The Effect of Limosilactobacillus reuteri on Social Behavior Is Independent of the Adaptive Immune System.
Gut microbes can modulate almost all aspects of host physiology throughout life. As a result, specific microbial interventions are attracting considerable attention as potential therapeutic strategies for treating a variety of conditions. Nonetheless, little is known about the mechanisms through which many of these microbes work. Recently, we and others have found that the commensal bacterium Limosilactobacillus reuteri (formerly Lactobacillus reuteri) reverses social deficits in several mouse models (genetic, environmental, and idiopathic) for neurodevelopmental disorders in a vagus nerve-, oxytocin-, and biopterin-dependent manner. Given that gut microbes can signal to the brain through the immune system and L. reuteri promotes wound healing via the adaptive immune response, we sought to determine whether the prosocial effect mediated by L. reuteri also depends on adaptive immunity. Here, we found that the effects of L. reuteri on social behavior and related changes in synaptic function are independent of the mature adaptive immune system. Interestingly, these findings indicate that the same microbe (L. reuteri) can affect different host phenotypes through distinct mechanisms. IMPORTANCE Because preclinical animal studies support the idea that gut microbes could represent novel therapeutics for brain disorders, it is essential to fully understand the mechanisms by which gut microbes affect their host's physiology. Previously, we discovered that treatment with Limosilactobacillus reuteri selectively improves social behavior in different mouse models for autism spectrum disorder through the vagus nerve, oxytocin reward signaling in the brain, and biopterin metabolites (BH4) in the gut. However, given that (i) the immune system remains a key pathway for host-microbe interactions and that (ii) L. reuteri has been shown to facilitate wound healing through the adaptive immune system, we examined here whether the prosocial effects of L. reuteri require immune signaling. Unexpectedly, we found that the mature adaptive immune system (i.e., conventional B and T cells) is not required for L. reuteri to reverse social deficits and related changes in synaptic function. Overall, these findings add new insight into the mechanism through which L. reuteri modulates brain function and behavior. More importantly, they highlight that a given bacterial species can modulate different phenotypes (e.g., wound healing versus social behavior) through separate mechanisms.


Eating Habits and Preferences of Polish Women Undergoing Treatment for Breast Cancer.
Objective: The objective of the study is the assessment of the nutrition as well as the eating habits and preferences of Polish women undergoing breast cancer treatment. Material and methods: The study included women undergoing breast cancer treatment aged over 50 years. Data were collected on 112 respondents, residents of a large city, for whom the average time elapsed since the completion of treatment was 5 years. Their eating habits and preferences were determined on the basis of the frequency of consumption of products with potentially beneficial and adverse effects on health, which made it possible to determine the pro-Healthy Diet Index-10 (pHDI-10) and non-Healthy Diet Index-14 (nHDI-14). The intensity of properties beneficially and adversely affecting health was assessed in three intervals: small, moderate, and large. On the basis of the BMI index persons with normal body proportions were identified as well as those above the norm. The effect of lifestyle and socioeconomic status on pHDI-10 and nHDI-14 was determined. Results: More than half of the studied women had normal body weight and 39% were overweight. One in three women was characterised by a low level of physical activity. The participants of the study followed diets with a low intensity of unhealthy properties with a weak influence of protective properties of nutrition. A significant, adverse effect of the nutritional knowledge and health self-assessment on pro-Healthy Diet Index-10 and non-Healthy Diet Index-14 was demonstrated. Bad habits related to lifestyle (excessive energy consumption/overweight, smoking cigarettes in the past) contributed to overconsumption of unhealthy products/dishes. Conclusion: The demonstrated dietary mistakes indicate that actions aiming to promote benefits of undertaking behaviour beneficial for health should also be carried out among women with breast cancer diagnosis after the completion of treatment.


Effects of fasting and intraluminal contrast enhancement on ultrasonographic appearance of the equine small intestine.
The equine small intestine is challenging to evaluate ultrasonographically. In humans, hydrosonography has been used to improve ultrasonographic images of the small intestine. We hypothesized that fasting horses for 24 h would enhance the ability to image the small intestine transabdominally by separating intestinal loops and reducing intraluminal gas, and that the administration of intragastric contrast agent would further improve that ability. Ten healthy horses were examined ultrasonographically under three treatment conditions: (a) regular diet, (b) after a 24-h fast, and (c) fasted plus intragastric administration of water and mineral oil. During each phase of the study, 30-s video clips were obtained from four predetermined abdominal windows, and were examined to determine diagnostic quality. Fasting improved the ability to obtain high-quality images of the small intestine significantly. The addition of contrast agent resulted in qualitative improvement in image quality, but differences did not result in statistically significant improvement.


[Characterization of Rhodococcus equi isolates from horse and man].
In the present investigation 19 and 22 R. equi-cultures isolated from diseased horses and humans, respectively, could be correctly identified by their morphological, biochemical and serological properties. The rod-coccus life cycle appeared to be a common feature of almost all cultures investigated. The cultures were typeable with the typing system described by Prescott (1981). The predominant serotypes among the R. equi-isolates belonged to serotypes 1 and 2. Among the R. equi-isolates from horses haemagglutination-positive cultures were mainly found among isolates of serotype 1, those of serotype 2 were haemagglutination-negative. The R. equi-cultures isolated from humans showed no relation between serotype and haemagglutinating properties. Determination of antibiotic susceptibility revealed that all cultures were susceptible to erythromycin, gentamicin, imipenem, minocycline, neomycin, rifampicin, streptomycin and vancomycin, 71% and 75% were resistant or at least moderate susceptible to tetracycline and penicillin G, respectively. Almost all cultures were resistant to ceftazidime and most cultures were susceptible to cefotaxime. The cultures could be further characterized by restriction endonuclease digestion and pulsed field gel electrophoresis of their chromosomal DNA. After digestion with the restriction enzyme AsnI the resulting DNA-profile allowed a strain-specific characterization.


Risk Factors for Poor Patient-Reported Quality of Life Outcomes After Posterior Lumbar Interbody Fusion: An Analysis of 2-Year Follow-up.
A retrospective review of prospectively collected data. The present study aimed to identify risk factors for poor patient-reported quality of life (QOL) outcomes, based on five categories (pain-related disorders, lumbar spine dysfunction, gait disturbance, social life dysfunction, and psychological disorders) of the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ), after posterior lumbar interbody fusion (PLIF) at the 2-year follow-up. Many studies have been reported on patient QOL outcomes after lumbar surgery; however, few reports have focused on risk factors for poor postoperative QOL outcomes in terms of the various disabilities and dysfunctions after PLIF. One hundred consecutive patients (39 men and 61 women; mean age 69.6 [44-84] yr) who underwent single- or two-level PLIF for degenerative spondylolisthesis and/or foraminal stenosis with a 2-year follow-up were included. The effectiveness of surgery in each category of the JOABPEQ was evaluated. Demographic and clinical data and radiographic parameters were reviewed. Risk factors for poor postoperative QOL outcomes in each category of the JOABPEQ were investigated by multivariate logistic regression analysis. Older age and spinopelvic malalignment (preoperative high pelvic tilt or postoperative decrease in lumbar lordosis [=postoperative increase in the mismatch between pelvic incidence and lumbar lordosis]) were risk factors for poor postoperative QOL outcomes in all categories of the JOABPEQ, except for lumbar spine dysfunction. In contrast, increase in number of PLIF segments, non-union, and radiographic adjacent segment degeneration were risk factors for poor postoperative QOL outcomes in lumbar spine dysfunction and gait disturbance. The risk factors for poor QOL outcomes after PLIF differed among the five categories of the JOABPEQ. In particular, surgery-related factors (e.g., increase in number of PLIF segments, nonunion, and radiographic adjacent segment degeneration) had a negative effect on the improvement of lumbar spine dysfunction and gait disturbance. 4.


Widar3.0: Zero-Effort Cross-Domain Gesture Recognition With Wi-Fi.
With the development of signal processing technology, the ubiquitous Wi-Fi devices open an unprecedented opportunity to solve the challenging human gesture recognition problem by learning motion representations from wireless signals. Wi-Fi-based gesture recognition systems, although yield good performance on specific data domains, are still practically difficult to be used without explicit adaptation efforts to new domains. Various pioneering approaches have been proposed to resolve this contradiction but extra training efforts are still necessary for either data collection or model re-training when new data domains appear. To advance cross-domain recognition and achieve fully zero-effort recognition, we propose Widar3.0, a Wi-Fi-based zero-effort cross-domain gesture recognition system. The key insight of Widar3.0 is to derive and extract domain-independent features of human gestures at the lower signal level, which represent unique kinetic characteristics of gestures and are irrespective of domains. On this basis, we develop a one-fits-all general model that requires only one-time training but can adapt to different data domains. Experiments on various domain factors (i.e. environments, locations, and orientations of persons) demonstrate the accuracy of 92.7% for in-domain recognition and 82.6%-92.4% for cross-domain recognition without model re-training, outperforming the state-of-the-art solutions.


Erythrocyte stiffness probed using atomic force microscope.
The stiffness of erythrocytes in patients (N=45) suffering from certain disorders, such as coronary disease, hypertension, and diabetes mellitus has been assessed using the Atomic Force Microscopy (AFM) and compared with that in a group of healthy individuals (N=13). For each blood sample, around 20 erythrocytes were selected at random and the stiffness of each one was probed in 20-30 arbitrarily chosen points. From these results, distributions of the cell Young's modulus (YM) were determined. Average values and widths of YM distributions significantly increased in samples taken from diabetes mellitus patients and cigarette smokers, as compared to those taken from healthy donors. At the same time, the average values of YM were found to increase as a function of the patient's age. We demonstrated that the atomic force microscope is a very sensitive tool for determination of cell stiffness with every prospect of a routine application as a diagnostic tool in quantitative analysis of the physiological and pathological states of red blood cells.


Temperature effects on polygraph detection of concealed information.
Thermoregulatory influences on electrodermal and cardiovascular activity may interfere with the detection of concealed information using a polygraph. This possibility was assessed by means of a mock terrorism scenario. Seventy-two participants were assigned to either a guilty or an innocent role. They were given a polygraph test at one of three ambient temperatures: 10°C, 22°C, or 34°C. Among guilty participants, electrodermal and cardiovascular measures were least effective at 10°C. Electrodermal results were optimal at 22°C, whereas cardiovascular results were optimal at 34°C. Among innocent participants, the effectiveness of these same measures was not affected by ambient temperature. Temperature had no significant impact on respiration results within the guilty or the innocent groups. Taken together, these findings have implications for those who use polygraphs in uncontrolled testing environments.


