A mathematical optimization model for efficient assignment of inpatients in an oncology center in China.
This paper addresses a problem for assignment of chemo-receiving inpatients in an oncology care center, which has not been addressed in the literature. Chemotherapy is regarded as one of the most effective treatments for cancer. In recent years, as cancer incidence increased, the number of patients admitted to a cancer treatment center has also been rising. How to balance the workload of medical service resources by planning admission of patients has become an essential problem that must be given consideration by policy- makers. The allocation of chemotherapy patients, different from that of the routine inpatients, is restrained by treatment agreements of patients and presents periodic features. Therefore, the allocation of chemotherapy patients is much more difficult than that of routine patients. A mixed integer programming (MIP) model was first formulated for this problem in order to maximize the usage of beds. Specific features of chemotherapy, such as chemotherapy protocols, were integrated into this model. The inpatient assignment problem was proved to be non-deterministic polynomial- complete and we propose an exact method to solve it. Numerical experiments on suitable use-case scenarios and a practical Chinese oncology center were performed to test and evaluate this model. The obtained results demonstrated the effectiveness of our method. Some useful managerial implication are provided for policy-makers through the analysis of obtained results. The models and methods suggested here can be effectively applied in similar departments of other countries and regions.


Deforestation and world population sustainability: a quantitative analysis.
In this paper we afford a quantitative analysis of the sustainability of current world population growth in relation to the parallel deforestation process adopting a statistical point of view. We consider a simplified model based on a stochastic growth process driven by a continuous time random walk, which depicts the technological evolution of human kind, in conjunction with a deterministic generalised logistic model for humans-forest interaction and we evaluate the probability of avoiding the self-destruction of our civilisation. Based on the current resource consumption rates and best estimate of technological rate growth our study shows that we have very low probability, less than 10% in most optimistic estimate, to survive without facing a catastrophic collapse.


[Neurologic complications of AIDS].
Clinical symptoms of the central and peripheral nervous system occur in about 40% of patients wit HIV infection. At autopsy, CNS lesions can be demonstrated in even higher percentages. Primary sequelae of HIV infection--either due to direct viral effects or the immunopathologic response of the human host--are acute aseptic meningitis or mengingo-encephalitis, HIV encephalopathy, myelopathy, neuropathy, and myositis. Secondary consequences of immunodeficiency in AIDS are opportunistic infections with other viruses, bacteria, fungi, and protozoa, e.g. CMV, HSV and HZV encephalitis, mycobacterial CNS infections, neurosyphilis, cryptococcal meningitis, and last but not least cerebral toxoplasmosis. The main secondary malignoma of the CNS is lymphoma. Together these disorders form a complex spectrum of central and peripheral neurological symptoms.


Hearing in 3D: Directional Auditory Sensitivity of Northern Saw-Whet Owls (Aegolius acadicus).
Northern saw-whet owls (Aegolius acadicus) are nocturnal predators that are able to acoustically localize prey with great accuracy; an ability that is attributed to their unique asymmetrical ear structure. While a great deal of research has focused on open loop sound localization prior to flight in owls (primarily barn owls), directional sensitivity of the ears may also be important in locating moving prey on the wing. Furthermore, directionally sensitive ears may also reduce the effects of masking noise, either from the owls' wings during flight or environmental noise (e.g., wind and leaf rustling), by enhancing spatial segregation of target sounds and noise sources. Here, we investigated auditory processing of Northern saw-whet owls in three-dimensional space using auditory evoked potentials (AEPs). We simultaneously evoked auditory responses in two channels (right and left ear) with broadband clicks from a sound source that could be manipulated in space. Responses were evoked from 66 spatial locations, separated by 30° increments in both azimuth and elevation. We found that Northern saw-whet owls had increased sensitivity to sound sources directly in front of and above their beaks and decreased sensitivity to sound sources below and behind their heads. The spatial region of highest sensitivity extends from the lower beak to the crown of the head and 30° left or right of the median plane, dropping off beyond those margins. Directional sensitivity is undoubtedly useful during foraging and predator evasion, and may also reduce the effect of masking noise from the wings during flight due to the spatial segregation of the noise and targets of interest.


Gelastic syncope: an unusual condition.
Gelastic syncope or laughter-induced syncope is a rare disease often misdiagnosed as narcolepsy or cataplexy. We report a 54-year-old man with syncopal episodes. Each episode started after laughter, leading to light-headedness with blurring of vision and loss of consciousness for a few seconds. The episodes resolved spontaneously. The treatment of gelastic syncope is the same as that for neurally mediated syncope.


Conjugal giant cell arteritis.
While the pathogenesis of giant cell arteritis (GCA) remains unclear, a number of factors may be contributory, including genetic, environmental, and immune. There have been few reports of GCA occurring in a conjugal pair, all originating from Northern Europe or the Northern United States. We document GCA occurring in a husband and wife from the southern Gulf Coast of the United States and discuss the implications of this, as well as the current understanding of the pathogenesis of GCA.


[99mTc Tetrofosmin in diagnosis of distant metastases from differentiated thyroid cancer].
Technetium 99mTc(TF), non-specific tumor-searching tracer was evaluated for its ability to detect distant metastases of differentiated thyroid carcinoma (DTC) and its reliability in the follow-up of DTC. Whole body scintigraphy (wbs) was performed 20-30 min after intravenous injection of 740 MBq 99mTc tetrofosmin by means of a dual-head gamma-camera (followed by spot images if needed) in 61 patients (pts) with DTC; 52 pts with distant metastases in 131I whole body scintigraphy (34) or in other methods (x-ray, CT, ultrasound) (7) or with negative 131I whole body scan and elevated thyroglobulin (11). In the group of 52 pts with signs of neoplasm dissemination, 36 showed positive TF whole body scan (69%), 16 (31%) pts were TF-negative. 23 of 34 131I positive wbs were also TF positive (68%), 11 out of 34 were TF negative (32%). In a group of 7 pts with metastases in x-ray, CT or ultrasound 4/7 were positive (57%), 3/7 were TF negative (18%). In a control group of 11 persons (2 diseases-free, 9 with DTC in clinical remission) TF whole body scans were negative in all cases. Technetium 99mTc tetrofosmin is clinically useful for detecting distant metastases of differentiated thyroid carcinoma and deserves complementary clinical application in follow-up in such patients.


Fluorescence Determination of Omethoate Based on a Dual Strategy for Improving Sensitivity.
Omethoate is a frequently used organophosphorus pesticide, and the establishment of a sensitive, selective, and simple method to determine omethoate is very important for food safety. In this paper, a dual strategy was applied to improve the detection sensitivity of omethoate. In the first strategy, graphene quantum dots (GQDs) were doped with nitrogen to increase the fluorescence quantum yield to 30%. By coupling N-GQDs with omethoate aptamer, an N-GQDs-aptamer probe was synthesized. The fluorescence of the N-GQDs-aptamer probe was turned off by graphene oxide (GO), but recovered by omethoate. Based on this principle, the fluorescence method for detecting omethoate was established with a detection limit of 0.041 nM. To further improve the detection sensitivity, the fluorescence polarization analysis method was applied as another strategy based on the polarization signal of GQDs. The detection limit was decreased to 0.029 pM by using the fluorescence polarization method. The detection limits in this paper were lower than those in other reports. The imaging of omethoate on plant leaves showed that the probe could be used for visual semiquantitative determination of omethoate.


[Treatment of Japanese cedar pollinosis and its impact on patient satisfaction].
Japanese cedar pollinosis is a major public health problem in Japan because of its severe symptom and high prevalence. However, patient satisfaction by treatment is poor according to current reports. As the treatments, pre-seasonal medication and single peroral anti-allergic drug on demand are frequently used in Japan. Against conventional methods, we treated 301 patients with Japanese cedar pollinosis by persistent use of combined drugs (topical steroid, peroral anti-allergic drug and eye drop) without pre-seasonal medication in 2003. Immunotherapy was also used in 90 patients treated. As a result, 97% of patients was satisfied in this treatment and immunotherapy contributed to reduction in the amount of drug and high treatment outcome.


Identification and characterization of Drosophila Snurportin reveals a role for the import receptor Moleskin/importin-7 in snRNP biogenesis.
Nuclear import is an essential step in small nuclear ribonucleoprotein (snRNP) biogenesis. Snurportin1 (SPN1), the import adaptor, binds to trimethylguanosine (TMG) caps on spliceosomal small nuclear RNAs. Previous studies indicated that vertebrate snRNP import requires importin-β, the transport receptor that binds directly to SPN1. We identify CG42303/snup as the Drosophila orthologue of human snurportin1 (SNUPN). Of interest, the importin-β binding (IBB) domain of SPN1, which is essential for TMG cap-mediated snRNP import in humans, is not well conserved in flies. Consistent with its lack of an IBB domain, we find that Drosophila SNUP (dSNUP) does not interact with Ketel/importin-β. Fruit fly snRNPs also fail to bind Ketel; however, the importin-7 orthologue Moleskin (Msk) physically associates with both dSNUP and spliceosomal snRNPs and localizes to nuclear Cajal bodies. Strikingly, we find that msk-null mutants are depleted of the snRNP assembly factor, survival motor neuron, and the Cajal body marker, coilin. Consistent with a loss of snRNP import function, long-lived msk larvae show an accumulation of TMG cap signal in the cytoplasm. These data indicate that Ketel/importin-β does not play a significant role in Drosophila snRNP import and demonstrate a crucial function for Msk in snRNP biogenesis.


