Impact of periodontal treatment in combination with tonsillectomy plus methylprednisolone pulse therapy and angiotensin blockade for pediatric IgA nephropathy.
We previously reported the efficacy of extensive eradication of infectious foci in oral and ENT lesions, combined with tonsillectomy plus methylprednisolone (MP) pulse therapy, for curing pediatric Henoch-Schönlein purpura (HSP) and HSP nephritis. In the present study, we used this therapy in patients with pediatric IgA nephropathy (IgAN) to assess whether similar results could be obtained. In 11 pediatric patients newly diagnosed with IgAN, exploration for infectious foci showed severe oral infection, including dental caries and apical periodontitis, in many. The overall decayed, missing and filled teeth score was elevated to 5.91. Two patients had rhinosinusitis. After extensive treatment of infectious foci, patients underwent tonsillectomy plus MP pulse therapy with angiotensin II receptor blockade. Clinical remission was achieved in all patients with pediatric IgAN (various histologic grades). Remission was achieved by 7.2 ± 5.7 months after initiation of steroid therapy, and disappearance of proteinuria by 3.3 ± 3.0 months. The mean duration of oral steroid administration was 9.5 ± 3.6 months. No relapse has occurred during follow-up of 4.3 ± 2.4 y. Careful examination and thorough elimination of infectious foci in oral and ENT lesions can optimize the effect of tonsillectomy plus MP pulse therapy, promoting recovery from IgAN.


Intermittent, chronic fenfluramine administration to rats repeatedly suppresses food intake despite substantial brain serotonin reductions.
The mechanisms by which fenfluramine suppresses food intake and body weight have been linked to its ability to enhance transmission across serotonin synapses in brain. This drug initially lowers body weight and suppresses food intake, yet after repeated administration food intake soon returns to normal and body weight no longer decreases. Fenfluramine also causes rapid and prolonged reductions in brain serotonin concentrations, which might account for its loss of appetite suppression. This possibility has been evaluated in rats by assessing if intermittent, chronic fenfluramine administration could suppress food intake during each treatment period, and if so, whether such an effect occurs in the presence of reduced brain serotonin levels. Rats were injected once daily with 10 mg/kg D,L-fenfluramine for 5 days, and then received no injections for the next 5 days. Control rats received only vehicle injections. This 10-day sequence was repeated five more times. During each period of fenfluramine administration, daily food intake dropped markedly the first 1-2 days of treatment, but returned to pretreatment values by day 5. Daily food intake was normal or slightly above normal during non-injection periods. Body weight dropped modestly during each period of fenfluramine administration, and rose during each subsequent period when injections had ceased. Serotonin concentrations and synthesis rates in several brain regions were markedly reduced at early, middle, and late periods of the experiment. Despite the long-term reduction in brain serotonin pools produced by fenfluramine, the drug continues to reduce food intake and body weight. Several possible interpretations of these findings are considered, based on the multiple mechanisms through which this drug has been proposed to modify synaptic serotonin transmission.


Evaluation of positron emission tomography as a method to visualize subsurface microbial processes.
Positron emission tomography (PET) provides spatiotemporal monitoring in a nondestructive manner and has higher sensitivity and resolution relative to other tomographic methods. Therefore, this technology was evaluated for its application to monitor in situ subsurface bacterial activity. To date, however, it has not been used to monitor or image soil microbial processes. In this study, PET imaging was applied as a "proof-of-principle" method to assess the feasibility of visualizing a radiotracer labeled subsurface bacterial strain (Rahnella sp. Y9602), previously isolated from uranium contaminated soils and shown to promote uranium phosphate precipitation. Soil columns packed with acid-purified simulated mineral soils were seeded with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)FDG) labeled Rahnella sp. Y9602. The applicability of [(18)F]fluoride ion as a tracer for measuring hydraulic conductivity and (18)FDG as a tracer to identify subsurface metabolically active bacteria was successful in our soil column studies. Our findings indicate that positron-emitting isotopes can be utilized for studies aimed at elucidating subsurface microbiology and geochemical processes important in contaminant remediation.


Effects of body size, seed density, and soil characteristics on rates of seed harvest by heteromyid rodents.
Although it is well established that coexisting heteromyid rodent species forage in different microhabitats, we do not yet know the basis for divergent microhabitat choice. One possibility is that seed harvest rates differ among microhabitats, and each species forages where it can extract seeds most efficiently. Microhabitats vary in several factors that could affect heteromyid foraging efficiency, including seed density, soil organic content and particle size distribution. We have explored the effect of each of these variables on harvest rates of several species feeding from petri dishes containing known densities of millet seeds embedded in soil of known particle size and density. Results indicate that the number of seeds harvested per second increases uniformly with seed density and soil density and decreases with soil particle size. Body size affects these relationships: larger animals have higher harvest rates for a given set of conditions and experience a greater relative change in harvest rate for a give change in conditions. This implies that heteromyids can be expected to exhibit species-specific microhabitat preferences while foraging in nature.


"Over-the-Top" Anterior Cruciate Ligament Reconstruction Associated With a Lateral Extra-Articular Tenodesis in Children.
Anterior cruciate ligament (ACL) tears are one of the most frequent injuries in growing children, and they are often associated with other injuries such as meniscal and chondral injuries. In the past, treatment of ACL tears in growing patients relied on activity modification and bracing. However, surgical treatment has prevailed over conservative treatment in recent years. A surgical technique is presented for ACL reconstruction using an "over-the-top" technique associated with a lateral extra-articular tenodesis procedure in children. An extra-articular lateral tenodesis is done first. The gracilis and semitendinous tendons are then extracted using a tenotome without releasing their distal desinsertions. The tibial guide is then centered over the ACL tibial footprint under arthroscopic vision and an image intensifier, proximal to the physis. Then, a Kocher-type forceps is used to pass a suture "over the top" from the posterolateral window to the tibial tunnel. The double-bundle graft and iliotibial tract graft are fixed within the tunnel in full extension and neutral rotation with an interference screw.


[Adolescence and type 1 diabetes: self-care and glycemic control].
Type 1 diabetes is one of the most frequent chronic diseases in children and adolescents. Self-care support is a crucial aspect of the medical care provided to adolescent patients with type 1 diabetes. In the perspective of health promotion, which seeks to empower people to become the actors of their own health, self-care may be operationalized in three dimensions: psychosocial life, general health, and disease. We looked at the process of autonomization in adolescents 13-15 years of age, and hypothesized that their level of glycemic control (HbA1c) would be related to their perceived level of self-care. We conducted an exploratory study through 32 in-depth interviews with adolescents aged 13-15 years. The data collected was analyzed quantitatively and qualitatively, based on the annual mean HbA1c level. Significantly higher scores of perceived self-care were associated with levels of HbA1c ≤ 7.5% (P=0.038). Overall, adolescents with good glycemic control reported greater autonomy and complexity in self-care behaviors in all three dimensions of self-care. Moreover, our results show that adolescents with poor glycemic control tend to restrict the definition of self-care to its medical dimension and to exclude the psychosocial dimension. Our study confirms the hypothesis of a relation between HbA1c and the self-reported level of self-care in adolescents with type 1 diabetes. Moreover, it emphasizes the need to better respond to the young patients' psychosocial needs, in order to improve the long-term follow-up of adolescents with type 1 diabetes.


Object attachment and decision-making.
The perceived value of our possessions extends well beyond their monetary worth or utility. Many possessions produce abiding attachments and contain deep conceptual meanings, which strongly influence our drive to acquire, retain, or relinquish them. In both the endowment effect and hoarding disorder (HD) research had focused on the degree that a fear of loss produces overvaluation by owners. There is evidence for this at both the behavioral and neural level, for example with self-reported negative emotions and activation in the insula and anterior cingulate cortex when one struggles to relinquish a good. However, there is also evidence from both fields that positive appraisals, motivations, and attachments participate in this process, with supporting activation in the dopaminergic mesolimbocortical system (e.g. nucleus accumbens and orbitofrontal cortex). These processes appear continuous between typical and clinical populations and with decisions about rewarding items in other contexts and species, such as food storing in rodents and offspring care in mammals. More research is needed on the degree that our attachment to and protection of goods reflect ancient neural systems for offspring care. We also need to study participants from other demographics and levels of wealth, and to consider how task framing shifts the proportion of associated negative and positive emotional states.


An efficient electrochemical assay for miR-3675-3p in human serum based on the nanohybrid of functionalized fullerene and metal-organic framework.
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unclear pathogenesis, for which diagnosis has been a great challenge. Recent researches have revealed that miR-3675-3p is a promising biomarker for IPF diagnosis. Herein, the present work describes a novel electrochemical microRNA biosensor for rapid and sensitive detection of miR-3675-3p based on multiple signal amplification strategies. First of all, fullerene (C60) is doped with poly(amidoamine) (PAMAM)-functionalized metal-organic framework (MOF) to form a new nanohybrid of C60@PAMAM-MOF, which exhibits more remarkable redox activity compared with the other two synthesized C60-based nanohybrids when triggered by tetraoctylammonium bromide (TOAB). C60@PAMAM-MOF also possesses a large specific surface area and abundant amino groups to anchor Au nanoparticles (AuNPs) for the immobilization of signal probe (SP) to form tracer label and enhance the electrochemical response signal. In addition, core@shell Au-Pt nanoparticles (Au@PtNPs) are absorbed on chitosan-acetylene black (CS-AB) to act as sensing platform, which can promote electron transfer and increase the loading of capture probe (CP). Under optimum conditions, the proposed biosensor displays a wide linear range for miR-3675-3p from 10 fM to 10 nM, with a limit of detection (LOD) as low as 2.99 fM. More significantly, this biosensor shows a lower LOD and wider linear range than that of qRT-PCR, and its trial application in human serum shows favorable results, which exhibits a promising prospect for IPF diagnosis.


