients with recurrent vulvovaginal candidiasis. The study was a clinical trial of 58 women diagnosed with recurrent VVC (≥4 culture-confirmed episodes in a 12-mo period). All patients were given 200 mg of fluconazole orally as an induction dose for 3 alternate days during the first treatment week. Afterward, the patients were given a new product formulated in slow-release vaginal tablets containing at least 0.4 billion live cells of each of lactobacillus L. fermentum LF10 and L. acidophilus LA02 (first phase of the prophylactic period), on alternate days for 10 consecutive nights. Patients who were still free of symptoms were given 1 vaginal tablet every week for the next 10 weeks (second phase of the prophylactic period). Patients asymptomatic after the total duration of the observation phase (7 mo) were considered as responders. During the second 10-week prophylactic phase, 49 of 57 (86.0%) patients remained free of clinical recurrence, whereas symptomatic VVC occurred in 8 patients (14.0%). During the 7-month follow-up, 42 patients of 49 (85.7%) were symptom free at the end of the protocol, whereas clinical recurrences occurred in 7 women (14.3%). Overall, 42 of 58 women enrolled in the study (72.4%) experienced no clinical recurrence throughout the 7-month observation phase (responders). This study strengthens the evidence supporting the use of specific lactobacilli with well-demonstrated activities associated with the creation and maintenance of a vaginal biofilm that hinders the persistence of an infection caused by Candida.


5-Hydroxytryptamine extraction by the lung.
Both 5-hydroxytryptamine and norepinephrine are removed from blood during a single passage through the pulmonary vasculature of the dog; 5-hydroxytryptamine is removed to a greater degree than is norepinephrine. The magnitude of extraction of both 5-hydroxytryptamine and norepinephrine is similar to that previously determined in man. In the intact dog, imipramine inhibits the uptake of 5-hydroxytryptamine by the lung in a dose-dependent manner.


Streptomycetes and micromycetes as perspective antagonists of fungal phytopathogens.
Among natural factors that permanently influence on the plants, the soil microorganisms play a special role for the growing of plants as habitants of their rhizosphere. Mainly they are the representatives of actinomycetes genus Streptomyces and fungal genus Penicillium and their metabolic products stimulate plant growth and inhibit the growth of pathogenic fungi and bacteria. The aim of our study was to determine the antagonism of actinomycetes and micromycetes isolated from soils of R. Moldova against the fungal pathogens of agricultural plants. The strains were isolated from 5 types of chernozem (black soil) from central zone of R. Moldova, with different concentration of humus. Most of micromycetes and streptomycetes were isolated from soil sample 1 (monoculture of maize) and soil sample 2 (Poltava road border) with similar humus content (2.4-2.6%). The antifungal activity of micromycetes strains was occurring mostly against Fusarium solani and Thelaviopsis basicola, at streptomycetes against Alternaria alternata and Botrytis cinerea. It was revealed the strains completely inhibit the growth of Alt. alternata (streptomycetes strains 23, 33, 37), B. cinerea (Streptomyces sp. 17), and F. solani (Penicillium sp. 104). Our results allow to consider the actinomycetes Streptomyces sp.9, Streptomyces sp. 12, Streptomyces sp. 17, Streptomyces sp. 37 Streptomyces sp. 66 and micromycetes Penicillium sp. 5, Penicillium sp. 65, Penicillium sp. 104 isolated from soils of R. Moldova, as prospective strains-antagonists against the phytopathogenic fungus, the causative agents of agricultural plants deseasis.


Roles of Signaling Pathways in the Epithelial-Mesenchymal Transition in Cancer.
The epithelial-mesenchymal transition (EMT) is a cellular process though which an epithelial phenotype can be converted into a phenotype of mesenchymal cells. Under physiological conditions EMT is important for embryogenesis, organ development, wound repair and tissue remodeling. However, EMT may also be activated under pathologic conditions, especially in carcinogenesis and metastatic progression. Major signaling pathways involved in EMT include transforming growth factor β(TGF-β), Wnt, Notch, Hedgehog and other signaling pathways. These pathways are related to several transcription factors, including Twist, Smads and zinc finger proteins snail and slug. These interact with each other to provide crosstalk between the relevant signaling pathways. This review lays emphasis on studying the relationship between EMT and signaling pathways in carcinogenesis and metastatic progression.


