Engineering and monitoring cellular barrier models.
Epithelia and endothelia delineate tissue compartments and control their environments by regulating the passage of ions and solutes. This barrier function is essential for the development and maintenance of multicellular organisms, and its dysfunction is associated with numerous human diseases. Recent advances in biomaterials and microfabrication technologies have evolved in vitro approaches for modelling biological barriers. Current microphysiological systems have become more efficient and reliable in mimicking the cell microenvironment. Additionally, methods for the quantification of barrier permeability have long provided significant insight into their underlying mechanisms. In this review, we outline the current techniques to quantify the barrier function of engineered tissues, and we also give an overview of recent microphysiological systems of biological barriers that emulate the microenvironment and microarchitecture of native tissues.


A case report on a patient who presented with myelofibrosis, developed breast cancer with myeloid metaplasia, and finally showed immature NK-cell leukemia or AML without maturation with CD56 expression transformation in the pleura with extramedullary hematopoiesis: a 25-year course.
This study reports a female patient who suffered from primary myelofibrosis at 38 years of age, breast cancer with myeloid metaplasia at 49 years of age, and pleural effusion and multiple subcutaneous nodules at 62 years of age. She was finally diagnosed with immature NK-cell leukemia or AML without maturation with CD56 expression transformation of extramedullary hematopoiesis that developed in the pleura, and died 11 months later. Atypical cells in the pleural effusion had surface markers of CD13, CD33, CD34, and CD56 using a fluorescence-activated cell sorter analysis, and were positive for myeloperoxidase, CD34, CD43, and CD56 in a cell block material using an immunohistochemical method. Megakaryocytic and erythroblastic cells were also seen in the pleural effusion.


Homology modelling and molecular docking studies of human placental cadherin protein for its role in teratogenic effects of anti-epileptic drugs.
Anti-epileptic drugs (AEDs) have high risk of teratogenic side effects, including neural tube defects while mother is on AEDs for her own prevention of convulsions during pregnancy. The present study investigated the interaction of major marketed AEDs and human placental (hp)-cadherin protein, in-silico, to establish the role of hp-cadherin protein in teratogenicity and also to evaluate the importance of Ca(2+) ion in functioning of the protein. A set of 21 major marketed AEDs were selected for the study and 3D-structure of hp-cadherin was constructed using homology modelling and energy minimized using MD simulations. Molecular docking studies were carried out using selected AEDs as ligand with hp-cadherin (free and bound Ca(2+) ion) to study the behavioural changes in hp-cadherin due to presence of Ca(2+) ion. The study reflected that four AEDs (Gabapentin, Pregabalin, Remacimide and Vigabatrine) had very high affinity towards hp-cadherin and thus the later may have prominent role in the teratogenic effects of these AEDs. From docking simulation analysis it was observed that Ca(2+) ion is required to make hp-cadherin energetically favourable and sterically functional.


Subclinical coronary atherosclerosis and neighbourhood deprivation in an urban region.
Inhabitants of deprived neighbourhoods are at higher risk of coronary heart disease. In this study we investigate the hypothesis that social inequalities at neighbourhood level become already manifest in subclinical coronary atherosclerosis, as defined by electron-beam computed tomography derived measures. Coronary artery calcification was assessed as a marker of atherosclerosis in a population based sample of 4301 men and women (45-75 years) without a history of coronary heart disease. Participants lived in three adjacent cities in Germany and were examined between 2000 and 2003 as part of the Heinz Nixdorf Recall Study. Individual level data was combined with neighbourhood level information about unemployment, welfare and living space per inhabitant. This dataset was analysed with descriptive and multilevel regression methods. An association between neighbourhood deprivation and subclinical coronary calcification was observed. After adjustment for age and individual socioeconomic status male inhabitants of high unemployment neighbourhoods had an odds ratio of 1.45 (1.11, 1.96) of exhibiting a high calcification score (>75th percentile) compared to men living in low unemployment areas. The respective odds for women was 1.29 (0.97, 1.70). Additional explorative analyses suggest that clustering of unhealthy lifestyles in deprived neighbourhoods contributes to the observed association. In conclusion, findings suggest that certain neighbourhood characteristics promote the emergence of coronary atherosclerosis. This might point to a pathway from neighbourhood deprivation to manifest coronary heart disease.


Optimal dose reduction of FOLFIRINOX for preserving tumour response in advanced pancreatic cancer: Using cumulative relative dose intensity.
FOLFIRINOX has increased efficacy but also toxicity. Despite various modified FOLFIRINOX regimens, how much reduction is acceptable remains unclear. This study aimed to find the optimal relative dose intensity (RDI, %) of FOLFIRINOX that preserves tumour responses in patients with advanced pancreatic cancer (PC). We reviewed 201 patients with PC treated with first-line FOLFIRINOX during 2012-2015. We established a modified Hryniuk model (http://www.rdicalc.com) and defined cumulative RDI (cRDI, %). The optimal cRDI thresholds for response rate (RR) and disease control rate (DCR) were assessed using receiver operating characteristic (ROC) analysis. Relationships between cRDI and haematologic toxicities (neutropenia and febrile neutropenia [FN]) were also analysed according to use of granulocyte colony-stimulating factor (G-CSF). Among 156 eligible patients, 133 (48 locally advanced PC and 85 metastatic PC) completed initial treatment plan prior to the first radiological evaluation (median 58 days; 71.8% cRDI). For optimal cRDI thresholds, ROC curves showed a 71.2% cRDI for RR (83.3% sensitivity, 64.7% specificity, and 0.746 area under the curve [AUC]) and a 55.3% cRDI for DCR (93.6% sensitivity, 62.5% specificity and 0.805 AUC). Among 96 patients who did not receive prophylactic G-CSF, cRDI ≥80.1% was a significant predictor for frequent FN (73.7% sensitivity, 72.7% specificity and 0.793 AUC). There was no correlation between cRDI and haematologic toxicities in patients receiving prophylactic G-CSF. To preserve optimal RR and DCR in advanced PC, cRDI values for FOLFIRINOX >70% and >55%, respectively, are recommended. If cRDI is >80%, primary G-CSF prophylaxis is needed.


Nonarbo-togaviridae: comparative hydrodynamic properties of the pestivirus genus. Brief report.
The sedimentation coefficient and buoyant density of hog cholera, bovine viral diarrhea and Border disease viruses, have been compared with those of representative members of the family togaviridae. It appears that the pestivirus genus is a homogeneous group which is not only antigenically but also structurally, unrelated to the other genera of the togavirus family.


Immobilization of Sb in a smelting residue by micro-sized zero-valent iron: Long-term performance under accelerated exposure to strong acid rain.
This study investigated the long-term leachability of antimony (Sb) in a smelting residue immobilized by three commercial micro-sized zero-valent iron (ZVI) products. Effect of oxic incubation time (14 days and 120 days) on the immobilization efficiency of Sb were compared, and the long-term leaching risk was evaluated by an accelerated exposure test, in which the slag was consecutively extracted by simulated strong acid rain (SSAR, HNO3: H2SO4 = 1:2, pH = 3.20). Notably, all ZVI treatments efficiently immobilized the Sb in this slag in a short term (14 days); the one-step SSAR-leached Sb was reduced by 89%-91% compared to the original slag (5.9 mg/L) and was far below the environmental standard (0.6 mg/L) established by the US EPA. The sequential SSAR leaching results reflected that the 14-d incubated slags after ZVI treatments had strong H+ resistance, and the immobilized Sb was not easily activated by continuous SSAR corrosion. The binding of Sb with amorphous phase Fe oxyhydroxides (e.g. ferrihydrite) derived from ZVI corrosion played a dominant role in the Sb immobilization efficiency. However, the longer aging process (120 days) easily resulted in the reduction of Sb immobilization by ZVI treatments. The changes in crystallinity of Fe oxyhydroxides (transformation from poorly-crystalline to crystalline ones) and the pH elevation to alkaline range might explain the weakening of the immobilization of Sb in ZVI-amended slags with 120 days of incubation. In total, the effectiveness of Sb immobilization in smelting residue greatly depended on the type of ZVI and the aging process. Our work has demonstrated that the ZVI treatment was potentially feasible to mitigate the Sb leaching risk from smelting slags; however, the ZVI type needs to be carefully selected and its long-term performance should be adequately verified before practical application.


Neonatal paracorporeal lung assist device for respiratory failure.
Neonates who experience respiratory failure despite maximal ventilatory support have only extracorporeal membrane oxygenation as a rescue therapy, but it has very poor outcomes as a bridge to transplantation. A pumpless lung-assist device has been used in adults as a bridge to lung transplantation. An alternative membrane oxygenator, the Quadrox iD, is a suitable size for neonatal blood flow. Here we report the use of the Quadrox iD membrane oxygenator with central cannulation as a paracorporeal respiratory support therapy for a neonate with alveolar capillary dysplasia awaiting lung transplantation.


A study of the quality and duration of survival following resection, endoscopic intubation and surgical intubation in oesophageal carcinoma.
A series of 130 cases of oesophageal carcinoma managed by one surgeon in a unit with a major interest in oesophageal disorders is reviewed. The management policy has been an active one of resection in suitably selected cases, less favourable ones being treated by operative intubation before 1979 and by endoscopic intubation since 1979. Operative mortality and morbidity have been compared between the three groups, together with duration of survival and quality of swallowing as measured by a modified Visick grading. In the intubated groups, endoscopic intubation carried a hospital mortality of 15.6 per cent compared with 40.8 per cent in the operative group. It was associated with less morbidity and a better quality of survival, although survival times were comparable and did not exceed 18 months in either group. In the resection group, hospital mortality was 12.2 per cent, and both the mean survival and quality of swallowing were greater than in either endoscopic group. It is concluded that in suitably selected cases, resection can be performed with a mortality considered acceptable for palliative intubation whilst conferring greater survival and restoration of normal swallowing. In less favourable cases, endoscopic intubation is superior to operative intubation in terms of reduced mortality and better restoration of swallowing.


