Implant-associated localized osteitis in murine femur fracture by biofilm forming Staphylococcus aureus: a novel experimental model.
Staphylococcus aureus (SA) is the most common causative agent for implant-associated osteitis. The present study characterizes a novel model of a low grade acute SA osteitis with bone defect in the femur which is stabilized by a titanium locking plate. Wild-type Balb/c mice were osteotomized, fixed by a locking plate and infected with SA. Mice underwent debridement 7 and 14 days later and were sacrificed at Day 28. At Days 7, 14, and 28 after inoculation local and systemic cell populations and IL-6 were analyzed. Fracture healing was quantified by radiography. The control group underwent the same procedure without infection. The bacterial load of implant-associated osteitis with biofilm formation was quantified by counting CFU and real-time PCR. Fracture healing determined by radiography was delayed in infected compared to non-infected mice. Throughout the investigation period CFU and leukocyte counts, as well as IL-6 levels were found to be significantly elevated in infected mice at the infection site but not systemically. Our murine model allows the detailed investigation of implant associated localized osteitis with biofilm producing SA and its influence on fracture healing. The model provides a tool to analyze therapeutic or prophylactic approaches to the problem of biofilm-associated osteitis.


Buccal exposure to human papillomavirus type 16 is a common yet transitory event of childhood.
High-risk human papillomaviruses, such as type 16 (HPV-16), are established etiological agents for cervical carcinoma. In most cases, this virus is transmitted sexually, though can also be spread from mother to infant at delivery. We have demonstrated previously a high prevalence ( approximately 52%) of HPV-16 DNA in the mouths of prepubertal children, albeit with low levels of transcription [Rice et al., 2000]. We investigated whether childhood buccal infections with HPV-16 are persistent or transient and whether children became infected through contact with their immediate family members. Two groups of children were selected: one group were all initially HPV-16 E5 DNA-positive in sensitive polymerase chain reaction tests of swabs from their buccal mucosa (n = 20), and the other group consisted of children who were all HPV-16 E5-negative (n = 19). Thirty months later, a second oral swab was collected from each child and tested for HPV DNA. At this second visit, 40% of the HPV-16-positive group had no detectable HPV-16 DNA; conversely, 63% of children who were originally HPV-16-negative had now acquired the virus. Three months later, a third sample was collected from eight children and their immediate families (seven were HPV-16 E5 DNA-positive at the second visit). Amongst the family samples tested, in two families a single previously untested child was HPV-16 DNA-positive. It is concluded that HPV-16 DNA in the oral cavities of children is a transient event and is most probably acquired from their peers.


Imaging solute distribution in capillary electrochromatography with laser scanning confocal microscopy.
A method for the direct observation of solute molecules interacting with a C18 stationary phase under real separation conditions in capillary electrochromatography (CEC) is investigated. The experiments were performed in a capillary electrochromatographic mode; however, the method and findings are useful both in CEC and revered-phase liquid chromatography. The distribution of solute molecules in the packed capillary is directly imaged with laser scanning confocal fluorescence microscopy. Conventional imaging techniques produce images where the C18 silica beads cannot be distinctively identified as a result of the deep depth of field. The optical sectioning capability of confocal imaging overcomes this problem to afford clearly defined images of the stationary-phase packing and the surrounding mobile phase. Fluorescein molecules are preferentially distributed in the mobile phase under reversed-phase chromatographic conditions. Nile Red and rhodamine 6G molecules prefer the environments of the porous C18 beads. Intensity distributions over time for areas within the stationary-phase beads differ from distributions of areas outside the beads in the mobile phase. Images taken at different depths into the capillary probe the internal structure of the C18 beads. While the internal structures of most beads are porous, confocal images show a small fraction (2%) of the silica beads have porous shells and nonporous cores. The capability of imaging the stationary phase distinctively from the mobile phase opens the possibilities of studying the quality of stationary phase, the structure of the column packing, and the mechanisms of separation.


C-Reactive Protein Level and the Genetic Variant rs1130864 in the CRP Gene as Prognostic Factors for 10-Year Cardiovascular Outcome.
Cardiovascular disease (CVD) is the primary cause of premature death and disability worldwide. There is extensive evidence that inflammation represents an important pathogenetic mechanism in the development and prognosis of CVD. C-reactive protein (CRP) is a potential marker of vascular inflammation and plays a direct role in CVD by promoting vascular inflammation. The objective of this study (ClinTrials.gov identifier: NCT01045070) was to assess the prognostic impact of CRP protein levels and genetic variants of CRP gene events on cardiovascular (CV) outcome (10-year follow-up) in patients suffering from CVD. CVD patients were prospectively included in this study (n = 1002) and followed up (10 years) regarding combined CV endpoint (CV death, death from stroke, myocardial infarction (MI), and stroke/transient ischemic attack (TIA)). CRP protein level (particle-enhanced immunological turbidity test) and genetic variants (rs1130864, rs1417938, rs1800947, rs3093077; polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) after DNA extraction from EDTA-blood) were evaluated. In survival analyses, increased CRP protein levels of ≥5 mg/L (log-rank test: p < 0.001, Cox regression: p = 0.002, hazard ratio = 1.49) and CT + TT genotype of rs1130864 (log-rank test: p = 0.041; Cox regression: p = 0.103, hazard ratio = 1.21) were associated with a weaker CV prognosis considering combined CV endpoint. Elevated CRP level and genetic variant (rs1130864) were proven to provide prognostic value for adverse outcome in CVD patients within the 10-year follow-up period.


Chondrosarcoma of the sphenoid--a case report and review.
The case of 57-year-old woman is presented with a chondrosarcoma of the sphenoid. The main symptom was rapid loss of vision and in order to halt this the tumour was debulked. The literature relating to chondrosarcomas of the head and neck is reviewed. These rare tumours are not radio-sensitive and surgery represents the best form of treatment at the present time. The prognosis is poor.


Chronic mandibular hypomobility related to a unilateral accessory condyle. A case report.
Chronic mandibular hypomobility is characterized by a long-standing limitation of the mouth opening related to multiple etiologies, including elongation of the coronoid apophysis. Unlike the most frequent pathologies that cause coronoid elongation, such as hyperplasia, osteoma (OM), and osteochondroma (OC), the accessory mandibular condyle (AMC) is a rare entity. Clinical Presentation: The AMC shows a configuration similar to a normal mandibular condyle with an articular surface covered by fibrocartilage that articulates with the temporal wall of the zygomatic bone, and histologically, does not show neoplastic growth. The patient was treated with a coronoidectomy, removing the coronoid apophysis as well as the AMC. This case report presents a case of an AMC to describe the clinical, imaging, surgical, and histological characteristics, establishing its differential diagnosis with hyperplasia, OM, and OC of the coronoid apophysis.


The relationship of stress, coping, effect expectancies and craving.
Based on theoretical models of craving and addiction, this study investigated the association between stress-related variables and negatively and positively reinforcing dimensions of craving (relief and reward craving) in 150 opiate addicts, 150 alcohol addicts and 150 non-addicted controls. Stress-distress was the most powerful predictor of both dimensions of craving, followed by a lack of positive coping strategies whereas expectancies of substance effects seemed to be less important. Positive coping strategies were related to reduced craving only when they were accompanied by low stress-distress. In non-addicted subjects, only positive coping strategies were negatively related to craving. This study confirms the important role of stress-distress for the occurrence of craving in addicts.


Do animacy effects persist in memory for context?
The adaptive view of human memory assumes that animates (e.g, rabbit) are remembered better than inanimates (e.g. glass) because animates are ultimately more important for fitness than inanimates. Previous studies provided evidence for this view by showing that animates were recalled or recognized better than inanimates, but they did not assess memory for contextual details (e.g., where animates vs inanimates occurred). In this study, we tested recollection of spatial information (Study 1) and temporal information (Study 2) associated with animate versus inanimate words. The findings showed that the two types of contextual information were remembered better when they were related to animates than to inanimates. These findings provide further evidence for an ultimate explanation of animacy effects.


Chronic haloperidol treatment results in a decrease in the expression of myelin/oligodendrocyte-related genes in the mouse brain.
Schizophrenia is a complex psychiatric illness that manifests as a combination of positive symptoms, negative symptoms, and cognitive deficits. Antipsychotic drugs, such as haloperidol, attenuate dopamine receptor signaling in neurons and constitute the frontline treatment for the positive symptoms of schizophrenia. However, haloperidol treatment has also been reported to exacerbate preexisting negative symptoms/cognitive deficits and the severity of these deficits has been correlated with white matter pathology in schizophrenia. Indeed, several studies implicate oligodendrocyte function in the pathophysiology of schizophrenia, but it is unknown whether these effects are related to drug treatment. It is well established that haloperidol alters gene expression in neurons. However, its effect on oligodendrocytes is unknown. In this study, we investigate the effects of chronic haloperidol treatment on the expression of eight genes known to play critical roles in myelin/oligodendrocyte function. We treated male mice with haloperidol (2 mg/kg/day) for 30 days and measured gene expression changes by using in situ hybridization analysis and quantitative densitometry. Haloperidol caused a decrease in the expression of these genes in several white matter regions of the mouse CNS. In contrast, clozapine (10 mg/kg/day) had no effect on the expression of a subset of these genes. This has important implications for both disease pathology and the consideration of treatment options for patients.


Cultural Competence Among Italian Nurses: A Multicentric Survey.
To assess Italian nurses' cultural competence, as they are increasingly called upon to care for people of foreign origins. A cross-sectional, multicentric study. From September 2013 to May 2014, a survey was carried out among Italian nurses. Cultural competence was assessed by the Cultural Competence Assessment tool, translated and adapted to the Italian context. Nurses who completed the survey numbered 1,432; 70.6% were female; 42.6% ranged in age from 41 to 50 years; and 50.0% were bachelor's prepared. More than 50% had participated in some kind of cultural diversity training. Overall, cultural competence was moderate, showing a moderately high level of cultural awareness and sensitivity (mean = 5.41; SD = 0.66) and a moderate level of culturally competent behaviors (mean = 4.33; SD = 1.10). Although Italian nurses' cultural competence was acceptable, given the growing diversity of the patient population, nurses should be better prepared to face the changing health requests. Providing culturally competent care has been associated with improved provider-client communication, higher satisfaction with care, and health status improvement, as full comprehension of health status, adherence to medications and lifestyle recommendations, and appropriate utilization of the health system. Healthcare providers need to be adequately trained to provide culturally competent care. This research provides, for the first time, a report on Italian nurses' levels of cultural competence, and strengthens the current literature underlining the need for continuous education to enhance cultural competence among nurses.


