Fetal anterior abdominal wall thickness between gestational diabetes and normal pregnant women.
To compare fetal anterior abdominal wall thickness (AAWT) between women with and without GDM during third trimester and to determine accuracy of AAWT to predict large for gestational age (LGA) infants. A total of 250 pregnant women, including 125 women with GDM and 125 women without GDM, were enrolled. Tansabdominal ultrasonographic examinations were performed at 28-30, 32-34 and 36-38 weeks. In addition to standard fetal biometries, AAWT was measured. Patient characteristics and ultrasonographic measurements were compared between groups. Sensitivity and specificity of AAWT for identifying LGA were evaluated. While standard fetal biometries were comparable, mean fetal AAWT in GDM women were significantly higher than those without GDM at 28-30 weeks (2.8 ± 0.8 vs. 2.6 ± 0.6, p = 0.006) and 32-34 weeks (4.0 ± 0.9 vs. 3.5 ± 0.8, p = 0.042). LGA infants had significantly higher fetal AAWT at each time point only in GDM women. Using cut off values of AAWT of ≥2.0, 3.0, and 4.0 mm at 28-30, 32-34, and 36-38 weeks, sensitivity for LGA diagnosis in GDM women were 94.4%, 93.9%, and 89.3%, respectively. The use of abdominal circumference (AC) at >90th percentile showed lower sensitivity but higher specificity, regardless of GDM status. Combination of both measurements increased sensitivity to approximately 90% or higher in every time point, especially among GDM women. Significant increase in fetal AAWT was observed in GDM women at 28-30 and 32-34 weeks. Fetal AAWT significantly increased among LGA infants and had higher sensitivity than AC in identifying LGA during third trimester. In GDM women at 28-30 weeks, AAWT ≥2.0 mm and AC >90th percentile had 97.2% sensitivity for LGA diagnosis.


Genetically engineered neural stem cells expressing cytosine deaminase and interferon-beta enhanced T cell-mediated antitumor immunity against gastric cancer in a humanized mouse model.
Gastric cancer (GC) is an invasive, fatal disease with a poor prognosis. Gene-directed enzyme prodrug therapy via genetically engineered neural stem cells (GENSTECs) has been widely studied in various malignancies, such as breast, ovarian, and renal cancer. In this study, the human neural stem cells expressing cytosine deaminase and interferon beta (HB1.F3.CD.IFN-β) cells were applied to convert non-toxic 5-fluorocytosine to cytotoxic 5-fluorouracil and secrete IFN-β. Human lymphokine-activated killer cells (LAKs) were generated by stimulating human peripheral blood mononuclear cells (PBMCs) by interleukin-2, and we evaluated the cytotoxic activity and migratory ability of LAKs co-cultured with GNESTECs or their conditioned media in vitro. A GC-bearing human immune system (HIS) mouse model was generated by transplanting human PBMCs followed by subcutaneous engraftment of MKN45 cells in NSG-B2m mice to evaluate the involvement of T cell-mediated anti-cancer immune activity of GENSTECs. In vitro studies showed the presence of HB1.F3.CD.IFN-β cells facilitated the migration ability of LAKs to MKN45 cells and activated their cytotoxic potential. In MKN45-xenografted HIS mice, treatment with HB1.F3.CD.IFN-β cells resulted in increased cytotoxic T lymphocyte (CTL) infiltration throughout the tumor, including the central area. Moreover, the group treated to HB1.F3.CD.IFN-β showed increased granzyme B expression in the tumor, eventually enhancing the tumor-killing potential of CTLs and significantly delaying tumor growth. These results indicate that the HB1.F3.CD.IFN-β cells exert anti-cancer effects on GC by facilitating the T cell-mediated immune response, and GENSTECs are a promising therapeutic strategy for GC.


Effect of early experience on neuronal and behavioral responses to con- and heterospecific odors in closely related Mus taxa: epigenetic contribution in formation of precopulatory isolation.
The most effective learning occurs during sensitive periods. Olfactory plasticity to main social olfactory cues is limited to a critical period to a large degree. The objective was to evaluate the influence of early olfactory experience on the behavioral and neuronal responses of males to con- and heterospecific odors of receptive females in two species, M. musculus (subspecies musculus, wagneri) and M. spicilegus, and thus to determine the potential role of epigenetic contribution in the formation of precopulatory isolation. Males were reciprocally cross-fostered shortly after the birth and were tested for response to con- and heterospecific urine odors of estrus females using two-choice tests at 70-85 days of age. Neuronal activity of non- and cross-fostered males was evaluated at 90-110 days of age in the MOB and AOB to con- and heterospecific female odor using fMRI (MEMRI). Non-cross-fostered males of three taxa demonstrated a strong preference for odor of conspecific females compared to odor of heterospecific ones. Spicilegus-nursed musculus preferred odor of heterospecific females. Wagneri-nursed spicilegus and spicilegus-nursed wagneri did not demonstrate significant choice of con - or heterospecific female odor. The level of MRI signal obtained from the evaluation of manganese accumulation in AOB neurons was significantly higher when the odor of conspecific estrus females was exposed, compared to urine exposure of heterospecific females. The response pattern changed to the opposite in males raised by heterospecific females. Response patterns of neuronal activity in the MOB to con- and heterospecific female odors were different in cross-fostered and control males. The maternal environment, including odor, had a greater effect on the level of MRI signal in the AOB than the genetic relationships of the recipient and the donor of the odor stimulus. Behavioral and neuronal responses to con- and heterospecific odors changed in closely related Mus taxa as a result of early experience. We demonstrated the importance of early learning in mate choice in adulthood in mice and the possibility of epigenetic contribution in the formation of precopulatory reproductive isolation.


Streptococcal infections in patients with chronic granulomatous disease: case report and review of the literature.
Streptococcus intermedius caused a liver abscess in a patient with chronic granulomatous disease (CGD). In contrast to typical staphylococcal abscesses in CGD, this abscess was liquid, easily drained, and resolved without surgery or steroids. This case and literature review provide insight into this organism's pathogenesis, including in CGD.


Women's wellness in the mountains: An exploration of medicinal plants among tibeto-burman groups in Thailand.
This study offers valuable insight into the traditional healing practices of women's healthcare within four Tibeto-Burman groups. By focusing on women's wellness, the research sheds light on the often-neglected yet significant contributions made by women in the field of traditional medicine. The study seeks to address the gap of studies on the ethnobotany of women healthcare of the Tibeto-Burman groups in Thailand and to analyst the factors that could affect the diversity of ethnobotanical knowledge. The study compiled data from 15 group-informants residing in 12 different villages. The information gathering process involved a combination of free-listing, semi-structured interviews, group discussion, and the walk-to-the-wood method. To analyze the data, the researchers used various methods such as use-reports, Relative Frequency of Citation (RFC), Relative Importance Index (RI), and Cluster analysis. This study identified 200 plant species used in traditional women's healthcare practices, with leaves being the most frequently used part. Drinking was the most common method for internal use, while bathing and steam were the most emphasized for external use. Blumea balsamifera and Buddleja asiatica had high RI and RFC. Cluster analysis revealed that group-informants were divided by ethnicity and geographical location. This study contributes to the understanding of traditional healthcare practices among Tibeto-Burman groups in Thailand, with a particular focus on women's wellness. The results provide insight into the ethnobotanical knowledge of these communities and highlight the important role played by women in traditional medicine. The study underscores the need for continued research in this field to preserve and utilize this valuable knowledge.


Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy.
Targeted radioimmunotherapy with yttrium-90 (90Y)-labeled ibritumomab tiuxetan (Zevalin, IDEC-Biogen, San Diego, CA) has shown significant activity in the treatment of relapsed or refractory CD20+ non-Hodgkin's lymphoma. Eligibility criteria used in phase I trials, and adopted in phase II and III trials, excluded patients with prior myeloablative therapy. We treated eight patients with 90Y ibritumomab tiuxetan who had prior autologous stem cell transplant, but met all other treatment criteria. Eight patients with CD20+ non-Hodgkin's lymphoma had extensive prior therapy including myeloablative chemotherapy but did not receive total body irradiation. Each had bone marrow cellularity of >15%, platelet count of >100,000/mm3, and one had documented lymphomatous bone marrow involvement of <25%. The standard course of 0.3 to 0.4 mCi/kg of 90Y ibritumomab tiuxetan was administered to patients at full dose. 18-Flouro-deoxyglucose positron emission tomography/computed tomography scans were done at pretreatment and approximately 12 weeks after treatment to assess patient response. Maximum toxicities were monitored and classified according to the Common Terminology Criteria for Adverse Events (ver. 3.0). Toxicities observed included grade 4 thrombocytopenia in three of eight evaluable patients and grade 4 neutropenia in one of eight evaluable patients. One patient had a neutropenic fever; all patients were off blood product support 12 weeks post-zevalin. Complete response by 18-flouro-deoxyglucose positron emission tomography/computed tomography imaging occurred in one of seven evaluable patients and one patient treated as consolidation had no evidence of disease. Our experience suggests that 90Y ibritumomab tiuxetan treatment is safe for use in patients with prior myeloablative therapy when the general inclusion criteria are fulfilled. In this small series, the response rates, however, are limited. Nevertheless, 90Y ibritumomab tiuxetan treatment may provide clinical benefit in carefully selected extensively pretreated patients.


The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models.
To evaluate the anticonvulsant profile and behavioral toxicity of rufinamide in animal seizure models compared to the established antiepileptic drugs (AEDs): phenytoin, phenobarbital, valproate, and ethosuximide, or vehicle. In acute studies of anticonvulsant efficacy, the AEDs were administered via oral (CF1 mice and Sprague-Dawley rats) and intraperitoneal (CF1 mice) routes. The AEDs were assessed for their ability to inhibit seizures induced by maximal electroshock (MES) or subcutaneous pentylenetetrazol, and ability to block seizures induced by subcutaneous strychnine, bicuculline, or picrotoxin. Tolerance of oral rufinamide was assessed in rats following 5-day (versus single-dose) treatment with oral rufinamide using the dose equivalent necessary to achieve a 50% decrease in seizure frequency (ED(50)). Metabolic tolerance was also evaluated using an in vitro liver microsomal assay. Oral rufinamide suppressed pentylenetetrazol-induced seizures in mice (ED(50) 45.8 mg/kg) but not rats, and was active against MES-induced tonic seizures in mice (ED(50) 23.9 mg/kg) and rats (ED(50) 6.1 mg/kg). Intraperitoneal rufinamide suppressed pentylenetetrazol-, bicuculline-, and picrotoxin-induced clonus in mice (ED(50) 54.0, 50.5, and 76.3 mg/kg, respectively). Rufinamide was partially effective in the mouse strychnine test. The behavioral toxicity of rufinamide was similar to or better than established AEDs tested in this study. In general, the protective index of rufinamide was greater than that of the other AEDs. The efficacy and behavioral toxicity profiles in these animal models suggest that rufinamide may be effective in the treatment of generalized and partial seizures.


