Interface seal of incremental placement of visible light-cured composite resins.
An investigation was conducted to determine the quality of seal at the interface when a visible light-cured composite resin was placed and cured in increments. Five samples of each of the following composite materials were tested: Aurafill, Command, Command Ultrafine, Durafill, Prisma-Fil, and Silux. Samples of each material were placed in a thermocycling dye bath that contained a 0.5% aqueous solution of basic fuchsin dye for 25 hours. The samples were removed from the dye bath, rinsed, dried, and prepared for examination with a x25 microscope by two examiners. Neither examiner reported dye penetration at the interface of the materials tested. These findings effectively highlight the practicality of the incremental placement of light-cured composite resins.


Can treatment increase the epidemic size?
Antiviral treatment is one of the key pharmacological interventions against many infectious diseases. This is particularly important in the absence of preventive measures such as vaccination. However, the evolution of drug-resistance in treated patients and its subsequent spread to the population pose significant impediments to the containment of disease epidemics using treatment. Previous models of population dynamics of influenza infection have shown that in the presence of drug-resistance, the epidemic final size (i.e., the total number of infections throughout the epidemic) is affected by the treatment rate. These models, through simulation experiments, illustrate the existence of an optimal treatment rate, not necessarily the highest possible rate, for minimizing the epidemic final size. However, the conditions for the existence of such an optimal treatment rate have never been found. Here, we provide these conditions for a class of models covered in the literature previously, and investigate the combination effect of treatment and transmissibility of the drug-resistant pathogen strain on the epidemic final size. For the first time, we obtain the final size relations for an epidemic model with two strains of a pathogen (i.e., drug-sensitive and drug-resistant). We also discuss this model with specific functional forms of de novo resistance emergence, and illustrate the theoretical findings with numerical simulations.


Development and optimisation of a label-free quantitative proteomic procedure and its application in the assessment of genetically modified tomato fruit.
A key global challenge for plant biotechnology is addressing food security, whereby provision must be made to feed 9 billion people with nutritional feedstuffs by 2050. To achieve this step change in agricultural production new crop varieties are required that are tolerant to environmental stresses imposed by climate change, have better yields, are more nutritious and require less resource input. Genetic modification (GM) and marker-assisted screening will need to be fully utilised to deliver these new crop varieties. To evaluate these varieties both in terms of environmental and food safety and the rational design of traits a systems level characterisation is necessary. To link the transcriptome to the metabolome, quantitative proteomics is required. Routine quantitative proteomics is an important challenge. Gel-based densitometry and MS analysis after stable isotope labeling have been employed. In the present article, we describe the application of a label-free approach that can be used in combination with SDS-PAGE and reverse-phase chromatography to evaluate the changes in the proteome of new crop varieties. The workflow has been optimised for protein coverage, accuracy and robustness, then its application demonstrated using a GM tomato variety engineered to deliver nutrient dense fruit.


Voluntary Assisted Dying/Euthanasia: Will This Have an Impact on Cancer Care in Future Years?
In considering the impact of medically hastened death (MHD) on cancer care, a wide range of variables needs to be considered including demographic factors, diagnoses, local cultural factors, and the legislative frameworks in place. Here, we present a synthesis of recently available published literature and empirical data collected following legislative change to enable MHD in Victoria, Australia to explore in detail the potential impact of MHD on cancer care with a focus on patients/families and professional groups. Our findings reveal that for patients and families, both physical and existential distress frequently underlie MHD requests, with the latter less readily recognised by health professionals. The responses of those around the patient making the request may have a very significant impact on relationships within families and upon the nature of the subsequent bereavement. For palliative care, while differing views may remain, it appears that there has been some accommodation of MHD into or alongside practice over time. The recognition of a shared commitment to relief of suffering of palliative care and MHD appears a helpful means of establishing how these practices may co-exist. In cancer practice more broadly, as individual professionals reflect upon their own roles, new relationships and pathways of patient movement (or referral) must be established in response to patients' requests. Our findings also highlight many unanswered questions in understanding the impact of MHD, including that upon those dying who choose not to access MHD, First Nations peoples, the participating health professionals' longer term, and the relief of suffering itself. A systematic approach to the evaluation of MHD legislation must be adopted in order to understand its full impact. Only then could it be determined if the aspirations for such legislative change were being met.


Interferon-α plus ribavirin yields 98 % sustained virologic response in children aged 1-5 years with iatrogenic chronic hepatitis C.
The clinical features and efficacies of antivirals for children with hepatitis C virus (HCV) infections that are acquired through different transmission routines are poorly understood worldwide. This study investigated the clinical characteristics of children who were infected via iatrogenic means and analyzed the efficacy of antiviral therapy in children with chronic hepatitis C (CHC). In total, 256 children with HCV infections aged 1 to 5 years were enrolled and surveyed. Interferon-α plus ribavirin was administered to 162 children with CHC for 24 or 48 weeks. The sustained virologic response (SVR) at 24 weeks post-treatment was determined. The median duration of infection was 11.5 (range 6-24) months. The median age was 2.7 years, and 64.5 % of the subjects were male. Ninety-three children (36.3 %, 93/256) exhibited spontaneous resolution of the HCV infection. The remaining 163 (63.7 %) were HCV RNA-positive and had HCV genotypes 1b and 2a, which were identified in 42 and 58 %, respectively, of the 133 tested children. Liver biopsies were performed in all HCV RNA-detectable children. A total of 23.9 % cases exhibited grade 2 activity, and 30.1 % exhibited stage 2/3 liver fibrosis. The serum HCV RNA levels were positively correlated with the aminotransferases. Of the 162 treated CHC children, 158 (97.5 %) achieved SVR. The side effects were mild, and 158 (97.5 %) of the treated patients tolerated the treatment well. This study revealed that histological liver disease can be present within 6-24 months of acquiring an HCV infection in children aged 1-5 years. Interferon-α plus ribavirin therapy is a highly effective and cost-effective means of managing children with early-stage chronic HCV infection.


Biodegradation performance and biofouling control of a halophilic biocarriers-MBR in saline pharmaceutical (ampicillin-containing) wastewater treatment.
This work develops a halophilic biocarriers-MBR for saline pharmaceutical wastewater treatment. The system has effectively treated the ampicillin-containing saline wastewater for 32 days, when the ampicillin concentration is lower than 20 mg/L. The system can tolerate the saline organic wastewater with a reasonable biodegradability (removals of COD over 75%) when the ampicillin concentration is 50 mg/L. The system has a bad performance in biodegradation (COD removals around 60-70%) and fouled within 16 days at a high ampicillin concentration of 100 mg/L. At high transmembrane pressures over 30 KPa, some ampicillin molecules may permeate through the membrane causing decreases in the ampicillin removal. The concentrations of protein and carbohydrate in EPS and SMP have increased over time and with increasing the ampicillin concentration. The method of biofouling control in MBR for the ampicillin situations has been proposed based on monitoring the concentrations of EPS and SMP. The drying-assisted monitoring of membrane biofoulants has showed a better efficiency than the monitoring of transmembrane pressure for membrane anti-biofouling in the treatment of pharmaceutical saline wastewaters where a spectroscopic detection can be hardly applied. This work may benefit relative research works for the control of biodegradation performance and membrane biofouling to better treat saline pharmaceutical wastewaters.


Adolescent pregnancy in the time of COVID-19: what are the implications for sexual and reproductive health and rights globally?
The COVID-19 pandemic has aggravated pre-existing challenges associated with adolescents' sexual and reproductive health and rights (SRHR). Evolving evidence suggest that it could adversely impact the progress made towards improving sexual and reproductive health outcomes among young people. The pandemic has stalled achievements in reducing adolescent pregnancy and child marriage by reinforcing contextual and structural determinants of these reproductive health outcomes, especially among girls. The pandemic has increased disruptions to schooling, decreased access to sexual and reproductive health services and compounded pre-existing socio-economic vulnerabilities. The consequences of neglecting adolescent sexual and reproductive health services over the past 2 years, to focus on COVID-19, continue to emerge. This commentary argues for targeted and responsive approaches to adolescent SRHR that tackle preventable consequences resulting from inequities faced by adolescents globally, particularly girls.


Perceptions versus interpretations, and domains for self-fulfilling prophesies.
I suggest two ways in which Jussim's extensive discussion (in his 2012 book) could be enriched: first, by exploring the distinction between perceptual judgments and interpretive judgments; second, by considering the power of expectations to be self-fulfilling in the case of young children and the case of fragile egos.


The effect of a full-time infection control nursing service in the prevention of multidrug-resistant organism in the orthopedic ward.
Our aim was to evaluate the effect of setting up a full-time infection control nursing service on reducing the prevalence of multidrug-resistant organism (MDRO) in the orthopedic ward. From January 2015 to March 2019, routine prevention and control measures were taken for patients infected/colonized with MDRO in this ward, which was set as the pre-intervention period. The intervention period was from April 2019 to June 2021. The study was designed to evaluate whether the establishment of a full-time infection control nursing service could reduce the positive density of MDRO in the hospital by using an interrupted time-series model of a quasi experimental study. There were 11,759 patients during pre-intervention period and 8142 patients during intervention period. The total number of MDRO isolated before intervention was 177, of which 145 were obtained in hospital and 32 were brought in from outside hospital. The total number of MDRO isolated after intervention was 47, of which 29 were obtained in hospital and 18 were brought in from outside hospital. Before intervention, the positive density of MDRO in the orthopedic ward showed an increasing trend (β1 = 0.02, P = 0.003). After intervention, the positive density of MDRO showed a downward trend (β3 = - 0.05, P = 0.018). The establishment of the full-time infection control nursing service in the orthopedic ward can effectively reduce the nosocomial prevalence of MDRO.


Reduced ocular blood flow in asymmetric glaucoma: cause or effect?
Carotid Doppler measures blood flow velocity and vascular resistance index in the central retinal arteries and short posterior ciliary arteries. The blood flow profile of the optic nerve in chronic angle-closure glaucoma (CACG), however, has not been well documented. We report a 48-year-old female patient who presented with grossly asymmetric CACG and was evaluated by carotid Doppler. The patient had coexistent reduced blood flow in the ophthalmic artery of the more afflicted eye. Color Doppler imaging clarifies hemodynamic alterations in the glaucomatous optic nerve and helps to identify vascular aspects of the disease and its treatment.