Identification of patients at high risk of secondary extramedullary multiple myeloma development.
Multiple myeloma (MM) is characterized by malignant plasma cell infiltration of the bone marrow. In extramedullary multiple myeloma (EMD), a subclone of these cells migrates out of the bone marrow. Out of 4 985 MM patients diagnosed between 2005 and 2017 in the Czech Republic, we analyzed 234 secondary EMD patients to clarify risk factors of secondary EMD development. We found younger age [<65 years; odds ratio (OR) 4·38, 95% confidence interval (CI): 2·46-7·80, P < 0·0001], high lactate dehydrogenase (LDH) levels (>5 μkat/l; OR 2·07, 95% CI: 1·51-2·84, P < 0·0001), extensive osteolytic activity (OR 2·21, 95% CI: 1·54-3·15, P < 0·001), and immunoglobulin A (IgA; OR 1·53, 95% CI: 1·11-2·11, P = 0·009) or the non-secretory type of MM (OR 2·83; 95% CI: 1·32-6·04, P = 0·007) at the time of MM diagnosis to be the main risk factors for secondary EMD development. Newly diagnosed MM (NDMM) patients with subsequent EMD had inferior median progression-free (PFS) and overall (OS) survival when compared to NDMM patients without future EMD [mPFS: 13·8 months (95% CI: 11·4-16·3) vs 18·8 months (95% CI: 17·7-19·9), P = 0·006; mOS: 26·7 months (95% CI: 18·1-35·4) vs 58·7 months (95% CI: 54·8-62·6), P < 0·001]. We found that NDMM patients with specific risk factors associated with secondary EMD development have a more aggressive disease course before secondary EMD develops.


Skeletal muscle mitochondria: the aerobic gate?
At an animal's maximum aerobic capacity (VO2max), the O2 flowing through the respiratory system is consumed by a functionally exclusive sink, skeletal muscle mitochondria. Thus, O2 consumption will never exceed the muscles O2 demand. If the system is ideally designed, structures upstream to the skeletal muscle O2 sink must be built to insure adequate O2 delivery to the working muscle. There are a number of structure-function solutions available to supply the demanded O2 to the muscle; these have been found to vary, often ontogenetically, with hypoxia, training, etc. But there is one relationship that is invariant: Total O2 uptake can be predicted by the total (active) skeletal muscle mitochondrial volume. In aerobic and sedentary animals, across a range of body sizes, maximum (in vivo) mitochondrial O2 consumption is constant among mammals (at approximately 2000 O2 molecules per square micron of inner mitochondrial membrane per second). Because the volume of mitochondria is one of the most plastic of all respiratory structures, we interpret this relationship as suggesting that skeletal muscle mitochondria alone sets the demand for O2 and, thus, the volume of skeletal muscle mitochondria dictates an animal's maximum aerobic capacity.


A direct access to heptasubstituted biguanides.
An efficient and experimentally simple copper-catalyzed carbon-nitrogen bond formation for the synthesis of [Formula: see text]-arylated biguanides starting from aryl halides, carbodiimides, and 1,1,3,3-tetramethylguanidine is reported. The potential diversity of this type of reaction, easily available starting materials, and commercially available low-cost catalysts are the incremental features of this methodology.


Determination and photodegradation of sertraline residues in aqueous environment.
Sertraline is an antidepressant drug that has been frequently reported in the aquatic environment and biota. While the research has mostly dealt with its occurrence and toxicity, there is a lack of information pertaining to its environmental transformation. The present study aimed to fill in these gaps by giving an insight into mechanisms of sertraline phototransformation in surface waters, which was recognized as the main transformation pathway for this contaminant. We performed photodegradation experiments in presence of photosensitizers or reaction quenchers to determine rate constants and used them to predict sertraline phototransformation kinetics by "Aqueous Photochemistry of Environmentally occurring Xenobiotics" (APEX) software. It was established that sertraline degrades by pseudo-first order kinetics mostly dominated by direct photolysis, while the presence of certain reactive species including •OH, CO3-• and 3CDOM* further accelerate the compound's breakdown rate. To validate the predicted results, sertraline-spiked surface water was irradiated by sunlight, where the half-life of sertraline at around 1.4 days was estimated. While following the photodegradation kinetics, we also identified five transformation products, of which three were determined in Slovenian surface waters. According to the ECOSAR toxicity prediction, these transformation products will either have comparable or lower toxicity than their parent compound.


Deciphering the floatation reversibility of anammox sludge: A balance between sludge rheological intensity and external hydraulic shearing.
Sludge floatation is inevitable in anammox granular reactors, which reduces the effective granules participating in anammox reaction and weakens the robust operation of anammox reactors. However, so far, the involved floatation mechanisms as well as the floatation mitigation measurements have not been well proposed. In this study, floating sludge (including irreversibly floating sludge (FSI) and reversibly floating sludge (FSR)) and settled granule sludge (SGS) were collected from an anammox expanded granular sludge bed (EGSB) reactor and compared in terms of morphological, physical, chemical and microbial properties. The particle size ranked FSI > SGS > FSR, and cavities were distinctly observed in FSI due to the gas pockets and cell lysis. Rheological measurements revealed that the storage modulus (represent intensity of sludge) of FSI and SGS were comparable, both of which were approximately1.4 times greater than that of FSR. High storage modulus indicated that the hydraulic shear force in the EGSB was not strong enough to destroy FSI and release the gases trapped in gas pocket, resulting in the irreversible floatation of FSI. Whereas, the dinitrogen gases adhered onto FSR were readily stripped from FSR under hydraulic shearing, which contributed to their reversible floatation property. It is concluded that sludge floatation is resulted from the gas accumulation or gas adhesion onto the sludges, while the sludge floatation reversibility depends on the sludge intensity and hydraulic shear force. Our findings elucidate the floatation properties of anammox sludge via rheological analysis, which will contribute to the proper sludge floatation control and facilitate the optimization of anammox granule fluidization in EGSB reactor.


Aging effects of haptic input on postural control under a dual-task paradigm.
Postural control relies on three principal sensory systems: vision, vestibular and proprioceptive; that are affected by aging. When performing a cognitive task concomitantly with a motor task, those sensory impairments lead to even greater deleterious effects on balance. We aimed to study the effects of a sensory aid (a light touch) on a dual task paradigm and sought to understand the different responses on balance due to aging. Fifty healthy and highly physical active women were divided in two groups: young (N = 25, 24.2 ± 4.0 years) and older adults (N = 25, 67.3 ± 4.2 years). In a random and balanced order, all participants performed five tasks: Stroop test while seated (Seated); Stroop test while standing quiet (ST); Standing quiet (BL); Standing quiet with a haptic input (LT); and Stroop test with a haptic input while standing quiet (SL). In the Stroop test, older women committed more errors (50 vs 11 errors, p < 0.001) and had higher reaction time (1.001 ± 0.191 vs 0.699 ± 0.081 s, p < 0.001). The haptic input (LT) reduced all body sway parameters, in both groups, regardless the condition. This means that postural control under a dual task paradigm (ST) deleterious effect can be mitigated by a haptic input.


"I have faith in my milk": the meaning of milk for mothers of very low birth weight infants hospitalized in the neonatal intensive care unit.
Mothers who deliver a premature infant often choose to provide milk because it is the "one thing that only the mother can do" to optimize her infant's outcome, helps mothers feel a connection with their infants, and helps relieve the guilt associated with the preterm birth. The purpose of this study was to describe the meaning of milk for mothers who are providing milk for their very low birth weight (VLBW; < 1500 g) infants hospitalized in the neonatal intensive care unit (NICU). Using a qualitative descriptive design, in-depth semistructured interviews were conducted with 23 mothers of VLBW infants hospitalized in a level III NICU. Mothers were asked to share their perceptions about what providing milk meant to them. Mothers had faith in the healing properties of their milk and equated providing milk with "giving life" to their infants, mitigating the effects of complications, keeping their infants healthy and stable, and helping themselves address the feelings of failure and guilt associated with the premature birth. Mothers' faith in their milk to achieve these outcomes was a maternal motivator to continue pumping, even for mothers who had not intended to provide milk or who experienced the paradox of disliking pumping but wanting to provide their milk. The experiences of these mothers reflect the importance of acknowledging mothers' faith in the healing properties of their milk as a motivating factor for sustaining lactation while coping with the stress and anxiety inherent during the infant's NICU hospitalization.


Preclosure of large bore venous access sites in patients undergoing transcatheter mitral replacement and repair.
We aim to report on the efficacy and safety of large bore venous access (LBVA) preclosure with Perclose™ (Abbott Vascular Devices) suture-mediated device use following transcatheter edge-to-edge (TEER) and replacement (TMVR). Patients requiring TEER and TMVR require LBVA. Clinical outcome data on the use of suture-mediated devices for LBVA site closure are limited. Between 2012 and 2019, 354 consecutive high-risk patients with mitral valvular heart disease underwent TEER (n = 287) with MitraClip and TMVR (n = 67) with Edwards Sapien Valves. Patients had LBVA with 24 or 16 French sheaths. All patients underwent preclosure of LBVA except for one that underwent manual hemostasis. There were no closure device failures. None of the cases required surgical repair of the access site following venous preclosure. Two cases had large hematomas (>6 cm) following Perclose in each group. Six cases had small hematomas (<6 cm and >2 cm) with three in each group. There was one major bleeding using Mitral Valve Academic Research Consortium 2 definition (retroperitoneal bleed from arterial puncture) unrelated to the venous closure. Transfusion related to vascular access complication was required in five cases. There were two immediate acute deep venous thromboses postprocedure; one of which occurred after preclosure. There were no arteriovenous malformations, pseudoaneurysms, or access site infections reported following Perclose. In this large sample size analysis, Proglide preclosure technique is a feasible and safe alternative approach to achieving hemostasis after removal of LBVA sheaths in patients undergoing TEER and TMVR. Randomized trials are needed to compare the different modalities of hemostasis.


A high-fat diet has sex-specific effects on nicotine vapor self-administration in mice.
Previous investigations have shown that fat-rich diets increase vulnerability to drug dependence, including nicotine. Despite this knowledge, few investigations into the neurochemical mechanisms have been completed. Our objective here was to examine if high-fat diet (HFD) impacted nicotine intake and in parallel examine potential changes in dopamine signaling. Adult male and female C57/BL6J mice were used in nicotine e-vape® self-administration (EVSA) assays after being maintained on a standard diet or HFD for 6 weeks. In a separate cohort of mice, dopamine release in the nucleus accumbens core was examined with fast-scan cyclic voltammetry. Female mice assigned to HFD exhibited increased nicotine EVSA during low-effort responding (FR1) when compared to standard-diet mice. HFD-assigned mice (male and female) also exhibited reduced active nose pokes in a progressive ratio task. Finally, HFD-mice exhibited reduced phasic dopamine release compared to standard-diet mice. These show that fat-rich diets alter nicotine intake (females increase at low effort, males and females decrease at high effort) and this may occur due to HFD-induced decreases in NAc dopamine release.