[Teratoma orbitae in the neonatal period].
The orbital teratoma is a rare congenital neoplasm. It develops from ectopic pluripotential germinal cells. In none of the cases so far described in the literature were there any signs of malignancy. The clinical appearance of the tumor is very typical; it can be diagnosed by means of ultrasound and CT scan, as shown in the present paper. Fewer than 20% of all published cases of congenital orbital teratoma were treated by methods aimed at preserving the ocular bulb. The reason why so many cases were treated by exenteration of the entire orbit was the fear of malignancy which seemed to derive from the rapid growth of the tumor. However, not a single confirmed case of malignant orbital teratoma has been described in the literature. Hence an attempt should be made to perform a local excision of the tumor without sacrificing the ocular bulb. There is then a chance that some vision will be preserved and that development of the bony structures of the orbit will be improved.


[Suppressive effects of GTW treatment on mesangial lesions in experimental irreversible glomerulosclerosis].
To examine suppressive effects of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW)on mesangial injury induced by two-injecti on of anti-Thy1. 1 monoclonal antibody(mAb) 1-22-3 in vitro. We established the irreversible model of glomerulosclerosis with anti-Thy1. 1 mAb 1-22-3. After 42 days of oral treatment with GTW (50 mg x kg(-1) BW)and vehicle (distilled water), to observe effects of GTW on proteinuria, renal function, mesangial morphological change, and mRNA expressions of collagen type I and TGF-beta by light microscope (LM), immunofluorescence (IF), and Reverse Transcription Polymerase Chain Reaction (RT-PCR). GTW ameliorated proteinuria (from day24 to day 42) and mesangial proliferation [total cell number, GTW group 65.67+/-3.43 vs. control group 87.02+/-2.41, P < 0.05; matrix expansion, GTW group 1.20+/-0.06 vs. control group 2.77+/-0.23, P < 0.05; alpha-smooth muscle actin(alpha-SMA) expression, GTW group 1.75+/-0.33 vs. control group 2.62+/-0.15, P < 0.05; collagen type I expression, GTW group 1.68+/-0.31 vs. control group 2.06+/-0.24, P < 0.05], moreover, significantly reduced the glomerular expression of mRNA for collagen type 1(53.5% to the control group, P < 0.05)and TGF-beta(14.7% to the control group, P < 0.05)on day 42day. GTW can not only decrease proteinuria, but also ameliorate mesangial alterations probably by the reduction of cytokines. GTW may be a promising agent for the prevention of progressive and irreversible glomerulosclerosis.


African American Parents' Perceived Vaccine Efficacy Moderates the Effect of Message Framing on Psychological Reactance to HPV Vaccine Advocacy.
This experiment assessed how the frame of promotional vaccine messages elicited psychological reactance differently for African American parents according to their level of perceived vaccine efficacy. We found that those with low perceived HPV vaccine efficacy experienced more psychological reactance in response to loss-framed messages compared to gain-framed messages, whereas message framing made little difference for those with high perceived HPV vaccine efficacy. In addition, the interaction between frame and perceived HPV vaccine efficacy indirectly affected parents' intentions to vaccinate their child for HPV via reactance. These results support current theorizing about framing effects under defensive message processing specifically as it applies to psychological reactance.


The use of isoelectric focusing to identify rhinoceros keratins.
Keratins represent the principal structural proteins of hair. They are also found in horn, nail, claw, hoof, and feather. Hair and nail samples from human and canine sources and hair samples from mule deer, white tail deer, cat, moose, elk, antelope, caribou, raccoon, and goat were studied. Parrot and goose feathers were also analyzed. Keratins are polymorphic, and species differences are known to exist. Proteinaceous extracts of deer and antelope antlers and bovine and rhinoceros horn were prepared by solubilizing 10 mg of horn sample in 200 microL of a solution containing 12M urea, 74mM Trizma base, and 78mM dithiothreitol (DTT). Extraction took place over a 48-h period. A 25-microL aliquot of extract was removed and incubated with 5 microL of 0.1 M DTT for 10 min at 25 degrees C. Keratins were then separated by isoelectric focusing (IEF) on 5.2% polyacrylamide gels for 3 h and visualized using silver staining. At least 20 bands could be observed for each species studied. However, band patterns differed in the position of each band, in the number of bands, and in band coloration resulting from the silver staining process. Horn from two species of rhinoceros was examined. For both specimens, most bands occurred in the pH range of 4 to 5. Although similar patterns for both species were observed, they differed sufficiently to differentiate one from the other. As might be expected, the closer two species are related phylogenetically, the greater the similarity in the IEF pattern produced from their solubilized keratin.(ABSTRACT TRUNCATED AT 250 WORDS)


A "molecular pivot-hinge" based on the pH-regulated intramolecular switching of Pt-Pt and pi-pi interactions.
The binuclear cycloplatinated complex {[Pt(L)]2(mu-dppm)}2+ (1), where HL is a new cyclometalating ligand 2-phenyl-6-(1H-pyrazol-3-yl)pyridine, is found to behave as a molecular pivot-hinge in which the closing and opening of the hinge is effected by the reversible formation and cleavage of the Pt-Pt d8-d8 interaction and the intramolecular pi-pi interaction mediated by the protonation/deprotonation of the 1-pyrazolyl-NH on the cyclometalating ligand L.


Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): A case report and review of literature.
Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently described inflammatory disease of central nervous system with distinct clinical and radiological features. The etiopathogenesis of this rare entity remains to be understood. The histopathological findings closely resemble chronic inflammatory diseases like sarcoidosis and malignancies like lymphoma. With advancements in serology, immunopathology and radiology CLIPPERS is identified as a distinct entity that differs considerably in its clinical presentation, immunopathology, radiological findings and response to steroids. We describe a case that presented to us with progressive quadriparesis and lower cranial nerve deficits whose radiological and pathological findings were consistent with CLIPPERS. The patient had a good outcome with long term immunosuppression.


Identification of a robust signature for clinical outcomes and immunotherapy response in gastric cancer: based on N6-methyladenosine related long noncoding RNAs.
Gastric cancer (GC) is a globally prevalent cancer, ranking fifth for incidence and fourth for mortality worldwide. The N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) were widely investigated in recent studies. Nevertheless, the underlying prognostic implication and tumor immune mechanism of m6A-related lncRNA in GC remain unknown. We systematically assessed the m6A modification expression of 407 GC clinical samples based on 23 m6A regulators and comprehensively associated these genes with lncRNAs. Then, we constructed a m6A-related lncRNA prognostic signature (m6A-LPS) to evaluate both status and prognosis of the disease. Immune-related mechanisms were explored via dissecting tumor-infiltrating cells as well as applying tumor immune dysfunction and the exclusion algorithm. Furthermore, we validated the latent regulative mechanism of m6A-related lncRNA in GC cell lines. The m6A-LPS containing nine hub lncRNAs was built, which possessed a superior capability to predict the outcomes of GC patients. Meanwhile, we found an intimate correlation between the m6A-LPS and tumor infiltrating cells, and that the low-risk group had a higher expression of immune checkpoints and responsed more to immunotherapy than the high-risk group. Clinically, these crucial lncRNAs expression levels were verified in ten pairs of GC samples. In in vitro experiments, the abilities of migration and proliferation were significantly enhanced via downregulating the lncRNA AC026691.1. Both migrative and proliferative capabilities of tumor cells were significantly enhanced via downregulating the lncRNA AC026691.1. in vitro. Collectively, the m6A-LPS could provide a novel prediction insight into the prognosis of GC patients and serve as an independent clinical factor for GC. These m6A-related lncRNAs might remodel the tumor microenvironment and affect the anti-cancer ability of immune checkpoint blockers. Importantly, lncRNA AC026691.1 could inhibit both migration and proliferation of GC by means of FTO regulation.


Persistent Environmental Toxicants in Breast Milk and Rapid Infant Growth.
Many environmental toxicants are passed to infants in utero and through breast milk. Exposure to toxicants during the perinatal period can alter growth patterns, impairing growth or increasing obesity risk. Previous studies have focused on only a few toxicants at a time, which may confound results. We investigated levels of 26 toxicants in breast milk and their associations with rapid infant growth, a risk factor for later obesity. We used data from the Norwegian HUMIS study, a multi-center cohort of 2,606 mothers and newborns enrolled between 2002 and 2008. Milk samples collected 1 month after delivery from a subset of 789 women oversampled by overweight were analyzed for toxicants including polychlorinated biphenyls (PCBs), heavy metals, and pesticides. Growth was defined as change in weight-for-age z-score between 0 and 6 months among the HUMIS population, and rapid growth was defined as change in z-score above 0.67. We used a Bayesian variable selection method to determine the exposures that most explained variation in the outcome. Identified toxicants were included in logistic and linear regression models to estimate associations with growth, adjusting for maternal age, smoking, education, pre-pregnancy body mass index (BMI), gestational weight gain, parity, child sex, cumulative breastfeeding, birth weight, gestational age, and preterm status. Of 789 infants, 19.2% displayed rapid growth. The median maternal age was 29.6 years, and the median pre-pregnancy BMI was 24.0 kg/m2, with 45.3% of mothers overweight or obese. Rapid growers were more likely to be firstborn. Hexachlorobenzene, β-hexachlorocyclohexane (β-HCH), and PCB-74 were identified in the variable selection method. An interquartile range (IQR) increase in β-HCH exposure was associated with a lower odds of rapid growth (OR 0.63, 95% CI 0.42-0.94). Newborns exposed to high levels of β-HCH showed reduced infant growth (β = -0.03, 95% CI -0.05 to -0.01 for IQR increase in breast milk concentration). No other significant associations were found. Our results suggest that early life β-HCH exposure may be linked to slowed growth. Further research is warranted on the potential mechanism behind this association and the longer-term metabolic effects of perinatal β-HCH exposure.