CXCR4 mediated chemotaxis is regulated by 5T4 oncofetal glycoprotein in mouse embryonic cells.
5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process important during embryonic development and metastatic spread of epithelial tumors. Investigation of the transcriptional changes in early ES differentiation showed upregulation of CXCL12 and down-regulation of a cell surface protease, CD26, which cleaves this chemokine. CXCL12 binds to the widely expressed CXCR4 and regulates key aspects of development, stem cell motility and tumour metastasis to tissues with high levels of CXCL12. We show that the 5T4 glycoprotein is required for optimal functional cell surface expression of the chemokine receptor CXCR4 and CXCL12 mediated chemotaxis in differentiating murine embryonic stem cells and embryo fibroblasts (MEF). Cell surface expression of 5T4 and CXCR4 molecules is co-localized in differentiating ES cells and MEF. By contrast, differentiating ES and MEF derived from 5T4 knockout (KO) mice show only intracellular CXCR4 expression but infection with adenovirus encoding mouse 5T4 restores CXCL12 chemotaxis and surface co-localization with 5T4 molecules. A series of chimeric constructs with interchanged domains of 5T4 and the glycoprotein CD44 were used to map the 5T4 sequences relevant for CXCR4 membrane expression and function in 5T4KO MEF. These data identified the 5T4 transmembrane domain as sufficient and necessary to enable CXCR4 cell surface expression and chemotaxis. Furthermore, some monoclonal antibodies against m5T4 can inhibit CXCL12 chemotaxis of differentiating ES cells and MEF which is not mediated by simple antigenic modulation. Collectively, these data support a molecular interaction of 5T4 and CXCR4 occurring at the cell surface which directly facilitates the biological response to CXCL12. The regulation of CXCR4 surface expression by 5T4 molecules is a novel means to control responses to the chemokine CXCL12 for example during embryogenesis but can also be selected to advantage the spread of a 5T4 positive tumor from its primary site.


Effect of interleukin 1 receptor antagonist gene transduction on human melanoma xenografts in nude mice.
Interleukin (IL)-1 is a pleiotropic inflammatory cytokine that promotes angiogenesis and enhances tumor growth and metastases. We evaluated the effects of IL-1 receptor antagonist (IL-1ra) on tumor growth and metastases in human melanoma xenografts. We selected two human melanoma lines (SMEL and PMEL) with differential (high versus low, respectively) constitutive production of IL-1 by ELISA. The IL-1ra gene was isolated from monocyte RNA by PCR and retrovirally transduced into SMEL and PMEL. In vitro cell proliferation was evaluated using a WST-1 assay. Athymic nude mice received s.c. or i.v. injection with parental, vector-transduced, or IL-1ra-transduced melanoma cells, and tumor growth, lung metastases, and histology were characterized. IL-1 was produced by SMEL in vitro and ex vivo (117 and 67 pg/ml/10(6) cells/24 h, respectively), but not by PMEL (15 and 0 pg/ml/10(6) cells/24 h, respectively). Neither made IL-1ra natively. Gene-transduced cell lines secreted >1000 pg/ml/10(6) cells/24 h of IL-1ra by ELISA. In vitro proliferation of each parental cell line was comparable to the proliferation rate of each transduced cell line. IL-1ra-transduced SMEL (SMEL/IL-1ra) showed significantly slower tumor growth compared with null-transduced and parental cell lines (P < 0.001, ANOVA-Bonferroni/Dunn). There was no difference in growth rates between PMEL and IL-1ra-transduced PMEL (PMEL/IL-1ra). A mixing study of SMEL and SMEL/IL-1ra showed significant inhibition of tumor growth at various ratios (P < 0.001, ANOVA-Bonferroni/Dunn). There were significantly fewer lung metastases with SMEL/IL-1ra versus SMEL (P < 0.002). IL-1ra decreases in vivo growth and metastatic potential of a human melanoma xenograft that constitutively secretes IL-1. This effect may be exploitable using clinically available IL-1ra for the treatment of human cancers.


Diagnostic and prognostic markers in sepsis.
Sepsis is a common and serious complication in intensive care unit patients. An important factor in optimizing survival rates in septic patients is the ability to start treatment early in the course of disease; there is, therefore, a need for accurate diagnostic tests. In recent years, there has been a move away from the rather vague and nonspecific signs that were previously used to diagnose sepsis towards the possible adjunctive role of biomarkers. Many biomarkers have been proposed and assessed clinically, but none alone is specific enough to definitively determine diagnosis. The future direction of research is most likely a greater focus on the use of panels or combinations of markers with clinical signs. Some biomarkers may also be useful for prognosis and guiding therapy. Here, the authors will review our changing approaches to sepsis diagnosis and discuss some of the markers that seem most relevant at the present time.


Combinatorial effects of NusA and NusG on transcription elongation and Rho-dependent termination in Escherichia coli.
The transcription factors NusA and NusG from Escherichia coli are modulators of the RNA polymerase elongation reaction and Rho-dependent transcription termination. NusA decreases the elongation rate and termination efficiency while NusG increases both activities. Both Nus factors are able to physically interact with Rho and with RNA polymerase. Experiments with purified components designed to determine whether these factors act independently or competitively showed that the change in elongation rate was a composite of their individual effects, that the combined effect on termination was dependent on the reaction conditions and that the two factors do not compete for their sites of action for either effect. The two factors were also found not to enhance significantly the slight (20%) inhibition of elongation caused by 200 microM guanosine 3',5'-bisdiphosphate (ppGpp) during transcription in vitro. The results also show that the effects of NusA and NusG on RNA polymerase elongation and Rho function are contrary to the inverse relationship between elongation and termination that is expected for a kinetic coupling of Rho action to RNA polymerase elongation. This property suggests that in addition to their known actions on RNA polymerase that influence the length of pausing, these factors act on some other rate-limiting step of the Rho-dependent termination process.


Molecular, structural, and functional comparison of N lobe and C lobe of the transferrin from rock bream, Oplegnathus fasciatus, with respect to its immune response.
The iron-withholding strategy of innate immunity is an effective antimicrobial defense mechanism that combats microbial infection by depriving microorganisms of Fe3+, which is important for their growth and propagation. Transferrins (Tfs) are a group of iron-binding proteins that exert their antimicrobial function through Fe3+ sequestration. The current study describes both structural and functional characteristics of a transferrin ortholog from rock bream Oplegnathus fasciatus (RbTf). The RbTf cDNA possesses an open reading frame (ORF) of 2079 bp encoding 693 amino acids. It has a molecular mass of approximately 74 kDa and an isoelectric point of 5.4. In silico analysis revealed that RbTf has two conserved domains: N-terminal domain and C-terminal domain. Pairwise homology analysis and phylogenetic analysis revealed that RbTf shared the highest identity (82.6%) with Dicentrarchus labrax Tf. According to the genomic analysis, RbTf possesses 17 exons and 16 introns, similar to the other orthologs. Here, we cloned the N terminal and C terminal domains of RbTf to evaluate their distinct functional features. Results obtained through the CAS (chrome azurol S) assay confirmed the iron-binding ability of the RbTf, and it was further determined that the iron-binding ability of rRbTfN was higher than that of rRbTfC. The antimicrobial functions of the rRbTfN and the rRbTfC were confirmed via the iron-dependent bacterial growth inhibition assay. Tissue distribution profiling revealed a ubiquitous expression with intense expression in the liver. Temporal assessment revealed that RbTf increased after stimulation of LPS, Edwardsiella tarda, and Streptococcus iniae post injection (p.i.). These findings demonstrated that RbTf is an important antimicrobial protein that can combat bacterial pathogens.


Customized breast cancer risk assessment in an ambulatory clinic: a portal for identifying women at risk.
Existing high-risk clinic models focus on patients with known risk factors, potentially missing many high-risk patients. Here we describe our experience implementing universal risk assessment in an ambulatory breast center. Since May 2017, all breast center patients completed a customized intake survey addressing known breast cancer risk factors and lifestyle choices. Patient characteristics, family history, risk scores, and lifestyle factors were examined; patients with high-risk breast lesions were excluded. Patients were considered at increased risk by model thresholds Gail 5-year risk > 1.7% (35-59 years), Gail 5-year risk > 5.5% (≥ 60 years), or Tyrer-Cuzick (T-C) v7 lifetime risk > 20% (any age). From May 2017-April 2018, there were 874 eligible patients-420 (48%) referred for risk assessment (RA) and 454 (52%) for non-specific breast complaints (NSBC). Overall, 389 (45%) were at increased risk of breast cancer. Gail 5-year risks were similar between RA and NSBC patients. However, RA patients more frequently met criteria by T-C score (P = 0.02). Of all patients at increased risk, 149 (39%) were overweight (BMI > 25) or obese (BMI > 30) and only 159 (41%) met recommended exercise standards. NSBC patients who met criteria were more frequently smokers (8% vs 1%, P < 0.01); all other demographic/lifestyle factors were similar among high-risk patients regardless of referral reason. Universal risk assessment in a comprehensive breast health center identified 45% of our population to be at increased risk of breast cancer. This clinical care model provides a unique opportunity to identify and address modifiable risk factors among women at risk.


Influence of type 2 diabetes mellitus on cardiovascular disease mortality: findings from the Hawaii-Los Angeles-Hiroshima study.
The present study addressed whether diabetes mellitus was a strong risk factor for cardiovascular disease (CVD) death. Between 1976 and 1984, 927 (404 men) Japanese-Americans in Hawaii aged 40-79 years participated at baseline examination including a 75 g oral glucose tolerance test. Diabetes was defined as fasting serum glucose >or=140 mg/dl, 2 h postload glucose >or=180 mg/dl, or the use of drugs for diabetes. Causes of death were classified by ICD-9 codes on the reports from the Hawaii State Public Health Bureau. Until 1994, 178 individuals suffered death; 81 were attributed to CVD and 43 to coronary heart disease (CHD). The age-adjusted and coronary risk factors-adjusted relative risks for CHD and CVD mortality were significant for diabetes both in men and women. The impact of diabetes on CHD mortality was greater for women. However, no gender difference in the contribution of diabetes to fatal CVD was observed. Serum fasting glucose levels tended to be associated with CHD death and were associated with CVD death in diabetic subjects. In conclusion, diabetes is a strong independent risk factor for CVD mortality in Japanese-American men and women. Hyperglycemia is associated with CVD mortality in diabetic subjects.