Trophic cascades across ecosystems.
Predation can be intense, creating strong direct and indirect effects throughout food webs. In addition, ecologists increasingly recognize that fluxes of organisms across ecosystem boundaries can have major consequences for community dynamics. Species with complex life histories often shift habitats during their life cycles and provide potent conduits coupling ecosystems. Thus, local interactions that affect predator abundance in one ecosystem (for example a larval habitat) may have reverberating effects in another (for example an adult habitat). Here we show that fish indirectly facilitate terrestrial plant reproduction through cascading trophic interactions across ecosystem boundaries. Fish reduce larval dragonfly abundances in ponds, leading to fewer adult dragonflies nearby. Adult dragonflies consume insect pollinators and alter their foraging behaviour. As a result, plants near ponds with fish receive more pollinator visits and are less pollen limited than plants near fish-free ponds. Our results confirm that strong species interactions can reverberate across ecosystems, and emphasize the importance of landscape-level processes in driving local species interactions.


[Therapeutic study of Daktacort in dermatological disorders (author's transl)].
The activity of Daktacort was studied in various types of mycotis skin ailments. A total of 40 cases were treated and results were very good in 34 cases and insufficient or nil in 6 cases. Tolerance was excellent.


Leukocytosis due to adrenal metastases from malignant melanoma: reversal after bilateral adrenalectomy with long-term survival.
Leukocytosis has been noted in association with many non-hematologic malignancies in the absence of concurrent infection or metastatic involvement of bone marrow. We report a case of sustained, neutrophilic leukocytosis in a patient with disseminated malignant melanoma which reversed after bilateral adrenalectomy for adrenal metastases.


Hypericin-photodynamic therapy (PDT) using an alternative treatment regime suitable for multi-fraction PDT.
Photodynamic therapy (PDT) outcome depends on the conditions under which it is carried out. Maintaining the tumour tissue oxygen level is important for PDT efficacy and using a low fluence rate can improve outcome. In this work we studied the response of human nasopharyngeal carcinoma tumours in murine models to hypericin-PDT carried out under low fluence and fluence rate. A drug-light interval (DLI) of 1h or 6h was used for 1h-PDT and 6h-PDT, respectively. Evan's blue test was used to assess necrosis and TUNEL staining for apoptosis. Nuclear microscopy was used to quantify elemental concentrations in tumours. Serum vascular endothelial growth factor (VEGF) levels were also determined. TUNEL results showed that 6h-PDT induced significantly more apoptosis compared to 1h-PDT (p<0.01). This was supported by nuclear microscopy showing an increase in calcium and a decrease in zinc levels (both known triggers of apoptosis) in 6h-PDT tumours compared to non-PDT tumours (p<0.05). These results further imply a zinc-mediated pathway in hypericin-PDT induced apoptosis. 6h-PDT also resulted in a significant increase in copper concentrations compared to non-PDT tumours (p<0.05). Serum VEGF levels measured after 6h-PDT were lower than those obtained after 1h-PDT. Overall tumour response to hypericin-PDT under low fluence and fluence rate and using a 6h DLI showed increased apoptosis and lower serum VEGF levels. This treatment regime is suitable for the alternative approach of multi-fraction PDT in which the tumour can be exposed to multiple PDT fractions for complete tumour response. This alternative approach might yield improved outcome.


Chronic blockade of endothelin receptors in cirrhotic rats: hepatic and hemodynamic effects.
Because controversial roles have been attributed to activation of the hepatic paracrine endothelin (ET) system in cirrhosis, this study assessed whether chronic ET receptor blockade modifies the development of portal hypertension in cirrhotic rats. Cirrhotic and control rats received the mixed ET receptor antagonist RO 48-5695 or vehicle daily for 10 weeks. At the end of the treatment period, portal pressure, systemic hemodynamics, standard renal and liver function tests, hepatic concentration of hydroxyproline, and liver messenger RNA (mRNA) expression of procollagen type I were measured. Cirrhotic rats had portal hypertension and hyperdynamic circulation with no differences between animals treated or not treated with the ET-receptor antagonist. However, cirrhotic rats receiving ET-receptor blockade long-term showed a higher hepatic hydroxyproline content and procollagen type I mRNA expression than cirrhotic animals receiving vehicle. The results indicate that the liver paracrine ET system does not play a major role in the pathogenesis of portal hypertension and support the concept that this system takes part in an autocrine loop that counteracts the development of liver fibrogenesis.


The pituitary in klinefelter syndrome.
Klinefelter syndrome is a genetically determined primary gonadal defect characterized by the XXY karyotype. The testes are small, blood testosterone levels are low, and blood gonadotropin levels are elevated. Pituitary changes in patients with Klinefelter syndrome have not been evaluated in detail. The first patient, a 76-yr-old man, was operated for a large sellar mass. The second and third patients, a 62- and a 52-yr-old man, respectively, died of cardiac failure. Both the latter pituitaries were normal-sized and removed at autopsy. The diagnosis of Klinefelter syndrome was confirmed by genetic testing in all three cases. The formalin-fixed and paraffin-embedded pituitaries of three patients were evaluated for adenohypophysial hormone immunoreactivity. For immunohistochemistry, the streptavidin- biotin-peroxidase (ABC) complex method was applied. In case 1, histology and immunohistochemistry revealed an oncocytic gonadotroph macroadenoma immunoreactive for FSH and alpha subunit. No pituitary gland was evident. The pituitary of case 2 featured hyperplasia of gonadotrophs, some with features of "gonadal deficiency cells," and a microadenoma immunoreactive for GH. The pituitary of case 3 similarly showed hyperplasia of gonadotrophs and the formation of gonadal deficiency cells. Protracted stimulation of gonadotrophs due to lack of androgen feedback might have been a factor in the formation of the gonadotroph adenoma in case 1 and in the development of gonadotroph hyperplasia in cases 2 and 3. The clinically silent GH microadenoma of case 2 was regarded as an incidental finding.


T-cell Lymphomas: Updates in Biology and Diagnosis.
Nodal-based peripheral T-cell lymphomas are heterogeneous malignancies with overlapping morphology and clinical features. However, the current World Health Organization classification scheme separates these tumors into prognostically relevant categories. Since its publication, efforts to uncover the gene expression profiles and molecular alterations have subdivided these categories further, and distinct subgroups are emerging with specific profiles that reflect the cell of origin for these tumors and their microenvironment. Identification of the perturbed biologic pathways may prove useful in selecting patients for specific therapies and associating biomarkers with survival and relapse.


An innovative approach to investigate the dynamics of the cerebrospinal fluid in the prepontine cistern: A feasibility study using spatial saturation-prepared cine PC-MRI.
Accurate measurements of the cerebrospinal fluid that flows through the prepontine cistern (PPC) are challenging due to artefacts originating from basilar artery blood flow. We aim to accurately quantify cerebrospinal fluid (CSF) flow and stroke volume in the PPC, which is essential before endoscopic third ventriculostomy. We developed a new PC-MRI sequence prepared with Hadamard saturation bands to accurately quantify CSF flow in the PPC by suppressing the blood signal in the surrounding vessels. In total, 28 adult hydrocephalic patients (age 59 ± 20 years) were scanned using conventional PC-MRI and our developed sequence. CSF was separately extracted from the PPC and the foramen of Magendie, and flow (min and max) and stroke volume were quantified. Our modifications result in a complete deletion of signal from flowing blood, resulting in significantly reduced CSF stroke volume (Conv = 446 ± 113 mm(3), Dev = 390 ± 119 mm(3), p = 0.006) and flow, both minimum (Conv = -1630 ± 486 mm(3)/s, Dev = -1430 ± 406 mm(3)/s, p = 0.005) and maximum (Conv = 2384 ± 657 mm(3)/s, Dev = 1971 ± 62 mm(3)/s, p = 0.002) compared with the conventional sequence, whereas no change in the area of interest was noted (Conv = 236 ± 65 mm(2), Dev = 249 ± 75 mm(2), p = 0.21). Accurate and reproducible CSF flow and stroke volume measurements in the PPC can be achieved with sat-band prepared cine PC-MRI.


The cingulate cortex and limbic systems for action, emotion, and memory.
Different limbic structures including the hippocampal memory system and the amygdala/orbitofrontal emotion system have very different connectivity and functions, and it has been suggested that we should no longer think of a single limbic system. A framework is provided for understanding the connectivity and functions of different parts of the cingulate cortex in action, emotion, and memory, in the context of connections of different parts of the cingulate cortex with other limbic and neocortical structures. First, the anterior cingulate cortex receives information from the orbitofrontal cortex about reward and nonreward outcomes. The posterior cingulate cortex receives action-related and spatial information from parietal cortical areas. It is argued that these are inputs that allow the cingulate cortex to perform action-outcome learning, with outputs from the midcingulate motor area to premotor areas. Damage to the anterior cingulate cortex impairs action-outcome learning and emotion because of its reward-related representations. Second, the posterior cingulate cortex provides "action" and "spatial" information from the parietal cortex into the hippocampal memory system via the parahippocampal gyrus, and the anterior cingulate cortex (receiving from the orbitofrontal cortex) provides reward-related input into the hippocampal memory system via the posterior cingulate and parahippocampal gyrus. Thus posterior cingulate damage can impair hippocampal episodic memory and retrieval, especially the spatial component. These functions are related to the place of this proisocortical limbic region in brain connectivity.


Client satisfaction in support of service planning within a regulatory framework: experience of a research hospital.
Research Operations at UHN provide services to a large, complex client research community with varying needs. This requires complex coordination and continual refining of service and resource targets to meet client, government and external stakeholder requirements. The UHN Research Operations model focuses on six key enablers: client education, service team expertise, direct communication, process improvement, quality assurance, and, systems and tools. Service departments that have deployed these enablers experience improved client satisfaction.