Water bolus for electron irradiation of the ear canal.
To demonstrate that water bolus in the external ear can decrease the dose inhomogeneity caused by auricular surface irregularities when the ear is in an electron-beam field. Three-dimensional (3D) dose distributions with and without water bolus in the external ear were calculated for a representative patient. The electron dose calculations were made using the Hogstrom pencil beam algorithm as implemented in 3D by Starkschall. To demonstrate the use of water bolus in the ear clinically, the case of a patient with squamous carcinoma of the concha who was treated with electrons is presented. Water bolus markedly lessens the dose heterogeneity caused by the surface irregularities of the ear and the air in the external auditory canal. In the test case, the maximum dose was reduced by 25% using this technique. When the ear is in an electron beam field, warm water should be placed in the external auditory canal and concha. This maneuver may reduce the incidence of auricular complications that occur after electron-beam therapy.


Fast dye salts provide fast access to azidoarene synthons in multi-step one-pot tandem click transformations.
This study examined whether commercially available diazonium salts could be used as efficient aromatic azide precursors in one-pot multi-step click transformations. Seven different diazonium salts, including Fast Red RC, Fast Blue B, Fast Corinth V and Variamine Blue B were surveyed under aqueous click reaction conditions of CuSO(4)/Na ascorbate catalyst with 1:1 t-BuOH:H(2)O solvent. Two-step tandem reactions with terminal alkyne and diyne co-reactants led to 1,2,3-triazole products in 66%-88% yields, while three-step tandem reactions with trimethylsilyl-protected alkyne and diyne co-reactants led to 1,2,3-triazole products in 61%-78% yields.


Early gene therapy-induced apoptotic response in BT4C gliomas by magnetic resonance relaxation contrast T1 in the rotating frame.
The design and evaluation of therapeutic gene transfection protocols and vectors are under extensive development. Magnetic resonance imaging (MRI) techniques can aid considerably in the development of experimental treatment approaches, as well as in determining treatment response by observing gross tissue morphology. However, through a unique set of contrast parameters, namely T1, T2, and diffusion, more information about tissue status can be obtained while delineating and classifying tumor characteristics in more detail. We show here that T1 relaxation in the rotating frame, T1rho, provides unique in vivo MRI contrast. Ganciclovir treatment of HSV-tk+BT4C gliomas, which effectively eradicates these tumors, resulted in significantly prolonged T1rho relaxation times in MRI already after 3 days of treatment, whereas conventional contrast parameters were elevated after 6-8 days of therapy. Interestingly, the prolonged T1rho values were observed while an increase in tumor volume was still taking place. The regions of elevated T1rho relaxation coincided with high apoptotic activity as determined by histology, suggesting that T1rho MRI contrast could be used as a novel early indicator of cytotoxic cell damage in gliomas.


[Kaposiform haemangioendothelioma associated with B-cell acute lymphoblastic leukemia].
Herein, we report the first case of kaposiform haemangioendothelioma (KHE) associated with acute B-lymphoblastic leukemia (B-ALL). A five-month-old infant presented a plaque of angiomatous appearance on the forearm that had increased in volume since birth, as well as pallor and cutaneous haematomas. Kasabach-Merritt syndrome (KMS) was evoked despite hepatomegaly and considerable splenomegaly. Laboratory tests revealed severe anaemia and thrombocytopenia as well as major hyperleukocytosis with 90% blasts. Skin biopsy revealed vast vascular lobules containing cohesive fusiform endothelial cells not expressing Glut1, bound up in a dense infiltrate of B-lymphoblast cells. It was in fact KHE associated with B-ALL confirmed by the myelogram. The child was treated with the INTERFANT 2006 protocol followed by allograft of haematopoietic stem cells, which resulted in complete haematological remission. At the same time, almost total regression of KHE was noted. In this infant, KHE had an inflammatory appearance and was associated with thrombocytopenia, evocative of KMS. Analysis of blood and marrow samples resulted in a diagnosis of B-ALL. Histopathological examination of the angioma revealed a typical appearance of KHE associated with dense lymphoblastic proliferation. This appearance could have resulted either from passive contamination by circulating blast cells or from active recruitment of tumor cells at the KHE site. HK mimicking KMS may reveal B-ALL.


Phosphorylation of FE65 at threonine 579 by GSK3β stimulates amyloid precursor protein processing.
Excessive generation of amyloid-β peptide (Aβ) by aberrant proteolysis of amyloid precursor protein (APP) is a key event in Alzheimer's disease (AD) pathogenesis. FE65 is a brain-enriched phospho-adaptor protein that interacts with APP and has been shown to modulate APP processing. However, the mechanism(s) that FE65 alters APP processing is still not fully understood. In the present study, we demonstrate that FE65 is phosphorylated at threonine 579 (T579) by glycogen synthase kinase 3β (GSK3β). Moreover, FE65 T579 phosphorylation potentiates γ- and β-secretases-mediated APP processing and Aβ liberation. Additionally, the phosphorylation suppresses FE65 PTB2 intermolecular dimerization but enhances FE65/APP complex formation. Hence, our findings reveal a novel mechanism that GSK3β stimulates amyloidogenic processing of APP by phosphorylation of FE65 at T579.


Prediction of donor-specific transfusion sensitization. I. A linear logistic model.
Using linear logistic regression, six factors were identified as important predictors of risk of DST sensitization in a group of 195 patients. Factors increasing the risk were: percent panel reactive antibody (PRA), previous transplants, and pregnancy; those decreasing the risk were HLA antigens matched, third-party blood transfusions, and Imuran administration. From this analysis, the magnitude of the effect of each factor on the risk of sensitization was obtained. An equation was then obtained that can be used to compute an estimated probability of sensitization (PS) for each patient. As a test of predictive ability of the model, the PS was calculated for 66 patients in an independent patient group. These observations were arranged according to the estimated probability and then divided into intervals of risk. Overall, for each interval, a very high level of agreement was found between the predicted and actual number of sensitized patients. A total of 16.13 patients were predicted to become sensitized and 17 actually did.


Retracted: Internet of Things and Edge Computing Model Optimization in Physical Training Status and Countermeasures in College Sports Basketball Optional Course.
[This retracts the article DOI: 10.1155/2021/4295319.].


Conflicts between motivational systems related to attachment trauma: Key to understanding the intra-family relationship between abused children and their abusers.
Research on disorganization of infant attachment provides evidence that it can be caused not only by violent aggression or very early sexual abuse, but also by covert maltreating behavior, which includes the abdication of the caregiver's responsibility to soothe the infant's distress. This paper argues that both overtly abusive caregivers and merely "abdicating" caregivers may cause disorganization of infant attachment through a simultaneous and conflicting activation of the motivational systems governing attachment and survival defense in the infant. Other inborn motivational systems-regulating caretaking, competitiveness, and sexuality-are disorderly activated, during personality development, within the intra-family relationships of children whose infant attachment has been disorganized. The paper argues that conflicts and abnormal tensions between different motivational systems explain some paradoxical features of the interactions between abusers and abused, and allow for a better understanding of the interpersonal processes involved in the surfacing and exacerbation of dissociative symptoms in the abused.


Study on the preparation and feasibility of a novel adding-type biological slow-release carbon source.
The development of slow-release carbon sources is an effective biological treatment to remove nutrients from wastewater with low carbon-to-nitrogen ratio (C/N). Most filling-type slow-release carbon could not fulfil the needs of current wastewater treatment plants (WWTPs) process. And most adding-type slow-release carbon sources were prepared using some expensive chemical materials. In this study, combining the advantages of the aforementioned types, a novel adding-type wastepaper-flora (AT-WF) slow-release carbon source was proposed, aiming to realise wastepaper recycling in WWTPs. The screening and identification of the mixed flora, AT-WF carbon source release behaviour, and denitrification performance were investigated. The results showed that through the proposed screening method, a considerable proportion of cellulose-degradation-related genera was enriched, and the cellulose degradation ability and ratio of readily available carbon sources of flora T4, S4 and S5 were effectively strengthened. AT-WF had significant carbon release ability and stability, with an average total organic carbon (TOC) release of 8.82 ± 2.36 mg/g. Kinetic analysis showed that the entire carbon release process was more consistent with the first-order equation. Piecewise fitting with the Ritger-Peppas equation exhibited that the rapid-release (RR) stage was skeleton dissolution and the slow-release (SR) stage was Fick diffusion. Denitrification efficiency can achieve a high average removal efficiency of 94.17%, which could theoretically contribute 11.2% more to the total inorganic nitrogen (TIN) removal. Thus, this study indicated that AT-WF could be utilised as an alternative carbon source in WWTPs.


Conceptual and methodological challenges to measuring political commitment to respond to HIV.
Researchers have long recognized the importance of a central government's political "commitment" in order to mount an effective response to HIV. The concept of political commitment remains ill-defined, however, and little guidance has been given on how to measure this construct and its relationship with HIV-related outcomes. Several countries have experienced declines in HIV infection rates, but conceptual difficulties arise in linking these declines to political commitment as opposed to underlying social and behavioural factors. This paper first presents a critical review of the literature on existing efforts to conceptualize and measure political commitment to respond to HIV and the linkages between political commitment and HIV-related outcomes. Based on the elements identified in this review, the paper then develops and presents a framework to assist researchers in making choices about how to assess a government's level of political commitment to respond to HIV and how to link political commitment to HIV-related outcomes. The review of existing studies identifies three components of commitment (expressed, institutional and budgetary commitment) as different dimensions along which commitment can be measured. The review also identifies normative and ideological aspects of commitment and a set of variables that mediate and moderate political commitment that need to be accounted for in order to draw valid inferences about the relationship between political commitment and HIV-related outcomes. The framework summarizes a set of steps that researchers can follow in order to assess a government's level of commitment to respond to HIV and suggests ways to apply the framework to country cases. Whereas existing studies have adopted a limited and often ambiguous conception of political commitment, we argue that conceiving of political commitment along a greater number of dimensions will allow researchers to draw a more complete picture of political commitment to respond to HIV that avoids making invalid inferences about the relationship between political commitment and HIV outcomes.