Simultaneous determination of eight major bioactive compounds in Dachengqi Tang (DT) by high-performance liquid chromatography.
Dachengqi Tang (DT) is a common traditional Chinese medicine formula for expelling neire ('internal heat') in the stomach and intestines. There was no reliable analytical method available for the quality control of DT. A high-performance liquid chromatography (HPLC) method with a reverse phase C18 column (150 x 4.6 mm) was developed. The mobile phase was methanol with 0.2% acetic acid. Eight markers including naringin, hesperidin, aloe emodin, rhein, honokiol, magnolol, emodin and chrysophanol were determined. Regression analysis revealed a linear relationship between the concentrations of the markers and the peak area ratio of the standards and internal standard. The limit of detection (S/N = 3) and the limit of qualification (RSD < 20%) ranged from 0.21 to 0.43 ng/microl and 0.76 to 1.74 ng/microl respectively. The recovery was between 95.6% and 103.4%. The tests on the samples from three batches of DT showed that the profiles of the markers did not vary significantly among batches. A reliable HPLC method for simultaneous determination of the eight markers in DT was developed.


Three dimensional MRF obtains highly repeatable and reproducible multi-parametric estimations in the healthy human brain at 1.5T and 3T.
Magnetic resonance fingerprinting (MRF) is highly promising as a quantitative MRI technique due to its accuracy, robustness, and efficiency. Previous studies have found high repeatability and reproducibility of 2D MRF acquisitions in the brain. Here, we have extended our investigations to 3D MRF acquisitions covering the whole brain using spiral projection k-space trajectories. Our travelling head study acquired test/retest data from the brains of 12 healthy volunteers and 8 MRI systems (3 systems at 3 T and 5 at 1.5 T, all from a single vendor), using a study design not requiring all subjects to be scanned at all sites. The pulse sequence and reconstruction algorithm were the same for all acquisitions. After registration of the MRF-derived PD T1 and T2 maps to an anatomical atlas, coefficients of variation (CVs) were computed to assess test/retest repeatability and inter-site reproducibility in each voxel, while a General Linear Model (GLM) was used to determine the voxel-wise variability between all confounders, which included test/retest, subject, field strength and site. Our analysis demonstrated a high repeatability (CVs 0.7-1.3% for T1, 2.0-7.8% for T2, 1.4-2.5% for normalized PD) and reproducibility (CVs of 2.0-5.8% for T1, 7.4-10.2% for T2, 5.2-9.2% for normalized PD) in gray and white matter. Both repeatability and reproducibility improved when compared to similar experiments using 2D acquisitions. Three-dimensional MRF obtains highly repeatable and reproducible estimations of T1 and T2, supporting the translation of MRF-based fast quantitative imaging into clinical applications.


Identification of an SP-1-like protein in non-pregnancy serum: isolation using a monoclonal antibody.
Human SP-1, a glycoprotein synthesized by the placenta during pregnancy, was shown to exist as polymers in maternal serum by a rapid passive transfer immunoblotting technique following conventional agarose electrophoresis. Moreover, the SP-1 polymers in serum were shown to dissociate into one main component upon treatment with 8 M urea prior to electrophoresis. However, an unexpected observation was the existence of an SP-1-like immunoreactive species in male serum with the sensitive immunoblotting technique. This SP-1-like protein in male serum had similar properties to its placentally derived counterpart in pregnancy serum, namely a propensity for complex formation and a reduced electrophoretic mobility following neuraminidase treatment. The relationship between the two SP-1 proteins was demonstrated by isolating them from their respective sera using an immobilized monoclonal antibody raised to purified SP-1 from pregnancy serum. Immunoblotting after sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed the existence of two major SP-1 species in pregnancy serum. These two SP-1 species had apparent molecular weights of 68,000 and 64,000. In addition, there were two minor bands at 35,000 and 32,000. These smaller SP-1 species did not appear to be subunits of the larger entities since they were detectable in the absence of reducing conditions. SDS-PAGE and immunoblotting showed that the immunoaffinity-purified SP-1 species from male and pregnancy sera had similar, but not identical, molecular weights.


Ligation of Intersphincteric Fistula Tract vs Ligation of the Intersphincteric Fistula Tract Plus a Bioprosthetic Anal Fistula Plug Procedure in Patients With Transsphincteric Anal Fistula: Early Results of a Multicenter Prospective Randomized Trial.
The purpose of this study was to compare the ligation of intersphincteric fistula tract (LIFT) with an additional plug (LIFT-plug) in the treatment of transsphincteric anal fistula. Both LIFT and LIFT-plug are recently reported effective alternatives of transsphincteric anal fistula. This multicenter prospective randomized study (NCT01478139) was conducted at 5 university hospitals throughout China. A total of 235 patients were randomly assigned to undergo LIFT (118 patients) or LIFT-plug (117 patients) between March 2011 and April 2013. The primary outcome measured was primary healing rate at 6 months postoperatively and healing time. Secondary outcomes included recurrence rate, postoperative pain, and incontinence rate. The LIFT procedure showed shorter operative time than the LIFT-plug procedure (26.7 min vs 28.5 min, P = 0.03). Median healing time was 22 days in LIFT-plug group vs 30 days in LIFT group (P < 0.001). The difference in visual analog scale scores across all time points was not statistically significant between the groups (P = 0.13). The primary healing rate was higher in LIFT-plug group than in LIFT group [94.0% (95% confidence interval 89.7%-98.3%) vs 83.9% (95% confidence interval 77.2%-90.6%), P < 0.001]. There were no reported incontinence and recurrence within the follow-up period of 6 months. In patients with transsphincteric anal fistulas, both LIFT-plug and LIFT are simple, safe, and effective procedures. LIFT-plug has the advantage of a higher healing rate, less healing time, and a lower early postoperative pain score.


Fat Grafting for Treatment of Facial Scars.
Autologous fat grafting has become more and more popular among plastic surgeons in the last few years due to recent discoveries on the mesenchymal stem cells stored in the harvested fat. These cells have a great regenerative potential and have the ability to restore the damaged tissues. The authors focused their practice on the treatment of the facial scars (derived from burns, trauma, degenerative diseases, and radiotherapy) and confirm that lipofilling is an excellent solution because it is able to improve the quality of the damaged tissues in terms of better scar color, pliability, thickness, relief, itching, pain, scar vascularization, and pigmentation.


General technoeconomic analysis for electrochemical coproduction coupling carbon dioxide reduction with organic oxidation.
Electrochemical processes coupling carbon dioxide reduction reactions with organic oxidation reactions are promising techniques for producing clean chemicals and utilizing renewable energy. However, assessments of the economics of the coupling technology remain questionable due to diverse product combinations and significant process design variability. Here, we report a technoeconomic analysis of electrochemical carbon dioxide reduction reaction-organic oxidation reaction coproduction via conceptual process design and thereby propose potential economic combinations. We first develop a fully automated process synthesis framework to guide process simulations, which are then employed to predict the levelized costs of chemicals. We then identify the global sensitivity of current density, Faraday efficiency, and overpotential across 295 electrochemical coproduction processes to both understand and predict the levelized costs of chemicals at various technology levels. The analysis highlights the promise that coupling the carbon dioxide reduction reaction with the value-added organic oxidation reaction can secure significant economic feasibility.


Characterization of recombinant homocitrate synthase from Candida albicans.
LYS21 and LYS22 genes from Candida albicans encoding isoforms of homocitrate synthase (HCS), an enzyme catalyzing the first committed step in the l-lysine biosynthetic pathway, were cloned and expressed as N-oligoHistagged fusion proteins in Escherichia coli. The purified gene products revealed HCS activity, i.e. catalyzed the condensation of α-ketoglutarate with acetyl-coenzyme A to yield homocitrate. The recombinant enzymes were purified to homogeneity and characterized for their physical properties and substrate specificities. As determined by size-exclusion chromatography (SEC) and native page electrophoresis, both isoenzymes adopt multiple quaternary structures, with the homotetrameric one being the most abundant. The KM (acetyl-CoA)=0.8±0.15mM and KM (α-ketoglutarate)=0.113±0.02mM for His6CaLys21p and KM (acetyl-CoA)=0.48±0.09mM and KM (α-ketoglutarate)=0.152±0.03mM values for His6CaLys22p were determined. Both enzyme versions were inhibited by l-Lys, i.e. the end product of the α-aminoadipate pathway but Lys22p was more sensitive than Lys21p, with Ki (L-Lys)=128±8μM for His6CaLys21p and Ki (L-Lys)=4.37±0.68μM for His6CaLys22p. The isoforms of C. albicans HCS exhibited differential sensitivity to several l-Lys analogues. Most notably, dl-α-difluoromethyllysine strongly inhibited His6CaLys22p (IC50 32±3μM) but was not inhibitory at all towards His6CaLys21p. Differential sensitivity of recombinant C. albicans Δlys21/LYS22, LYS21/Δlys22 and Δlys21/Δlys22 mutant strains to lysine analog, 2-aminoethyl-l-cysteine and biochemical properties of homocitrate synthase isoforms suggest different roles of two HCS isoenzymes in α-aminoadipate pathway.


Getting back to zero with nucleated red blood cells: following trends is not necessarily a bad thing.
The presence of nucleated red blood cells (NRBCs) has been identified as a poor prognostic indicator. We investigated the relationship of NRBC trends in patients with and without trauma. We retrospectively reviewed surgical intensive care unit admissions over 4 years, categorizing trauma and nontrauma patients and subdividing them into 3 groups: group A, all-zero NRBC; group B, positive NRBC value returning to zero; and group C, positive NRBC value that did not return to zero. We analyzed all groups for outcomes of length of stay and mortality. Group A was the largest and had the shortest length of stay and least mortality. Group C had the highest mortality rate. No statistical difference was observed with mortality. Any positive NRBC was associated with poor outcome, and increasing NRBC was associated with increasing mortality. Trends in NRBC values showed that returning to zero was protective.


Evaluation of the performance of calix[8]arene derivatives as liquid phase extraction material for the removal of azo dyes.
This paper presents a study on the removal of azo dyes (Reactive Black 5, Trapaeolin 000, Methyl Orange and Direct Violet 51) with calix[n]arene derivatives from aqueous solution into the organic phase in order to explore the potential use of calixarenes as low-cost efficient extractants for wastewater dye removal. The carboxylic acid derivative of calix[8]arene shows highest affinity towards the azo dyes. The influence of NaCl (present in the solution) on extraction process was also studied. The extent of the dye removal increased with the addition of NaCl. The proposed extraction mechanism involves several kinds of interactions: electrostatic repulsion between carboxylic acid groups of calix[8]arenes and sulfonate groups of azo dyes, hydrogen bonding and formation of an inclusion complex due to three dimensional cavity type calix[n]arene molecules through host-guest interactions.