Automated robust human emotion classification system using hybrid EEG features with ICBrainDB dataset.
Emotion identification is an essential task for human-computer interaction systems. Electroencephalogram (EEG) signals have been widely used in emotion recognition. So far, there have been several EEG-based emotion recognition datasets that the researchers have used to validate their developed models. Hence, we have used a new ICBrainDB EEG dataset to classify angry, neutral, happy, and sad emotions in this work. Signal processing-based wavelet transform (WT), tunable Q-factor wavelet transform (TQWT), and image processing-based histogram of oriented gradients (HOG), local binary pattern (LBP), and convolutional neural network (CNN) features have been used extracted from the EEG signals. The WT is used to extract the rhythms from each channel of the EEG signal. The instantaneous frequency and spectral entropy are computed from each EEG rhythm signal. The average, and standard deviation of instantaneous frequency, and spectral entropy of each rhythm of the signal are the final feature vectors. The spectral entropy in each channel of the EEG signal after performing the TQWT is used to create the feature vectors in the second signal side method. Each EEG channel is transformed into time-frequency plots using the synchrosqueezed wavelet transform. Then, the feature vectors are constructed individually using windowed HOG and LBP features. Also, each channel of the EEG data is fed to a pretrained CNN to extract the features. In the feature selection process, the ReliefF feature selector is employed. Various feature classification algorithms namely, k-nearest neighbor (KNN), support vector machines, and neural networks are used for the automated classification of angry, neutral, happy, and sad emotions. Our developed model obtained an average accuracy of 90.7% using HOG features and a KNN classifier with a tenfold cross-validation strategy.


High Trypanosoma vivax infection rates in water buffalo and cattle in the Brazilian Lower Amazon.
Highly sensitive and accurate molecular diagnostic methods have not yet been employed for livestock trypanosomosis in the Brazilian Lower Amazon although the first reports of Trypanosoma vivax and Trypanosoma evansi in Brazil were in water buffalo (Bubalus bubalis) in this region. The present study assessed trypanosomosis in buffalo and cattle raised in communal and seasonally flooding pastures in the state of Pará using the fluorescent fragment length barcoding (FFLB) method. T. evansi was not detected, but high infection rates of T. vivax and T. theileri were revealed by a simplified FFLB standardized in the present study that discriminates all trypanosome species infective to livestock in South America. T. vivax infection rates detected by TviCATL-PCR were 24.6% for cattle (n = 61) and 28.1% for buffalo (n = 89). Using the FFLB method, overall T. vivax infection rates increased to 59.6% and 44.3% for buffalo and cattle, respectively. Furthermore, the predominance of a single microsatellite-based genotype of T. vivax was reinforced in the Lower Amazon. Relevant T. vivax infection rates detected in clinically healthy buffalo and cattle through the sampled years (2008-2017) highlight the need for systematic studies to demonstrate the endemic steady state of T. vivax in this region. Our findings provide baseline information for livestock management, including control of T. vivax dispersal, and the introduction of naïve animals. The growing international trade of live livestock from this very important livestock breeding region represents a serious risk for T. vivax spreading outside Amazonia and Brazil.


[Frequency and clinical profile of Parkinson's disease and other Parkinsonian syndromes seen in the Department of Neurology at the Befelatanana Hospital Antananarivo].
Currently we have no precise data on the parkinsonian syndromes in Madagascar. This study aims to collect data on these diseases and to describe the frequency and the clinical profile of parkinsonian syndromes in our Department of Neurology. We conducted a retrospective and descriptive study in the Department of Neurology, in Befelatanana from January 2014 to June 2018. The demographic and clinical data of patients diagnosed as having a parkinsonian syndrome were collected. We assessed data rates and characteristics and then we compared patients with idiopathic Parkinson's disease and patients with other parkinsonian syndromes. Data were processed using R. software. The study included 104 of 3528 patients, seen in our Department. Among the patients with parkinsonian syndrome, 67(64.42%) had idiopathic Parkinson's disease (PD) and 37 (35.47%) another parkinsonian syndrome. The average interval between the onset of the disease and the consultation or the hospitalization in the Department was 2.5 years. For MP, the median age at onset was 58.5 [23; 80] years, the median age at diagnosis was 62 [28; 83] years and the sex ratio were 1.97. The median Hoehn and Yahr score were 2.0. Tremor-dominant Parkinson's disease was found in 24 (35.42%) of cases, a mixed phenotype was found in 28 (41.71%) of cases while akineto-rigid Parkinson's disease was found in 15 (22.38%) of cases. The other parkinsonian syndromes ocuurred in 27 (72.97%) men, with a median age at onset of 57.5 [26; 83] years, a median age at diagnosis of 59.3 [26; 83] years. Etiologies were dominated by Multiple System Atrophy 17/37 (46.64%). Patients with other parkinsonian syndromes had several cognitive disorders (p=0,0306) and MPs were more sensitive to dopamine (p=0.006). The patients with idiopathic parkinsonian syndrome had features different from those of patients with parkinsonism. There was a diagnostic delay as in other developing countries.


EMPEROR-Preserved: A promise fulfilled.
Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in medicine. In the EMPEROR-Preserved trial, recently reported in the NEJM, the SGLT2 inhibitor empagliflozin reduced the primary outcome of heart failure hospitalizations and cardiovascular death by 21% in patients with HFpEF. This represents an important breakthrough in the war against heart failure.


Resveratrol cocrystals with enhanced solubility and tabletability.
Two new 1:1 cocrystals of resveratrol (RES) with 4-aminobenzamide (RES-4ABZ) and isoniazid (RES-ISN) were synthesized by liquid assisted grinding (LAG) and rapid solvent removal (RSR) methods using ethanol as solvent. Their physiochemical properties were characterized using PXRD, DSC, solid state and solution NMR, FT-IR, and HPLC. Pharmaceutically relevant properties, including tabletability, solubility, intrinsic dissolution rate, and hygroscopicity, were evaluated. Temperature-composition phase diagram for RES-ISN cocrystal system was constructed from DSC data. Both cocrystals show higher solubility than resveratrol over a broad range of pH. They are phase stable and non-hygroscopic even under high humidity conditions. Importantly, both cocrystals exhibit improved solubility and tabletability compared with RES, which make them more suitable candidates for tablet formulation development.


Comparison of three cardioverter defibrillator implantation techniques: initial results with transvenous pectoral implantation.
A total of 121 patients underwent epicardial (n = 32), transvenous abdominal (n = 30), and transvenous pectoral (n = 59) ICD implants. Perioperative complications were defined as those occurring within 30 days after surgery. Hospital costs were calculated with $750 per day as a fixed charge. Duration of surgery was the time between the first skin incision and the last skin suture. Severe perioperative complications that were life-threatening or required surgical intervention occurred in the epicardial (6%) and transvenous (10%) abdominal groups, but not in the pectoral group. Perioperative mortality occurred only in the epicardial abdominal group, predominantly in patients with concomitant surgery (18%), and in 5% of patients without concomitant surgery. The duration of surgery was significantly shorter for transvenous pectoral implantation (58 +/- 15 min, P < 0.05) compared to transvenous abdominal implantation (115 +/- 38 min). Epicardial abdominal ICD implantation had the longest procedure time (154 +/- 31 min). The postimplant hospital length of stay was significantly shorter for pectoral implantation (5 +/- 3 days, P < 0.05) compared to transvenous (13 +/- 5) and epicardial (19 +/- 5) abdominal implantation. Total hospitalization costs significantly decreased in the pectoral implantation group ($4,068 +/- $2,099 for the pectoral group vs $14,887 +/- $4,415 and $9,975 +/- $3,657 for the epicardial and the transvenous abdominal group, respectively, P < 0.05). These initial results demonstrate the advantage of transvenous pectoral ICD implantation in terms of perioperative complications, procedure time, hospital length of stay, and hospitalization costs.


Examination of swallowing maneuver training and transfer of practiced behaviors to laryngeal vestibule kinematics in functional swallowing of healthy adults.
Swallowing maneuvers are routinely trained in dysphagia rehabilitation with the assumption that practiced behaviors transfer to functional swallowing, however transfer is rarely examined in the deglutition literature. The goal of this study was to train the volitional laryngeal vestibule closure (vLVC) maneuver, which is a swallowing maneuver that targets prolonged laryngeal vestibule closure (LVC). In two different training experiments, 69 healthy adults underwent Long-hold (hold vLVC as long as possible) or Short-hold vLVC training (hold vLVC for 2s). Before and after vLVC training, natural swallows (swallowing without a therapeutic technique) were completed. The outcome variables included laryngeal vestibule closure reaction time and the duration of laryngeal vestibule closure. Results indicate that during both Long-hold and Short-hold vLVC trainings, vLVC swallows had faster laryngeal vestibule closure reaction times and longer durations of laryngeal vestibule closure than in pre-training 5ml liquid swallows. However, only faster laryngeal vestibule closure reaction times transferred to post-training 5ml liquid swallows (20-24% faster), but not prolonged durations of laryngeal vestibule closure. Our findings suggest that swallowing maneuver training has the potential to induce transfer of what was practiced to functional swallowing behavior, although not all practiced behaviors may generalize. These findings are significant for bolstering the effectiveness of dysphagia management in medical settings and should be tested in individuals with dysphagia.


The use of fluorescent probes to identify regions of transient perfusion in murine tumors.
Sequential intravenous injection of two fluorescent stains, Hoechst 33342 and DiOC7(3), can be used to quantify transient perfusion in experimental tumors. Regions of unmatched staining, indicative of intermittent perfusion, occur when vessels open or close in the 20 minute interval between administration of the dyes. In the murine SCCVII carcinoma, 8.9 +/- 2.4% (SD) of vessels in 0.5 g subcutaneous tumors had labelling of adjacent cells with only one stain, suggesting complete vessel closure lasting at least 5 minutes. Regions of intermittent perfusion were not homogeneously distributed throughout the tumor and larger tumors exhibited more mismatch than smaller tumors. Transient perfusion was observed in both subcutaneous and intramuscular tumor implants and was not significantly affected by restraint of the animal or by ketamine/diazepam anesthesia.


High-Precision Single-Photon Laser Time Transfer with Temperature Drift Post-Compensation.
Laser time transfer is of great significance in timing and global time synchronization. However, temperature drift may occur and affect the delay of the electronics system, optic generation and detection system. This paper proposes a post-processing method for the compensation of temperature-induced system delay, which does not require any changes to the hardware setup. The temperature drift and time stability of the whole system are compared with and without compensation. The results show that propagation delay drift as high as 240 ps caused by temperature changes is compensated. The temperature drift coefficient was diminished down to ~0.05 ps/°C from ~20.0 ps/°C. The system precision was promoted to ~2 ps from ~11 ps over a time period of 80,000 s. This method performs significant compensation of single-photon laser time transfer system propagation drift and will to help establish an ultra-stable laser time transfer link in a space application.