Prevalence of adenoid hypertrophy and nocturnal enuresis in primary school children in Istanbul, Turkey.
The purpose of this study is to investigate the prevalence of an existing relationship between adenoid hypertrophy and nocturnal enuresis in primary school children. The study was performed in four primary schools that were chosen randomly in Kartal, Istanbul. The children's parents were asked to fill out a questionnaire that included questions concerning the associated symptoms of adenoid hypertrophy and nocturnal enuresis. The interrelations between adenoid hypertrophy and nocturnal enuresis items were examined by X2 tests. The study population consisted of 1132 (625 girls, 621 boys) primary school children between 5 and 14 years of age (mean 9.59+/-2.60 years). The children were divided into three groups with 5-7 years old children in Group I (n=232), 8-10 years old children in Group II (n=506) and 11-14 years old children in Group III (n=394). Of the 1132 distributed questionnaires, 1090 (87.4%) were filled in adequately and were accepted for evaluation. Prevalence of adenoid hypertrophy in school children was found to be 58 in Group I (27%), 94 in Group II (19.5%) and 78 in Group III (19.9%). Prevalence of nocturnal enuresis in school children was found to be 35 in Group I (15.1%), 51 in Group II (10.1%) and 18 in Group III (4.6%). No statistically significant association was present between adenoid hypertrophy and nocturnal enuresis in either Group I, II or III school children. In contrast to previous studies, our prevalence study did not find an association between adenoid hypertrophy and nocturnal enuresis. Thus, this prevalence study provides otolaryngologists new and interesting information.


[2,6-Bis(isopropylthiomethyl)phenyl-kappa3S,C1,S']bromopalladium(II).
The title compound, [PdBr(C(14)H(21)S(2))] or [PdBr[C(6)H(3)(CH(2)S(i)Pr)(2)-2,6]], exhibits square-planar geometry at the Pd centre, with three atoms of the square plane provided by the rigid thiopincer ligand, i.e. 1,3-bis(thiomethyl)benzene.


Cloning and sequencing of bovine apolipoprotein A-I cDNA and molecular evolution of apolipoproteins A-I and B-100.
We have cloned and sequenced bovine apoA-I cDNA. Comparison with the apoA-I sequences of six other vertebrates shows the bovine gene to be most similar to that of the dog. Estimates of substitution rates show that apoA-I evolves approximately 25% faster than an average gene in mammalian lineages. All portions of the coding region evolve at roughly similar rates, suggesting that global conformation is conserved. However, a region of the rat protein has evolved rapidly both relative to other portions of the rat sequence and relative to homologous regions in other mammals. To extend our analysis to other apolipoproteins, we compared four vertebrate apoB-100 sequences. Conserved regions were found to include two putative LDL receptor binding domains, in addition to several regions of unidentified function. Comparison of the apoA-I sequences and the apoB-100 sequences indicates that the latter evolve approximately 40% faster than the former and at twice the average rate for mammalian proteins.


Primary health care professionals' activity in intervening in patients' alcohol drinking: a patient perspective.
To test the hypothesis that primary health care professionals' activity in intervening in patients' alcohol drinking is low. A patient questionnaire survey after consultation blind to the primary health care professionals. Subjects were 1000 16-65 -year-old consecutive patients consulting a general practitioner. The response rate was 66.5%. Of all participants 6.3% and of excessive drinkers 11.9% were asked about alcohol drinking at the consultation in question. Of all 64.7% and of excessive drinkers 52.4% had never been asked about drinking. Of all 6.0% and of excessive drinkers 19.0% were advised about alcohol drinking at the consultation in question. Alcohol drinking is rarely brought up in discussion by primary health care professionals, even in the case of excessive drinkers.


Switching from high-fat diet to normal diet ameliorate BTB integrity and improve fertility potential in obese male mice.
Obesity is a prominent risk factor for male infertility, and a high-fat diet is an important cause of obesity. Therefore, diet control can reduce body weight and regulate blood glucose and lipids, but it remains unclear whether it can improve male fertility and its mechanism. This study explores the effects of switching from a high-fat diet (HFD) to a normal diet (ND) on the fertility potential of obese male mice and its related mechanisms. In our study, male mice were separated into three groups: normal diet group (NN), continuous high-fat diet group (HH), and return to normal diet group (HN). The reproductive potential of mice was tested through cohabitation. Enzymatic methods and ELISA assays were used to measure metabolic indicators, follicle-stimulating hormone (FSH) levels and intratesticular testosterone levels. Transmission electron microscopy and immunofluorescence with biotin tracers assessed the integrity of the blood-testis barrier (BTB). Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were inspected for the assessment of oxidative stress. The expression and localization of BTB-related proteins were detected through the immunoblot and immunofluorescence. The mice in the high-fat diet group indicated increased body weight and epididymal fat weight, elevated serum TC, HDL, LDL, and glucose, decreased serum FSH, and dramatic lipid deposition in the testicular interstitium. Analysis of fertility potential revealed that the fertility rate of female mice and the number of pups per litter in the HH group were significantly reduced. After the fat intake was controlled by switching to a normal diet, body weight and epididymal fat weight were significantly reduced, serum glucose and lipid levels were lowered, serum FSH level was elevated and the deposition of interstitial lipids in the testicles was also decreased. Most significantly, the number of offspring of male mice returning to a normal diet was significantly increased. Following further mechanistic analysis, the mice in the sustained high-fat diet group had disrupted testicular BTB integrity, elevated levels of oxidative stress, and abnormal expression of BTB-related proteins, whereas the restoration of the normal diet significantly ameliorated the above indicators in the mice. Our study confirms diet control by switching from a high-fat diet to a normal diet can effectively reduce body weight, ameliorate testicular lipotoxicity and BTB integrity in male mice, and improve fertility potential, providing an effective treatment option for obese male infertility.


Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas.
To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects.


Risk factors of persistent diplopia following secondary intraocular lens implantation in patients with sensory strabismus from uncorrected monocular aphakia.
We aimed to compare clinical characteristics between diplopia-free and diplopia-persistent patients after successful strabismus surgery, when patients complained of diplopia following secondary intraocular lens (IOL) implantation after prolonged aphakia accompanied by sensory strabismus. Retrospective review of medical records of patients who complained of diplopia following secondary IOL placement with sensory strabismus after prolonged uncorrected monocular aphakia from isolated ocular trauma was done. We classified patients into two groups according to persistency of diplopia, 6 months after successful strabismus surgery. Clinical characteristics were compared between groups. A total of 31 patients were included. The diplopia-persistent group showed longer duration of uncorrected aphakia (p = 0.02), less severe corneal astigmatism (p = 0.04), a smaller exodeviation angle (p = 0.02), and more frequent vertical deviation (p = 0.015), extorsion (p = 0.022) and monocular nystagmus (p = 0.028) than the diplopia-free group. In all patients in the diplopia-free group, diplopia could be eliminated prior to strabismus surgery using loose prisms in free space, whereas seven patients in the diplopia-persistent group prior to surgery could not resolve diplopia. Our data will be helpful for ocular surgeons in determining whether to insert secondary IOL in prolonged aphakia with sensory strabismus, or whether strabismus surgery will eliminate diplopia that develops following secondary IOL placement in this situation.


Electrophysiology of spatial scene analysis: the mismatch negativity (MMN) is sensitive to the ventriloquism illusion.
The ventriloquism effect is the tendency to underestimate the spatial separation between synchronous auditory and visual signals moderately separated in space. If, as it is thought, this effect is pre-attentive, it could modulate the mismatch negativity (MMN) that indexes the automatic, pre-attentive detection of deviant auditory stimuli rarely occurring in a sequence of standard stimuli. We assessed the existence of an MMN evoked by auditory and visual signals made up of standard sounds coming from the same location as the visual signal and deviant sounds coming from lateral deviations (20 or 60 degrees). As first observed in a behavioral study, a ventriloquism effect occurred for 20 degrees spatial separation but not for 60 degrees. Cortical evoked potentials were recorded using the oddball paradigm on 8 adults in auditory alone and audiovisual conditions. In the auditory alone condition, each spatial localization contrast elicited a significant MMN. In the audiovisual condition, a significant MMN was only evoked for the 60 degrees contrasts. The MMN evoked by spatial separation contrasts (20 and 60 degrees) in the auditory alone condition was suppressed by the corresponding audiovisual condition only when the latter yielded a ventriloquism effect, suggesting that this effect occurs at an early perceptual level.


The phosphoinositide-3-OH-kinase-related kinases of Arabidopsis thaliana.
The phosphoinositide-3-OH-kinase-related kinases (PIKKs) are atypical protein kinases exclusive to eukaryotes. They mediate the cellular response to a range of stresses, including genome and RNA surveillance and availability of nutrients for growth. Orthologues of five out of the six PIKK family members are present in plant genomes. Recent studies in plant PIKKs have revealed features unique to, and in common with, other PIKKs. This review summarizes the basic knowledge of these proteins in mammals and yeast in comparison with what is known for Arabidopsis and other plants.