Lhermitte-Duclos disease with cervical paraspinal arteriovenous fistula.
A 38-year-old man presented with a dysplastic cerebellar gangliocytoma associated with a paraspinal arteriovenous fistula (AVF) at the upper cervical portion. Neuroimaging examination indicated the diagnosis of Lhermitte-Duclos disease. The patient was treated by embolization of the AVF followed by partial resection of the cerebellar tumor. Genetic examination showed a mutation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene. Histological examination confirmed the diagnosis. Lhermitte-Duclos disease is a rare dysplastic gangliocytoma manifesting as a slowly growing mass in the cerebellum and is usually asymptomatic. This case of Lhermitte-Duclos disease associated with paraspinal AVF and mutation of the PTEN gene suggests a relationship between Lhermitte-Duclos disease and Cowden disease.


Inappropriate alloantigen-like specificities detected on reticulum cell sarcomas of SJL/J mice: characterization and biologic role.
SJL/J (H-2s) reticulum cell sarcomas (RCS) of different origins (spontaneous, transplantable, and cell lines) carry antigens that cross-react with BALB/c (H-2d) and C57BL/6 (H-2b) alloantigens in tests measuring cell-mediated cytotoxicity, antibody-dependent cytotoxicity, and immunofluorescence. These inappropriate antigens on RCS cells were not detected on normal SJL/J splenocytes. Immunochemical analysis of the inappropriate antigens by two-dimensional gel electrophoresis was performed with SJL/J anti-BALB/c and monospecific anti-H-2Dd sera. These sera precipitated 45,000 molecular weight molecules from BALB/c lymph node cells and from SJL/J in vivo and in vitro RCS tumor that appeared very similar. The sera also precipitated molecules from SJL/J lymph node cells that resemble the BALB/c and RCS molecules. Because of the highly immunogenic nature of RCS in vivo, we examined antigen-reactive cell opsonization (ARCO) as a possible mechanism of tumor enhancement. 125IUdR-labeled SJL/J anti-RCS lymphocyte (*ARC) were diverted to the liver (opsonized) when injected i.v. into syngeneic tumor-bearing mice. Furthermore, SJL/J anti-BALB/c *ARC were opsonized in mice with BALB/c positive spontaneous tumors but not in mice with H-2d negative tumors. Our results show that RCS tumors express inappropriate alloantigens (cryptic on normal cells) that are immunogenic in vivo. Specific antitumor ARC are opsonized in tumor bearers provoking ineffective immunity and survival of antigenic spontaneous RCS tumors.


Biphasic growth in fish I: theoretical foundations.
We develop the theory of biphasic somatic growth in fish using models based on the distinction between pre- and post-maturation growth and an explicit description of energy allocation within a growing season. We define a 'generic biphasic' (GB) model that assumes post-maturation growth has a von Bertalanffy (vB) form. For this model we derive an explicit expression for the gonad weight/somatic weight ratio (g) which may either remain fixed or vary with size. Optimal biphasic models are then developed with reproductive strategies that maximise lifetime reproductive output. We consider two optimal growth models. In the first (fixed g optimal), gonad weight is constrained to be proportional to somatic weight. In the second (variable g optimal) model, allocation to reproduction is unconstrained and g increases with size. For the first of these two models, adult growth in a scaled measure of length has the exact vB form. When there are no constraints on allocation, growth is vB to a very good approximation. In both models, pre-maturation growth is linear. In a companion paper we use growth data from lake trout (Salvelinus namaycush) to test the bioenergetics assumptions used to develop these models, and demonstrate that they have advantages over the vB model, both in quality of fit, and in the information contained in the fitted parameters.


Design of a sorbitol-activated nitrogen metabolism-dependent regulatory system for redirection of carbon metabolism flow in Bacillus licheniformis.
Synthetic regulation of metabolic fluxes has emerged as a common strategy to improve the performance of microbial cell factories. The present regulatory toolboxes predominantly rely on the control and manipulation of carbon pathways. Nitrogen is an essential nutrient that plays a vital role in growth and metabolism. However, the availability of broadly applicable tools based on nitrogen pathways for metabolic regulation remains limited. In this work, we present a novel regulatory system that harnesses signals associated with nitrogen metabolism to redirect excess carbon flux in Bacillus licheniformis. By engineering the native transcription factor GlnR and incorporating a sorbitol-responsive element, we achieved a remarkable 99% inhibition of the expression of the green fluorescent protein reporter gene. Leveraging this system, we identified the optimal redirection point for the overflow carbon flux, resulting in a substantial 79.5% reduction in acetoin accumulation and a 2.6-fold increase in acetate production. This work highlight the significance of nitrogen metabolism in synthetic biology and its valuable contribution to metabolic engineering. Furthermore, our work paves the way for multidimensional metabolic regulation in future synthetic biology endeavors.


The role of psychotherapy in integrated care.
The current emphasis on integrated psychiatric and medical care for people with mental illnesses raises hopes for more favorable clinical outcomes as well as concerns about the quality of the actual care being delivered. The author writes from the perspective of a long career as a psychiatrist and psychoanalyst in a full service medical building in which communication and, at times, collaboration between mental health and general health providers yielded significant benefits to patients. Psychotherapy played a major role in these favorable outcomes, as did accessibility to general medical services when needed and working relationships between physicians of different specialties. However, conditions in current integrated systems pose seemingly insurmountable obstacles to offering full service psychiatric care. The overwhelming disproportion between the numbers of patients in serious need and the available psychiatric resources creates wrenching clinical dilemmas. The hard-nosed administrative approaches to the challenge appear to leave out the factors of human relationships and the conditions necessary for effective psychotherapy beyond simple triage and ultra-brief supportive therapy in crises. Where it is possible for psychiatrists to work closely with other physicians, certain conditions are necessary to maintain the integrity of the psychotherapeutic relationship and the psychiatrist's psychotherapeutic skills.


Sonlicromanol's active metabolite KH176m normalizes prostate cancer stem cell mPGES-1 overexpression and inhibits cancer spheroid growth.
Aggressiveness of cancers, like prostate cancer, has been found to be associated with elevated expression of the microsomal prostaglandin E synthase-1 (mPGES-1). Here, we investigated whether KH176m (the active metabolite of sonlicromanol), a recently discovered selective mPGES-1 inhibitor, could affect prostate cancer cells-derived spheroid growth. We demonstrated that KH176m suppressed mPGES-1 expression and growth of DU145 (high mPGES-1 expression)-derived spheroids, while it had no effect on the LNCaP cell line, which has low mPGES-1 expression. By addition of exogenous PGE2, we found that the effect of KH176m on mPGES-1 expression and spheroid growth is due to the inhibition of a PGE2-driven positive feedback control-loop of mPGES-1 transcriptional regulation. Cancer stem cells (CSCs) are a subset of cancer cells exhibiting the ability of self-renewal, plasticity, and initiating and maintaining tumor growth. Our data shows that mPGES-1 is specifically expressed in this CSCs subpopulation (CD44+CD24-). KH176m inhibited the expression of mPGES-1 and reduced the growth of spheroids derived from the CSC. Based on the results obtained we propose selective mPGES-1 targeting by the sonlicromanol metabolite KH176m as a potential novel treatment approach for cancer patients with high mPGES-1 expression.


Review-Microwave Radar Sensing Systems for Search and Rescue Purposes.
This paper presents a survey of recent developments using Doppler radar sensor in searching and locating an alive person under debris or behind a wall. Locating a human and detecting the vital signs such as breathing rate and heartbeat using a microwave sensor is a non-invasive technique. Recently, many hardware structures, signal processing approaches, and integrated systems have been introduced by researchers in this field. The purpose is to enhance the accuracy of vital signs' detection and location detection and reduce energy consumption. This work concentrates on the representative research on sensing systems that can find alive people under rubble when an earthquake or other disasters occur. In this paper, various operating principles and system architectures for finding survivors using the microwave radar sensors are reviewed. A comparison between these systems is also discussed.


Organization and expression of basement membrane collagen IV genes and their roles in human disorders.
Six distinct genes have been identified as belonging to the type IV collagen gene family. They can be organized into three sets, i.e., COL4A1/COL4A2, COL4A3/COL4A4, and COL4A5/COL4A6, which are localized on three different chromosomes in humans, 13, 2, and X, respectively. Within each set the genes are aligned head-to-head and their expression is regulated by bidirectional promoters between the genes. Transcriptional regulation of the COL4A1/COL4A2 set has been well characterized. The transcription of COL4A6 seems to be controlled by two alternative promoters. While collagen IV molecules composed of alpha1 and alpha2 chains are broadly distributed, molecules comprising combinations of the other four chains, alpha3-alpha6, are important components of specialized basement membranes. The precise chain composition of triple-helical molecules assembled from the alpha3-alpha6 chains is not entirely clear, but it is hypothesized that alpha3-alpha5 chains and alpha5 and alpha6 chains form heterotrimeric molecules. Several pieces of evidence indicate that alpha3/alpha4/alpha5 molecules and alpha5/alpha6 molecules are components of the basement membrane network. This helps explain the observation that the kidney and skin basement membranes from patients with Alport syndrome caused by mutations in the alpha5 coding gene, COL4A5, are defective in the alpha3, alpha4, and alpha6 chains together with the alpha5 chain. Large deletions involving the COL4A5 and COL4A6 genes have been found in rare cases of diffuse leiomyomatosis associated with Alport syndrome.