[Comparative analysis of distribution of mutant alleles of the gene coding for the CCR-5 chemokine receptor, among people in Russia, infected and not infected with HIV-1].
Comparative analysis of the distribution of deletion mutations of CC-chemokine receptor 5 (CCR-5) gene among HIV-1 infected and not infected subjects in Russia showed the incidence of the heterozygous genotype to be 17.8% among both HIV-infected and seronegative subjects. The incidence of the homozygous genotype for the deletion among seronegative individuals was 0.6%, but no homozygotes were found among HIV-1 infected patients. Study of the incidence of the mutant CCR-5 allele among patients infected with different HIV-1 subtypes showed that the susceptibility of heterozygotes to HIV-1 infection was not associated with any special genetic subtype.


FSFI scores of women with persistent genital arousal disorder compared with published scores of women with female sexual arousal disorder and healthy controls.
Although persistent genital arousal disorder (PGAD) has been mistaken for hypersexuality, there is no research documenting the sexual functioning of PGAD women to support or refute such an assumption. To compare the Female Sexual Function Index (FSFI) scores of PGAD women to that of women diagnosed with female sexual arousal syndrome (FSAD) and healthy controls. The FSFI scores of heterosexual women who met all five features qualifying for a diagnosis of PGAD (N = 172) on an online questionnaire were compared with previously published FSFI scores of women diagnosed with FSAD (N = 128) and healthy controls (N = 131). Total and subscale scores on the FSFI. On every subscale of the FSFI with the exception of desire, the PGAD women obtained scores between that of the FSAD and the healthy control group. The FSAD women displayed the greatest problems in desire, arousal, lubrication, orgasm, and pain while women with PGAD reported somewhat more desire than the control group but did not meet the cutoff score for sexual dysfunction. PGAD women are more similar to the normal control group than women with FSAD. There is no evidence to support the belief that women who meet criteria for a diagnosis of PGAD are "hypersexual." In fact, their overall sexual functioning falls within the normal range and is significantly better than that of women diagnosed with FSAD.


Size analysis of a pressurized metered dose inhaler-delivered solution formulation by an Aerosizer-LD time-of-flight aerosol particle size spectrometer.
In a previous study, an Aerosizer-LD time-of-flight (TOF) aerosol spectrometer was shown to underestimate significantly the aerodynamic size of airborne particles produced following actuation of a suspension-based formulation delivered from a pressurized metered-dose inhaler (pMDI) via a nonelectrostatic valved holding chamber (VHC). It was postulated that the nonspecific nature of the particle detection system in terms of chemical composition was responsible for the inclusion of smaller non-drug-containing excipient particles in the measured size distribution data from this analyzer. This limitation may not apply to certain solution formulations in which the only particles remaining after the evaporation of propellant and volatile excipient (solubilizer) are composed of pure drug substance. Such a formulation (QVAR, HFA-formulated beclomethasone di-propionate [BDP]) has recently become available, and the present investigation was therefore designed to test this hypothesis. Aerosizer-LD measured mass-weighted size distribution data for QVAR had a mass median aerodynamic diameter (MMAD) close to 1.1 microm, very similar to published data for this parameter, based on measurement of the aerosol by cascade impactor followed by drug-specific assay. However, the Aerosizer-LD underestimated the spread of the size distribution significantly. The causes are believed to be a combination of two separate effects: (1) lack of sensitivity of the particle detection system to particles finer than about 0.7 microm aerodynamic diameter and (2) preferential removal of particles larger than the MMAD, either by evaporation of residual solvent (ethanol) or by inertial/gravitational deposition in the sampling arrangement upstream of the measurement zone.


Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in Burkitt's lymphoma cells.
Apoptosis, a form of physiological cell death, is a genetically determined program essential for normal development and maintenance of tissues, which has been linked to a variety of gene products. We have examined the susceptibility to radiation-induced apoptosis of cell lines derived from the human B cell tumour, Burkitt's lymphoma (BL), displaying a variety of phenotypic characteristics and expressing genes implicated in apoptosis at different levels. The susceptibility to apoptosis following gamma radiation varied significantly amongst the lines. Cell lines with wild type p53 were susceptible to radiation-induced apoptosis but two of five BL lines with only mutant p53 allele also displayed similar susceptibility. Some BL cell lines that expressed bcl-2 at levels comparable with Epstein-Barr virus (EBV) transformed normal B cells were highly susceptible to gamma radiation-induced apoptosis, whereas others expressing low levels were resistant. When these lines were analysed for bax and bcl-X(L) expression again no correlation was observed with susceptibility or resistance to apoptosis. Two BL cell lines having deregulated expression of c-myc were resistant to the induction of apoptosis while two others which had regulated c-myc expression were susceptible. Thus the status of p53, c-myc, bcl-2, bcl-X(L) and bax is not sufficiently informative in BL lines to predict susceptibility to radiation-induced apoptosis.