A refractive index sensor based on the resonant coupling to cladding modes in a fiber loop.
We report an easy-to-build, compact, and low-cost optical fiber refractive index sensor. It consists of a single fiber loop whose transmission spectra exhibit a series of notches produced by the resonant coupling between the fundamental mode and the cladding modes in a uniformly bent fiber. The wavelength of the notches, distributed in a wavelength span from 1,400 to 1,700 nm, can be tuned by adjusting the diameter of the fiber loop and are sensitive to refractive index changes of the external medium. Sensitivities of 170 and 800 nm per refractive index unit for water solutions and for the refractive index interval 1.40-1.442, respectively, are demonstrated. We estimate a long range resolution of 3 × 10(-4) and a short range resolution of 2 × 10(-5) for water solutions.


Diagnostic considerations in patients with back pain.
It should be obvious from this article that usually only a focused history and physical examination are needed to evaluate a back patient. A summary of guideline recommendations presented by the Agency for Health Care Policy and Research is provided in Table 7. If followed, few serious mistakes will occur, and a more cost-effective management of the back patient will be possible.


Validation of the Self Reporting Questionnaire 20-Item (SRQ-20) for Use in a Low- and Middle-Income Country Emergency Centre Setting.
Common mental disorders are highly prevalent in emergency centre (EC) patients, yet few brief screening tools have been validated for low- and middle-income country (LMIC) ECs. This study explored the psychometric properties of the SRQ-20 screening tool in South African ECs using the Mini Neuropsychiatric Interview (MINI) as the gold standard comparison tool. Patients (n=200) from two ECs in Cape Town, South Africa were interviewed using the SRQ-20 and the MINI. Internal consistency, screening properties and factorial validity were examined. The SRQ-20 was effective in identifying participants with major depression, anxiety disorders or suicidality and displayed good internal consistency. The optimal cutoff scores were 4/5 and 6/7 for men and women respectively. The factor structure differed by gender. The SRQ-20 is a useful tool for EC settings in South Africa and holds promise for task-shifted approaches to decreasing the LMIC burden of mental disorders.


Recent trends and advancements in microbial tannase-catalyzed biotransformation of tannins: a review.
The outburst of green biotechnology has facilitated a substantial upsurge in the usage of enzymes in a plethora of industrial bioconversion processes. The tremendous biocatalytic potential of industrial enzymes provides an upper edge over chemical technologies in terms of safety, reusability, and better process control. Tannase is one such enzyme loaded with huge potential for bioconversion of hydrolysable tannins to gallic acid. Tannins invariably occur in pteridophytes, gymnosperms, and angiosperms and predominately cumulate in plant parts like fruits, bark, roots, and leaves. Furthermore, toxic tannery effluents from various tanneries are loaded with significant levels of tannins in the form of tannic acid. Tannase can be principally employed for debasing the tannins that predominately occur in the toxic tannery effluents thus providing a relatively much cheaper measure for their biodegradation. Over the years, microbial tannase-catalyzed tannin degradation has gained momentum. The plentious availability of tannin-containing agro- and industrial waste paves a way for efficient utilization of microbial tannase for tannin degradation eventually resulting into gallic acid production. Gallic acid has received a great deal of attention as a molecule of enormous therapeutic and indusrial potential. The current worldwide demand of gallic acid is 8000 t per annum. As a matter of fact, bioconversion of tannins into gallic acid through fermentation has not been exploited completely. This necessitates further studies for development of more efficient, economical, productive processes and improved strains for gallic acid production so as to meet its current demand.


Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.
Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.


Kinetic properties of the human liver cytosolic aldehyde dehydrogenase for retinal isomers.
Retinoic acid exerts pleiotropic effects by acting through two families of nuclear receptors, RAR and RXR. All-trans and 9-cis retinoic acid bind RARs, whereas 9-cis retinoic acid binds and activates only the RXRs. To understand the role of human liver cytosolic aldehyde dehydrogenase (ALDH1) in retinoic acid synthesis, we examined the ability of ALDH 1 to catalyze the oxidation of the naturally occurring retinal isomers. ALDH1 catalyzed the oxidation of all-trans, 9-cis, and 13-cis retinal with equal efficiency. However, the affinity to all-trans retinal (Km = 2.2 microM) was twofold higher than to 9-cis (Km = 5.5 microM) and 13-cis (Km = 4.6 microM) retinal. All-trans retinol was a potent inhibitor of ALDH1 activity, and inhibited all-trans retinal oxidation uncompetitively. Comparison of the kinetic properties of ALDH1 for retinal isomers with those of previously reported rat kidney retinal dehydrogenase showed distinct differences, suggesting that ALDH1 may play a different role in retinal metabolism in liver.


Clinical profile of a male with Rett syndrome.
We describe a clinical profile of a male with Rett syndrome who presented initially with significant axial and peripheral hypotonia, head and truncal titubation and global delay. He is non-ambulatory, lost the few words he had learned and gradually developed hand stereotypes, breathing difficulties, seizures, scoliosis and has osteoporosis sleep problems and sludging in his gall bladder. Prior to diagnosis he underwent comprehensive neurological, metabolic and genetic investigations. After his older sister was diagnosed with atypical Rett syndrome; MECP2 mutation studies on him revealed a pathogenic mutation. His mother is a Rett carrier with a skewed inactivation of chromosome X. Clinical signs and symptoms required to meet the criteria for diagnosis of Rett syndrome have gradually evolved over time. This case demonstrates an unusual family history for Rett syndrome and alerts readers to the utility of screening males for Rett syndrome.


Leucosiid crabs (Crustacea: Decapoda: Brachyura) from Taiwan, with three new records.
Four leucosiid species from Taiwan are presented. Ebalia nudipes Sakai, 1963, with its male first gonopod figured for the first time. Galilia petricola Komai & Tsuchida, 2014, is recorded on the basis of a larger specimen, and distinguishing features with its only congener, G. narusei Ng & Richer de Forges, 2007, reappraised. Nursia rhomboidalis (Miers, 1879), previously known only from Japan, Korea, and mainland China, is also recorded from Taiwan. Myra fugax (Fabricius, 1798) is now formally recorded from Taiwan, and female characters identified to help separate the three known Taiwanese species of Myra.


Effect of lysyl hydroxylase inhibitor, minoxidil, on ultrastructure and behavior of cultured rabbit subconjunctival fibroblasts.
Minoxidil is an inhibitor of lysyl hydroxylase, an enzyme involved in collagen production, and decreases collagen production in vitro. We investigated the in vitro effects of minoxidil on behavior such as proliferation and migration of rabbit subconjunctival fibroblasts (SCFs). The ultrastructural effect of the drug on SCFs was also examined. Proliferation of SCFs and closure of the defect produced in monolayer cultures in the presence or absence of minoxidil was studied. The ultrastructure of SCFs treated with minoxidil was also examined. Minoxidil inhibited SCF proliferation and the closure of the defect produced in monolayer cell sheets. Ultrastructural observations revealed extensive areas of irregularly dilated endoplasmic reticulum in cells treated with minoxidil, indicating the accumulation of protein, probably underhydroxylated collagen precursors, in the cisternae of endoplasmic reticulum. The results indicated that minoxidil attenuated cellular activities of SCFs such as proliferation and migration in vitro. The exact mechanism of the inhibitory effects of minoxidil on these cellular activities is unknown. The findings suggest that the drug might help to prevent bleb scarring after glaucoma filtering surgery.


Retrolental fibroplasia. Experience over two decades in one institution.
We examined 1,849 consecutively admitted premature infants weighing 2000 gm or less at birth for retrolental fibroplasia (RLF). Proliferative RLF was diagnosed frequently in low birth weight infants who were more likely to survive with modern neonatal intensive care. Cicatricial RLF was more likely to result from proliferative RLF and to be more severe in lower birth weight infants, but most affected eyes retained useful vision. Comparison of cases diagnosed over the 20 years of this study suggest that cicatricial RLF in recent years is less likely to result in severe visual disability. Improving survival rates for lower birth weight infants mandate continued surveillance for RLF and study of improved oxygen monitoring techniques.


Women in Arab countries: challenging the patriarchal system?
Progress in the empowerment of Arab women was found to be low in a 2002 report. Yet Arab women's status is not reflected in continuing high fertility, which in 2000 had dropped sharply in one generation to 3.4. This paper discusses why fertility decline could nevertheless have taken place in the Arab countries. Islam has not stood in the way of fertility decline, as Iran and Algeria show. From the mid- 1970s to 1980s, subsidised consumption through oil wealth redistribution reduced the cost of children, and social conservatism kept married women out of the labour force, both of which promoted higher fertility. The early stages of fertility decline were mainly due to longer length of education of girls, rising female age at first marriage, e.g. 28 in urban Morocco and 29 in Libya, and entry into the labour force of young, single women. There is also a growing population sub-group of never-married young women. Collapsing oil prices and structural adjustment reduced household resources and became an effective fertility regulation factor. Girls born since the 1950s have not only been educated longer than their mothers, but also their fathers, which increases their authority. These factors, and women's activism and civil and political lobbying for the reform of personal status now underway in a number of Arab countries, could all challenge the patriarchal system.


Pharmacological study of modified intermediate-dose cytarabine therapy in patients with acute myeloid leukemia.
Instead of the original intermediate dose (0.5 g/m2), a modified intermediate-dose 1-beta-D-arabinofuranosylcytosine (ara-C) therapy (1 g/m2, 1-h intravenous infusion) was pharmacologically studied in 11 leukemic patients. The concentrations of ara-C and its inactive metabolite, 1-beta-D-arabinofuranosyluracil (ara-U) in the plasma, urine and cerebrospinal fluid were determined using high performance liquid chromatography. The plasma ara-C reached a peak (61.2 +/- 52.7 microM) that far surpassed the saturating level for intracellular activation of the drug. The plasma ara-U reached its peak (139.8 +/- 40.0 microM) and was maintained with a half-life of 277 +/- 76 min. About 60% of the administered drug was recovered, mainly as ara-U in urine within 12 h. In contrast to the original intermediate dose, the therapeutic ara-C levels (above 0.4 microM) persisted in the central nervous system. The therapy salvaged one relapsed leukemia patient with central nervous system involvement. Modified intermediate-dose ara-C provides a sufficient plasma ara-C level with a concomitant therapeutic concentration in the cerebrospinal fluid.