Effective, safe, practical and affordable periodontal antimicrobial therapy: where are we going, and are we there yet?
Several important trends are noticeable in the management of periodontal disease. Searching for specific risk factors for periodontal disease permits therapy planning with the intention of doing less for low-risk patients and increasing the preventive and therapeutic modalities for high-risk patients. Also, significant progress in the area of chemotherapeutic development enables dentists to increase the number of periodontitis patients receiving nondisruptive antimicrobial therapy and decreases the need for surgical treatment. Use of anti-infective chemotherapeutic and antibiotic agents has become a specialized and increasingly effective means of preventing and treating destructive periodontal disease. Local care, including subgingival application of some type of antiseptics, is widely accepted. The use of systemic antibiotics is not routine and should be reserved for aggressive and refractory periodontal infections. In general, it is better to be thoroughly familiar with a limited number of drugs and treatment methods and use them properly than to try to master a plethora of antimicrobial therapies. Combating periodontal infections is best accomplished by combined mechanical and chemotherapeutic efforts of the dental professional and the patient. The trend during recent years has been to treat periodontal infections aggressively, employing short-course antimicrobial therapy using a battery of safe and affordable antimicrobial agents, each exhibiting high activity against various periodontal pathogens and administered in ways to concurrently affect pathogens residing in different oral ecological niches, followed by regular maintenance visits having a strong anti-infective emphasis. At the beginning of therapy, patients should be assigned self-help tasks having maximal antimicrobial effectiveness, with a focus on control of the subgingival periodontopathic microbiota. When patients see positive clinical results from their daily oral hygiene efforts, they are motivated to remain active participants in managing their periodontal condition. This article emphasizes anti-infective periodontal therapies that are effective and, when properly administered, are essentially nontoxic; are widely available around the world to dentists as well as to patients; and are acceptable to most patients in terms of methods of application, supporting oral hygiene efforts and financial costs. We believe that, with improved knowledge of the periodontopathic microbiota, with the availability of microbiological tests to identify periodontal pathogens and optimal therapy, with various safe and affordable yet effective antimicrobial agents and therapies and, eventually, with the development of one or more effective vaccines, the future looks very bright for patients at risk for or suffering from destructive periodontal disease.


Dental plaque morphology as revealed by direct observation and by replicating techniques.
The ability of four elastomer impression materials to reproduce details of bacterial plaque structures was studied by comparing areas of the replica models with corresponding areas of the replicated plaque. Plaque was grown on hydroxyapatite splint segments for 48 hours and replica models were made from three different resins. One of the resins, a methacrylate material, was not suited for this purpose due to its content of spherical particles. The polysulfide and polyether impression materials reacted with the heat curing epoxy resin, and less satisfactory results were obtained with cold curing epoxy resin. Best results were obtained by a combined use of low viscosity silicone impression materials and cold or heat curing epoxy resins as model materials. However, a considerable loss of detail occurred in the replica models compared with observations of plaque directly on splint surfaces. Outlines of individual bacteria could sometimes be seen in the models, but generally several cells seemed to fuse, and appeared like small globular structures where cells and pellicle were difficult to distinguish. The bacterial colonization started near the gingival border of the surface, initiated by attachment of individual bacteria to the pellicle surface.


Pig Induced Pluripotent Stem Cell-Derived Neural Rosettes Parallel Human Differentiation Into Sensory Neural Subtypes.
The pig is the large animal model of choice for study of nerve regeneration and wound repair. Availability of porcine sensory neural cells would conceptually allow for analogous cell-based peripheral nerve regeneration in porcine injuries of similar severity and size to those found in humans. After recently reporting that porcine (or pig) induced pluripotent stem cells (piPSCs) differentiate into neural rosette (NR) structures similar to human NRs, here we demonstrate that pig NR cells could differentiate into neural crest cells and other peripheral nervous system-relevant cell types. Treatment with either bone morphogenetic protein 4 or fetal bovine serum led to differentiation into BRN3A-positive sensory cells and increased expression of sensory neuron TRK receptor gene family: TRKA, TRKB, and TRKC. Porcine sensory neural cells would allow determination of parallels between human and porcine cells in response to noxious stimuli, analgesics, and reparative mechanisms. In vitro differentiation of pig sensory neurons provides a novel model system for neural cell subtype specification and would provide a novel platform for the study of regenerative therapeutics by elucidating the requirements for innervation following injury and axonal survival.


Importance of greater interdisciplinarity and geographic scope when tackling the driving forces behind biological invasions.
Invasive non-native species are important drivers of ecosystem change, yet the driving forces of biological invasions themselves are poorly understood. Such information is essential to ensure policies focus on the most relevant drivers, and that future scenarios capture the full range of potential outcomes for invasive non-native species. I carried out a bibliometric analysis of articles published from 2000 to 2020 that address either invasive non-native species or biodiversity and ecosystem services and that also mention 1 or more drivers of ecosystem change. I examined 5 indirect drivers (demographic, economic, governance, sociocultural, and technological) and 6 direct drivers (climate change, invasive non-native species, land-use or sea-use change, natural hazards, pollution, and resource extraction). Using the Web of Science core collection of citation indexes, I undertook searches of article titles and keywords and retrieved 27,462 articles addressing invasive non-native species and 110,087 articles dealing with biodiversity or ecosystem services. Most research to date on biological invasions as well as on biodiversity and ecosystem services has focused on anthropogenic direct drivers of ecosystem change rather than indirect drivers. Yet currently, less than 18% of articles addressing biological invasions examined drivers of ecosystem change, a similar level to that found over 20 years ago for biodiversity or ecosystem services. Knowledge of the drivers of biological invasions is limited, emphasizes tractable drivers over those that require an interdisciplinary approach, and is biased toward developed economies. Drivers generally deemed important for biological invasions, such as governance and resource extraction, accounted for less than 2% of research effort. The absence of a systematic understanding of the forces that drive invasive non-native species and how they interact means that attempts to mitigate or forecast biological invasions are likely to fail. To address biological invasions requires a much better orientation of national and international research on drivers in relation to both their actual importance as well as their policy relevance.


Galectin-3 correlates with arrhythmogenic right ventricular cardiomyopathy and predicts the risk of ventricular -arrhythmias in patients with implantable defibrillators.
Background Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterized by fibro-fatty replacement of right ventricular myocytes, increased risk of ventricular arrhythmias, and sudden cardiac death. Galectin-3 (GAL3) is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between GAL3 levels and cardiac fibrosis in heart failure. However, the role of GAL3 in the pathogenesis of ARVD and ventricular arrhythmias has not yet been evaluated thoroughly. The aim of this study was to explore GAL3 levels in patients with ARVD and its association with ventricular arrhythmias. Methods Twenty-nine patients with ARVD and 24 controls were included. All patients with ARVD had an implantable cardiac defibrillator (ICD) for primary or secondary prevention. Ventricular arrhythmia history was obtained from a chart review and ICD data interrogation. Galectin-3 levels were measured using an enzyme-linked immunosorbent assay. Results Patients with ARVD had higher plasma GAL3 levels (16.9 ± 2.6 ng/mL vs 11.3 ± 1.8 ng/mL, P < 0.001) than the control group. Ten patients had sustained or non-sustained ventricular arrhythmias during follow-up. In the multivariable analysis, left ventricular disease involvement (HR: 1.05; 95% CI: [1.01-1.12]; P = 0.03); functional capacity >2 (HR: 1.21; 95% CI: [1.13-1.31]; P < 0.005); and GAL3 levels (HR: 1.05; 95% CI: [1.00-1.11]; P = 0.01) independently predicted VT/VF. Conclusion We demonstrated that serum GAL3 was significantly elevated in patients with ARVD. Also, serum GAL 3 levels could be regarded as a candidate biomarker in the diagnosis of ARVD which needs to be tested in larger prospective studies. In addition, GAL3 levels were higher in patients with VT/VF as compared with those without VT/VF.


Neuronal transcriptome of Aplysia: neuronal compartments and circuitry.
Molecular analyses of Aplysia, a well-established model organism for cellular and systems neural science, have been seriously handicapped by a lack of adequate genomic information. By sequencing cDNA libraries from the central nervous system (CNS), we have identified over 175,000 expressed sequence tags (ESTs), of which 19,814 are unique neuronal gene products and represent 50%-70% of the total Aplysia neuronal transcriptome. We have characterized the transcriptome at three levels: (1) the central nervous system, (2) the elementary components of a simple behavior: the gill-withdrawal reflex-by analyzing sensory, motor, and serotonergic modulatory neurons, and (3) processes of individual neurons. In addition to increasing the amount of available gene sequences of Aplysia by two orders of magnitude, this collection represents the largest database available for any member of the Lophotrochozoa and therefore provides additional insights into evolutionary strategies used by this highly successful diversified lineage, one of the three proposed superclades of bilateral animals.


Human T cells loaded with superparamagnetic iron oxide nanoparticles retain antigen-specific TCR functionality.
Immunotherapy of cancer is an emerging field with the potential to improve long-term survival. Thus far, adoptive transfer of tumor-specific T cells represents an effective treatment option for tumors of the hematological system such as lymphoma, leukemia or myeloma. However, in solid tumors, treatment efficacy is low owing to the immunosuppressive microenvironment, on-target/off-tumor toxicity, limited extravasation out of the blood vessel, or ineffective trafficking of T cells into the tumor region. Superparamagnetic iron oxide nanoparticles (SPIONs) can make cells magnetically controllable for the site-specific enrichment. In this study, we investigated the influence of SPION-loading on primary human T cells for the magnetically targeted adoptive T cell therapy. For this, we analyzed cellular mechanics and the T cell response after stimulation via an exogenous T cell receptor (TCR) specific for the melanoma antigen MelanA or the endogenous TCR specific for the cytomegalovirus antigen pp65 and compared them to T cells that had not received SPIONs. SPION-loading of human T cells showed no influence on cellular mechanics, therefore retaining their ability to deform to external pressure. Additionally, SPION-loading did not impair the T cell proliferation, expression of activation markers, cytokine secretion, and tumor cell killing after antigen-specific activation mediated by the TCR. In summary, we demonstrated that SPION-loading of T cells did not affect cellular mechanics or the functionality of the endogenous or an exogenous TCR, which allows future approaches using SPIONs for the magnetically enrichment of T cells in solid tumors.