Roles of Progesterone, Testosterone and Their Nuclear Receptors in Central Nervous System Myelination and Remyelination.
Progesterone and testosterone, beyond their roles as sex hormones, are neuroactive steroids, playing crucial regulatory functions within the nervous system. Among these, neuroprotection and myelin regeneration are important ones. The present review aims to discuss the stimulatory effects of progesterone and testosterone on the process of myelination and remyelination. These effects have been demonstrated in vitro (i.e., organotypic cultures) and in vivo (cuprizone- or lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis (EAE)). Both steroids stimulate myelin formation and regeneration by acting through their respective intracellular receptors: progesterone receptors (PR) and androgen receptors (AR). Activation of these receptors results in multiple events involving direct transcription and translation, regulating general homeostasis, cell proliferation, differentiation, growth and myelination. It also ameliorates immune response as seen in the EAE model, resulting in a significant decrease in inflammation leading to a fast recovery. Although natural progesterone and testosterone have a therapeutic potential, their synthetic derivatives-the 19-norprogesterone (nestorone) and 7α-methyl-nortestosterone (MENT), already used as hormonal contraception or in postmenopausal hormone replacement therapies, may offer enhanced benefits for myelin repair. We summarize here a recent advancement in the field of myelin biology, to treat demyelinating disorders using the natural as well as synthetic analogs of progesterone and testosterone.


Crimpy inhibits the BMP homolog Gbb in motoneurons to enable proper growth control at the Drosophila neuromuscular junction.
The BMP pathway is essential for scaling of the presynaptic motoneuron arbor to the postsynaptic muscle cell at the Drosophila neuromuscular junction (NMJ). Genetic analyses indicate that the muscle is the BMP-sending cell and the motoneuron is the BMP-receiving cell. Nevertheless, it is unclear how this directionality is established as Glass bottom boat (Gbb), the known BMP ligand, is active in motoneurons. We demonstrate that crimpy (cmpy) limits neuronal Gbb activity to permit appropriate regulation of NMJ growth. cmpy was identified in a screen for motoneuron-expressed genes and encodes a single-pass transmembrane protein with sequence homology to vertebrate Cysteine-rich transmembrane BMP regulator 1 (Crim1). We generated a targeted deletion of the cmpy locus and find that loss-of-function mutants exhibit excessive NMJ growth. In accordance with its expression profile, tissue-specific rescue experiments indicate that cmpy functions neuronally. The overgrowth in cmpy mutants depends on the activity of the BMP type II receptor Wishful thinking, arguing that Cmpy acts in the BMP pathway upstream of receptor activation and raising the possibility that it inhibits Gbb activity in motoneurons. Indeed, the cmpy mutant phenotype is strongly suppressed by RNAi-mediated knockdown of Gbb in motoneurons. Furthermore, Cmpy physically interacts with the Gbb precursor protein, arguing that Cmpy binds Gbb prior to the secretion of mature ligand. These studies demonstrate that Cmpy restrains Gbb activity in motoneurons. We present a model whereby this inhibition permits the muscle-derived Gbb pool to predominate at the NMJ, thus establishing the retrograde directionality of the pro-growth BMP pathway.