Application of empirical mode decomposition, particle swarm optimization, and support vector machine methods to predict stream flows.
Modeling stream flows is vital for water resource planning and flood and drought management. In this study, the performance of hybrid models constructed by combining least square support vector machines (LSSVM), empirical model decomposition (EMD), and particle swarm optimization (PSO) methods in modeling monthly streamflow was evaluated. For establishing the models, 42 years of monthly average streamflow data was used in two hydrometer stations located in the Konya Closed Basin, covering 1964 to 2005. Lagged streamflow values were selected as inputs according to partial autocorrelation values in establishing the models. The dataset was divided into 70% training and 30% testing. Model performances were evaluated according to mean square error, root mean square error, correlation coefficients, scatter plot, and Taylor and Violin diagrams. As a result of the analysis, it was determined that the PSO-LSSVM and EMD-LSSVM models were slightly more successful than the single LSSVM model, and the best model was obtained with the EMD-PSO-LSSVM. In addition, in estimating monthly stream flows, 1-, 9-, 10-, 11-, and 12-month lagged streamflow values were the input combination that gave the best results in semi-arid climatic regions. This result demonstrated that EMD improved the performance of both LSSVM and PSO-LSSVM models by 1% to 5% based on correlation coefficient (R) values.


Nanoparticle-based vaccine development and evaluation against viral infections in pigs.
Virus infections possess persistent health challenges in swine industry leading to severe economic losses worldwide. The economic burden caused by virus infections such as Porcine Reproductive and Respiratory Syndrome Virus, Swine influenza virus, Porcine Epidemic Diarrhea Virus, Porcine Circovirus 2, Foot and Mouth Disease Virus and many others are associated with severe morbidity, mortality, loss of production, trade restrictions and investments in control and prevention practices. Pigs can also have a role in zoonotic transmission of some viral infections to humans. Inactivated and modified-live virus vaccines are available against porcine viral infections with variable efficacy under field conditions. Thus, improvements over existing vaccines are necessary to: (1) Increase the breadth of protection against evolving viral strains and subtypes; (2) Control of emerging and re-emerging viruses; (3) Eradicate viruses localized in different geographic areas; and (4) Differentiate infected from vaccinated animals to improve disease control programs. Nanoparticles (NPs) generated from virus-like particles, biodegradable and biocompatible polymers and liposomes offer many advantages as vaccine delivery platform due to their unique physicochemical properties. NPs help in efficient antigen internalization and processing by antigen presenting cells and activate them to elicit innate and adaptive immunity. Some of the NPs-based vaccines could be delivered through both parenteral and mucosal routes to trigger efficient mucosal and systemic immune responses and could be used to target specific immune cells such as mucosal microfold (M) cells and dendritic cells (DCs). In conclusion, NPs-based vaccines can serve as novel candidate vaccines against several porcine viral infections with the potential to enhance the broader protective efficacy under field conditions. This review highlights the recent developments in NPs-based vaccines against porcine viral pathogens and how the NPs-based vaccine delivery system induces innate and adaptive immune responses resulting in varied level of protective efficacy.


Synthesis, DNA binding and cleavage activity of macrocyclic polyamines bearing mono- or bis-acridine moieties.
Two acridine-pendant cyclen (1,4,7,10-tetraazacyclododecane) derivatives 1 and 2 were synthesized, and their DNA interactions have been systematically investigated by UV absorption, fluorescence titration, viscosity measurement, DNA melting and gel electrophoresis experiments. The results showed that acridine-cyclen derivatives could bind to DNA in intercalative mode, and bis-acridine 2 has higher DNA binding ability than that of mono-acridine 1. Moreover, both compounds exhibited preferential interactions with G-rich DNA sequences. Their copper(II) complexes could cleave DNA without the existence of other additives under physiological conditions through an oxidative pathway.


Does the physician order-entry system increase the revenue of a general hospital?
The purpose of this study was to examine whether the physician order-entry system (POE) could increase the outpatient and inpatient revenue of hospitals. We analyzed the inpatient and outpatient revenue data of all general hospitals (212) in South Korea obtained from the Korean National Health Insurance Corporation (KNHIC) during the period from 1996 to 1999 using the mixed model for repeated measure data. Analysis of the 4-years' panel data showed that both outpatient and inpatient revenues increased significantly after POE introduction. The hospital characteristics significantly influencing inpatient revenue were the number of beds, number of physicians and the tertiary status of a hospital; whereas those for outpatient revenue were the number of beds, number of physicians, the private status of a hospital, the tertiary status of a hospital and the urban status of a hospital. The revenues from both outpatients and inpatients were found to be increased after the introduction of the POE, while controlling for population size, competition, income, hospital location, hospital size, tertiary status and public status.


Robot-based assessment of motor and proprioceptive function identifies biomarkers for prediction of functional independence measures.
Neurological impairments following stroke impact the ability of individuals to perform daily activities, although the relative impact of individual impairments is not always clear. Recovery of sensorimotor function following stroke can vary widely, from complete recovery to modest or minimal improvements, across individuals. An important question is whether one can predict the amount of recovery based on initial examination of the individual. Robotic technologies are now being used to quantify a range of behavioral capabilities of individuals post-stroke, providing a rich set of biomarkers of sensory and motor dysfunction. The objective of the present study is to use mathematical models to identify which biomarkers best predict the ability of subjects with stroke to perform daily activities before and after rehabilitation. The Functional Independence Measure (FIM) was quantified approximately 2 weeks and three months post-stroke in 61 ischemic and 24 hemorrhagic subjects with stroke. At 2 weeks post-stroke, subjects also completed clinical assessments and robotic assessments of sensory and motor function. A computational search algorithm, known as Fast Orthogonal Search, was used to identify the robotic and clinical biomarkers that best estimated Functional Independence Measures. Clinical and robot-based biomarkers were statistically similar at predicting FIM scores at 2 weeks (r = 0.817 vs. 0.774, respectively) and 3 months (r = 0.643 vs. 0.685, respectively). Importantly, robot-based biomarkers highlighted that parameters related to proprioception were influential for predicting FIM scores at 2 weeks, whereas biomarkers related to bimanual motor function were influential for predicting FIM scores at 3 months. The present study provides a proof of principle on the use of robot-based biomarkers of sensory and motor dysfunction to estimate present and future FIM scores. The addition of other behavioral tasks will likely increase the accuracy of these predictions, and potentially help guide rehabilitation strategies to maximize functional recovery.


Distinct gray matter abnormalities in children/adolescents and adults with history of childhood maltreatment.
Gray matter (GM) abnormalities have been reported in both adults and children/adolescents with histories of childhood maltreatment (CM). A comparison of effects in youth and adulthood may be informative regarding life-span effects of CM. Voxel-wise meta-analyses of whole-brain voxel-based morphometry studies were conducted in all datasets and age-based subgroups respectively, followed by a quantitative comparison of the subgroups. Thirty VBM studies (31 datasets) were included. The pooled meta-analysis revealed increased GM in left supplementary motor area, and reduced GM in bilateral cingulate/paracingulate gyri, left occipital lobe, and right middle frontal gyrus in maltreated individuals compared to the controls. Maltreatment-exposed youth showed less GM in the cerebellum, and greater GM in bilateral middle cingulate/paracingulate gyri and bilateral visual cortex than maltreated adults. Opposite GM alterations in bilateral middle cingulate/paracingulate gyri were found in maltreatment-exposed adults (decreased) and children/adolescents (increased). Our findings demonstrate different patterns of GM changes in youth closer to maltreatment events than those seen later in life, suggesting detrimental effects of CM on the developmental trajectory of brain structure.


Dose and temporal evaluation of ethylene oxide-induced mutagenicity in the lungs of male big blue mice following inhalation exposure to carcinogenic concentrations.
Ethylene oxide (EO) is a direct acting alkylating agent; in vitro and in vivo studies indicate that it is both a mutagen and a carcinogen. However, it remains unclear whether the mode of action (MOA) for cancer for EO is a mutagenic MOA, specifically via point mutation. To investigate the MOA for EO-induced mouse lung tumors, male Big Blue (BB) B6C3F1 mice (10/group) were exposed to EO by inhalation, 6 hr/day, 5 days/week for 4 (0, 10, 50, 100, or 200 ppm EO), 8, or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples were analyzed for cII mutant frequency (MF) at 4, 8 and 12 weeks of exposure; the mutation spectrum was analyzed for mutants from control and 200 ppm EO treatments. Although EO-induced cII MFs were 1.5- to 2.7-fold higher than the concurrent controls at 4 weeks, statistically significant increases in the cII MF were found only after 8 and 12 weeks of exposure and only at 200 ppm EO (P ≤ 0.05), which is twice the highest concentration used in the cancer bioassay. Consistent with the positive response, DNA sequencing of cII mutants showed a significant shift in the mutational spectra between control and 200 ppm EO following 8 and 12 week exposures (P ≤ 0.035), but not at 4 weeks. Thus, EO mutagenic activity in vivo was relatively weak and required higher than tumorigenic concentrations and longer than 4 weeks exposure durations. These data do not follow the classical patterns for a MOA mediated by point mutations. Environ. Mol. Mutagen. 58:122-134, 2017. © 2017 Wiley Periodicals, Inc.


A Literature Review of Taste Change and Zinc Deficiency After Bariatric Surgery: Could There Be a Causal Link?
In this review, we collated evidence relating to taste change and zinc deficiency in relation to bariatric surgery (BS) and effects of zinc replacement on taste perception and speculate on the possible role of zinc deficiency to induce taste change after BS. A literature search was conducted (33 studies, N = 3264). We showed that taste change and zinc deficiency are frequent complications after BS, which both typically occurred at 6 months post-surgery. Our analysis did not support a causal link between the two, but similar onset of incidences indirectly indicates a link. Supplementation with 45-50 mg of zinc sulphate, higher than current recommendation, was effective in improving taste. Further studies are required to establish the causal link between the two in the context of BS.