Tailoring liquid crystalline self-assembly and de Vries behavior of azulenes via lateral and core substitution.
The azulene moiety is a highly attractive building block in optoelectronic applications due to its unique properties. For high-performing devices, the molecular orientation is crucial and can be controlled through liquid-crystalline self-assembly. Recent work showed that liquid crystalline derivatives bearing the 2-phenyl-azulene-1-nitrile core formed broad de Vries-type SmA and SmC phases. For exact understanding of the structure-property relationship, a series of 2-(hetero)aryl-azulenes has been synthesized varying the chain linkage, the lateral substituent, and the aromatic ring. Small changes of the molecular structure determined whether the orthogonal SmA phase or the tilted SmC phase is predominant. Implementation of alkyne chains instead of alkoxy chains resulted in the reduction of phase transition temperatures and formation of mesophases at room temperature. Furthermore, de Vries-like behavior was investigated and reduction values between R = 0.35 and 0.74 were measured which supported the hypothesis that in this system de Vries-like behavior is caused by steric repulsion of the lateral substituent. The control of the phase geometry by the molecular structure might be used for improved molecular orientation in optoelectronic materials.


Desensitization and sequestration of human m2 muscarinic acetylcholine receptors by autoantibodies from patients with Chagas' disease.
Chronic Chagas' disease is associated with pathologic changes of the cardiovascular, digestive, and autonomic nervous system, culminating in autonomic denervation and congestive heart failure. Previously, circulating autoantibodies that activate signaling by cardiac muscarinic acetylcholine receptors (mAChRs) have been described. However, it remains unclear whether the chagasic IgGs directly interact with the m2 mAChRs (predominant cardiac subtype), and, if so, whether chronic exposure of the mAChRs to such activating IgGs would result in receptor desensitization. Here we performed studies with purified and reconstituted hm2 mAChRs and demonstrate that IgGs from chagasic serum immunoprecipitated the mAChRs in a manner similar to an anti-m2 mAChR monoclonal antibody tested in parallel. The chagasic antibodies did not directly interact with the ligand binding site, because the binding of radiolabeled antagonist was unchanged by the addition of the chagasic IgG. In intact cells stably expressing the hm2 mAChR, the chagasic IgGs, but not normal IgGs, mimicked the ability of the agonist acetylcholine to induce two effects associated with agonist-induced receptor desensitization: a decrease in affinity for agonist binding to m2 mAChR and sequestration of the hm2 mAChRs from the cell surface. The results demonstrate that the chagasic IgGs can directly interact with and desensitize m2 mAChRs and provide support for the hypothesis of autoimmune mechanisms having a role in the pathogenesis of Chagas' cardioneuromyopathy.


Entropy values of intellectually-disabled and normal children undergoing deep intravenous sedation for dental treatment.
Intravenous sedation is an efficient method to facilitate dental treatment delivery to uncooperative children. Entropy is used for monitoring anesthetic depth. Nonetheless, scarce data is found on entropy monitoring in intellectually-disabled patients during sedation. This comparative study set out to evaluate entropy values of normal and intellectually-disabled patients during the steady state period of deep sedation and awakening. Additionally, the study aimed to establish whether normal and intellectually-disabled patients reached a comparable clinically assessed state of sedation and the doses of total anesthetic drugs administered. 30 patients were included in the study and divided into two groups: 16 normal and 14 intellectually-disabled children. Ages ranged between 2 to 16 years. All patients were assigned to receive dental treatment under intravenous sedation. Entropy tracings were recorded for all patients. Clinical sedation level was assessed every 5 minutes. Drug administration was guided clinically. The anesthesiologist was blinded to entropy tracing. Although sedation levels assessed clinically were similar between groups, entropy values were significantly lower in the group of intellectually-disabled patients both during sedation steady state and waking. The total amount of anesthetic drugs administered to normal patients was higher compared to intellectually-disabled patients. In this study, entropy monitoring was found to be a more sensitive modality for assessing intra-operative brain activity during steady state sedation compared to clinical assessment of sedation. Despite similar clinical assessment of sedation level, brain activity was lower in the intellectually-disabled group as were their anesthetic drug requirements. We conclude that intellectually-disabled patients may need less anesthetic drugs to reach a good level of sedation. Whether the lower level of brain activity during sedation, reflected by lower entropy tracings, is characteristic of the intellectually disabled warrants additional studies.


Role of syndromic management using dynamic machine learning in future of e-Health in Pakistan.
Sexually Transmitted Diseases (STDs) constitute important primary health issues in Pakistan which face inadequacy of resources required in early detection and investigative procedures for their diagnosis and treatment. Syndromic approach to management of STDs is based on the identification of a consistent group of symptoms and syndromes to classify the exact disease or infection beforehand, so that further investigations are sought for based on these initial criteria. This paper envisions the results based on two different approaches: Human and Artificial Intelligence (AI) along with some examples of on-going usage e of Artificial Intelligence in Medicine. Pakistan is in an early stage regarding the use of informatics in health care for sustainable health system but is also under international obligation to adapt it & WHO EMRO has developed an e-Health plan for the member countries including Pakistan. The paper presents an informatics application model for a very common but important problem & development of such e-health applications, as starting point, will certainly have positive impact the future of development of e-Health in Pakistan.


Cervical cancer screening in low resource settings using visual inspection with acetic acid.
Cervical cancer is one of the leading causes of death for middle-aged women in the developing world, yet it is almost completely preventable, if precancerous lesions are identified and treated in a timely manner. Cervical cancer screening based on cytologic examination is largely unavailable in developing countries or made available to a small, select group of women in private facilities, maternal child health sites, or family-planning clinics, missing the age groups at highest risk for precancerous lesions. Visual inspection with acetic acid (VIA) can be used to screen women. It can be done by nurses or midwives with appropriate training. Although still under investigation, research results show that VIA is simple, accurate, cost-effective, and acceptable to most women. This article reviews the natural history of cervical cancer and important aspects to consider related to cervical cancer screening in low resource settings. The VIA technique is described in detail.


Antiviral agents for the control of viral diseases.
Infectious viral diseases are an important worldwide problem and as a result of more efficient epidemiological studies and improved techniques of viral diagnosis "new" diseases are periodically identified. More importantly, as we learn to control cancer and perform tissue and organ transplants, the immunosuppressed patient is at greater risk of viral infection. There are currently very few generally accepted antiviral agents, but recent research efforts are encouraging. The status of the approved agents and of those showing the greatest promise is discussed in this article.


Long-term survival of semi-constrained total knee arthroplasty for revision surgery.
Semi-constrained implants provide stability in the setting of soft-tissue deficiency in revision total knee arthroplasty (TKA). This study evaluated our institution's long-term survival results with a semi-constrained implant used in the revision TKA setting. 234 semi-constrained revision total knee arthroplasties were performed in 209 patients. The average follow-up was 9 years. Forty repeat revisions were performed. 5-year survival was 91% and 10-year survival was 81%. Male gender significantly increased the risk of revision. At 10 years the average range of motion, pain level, and Knee Society score improved significantly (P < 0.001). Ninety percent of patients reported an improvement in their knee. The semi-constrained implant used in revision knee arthroplasty has acceptable implant survival and functional outcomes in the long-term follow-up period.


Three causes of variation in the photochemical reflectance index (PRI) in evergreen conifers.
The photochemical reflectance index (PRI) reflects diurnal xanthophyll cycle activity and is also influenced by seasonally changing carotenoid : Chl pigment ratios. Both changing pigment pools and xanthophyll cycle activity contribute to photoprotection in evergreen conifers exposed to boreal winters, but they operate over different timescales, and their relative contribution to the PRI signal has often been unclear. To clarify these responses and their contribution to the PRI signal, leaf PRI, pigment composition, temperature and irradiance were monitored over 2 yr for two evergreen conifers (Pinus contorta and Pinus ponderosa) in a boreal climate. PRI was affected by three distinct processes operating over different timescales and exhibiting contrasting spectral responses. Over the 2 yr study period, the greatest change in PRI resulted from seasonally changing carotenoid : Chl pigment ratios, followed by a previously unreported shifting leaf albedo during periods of deep cold. Remarkably, the smallest change was attributable to the xanthophyll cycle. To properly distinguish these three effects, interpretation of PRI must consider temporal context, physiological responses to evolving environmental conditions, and spectral response. Consideration of the separate mechanisms affecting PRI over different timescales could greatly improve efforts to monitor changing photosynthetic activity using optical remote sensing.


Experimental inhalation injury with concomitant surface burn: dextran resuscitation improves lung water and oxygenation.
The role of extravascular lung water (EVLW) in the pathogenesis of inhalation injury (INH) when associated with concomitant major burn (B) remains controversial. Previous experimental models have investigated isolated INH without surface burn. This study measured the effects of isolated and combined INH on EVLW and pO2 in a porcine experimental model. The beneficial effects of early resuscitation with dextran-40 (DEX) were assessed, using a control group receiving standard Parkland formula (LR). In the first part of the study (INH vs. INH + B), a group of animals with a standardized INH was compared to a group also receiving a standardized 40% BSA third-degree surface burn (n = 8, each group). With serial measurements for 5 hours, EVLW was only modestly increased unless INH was accompanied by surface burn: 20.3 +/- 4.2 vs. 32.0 +/- 4.1 ml/kg at 5 hours (p less than 0.01). Similarly, pO2 fell much more dramatically in the INH + B group, 61 +/- 5 vs. 37 +/- 5 torr (p less than 0.05). The second part of the study compared standard Parkland crystalloid resuscitation with dextran-40 resuscitation in animals receiving a combined INH + B injury (LR vs. DEX, n = 8, each group). DEX resuscitation resulted in substantially lower accumulation of EVLW out to 5 hours, 34.1 +/- 5.0 vs. 13.1 +/- 3.0 ml/kg (p less than 0.01), and significantly better pO2, 35 +/- 5 vs. 64 +/- 4 torr (p less than 0.01). Inhalation injury did not dramatically increase EVLW in this animal model unless accompanied by concomitant major surface burn. The deterioration in EVLW and pO2 seen in the combined injury was significantly improved with DEX resuscitation when compared to standard crystalloid resuscitation. Further study is indicated and clinical trials may be warranted.


