Double immunofluorescence staining of whole-mount small intestinal mucosa samples as a tool for characterization of three-dimensional paratuberculosis granulomas.
Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (Map). The progression of PTB from subclinical to the clinical stage of the disease is determined locally at the level of the granuloma, a host defence hallmark against mycobacterial infection. Therefore, in-depth characterization of distinct cell populations controlling granuloma formation is critical to understanding PTB progression. Confocal laser scanning microscopy (CLSM) has been extensively used to visualize two or more proteins of interest concomitantly within a variety of cellular structures. As such, it is an invaluable tool for the correct identification and characterization of different cell populations. In this study, a novel approach, CLSM of whole-mount small intestinal mucosa samples, is used to characterize three-dimensional (3-D) paratuberculosis granulomas and epithelioid macrophages. Detailed optimized procedures to perform CLSM in whole mount small intestinal mucosa samples and also in formalin fixed paraffin embedded (FFPE) intestinal tissue sections of Holstein Friesian cows presenting different types of PTB-associated histological lesions are described.


Metacarpal bone diameter increases constantly in adult females, but escalated resorption of the inner surface at menopause explains the observed decreased bone mineral density at digital X-ray radiogrammetry.
To assess how bone morphology and mineralization changes with age, in women by digital X-ray radiogrammetry (DXR). DXR has potential as a screening tool for osteoporosis, as it can evaluate bone mineralization similarly to dual-energy X-ray absorptiometry. The nondominant hand was analyzed with DXR in 13,285 women ages 40-74 years undergoing mammography. 1,556 women attended two consecutive examinations with 18 to 24 months interval. Changes in bone parameters were calculated and compared in 5-year age groups. Regression analysis and ANOVA tests were performed. Univariate linear regression showed no significant difference in age or bone size between the groups with single or consecutive measurements. In the group with consecutive measurements, the average inner diameter (DXR-ID) of the metacarpals significantly increased with age from 0.38 cm in the 40-45 years age span to 0.47 cm in the 65+ age group (P < 0.001), whereas DXR bone mineral density (DXR-BMD) decreased from 0.59 g/cm2 to 0.50 g/cm2 in the same age groups (P < 0.001). Intraindividual measurements showed a fourfold increase in yearly DXR-ID increase and concurrent DXR-BMD loss between 50 and 59 years of age (P < 0.001). The outer diameter only increased significantly between the youngest and oldest age group (P < 0.001). The faster decrease in DXR-BMD observed during and after menopause is caused by resorption of the inner cortical surface, not matched by outer diameter increase. We speculate that most bones in the human body grow in the same pattern as observed in the metacarpals, partly explaining decreasing BMD at DXR and dual-energy X-ray absorptiometry.


Precision measurements of the RSA method using a phantom model of hip prosthesis.
Radiostereometric analysis (RSA) has become one of the recommended techniques for pre-market evaluation of new joint implant designs. In this study we evaluated the effect of repositioning of X-ray tubes and phantom model on the precision of the RSA method. In precision measurements, we utilized mean error of rigid body fitting (ME) values as an internal control for examinations. ME value characterizes relative motion among the markers within each rigid body and is conventionally used to detect loosening of a bone marker. Three experiments, each consisting of 10 double examinations, were performed. In the first experiment, the X-ray tubes and the phantom model were not repositioned between one double examination. In experiments two and three, the X-ray tubes were repositioned between one double examination. In addition, the position of the phantom model was changed in experiment three. Results showed that significant differences could be found in 2 of 12 comparisons when evaluating the translation and rotation of the prosthetic components. Repositioning procedures increased ME values mimicking deformation of rigid body segments. Thus, ME value seemed to be a more sensitive parameter than migration values in this study design. These results confirmed the importance of standardized radiographic technique and accurate patient positioning for RSA measurements. Standardization and calibration procedures should be performed with phantom models in order to avoid unnecessary radiation dose of the patients. The present model gives the means to establish and to follow the intra-laboratory precision of the RSA method. The model is easily applicable in any research unit and allows the comparison of the precision values in different laboratories of multi-center trials.


Influence of pre-analytical conditions on the interpretation of zopiclone concentrations in whole blood.
Zopiclone is a short-acting hypnotic drug used for treatment of insomnia and its stability has been described in some detail. However, data especially on short-term pre-analytical stability is missing. This study investigated zopiclone stability differences between spiked and authentic whole blood from subjects dosed with zopiclone. In this way influence from physiological factors such as drug interactions, matrix composition and plasma protein levels were minimized. Nine volunteers participated in the study. Whole blood was obtained before and after oral administration of 10mg Imovane(®). Aliquots of 1g of authentic and spiked blood were after initial measuring, stored at 20°C during 5 days, 5 or -20°C during 3 months, and zopiclone was measured by gas chromatography with nitrogen phosphorus detection. The results showed no stability differences between authentic and spiked blood but confirmed the very short stability in whole blood at ambient temperature. In summary, the stability was less than 1 day at 20°C, less than 2 weeks at 5°C but stable for 3 months at -20°C. This study demonstrates the importance of controlling pre-analytical conditions from sampling to analysis to avoid misinterpretation of toxicological results.


Preclinical evaluation of sentinel node localization in the stomach via mannose-labelled magnetic nanoparticles and indocyanine green.
Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. Mannose-labelled magnetic tracer 'FerroTrace' and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6). Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.


Pharmacologic Management of Pain, Agitation, and Delirium in Burn Patients.
The majority of hospitalized burn patients experience pain, agitation, and delirium. The development of each one of these conditions can also lead to, or worsen, the others. Providers, therefore, need to thoroughly assess the underlying issue to determine the most effective treatment. Multimodal pharmacologic regimens are often used in conjunction with non-pharmacologic strategies to manage pain, agitation, and delirium. This review focuses on the pharmacologic management of these complicated patients in a critical-care setting.


Trans-10-Hydroxy-2-Decenoic Acid Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice via Regulating the Inflammasome-Mediated Pyroptotic Pathway and Enhancing Colonic Barrier Function.
The objective of this study is to explore the effects of 10-hydroxy-2-decenoic acid (10-HDA), the major fatty acid in royal jelly, on dextran sodium sulfate (DSS)-induced mice ulcerative colitis (UC) and its potential mechanism of action. Forty male C57BL/6 mice are randomly divided into five experimental groups: control, DSS, DSS + 25 (or 100)mg kg-1 d-1 10-HDA, and DSS + 200 mg kg-1 d-1 mesalazine (ME). UC is induced in mice using 2.5% DSS in drinking water for 7 days. During the induction, these UC mice are orally administrated 10-HDA or ME per day. Meanwhile, lipopolysaccharide (LPS)/adenosine-triphosphate (ATP)-stimulated THP1 cells are used as a model to test the effects of 10-HDA. 10-HDA reduces DSS-induced pathological damage, reactive oxygen species (ROS) accumulation, neutrophil infiltration, and cytokine production in colonic tissue. Compared with the DSS group, the expressions of thioredoxin interacting protein (TXNIP), NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1), gasdermin-D (GSDMD), N-terminal domain of gasdermin-D (N-GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in the colon are decreased after administration of 10-HDA. 10-HDA also elevates the barrier integrity and the expressions of zonula occludens-1 (ZO-1) and Occludin in colonic epithelium exposed to DSS. In THP1 cells, the inflammasome-mediated pyroptosis induced by LPS/ATP is inhibited by 10-HDA pretreatment. 10-HDA alleviates DSS-induced colitis by regulating the NLRP3 inflammasome-mediated pyroptotic pathway and enhancing colonic barrier function.


Introduction of a benzoyl group onto 6-chloropurine riboside in aqueous solution and its application to the synthesis of nucleoside derivatives.
A benzoyl group was introduced onto the 3'-hydroxyl group of 6-chloropurine riboside by treatment with benzoic anhydride in the presence of a base in aqueous solution. The product (3b) was converted to 9-(2,3-Di-deoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (1, FddA) in 6 steps, including radical deoxygenation.


Continuous countercurrent extraction of hemicellulose from pretreated wood residues.
Two-stage dilute acid pretreatment followed by enzymatic cellulose hydrolysis is an effective method for obtaining high sugar yields from wood residues such as softwood forest thinnings. In the first-stage hydrolysis step, most of the hemicellulose is solubilized using relatively mild conditions. The soluble hemicellulosic sugars are recovered from the hydrolysate slurry by washing with water. The washed solids are then subjected to more severe hydrolysis conditions to hydrolyze approx 50% of the cellulose to glucose. The remaining cellulose can further be hydrolyzed with cellulase enzyme. Our process simulation indicates that the amount of water used in the hemicellulose recovery step has a significant impact on the cost of ethanol production. It is important to keep water usage as low as possible while maintaining relatively high recovery of soluble sugars. To achieve this objective, a prototype pilot-scale continuous countercurrent screw extractor was evaluated for the recovery of hemicellulose from pretreated forest thinnings. Using the 274-cm (9-ft) long extractor, solubles recoveries of 98, 91, and 77% were obtained with liquid-to-insoluble solids (L/IS) ratios of 5.6, 3.4, and 2.1, respectively. An empirical equation was developed to predict the performance of the screw extractor. This equation predicts that soluble sugar recovery above 95% can be obtained with an L/IS ratio as low as 3.0.


Dispersion-managed semiconductor mode-locked ring laser.
A novel breathing-mode external sigma-ring-cavity semiconductor mode-locked laser is developed. Intracavity pulse compression and stretching produce linearly chirped pulses with an asymmetric exponential temporal profile. External dispersion compensation reduces the pulse duration to 274 fs (within 10% of the bandwidth limit).


Intravitreal triamcinolone for cystoid macular edema related to branch retinal vein occlusion.
We retrospectively evaluated the effectiveness of intravitreal triamcinolone in treating 19 eyes with macular edema related to branch retinal vein occlusion (BRVO). Eyes with nonischemic BRVO respond more favorably than those with ischemic BRVO. A single injection of intravitreal triamcinolone led to elevated intraocular pressure in 3 of 19 eyes (16%). Half of phakic eyes had progression of cataract. Retreatment may be necessary.


Lumbar plexus neuropathy resulting from retroperitoneal hemorrhage.
A case of lumbar plexus neuropathy occurring in the setting of heparin therapy is reported. Documentation of the site of a retroperitoneal hematoma by CT scan was made prior to the full clinical evolution of lumbar plexus neuropathy resulting from a psoas-muscle hematoma. Two patterns of retroperitoneal bleeding and their respective clinical manifestations are discussed. Early diagnosis of these syndromes may allow for intervention before neurologic compromise is established.


Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)-sensitive workers.
Workers with "sensitivity" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.


Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis.
To examine and estimate the efficacy of cognitive-behavioural therapy (CBT) for late-life anxiety disorders. A systematic review and meta-analysis of randomized controlled trials comparing CBT with i) a waiting-list control condition and ii) an active control condition controlling for non-specific effects in patients aged over 60 years and suffering from an anxiety disorder. The main outcome parameter of individual studies, i.e. effect on anxiety, was pooled using the standardized mean difference (SMD). Seven papers fulfilled the inclusion criteria, including nine randomized controlled comparisons for 297 patients. Anxiety symptoms were significantly more reduced following CBT than after either a waiting-list control condition [SMD = -0.44 (95 CI: -0.84 -0.04), P = 0.03] or an active control condition [SMD = -0.51 (95 CI: -0.81, -0.21), P<0.001]. Additionally, CBT significantly alleviated accompanying symptoms of worrying and depression. Cognitive-behavioural therapy is efficacious for the treatment of late-life anxiety disorders.


A Strategy to Battle Coronavirus Disease 2019 in the Hospital: Identify and Use the Power of "Immune Survivors".
The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses serious health and economic problems worldwide. One of the worst scenarios is the collapse of the medical care system due to nosocomial infections. SARS-CoV-2 quickly spreads in closed spaces, crowded areas, and close physical distances, which frequently occur in Japanese medical facilities. Although we are making efforts to avoid such situations, healthcare workers always face the risk of developing a SARS-CoV-2 infection in the workplace because of proximity. Thus, we need to battle SARS-CoV-2 using a unique strategy. We propose a novel strategy to eliminate SARS-CoV-2 infections: measurement of antibodies against SARS-CoV-2 and using the power of "immune survivors." We agree with using standard precautions and early isolation of patients with coronavirus disease 2019 (COVID-19) to block the spread of SARS-CoV-2 infection. However, we face difficulties carrying out these fundamental missions. Now, we focus on "immune survivors." If healthcare workers acquired the neutralizing antibody against SARS-CoV-2, they are considered "immune survivors" with a low risk of reinfection with SARS-CoV-2. These "immune survivors" can contribute to the care of patients with COVID-19 on the front line. Also, these "immune survivors" can function as an envelope by surrounding COVID-19 patients. As a result, "immune survivors" can eliminate the spread of SARS-CoV-2 in medical facilities as well as in society. We understand that the concept of "immune survivors" needs further discussion. No information is available on how long or the titer of neutralizing antibody required for protection from infection. We have just started to measure antibody levels against SARS-CoV-2 in healthcare workers in our hospital. This project will provide further information in the battle against the SARS-CoV-2 infection. (Clinical trial registration number: UMIN 000039997).


Effects of a lengthy period of undernutrition from birth and subsequent nutritional rehabilitation on the synapse: granule cell neuron ratio in the rat dentate gyrus.
Recent evidence showing alterations in spatial memory due to a period of undernutrition during early life has implicated the hippocampus as one of the brain centres that may be particularly adversely affected. However, there are very few quantitative morphological studies that have examined the neuronal and synaptic populations of the hippocampi from undernourished animals. We decided to carry out such experiments, paying particular attention to the granule cell of the dentate gyrus. Male rats were undernourished from the 18th day of gestation until 21, 75, or 150 days of age. Some of these previously undernourished rats were nutritionally rehabilitated between 150 and 250 days of age. Groups of well-fed control and experimental rats were killed by intracardiac perfusion with 2.5% sodium-cacodylate-buffered glutaraldehyde. The right hippocampus from each rat was dissected out and processed for electron microscopy. Stereological procedures at the light and electron microscopical levels were used to estimate the numerical densities of granular cell neurons and molecular layer synapses in the dorsal lip of the dentate gyrus. These estimates were used to calculate synapse: neuron ratios. There were 5,056 +/- 347 (mean +/- SE) and 5,002 +/- 190 synapses per neuron in 21-day-old control and undernourished rats, respectively. By 75 days these values had increased to 9,215 +/- 588 and 6,683 +/- 237. The difference was statistically significant. By 150 days of age the value for control animals had fallen once again to 6,518 +/- 209 whereas undernourished rats had increased slightly to 7,689 +/- 288 (P less than .01); 250-day-old rats, previously undernourished from birth to 150 days of age, showed a substantial increase in the synapse: neuron ratio during the period of nutritional rehabilitation. Thus these nutritionally rehabilitated rats had 9,407 +/- 365 synapses per neuron whereas age-matched controls had only 6,323 +/- 239 (P less than .01). These results indicate that the rat dentate gyrus is vulnerable to undernutrition even during the postweaning period and that a lengthy period of undernutrition can alter the developmental growth curve for synapse: neuron ratios.


Mycobacterium paratuberculosis zoonosis is a One Health emergency.
A singular pathogen has been killing animals, contaminating food and causing an array of human diseases. Mycobacterium avium subspecies paratuberculosis (MAP) is the cause of a fatal enteric infectious disease called Johne's (Yo'-nees), a disorder mostly studied in ruminant animals. MAP is globally impacting animal health and imparting significant economic burden to animal agriculture. Confounding the management of Johne's disease is that animals are typically infected as calves and while commonly not manifesting clinical disease for years, they shed MAP in their milk and feces in the interval. This has resulted in a "don't test, don't tell" scenario for the industry resulting in greater prevalence of Johne's disease; furthermore, because MAP survives pasteurization, the contaminated food supply provides a source of exposure to humans. Indeed, greater than 90% of dairy herds in the US have MAP-infected animals within the herd. The same bacterium, MAP, is the putative cause of Crohn's disease in humans. Countries historically isolated from importing/exporting ruminant animals and free of Johne's disease subsequently acquired the disease as a consequence of opening trade with what proved to be infected animals. Crohn's disease in those populations became a lagging indicator of MAP infection. Moreover, MAP is associated with an increasingly long list of human diseases. Despite MAP scientists entreating regulatory agencies to designate MAP a "zoonotic agent," it has not been forthcoming. One Health is a global endeavor applying an integrative health initiative that includes the environment, animals and humans; One Health asserts that stressors affecting one affects all three. Recognizing the impact MAP has on animal and human health as well as on the environment, it is time for One Health, as well as other global regulatory agencies, to recognize that MAP is causing an insidious slow-motion tsunami of zoonosis and implement public health mitigation.


Microcarriers in application for cartilage tissue engineering: Recent progress and challenges.
Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wide range of medical fields, especially the cartilage tissue engineering (TE). Notably, microcarrier systems provide an attractive method for regulating cell phenotype and microtissue maturations, they also serve as powerful injectable carriers and are combined with new technologies for cartilage regeneration. In this review, we introduced the typical methods to fabricate various types of microcarriers and discussed the appropriate materials for microcarriers. Furthermore, we highlighted recent progress of applications and general design principle for microcarriers. Finally, we summarized the current challenges and promising prospects of microcarrier-based systems for medical applications. Overall, this review provides comprehensive and systematic guidelines for the rational design and applications of microcarriers in cartilage TE.


Cortical and subcortical components of the pattern VEP.
Studies in the past have shown that wavelength related VEPs can be recorded from both cortical and noncortical sites. Elements of pattern-specific VEPs for both transient and pattern-reversal stimuli are also obtained from these sites. From the noncortical montage consistent responses are obtained with a major component at about 100 msec, which has been found for both the wavelength related and pattern related VEP. In contrast, the cortical VEP to both types of stimuli include two major components, at around 100 and 200 msec. In pattern reversal these components react quite differently to changes in spatial frequency. The component around 100 msec reacts strongly to a wide range of spatial frequencies when recorded from either cortical or noncortical sites. In contrast, the component around 200 msec, obtained with cortical recording, reacts very strongly to high spatial frequencies and very weakly to low spatial frequencies. This finding corresponds to recent results of single-cell studies in the macaque LGN and striate cortex.


Downy woodpecker foraging behavior: foraging by expectation and energy intake rate.
I describe an artificial patch system that was used to study the foraging behavior of free-roaming downy woodpeckers (Picoides pubescens) in a woodlot in southeastern Michigan. The artificial "patches" used were thin logs into which were drilled small holes to hold food items (bits of sunflower seed kernels). Downy woodpeckers would systematically search the holes of a patch for food items and thus by manipulating the food distribution within the patches, the birds could be made to experience differing rates of energy intake while foraging.Simple deterministic theories of optimal foraging in patchy environments indicate that an optimal forager, who experiences a decreasing rate of energy intake while foraging in a patch, should leave a patch when its rate of energy intake falls below the average intake rate for the overall environment. In other words, an optimal forager is continually assessing the quality of a patch and makes decisions as to when to leave a patch via its energy intake rate. When the downy woodpeckers studied could encounter any one of several types of patches each with differing, decreasing rates of energy intake, they followed a patch quality assessment strategy similar to that suggested by theory. Upon encountering a single type of patch for a number of consecutive days, however, the birds appeared to forage according to prior expectations of patch quality and not according to a quality assessment strategy based on energy intake rates. The observed expectations were not related to the number of food items per patch but they appeared to be based on expectations of when or where to leave a patch.


Evaluation of the generation of reactive oxygen species and antibacterial activity of honey as a function of its phenolic and mineral composition.
The antibacterial activity (ABA) of honey is associated with the generation of reactive oxygen species (ROS), where polyphenols (PFs) play a key role due to their pro-oxidant action modulated by metallic cations. In this work, the contents of PFs, H2O2, OH radicals, Cu, Fe, Mn, Zn, and ABA against Staphylococcus epidermidis and Pseudomonas aeruginosa were determined in honeys from central Chile. Then, their relationships were evaluated through partial least squares regression. The average contents of phenolic acids, flavonoids and metals in honey ranged from 0.4 to 4 μg/g, 0.3-1.5 μg/g and 3-6 μg/g, respectively. All honeys showed accumulation of H2O2 (1-35 μg/g) and OH radicals. The PLS showed that gallic acid, p-coumaric acid, chrysin, kaempferol, Fe, and Mn stimulate the generation of ROS. Quercetin, Cu, and Zn showed marginal antioxidant effects. PFs favor the ABA of honey against both bacteria and H2O2 against S. epidermidis.


Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.
The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans. Reports from 15 individuals have described RFX-associated phenotype as a neurobehavioural disease, manifesting primarily with global developmental delay and intellectual disability. Autism spectrum disorder and attention deficit hyperactivity disorder have also been described in some children. Here we report a case of a 19-month-old with a de novo missense variant in RFX7 resulting in severe global developmental delay including significant speech delay, microcephaly, dyskinetic movements, and failure to thrive. This is the first association between variants in RFX7 and failure to thrive, expanding the phenotype of this newly described gene. In this report we will also show RFX7 associated progressive central nervous system involvement through serial brain imaging.


Endothelium-derived relaxing factor inhibits platelet aggregation in human whole blood in vitro and in the rat in vivo.
Carbachol (0.03-10 microM) or histamine (0.06-10 microM) challenge of indomethacin-pretreated rat aortic rings inhibited ADP-induced aggregation of platelets suspended in anticoagulated human whole blood. The maximum inhibition of platelet aggregation achieved with either drug was approximately 50%. No such inhibition was observed in rat aortic rings rubbed to remove endothelial cells or in intact vessels preincubated with nordihydroguaiaretic acid (NDGA, 10 microM), mepacrine (10 microM) or methylene blue (100 microM). Intravenously (i.v.) injected carbachol (0.5-5 micrograms/kg) also inhibited ADP-induced accumulation of 111indium-labelled platelets in the pulmonary circulation of urethane-anaesthetised rats. This effect of carbachol was inhibited by i.v. injected methylene blue (10 mg/kg) but unaffected by indomethacin (3 mg/kg) or hexamethonium (10 mg/kg) suggesting that PGI2 or adrenaline release did not account for the inhibition of platelet activation observed. Similarly, the platelet inhibitory effect of carbachol in vivo was not related to increased pulmonary vascular blood flow (assessed by accumulation of 111indium-labelled erythrocytes) or blood fibrinolytic activity (measured by euglobulin clot bioassay). The present results suggest that endothelium-derived relaxing factor or a like substance inhibits human platelet aggregation in vitro and rat platelet aggregation in vivo.


Stimulation of histamine synthesis in rat mast cells by compound 48/80 in vitro.
The histamine content of rat peritoneal fluid cells is doubled within 20 min by 0.5 microgram/ml of compound 48/80. Histamine catabolism inhibitors do not reproduce this effect; cells pre-incubated with alpha-fluoromethylhistidine are unresponsive to compound 48/80 which therefore activates pre-formed histidine decarboxylase rather than 'inducing' it. Non-mast cells showed no change after treatment with compound 48/80.


Prediction of diagnosis of immunoglobulin A nephropathy prior to renal biopsy and correlation with urinary sediment findings and prognostic grading.
Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN.


Synthesis of novel ion-imprinted polymeric nanoparticles based on dibenzo-21-crown-7 for the selective pre-concentration and recognition of rubidium ions.
In this work, we report the first application of ion-imprinted technology via precipitation polymerization for simple and practical determination of rubidium ions. The rubidium-ion-imprinted polymer nanoparticles were prepared using dibenzo-21-crown-7 as a selective ligand, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross linker, and 2,2'-azobisisobutyronitrile as radical initiator. The resulting powder material was characterized using scanning electron microscopy, which showed colloidal nanoparticles of 100-200 nm in diameter and slightly irregular in shape. The maximum adsorption capacity of the ion imprinted particles was 63.36 μmol/g. The experimental conditions such as nature and concentration of eluent, pH, adsorption and desorption times, weight of the polymer material, aqueous phase and desorption agent volumes were also studied. Finally, selectivity of the prepared IIP particles toward rubidium ion was investigated in the presence of some foreign metal ions.


Post-mortem thermal angiography: a pilot study on swine coronary circulation.
Thermal imaging (TI) allows the detection of thermal patterns emitted from objects as a function of their temperature in the long-infrared spectrum and produces visible images displaying temperature differences. The aim of this pilot study was to test TI to visualize the coronary circulation of swine hearts. Thirty swine hearts were prepared for ex situ coronarography, and thermal images were acquired through a FlirOne thermal camera (FLIR Systems®) paired with a Google Android Smartphone. Coronary arteries were cannulated, namely the anterior interventricular artery, the circumflex branch of the left coronary artery, and the right coronary artery. The heart was cooled, and contrast medium (CM) consisting of distilled water heated to 40 °C was injected in a coronary vessel, while thermal images were captured. These steps were repeated for each coronary vessel and under experimentally simulated coronary heart disease. Thermal imaging coronarography (TIC) allowed a clear representation of the morphology and course of the coronary vessels and of experimentally simulated coronary heart disease, moreover, demonstrated to be easy to perform during or after autopsies on ex situ hearts, non-destructive, reproducible, and cheap. On the basis of these preliminary results, TIC might allow a subsequent more focused and comprehensive cardiopathological examination of the heart, which remains mandatory for the definitive diagnosis of coronary heart disease. Although these preliminary results seem encouraging, further systematic studies on human hearts, both normal and pathological, are necessary for estimating the sensitivity and specificity of the proposed method and to draw any definitive conclusion.


A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin.
Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E-cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of β-catenin at Tyr 142 and enhances the interaction between α- and β-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced "zipper-like" cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E-cadherin adherens junctions through promoting the dephosphorylation of β-catenin.


A prototype power assist wheelchair that provides for obstacle detection and avoidance for those with visual impairments.
Almost 10% of all individuals who are legally blind also have a mobility impairment. The majority of these individuals are dependent on others for mobility. The Smart Power Assistance Module (SPAM) for manual wheelchairs is being developed to provide independent mobility for this population. A prototype of the SPAM has been developed using Yamaha JWII power assist hubs, sonar and infrared rangefinders, and a microprocessor. The prototype limits the user to moving straight forward, straight backward, or turning in place, and increases the resistance of the wheels based on the proximity of obstacles. The result is haptic feedback to the user regarding the environment surrounding the wheelchair. The prototype has been evaluated with four blindfolded able-bodied users and one individual who is blind but not mobility impaired. For all individuals, the prototype reduced the number of collisions on a simple navigation task. The prototype demonstrates the feasibility of providing navigation assistance to manual wheelchair users, but several shortcomings of the system were identified to be addressed in a second generation prototype.


Potential dual inhibition of SE and CYP51 by eugenol conferring inhibition of Candida albicans: Computationally curated study with experimental validation.
Ergosterol is the key sterol component in the cell membrane of fungi including moulds and yeasts. Any decrease in the levels of ergosterol in the cell membrane of fungi render them venerable to cell membrane damage and even its death. Majority of antifungal drug targets the key enzymes involved in ergosterol biosynthesis pathway. The biochemical pathway for the synthesis of Ergosterol is a complex one, though the reactions carried by Squalene Epoxidase (SE) and 14α-demethylase (CYP51- a member of Cytochrome P450 family) serves to the key rate limiting reactions that can impact the overall production of Ergosterol. Allylamines class of antifungal drug target SE while Azoles target the CYP51. Currently advancement in the drug development is focused to introduce newer drugs that can simultaneously inhibit both this rate limiting enzymes. However, natural compounds established to possess antifungal activity but the major loophole about their understanding lies in the fact that their mode of action are severely unstudied. One such well-established antifungal natural phytochemical is Eugenol, and in current manuscript we investigated its efficacy to interact with both, SE and CYP51 of Candida albicans using molecular Docking, Free energy change calculations and Molecular Dynamics (MD) simulation, showing promising outcomes. For experimental studies, terbinafine, clotrimazole and eugenol showed 4 μg/ml, 2 μg/ml, and 512 μg/ml MIC90 values, respectively against C. albicans and also showed reduction in Ergosterol production at sub-MIC levels. The obtained result indicates the involvement of eugenol in the inhibition of enzymes require in the ergosterol biosynthesis pathway.


Motor representation of the hand in the human cortex: an f-MRI study with a conventional 1.5 T clinical unit.
The purpose of this study was to show a gradient of possible bilateral activation for movements of the non-dominant vs. dominant hand, as well as for areas involved in complex vs. simple hand movements. A standard 1.5 T magnetic resonance imaging (MRI) system has been utilized to localize the cortical motor hand areas, using the blood oxygen level dependent contrast (BOLDc) technique and single-section fast low-angle shot (FLASH) imaging. Ten normal right-handed subjects volunteered for the study. The motor tasks consisted of simple (flexion-extension) finger movements of either hand, and complex movements (finger-to-thumb opposition in a repeating, pre-planned sequence) of the non-dominant hand. Simple movements caused contralateral activation of the primary motor area (MA); ipsilateral activation was observed for the non-dominant hand only. Supplementary motor area (SMA) was also activated, with a clear contralateral prevalence. The ratio of bilateral activation of MA did not change with complex movements of the non-dominant hand, while SMA as well as lateral premotor area were largely bilaterally activated in this task. In conclusion, the ipsilateral MA is activated for movements--even simple--performed with the non-dominant hand. There is widespread functional activity, involving both contralateral and ipsilateral SMA, for complex movements.


Passage of postovulatory follicular fluid into the peritoneal cavity and the effect on concentrations of circulating hormones in mares.
Reported data were reviewed and reexamined to evaluate the concept that most of the follicular fluid enters the peritoneal cavity at ovulation in mares and transiently alters the circulating concentrations of LH, FSH, estradiol, and inhibin. A transrectal ultrasonographic study supported the hypothesis that the large volume (40-50 ml) of evacuated follicular fluid passes through the infundibular fimbriae into the peritoneal cavity. A spike in circulating inhibin and a decrease in the rate of reduction in circulatory estradiol occurs at ovulation. Simultaneously, a disruption occurs in the increasing concentrations of the ovulatory LH surge and in the FSH surge that begins before ovulation. The concept was further supported by the present finding that the estradiol content of follicular fluid within a few hours before ovulation is equivalent to the amount reported to be needed for a negative effect on LH and for a synergistic negative effect of estradiol and inhibin on FSH.


Progesterone treatment improves cognitive outcome following experimental traumatic brain injury in rats.
Progesterone (PROG) has recently been shown to have a neuroprotective effect and improve cognitive outcome in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. This study was aimed to investigate the inhibitory effects of PROG on inflammation and apoptosis in the hippocampus after TBI and its influence on the cognitive outcome. In this study, the model of TBI was established by modified Feeney's weight-dropping method. The PROG was given in a dose of 16 mg/kg by intraperitoneal injection 1h post injury and subsequent injections subcutaneously at 6h and 12 h after TBI. Brain samples were extracted at 24 h after trauma. The expression of COX-2 and caspase-3 was measured by immunohistochemistry and western blot technique. The cognitive outcome was assessed by Morris water maze test (MWM). The results revealed that the expression of COX-2 and caspase-3 in TBI-PROG group was distinctly less than those of the TBI group (p < 0.05). In addition, the performance of Morris water maze showed that progesterone treatment exhibited shorter latencies, more platform crossings and more time swimming in the quadrant area in the TBI+PROG rats compared to the TBI rats. In conclusion, post-TBI PROG administration may attenuate inflammation and apoptosis in the hippocampus, and this may be one of the mechanisms by which PROG improves cognitive outcome following TBI.


Towards elucidating the radiochemistry of astatine - Behavior in chloroform.
Targeted alpha therapy of disseminated cancer is an emerging technique where astatine-211 is one of the most promising candidate nuclides. Although astatine has been known for over 70 years, its chemistry is still largely unexplored, mainly due to the lack of stable or long-lived isotopes. However, substantial amounts of astatine-211 can be produced in cyclotrons by the bombardment of natural bismuth. The astatine can be recovered from the resulting irradiated target material through either wet extraction or dry-distillation. Chloroform has become an important intermediate solvent for the recovery of astatine after production, especially following dry distillation. In this work, the radiochemistry of astatine in chloroform was investigated using evaporation, solvent extraction, chromatographic methods and molecular modeling. The extraction of astatine in chloroform led to the formation of multiple astatine species, allowing for evaporation of the solvent to dryness without any loss of activity. Radiolysis products of chloroform were shown to play an important role in the speciation of astatine forming both reactive and kinetically stable compounds. It was hypothesized that reactions with chlorine, as well as trichloromethyl hydroperoxide, forming polar astatine compounds are important reactions under the current experimental conditions.


Experimental study of intracellular ice growth in human umbilical vein endothelial cells.
Study of the intracellular ice formation (IIF) and growth is essential to the mechanistic understanding of cellular damage through freezing. In the aid of high speed and high resolution cryo-imaging technology, the transient intracellular ice formation and growth processes of the attached human umbilical vein endothelial cells (HUVEC) were successfully captured during freezing. It was found that the intracellular ice nucleation site was on the cell membrane closer to the nucleus. The ice growth was directional and toward the nucleus, which covered the whole nucleus before growing into the cytoplasm. The crystal growth rate in the nucleus was much larger than that in the cytoplasm, and its morphology was influenced by the cooling rate. During the thawing process, small crystals fused into larger ones inside the nucleus. Moreover, the cumulative fraction of the HUVEC with IIF was mainly dependent on the cooling rate not the confluence of the cells attached.


Water consumption by rinse-off cosmetic products: The case of the shower.
This article measures and discusses the effects of different shower gels on the consumption of water used during a shower. A sensory panel was created for quantifying water consumption associated with the use of shower gels. Fifteen French panellists were recruited (age: 59 ± 7, height: 163 cm ± 9 and weight: 68 kg ± 20) and trained to assess rinsed skin in a standardized way. Effective panellists were then asked to assess 25 shower gels covering the variety of existing products on the market. Results showed that the average volume was 4.77 L for heating the water and wetting the body and 4.15 L for rinsing the shower gel off the full body. We observed a significant shower gel effect (p < 0.0001) with the water volume needed to rinse the 25 shower gels ranging 3.21 L to 5.65 L. This paper demonstrates the impact of shower gel formulation on water consumption during a shower. It thus demonstrates the importance of formulating shower gels to reduce the total amount of water needed to shower. It also introduces the distinction between 'useful water' which refers strictly to the volume of water objectively needed to rinse off a product and the 'used water' which refers to the total shower volume of water. This distinction helps to better strategize actions in order to reduce water consumption from rinse-off cosmetic products used during showers.


Postmortem Electrical Conductivity Changes of Dicentrarchus labrax Skeletal Muscle: Root Mean Square (RMS) Parameter in Estimating Time since Death.
Electric impedance spectroscopy techniques have been widely employed to study basic biological processes, and recently explored to estimate postmortem interval (PMI). However, the most-relevant parameter to approximate PMI has not been recognized so far. This study investigated electrical conductivity changes in muscle of 18 sea bass specimens, maintained at different room temperatures (15.0 °C; 20.0 °C; 25.0 °C), during a 24 h postmortem period using an oscilloscope coupled with a signal generator, as innovative technology. The root mean square (RMS) was selected among all measured parameters, and recorded every 15 min for 24 h after death. The RMS(t) time series for each animal were collected and statistically analyzed using MATLAB®. A similar trend in RMS values was observed in all animals over the 24 h study period. After a short period, during which the RMS signal decreased, an increasing trend of the signal was recorded for all fish until it reached a peak. Subsequently, the RMS value gradually decreased over time. A strong linear correlation was observed among the time series, confirming that the above time-behaviour holds for all animals. The time at which maximum value is reached strongly depended on the room temperature during the experiments, ranging from 6 h in fish kept at 25.0 °C to 14 h in animals kept at 15.0 °C. The use of the oscilloscope has proven to be a promising technology in the study of electrical muscle properties during the early postmortem interval, with the advantage of being a fast, non-destructive, and inexpensive method, although more studies will be needed to validate this technology before moving to real-time field investigations.


Effect of moisture content on the evolution of bacterial communities and organic matter degradation during bioaugmented biogas residues composting.
Composting is an excellent way to recycle biogas residues into a stable, non-toxic agricultural end product. In this study, the dynamic changes of physical-chemical parameters and bacterial community in three groups of bioaugmentation composting systems at different moisture contents (MC) of 50% (MC50), 60% (MC60) and 70% (MC70) were monitored. The differences of bacterial communities in composts with different initial MC were compared, and the interaction between biological and non-biological parameters was also explored. The results revealed that after 30 days of composting, the biogas residues compost in MC60 reached highest temperature of 64 °C, total Kjeldahl nitrogen (TKN) of 2%, seed germination index (GI) of 110%, and the longest thermophilic period duration of 5 days (55 °C). Additionally, the result of high-throughput sequencing showed that the diversity of bacterial communities in MC60 was the highest, and the abundance of Actinobacteria (16.93-52.63%), Firmicutes (8.71-56.75%), and Proteobacteria (16.88-46.95%) in all groups were the highest at phylum level. The LEfSe analysis indicated that the abundance of Ochrobactrum and Cellulomonadaceae in MC60 was significantly (p < 0.05) higher than with other treatments. Moreover, canonical correspondence analysis (CCA) indicated thermophilic period duration is significantly (p < 0.05) positively correlated with Paenibacillus. Besides, it was found the relative abundance of Nocardiopsis and Georgenia has a significant (p < 0.01) correlation with the fertilizer efficiency of compost. These results showed that controlling the initial moisture content at 60% can improve the maturity and fertilizer efficiency of compost, and enable the bacteria beneficial to composting to gain the advantage of proliferation.


Circulation of gut-preactivated naïve CD8+ T cells enhances antitumor immunity in B cell-defective mice.
The gut microbiome has garnered attention as an effective target to boost immunity and improve cancer immunotherapy. We found that B cell-defective (BCD) mice, such as µ-membrane targeted deletion (µMT) and activation-induced cytidine deaminase (AID) knockouts (KOs), have elevated antitumor immunity under specific pathogen-free but not germ-free conditions. Microbial dysbiosis in these BCD mice enriched the type I IFN (IFN) signature in mucosal CD8+ T cells, resulting in up-regulation of the type I IFN-inducible protein stem cell antigen-1 (Sca-1). Among CD8+ T cells, naïve cells predominantly circulate from the gut to the periphery, and those that had migrated from the mesenteric lymph nodes (mLNs) to the periphery had significantly higher expression of Sca-1. The gut-educated Sca-1+ naïve subset is endowed with enhanced mitochondrial activity and antitumor effector potential. The heterogeneity and functional versatility of the systemic naïve CD8+ T cell compartment was revealed by single-cell analysis and functional assays of CD8+ T cell subpopulations. These results indicate one of the potential mechanisms through which microbial dysbiosis regulates antitumor immunity.


Hyperglycemia alters lipid metabolism and ultrastructural morphology of cerebellum in brains of diabetic rats: Therapeutic potential of raffia palm (Raphia hookeri G. Mann & H. Wendl) wine.
The present study investigated the effect of raffia palm (Raphia hookeri) wine (RPW) on hyperglycemia-mediated lipid metabolites and pathways, functional chemistry and ultrastructural morphology of cerebellums in type 2 diabetes (T2D). T2D was induced in male Sprague-Dawley rats by feeding with 10% fructose ad libitum for 2 weeks before injecting intraperitoneally with 40 mg/kg bodyweight (bw) streptozotocin. Following confirmation of hyperglycemia at blood glucose >200 mg/dL, diabetic rats were treated with RPW at 150 and 300 mg/kg bw respectively. Metformin served as the standard drug. Negative and normal controls consisted of untreated diabetic and non-diabetic rats, respectively. After 5 weeks of treatment, the rats were humanely sacrificed, and their cerebellum excised from the harvested brains. GC-MS analysis revealed significant alterations in cerebellar lipid metabolites depicted by changes in unsaturated and saturated fatty acids, fatty - esters, alcohols, and amides, glycols and steroids on induction of T2D. Pathway enrichment analysis of the lipid metabolites revealed inactivation of arachidonic metabolic pathway following T2D induction. Treatment with both doses of RPW restored most of the metabolites, while reactivating arachidonic acid metabolism (high dose only). Low dose of RPW led to the activation of retinol metabolism. Both doses of RPW maintained cerebellar functional chemistry as revealed by FTIR analysis. TEM analysis revealed swollen mitochondria, depleted numbers of synaptic vesicles, and shrunk synaptic clefts following induction of T2D. These ultrastructural morphologies were improved in RPW-treated rats. These results portray the therapeutic potential of raffia palm wine in the management of neurodegenerative complications in T2D.


miRNA-Microbiota Interaction in Gut Homeostasis and Colorectal Cancer.
Gut homeostasis is maintained by dynamic host-microbiota interactions. Recently, miRNAs have emerged as key molecular regulators in the mediation of such interactions. Here, we discuss the role of a host miRNA-microbiome axis in gut homeostasis and colorectal cancer (CRC) and the involvement of diet and microbial metabolites in miRNA-mediated intestinal health.


Selective determination of gold(III) ion using CuO microsheets as a solid phase adsorbent prior by ICP-OES measurement.
We have prepared calcined CuO microsheets (MSs) by a wet-chemical process using reducing agents in alkaline medium and characterized by UV/vis., fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD), and field-emission scanning electron microscopy (FESEM) etc. The detailed structural, compositional, and optical characterizations of the MSs were evaluated by XRD pattern, FT-IR, X-ray photoelectron spectroscopy (XPS), and UV-vis spectroscopy, respectively which confirmed that the obtained MSs are well-crystalline CuO and possessed good optical properties. The CuO MSs morphology was investigated by FESEM, which confirmed that the calcined nanomaterials were sheet-shaped and grown in large-quantity. Here, the efficiency of the CuO MS was applied for a selective adsorption of gold(III) ion prior to its detection by inductively coupled plasma-optical emission spectrometry (ICP-OES). The selectivity of CuO MSs towards various metal ions, including Au(III), Cd(II), Co(II), Cr(III), Fe(III), Pd(II), and Zn(II) was analyzed. Based on the adsorption isotherm study, it was confirmed that the selectivity of MSs phase was mostly towards Au(III) ion. The static adsorption capacity for Au(III) was calculated to be 57.0 mg g(-1). From Langmuir adsorption isotherm, it was confirmed that the adsorption process was mainly monolayer-adsorption onto a surface containing a finite number of adsorption sites.


The effect of biotinylation on the antigenic specificity of anti-defensin monoclonal antibodies.
We studied the effects of biotinylation on three monoclonal antibodies (Mabs) that were raised against carrier protein conjugates of human defensin HNP-1, and of rabbit defensins NP-2 and NP-5 respectively. Before biotinylation, each Mab specifically bound to its peptide hapten. Biotinylation of these Mabs by the N-hydroxysuccinimide-biotin (NHS-biotin) resulted in crossreactivity of each Mab with the two irrelevant defensin peptides. In contrast, Mab specificity was preserved after biotinylation with biotin hydrazide, which links biotin to the glycan moiety of antibodies. The effects of NHS-biotinylation were in part mimicked by 2,4-dinitrofluorobenzene, another agent that modified primary amine groups of proteins, suggesting that this modification contributed to the change in antibody specificity. When a high degree of antigenic specificity against peptide immunogens is required, biotinylation on the glycan moiety of Mabs may be preferable.


Voxel-based clustered imaging by multiparameter diffusion tensor images for predicting the grade and proliferative activity of meningioma.
Meningiomas are the most common primary central nervous system tumors. Predicting the grade and proliferative activity of meningiomas would influence therapeutic strategies. We aimed to apply the multiple parameters from preoperative diffusion tensor images for predicting meningioma grade and proliferative activity. Nineteen patients with low-grade meningiomas and eight with high-grade meningiomas were included. For the prediction of proliferative activity, the patients were divided into two groups: Ki-67 monoclonal antibody labeling index (MIB-1 LI) < 5% (lower MIB-1 LI group; n = 18) and MIB-1 LI ≥ 5% (higher MIB-1 LI group; n = 9). Six features, diffusion-weighted imaging, fractional anisotropy, mean, axial, and radial diffusivities, and raw T2 signal with no diffusion weighting, were extracted as multiple parameters from diffusion tensor imaging. The two-level clustering approach for a self-organizing map followed by the K-means algorithm was applied to cluster a large number of input vectors with the six features. We also validated whether the diffusion tensor-based clustered image (DTcI) was helpful for predicting preoperative meningioma grade or proliferative activity. The sensitivity, specificity, accuracy, and area under the curve of receiver operating characteristic curves from the 16-class DTcIs for differentiating high- and low-grade meningiomas were 0.870, 0.901, 0.891, and 0.959, and those from the 10-class DTcIs for differentiating higher and lower MIB-1 LIs were 0.508, 0.770, 0.683, and 0.694, respectively. The log-ratio values of class numbers 13, 14, 15, and 16 were significantly higher in high-grade meningiomas than in low-grade meningiomas (p < .001). With regard to MIB-1 LIs, the log-ratio values of class numbers 8, 9, and 10 were higher in meningiomas with higher MIB-1 groups (p < .05). The multiple diffusion tensor imaging-based parameters from the voxel-based DTcIs can help differentiate between low- and high-grade meningiomas and between lower and higher proliferative activities.


Hypertrophic cardiomyopathy mimicking athlete heart: risk of progression and opportunity for a bioptical approach.
A case of hypertrophic cardiomiopathy (HCM) mimicking athlete heart, is reported. Performing competitive activity was followed by progression of HCM to cardiac dilation and hypokinesis so that transplant was needed at young age. The Authors suggest a more aggressive approach possibly inclusive of cardiac biopsy when doubtful cases of athlete heart require permission for competitive sports.


Monitoring dihydrodiol polyaromatic hydrocarbon metabolites produced by the freshwater microalgae Selenastrum capricornutum.
We found that microalgae exposed to a mixture of polycyclic aromatic hydrocarbons (PAHs) did not show growth inhibition. Thus, we assumed that they could metabolize these compounds. In this study, the dihydrodiol-type PAH metabolites of benzo(a)pyrene (BaP), benzo(a)anthracene (BaA), benzo(b)fluoranthene (BbF) and benzo(k)fluoranthene (BkF) produced by the freshwater microalgae Selenastrum capricornutum were monitored and quantified using high-performance liquid chromatography with fluorescence detection (HPLC-FD) techniques. Exposure bioassays with S. capricornutum were performed using a 266 ng mL(-1) mixture of PAHs at different exposure times (0.75, 1, 3, 8, 16, 24 and 48 h) under controlled temperature (25 °C); the dihydrodiol metabolites formed in the liquid medium and the biomass were quantified. Metabolite identities were confirmed using HPLC-mass spectrometry; most of the metabolites formed were derived from BaA degradation. At 48 h after exposure 5,6-dBaA and 8,9-dBaA/10,11-dBaA were present in the liquid medium at 20% and 67% of the initial mass of BaA, respectively. Three metabolites of BaP were monitored in the liquid medium and biomass and, at 24 h, 4,5-dBaP accounted for 19%; , 7,8-dBaP, 5%; and 9,10-dBaP, 5% relative to the initial BaP mass. Microalgae exposed to BbF showed the presence of 1,2-dBbF and 9,10-dBbF (at 0.3% and 0.1% of the initial BbF mass, respectively) and those exposed to BkF produced 8,9-dBkF (6.5% of the initial BkF mass) in the liquid medium. Seven unknown compounds were formed after exposure; two compounds were identified as the metabolites of BaA and BaP. The results could facilitate the elucidation of the controversial biodegradation mechanism in microalgae.


Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database.
On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.


Inter-cultivar variation in soil-to-plant transfer of radiocaesium and radiostrontium in Brassica oleracea.
Radiocaesium and radiostrontium enter the human food chain primarily via soil-plant transfer. However, uptake of these radionuclides can differ significantly within species (between cultivars). The aim of this study was to assess inter-cultivar variation in soil-to-plant transfer of radiocaesium and radiostrontium in a leafy crop species, Brassica oleracea. This study comprised four independent experiments: two pot experiments in a controlled environment artificially contaminated with radiocaesium, and two field experiments in an area contaminated with radiocaesium and radiostrontium in the Chernobyl Exclusion Zone. Radiocaesium concentration ratios varied 35-fold among 27 cultivars grown in pots in a controlled environment. These 27 cultivars were then grown with a further 44 and 43 other cultivars in the Chernobyl Exclusion Zone in 2003 and 2004, respectively. In the field-grown cultivars radiocaesium concentration ratios varied by up to 35-fold and radiostrontium concentration ratios varied by up to 23-fold. In three of these experiments (one pot experiment, two field experiments) one out of the 27 cultivars was found to have a consistently lower radiocaesium concentration ratio than the other cultivars. The two field experiments showed that, five out of the 66 cultivars common to both experiments had consistently lower radiocaesium concentration ratios, and two cultivars had consistently lower radiostrontium concentration ratios. One cultivar had consistently lower radiocaesium and radiostrontium concentration ratios. The identification of cultivars that have consistently lower radiocaesium and/or radiostrontium concentration ratios suggests that cultivar selection or substitution may be an effective remediation strategy in radiologically contaminated areas. Future research should focus on plant species that are known to be the largest contributors to human dose.


Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania.
Zanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts.


Efficacy of Carbohydrate Supplementation Compared With Bolus Insulin Dose Reduction Around Exercise in Adults With Type 1 Diabetes: A Retrospective, Controlled Analysis.
Individuals with type 1 diabetes try to manage the risk of exercise-induced hypoglycemia by either pre-exercise/pre-meal bolus insulin dose reductions and/or consuming additional carbohydrates during exercise. Both strategies have proven to be effective in offsetting hypoglycemia, but it remains unclear which one is more beneficial. The aim of this study was to assess the efficacy of carbohydrate supplementation vs bolus insulin dose reduction in prevention of hypoglycemia during moderate-intensity exercise in those with type 1 diabetes. This investigation was a retrospective, controlled analysis of 2 independent clinical trials. All participants performed continuous, moderate-intensity cycle ergometer exercise for ∼45 minutes. Two therapy management groups and a control group were compared. Group A was supplemented with 15 to 30 g carbohydrates at a glycemic threshold of 7.0 mmol/L during exercise, group B reduced their individual bolus insulin dose by 50% with their last meal before exercise and group C served as a control. No hypoglycemic events occurred in group A, whereas 4 events were recorded in groups B (p=0.02) and C (p=0.02). Carbohydrate supplementation was superior to bolus insulin reduction for prevention of hypoglycemia during exercise in people with type 1 diabetes.


Induction of fetal wastage in pregnant mice passively immunized to murine alpha-fetoprotein.
Pregnant mice of various gestational ages were injected with purified rabbit IgG preparations of antibodies to mouse alpha-fetoprotein (AFP). Abortion of the fetuses was induced using 5-10 mg of total IgG, while 1.0 mg or less produced fetal wastage (death) depending on gestational age. While antibody-induced abortion occurred within 24 hrs, fetal death required 48-72 hrs for completion. Various non-IgG and control IgG solutions at comparable concentrations showed little or no effect in age-matched control mice. IgG preparations rendered devoid of specific anti-AFP antibodies were incapable of inducing fetal death following 3 cycles through immunoabsorbent chromatography. It was further observed that: 1) low concentrations of anti-AFP IgG appeared responsible for fetal death in early pregnancy and, 2) that antibodies, which did not readily bind to an affinity column, may possibly have caused fetal resorption. Finally, comparable studies in pregnant rats administered rabbit anti-rat AFP IgG did not exhibit abortion but only meager fetotoxic effects.


Visual neurons: categorization-based selectivity.
A computational framework that can account for object categorization and identification has gained empirical support from recent studies of monkey behavior and neurophysiology.


Application of Raman spectroscopy to forensic fibre cases.
Five forensic fibre cases in which Raman spectroscopy proved to be a good complementary method for microspectrophotometry (MSP) are described. Absorption spectra in the visible range are indeed sometimes characteristic ofa certain dye but this one can be subsequently identified unambiguously by Raman spectroscopy using a spectral library. In other cases the comparison of Raman spectra of reference fibres and suspect fibres led to an improvement of the discrimination power. The Raman measurements have been performed directly on mounted fibres and the spectra showed only little interference from the mounting resin and glass. Raman spectroscopy is therefore a powerful method that can be applied in routine fibre analysis following optical microscopy and MSP measurements.


Transition into a new job.
Tips and suggestions on how to successfully transition in the first 100 days in a new job.


Endoscopic Molecular Imaging plus Photoimmunotherapy: A New Strategy for Monitoring and Treatment of Bladder Cancer.
Due to the high recurrence and progression rate of non-muscle invasive bladder cancer after transurethral resection of bladder tumor, some new optical imaging technologies have arisen as auxiliary imaging modes for white light cystoscopy to improve the detection rate of small or occult tumor lesions, such as photodynamic diagnosis, narrow-band imaging, and molecular imaging. White light cystoscopy is inadequate and imperfect for bladder cancer detection, and thus residual tumors or coexisting flat malignant lesions, especially carcinoma in situ, would be ignored during conventional resection. The bladder, a hollow organ with high compliance, provides an ideal closed operation darkroom for endoscopic molecular imaging free from interference of external light sources. Also, intravesical instillation of a molecular fluorescent tracer is simple and convenient before surgery through the urethra. Molecular fluorescent tracer has high sensitivity and specificity to tumor cells, and its mediated molecular imaging allows small or occult tumor lesion detection while minimizing false-positive results. Meanwhile, endoscopic molecular imaging provides a real-time and dynamic image during surgery, which helps urologists to perform high-quality and complete tumor resection through accurate judgment of tumor boundaries and depth of invasion. Photoimmunotherapy is a novel molecular targeted therapeutic pattern of photodynamic therapy that kills malignant cells selectively and minimizes the cytotoxicity to normal tissues. The combination of endoscopic molecular imaging and photoimmunotherapy used in initial treatment may avoid the need of repeat transurethral resection in strictly selected patients and improve oncological outcomes such as recurrence-free survival and overall survival after operation.


Extended-wear contact lenses in patients with corneal grafts and aphakia.
Extended-wear contact lenses (EWCL) were fitted successfully on 61 aphakic eyes with penetrating corneal grafts. In two- to 32-months follow-up there were 26 eyes that had varying amounts of superficial neovascularization of the grafts and one Staphylococcus epidermidis corneal graft ulcer. There were five homograft rejections, all occurring in severely diseased eyes. Variable vision and visual acuity less than that with hard contact lenses or aphakic spectacles were the most frequent problems. Both were due to the high corneal astigmatism present in many patients. The results indicate that EWCLs may be used safely by patients with penetrating corneal grafts and aphakia, particularly if there is no host corneal edema, scarring, or vascularization, if these are no synechias to the graft wound, and if the astigmatism is less than 3.0 diopters.


Fatty acid and carotenoid composition of Rhodotorula strains.
Lipid content and composition of fatty acids with 6-25 carbon atoms were studied on strains of the 13 pink or red yeast species belonging to the genus Rhodotorula. The total amount of lipid represented an average of 13% of the dry weight. The neutral and polar lipid fractions were analyzed separately. For all the strains studied, the major fatty acids in both fractions were oleic, linoleic and palmitic acids, which formed 80% of the total number of fatty acids. A notable amount of arachidonic acid, a precursor of eicosanoid hormones, was found in R. acheniorum, R. aurantiaca and R. bacarum. Depending on the strain, 1-10 carotenoid pigments were detected; beta-carotene was always the major carotenoid present.


Characterization of the New World monkey homologues of human poliovirus receptor CD155.
In contrast to Old World monkeys, most New World monkeys (NWMs) are not susceptible to poliovirus (PV), regardless of the route of infection. We have investigated the molecular basis of restricted PV pathogenesis of NWMs with two kidney cell lines of NWMs, TMX (tamarin) and NZP-60 (marmoset), and characterized their PV receptor homologues. TMX cells were susceptible to infection by PV1 (Mahoney) and PV3 (Leon) but not by PV2 (Lansing). Binding studies to TMX cells indicated that the formation of PV/receptor complexes increased when measured first at 4 degrees C and then at 25 degrees C, whereas PV2 did not significantly bind to TMX cells at either temperature. On the other hand, NZP-60 cells were not susceptible to infection by any of the PV serotypes. However, a low amount of PV1 bound to NZP-60 cells at 4 degrees C, but there was no increase of binding at 25 degrees C. In contrast, both NWM cell lines supported genome replication and virion formation when transfected with viral RNAs of either serotype, an observation indicating that infection was blocked in receptor-virus interaction. To overcome the receptor block, we substituted 3 amino acids in the marmoset receptor (nCD155), H80Q, N85S, and P87S, found in the human PV receptor, hCD155. Cells expressing the mutant receptor (L-nCD155mt) were now susceptible to infection with PV1, which correlated with an increase in PV1-bound receptor complexes from 4 degrees C to 25 degrees C. L-nCD155mt cells were, however, still resistant to PV2 and PV3. These data show that an increase in the formation of PV/receptor complexes, when measured at 4 degrees C and at 25 degrees C, correlates with and is an indicator of successful infection at 37 degrees C, suggesting that the complex formed at 25 degrees C may be an intermediate in PV uptake.


Effect of chlorine dioxide and its metabolites in drinking water on fetal development in rats.
The chlorination of surface waters is known to form trihalomethanes. Therefore, chlorine dioxide (C1O2) is being considered as an alternative disinfectant. This study was designed to determine the effect of chlorine dioxide and its metabolites, chlorite (C1O-2) and chlorate (C1O-3), on rat fetuses exposed in utero. Female rats were administered C1O2 at 0, 1, 10 and 100 mg 1(-1) and C1O-2 or C1O-3 at 1 and 10 mg 1(-1) daily in the drinking water for 2 1/2 months prior to the throughout gestation. Rats were killed on day 20 and fetuses examined for external, skeletal and visceral malformations. Slight decreases in weight gain during pregnancy were seen in the C1O2 administered groups. A significant dose-response relationship in the decreases of the numbers of implants and live fetuses were observed in the C1O2 groups. Although there were increased incidences of resorptions in the C1O-2 and C1O-3 groups, no statistically significant increase was found in the groups. Fetal weight was significantly increased in the 100 mg 1(-1) C1O2 group. Also, fetal length was increased in the 10 mg 1(-1) C1O-2 and C1O-3 treatment groups. Skeletal defects, such as incompletely ossified or missing sternebrae, rudimentary ribs and incompletely ossified skull bones were increased in all treatment groups, but none were significantly different from the control group. A few cases of hypoplastic kidney, hydronephrosis and dextrocardia were observed in the treatment groups.


Three polymorphisms of renin-angiotensin system and preeclampsia risk.
Some data suggest an association between the single nucleotide polymorphisms AGT T704C, ACE I/D, and AT1R A1166C and preeclampsia, but overall, the data are conflicting; the aim of our study was to discover a more stable and reliable association between these polymorphisms and PE risk. A comprehensive literature search for this meta-analysis was conducted. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength, and heterogeneity test was conducted. Trial sequential analysis was also performed. A total of forty studies were finally included in our meta-analysis. The AGT T704C polymorphism was associated with PE risk in three genetic models (dominant OR = 1.33, 95%CI = 1.12-1.59; heterozygote OR = 1.26, 95%CI = 1.05-1.52; homozygote OR = 1.44, 95%CI = 1.14-1.83). No heterogeneity was observed in the three genetic models for the ACE I/D polymorphism. For subgroup analysis by geography, no significant association was detected. Significant associations were observed in mixed race, early-onset, late-onset, and more than 200 subgroups for the AT1R A1166C polymorphism; however, only one study was analyzed in these subgroups. Our results indicated the AGT T704C and ACE I/D polymorphisms were associated with an increased risk of PE. Increased risks were also observed for the two polymorphisms in subgroups including Asians, Europeans, Caucasoid, and Mongoloid. Moreover, an increased PE risk with the ACE I/D polymorphism in the severe PE population was also detected. Regarding the AT1R A1166C polymorphism, weak associations were observed, but further studies are required.


Mechanism of the decreased renal blood flow in the potassium-depleted conscious rat.
Although chronic potassium deficiency is a common clinical problem, the hemodynamic consequences of chronic sustained potassium depletion have not been clearly delineated. In this study, the hemodynamic consequences of chronic potassium depletion were evaluated in the conscious rat. Potassium-depleted rats had a decrease in mean arterial pressure which was caused by a decrease in systemic vascular resistance. In association with these changes in systemic hemodynamics, renal blood flow (RBF) was also decreased. The decreased renal blood flow was caused by an increased renal vascular resistance (RVR). Because plasma renin activity was increased the role of angiotensin II as a renal vasoconstrictor was evaluated by utilizing two angiotensin antagonists. Although the administration of saralasin to potassium-depleted rats did not alter systemic hemodynamics, RVR was decreased and RBF was increased. Similar results were obtained with the converting enzyme inhibitor teprotide. Because products of endoperoxide metabolism may cause renal vasoconstriction, the role of prostaglandins and thromboxanes as renal vasoconstrictors were evaluated by utilizing cyclo-oxygenase and thromboxane synthetase inhibitors. None of these agents altered systemic hemodynamics. Following the administration of indomethacin, RVR was decreased and RBF was increased in potassium-depleted rats. Similar results were obtained with another cyclo-oxygenase inhibitor, meclofenamate, and with imidazole, an inhibitor of thromboxane synthetase. Because neither angiotensin II nor products of endoperoxide metabolism could alone account for the increased renal vascular resistance of potassium depletion, studies were performed in potassium-depleted rats treated with indomethacin plus either saralasin or teprotide. In these potassium-depleted animals, renal blood flow was restored to normal. In conclusion, the decrease in renal blood flow and the increase in renal vascular resistance in potassium depletion is mediated by angiotensin II and a product of prostaglandin endoperoxide metabolism, most likely, thromboxane.


Nitrogen removal and microbial community shift in an aerobic denitrification reactor bioaugmented with a Pseudomonas strain for coal-based ethylene glycol industry wastewater treatment.
An aerobic denitrification system, initially bioaugmented with Pseudomonas strain T13, was established to treat coal-based ethylene glycol industry wastewater, which contained 3219 ± 86 mg/L total nitrogen (TN) and 1978 ± 14 mg/L NO3--N. In the current study, a stable denitrification efficiency of 53.7 ± 4.7% and nitrite removal efficiency of 40.1 ± 2.7% were achieved at different diluted influent concentrations. Toxicity evaluation showed that a lower toxicity of effluent was achieved when industry wastewater was treated by stuffing biofilm communities compared to suspended communities. Relatively high TN removal (~50%) and chemical oxygen demand removal percentages (>65%) were obtained when the influent concentration was controlled at below 50% of the raw industry wastewater. However, a further increased concentration led to a 20-30% decrease in nitrate and nitrite removal. Microbial network evaluation showed that a reduction in Pseudomonas abundance was induced during the succession of the microbial community. The napA gene analysis indicated that the decrease in nitrate and nitrite removal happened when abundance of Pseudomonas was reduced to less than 10% of the overall stuffing biofilm communities. Meanwhile, other denitrifying bacteria, such as Paracoccus, Brevundimonas, and Brucella, were subsequently enriched through symbiosis in the whole microbial network.


Dealing with stress and trauma in families.
Traditional models of individual adaptation to stress increasingly are being supplemented with family-based conceptualizations of stress appraisal, coping, and resiliency. This article begins with a brief description of a theoretic framework for understanding how families evaluate stressors and their own coping resources and how this process guides their response to stress. Characteristics associated with successful family adaptation to stress then are outlined in relation to a number of both normative and unexpected stressors. Most families at some point experience stress in the context of normative transitions, such as changes in family composition through birth, maturation, or family break-up. Severe unexpected stressors that place significant strain on family functioning include serious illness, death, violence, and both natural and man-made disasters. Recommendations for therapeutic interventions with families are provided.


Characterization of a novel T-cell lymphoma cell line established from a patient with systemic lupus erythematosus-associated lymphoma.
A malignant lymphoma developed in a 46-year-old male patient who had had systemic lupus erythematosus (SLE) for 18 years. The lymphoma was at disease stage IV at initial examination, and the patient died shortly thereafter. The lymphoma cells were cultured in vitro, and a continuous cell line, named SMZ-1, was established. The SMZ-1 cells, as well as the parental lymphoma cells, were of helper/inducer T-cell immunophenotype; they were positive for CD2, CD3, and CD4 antigens, and negative for CD8. Expression of CD5 and CD7 antigens was observed in a small percentage of the cells. The activation markers identified by antibodies against CD25, CD71, and HLA-DR antigens were positive. Cytogenetic analysis revealed that the SMZ-1 cells had a characteristic translocation between chromosomes 6 and 14 [t(6;14)(p21.1;q24)]. Southern blot analysis of DNA extracted from the cells demonstrated clonal rearrangement of the T cell receptor beta-chain gene. Integration of the human T-cell lymphotrophic virus type I (HTLV-I) genome was negative. The SMZ-1 cell lines should thus provide a useful model for characterization of peripheral T-cell lymphomas.