Polyphagy and adult body size in geometrid moths.
We compared the average body size (wing span) of Finnish geometrid moth species in relation to their degree of polyphagy and quality of food. The first hypothesis, originally constructed for mammals and birds, states that smaller species should more often be specialists than large species, because of the different relationships between body size and home range size, and body size and daily energy requirements. According to the second hypothesis, smaller species should feed more often on herbs than do larger species, because of the different defence mechanisms of herbs and woody plants. The results support both of these hypotheses. Specialist species are smaller than oligophagous or polyphagous species, and small species concentrate on herbs. We conclude that quality and quantity of food resources may explain the pattern.


Inadequate Antioxidative Responses in Kidneys of Brain-Dead Rats.
Brain death (BD)-related lipid peroxidation, measured as serum malondialdehyde (MDA) levels, correlates with delayed graft function in renal transplant recipients. How BD affects lipid peroxidation is not known. The extent of BD-induced organ damage is influenced by the speed at which intracranial pressure increases. To determine possible underlying causes of lipid peroxidation, we investigated the renal redox balance by assessing oxidative and antioxidative processes in kidneys of brain-dead rats after fast and slow BD induction. Brain death was induced in 64 ventilated male Fisher rats by inflating a 4.0F Fogarty catheter in the epidural space. Fast and slow inductions were achieved by an inflation speed of 0.45 and 0.015 mL/min, respectively, until BD confirmation. Healthy non-brain-dead rats served as reference values. Brain-dead rats were monitored for 0.5, 1, 2, or 4 hours, after which organs and blood were collected. Increased MDA levels became evident at 2 hours of slow BD induction at which increased superoxide levels, decreased glutathione peroxidase (GPx) activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased plasma creatinine levels were evident. At 4 hours after slow BD induction, superoxide, MDA, and plasma creatinine levels increased further, whereas GPx activity remained decreased. Increased MDA and plasma creatinine levels also became evident after 4 hours fast BD induction. Brain death leads to increased superoxide production, decreased GPx activity, decreased glutathione levels, increased inducible nitric oxide synthase and heme-oxygenase 1 expression, and increased MDA and plasma creatinine levels. These effects were more pronounced after slow BD induction. Modulation of these processes could lead to decreased incidence of delayed graft function.


The Selective NLRP3-inflammasome inhibitor MCC950 Mitigates Post-resuscitation Myocardial Dysfunction and Improves Survival in a Rat Model of Cardiac Arrest and Resuscitation.
To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.


Ubiquitin of Entamoeba histolytica deviates in six amino acid residues from the consensus of all other known ubiquitins.
The amino acid sequence of ubiquitin from Entamoeba histolytica, as deduced from a cDNA nucleotide sequence, deviated at six positions from the consensus of all other known ubiquitins (ranging from Trypanosoma cruzi to Homo sapiens). The corresponding residues were scattered over the primary sequence, but came close together on the surface of the folded protein structure. We conclude that (i) E. histolytica branched off very early from the main eukaryotic line, and (ii) this organism may yield clues as to the evolutionary development of the ubiquitin system.


Pulpotomy as an alternative to canine tooth extraction in monkeys [Macaca mulatta].
An effective method for sealing pulp canals after partial removal of canine tooth crowns from adult rhesus monkeys is described.


[Conditions affecting the application of the method of determining blood volume by the injection of labeled (iodine 131) serum albumin to small animals (chick embryo)].
The isotopic dilution method is really suitable for the determination of blood volume in small animals. The main purpose of this study is to find the limits of measuring errors made during the injection procedures (injected volumes about one microliter) and the sampling of blood (blood samples less than one milliliter). After evaluation of the extravascular rate of diffusion of the radioactive iodinated human serum-albumin, the blood volume of the 17 days incubated chick embryo is measured by this method for control purposes.


Bladder rupture in premature infant during voiding cystourethrography.
We report what we believe to be the youngest patient with bladder rupture during voiding cystourethrography. If voiding cystourethrography needs to be done in a premature infant, the filling pressures should be minimized, multiple filling cycles should be avoided, and the voiding pressures should be minimized by using a small, balloon-less catheter.


Appropriate use of anti-thrombotic therapy in patients with atrial fibrillation at single-center experience, Northwest Ethiopia.
Atrial fibrillation (AF) is the commonest clinically significant ECG-evidenced sustained cardiac arrhythmia in clinical practice. Disability and mortality attributed to AF is high in low-income regions like sub-Saharan Africa. The risk of stroke/TIA in patients with AF can be significantly reduced with anti-thrombotic therapy. Despite the existing evidence of its benefit, significant percentages of AF patients eligible for anti-thrombotic therapy are undertreated in the region. A hospital-based cross-sectional study was conducted to determine the appropriate use of anti-thrombotic therapy in patients with AF between December 1, 2018 and September 30, 2019 at Cardiac Clinic, University of Gondar hospital, Northwest Ethiopia. Consecutive sampling method was used to recruit 210 study subjects. Patients were interviewed to obtain socio-demographic data. Relevant medical history and laboratory parameters were obtained from patients' records. Diagnosis of atrial fibrillation was based on detection of irregular arterial pulse and presence of 'f' waves on 12-lead ECG tracing. Clinical evaluation, echocardiography, chest X-ray and blood chemistry were used to diagnose underlying causes of AF. Data was entered into EPI Info version 4.4.1 and analyzed using SPSS version 20. Bi-variate and multi-variate logistic regression analyses were used to identify associated factors with appropriate use of anti-thrombotic therapy in patients with atrial fibrillation. P-values < 0.05 were used to declare significant association. A total of 210 patients were included in the study. The mean age of patients was 51.29 ± 17.2 years. Two-thirds (145/210) of participants were females. Seventy-four (35%) had valvular AF, while 136/210 (65%) had non-valvular AF. Sixty-six percent (139/210) of study subjects were appropriately treated with anti-thrombotic therapy. Appropriately treated subjects in valvular AF group and non-valvular AF group were 58/74 (78%) and 81/136 (60%) respectively. On multi-variate analysis, 'can afford for regular INR monitoring' (AOR = 2.60 95% CI: 1.10-6.10, P = 0.001) was significantly associated with appropriate use of anti-thrombotic therapy. Sixty-six percent of AF patients eligible for anti-thrombotic therapy were appropriately treated. Intervention program to access 'regular INR monitoring' should be practiced to escalate utilization rate of anti-thrombotic therapy (warfarin) in eligible AF patients.


Developmental differences in antagonism of NMDA toxicity by the polyamine site antagonist ifenprodil.
Antagonists of 4 distinct regulatory sites on the N-methyl-D-aspartate (NMDA) receptor were tested for their ability to attenuate NMDA-mediated acute excitotoxicity in isolated chick retina of various embryonic ages between days 11 and 19 in ovo. Acute excitotoxicity was monitored by histology and by release of endogenous gamma-aminobutyric acid (GABA) into the medium during 30 min of incubation with 50 microM NMDA. The uncompetitive PCP channel site antagonist, MK-801, the competitive antagonist, CGS 19755, and the strychnine-insensitive glycine site antagonist, 7-chlorokynurenate, completely blocked NMDA-induced cell swelling and increased GABA release at all ages tested. Potencies versus NMDA were MK-801 greater than CGS 19755 greater than 7-chlorokynurenate with IC50S of 0.02, 0.62, and 15 microM, respectively. NMDA antagonism by the polyamine site antagonist, ifenprodil, differed from other classes of antagonists in several respects. At the earlier embryonic ages tested (E12-13) ifenprodil provided differential protection; completely blocking somal and neuritic swelling in most but not all inner nuclear layer neurons and inner plexiform processes. In dose-response studies, ifenprodil attenuated the NMDA-induced increase in medium GABA at all ages tested with an Imax of 10 microM. Ifenprodil, however, showed a decreased ability to completely protect some NMDA-sensitive neurons. This was reflected both histologically and by GABA release. Maximal attenuation of NMDA evoked GABA release was 83, 80, 62 and 50% at days E12, 13, 15 and 19, respectively. Histologically, differential protection was seen at E12 and 13, in limited areas at E15, and was no longer present at E19.(ABSTRACT TRUNCATED AT 250 WORDS)


Kinematics of the midcarpal and radiocarpal joints in radioulnar deviation: an in vitro study.
Carpal kinematics have been studied widely yet remain difficult to understand fully. The noninvasive measurement of carpal kinematics through medical imaging has become popular. Studies have shown that with radial deviation the scaphoid and lunate flex whereas the capitate moves radiodorsally relative to the lunate. This study investigated the midcarpal and radiocarpal contributions to radial and ulnar deviation of the wrist. This was accomplished through noninvasive characterization of the scaphoid, lunate, and capitate using 3-dimensional medical imaging of the wrist in radial and ulnar deviation. Eight fresh-frozen and thawed cadaveric wrists were used in an experimental set-up that positioned the wrist through spring-scale actuation of the 4 wrist flexor and extensor tendon groups. The wrists were scanned by computed tomography in neutral and full radial and ulnar deviation. Body mass-based local coordinate systems were used to track the motion of the capitate, lunate, and scaphoid with the radius as a fixed reference. Helical axis motion and Euler angles were calculated from neutral to radial and ulnar deviation for the capitate relative to the radius, lunate, and scaphoid and for the lunate and scaphoid relative to the radius. The capitate, scaphoid, and lunate moved in a characteristic manner relative to the radius and to one another. Radial and ulnar deviation occurred primarily in the midcarpal joint. Midcarpal motion accounted for 60% of radial deviation and 86% of ulnar deviation. In radial deviation the proximal row flexed and the capitate extended; the converse was true in ulnar deviation. Radioulnar deviation (in-plane motion) occurred mostly through the midcarpal joint, with a lesser contribution from the radiocarpal joint. The results of our study agree with previous investigations that found the scaphoid and lunate flex in radial deviation (out-of-plane motion) relative to the radius whereas the capitate extends (out-of-plane motion) relative to the scaphoid/lunate (with the converse occurring in ulnar deviation). Our study shows how these out-of-plane motions combine to produce in-plane wrist radioulnar deviation. The use of 3-dimensional visualization greatly aids in the understanding of these motions. The results of our study may be useful clinically in understanding the consequences of isolated midcarpal fusions in the treatment of wrist instability.