Comparative Efficacy and Safety of Peficitinib 25, 50, 100, and 150 mg in Patients with Active Rheumatoid Arthritis: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.
Peficitinib, a JAK3-selective inhibitor that blocks the signal transduction and then suppresses immune responses, has been developed for the treatment of patients with moderate to severe active rheumatoid arthritis (RA). We assessed the relative efficacy and safety of once-daily administration of peficitinib (a JAK3-selective inhibitor) 25 mg, 50 mg, 100 mg, and 150 mg in patients with active RA. A Bayesian network meta-analysis was conducted to combine direct and indirect evidence from eligible randomized controlled trials (RCTs). The literature search was performed up to May 2019 using MEDLINE, Embase, and the Cochrane Controlled Trials Register. Three RCTs involving 948 patients met the inclusion criteria. There were ten pairwise comparisons, including five direct comparisons and five interventions. The American College of Rheumatology 20% (ACR20) response rate was significantly higher in the peficitinib 150-mg group than in the placebo group (odds ratio (OR): 3.61; 95% credible interval (CrI): 2.35-5.57). Similarly, the ACR20 response rate was significantly higher in the peficitinib 100-mg group than in the placebo group (OR: 2.33, 95% CrI: 1.51-3.56). The peficitinib 50-mg group had a significantly higher ACR20 response rate than the placebo group. However, the ACR20 response rate was not significantly higher in the peficitinib 25-mg group than in the placebo group. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that peficitinib 150 mg was likely to achieve the best ACR20 response rate (SUCRA = 0.995), followed by peficitinib 100 mg (SUCRA = 0.696), peficitinib 50 mg (SUCRA = 0.558), peficitinib 25 mg (SUCRA = 0.153), and placebo (SUCRA = 0.098). The ACR50 and ACR70 response rates showed a similar distribution pattern to the ACR20 response rate. The difference in the number of patients with adverse events (AEs) among the intervention groups was not statistically significant. Peficitinib 50, 100, and 150 mg once daily was effective in treating active RA, without causing a significant risk for AEs.


Substance use, suicidality, and adolescent-onset schizophrenia: an Israeli 10-year retrospective study.
The aim of this study was to investigate the link between the use of specific types of substances and suicidality in adolescent inpatients with schizophrenia and schizoaffective disorder. We performed a 10-year naturalistic retrospective study of 178 adolescent inpatients diagnosed as suffering from either schizophrenia or schizoaffective disorder. A comparison was made between the suicide-attempting adolescent inpatients and the non-attempting subjects, by the use of specific types of substances, measurements of psychotic, depressive, and aggressive symptoms, and clinical data reported during their hospitalization. The suicide attempters reported considerably greater usage of inhalants and lysergic acid diethylamide (LSD). Alcohol and methylene-dioxy-methylamphetamine (MDMA) were also used significantly more by this group. However, no differences were found in the usage of cannabis, amphetamines, cocaine, and opiates. The suicide-attempting patients were found to have had more previous psychiatric admissions, a greater level of deliberate self-harm behavior, and a higher level of suicide ideation, but a decreased severity of psychotic symptoms. This study is the first report of the association between specific types of substances and suicidality in the high-risk population of adolescent psychotic inpatients. The strong association between inhalants, LSD, alcohol, and MDMA with suicidality is relevant to suicide prevention and intervention programs in adolescent-onset schizophrenia.


A review of the structure and function of vital registration system in Ghana: towards improvement in mortality data quality for health policy analysis.
Vital registration systems (VRS) are important in the collection of routine data on indicators of development. These are particularly useful if they are properly built to address weaknesses in the system leading to poor data quality. For instance, routine data on health events (e.g. morbidity, mortality etc.) are crucial for rapid assessment of disease burden and mortality trends in the population. They are also useful in the identification of vulnerable groups in populations. Despite their usefulness, VRS in many developing countries including Ghana are poorly structured raising questions about the quality of the output data from these systems. The present study aimed at assessing and documenting the structure and function of the VRS in Ghana, as well as at identifying the structural features that potentially compromise the reliability and validity of the output data from the Ghanaian VRS. To perform this study, collection and review of policy and legal documents establishing the VRS, documentation and evaluation of component structures of the system, assessment of procedural protocols guiding data collection processes and in-depth interviews with staff at the Ghana Births and Deaths Registry were performed. The assessment of the structure of the Ghana VRS, policy documents setting it up and the operational procedures reveals important lapses (e.g. presence of outmoded practices, imperfections in Births and Deaths Registry Act, 1965, Act 301 and imperfect system design) in the system that could compromise validity and reliability of the data generated from the VRS in Ghana.


Deformation and strain characteristics along the length of the anterior band of the inferior glenohumeral ligament.
Efficacious surgical treatment of anterior glenohumeral instability often requires repair of the anteroinferior capsulolabral structures, including the glenoid origin of the anterior band of the inferior glenohumeral ligament. Rupture in this location, the Bankart lesion, may be accompanied by nonrecoverable stretching of the anterior band. The purpose of this study was to evaluate the amount and location of nonrecoverable stretching with tensile testing. Twelve glenoid-soft tissue-humerus complexes from fresh-frozen glenohumeral joints were studied by means of a custom jig, an Instron machine, and a video digitizing system. The joints were positioned to simulate that known to cause apprehension for anterior instability. Nonrecoverable deformation differed along the length of the anterior band but was slight in all locations. For those that failed at the glenoid insertion region, the mean nonrecoverable deformation was 0.10 +/- 0.16 mm (mean +/- SEM) at the bone-labral junction of the glenoid insertion region and 0.38 +/- 0.23 mm at the labral-ligament junction of the glenoid insertion region. It was 0.53 +/- 0.23 mm at the ligament midsubstance and 0.04 +/- 0.10 mm at the humeral insertion region. For those that failed at the glenoid insertion region, the nonrecoverable stretching was 1.4% +/- 1.9% at the bone-labral junction of the glenoid insertion region and 3.5% +/- 2.0% at the labral-ligament junction of the glenoid insertion region. It was 2.3% +/- 1.1% at the ligament midsubstance and 0.0% +/- 1.4% at the humeral insertion region. Rupture of the anterior band resulted in little nonrecoverable stretching at both the site of failure and elsewhere along the length, remote from the failure site. Surgical repairs after initial dislocation may restore the length of the anterior band of the inferior glenohumeral ligament with little shortening.


Description of an early intervention to prevent substance abuse and psychopathology in recent rape victims.
Approximately 683,000 adult women are raped each year. Only one in seven of these victims report the assault to police and receive forensic exams and other professional services. For many rape victims, this may be the only professional contact with service providers; however these services are typically limited to evidence collection and prophylactic STD treatment. Yet this exam also presents a unique opportunity for a preventive intervention to help prepare women to cope with potential stress related to rape-exam procedures and to address potential post rape psycho-pathology. This article reviews psychological interventions for trauma victims used in the acute post rape time frame and provides data from an ongoing clinical trial that evaluates delivery of a preventive intervention for victims presenting for forensic rape exams.


Traumatic Pneumoperitoneum After Vaginal Intercourse.
Pneumoperitoneum with peritonitis, although uncommon, is a serious injury encountered in the pediatric emergency department. Although the patients may often appear ill or toxic, they can have normal vital signs at initial presentation. Patients with such injury can present with a variety of complaints because of the nature of referred pain. As a result, some patients may be more or less straightforward, thus illustrating the importance of obtaining a detailed history and performing a thorough physical examination. We discuss an uncommon case report of pneumoperitoneum with peritonitis in an adolescent patient presenting with vaginal bleeding and abdominal pain hours after vigorous coitus. Examination under anesthesia, flexible sigmoidoscopy, and exploratory laparoscopy revealed a vaginal laceration and a 2- to 3-cm perforated area at the left edge of the vaginal laceration that involved the rectovaginal septum entering the peritoneal cavity. Pneumoperitoneum resulting from vaginal intercourse in an otherwise healthy adolescent female is a rare cause of peritonitis. Although it has been described in the adult literature, this case illustrates the importance of considering sexual history as a contributory factor in pediatric patients presenting with an acute abdomen.


Band structure, phonon scattering, and the performance limit of single-walled carbon nanotube transistors.
Semiconducting single-walled carbon nanotubes are studied in the diffusive transport regime. The peak mobility is found to scale with the square of the nanotube diameter and inversely with temperature. The maximum conductance, corrected for the contacts, is linear in the diameter and inverse temperature. These results are in good agreement with theoretical predictions for acoustic phonon scattering in combination with the unusual band structure of nanotubes. These measurements set the upper bound for the performance of nanotube transistors operating in the diffusive regime.


Initial implementation of a Thomson scattering diagnostic for Proto-MPEX.
Internal funds have been used at Oak Ridge National Laboratory to enable the initial installation of a laser based, Thomson scattering (TS) diagnostic on the prototype Material-Plasma Exposure eXperiment (Proto-MPEX). Since the funds are limited in amount and duration, the initial TS system has followed a low cost design and rapid implementation. This paper will discuss the design elements of the initial TS configuration on Proto-MPEX and issues encountered during installation. Avenues of response to system limitations will be discussed, along with considerations for further optimization. The laser system will undergo reconfiguration to enable additional project milestones, e.g., laser induced break-down spectroscopy.


Early behavioral and metabolomic change after mild to moderate traumatic brain injury in the developing brain.
Pathophysiology of developmental traumatic brain injury (TBI) is unique due to intrinsic differences in the developing brain. Energy metabolic studies of the brain during early development (P13 to P30) have indicated acute oxidative energy metabolic decreases below 24 h after TBI, which generally recovered by 48 h. However, marked neurodegeneration and altered neural functional connectivity have been observed at later stages into adolescence. As secondary neurodegeneration is most prominent during the first week after TBI in the rat model, we hypothesized that the subacute TBI-metabolome may contain predictive markers of neurodegeneration. Sham and TBI metabolomes were examined at 72 h after a mild to moderate intensity TBI in male Sprague-Dawley rats aged P31. Sensorimotor behavior was assessed at 24, 48 and 72 h after injury, followed by 72-hour postmortem brain removal for metabolomics using Liquid Chromatography/Mass Spectrometry (LC-MS) measurement. Broad TBI-induced metabolomic shifts occurred with relatively higher intensity in the injury-lateralized (ipsilateral) hemisphere. Intensity of metabolomic perturbation correlated with the extent of sensorimotor behavioral deficit. N-acetyl-aspartate (NAA) levels at 72 h after TBI, predicted the extent of neurodegeneration assessed histochemically 7-days post TBI. Results from the multivariate untargeted approach clearly distinguished metabolomic shifts induced by TBI. Several pathways including amino acid, fatty acid and energy metabolism continued to be affected at 72 h after TBI, whose collective effects may determine the overall pathological response after TBI in early development including neurodegeneration.