A probable role of dihydropyridine receptors in repression of Ca2+ sparks demonstrated in cultured mammalian muscle.
To activate skeletal muscle contraction, action potentials must be sensed by dihydropyridine receptors (DHPRs) in the T tubule, which signal the Ca(2+) release channels or ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) to open. We demonstrate here an inhibitory effect of the T tubule on the production of sparks of Ca(2+) release. Murine primary cultures were confocally imaged for Ca(2+) detection and T tubule visualization. After 72 h of differentiation, T tubules extended from the periphery for less than one-third of the myotube radius. Spontaneous Ca(2+) sparks were found away from the region of cells where tubules were found. Immunostaining showed RyR1 and RyR3 isoforms in all areas, implying inhibition of both isoforms by a T tubule component. To test for a role of DHPRs in this inhibition, we imaged myotubes from dysgenic mice (mdg) that lack DHPRs. These exhibited T tubule development similar to that of normal myotubes, but produced few sparks, even in regions where tubules were absent. To increase spark frequency, a high-Ca(2+) saline with 1 mM caffeine was used. Wild-type cells in this saline plus 50 microM nifedipine retained the topographic suppression pattern of sparks, but dysgenic cells in high-Ca(2+) saline did not. Shifted excitation and emission ratios of indo-1 in the cytosol or mag-indo-1 in the SR were used to image [Ca(2+)] in these compartments. Under the conditions of interest, wild-type and mdg cells had similar levels of free [Ca(2+)] in cytosol and SR. These data suggest that DHPRs play a critical role in reducing the rate of spontaneous opening of Ca(2+) release channels and/or their susceptibility to Ca(2+)-induced activation, thereby suppressing the production of Ca(2+) sparks.


Stabilization of F-actin by tropomyosin isoforms regulates the morphology and mechanical behavior of red blood cells.
The short F-actins in the red blood cell (RBC) membrane skeleton are coated along their lengths by an equimolar combination of two tropomyosin isoforms, Tpm1.9 and Tpm3.1. We hypothesized that tropomyosin's ability to stabilize F-actin regulates RBC morphology and mechanical properties. To test this, we examined mice with a targeted deletion in alternatively spliced exon 9d of Tpm3 (Tpm3/9d-/- ), which leads to absence of Tpm3.1 in RBCs along with a compensatory increase in Tpm1.9 of sufficient magnitude to maintain normal total tropomyosin content. The isoform switch from Tpm1.9/Tpm3.1 to exclusively Tpm1.9 does not affect membrane skeleton composition but causes RBC F-actins to become hyperstable, based on decreased vulnerability to latrunculin-A-induced depolymerization. Unexpectedly, this isoform switch also leads to decreased association of Band 3 and glycophorin A with the membrane skeleton, suggesting that tropomyosin isoforms regulate the strength of F-actin-to-membrane linkages. Tpm3/9d-/- mice display a mild compensated anemia, in which RBCs have spherocytic morphology with increased osmotic fragility, reduced membrane deformability, and increased membrane stability. We conclude that RBC tropomyosin isoforms directly influence RBC physiology by regulating 1) the stability of the short F-actins in the membrane skeleton and 2) the strength of linkages between the membrane skeleton and transmembrane glycoproteins.


2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway.
2,5-Dihydroxyacetophenone (DHAP) is an active compound obtained from Radix rehmanniae preparata, which is widely used as a herbal medicine in many Asian countries. DHAP has been found to possess anti-inflammatory, anti-anxiety, and neuroprotective qualities. For the present study, we evaluated the anti-cancer effects of DHAP on multiple myeloma cells. It was discovered that DHAP downregulated the expression of oncogenic gene products like Bcl-xl, Bcl-2, Mcl-1, Survivin, Cyclin D1, IAP-1, Cyclin E, COX-2, and MMP-9, and upregulated the expression of Bax and p21 proteins, consistent with the induction of G2/M phase cell cycle arrest and apoptosis in U266 cells. DHAP inhibited cell proliferation and induced apoptosis, as characterized by the cleavage of PARP and the activation of caspase-3, caspase-8, and caspase-9. Mitogen-activated protein kinase (MAPK) pathways have been linked to the modulation of the angiogenesis, proliferation, metastasis, and invasion of tumors. We therefore attempted to determine the effect of DHAP on MAPK signaling pathways, and discovered that DHAP treatment induced a sustained activation of JNK, ERK1/2, and p38 MAPKs. DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma.


[Significance of renovasography in the elucidation of hypertension].
About 10% of all cases of hypertension are nephrogeneously conditioned. The renovasography gives the clearest evidence for the morphological diagnostics of changes of the renal arteries and the parenchyma. In 180 hypertensive patients with pathological findings of the renal angiography most frequently pyelonephritic changes were proved. Then follow changes of the arteries, kidneys with urinary stasis, polycystic degenerations and hypoplasias. These diseases were, however, also found in 108 patients with normal values of blood pressure. Possibly cases are concerned in which no haemodynamic effect of the disease is present. In advanced findings reductions of organs were registered. In a part of the cases the sizes of the kidneys were found within the normal values. Only some patients with hypertension had enlargements of the organs. When multiple renal arteries were present a hypertension was significantly more frequent than in a supply of the kidneys by means of one artery each.