Sleep, major depressive disorder, and Alzheimer disease: A Mendelian randomization study.
To explore the causal relationships between sleep, major depressive disorder (MDD), and Alzheimer disease (AD). We conducted bidirectional 2-sample Mendelian randomization analyses. Genetic associations were obtained from the largest genome-wide association studies currently available in UK Biobank (n = 446,118), Psychiatric Genomics Consortium (n = 18,759), and International Genomics of Alzheimer's Project (n = 63,926). We used the inverse variance-weighted Mendelian randomization method to estimate causal effects and weighted median and Mendelian randomization-Egger for sensitivity analyses to test for pleiotropic effects. We found that higher risk of AD was significantly associated with being a "morning person" (odds ratio [OR] 1.01, p = 0.001), shorter sleep duration (self-reported: β = -0.006, p = 1.9 × 10-4; accelerometer based: β = -0.015, p = 6.9 × 10-5), less likely to report long sleep (β = -0.003, p = 7.3 × 10-7), earlier timing of the least active 5 hours (β = -0.024, p = 1.7 × 10-13), and a smaller number of sleep episodes (β = -0.025, p = 5.7 × 10-14) after adjustment for multiple comparisons. We also found that higher risk of AD was associated with lower risk of insomnia (OR 0.99, p = 7 × 10-13). However, we did not find evidence that these abnormal sleep patterns were causally related to AD or for a significant causal relationship between MDD and risk of AD. We found that AD may causally influence sleep patterns. However, we did not find evidence supporting a causal role of disturbed sleep patterns for AD or evidence for a causal relationship between MDD and AD.


Associations between preprocedural carotid artery perivascular fat density and early in-stent restenosis after carotid artery stenting.
This study investigated the association between perivascular fat density (PFD) via preoperative computed tomographic angiography (CTA) and early in-stent restenosis (ISR) after carotid artery stenting (CAS). We retrospectively evaluated 248 consecutive patients who had undergone initial CAS and received a preoperative cervical CTA examination between January 2019 and October 2020. The patients were categorized into two according to whether they sustained ISR during the 2 years postoperative follow-up period. Correlations between PFD and ISR were assessed, and multivariate regression for evaluating predictors of ISR was conducted. Receiver operating characteristic (ROC) curves were used to determine the cutoff value for the PFD. A total of 181 eligible patients (mean age 61.25 ± 10.35 years, 57 male) were enrolled. The ISR group had a higher proportion of closed-cell stents (48.8% versus 27.5%; p = 0.009) and a greater degree of residual stenosis (28[20,33] % versus 20[14.75,30] %; p < 0.001) than the non-ISR group. The ISR group had a higher mean HU value of PFD than the non-ISR group on the operated side (-42.26 ± 6.81 versus -59.66 ± 10.75; p < 0.001). The degree of residual stenosis (OR 1.146, 95%CI 1.071-1.226, p < 0.001) and PFD on the operated side (OR1.353, 95%CI 1.215-1.506, p < 0.001) were significantly associated with the ISR. The occurrence of the early ISR after CAS is associated with a higher PFD on the operated side. The results indicate that PFD is a promising marker to predict the ISR after CAS.


Tat acetyl-acceptor lysines are important for human immunodeficiency virus type-1 replication.
The human immunodeficiency virus type-1 trans-activator Tat is a transcription factor that activates the HIV-1 promoter through binding to the trans-activation-responsive region (TAR) localized at the 5'-end of all viral transcripts. We and others have recently shown that Tat is directly acetylated at lysine 28, within the activation domain, and lysine 50, in the TAR RNA binding domain, by Tat-associated histone acetyltransferases p300, p300/CBP-associating factor, and hGCN5. Here, we show that mutation of acetyl-acceptor lysines to arginine or glutamine affects virus replication. Interestingly, mutation of lysine 28 and lysine 50 differentially affected Tat trans-activation of integrated versus nonintegrated long terminal repeat. Our results highlight the importance of lysine 28 and lysine 50 of Tat in virus replication and Tat-mediated trans-activation.


Timing optimizes sustained-release indomethacin treatment of osteoarthritis.
Chronopharmacologic studies of indomethacin have indicated that time of dosing influences tolerance and effectiveness. A double-blind, crossover chronotherapeutic trial was undertaken in 66 subjects with osteoarthritis of the hip or knee who were treated with an indomethacin sustained-release (ISR) oral preparation once a day. Varying the ISR dosing time resulted in a quadrupling of tolerance and a doubling of analgesic effectiveness. Three dosing times (8 a.m., noon, and 8 p.m.), each tested during 1-wk spans and randomized for sequencing, were compared in each subject. Subjects self-rated pain intensity every other hour before (1 to 2 days) and during each week of treatment. Morning dosing was associated with a 32% incidence of undesirable effects, whereas the comparable rate was 7% for evening dosing. Ninety-five percent of the subjects reported increased drug effectiveness with a change in ISR ingestion time. The time of dosing that resulted in optimal effectiveness differed among subjects. This was explainable by large interindividual differences in the circadian variation of self-rated pain intensity. Evening dosing was most effective in subjects with predominantly nocturnal or morning pain; conversely, morning or noon dosing was most effective in subjects with greater afternoon or evening pain. The differences that resulted from varying the timing of the identical ISR dose in the same subject greatly exceeded those reported for other nonsteroidal anti-inflammatory drugs.


A series of heterocyclic inhibitors of phenylalanyl-tRNA synthetases with antibacterial activity.
A series of novel heterocyclic analogues have been synthesized and evaluated for their ability to inhibit phenylalanyl-t-RNA synthetases and act as antibacterial agents. Several analogues have good antibacterial activity against Staphylococcus aureus.


Lactobacillus plantarum promotes Drosophila systemic growth by modulating hormonal signals through TOR-dependent nutrient sensing.
There is growing evidence that intestinal bacteria are important beneficial partners of their metazoan hosts. Recent observations suggest a strong link between commensal bacteria, host energy metabolism, and metabolic diseases such as diabetes and obesity. As a consequence, the gut microbiota is now considered a "host" factor that influences energy uptake. However, the impact of intestinal bacteria on other systemic physiological parameters still remains unclear. Here, we demonstrate that Drosophila microbiota promotes larval growth upon nutrient scarcity. We reveal that Lactobacillus plantarum, a commensal bacterium of the Drosophila intestine, is sufficient on its own to recapitulate the natural microbiota growth-promoting effect. L. plantarum exerts its benefit by acting genetically upstream of the TOR-dependent host nutrient sensing system controlling hormonal growth signaling. Our results indicate that the intestinal microbiota should also be envisaged as a factor that influences the systemic growth of its host.


Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression : Astragalus polysaccharide regulates SONFH via SP1.
Steroid-induced osteonecrosis of the femoral head (SONFH) is the necrosis of the femur bone caused by prolonged and massive use of corticosteroids. The present study probed into the significance of Astragalus polysaccharide (APS) in SONFH progression. SONFH cell model was constructed using murine long bone osteocyte Y4 (MLO-Y4) cells and then treated with APS. mRNA microarray analysis selected differentially expressed genes between control group and SONFH group. RT-qPCR determined SP1 and miR-200b-3p expression. Levels of SP1, β-catenin, autophagy-related proteins (LC3II/LC3I, Beclin1, p62) and apoptosis-related proteins (Bax, C-caspase3, C-caspase9, Bcl-2) were tested by Western blot. ChIP and luciferase reporter assays confirmed relationship between SP1 and miR-200b-3p. Fluorescence intensity of LC3 in cells was detected by immunofluorescence. Flow cytometry assessed cell apoptosis. Osteonecrosis tissues from SONFH mice were examined by HE and TRAP staining. APS induced autophagy and suppressed apoptosis in SONFH cell model. APS inhibited SP1 expression and SP1 overexpression reversed effects of APS on SONFH cell model. Mechanistically, SP1 targeted miR-200b-3p to inhibit Wnt/β-catenin pathway. MiR-200b-3p depletion rescued the promoting effect of SP1 on SONFH cell model by activating Wnt/β-catenin pathway. HE staining showed that APS treatment reduced the empty lacunae and alleviated inflammation in trabecular bone of SONFH mice. TRAP staining revealed decreased osteoclasts number in SONFH mice after APS treatment. APS regulated osteocyte autophagy and apoptosis via SP1/miR-200b-3p axis and activated Wnt/β-catenin signaling, thereby alleviating SONFH, shedding new insights for therapy of SONFH.


Clinical isolates of dengue virus with distinctive susceptibility to nitric oxide radical induce differential gene responses in THP-1 cells.
In the present study, 10 clinical isolates of dengue virus were selected according to their susceptibility to the inhibitory effect of nitric oxide radical, NO. Five of them are nitric oxide-susceptible viruses while the other five are nitric oxide-resistant viruses. These isolates were investigated to identify genetic factors that are responsible for the different phenotypes. Due to the evidence showing that NO suppresses DENV RNA polymerase activity, we, therefore, hypothesized that the RdRp domain of NS5 may responsible for NO inhibition. To answer this question, sequences of NS5 gene of NO-susceptible viruses and NO-resistant viruses were compared. We found that these two groups of viruses contain different amino acid sequence at position 621 to 646 in the active site of NS5. These data suggested that response to the inhibitory effect of nitric oxide radical may, at least in part, be regulated by NS5. The effect of these two different phenotypes of viruses on host cells was studied using cDNA array screening. The cDNA array analysis demonstrated that the nitric oxide-resistant group had a stronger influence on host cells since it induced changes in the expression of a greater number of genes than did the nitric oxide-susceptible group, 97 genes versus 71 genes, respectively. The NO-resistant virus also stimulated cytokines known to be virulent factors, such as IL 6, IL 8, RANTES, and the inflammatory factors. In conclusion, our data demonstrated that dengue viruses isolated from patients show genotypic and phenotypic differences which may correlate with virulence.


Towards a generalized model of encystment (cryptobiosis) in ciliates: a review and a hypothesis.
In this work we propose a generalized model to explain encystment (cryptobiosis) in ciliates. The model is elaborated from both structural and physiological studies previously reported, and some hypothetical considerations. The main features of this model are the following: (a) starvation is considered as the most important inducer of ciliate encystment, and it constitutes the first trigger of this cell differentiation process; (b) the "switch on" of encystment genes involves the appearance of several new transcripts; (c) starvation involves cell autophagy and protein turnover, which provides material to synthesize the new cystic proteins; (d) cytoplasmic dehydration has an important role during the resting cyst formation; (e) a gradual loss of intracellular water can inactivate cell metabolism, leading to an ametabolic state (cryptobiosis); (f) as a late precystic event, the encysting cell forms a barrier (cyst wall), that isolates the cell from the hostile environment.


Reform of how health care is paid for in China: challenges and opportunities.
China's current strategy to improve how health services are paid for is headed in the right direction, but much more remains to be done. The problems to be resolved, reflecting the setbacks of recent decades, are substantial: high levels of out-of-pocket payments and cost escalation, stalled progress in providing adequate health insurance for all, widespread inefficiencies in health facilities, uneven quality, extensive inequality, and perverse incentives for hospitals and doctors. China's leadership is taking bold steps to accelerate improvement, including increasing government spending on health and committing to reaching 100% insurance coverage by 2010. China's efforts are part of a worldwide transformation in the financing of health care that will dominate global health in the 21st century. The prospects that China will complete this transformation successfully in the next two decades are good, although success is not guaranteed. The real test, as other countries have experienced, will come when tougher reforms have to be introduced.


Prevalence estimation of celiac disease in the general adult population of Latvia using serology and HLA genotyping.
Prevalence estimates for celiac disease (CD) depend on the method used. The role of deamidated gliadin peptide (DGP) and genetic testing in epidemiological studies and diagnostic settings of celiac disease (CD) has still to be established. The objective of this article is to assess the prevalence of CD in Latvia by combining serological tests with DQ2.5/DQ8 testing. A total of 1444 adults from a randomly selected cross-sectional general population sample were tested by ELISA for tTG IgA, DGP IgA and IgG antibodies (QUANTA Lite®, Inova Diagnostics Inc). Samples with tTG IgA ≥20U were tested for EMA IgA by indirect immunofluorescence assay, and all specimens with tTG IgA ≥15U were tested by QUANTA-Flash® chemiluminescent assays (CIA) (Inova Diagnostics Inc) for tTG IgA, DGP IgA and IgG. DQ2.5/8 was detected in individuals with any positive ELISA test and a subgroup of controls. Forty-three individuals (2.98%; 95% CI: 2.10-3.86%) tested positive by at least one ELISA test; 41.86% of the serology-positive individuals (any test above the cutoff) were DQ positive. Six individuals (0.42%; 95% CI: 0.09-0.75%) were triple ELISA positive, and DQ2.5 or DQ8 was positive in all; 0.35% (95% CI: 0.05-0.65%) were tTG IgA and EMA positive. Two tTG IgA-negative cases were both DGP IgG and IgA positive, both being DQ positive; including them in the "serology-positive" group would increase the prevalence to 0.49% (95% CI: 0.13-0.85%). CIA tests revealed 2 tTG IgA-positive and EMA-negative cases with a positive genotype. DQ2.5 or DQ8 genotype was positive in 28.6% of the serology-negative population. Estimates of the prevalence of CD in Latvia based on the serogenetic testing approach range from 0.35% to 0.49% depending on the criteria used. There is a rationale for combining serological tests and DQ2.5/8 genotyping.


Properties of Langmuir and solid supported lipid films with sphingomyelin.
Biological cell membranes play a crucial role in various biological processes and their functionality to some extent is determined by the hydrophilic/hydrophobic balance. A significant progress in understanding the membrane structure was the discovery of laterally segregated lipid domains, called the lipid rafts. These raft domains are of ordered lamellar liquid-crystalline phase, while rest of the membrane exists in a relatively disordered lamellar liquid-crystalline phase. Moreover, the chemical constitution of the lipid rafts consists of a higher content (up to 50%) of cholesterol (Chol) and sphingomyelin (SM). Sphingomyelin also plays a significant role in the red cells of blood and nerves, in some diseases, as a precursor to ceramides, and other sphingolipid metabolites. In this paper properties of Langmuir and solid supported mixed lipid films of DPPC/SM, DOPC/SM, and Chol/SM are described. Special attention has been paid to wetting properties (hydrophobic/hydrophilic balance) of these films transferred onto a hydrophilic glass surface. To our knowledge such results have not yet been published in the literature. The properties were determined via contact angle measurements and then calculation of the films' apparent surface free energy. The films' wettability and their apparent surface free energy strongly depend on their composition. The energy is affected by both the structure of hydrocarbon chains of glycerophospholipids (DPPC and DOPC) and their interactions with SM. Properties of mixed Chol/SM monolayer depend also on the film stoichiometry. At a low Chol content (XChol=0.25) the interactions between SM and Chol are strong and hence the formation of binary complex is possible. This is accompanied by a decrease in the film surface free energy in comparison to that of pure SM monolayer, contrary to a higher Chol content where the monolayer energy increases. This suggests that cholesterol is excluded from the membrane thus increasing the film hydrophilicity. These results are consistent with the literature data and somehow confirm the hypothesis of lipid raft formation. The roughness of the investigated monolayer surfaces was also determined using optical profilometry. The roughness parameters of the DPPC, SM, and mixed DPPC/SM generally correlate with the changes of their apparent surface free energy, i.e. with the decreasing roughness the apparent surface free energy also decreases. However, this is not the case for mixed DOPC/SM monolayers. Although the roughness increases with SM content the apparent surface free energy decreases. Therefore some other factors, like the presence of unsaturated bonds in the DOPC molecule, influence the film phase state and the energy too. More experiments are needed to explain this hypothesis.


Turnover analysis of glutamate receptors identifies a rapidly degraded pool of the N-methyl-D-aspartate receptor subunit, NR1, in cultured cerebellar granule cells.
The number, composition, and location of receptors in neurons are critically important factors in determining the neuron's response to neurotransmitters. The functional expression of receptors appears to be regulated both generally, at the level of transcription or translation, and locally, at the level of the individual synapse. A key component in the regulation of any protein is its turnover rate, which, measured in half-lives, ranges from a few minutes to several days. In the present study, we measured the turnover rates of subunits of N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, the two major ionotropic glutamate receptors, using cultured cerebellar granule cells. Turnover rates for NR1, NR2A/B, GluR2/3, and GluR4 subunits were determined by pulse-chase labeling of cells with [35S]methionine. Half-lives were found to be 18 +/- 5 h and 23 +/- 8 h for the AMPA receptor subunits GluR2/3 and GluR4, respectively, and 16 +/- 5 h for NR2A. The NR1 subunit showed a biphasic decay with half-lives of 2 and 34 h for the rapidly and slowly degraded populations, respectively. Splice variants of the NR1 subunit with different carboxyl-terminal cassettes, C2 and C2', showed similar biphasic degradation patterns. To further characterize the rapidly degraded pool of NR1, surface receptors were labeled by biotinylation, and half-lives of the biotinylated proteins were determined. All surface NR1 was slowly degraded with a pattern similar to that of NR2A, GluR2/3, and GluR4, suggesting that the rapidly degraded pool is confined to the cytoplasm and not assembled with NR2 subunits. A significant amount of NR1 was not immunoprecipitated by NR2 subunit-specific antibodies after solubilization with deoxycholate. This unassembled pool, but not the assembled one, was greatly diminished following treatment of cycloheximide for 5 h, indicating that the rapidly degraded pool of NR1 is not assembled with NR2. These results show that NMDA and AMPA receptors have similar turnover rates, but NMDA receptors have a separate pool of NR1 subunits that is rapidly degraded and accounts for most of the intracellular pool.


Mapping of dust source susceptibility by remote sensing and machine learning techniques (case study: Iran-Iraq border).
A dust storm is a major environmental problem affecting many arid regions worldwide. The novel contribution of this study is combining indicators extracted from RS- and statistic-based predictive models to spatial mapping of land susceptibility to dust emissions in a very important dust source area in the borders of Iran and Iraq (Khuzestan province in Iran and Al-Basrah and Maysan provinces in Iraq). In this research, remote sensing (RS) techniques and machine learning techniques, including multivariate adaptive regression spline (MARS), random forest (RF), and logistic regression (LR), were used for dust source identification and susceptibility map preparation. To this end, 152 DSA for the period of 2005-2020 were identified in the study area. Of these DSA data, 70% was assigned to the Dust Source Susceptibility Mapping (DSSM) (training dataset) and 30% to model validation. Consequently, six factors (i.e., soil, lithology, slope, normalized vegetation differential index (NDVI), geomorphology, and land use units) were prepared as DSA's independent and effective variables. The results of all three models indicated that land use had the most impact on DSA. The validation results of these models using the test data showed sub-curves of 0.92, 0.86, and 0.76 for the RF, MARS, and LR models, respectively. Also, results showed that the RF model outperformed MARS (AUC = 0.89) and LR (AUC = 0.78) methods. In all three models, high and very high susceptibility classes generally covered a large percentage of the case study. The highest percentage of dust source points was also in this susceptibility category. Overall, the results of this study can be useful for planners and managers to control and reduce the risk of negative dust consequences.


Conserved N-terminal sequences in the flagellins of archaebacteria.
Methanococcus voltae produces two flagellins of molecular weight 31,000 and 33,000. Amino acid analysis as well as peptide mapping with cyanogen bromide, chymotrypsin and Staphylococcus aureus V-8 protease indicates that the two flagellins are distinct. N-terminal sequencing of the 31,000 Mc. voltae flagellin as well as the 24,000 and 25,000 molecular weight flagellins of Methanospirillum hungatei GP1 shows an extensive homology with the reported N-terminus of the flagellins from Halobacterium halobium, deduced from the nucleotide sequence of the cloned genes. However, the N-termini of all three sequenced methanogen flagellins lack a terminal methionine and start at position 13 from the N-terminus of H. halobium flagellins. This initial 12 amino acid stretch may be a leader peptide which is subsequently cleaved to generate the mature flagellin, which could suggest flagellar assembly in archaebacteria occurs by a mechanism distinct from that in eubacteria. The high degree of conservation of the N-terminus of the flagellins from Mc. voltae, Msp. hungatei and H. halobium suggests an important role for this sequence, and that the archaebacteria share a common mechanism for flagellar biosynthesis.