Estimation of the Mismatch between Admission and Discharge Diagnosis for Respiratory Patients, and Implications on the Length of Stay and Hospital Charges.
Admission and discharge diagnoses in hospitals are often in discord, and this has significant implications for the cost of care and patient safety. In this paper we used medical claims data to examine these differences for beneficiaries with respiratory conditions and quantified the degree to which specific respiratory conditions are mistaken for other ones, on admission. Since respiratory problems have seasonality, we performed two separate analyses, for summer and for winter admissions. The length of stay and hospital charges were compared between matching and non-matching {admission, discharge Dx} pairs, using independent samples t-test analysis. Results were integrated into a standalone application where physicians can select an admission diagnosis to see (i) the probability for this diagnosis to be correct (matching the discharge Dx), (ii) the probabilities for mismatch and (iii) pair-specific differential diagnosis criteria to consider reassessing the patient before confirming the admission diagnosis.


Do plant populations on distinct inselbergs talk to each other? A case study of genetic connectivity of a bromeliad species in an Ocbil landscape.
Here, we explore the historical and contemporaneous patterns of connectivity among Encholirium horridum populations located on granitic inselbergs in an Ocbil landscape within the Brazilian Atlantic Forest, using both nuclear and chloroplast microsatellite markers. Beyond to assess the E. horridum population genetic structure, we built species distribution models across four periods (current conditions, mid-Holocene, Last Glacial Maximum [LGM], and Last Interglacial) and inferred putative dispersal corridors using a least-cost path analysis to elucidate biogeographic patterns. Overall, high and significant genetic divergence was estimated among populations for both nuclear and plastid DNA (ΦST(n) = 0.463 and ΦST(plastid) = 0.961, respectively, p < .001). For nuclear genome, almost total absence of genetic admixture among populations and very low migration rates were evident, corroborating with the very low estimates of immigration and emigration rates observed among E. horridum populations. Based on the cpDNA results, putative dispersal routes in Sugar Loaf Land across cycles of climatic fluctuations in the Quaternary period revealed that the populations' connectivity changed little during those events. Genetic analyses highlighted the low genetic connectivity and long-term persistence of populations, and the founder effect and genetic drift seemed to have been very important processes that shaped the current diversity and genetic structure observed in both genomes. The genetic singularity of each population clearly shows the need for in situ conservation of all of them.


Evaluation of the effects of porcine genogroup 1 torque teno virus in gnotobiotic swine.
To determine whether porcine genogroup 1 torque teno virus (g1-TTV) can infect and cause disease in gnotobiotic swine. 20 conventional baby pigs and 46 gnotobiotic baby pigs. Porcine g1-TTV was transmitted from conventional swine to gnotobiotic pigs via pooled leukocyte-rich plasmas (n=18) that had positive results for g1-TTV DNA. Bone marrow-liver homogenates that had positive results for torque teno virus (TTV) were used in 4 serial passages in gnotobiotic pigs (2 pigs/passage). A pathogenesis experiment was conducted with in vivo passages of g1-TTV in various groups of gnotobiotic pigs. All g1-TTV inoculated pigs had no clinical signs but developed interstitial pneumonia, transient thymic atrophy, membranous glomerulonephropathy, and modest lymphocytic to histiocytic infiltrates in the liver after inoculation with the TTV-containing tissue homogenate; these changes were not detected in uninoculated control pigs or pigs injected with tissue homogenate devoid of TTV DNAs. In situ hybridization was used to identify g1-TTV DNAs in bone marrow mononuclear cells. Analysis of these data revealed that porcine g1-TTV was readily transmitted to TTV-naïve swine and that infection was associated with characteristic pathologic changes in gnotobiotic pigs inoculated with g1-TTV. Thus, g1-TTV could be an unrecognized pathogenic viral infectious agent of swine. This indicated a directly associated induction of lesions attributable to TTV infection in swine for a virus of the genus Anellovirus.


Basins of attraction for species extinction and coexistence in spatial rock-paper-scissors games.
We study the collective dynamics of mobile species under cyclic competition by breaking the symmetry in the initial populations and examining the basins of the two distinct asymptotic states: extinction and coexistence, the latter maintaining biodiversity. We find a rich dependence of dynamical properties on initial conditions. In particular, for high mobility, only extinction basins exist and they are spirally entangled, but a basin of coexistence emerges when the mobility parameter is decreased through a critical value, whose area increases monotonically as the parameter is further decreased. The structure of extinction basins for high mobility can be predicted by a mean-field theory. These results provide a more comprehensive picture for the fundamental issue of species coexistence than previously achieved.


Astrovirus induces diarrhea in the absence of inflammation and cell death.
Astroviruses are a leading cause of infantile viral gastroenteritis worldwide. Very little is known about the mechanisms of astrovirus-induced diarrhea. One reason for this is the lack of a small-animal model. Recently, we isolated a novel strain of astrovirus (TAstV-2) from turkeys with the emerging infectious disease poult enteritis mortality syndrome. In the present studies, we demonstrate that TAstV-2 causes growth depression, decreased thymus size, and enteric infection in infected turkeys. Infectious TAstV-2 can be recovered from multiple tissues, including the blood, suggesting that there is a viremic stage during infection. In spite of the severe diarrhea, histopathologic changes in the intestine were mild and there was a surprising lack of inflammation. This may be due to the increased activation of the potent immunosuppressive cytokine transforming growth factor beta during astrovirus infection. These studies suggest that the turkey will be a useful small-animal model with which to study astrovirus pathogenesis and immunity.


[Patterns of lipofuscin accumulation in ganglionic nerve cells of superior cervical ganglion in humans].
Considering available literature lipofuscin is a classical age pigment of postmitotic cells, and a consistently recognized phenomenon in humans and animals. Lipofuscin accumulation is characteristic for nerve cells that are postmitotic. This research was focused on lipofuscin accumulation in ganglionic cells (GC) (postganglionic sympathetic cell bodies) of superior cervical ganglion in humans during ageing. We analysed 30 ganglions from cadavers ranging from 20 to over 80 years of age. As material the tissue samples were used from the middle portion of the ganglion, which was separated from the surrounding tissue by the method of macrodissection. The tissue samples were routinely fixed in 10% neutral formalin and embedded in paraffin for classical histological analysis, then three consecutive (successive) sections 5 microm thick were made and stained with hematoxylin and eosin method (HE), silver impregnation technique by Masson Fontana and trichrome stain by Florantin. Immersion microscopy was used to analyse patterns of lipofuscin accumulation during ageing making possible to distinguish diffuse type (lipofuscin granules were irregularly distributed and non-confluent), unipolar type (lipofuscin granules were grouped at the end of the cell), bipolar type (lipofuscin granules were concentrated at the two opposite ends of a cell with the nucleus in between at the center of a cell), annular type (lipofuscin granules were in the shape of a complete or incomplete ring around the nucleus) and a cell completely filled with lipofuscin (two subtypes distinguishing, one with visible a nucleus, and the other with invisible one). Even at the age of 20 there were cells with lipofuscin granules accumulated in diffuse way, but in smaller numbers; the GC without lipofuscin were dominant. Growing older, especially above 60 years, all of the above mentioned patterns of lipofuscin accumulation were present with the evident increase in cells completely filled with lipofuscin, but cells without lipofuscin were also present even in the oldest persons. Lipofuscin is present in all periods of ageing with a different intensity of accumulation. GC without the pigment, diffusely distributed, as well as very rare cells with a unipolar type of lipofuscin distribution are characteristic for the age of 20-60 years. In the age above 60 years, except the cells without pigment and diffuse accumulation type, there are also bipolar and annular types and forms in which cells are completely filled with lipofuscin granules.


Endometrial carcinoma tumorigenesis and pharmacotherapy research.
Endometrial carcinoma is the common malignant tumor of the female genital tract, and its incidence is increasing. Two different clinicopathological subtypes are recognized based on epidemiology, genetic carcinogenesis and clinical behavior. Understanding and identifying molecular biology and genetics is essential to the development of novel therapies. This article reviews the current understanding of its risk factors, recent conceptions on its tumorigenesis and advances on its drug therapies.


Lysophosphatidic acid and thrombin receptors require both G alpha12 and G alpha13 to regulate axonal morphology in hippocampal neurons.
The G alpha subunits of the G(12) family of heterotrimeric guanine nucleotide-binding proteins (G proteins), defined by G alpha(12) and G alpha(13), have many cellular functions in common, including stimulation of stress fiber formation and focal adhesion assembly via the small GTPase RhoA activation. We and others previously showed that G alpha(12) and G alpha(13) mediate neurite retraction in neuronal cell lines, but their roles in primary cultured neurons have not been adequately understood. Here, we found that expression of constitutively active mutants of G alpha(12) or G alpha(13) caused growth cone collapse dependent on Rho-kinase activity in hippocampal neurons. The stimulation of thrombin and lysophosphatidic acid (LPA) receptors, which have been thought to selectively couple to G alpha(12) and G alpha(13), respectively, caused growth cone collapse and suppressed axon branching dependent on Rho-kinase activity in hippocampal neurons. Thrombin- and LPA-induced growth cone collapse was suppressed by both single knockdown of G alpha(12) and G alpha(13) with short hairpin RNAs and this suppression was augmented by double knockdown of both G alpha(12) and G alpha(13). These results suggest that thrombin and LPA receptors couple to both G alpha(12) and G alpha(13) for growth cone collapse.


Immunotherapy for type 1 diabetes.
Although many approaches have been tested to overcome the insulin dependence caused by the pancreatic β-cells destruction observed in individuals affected by type 1 diabetes (T1D), medical research has largely failed to halt the onset or to reverse T1D. In this work, the state of the art of immunotherapy will be examined, and the most important achievement in the field will be critically discussed. Particularly, we will focus on the clinical aspect, thus avoiding the tedious preclinical work done in NOD mice, which has been so poorly translated to the bedside. Stem cell therapies achieved thus this far the most promising results, while immune ablation and standard immunosuppressants did not maintain the premises of preclinical results. The next step will be to generate a feasible and safe clinical approach in order to cure the thousands of patients affected by T1D.


Canine olfactory detection and its relevance to medical detection.
The extraordinary olfactory sense of canines combined with the possibility to learn by operant conditioning enables dogs for their use in medical detection in a wide range of applications. Research on the ability of medical detection dogs for the identification of individuals with infectious or non-infectious diseases has been promising, but compared to the well-established and-accepted use of sniffer dogs by the police, army and customs for substances such as money, explosives or drugs, the deployment of medical detection dogs is still in its infancy. There are several factors to be considered for standardisation prior to deployment of canine scent detection dogs. Individual odours in disease consist of different volatile organic molecules that differ in magnitude, volatility and concentration. Olfaction can be influenced by various parameters like genetics, environmental conditions, age, hydration, nutrition, microbiome, conditioning, training, management factors, diseases and pharmaceuticals. This review discusses current knowledge on the function and importance of canines' olfaction and evaluates its limitations and the potential role of the dog as a biomedical detector for infectious and non-infectious diseases.