Accuracy evaluation of a Compton X-ray spectrometer with bremsstrahlung X-rays generated by a 6 MeV electron bunch.
A Compton-scattering-based X-ray spectrometer is developed to obtain the energy distribution of fast electrons produced by intense laser and matter interactions. Bremsstrahlung X-rays generated by fast electrons in a material are used to measure fast electrons' energy distribution in matter. In the Compton X-ray spectrometer, X-rays are converted into recoil electrons by Compton scattering in a converter made from fused silica glass, and a magnet-based electron energy analyzer is used to measure the energy distribution of the electrons that recoil in the direction of the incident X-rays. The spectrum of the incident X-rays is reconstructed from the energy distribution of the recoil electrons. The accuracy of this spectrometer is evaluated using a quasi-monoenergetic 6 MeV electron bunch that emanates from a linear accelerator. An electron bunch is injected into a 1.5 mm thick tungsten plate to produce bremsstrahlung X-rays. The spectrum of these bremsstrahlung X-rays is obtained in the range from 1 to 9 MeV. The energy of the electrons in the bunch is estimated using a Monte Carlo simulation of particle-matter interactions. The result shows that the spectrometer's energy accuracy is ±0.5 MeV for 6.0 MeV electrons.


Structural Basis for Regulation of ESCRT-III Complexes by Lgd.
The ESCRT-III complex induces outward membrane budding and fission through homotypic polymerization of its core component Shrub/CHMP4B. Shrub activity is regulated by its direct interaction with a protein called Lgd in flies, or CC2D1A or B in humans. Here, we report the structural basis for this interaction and propose a mechanism for regulation of polymer assembly. The isolated third DM14 repeat of Lgd binds Shrub, and an Lgd fragment containing only this DM14 repeat and its C-terminal C2 domain is sufficient for in vivo function. The DM14 domain forms a helical hairpin with a conserved, positively charged tip, that, in the structure of a DM14 domain-Shrub complex, occupies a negatively charged surface of Shrub that is otherwise used for homopolymerization. Lgd mutations at this interface disrupt its function in flies, confirming functional importance. Together, these data argue that Lgd regulates ESCRT activity by controlling access to the Shrub self-assembly surface.


Poverty, Caregiving, and HPA-Axis Activity in Early Childhood.
The association between poverty and the activity of the hypothalamic pituitary adrenal (HPA) axis in early childhood is well established. Both ecological and transactional theories suggest that one way in which poverty may influence children's HPA-axis activity is through its effects on parents' behaviors, and over the past three decades a substantial literature has accumulated indicating that variations in these behaviors are associated with individual differences in young children's HPA-axis activity. More recent research suggests that non-parental caregiving behaviors are associated with HPA-axis activity in early childhood as well. Here we systematically review the literature on the association between both parental and non-parental caregiving behaviors in the context of poverty and the activity of the HPA-axis in early childhood. We conclude by noting commonalities across these two literatures and their implications for future research.


Utility of WT1 as a reliable tool for the detection of minimal residual disease in children with leukemia.
WT1 encodes a transcription factor involved in the pathogenesis of Wilms' tumor. A high level of expression has been reported in blasts from patients with various hematological malignancies. The study was performed to evaluate the utility of monitoring WT1 expression in children with leukemia at diagnosis, during therapy, and following bone marrow transplant. We tested a total of 204 samples prospectively. These included samples from patients with the following diagnoses: acute lymphoblastic leukemia (ALL) at diagnosis (n = 45), at relapse (n = 14), and in remission (n = 45); acute non-lymphoblastic leukemia (ANLL) at diagnosis (n = 14), at relapse (n = 5), and in remission (n = 12); and chronic myelogenous leukemia (CML) in blast crisis (n = 1) and in chronic phase (n = 1). A total of 33 of these patients were transplanted: 19 ALL, 12 ANLL, and 2 CML. In addition, samples from 5 patients with aplastic anemia and 28 controls were obtained from peripheral blood (n = 17), cord blood (n = 3), and bone marrow (n = 8). Primer pairs were designed to locate specific nucleotide sequences for mRNA of WT1. RT-PCR was performed in all samples and compared with K562 cells from ATCC (defined as 1.0) as positive control. A positive test was arbitrarily defined as WT1/K562 > 0.5. Samples at diagnosis and relapse, including 56 out of 59 ALL (95%), 26 ANLL (100%), and 1 CML in blast crisis, demonstrated high levels of WT1 expression. In contrast, only 5 of 90 samples obtained in remission or post-transplant showed high levels of WT1 expression ( P < 0.0001; 95% CI = 0.66-0.94). The five patients with high WT1 expression during follow-up relapsed within 2 to 6 months. In conclusion, we have found that WT1 is consistently elevated in children with leukemia. Significant differences in the level of WT1 expression were noted between these patients during diagnosis and at relapse, and those during remission. More importantly, following bone marrow transplant, a significant high level of WT1 expression preceded clinical relapse by 2 to 6 months. Therefore, WT1 is a reliable marker for monitoring minimal residual disease during therapy as well as in the post-transplant period.


Potential rainfall-intensity and pH-driven shifts in the apparent fluorescent composition of dissolved organic matter in rainwater.
Perturbations of rainwater chromophoric dissolved organic matter (CDOM) fluorescence induced by changes in rainfall intensity and pH were investigated by field observations and laboratory pH titrations. Microbial humic-like fluorophores dominated the rainwater CDOM pool, followed by tryptophan-like and tyrosine-like substances. Increased rainfall intensity had notable dilution effects on all six fluorescent components (C1-C6) identified using parallel factor (PARAFAC) analysis, the effect being especially pronounced for the microbial humic-like C1, tryptophan-like C3, and tyrosine-like C5. The results also indicated that increasing pH from 7 to 9 led to decreased fluorescence intensity (Fmax) of all the six components, while a pH increase from 5 to 7, resulted in increasing Fmax of terrestrial humic-like C2, tyrosine-like C5, and tryptophan-like C6 and decreasing microbial humic-like C1, tryptophan-like C3, and fulvic-like C4. Two-dimensional correlation spectroscopy (2D-COS) demonstrated that synchronous fluorescence responded first to pH modifications at fulvic-like wavelength (λEx/λEm = ∼316/416 nm), followed by tyrosine-like wavelength (λEx/λEm = ∼204/304 nm), tryptophan-like wavelength (λEx/λEm = ∼226/326 nm), microbial humic-like wavelength (∼295/395 nm), and finally terrestrial humic-like wavelength (∼360/460 nm). Our results suggest that a decrease in areas affected by acid rain in South China occurring at present may possibly result in apparent compositional changes of CDOM fluorescence. The decreased rainfall in South-West China and increased rainfall in North-West China during the past five decades may possibly accordingly result in increased and decreased Fmax of all the six components identified in South-West and North-West China, respectively.


CHIR99021 causes inactivation of Tyrosine Hydroxylase and depletion of dopamine in rat brain striatum.
CHIR99021, also known as laduviglusib or CT99021, is a Glycogen-synthase kinase 3β (GSK3β) inhibitor, which has been reported as a promising drug for cardiomyocyte regeneration or treatment of sensorial hearing loss. Since the activation of dopamine (DA) receptors regulates dopamine synthesis and they can signal through the β-arrestin pathway and GSK3β, we decided to check the effect of GSK3β inhibitors (CHIR99021, SB216763 and lithium ion) on the control of DA synthesis. Using ex vivo experiments with minces from rat brain striatum, we observed that CHIR99021, but not SB216763 or lithium, causes complete abrogation of both DA synthesis and accumulation, pointing to off-target effects of CHIR99021. This decrease can be attributed to tyrosine hydroxylase (TH) inhibition since the accumulation of l-DOPA in the presence of a DOPA decarboxylase inhibitor was similarly decreased. On the other hand, CHIR99021 caused a dramatic increase in the DOPAC/DA ratio, an indicator of DA metabolization, and hindered DA incorporation into striatum tissue. Tetrabenazine, an inhibitor of DA vesicular transport, also caused DA depletion and DOPAC/DA ratio increase to the same extent as CHIR99021. In addition, both CHIR99021 or SB216763, but not lithium, decreased TH phosphorylation in Ser19, but not in Ser31 or Ser40. These results demonstrate that CHIR99021 can lead to TH inactivation and DA depletion in brain striatum, opening the possibility of its use in DA-related disorders, and shows effects to be considered in future clinical trials. More work is needed to find the mechanism exerted by CHIR99021 on DA accumulation.


Preemptive Analgesic Efficacy of Dexamethasone and Diclofenac in Mitigating Post-surgical Complications After Mandibular Third-Molar Surgery: A Systematic Review.
Mandibular third-molar extraction is a frequently executed minor oral surgical procedure, with a subsequent recovery period lasting several days. Typically, preemptive administration of non-steroid anti-inflammatory drugs (NSAIDs) and steroids has been employed, resulting in a notable decrease in postoperative complications like pain, facial swelling, trismus, and alveolar osteitis. This systematic review's primary goal was to investigate the efficacy of preemptive analgesia with dexamethasone and diclofenac in minimizing the post-surgical complications following the surgical extraction of the mandibular third molars. The systematic search was carried out to identify relevant literature in digital databases including PubMed®, Cochrane Library, Web of Science, and Scopus, from January 1990 to January 2022. The search used specific keywords. The randomized clinical trials assessing the efficacy of dexamethasone and diclofenac or dexamethasone alone compared to diclofenac or placebo as preemptive analgesics were considered inclusion criteria for this systematic review. Case reports, literature reviews, letters to the editor, and non-English publications were not included. Two authors screened the titles and abstracts, and articles fulfilling the study criteria were included. After reading the full text and data collection, analysis was performed. The included article's bias was evaluated by the Risk of Bias 2 (RoB 2) tool. A digital database search yielded a total of 207 articles. After excluding duplicates and articles written in languages other than English, 90 were removed. Based on the title and abstract, out of 177, 95 studies were excluded. After full-text reading of 22 articles, 17 were eliminated because they did not meet the inclusion and exclusion criteria. The remaining five studies were found eligible and included in the systematic review. Four studies were of low risk, while one study had some concerns. Two studies evaluated the combination of dexamethasone with diclofenac, while three evaluated dexamethasone alone. Total samples included samples of 436 third-molar surgeries in 420 patients. There was a substantial decrease in the mean pain score and swelling measurement when diclofenac alone was compared with coadministration of diclofenac and dexamethasone. Preemptive administration of dexamethasone and diclofenac has been shown to effectively reduce pain and facial swelling, with the exception of trismus, in third-molar surgeries when compared to diclofenac alone. As a result, it is recommended to administer these drugs prior to the commencement of third-molar extraction. However, further research is mandatory, specifically good quality randomized controlled trials involving large cohorts, in order to assess any significant variations and validate these findings.