Impaired tumorigenicity and decreased liver metastasis of murine neuroblastoma cells engineered to secrete interleukin-2 or granulocyte macrophage colony-stimulating factor.
We have examined the antitumor effect of murine neuroblastoma cells (C1300) engineered to produce cytokines. Retrovirally transduced cells with human interleukin-2 (IL-2) or murine GM-CSF gene, but not murine IL-4 gene, abolished their tumorigenicity in syngeneic mice, although their in vitro growth rate and expression of class I antigens of the major histocompatibility complex were unchanged. Inoculation of wild-type cells into the mice, which had rejected IL-2 or GM-CSF producers, did not develop tumors, indicating that protective immunity was induced. In an experimental hematogenous metastasis model, we found that the numbers of metastatic foci in the liver caused by intravenous administration of IL-2 or GM-CSF producers were significantly reduced compared with those by the injection of wild-type or vector virus-transduced cells. No significant differences in their adhesiveness to extracellular matrices and ability to differentiate were observed among parent and transduced cells. Thus, these results indicate that IL-2 or GM-CSF secretion, in the vicinity of neuroblastoma cells, produced antitumor effect and reduced metastatic ability.


Microbial biotechnology addressing the plastic waste disaster.
Oceans are a major source of biodiversity, they provide livelihood, and regulate the global ecosystem by absorbing heat and CO2 . However, they are highly polluted with plastic waste. We are discussing here microbial biotechnology advances with the view to improve the start and the end of life of biodegradable polymers, which could contribute to the sustainable use of marine and coastal ecosystems (UN Sustainability development goal 14).


Successful control of refractory ventricular premature beat with an estrogen-progesterone compound.
Drug resistant ventricular premature contractions (VPCs) in a 35-yr-old woman were successfully controlled with a contraceptive agent containing estrogen-progesterone. The VPCs in this patient always showed an R on T phenomenon resulting in occasional short run of ventricular tachycardia. Apart from the VPCs, her ECG exhibited no abnormalities. The family history revealed 9 instances of sudden unexpected death over 3 generations. The findings of myocardial biopsy of the right ventricular endocardium were characteristic of cardiomyopathy. This report discusses the possibility that a contraceptive agent successfully suppressed VPCs in a particular woman who showed a close relation between a certain period of her menstrual cycle and the occurrence of VPCs.


Persistent nonequilibrium effects in generalized Langevin dynamics of nonrelativistic and relativistic particles.
Persistent nonequilibrium effects such as the memory of the initial state, the ballistic diffusion, and the break of the equipartition theorem and the ergodicity in Brownian motions are investigated by analytically solving the generalized Langevin equation of nonrelativistic Brownian particles with colored noise. These effects can also be observed in the Brownian motion of relativistic particles by numerically solving the generalized Langevin equation for specially chosen memory kernels. Our analyses give rise to think about the possible anomalous motion of heavy quarks in relativistic heavy-ion collisions.


Genome-Assisted Prediction of Quantitative Traits Using the R Package sommer.
Most traits of agronomic importance are quantitative in nature, and genetic markers have been used for decades to dissect such traits. Recently, genomic selection has earned attention as next generation sequencing technologies became feasible for major and minor crops. Mixed models have become a key tool for fitting genomic selection models, but most current genomic selection software can only include a single variance component other than the error, making hybrid prediction using additive, dominance and epistatic effects unfeasible for species displaying heterotic effects. Moreover, Likelihood-based software for fitting mixed models with multiple random effects that allows the user to specify the variance-covariance structure of random effects has not been fully exploited. A new open-source R package called sommer is presented to facilitate the use of mixed models for genomic selection and hybrid prediction purposes using more than one variance component and allowing specification of covariance structures. The use of sommer for genomic prediction is demonstrated through several examples using maize and wheat genotypic and phenotypic data. At its core, the program contains three algorithms for estimating variance components: Average information (AI), Expectation-Maximization (EM) and Efficient Mixed Model Association (EMMA). Kernels for calculating the additive, dominance and epistatic relationship matrices are included, along with other useful functions for genomic analysis. Results from sommer were comparable to other software, but the analysis was faster than Bayesian counterparts in the magnitude of hours to days. In addition, ability to deal with missing data, combined with greater flexibility and speed than other REML-based software was achieved by putting together some of the most efficient algorithms to fit models in a gentle environment such as R.