Characterization of internal ribosomal entry sites of Triatoma virus.
Triatoma virus (TrV) belongs to a new family of RNA viruses known as Dicistroviridae. Nucleotide sequence comparisons between different dicistroviruses allowed two putative internal ribosomal entry sites (IRESs) in the TrV RNA to be defined: the 5'UTR IRES of 548 nt and the intergenic region (IGR) IRES of 172 nt. Using monocistronic and bicistronic RNAs, it was shown that the TrV genome contains two functional IRESs that mediate translation initiation in a cap-independent manner. In addition, it was found that the two TrV IRESs were able to direct efficient translation of reporter genes in microinjected Xenopus oocytes, suggesting minimum requirements for host factors. The IGR IRES begins with a non-canonical CUC; however, mutations of this triplet to AUG or CCU did not impair IRES function, indicating that the CUC is not essential for the initiation process. Furthermore, translation efficiency from two TrV IRESs was differentially modulated by IFN-alpha and viral infection.


Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.
Molecular chaperones and co-chaperones, which are part of the protein quality control machinery, have been shown to regulate distinct aspects of Alzheimer's Disease (AD) pathology in multiple ways. Notably, the co-chaperone STI1, which presents increased levels in AD, can protect mammalian neurons from amyloid-β toxicity in vitro and reduced STI1 levels worsen Aβ toxicity in C. elegans. However, whether increased STI1 levels can protect neurons in vivo remains unknown. We determined that overexpression of STI1 and/or Hsp90 protected C. elegans expressing Aβ(3-42) against Aβ-mediated paralysis. Mammalian neurons were also protected by elevated levels of endogenous STI1 in vitro, and this effect was mainly due to extracellular STI1. Surprisingly, in the 5xFAD mouse model of AD, by overexpressing STI1, we find increased amyloid burden, which amplifies neurotoxicity and worsens spatial memory deficits in these mutants. Increased levels of STI1 disturbed the expression of Aβ-regulating enzymes (BACE1 and MMP-2), suggesting potential mechanisms by which amyloid burden is increased in mice. Notably, we observed that STI1 accumulates in dense-core AD plaques in both 5xFAD mice and human brain tissue. Our findings suggest that elevated levels of STI1 contribute to Aβ accumulation, and that STI1 is deposited in AD plaques in mice and humans. We conclude that despite the protective effects of STI1 in C. elegans and in mammalian cultured neurons, in vivo, the predominant effect of elevated STI1 is deleterious in AD.


The Development of a Novel Nanobody Therapeutic for SARS-CoV-2.
Combating the COVID-19 pandemic requires potent and low-cost therapeutics. We identified a novel series of single-domain antibodies (i.e., nanobody), Nanosota-1, from a camelid nanobody phage display library. Structural data showed that Nanosota-1 bound to the oft-hidden receptor-binding domain (RBD) of SARS-CoV-2 spike protein, blocking out viral receptor ACE2. The lead drug possessing an Fc tag ( Nanosota-1C-Fc ) bound to SARS-CoV-2 RBD with a K d of 15.7picomolar (∼3000 times more tightly than ACE2 did) and inhibited SARS-CoV-2 infection with an ND 50 of 0.16microgram/milliliter (∼6000 times more potently than ACE2 did). Administered at a single dose, Nanosota-1C-Fc demonstrated preventive and therapeutic efficacy in hamsters subjected to SARS-CoV-2 infection. Unlike conventional antibody drugs, Nanosota-1C-Fc was produced at high yields in bacteria and had exceptional thermostability. Pharmacokinetic analysis of Nanosota-1C-F c documented a greater than 10-day in vivo half-life efficacy and high tissue bioavailability. Nanosota-1C-Fc is a potentially effective and realistic solution to the COVID-19 pandemic. Potent and low-cost Nanosota-1 drugs block SARS-CoV-2 infections both in vitro and in vivo and act both preventively and therapeutically.


STIP overexpression confers oncogenic potential to human non-small cell lung cancer cells by regulating cell cycle and apoptosis.
Sip1/tuftelin-interacting protein (STIP), a multidomain nuclear protein, is a novel factor associated with the spliceosome, yet its role and molecular function in cancer remain unknown. In this study, we show, for the first time, that STIP is overexpressed in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal lung tissues. The depletion of endogenous STIP inhibited NSCLC cell proliferation in vitro and in vivo, caused cell cycle arrest and induced apoptosis. Cell cycle arrest at the G2/M phase was associated with the expression and activity of the cyclin B1-CDK1 (cyclin-dependent kinase 1) complex. We also provide evidence that STIP knockdown induced apoptosis by activating both caspase-9 and caspase-3 and by altering the Bcl-2/Bax expression ratio. RNA sequencing data indicated that the MAPK mitogen-activated protein kinases, Wnt, PI3K/AKT, and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signalling pathways might be involved in STIP-mediated tumour regulation. Collectively, these results suggest that STIP may be a novel potential diagnostic and therapeutic target for NSCLC.


Porto-sinusoidal vascular disorder (PSVD): Application of new diagnostic criteria in a multicenter cohort of patients.
The term porto-sinusoidal vascular disorder (PSVD) was recently proposed to replace that of idiopathic non-cirrhotic portal hypertension (INCPH) to describe patients with typical histological lesions in absence of cirrhosis, irrespective of the presence/absence of portal hypertension (PH), and new diagnostic criteria were defined. The study aimed to compare the applicability between the diagnostic criteria of PSVD and those of INCPH. 53 patients affected by PSVD were enrolled. Biochemical, clinical, ultrasound and histological data, the presence and type of associated diseases were recorded in a database. According to the new criteria, histological data and signs of PH were divided into specific and non-specific. Percutaneous and transjugular biopsies were compared to establish the usability of the two methods for diagnostic purposes. In 85% of the patients the diagnosis of PSVD was obtained by applying the first criterion (25 had specific histological signs with specific signs of PH); one patient presented with specific histological signs but no PH. In 8 patients the diagnosis was obtained by applying the second criterion. 19% of patients had portal vein thrombosis. Finally, the prevalence of the various histological lesions was similar between the patients submitted to percutaneous and transjugular liver biopsy. The study confirms that the diagnostic criteria of PSVD lead to the inclusion of a greater number of patients than INCPH.


Diagnostic Efficacy of Ultrasonographic Characteristics of Thyroid Carcinoma in Predicting Cervical Lymph Node Metastasis.
The goals of this study were to determine the ultrasonographic characteristics of thyroid carcinoma (TC) and to explore the diagnostic efficacy of these ultrasonographic characteristics in predicting cervical lymph node metastasis (LNM). From June 2012 to June 2014, a total of 186 TC patients were recruited from the Central Hospital of Chengde City, Hebei, China. We divided them into two groups: the metastatic group comprised 129 nodules (n = 86), and the non-metastatic group 117 nodules (n = 100). Univariate and multivariate analyses were used to evaluate the relationship between ultrasonographic characteristics and cervical LNM. Spectral Doppler ultrasound was employed to estimate peak systolic velocity, pulsatility index and resistive index. Receiver operating characteristic curves were drawn to evaluate the efficacy of ultrasonographic characteristics in predicting cervical LNM. The sensitivity, specificity, positive predictive value and negative predictive value of ultrasonographic diagnosis were 81.40% (105/129), 92.32% (108/117), 92.11% (105/114) and 81.82% (108/132), respectively. Cervical LNM in TC frequently occurred at the cervical level VI (37.98%) and was located mainly in the middle pole (46.51%) or lower pole (41.09%). Peak systolic velocity and resistive index values were significantly higher in the metastatic group than in the non-metastatic group (both p < 0.001). Multivariate analysis revealed that nodular diameter, capsular invasion, microcalcification and flow grade were risk factors for TC patients with cervical LNMs (all p < 0.05). Furthermore, receiver operating characteristic curve analysis revealed that nodular diameter, capsular invasion, microcalcification and flow grade had excellent accuracy in predicting cervical LNM. We conclude that ultrasonographic characteristics of TC, including maximum nodular diameter, capsular invasion, microcalcification and flow grade, may predict cervical LNM.


[Unilateral anophthalmia in association with learning handicap and affective disorders--contribution to Lenz syndrome].
The case of an 18-year-old debile boy with leftside anophthalmia, premature craniosynostosis and dysmorphias characteristic for LENZ-syndrome as well as episodic affective disorders is reported. Special emphasis is laid on the differential diagnosis of the dysmorphia retardation syndrome.


High-throughput system for screening of Cephalosporin C high-yield strain by 48-deep-well microtiter plates.
Improvement of microbial strains for the high-production of industrial products has been the hallmark of all commercial fermentation processes. Strain improvement has been conventionally achieved through mutation and selection. However, most of the screenings were performed in shake flasks, which made the screening procedure very complex, time-consuming, and inefficient. Most mutant spore suspension had no chance to be screened due to the low-throughput of shake flasks and had to be sacrificed. In this paper, in order to get a Cephalosporin C (CPC) high-yield stain, traditional mutagenesis was employed to obtain the mutant library and gave them the equal screening chance by a novel mixture culture method combined with high-throughput screening method. The good correlation of fermentation results between differing-scale cultivations confirmed the feasibility of utilizing the 48-deep microtiter plates as a scale-down tool instead of shake flasks for culturing high-aerobic microbes with long cultivation period. The microbioassay based on the antibacterial activity of CPC against Alcaligenes faecalis was used to select mutants. As a result, the high-yield strain W-6 was successfully screened out and the CPC titer was nearly 50 % higher than that of the parental strain in the shake flask. The CPC production of strain W-6 was further validated in 50 l bioreactor, and the CPC production reached 32.0 g/l, twofold higher than that of the wild strain.


Editorial Commentary: The Pivot-Shift Phenomenon Is Multifactorial.
The biomechanical study on the role of the anterior cruciate ligament and anterolateral structures in controlling internal tibial rotation has some major limitations: creation of a large injury to the anterolateral structures, examination only at 30° of flexion, only one outcome variable (internal rotation), and no application of different combined forces. This "worst-case scenario" does not represent the typical injury pattern, and therefore the results might overestimate the influence of these structures on rotatory laxity. Essentially, the pivot-shift phenomenon is multifactorial and injuries or insufficiency of the anterolateral structures are only one explanation.