Chemistry of gluten proteins.
Gluten proteins play a key role in determining the unique baking quality of wheat by conferring water absorption capacity, cohesivity, viscosity and elasticity on dough. Gluten proteins can be divided into two main fractions according to their solubility in aqueous alcohols: the soluble gliadins and the insoluble glutenins. Both fractions consist of numerous, partially closely related protein components characterized by high glutamine and proline contents. Gliadins are mainly monomeric proteins with molecular weights (MWs) around 28,000-55,000 and can be classified according to their different primary structures into the alpha/beta-, gamma- and omega-type. Disulphide bonds are either absent or present as intrachain crosslinks. The glutenin fraction comprises aggregated proteins linked by interchain disulphide bonds; they have a varying size ranging from about 500,000 to more than 10 million. After reduction of disulphide bonds, the resulting glutenin subunits show a solubility in aqueous alcohols similar to gliadins. Based on primary structure, glutenin subunits have been divided into the high-molecular-weight (HMW) subunits (MW=67,000-88,000) and low-molecular-weight (LMW) subunits (MW=32,000-35,000). Each gluten protein type consists or two or three different structural domains; one of them contains unique repetitive sequences rich in glutamine and proline. Native glutenins are composed of a backbone formed by HMW subunit polymers and of LMW subunit polymers branched off from HMW subunits. Non-covalent bonds such as hydrogen bonds, ionic bonds and hydrophobic bonds are important for the aggregation of gliadins and glutenins and implicate structure and physical properties of dough.


A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation.
The incidence of postmenopausal osteoporosis research 50% in middle-aged and older women, however, effects of existing therapy are not ideal. Emerging evidence have proved that long noncoding RNAs (lncRNAs) was correlated with multiple physiological and pathology processes including development, carcinogenesis, and osteogenesis. However, reports on lncRNAs regulating bone formation were relatively limited. In this study, we screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene coexpression analysis. The biological function of the screened lncRNA was assessed both in vitro and in vivo. The effects of the lncRNA on osteogenic transcription factors were also evaluated. We identified AK016739, which was correlated with osteogenic differentiation and enriched in skeletal tissues of mice. The expression levels of AK016739 in bone-derived mesenchymal stem cells were increased with age and negatively correlated with osteogenic differentiation marker genes. Experiments showed that AK016739 inhibited osteoblast differentiation, and in vivo inhibition of AK016739 by its small interfering RNA would rescue bone formation in ovariectomized osteoporosis mice model. In addition, AK016739 suppressed both expression levels and activities of osteogenic transcription factors. This newly identified lncRNA AK016739 has revealed a new mechanism of osteogenic differentiation and provided new targets for treatment of skeletal disorders.


A role for oligonucleotide-based RNA-knock down technologies in functional genomics.
Functional genomics is inundating the pharmaceutical industry with large numbers of potential gene targets from several sources such as gene expression profiling experiments (DNA microchips, proteomics) or database mining. Oligonucleotide-based RNA-knock down technologies such as antisense or RNA interference can aid in the filtering and prioritization of target candidates in the drug discovery process.


Nutritional status of the tribal elderly in India.
The objective of the paper is to assess the diet and nutritional status of the tribal elderly (> or = 60 years) using data from a cross-sectional study carried out by National Nutrition Monitoring Bureau (NNMB) exclusively in Integrated Tribal Development Project (ITDP) villages of 9 provincial States in India during 1998-1999. A total of 1,239 elderly completed the diet survey (24-hour recall) and 3,932 elderly completed anthropometric measurements. In general, the mean consumption of all the foods and the median intakes of all the nutrients were below the Recommended Dietary Intakes (RDI) in both men and women. The mean heights and weights significantly decreased with increase in age in both males and females (p < 0.001). The prevalence of Chronic Energy Deficiency (CED = BMI < 18.5) was relatively higher (65.4%) in females compared with their male counterparts (61.8%). The prevalence of CED was significantly higher (p < 0.001) among the elderly living in kutchaand landless households. The tribal elderly are subsisting on inadequate diets, which are reflected in the poor intakes of all the nutrients and higher prevalence of undernutrition. Significantly higher proportion of tribal elderly are undernourished compared with their rural counterparts (p < 0.001).


In-vitro and in-silico studies of annelated 1,4,7,8-tetrahydroazocine ester derivatives as nanomolar selective inhibitors of human butyrylcholinesterase.
Based on previous finding showing 2,3,6,11-tetrahydro-1H-azocino[4,5-b]indole as suitable scaffold of novel inhibitors of acetylcholinesterase (AChE), a main target of drugs for the treatment of Alzheimer's disease and related dementias, herein we investigated diverse newly and previously synthesized β-enamino esters (and ketones) derivatives of 1,4,7,8-tetrahydroazocines (and some azonines) fused with benzene, 1H-indole, 4H-chromen-4-one and pyrimidin-4(3H)-one. Twenty derivatives of diversely annelated eight-to-nine-membered azaheterocyclic ring, prepared through domino reaction of the respective tetrahydropyridine and azepine with activated alkynes, were assayed for the inhibitory activity against AChE and butyrylcholinesterase (BChE). As a major outcome, compound 7c, an alkylamino derivative of tetrahydropyrimido[4,5-d]azocine, was found to be a highly potent BChE-selective inhibitor, which showed a noncompetitive/mixed-type inhibition mechanism against human BChE with single digit nanomolar inhibition constant (Ki = 7.8 ± 0.2 nM). The four-order magnitude BChE-selectivity of 7c clearly reflects the effect of lipophilicity upon binding to the BChE binding cavity. The ChEs' inhibition data, interpreted by chemoinformatic tools and an in-depth in-silico study (molecular docking combined with molecular dynamics calculations), not only highlighted key structural factors enhancing inhibition potency and selectivity toward BChE, but also shed light on subtle differences distinguishing the binding sites of equine BChE from the recombinant human BChE. Compound 7c inhibited P-glycoprotein with IC50 of 0.27 μM, which may support its ability to permeate blood-brain barrier, and proved to be no cytotoxic in human liver cancer cell line (HepG2) at the BChE bioactive concentrations. Overall, the biological profile allows us to envision 7c as a promising template to improve design and development of BChE-selective ligands of pharmaceutical interest, including inhibitors and fluorogenic probes.


Dynamics of amino acid redistribution in the carnivorous Venus flytrap (Dionaea muscipula) after digestion of 13 C/15 N-labelled prey.
Amino acids represent an important component in the diet of the Venus flytrap (Dionaea muscipula), and supply plants with much needed nitrogen resources upon capture of insect prey. Little is known about the significance of prey-derived carbon backbones of amino acids for the success of Dionaea's carnivorous life-style. The present study aimed at characterizing the metabolic fate of 15 N and 13 C in amino acids acquired from double-labeled insect powder. We tracked changes in plant amino acid pools and their δ13 C- and δ15 N-signatures over a period of five weeks after feeding, as affected by contrasting feeding intensity and tissue type (i.e., fed and non-fed traps and attached petioles of Dionaea). Isotope signatures (i.e., δ13 C and δ15 N) of plant amino acid pools were strongly correlated, explaining 60% of observed variation. Residual variation was related to contrasting effects of tissue type, feeding intensity and elapsed time since feeding. Synthesis of nitrogen-rich transport compounds (i.e., amides) during peak time of prey digestion increased 15 N- relative to 13 C- abundances in amino acid pools. After completion of prey digestion, 13 C in amino acid pools was progressively exchanged for newly fixed 12 C. The latter process was most evident for non-fed traps and attached petioles of plants that had received ample insect powder. We argue that prey-derived amino acids contribute to respiratory energy gain and loss of 13 CO2 during conversion into transport compounds (i.e., 2 days after feeding), and that amino-nitrogen helps boost photosynthetic carbon gain later on (i.e., 5 weeks after feeding).


Synthesis and antimicrobial study of linked heterocyclics containing Pyrazole-pyrimidine-thiazolidin-4-one.
A new series of linked heterocyclics, 3-[4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinyl]-2-(aryl/heteryl)-1,3-thiazolan-4-ones (6a-j), has been synthesized by the one-pot cyclo-condensation of 4-(4-chlorophenyl)-6-(3,5-dimethyl-1-phenyl-1H-4-pyrazolyl)-2-pyrimidinamine (5), aryl/heteroaryl aldehyde and thioglycolic acid. The structures of the synthesized compounds have been confirmed via IR, (1)H-NMR, (13)C-NMR, MS and elemental analyses. Further, all the newly synthesized compounds 6a-j have been assayed for their antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi. The compounds containing moieties like 4-nitrophenyl (6c), 3-nitrophenyl (6d), 4-dimethylaminophenyl (6g), 2-furyl (6i) and 1,3-benzodioxole (6j), at 2-position of thiazolidin-4-one ring exhibited good inhibitory activity against all the tested organisms.