Emerging targets for the treatment of scleroderma.
Scleroderma is an often-fatal autoimmune connective tissue disease. Recommendations for treating digital ulcers and pulmonary hypertension in scleroderma have recently been established by the European League Against Rheumatism. Conversely, although many valuable insights have been generated into the molecular mechanism underlying the persistent fibrotic phenotype in scleroderma, no safe, clinically proven effective treatment has been found for this aspect of the disease. Recent evidence suggests that, based on genome-wide molecular profiling, scleroderma can be loosely divided into 'fibroproliferative' and 'inflammatory' cohorts. The latter cohort contains patients with localized and 'limited' disease, as well as a small subset of those with 'diffuse' disease. Drugs targeting either B cells or ILs might be useful to treat patients who possess an 'inflammatory' gene expression signature. In the future, a 'personalized medicine' approach might be used to treat patients with scleroderma: individuals with an 'inflammatory' gene expression signature may be successfully treated with drugs specifically targeting the immune system. Indeed, drugs currently approved for other rheumatic disease might also be used to treat scleroderma patients bearing an 'inflammatory' gene expression profile.


[A study of gene amplification and expression of cyclin D1 in hepatocellular carcinoma].
To investigate gene amplification of CCND1 and expression of cyclin D1 in hepatocellular carcinoma (HCC) and to explore the possible relationship between CCND1 gene status and carcinogenesis of HCC. Differential PCR, RT-PCR and immunohistochemistry were used to detect gene amplification, mRNA and protein expression of cyclin D1 in 20 HCC cases respectively. The relationship between the gene amplification rate and the expression level of cyclin D1 and the histological grades of HCC was analyzed. CCND1 gene amplification was detected in 30% of the cases HCC. An overexpression of cyclin D1 mRNA and protein could be demonstrated in 45% and 70% cases respectively. The expression of cyclin D1 mRNA correlated with its gene amplification status (P < 0.05) and was responsible for the protein expression level (P < 0.05). There was a close relationship between the expression level of cyclin D1 protein and HCC histological grades (P < 0.05). CCND1 gene amplification is a common phenomenon in HCC and may be directly responsible for the cyclin D1 mRNA and protein overexpression. Cyclin D1 protein expression level is directly related to HCC histological grades. Therefore, CCND1 amplification and cyclin D1 overexpression may play an important role in development and differentiation of HCC.


[(1,2,5,6-η)-Cyclo-octa-1,5-diene](1-ethyl-3-isopropyl-1,3-imidazol-2-yl-idene)(tri-phenyl-phosphane)rhodium(I) tetra-fluorido-borate.
A new N-heterocyclic cationic rhodium(I) complex with a tetra-fluorido-borate counter-anion, [Rh(C8H14N2)(C8H12)(C18H15P)]BF4, has been prepared and structurally characterized. The cationic complex exhibits a distorted square-planar environment around the rhodium(I) ion. Two connections are made from rhodium(I) to the carbon atom of an N-heterocylic carbene ligand and to the phospho-rus atom of a tri-phenyl-phosphane ligand. The remaining two coordination sites are made via a bidentate inter-action from the two olefinic bonds of cyclo-octa-diene to the rhodium(I) ion. The compound includes an out-sphere tetra-fluorido-borate counter-anion. Within the crystal of the compound exist several weak inter-molecular C-H⋯F inter-actions.


Laparoscopic retrieval of a retained surgical sponge: a case report.
A retained laparotomy pad after abdominal surgery is a complication that usually requires a second laparotomy. We report a case in which a laparotomy pad and ring were removed laparoscopically 1 week postoperative.


Discovering the elusive Beauchêne: the originator of the disarticulated anatomic technique.
The identity of the Beauchêne bearing the name of the widely used disarticulated anatomic technique has remained elusive over the years. This article traces the skull technique to its originator, Edmé François Chauvot de Beauchêne (ca. 1780-1830), an anatomist and surgeon. In addition to pioneering this innovative anatomic preparation, Edmé François reported the first known case of an intraneural cyst in 1810 and pulmonary air embolism in 1818. The credit has been incorrectly attributed to Claude Beauchêne, an imaginary anatomist in Paris in the 1850s, or to his famous father, Edmé Pierre Chauvot de Beauchêne (1749-1825), a psychologist and physician. The significant accomplishments of Edmé François Chauvot de Beauchêne (Beauchêne fils or Beauchêne son) in medicine have been overshadowed by those of his distinguished father and should be fully recognized.


Laboratory diagnosis and management of COVID-19 cases: creating a safe testing environment.
COVID-19 disease has had a profound impact worldwide since it was discovered in Wuhan, China, in December 2019. Laboratory testing is crucial to prompt identification of positive cases, initiation of treatment and management strategies. However, medical scientists are vulnerable to infection due to the risk of exposure in the laboratory and the community. This study sought to determine the awareness of laboratory safety measures, assess the personal efforts of medical scientists in creating a safe laboratory environment for testing and examine the laboratory safety enabling factors. The data used for the study were generated among medical scientists in Nigeria through an internet-broadcasted questionnaire and were analyzed using IBM SPSS Statistics (version 25). The majority of the respondents had a high awareness of laboratory safety measures (60.3%) and demonstrated good personal efforts in creating a safe laboratory testing environment (63%). The level of awareness of laboratory safety measures was significantly associated with respondents' level of education (χ2 = 6.143; p = 0.046) and influences respondents' efforts in creating a safe laboratory testing environment (p = 0.007). However, just a few respondents could convincingly attest to the availability of adequate and appropriate PPE with proper utilization training (45.1%), adequate rest and other welfare packages (45.8%) as well as access to appropriate Biological Safety Cabinets (BSCs) and other essential equipment in their laboratories (48.8%). Furthermore, a significant association existed between the availability of laboratory safety enabling factors and respondents' efforts in creating a safe environment for testing with the p-value ranging between < 0.0001 and 0.003. This study revealed that despite the high awareness of safety measures and good personal efforts of the study participants in creating a safe laboratory-testing environment, there was poor availability of safety facilities, equipment, support and welfare packages required to enhance their safety. It is, therefore, crucial to provide necessary laboratory biosafety equipment and PPE in order not to compromise medical scientists' safety as they perform their duties in COVID-19 pandemic response.


Ventricular exclusion during Fontan operation: an evolving technique.
The modified Fontan operation, which consists of ventricular exclusion by obliteration of the right atrioventricular ostium, requires a technique that provides firm and permanent occlusion while preserving the atrioventricular node and bundle. Ten patients underwent such an operation. In 5 of them, closure of the right atrioventricular ostium was achieved by suturing a patch into the valve leaflets; in the other 5, the ventricle was excluded by a patch sutured into the right atrial wall above the annulus fibrosus. None of the patients who underwent this procedure experienced heart block postoperatively. However, three instances of late patch dehiscence occurred, each in the group of patients in whom the patch had been attached to the valve leaflets. We conclude that both patching techniques are safe as far as the atrioventricular node and bundle are concerned but that permanent occlusion is better obtained by implanting the patch into the atrial wall. Therefore, we prefer to use this technique.


[Study on the mechanism of erythritol effecting on Streptococcus mutans].
To evaluate the effect of erythritol on cell wall structure of Streptococcus mutans (S. mutans) and explore its potential mechanism. Enzyme activities of lactate dehydrogenase (LDH) in bacterial solution were detected under respective condition of sucrose and erythritol. A scanning electron microscope (SEM) was used to investigate the change of S. mutans' cell wall under the condition of sucrose and erythritol. Enzyme activities of LDH in erythritol culture medium were different from that in sucrose, but the difference was slight. SEM observation showed the integrity of cell wall was not destroyed and no content leaked out. It's suggested that erythritol has an antibacterial effect on S. mutans through no affecting on the normal structure of the cell wall of S. mutans.


Prognostic value of systemic immune-inflammation index/ albumin for transcatheter arterial chemoembolization treatment.
In the process of tumor occurrence, evolution and development, immune, inflammation and nutrition are principal elements. The purpose of this study was to assess the prognostic value of systemic immune-inflammation index/albumin (SII/ALB) for patients with HBV-related hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE). A total of 125 HBV-related HCC patients met inclusion criteria and were all enrolled in this research. The survminer R package. was used to calculate the best SII/ALB cutoff values. Chi-square test was used to analyze the relationship between SII/ALB and clinicopathological parameters. Kaplan-Meier curves and Cox proportional hazards models were used to investigate the effect of SII/ALB on overall survival (OS). The cutoff value of SII/ALB was 2.992. In the derivation cohort, the patients were divided into SII/ALB-low (SII/ALB≤2.992) and SII/ALB-high (SII/ALB >2.992) groups. SII/ALB-high was found in patients with tumor size ≥3 (cm), white blood cell ≥3.5 (109/L), platelet ≥100 (109/L), neutrophils ≥1.8 (109/L), PT ≥ 14(s), SII ≥100, NLR ≥1.50 and PLR ≥60, (P < 0.05). The Kaplan-Meier curves showed that elevated SII/ALB were associated with decreased OS. OS rate of SII/ALB-low and SII/ALB-high groups at 1 and 2 years were 96.6% vs. 70.3% and 87.8% vs. 48.5%, respectively (C2 = 9.804, P = 0.002). The BCLC stage, tumor number, tumor size, vascular invasion, AST, SII/ALB, SII, NLR and PNI were all significant prognostic indicators of OS. The SII/ALB (HR: 17.98; 95%CI: 1.82-177.32) and tumor size (HR: 3.26; 95%CI: 1.27-8.35) were all independent prognostic factors for OS, (p < 0.05).Conclusion: we found that SII/ALB could be an important prognostic parameter for HBV-related HCC patients after TACE treatment.


Which lives matter in reproductive biomedicine?
The most recent Black Lives Matter moment provides an important opportunity for consideration of the interlocking social and political systems that contribute to ongoing racism and racial inequality. What does this mean in the context of reproductive biomedicine? Which lives do reproductive biomedicine devalue and how? In this commentary, I address why reproductive biomedicine is an important site for reflection on race, and how the Reproductive Justice Movement calls on us to shift our thinking. I argue for the need to recognize the deep connections between reproductive biomedicine and eugenics, and then offer some examples of racialization in reproductive biomedicine through assisted reproductive technology. Finally, I consider what steps practitioners might take to be part of the change for which this Black Lives Matter moment calls.


Solidification/stabilization of flue gas desulfurization brine and coal fly ash for heavy metals and chloride immobilization: Effects of S/S conditions and zero-valent-iron pretreatment.
Effective management of flue-gas-desulfurization (FGD) wastewater and coal-combustion-residues (CCRs) are major challenges in the coal-fired power industry. The zero-liquid-discharge (ZLD) method of combining FGD brines and CCRs in solidification/stabilization (S/S) is promising due to its potential of treating both wastes in the same process. This study evaluated the performance of such a ZLD method for immobilizing heavy metals (Se, As, Cd and Cr) and chloride in FGD wastewater and/or CCRs. Effects of different coal fly ash (bituminous (BCFA) and sub-bituminous (SCFA)), activating agent (Portland cement (PC) and lime) and pretreatment of brines by zero valent iron (ZVI) on the S/S process were evaluated. Short-term and long-term leaching tests were conducted to evaluate performance of the S/S solids in pollutant retainment. The pre-treatment of FGD brine by ZVI enhanced the retainment of heavy metals when BCFA was used, but not when SCFA was used since it already performed quite well without ZVI pretreatment. Quantitative X-ray diffraction and scanning electron microscopy analyses strongly indicated the formation of Friedel's salt, Ca2Al(OH)6(Cl,OH)·2H2O, is critical in the retainment of heavy metals and chloride. SCFA contained higher lime and reactive aluminate contents than BCFA; thus, S/S solids made with SCFA contained higher amounts of Friedel's salt.


Factors influencing insulin secretion after pancreatoduodenectomy.
Preoperative patients with periampullary cancer had a higher mean sigma IRI value than that of normal controls, and also had a delayed pattern of insulin response and a lower insulinogenic index during oral-GTT. sigma IRI levels after pancreatoduodenectomy were similar to those of normal controls when the pancreatic remnants were histologically intact at the time of surgery. Postoperative sigma IRI levels could not be predicted based on the extent of histological fibrosis of the distal pancreas at the time of surgery. Patency of pancreatojejunostomy was obtained with the modified Warren's method in 39 out of 40 patients, and sigma IRI levels were maintained up to 5 years postoperatively. No significant difference was found in sigma IRI levels between pancreatoduodenectomised patients with the conventional Roux-en-Y procedure and those with the inverted Roux-en-Y with jejunal interposition. The mean insulin peak value and sigma IRI level were higher in pancreatoduodenectomised patients than in normal controls, and higher in gastrectomised patients than in pancreatoduodenectomised patients. Pancreatoduodenectomy with superior mesenteric arterial dissection resulted in remarkably low sigma IRI levels.


Bone-Targeted Bortezomib Inhibits Bortezomib-Resistant Multiple Myeloma in Mice by Providing Higher Levels of Bortezomib in Bone.
Limited treatment options exist for cancer within the bone, as demonstrated by the inevitable, pernicious course of metastatic and blood cancers. The difficulty of eliminating bone-residing cancer, especially drug-resistant cancer, necessitates novel, alternative treatments to manipulate tumor cells and their microenvironment, with minimal off-target effects. To this end, bone-targeted conjugate (BP-Btz) was generated by linking bortezomib (Btz, an anticancer, bone-stimulatory drug) to a bisphosphonate (BP, a targeting ligand) through a cleavable linker that enables spatiotemporally controlled delivery of Btz to bone under acidic conditions for treating multiple myeloma (MM). Three conjugates with different linkers were developed and screened for best efficacy in mouse model of MM. Results demonstrated that the lead candidate BP-Btz with optimal linker could overcome Btz resistance, reduced tumor burden, bone destruction, or tumor metastasis more effectively than BP or free Btz without thrombocytopenia and neurotoxicity in mice bearing myeloma. Furthermore, pharmacokinetic and pharmacodynamic studies showed that BP-Btz bound to bone matrix, released Btz in acidic conditions, and had a higher local concentration and longer half-life than Btz in bone. Our findings suggest the potential of bone-targeted Btz conjugate as an efficacious Btz-resistant MM treatment mechanism. © 2021 American Society for Bone and Mineral Research (ASBMR).


Postsurgery echocardiography can predict the amount of ischemia-reperfusion injury and the resultant scar size.
Despite advances in the diagnosis and treatment of ischemic heart disease (IHD), it remains the leading cause of death globally. Thus, there is a need to investigate the underlying pathophysiology and develop new therapies for the prevention and treatment of IHD. Murine models are widely used in IHD research because they are readily available, relatively inexpensive, and can be genetically modified to explore mechanistic questions. Ischemia-reperfusion (I/R)-induced myocardial infarction in mice is produced by the blockage followed by reperfusion of the left anterior descending branch (LAD) to imitate human IHD disease and its treatment. This I/R model can be widely used to investigate the potential reparative effect of putative treatments in the setting of reperfusion. However, the surgical technique is demanding and can produce an inconsistent amount of damage, which can make identification of treatment effects challenging. Therefore, determining which hearts have been significantly damaged by I/R is an important consideration in studies designed to either explore the mechanisms of disrupted function or test possible therapies. Noninvasive echocardiography (ECHO) is often used to determine structural and functional changes in the mouse heart following injury. In the present study, we determined that ECHO performed 3 days post I/R surgery could predict the permanent injury produced by the ischemic insult.NEW & NOTEWORTHY We believe our work is noteworthy due to its creation of standards for early evaluation of the level of myocardial injury in mouse models of ischemia-reperfusion. This improvement to study design could reduce the sample sizes used in evaluating therapeutics and lead to increased confidence in conclusions drawn regarding the therapeutic efficacy of treatments tested in these translational mouse models.


Cell sorting and morphogenesis in early Drosophila embryos.
The regionalisation of growing tissues into compartments that do not mix is thought to be a common motif of animal development. Compartments and compartmental boundaries were discovered by lineage studies in the model organism Drosophila. Since then, many compartment boundaries have been identified in developing tissues, from insects to vertebrates. These are important for animal development, because boundaries localize signalling centres that control tissue morphogenesis. Compartment boundaries are boundaries of lineage restriction, where specific mechanisms keep boundaries straight and cells segregated. Here, we review the mechanisms of cell sorting at boundaries found in early Drosophila embryos. The parasegmental boundaries, separating anterior from posterior compartments in the embryo, keep cells segregated by increasing actomyosin contractility at boundary cell-cell interfaces. Differential actomyosin contractility in turn promotes fold formation and orients cell division. Earlier in development, actomyosin differentials are also important for cell sorting during axis extension. Specific cell surface asymmetries and signalling pathways are required to initiate and maintain these actomyosin differentials.


Working life job strain status and cognitive aging in Europe: A 12-year follow-up study.
To examine the association of job strain with cognitive ability and the influence of life-course job strain on later life cognitive decline. Data were derived from six waves of the Survey of Health, Aging, and Retirement in Europe. The study sample consists of 13349 participants aged 50 to 98 years at wave 2 and has been followed up for 12-years. Job strain status across working life was assessed using a short demand-control job strain model containing two core dimensions: job demands and job control collected in wave 3. Cognitive abilities concerning episodic memory was assessed by immediate recall and delayed recall tests, executive function was evaluated by verbal fluency test collected in all waves (waves 2-7) except wave 3. Mixed-effects model was used to estimate working life job strain and its cumulative effect on cognitive decline. Both passive and high strain jobs were associated with lower levels of cognitive ability (episodic memory and verbal fluency) in comparison with active job. Long exposure to active- or low strain-job was associated with higher cognitive ability whereas long exposure to passive job or moderate duration of high strain job was associated with lower cognitive ability. The rate of memory decline was positively related to moderate duration of passive job and negatively related to long-term exposure to low strain job. Information on working conditions was based on self-reported recollections. Working life variation in job strain status and their duration may explain individual differences in cognitive ability in later life.


Mitochondrial metabolism transition cooperates with nuclear reprogramming during induced pluripotent stem cell generation.
Induced pluripotent stem cells (iPSCs) hold great clinical potential for regenerative medicine. Much work has been done to investigate the mechanisms of their generation, focusing on the cell nucleus. However, the roles of specific organelles and in particular mitochondria in the potential mechanisms of nuclear reprogramming remain unclear. In this study, we sought to determine the role of mitochondrial metabolism transition in nuclear reprogramming. We found that the mitochondrial cristae had remodeled in iPSCs. The efficiency of iPSC generation was significantly reduced by down-regulation of mitochondrial inner membrane protein (IMMT), which regulates the morphology of mitochondrial cristae. Moreover, cells with the oxidative phosphorylation (OXPHOS) advantage had higher reprogramming efficiency than normal cells and the glycolysis intermediate lactic acid enhanced the efficiency of iPSCs generation. Our results show that the remodeling of mitochondrial cristae couples with the generation of iPSCs, suggesting mitochondrial metabolism transition plays an important role in nuclear reprogramming.


Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response.
Through the use of a chronic microdrive recording system, neuronal unit activity was recorded throughout the brainstem of the rabbit during performance of the classically conditioned nictitating membrane (NM) extension/eyeblink response using an acoustical conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS). Regions which exhibited neuronal responses near the onset of the learned response were found to be relatively localized to: the abducens, accessory abducens, and facial nuclei (the motoneurons known to innervate the muscles responsible for expression of the conditioned response); the sensory nuclei of the fifth (probably representing somatosensory or proprioceptive feedback from the conditioned response); the superior colliculus; the periaqueductal gray; various reticular regions and the brainstem nuclei directly connected with the cerebellum (pontine nuclei, tegmental reticular nucleus (Bechterew), red nucleus, and perhaps the inferior olive). Stimulus (tone-airpuff) evoked responses were found within all classical auditory nuclei of the brainstem; the superior colliculus; the periaqueductal gray; pontine nuclei; fifth sensory nuclei, and various reticular regions. Recent lesion studies have shown the ipsilateral cerebellum to be essential for the learning and retention of this response. Collectively these results indicate that the cerebellum and its related brainstem nuclei are critically involved in the control and production of the classically conditioned NM/eyeblink response and may contain essential long term neuronal changes--the 'memory trace'--which serves to encode this learned response.


[Perioperative Ketoacidosis under SGLT2-Inhibitors].
Sodium-glucose cotransporter-2-inhibitors are relatively new substances for treating patients with diabetes mellitus. Not least because of their rare, but severe side effects - especially euglycemic ketoacidosis - anaesthesiologists and physicians in intensive care should know about the pharmacologic properties and risk profile of sodium-glucose cotransporter-inhibitors. The present case report demonstrates typical laboratory findings of severe euglycemic ketoacidosis in a patient with only unspecific symptoms under therapy with gliflozins in the perioperative period. It describes the diagnostic and therapeutic steps and emphasizes the importance of withholding the substances under catabolic conditions. Especially in the perioperative setting it is highly relevant to consider euglycemic ketoacidosis as a differential diagnosis in the presence of a metabolic acidotic state, because a delayed diagnosis and treatment could be life-threatening for the affected person.


Increased mitochondrial oxidative damage in patients with sporadic amyotrophic lateral sclerosis.
To investigate whether mitochondrial oxidative damage contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis (sALS), we used high-performance liquid chromatography with an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q10 (CoQ10) in the cerebrospinal fluid (CSF) of 30 patients with sALS and 17 age-matched controls with no neurological diseases. The percentage of oxidized CoQ10 in the CSF of sALS patients were significantly greater than those in the CSF of controls (P<0.002) and were negatively correlated with duration of illness (rho=-0.64, P<0.001). These results suggest that mitochondrial oxidative damage contributes to the pathogenesis of sporadic amyotrophic lateral sclerosis.


Effect modification of aortic atheroma on the prognostic value of heart rate in hypertension.
Although some epidemiological studies have advocated a prognostic value of heart rate (HR) in hypertensive patients, the influence of vascular damages on this prognostic value has not been tested yet. HRs were collected by pulse palpation in 1204 primary hypertensive patients in sinus rhythm without cardiac-slowing drugs. Aortic damages were assessed by aortography, whereas cardiac disease was assessed by medical history, symptoms and electrocardiogram. In a multivariable Cox model adjusted for major confounders, HR was of prognostic significance for all-cause [hazard ratio 1.12 (1.06-1.19) for 10 bpm increment and 1.39 (1.18-1.64) for HR ≥82 vs. <82 bpm] and cardiovascular death [hazard ratio 1.10 (1.02-1.20) for 10 bpm increment and 1.37 (1.09-1.72) for HR ≥82 vs. <82 bpm] after 35 years of follow-up. This association was particularly manifested at 15 years of follow-up. At that time, with the same multivariable survival model, the association between HR and cardiovascular death was stronger in patients with aortic atheroma [2.76 (1.47-5.18) for an HR ≥82 vs. <82 bpm] than in patients without [hazard ratio 1.36 (0.76-2.43) for an HR ≥82 vs. <82 bpm, P for interaction = 0.054]. Similarly, the association between HR and cardiovascular death was stronger in patients with an overt cardiac disease than those without (P for interaction = 0.044). In hypertensive patients, the prognostic significance of HR for cardiovascular outcome is modulated by the presence of aortic atherosclerosis or cardiac disease. This should prompt us to a thorough examination of cardiovascular damages in hypertensive patients when HR is elevated.


Effect of two sedative protocols and hepatosplenic disease on Doppler indices of splenic arteries in dogs: a preliminary study.
Doppler flow indices (DFIs), such as the resistive index (RI) and the pulsatility index (PI), are commonly used to characterize blood flow. Parenchymal infiltration of an organ and administration of sedative and anaesthetic drugs can affect DFIs by altering resistance to blood flow. In this prospective study, the effect on DFIs of two sedative protocols (acepromazine or dexmedetomidine, each combined with butorphanol) and the presence or absence of hepatic and/or splenic disease, was investigated in the splenic arteries of 75 dogs. The RI and PI in splenic arteries of dogs sedated with dexmedetomidine and butorphanol were lower than those of dogs sedated with acepromazine and butorphanol. PI in splenic arteries was higher in animals with hepatosplenic disease than in healthy animals. Receiver Operating Characteristic (ROC) curves suggested that PI measured in canine splenic arteries could be useful in predicting the presence of hepatosplenic disease in the absence of other abdominal disease.


Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart.
Extraneuronal accumulation of isoproterenol in atria and ventricle of perfused rat heart was investigated. Rat hearts were perfused with various concentrations of 3H-isoproterenol for 30 min in the absence and the presence of catechol-O-methyltransferase (COMT) inhibitor (tropolone). When COMT was intact, the accumulation of 3H-isoproterenol in both atria and ventricle after perfusion with low concentration of 3H-isoproterenol (0.01 to 1 mumol/l) was less than that of perfusing concentration; the tissue/medium ratio (T/M) of isoproterenol for artia was lower than that for ventricle. The T/M of isoproterenol after perfusion with 10 and 20 mumol/l of 3H-isoproterenol were 0.94 and 1.76 for atria and 3.25 and 2.95 for ventricle, respectively. When COMT was inhibited by tropolone, the T/M increased 6.3-9.0 folds for atria and 5.1-6.7 folds for ventricle after perfusion with 3H-isoproterenol (0.01 to 1 mumol/l). From these results, it was concluded that both atria and ventricle of the rat heart have an extraneuronal O-methylating system as reported in rat whole heart, and was suggested that there might be different capacities of extraneuronal uptake and COMT between them.


Structure and polymorphism of the Chironomus thummi gene encoding special lobe-specific silk protein, ssp160.
cDNA encoding Chironomus thummi ssp160 was used to isolate a genomic clone that hybridized in situ to band A2b on polytene chromosome IV, the site of the ssp160 gene. DNA sequencing, primer extension and gene/cDNA nucleotide sequence alignment revealed the gene contains six exons and five introns; 70% of ssp160 is encoded in exon 3. Variations between cDNA and gene sequences led to the design of a polymerase chain reaction, restriction fragment length polymorphism assay that was subsequently used to demonstrate the existence of polymorphic alleles whose distribution varied between geographically separated populations of larvae. The polymorphism is associated with codon deletions in a six-amino-acid repeat containing an N-linked glycosylation motif. These deletions may have resulted from slipped-strand mispairing during DNA replication.


Production and processing of aptamer microarrays.
Aptamers are nucleic acid species that are selected in vitro for their specific binding properties. We describe methods for the production and processing of aptamer microarrays, including detailed procedures for the high-throughput, enzymatic synthesis of 5' RNA biotinylated aptamers and for arraying them onto streptavidin-coated glass slides. Also presented are methods for processing the aptamer microarrays, including blocking, washing, drying, and scanning. Examples are shown for the specific capture of fluorescently labeled target proteins either alone in binding buffer or in competition with labeled intracellular proteins from cell lysates. Consideration is given to the challenges involved in producing multiplex aptamer chips composed of aptamers taken from disparate literature sources, and to the development of standardized methods for characterizing the performance of capture reagents used in biosensors.


Calcineurin enhances L-type Ca(2+) channel activity in hippocampal neurons: increased effect with age in culture.
The Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, modulates a number of key Ca(2+) signaling pathways in neurons, and has been implicated in Ca(2+)-dependent negative feedback inactivation of N-methyl-D-aspartate receptors and voltage-sensitive Ca(2+) channels. In contrast, we report here that three mechanistically disparate calcineurin inhibitors, FK-506, cyclosporin A, and the calcineurin autoinhibitory peptide, inhibited high-voltage-activated Ca(2+) channel currents by up to 40% in cultured hippocampal neurons, suggesting that calcineurin acts to enhance Ca(2+) currents. This effect occurred with Ba(2+) or Ca(2+) as charge carrier, and with or without intracellular Ca(2+) buffered by EGTA. Ca(2+)-dependent inactivation of Ca(2+) channels was not affected by FK-506. The immunosuppressant, rapamycin, and the protein phosphatase 1/2A inhibitor, okadaic acid, did not decrease Ca(2+) channel current, showing specificity for effects on calcineurin. Blockade of L-type Ca(2+) channels with nimodipine fully negated the effect of FK-506 on Ca(2+) channel current, while blockade of N-, and P-/Q-type Ca(2+) channels enhanced FK-506-mediated inhibition of the remaining L-type-enriched current. FK-506 also inhibited substantially more Ca(2+) channel current in 4-week-old vs. 2-week-old cultures, an effect paralleled by an increase in calcineurin A mRNA levels. These studies provide the first evidence that calcineurin selectively enhances L-type Ca(2+) channel activity in neurons. Moreover, this action appears to be increased concomitantly with the well-characterized increase in L-type Ca(2+) channel availability in hippocampal neurons with age-in-culture.


Relationship between turnover intention and workplace personal relations among care workers employed by elder care facilities.
This study focuses on care workers at elder care facilities to examine what factors (including workplace personal relations) influence turnover intention and to what extent. Based on this analysis, the study discusses the content of workplace personal relations problems in qualitative terms. The study targeted care workers at elder care facilities. There were 406 participants with no missing data who were analyzed. The survey period ranged from September to November 2021. Questions consisted of basic attributes, turnover intention, problems with workplace personal relations, content of personal relation problems, and psychological distress. Female care workers were 2.25 times more likely than male care workers to have turnover intention. Care workers with workplace personal relation problems were 1.97 times more likely than those without these problems to have high turnover intention. Moreover, with regard to psychological distress, the ratio increased to 4.99 times. The following six categories were extracted from the text data on workplace personal relation problems: insufficient communication, bullying, sense of unfair workload, different attitudes to care work, difficulty in guidance for subordinates/new staff, and labelling. Gender, workplace personal relation problems, and psychological distress have shown to affect care workers' turnover intentions. To prevent care worker turnover, future studies should focus on the development and impact of strategies to improve workplace personal relations specific to care workers, targeting the six factors identified in this study.


Altered NAD(P)H production in neonatal rat islets resistant to H2O2.
We determined the involvement of NAD(P)H generation ability on the resistance of pancreatic islets B-cells to oxidative stress caused by culture exposition to H2O2. We cultured isolated neonatal Wistar rat islets for four days in medium containing 5.6 or 20 mM glucose, with or without H2O2 (200 microM), and analyzed several parameters associated with islet survival in different media. High glucose was used since it protects neonatal islets against the loss of GSIS. While none of the culture conditions increased the rate of NAD(P)H content at 16.7 mM glucose, the islets resistant to H2O2 and those exposed to 20 mM glucose showed a greater use of the pentose phosphate pathway and increased ATP synthesis from glucose. Oxidative stress contributes to the loss of glucose-induced insulin secretion (GSIS) during the onset of diabetes mellitus. Although immature rat islets have reduced GSIS compared to mature islets, they adapt better to oxidative stress and are a good model for understanding the causes involved in the destruction or survival of islet cells. These data support the idea that GSIS and resistance against oxidative stress in immature islets rely on NADH shuttle activities, with little contribution of reduced equivalents from the tricarboxylic acid cycle (TCAC).


Transport of a new erectogenic udenafil in Caco-2 cells.
P-glycoprotein, an ATP-dependent efflux pump, is a membrane transporter that influences the absorption and excretion of drugs. There is a striking overlap between the substrates for CYP3A4 and P-glycoprotein. This study was designed to assess whether udenafil, a substrate of CYP3A4, is also a P-glycoprotein substrate. Udenafil stimulated P-glycoprotein ATPase activity, a putative measure of P-glycoprotein affinity, although with lower affinity than a proven substrate, verapamil. Bidirectional transport studies of udenafil using Caco-2 cell monolayers showed that its efflux (15.9-22.8 x 10(-6) cm/s) was significantly higher than its influx (3.7-9.1 x 10(-6) cm/s). P-glycoprotein inhibitors such as cyclosporine, tariquidar and verapamil significantly increased the influx of udenafil and decreased the efflux of udenafil. These results indicate that udenafil is a substrate for P-glycoprotein. The low bioavailability, variable absorption and drug-drug interactions of udenafil may be related to the variability of CYP3A4 and P-glycoprotein expression and to possible CYP3A4 and P-glycoprotein interactions.


Nonlinear transport through a nanoscale molecule.
A simple model of electrical transport through a metal-aromatic molecule-metal system that includes charging effects as well as aspects of the electronic structure of the molecule, is presented. The interplay of a large charging energy and an asymmetry of the metal-molecule coupling can lead to various effects in nonlinear electrical transport. In particular, strong negative differential conductance is observed under certain conditions.


Comparing Early Outcomes using Non Absorbable Polypropylene Mesh and Partially Absorbable Composite Mesh through Laparoscopic Transabdominal Preperitoneal Repair of Inguinal Hernia.
Laparoscopic hernia repair is in vogue in the present era. Both the operating surgeon and the patient are concerned about the postoperative inguinodynia which has now replaced recurrence as the predominant factor affecting quality of life. Our study aimed to compare early postoperative outcomes with the standard non absorbablepolypropylene and the newer partially absorbable composite meshes. A total of 60 patients with unilateral uncomplicated inguinal hernia were included in the study and randomly divided into two groups, one each for one kind of mesh. Patients underwent Transabdominal Preperitoneal (TAPP) repair of hernia after taking written informed consent. Follow up was done in the immediate postoperative period and at three months. Patients were compared for inguinodynia, sensation of heaviness, seroma/haematoma formation and return to work activities. Standard statistical tests were applied and a p-value <0.05 was taken as significant. Patients in the composite group complain of significantly less pain as compared to those with the non absorbable mesh at three months (p-value 0.003). They also report less sensation of heaviness over the groin area. However, incidence of seroma formation was higher in the composite group (20%) when compared to the non absorbable group (6.67%). An earlier return to work was seen in the patients with composite mesh. Use of composite mesh in TAPP is associated with better patient outcomes in terms of less postoperative pain and an earlier return to work.


Arthroscopic acetabular labrum reconstruction with capsular autograft: clinical outcome and preliminary results.
To introduce a novel technique to reconstruct the acetabular labrum using capsular autograft, and to evaluate the preliminary clinical outcome, a retrospective review of a prospectively collected registry was undertaken that identified 21 patients (21 hips) who underwent arthroscopic reconstruction of the labrum by capsular autograft from January 2016 to January 2018. Modified Harris Hip Score (mHHS), Hip Outcome Score (HOS), and Hip Outcome Score-Activities of Daily Living (HOS-ADL) were recorded preoperatively and postoperatively. Clinical outcome was analyzed to evaluate the effectiveness of this technique. Twenty-one patients, with an average follow-up time of 25.4 ± 1.6 months, were included in this study: 7 patients were diagnosed with hypoplastic labrum (width <5 mm), 9 patients with complex tear of labrum, and 5 patients with degenerative labrum. The mHHS (61.3 ± 5.5 vs. 87.5 ± 4.2, P<0.001), HOS (52.5 ± 5.1 vs. 87.3 ± 3.8, P<0.001) and HOS-ADL (48.5 ± 5.8% vs. 75.2 ± 3.5%, P<0.001) between preoperative and the 6-month follow-up were significantly different. Gender exerts no influence on the outcome of mHHS, HOS and HOS-ADL. Therefore, local capsular autograft is readily available during arthroscopy with no donor-site morbidity. The reconstruction of the hip labrum may be valuable for patients with hypoplastic or dysplastic labrum, complex tear of labrum and severe degeneration. With appropriate patient selection, this technique is promising in preliminary clinical outcome.


Successful cadaver kidney transplantation in patients highly sensitized by blood transfusions. Unimportance of the most reactive serum in the pretransplant crossmatch.
Six patients who underwent a prospective blood transfusion protocol developed antibodies reactive with 41-95% of a lymphocyte panel. These antibodies disappeared 9-18 months later, and all six patients were successfully transplanted with cadaver kidneys in spite of positive crossmatches with donor T and B cells using their most reactive noncurrent sera. Crossmatches with their current sera were negative. No patient underwent plasmapheresis, blood transfusions, or immunosuppression between the time of maximum panel reactivity and transplantation. Graft survival was 100% after a mean of 22.3 months, and the mean serum creatinine level was 2.1 mg/dl one year after grafting. A positive anti-donor T or warm B cell crossmatch with the most reactive serum may be disregarded if the most recent serum is crossmatch-negative with a cadaver kidney transplant donor.


Mutation spectrum of chinese amyotrophic lateral sclerosis patients with frontotemporal dementia.
Studies have reported that a noncoding hexanucleotide repeat in C9ORF72, is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) among Caucasian population, nevertheless it is rare in Chinese population. Therefore, we aimed to investigate the mutation spectrum of Chinese ALS patients with FTD (ALS-FTD). ALS patients with and without cognitive impairments were enrolled. Clinical features were collected including age, sex, disease duration, ALSFRS-r, family history and cognitive evaluation. Thirty-six ALS genes were screened by whole exome sequencing (WES) and repeat-primed polymerase chain reaction (PCR) were used for detection of and abnormal repeat expansions of C9ORF72. A total of 1208 patients, including 66 familial ALS (FALS) and 1142 sporadic ALS (SALS) patients were included. Twenty-three patients with sporadic ALS and one familial ALS index had concomitant FTD, which accounts for 1.99% (24/1208) of patients with ALS. In sporadic ALS-FTD, one case harboring C9ORF72 expansion variant, two cases harboring ANXA11 variants and one individual carrying CCNF variant were identified. A recurrent UBQLN2 variant was detected in a familial ALS-FTD patient. All of the ALS-FTD patients carrying variants in known causative genes manifested motor symptom onset (two bulbar onset and three limb onset) and developed cognitive impairment thereafter. It is not easy to draw a conclusion of the genotype-phenotype association in ALS-FTD with certain variants, limited by the small number of patients. Our findings provide an overview of spectrum of genetic variants in Chinese ALS-FTD patients. Variants of uncertain significance in UBQLN2, ANXA11 and CCNF were identified and further studies are required for causal relations of these variants with ALS-FTD.


Monoamine oxidase a polymorphism in Brazilian patients: risk factor for late-onset Alzheimer's disease?
Different studies have attempted to find polymorphisms involved in the serotonergic pathway that could be involved in mood disorders and late-onset Alzheimer's disease (LOAD) symptoms. Here, we compared the frequency of two polymorphisms: monoamine oxidase A (MAOA) and serotonin transporter in LOAD patients versus controls. No evidence of association was observed when these polymorphisms were compared separately; however, the combination of the MAOA allele 1+the short allele of 5-HTTLPR+ApoE-epsilon4 was significantly more frequent in patients than in controls. It reinforces the hypothesis that different genes acting together might play a role in AD susceptibility. Based on these data, we suggest replicating these studies in larger samples of LOAD patients belonging to different ethnic groups.


Paroxysmal sympathetic storm.
Paroxysmal sympathetic storm (PSS) is a rare syndrome characterized by episodic hypertension, hyperhydrosis, hyperthermia, tachycardia, tachypnea, and extensor posturing. This article describes two cases of PSS: one following traumatic brain injury and the other following cardiac arrest. The first responded to labetalol, morphine, and codeine, whereas the second responded to labetalol. These observations underscore the importance of central opioid receptors and nonselective beta-adrenergic antagonists in modulating catecholamine pathways.


Community structure of metazoan parasites from Pimelodus blochii in two rivers of the Western Brazilian Amazon: same seasonal traits, but different anthropogenic impacts.
The present investigation evaluated the influence of seasonality and locality on the structure of the parasite community of the catfish Pimelodus blochii. A total of 160 fish were collected from two rivers in the State of Acre, western Brazilian Amazon: 80 fish in River Acre and 80 in River Iaco, with 40 in each season (rainy and drought). The overall prevalence was 78.7% and 1461 parasite specimens (adults and larvae) were allocated in 22 taxa: 5 of Monogenea, 10 of Nematoda, 3 of Digenea, 1 of Cestoda and 3 of Crustacea. In drought season, Procamallanus (Spirocamallanus) pimelodus and Demidospermus peruvianus were more prevalent in River Acre and Iaco, respectively. The parasite diversity (Brillouin index) as well as the prevalence and abundance of the monogeneans D. peruvianus, D. striatus, Demidospermus sp. and Ameloblastella sp. were higher in River Acre. The parasite community structure were dissimilar among rivers, and seasonally in River Iaco. These results suggest that environmental traits may overshadow seasonal influences on the parasite community structure, which may be related to the higher anthropization in River Acre. Furthermore, seasonality exerted less influence on the parasite community than expected, probably because the two rivers have different hydrological traits than those of other rivers in the Brazilian Amazon. New host and locality records expanded our knowledge of parasite biodiversity of P. blochii.


Goal selection and feedback for solving math word problems.
Solving Math Word Problems (MWPs) automatically is a challenging task for AI-tutoring in online education. Most of the existing State-Of-The-Art (SOTA) neural models for solving MWPs use Goal-driven Tree-structured Solver (GTS) as their decoders. However, owing to the defects of the tree-structured recurrent neural networks, GTS can not obtain the information of all generated nodes in each decoding time step. Therefore, the performance for long math expressions is not satisfactory enough. To address such limitations, we propose a Goal Selection and Feedback (GSF) decoding module. In each time step of GSF, we firstly feed the latest result back to all goal vectors through goal feedback operation, and then the goal selection operation based on attention mechanism is designed for generate the new goal vector. Not only can the decoder collect the historical information from all generated nodes through goal selection operation, but also these generated nodes are always updated timely by goal feedback operation. In addition, a Multilayer Fusion Network (MFN) is proposed to provide a better representation of each hidden state during decoding. Combining the ELECTRA language model with our novel decoder, experiments on the Math23k, Ape-clean, and MAWPS datasets show that our model outperforms the SOTA baselines, especially on the MWPs of complex samples with long math expressions. The ablation study and case study further verify that our model can better solve the samples with long expressions, and the proposed components are indeed able to help enhance the performance of the model.


Radioprotectant Activity of Dicopper(II) Tetrakis(3,5- Diisopropylsalicylate) and Manganese(II) bis(3,5- Diisopropylsalicylate) Alone and in Combination.
Dicopper(ll) tetrakis(3,5-diisopropylsalicylate), (Cu(II)(2)(3,5-DIPS)(4), manganese(II) bis(3,5-diisopropylsalicylate), Mn(II)3,5-DIPS)(2) or combinations of them were used to treat gamma-irradIated mice in examining the possibility that combination treatments might be more effective in increasing survival than treatment with either complex alone. Doses of 0, 10, 20, or 40 mumol of each complex per kilogram of body mass were administered subcutaneously in a factorial design before 9 Gy gamna irradiation, an LD(90) dose of irradiation. Doses of 0, 10, 20, or 40 mumol Cu(II)(2)(3, 5-DIPS)(4) per kg of body mass produced 12, 28, 28, or 36 % survival, respectively, while doses of 0, 10, 20, or 40 mumol (II)(3), 5-DIPS)(2) per kg of body mass prduced 12, 36, 20, or 24 % survival, respectively. However, the combination of 20 mumol Cu(II)(2)(3, 5-DIPS)(4) and 10 mumol Mn(II)(3, 5-DIPS)(2) produced the greatest survival, 48 %, which was 300 % greater than vehicle-treated mice (P=0.01). It is concluded that specific combination treatments can be used to maximize survival of lethally irradiated mice.


Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin.
Plasmepsin (Plm) is a potential target for new antimalarial drugs, but most reported Plm inhibitors have relatively low antimalarial activities. We synthesized a series of dipeptide-type HIV protease inhibitors, which contain an allophenylnorstatine-dimethylthioproline scaffold to exhibit potent inhibitory activities against Plm II. Their activities against Plasmodium falciparum in the infected erythrocyte assay were largely different from those against the target enzyme. To improve the antimalarial activity of peptidomimetic Plm inhibitors, we attached substituents on a structure of the highly potent Plm inhibitor KNI-10006. Among the derivatives, we identified alkylamino compounds such as 44 (KNI-10283) and 47 (KNI-10538) with more than 15-fold enhanced antimalarial activity, to the sub-micromolar level, maintaining their potent Plm II inhibitory activity and low cytotoxicity. These results suggest that auxiliary substituents on a specific basic group contribute to deliver the inhibitors to the target Plm.


Imagery and visual working memory: one and the same?
Although visual imagery and visual working memory are both defined by the ability to actively represent and manipulate visual information, it is not known whether they rely on common mechanisms. A recent study by Albers and colleagues directly investigates this issue, finding evidence of common internal representations in early visual areas.


Revision of the genus Melanagromyza in California, with descriptions of three new species (Diptera: Agromyzidae).
The 27 Californian species of the genus Melanagromyza Hendel (Diptera: Agromyzidae) are reviewed, including descriptions of three new species (Melanagromyza californiana sp. nov., M. chemsaki sp. nov. and M. gonzalesina sp. nov.) and the first record for one species (Melanagromyza martini Spencer) for California and the USA. All species in California are described or redescribed, with illustrations and photographs, and a key to the species is presented. Maps for the species in California, along with host distributions, are provided, with comments on biology and host plants.


Soma size comparison of the trigeminal ganglion cells giving rise to the ascending and descending tracts: a horseradish peroxidase study in the cat.
Soma size was compared between the trigeminal ganglion cells projecting to the main sensory trigeminal nucleus (Vs) and those projecting to the nucleus caudalis (Vc) of the spinal trigeminal nucleus in the cat after injection of horseradish peroxidase (HRP) into each nucleus. The results showed that the cells projecting to the Vc (Vc cells) contained by far a greater percentage of small cells than do those projecting to the Vs (Vs cells). In the Vc case, about one-half the total number of measured labeled cells were the smallest with a diameter less than 36 microns, whereas in the Vs cases, only a small proportion of the total number of measured labeled cells were that small. In addition, the results also made it clear that the Vs cells in the ophthalmic and maxillary divisions contained a higher percentage of larger cells than those in the mandibular division.


A systematic review of predictive models for asthma development in children.
Asthma is the most common pediatric chronic disease affecting 9.6 % of American children. Delay in asthma diagnosis is prevalent, resulting in suboptimal asthma management. To help avoid delay in asthma diagnosis and advance asthma prevention research, researchers have proposed various models to predict asthma development in children. This paper reviews these models. A systematic review was conducted through searching in PubMed, EMBASE, CINAHL, Scopus, the Cochrane Library, the ACM Digital Library, IEEE Xplore, and OpenGrey up to June 3, 2015. The literature on predictive models for asthma development in children was retrieved, with search results limited to human subjects and children (birth to 18 years). Two independent reviewers screened the literature, performed data extraction, and assessed article quality. The literature search returned 13,101 references in total. After manual review, 32 of these references were determined to be relevant and are discussed in the paper. We identify several limitations of existing predictive models for asthma development in children, and provide preliminary thoughts on how to address these limitations. Existing predictive models for asthma development in children have inadequate accuracy. Efforts to improve these models' performance are needed, but are limited by a lack of a gold standard for asthma development in children.


Evolving strategies and application of proteins and peptide therapeutics in cancer treatment.
Several proteins and peptides have therapeutic potential and can be used for cancer therapy. By binding to cell surface receptors and other indicators uniquely linked with or overexpressed on tumors compared to healthy tissue, protein biologics enhance the active targeting of cancer cells, as opposed to the passive targeting of cells by conventional small-molecule chemotherapeutics. This study focuses on peptide medications that exist to slow or stop tumor growth and the spread of cancer, demonstrating the therapeutic potential of peptides in cancer treatment. As an alternative to standard chemotherapy, peptides that selectively kill cancer cells while sparing healthy tissue are developing. A mountain of clinical evidence supports the efficacy of peptide-based cancer vaccines. Since a single treatment technique may not be sufficient to produce favourable results in the fight against cancer, combination therapy is emerging as an effective option to generate synergistic benefits. One example of this new area is the use of anticancer peptides in combination with nonpeptidic cytotoxic drugs or the combination of immunotherapy with conventional therapies like radiation and chemotherapy. This review focuses on the different natural and synthetic peptides obtained and researched. Discoveries, manufacture, and modifications of peptide drugs, as well as their contemporary applications, are summarized in this review. We also discuss the benefits and difficulties of potential advances in therapeutic peptides.


Clinical significance of circulating tumor cells in peripheral blood from patients with gastric cancer.
The authors hypothesized that circulating tumor cells (CTCs) in patients with gastric cancer are associated with prognosis and disease recurrence. In this study, they evaluated CTCs in gastric cancer and clarified the clinical impact of CTCs. In total, 265 consecutive patients with gastric cancer were enrolled. Fourteen patients were excluded from the analysis, including 12 patients who another cancer and 2 patients who refused the treatment. The remaining 251 patients were divided into 2 groups: 148 patients who underwent gastrectomy (the resection group) and 103 patients who did not undergo gastrectomy (the nonresectable group). Peripheral blood samples were collected before gastrectomy or chemotherapy. A proprietary test for capturing, identifying, and counting CTCs in blood was used for the isolation and enumeration of CTCs. CTCs were detected in 16 patients (10.8%) from the resection group and in 62 patients (60.2%) from the nonresectable group. The overall survival rate for the entire cohort was significantly lower in patients with CTCs than in those without CTCs (P < .0001). In the resection group, relapse-free and overall survival in patients with CTCs was significantly lower than in patients without CTCs (P < .0001). It was noteworthy that the expression of CTCs was an independent factor for determining the overall survival of patients with gastric cancer in multivariate analysis (P = .024). In the nonresectable group, the overall survival rate was significantly lower in patients with CTCs than in those without CTCs (P = .0044). The evaluation of CTCs in peripheral blood may be a useful tool for predicting tumor progression, prognosis, and the effect of chemotherapy in patients with gastric cancer.


Prevalence of human papillomavirus type-18 in head and neck cancer among the Chinese population: A PRISMA-compliant meta-analysis.
China has a high burden of head and neck cancer globally and oncogenic human papillomavirus (HPV) has been hypothesized as a risk factor for head and neck cancer, but research was absent for establishing HPV prevalence in China. We aimed to conduct a meta-analysis to estimate the high-risk HPV-18 prevalence of head and neck cancer in the Chinese population. This meta-analysis was reported following the guideline of PRISMA. The reports on HPV and head and neck cancer in a Chinese population published between Jan 1, 2006 and May 31, 2018 were retrieved via CNKI/WANFANG/MEDLINE/EMBASE/COCHRANE databases. A random-effect model was used to calculate pooled prevalence and corresponding 95% confidence intervals. A total of 1881 head and neck cancer cases from 19 studies were included in this meta-analysis. Overall, the pooled HPV-18 prevalence among head and neck cancer cases was 6.0% (4.1%-7.9%) in China, 31.2% (13.0%-49.4%) in laryngeal cancer, 7.2% (3.9%-10.5%) in oral cancer and 0.6% (0.0%-1.3%) in oropharyngeal cancer, 18.7% (6.2%-31.2%) in fresh or frozen biopsies and 4.3% (2.5%-6.1%) in paraffin-embedded fixed biopsies, 29.5% (15.6%-43.3%) by E6/E7 region and 3.9% (0.5%-7.4%) by L1 region of HPV gene. The highest HPV-18 prevalence was found in Central China. High prevalence of HPV-18 was found in the samples of Chinese head and neck cancers. Prophylactic HPV-vaccination may reduce the burden of HPV-related head and neck cancer in China.


Nonlinear sequence-dependent structure of nigral dopamine neuron interspike interval firing patterns.
Firing patterns of 15 dopamine neurons in the rat substantia nigra were studied. These cells alternated between two firing modes, single-spike and bursting, which interwove to produce irregular, aperiodic interspike interval (ISI) patterns. When examined by linear autocorrelation analysis, these patterns appeared to reflect a primarily stochastic or random process. However, dynamical analysis revealed that the sequential behavior of a majority of these cells expressed "higher-dimensional" nonlinear deterministic structure. Dimensionality refers to the number of degrees of freedom or complexity of a time series. Bursting was statistically associated with some aspects of nonlinear ISI sequence dependence. Controlling for the effects of nonstationarity substantially increased overall predictability of ISI sequences. We hypothesize that the nonlinear deterministic structure of ISI firing patterns reflects the neuron's response to coordinated synaptic inputs emerging from neural circuit interactions.


High potassium concentration improves the rate of acrosome reaction in human spermatozoa.
Progressively motile spermatozoa recovered by swim-up method from semen of two fertile men were incubated for 24 hours in culture media containing either 4.7, 15, or 25 mM of potassium (K). Aliquots of each culture condition were obtained at 0, 1, 5, 10, and 24 hours of incubation for the assessment of progressive motility, percentage of dead spermatozoa, and percentage of acrosome reaction (AR), as measured by triple-stain technique. A total of ten experiments including each K concentration were analyzed. The results of this study showed no effect of K concentration on the percentage of progressively motile spermatozoa, irrespective of the time of incubation. The percentage of live spermatozoa was significantly greater in culture medium containing 25 mM K (P less than 0.05). There was a greater percentage of reacted spermatozoa with 25 mM K, as compared with 4.7 and 15 mM (P less than 0.05). Furthermore, the time taken to achieve 20% of AR was 2 hours at 25 mM K compared with 10.9 hours at 4.7 mM K.


Collateral ligaments of the distal sesamoid bone in the digit of Equus: re-evaluating midstance function.
The distal forelimb of the horse has a complex array of ligaments that play a critical role in determining function of the digit and are often associated with the initiation of foot pathologies. The collateral ligaments of the distal sesamoid bone (CLDS) play an important role in digit stabilization near the end of foot contact and there is also limited evidence to suggest that the CLDS stabilize the proximal interphalangeal joint (PIPJ) during weight bearing. By virtue of their anatomical attachments where the ligaments pass dorsal to the axis of rotation of the PIPJ, it is reasonable to assume that the CLDS prevent flexion of the PIPJ during weight bearing or midstance in a moving horse. To test this functional hypothesis, forelimb specimens from three mixed-breed horses were loaded in compression in a materials testing frame. Limb loading was applied with the CLDS intact and following transection. Average PIPJ angle and metacarpophalangeal joint (MCPJ) angle at maximum load (approximately 3000 N) were calculated from angular changes of proximal and middle phalanges and the third metacarpal, which were compared between intact and transected trials. PIPJ angles were found to be the same (175 degrees) at maximum load for intact and transected trials. The proximal and middle phalanges rotated together remaining aligned, regardless of the CLDS condition. Contrary to expectation, however, the combined proximal and middle phalanges unit rotates less relative to the third metacarpal under load after transection, indicating less digit extension at the metacarpophalangeal (fetlock) joint without the influence of CLDS. Since the mechanical properties of the fetlock joint are unchanged by CLDS transection, observed proximal and middle phalanx motion is dependent on increased rotation of the distal phalanx after transection. The original hypothesis was not supported and the results suggest that at midstance the CLDS function primarily to stabilize the articulation of the middle phalanx about the distal phalanx to limit distal interphalangeal joint extension during weight bearing. Establishing the functional role of the CLDS may help to better understand the biomechanical consequences of ligament injuries and diseases of the pastern.


Selenium reference ranges in New Zealand cattle.
To compare serum selenium and liver selenium concentrations with whole blood concentrations in samples taken at the same time from unsupplemented cattle, and to use these comparisons to establish a reference range for use in diagnosing selenium deficiency. Selenium was measured in concurrent whole blood, serum and liver samples obtained from cattle in unsupplemented herds in the Manawatu, Waikato and Wairarapa regions of New Zealand. The results were statistically analysed. The revised reference ranges are as follows. [table: see text] The serum and liver selenium concentrations used as reference values prior to this study were inaccurate for the detection of selenium deficiency.


Rotational Resonance in milli-tesla fields detected by Field Cycling NMR.
Rotational Resonance (R(2)) between different spin Zeeman levels in samples of adamantane C(10)H(16) (homonuclear R(2)) and a mixture of C(10)H(16) and C(10)D(16) (both homonuclear and heteronuclear R(2)) has been studied. A Field Cycling NMR instrument was used to match the external field frequency ν(0) to a fixed frequency of sample rotation ν(r) at ν(r) = 40, 50 or 60 kHz. Rotational Resonance is observed at rational frequency ratios of ν(0)/ν(r), such as 12, 23, 32 and 1. The method may prove to become a useful tool for the determination of spin-spin distances in condensed matter.


High capacity in vitro micronucleus assay for assessment of chromosome damage: results with quinolone/naphthyridone antibacterials.
A high capacity in vitro micronucleus assay was developed to evaluate the ability of selected 6-fluorinated quinolone and naphthyridone antibacterial compounds to induce micronuclei (MN) in vitro in V79 Chinese hamster lung cells. Log-phase cells in six-well cluster dishes were exposed for 3 h in the absence of S9 to 34 compounds. After treatment, cells were refed with media containing cytochalasin B, incubated for 16 h, and harvested for cell-cycle kinetics (CCK) and MN analyses. The quinolones tested were grouped according to the substituent at the 8-position. All 4 compounds having a halogen substitution at position 8, five of the six 8-trifluoromethyl quinolones, and all eight 8-methoxy-substituted compounds induced a significant increase in MN. Only 5 of the 10 naphthyridone compounds tested, having a variety of substituents at the 7-position, were inducers of MN and the overall magnitude of the response was less than with the quinolones. The minimum clastogenic concentration for the quinolones ranged from 4 to 400 micrograms/ml and for the naphthyridones this range was from 22.5 to 100 micrograms/ml. In the groups examined, napthyridone compounds were less likely than quinolones to induce in vitro MN, particularly when the substituent at the 7-position in the naphthyridone contains some bulk (methyl groups) around the amine side-chain. Most of the quinolones tested induced MN, irrespective of the substituents at positions 7 or 8.


Reactivity of neutralizing antibodies with different specificities to H particles of poliovirus.
In order to elucidate the antigenic structure of poliovirus, the reactivity of antibody produced with H antigenic particles of Mahoney strain (polio type 1) was investigated. Injection of H particles of Mahoney strain into rabbits yielded neutralizing antibody as well as CF-N and CF-H antibodies. This result coincided with the report by Hinuma and coworkers. Neutralization tests with inhibitor resistant Mahoney mutants revealed that the neutralizing antibody produced with H particles was of HN31 type, one of the five different kinds of polio neutralizing antibodies reported previously (14). Absorption experiments with H particles on different neutralizing antibodies and analysis of antibody eluted by acid dissociation from antiserum-treated H particles also showed that the HN31 type antibody specifically combined with H particles of Mahoney strain. Since the H particle of poliovirus is known to be deficient in VP4, these results seems to indicate that the HN31 type antibody reacts with a structural part(s) of poliovirus other than VP4.


Trials of Improved Practices (TIPs) to Enhance the Dietary and Iron-Folate Intake during Pregnancy- A Quasi Experimental Study among Rural Pregnant Women of Varanasi, India.
Behavior Change Communications (BCC) play a decisive role in modifying socio-cultural norms affecting the perception and nutritional practices during pregnancy. To examine the effectiveness of 'Trials of Improved Practices' (TIPs) on dietary and iron-folate intake during pregnancy. Community based quasi experimental study with a control group. Four villages of Chiraigaon Community Development Block of Varanasi, India from May 2010 and recruited from August 2010. End line assessment, after 12 weeks of intervention, was completed in April 2011. Pregnant women in 13-28 weeks of gestation. TIPs was implemented in addition to ongoing essential obstetric care services in two villages through 3 home (assessment, negotiation and evaluation) visits and only assessment and evaluation visits in the other two control villages. Interpersonal communication, endorsing the active participation of family members and home based reminder materials were the TIPs based strategies. The effect of TIPs was assessed by comparing key outcome variables at baseline and after 12 weeks of intervention. Hemoglobin%, anemia prevalence, weight gain, compliance for iron-folate supplementation and dietary intake of calorie, protein, calcium and iron. A total of 86 participants completed the study. At the end, mean hemoglobin levels were 11.5±1.24 g/dl and 10.37±1.38 g/dl in the TIPs and control groups, respectively. The prevalence of anemia reduced by half in TIPs group and increased by 2.4% in the control group. Weight gain (grams/week) was significantly (p<0.01) higher in TIPs group (326.9±91.8 vs. 244.6±97.4). More than 85% of the PW in TIPs group were compliant for Iron-folate and only 38% were compliant among controls. The mean intake of protein increased by 1.78gm in intervention group and decreased by 1.81 gm in controls (p<0.05). More than two thirds of PW in TIPs group were taking one extra meal and only one third of controls were doing the same. TIPs found to be an effective approach to improve the nutritional status of pregnant women in the study area. TIPs strategy could be further explored on larger sample representing different socio-cultural and geographical areas. Clinical Trial Registry of India CTRI/2015/02/005517.


Interventional management and diagnostic follow-up of a large pancreatic pseudocyst: A case report.
We present a case of a large pancreatic pseudocyst in a 69-year-old man following post biopsy pancreatitis. Radiological findings revealed a thick-walled, fluid filled mass in proximity to the pancreas. Although pancreatic pseudocysts generally self-resolve, extensive or complicated cysts may require surgical or interventional management. Pseudocyst size >6 cm, compression of the inferior vena cava or biliary duct, and severe symptoms often prognosticate the need for intervention.


Solid-phase extraction and gas chromatographic-mass spectrometric determination after hydrolysis of 2-aminofluorene haemoglobin adducts in blood of rats.
2-Nitrofluorene is an environmental pollutant that binds covalently to haemoglobin after nitroreduction and successive N-hydroxylation. these haemoglobin adducts can be cleaved in vitro by mild base-catalysed hydrolysis. For the enrichment of arylamines from the aqueous hydrolysate, an extraction procedure with an organic solvent is widely used. Because of the formation of a thick emulsion layer between the aqueous and organic solvent layers, the extraction is laborious and inefficient. The use of Amberlite XAD2 provides a simple extraction procedure yielding a recovery of ca. 70%. Calibration curves in haemoglobin solution were prepared with a correlation coefficient of 0.998 (n = 12). The inter-day coefficient of variation amounted to 14%.


Isolation and quantitation of metallothionein isoforms using reversed-phase high-performance liquid chromatography.
Reversed-phase high-performance liquid chromatography (RP-HPLC) was used to isolate, characterize and quantitate liver and kidney metallothionein (MT) isoforms from a variety of animal species. The isoMTs were eluted from a radially compressed C18 column with a neutral sodium phosphate buffer and detected by UV absorbance (214 nm). Rabbit liver and horse kidney MTs were each found to be comprised of seven distinct isoforms. Pig liver and kidney MTs each exhibited three predominant isoforms, two of which were found to be subspecies of the MT-2 isoform. Rat liver MT was characterized by a less complex isoform pattern with only two major isoforms corresponding to the MT-1 and MT-2 isoMTs. Similarly, avian liver MT exhibited a distinct isoform pattern characterized by a low degree of complexity with the MT-2 isoform much more abundant than the MT-1 species. It was possible to apply the RP-HPLC separation to the resolution of individual MT isoforms from complex mixtures such as heat-treated cytosol. A standard curve was constructed using purified turkey hen liver MT-2 which demonstrated excellent linear correlation between integrated peak area and the quantity of MT injected onto the column. Recovery of MT from RP-HPLC was estimated to exceed 90%. Liver tissue from chicks injected on consecutive days with a dose of zinc was assayed for both MT-1 and MT-2 isoforms using the RP-HPLC analysis of cytosol samples. The MT-2 isoform was found to be preferentially expressed in response to zinc induction.


The synergistic effect of biomimetic electrical stimulation and extracellular-matrix-mimetic nanopattern for upregulating cell activities.
Endogenous bioelectric signaling and the extracellular matrix (ECM) are factors that have a great effect on the performance of cellular functions. Presenting an experimental platform to confirm the synergy effects of an electrical stimulation, which simulates endogenous bioelectricity, and nanopatterns that can be precisely fabricated in various patterns sizes makes it possible to consider those factors effectively. Herein, we have performed a comparison of cellular response to each of general electrical stimulation and biomimetic electrical stimulation (BES) and demonstrated the synergy effects of electrical stimulation and ECM-mimetic nanopatterns. BES has provided the most remarkable proliferation among different types of electrical stimulation and upregulated the behavior of cells through synergy effects with ECM-mimetic nanopatterns. Thus, it is believed that using the synergy effects of BES and ECM-like nanopatterns has broad applications in the biomedical field, such as cell culture with electrical stimulation, induction of cell growth, tissue repair, etc.


Psychological impact of amniocentesis on low-risk women.
The study comprised 85 young (25-34 years old) women who underwent genetic amniocentesis, 80 comparable young women who had an ultrasoundscan at the same gestational age and 74 women (35-40 years old) who had amniocentesis. The State-Trait Anxiety Inventory and Visual Analogue Scales concerning anxiety and worry were used on four occasions to evaluate psychological changes during pregnancy. The anxiety level in the younger women decreased after amniocentesis and a further decrease was observed after the results were communicated to them. However, similar changes were seen in the group of younger women after ultrasonography, and there was no difference in anxiety level between the two groups of younger women in the 16th or in the 35th week of pregnancy. Thus, in younger women at low genetic risk amniocentesis was neither anxiety-relieving, nor anxiety-creating. The level of anxiety before amniocentesis was not higher in the older than in the younger women having amniocentesis. However, in the younger women a significant decrease in anxiety was seen as soon as amniocentesis had been performed, while in the older women this decrease was delayed until after the results were known.


Introduction: Patient organization movements and new metamorphoses in patienthood.
In this introduction, we examine health activism as one expression of an emergent 'politics of vitality' or flurry of activity around health matters that includes: advances in technoscientific medicine, healthcare restructurings, and a re-thinking of science-society contracts. In querying politicized mobilizations around 'health matters and the mattering of health,' we provocatively entitle our discussion 'patient organization movements'. This marks an invitation to interrogate (in reverse order) each term along the way, pausing in our concluding discussion to turn our attentions to the patient. The figure of the patient is thematized as an historical inscription and a formidable dimension of personhood under modernity/late modernity. Moreover, we argue that conventional categorizations of the patient are undergoing accelerated processes of change at the present time. We characterize three transformational trends: moves to author and authorize patienthood, mutiny from patienthood, and mutations in the category of the patient. Such metamorphoses in patienthood represent both reflections and repercussions--at once consequences and catalysts--of the proposed politics of vitality. We explore the pluralization of the patient's persona via a closer look at the 11 empirical studies of health activism that comprise this collection.


Systemic Moxifloxacin in Streptococcus viridans Endophthalmitis.
To evaluate the effectiveness of prophylactic systemic moxifloxacin in a rabbit model of Streptococcus viridans (S. viridans) endophthalmitis. Animals (n=60) were divided into three groups. Intravenous moxifloxacin, vancomycin, normal saline was administered to 20 animals in each group and two hours later, 104 colony-forming units (CFU) of S. salivarius were intravitreally injected into the left eye. Intravenous antibiotics injection was repeated on days 1, 2, and 3 after inoculation. The clinical features, bacterial culture from vitreous aspirates of 10 eyes from each group were evaluated on days 1, 3, 5, and 7. On day 7, eyes for clinical feature examination were enucleated for histopathologic examination. Clinical scores and log10CFU/ml values were lower in moxifloxacin group on all examination days. Histopathologic examination showed less inflammation and relatively well-preserved retina in the moxifloxacin group. Systemic moxifloxacin may have a prophyactic effect for S. viridans endophthalmitis after intraocular procedure.


The transformation suppressor protein Pdcd4 shuttles between nucleus and cytoplasm and binds RNA.
The Pdcd4 gene has originally been isolated in a search for genes that are activated in cells undergoing apoptosis. Independent of these studies, the Pdcd4 gene has been implicated in the suppression of tumor-promoter-mediated transformation of keratinocytes and as a downstream target of Myb in hematopoietic cells. The Pdcd4 protein has weak homology to the eucaryotic translation initiation factor eIF4G and has been shown to interact with certain translation initiation factors. To explore the molecular function of the Pdcd4 protein, we have studied its subcellular localization. We show that the Pdcd4 protein is a predominantly nuclear protein under normal growth conditions and that it is exported from the nucleus by a leptomycin B-sensitive mechanism upon serum withdrawal. The protein contains two nuclear export signals, one of which is very potent. In addition, we demonstrate that the Pdcd4 protein has RNA-binding activity and that the sequences involved in RNA-binding are located in the amino-terminal part of the protein. Taken together, our data raise the possibility that Pdcd4 is involved in some aspect of nuclear RNA metabolism in addition to its suspected role in protein translation.


Conserved gene sequences for species identification: PCR analysis of the 3' UTR of the SON gene distinguishes human and other mammalian DNAs.
In this paper we show that the polymerase chain reaction (PCR) can be used on regions of highly conserved genes, such as the 3' untranslated region (3' UTR) of the SON gene, to identify the mammalian origin of a sample. Using this test, we have been able to distinguish human, monkey, cat, dog, mouse and hamster DNAs. We have also determined the DNA sequence of these different PCR products, which can be used to reinforce species identification. The advantages of this test are that: (i) no prior information is required on the possible species origin of a sample, (ii) the reaction produces a single PCR product which varies in size according to the species of origin, making the test simple to interpret, and (iii) the target region of DNA amplified in these experiments is small and can easily be sequenced and sized using automated techniques. This small size has enabled us to successfully amplify this product from DNA extracted from compromised material (human bone samples) and so demonstrate that the test is valuable for the characterisation of remains in which DNA is degraded.


Genetic evidence for cell death mediated by nerve growth factor and the neurotrophin receptor p75 in the developing mouse retina and spinal cord.
The role of nerve growth factor (NGF) and of the neurotrophin receptor p75 (p75(NTR)) in programmed cell death was investigated in the retina and the spinal cord of mouse embryos. Large numbers of cells express p75(NTR) in and along the developing optic nerve and in the mantle zone of the spinal cord. In embryos carrying deletions in the ngf or the p75(NTR) gene, cell death was reduced in the retina and in the spinal cord. Increased numbers of Islet-1-immunoreactive cells were detected in the dorsal spinal cord, and the mantle zone was enlarged in both mutants. These results indicate that NGF/p75(NTR)-dependent mechanisms are used to remove cells when axonal tracts elongate in developing neuroepithelia.


Surface modified BaTiO3 nanoparticles as the matrix for phospholipids and as extracting probes for LLME of hydrophobic proteins in Escherichia coli by MALDI-MS.
In this paper, we report the dual function of 12-hydroxy octadecanoic acid (HOA)-modified barium titanate nanoparticles (BaTiO3 NPs) as the matrix for phospholipids (PLs) and as hydrophobic affinity probes for liquid-liquid microextraction (LLME) of hydrophobic proteins in Escherichia coli prior to their identification by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-MS). FT-IR, SEM and TEM were used for the characterization of the HOA-modified BaTiO3 NPs. The surface modified BaTiO3 NPs acted as multifunctional probes (as extracting probes and as the matrix) for the analysis of PLs by MALDI-MS. Compared to 2,5-dihydroxybenzoic acid (2,5-DHB), the HOA-modified BaTiO3 NPs provided good PLs mass spectra with similar or improved signal-to-noise (S/N) ratio, which demonstrated the potentiality of HOA-modified BaTiO3 NPs as a PLs purpose matrix. This method was found to be linear in concentration ranges of 1.0-5.0 μM and 1.0-10.0 μM for L-A-phosphatidyl-l-serine (PS) and L-A-phsophatidic acid sodium (PA) with correlation coefficient (R(2)) values from 0.9905 to 0.9987. The detection limits were 0.20-0.35 μM and 0.25-0.40 μM for PS and PA, respectively. We also demonstrated the HOA-modified BaTiO3 NPs as extracting and as preconcentrating probes for the LLME of hydrophobic proteins in E. coli prior to their identification by MALDI-MS. Thus, the surface modified BaTiO3 NPs-assisted LLME coupled with MALDI-MS provides a simple methodology for the efficient extraction and determination of hydrophobic molecules in biological samples.


Proliferation of Pasteurella haemolytica in the calf respiratory tract after an abrupt change in climate.
Two groups of four calves were exposed to a poly-disperse aerosol of 1.3 X 10(4) to 16 X 10(4) colony forming units (CFU) of nalidixic acid resistant Pasteurella haemolytica type A1 litre-1 of air with a mass median aerodynamic diameter of 2.6 +/- 0.8 microns. One group of calves was kept at 5 degrees C, 72 per cent relative humidity (RH) and the second was subjected to an abrupt change in climate directly after aerosol exposure from 5 degrees C, 75 per cent RH to 13 degrees C, 84 per cent RH. Clearance of the organism from the respiratory tract of the calves was monitored over the subsequent 23 hours by a method of tracheal and nasopharyngeal swabbing. Clearance measured at the trachea in all calves in both groups was not a continuous, uninterrupted process but exhibited a temporary decline between eight and 14 hours. Calves subjected to an abrupt change in climate after aerosol challenge had raised respiratory rates eight to 14 hours later and P haemolytica proliferated in the nasopharynx over the entire 23 hours. There was no apparent effect of climate on P haemolytica in the trachea. It is suggested that rapid growth of P haemolytica accompanying a change in climate may be an important aetiological factor in pneumonic pasteurellosis of calves.