Multicolor 3D fluorescence in situ hybridization for imaging interphase chromosomes.
Fluorescence in situ hybridization (FISH) of specific DNA probes has become a widely used technique mostly for chromosome analysis and for studies of the chromosomal location of specific DNA segments in metaphase preparations as well as in interphase nuclei. FISH on 3D-preserved nuclei (3D-FISH) in combination with 3D-microscopy and image reconstruction is an efficient tool to analyze the spatial arrangement of targeted DNA sequences in the nucleus. Recent developments of a "new generation" of confocal microscopes that allow the distinct visualization of at least five different fluorochromes within one experiment opened the way for multicolor 3D-FISH experiments. Thus, numerous differently labeled nuclear targets can be delineated simultaneously and their spatial interrelationships can be analyzed on the level of individual nuclei.In this chapter, we provide protocols for the preparation of complex DNA-probe sets suitable for 3D-FISH with up to six different fluorochromes, for 3D-FISH on cultured mammalian cells (growing in suspension or adherently) as well as on tissue sections, and for 3D immuno-FISH.In comparison with FISH on metaphase chromosomes and conventional interphase cytogenetics, FISH on 3D-preserved nuclei requires special demands with regard to probe quality, fixation, and pretreatment steps of cells in order to achieve the two goals, namely the best possible preservation of the nuclear structure and at the same time an efficient probe accessibility.


Generation of Human Neurons by microRNA-Mediated Direct Conversion of Dermal Fibroblasts.
MicroRNAs (miRNAs), miR-9/9*, and miR-124 (miR-9/9*-124) display fate-reprogramming activities when ectopically expressed in human fibroblasts by erasing the fibroblast identity and evoking a pan-neuronal state. In contrast to induced pluripotent stem cell-derived neurons, miRNA-induced neurons (miNs) retain the biological age of the starting fibroblasts through direct fate conversion and thus provide a human neuron-based platform to study cellular properties inherent in aged neurons and model adult-onset neurodegenerative disorders using patient-derived cells. Furthermore, expression of neuronal subtype-specific transcription factors in conjunction with miR-9/9*-124 guides the miNs to distinct neuronal fates, a feature critical for modeling disorders that affect specific neuronal subtypes. Here, we describe the miR-9/9*-124-based neuronal reprogramming protocols for the generation of several disease-relevant neuronal subtypes: striatal medium spiny neurons, cortical neurons, and spinal cord motor neurons.


Effects of active and sham tDCS on the soleus H-reflex during standing.
Weak transcranial direct current stimulation (tDCS) is known to affect corticospinal excitability and enhance motor skill acquisition, whereas its effects on spinal reflexes in actively contracting muscles are yet to be established. Thus, in this study, we examined the acute effects of Active and Sham tDCS on the soleus H-reflex during standing. In fourteen adults without known neurological conditions, the soleus H-reflex was repeatedly elicited at just above M-wave threshold throughout 30 min of Active (N = 7) or Sham (N = 7) 2-mA tDCS over the primary motor cortex in standing. The maximum H-reflex (Hmax) and M-wave (Mmax) were also measured before and immediately after 30 min of tDCS. The soleus H-reflex amplitudes became significantly larger (by 6%) ≈1 min into Active or Sham tDCS and gradually returned toward the pre-tDCS values, on average, within 15 min. With Active tDCS, the amplitude reduction from the initial increase appeared to occur more swiftly than with Sham tDCS. An acute temporary increase in the soleus H-reflex amplitude within the first minute of Active and Sham tDCS found in this study indicates a previously unreported effect of tDCS on the H-reflex excitability. The present study suggests that neurophysiological characterization of Sham tDCS effects is just as important as investigating Active tDCS effects in understanding and defining acute effects of tDCS on the excitability of spinal reflex pathways.


Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study.
Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice. A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%-125% of the reference. Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93-119)/97% (87-108)/96% (74-124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100-122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63-78)/66% (51-85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96-118)/86% (82-91)/84% (69-103), respectively. Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.


Taming systems to create enabling environments for HCV treatment: negotiating trust in the drug and alcohol setting.
HCV (hepatitis C) treatment uptake among the population most affected - people who inject drugs - is suboptimal. Hospital based treatment provision is one evidenced barrier to HCV treatment uptake. In response, HCV treatment is increasingly located in treatment settings seen as more amenable to people who inject drugs, such as drug and alcohol services. We explored the accessibility of HCV treatment provision at two such partnerships. Data collection comprised qualitative interviews collected in 2011 and 2012 with 35 service users and 14 service providers of HCV treatment in London, United Kingdom. We draw here primarily on thematic analyses of service provider accounts, yet narratives relating to trust and environment emerged unsolicited in both user and provider accounts of negotiated HCV treatment access. A key theme in service provider accounts were strategies they deployed to 'tame' the treatment system so as to create an 'enabling environment' of care, in which trust was a critical feature. This 'taming' of the system was enacted through practices of 'negotiated flexibility', including in relation to appointments, eligibility, and phlebotomy. Service user accounts accentuated familiar environments and known health providers as those most trusted, and the potentially stigmatising effects of negotiating treatment in unfamiliar territory, especially hospital settings. Whilst noting the effects of provider strategies to negotiate flexibility on behalf of would-be patients seeking treatment, we conclude by noting the limits of trust relations in settings of constrained choice.


Pathology of ureterorenal units in various ureteral anomalies with particular reference to the genesis of renal dysplasia.
Renal morphology of various congenital ureteral anomalies was investigated to gain further insight into the genesis of associated renal dysplasia. Abnormality in the ureteral bud explains the genesis of renal dysplasia as long as the adjoining ureter is cranially ectopic. In caudal ectopy of either single or duplex system, no difference was found in the histologic quality of kidneys with G and H position orifice. In the single system kidneys of H position orifice, however, occurrence of renal dysplasia was not associated with obstruction, suggesting the operation of the "bud theory" even in single system caudal ectopy. In anomalies in which the ureteral orifice was not ectopic, it was suggested that renal parenchymal development was impaired by complete, but not by incomplete obstruction. The association of dysplastic ureter and renal dysplasia was not so frequent as anticipated and the hypodysplastic values of the kidneys with and without dysplastic ureters were similar, suggesting no direct causal relationship between them.


In-vitro activity of moxifloxacin and other fluoroquinolones against Chlamydia species.
The in-vitro activity of moxifloxacin, a new fluoroquinolone, against Chlamydia species was investigated. The minimal inhibitory concentration of moxifloxacin for 10 standard strains of different Chlamydia species and 15 wild-type strains of Chlamydia pneumoniae isolated in Japan, which were morphologically different from clinical isolates from the United States, ranged from 0.031 to 0.125 microg/ml. The activity of moxifloxacin was almost the same as those of sparfloxacin, and it was 16, 8, 2, and 2 times more active than ciprofloxacin, levofloxacin, grepafloxacin, and tosufloxacin, respectively. The minimal chlamydiacidal concentration of moxifloxacin ranged from 0.031 to 0.125 microg/ml. These results suggest that moxifloxacin has potential effects against Chlamydia species.


Cytogenetic differences in breast cancer samples between German and Japanese patients.
Japanese and German breast cancer cases differ substantially in the frequency of egfr amplification. To unravel further the cytogenetic differences between Japanese and German breast cancer cases. Forty one Japanese breast cancer cases were evaluated by means of comparative genomic hybridisation (CGH). The results were compared with the CGH results from 161 German breast cancer cases. The mean number of genetic alterations/case was significantly higher in German premenopausal patients with breast cancer than in their Japanese counterparts. Japanese breast cancer cases revealed a higher number of chromosome 17p losses. Losses of 8p were associated with oestrogen receptor (ER) negativity in Japanese patients with breast cancer, whereas in the German patients gains of 3q and 6q were associated with the lack of ER expression. The interethnic differences of invasive breast cancer are reflected by cytogenetic aberrations, which are also associated with the differential expression of the ER.


Kinetics modeling of dynamic pyrolysis of bagasse fibers.
The thermal decomposition mechanism of raw and treated bagasse fibers was modeled with three parallel independent first-order reactions. The kinetic parameters and pseudo components which best fit the experimental dynamic pyrolysis rate of bagasse was determined by means of the Matlab program using the least-square method. The calculated rate of thermal decomposition for each bagasse sample was consistent with experimental pyrolysis rate very well. A method was adopted to calculate the contents of cellulose, hemicelluloses, and lignin for bagasse fiber based on the dynamic pyrolysis model. The calculated contents of the untreated bagasse fiber agreed very well with some reported values from the literature. The effect of treatment conditions on the bagasse fiber compositions was also studied. From the three-dimensional plot for each of the three components, it could be observed that bagasse fibers treated under the intermediate alkaline condition could achieve the higher content of cellulose.


'Mindful eating' for reducing emotional eating in patients with overweight or obesity in primary care settings: A randomized controlled trial.
The primary aim of this study was to analyse the efficacy of a 'mindful eating' programme for reducing emotional eating in patients with overweight or obesity. A cluster randomized controlled trial (reg. NCT03927534) was conducted with 76 participants with overweight/obesity who were assigned to 'mindful eating' (7 weeks) + treatment as usual (TAU), or to TAU alone. They were assessed at baseline, posttreatment and 12-month follow-up. The main outcome was 'emotional eating' (Dutch Eating Behaviour Questionnaire, DEBQ); other eating behaviours were also assessed along with psychological and physiological variables. 'Mindful eating' + TAU reduced emotional eating both at posttreatment (B = -0.27; p = 0.006; d = 0.35) and follow-up (B = -0.53; p < 0.001; d = 0.69) compared to the control group (TAU alone). 'External eating' (DEBQ) was also significantly improved by the intervention at both timepoints. Significant effects at follow-up were observed for some secondary outcomes related to bulimic behaviours, mindful eating, mindfulness, and self-compassion. Weight and other physiological parameters were not significantly affected by 'mindful eating' + TAU. These findings support the efficacy of the 'mindful eating' + TAU programme for reducing emotional and external eating, along with some other secondary measures, but no significant changes in weight reduction were observed.