The UL55 and UL56 genes of herpes simplex virus type 1 are not required for viral replication, intraperitoneal virulence, or establishment of latency in mice.
A critical determinant for intraperitoneal virulence of Herpes Simplex Virus Type 1 (HSV-1) strain F has been ascribed to the BamHI-B fragment of the genome. This region contains two nonessential genes, UL55 and UL56, of unknown function. To investigate the contribution of these genes to viral pathogenesis, we have generated two recombinant HSV-1 viruses, inUL55 and inUL56, in which the corresponding gene was inactivated in strain F by insertion of an ICP6::lacZ cassette. Strains inUL55 and inUL56, which did not express the UL55 and UL56 RNA, respectively, were virulent in mice inoculated intraperitoneally. Strains inUL55 and inUL56 also established latent infections in the trigeminal ganglia of mice inoculated via the cornea. These results demonstrate that the HSV-1 UL55 and UL56 genes are not critical for intraperitoneal virulence or establishment of latent infection.


Synthesis of zona pellucida proteins by denuded and follicle-enclosed mouse oocytes during culture in vitro.
During growth of the ovarian follicle, the mammalian oocyte becomes surrounded by an acellular coat called the zona pellucida. Whether the zona pellucida originates from the oocyte, surrounding follicle cells, or both has remained an unresolved issue. In experiments described here, denuded and follicle-enclosed mouse oocytes at various stages of growth were isolated and cultured in vitro in the presence of either [(35)S]methionine or [(3)H]fucose in order to determine the site of synthesis of the three, recently identified, zona pellucida proteins, ZP1, ZP2, and ZP3 [Bleil, J. D. & Wassarman, P. M. (1980) Dev. Biol., in press]. Approximately 1.5% of the [(35)S]methionine, and as much as 45% of the [(3)H]fucose, that was incorporated into trichloroacetic acid-insoluble material by denuded or follicle-enclosed oocytes during a 12-hr culture period was found associated with zonae pellucidae removed from the cultured oocytes. Incorporation of [(35)S]methionine into zona pellucida proteins was depressed to less than 1/50th when denuded oocytes were cultured in the presence of puromycin, and secretion of zona pellucida proteins by denuded oocytes was demonstrated by pulse-chase experiments. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of [(35)S]methionine- and [(3)H]fucose-labeled proteins present in oocytes, zonae pellucidae, and follicle cells revealed that denuded oocytes synthesize and secrete zona pellucida proteins, whereas no evidence was obtained to suggest that follicle cells synthesize these proteins. Denuded oocytes, ranging in diameter from 48 to 68 mum, incorporated both [(35)S]methionine and [(3)H]fucose into zona pellucida proteins during culture in vitro, whereas zonae pellucidae removed from fully-grown oocytes (85 mum) were not radiolabeled to a significant extent. After culture of denuded or follicle-enclosed oocytes for 12 hr, more than 95% of the [(3)H]fucose incorporated into oocyte proteins was found in ZP1, ZP2, and ZP3, indicating that the zona pellucida proteins are the major class of proteins glycosylated during oocyte growth. These results provide biochemical evidence supporting the idea that the zona pellucida originates from the mammalian oocyte itself, rather than from the surrounding follicle cells.


Environment-genetic influences on immunocompetence.
The immunological responses of an animal are changing continually in response to perceived environmental changes. This is because the genetic background, the lifelong environment of animals and their interaction greatly influence immunological responsiveness. An animal's genetic background influences all factors related to immunocompetence. Among these are age of onset of immunocompetence, responsiveness to specific antigens, antibody titers, type of antibody and immune response, as well as the persistence of the responses. Defense by immunity must require considerable resources, because chickens with a high antibody response are smaller and have poorer feed efficiencies than those chickens whose antibody response is lower. An increase in the effectiveness of one defensive factor may result in reduced effectiveness of another factor. For example, chickens selected for a high antibody titer response to antigen have reduced effectiveness of macrophages. Environmental stresses influence the immune response. Stress at the time of the animal's contact with antigen results in a reduced antibody response. After the antibody response begins, stress has little effect. Stress promotes the sensitization of cell-mediated immunity but inhibits its effectiveness. A short-term stressor such as weaning is followed, in about 24 h, by a short period of reduced immunocompetence, even though lymphoid mass may be reduced. Reduced immunocompetence during stressful periods can be reduced by employing adrenal blocking chemicals, or by socializing animals to their handlers.