Cat allergen content of commercial house dust extracts: comparison with dust extracts from cat-containing environment.
Eighteen lots of house dust extract from nine commercial sources (obtained as weight per volume or protein nitrogen unit per cubic centimeter) were analyzed for cat allergen content by direct quantitative immunoelectrophoresis after concentration. Cat allergen 1 was measurable (greater than 0.3 units) in 11 extracts with a mean (range) of 5.8 (1.3 to 31.0) U/gm of source material. Cat albumin was measurable (greater than 2.4 units) in 12 extracts with a mean (range) of 53.4 (11.5 to 319.7) U/gm. In order to evaluate whether the cat allergen 1 content is a significant contribution to the allergenic activity of the extract, 17 cat-allergic subjects were tested by prick test with a purified preparation of cat allergen 1. The mean (range) concentration that produced a 3 mm wheal was 0.01 (0.0013 to 1.33) U/ml. Therefore, the commercial house dust extracts studied, when these extracts were diluted to a concentration commonly used for prick testing, would frequently contain enough cat allergen 1 to produce strong prick test reactions in cat-allergic subjects. It is difficult to justify the use of such commercial dust extracts as diagnostic reagents. For comparison purposes, nine dust samples from an apartment housing two cats were similarly analyzed. Cat allergen 1 was measurable in seven samples with a mean (range) of 23.8 (1.8 to 64.3) U/gm. Cat albumin could be measured in all nine samples with a mean (range) of 32.3 (0.16 to 70.8) U/gm. The average amount of cat allergen 1 that could be washed off the surface of the cats was 270 units. Large reservoirs of cat allergen 1 were present.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of methodological and patient factors on serum NMDAR IgG antibody detection in psychotic disorders: a meta-analysis of cross-sectional and case-control studies.
Antibodies targeting the N-methyl-D-aspartate receptor (NMDAR) have been detected in patients with psychosis. However, studies measuring the IgG subclass in serum have provided variable estimates of prevalence, and it is unclear whether these antibodies are more common in patients than controls. Because these inconsistencies could be due to methodological approaches and patient characteristics, we aimed to investigate the effect of these factors on heterogeneity. We searched Web of Science and Ovid (MEDLINE and PsycINFO) for cross-sectional and case-control studies published between Jan 1, 2000, and May 5, 2019, that reported NMDAR IgG antibody seropositivity in patients with psychosis. Pooled proportions and odds ratios (ORs) were derived using random-effects models. We estimated between-study variance (τ2) and the proportion of observed variance due to heterogeneity (I2). We then used univariable random-effects meta-regression analysis to investigate the effect of study factors on heterogeneity of proportions and ORs. Our protocol was registered on PROSPERO (CRD42018099874). Of 1276 articles in the initial search, 28 studies were eligible for inclusion, including 14 cross-sectional studies and 14 case-control studies. In cross-sectional studies, NMDAR IgG antibodies were detected in 0·73% (95% CI 0·09-1·38; I2 56%; p=0·026) of patients with psychosis, and in case-control studies, patients with psychosis were not significantly more likely to be seropositive than healthy individuals (OR 1·57, 95% CI 0·78-3·16; I2 15%; p=0·20). Meta-regression analyses indicated that heterogeneity was significantly associated with assay type across both study designs, illness stage in cross-sectional studies, and study quality in case-control studies. Compared with studies using a fixed cell-based assay, cross-sectional and case-control studies using the live method yielded higher pooled prevalence estimates (0·36% [95% CI -0·23 to 0·95] vs 2·97% [0·70 to 5·25]) and higher ORs (0·65 [0·33 to 1·29] vs 4·43 [1·73 to 11·36]). In cross-sectional studies, the prevalence was higher in exclusively first-episode samples than in multi-episode or mixed samples (2·18% [0·25 to 4·12] vs 0·16% [-0·31 to 0·63]), and in case-control studies, higher ORs were reported in low-quality studies than in high-quality studies (3·80 [1·47 to 9·83] vs 0·72 [0·36 to 1·42]). Higher estimates of NMDAR IgG antibody prevalence have been obtained with the live cell-based assay, and studies using this method find that seropositivity is more common in patients with psychosis than in controls. The effects of illness stage and study quality on heterogeneity were not consistent across study designs, and we provide clear recommendations for clinicians and researchers regarding interpreting these findings. None.


Pharmacokinetics of quinine in children.
Serum quinine concentrations were measured in seven children after intravenous infusion of quinine dihydrochloride, in eight children after intramuscular injection of quinine dihydrochloride, and in six children after nasogastric administration of a solution of quinine dihydrochloride. The mean (+/- SD) half-life of quinine was 11.1 +/- 4.8 hours, and the volume of distribution was 1.39 +/- 0.37 L/kg. To attain a serum level of 10 microgram/ml quinine, we suggest that children with severe malaria be given a loading dose of 20 mg/kg quinine dihydrochloride parenterally, followed by 7.5 mg/kg every 8 hours. Once recovery begins, quinine sulphate 10 mg/kg may be given orally every 8 hours. Serum concentrations should be monitored, if possible, because they vary greatly from person to person. Quinine is rapidly and completely absorbed after either intramuscular or nasogastric administration.


The ESAT-6/WXG100 superfamily -- and a new Gram-positive secretion system?
ESAT-6 is a small secreted protein of unknown function from Mycobacterium tuberculosis that is of fundamental importance in virulence and protective immunity. A PSI-BLAST search has identified distant homologues of ESAT-6 in more tractable bacteria, including Bacillus subtilis, Bacillus anthracis, Staphylococcus aureus and Clostridium acetobutylicum. The genes for ESAT-6-like proteins often cluster with genes encoding homologues of B. subtilis YukA. I speculate that the ESAT-6-like and YukA-like proteins form a novel Gram-positive secretion system potentially driven by the FtsK/SpoIIIE ATPase domains in the YukA-like proteins. The way is now open to investigate this hypothesis in organisms that are easier to manipulate than pathogenic mycobacteria.


Species diversity among the genus Monorchis (Digenea: Monorchiidae) parasitic in marine teleosts: molecular, morphological and morphometrical studies with a description of Monorchis blennii n. sp.
Molecular, morphological and morphometrical studies were conducted on two species of the genus Monorchis (Monorchiidae), Monorchis parvus and Monorchis monorchis, collected in different fish hosts from the Mediterranean Sea. The analysis of internal transcribed spacer 1 sequences of ribosomal DNA showed that M. monorchis specimens from Parablennius gattorugine were strongly divergent (12.9%) from specimens of this species collected in Spondyliosoma cantharus and Diplodus puntazzo. This high genetic variation was confirmed by the analysis of morphological structures and morphometrics, which showed that M. monorchis specimens from P. gattorugine can be distinguished from those of S. cantharus and D. puntazzo by several morphological characteristics, including body size, number and distribution of vitelline follicles, testis shape, structure of the cirrus pouch, and number of eggs. Our results show that M. monorchis specimens isolated from P. gattorugine represent a clearly distinct entity from M. monorchis found in the other hosts, which has enabled us to describe a new species, Monorchis blennii n. sp.


Relationship between histologic features and outcomes of carotid revascularization for radiation-induced stenosis.
This study aimed to elucidate the relationships between preoperative carotid imaging results, histologic characteristics, and surgical treatment outcomes of radiation-induced carotid stenosis (RICS), using control subjects without RICS for comparison. We retrospectively reviewed records of 17 patients who underwent carotid revascularization for 22 instances of RICS, including 10 cases of carotid artery stenting (CAS), 11 cases of carotid endarterectomy (CEA), and 1 case of CEA with retrograde CAS, between July 2004 and April 2013. The controls were 475 patients with no history of radiation therapy who underwent carotid revascularization in a similar period. Preoperative magnetic resonance imaging (MRI), ultrasonography (US), and computed tomography angiography results were correlated with outcomes of histologic analysis of CEA specimens. End points included ipsilateral and contralateral stroke, myocardial infarction, restenosis, in-stent thrombosis, and target lesion revascularization. Vulnerable plaques on carotid MRI (86% vs 64.2%; P = .010) and mobile (27% vs 8.0%; P = .008) and ulcerative (50% vs 15.8%; P < .001) plaques on US were more frequent in the RICS group. All revascularization procedures were successful, and no occlusion occurred. Adverse events in the CAS group, including one minor stroke and one transient ischemic attack within 30 days as well as five ipsilateral neurologic events after 30 days, including three minor strokes and two transient ischemic attacks, were significantly more frequent than in the CEA group. All three cases of late ipsilateral stroke displayed vulnerable plaque on preoperative MRI and late in-stent thrombosis or restenosis on US. Our radiologic and histologic analyses revealed that advanced RICS is often accompanied by formation of vulnerable plaque. CEA can prevent undesirable late outcomes in such cases.


Relevance of multilamellar and multicompartmental vesicles in biological fluids: understanding the significance of proportional variations and disease correlation.
Extracellular vesicles (EVs) have garnered significant interest in the field of biomedical science due to their potential applications in therapy and diagnosis. These vesicles participate in cell-to-cell communication and carry a diverse range of bioactive cargo molecules, such as nucleic acids, proteins, and lipids. These cargoes play essential roles in various signaling pathways, including paracrine and endocrine signaling. However, our understanding of the morphological and structural features of EVs is still limited. EVs could be unilamellar or multilamellar or even multicompartmental structures. The relative proportions of these EV subtypes in biological fluids have been associated with various human diseases; however, the mechanism remains unclear. Cryo-electron microscopy (cryo-EM) holds great promise in the field of EV characterization due to high resolution properties. Cryo-EM circumvents artifacts caused by fixation or dehydration, allows for the preservation of native conformation, and eliminates the necessity for staining procedures. In this review, we summarize the role of EVs biogenesis and pathways that might have role on their structure, and the role of cryo-EM in characterization of EVs morphology in different biological samples and integrate new knowledge of the alterations of membranous structures of EVs which could be used as biomarkers to human diseases.