Clinical Trials with Oncolytic Viruses: Current and Future Prospects.
Reviewing the research in the field of oncolytic virus therapy (OVT) of the past two decades, it is inspiring to see the enormous amount of success accomplished by the scholars of this innovative therapeutic technique. Though the experimental trials have been ongoing from 1990s, however, it took a leap forward with approval of the clinical trials in China, 2005. The world's first oncolytic virus to be approved by their government was adenovirus (with E1B 55K gene deletion) for head and neck cancer therapy along with chemotherapy.


Divergence in the internal genital morphology of females and correlated divergence in male intromittent structures among populations of a millipede.
Our understanding of genital evolution comes largely from studies of male genitalia. Females have received far less attention because of the difficulties inherent in quantifying the shapes of their internal genital structures. Here we combine advances in micro-computed tomography with a new landmark free method of quantifying three-dimensional trait shape, to document patterns of divergence in female genital shape, and the correlated divergence of male genitalia among populations of the millipede Antichiropus variabilis. We used single-nucleotide polymorphisms to estimate levels of neutral genetic divergence among seven populations of millipede. Genetic divergence was high and correlated with geographic distance. Comparing phenotypic divergence in genital shape to neutral genetic divergence, we found that genital shape for both females and males has diverged more than would be expected from random drift, consistent with a pattern of directional selection. While there was significant covariation between female and male genital shape across populations, the magnitude of divergence in genital shape between the sexes was not correlated. Our results demonstrate the utility of using three-dimensional scanning technologies to examine female genital traits and add to a small but growing number of studies showing that like male genitalia, female genitalia can be under strong directional selection.


Regulation of sialic acid transport and catabolism in Haemophilus influenzae.
Virulence of nontypeable Haemophilus influenzae (NTHi) is dependent on the decoration of lipooligosaccharide with sialic acid. This sugar must be derived from the host, as NTHi cannot synthesize sialic acids. NTHi can also use sialic acid as a carbon source. The genes encoding the sialic acid transporter and the genes encoding the catabolic activities are localized to two divergently transcribed operons, the siaPT operon and the nan operon respectively. In this study, we identified SiaR as a repressor of sialic acid transport and catabolism in NTHi. Inactivation of siaR resulted in the unregulated expression of the genes in both operons. Unregulated catabolism of sialic acid in the siaR mutant resulted in the reduction of surface sialylation and an increase in serum sensitivity. In addition to SiaR-mediated repression, CRP, the cAMP receptor protein, was shown to activate expression of the siaPT operon but not the nan operon. We describe a model in which SiaR and CRP work to modulate intracellular sialic acid levels. Our results demonstrate the importance of SiaR-mediated regulation to balance the requirement of surface sialylation and the toxic accumulation of intracellular sialic acid.


A plant-derived morphinan as a novel lead compound active against malaria liver stages.
The global spread of multidrug-resistant malaria parasites has led to an urgent need for new chemotherapeutic agents. Drug discovery is primarily directed to the asexual blood stages, and few drugs that are effective against the obligatory liver stages, from which the pathogenic blood infection is initiated, have become available since primaquine was deployed in the 1950s. Using bioassay-guided fractionation based on the parasite's hepatic stage, we have isolated a novel morphinan alkaloid, tazopsine, from a plant traditionally used against malaria in Madagascar. This compound and readily obtained semisynthetic derivatives were tested for inhibitory activity against liver stage development in vitro (P. falciparum and P. yoelii) and in vivo (P. yoelii). Tazopsine fully inhibited the development of P. yoelii (50% inhibitory concentration [IC50] 3.1 muM, therapeutic index [TI] 14) and P. falciparum (IC50 4.2 muM, TI 7) hepatic parasites in cultured primary hepatocytes, with inhibition being most pronounced during the early developmental stages. One derivative, N-cyclopentyl-tazopsine (NCP-tazopsine), with similar inhibitory activity was selected for its lower toxicity (IC50 3.3 muM, TI 46, and IC50 42.4 muM, TI 60, on P. yoelii and P. falciparum hepatic stages in vitro, respectively). Oral administration of NCP-tazopsine completely protected mice from a sporozoite challenge. Unlike the parent molecule, the derivative was uniquely active against Plasmodium hepatic stages. A readily obtained semisynthetic derivative of a plant-derived compound, tazopsine, has been shown to be specifically active against the liver stage, but inactive against the blood forms of the malaria parasite. This unique specificity in an antimalarial drug severely restricts the pressure for the selection of drug resistance to a parasite stage limited both in numbers and duration, thus allowing researchers to envisage the incorporation of a true causal prophylactic in malaria control programs.


Development of quantitative vitellogenin-ELISAs for fish test species used in endocrine disruptor screening.
The yolk protein precursor vitellogenin (Vtg) in plasma has proved to be a simple and sensitive biomarker for assessing exposure of fish to environmental estrogens. Within international bodies such as the Organization for Economic Cooperation and Development (OECD) work is ongoing to develop screening and testing programmes for endocrine disrupting effects of new chemicals, and in the focus of this development are the fish test species common carp (Cyprinus carpio), fathead minnow (Pimephales promelas), zebrafish (Danio rerio) and Japanese medaka (Oryzias latipes). In this study we have developed quantitative enzyme linked immunosorbent assays (ELISAs) for Vtg in common carp/fathead minnow, zebrafish and Japanese medaka. The assays were developed using a combination of monoclonal and polyclonal fish Vtg antibodies in a sandwich format, using stabilized Vtg from the test species as a standard. The carp Vtg ELISA has a working range of 1-63 ng/mL, a minimal detection limit of 0.6 ng/mL, and may also be used for quantification of Vtg in fathead minnow. In fathead minnow whole-body homogenate samples, the practical detection limit is 400 ng/mL due to the matrix effect. The zebrafish Vtg ELISA has a working range of 0.5-63 ng/mL, a minimal detection limit of 0.4 ng/mL, and a practical detection limit of 200 ng/mL in whole-body homogenate samples. The medaka Vtg ELISA has a working range of 0.25-16 ng/mL, a minimal detection limit of 0.1 ng/mL, and a practical detection limit of 125 ng/mL in whole-body homogenate samples. The intra- and inter-assay variations were below 20% for all assays. The assays were evaluated with sets of representative samples spanning the wide dynamic range of Vtg-levels found in fish exposed to environmental estrogens, and all three assays are currently undergoing international inter-laboratory validation.


Simulating energy transfer dynamics in the Fenna-Matthews-Olson complex via the modified generalized quantum master equation.
The generalized quantum master equation (GQME) provides a general and formally exact framework for simulating the reduced dynamics of open quantum systems. The recently introduced modified approach to the GQME (M-GQME) corresponds to a specific implementation of the GQME that is geared toward simulating the dynamics of the electronic reduced density matrix in systems governed by an excitonic Hamiltonian. Such a Hamiltonian, which is often used for describing energy and charge transfer dynamics in complex molecular systems, is given in terms of diabatic electronic states that are coupled to each other and correspond to different nuclear Hamiltonians. Within the M-GQME approach, the effect of the nuclear degrees of freedom on the time evolution of the electronic density matrix is fully captured by a memory kernel superoperator, which can be obtained from short-lived (compared to the time scale of energy/charge transfer) projection-free inputs. In this paper, we test the ability of the M-GQME to predict the energy transfer dynamics within a seven-state benchmark model of the Fenna-Matthews-Olson (FMO) complex, with the short-lived projection-free inputs obtained via the Ehrenfest method. The M-GQME with Ehrenfest-based inputs is shown to yield accurate results across a wide parameter range. It is also found to dramatically outperform the direct application of the Ehrenfest method and to provide better-behaved convergence with respect to memory time in comparison to an alternative implementation of the GQME approach previously applied to the same FMO model.


[Risk factors of evolution of postpartum hemorrhage towards severe postpartum hemorrhage: A case-control study].
To describe the incidence and risk factors for evolution of postpartum haemorrhage towards severe. Epidemiologic, observational, analytical, case-control study was done from total data of deliveries in Complexo Hospitalario de Ourénse between January 1st 2004 and June 30th 2014. Mann-Whitney U test was used to determine the differences between cases and controls. The statistical analyses were made with the informatic programs Spss 15.0 y Epidat 3.0. We considered statistical significance for p < 0.05. The initial size of the sample was 17,116 deliveries from which we selected 150 patients with the diagnosis of postpartum haemorrhage. The incidence for HPSe form all deliveries was 3.3% reaching 36% of the total of postpartum haemorrhages. 79.63% of HPSe showed symptoms withing the first 24h postpartum, but we found that 20.37% debuted as secondary postpartum haemorrhages. BMI ≥ 35, hypertensive gestational manifestations, labor's second phase ≥ 120 minutes and weight at birth > 4000 g presented statistical significance as risk factor for evolution to severe postpartum haemhorrage. The relative risk for evolution towards HPSe was 2.81 for instrumental delivery and 3.55 for cesarean section. The most prevalent etiology was uterine atony. The incidence of HPSe in our hospital is low, as well as secondary maternal mortality. The major risk factor for the appearance of the clinical symptoms is cesarean section, followed, in less proportion by instrumental delivery. It is possible for the HPSe to make its appearance delayed after delivery, usually secondary to infrequent and non well-known clinical presentations.


Switch to Aflibercept in Diabetic Macular Edema Patients Unresponsive to Previous Anti-VEGF Therapy.
Purpose. The aim was to evaluate the efficacy of aflibercept in patients with diabetic macular edema (DME) unresponsive to prior anti-VEGF therapy. Methods. Retrospective review of DME unresponsive to previous anti-VEGF switched to aflibercept with 3 months of follow-up. Changes in best correct visual acuity (BCVA), central retinal thickness (CRT), and frequency of injections were analyzed. The percentage of subjects who had ≥20/40 (logMAR equivalent 0.3) and ≤20/200 (logMAR equivalent 1) was evaluated. Results. A total of 32 eyes from 26 patients were included. Mean age was 65 ± 10 years old. The mean number of previous anti-VEGF injections was 5.34 ± 2.38, and the mean number of aflibercept injections at the end of the study was 2.00 ± 0.00. The CRT at baseline was 501.47 ± 150.51 μm and 367.97 ± 124.61 μm at 3 months of follow-up (P < 0.001). The logMAR BCVA at baseline was 0.71 ± 0.36 and 0.65 ± 0.33 at the end of the follow-up (P = 0.037). At baseline, 12.5% of patients had ≥20/40 compared with 25% at the end of follow-up. At baseline, 28.13% of patients had 20/200 or inferior vision compared with 15.63% at the end of the follow-up. Conclusions. DME patients unresponsive to previous multiple ranibizumab injections demonstrate a significant anatomical and functional improvement with the switch to aflibercept.