Tibial component fixation with a peri-apatite coating: evaluation by radiostereometric analysis in a canine total knee arthroplasty model.
Cementless fixation for the tibial component in total knee arthroplasty (TKA) remains problematic. Peri-Apatite (PA), a solution-deposited hydroxyapatite, is under investigation as an option for improving the fixation of cementless tibial components. In this study, radiostereometric analysis was used to document implant migration in 48 dogs that underwent TKA with cementless, PA-coated, or cemented tibial components. Migration at 12 weeks was similar in the 2 groups. At 12 months, there was greater migration in the PA-coated group, but the difference between the 2 groups was below the threshold considered clinically significant. In this canine TKA model, cementless fixation with PA performed less well than did cemented fixation, but not to a degree that would make a clinical difference in the short term.


Interference of lysozyme in the sandwich enzyme-linked immunosorbent assay (ELISA).
Lysozyme can cause unreliable results in sandwich ELISA procedures, since it strongly associates with proteins with low isoelectric points. As immunoglobulins have an isoelectric point of about 5, lysozyme may form a bridge between the IgG in the coat and the IgG of the enzyme-labeled antibodies. For reliable ELISA results, it is necessary either to remove lysozyme from samples or to mask it. Both Cu2+ ions and ovalbumin were very effective in masking lysozyme and thus avoiding its linkage to immunoglobulins. Ovalbumin was not always as effective as Cu2+ ions because in test samples other proteins with high isoelectric points may be present which may compete with lysozyme for association with ovalbumin.


Evaluation of long term outcome of auditory training programs in children with auditory processing disorders.
To evaluate the long term effects of Arabic auditory training 'AT' programs in Egyptian school-aged children with auditory processing disorders 'APD'. Thirty children with APD who received the proper regular AT for minimum duration of 2 months were included. They were subjected to functional measures 'questionnaire for APD' and psychophysical test battery. It comprised dichotic digits, pitch pattern sequence 'PPS', gap in noise detection 'GIN' and the memory tests. New bench mark battery was applied in the form of the duration pattern, the dichotic rhyme and the informal memory tests. The results of different tests were compared across the evaluation sessions 'pre-training, immediate post training, and the late outcome'. The children were evaluated after mean duration 24.5 months, ranged 7-42 months from the end of AT. No deterioration in the scores of Arabic questionnaire or the psychophysical tests was observed compared to the immediate post training evaluation. The bench mark tests scores matched the age based norms. A statistical significant correlation existed between PPS, GIN tests and the functional measures. The outcome of the AT program showed long term consistency. The temporal processing tests (PPS, GIN) were sensitive tools in monitoring the progress of training. The new bench mark test battery used was effective as the diagnostic test battery in assessing the long term effects of AT program.


Deployment of a mixed-mode data collection strategy does not reduce nonresponse bias in a general population health survey.
To assess nonresponse bias in a mixed-mode general population health survey. Secondary analysis of linked survey sample frame and administrative data, including demographic and health-related information. The survey was administered by mail with telephone follow-up to nonrespondents after two mailings. To determine whether an additional mail contact or mode switch reduced nonresponse bias, we compared all respondents (N = 3,437) to respondents from each mailing and telephone respondents to the sample frame (N = 6,716). Switching modes did not minimize the under-representation of younger people, nonwhites, those with congestive heart failure, high users of office-based services, and low-utilizers of the emergency room but did reduce the over-representation of older adults. Multiple contact and mixed-mode surveys may increase response rates, but they do not necessarily reduce nonresponse bias.


Potent inhibition of local and disseminated tumor growth in immunocompetent mouse models by a bispecific antibody construct specific for Murine CD3.
Bispecific single-chain antibody constructs specific for human CD3 have been extensively studied for antitumor activity in human xenograft models using severe combined immunodeficient mice supplemented with human T cells. High efficacy at low effector-to-target ratios, independence of T cell costimuli and a potent activation of previously unstimulated polyclonal T cells were identified as hallmarks of this class of bispecific antibodies. Here we studied a bispecific single-chain antibody construct (referred to as 'bispecific T cell engager', BiTE) in an immunocompetent mouse model. This was possible by the use of a murine CD3-specific BiTE, and a syngeneic melanoma cell line (B16F10) expressing the human Ep-CAM target. The murine CD3-specific BiTE, called 2C11x4-7 prevented in a dose-dependent fashion the outgrowth of subcutaneously growing B16/Ep-CAM tumors with daily i.v. injections of 5 or 50 microg BiTE which was most effective. Treatment with 2C11x4-7 was effective even when it was started 10 days after tumor cell inoculation but delayed treatments showed a reduction in the number of cured animals. 2C11x4-7 was also highly active in a lung tumor colony model. When treatment was started on the day of intravenous tumor cell injection, seven out of eight animals stayed free of lung tumors, and three out of eight animals when treatment was started on day 5. Our study shows that BiTEs also have a high antitumor activity in immunocompetent mice and that there is no obvious need for costimulation of T cells by secondary agents.


Characteristics of light intensity enhancement of a silver nanoprism with rounded corners.
We have fabricated silver nanoprisms of 100-600 nm side length by focussed ion beam lithography and measured the light intensity scattering spectra using dark-field microscopy. Two resonance peaks due to localized surface plasmon excitation were observed in the spectra and their central frequency shown to depend on the prism size. The near-field electromagnetic intensity distribution with TE-polarized light at the vacuum wavelength of 632.8 nm was measured. We have obtained a much lower light intensity enhancement than previously numerically predicated. However, scattering spectra obtained numerically, taking into account roundness of the prism corners, agree well with experimental ones. At the same time, the numerically determined field distribution was different to the near-field intensity obtained experimentally. Our results suggest the particular shape of the corner region of the prism is a key factor for obtaining a large light intensity enhancement and shaping the local field distribution.


Detection of the Oxidation Area by Spectrophotometry: Regional and Temporal Changes in Anodic Oxidation on Titanium in Bipolar Electrochemistry.
This study investigated the temporal change in the oxidation area on a titanium (Ti) bipolar electrode (BPE) subjected to bipolar anodization in a direct current (DC) electric field using a spectrophotometer. The rectangular Ti sheet used as a BPE was horizontally positioned at the center of a cell. After the DC bipolar anodization, the oxidized area was detected nondestructively and visually using a specific interference color that depends on the thickness of the barrier-type oxide film formed on the Ti BPE. The change in the L*a*b* color space corresponding to each interference color revealed that the oxidation area increased along the longitudinal axis of the BPE with the increasing electrolysis time by reflecting the change in the potential distributions on the BPE. As visually demonstrated, the area where the anodic reaction proceeded reached saturation at 90% of the BPE surface area.


Role of adiponectin, resistin and monocyte chemo-attractant protein-1 in overweight/obese asthma phenotype in children.
Asthma is a chronic inflammatory disorder of the airways with diverse overlapping pathologies and phenotypes contributing to a significant heterogeneity in clinical manifestations. Obesity may modify asthma risk, phenotype, and prognosis. A suggested mechanism linking obesity and asthma is through systemic inflammation. Adipokines secreted by adipose tissue were suggested to provide a link between obesity and asthma. To have an understanding for the contribution of adiponectin, resistin and MCP-1 to development of distinct asthma phenotype in overweight/obese children through assessment of their serum level and correlation to pulmonary function tests. The study included 29 normal weight asthmatics, 23 overweight/obese asthmatic children and 30 controls. All cases were subjected to detailed history taking, thorough examination and pulmonary function tests. Serum adiponectin, resistin, MCP-1 and IgE were assessed to all recruited subjects. Adiponectin level was significantly higher in overweight/obese asthmatics (24900 ± 1600 ng/ml) compared to normal weight asthmatics (21700 ± 1700 ng/ml) and control (23000 ± 3200 ng/ml), (p < 0.001 & 0.051 respectively). Normal weight asthmatics had significantly lower adiponectin level than control, (p = 0.039). A significant low level of MCP-1 in overweight/obese asthmatics (149.5 (20-545) ng/L) compared to control (175 (28 -1123.5) ng/L), p = 0.037. No significant difference was found regarding resistin. Normal weight asthmatics had significantly lower FEV1% and FVC% compared to overweight/obese asthmatics (p = 0.036, 0.016 respectively). A significant positive correlation was found between (FEV1%, FVC) and BMI in normal weight asthmatics (P = 0.01, < 0.01 respectively) and a significant negative correlation between PEF and BMI (-0.42, p = 0.05) in obese/overweight asthmatics. Resistin/adiponectin ratio was not affected by sex, degree of asthma severity or level of asthma control in either normal weight or overweight/obese asthmatic. This work could suggest that adiponectin may play a role in overweight/obese asthma phenotype where it is possible to have a dual action (pro & anti- inflammatory). It seems that resistin had no role in asthma pathogenesis.


Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot.
A 6-year-old Egyptian boy with frontonasal dysplasia (FND) and lipoma of the corpus callosum associated with tetralogy of Fallot is reported. The main features were severe hypertelorism, downward slanted palpebral fissures, bilateral epicanthal folds, a grossly deformed nose with notched alae nasi, absent nasal tip and long philtrum. A computerized tomography (CT) scan of the brain showed cerebral atrophy and lipoma of the corpus callosum. While marked neurological symptoms have been reported in cases with lipoma of the corpus callosum in the absence of FND, the present case and previous reports showed minor neurological alterations when lipoma of the corpus callosum was associated with FND. From the findings in this case and previous reports, it is possible to conclude that lipoma of the corpus callosum associated with FND is always located in the anterior part of the corpus callosum. The etiology of FND remains uncertain. While multifactorial inheritance has been proposed, parental consanguinity with young parental age in the present case cannot exclude autosomal recessive inheritance.