Effects of Voluntary Physical Exercise on the Neurovascular Unit in a Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Histopathologically, AD presents two pathognomonic hallmarks: (1) neurofibrillary tangles, characterized by intracellular deposits of hyperphosphorylated tau protein, and (2) extracellular amyloid deposits (amyloid plaques) in the brain vasculature (cerebral amyloid angiopathy; CAA). It has been proposed that vascular amyloid deposits could trigger neurovascular unit (NVU) dysfunction in AD. The NVU is composed primarily of astrocytic feet, endothelial cells, pericytes, and basement membrane. Although physical exercise is hypothesized to have beneficial effects against AD, it is unknown whether its positive effects extend to ameliorating CAA and improving the physiology of the NVU. We used the triple transgenic animal model for AD (3xTg-AD) at 13 months old and analyzed through behavioral and histological assays, the effect of voluntary physical exercise on cognitive functions, amyloid angiopathy, and the NVU. Our results show that 3xTg-AD mice develop vascular amyloid deposits which correlate with cognitive deficits and NVU alteration. Interestingly, the physical exercise regimen decreases amyloid angiopathy and correlates with an improvement in cognitive function as well as in the underlying integrity of the NVU components. Physical exercise could represent a key therapeutic approach in cerebral amyloid angiopathy and NVU stability in AD patients.


[Behavior and well-being of people with dementia in a social care group. Observation study with dementia care mapping].
Social care groups for people with dementia areone way to relieve family caregivers and to activate individuals with dementia. This study aimed to describe one social care group and investigate the well-being of the groups members. The research question therefore was: What are people with dementia doing and how do they feel in a social care group? In this descriptive observation study we observed three group sessions in one social care group with five members in North Rhine-Westphalia (Germany) using Dementia Care Mapping (DCM). The results show that there was a special course of action fixed by meals, welcoming and farewell. The behaviour and well-being varied. Leisure like doing handicraft and interaction were depicted as main activities. The well-being was high, if participants had energetic activities and the course of action of the different group members was similar. Interestingly one person was excluded from almost all activities. It is important for staff to know the constellation of the group and to include all visitors.


Teratosphaeria stem canker of Eucalyptus: two pathogens, one devastating disease.
Teratosphaeria gauchensis and T. zuluensis are closely related fungi that cause Teratosphaeria (previously Coniothyrium) stem canker disease on Eucalyptus species propagated in plantations for commercial purposes. This disease is present in many countries in which Eucalyptus trees are planted, and continues to spread with the international trade of infected plant germplasm. Fungi, Ascomycota, Pezizomycotina, Dothideomycetes, Dothideomycetidae, Capnodiales, Teratosphaeriaceae, Teratosphaeria. The causal agents form dark masses of pycnidia that are visible on the surface of distinct stem cankers that typically form on young green stem tissues. Accurate diagnosis of the causal agents requires DNA sequence data. Nine species of Eucalyptus are known to be affected. Of these, E. grandis and its hybrids, which include some of the most important planting stock globally, appear to be particularly vulnerable. Small necrotic lesions develop on young green stem tissue. These lesions coalesce to form large cankers that exude gum. Epicormic shoots develop below the girdling canker and, in severe cases, trees die. Mycobank, https://www.mycobank.org; Publications of the Forestry and Agricultural Biotechnology Institute (FABI), https://www.fabinet.up.ac.za/index.php/journals.


Stat3 and CCAAT enhancer-binding protein β (C/ebpβ) activate Fanconi C gene transcription during emergency granulopoiesis.
Interferon consensus sequence-binding protein (Icsbp) is required for terminating emergency granulopoiesis, an episodic event responsible for granulocyte production in response to infections and a key component of the innate immune response. Icsbp inhibits the expression of Stat3 and C/ebpβ, transcription factors essential for initiating and sustaining granulopoiesis, and activates transcription of Fanconi C (FANCC), a DNA repair protein. In prior studies, we noted accelerated bone marrow failure in Fancc-/- mice undergoing multiple episodes of emergency granulopoiesis, associated with apoptosis of bone marrow cells with unrepaired DNA damage. Additionally, we found increased expression of Fanconi C and F proteins during emergency granulopoiesis. These findings suggest that Icsbp protects the bone marrow from DNA damage by increasing activity of the Fanconi DNA repair pathway, but the mechanisms for FANCC activation during initiation of emergency granulopoiesis are unclear. In this study, we observed that Stat3 and C/ebpβ activate FANCC transcription and contribute to DNA repair. Our findings indicate that FancC expression is increased during Stat3- and C/ebpβ-induced initiation of emergency granulopoiesis by these transcription factors and is maintained through termination by Icsbp. Our work reveals that Stat3- and C/ebpβ-mediated FancC expression is a critical component for initiating and sustaining key innate immune responses.


Expression of HLA-DR antigen in skin from patients with psoriasis.
Using murine monoclonal antibodies against human HLA-DR antigen and against human T cells, we investigated the indirect immunofluorescence staining pattern of involved and uninvolved skin from patients with psoriasis. The staining pattern of involved psoriatic epidermis is different from the pattern seen in uninvolved skin from the same patient and consists of scattered, single HLA-DR positive cells alternating with groups of HLA-DR positive cells. These HLA-DR positive cell clusters can be seen at any level of the epidermis. In some patients, the dermis of involved skin shows prominent accumulations of T cells which are HLA-DR positive and thus represent activated T cells.


Association of Adjuvant Chemotherapy With Overall Survival Among Patients With Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy.
Neoadjuvant chemotherapy (NAC) is a standard treatment option for locally advanced gastric cancer (LAGC); however, the indications for adjuvant chemotherapy (AC) in patients with LAGC who received NAC remain controversial. To compare survival rates between patients with LAGC who received AC and those who did not after NAC followed by surgery. This multicenter, international cohort study included 353 patients with LAGC undergoing curative-intent gastrectomy after NAC at 2 tertiary referral teaching hospitals in China between June 1, 2008, and December 31, 2017. To externally validate the findings in the Chinese patients, 109 patients from the US and Italy between June 1, 2006, and June 30, 2013, were reviewed. The follow-up period of the Chinese patients was completed in December 2020, and the follow-up period of the Western patients was completed between February and July 2017. Data analysis was performed from December 1, 2020, to February 28, 2021. Patients who received AC and those who did not were propensity score matched to evaluate the association of AC with survival. Overall survival (OS), disease-free survival, and disease-specific survival. Of 353 patients from China (275 [78.1%] male; mean [SD] age, 58.0 [10.7] years), 262 (74.1%) received AC and 91 (25.9%) did not. After propensity score matching, the 3-year OS was significantly higher in patients who received AC (60.1%; 95% CI, 53.1%-68.1%) than in those who did not (49.3%; 95% CI, 39.8%-61.0%) (P = .02). Lymph node ratio (LNR) was significantly associated with AC benefit (P < .001 for interaction), and a plot of the interaction between LNR and AC demonstrated that AC was associated with improved OS in patients with higher (≥9%) LNRs (3-year OS: 46.6% vs 21.7%; P < .001), but not in patients with LNRs less than 9% (3-year OS: 73.9% vs 71.3%; P = .30). When stratified by AC cycles, only those patients who completed at least 4 AC cycles exhibited a significant survival benefit in the 6-month (hazard ratio, 0.56; 95% CI, 0.33-0.96; P = .03) and 9-month landmark analysis (hazard ratio, 0.50; 95% CI, 0.27-0.94; P = .03). In the external cohort, improved OS with AC administration was also found in patients with LNRs of 9% or greater (3-year OS: 53.0% vs 26.3%; P = .04). In this cohort study, the administration of AC after NAC and resection of LAGC was associated with improved prognosis in patients with LNRs of 9% or greater. These findings suggest that LNR might be valuable in AC selection in future decision-making processes.


Correlates of poor oral health related quality of life in a cohort of people who use methamphetamine in Australia.
Methamphetamine use impacts oral health, but little is known about its impacts on oral health related quality of life (OHRQoL). In this study we examined OHRQoL in a cohort of people who use methamphetamine and assessed associations with sociodemographic, behavioural, psychosocial and dental service utilisation correlates. A secondary aim was to examine the relationship between methamphetamine route of administration and OHRQoL, to test whether smoking the drug is associated with reduced OHRQoL. Cross-sectional analysis was performed, using data from VMAX, a cohort of people who use methamphetamine at least monthly in Victoria, Australia (n = 194). Utilising the oral health impact profile (OHIP-14), we assessed three OHRQoL outcomes: OHIP-14 prevalence, OHIP-14 extent and OHIP-14 severity. Regression analyses examined associations between independent variables and the three OHIP-14 outcome measures. A significant segment of the cohort (35%) reported poor OHRQoL. Overall, no statistically significant association was detected between methamphetamine route of administration and the three OHIP-14 outcomes. Participants living in rural areas, with moderate-to-severe self-reported depression and with methamphetamine dependence had significantly worse OHRQoL levels, which persisted after adjusting for other covariates. Overall, VMAX cohort participants reported reduced OHRQoL levels. Our findings highlight the need for upstream interventions to improve the OHRQoL of people who use methamphetamine, with specific focus on those living in rural locations. Further research on the links between OHRQoL and mental health among people who use methamphetamine is required.


Heterologous expression of geraniol dehydrogenase for identifying the metabolic pathways involved in the biotransformation of citral by Acinetobacter sp. Tol 5.
The biotransformation of citral, an industrially important monoterpenoid, has been extensively studied using many microbial biocatalysts. However, the metabolic pathways involved in its biotransformation are still unclear, because citral is a mixture of the trans-isomer geranial and the cis-isomer neral. Here, we applied the heterologous expression of geoA, a gene encoding geraniol dehydrogenase that specifically converts geraniol to geranial and nerol to neral, to identify the metabolic pathways involved in the biotransformation of citral. Acinetobacter sp. Tol 5 was employed in order to demonstrate the utility of this methodology. Tol 5 transformed citral to (1R,3R,4R)-1-methyl-4-(1-methylethenyl)-1,3-cyclohexanediol and geranic acid. Biotransformation of citral precursors (geraniol and nerol) by Tol 5 transformant cells expressing geoA revealed that these compounds were transformed specifically from geranial. Our methodology is expected to facilitate a better understanding of the metabolic pathways involved in the biotransformation of substrates that are unstable and include geometric isomers.