The feasibility of a randomized controlled crossover trial to assess the effect of probiotic and prebiotic supplementation on the health of elite wheelchair athletes.
Gastrointestinal (GI) problems represent a health burden in Para athletes and can ultimately reduce athletic performance. This study aimed to evaluate the feasibility of a randomized controlled crossover trial (RCCT) assessing the effects of probiotic and prebiotic supplementation on the health of Swiss elite wheelchair athletes. The RCCT was conducted between March 2021 and October 2021. Athletes were randomized to receive either a daily probiotic (3 g of probiotic preparation, including eight bacterial strains), or a daily prebiotic (5 g of oat bran) supplementation first. After the first supplementation phase (4 weeks), a washout period (4 weeks) and the second crossover supplementation phase (4 weeks) followed. Data were collected at four study visits (every 4 weeks) and included 3-day training and nutrition diaries, the Gastrointestinal Quality of Life Index (GIQLI) questionnaire, stool samples, and fasting blood samples. The study assessed the feasibility criteria such as recruitment rate, retention rate, success of data collection, adherence to the protocol, willingness to participate, and safety. This pilot study met the majority of the predefined minimum requirements for the feasibility criteria. Out of 43 invited elite wheelchair athletes, 14 (33%) consented (mean (standard deviation) age: 34 (9) years, eight females, 11 with a spinal cord injury). The desired sample size was not reached, but the achieved recruitment rate was modest, especially considering the population studied. All participating athletes completed the study. With the exception of one missing stool sample and two missing diaries, data were successfully collected for all athletes at all four visits. Most athletes adhered to the daily intake protocol for at least 80% of the days, both for probiotics (n = 12, 86%) and prebiotics (n = 11, 79%). Ten (71%) athletes would be willing to participate in a similar study again. No serious adverse events occurred. Despite the limited number of elite wheelchair athletes in Switzerland and the modest recruitment rate, the implementation of a RCCT in elite wheelchair athletes is feasible. The data collected in this study provide essential information for the design of the subsequent study which will include a larger cohort of physically active wheelchair users. Swiss Ethics Committee for Northwest/Central Switzerland (EKNZ), 2020-02337). gov, NCT04659408.


Exploring the Contextual Factors of Religious Leader Participation in Health Communication: Evidence from a Qualitative Study in Sierra Leone.
As there are many and sometimes ambivalent intersections of health and religion, strategic collaborations with religious opinion leaders in health campaigns have been increasingly explored. Despite the known influence of distinct contextual factors within emergency and non-emergency settings, existing research seldom distinguishes between those different factors and their impact on the inclusion of religious leaders as health messengers. To compare the contextual factors of religious leaders as health messengers during emergency and non-emergency situations in a setting with high religious affiliations, this study used a qualitative approach and triangulated the perspectives of three different samples, including (religious) opinion leaders, members of religious communities, and developers of health communication strategies in Sierra Leone. The results provide multifaceted insights into contextual factors applicable to emergency and non-emergency settings as well as the risks and opportunities. Recommendations for the incorporation of religious leaders in health promotion activities in consideration of different contextual factors are provided.


Recent advances in cardiac positron emission tomography for quantitative perfusion analyses and molecular imaging.
Positron emission tomography (PET) has been used to noninvasively evaluate myocardial perfusion and metabolism. For clinical assessments of myocardial perfusion, the quantitative capability of PET permits precise assessments of ischemia and microcirculatory dysfunction, playing an important role in patient management and outcome analyses. 18F-fluorodeoxyglucose (FDG) PET has recently been used to identify active cardiovascular lesions such as cardiac sarcoidosis, endocarditis, and aortitis. This may hold promise for the early and accurate diagnosis of such fatal diseases, as well as for patient management. This review covers new and clinical roles of cardiac PET in treatment strategies and patient outcomes.


Differential effects of L-dopa and apomorphine on glucagon secretion in man: evidence against central dopaminergic stimulation of glucagon.
In 6 normal subjects, L-dopa (500 mg PO) and apomorphine (0.6 mg sc) increased circulating growth hormone and suppressed prolactin levels in a parallel and quantitatively similar fashion, but only L-dopa induced a rise in plasma glucagon, glucose, and insulin levels. The failure of apomorphine to affect glucagon secretion, despite a substantial effect on growth hormone and prolactin, was also observed in insulin-dependent diabetics known to exhibit A-cell hyperresponsiveness to various stimuli. In view of the highly dissimilar molecular and pharmacologic characteristics of L-dopa and apomorphine, these data do not exclude a local dopaminergic effect of L-dopa at the pancreatic level, but strongly militate against a central dopaminergic pathway for glucagon stimulation.


Biphasic extrathoracic pressure CPR. A human pilot study.
Alternating intrathoracic pressure by means of a chest cuirass can cause perfusion and ventilation equal to or better than standard cardiopulmonary resuscitation (CPR) for humans in cardiac arrest. Nonrandomized, nonblinded, crossover pilot study. Large urban emergency department. Five adult normothermic, nontraumatic, out-of-hospital cardiac arrest patients unresponsive to standard advanced cardiac life support. Right atrial and aortic catheters were inserted for pressure measurement and blood gas analysis while the patient was receiving standard CPR by a pneumatic compression device (Thumper). The Thumper was then replaced by a chest cuirass (Hayek Oscillator). Pressure and blood gas measurements were then repeated. The coronary perfusion pressure increased from -1.2 +/- 8.6 mm Hg to 6.2 +/- 6.9 mm Hg for a mean change of 7.4 +/- 3.1 mm Hg (p = 0.006). The compression phase gradient increased 10.0 +/- 21.9 mm Hg (p = 0.364). The venous to arterial PCO2 gradient decreased 44.5 +/- 32.3 mm Hg (p = 0.070). The oxygen extraction ratio increased 1.6 +/- 9.4 percent (p = 0.761). The mean arterial PO2 and PCO2 changed from 252 to 240 mm Hg (p = 0.836) and from 53 to 66 (p = 0.172) mm Hg, respectively. The Hayek Oscillator chest cuirass produced a significant improvement in the coronary perfusion pressure. There was a trend for improved systemic perfusion as indicated by an improved compression phase gradient and venous to arterial PCO2 gradient, although this was not supported by the lack of improvement in the oxygen extraction ratio. The cuirass also adequately oxygenates and ventilates unassisted by positive pressure ventilation.


Chlordecone lacks estrogenic properties in the male rat.
The reproductive toxicity of chlordecone has been hypothesized to derive from estrogen mimicry. To test this hypothesis, the effects of estradiol-17 beta, testosterone, and chlordecone on the male reproductive tract of 60-day-old male rats were compared after 72 days of exposure. Estradiol-17 beta (25 micrograms/week) and testosterone (945 micrograms/week), administered by polydimethylsiloxane capsules implanted subdermally, caused significant reductions in spermatogenesis, sperm motility, testicular capacity for secreting testosterone, and the weights of testes and epididymides. Estradiol-17 beta also caused significant declines in serum testosterone concentrations, and the weight of the prostate and seminal vesicles. Chlordecone, administered either by polydimethylsiloxane capsule or by ip injection, had no effect on any of these parameters, except to reduce significantly seminal vesicle weight at the highest dose of injected chlordecone, 7.5 mg/week. Therefore, chlordecone does not mimic estrogen in its effects on the reproductive system of the male rat.


Integrating predictive biomarkers and classifiers into oncology clinical development programmes.
The future of drug development in oncology lies in identifying subsets of patients who will benefit from particular therapies, using predictive biomarkers. These technologies offer hope of enhancing the value of cancer medicines and reducing the size, cost and failure rates of clinical trials. However, examples of the failure of predictive biomarkers also exist. In these cases the use of biomarkers increased the costs, complexity and duration of clinical trials, and narrowed the treated population unnecessarily. Here, we present methods to adaptively integrate predictive biomarkers into clinical programmes in a data-driven manner, wherein these biomarkers are emphasized in exact proportion to the evidence supporting their clinical predictive value. The resulting programme demands value from predictive biomarkers and is designed to optimally harvest this value for oncology drug development.


Prevalence of malaria and its risk factors in Lake Tana and surrounding areas, northwest Ethiopia.
In Ethiopia, malaria is a major concern to the health, and socio-economic development of the country because of its occurrence at the peak agricultural activities. Factors such as environmental, human host, parasite, and vector determine malaria transmission. Therefore, the present study was conducted to determine the prevalence and associated factors of malaria among febrile patients who visited selected health centres. Institutional-based cross-sectional study was conducted between October 2020 to July 2021 in eight selected health centres located in Lake Tana and its surrounding areas. A simple random sampling technique was used to select febrile patients. Thick and thin blood films were prepared and processed according to the WHO guidelines. Socio-demographic and malaria risk factors were collected from study participants who could read and write using a self-administered questionnaire, whereas face-to-face interview was used to collect information from those participants who could not write and read. The strength of association between risk factors and malaria was assessed using univariate and multivariate logistic regression models. Of the total (531) febrile patients, 75.3% were malaria negative and 24.7% (overall prevalence) were malaria confirmed cases. Most of the infections were caused by Plasmodium falciparum (72.5%) followed by Plasmodium vivax (23.7%) and mixed-species (3.8%). The highest prevalence was recorded in Kidist Hana (51.5%) followed by Robit (34.8%), Gorgora (30.3%), and Wusha Tiris (25%) health centres. In terms of months, the highest prevalence (37.5%) was detected in October whereas the lowest (14%) was in March. Logistic regression analysis revealed that gender (p = 0.023), educational level (p = 0.025), study month (p = 0.036), presence of eave in the house (p = 0.002) and wall openings (p = 0.041), not using bed nets (p = 0.001), sleeping in the same house with cattle (p = 0.031) and the distance between mosquito-breeding site and living house (p = 0.020) were explanatory risk factors significantly associated with malaria among studied participants. In this study, we confirmed that the occurrence of malaria prevalence was high and continued against the Ethiopian malaria elimination plan of 2021-2025. Therefore, to meet the goals of this plan, the current prevention and control efforts should be stepped up even better in the coming years.