Effect of Surfagon on Open Field and Elevated Plus Maze Behavior of Gonadectomized and Non-Gonadectomized Male Rats.
We studied the effect of gonadotropin-releasing hormone agonist surfagon (2 μg/kg, once, intraperitoneally) on anxious behavior of adult gonadectomized and non-gonadectomized male rats. It was shown that surfagon significantly increased anxiety of both gonadectomized and non-gonadectomized rats in the open-field test and in elevated plus maze.


Antibodies to single-stranded DNA: an aid in diagnosis of viral hepatitis.
In clinical and subclinical viral hepatitis a significant increase of antibodies to single-stranded DNA revealed by the prepatent stage of the disease before any elevation of serum transaminases. In type A hepatitis, a rise in anti-DNA titers was detectable one to two weeks before onset of clinical and biochemical signs; in type B hepatitis, the rise of anti-DNA coincided with or preceded the appearance of HBSAg, several weeks before the onset of clinical illness. In both hepatitis types anti-DNA titers reached a peak (640--2,560) at onset and dropped shortly after serum transaminases returned to normal at the end of acute illness. The anti-DNA response in non-A/non-B hepatitis was of similar magnitude. Anti-DNA elevation was the only positive sign found in most silent infections of either type that later showed specific seroconversion. Anti-DNA levels in noninfected contacts were in the same range as those found in a group of health individuals. The anti-DNA test is useful for early diagnosis of viral hepatitis and should be a valuable addition to current epidemiological and clinical procedures.


Semantic content analysis and annotation of histological images.
This paper presents a novel two-dimensional (2-D) stochastic method for semantic analysis of the content of histological images Specifically, we propose a 2-D generalization of the traditional hidden Markov model (HMM). The generalization is called spatial-hidden Markov model (SHMM) that captures the contextual characteristics of complex biological features in histological images The model employs a second-order neighborhood system and assumes the conditional independence of vertical and horizontal transitions between hidden states. The notion of 'past' in SHMM is defined as what have been observed in a row-wise raster scan. This paper focuses on two fundamental problems: the best states decoding problem and the estimation of generation probability of an image by a SHMM. Based on our independence assumption of horizontal and vertical transitions, we derive computational tractable solutions to those problems. These solutions are direct extensions of their counterparts, i.e., the Viterbi algorithm and Forward-Backward algorithm, for 1-D HMM. Our experiments were carried on a medical image database with 200 images and compared with a state-of-the-art approach that was run on the same database. The annotation results demonstrated that SHMM consistently outperforms the previous approach and ameliorates many of its drawbacks. In addition, performance comparison with HMM has also validated the superiority of SHMM.


Anal incontinence affects more than 7% of the population, but it is likely to be underreported due to its sensitive nature. This review summarises the current knowledge of managing this condition. Initial diagnosis and evaluation of anal incontinence, as well as basic conservative treatment, can be managed in primary care. This may include patient education about the nature of the condition, as well as advice about appropriate diet, toilet routine, and lifestyle adjustments. Incontinence due to diarrhoea or constipation may be treated pharmacologically. If necessary, patients should be referred for specialised evaluation and treatment.


Work pace, stress, and cumulative trauma disorders.
This paper discusses the potential roles of work pace and work pressure as risk factors in the development of cumulative trauma disorders. Specifically, electromyographic (EMG) data were collected from the forearm flexor muscles of workers performing a highly repetitive task. This task had previously been identified as one that involved a high incidence of cumulative trauma disorders. Workers were asked to increase and decrease their work pace for short periods of time. The EMG data indicated that faster work paces were accompanied by higher forces. However, it was also noted that unsuccessful attempts to speedup or slowdown produced similar increases and decreases in EMG activity, indicating that speed of movement was not the only factor contributing to the changes in muscular activity. The results are discussed in relation to the stress and tension associated with work pressure caused by machine pacing, production standards, and incentive systems.


Draft Genome Sequence of Dematiaceous Coelomycete Pyrenochaeta sp. Strain UM 256, Isolated from Skin Scraping.
Pyrenochaeta, classified under the order Pleosporales, is known to cause diseases in plants and humans. Here, we report a draft genome sequence of a Pyrenochaeta sp. isolated from a skin scraping, with an estimated genome size of 39.4 Mb. Genes associated with the synthesis of proteases, toxins, plant cell wall degradation, and multidrug resistance were found.


Accuracy of Axis Drill Guides in the Cases of Atlantoaxial Instabilities Associated With High-Riding Vertebral Arteries, Narrow Pedicles, and Complex Deformities: Comparison of 3 Fixation Methods.
To contrast the accuracy of C2 navigation template-assisted versus freehand pedicle and/or pars screw fixation in high-risk cases where a high-riding vertebral artery (VA) or narrow pedicle and complex deformities were associated. In our hospital, computed tomography (CT) data of 30 patients with pathology on C0-1-2, who had risk factors for VA injury, that were complex cervical deformities, atlantoaxial instabilities with narrow C2 pedicle and/or HRVA variations were retrospectively reviewed. Using computer-aided design software and desktop printer we printed 3 sets of high cervical models per case. We divided them into 3 groups using 3 different C2 screw fixation techniques: the freehand pars screw fixation group, the freehand pedicle screw fixation group, and the navigation template-assisted pedicle screw fixation group. After 180 screw placements were finished, the parts underwent a CT scan. Then the breach rates on postoperative scans were measured. Our results showed that the accurate placement rate is not noticeably different between navigation template-assisted and freehand pedicle screws, where the high-riding vertebral artery and narrow pedicles were associated, but was better in the navigational template group with complex deformities. Pars screws were found to be superior in terms of accuracy. The current study suggests that navigational template-assisted pedicle screws are risky for high-risk individuals with abnormal anatomy, such as those with a high-riding vertebral artery, a narrow pedicle, and complex abnormalities, and alternative C2 pars screws may be a reliable option for such individuals.


Anatomical identification of the presumed electroreceptors of two air breathing catfishes, Clarias batrachus and Heteropneustes fossilis.
Histological preparations for light microscopy have revealed for the first time the structure of the electrorecoptor of Clarias batrachus and Heteropneustes fossilis, the 2 Indian air-breathing catfishes. These sensory organs are found to resemble the ampullary organs of many weakly electric and nonelectric electroreceptive teleost.


Reductions in self-reported stress and anticipatory heart rate with the use of a semi-automated parallel parking system.
Drivers' reactions to a semi-autonomous technology for assisted parallel parking system were evaluated in a field experiment. A sample of 42 drivers balanced by gender and across three age groups (20-29, 40-49, 60-69) were given a comprehensive briefing, saw the technology demonstrated, practiced parallel parking 3 times each with and without the assistive technology, and then were assessed on an additional 3 parking events each with and without the technology. Anticipatory stress, as measured by heart rate, was significantly lower when drivers approached a parking space knowing that they would be using the assistive technology as opposed to manually parking. Self-reported stress levels following assisted parks were also lower. Thus, both subjective and objective data support the position that the assistive technology reduced stress levels in drivers who were given detailed training. It was observed that drivers decreased their use of turn signals when using the semi-autonomous technology, raising a caution concerning unintended lapses in safe driving behaviors that may occur when assistive technologies are used.


In vitro digestion of emulsified lard-based diacylglycerols.
Diacylglycerols as a fat substitute in meat products is a growing area of interest. This study was conducted to analyze the digestion rate, digestion extent, and changes in interfacial properties of lard, glycerolized lard (GL), and purified GL (PGL) in an emulsions system by pH-stat in vitro digestion. PGL had significantly higher hydrolysis rate and final digestion extent than lard (P ≤ 0.05) during in vitro digestion. The analysis on diameter variations of lard, GL, and PGL during digestion indicated that the surface- and volume-weighted mean particle diameters of all samples had the same variation trend, but variation degree was different. Concurrently, the ζ-potential analysis of the lard, GL, and PGL during the digestion process showed that the absolute values of the ζ-potentials of the three types of lipids increased at first and subsequently decreased. The microstructure changes results for lard, GL, and PGL showed there was no obvious flocculation, and the particle size of lard throughout the digestion process was larger than that of GL and PGL. This study showed that lard-based diacylglycerols had high digestibility characteristics and could be applied as a functional lipid in meat products to improve human health. © 2020 Society of Chemical Industry.


Development of a fresh cadaver model for instruction of ultrasound-guided breast biopsy during the surgery clerkship: pre-test and post-test results among third-year medical students.
The aim of our study was to determine if a fresh cadaver model is a viable method for teaching ultrasound (US)-guided breast biopsy of palpable breast lesions. Third-year medical students were assessed both preinstruction and postinstruction on their ability to perform US-guided needle aspiration or biopsy of artificially created masses using a 10-item checklist. Forty-one third-year medical students completed the cadaver laboratory as part of the surgery clerkship. Eight items on the checklist were found to be significantly different between pre-testing and post-testing. The mean preinstruction score was 2.4, whereas the mean postinstruction score was 7.10 (P < .001). Fresh cadaver models have been widely used in medical education. However, there are few fresh cadaver models that provide instruction on procedures done in the outpatient setting. Our model was found to be an effective method for the instruction of US-guided breast biopsy among medical students.


Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer.
Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300×18nm with a 4nm-wide central channel. Heat-transformation can be applied to TMV yielding spherical nanoparticles (SNPs) measuring ~50nm in size. While bioconjugate chemistries have been established to modify the TMV rod, such methods have not yet been described for the SNP platform. In this work, we probed the reactivity of SNPs toward bioconjugate reactions targeting lysine, glutamine/aspartic acid, and cysteine residues. We demonstrate functionalization of SNPs using these chemistries yielding efficient payload conjugation. In addition to covalent labeling techniques, we developed encapsulation techniques, where the cargo is loaded into the SNP during heat-transition from rod-to-sphere. Finally, we developed TMV and SNP formulations loaded with the chemotherapeutic doxorubicin, and we demonstrate the application of TMV rods and spheres for chemotherapy delivery targeting breast cancer.


In vitro and in vivo efficacy of methyl oleate and palmitic acid against ESBL producing MDR Escherichia coli and Klebsiella pneumoniae.
Antibiotic resistance is a huge problem that stays to challenge the healthcare sector in a large part of the world in both developing and developed countries. The spread of multi drug resistant (MDR) bacteria in hospital and community settings remains a widely uncertain problem and a heavy burden to health services. This study unveils the in vitro and in vivo anti-ESBL potential of Methyl oleate (MO) and Palmitic acid (PA) against ESBL producing MDR bacterial pathogens such as Escherichia coli and Klebsiella pneumoniae. Microscopic observations unveiled the anti-ESBL efficacy of test compounds. MTT assay, in vivo anti-infective efficiency of MO and PA was tested with different concentrations. The pure compounds of MO and PA from Oxynema thaianum demonstrated high inhibitory activity in MIC and MBC assays against MDR E. coli and K. pneumoniae. Moreover, the anti-ESBL potential of MO and PA was validated through light, confocal laser scanning and scanning electron microscopic analyses. The IC50 values of MO and PA against A549 cells was recorded as 625 μg mL-1 and 514 μg mL-1, respectively. In Artemia nauplii cytotoxicity assay, the LC50 value of MO and PA were recorded as 53.33 μg mL-1 and 50 μg mL-1 respectively. The 96 h lethal concentrations obtained for Lobeo rohita treated with different concentrations of Methyl oleate and Palmitic acid. The LC50 for MO and PA was 50 mg L-1 and 100 mg L-1, respectively. Therefore the study concluded that the promising effects of MO and PA can be used as an alternative biological agent which could be positively explored to treat ESBL producing MDR pathogens.


Effects of Military activity and habitat quality on DNA damage and oxidative stress in the largest population of the Federally threatened gopher tortoise.
Department of Defense lands are essential for providing important habitat for threatened, endangered, and at-risk species (TER-S). However, there is little information on the effects of military-related contaminants on TER-S on these lands in field situations. Thus, this study examined genotoxicity and oxidative stress in gopher tortoises (Gopherus polyphemus) on Camp Shelby, MS-the largest known population of this species, which is listed as an "endangered species" in Mississippi and a "threatened species" by the U.S. government. Blood was collected from tortoises at 19 different sites on the base with different levels of habitat quality (high-quality and low-quality habitat) and military activity (high, low, and no military activity). Oxidative stress was quantified as lipid peroxidation and GSSG/GSH ratios, while DNA damage was determined using flow cytometry. Our results suggest that: (1) for tortoises residing in low-quality habitats, oxidative stress and DNA damage increased with increasing military activity, while in high-quality habitats, oxidative stress and DNA damage decreased with increasing military activity; (2) in the absence of military activity, tortoises in high-quality habitat had higher levels of oxidative stress and DNA damage than those in low-quality habitat, and (3) there were interactions between military activity, habitat quality, and landuse in terms of the amount of observable DNA damage and oxidative stress. In particular, on high-quality habitat, tortoises from areas with high levels of military activity had lower levels of oxidative stress and DNA damage biomarkers than on reference sites. This may represent a compensatory or hormetic response. Conversely, on low-quality habitats, the level of oxidative stress and DNA damage was lower on the reference sites. Thus, tortoises on higher-quality habitats may have a greater capacity for compensatory responses. In terms of management implications, it is suggested that low quality habitats should be a higher priority for remediation, and lower priority for conducting military activities.


Identification of plasmid IncQ1 and NTEKPC-IId harboring bla KPC-2 in isolates from Klebsiella pneumoniae infections in patients from Recife-PE, Brazil.
This study investigated the genetic environment of bla KPC-2 in Klebsiella pnemoniae multi-drug resistant clinical isolates. Four carbapenemase gene isolates resistant to carbapenems, collected from infected patients from two hospitals in Brazil, were investigated using polymerase chain reaction and plasmid DNA sequencing. The bla KPC-2 gene was located between ISKpn6 and a resolvase tnpR in the non-Tn4401 element (NTEKPC-IId). It was detected on a plasmid belonging to the IncQ1 group. To our knowledge, this is the first report of the presence of the bla KPC-2 gene in the NTEKPC-IId element carried by plasmid IncQ1 from infections in Brazil.


Stress enhanced reduction in peripheral blood lymphocyte numbers in dairy cows during endotoxin-induced mastitis.
Two groups of Holstein dairy cows, which showed either high- (HC; n = 8) or low (LC; n = 10) plasma cortisol concentrations in response to a psychological stressor (novel-environment test) in their first lactation, were used 1 year later for studying the effects of psychological stress on various aspects of the host defence during endotoxin-induced mastitis. Social isolation was used as a stressor; endotoxin was used to activate the host defence. HC-cows appeared to be more stressed by the experimental procedure than LC-cows. One hour after having been isolated, rectal temperature increased (+0.59 degrees C) in HC- but not in LC-cows. Handling, related to the intra-mammary administration of endotoxin, induced a higher increase in cortisol concentration in HC- than in LC-cows 1 h after injection. In addition, HC-cows vocalised significantly more frequently (595 +/- 222) than LC-cows (81 +/- 24) between 1.5 and 9.5 h after isolation. Between 3 and 5.5 h after endotoxin-treatment, cortisol concentrations increased profoundly in both LC- and HC-cows and peaked at 24.6 +/- 3.8 and 22.8 +/- 3.1 ng ml(-1), respectively. The rise in plasma cortisol concentration was associated with a decrease in the number of circulating lymphocytes between 0 and 8 h post injection (PI). Between 8 and 10 h PI, the number of circulating lymphocytes in HC-cows further decreased (40%) to 1.58x10(6) cells ml(-1) and remained so until 21 h PI. This was not the case with the LC-cows. The results show that a differing sensitivity of dairy cows to environmental stressors is associated with a significant difference in the number of circulating leukocytes following intra-mammary administration of endotoxin during a period of social isolation. The results further suggest that, apart from adrenocortical hormones, other factors related to general stress-responsiveness modulate the number of peripheral lymphocytes in dairy cows during endotoxin-induced mastitis. During environmental stress, these factors may enhance endotoxin-induced reduction in circulating lymphocyte numbers, particularly in cows that are sensitive to environmental stressors. As to the clinical relevance of these differences in stress responsiveness, no differences between LC- and HC-cows were found in disease incidence nor in duration of a disease episode during both the 1st and 2nd lactation. In the 2nd lactation. HC-cows tended to produce less milk than LC-cows.


Reversal of cluster headache side following treatment of arteriovenous malformation.
We describe the case of a forty-four year old man who had typical right sided cluster headaches and an arteriovenous malformation supplied mainly by the right anterior cerebral artery. Following endovascular embolisation of this artery the AVM was supplied mainly by the left anterior cerebral artery. Subsequent headaches have always been on the left. Transcranial Doppler studies now suggested an increase of middle cerebral artery flow velocity. We suggest that the change in haemodynamics was responsible for the change in headache side.


Cooperation of TGF-β and FGF signalling pathways in skin development.
The skin is a multi-layered structure composed of the epidermis, dermis and hypodermis. The epidermis originates entirely from the ectoderm, whereas the dermis originates from various germ layers depending on its anatomical location; thus, there are different developmental patterns of the skin. Although the regulatory mechanisms of epidermal formation are well understood, mechanisms regulating dermis development are not clear owing to the complex origin. It has been shown that several morphogenetic pathways regulate dermis development. Of these, transforming growth factor-β (TGF-β) and fibroblast growth factor (FGF) signalling pathways are the main modulators regulating skin cell induction, fate decision, migration and differentiation. Recently, the successful generation of human skin by modulating TGF-β and FGF signals further demonstrated the irreplaceable roles of these pathways in skin regeneration. This review provides evidence of the role of TGF-β and FGF signalling pathways in the development of different skin layers, especially the disparate dermis of different body regions. This review also provides new perspectives on the distinct developmental patterns of skin and explores new ideas for clinical applications in the future.


Decisions under uncertainty are more messy than they seem.
Conviction Narrative Theory (CNT) is conceptually so multifaceted as to make critical evaluation difficult. It also omits one course of action: Active engagement with the world. Parsing the developmental and mechanistic processes within CNT would allow for a rigorous research programme to put the account under test. I propose a unifying account based on active inference.


Recent advances in cascade isothermal amplification techniques for ultra-sensitive nucleic acid detection.
Nucleic acid amplification techniques have always been one of the hot spots of research, especially in the outbreak of COVID-19. From the initial polymerase chain reaction (PCR) to the current popular isothermal amplification, each new amplification techniques provides new ideas and methods for nucleic acid detection. However, limited by thermostable DNA polymerase and expensive thermal cycler, PCR is difficult to achieve point of care testing (POCT). Although isothermal amplification techniques overcome the defects of temperature control, single isothermal amplification is also limited by false positives, nucleic acid sequence compatibility, and signal amplification capability to some extent. Fortunately, efforts to integrating different enzymes or amplification techniques that enable to achieve intercatalyst communication and cascaded biotransformations may overcome the corner of single isothermal amplification. In this review, we systematically summarized the design fundamentals, signal generation, evolution, and application of cascade amplification. More importantly, the challenges and trends of cascade amplification were discussed in depth.