Conservative surgery in the Zollinger-Ellison syndrome.
Laparotomy failed to show an obvious primary lesion in two patients with the Zollinger-Ellison syndrome (ZES), one of whom had metastatic gastrinoma in a solitary lymph node which was removed. Both patients underwent a truncal vagotomy and pyloroplasty. Postoperative acid studies have shown a marked and sustained diminution in acid hypersecretion which was particularly striking in the patient with a solitary metastatic lymph node. The patient without a detectable lesion is now well-controlled on half the dose of cimetidine required pre-operatively and the other no longer requires therapy. We believe that patients in whom pre-operative investigations have shown no evidence of extensive metastases should undergo laparotomy in the hope of finding a solitary primary or isolated metastatic lesions unassociated with an obvious primary in the pancreas. Available evidence suggests that simple removal of such lesions offers the patient an excellent chance of long-term remission. However, if no such lesion is discovered, vagotomy may be the logical procedure to assist in the subsequent pharmacological control of the acid hypersecretory state.


Paratesticular Angiomyofibroblastoma-Like Tumor: Unusual Case of a Solidocystic Form.
The angiomyofibroblastoma-like tumor of the male genital tract is a rare benign tumor. A total of 34 cases have been reported in the literature. We herein report an exceptional case of solidocystic form in its paratesticular location, in a 79-year-old man. Clinical examination objectified a right testicular induration. Macroscopic examination of the orchidectomy objectified a paratesticular solidocystic tumor formation. Microscopically, the solid area was composed of vessels with small caliber and turgidity of endothelial cells. These vessels were surrounded by clusters of epithelioid cells, sometimes having the appearance of giant cells. They were associated with spindle cells. The cystic area was uncoated. Immunohistochemically, the fusiform cells expressed Desmin and Smooth Muscle Actin. Endothelial cells and clusters of cells surrounding large vessels expressed CD34. The expression of receptors for estrogen and progesterone was negative. To our knowledge, this is the second solidocystic case of angiomyofibroblastoma-like tumor of male genital tract.


Prospective multicenter study of bronchiolitis: predictors of an unscheduled visit after discharge from the emergency department.
There is little evidence about which children with bronchiolitis will have worsened disease after discharge from the emergency department (ED). The objective of this study was to determine predictors of post-ED unscheduled visits. The authors conducted a prospective cohort study of patients discharged from 2004 to 2006 at 30 EDs in 15 U.S. states. Inclusion criteria were diagnosis of bronchiolitis, age <2 years, and discharge home; the exclusion criterion was previous enrollment. Unscheduled visits were defined as urgent visits to an ED/clinic for worsened bronchiolitis within 2 weeks. Of 722 patients eligible for the current analysis, 717 (99%) had unscheduled visit data, of whom 121 (17%; 95% confidence interval [CI] = 14% to 20%) had unscheduled visits. Unscheduled visits were more likely for children age <2 months (11% vs. 6%; p = 0.04), males (70% vs. 57%; p = 0.007), and those with history of hospitalization (27% vs. 18%; p = 0.01). The two groups were similar in other demographic and clinical factors (all p > 0.10). Using multivariable logistic regression, independent predictors of unscheduled visits were age <2 months, male, and history of hospitalization. In this study of children age younger than 2 years with bronchiolitis, one of six children had unscheduled visits within 2 weeks of ED discharge. The three predictors of unscheduled visits were age under 2 months, male sex, and previous hospitalization.


Separation of populations of sensitized lymphoid cells into fractions inhibiting and fractions enhancing syngeneic tumor growth in vivo.
Separation of subpopulations of lymphoid cells sensitized against a syngeneic tumor was attempted by means of velocity sedimentation and the fractions were injected together with tumor cells into syngeneic hosts. Spleen cells from tumor-bearing mice or spleen cells sensitized on tumor cell monolayers could be fractionated into a subpopulation capable of inhibiting growth of the same tumor and a separable fraction which enhanced tumor growth. Activity of the tumor-inhibiting lymphocytes was not apparent in the presence of the tumor-enhancing cells. The former activity was associated with small lymphocytes and the latter with injection of larger cells. Preliminary experiments investigated the developmental relation between the cells responsible for these opposing activities.


A Summary of Selective Experimental Research on Psychosocial Interventions for Sexually Abused Children.
This study was conducted to explore current trends in psychosocial interventions for sexually abused children through a review of recent research. Our comprehensive review is limited to published (quasi) experimental studies in the English language over a period of 2000-2013. It provides a detailed analysis of the final 18 articles that met our inclusion criteria, from the 670 potentially relevant articles that were identified. Reviewers analyzed candidate articles to determine whether they met inclusion or exclusion criteria. The retrieved studies reported positive results with respect to improvements in the negative psychosocial sequelae of child sexual abuse following the use of a diverse set of treatment strategies. Of the various interventions, cognitive behavioral therapy was shown to be the most promising type of intervention for sexually abused children. In this review, we discuss some of the implications of psychosocial interventions for victims of child sexual abuse, citing both the methodological and ethical issues that should be considered.


Why evolutionary biologists should be demographers.
Evolution is driven by the propagation of genes, traits and individuals within and between populations. This propagation depends on the survival, fertility and dispersal of individuals at each age or stage during their life history, as well as on population growth and (st)age structure. Demography is therefore central to understanding evolution. Recent demographic research provides new perspectives on fitness, the spread of mutations within populations and the establishment of life histories in a phylogenetic context. New challenges resulting from individual heterogeneity, and instances where survival and reproduction are linked across generations are being recognized. Evolutionary demography is a field of exciting developments through both methodological and empirical advances. Here, we review these developments and outline two emergent research questions.


RUNX3 suppresses migration, invasion and angiogenesis of human renal cell carcinoma.
RUNX3 (runt-related transcription factor-3) is a known tumor suppressor gene which exhibits potent antitumor activity in several carcinomas. However, little is known about the role of RUNX3 in human renal cell carcinoma (RCC). To investigate the clinical relevance of RUNX3 in RCC patients, immunohistochemistry was performed to detect the clinical relevance of RUNX3 in 75 RCC tissues and paired non-cancerous tissues by using tissue microarray (TMA). We also investigated the role of RUNX3 in RCC cell migration, invasion and angiogenesis. The RUNX3 expression was decreased dramatically in human RCC tissue. The RUNX3 expression was significantly correlated with tumor size (P<0.001), depth of invasion (P<0.001), and of TNM stage (P<0.001). Restoration of RUNX3 significantly decreased renal carcinoma cell migration and invasion capacity compared with controls. In addition, we found that overexpression of RUNX3 reduced the proliferation and tube formation of human umbilical vascular endothelial cells (HUVECs). Gelatin zymography and Western blot showed that RUNX3 expression suppressed matrix metalloproteinase-9 (MMP-9) protein level and enzyme activity. Western blot and ELISA showed that RUNX3 restoration inhibited the expression and secretion of vascular endothelial growth factor (VEGF). Taken together, our studies indicate that decreased expression of RUNX3 in human RCC tissue is significantly correlated with RCC progression. Restoration of RUNX3 expression significantly inhibits RCC cells migration, invasion and angiogenesis. These findings provide new insights into the significance of RUNX3 in migration, invasion and angiogenesis of RCC.


Rotavirus serology and excretion in hospitalized non-diarrhoeal patients.
Despite the well-recognized association between rotavirus (RV) and infantile diarrhoeal disease, a few studies have shown that the isolation rate of RV from the faeces of non-diarrhoeal patients can be high, suggesting that the finding of RV in the stools of individual gastro-enteritis (GE) patients need not necessarily denote an aetiological relationship. A prospective study of rotavirus serology and stool excretion was carried out in a group of non-diarrhoeal paediatric patients. A positive ELISA for RV antigen was found in 13.3% children, which compared favourably with an asymptomatic RV-excretion rate of 16.2% found in normal subjects in the community, but differed significantly from the 54.6% RV-excretion rate found in hospitalized GE patients. This confirms that RV is an important enteropathogen. Furthermore, approximately half of the non-diarrhoeal infants acquired nosocomial RV infections in hospital, most of these being asymptomatic. One-sixth of asymptomatic RV excretors showed evidence of prior exposure to rotavirus.


[Asthma-COPD overlap syndrome (ACOS)].
Asthma and COPD, once regarded as distinct disease entities, often overlaps especially in the elderly and smokers. GINA/GOLD joint document 2014 has proposed a clinical entity of ACOS (asthma-COPD overlap syndrome) characterized by irreversible airflow limitation with clinical features of both asthma and COPD, although evidences for definite diagnosis and treatment are limited. ACOS includes several different phenotypes such as severe asthma with airway remodeling, incomplete airflow reversibility as a consequence of childhood asthma and smoking, eosinophilic phenotype of COPD, and so on. Considering the therapeutic modalities currently available for asthma and COPD, it is important to identify the patients who respond well to inhaled corticosteroids.