A meta-analysis comparing the outcomes of LigaSure Small Jaw versus clamp-and-tie technique or Harmonic Focus Scalpel in thyroidectomy.
LigaSure (LS) Small Jaw is a surgical hemostasis equipment that is newly introduced in thyroid surgery. The objective of this study is to assess the short-term efficacy and safety outcomes of LS Small Jaw compared with clamp-and-tie technique or Harmonic Focus Scalpel in thyroidectomy. A literature search was performed in the PubMed and Embase databases (until June 12, 2016) that reported the comparisons between LS Small Jaw and other techniques in thyroidectomy. Quality assessments were performed according to The Cochrane Collaboration's risk of bias tool and a modification of the Newcastle-Ottawa Scale in randomized controlled trials (RCTs) and non-RCTs, respectively. All statistical analyses were conducted using RevMan 5.3. Finally, 7 studies with 813 patients were included into the meta-analysis, and all included studies were comparable with moderate-to-high quality. There was significant reduced operative time in LS Small Jaw, compared with clamp-and-tie (mean difference [MD] = -17.49, 95% confidence interval [CI]: -22.20 to 12.77, P < 0.00001) or Harmonic Focus Scalpel (MD = -2.29, 95% CI: -3.19 to 1.39, P < 0.00001). Besides, other perioperative outcomes including intraoperative blood loss and postoperative blood loss favored LS Small Jaw compared with clamp-and-tie. In terms of complications, less-temporary hypocalcemia rate was observed in LS Small Jaw compared with clamp-and-tie (odds ratio [OR] = 0.49, 95% CI: 0.27-0.90, P = 0.02), although no significant difference was detected compared with Harmonic Focus Scalpel (OR = 0.47, 95% CI: 0.14-1.56, P = 0.22). Other complications such as length of hospital stay, permanent hypocalcemia, temporary or permanent recurrent laryngeal nerve palsy, and hematomas were not significant. In conclusion, LS Small Jaw is more favorable than clamp-and-tie technique or Harmonic Focus Scalpel in thyroidectomy.


Environmental factors and autoimmune thyroiditis.
Autoimmune thyroiditis, of which Hashimoto thyroiditis represents the most frequent form, is an inflammatory state of the thyroid gland that results from the interaction between genetic variants that promote susceptibility and environmental factors. High iodine intake, selenium deficiency, pollutants such as tobacco smoke, infectious diseases such as chronic hepatitis C, and certain drugs are implicated in the development of autoimmune thyroiditis, primarily in genetically predisposed people. Long-term iodine exposure leads to increased iodination of thyroglobulin, which increases its antigenicity and initiates the autoimmune process in genetically susceptible individuals. Selenium deficiency decreases the activity of selenoproteins, including glutathione peroxidases, which can lead to raised concentrations of hydrogen peroxide and thus promote inflammation and disease. Such environmental pollutants as smoke, polychlorinated biphenyls, solvents and metals have been implicated in the autoimmune process and inflammation. Environmental factors have not yet, however, been sufficiently investigated to clarify their roles in pathogenesis, and there is a need to assess their effects on development of the autoimmune process and the mechanisms of their interactions with susceptibility genes.


A Framework for Simulating Cardiac MR Images With Varying Anatomy and Contrast.
One of the limiting factors for the development and adoption of novel deep-learning (DL) based medical image analysis methods is the scarcity of labeled medical images. Medical image simulation and synthesis can provide solutions by generating ample training data with corresponding ground truth labels. Despite recent advances, generated images demonstrate limited realism and diversity. In this work, we develop a flexible framework for simulating cardiac magnetic resonance (MR) images with variable anatomical and imaging characteristics for the purpose of creating a diversified virtual population. We advance previous works on both cardiac MR image simulation and anatomical modeling to increase the realism in terms of both image appearance and underlying anatomy. To diversify the generated images, we define parameters: 1)to alter the anatomy, 2) to assign MR tissue properties to various tissue types, and 3) to manipulate the image contrast via acquisition parameters. The proposed framework is optimized to generate a substantial number of cardiac MR images with ground truth labels suitable for downstream supervised tasks. A database of virtual subjects is simulated and its usefulness for aiding a DL segmentation method is evaluated. Our experiments show that training completely with simulated images can perform comparable with a model trained with real images for heart cavity segmentation in mid-ventricular slices. Moreover, such data can be used in addition to classical augmentation for boosting the performance when training data is limited, particularly by increasing the contrast and anatomical variation, leading to better regularization and generalization. The database is publicly available at https://osf.io/bkzhm/ and the simulation code will be available at https://github.com/sinaamirrajab/CMRI.


Loss of consciousness as criterion of +Gz tolerance at Institute of Aviation Medicine MMA during +Gz acceleration selective test.
+Gz induced loss of consciousness (G-LOC) is one of the most serious threats to aircrews flying high performance fighter aircraft. From the early beginning of use of our Centrifuge, use in selection was primary task. As a functional "endpoints" we use criteria: loss of peripheral vision, extreme pulse rate (above 180 b.p.m.), arrhythmias and loss of consciousness. The key-method in selection the candidate who tolerates +Gz stress on the best way is selection by common selective centrifuge "Test of linear increasing of acceleration" (TOLIA). We used gradual onset rate (GOR--0.1 G/s) and maximum/peak value: +5.5 Gz, +6.0 Gz and 7.0 Gz. Applied peak value depends on the goal of the test. The lowest peak value is for candidates planned for Air Academy, higher peak value is for those pilots planned for training to supersonic combat aircrafts and the highest peak value is for pilots who are planned to fly High performance combat aircrafts. We examined 2192 candidates in the last 20 years. Eleven subjects experienced G-LOC episodes. All episodes of G-LOC had occurred occasionally and without warning symptoms (loss of peripheral vision, gray out, blackout). The percentage of subjects having G-LOC episodes was 0.50%. Nine subjects experienced G-LOC during primary selection (+5.5 Gz), one G-LOC were observed at secondary selection (+6.0 Gz) and one G-LOC was observed during tertiary selection (+7 Gz). G-LOC is the only "endpoint" in the centrifuge selection which disqualifies the candidate at once and forever for planned flying duties. The other "endpoints" (loss of peripheral vision, heart rate above 180 b.p.m., arrhythmias) allow one more testing, not less than seven days later.


Modeling impact and cost-effectiveness of driving-Y gene drives for malaria elimination in the Democratic Republic of the Congo.
Malaria elimination will be challenging in countries that currently continue to bear high malaria burden. Sex-ratio-distorting gene drives, such as driving-Y, could play a role in an integrated elimination strategy if they can effectively suppress vector populations. Using a spatially explicit, agent-based model of malaria transmission in eight provinces spanning the range of transmission intensities across the Democratic Republic of the Congo, we predict the impact and cost-effectiveness of integrating driving-Y gene drive mosquitoes in malaria elimination strategies that include existing interventions such as insecticide-treated nets and case management of symptomatic malaria. Gene drive mosquitoes could eliminate malaria and were the most cost-effective intervention overall if the drive component was highly effective with at least 95% X-shredder efficiency at relatively low fertility cost, and associated cost of deployment below 7.17 $int per person per year. Suppression gene drive could be a cost-effective supplemental intervention for malaria elimination, but tight constraints on drive effectiveness and cost ceilings may limit its feasibility.


Improving data collection processes for routine evaluation of treatment cost-effectiveness.
The healthcare system in Finland has begun routine collection of health-related quality of life (HRQoL) information for patients in hospitals to support more systematic cost-effectiveness analysis (CEA). This article describes the systematic collection of HRQoL survey data, and addresses challenges in the implementation of patient surveys and acquisition of cost data in the case hospital. Challenges include problems with incomplete data and undefined management processes. In order to support CEA of hospital treatments, improvements are sought from the process management literature and in the observation of healthcare professionals. The article has been written from an information system and process management perspective, concluding that process ownership, automation of data collection and better staff training are keys to generating more reliable data.


Comparison of the level of cellular retinoid-binding proteins and susceptibility to retinoid-induced growth inhibition of various neoplastic cell lines.
The presence and level of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) were determined in several neoplastic cell lines. These cells exhibited different degrees of susceptibility to growth inhibition in culture by two retinoids, retinyl acetate and retinoic acid. CRABP was detected in 10 and CRBP in 3 of the 11 tested cell lines. The levels of CRBP and CRABP were in the ranges 15-3,400 and 4-1,290 pmol per 10(9) cells, respectively, as determined by sucrose gradient centrifugation. Cell lines that contained CRABP included S91 and B16 melanomas; Mm5mT and DMBA No. 8 mammary adenocarcinomas; BW5147, BW5147.RicR, and P3 neoplastic lymphoid cells; F361.2 (a hybrid cell line obtained by fusion of MSV3T3 and BW5147); MSV3T3 sarcoma; and RAW8 lymphosarcoma. All but the last two cell lines were inhibited by retinoic acid in culture. CRBP was detected in extracts of S91, Mm5mT, and RAW8. Retinyl acetate inhibited the growth of all cell lines with the exception of RAW8, MSV3T3, and F361.2. No correlation was found between the level of either binding protein and the extent of growth inhibition by either retinyl acetate or retinoic acid. Neither of the binding proteins was detected in L1210-A5 leukemia cells, whose proliferation can be inhibited by both retinyl acetate and retinoic acid. These data indicated that screening cell lines for the presence and level of CRBP and CRABP is not sufficient to predict the susceptibility of cultured cells to growth inhibition by retinoids.