Unattended versus two attended, ambulatory and central blood pressure measurements in hypertensive patients with and without diabetes.
To compare unattended blood pressure (BP) with two attended BP, with 24-h ambulatory (ABPM) and central BP measurements in hypertensive patients with (DMs) and without diabetes (HTs). In the same hypertension clinic we evaluate 129 consecutive HTs (56% female, 59 + 16 yrs) and 91 DMs (62% female, 64 + 9 yrs) who were referred for 24-h ABPM. During 48 hours they underwent a first attended BP (5 minutes resting, 3 recordings 2 minutes apart), (AT1), an unattended BP (UnAT), 3 measurements 2 minutes apart with a pre-programmed oscillometric Omron M10- IT, a second attended BP (AT2) similar to AT1, a 24-h ABPM and an evaluation of central BP (C) from the aortic wave form (SpygmoCor). BP (mm Hg) and differences (Δ) from UnAT = 135/82 ± 17/10 were 1AT = +13.8/3.9 ± 10.3/5.6, AT2 = +7.3/2.9 ± 7.4/4.9, 24-h = -1.3/-1.7 ± 7.5/7.5 and C = -2.4/1.2 ± 10.3/9.1, all p < .01 vs UnAT. Limits of agreement (2 SDs in Bland-Altman plots) were between AT1 and UnAT systolic BP, +34.2 to -6.8 mm Hg and between AT2 and UnAT BP were +21.7 to -7.0 mm Hg. Unattended systolic BP values were similar to that of 24-h in HTs and to that of daytime in DMs. Intraclass correlation coefficients of systolic BP and diastolic BP between UnAT and AT1 and between UnAT and AT2 were within the range 0.78 to 0.83, all p < .01. In HTs with and without DM the unattended BP significantly underestimates attended BP being more close to ambulatory BP values. These differences should be taken into account since targets based on these BP measurements are not equivalent.


[Diffusion tensor imaging (DTI) in the differential diagnosis of normal pressure hydrocephalus and brain atrophy].
Clinical symptomatology of idiopathic normal pressure hydrocephalus, due to its overlap with dementias and neurodegenerative brain disorders, makes diagnosis challenging. As the neurological deficits are reversible there is a need for prompt and reliable noninvasive testing. The aim was to try to use and introduction into clinical practice of new non-invasive method--diffusion tensor imaging (DTI-Diffusion Tensor Imaging) discriminating patients classified as normal pressure hydrocephalus and patients diagnosed with brain atrophy. Using magnetic resonance-diffusion tensor imaging, we examined white matter changes within the brains of patients diagnosed with idiopathic normal pressure hydrocephalus, cerebral atrophy and controls. Diffusion tensor brain images were obtained with 3Tesla and 1.5 Tesla MR-scanners. Fractional anisotropy brain maps were generated using a computer-automated method, and tract-based spatial statistics were then applied to compare the fractional anisotropy values in the clinical groups. The fractional anisotropy data were further investigated using region-of- interest analysis set within: fibre commissural the lateral ventricles (Fclv), forceps minor of corpus callosum (Fmin), cingulum (Cg), optic radiation (Orad), superior cerebellarpeduncle (Scp), substantia nigra (nucleus ruber) (Sn). Compared with the cerebral atrophy or control group, the FA values in the hydrocephalus group were significantly different in the posterior cingulate (Cg) and the forceps minor of the corpus callosum (Fmin). The pattern of white matter tracts changes in select brain regions distinguishes it from cerebral atrophy and control brains. Our pilot study adds to the body of knowledge advancing the understanding of the white matter pathology of idiopathic normal- pressure hydrocephalus.


A novel, volumizing cosmetic formulation significantly improves the appearance of target Glabellar lines, nasolabial folds, and crow's feet in a double-blind, vehicle-controlled clinical trial.
Facial lines and wrinkles are caused by many factors including constant exposure to external elements, such as UV rays, as well as the dynamic nature of facial expression. Many cosmetic products and procedures provide global improvement to aging skin, whereas injectable therapies are frequently utilized to diminish specific, target wrinkles. Despite their broad availability, some patients are unwilling to undergo injectables and would benefit from an effective topical option. A noninvasive option to volumize target wrinkle areas could also extend benefits of commonly used cosmetic anti-aging products. To this end, a two-step formulation containing the novel, cosmetic anti-aging ingredient, N-acetyl tyrosinamide, was developed for use on targeted wrinkle areas. The tolerability and efficacy of the serum plus cream were tested for 16 weeks in women with moderate facial photodamage on predetermined wrinkle areas (glabellar lines, nasolabial folds, under eye lines, and lateral canthal (crow's feet) wrinkles) in a single-center, randomized, double-blind, vehicle-controlled, clinical trial. Seventy women (47 Active group, 23 Vehicle group) completed the study. Digital photography, clinical grading, ultrasound and self-assessment scores confirmed improvement to wrinkle areas. The topical cosmetic formulation was statistically superior (P<0.05) to its vehicle in visually improving nasolabial folds, glabellar lines, crow's feet, and under eye wrinkles and in reducing pinch recoil time. Both the test formulation and its vehicle were tolerated well. The novel, two-step cosmetic formulation reduced the appearance of wrinkles and increased skin elasticity thus providing an effective anti-aging option for target wrinkle areas. This study suggests that in addition to its use as monotherapy for reducing targeted lines and wrinkles this cosmetic formulation may be also serve as an adjuvant to injectable therapies.


Luminescent Ni0 Diisocyanide Chelates as Analogues of CuI Diimine Complexes.
The first two homoleptic Ni0 isocyanide complexes that exhibit photoluminescence from long-lived excited states are presented. Electrochemical studies indicate that in one of the complexes significant geometrical distortion occurs upon metal oxidation. The observation of luminescence, even though currently restricted to low temperatures, is an important proof-of-concept in the search for earth-abundant alternatives to photoactive complexes made from precious metals. The prospect of using Ni0 isocyanide complexes as luminophores, photoredox catalysts, or dyes in solar cells, is highly attractive.


Portal pressure regulation following Kupffer cell activation: control of prostaglandin production by heme oxygenases.
Portal pressure (PP) results from the interplay of vasoconstrictors and vasodilators. Recently, we have shown that Kupffer cell (KC) activation increases PP. The role of the vasodilating compounds nitric oxide (NO) and carbon monoxide (CO) was studied. The hypothesis of the present study was that these vasodilators counteract the PP increase following KC activation. Livers of rats weighing 180-200 g were isolated and perfused. KCs were activated by zymosan A (cell wall particles from yeast; 150 µg/ml). The effects of NO and guanylate cyclase (GC) were evaluated by the NO synthase inhibitor N(G)-nitro-L-arginine methylester (L-NAME; 0.3 mM, and the GC inhibitor 4H-8-bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one (NS-2028, 1.0 µM); the effects of the heme oxygenase (HO) derived compound CO were evaluated by direct administration of CO or inhibition of HO by zinc protoporphyrin IX (ZnPP IX, 1.0 µM). In isolated perfused rat livers, administration of L-NAME or NS-2028 further raised PP increase following KC activation. This effect could be reduced by the cGMP analogue 8-Br-cGMP. Inhibition of HO caused marked amplification of PP increase in zymosan-treated organs. CO prevented this PP increase cGMP independently. Interestingly, KC activation and simultaneous inhibition of HO augmented the production of prostaglandins D2 and F2α and of thromboxane A2. Accordingly, indomethacin blunted the increase of PP in zymosan/ZnPP-treated livers. NO restricts the initial PP increase after KC activation by GC-mediated cGMP. CO from heme degradation limits the increase of PP after KC activation eicosanoid dependently, but cGMP independently.


Efficacy and longevity of a new formulation of temephos larvicide tested in village-scale trials against larval Aedes aegypti in water-storage containers.
Field trials on the initial and long-term efficacy of a new formulation of temephos granules (1% on zeolite) applied at 1 ppm active ingredient (AI) were conducted in water-storage containers against Aedes aegypti in 3 villages in the Kanchanaburi Province in Thailand. A total of 316 water-storage containers of various types and sizes were included in the study. In the initial survey, we found that some containers were positive for larval Ae. aegypti, whereas others were devoid of larvae before the initiation of treatments. The containers all were numbered with paint and divided into 4 groups: with larvae and treated, without larvae and treated, with larvae untreated, and without larvae and untreated. Assessment of larval abundance was made 48 h after treatment and monthly thereafter for 5 months. Containers with larvae and that were treated exhibited almost complete absence of larval Ae. aegypti for 2 months, but a small proportion became positive after 3 months. Most of these positive containers were devoid of zeolite granules, which are visible in the containers. The number of positive containers increased in months 4 and 5, despite the fact that residues of temephos granules were present in some of the larvae-positive containers. The containers initially without larvae and treated with temephos essentially were devoid of larvae for 2 months. After 3, 4, and 5 months, about 6-23% of the containers became positive despite the fact that some had visible amounts of temephos granules. In the 2 control groups initially with and without larvae, sustained and consistent production of larvae occurred. Even in the group initially without a larval population, the containers became positive for larvae 1 month after the start of the experiment and the positivity rate increased as the trial progressed. From these studies, the conclusion can be made that a single application of temephos zeolite granules at 1 ppm AI can provide highly satisfactory control of larval Ae. aegypti in water-storage containers for at least 3 months in the field under normal water-use practices.


Biologic therapy in lupus nephritis.
This position paper critically analyzes the available controlled data regarding biologic therapy in lupus nephritis (LN). Rather than an exhaustive review of all published evidence, the stress is put on the unmet medical needs in LN, the design of trials aimed at testing the effect of a biologic in LN, the possible reasons for LN trial failures and the future of biological therapy in LN.


Trends in neural tube defects in Western Australia in Indigenous and non-Indigenous populations.
Neural tube defects (NTD) were 43% more common in Indigenous than in non-Indigenous infants in Western Australia in the 1980s, and there has been a fall in NTD overall in Western Australia since promotion of folate and voluntary fortification of food has occurred. In order to investigate whether the fall had occurred in both indigenous and non-Indigenous infants, data on NTD (births and terminations) were obtained from the WA Birth Defects Registry, and on all births from the Maternal and Child Health Research Data Base. Knowledge of folate was asked in a survey of indigenous women interviewed postpartum. Before the promotion of folate (1980-92), there has been a 42% increase in NTD in Indigenous compared with non-Indigenous infants (prevalence ratio (PR)=1.42 [95% confidence interval (CI) 1.04, 1.94]); while in the most recent period (1996-2000), the prevalence in Indigenous infants was almost twice that of non-Indigenous infants (PR 1.98 [CI 1.25, 3.15]). Fifty-five per cent of Indigenous women knew about folate in pregnancy. Similar to sudden infant death syndrome, this study has highlighted health promotion that has been successful in reducing the risk of a childhood condition overall, but has failed to be effective for Indigenous children.


[Postviral rhinosinusitis, focus on pathogenetic therapy].
Currently, the problem of acute rhinosinusitis continues to be relevant due to the frequent occurrence of this pathology. A certain difficulty is caused by the differential diagnosis of viral, post-viral and bacterial forms of rhinosinusitis, which carries the risks of irrational therapy. The authors of the article discuss the role of a viral infection in the etiology and pathogenesis of acute rhinosinusitis, the stages in the development of an inflammatory reaction on the mucous membrane of the nose and paranasal sinuses, and the disruption of mucociliary clearance. The authors consider options for the pathogenetic therapy of postviral sinusitis, concluding that the use of local combined preparations containing the mucolytic acetylcysteine and the vasoconstrictor component of tuaminoheptane sulfate is effective.


Pathogenesis and treatment of HIV-1 infection: recent developments.
Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS) and is estimated to presently infect 24 million adults and 1.5 million children, worldwide. The pathogenesis of HIV-1-induced disease is complex and characterized by the interplay of both viral and host factors, which together determine the outcome of infection. An improved understanding of the pathogenic mechanisms of AIDS, combined with recent insights into the dynamics of viral infection, and the cellular co-receptors for HIV-1, may provide powerful new opportunities for therapeutic intervention against this virus.


Dopaminergic damage pattern predicts phenoconversion time in isolated rapid eye movement sleep behavior disorder.
The exact phenoconversion time from isolated rapid eye movement (REM) sleep behavior disorder (iRBD) to synucleinopathies remains unpredictable. This study investigated whole-brain dopaminergic damage pattern (DDP) with disease progression and predicted phenoconversion time in individual patients. Age-matched 33 iRBD patients and 20 healthy controls with 11C-CFT-PET scans were enrolled. The patients were followed up 2-10 (6.7 ± 2.0) years. The phenoconversion year was defined as the base year, and every 2 years before conversion was defined as a stage. Support vector machine with leave-one-out cross-validation strategy was used to perform prediction. Dopaminergic degeneration of iRBD was found to occur about 6 years before conversion and then abnormal brain regions gradually expanded. Using DDP, area under curve (AUC) was 0.879 (90% sensitivity and 88.3% specificity) for predicting conversion in 0-2 years, 0.807 (72.7% sensitivity and 83.3% specificity) in 2-4 years, 0.940 (100% sensitivity and 84.6% specificity) in 4-6 years, and 0.879 (100% sensitivity and 80.7% specificity) over 6 years. In individual patients, predicted stages correlated with whole-brain dopaminergic levels (r = - 0.740, p < 0.001). Our findings suggest that DDP could accurately predict phenoconversion time of individual iRBD patients, which may help to screen patients for early intervention.


Vasoactive intestinal peptide and intraocular pressure: adenylate cyclase activation and binding sites for vasoactive intestinal peptide in membranes of ocular ciliary processes.
Vasoactive intestinal peptide (VIP)-responsive adenylate cyclase and VIP binding sites were investigated in membranes prepared from ciliary processes dissected from albino rabbit eyes. High-affinity binding sites for VIP (Kd, 0.95 nM; 607 fmol/mg of protein), in addition to beta adrenergic sites labeled by dihydroalprenolol (Kd, 0.48 nM; 123 fmol/mg of protein), were present. Activation of adenylate cyclase by VIP had a Ka of 65 nM, and the maximal response was 3.3-fold greater than that for I-isoproterenol (Ka, 102 nM). A peptide fragment of VIP (sequence 10-28) was inactive in all assays and did not inhibit VIP-stimulated adenylate cyclase at 10 microM. Responses to VIP and isoproterenol in combination were additive at lower doses but less than additive at maximal doses. Responses to VIP in combination with a low dose of forskolin (0.1 microM) were potentiated at all dose levels, whether assays were done in presence of MgCl2 or MnCl2. VIP- and forskolin-activated adenylate cyclase was associated with the nonpigmented epithelial cell fraction and not with pigmented epithelial cells separated on Percoll density gradients after dissociation of cells from processes by collagenase digestion. Intravitreous injection of 10 nmol of VIP into the rabbit eye caused a maximal reduction in intraocular pressure at 40 to 50 hr lasting beyond 72 hr. VIP-responsive and beta adrenergic-responsive adenylate cyclase are present on the same cell type (nonpigmented epithelial cells) and appear to share components of the adenylate cyclase system in the same membrane. VIP may participate in the physiologic regulation of aqueous humor secretion at the level of the epithelial cell membrane.


Toll-like receptor 9 suppresses lupus disease in Fas-sufficient MRL Mice.
Genetic deficiency in TLR9 accelerates pathogenesis in the spontaneous polygenic MRL.Faslpr murine model of systemic lupus erythematosus, despite the absence of anti-nucleosome autoantibodies. However, it could be argued that this result was dependent on Fas-deficiency rather than lupus-promoting genes in the MRL genetic background. Here we report the effects of TLR9 deficiency on autoimmune disease independent of the lpr mutation in Fas by characterizing Tlr9-/- and Tlr9+/+ mice on the Fas-intact MRL/+ genetic background. By 30 weeks of age, Tlr9-deficient MRL/+ had more severe renal disease, increased T cell activation, and higher titers of anti-Sm and anti-RNA autoantibodies than Tlr9-intact animals, as had been the case in the MRL.Faslpr model. In addition, Tlr9-deficient MRL/+ mice had increased numbers of germinal center phenotype B cells and an increase in splenic neutrophils and conventional dendritic cell populations. Thus, the disease accelerating effects of Tlr9 deficiency are separable from those mediated by the Fas mutation in the lupus-prone MRL genetic background. Nonetheless, disease acceleration in Tlr9-deficient MRL/+ mice was phenotypically distinct from that in Fas-deficient counterparts, which has important implications.


Microvascular obstruction complicating acute right ventricular myocardial infarction.
This case history describes a man with inferior myocardial infarction (MI) with right-ventricular involvement, treated with a right coronary artery stent. Magnetic resonance showed akinesia of left-ventricular inferior and inferolateral walls and right-ventricular inferior free wall with an impairment of global systolic function. There was late gadolinium enhancement (LGE) of left-ventricular inferior and inferolateral walls with microvascular obstruction (MVO). LGE of the right-ventricular inferior wall was seen with a hypointense core within hyperenhanced myocardium, consistent with MVO of the infarcted right-ventricular myocardium. At follow-up there was persistent akinesia of left-ventricular inferior and inferolateral walls and right-ventricular systolic dysfunction. LGE was still evident with resolution of MVO.


Neoplastic cauda equina syndrome: a neuroimaging-based review.
Cauda equina syndrome refers to dysfunction of the cauda equina, the collection of ventral and dorsal lumbar, sacral and coccygeal nerve roots that surround the filum terminale. This most commonly occurs as a result of compression by a herniated lumbosacral disc. However, the syndrome may also complicate metastatic cancer or a primary neoplasm within or infiltrating the spinal canal. An accurate and timely diagnosis is critical to avoid irreversible loss of neurological function. The clinician and radiologist must therefore be aware of the many possible causes to guide timely management. Here we review the diverse neoplastic causes affecting the cauda equina nerve roots from a neuroimaging-based perspective. We divide them by location into intramedullary neoplasms at the conus (such as astrocytoma), intradural-extramedullary neoplasms (such as schwannoma and leptomeningeal metastases) and extradural neoplasms (such as spinal metastases from systemic neoplasms). We also discuss the clinical features associated with cauda equina tumours, with special focus on cauda equina syndrome.


Tidal peritoneal dialysis: a pediatric experience.
The objective of this study was to assess whether eight hours of nightly tidal peritoneal dialysis (TPD) can provide uremia control equal that of CCPD/CAPD. A pilot study collected data from patients who volunteered to use TPD at home. Six children, ages 5 to 16, who required regular dialysis and lived within a 175 miles of the training center volunteered to use home TPD. These subjects were trained and followed at the University of Iowa Hospitals and Clinics. Dialysate creatinine and urea nitrogen were measured during both CCPD and TPD. Clearances were measured for tidal dialysis using multiple dialysate flow rates. Dialysate urea clearance (KU - ml/min normalized to 70 kg.) increased with dialysate flow (QD - ml/kg/H) [KU = 9.566 + 0.251 X (QD)], and dialysate urea nitrogen losses equaled those of CCPD. Eight hours of tidal dialysis can provide dialysis efficiency equal that of CAPD/CCPD.


cDNA cloning of biotransformation enzymes belonging to the cytochrome P450 family in the antennae of the noctuid moth Mamestra brassicae.
The involvement of cytochrome P450 enzymes in olfaction was demonstrated in vertebrates some time ago. In insects these enzymes are well known for their role in insecticide resistance, but the involvement of P450 in pheromone degradation was only recently demonstrated. Using a PCR strategy, we have isolated two cDNAs from the antennae of the cabbage armyworm Mamestra brassicae - CYP4L4 and CYP4S4 - which encode microsomal P450s. CYP4S4 expression is restricted to the antennae, whereas CYP4L4 is also found in the proboscis and legs. Moreover, the two genes are strongly expressed in one type of sensory unit of the antennae - the sensilla trichodea - which are tuned to the detection of odourants. The putative function of the corresponding enzymes is discussed with regard to their respective expression patterns.


Anesthetic management of a child with Cornelia de Lange Syndrome undergoing open heart surgery: A case report.
Cornelia de Lange syndrome (CdLS) is a congenital multisystemic genetic disorder. The expected lifespan of children with this disorder has been prolonged in parallel with the advances in medicine in recent years. However, they still more frequently undergo cardiac surgery. There are some challenges for clinicians when faced with CdLS patients. We present the perioperative management of a child with CdLS undergoing open-heart surgery. Severe pulmonic and subpulmonic valvular stenosis, enlargement of the right side of the heart, mild tricuspid regurgitation, atrial septal defect, and patent ductus arteriosus were diagnosed in a 14-month-old boy with manifested cyanosis, developmental delay, and malnutrition. Attempted balloon valvuloplasty was unsuccessful due to a severe stenotic pulmonary valve, therefore it was decided to perform an open surgical repair. Following a successful and uncomplicated intraoperative course, the patient was extubated on postoperative day 5, and adrenalin and dopamine infusions were gradually decreased and stopped on postoperative days 6 and 10, respectively. Moderate laryngomalacia and suboptimal vocal cord movements were diagnosed, and tracheotomy and percutaneous endoscopic gastrostomy were performed under general anesthesia in the same session at postoperative day 32. The patient was discharged on postoperative day 85 after a challenging postoperative period with additional airway and nutritional problems. This is the first report of the perioperative anesthetic and clinical management of a CdLS patient undergoing open-heart surgery.


Vesicle-associated membrane protein and synaptophysin are associated on the synaptic vesicle.
The synaptic vesicle membrane protein VAMP (vesicle-associated membrane protein or synaptobrevin) has been implicated in synaptic vesicle docking and fusion. Synaptophsin (p38), also a synaptic vesicle membrane protein, has four transmembrane domains and may function as a gap junction-like pore or channel. Here we report evidence for a direct interaction between VAMP and synaptophysin using chemical cross-linking followed by the identification of immunoreactive protein complexes. A prominent complex of 56 kDa was found to consist of VAMP and synaptophysin. Furthermore, we demonstrate that this VAMP-synaptophysin complex is enriched in the synaptic vesicle fraction of rat brain, is independent of detergent solubilization, and is present in PC12 cells subjected to in vivo cross-linking.


The association between cold hypersensitivity in the hands and feet and chronic disease: results of a multicentre study.
Cold hypersensitivity in the hands and feet (CHHF) is a common symptom in Korea and patients with CHHF complain of coldness in the hands and feet in an environment that is not considered cold by unaffected people. In traditional East Asian medicine, CHHF is believed to be accompanied by various diseases and symptoms, and is considered a symptom that needs active treatment. CHHF is used for pattern identification in the cold pattern, yang deficiency, and constitution. This study aimed to examine the differences in frequencies of chronic diseases with respect to the presence of CHHF. Disease history, CHHF, body measurements, and blood test survey data from 6149 patients collected by 25 medical institutes in Korea were obtained from the Korean Medicine Data Center. The participants were divided into CHHF (n = 1909) and non-CHHF groups (n = 3017) according to the CHHF survey. The differences in frequencies of 18 diseases were analysed using chi-square tests, and the odds ratios (ORs) for each disease according to CHHF status were examined via logistic regression with adjustment for age, sex, and body mass index (BMI). Based on chi-square test results, the CHHF group showed a higher frequency of the following diseases: anaemia, hypotension, chronic gastritis, reflux oesophagitis, chronic rhinitis, dysmenorrhoea, and gastroduodenal ulcer. Diseases found in lower frequencies were as follows: hypertension, diabetes mellitus, impaired fasting glucose, dyslipidaemia, stroke, fatty liver, and angina pectoris. In addition, from the logistic regression with adjustment for age, sex, and BMI, the CHHF group showed a lower OR in diabetes mellitus and dyslipidaemia than the non-CHHF group, but a higher OR in degenerative arthritis, chronic gastritis, gastroduodenal ulcer, reflux oesophagitis, and chronic rhinitis. This study showed that CHHF is associated with chronic disease. Further large-scale prospective studies are needed to validate these associations.


Protocol for establishing a model for integrated influenza surveillance in Tamil Nadu, India.
The potential for influenza viruses to cause public health emergencies is great. The World Health Organisation (WHO) in 2005 concluded that the world was unprepared to respond to an influenza pandemic. Available surveillance guidelines for pandemic influenza lack the specificity that would enable many countries to establish operational surveillance plans. A well-designed epidemiological and virological surveillance is required to strengthen a country's capacity for seasonal, novel, and pandemic influenza detection and prevention. Here, we describe the protocol to establish a novel mechanism for influenza and SARS-CoV-2 surveillance in the four identified districts of Tamil Nadu, India. This project will be carried out as an implementation research. Each district will identify one medical college and two primary health centres (PHCs) as sentinel sites for collecting severe acute respiratory infections (SARI) and influenza like illness (ILI) related information, respectively. For virological testing, 15 ILI and 10 SARI cases will be sampled and tested for influenza A, influenza B, and SARS-CoV-2 every week. Situation analysis using the WHO situation analysis tool will be done to identify the gaps and needs in the existing surveillance systems. Training for staff involved in disease surveillance will be given periodically. To enhance the reporting of ILI/SARI for sentinel surveillance, trained project staff will collect information from all ILI/SARI patients attending the sentinel sites using pre-tested tools. Using time, place, and person analysis, alerts for abnormal increases in cases will be generated and communicated to health authorities to initiate response activities. Advanced epidemiological analysis will be used to model influenza trends over time. Integrating virological and epidemiological surveillance data with advanced analysis and timely communication can enhance local preparedness for public health emergencies. Good quality surveillance data will facilitate an understanding outbreak severity and disease seasonality. Real-time data will help provide early warning signals for prevention and control of influenza and COVID-19 outbreaks. The implementation strategies found to be effective in this project can be scaled up to other parts of the country for replication and integration.


Soluble fas and the -670 polymorphism of fas in lupus nephritis.
This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the -670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the -670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA. Additionally, the WT-1 protein level in urine was measured. The Fas receptor was determined in biopsies by immunohistochemistry (IHC) and in situ hybridization (FISH) and apoptotic features by TUNEL. Results. The -670 Fas polymorphism showed that the G allele was associated with increased SLE susceptibility, with an odds ratio (OR) of 1.86. The sFas was significantly higher in LN patients with the G/G genotype, and this subgroup exhibited correlations between the sFas level and proteinuria and increased urinary WT-1 levels. LN group shows increased expression of Fas and apoptotic features. In conclusion, our results indicate that the G allele of the -670 polymorphism of Fas is associated with genetic susceptibility in SLE patients with elevated levels of sFas in LN with proteinuria.


Feedforward consequences of isometric contractions: effort and ventilation.
The onset of voluntary muscle contractions causes rapid increases in ventilation and is accompanied by a sensation of effort. Both the ventilatory response and perception of effort are proportional to contraction intensity, but these behaviors have been generalized from contractions of a single muscle group. Our aim was to determine how these relationships are affected by simultaneous contractions of multiple muscle groups. We examined the ventilatory response and perceived effort of contraction during separate and simultaneous isometric contractions of the contralateral elbow flexors and of an ipsilateral elbow flexor and knee extensor. Subjects made 10-sec contractions at 25, 50, and 100% of maximum during normocapnia and hypercapnia. For simultaneous contractions, both muscle groups were activated at the same intensities. Ventilation was measured continuously and subjects rated the effort required to produce each contraction. As expected, ventilation and perceived effort increased proportionally with contraction intensity during individual contractions. However, during simultaneous contractions, neither ventilation nor effort reflected the combined muscle output. Rather, the ventilatory response was similar to when contractions were performed separately, and effort ratings showed a small but significant increase for simultaneous contractions. Hypercapnia at rest doubled baseline ventilation, but did not affect the difference in perceived effort between separate and simultaneous contractions. The ventilatory response and the sense of effort at the onset of muscle activity are not related to the total output of the motor pathways, or the working muscles, but arise from cortical regions upstream from the motor cortex.


Isolation of Rho GTPase effector pathways during axon development.
The Rho GTPases Rac1 and Cdc42 have been implicated in the regulation of axon outgrowth and guidance. However, the downstream effector pathways through which these GTPases exert their effects on axon development are not well characterized. Here, we report that axon outgrowth defects within specific subsets of motoneurons expressing constitutively active Drosophila Rac1 largely persist even with the addition of an effector-loop mutation to Rac1 that disrupts its ability to bind to p21-activated kinase (Pak) and other Cdc42/Rac1 interactive-binding (CRIB)-motif effector proteins. While hyperactivation of Pak itself does not lead to axon outgrowth defects as when Rac1 is constitutively activated, live analysis reveals that it can alter filopodial activity within specific subsets of neurons similar to constitutive activation of Cdc42. Moreover, we show that the axon guidance defects induced by constitutive activation of Cdc42 persist even in the absence of Pak activity. Our results suggest that (1) Rac1 controls axon outgrowth through downstream effector pathways distinct from Pak, (2) Cdc42 controls axon guidance through both Pak and other CRIB effectors, and (3) Pak's primary contribution to in vivo axon development is to regulate filopodial dynamics that influence growth cone guidance.


Spin-order driven Fermi surface reconstruction revealed by quantum oscillations in an underdoped high Tc superconductor.
We use quantum oscillation measurements to distinguish between spin and orbital components of the lowest energy quasiparticle excitations in YBa(2)Cu(3)O(6.54), each of which couple differently to a magnetic field. Our measurements reveal the phase of the observed quantum oscillations to remain uninverted over a wide angular range, indicating that the twofold spin degeneracy of the Landau levels is virtually unaltered by the magnetic field. The inferred suppression of the spin degrees of freedom indicates a spin-density wave is responsible for creation of the small Fermi surface pockets in underdoped YBa(2)Cu(3)O(6+x)--further suggesting that excitations of this phase are important contributors to the unconventional superconducting pairing mechanism.


Is dementia a mental illness?
To examine whether dementia is a mental illness. An analysis of decisions in the Supreme Court of New South Wales that dementia per se was not a mental illness in terms of the 1958 Mental Health Act. A brief review of the extrusion of other diseases from psychiatry. Concepts in legislation are based on a dichotomy between mental infirmity and mental illness that has changed over time. This change is the result of shifting perceptions about the basis of illness and disease and the causation of mental symptoms. Mental health legislation is aimed as much at social control of feared behaviour as protecting the ill/incompetent. Guardianship legislation offers a more holistic response that better meets the patient's needs and could be extended to supplant mental health legislation. Dementia's departure from mental illness reflects psychiatry's continuing marginalization within medicine on an outdated mind/body or illness/disease split. This underlines one of the psychiatrist's roles as the vehicle to 'medically' explain abnormal behaviour. This model means that behaviour, once explained in terms of disease as opposed to illness, can be moved from the direct responsibility of psychiatry into other areas of medicine. Paradoxically, this suggests that the future of psychiatry will be in a completely different direction from its current biological focus.


Associations of Biomarkers of Inflammation and Breast Cancer in the Breast Adipose Tissue of Women with Combined Measures of Adiposity.
Mechanisms underlying the obesity-breast cancer link involve inflammation but need to be elucidated. Determining obesity by combining body mass index (BMI) with the waist circumference (WC) may clarify the role of inflammatory and hormonally related markers in breast cancer. We examined the effect of combining adiposity indices (BMI/WC) with the gene expression of several biomarkers involved in breast cancer. Expression of cytochrome P450 family 19 subfamily A member 1 (CYP19A1), estrogen receptor-alpha (ER-α), allograft inflammatory factor 1 (AIF1), cyclooxygenase-2 (COX2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and leptin (LEP) in 141 adipose breast tissues was quantified using qPCR method. BMI and WC were measured by a trained nurse and categorized using the median split, BMILOWCLO, BMILOWCHI, BMIHIWCLO, and BMIHIWCHI. Gene expression of IL-6 (3-fold), TNF-α (2-fold), and LEP (2-fold) was higher in the breast adipose tissue of women with high WC regardless of BMI, that is, BMILOWCHI and BMIHIWCHI women (all P < 0.01). Compared to BMILOWCLO women, gene expression of CYP19A1, COX2, and AIF1 was increased by two-fold in breast adipose tissue of BMIHIWCHI women (P < 0.10). ER-α was not different across adiposity categories. The expression of some biomarkers, particularly those related to inflammation, is elevated in breast adipose tissue of women with a high WC independent of BMI. Obesity monitoring should also include women with normal or low BMI, but with central adiposity.


Arthrocentesis in TMJ Internal Derangement: A Prospective Study.
To evaluate improvement in symptoms following arthrocentesis: Pain, Maximum Mouth Opening, Clicking/Crepitation. Eleven patients who reported to the department of Oral and Maxillofacial Surgery, M S Ramaiah Dental College, Bangalore clinically diagnosed to have Internal Derangement of the TMJ underwent Arthrocentesis. Patients were evaluated at the end of 1 week, 1 and 3 months and results tabulated. 11 patients with clinically diagnosed Internal Derangement underwent Arthrocentesis and were followed up for 3 months. There was significant improvement in Pain, Maximum Mouth Opening and Clicking/Crepitation. All the results were statistically significant. There was no serious post operative complication. Arthrocentesis can be recommended as a simple chair-side procedure for the treatment of TMJ Internal Derangement refractory to conservative management.


Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen.
The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.


Transcription factors relevant to auxin signalling coordinate broad-spectrum metabolic shifts including sulphur metabolism.
A systems approach has previously been used to follow the response behaviour of Arabidopsis thaliana plants upon sulphur limitation. A response network was reconstructed from a time series of transcript and metabolite profiles, integrating complex metabolic and transcript data in order to investigate a potential causal relationship. The resulting scale-free network allowed potential transcriptional regulators of sulphur metabolism to be identified. Here, three sulphur-starvation responsive transcription factors, IAA13, IAA28, and ARF-2 (ARF1-Binding Protein), all of which are related to auxin signalling, were selected for further investigation. IAA28 overexpressing and knock-down lines showed no major morphological changes, whereas IAA13- and ARF1-BP-overexpressing plants grew more slowly than the wild type. Steady-state metabolite levels and expression of pathway-relevant genes were monitored under normal and sulphate-depleted conditions. For all lines, changes in transcript and metabolite levels were observed, yet none of these changes could exclusively be linked to sulphur stress. Instead, up- or down-regulation of the transcription factors caused metabolic changes which in turn affected sulphur metabolism. Auxin-relevant transcription factors are thus part of a complex response pattern to nutrient starvation that serve as coordinators of the metabolic shifts driving sulphur homeostasis rather then as direct effectors of the sulphate assimilation pathway. This study provides the first evidence ever presented that correlates auxin-related transcriptional regulators with primary plant metabolism.


Focal Amyloidosis of the Orbit Presenting as a Mass: MRI and CT Features.
Focal orbital amyloidosis is a rare entity and little is known about its magnetic resonance imaging (MRI) features. In this case report, imaging features of a case of focal orbital amyloidosis presenting as a mass have been documented together with its histopathological findings. On MRI, a well-defined mass was seen as isointense with rectus muscle on T1-weighted images and heterogeneously hypointense on T2-weighted images. Punctuate calcifications were observed on the computerized tomography (CT) examination.


Radiofrequency catheter ablation: the effect of electrode size on lesion volume in vivo.
Radiofrequency current is a promising alternative to high voltage direct current defibrillator discharges for catheter ablation of arrhythmias. However, lesions produced with radiofrequency current are relatively small and use of high power is limited by the impedance rise that occurs with desiccation of tissue and coagulum formation. The effect of electrode size on radiofrequency ablation was assessed by comparing results of radiofrequency application using a standard 6 French electrode catheter (distal electrode 2 mm in length) to those using catheters modified with longer distal electrodes (3, 4, 6, 8, and 10 mm in length). Radiofrequency ablation was performed at 47 left ventricular endocardial sites in 20 anesthetized dogs. A constant power of 13.3 +/- 1.3 watts at 550 kHz was applied between the distal catheter electrode and a skin electrode until a total of 500 joules had been delivered or a rise in impedance occurred. Increasing electrode length from 2 to 4 mm more than doubled lesion volume from a mean of 143 to 326 mm3 (P = 0.025). Increasing electrode length beyond 4 mm produced progressively smaller lesions (157 mm3, 155 mm3, and 67 mm3 for 6-, 8-, and 10-mm electrode lengths, respectively). Impedance rise was significantly less likely with larger electrodes and took longer to occur. Increasing the size of electrodes used for radiofrequency ablation allows application of higher power without an impedance rise. Optimizing electrode size (3 or 4 mm in this study) results in larger lesions and may improve the effectiveness of radiofrequency ablation of arrhythmias.


Synthesis of ultralong copper nanowires for high-performance transparent electrodes.
Cu nanowires hold great promise for the fabrication of low-cost transparent electrodes. However, their current synthesis is mainly performed in aqueous media with poor nanowire dispersibility. We report herein the novel synthesis of ultralong single-crystalline Cu nanowires with excellent dispersibility, providing an excellent candidate material for high-performance transparent electrode fabrication.


[Expression of human HMGB1 A box in E. coli and its inhibitory effects on monocytes].
To clone human high mobility guoup box1 A box (HMGB1 A box) and express it in escherichia coli effectly, investigate the inhibit effection of the purpose protern to the activation of monocytes stimulated by immunocomplex. According to human HMGB1 gene order which was optimized by our laboratory the PCR primer was designed which containing restriction enzyme cutting site. The HMGB1 A box gene was cloned following the whole gene synthesis template of human HMGB1, then the PCR product was inserted into clone vector pMD19-T. The positive colone was identified by colony PCR, zymography analysis and DNA sequencing. Recombinant colne vector was digested by restriction enzymes Nde I and Xho I and separated by agarose gel electrophoresis, then the fragment was inserted into the corresponding sites of expression vector pQE-T7-2. The positive recombinant expression vector was identified by colony PCR and the recombinant strains was induced by IPTG, then the purpose protein was identified by SDS-PAGE and Western blot. The recombinant protein of human HMGB1 A box was purificated by Ni(2+)-NTA chromatography and the inhibit effection of the purpose protern to the activation of monocyte stimulated by immunocomplex was identified by RT-PCR. We acquired expression strains of recombinant human HMGB1 A box, the target protein account for up to 40% of the whole protein of E.coli. Western blot showed recombinant protein can specificly reacted with anti-human HMGB1 polyclonal antibody and anti-His-Tag polyclonal antibody.The purpose protein was found more than 90% after purified, and can effectively inhibit the production of BAFF, IFN-gamma and TNF-alpha in monocyte which were induced by IC. A recombinant bacterial strain for expressing human HMGB1A box with biological activities was constructed successfully.


Abuse history and pathological dissociation among Israeli and American college students: a comparative study.
This paper has three objectives: (1) to compare the abuse histories of American and Israeli college students, (2) to closely examine the different types of dissociative experiences among these students, and (3) to compare the dissociative experiences of American and Israeli college students. The US sample reported higher levels of abuse than the Israeli sample. The US and Israeli samples did not differ in overall level of dissociation but the US sample had higher rank-ordered scores for five kinds of dissociation: Flashbacks, Somatoform Dissociation, Persecutory Voices, Temporarily Dissociated Knowledge or Skills, and Being Told of Disremembered Behavior.


Progression of Clinical Features in Lewy Body Dementia Can Be Detected Over 6 Months.
This study aimed to quantify the trajectory and magnitude of change of the key clinical features and corresponding symptom domains of dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD), including global cognition, parkinsonism, recurrent visual hallucinations, cognitive fluctuations, and sleep disturbance. One hundred sixteen patients with Lewy body dementia (DLB = 72, PDD = 44) underwent assessment at baseline and 3 and 6 months as part of a prospective multicenter randomized controlled trial. Linear mixed models were constructed for core outcome measures using the Mini-Mental State Examination (MMSE), motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III), Dementia Cognitive Fluctuations Scale (DCFS), and Neuropsychiatric Inventory (NPI). Within the time frame of our study (6 months), we were able to identify a significant cognitive decline of 1.3 points on the MMSE (p = 0.002) and significant worsening of motor parkinsonism with an increase in UPDRS-III score of 3.2 points (p = 0.018). Fluctuation severity also increased using the DCFS with a 6-month change in score of 1.3 points (p = 0.001). Uniquely, a signal for increased severity of sleep symptoms of 1.2 points (NPI-sleep) was also detectable (p = 0.04). Significant changes in neuropsychiatric symptoms were not detected. There was no difference in rates of change of scores between DLB and PDD. Clinically significant rates of change in core clinical features can be detected and quantified in Lewy body dementia over a relatively short period (6 months) using common clinical instruments and thus may be useful as clinical endpoints for therapeutic trials of disease-modifying and symptomatic agents.


Amelioration of Behavioral Impairments and Neuropathology by Antiepileptic Drug Topiramate in a Transgenic Alzheimer's Disease Model Mice, APP/PS1.
Alzheimer's disease (AD) is a neurodegenerative disease that is the main cause of dementia in the elderly. The aggregation of β-amyloid peptides is one of the characterizing pathological changes of AD. Topiramate is an antiepileptic drug, which in addition, is used in the treatment of many neuropsychiatric disorders. In this study, the therapeutic effects of topiramate were investigated in a transgenic mouse model of cerebral amyloidosis (APP/PS1 mice). Before, during, and after topiramate treatment, behavioral tests were performed. Following a treatment period of 21 days, topiramate significantly ameliorated deficits in nest-constructing capability as well as in social interaction. Thereafter, brain sections of mice were analyzed, and a significant attenuation of microglial activation as well as β-amyloid deposition was observed in sections from topiramate-treated APP/PS1 mice. Therefore, topiramate could be considered as a promising drug in the treatment of human AD.