Detrimental psychophysiological effects of early maternal deprivation in adolescent and adult rodents: altered responses to cannabinoid exposure.
Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation (MD), consisting of a single 24-h maternal deprivation episode during early neonatal life, has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. Despite first onset of mental disorders usually occur during adolescence, characterization of MD has been mostly developed in adult animals. We review here a series of experiments that were conducted on rats and mice, in which we analyzed the psychoimmunoendocrine outcomes of MD at both adolescence and adulthood. As a whole our results indicate that MD might promote a depressive-like trait that may be present from adolescence to maturity. Maternally deprived adolescent animals also displayed altered locomotor responses, a reduced interest for social investigation and seemed prone for impulsive behavior. Therefore, MD in rodents is further confirmed as a suitable animal model for the study of neuropsychiatric disorders that might become evident during adolescence. Given the increasing consumption of cannabis derivatives among the juvenile population and the reported comorbidity of neuropsychiatric symptoms with cannabis abuse, we also discuss our results indicating altered responses of maternally deprived adolescent animals to cannabinoid compounds.


Aging and strength of bone as a structural material.
There is a general, age-related reduction in the material strength and stiffness of bone in both men and women. Between the ages of 35 and 70, cortical bone strength in bending is diminished by about 15-20%, and cancellous bone strength in compression is reduced about 50%. In addition, bone becomes increasingly brittle and fractures with less energy. It is hypothesized that this tendency is driven by the need for remodeling to repair fatigue damage, and the fact that most osteonal and endotrabecular remodeling events fail to replace all the bone that they remove. Each remodeling event also introduces cement line interfaces, which although affording protection against fatigue failure, weaken bone for monotonic loading. Remodeling also affects collagen fiber orientation, mineralization, and the amount of unrepaired fatigue damage, which are additional determinants of bone strength and stiffness. Mechanical factors apparently inhibit age-related bone loss where stresses are higher by reducing remodeling rates and/or the deficit at each remodeling site. They may also stimulate modeling responses, primarily in the form of periosteal bone formation, which, in men more than women, alter bone size and shape to effectively compensate for loss of material strength. Suggested directions for future research include elucidation of the relationships between (1) histologically observable microcracks and bone fragility, (2) remodeling and the repair of fatigue damage, and (3) estrogen and other hormones and mechanically adaptive responses.


Interoceptive abilities facilitate taking another's spatial perspective.
Information can be perceived from a multiplicity of spatial perspectives, which is central to effectively understanding and interacting with our environment and other people. Interoception, the sense of the physiological state of our body, is also a fundamental component contributing to our perception. However, whether the perception of our inner body signals influences our ability to adopt and flexibly change between different spatial perspectives remains poorly understood. To investigate this, 90 participants completed tasks assessing multiple dimensions of interoception (interoceptive sensibility, cardiac interoceptive accuracy and awareness) and the Graphesthesia task to assess tactile spatial perspective-taking and its flexibility. The results revealed that higher cardiac interoceptive awareness is associated with greater consistency in adopting a perspective decentred from the self. Second, higher cardiac interoceptive accuracy was associated with slower and less accurate performance in switching from a decentred to an egocentred perspective. These results show that interoceptive abilities facilitate decentred spatial perspective-taking, likely reflecting stronger perceived boundaries between internal states and the external world.


Protocol to study the role of a human nuclear m6A RNA reader on chromatin-associated RNA targets.
Here, we present a detailed protocol to study the role of a human nuclear m6A RNA reader, YTHDC1, on chromatin-associated RNA targets. We describe steps for RNA extraction coupled to subnuclear fractionation to identify and study RNA-based regulations that take place in the chromatin-associated fraction. We then detail an RNA immunoprecipitation procedure adapted to identify chromatin-associated RNA targets. This protocol can be adapted to other human or mammalian chromatin-associated RNA binding proteins. For complete details on the use and execution of this protocol, please refer to Timcheva et al.1.


Bioplast fibrin implants in nasoseptal perforation.
This study includes 9 cases of nasoseptal perforation following submucous septectomy. Sheets from Bioplast fibrin, an absorbable biomaterial, were implanted to prevent thepersistence of perforations. Postoperative mucosal growth on both implant surfaces ensured closure in 6 of the 9 cases. The method has the advantage of simplicity and it is commendable in the case of smaller defects when the mucosa is not markedly atrophic.


Intra-arterial tenecteplase is safe and may improve the first-pass recanalization for acute ischemic stroke with large-artery atherosclerosis: the BRETIS-TNK trial.
The first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients. The BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b. The first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11). This is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.


TMS-EEG and resting-state EEG applied to altered states of consciousness: oscillations, complexity, and phenomenology.
Exploring the neurobiology of the profound changes in consciousness induced by classical psychedelic drugs may require novel neuroimaging methods. Serotonergic psychedelic drugs such as psilocybin produce states of increased sensory-emotional awareness and arousal, accompanied by increased spontaneous electroencephalographic (EEG) signal diversity. By directly stimulating cortical tissue, the altered dynamics and propagation of the evoked EEG activity can reveal drug-induced changes in the overall brain state. We combine Transcranial Magnetic Stimulation (TMS) and EEG to reveal that psilocybin produces a state of increased chaotic brain activity which is not a result of altered complexity in the underlying causal interactions between brain regions. We also map the regional effects of psilocybin on TMS-evoked activity and identify changes in frontal brain structures that may be associated with the phenomenology of psychedelic experiences.


Effect of the jimpy mutation on expression of myelin proteins in heterozygous and hemizygous mouse brain.
The levels of myelin basic protein, proteolipid protein, and 2',3'-cyclic nucleotide 3'-phosphohydrolase (EC 22.214.171.124) in cerebral hemispheres of wild-type, heterozygous jp/+, and hemizygous jp/Y mice of different ages were determined by radioimmunoassay and immunoblotting. In jp/Y brain the level of myelin basic protein was 8% that of wild-type at all ages. All forms of the protein were reduced although the 21.5K Mr form was relatively spared at early ages compared to the 18.5K, 17K, and 14K Mr forms. The level of 2',3'-cyclic nucleotide 3'-phosphohydrolase was 8% that of wild-type at all ages, and proteolipid protein was undetectable at any age. These results are consistent with the hypothesis that the jimpy mutation blocks myelin morphogenesis subsequent to incorporation of 21.5K Mr myelin basic protein but prior to incorporation of proteolipid protein. In jp/+ brain the levels of the three proteins were reduced commensurately to 60-70% those of wild-type. The deficit was apparent as early as 10 days after birth and remained proportionately constant throughout development. These results suggest that in jp/+ mice, X-chromosome inactivation produces a mosaic population of functionally wild-type and functionally jimpy oligodendrocytes. The former elaborate normal amounts of myelin but do not completely compensate for the myelin deficit due to the latter.


The Legionella Effector Kinase LegK7 Hijacks the Host Hippo Pathway to Promote Infection.
The intracellular pathogen Legionella pneumophila encodes translocated effector proteins that modify host cell processes to support bacterial survival and growth. Here, we show that the L. pneumophila effector protein LegK7 hijacks the conserved Hippo signaling pathway by molecularly mimicking host Hippo kinase (MST1 in mammals), which is the key regulator of pathway activation. LegK7, like Hippo/MST1, phosphorylates the scaffolding protein MOB1, which triggers a signaling cascade resulting in the degradation of the transcriptional regulators TAZ and YAP1. Transcriptome analysis revealed that LegK7-mediated targeting of TAZ and YAP1 alters the transcriptional profile of mammalian macrophages, a key cellular target of L. pneumophila infection. Specifically, genes targeted by the transcription factor PPARγ, which is regulated by TAZ, displayed altered expression, and continuous interference with PPARγ activity rendered macrophages less permissive to L. pneumophila intracellular growth. Thus, a conserved L. pneumophila effector kinase exploits the Hippo pathway to promote bacterial growth and infection.


Exercise-induced Brugada pattern and ventricular tachycardia during Capecitabine treatment.
We report the case of a 59-year-old female patient with no previous cardiovascular disease treated for Breast cancer with Capecitabine. Shortly after starting treatment, she developed recurrent angina. An exercise stress echocardiogram was performed, which induced a type 1 Brugada pattern 12 s of a non-sustained pleomorphic ventricular tachycardia ensued.


Amelogenins modulate cytokine expression in LPS-challenged cultured human macrophages.
Amelogenins are enamel matrix proteins with a proven ability to restore tissues in patients with advanced periodontitis and chronic skin wounds. To explore the mechanisms of action of amelogenins in wound inflammation, the in vitro effect on the expression of selected cell mediators involved in inflammation and tissue repair from human monocyte-derived macrophages was studied. Macrophages were treated with amelogenins in serum-enriched medium with simultaneous lipopolysaccharide (LPS) stimulation, for 6, 24 and 72 h, and the conditioned culture medium was analysed for 28 different cytokines. Amelogenin treatment directed the LPS-induced release of both pro- and anti-inflammatory cytokines towards an alternatively activated macrophage phenotype. This change in activation was also demonstrated by the amelogenin-induced secretion of alternative macrophage activation-associated CC chemokine-1 (AMAC-1, also known as CCL18; p<0.001), a well-documented marker of alternative activation. Amelogenins were also shown significantly to increase the macrophage expression of vascular endothelial growth factor and, to a lesser but significant extent, insulin-like growth factor-1 after 24h of culture. The results of the present in vitro study show that monocyte-derived macrophages stimulated by inflammatory agonist LPS respond to the treatment with amelogenins by reducing the pro-inflammatory activity and increasing the expression of tissue repair mediators.


First HIV legal precedent in Kyrgyzstan: breach of medical privacy.
A recent court case of a breach of the privacy rights of a person living with HIV/AIDS in Kyrgyzstan is the first of its kind in Central Asia, write Erik Iriskulbekov and Asylgul Balybaeva. ADILET, the NGO that brought the case to court, is one of only a few NGOs in Central Asia that provide legal assistance related to HIV and AIDS.


The "forgotten" goiter after total thyroidectomy.
"Forgotten" goiter is an extremely rare disease which is defined as a mediastinal thyroid mass found after total thyroidectomy. We report two cases with forgotten goiter. One underwent total thyroidectomy due to thyroid papillary cancer and TSH level was in normal range one month after surgery. The thyroid scintigraphy scan revealed mediastinal thyroid mass. The second case underwent total thyroidectomy due to Graves' disease and TSH level was low after surgery. At postoperative seventh year, patients were admitted to our Endocrinology Division due to persistent hyperthyroidism and CT scan revealed forgotten thyroid at mediastinum. Both patients underwent median sternotomy and mass excision, there was no morbidity detected after second surgical procedures. In the majority of cases forgotten goiter is the consequence of the incomplete removal of a plunging goiter. Although in some cases, it may be attributed to a concomitant, unrecognized mediastinal goiter which is not connected to the thyroid with a thin fibrous band or vessels. Absence of signs like mediastinal mass or tracheal deviation in preoperative chest X-ray do not excluded the substernal goiter. Retrosternal goiter should be suspected if the lower poles could not be palpated on physical examination and when postoperative TSH levels remained unchanged.