Dr. Browse, a digital image file format Browser.
The emerging widespread adoption of the Digital Imaging Communications in Medicine (DICOM) standard will increase the demand for radiologic image transfer between radiologic image acquisition, archive, display and printing devices. Unfortunately, there are and will continue to be many devices that do not and will not support this standard, especially older radiologic equipment and devices from nonradiologic vendors. Determining the image file format characteristics of images from such equipment is often difficult, and done on an ad hoc basis. We have developed a software tool that assists users in determining the image file format parameters of unknown radiologic images.


Selection Probability for Rare Variant Association Studies.
In human genome research, genetic association studies of rare variants have been widely studied since the advent of high-throughput DNA sequencing platforms. However, detection of outcome-related rare variants still remains a statistically challenging problem because the number of observed genetic mutations is extremely rare. Recently, a power set-based statistical selection procedure has been proposed to locate both risk and protective rare variants within the outcome-related genes or genetic regions. Although it can perform an individual selection of rare variants, the procedure has a limitation that it cannot measure the certainty of selected rare variants. In this article, we propose a selection probability of individual rare variants, where selection frequencies of rare variants are computed based on bootstrap resampling. Therefore, it can quantify the certainty of both selected and unselected rare variants. Also, a new selection approach using a threshold of selection probability is introduced and compared with some existing selection procedures from extensive simulation studies and real sequencing data analysis. We have demonstrated that the proposed approach outperforms the existing methods in terms of a selection power.


Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction.
To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the same composition were prepared: 1. Spray dried dispersion (SDD) that is homogenous at molecular level, 2. Physical blend of SDD (80% drug loading) and pure polymer (SDD-PB) that is homogenous only at powder level. Flory-Huggins interaction parameters (χ) between KTZ and the four polymers were obtained by Flory-Huggins model fitting. Solution (13)C NMR and FT-IR were conducted to investigate the specific drug-polymer interaction in the solution and solid state, respectively. Intrinsic dissolution of both the drug and the polymer from ASDs were studied using a Higuchi style intrinsic dissolution apparatus. PXRD and confocal Raman microscopy were used to confirm the absence of drug crystallinity on the tablet surface before and after dissolution study. In solid state, KTZ is completely miscible with PVP, PVP-VA, or HPMC-AS, demonstrated by the negative χ values of -0.36, -0.46, -1.68, respectively; while is poorly miscible with HPMC shown by a positive χ value of 0.23. According to solution (13)C NMR and FT-IR studies, KTZ interacts with HPMC-AS strongly through H-bonding and dipole induced interaction; with PVPs and PVP-VA moderately through dipole-induced interactions; and with HPMC weakly without detectable attractive interaction. Furthermore, the "apparent" strength of drug-polymer interaction, measured by the extent of peak shift on NMR or FT-IR spectra, increases with the increasing number of interacting drug-polymer pairs. For ASDs with the presence of considerable drug-polymer interactions, such as KTZ/PVPs, KTZ/PVP-VA, or KTZ /HPMC-AS systems, drug released at the same rate as the polymer when intimate drug-polymer mixing was ensured (i.e., the SDD systems); while drug released much slower than the polymer when molecular level mixing or drug-polymer interaction was absent (SDD-PB systems). For ASDs without drug-polymer interaction (i.e., KTZ/HPMC systems), the mixing homogeneity had little impact on the release rate of either the drug or the polymer thus SDD and SDD-PB demonstrated the same drug or polymer release rate, while the drug released slowly and independently of polymer release. The initial drug release from an ASD was controlled by 1) the polymer release rate; 2) the strength of drug-polymer interaction, including the intrinsic interaction caused by the chemistry of the drug and the polymer (measured by the χ value), as well as that the apparent interaction caused by the drug-polymer ratio (measure by the extent of peak shift on spectroscopic analysis); and 3) the level of mixing homogeneity between the drug and polymer. In summary, the selection of polymer, drug-polymer ratio, and ASD processing conditions have profound impacts on the dissolution behavior of ASDs. Graphical Abstract Relationship between initial drug and polymer dissolution rates from amorphous solid dispersions with different mixing uniformity and drug-polymer interactions.


Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers.
It is well known that tumor-infiltrating lymphocytes (TILs) and, to a lesser extent, peripheral blood lymphocytes from patients with advanced-stage cancer have a poor immune response. Regulatory T cells (T-regs), characterized by coexpression of CD4 and CD25 markers, can inhibit the immune response mediated by CD4+/CD25- and CD8+ T cells. In the present study, we evaluated the prevalence of T-regs in peripheral blood and TILs in patients with gastric and esophageal cancers. The population of CD4+/CD25+ cells as a percentage of total CD3+ cells was evaluated by flow cytometric analysis with triple-color staining. To assess the functional activity of CD4+/CD25+ cells, CD4+/CD25+ or CD4+/CD25- cells were purified from peripheral blood mononuclear cells with magnetic beads. The cytokine production [interleukin (IL)-10 and IFN-gamma] from the CD4+/CD25+ cells in response to anti-CD3 stimulation was evaluated. Also, the antiproliferative function of CD4+/CD25+ cells was measured by evaluating the proliferative activity of CD4+/CD25- cells in response to anti-CD3 plus anti-CD28 in the presence of autologous CD4+/CD25+ cells. The prevalence of peripheral blood CD4+/CD25+ cells in both gastric (n = 20; 14.2 +/- 4.9%) and esophageal cancer patients (n = 10; 19.8 +/- 6.9%) was significantly higher than that in healthy donors (n = 16; 7.2 +/- 2.1%). The population of CD4+/CD25+ cells in the TILs of gastric cancer patients with advanced disease (19.8 +/- 4.5%) was significantly higher than that in TILs of patients with early-stage disease (4.8 +/- 2.1%) or that in intraepithelial lymphocytes of normal gastric mucosa (4.0 +/- 1.2%). As a functional consequence, CD4+/CD25+ cells did not produce IFN-gamma, whereas CD4+/CD25- cells secreted IFN-gamma. Moreover, CD4+/CD25+ cells produced large amounts of IL-10, whereas CD4+/CD25- cells secreted little IL-10. The proliferation of CD4+/CD25- cells was inhibited in the presence of CD4+/CD25+ cells in a dose-dependent manner, confirming that CD4+/CD25+ has an inhibitory activity corresponding to T-regs. The populations of CD4+/CD25+ T-regs in peripheral blood and TILs in patients with gastric and esophageal cancers were significantly higher in comparison with those in healthy donors or normal mucosa.


Inhibition of Inwardly Rectifying Potassium (Kir) 4.1 Channels Facilitates Brain-Derived Neurotrophic Factor (BDNF) Expression in Astrocytes.
Inwardly rectifying potassium (Kir) 4.1 channels in astrocytes regulate neuronal excitability by mediating spatial potassium buffering. Although dysfunction of astrocytic Kir4.1 channels is implicated in the development of epileptic seizures, the functional mechanisms of Kir4.1 channels in modulating epileptogenesis remain unknown. We herein evaluated the effects of Kir4.1 inhibition (blockade and knockdown) on expression of brain-derived neurotrophic factor (BDNF), a key modulator of epileptogenesis, in the primary cultures of mouse astrocytes. For blockade of Kir4.1 channels, we tested several antidepressant agents which reportedly bound to and blocked Kir4.1 channels in a subunit-specific manner. Treatment of astrocytes with fluoxetine enhanced BDNF mRNA expression in a concentration-dependent manner and increased the BDNF protein level. Other antidepressants (e.g., sertraline and imipramine) also increased the expression of BDNF mRNA with relative potencies similar to those for inhibition of Kir4.1 channels. In addition, suppression of Kir4.1 expression by the transfection of small interfering RNA (siRNA) targeting Kir4.1 significantly increased the mRNA and protein levels of BDNF. The BDNF induction by Kir4.1 siRNA transfection was suppressed by the MEK1/2 inhibitor U0126, but not by the p38 MAPK inhibitor SB202190 or the JNK inhibitor SP600125. The present results demonstrated that inhibition of Kir4.1 channels facilitates BDNF expression in astrocytes primarily by activating the Ras/Raf/MEK/ERK pathway, which may be linked to the development of epilepsy and other neuropsychiatric disorders.


Heart Rate and Blood Pressure Centile Curves and Distributions by Age of Hospitalized Critically Ill Children.
Heart rate (HR) and blood pressure (BP) form the basis for monitoring the physiological state of patients. Although norms have been published for healthy and hospitalized children, little is known about their distributions in critically ill children. The objective of this study was to report the distributions of these basic physiological variables in hospitalized critically ill children. Continuous data from bedside monitors were collected and stored at 5-s intervals from 3,677 subjects aged 0-18 years admitted over a period of 30 months to the pediatric and cardiac intensive care units at a large quaternary children's hospital. Approximately 1.13 billion values served to estimate age-specific distributions for these two basic physiological variables: HR and intra-arterial BP. Centile curves were derived from the sample distributions and compared to common reference ranges. Properties such as kurtosis and skewness of these distributions are described. In comparison to previously published reference ranges, we show that children in these settings exhibit markedly higher HRs than their healthy counterparts or children hospitalized on in-patient wards. We also compared commonly used published estimates of hypotension in children (e.g., the PALS guidelines) to the values we derived from critically ill children. This is a first study reporting the distributions of basic physiological variables in children in the pediatric intensive care settings, and the percentiles derived may serve as useful references for bedside clinicians and clinical trials.


Directional visible light scattering by silicon nanoparticles.
Directional light scattering by spherical silicon nanoparticles in the visible spectral range is experimentally demonstrated for the first time. These unique optical properties arise because of simultaneous excitation and mutual interference of magnetic and electric dipole resonances inside a single nanosphere. Such behaviour is similar to Kerker's-type scattering by hypothetic magneto-dielectric particles predicted theoretically three decades ago. Here we show that directivity of the far-field radiation pattern of single silicon spheres can be strongly dependent on the light wavelength and the nanoparticle size. For nanoparticles with sizes ranging from 100 to 200 nm, forward-to-backward scattering ratio above six can be experimentally obtained, making them similar to 'Huygens' sources. Unique optical properties of silicon nanoparticles make them promising for design of novel low-loss visible- and telecom-range metamaterials and nanoantenna devices.


Stage- and segment-specific expression of cell-adhesion molecules N-CAM, A-CAM, and L-CAM in the kidney.
CAM expression was investigated immunohistochemically in tissue sections and in pure cultures of human proximal and distal tubular cells. In the fetal kidney, N-CAM immunoreactivity was detected in the non-induced and condensing metanephrogenic mesenchyme, and in all stages until the S-shaped bodies. A-CAM (N-cadherin) first appeared in the non-induced mesenchyme and remained present thereafter. Its expression became exclusively associated with the lower limb of the S-shaped bodies and the developing proximal tubule. In contrast, L-CAM (E-cadherin; uvomorulin) staining was observed in the fetal collecting duct, the upper limb of the S-shaped bodies, and the developing distal tubule. This segment-specific expression of A-CAM and L-CAM in the early developing nephron was maintained in the adult kidney: A-CAM staining was restricted to adherens junctions in the proximal tubule and thin limb, whereas L-CAM was expressed in Bowman's capsule and in all tubular segments except the proximal convoluted and straight tubule. Also after in vitro culture, A-CAM expression was an exclusive property of proximal tubular cells, while L-CAM was confined to distal tubular cells. In conclusion, each major subdivision of the fetal and adult nephron displays a characteristic combination of L-CAM and A-CAM, suggesting that they may be the basis of segmental differentiation and border formation between adjacent nephron segments.


[Comparative analysis of patient-centered outcome of total hip and knee arthroplasty].
The aim of the present study was a comparative investigation of the functional improvement reported by patients suffering from primary osteoarthritis of the knee or hip undergoing total joint replacement and assessed at 3 months. In a prospective, controlled clinical trial, 56 patients with primary osteoarthritis of the hip and 59 patients with primary osteoarthritis of the knee undergoing total joint replacement were assessed at two measuring times (day of admission = t1 and 3-month follow-up = t2) using the XSMFA-D (Extra Short Musculoskeletal Function Assessment Questionnaire--German version), WOMAC (Western Ontario and McMasters Universities) arthrosis index and FFb-H OA (Function Assessment Questionnaire Hannover Osteoarthritis). The statistical analysis included effect sizes as standardised response mean, t-test and covariance analysis. Both groups of patients demonstrated significant improvements of the musculoskeletal functions measured. The effect sizes between baseline scores and 3-month follow-up scores range from 0.4 to 2.0 and can be considered as large effects. The covariance analysis showed significant differences between patients with osteoarthritis of the hip and knee for almost every score examined. Patients with hip replacement showed large improvements. A significant influence of the presurgery baseline score on the 3-month score was found consistently. Further analysis showed that patients with medium or strong degrees of disability according to the Function index of the XSMFA-D showed the strongest effects of change at 3 months. However, their scores at t2 were less than the scores of the less disabled patients at t1. We conclude that patients with hip replacement show more improvement 3 months after the surgery than patients with knee replacement. Furthermore, it was seen that patients who were more disabled before surgery achieved more improvement than the less-disabled patients. However, they did not achieve the level of the less disabled patients. Thus, the recommendation that total joint replacement should be performed as late as possible should be reviewed.


Is Sweet Taste Perception Associated with Sweet Food Liking and Intake?
A range of psychophysical taste measurements are used to characterize an individual's sweet taste perception and to assess links between taste perception and dietary intake. The aims of this study were to investigate the relationship between four different psychophysical measurements of sweet taste perception, and to explore which measures of sweet taste perception relate to sweet food intake. Forty-four women aged 20-40 years were recruited for the study. Four measures of sweet taste perception (detection and recognition thresholds, and sweet taste intensity and hedonic liking of suprathreshold concentrations) were assessed using glucose as the tastant. Dietary measurements included a four-day weighed food record, a sweet food-food frequency questionnaire and a sweet beverage liking questionnaire. Glucose detection and recognition thresholds showed no correlation with suprathreshold taste measurements or any dietary intake measurement. Importantly, sweet taste intensity correlated negatively with total energy and carbohydrate (starch, total sugar, fructose, glucose) intakes, frequency of sweet food intake and sweet beverage liking. Furthermore, sweet hedonic liking correlated positively with total energy and carbohydrate (total sugar, fructose, glucose) intakes. The present study shows a clear link between sweet taste intensity and hedonic liking with sweet food liking, and total energy, carbohydrate and sugar intake.


Automated System for Identifying COVID-19 Infections in Computed Tomography Images Using Deep Learning Models.
Coronavirus disease 2019 (COVID-19) is a novel disease that affects healthcare on a global scale and cannot be ignored because of its high fatality rate. Computed tomography (CT) images are presently being employed to assist doctors in detecting COVID-19 in its early stages. In several scenarios, a combination of epidemiological criteria (contact during the incubation period), the existence of clinical symptoms, laboratory tests (nucleic acid amplification tests), and clinical imaging-based tests are used to diagnose COVID-19. This method can miss patients and cause more complications. Deep learning is one of the techniques that has been proven to be prominent and reliable in several diagnostic domains involving medical imaging. This study utilizes a convolutional neural network (CNN), stacked autoencoder, and deep neural network to develop a COVID-19 diagnostic system. In this system, classification undergoes some modification before applying the three CT image techniques to determine normal and COVID-19 cases. A large-scale and challenging CT image dataset was used in the training process of the employed deep learning model and reporting their final performance. Experimental outcomes show that the highest accuracy rate was achieved using the CNN model with an accuracy of 88.30%, a sensitivity of 87.65%, and a specificity of 87.97%. Furthermore, the proposed system has outperformed the current existing state-of-the-art models in detecting the COVID-19 virus using CT images.


Evaluation of a self-inactivating lentiviral vector expressing simian immunodeficiency virus gag for induction of specific immune responses in vitro and in vivo.
Humoral and cellular immune responses have been shown to play a fundamental role in controlling simian and/or simian-human immunodeficiency virus (SIV-SHIV) replication in infected macaques. Therefore, the appropriate induction of both compartments of the immune system should be elicited after immunization. In this context, viral vectors have been proven effective in inducing both humoral and cellular immune responses during immunization protocols after direct injection in vivo. Among them, recombinant self-inactivating lentiviral vectors represent a useful strategy for vaccine development because they efficiently transduce and express foreign genes into a wide variety of mammalian cells. Here we report on the development and evaluation of a self-inactivating HIV-based lentiviral vector expressing a codon-optimized SIV Gag sequence (TY2-SIVGagDX), which when used to transduce dendritic cells mediated in vitro expansion of Gag-specific T cells derived from an SHIV-infected cynomolgus monkey, as measured by interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) and (51)Cr release standard assays. To evaluate the ability to elicit specific immune responses in vivo, TY2-SIVGagDX was also employed in a vaccination protocol after a single intramuscular injection in BALB/c mice. Results indicated that the vector was able to efficiently induce both cellular and humoral responses, as measured by IFN-gamma ELISPOT assay and antibody production. These data further confirm that lentiviral vectors encoding viral genes represent an advantageous delivery system for vaccine development.


Transcription factors in the cellular signaling network as prime targets of chemopreventive phytochemicals.
Accumulating evidence from epidemiologic and laboratory studies support an inverse relationship between a regular consumption of fruits and vegetables and the risk of specific cancers. Numerous phytochemicals derived from edible plants have been reported to possess ability to interfere with a specific stage of carcinogenic process. Multiple mechanisms have been proposed to account for the anti-carcinogenic actions of dietary constituents, but more attention has recently focussed on intracellular signaling cascades as common molecular targets of a wide variety of chemopreventive phytochemicals.


Bizionia sediminis sp. nov., isolated from coastal sediment.
A Gram-stain-negative, aerobic, non-gliding, rod-shaped and orange-coloured bacterium, designated strain P131T, was isolated from marine sediment of the coast of Weihai, China, and subjected to a polyphasic study. Strain P131T was found to grow optimally at 28-30 °C, at pH 7.0-7.5 and in the presence of 2-3 % (w/v) NaCl. In a phylogenetic analysis based on 16S rRNA gene sequences, strain P131T was found to belong to the genus Bizionia and exhibited 94.6-97.0 % 16S rRNA gene sequence similarity with recognized Bizionia species. The dominant cellular fatty acids of strain P131T were identified as iso-C15 : 0, iso-C15 : 0 G, iso-C17 : 0 3-OH and iso-C17 : 1ω9c. The predominant polar lipids were phosphatidylethanolamine, phospholipid, two aminolipids and two unidentified lipids. The predominant respiratory quinone was menaquinone MK-6 and the DNA G+C content was 36.7 mol%. On the basis of the phylogenetic and phenotypic evidence presented, strain P131T represents a novel species of the genus Bizionia, for which the name Bizionia sediminis sp. nov. is proposed. The type strain is P131T (=KCTC 42587T=MCCC 1H00124T).


Increased post-operative haemorrhage seen in adult coblation tonsillectomy.
Coblation is a new soft tissue surgical technique that is being used for tonsillectomy. Published results show a significant decrease in the amount of post-operative pain experienced by patients undergoing coblation tonsillectomy. There has been no published work to date on the incidence of post-operative haemorrhage. From August 2001 to November 2002 one surgeon performed 36 coblation tonsillectomies on adults. On another list he performed 29 by his standard method of dissection and bipolar coagulation. Retrospective analysis found a significant increase in the secondary haemorrhage rate in adult patients undergoing coblation tonsillectomy (22.2 vs. 3.4 per cent). At our department coblation tonsillectomy has been abandoned until further work into its safety has been published.


Safety and efficacy of Mycoplasma gallisepticum TS-11 vaccine for the protection of layer pullets against challenge with virulent M. gallisepticum R-strain.
Mycoplasma gallisepticum TS-11 vaccine was studied for its safety and protective ability in 49-day-old M. gallisepticum-free and Mycoplasma synoviae-free commercial Tetra SL layer chickens. Sixty birds were distributed into four groups: 15 were unvaccinated but were challenged with M. gallisepticum R-strain, 15 were vaccinated by eye drop and then challenged with virulent M. gallisepticum R-strain 4 weeks post vaccination, 15 were designated as controls without vaccination and challenge, and 15 received TS-11 vaccine but no challenge. Based on the post-challenge clinical signs, body weight gain, gross pathological examination of air sacs and peritoneum, histological examination of the trachea, lung, spleen and liver, and reisolation of mycoplasmas from inner organs, the TS-11 vaccine is safe and does not produce clinical signs, a major decrease of body weight gain or pathological lesions. Vaccination induced a slight serological response to M. gallisepticum antigen in serum plate agglutination and blocking enzyme-linked immunosorbent assay tests and prevented development clinical signs of airsacculitis, peribronchitis and interstitial pneumonia on M. gallisepticum challenge.