Growth kinetic study of human hepatocellular carcinoma using proliferating cell nuclear antigen and Lewis Y antigen: their correlation with transforming growth factor-alpha and beta 1.
The factors which control the balance between proliferation and cell death in hepatocellular carcinoma (HCC) remain unclear. The kinetic state of the tumor growth was investigated in the present study with references to transforming growth factor (TGF)-alpha and -beta 1 in 50 resected HCCs without preceding therapies. three-micrometer sections were cut from formalin-fixed, paraffin-embedded tumors. Proliferating cell nuclear antigen (PCNA), Lewis Y antigen (LeY). TGF-alpha, and -beta 1 were immunohistochemically stained and quantitatively assessed with an image analyzer. By means of immunohistochemical staining, a reciprocal correlation was observed between PCNA and LeY. A similar pattern was found between TGF-alpha and -beta 1, although not so strikingly as in the case of PCNA and LeY. The expression of LeY and PCNA labeling index (LI) ranged from 0 to 56.1% and from 0 to 52.8%, respectively. A correlation was observed between LeY and tumor size (r = 0.302, p < 0.04), while there was no significant relationship between PCNA LI and tumor size (r = -0.048, p > 0.05). The positive area ranged from 0 to 61.6% for TGF-alpha, and from 0.6 to 71.5% for TGF-beta 1. Analysis of these data showed a significant correlation between TGF-beta 1 and tumor size (r = -0.327, p < 0.03). Among HCCs < 5 cm, PCNA LI positively correlated with tumor size (r = 0.399, p < 0.04), but negatively with TGF-beta 1 (r = -0.431, p < 0.03). In conclusion, the present investigation indicates that the simultaneous analyses of proliferating and apoptotic activities by means of PCNA and LeY could yield more accurate data to determine the kinetic state of the tumor growth compared with either alone. In addition, TGF-beta 1 might act as a suppressive factor in the growth of HCC < 5 cm.


Plugging a hole and lightening the burden: a process evaluation of a practice education team.
To investigate the perceptions of clinical and senior managers about the role of practice educators (PEs) employed in one acute hospital in the UK. Producing nurses who are fit for practice, purpose and academic award is a key issue for nurse education partnership providers in the UK. Various new models for practice learning support structures and new roles within health care institutions have been established. To sustain funding and policy support for these models, there is a need for evaluation research. A process evaluation methodology was employed to determine the current value of a practice education team and to provide information to guide future direction. Data were collected through semi-structured telephone interviews using a previously designed schedule. All senior nurse managers (n = 5) and a purposive sample of Clinical Managers (n = 13) who had personal experience of and perceptions about the role of PEs provided the data. Interview notes were transcribed, coded and a thematic framework devised to present the results. A number of key themes emerged including: qualities needed for being a successful practice educator; visibility and presence of PEs; providing a link with the university; 'plugging a hole' in supporting learning needs; providing relief to practitioners in dealing with 'the burden of students;' alleviating the 'plight of students;' and effects on student attrition. Findings provided evidence for the continued funding of the practice educator role with improvements to be made in dealing with stakeholder expectations and outcomes. In the UK, there still remain concerns about the fitness for practice of newly Registered Nurses, prompting a recent national consultation by the professional regulating body. Despite fiscal pressures, recommendations for further strengthening of all systems that will support the quality of practice learning may continue to sustain practice learning support roles.


Effects of interleukin-1 on hormone release from normal rat pituitary cells in primary culture.
The present study was performed mainly to determine whether interleukin-1 (IL-1), a polypeptide produced by immunologically activated monocytes, plays a physiological role in the regulation of adrenocorticotropic hormone (ACTH) using primary monolayer cultures of rat anterior pituitary cells. Neither human IL-1 alpha nor IL-1 beta stimulated the ACTH release from normal pituitary cells in concentrations ranging from 0.01 to 10 nM. IL-1 beta caused a slight, but significant, increase in ACTH release at a concentration of 100 nM, while IL-1 alpha did not, even at the highest dose tested. IL-1 beta exhibited a synergistic action with corticotropin-releasing factor (CRF) in ACTH secretion at 10 and 100 nM of CRF, but the interaction was not striking. Both of the monokines failed to cause any change in the secretions of growth hormone, prolactin, follicle-stimulating hormone and luteinizing hormone throughout concentrations ranging from 0.01 to 100 nM. The effects of possible sex-related differences and prolonged preincubation of cultured pituitary cells in serum-free medium prior to assay incubation were also tested, providing no significantly different findings. These results suggest that the physiological significance of IL-1 as a tissue CRF is indeed questionable and should be further clarified.


15Alpha-hydroxyprogesterone in male sea lampreys, Petromyzon marinus L.
There is growing evidence that sea lampreys, Petromyzon marinus L., produce gonadal steroids differing from those of other vertebrates by possessing an additional hydroxyl group at the C15 position. Here we demonstrate that sea lamprey testes produce 15alpha-hydroxyprogesterone (15alpha-P) in vitro when incubated with tritiated progesterone, that 15alpha-P is present in the plasma of sea lampreys, and that plasma concentrations of immunoreactive (ir) 15alpha-P rise dramatically in response to injections of gonadotropin-releasing hormone (GnRH). The identity of the tritiated 15alpha-P produced in vitro was confirmed by co-elution with standard 15alpha-P on high performance liquid chromatography, co-elution with standard and acetylated 15alpha-P on thin layer chromatography, and specific binding to antibodies raised against standard 15alpha-P. The in vitro conversion was used to produce tritiated 15alpha-P label for a radioimmunoassay (RIA), which is able to detect 15alpha-P in amounts as low as 2 pg per tube. The RIA has been used to measure the plasma concentrations of 15alpha-P in males given two serial injections, 24 h apart, of either lamprey GnRH I or GnRH III (50, 100, or 200 microg/kg) or saline control, with plasma being sampled 8 and 24 h after the second injection. Plasma concentrations of ir-15alpha-P rose from < 1 to 36 ng/ml (mean of all treatments) 8 h after injection and declined within 24 h. This is the first time that an RIA has detected such high steroid concentrations in lampreys. This finding is suggestive of a role for 15alpha-P in control of reproduction in the sea lamprey.


A two-dimensional conjugated aromatic polymer via C-C coupling reaction.
The fabrication of crystalline 2D conjugated polymers with well-defined repeating units and in-built porosity presents a significant challenge to synthetic chemists. Yet they present an appealing target because of their desirable physical and electronic properties. Here we report the preparation of a 2D conjugated aromatic polymer synthesized via C-C coupling reactions between tetrabromopolyaromatic monomers. Pre-arranged monomers in the bulk crystal undergo C-C coupling driven by endogenous solid-state polymerization to produce a crystalline polymer, which can be mechanically exfoliated into micrometre-sized lamellar sheets with a thickness of 1 nm. Isothermal gas-sorption measurements of the bulk material reveal a dominant pore size of ~0.6 nm, which indicates uniform open channels from the eclipsed stacking of the sheets. When employed as an organic anode in an ambient-temperature sodium cell, the material allows a fast charge/discharge of sodium ions, with impressive reversible capacity, rate capability and stability metrics.


Stimulation of prolactin secretion by neuroleptics in rats with medial basal hypothalamic lesions.
The ability of dopamine receptor antagonists to stimulate prolactin release in rats with medial basal hypothalamic lesions was investigated. Starting levels of prolactin were elevated to approximately 400 ng/ml in animals in which the tuberoinfundibular dopaminergic neurons were completely destroyed by the lesion. In lesioned animals, chlorpromazine administration at doses of 0.1 and 5 mg/kg induced a further 2- to 3-fold significant increase in plasma prolactin levels. the incubation of anterior pituitaries from lesioned animals with 10(6) M chlorpromazine had no effect on prolactin secretion, thereby eliminating the possibility that chlorpromazine itself stimulates prolactin release from the anterior pituitary. A similar increase in plasma prolactin in lesioned rats was also observed with the potent dopamine antagonist d-butaclamol (1 mg/kg). The effect was stereospecific since the inactive isomer l-butaclamol did not produce any change in the circulating levels of prolactin. Pimozide, another dopaminergic antagonist, was ineffective in inducing a further increase in prolactin in lesioned rats when 0.63 mg/kg was used. However, at a 10-fold lower concentration (0.63 mg/kg), pimozide stimulated a significant increase in prolactin in lesioned rats. The involvement of an alpha-adrenergic mechanism was ruled out by the inability of phentolamine (2.5 mg/kg) to increase prolactin secretion. These data suggest that dopaminergic antagonists can further increase prolactin levels in medial basal hypothalamus-lesioned rats possibly by blocking the inhibitory action of dopamine from nonhypothalamic sources, or by releasing a substance which possesses prolactin-releasing activity.


Catalytic Fast Pyrolysis of Wild Reed Over Nanoporous SBA-15 Catalysts.
Wild reed was pyrolyzed over two nanoporous SBA-15 catalysts with different acid characteristics: Si-SBA-15 and Al-SBA-15. Al was grafted on Si-SBA-15 to increase the acidity and enhance the catalytic activity. Fast pyrolysis was carried out using a pyrolysis-gas chromatography/mass spectrometry system at 550 degrees C for real-time analysis of the products. Significant improvement of the product bio-oil quality was attained by catalytic reforming over nanoporous Al-SBA-15. The fraction of total oxygenates was reduced because of the decrease in. the fraction of ketones, aldehydes, and carboxylates, which deteriorate the fuel quality of bio-oil. On the other hand, the fractions of furans and aromatics, which are the chemicals with high value-added, were increased by the catalytic reforming. The catalytic activity of Al-SBA-15 was considerably higher than that of Si-SBA-15 because the incorporation of Al increased the catalyst acidity.


Hydroxycholesterol binds and enhances the anti-viral activities of zebrafish monomeric c-reactive protein isoforms.
C-reactive proteins (CRPs) are among the faster acute-phase inflammation-responses proteins encoded by one gene (hcrp) in humans and seven genes (crp1-7) in zebrafish (Danio rerio) with importance in bacterial and viral infections. In this study, we described novel preferential bindings of 25-hydroxycholesterol (25HOCh) to CRP1-7 compared with other lipids and explored the antiviral effects of both 25HOCh and CRP1-7 against spring viremia carp virus (SVCV) infection in zebrafish. Both in silico and in vitro results confirmed the antiviral effect of 25HOCh and CRP1-7 interactions, thereby showing that the crosstalk between them differed among the zebrafish isoforms. The presence of oxidized cholesterols in human atherosclerotic plaques amplifies the importance that similar interactions may occur for vascular and/or neurodegenerative diseases during viral infections. In this context, the zebrafish model offers a genetic tool to further investigate these interactions.