Course of enterovesical fistulas in Crohn's disease.
Enterovesical fistulas occurred in 38 of 683 patients (5.6 percent) with Crohn's disease admitted to The Mount Sinai Hospital between 1960 and 1977. There were 22 ileovesical fistulas, 8 colovesical fistulas, and 8 fistulas of combined ileal and colonic origin. These cases fell into three different pathophysiologic categories: 16 patients presented with sepsis after a mean duration of 7 years of Crohn's disease, 19 presented without sepsis after a mean of 10 years of disease, and 3 elderly cancer patients presented with an average 25 years disease duration. Sepsis was usually due to deep pelvic or lower quadrant abscess with spontaneous rupture into the bladder. Nonseptic fistulization was a later, more gradual process, reflecting slow penetration into the bladder from a site of chronic cicatrizing bowel disease. Cancer was a very late complication, arising in each patient from an excluded loop. Although medical treatment was successful in delaying surgery in 6 patients and obviated surgery altogether in 2 patients, 36 of 38 patients (95 percent) eventually required operation. Postoperative mortality in this series was limited to two patients (5 percent) with preoperative intraabdominal abscess and sepsis. Five other deaths, unrelated to urinary complications, were caused by intestinal cancer in three patients and by intestinal complications of recurrent Crohn's disease in two patients. The urologic course of patients with enterovesical fistula was completely benign. All operated patients were cured of their enterovesical fistulas, and no urologic sequelae developed. Subsequent reoperations that were required in 45 percent of these patients were all for recurrent bowel disease and not for fistula or other urologic problems.


Treatment of neonatal abstinence syndrome in preterm and term infants.
Neonatal abstinence syndrome (NAS) is treated with a variety of drug preparations. With the optional treatment of NAS with chloral hydrate, phenobarbital or morphine the cumulative drug consumption of the mentioned drugs, the length of hospital stay and treatment duration was evaluated in preterm and term neonates. Retrospective, uncontrolled study which evaluates different therapies of neonatal abstinence syndrome (NAS) in preterm and term neonates. During the past 16 years data were obtained from medical records of 51 neonates with NAS; 9 preterm and 35 term neonates were evaluated and 7 were excluded because of incomplete data sets. 31 (72.1%) received a pharmacological treatment (6 preterm and 25 term neonates). Treatment started at 4.3 [3.3-5.3] d. Mean duration of treatment was 11.7 [6.6-16.7] d. In our study chloral hydrate (ch) and phenobarbital (pb) were first line medication escalated by the morphine (mp) solution. Mean cumulative dosage of ch was 643.5 [260.3-1 026.7] mg, of pb 53.2 [19.7-86.8] mg and of mp 4.22 [0-8.99] mg. Our study group showed similar treatment duration and length of hospital stay compared to other studies. The cumulative dose of mp was lower compared to most studies. This benefit resulted at the expense of a further medication with pb and ch. However, 6 of 9 preterm neonates needed significantly less pharmacological therapy compared to term neonates indicating less susceptibility of immature brain to abstinence of maternalo-pioids.


Tumid Lupus Erythematosus and Systemic Lupus Erythematosus: A Report on Their Rare Coexistence.
Tumid lupus erythematosus (TLE) is a rare variant of cutaneous lupus erythematosus. Clinically, it lacks typical changes found in discoid lupus and antinuclear antibodies (ANA) levels are elevated in only 10% of the patients. Coexistent systemic lupus erythematosus (SLE) has been reported to be rare, and literature shows only a few case reports. We present a case of coexistent tumid lupus and SLE. We present a case of a 48-year-old Caucasian female who presented with chronic facial rash, photosensitivity, intermittent oral ulcers, joint pain with morning stiffness, and unintentional weight loss. Laboratory studies showed positive ANA at 1:640, elevated erythrocyte sedimentation rate, positive anticardiolipin immunoglobulin (Ig) G, anticardiolipin IgM, and anti-beta-2 glycoprotein IgM. Skin biopsy of the rash showed a superficial and deep dense lymphocytic infiltrate with mucin deposition, histopathology favoring tumid lupus. The patient was diagnosed with TLE with SLE and was started on hydroxychloroquine with improvement in her rash. Ultraviolet light and certain medications have been proven to play a role in the pathogenesis of tumid lupus. It usually responds to photoprotection, topical treatment, or oral antimalarial therapy.


Tetrakis(5-tert-butylpyrazole-1kappaN2)tetrachloro-1kappaCl,2kappa3Cl-micro-oxo-1:2kappa2O-diiron(III).
The title compound, [Fe(2)Cl(4)O(C(7)H(12)N(2))(4)], contains vertex-sharing distorted tetrahedral [FeOCl(3)](-) and octahedral [FeOCl(Hpz(t)Bu)(4)](+) moieties (Hpz(t)Bu is 5-tert-butylpyrazole), linked by a bent oxo bridging ligand. The two Fe(III) centres are also bridged by intramolecular hydrogen bonds between the pyrazole N-H groups and the O(2-) and Cl(-) ligands.


[Iohexol in studies of the spinal canal. Multicenter study].
The author presents the results of a multicentric study of Iohexol in investigation of the spinal canal undertaken at the request of Winthrop Laboratories in 32 Radiological departments. The study involved 329 adults of both sexes. It confirmed the excellent quality of results obtained with this preparation in the literature and its excellent tolerance. On the basis of these results Iohexol may be considered to be definitely one of the best currently available preparations for investigation of the spinal canal.


Coalition Game-Based Secure and Effective Clustering Communication in Vehicular Cyber-Physical System (VCPS).
In this paper, we address the low efficiency of cluster-based communication for the crossroad scenario in the Vehicular Cyber-Physical System (VCPS), which is due to the overload of the cluster head resulting from a large number of transmission bandwidth requirements. After formulating the issue as a coalition formation game, a coalition-based clustering strategy is proposed, which could converge into a Nash-stable partition to accomplish the clustering formation process. In the proposed strategy, the coalition utility is formulated by the relative velocity, relative position and the bandwidth availability ratio of vehicles among the cluster. Employing the coalition utility, the vehicles are denoted as the nodes that make the decision whether to switch to a new coalition or stay in the current coalition. Based on this, we can make full use of the bandwidth provided by cluster head under the requirement of clustering stability. Nevertheless, there exist selfish nodes duringtheclusteringformation,soastointendtobenefitfromnetworks. Thisbehaviormaydegrade the communication quality and even destroy the cluster. Thus, we also present a reputation-based incentive and penalty mechanism to stop the selfish nodes from entering clusters. Numerical simulation results show that our strategy, CG-SECC, takes on a better performance for the tradeoff between the stability and efficiency of clustering communication. Besides, a case study demonstrates that the proposed incentive and penalty mechanism can play an important role in discovering and removing malicious nodes.


A Multiparametric Approach Based on NT-proBNP, ST2, and Galectin3 for Stratifying One Year Prognosis of Chronic Heart Failure Outpatients.
Galectin-3 and ST2 are emerging biomarkers involved in myocardial fibrosis. We evaluate the relevance of a multiparametric biomarker approach based on increased serum levels of NT-proBNP, galectin-3, and ST2 in stratifying the prognosis of chronic heart failure (CHF) outpatients. In 315 CHF outpatients in stable clinical condition clinical and echocardiographic evaluations were performed. Routine chemistry and serum levels of NT-proBNP, galectin-3, and ST2 were also assessed. During a 12 month follow-up, cardiovascular death, and/or heart failure (HF) occurred in 64 patients. The presence of NT-proBNP, galectin-3, and ST2 were higher than the recommended cutoffs and were all associated with events at univariate Cox regression analysis, as well as in a multivariate analysis including the three biomarkers. When a score based on the number of biomarkers above the recommended cut-offs was used (in a range of 0-3), it was associated with events both with respect to the univariate (HR 2.96, 95% CI 2.21-3.95, p < 0.001, C-index 0.78) and the multivariate (HR 1.52, 95% CI 1.06-2.17, p: 0.023, C-index 0.87) analyses, after correction for the variables of a reference model. Our results suggest that an easy prognostic approach based on the combination of three biomarkers, although with partially-overlapping pathophysiological mechanisms, is able to identify patients with the highest risk of heart failure progression.