Impact of sarcopenia on post-liver transplant morbidity and mortality in cirrhotic patients.
Modalities available for severity assessment and prediction of complications after liver transplant (LT) in cirrhotic patients are model for end-stage liver disease-sodium (MELD-Na) and Child-Turcotte-Pugh (CTP) scores. The limitation of these scores is the lack of assessment of nutritional and functional status. Sarcopenia is a newer modality, which is developed for objective assessment of nutritional status. The aim of this study is to analyze the significance of sarcopenia in predicting 1-year mortality and morbidity in post-LT patients. In this retrospective study, patients who underwent LT for cirrhosis between January 2013 and December 2018 were included. A computerized tomography (CT) image was used to analyze the psoas muscle index at the L3 vertebra (L3-PMI), and sarcopenia was defined as the values belonging to the lowest quartile of L3-PMI. The effect of sarcopenia on mortality and morbidity in terms of requirement for mechanical ventilation, duration of hospital stay, and occurrence of infections was studied. Among the study population (n = 74), 71 were men and the mean age was 51 years. Sarcopenia was observed in 27% (n = 20). Fifteen recipients had mortality within 1 year after transplant. In our analysis, sarcopenia was significantly associated with 1-year mortality (sensitivity 60%, specificity 81%; positive predictive value [PPV] 45%; negative predictive value [NPV] 88%; and p-value 0.001). Duration of mechanical ventilation, total hospital stay, and occurrence of infection were not significantly associated with sarcopenia. Sarcopenia was found as an independent predictor of mortality on binary logistic regression. The preoperative sarcopenia index in cirrhotic patients can predict the risk of mortality in post-liver transplant patients.


[Synthesis of several benzyloxphenyl derivatives with local anesthetic activity (author's transl)].
Several 2- and 4-benzyloxy- and 4-(2'- and 4'-substituted) benzyloxy-beta-substituted amino-propiophenones, some of the corresponding alcohols, some 4-benzyloxy-alpha-substituted amino-acetophenones were synthetised and tested for their pharmacological activity.


Dietary Intake of Minerals, Vitamins, and Trace Elements Among Geriatric Population in India.
The geriatric population is at a high risk of developing deficiencies of essential micronutrients such as minerals, vitamins, and trace elements and their related deficiency signs and symptoms. Scarce data is available on the dietary intake of essential micronutrients among geriatric subjects in India. Hence, to fill the gap in the existing knowledge, a community-based cross-sectional study was conducted during 2015-2016 in District Nainital, Uttarakhand State, India. A total of 255 geriatric subjects were enrolled from 30 clusters (villages) identified by using population proportionate to size sampling methodology. Data were collected on sociodemographic profile and dietary intake of essential micronutrients (24-h dietary recall, food frequency questionnaire) from all the geriatric subjects. A high percentage of geriatric subjects did not consume the recommended daily intake for essential micronutrients such as energy (78%), protein (78%), calcium (51%), thiamine (33%), riboflavin (64%), niacin (88%), vitamin C (42%), iron (72%), folic acid (72%), magnesium (48%), zinc (98%), copper (81%) and chromium (89%) adequately. Food groups rich in essential micronutrients such as pulses, green leafy vegetables, roots and tubers, other vegetables, fruits, nonvegetarian food items, and milk and milk products were consumed irregularly by the subjects. The overall intake of energy and essential micronutrients was inadequate among the geriatric population in India, possibly due to poor quality and quantity of the diet consumed.


[Histological diagnosis of inflammatory skin diseases. Use of a simple algorithm and modern diagnostic methods].
The histological diagnosis of inflammatory skin diseases on a day-to-day routine basis poses the difficult task to characterise a dynamic clinical process by histomorphological analysis of one single lesion. Very complex algorithms which are meant to lead to the correct diagnosis are difficult to use. To facilitate the process and reduce the number of algorithms the following method is proposed: 1. Histological examination under low power Definition of lesions altered by scratching 2. Localisation of the significant pathological alterations as follows: Changes in epidermis and dermis Blister formation Changes in dermis/subcutis without characteristic changes in the epidermis Changes mainly in the subcutis 3. Closer examination using a simple algorithm and planning of further investigations following defined criteria: In the case of changes in epidermis and dermis definition of spongiotic, psoriasiform or lichenoid dermatitis (Abb. 1). In the case of blister formation definition of the blister following the given algorithm (Abb. 1). In the case of changes in dermis/subcutis without characteristic changes in the epidermis after exclusion of vasculitis and lymphoma definition of the main pattern as lymphocytic, neutrophilic, eosinophilic, lymphoplasmocytic or granulomatous and following the given algorithm (Abb. 2). In the case of changes mainly in the subcutis after exclusion of vasculitis and lymphoma definition of the main pattern of panniculitis as septal or/and lobular (Abb. 2). Exclusion of PAS positive microorganisms and checking if the general pattern fits into infectious correlation. Use of clinicopathological correlation.


[Comparative activity of cefepime, ceftazidime and imipenem in a mouse infection caused by Klebsiella pneumoniae producing a broad spectrum beta-lactamase].
Mice experimentally infected with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains were injected twice daily for three days with ceftazidime, cefepime, or imipenem (25, 50, or 100 mg/kg/injection). Treatment efficacy was based on five-day survival and on the spleen viable bacteria count 16 hours after the last treatment dose. Under these experimental conditions, ceftazidime showed some activity on strains with low levels of resistance to ceftazidime. Cefepime used in a dose of 50 or 100 mg per injection demonstrated good activity but was slightly less effective than imipenem.


Prevalence of colonisation with group B Streptococci in pregnant women of a multi-ethnic population in The Netherlands.
This study was performed to determine the prevalence of GBS and to identify GBS colonisation risk factors in a multicultural population of pregnant women in The Netherlands. We calculated predictive values of cultures in pregnancy for intrapartum GBS carriage. From a total of 1702 women visiting several antenatal outpatient departments, rectovaginal swabs were collected at 35-37 weeks' gestation. In 761 women swabs were repeated at time of delivery. Carriage of GBS late in third trimester and at time of delivery was analysed in relation to age, parity, ethnicity and socio-economic status. Twenty-one percent was GBS carrier late in pregnancy. Compared to Europeans, African women were at a higher risk (29%, RR 1.4, CI 1.1-1.7) and Asian women were at lower risk (13%, RR 0.6, CI 0.4-0.8) for GBS carriage. No differences in colonisation were found between women with respect to age, parity or socio-economic background. Positive predictive value of GBS carriage at 35-37 weeks' gestation for carriage at time of parturition was 79% and negative predictive value was 93%. It was not possible to identify a group of pregnant women at high risk for GBS colonisation. Predictive values of antenatal genital group B streptococci cultures at 35-37 weeks' gestation for intrapartum GBS carriage are lower than previously reported.


Revisiting Javal's rule: a fresh and improved power vector approach according to age.
The scientific community has established Javal's rule as a model linking refractive (RA) and keratometric (KA) astigmatism since its appearance more than 100 years ago. The aim was to improve the accuracy of this relationship according to subject's age by applying the power vector analysis. Posterior corneal curvature has also been studied. The IOLMaster 700 optical biometer was used to measure the corneal thickness and the radius of curvature of the anterior and posterior corneal surfaces. Refractive error was determined by a non-cycloplegic subjective refraction process with trial lenses. Linear regression analyses were applied using J0 and J45 power vector components. An evaluation was carried out according to the subject's age resulting into eight regression relationships for each astigmatic vector component for each relationship. A total of 2254 right eyes from 2254 healthy subjects were evaluated. A trend towards against-the-rule astigmatism (ATR) was found with aging, both for refractive astigmatism (RA) and keratometric astigmatism (KA), with 95.2% of subjects under 20 years old having with-the-rule (WTR) KA, and only 22.8% above 79 years old. The following regression equations were found between RA and KA: [Formula: see text] = 0.73 × [Formula: see text] - 0.18 (R = 0.78) and [Formula: see text] = 0.70 × [Formula: see text] + 0.04 (R = 0.69) and between RA and total corneal astigmatism (TCA): [Formula: see text] = 0.73 × [Formula: see text] + 0.13 (R=0.78) and [Formula: see text] = 0.70 × [Formula: see text] - 0.06 (R = 0.68) for the whole sample, but with sensible differences among age groups, both in the slope and in the intercept. Ignoring the age of the subject when using Javal's rule could lead to an error in the final cylinder calculation that would increase in high astigmatisms. Applying this new power vector approach based on subject's age could improve the accuracy of the astigmatism prediction.


Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies.
von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this study, intracellular co-expression of FVIII and VWF was studied, with particular reference to complex assembly and high-affinity interaction. Using yellow fluorescent protein-tagged FVIII (FVIII-YFP) and cyan fluorescent protein-tagged VWF (VWF-CFP), we studied intracellular trafficking in human embryonic kidney (HEK293) cells and human umbilical vein endothelial cells (HUVEC). The role of the high-affinity interaction between FVIII and VWF was assessed using a FVIII-YFP variant carrying a Tyr1680Phe substitution, which abolishes high-affinity binding to VWF. Cellular trafficking studies were complemented by binding studies employing purified proteins. Solid phase binding assays employing FVIII-YFP demonstrated that the presence of the fluorescent moiety did not compromise high-affinity binding (K(d) = 0.065 +/- 0.008 nm) whereas the binding of the Tyr1680Phe FVIII-YFP variant was significantly reduced. Co-expression studies in HEK293 cells revealed intracellular co-storage of both FVIII-YFP and Tyr1680Phe FVIII-YFP within VWF-containing storage organelles. In addition, expression of FVIII-YFP and Tyr1680Phe FVIII-YFP in HUVEC demonstrated co-trafficking with endogenous VWF to authentic Weibel-Palade bodies (WPBs). Our findings demonstrate that FVIII trafficking to WPBs is independent of Tyr1680 and high-affinity binding to VWF. We therefore conclude that the structural requirements that determine intracellular co-trafficking differ from those that determine complex assembly in circulation.