Follow-up studies in patients with right bundle branch block and left anterior hemiblock: significance of H-V interval.
Thirty-eight patients with right bundle branch block and left anterior hemiblock who had undergone His bundle recordings were prospectively followed for development of heart block. Twenty-five were male and thirteen female. Their ages ranged from 35 to 92 with an average age of 74 years. The mean follow-up period was 28.5 months (range 2-52 months). The H-V interval was 55 msec or less in 17 patients (Group A), between 56 and 75 msec in 13 (Group B), and more than 75 msec in eight (Group C). Ten patients (26%) died during the follow-up period. Of these, three were in Group A (mortality rate 8% per year), three in Group B 10% per year), and four in Group C (21% per year). None of the deaths in Groups A and B were sudden, while one possible sudden death occurred in Group C. Mode of death in one patient each from Groups B and C remained unknown. Heart block was not seen in any patient from Group A and B, while two patients from Group C progressed to complete heart block during the follow-up period. It is concluded that patients with right bundle branch block and left anterior hemiblock with prolonged H-V intervals tend to show a higher mortality when compared to those with normal H-V intervals. A definite risk of heart block exists in patients with H-V intervals of more than 75 msec.


The hydrophobic amino acid residues in the membrane-proximal C tail of the G protein-coupled vasopressin V2 receptor are necessary for transport-competent receptor folding.
It is believed that the membrane-proximal C tail of the G protein-coupled receptors forms an additional alpha helix with amphipathic properties (helix 8). It was previously shown for the vasopressin V2 receptor (V2R) that a conserved dileucine motif (L(339), L(340)) in this putative helix 8 is necessary for endoplasmic reticulum (ER) to Golgi transfer of the receptor. Here, we demonstrate that the other hydrophobic residues forming the non-polar side of this helix (F(328), V(332) and L(336)) are also transport-relevant. In contrast, the multiple serine residues contributing to the more hydrophilic side (S(330), S(331), S(333), S(334), S(338)) do not influence receptor trafficking. In addition, we show unambiguously by the use of pharmacological chaperones that the hydrophobic residues of the putative helix 8 do not form a transport signal necessary for receptor sorting into ER to Golgi vesicles. Instead, they are necessary to establish a transport-competent folding state in the early secretory pathway.


High-rhythm automatic driver for bone traction: an experimental study in rabbits.
The distractors currently used in clinics are activated manually by intermittent advancement. An automatic driver has been developed to attach to custom-made or commercially available distractors and activate advancement at a high rhythm of 8 steps per second. One 1.5-V lithium button battery is used as the power source to drive a step motor and the driving torque is transmitted to the distractor through a flexible shaft at a rate of 2 revolutions per day. This automatic driver was tested in 5 rabbits for mandibular lengthening. Osteotomy was performed on one side of the mandible and the custom-made distractor was adapted. After a latency period of 3 days, the automatic driver was attached to the distractor's arm and mandibular lengthening was activated. After 11 days of continuous distraction the automatic driver was detached from the distractor's arm. All the rabbits were euthanized after 4 weeks of consolidation. The distraction regenerates were analysed by plain radiography, micro-computerized tomography and histological examination. All 5 rabbits completed the experimental process and healed uneventfully. The mandibles were confirmed to have lengthened successfully and the distraction gap was filled with newly formed bone.


Relation between translingual potential changes induced by NaCl in the bullfrog tongue and taste nerve activity.
NaCl at various concentrations applied to the dorsal surface of the bullfrog tongue induced slow potential changes across the tongue. They were almost in parallel with changes in impulse discharges simultaneously recorded from the glossopharyngeal nerve.


LncRNA Uc003xsl.1-Mediated Activation of the NFκB/IL8 Axis Promotes Progression of Triple-Negative Breast Cancer.
Aberrant activation of NFκB orchestrates a critical role in tumor carcinogenesis; however, the regulatory mechanisms underlying this activation are not fully understood. Here we report that a novel long noncoding RNA (lncRNA) Uc003xsl.1 is highly expressed in triple-negative breast cancer (TNBC) and correlates with poor outcomes in patients with TNBC. Uc003xsl.1 directly bound nuclear transcriptional factor NFκB-repressing factor (NKRF), subsequently preventing NKRF from binding to a specific negative regulatory element in the promoter of the NFκB-responsive gene IL8 and abolishing the negative regulation of NKRF on NFκB-mediated transcription of IL8. Activation of the NFκB/IL8 axis promoted the progression of TNBC. Trop2-based antibody-drug conjugates have been applied in clinical trials in TNBC. In this study, a Trop2-targeting, redox-responsive nanoparticle was developed to systematically deliver Uc003xsl.1 siRNA to TNBC cells in vivo, which reduced Uc003xsl.1 expression and suppressed TNBC tumor growth and metastasis. Therefore, targeting Uc003xsl.1 to suppress the NFκB/IL8 axis represents a promising therapeutic strategy for TNBC treatment. These findings identify an epigenetic-driven NFκB/IL8 cascade initiated by a lncRNA, whose aberrant activation contributes to tumor metastasis and poor survival in patients with triple-negative breast cancer.


Continuing Medical Education Questions: November 2019.
Article Title: Morbidity and Mortality Following Surgery for Non-Malignant Colorectal Polyps: A 10-Year Nationwide Analysis.


Lower Gastrointestinal Bleeding in Children.
This article provides an overview of the evaluation and management of lower gastrointestinal bleeding (LGIB) in children. The common etiologies at different ages are reviewed. Conditions with endoscopic importance for diagnosis or therapy include solitary rectal ulcer syndrome, polyps, vascular lesions, and colonic inflammation and ulceration. Diagnostic modalities for identifying causes of LGIB in children include endoscopy and colonoscopy, cross-sectional and nuclear medicine imaging, video capsule endoscopy, and enteroscopy. Pre-endoscopic preparation and decision-making unique to pediatrics is highlighted. The authors conclude with a summary of current and emerging therapeutic hemostatic techniques that can be used in pediatric patients.


The mechanism of rapid shallow breathing due to histamine and phenyldiguanide in cats and rabbits.
In anaesthetized cats and rabbits we analyzed the rapid shallow breathing following exposure to histamine aerosol (mainly an irritant receptor stimulant) and i.v. injection of phenyldiguanide (mainly a J receptor stimulant). Both drugs caused a marked leftward displacement of the tidal volume (VT) vs inspiratory time (TI) relationship (Hering-Breuer threshold curve) without a corresponding increase in inspiratory flow rate so that inspiration was cut off at a lower VT and TI. The leftward displacement of the VT vs TI relationship occurred with a great shortening of the duration of inspiration during occluded breaths (T0I) accompanied by a shortening of the expiratory phase (T0E). These parameters monitored the central respiratory rhythm in absence of the phasic lung volume related vagal loop. It is suggested that the increased central respiratory frequency was due to the augmented firing of fibers from stimulated irritant and J receptors. Stimulation of these endings also caused the TE vs TI relationship to become steeper in cats and to be displaced downwards in rabbits.


Using reusable learning objects (RLOs) in wound care education: Undergraduate student nurse's evaluation of their learning gain.
Both nationally and internationally concerns have been expressed over the adequacy of preparation of undergraduate nurses for the clinical skill of wound care. This project describes the educational evaluation of a series of Reusable Learning Objects (RLOs) as a blended learning approach to facilitate undergraduate nursing students learning of wound care for competence development. Constructivism Learning Theory and Cognitive Theory of Multimedia Learning informed the design of the RLOs, promoting active learner approaches. Clinically based case studies and visual data from two large university teaching hospitals provided the authentic learning materials required. Interactive exercises and formative feedback were incorporated into the educational resource. Evaluation of student perceived learning gains in terms of knowledge, ability and attitudes were measured using a quantitative pre and posttest Wound Care Competency Outcomes Questionnaire. The RLO CETL Questionnaire was used to identify perceived learning enablers. Statistical and deductive thematic analyses inform the findings. Students (n=192) reported that their ability to meet the competency outcomes for wound care had increased significantly after engaging with the RLOs. Students rated the RLOs highly across all categories of perceived usefulness, impact, access and integration. These findings provide evidence that the use of RLOs for both knowledge-based and performance-based learning is effective. RLOs when designed using clinically real case scenarios reflect the true complexities of wound care and offer innovative interventions in nursing curricula.


Microgenesis of surface completion in visual objects: evidence for filling-out.
Using metacontrast masking we examined the temporal dynamics of surface completion in object vision. By varying the stimulus onset asynchrony between the target object and the flanking mask(s), we obtained estimates of the time required for the entire surface contrast to fill out within the area delimited by the contours/edges of the target. The estimated speed of the filling-out process was 36.0 deg/s. Using existing estimates of cortical magnification, the computed filling-out speed in terms of cortical distance is .385 m/s, a value that approximates the estimated cortical filling-in speed and the speed of horizontal propagation in monkey V1. We discuss our results in relation to (1) prior findings of filling-in and filling-out phenomena, using surface completion in cortical space as the unifying principle, and (2) extant computational models of object vision.


Malnutrition and its determinants among older adults people in Addis Ababa, Ethiopia.
In Ethiopia, malnutrition among older adults is under detected and, neglected area because the entire problem related with aging considered as fate of aging. Also, older adults are often omitted from public health research. Literatures are scarce in Ethiopia; there is limited information in the current study area among older adults using Min Nutritional Assessment (MNA). Therefore, this paper investigated the prevalence of malnutrition and its predictors among older adults people aged 65 years or above in Addis Ababa, Ethiopia. A community-based cross-sectional study was employed from January 1 to march 30, 2020 in Addis Ababa. Nutritional status of the older adults was measured by using Min nutritional assessment (MNA). Data from 662 older adults were collected through face to face interviews using a structured questionnaire. Bivariable and multivariable logistic regression analysis was done to identify factors associated with malnutrition. The prevalence of malnutrition among older adults was found to be 26.6%[95% Confidence interval (CI):22.8, 30.1]. Depression [Adjusted Odds Ratio (AOR) = 7.57 95%CI: 5.01, 11.45], being poor [AOR = 1.95 95% CI: 1.166, 3.25], occupation; daily laborer and guard [AOR = 2.78 95% CI: 1.12, 7.17] and being old old [AOR = 2.62 95% CI: 1.62, 4.25] were significantly associated with the higher odds of malnutrition. This study illustrated that considerably high proportion of older adults were malnourished in Addis Ababa. Socio-economic characteristics and depression were significantly associated with malnutrition. Therefore, nutritional and social support activities are essential for older adults, particularly of those who are socio-economically disadvantaged and advanced age. In addition, regular nutritional screening and management as well as behavioral interventions should be strengthened as a pillar component of therapeutic interventions. Specific nutritional requirements, at later stages of life is changing, and with the population aged over 65 years increasing in low-income countries like Ethiopia, the research in this field is likely to increase further.


Non-destructive techniques for biomonitoring of spatial, temporal, and demographic patterns of mercury bioaccumulation and maternal transfer in turtles.
Mercury (Hg) is a globally ubiquitous pollutant that has received much attention due to its toxicity to humans and wildlife. The development of non-destructive sampling techniques is a critical step for sustainable monitoring of Hg accumulation. We evaluated the efficacy of non-destructive sampling techniques and assessed spatial, temporal, and demographic factors that influence Hg bioaccumulation in turtles. We collected muscle, blood, nail, and eggs from snapping turtles (Chelydra serpentina) inhabiting an Hg contaminated river. As predicted, all Hg tissue concentrations strongly and positively correlated with each other. Additionally, we validated our mathematical models against two additional Hg contaminated locations and found that tissue relationships developed from the validation sites did not significantly differ from those generated from the original sampling site. The models provided herein will be useful for a wide array of systems where biomonitoring of Hg in turtles needs to be accomplished in a conservation-minded fashion.


Multimodal Migraine Management and the Pursuit of Migraine Freedom: A Narrative Review.
Migraine is a neurologic disease with a complex pathophysiology that can be controlled with current treatment options but not cured. Therefore, treatment expectations are highly variable. The concept of migraine freedom was recently introduced and can mean different things, with some, for example, expecting complete freedom from headache and associated symptoms and others accepting the occasional migraine attack if it does not impact functioning. Therefore, migraine management should be optimized so that patients can have the best opportunity to achieve their optimal treatment goals. With migraine freedom as a goal and, given the complex pathophysiology of migraine and the high incidence of comorbidities among individuals with migraine, treatment with a single modality may be insufficient, as it may not achieve migraine freedom in those with more frequent or disabling attacks. In this clinical perspective article, we have identified four key, partially overlapping principles of multimodal migraine treatment: (1) manage common comorbidities; (2) control modifiable risk factors for progression by addressing medication and caffeine overuse; (3) diagnose and treat secondary causes of headache, if present; and (4) individualize acute and preventive treatments to minimize pain, functional disability, and allodynia. There are many barriers to pursuing migraine freedom, and strategies to overcome them should be optimized. Migraine freedom should be an aspirational goal both at the individual attack level and for the disease overall. We believe that a comprehensive and multimodal approach that addresses all barriers people with migraine face could move patients closer to migraine freedom.


Identification and functional analysis of the activator gene involved in the biosynthesis of Co-type nitrile hydratase from Aurantimonas manganoxydans.
Nitrile hydratase (NHase) has attracted considerable attention to synthesize valuable amides. Here, the gene cluster of Co-type NHase from Aurantimonas manganoxydans ATCC BAA-1229 (NHase1229) was identified through Edman degradation and recombinant expression, including α-subunit, β-subunit, and activator. The activator gene contained 408 bases, which was essential for the biosynthesis of NHase1229 in Escherichia coli. The activator gene can be substituted by Co-type activator from Pseudonocardia thermophila JCM3095 and Pseudomonas putida 5B to assist in the functional expression of NHase1229, not by that of Fe-type NHase from Pseudomonas putida F1. Multi-sequence alignment showed that the activator contained conserved amino acid residues (Trp34, Trp53, Phe 85, Gln35, Glu39, and Glu90), but these residues had no significant effect on activator function. Histidine residues (His112, His120, and His134) at the C-terminus only partially participated in the activator function. Furthermore, the successive α-helices in domain TIGR03889 were identified to be critical for the activator function. The integration efficiency of cobalt into the active site was decreased with the interruption of α-helices. Therefore, Co-type and Fe-type activators have specific functions for the integration of different metal ions, and four conserved α-helices in Co-type activator affect the integration of cobalt. These knowledge is useful for understanding the biosynthesis of Co-type NHase.


Validation of uterine artery embolization before surgical laparoscopic myomenucleation compared to single surgical laparoscopic myomenucleation for the treatment of large fibroids and uterus myomatosus.
To determine the efficacy of preoperative uterine artery embolization (uterine artery embolization; UAE) prior to elective laparoscopic fibroid removal compared to single laparoscopic fibroid removal in women with large uterine fibroids and women with uterus myomatosus. A total of 202 women with symptomatic uterine fibroids who were scheduled for elective fibroid enucleation were included in this retrospective, monocentric, non-randomized study. Two procedures were compared: women who received percutaneous UAE 24 h prior to elective laparoscopic fibroid eviction for large uterine fibroids (>6 cm) and uterus myomatosus. And women who received laparoscopic fibroid enucleation alone for large uterine fibroids and uterus myomatosus. Outcome parameters for effectiveness were the hospital stay, the operating time and the intraoperative blood loss. Women who underwent preoperative percutaneous embolization of the uterine arteries, both for large fibroids and uterus myomatosus, had significantly less blood loss, shorter hospital stays, and shorter operating times. Especially women with large uterine fibroids and women with uterus myomatosus after having children can benefit from the combination therapy of preoperative percutaneous uterine embolization with subsequent laparoscopic myoma enucleation.


Human nasal mucosal function at controlled temperatures.
We exposed 16 healthy human volunteers to air temperatures ranging from 7 to 39 degrees C and measured nasal mucus flow, nasal airflow resistance, forced vital capacity, rectal and body surface temperature, and air temperature within the nasal passage. A moderate fall in nasal mucus flow rate in the anterior and middle parts of the nose was observed with temperature above or below 23 degrees C. The nasal airflow resistance decreased in warm air and tended to increase in cold air. No significant changes in forced vital capacities or rectal temperature were observed. Nasopharyngeal end inspiratory air temperatures at 23 degrees C averaged 32.6 degrees C. At environmental temperatures of 15 and 31 degrees C they average 28.1 and 32.8 degrees C, respectively. Although we found alterations in upper airway function associated with altered inspired air temperature, over the range of 32 degrees C studied these changes were of minor physiological significance.


New technology for imaging and documenting urologic procedures.
Recent advances in fiber optics and digital technology have dramatically improved the ability of the urologic surgeon to accurately image and document endoscopic and laparoscopic procedures. In addition, the development of digital endoscopes has expanded the armamentarium of the endoscopic surgeon greatly. Finally, new virtual reality technology has allowed increased visualization during surgery and provides excellent training for surgeons. This article details new imaging and documentation technology currently utilized during urologic procedures.


Recognition, isolation, and characterization of rat liver D-methylmalonyl coenzyme A hydrolase.
Certain amino acids and other compounds are metabolized via: Propionyl-CoA carboxylase in equilibrium D-methylmalonyl-CoA racemase in equilibrium L-methylmalonyl-CoA (adenosylcobalamin) mutase in equilibrium succinyl-CoA in equilibrium tricarboxylic acid cycle. In cobalamin deficiency and in genetic disorders involving adenosylcobalamin or the mutase, large amounts of methylmalonic acid are excreted in the urine. Its origin is unknown, however, since nonesterified methylmalonic acid is not present in the above or other known pathways. To investigate the origin of methylmalonic acid, we fractionated rat liver by gel filtration and found a single peak (Mr = 35,000) of activity for the hydrolysis of DL-methylmalonyl-CoA to methylmalonic acid and CoA. The enzyme has been purified 3,100-fold with a yield of 2.1% from 1.6 kg of rat liver using a purification scheme consisting of ammonium sulfate fractionation, ion exchange chromatography on CM (carboxymethyl)-cellulose and DEAE-cellulose, affinity chromatography on CoA-agarose, and gel filtration on Sephadex G-100. The final preparation gave a single band on polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme is 35,000 based on gel filtration, and sodium dodecyl sulfate-polyacrylamide electrophoresis in the presence and absence of 1% 2-mercaptoethanol. The enzyme was shown to be active on the D-isomer, but not on the L-isomer, of methylmalonyl-CoA by CD spectropolarimetry. The Km for D-methylmalonyl-CoA is 0.7 mM and the molar activity is 1,400 molecules of substrate/min/molecule of enzyme. At substrate concentrations of 0.5 mM, the relative rate of hydrolysis of CoA esters was as follows: D-methylmalonyl-CoA (100%), malonyl-CoA (16%), propionyl-CoA (3%), acetyl-CoA (1%), succinyl-CoA (less than 1%), and palmitoyl-CoA (less than 1%). This enzyme appears to account for the markedly increased amounts of methylmalonic acid that are excreted in the urine in cobalamin deficiency and in genetic disorders involving adenosylcobalamin or L-methylmalonyl-CoA mutase.


The antagonism of amino acid-induced excitation of spinal neurones in the cat.
DL-alpha-Aminoadipate (DLalphaAA) and L-glutamic acid diethylester (GDEE) were compared as antagonists of the excitatory effects of a number of amino acids on interneurones, and also of acetylcholine on Renshaw cells of the cat spinal cord. The excitants could be ranked in order of their sensitivity of the two antagonists. Ibotenate and the optical isomers of N-methylaspartate were the most readily antagonised by DLalphaAA and the least by GDEE; L-glutamate and quisqualate were most affected by GDEE and least by DLalphaAA; the actions of L-cysteate, L-aspartate and D- and L-homocysteate were reduced to some extent by both; and kainate was relatively insensitive to both antagonists. Acetylcholine excitations of Renshaw cells were often reduced by GDEE and occasionally by DLalphaAA. The results indicate the existence on spinal neurones of at least two populations of amino acid receptors which have differing sensitivities to the antagonists, and which do not precisely conform to the "glutamate-perferring" and "aspartate-preferring" categories which have been proposed on other grounds.