Impact of spiked concentrations of Cd, Pb, As and Zn in growth medium on elemental uptake of Nasturtium officinale (Watercress).
This study is aimed at investigating the impact of water quality on the uptake and distribution of three non-essential and toxic elements, namely, As, Cd and Pb in the watercress plant to assess for metal toxicity. The plant was hydroponically cultivated under greenhouse conditions, with the growth medium being spiked with varying concentrations of As, Cd and Pb. Plants that were harvested weekly for elemental analysis showed physiological and morphological symptoms of toxicity on exposure to high concentrations of Cd and Pb. Plants exposed to high concentrations of As did not survive and the threshold for As uptake in watercress was established at 5 ppm. Translocation factors were low in all cases as the toxic elements accumulated more in the roots of the plant than the edible leaves. The impact of Zn on the uptake of toxic elements was also evaluated and Zn was found to have an antagonistic effect on uptake of both Cd and Pb with no notable effect on uptake of As. The findings indicate that phytotoxicity or death of the watercress plant would prevent it from being a route of human exposure to high concentrations of As, Cd and Pb in the environment.


Checkpoints and restriction points in bacteria and eukaryotic cells.
Bacterial checkpoints, analogous to those proposed to exist in eukaryotic cells, offer insights into the definition of a checkpoint. Examination of bacterial "checkpoint" or arrest phenomena illustrate problems with a too-casual application of the checkpoint idea to eukaryotic phenomena. The question raised here is whether there are cellular processes that "check" whether a cellular process is completed. It is possible that many eukaryotic "checkpoints" may not have "checking" functions. Some of the ubiquitous checkpoint phenomena widely described may be merely the result of the inherent incompleteness of earlier events preventing the initiation of subsequent events.


Patterns of preventive dental behavior.
Preventive dental behavior was examined using data from the National Health and Nutrition Examination Survey of 1971-75 conducted by the National Center for Health Statistics. Most research to date has dealt with the use of all types of dental services, with relatively few studies focusing on utilization of dental services for preventive purposes or on preventive dental behavior. Economic theory on the demand for health services and the Andersen model of health services utilization were applied to examine predisposing, enabling, and need characteristics which may influence use of preventive dental health services and preventive dental behavior. The associations between each of three measures of preventive dental behavior and the three sets of characteristics from Andersen's model were analyzed using multiple regression analysis. The enabling factors (income and a regular source of care) were the most important determinants of use of preventive dental services. Need characteristics, measured by self-evaluated condition of teeth, were also significant determinants of use, while the predisposing variables were the least important of the three types. In contrast, for the home care measure, frequency of brushing, the predisposing variables were the most important, with gender and education ranking highest. Consideration of these results may be useful to health educators and to those who formulate policies affecting the distribution of preventive dental services and dental insurance coverage.


CD44 is a marker of endocervical neoplasia.
The expression of CD44s, CD44v4, CD44v5, CD44v7-8, and CD44v10 was investigated immunohistochemically in a variety of neoplastic cervical lesions. Normal endocervical columnar cells exhibited no reactivity for any of the antibodies, whereas the subcolumnar reserve cells were strongly positive for CD44s, CD44v5, and CD44v7-8. In some cases, positive cells were identified in the stroma surrounding the endocervical glands and adjacent to reserve cells. Cervical glandular intraepithelial neoplasia and adenocarcinoma showed consistent immunoreactivity for CD44v5. There was no significant change in CD44 immunoreactivity in squamous cell carcinoma compared with normal epithelia and cervical intraepithelial neoplasia. These findings lend support to the origin of carcinoma of the cervix from a common progenitor reserve cell and suggest the origin of reserve cells from the stroma. CD44v5 may be useful as a diagnostic marker of endocervical neoplasia and could provide a target for therapeutic approaches directed against specific epitopes.


Some of the most interesting CASP11 targets through the eyes of their authors.
The Critical Assessment of protein Structure Prediction (CASP) experiment would not have been possible without the prediction targets provided by the experimental structural biology community. In this article, selected crystallographers providing targets for the CASP11 experiment discuss the functional and biological significance of the target proteins, highlight their most interesting structural features, and assess whether these features were correctly reproduced in the predictions submitted to CASP11. Proteins 2016; 84(Suppl 1):34-50. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.


Emergence and treatment of chikungunya arthritis.
To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis. Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used. CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.


Control of plant leaf movements by the lunisolar tidal force.
Investigations into the diurnal ascent and descent of leaves of beans and other species, as well as experimental interventions into these movements, such as exposures to light at different times during the movement cycle, led to the concept of an endogenous 'clock' as a regulator of these oscillations. The causal origin of leaf movement can be traced to processes that modulate cell volume in target tissues of the pulvinus and petiole. However, these elements of the leaf-movement process do not sufficiently account for the rhythms that are generated following germination in constant light or dark conditions, or when plants are transferred to similar free-running conditions. To further unravel the regulation of leaf-movement rhythms, many of the published time courses of leaf movements that provided evidence for the concept of the endogenous clock were analysed in conjunction with the contemporaneous time courses of the lunisolar tidal acceleration. This was accomplished by application of the Etide program, which estimates, with high temporal resolution, local gravitational changes as a consequence of the diurnal variations of the lunisolar gravitational force due to the orbits and relative positions of Earth, Moon and Sun. To substantiate the results obtained in earthbound laboratories additional experiments were performed in the International Space Station (ISS). Tidal recurrence within the ISS exhibited a periodicity of 45 min. In all instances investigated, it was evident that a synchronism exists between the times of the turning points of both the lunisolar tide and of the leaftide when the direction of leaf movement changes. This finding of synchrony documents that the lunisolar tide is a regulator of the leaftide, and that the rhythm of leaf movement is not of endogenous origin but is an expression of an exogenous lunisolar clock impressed upon the leaf-movement apparatus. A huge number of correlations between leaftide and Etide time courses were established for leaf movement rhythms in natural conditions of the greenhouse, in conditions of constant light or dark, and under the microgravity conditions of the International Space Station. Even the apparently spontaneous short-period, small-amplitude rhythms recorded from leaves under unusual growth conditions are consistent with the hypothesis of a lunisolar zeitgeber. Synchronism between leaftide and Etide is discussed in terms of classical and quantum mechanics.


Assessment of the use of cryopreserved x freeze-dried amniotic membrane (AM) for reconstruction of ocular surface in rabbit model.
To determine the efficacy of freeze-dried amniotic membrane (AM) for reconstruction of the ocular surface in rabbit eyes. The sterilized, freeze-dried amniotic membrane (lyophilized or FD-AM) is a preservative method that uses the drying by freezing process to maintain the AM well preserved for a long time even at room temperature. This paper is an experimental animal interventional study. One eye of each of 15 male New Zealand rabbits (1.5 - 3.0 kg) had the central cornea marked with a 6.0 mm trephine. The marked area was deepithelialized with a No.15 blade. The denuded corneal surface was covered as follows: Group 1: cryopreserved AM (n=6); Group 2: freeze-dried AM (n=6); and Group 3: not covered (control group, n=3). The AM in group 1 and 2 and the periphery of the denuded area in group 3 were secured with continuous 10-0 nylon sutures. The clinical evaluation was made by a blinded observer and graded on a four-point scale (1= minimal, 4= marked) for conjunctival and ciliary hyperemia, eyelid edema, corneal neovascularization, corneal opacity and reepithelialization on postoperative (PO) days 1, 7 and 30 . After PO day 30, the rabbits were euthanized and their corneas were sent for histopathological and ultrastructural analysis to evaluate tissue inflammation, reepithelialization, and basement membrane integrity. Two eyes in group 2 had a corneal infection and were excluded from the analysis. No statistically significant differences among the three groups were found (p>0.05) regarding the clinical evaluation on 1st, 7th and 30th PO days. On transmission electron microscopy, the basement membrane in lyophilized and control groups was more continuous and homogeneous than in the glycerol group. The freeze-drying method seems to be a good option to preserve human amniotic membrane to be used in ocular surface reconstruction. This preservative method reduces the preservation costs and may enhance the use of AM, facilitating its storage and transport.


Repetitive Gly-Leu-Lys-Gly-Glu-Asn-Arg-Gly-Asp peptide derived from collagen and fibronectin for improving cell-scaffold interaction.
Suitable scaffolds for tissue engineering should provide a microenvironment for cell dwelling and directing cell behavior that resemble the native environment. Three-dimensional geometry of electrospun scaffolds well supports cell deposition, but they often lack biomacromolecules to induce cell responses. In this work, the repetitive collagen and fibronectin motif (rCF) peptide containing multiple repeats of Gly-Leu-Lys-Gly-Glu-Asn-Arg-Gly-Asp sequence derived from the cell adhesion motifs of collagen and fibronectin was produced as the alternative agent to induce cell-scaffold interaction. The DNA fragment encoding rCF peptide was amplified by a polymerase chain reaction using overlap primers without a DNA template, cloned into a protein expression vector, and expressed as a His-tag fusion peptide in Escherichia coli. The purified rCF peptide possessed cell adhesion activity about 1.5-fold of the commercial RGD peptide. The rCF peptide was grafted onto the electrospun PCL scaffold via RF plasma of Ar/O2 discharge and acrylic acid treatment. The immobilized rCF peptide significantly increased surface hydrophilicity and enhanced cell proliferation of the electrospun PCL scaffold. These findings suggest the potential application of rCF peptide for improving the biomimetic functions of polymeric scaffolds for tissue engineering.


Polymeric microbubbles as delivery vehicles for sensitizers in sonodynamic therapy.
Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitizer drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitizer drugs to their surface results in a significant reduction in particle stability. In this Article, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumors (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumor volume by 34% 4 days after treatment while tumors treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitizers in SDT.


Effect of promegestone, tamoxifen, 4-hydroxytamoxifen and ICI 164,384 on the oestrone sulphatase activity of human breast cancer cells.
In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer.