Neurophysiology of Tourette's syndrome: pathophysiological considerations.
At present the neurophysiology of Tourette's syndrome (TS) has been investigated largely from two perspectives; one for evaluation of the dysfunction of the cerebral cortex and the other for clarification of the neuronal mechanisms that underlie tics and related symptoms. For the former the following examinations have been conducted: quantitative analyses of scalp electroencephalography (EEG), premovement EEG potentials, contingent negative variation, transcranial magnetic stimulation, and neuroimaging studies, including echo-planar images and positron emission tomography scans. These explorations have revealed the likely involvement of the subcortical and the cortical structures, particularly of the basal ganglia, in the pathophysiology of TS. For the latter, surface electromyography, evoked potentials, saccadic eye movements, and polysomnographies have been performed, and again have suggested a dysfunction of the basal ganglia and the brainstem neurons in TS patients. These neurophysiological studies suggest dysfunction of both motor and non-motor basal ganglia-thalamocortical circuitries in TS patients, which is hypothesized to be caused by hypofunction of the dopamine (DA) neurons associated with DA receptor supersensitivity, a well as hypofunction of the serotonergic neurons of the brainstem. Polysomnographical examination suggests that the dysfunction of the nigrostriatal (NS)-DA neurons is not a progressive process, but that the dysfunction is closely associated with an early occurrence of the developmental decrement of the activities of the NS-DA system to mature in a normal fashion. The associated DA receptor supersensitivity is assumed to be a consequence of this developmental abnormality and not due to denervation supersensitivity.


[Expression of extracellular matrix metalloproteinase inducer during normal pregnancy].
To study the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) during normal pregnancy. The expression of EMMPRIN was studied with immunohistochemistry in normal pregnancy. The expression of EMMPRIN was obvious, and appeared mainly on membrane of cytotrophoblast, syncytiotrophoblast, cytotrophoblast column of the villi of gestational weeks 6 to 9, mid-term and term placenta and extravillous cytotrophoblast of deciduas of mid-term and term placenta. The expression reached a peak level at gestational week 6 and gradually decreased from week 7 and stabilized to a low level at mid-term and term placenta when the expression of extravillous cytotrophoblast of deciduas was increased. EMMPRIN may be an important factor for implantation during early pregnancy and participate in maintaining gestation during mid-term and term pregnancy.


Hyperoxic exposure leads to cell death in the developing brain.
Premature infants have high incidence of motor and cognitive impairment in later life. Supraphysiological oxygen concentrations are routinely used in neonatal intensive care units and elicit injury to premature lungs and retina. Since the effects of hyperoxia on the developing brain are scarce, we studied the effects of high oxygen on this tissue. Wistar rat pups were exposed from birth until day 5 to 21% or 80% oxygen. The neuronal density and apoptosis in CA1 and dentate gyrus of hippocampus, prefrontal cortex, parietal cortex, subiculum, and retrosplenial cortex were assessed by immunohistochemistry and ELISA cell death assay. Neuronal density of the investigated brain areas were significantly decreased in the hyperoxia group. Furthermore, using ELISA cell death and TUNEL assays, we observed increased cell death in the developing brain. Our results show that hyperoxia induces cell death in the developing rat brain. This may be one of the important mechanisms that cause motor and cognitive impairment in later life of premature infants.


Chemoprevention of colorectal cancer in ulcerative colitis.
Patients with ulcerative colitis (UC) are at greater risk of developing colorectal cancer (CRC) than the general population. Both duration and extent of UC are important risk factors for CRC, as is the presence of primary sclerosing cholangitis, family history of CRC, and (in some studies) early age at diagnosis of UC. Efforts to reduce this risk have focused on colonoscopic surveillance as the best alternative to the more definitive, but less appealing, approach of prophylactic colectomy. However, spurred on by findings in the sporadic CRC literature, there has been a growing interest in a possible role for chemoprevention of CRC in patients with UC. Published evidence to date indicates that 5-aminosalicylic acid agents are protective against the development of dysplasia and CRC. Oral, but not topical, steroids also appear to be chemoprotective, but their chronic use cannot be recommended for this indication. Ursodeoxycholic acid has been shown to reduce the risk of neoplasia in UC patients with primary sclerosing cholangitis. Evidence suggests, but does not prove, that folic acid is chemopreventive in patients with UC. Further studies are needed to fully define the chemoprotective role of these and other agents.


Zika Virus: What Pediatric Emergency Medicine Physicians Need to Know.
Zika virus is a mosquito-borne Flavivirus. It has emerged as an important infectious agent in the recent past, mainly because of its teratogenic effects on the fetus. This review highlights the epidemiology, diagnosis, and treatment of this emerging infection.


Computational methods for biomolecular electrostatics.
An understanding of intermolecular interactions is essential for insight into how cells develop, operate, communicate, and control their activities. Such interactions include several components: contributions from linear, angular, and torsional forces in covalent bonds, van der waals forces, as well as electrostatics. Among the various components of molecular interactions, electrostatics are of special importance because of their long range and their influence on polar or charged molecules, including water, aqueous ions, and amino or nucleic acids, which are some of the primary components of living systems. Electrostatics, therefore, play important roles in determining the structure, motion, and function of a wide range of biological molecules. This chapter presents a brief overview of electrostatic interactions in cellular systems, with a particular focus on how computational tools can be used to investigate these types of interactions.


Binding of lithium and boron to human plasma proteins II: results for a bipolar patient not on lithium therapy.
We report further measurements of lithium and boron bound to human plasma proteins using the techniques of gel chromatography, thermal-neutron activation, and high-sensitivity helium isotope mass spectrometry. The plasma sample was donated by a bipolar patient who had never been on lithium therapy. The plasma lithium-binding pattern for the bipolar patient is distinctly different from that previously observed in this laboratory for plasma donated by a normal individual. In the bipolar case, virtually all of the lithium is bound to low-molecular-weight proteins (approx 1000 amu), whereas in the normal case, most of the lithium eluted from the gel column was bound to five high-molecular-weight proteins (approx 50,000 amu to approx 1,000,000 amu). The gel elution profiles for boron were roughly similar for the normal and bipolar cases. The lithium results are in agreement with our previous speculation that lithium-binding plasma proteins are missing or exist in very low concentrations in some individuals suffering from affective disorders.


Hummingbirds as net rate maximisers.
The behaviour of foraging hummingbirds can be accounted for by assuming the maximisation of net rate. The currency, net energy per unit volume consumed suggested by Montgomerie et al. (1984), is shown to be an unnecessary means of interpreting behaviour when compared alongside an extended net rate model. The reason for the failure of previous net rate models to account for observed hummingbird feeding times lies in their negleet of the associated costs outside of the foraging period.


Local anaesthetics block hyperpolarization-activated inward current in rat small dorsal root ganglion neurones.
(1) Hyperpolarizing voltage steps evoke slowly activating inward currents in a variety of neurones and in cardiac cells. This hyperpolarization-activated inward current (I(h)) is thought to play a significant role in cell excitability, firing frequency, or in setting of the resting membrane potential in these cells. We studied the effects of lidocaine, mepivacaine, QX-314 and bupivacaine as well as its enantiomers on I(h) in the membrane of dorsal root ganglion neurones (DRG). (2) The patch-clamp technique was applied to small dorsal root ganglion neurones identified in 200 micro M thin slices of young rat DRGs. Under voltage-clamp conditions, the whole-cell I(h) current was recorded in the presence of different concentrations of the local anaesthetics. In current-clamp mode the resting membrane potential and the voltage response of DRG neurones to injected current pulses were investigated. (3) I(h) was reversibly blocked by bupivacaine, lidocaine and mepivacaine applied externally in clinically relevant concentrations. Concentration-response curves gave half-maximum inhibiting concentrations of 55, 99 and 190 micro M, respectively. Bupivacaine block of the I(h) current was not stereoselective. No significant effect was observed when QX-314 was applied to the external surface of the membrane. (4) In current-clamp experiments 60 micro M bupivacaine slightly hyperpolarized the membrane. The membrane stimulation by low-amplitude current pulses in the presence of bupivacaine showed an increase of the hyperpolarizing responses. (5) Our findings suggest an important role of the I(h)-block by local anaesthetics in the complex mechanism of drug action during epidural and spinal anaesthesia.


Does proximity to coal-fired power plants influence fish tissue mercury?
Much of the mercury contamination in aquatic biota originates from coal-fired power plants, point sources that release mercury into the atmosphere. Understanding mercury dynamics is primarily important because of the toxic threat mercury poses to wildlife and humans through the consumption of contaminated fish. In this study, we quantified the relative importance of proximity to coal-fired power plants on mercury accumulation in two fish species of different trophic positions. Fish, water and sediment were collected and analyzed from 14 lakes, seven near to (<10 km) and seven far from (>30 km) coal-fired power plants. Lower tissue mercury and higher tissue selenium concentrations were measured in fish collected near power plants. Moreover, mercury accumulation in fish was driven by biotic characteristics (e.g., trophic position, total length, age), waterbody characteristics (e.g., pH, dissolved organic carbon and sulfate) and distance from power plants. Proximity to an atmospheric point-source of mercury and selenium, such as a coal-fired power plant, affects the quantities of mercury and selenium accumulated in fish tissue. Differences in accumulation are hypothesized to be driven in part by selenium-mitigated reductions in fish tissue mercury near power plants. Although reduced fish tissue mercury in systems near power plants may decrease mercury-specific risks to human consumers, these benefits are highly localized and the relatively high selenium associated with these tissues may compromise ecological health.


The Effects of Interleukin-17 (IL-17)-Related Inflammatory Cytokines and A20 Regulatory Proteins on Astrocytes in Spinal Cord Cultured In Vitro.
This study focused on investigating the expression of several inflammatory cytokines and chemokines, including regulatory proteins in the astrocytes of mice stimulated with IL-17. The cultured astrocytes from the spinal cords of mice were stimulated with IL-17. The expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), monocyte chemotactic protein-1/5 (MCP-1/5) and macrophage inflammatory protein-2 (MIP-2) stimulated with IL-17 (50 ng/ml) at different time points (3 h, 6 h, 12 h, 24 h and 48 h) were determined using real-time PCR and ELISA. The expressions of A20 (tumor necrosis factor α inducible protein 3, TNFAIP3) and NF-x03BA;B were examined using real-time PCR and western blotting. Compared with the control group, the mRNA expression levels of IL-6, TNF, MCP-1/5 and MIP-2 increased significantly at 6 h after IL-17 stimulation, while the protein expression levels also increased significantly and peaked at 12 h. The mRNA expression level of NF-x03BA;B increased and peaked at 6 h before gradually declining, while the expression of A20 decreased. The protein expression level of NF-x03BA;B increased and peaked at 12 h, while the expression A20 had an opposite response. The study showed that NF-x03BA;B may have an effect on the cytokines secreted by astrocytes after IL-17 stimulation. Moreover, both A20 and NF-x03BA;B could regulate the expression and secretion of inflammatory mediators.


Effects of short-term intravaginal progestagens on the onset and features of estrus, preovulatory LH surge and ovulation in sheep.
In the present study, there was a comparison among classical long-term progestagen (fluorogestone acetate) protocols for synchronization of estrus and ovulation (14 days; group FGA14, n = 9 ewes) and short-term protocols based on 7 days of progestagen treatment plus a dose of prostaglandin F2α at either insertion (PG-FGA7, n = 11) or removal (FGA7-PG, n = 12). There were no significant differences in the ovulation rate and progesterone secretion among treatments. The FGA7-PG group, however, had a similar percentage of ewes expressing estrous behavior than the group FGA14 (90.9 and 100%, respectively, with a trend for a lesser percentage in the PG-FGA7 group, 63.6%) and about 90% of the ewes in the FGA7-PG group had the preovulatory surge release of LH 8 h after the onset of estrous behavior. These features may be related to a greater number of preovulatory follicles during growing phases (P < 0.05) and a greater plasma estradiol concentration (P < 0.05) in this group than in the classical 14-day group, which suggest these are more functional preovulatory follicles. In conclusion, therefore, the use of the FGA7-PG treatment may favor efficiency of progestagen-based protocols for reproductive management.


Gene transfection of multicellular spheroid of hepatocytes on an artificial substrate.
The handling of hepatocytes, a major cell population in the liver, is an important technique in both liver tissue engineering and hepatology. However, these cells are so fragile that it has been impossible to harvest hepatocytes with high viability from tissue culture dishes after a period of culture in vitro. In this study, we employed an artificial substrate for transfection of multilayer hepatocytes and harvested these cells with high viability after transfection. Hepatocytes cultured on an amphiphilic artificial substrate form multilayer aggregates (spheroids) in the presence of growth factors during gene transfection with cation liposomes. Compared to cells cultured on a collagen-coated plate, these spheroids are easily harvested with high viability by pipetting in EDTA solution. In addition, these spheroids rapidly spread on collagen after transfer from the artificial substrate, demonstrating that hepatocytes in the center of the spheroids were viable. Epidermal growth factor (EGF) increased the transfection efficiency into hepatocytes while hepatocyte growth factor (HGF) alone did not increase the efficiency. However, HGF synergestically increased the effect of EGF on transfection. Interestingly, this transfection required the process of spheroid formation because the gene was not transfected once the spheroid formation completed or under conditions where hepatocytes did not form spheroids. This method using spheroidal hepatocytes for in vitro transfection is promising for the development of ex vivo gene therapy.


Evaluation of pertinent parameters of a new identification system for non-enteric gram-negative rods.
The API 20 NE (Rapid NFT) system for identification of non-enteric aerobic gram-negative rods was evaluated using 431 strains of species covered by the analytical profile index and previously identified by conventional methods. In an analysis of several parameters, 343 (80%) of the strains were identified correctly with good to excellent probabilities of positive reactions (80.0-99.9%), 190 (55%) of these within 24 h; 74 (17%) yielded primary identifications with lower probabilities. Only 3% of the strains could not be correctly identified. The system is very satisfactory for routine use, but could be improved by modified pre-testing of the strains and by including more species in the profile index.


Long-Term Survival and Outcomes According to VARC-2 Criteria for Subclavian, Direct Aortic, Femoral, and Apical Implantation: An 8-Year United Kingdom TAVI Surgical Experience.
The use of transcatheter aortic valve implantation (TAVI) has expanded as an alternative to aortic valve replacement, and more than 500,000 patients have been treated worldwide since April, 2002. The aim of this study was to compare complications and morbidity/mortality associated with different TAVI approaches as alternatives to a surgical-femoral approach. From January 2007 to January 2015, 2,863 patients underwent TAVI surgery in 36 United Kingdom TAVI centers. Primary outcomes were complications according to VARC-2 criteria. The secondary outcome was long-term survival. The enrolled patients were distributed as follows: 1,150 in the surgical-femoral (SF) group, 1,216 in the trans-apical (TA) group, 207 in the direct-aortic (DA) group, and 290 in the subclavian (SC) group. There were no differences in the rates of acute myocardial infarction, emergency valve-in-valve, cardiac tamponade, or TIA among the groups. The rates of stroke and renal replacement therapy, as well as in-hospital stay, in-hospital death, and 30-day and 12-month mortality in DA and TA were higher than those in SC and SF. The rates of paravalvular leak and balloon post-dilatation in SC and DA were higher than those in TA and SF. The rates of vascular injuries and permanent pacemaker implantation in SC and SF were higher than those in DA and TA. SF provided the best long term-survival (p = 0.008). This was a large study that compared outcomes and long-term survival among different TAVI surgical approaches in a national real-world setting. According to our results, SF provided the best survival. While SC provided worse survival than SF, it was still better than TA and DA, and thus may represent the safest non-femoral access if use of the femoral approach is precluded.


Measurement of the absolute gamma-ray emission intensities from the decay of 147Nd.
The 2011 Decay Data Evaluation Project (DDEP) evaluation for 147Nd includes recommended absolute emission intensities for the two main gamma-rays at 91.105 (2) keV and 531.016 (22) keV of 0.284 (18) and 0.127 (9) respectively, i.e. with uncertainties of 6.3% and 7.1%. These large uncertainties stem from inconsistencies in the published data and are unfit for modern purposes, since the production of 147Nd is used as an important neutron flux dosimeter. The LNE-LNHB has undertaken new absolute gamma-ray emission intensity measurements. The results of these measurements will be presented, along with a full uncertainty budget, and their effect on the recommended data uncertainties will be discussed.


Bilateral elastofibroma dorsi.
Elastofibroma dorsi was diagnosed in a 48-year-old woman with bilateral subscapular tumor masses diagnosed asynchronously in an interval of 4 months in spite of presence of another lesion at first admittance. She underwent subsequent resections of the lesions. They were diagnosed as elastofibroma. Reevaluation of the initial computerized tomography of thorax indicated an omitted small lesion with a 2-cm diameter and 25.2-day doubling time. Although the real neoplastic nature of elastofibroma is unknown, bilateral presence of the masses with different sizes and relatively short doubling times of the lesions must be kept in mind.


Airway management in general anesthesia for endovascular treatment of cerebral arteriovenous malformation: a retrospective observational study.
This retrospective and observational study aimed to retrospectively evaluate the use of the endotracheal tube (ETT) and the Laryngeal Mask Airway (LMA) for the airway management with respect to airway safety, hemodynamic stability, adverse respiratory events, and recovery characteristics in patients who underwent endovascular treatment (EVT) for cerebrovascular arteriovenous malformation under general anesthesia between 2011 and 2018. The study included data from the patient's electronic medical records and anesthesia files. The primary outcome measure was the incidence of hemodynamic disturbances and respiratory adverse events during airway management. The secondary outcome measure was the comparison of recovery characteristics. The airway was secured using ETT in 41 patients and LMA in 39 patients. Airway safety was established in all patients without a complication throughout the procedure. Mean arterial blood pressure and heart rate were increased to > 20% of baseline levels at intubation and extubation periods in more patients in the ETT group than the LMA group (27 vs. 3; p = 0.07, and 11 vs. 2; p = 0.021). Respiratory adverse events including straining and coughing were observed in ten patients in the ETT group but only in one patient in the LMA group (p = 0.013). Time to extubation, to neurological assessment, and to discharge from the angiography unit were similar (p > 0.05). It was concluded that LMA provided sufficient airway safety as with ETT and may be used as an alternative to ETT for EVTs under general anesthesia.


Methotrexate and low-dose corticosteroid: An effective alternate against corticosteroid-resistant granulomatous lobular mastitis.
Granulomatous lobular mastitis (GM) is an inflammatory breast disease with unknown etiology. Studies showed that some patients could achieve complete remission with corticosteroids and excisional surgery. However, some patients would suffer from corticosteroid resistance. We aim to report our single-center experience with the highest number of corticosteroid-resistant GM patients treated by methotrexate and low-dose corticosteroid. The medical record database in our center was searched retrospectively for GM patients between January 2015 and January 2022. Patients suffered corticosteroid resistance and received methotrexate-containing regimen were included in this study. The clinical characteristics, management and outcomes were collected and analyzed. Eighty-one patients with the median follow-up of 18 months (range 5-61 months) were included. The median age was 30 years old (range 21-48 years). The common initial complaints were breast mass, pain, and erythema. The initial treatment of 80 (98.8%) patients was methylprednisolone. Patients were switched to methotrexate and low-dose corticosteroid due to corticosteroid resistance. Complete remission was achieved in 61 (75.3%) patients who received methotrexate and low-dose corticosteroid with or without segmental dissection. Nineteen methotrexate-resistant patients were referred for antimycobacterial treatment with the exception that one patient was lost during follow-up. Thirteen of them achieved complete remission, and the other five gained partial remission and received segmental dissection. None of these methotrexate-resistant patients recured. An approach with methotrexate and low-dose corticosteroid should be considered as an alternative method to corticosteroid-resistant GM patients.


Delay of total joint replacement is associated with a higher 90-day revision rate and increased postoperative complications.
Delay of elective surgeries, such as total joint replacement (TJR), is a common procedure in the current pandemic. In trauma surgery, postponement is associated with increased complication rates. This study aimed to evaluate the impact of postponement on surgical revision rates and postoperative complications after elective TJR. In a retrospective analysis of 10,140 consecutive patients undergoing primary total hip replacement (THR) or total knee replacement (TKR) between 2011 and 2020, the effect of surgical delay on 90-day surgical revision rate, as well as internal and surgical complication rates, was investigated in a university high-volume arthroplasty center using the institute's joint registry and data of the hospital administration. Moreover, multivariate logistic regression models were used to adjust for confounding variables. Two thousand four hundred and eighty TJRs patients were identified with a mean delay of 13.5 ± 29.6 days. Postponed TJR revealed a higher 90-day revision rate (7.1-4.5%, p < 0.001), surgical complications (3.2-1.9%, p < 0.001), internal complications (1.8-1.2% p < 0.041) and transfusion rate (2.6-1.8%, p < 0.023) than on-time TJR. Logistic regression analysis confirmed delay of TJRs as independent risk factor for 90-day revision rate [OR 1.42; 95% CI (1.18-1.72); p < 0.001] and surgical complication rates [OR 1.51; 95% CI (1.14-2.00); p = 0.04]. Alike trauma surgery, delay in elective primary TJR correlates with higher revision and complication rates. Therefore, scheduling should be performed under consideration of the current COVID-19 pandemic. Level III-retrospective cohort study.


Depression 12-months after coronary artery bypass graft is predicted by cortisol slope over the day.
Alterations in the diurnal profile of cortisol have been associated with depressed mood in patients with coronary heart disease. The relationship between cortisol output and depressed mood has not been investigated prospectively in coronary artery bypass graft (CABG) patients before. We aimed to study the relationship between cortisol measured pre- and post-operatively and depression symptoms measured 12 months after CABG surgery. We analysed data from 171 patients awaiting first-time, elective CABG surgery from the pre-assessment clinic at St. George's Hospital, London. The Beck Depression Inventory (BDI) was used to assess depression symptoms and saliva samples were collected to measure diurnal cortisol. Baseline assessments of depression and cortisol were obtained an average 29days before surgery, short-term follow-up of cortisol occurred 60days after surgery and long-term follow-up of depression was assessed 378days after surgery. Baseline cortisol slope was not associated with depression at 12-month follow-up. However, a steeper cortisol slope measured 60days after surgery predicted reduced odds of depression (BDI≥10) 12 months after surgery (odds ratio 0.661, 95% confidence interval 0.437-0.998, p=0.049) after controlling for covariates. These findings suggest interventions aimed at improving adaptation in the early recovery period may have long-term benefits in this patient group.


Interactions among factors affecting growth, development and survival in experimental populations of Bufo terrestris (Anura: Bufonidae).
We designed a series of field experiments to investigate the importance of interactions between biotic and abiotic factors on the survival and development of larval cohorts of Bufo terrestris. Five "blocks" in a large pond represented environments of varying physical harshness. In the more severe blocks, increased density inhibited growth rates, yet in the more benign blocks, increased density enhanced growth rate. Although different blocks produced very different levels of survival to metamorphosis and size at metamorphosis, there were no interactions with density. Increased density produced lengthened development times in the harsher blocks, but had no effect in the less stressful blocks. Hatchlings that were in the lowest of 3 initial size classes never caught up with their larger contemporaries and survived poorly. Hatchlings in the middle and largest size classes performed equivalently in all parameters of growth and development, but hatchlings from the middle size class were less likely to survive than their larger contemporaries. The effects of initial size did not interact with block. The inhibitory patterns displayed by density in conjunction with varying physical environments are similar to those found in comparable experiments with plants.


Flexible complementary circuits operating at sub-0.5 V via hybrid organic-inorganic electrolyte-gated transistors.
Electrolyte-gated transistors (EGTs) hold great promise for next-generation printed logic circuitry, biocompatible integrated sensors, and neuromorphic devices. However, EGT-based complementary circuits with high voltage gain and ultralow driving voltage (<0.5 V) are currently unrealized, because achieving balanced electrical output for both the p- and n-type EGT components has not been possible with current materials. Here we report high-performance EGT complementary circuits containing p-type organic electrochemical transistors (OECTs) fabricated with an ion-permeable organic semiconducting polymer (DPP-g2T) and an n-type electrical double-layer transistor (EDLT) fabricated with an ion-impermeable inorganic indium-gallium-zinc oxide (IGZO) semiconductor. Adjusting the IGZO composition enables tunable EDLT output which, for In:Ga:Zn = 10:1:1 at%, balances that of the DPP-g2T OECT. The resulting hybrid electrolyte-gated inverter (HCIN) achieves ultrahigh voltage gains (>110) under a supply voltage of only 0.7 V. Furthermore, NAND and NOR logic circuits on both rigid and flexible substrates are realized, enabling not only excellent logic response with driving voltages as low as 0.2 V but also impressive mechanical flexibility down to 1-mm bending radii. Finally, the HCIN was applied in electrooculographic (EOG) signal monitoring for recording eye movement, which is critical for the development of wearable medical sensors and also interfaces for human-computer interaction; the high voltage amplification of the present HCIN enables EOG signal amplification and monitoring in which a small ∼1.5 mV signal is amplified to ∼30 mV.


The Equine Neonatal Cardiovascular System in Health and Disease.
The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids.


A case of IgA nephropathy associated with vitiligo, primary hypothyroidism and primary adrenocortical insufficiency.
A 14 year old boy presented with recurrent attacks of macroscopic haematuria preceded by tonsillitis. Clinical examination revealed generalised vitiligo. Renal function was normal with microscopic haematuria. Percutaneous renal biopsy showed mesangial proliferation on light microscopy with deposition of IgA and IgM in a granular pattern in the mesangium and glomerular basement membrane compatible with a diagnosis of IgA nephropathy. Biochemical investigations revealed primary hypothyroidism and primary adrenocortical insufficiency with negative organ specific autoimmune screen. Renal function has not deteriorated after three years follow-up. This particular association has not been previously described to our knowledge.


RAD51 paralogs: Expanding roles in replication stress responses and repair.
Mammalian RAD51 paralogs are essential for cell survival and are critical for RAD51-mediated repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the molecular mechanism by which RAD51 paralogs participate in HR is largely unclear. Germline mutations in RAD51 paralogs are associated with breast and ovarian cancers and Fanconi anemia-like disorder, underscoring the crucial roles of RAD51 paralogs in genome maintenance and tumor suppression. Despite their discovery over three decades ago, the essential functions of RAD51 paralogs in cell survival and genome stability remain obscure. Recent studies unravel DSB repair independent functions of RAD51 paralogs in replication stress responses. Here, we highlight the recent findings that uncovered the novel functions of RAD51 paralogs in replication fork progression, its stability, and restart and discuss RAD51 paralogs as a potential therapeutic target for cancer treatment.


Tourette's syndrome is not associated with interleukin-10 receptor 1 variants on chromosome 11q23.3.
Interleukin-10 receptor 1 (IL-10R1) single nucleotide polymorphisms, located on chromosome 11q23 - a strong candidate for linkage with Tourette's syndrome (TS) - have been investigated for association with TS. DNA of 77 patients with a DSM-IV (Diagnostic and Statistical Manual IV) diagnosis of TS and 250 healthy controls was genotyped. IL-10R1 was not associated with TS.


Retracted: Practical Research on Artificial Intelligence Algorithms, Paleontology, Data Mining, and Digital Restoration of Public Information.
[This retracts the article DOI: 10.1155/2022/3068686.].


Feasibility and Safety of Laparoscopic-Assisted Bowel Segmental Resection for Deep Infiltrating Endometriosis: A Retrospective Cohort Study With Description of Technique.
To evaluate the feasibility and safety of laparoscopic segmental bowel resection for deep infiltrating endometriosis (DIE). Retrospective clinical study (Canadian Task Force classification II-3). Endoscopica Malzoni-Center for Advanced Endoscopic Gynecological Surgery, Avellino, Italy. A retrospective cohort of 248 patients who underwent laparoscopic segmental bowel resection between January 1, 2011, and December 31, 2014. Laparoscopic segmental bowel resection for DIE. Bowel endometriosis was histologically confirmed in all 248 of the 248 patients (100%). The mean length of the resected specimens was 11.83 ± 4.56 cm. In all cases, margins were free of disease. The muscular layer was infiltrated up to the submucosal layer in all 248 patients (100%), whereas the mucosal layer showed signs of infiltration in only 4 patients (1.6%). Two nodules were found in 36 patients (14.5%), and 3 nodules were found in only 8 patients (3.2%). None of the resected bowel segments had nodules shorter than 3 cm, and the majority of lesions had a longitudinal diameter of 3 to 7 cm. In the majority of cases, resected segments involved the mid to low rectum (distance from the lower margin of resected segment from the anal verge of 4 to 12 cm), whereas in 6% of cases, ultra-low resections (≤4 cm) were performed. No intraoperative complications occurred, and conversion to laparotomy was not required for any patient. Major perioperative and early and late postoperative complications occurred in 20 patients (8.06%). Significantly reduced pain associated with disease was observed up to the 1-year follow-up irrespective of postoperative hormonal treatment. Pelvic relapse was found in up to 50% of patients, especially in patients without hormonal suppression, but only in the form of endometriomas or adherences, with no recurrent deep lesions observed. This large single-center series demonstrates that laparoscopic bowel resection for DIE is a feasible technique, with low complication rates. In symptomatic patients, treating deep fibrotic endometriosis nodules by laparoscopic segmental resection is very effective in reducing pain and restoring bowel function. This surgical approach is safe but complex, requiring specific skills in laparoscopic urologic and colorectal procedures, and should be performed only in specialized high-volume centers by high-volume surgeons.


Coronary vascular growth matches IGF-1-stimulated cardiac growth in fetal sheep.
As loss of contractile function in heart disease could often be mitigated by increased cardiomyocyte number, expansion of cardiomyocyte endowment paired with increased vascular supply is a desirable therapeutic goal. Insulin-like growth factor 1 (IGF-1) administration increases fetal cardiomyocyte proliferation and heart mass, but how fetal IGF-1 treatment affects coronary growth and function is unknown. Near-term fetal sheep underwent surgical instrumentation and were studied from 127 to 134 d gestation (term = 147 d), receiving either IGF-1 LR3 or vehicle. Coronary growth and function were interrogated using pressure-flow relationships, an episode of acute hypoxia with progressive blockade of adenosine receptors and nitric oxide synthase, and by modeling the determinants of coronary flow. The main findings were that coronary conductance was preserved on a per-gram basis following IGF-1 treatment, adenosine and nitric oxide contributed to hypoxia-mediated coronary vasodilation similarly in IGF-1-treated and Control fetuses, and the relationships between coronary flow and blood oxygen contents were similar between groups. We conclude that IGF-1-stimulated fetal myocardial growth is accompanied by appropriate expansion and function of the coronary vasculature. These findings support IGF-1 as a potential strategy to increase cardiac myocyte and coronary vascular endowment at birth.


Time Trends of Crohn's Disease in Catalonia from 2011 to 2017. Increasing Use of Biologics Correlates with a Reduced Need for Surgery.
Data from clinical trials suggest that biological drugs may improve the outcomes in Crohn's disease (CD) by reducing the need for surgery or hospitalization. The aim of this study is to evaluate the time-trends of the use of biological drugs and other treatments for CD, and its relationship with outcomes in Catalonia. All patients with CD included in the Catalan Health Surveillance System (containing data on a population of more than 7.5 million) from 2011 to 2017 were identified. The exposures to different treatments for inflammatory bowel disease were retrieved from electronic invoicing records. Between 2011 and 2017, the use of salicylates, corticosteroids and immunosuppressive treatment fell from 28.8% to 17.1%, 15.8% to 13.7%, and 32.9% to 29.6%, respectively (p < 0.001). Biological treatment use rose from 15.0% to 18.7% (p < 0.001). Ostomy rates per 1000 patients/year fell from 13.2 in 2011 to 9.8 in 2017 (p = 0.003), and surgical resection rates from 24.1 to 18.0 (p < 0.001). The rate of CD-related hospitalizations per 1000 patients/year also fell, from 92.7 to 72.2 (p < 0.001). Biological drug use rose from 15.0% to 18.7% between 2011 and 2017. During this period, we observed an improvement in the outcomes of CD patients.


Multigenerational effects of the insecticide Pyriproxyfen and recovery in Daphnia magna.
In the present study, an ecotoxicological approach to the evaluation of the insecticide Pyriproxifen in the crustacean Daphnia magna was done. Acute toxicity tests (48 h), feeding behavior test (5 h) and chronic toxicity test (21 days) were carried out on a parental daphnid generation (F0). Pyriproxifen D. magna EC50 value in our experimental conditions was 336.47 μg/L. Based on this result, sublethal test concentrations were selected for the feeding study and the F0 chronic experiment. Filtration and ingestion rates of D. magna exposed animals did not show any significant difference respect to control daphnids. However, daphnids from the parental F0 generation when exposed to the insecticide during 21 days showed a decreased in all the reproductive parameters tested (mean total neonates per female, mean brood size, time to first brood, and mean number of broods per female) as well as in the population statistic growth rate (r), although survival was not affected. On the other hand, offspring from F0 females exposed to the highest Pyriproxifen concentration (14.02 μg/L) were separated in two F1 generation experiments. One group was transferred during 21 days to a medium free of toxicant (F1 generation-TC group) while the other group was exposed during 21 days to the same insecticide concentration as their mothers (14.02 μg/L) (F1 generation-TT group). Results from both experiments determined a decreased in most of the reproductive parameters which was higher in the F1-TT group, although some of them were recovered in the F1-TC group. On the other hand, the morphological analysis of the daphnids showed that the coloration pattern was altered in the daphnids exposed to the insecticide, together with a significant size decreased, and neonates from F0 progeny with the same morphological abnormality. Finally, we determined that the insecticide caused the appearance of males among the offspring generated by the F0.


Quality of life and physical activity associated to lower prevalence of depression in community-dwelling elderly subjects from Sao Paulo.
Studies investigating major depression and associated factors in older people from developing countries are scarce. Cross-sectional study of a community-based sample of 1563 elderly subjects aged 60 years or older from Sao Paulo, Brazil. The frequency of major depression (MD) and the relationship with sociodemographic factors, cognitive and functional impairment (CFI), clinically significant depressive symptoms (CSDS) and clinical diseases were analyzed. A brief instrument for screening of depressive symptoms in elderly people, the Mini Mental State Examination, the Fuld Object Memory Evaluation, the Informant Questionnaire on Cognitive Decline in the Elderly, the Bayer Activities of Daily Living Scale, the Cambridge Mental Disorders of the Elderly Examination, and a sociodemographic and clinical questionnaire were applied to the subjects. Major depression was diagnosed in 60 patients (3.8%). A higher odds ratio of MD was associated with female gender, being widowed, previous depressive episode, hypertension, use of psychotropic medication, (CFI), and alcohol use. A lower odds ratio of depression diagnosis was associated with physical activity and going to cinema. The cross-sectional design of the study; our sample was restricted only to community residents, excluding persons in hospitals or nursing homes. Our study shows significant association between depression and potentially modifiable factors, reinforcing the benefit of probable preventive measures, to incentive healthy lifestyle, leisure activities and the practice of physical exercise, as well as the diagnosis and treatment of CSDS, especially in primary care.


Scaffold-based three-dimensional cell model of pancreatic cancer is more suitable than scaffold-free three-dimensional cell model of pancreatic cancer for drug discovery.
Pancreatic cancer is one of the deadliest malignancies. Three-dimensional (3D) pancreatic cancer cell models for drug screening have been established to improve treatment for pancreatic cancer. However, few studies focus on different drug responses and drug-related molecular mechanisms in various types of 3D cell models. In this study, we constructed 3D scaffold-free cell models and 3D scaffold-based cell models of pancreatic cancer, evaluated chemotherapeutic drug responses in different 3D models, assessed clinical relevance of the models, and investigated molecular mechanisms of chemoresistance and drug pathways in different 3D models. Both types of 3D models showed resistance to chemotherapeutic drugs, and scaffold-based pancreatic cancer models could better reflect in vivo drug efficacy than 2D and scaffold-free pancreatic cancer models did. Increased cell adhesion, extracellular matrix (ECM) synthesis and drug transport were essential for drug resistance in 3D models, and anti-apoptosis might contribute to extreme chemoresistance in scaffold-free models. Moreover, scaffold-based pancreatic cancer models were more suitable than scaffold-free models for drug pathway research.


Biological control of the larger grain borer Prostephanus truncatus (Coleoptera: Bostrichidae) in Kenya using a predatory beetle Teretrius nigrescens(Coleoptera: Histeridae).
The establishment of the predatory histerid beetle, Teretrius nigrescens Lewis, following its field release in south eastern Kenya in 1992, and its impact on populations of the larger grain borer, Prostephanus truncatus (Horn), in woodland habitats is evaluated. Pheromone trap catch data show a single strong peak of P. truncatus from November to January, coincident with the short rains. Comparisons of P. truncatus pheromone trap catches before and after predator establishment, and in areas with and without T. nigrescens, show a sustained decline of over 80% in P. truncatus abundance over a 5-year period, following the establishment T. nigrescens. Concurrent laboratory studies of the impact of T. nigrescens on populations of P. truncatus raised on a wood substrate showed a 77% reduction in the growth of the pest population. These results are compared with published findings of the impact of T. nigrescens as a biological control agent of P. truncatus in west Africa.


Imaging of cell/substrate contacts of living cells with surface plasmon resonance microscopy.
We have developed a new method for observing cell/substrate contacts of living cells in culture based on the optical excitation of surface plasmons. Surface plasmons are quanta of an electromagnetic wave that travel along the interface between a metal and a dielectric layer. The evanescent field associated with this excitation decays exponentially perpendicular to the interface, on the order of some hundreds of nanometers. Cells were cultured on an aluminum-coated glass prism and illuminated from below with a laser beam. Because the cells interfere with the evanescent field, the intensity of the reflected light, which is projected onto a camera chip, correlates with the cell/substrate distance. Contacts between the cell membrane and the substrate can thus be visualized at high contrast with a vertical resolution in the nanometer range. The lateral resolution along the propagation direction of surface plasmons is given by their lateral momentum, whereas perpendicular to it, the resolution is determined by the optical diffraction limit. For quantitative analysis of cell/substrate distances, cells were imaged at various angles of incidence to obtain locally resolved resonance curves. By comparing our experimental data with theoretical surface plasmon curves we obtained a cell/substrate distance of 160 +/- 10 nm for most parts of the cells. Peripheral lamellipodia, in contrast, formed contacts with a cell substrate/distance of 25 +/- 10 nm.


A comparison of GABAergic influences on the analgesic responses to morphine and pentazocine.
1. The interactions of three GABAergic compounds, gamma-acetylenic GABA, gamma-vinyl GABA and ethylenediamine with the analgesic effects of morphine and pentazocine were examined in mice using the hot plate and tail immersion tests. 2. A significant increase in reaction time induced by morphine was noted in the tail immersion test after pretreatment with the drugs acting through GABA functions. 3. The inhibitors of GABA transaminase, gamma-acetylenic GABA and gamma-vinyl GABA, and the GABAmimetic ethylenediamine did not significantly change the analgesic action induced by pentazocine. 4. In the hot plate test the three GABAergic compounds antagonized the analgesic effects of pentazocine in contraposition with previous results indicating that morphine-induced analgesia is increased by pretreatment with those agents. 5. These findings suggest that GABAergic and opiopeptidergic systems are interconnected through mu receptors, whereas the kappa opiate systems seem to be unrelated to GABA functions.


Excitation energy transfer in Rhodopseudomonas sphaeroides chromatophore membranes fused with liposomes.
The role of phospholipid in the structural organization of the light-harvesting complexes of Rhodopseudomonas sphaeroides was examined in photosynthetic (chromatophore) membrane vesicles fused with liposomes. Photochemically active preparations with progressive phospholipid enrichment up to greater than 15-fold were obtained by both polyethylene glycol- and acidic-pH-induced fusion. Their fluorescence emission at approximately 300 and 77 K was increased by 2-3.5-fold from the peripheral B800-850 antenna relative to that from the core B875 antenna. Up to 30-40% reduction in the efficiency of excitation energy transfer between B850 and B875 was also observed at 77 K suggesting a selective, phospholipid-induced dissociation of a portion of the B800-850 from the rest of the light-harvesting system.


A novel method for identifying nonlinear gene-environment interactions in case-control association studies.
The genetic influences on complex disease traits generally depend on the joint effects of multiple genetic variants, environmental factors, as well as their interplays. Gene × environment (G × E) interactions play vital roles in determining an individual's disease risk, but the underlying genetic machinery is poorly understood. Traditional analysis assuming linear relationship between genetic and environmental factors, along with their interactions, is commonly pursued under the regression-based framework to examine G × E interactions. This assumption, however, could be violated due to nonlinear responses of genetic variants to environmental stimuli. As an extension to our previous work on continuous traits, we proposed a flexible varying-coefficient model for the detection of nonlinear G × E interaction with binary disease traits. Varying coefficients were approximated by a non-parametric regression function through which one can assess the nonlinear response of genetic factors to environmental changes. A group of statistical tests were proposed to elucidate various mechanisms of G × E interaction. The utility of the proposed method was illustrated via simulation and real data analysis with application to type 2 diabetes.


Effect of surgical scrub on microbial population under the fingernails.
The effectiveness of two methods of presurgical hand preparation, the 10 minute routine scrub and the 90 second Hydroscrub, in reducing microbial numbers under the fingernails was determined. Bacteriologic cultures of 162 subungual areas of nine subjects revealed prescrub microbial counts of up to 1.9 X 10(5) colony-forming units per area. After the surgical scrub, bacterial concentrations were reduced to a different degree among the persons tested. The mean values of 3.0 X 10(3) to 7.8 X 10(3) colony-forming units immediately after scrub indicated that neither of the two methods tested reduced the microbial population under the fingernails of most persons to acceptable levels. The finding of high postscrub microbial counts under the fingernails is of particular interest and significance in view of the relatively low counts on the fingertips. On the basis of the results of this study, we conclude that degerming of the areas under the fingernails by present methods is not satisfactory. The implication of these findings is discussed.


[Surgical treatment of dissecting aneurysm of the interventricular septum].
To report a kind of extremely rare disease, dissecting aneurysm of the interventricular septum. Between May 1992 and January 1998, 4 patients underwent surgical treatment of dissecting aneurysm of the interventricular septum in Fuwai Hospital, Beijing. The cause of the disease was different in these four patients. Two patients may be attributable to the aneurysm of coronary sinus of valsava, 1 to the result of trauma, and the other to big perforation (diameter: 2 cm) in the bottom of the right coronary sinus of valsava, through which the blood rushed into the cavity of dissecting aneurysm of the interventricular septum. The aneurysm was resected or repaired in these patients. Three of them were subjected to aortic valve replacement and one received repair of the perforation of the right vaslava sinus. Two patients had successful reoperation and the other 2 suceeded in the first operation. All of them were uneventfully recovered. The development of dissecting aneurysm of the interventricular septum is rapid. Its prognosis is poor. Early diagnosis and operation are necessary. The pathogenic mechanism of dissecting aneurysm of the interventricular septum is unknown, but echocardiogram, electrocardiogram and nuclear magnetic resonance (NMR) are valuable for diagnosis. Surgical operation should involve the treatment of aortic valve disease. The wall of the aneurysm should be resected and the interventricular septum should be reconstructed. Good exposure can be obtained from the incision of the ascending aorta and right ventricular outflow tract. The A-V block should be treated simultaneously.


Hot-blooded singers: endothermy facilitates crepuscular signaling in African platypleurine cicadas (Hemiptera: Cicadidae: Platypleura spp.).
The cicada genus Platypleura has a wide distribution across Africa and southern Asia. We describe endothermic thermoregulation in four South African species that show crepuscular signaling behavior. This is the first evidence of thermoregulation in platypleurine cicadas. Field measurements of body temperature ( T(b)) show that these animals regulate T(b) through endogenous heat production. Maximum T(b) measured was 22.1 degrees C above ambient temperature during calling activity at dusk. The mean T(b) during dusk activity did not differ from the mean T(b) during diurnal activity. A unique behavior for cicadas, a temperature-dependent telescoping pulsation of the abdomen, was observed in the laboratory during endogenous warm-up. This behavior is part of a unique method of heat generation in endothermic cicadas. Males generally call from trunks and branches within the canopy and appear to use endothermy even when the sun is available to elevate T(b). Endothermy may provide the cicadas with the advantage of decreasing predation and acoustic competition by permitting calling from perches that most complement their cryptic coloration patterns and that ectotherms cannot use due to thermal constraints. In addition, endothermy may permit calling activity during crepuscular hours when atmospheric conditions are optimal for acoustic communication and predation risks are minimal.


Deneddylation of ribosomal proteins promotes synergy between MLN4924 and chemotherapy to elicit complete therapeutic responses.
The neddylation inhibitor MLN4924/Pevonedistat is in clinical trials for multiple cancers. Efficacy is generally attributed to cullin RING ligase (CRL) inhibition, but the contribution of non-CRL targets is unknown. Here, CRISPR screens map MLN4924-monotherapy sensitivity in retinoblastoma to a classic DNA damage-induced p53/E2F3/BAX-dependent death effector network, which synergizes with Nutlin3a or Navitoclax. In monotherapy-resistant cells, MLN4924 plus standard-of-care topotecan overcomes resistance, but reduces DNA damage, instead harnessing ribosomal protein nucleolar-expulsion to engage an RPL11/p21/MYCN/E2F3/p53/BAX synergy network that exhibits extensive cross-regulation. Strikingly, unneddylatable RPL11 substitutes for MLN4924 to perturb nucleolar function and enhance topotecan efficacy. Orthotopic tumors exhibit complete responses while preserving visual function. Moreover, MLN4924 plus melphalan deploy this DNA damage-independent strategy to synergistically kill multiple myeloma cells. Thus, MLN4924 synergizes with standard-of-care drugs to unlock a nucleolar death effector network across cancer types implying broad therapeutic relevance.


26th Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, 3-6 December 2003: update on preclinical and translational research.
The San Antonio Breast Cancer Symposium is the largest annual meeting devoted solely to breast cancer research. The late William L McGuire's vision for this meeting was to stimulate 'translational research', many years before this term became popular. In this way, the San Antonio Breast Cancer Symposium represents a forum in which basic and clinical researchers present their research side by side. Each year sees the continued evolution of our understanding of the basic mechanisms of breast cancer initiation and progression, and the clinical application of this knowledge. Major topics of discussion at the symposium this year were the cell cycle, new evolving concepts of estrogen receptor action, breast cancer stem cells, new predictive and prognostic markers (including microarray studies), and continued exploration of the mechanisms of drug resistance. This report will summarize preclinical and translational highlights from the meeting.


Multicultural Transitions: Caregiver Presence and Language-Concordance at Discharge.
Patients with low health literacy (HL) and minority patients encounter many challenges during hospital to community transitions. We assessed care transitions of minority patients with various HL levels and tested whether presence of caregivers and provision of language-concordant care are associated with better care transitions. A prospective cohort study of 598 internal medicine patients, Hebrew, Russian, or Arabic native speakers, at a tertiary medical center in central Israel, from 2013 to 2014.HL was assessed at baseline with the Brief Health Literacy Screen. A follow-up telephone survey was used to administer the Care Transition Measure [CTM] and to assess, caregiver presence and patient-provider language-concordance at discharge. Patients with low HL and without language-concordance or caregiver presence had the lowest CTM scores (33.1, range 0-100). When language-concordance and caregivers were available, CTM scores did not differ between the medium-high and low HL groups (68.7 and 66.9, respectively, p = 0.118). The adjusted analysis, showed that language-concordance and caregiver presence during discharge moderate the relationship between HL and patients' care transition experience (p < 0.001). Language-concordance care and caregiver presence are associated with higher patients' ratings of the transitional-care experience among patients with low HL levels and among minorities.


Interactive deciphering electron-shuttling characteristics of Coffea arabica leaves and potential bioenergy-steered anti-SARS-CoV-2 RdRp inhibitor via microbial fuel cells.
Due to the pandemics of COVID-19, herbal medicine has recently been explored for possible antiviral treatment and prevention via novel platform of microbial fuel cells. It was revealed that Coffea arabica leaves was very appropriate for anti-COVID-19 drug development. Antioxidant and anti-inflammatory tests exhibited the most promising activities for C. arabica ethanol extracts and drying approaches were implemented on the leaf samples prior to ethanol extraction. Ethanol extracts of C. arabica leaves were applied to bioenergy evaluation via DC-MFCs, clearly revealing that air-dried leaves (CA-A-EtOH) exhibited the highest bioenergy-stimulating capabilities (ca. 2.72 fold of power amplification to the blank). Furthermore, molecular docking analysis was implemented to decipher the potential of C. arabica leaves metabolites. Chlorogenic acid (-6.5 kcal/mol) owned the highest binding affinity with RdRp of SARS-CoV-2, showing a much lower average RMSF value than an apoprotein. This study suggested C. arabica leaves as an encouraging medicinal herb against SARS-CoV-2.


Vermicomposting of livestock manure as affected by carbon-rich additives (straw, biochar and nanocarbon): A comprehensive evaluation of earthworm performance, microbial activities, metabolic functions and vermicompost quality.
Vermicomposting is an eco-friendly method for treating organic wastes. This study investigated the effects of the addition of straw (S), biochar (B), nanocarbon (N), S + B and S + N to cow dung (CD) on earthworm (Eisenia fetida) performance, microbial properties and vermicompost quality. In general, the earthworm growth rate and cocoon production were enhanced by straw addition, but were inhibited by biochar or nanocarbon addition. However, biochar and nanocarbon increased microbial communities associated with organic matter decomposition, and improved metabolic functions, enzyme activities and vermicompost properties. Moreover, addition of straw in combination with nanocarbon resulted in the highest vermicompost quality index (VQI), and significantly increased the biomass of three different test crops (radish, lettuce and pakchoi). These results indicated that biochar and nanocarbon mainly improved microbial activities, while straw primarily enhanced earthworm performance during vermicomposting. In addition, straw combined with nanocarbon can be used to enhance the agronomic performance of vermicompost.


Optimal β-galactosidases for producing high-titer 3,6-anhydro-L-galactose from red-algal agarobiose.
3,6-Anhydro-L-galactose (L-AHG) is a monomeric sugar in agarose derived from red macroalgae. Owing to its various physiological activities such as anti-inflammation, moisturizing, skin whitening, anti-colon cancer, and anti-cariogenicity, L-AHG is a potential functional ingredient. In our previous study, a simple and efficient two-step L-AHG production process was designed for high-titer L-AHG production, where a single enzyme was used after the liquefaction of agarose by acid prehydrolysis. However, the enzyme used did not completely hydrolyze agarobiose (AB). Therefore, in this study, for the efficient hydrolysis of AB and the high-titer production of L-AHG, various β-galactosidases belonging to glycoside hydrolase families 1, 2, 35, and 42 were compared by testing their substrate specificities and kinetic parameters. Among the five β-galactosidases, Bga42A, originating from Bifidobacterium longum ssp. infantis ATCC 15,697, showed the highest substrate specificity. Consequently, the two-step process utilizing Bga42A as a single enzyme resulted in a high-titer production of L-AHG at 85.9 g/L, demonstrating the feasibility of producing L-AHG from agarose. KEY POINTS: • L-AHG derived from red macroalgae has various physiological activities. • Various β-galactosidases were evaluated to efficiently hydrolyze agarobiose. • Bga42A showed the highest substrate specificity against agarobiose. • The highest amount of L-AHG with 85.9 g/L was simply produced.


An R2R3-MYB Transcription Factor Regulates Eugenol Production in Ripe Strawberry Fruit Receptacles.
Eugenol is a volatile phenylpropanoid that contributes to flower and ripe fruit scent. In ripe strawberry (Fragaria × ananassa) fruit receptacles, eugenol is biosynthesized by eugenol synthase (FaEGS2). However, the transcriptional regulation of this process is still unknown. We have identified and functionally characterized an R2R3 MYB transcription factor (emission of benzenoid II [FaEOBII]) that seems to be the orthologous gene of PhEOBII from Petunia hybrida, which contributes to the regulation of eugenol biosynthesis in petals. The expression of FaEOBII was ripening related and fruit receptacle specific, although high expression values were also found in petals. This expression pattern of FaEOBII correlated with eugenol content in both fruit receptacle and petals. The expression of FaEOBII was repressed by auxins and activated by abscisic acid, in parallel to the ripening process. In ripe strawberry receptacles, where the expression of FaEOBII was silenced, the expression of cinnamyl alcohol dehydrogenase1 and FaEGS2, two structural genes involved in eugenol production, was down-regulated. A subsequent decrease in eugenol content in ripe receptacles was also observed, confirming the involvement of FaEOBII in eugenol metabolism. Additionally, the expression of FaEOBII was under the control of FaMYB10, another R2R3 MYB transcription factor that regulates the early and late biosynthetic genes from the flavonoid/phenylpropanoid pathway. In parallel, the amount of eugenol in FaMYB10-silenced receptacles was also diminished. Taken together, these data indicate that FaEOBII plays a regulating role in the volatile phenylpropanoid pathway gene expression that gives rise to eugenol production in ripe strawberry receptacles.


Identification of P4HA1 as a prognostic biomarker for high-grade gliomas.
Prolyl 4-Hydroxylase Subunit Alpha 1 (P4HA1) is the active catalytic component of prolyl 4-hydroxylase and plays a crucial role in modulating extracellular matrix hemostasis. P4HA1 has been reported to promote tumor progression by enhancing invasion and angiogenesis. Overexpression of P4HA1 is associated with decreased survival for patients with breast and prostate cancer. However, the prognostic significance of P4HA1 for glioma patients remains undefined. The expression of P4HA1 in 290 gliomas (WHO grade II-IV) and 10 normal brain tissues was examined with TMA-based immunohistochemistry assay. The correlation between P4HA1 expression and clinicopathological parameters as well as the prognosis of glioma patients was investigated. Cytoplasmic expression of P4HA1 is high in 37.93% of all glioma cases, with 44.98% in high-grade gliomas and 19.75% in low-grade gliomas respectively. Increased P4HA1 level was correlated with advanced histological grade (p<0.01) and old age (p=0.01). Upregulation of P4HA1, as well as histological grade, was an independent risk factor for unfavorable prognosis. Subgroup analysis demonstrated that high P4HA1 expression was significantly associated with poor prognosis for high-grade gliomas (p<0.01) but not for low-grade gliomas. P4HA1 was upregulated in gliomas. High expression of P4HA1 was correlated with the malignancy of gliomas and could serve as a prognostic indicator for patients with high-grade gliomas.


The one-two punch: combination treatment in chronic myeloid leukemia.
Despite the success of tyrosine kinase inhibitor (TKI) therapy in patients with chronic myeloid leukemia (CML), minimal residual disease persists, requiring indefinite treatment. Accumulated evidence has shown that leukemic stem cells (LSCs) in the bone marrow can survive TKI treatment via downstream BCR-ABL1-independent signaling pathways that are activated by soluble growth factors and interactions with the extracellular matrix in the bone marrow microenvironment. Research efforts have therefore turned to the identification and development of agents that target LSCs, and together with TKIs, have the potential to eradicate CML. A number of such agents are now under clinical investigation, and others are soon to enter early-phase studies. This review examines the pathways, molecular targets, and potential new therapeutics that, with TKIs, may provide an effective "one-two punch" to cure CML.


The impact of institutional clinical trial recruitment versus hospital volume on survival outcomes of patients with head and neck cancer: An analysis of the PET-NECK trial outcomes, UKCRN portfolio, and Hospital Episode Statistics (HES) in England.
High institutional clinical trial recruitment and high hospital volume are reported to be independent indicators of better patient outcomes following cancer treatment. However, their relationship in head and neck cancers (HNC) remains less clear. We aimed to assess the relationship between institutional clinical trial recruitment, hospital throughput of HNC cases, and survival of patients with advanced HNC treated with primary chemoradiotherapy at hospitals which recruited to the PET-NECK trial (2008-2012). The impact on outcome was assessed using Cox's proportional hazards regression analysis and multivariate analysis. HNC RCT recruitment positively correlated with hospital throughput (r = 0.57, p < 0.0001). Low-recruiters (1-5 patients) had a 107% increased risk of death when compared to high-recruiters (>5 patients) (HR = 2.07, p = 0.05). There was no significant impact of hospital throughput on overall or disease-specific HNC survival. Multivariate analysis identified p16 status, N-stage, smoking, and RCT recruitment volume as the only significant predictors of survival. There was a significant difference in chemotherapy regimen between low and high-recruiters (p = 0.003) where a higher proportion of patients (50%, n = 13) in low-recruiting compared to high-recruiting hospitals (29%, n = 92) received neoadjuvant chemotherapy. A higher proportion of these patients died at low-recruiting hospitals (46% versus 23%). A significant association exists between high recruitment and better OS for patients with HNC. However, no significance was found between hospital throughput and outcomes. The significance of individual centre differences in chemotherapy regimen needs further investigation. Future studies need a greater number of patient outcome events to support the trends found in this study.


The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila.
The mushroom body (MB), a bilateral brain structure possessing about 2000-2500 neurons per hemisphere, plays a central role in olfactory learning and memory in Drosophila melanogaster. Extensive studies have demonstrated that three major types of MB neurons (α/β, α'/β' and Γ) exhibit distinct functions in memory processing, including the critical role of approximately 1000 MB α/β neurons in retrieving long-term memory. Inspired by recent findings that MB α/β neurons can be further divided into three subdivisions (surface, posterior and core) and wherein the α/β core neurons play an permissive role in long-term memory consolidation, we examined the functional differences of all the three morphological subdivisions of MB α/β by temporally precise manipulation of their synaptic outputs during long-term memory retrieval. We found the normal neurotransmission from a combination of MB α/β surface and posterior neurons is necessary for retrieving both aversive and appetitive long-term memory, whereas output from MB α/β posterior or core subdivision alone is dispensable. These results imply a specific requirement of about 500 MB α/β neurons in supporting long-term memory retrieval and a further functional partitioning for memory processing within the MB α/β region.


Updates in Anti-anginal and Anti-ischemic Therapies for Acute Coronary Syndromes.
Acute coronary syndrome is a major health problem affecting ~ 1.5 million individuals a year in the USA. We review the contemporary role of anti-anginal and anti-ischemic therapies in the management of an individual presenting with an acute coronary syndrome. Early diagnosis and appropriate evidence-based therapies significantly improve clinical outcomes in acute coronary syndrome patients. Typically, acute coronary syndrome is associated with rupture of an atherosclerotic plaque and either partial or complete thrombotic occlusion of a coronary artery. Management of an acute coronary syndrome is targeted towards this underlying pathophysiology. The last few years have seen significant advances in anti-anginal and anti-ischemic therapies in the management of patients with acute coronary syndrome. It is important to have a team effort to target risk reduction measures and to emphasize medication and dietary compliance. Long-term pharmacotherapy should include aspirin, beta-blocker, DAPT (for at least 1 year), statins, and ACE inhibitors and PCSK9 inhibitors if indicated.


Synaptic responses of reticulospinal neurons in the cat: spinal cord dorsal funiculi are an effective source.
Stimulation of spinal cord dorsal funiculi (DF), as compared with stimulation of ventrolateral fascicle (VLF) in which the spinoreticular pathways are located, activated a higher percentage of reticulospinal (RS) neurons (95% vs. 75%). Polysynaptic EPSPs evoked from DF at C2 segment had shorter latency (10.1 msec +/- vs. VLF C2-13.2 msec +/- 0.9-mean +/- S.E.M.). When the intensity of stimulation was close to threshold (1.5 T), EPSPs from DF had steeper slopes on the increasing phase and were of longer duration. Threshold for setting up of synaptic activity from DF at the majority of observed RS neurons was low; recording of antidromic responses in hindlimb nerves showed that fast-conducting myelinized afferents were activated. The functional connection between DF and RS systems may participate in prompt and generalized reflex reactions.


[Addressed modification of the promoter region of DNA in a complex with RNA polymerase by alkylating oligonucleotide derivatives].
Addressed chemical modification of double-stranded DNA unwound with the specific protein has been demonstrated. 4(N-2-chloroethyl-N-methylamino)benzyl-5'-phosphoamides of oligonucleotides d(CG)rC, d(ATCG)rC, d(AATCG)rC, which can serve as primers in the RNA polymerase-catalyzed transcription, alkylated A2 promoter region of pSK-A2 plasmid in its "open" complex with E. coli RNA polymerase.


Effects of regulatory peptides on the porcine lower oesophageal sphincter.
Studies were performed to investigate the effects of neurotransmitters and neurotransmitter candidates (substance P, VIP, somatostatin, Met-enkephalin, gastrin-17, CCK-4 and -8, neurotensin and TRH) of the newly discovered peptidergic nervous system on lower oesophageal sphincter pressure in anaesthetized pigs. All neuropeptides were infused over 2 min periods in 6 different doses, separated by resting periods of at least 1 min, directly into the arterial supply of the lower oesophageal sphincter. Substance P caused a dose-dependent increase in lower oesophageal shpincter pressure; the threshold dose was 9 pmol . kg-1 . min-1 and half maximal response occurred at 72 pmol . kg-1 . min-1. None of the other polypeptides, however, influenced the resting lower oesophageal sphincter. These studies show that substance P is a potent stimulant of smooth muscle in the lower oesophageal sphincter, suggesting that this peptide may be an important regulator of lower oesophageal sphincter pressure.


New treatments in atopic dermatitis.
To discuss the efficacy and safety of novel and emerging topical and systemic therapeutic agents for atopic dermatitis (AD). The review of the published literature was performed using the PubMed database, published abstracts and virtual presentations from scientific meetings, posted results on ClinicalTrials.gov, and data from industry press releases. Primary manuscripts with trial results, case reports, case series, clinical trial data from ClinicalTrials.gov, and articles highlighting expert perspectives on management of AD were selected. Emerging topical and systemic therapies primarily target the type 2 immune pathway. Moreover, 2 newer targeted medications are now approved by the Food and Drug Administration for both children and adults, crisaborole 2% ointment and dupilumab, with several others in the therapeutic pipeline. New directions in developing topical medications include Janus kinase inhibitors, tapinarof (an aryl hydrocarbon receptor agonist), and agents to correct microbial dysbiosis. In addition to the subcutaneously injected monoclonal antibody targeting the interleukin (IL) 4 receptor (dupilumab), other biologics targeting IL-13, IL-31, IL-33, OX40, and thymic stromal lymphopoietin are currently being tested. Oral Janus kinase inhibitors are showing outstanding efficacy and no serious safety signs, but safety concerns remain. Given the tremendous burden of AD on physical, mental, and social health, the need is high to develop new, targeted therapies. Advances in our understanding of AD pathogenesis have paved the way toward the development of new therapies that promise to revolutionize our management of AD. Future research will focus on long-term efficacy and safety and creating predictive models for choosing best management options on a personalized basis.


Changes in the blink responses to combined trigeminal, acoustic and visual repetitive stimulation, studied in the human subject.
Habituation of blink reflexes as measured by amplitude decrement in the orbicularis oculi EMG was examined in 9 human subjects using combinations of repetitive electric stimuli to the bridge of the nose (trigeminal stim.), short clicks (acoustic stim.), and flashes (visual stim.). With trains of paired stimuli, both homogeneous and mixed, habituation was increased when the two stimuli were separated by 250 msec but was decreased when the interval was 30 (50) msec, as compared to single stimulus trains of identical repetition rate. Following acoustic or visual prehabituation the habituation to trigeminal stimuli was enhanced. This "transfer of habituation' was also obtained with acoustic before visual stimuli and vice versa. Regarding dishabituation, interposition of single extrastimuli, for example visual or acoustic within repeated trigeminal stimulation, was more effective than a simple pause by omitting one electric pulse. The results suggest the existence of a pool of interneurones that is that the common final relay for the blink relfex afferents from the trigeminal, acoustic and visual input.


Evaluation of the psychometric properties of the Multidimensional Revenge Attitudes Inventory-21.
Despite a few hypothesized associations between revenge and suicide in the suicide literature, the potential of revenge as a multidimensional construct related to suicide has remained unexplored. Using data from undergraduate samples across 2 studies, we examined support for the psychometric properties and nomological network of scores on the Multidimensional Revenge Attitudes Inventory-21 (MRAI-21), a new self-report instrument composed of 3 dimensions: craving for revenge, revenge rumination, and suicide-related revenge. Results from Study 1 (N = 510), suggested that a 3-factor oblique solution obtained through contemporary factor analytic methods provided the best fit for the sample data. Estimates of internal consistency reliability for the MRAI-21 scale scores were above .90. In Study 2 (N = 380), we examined internal consistency reliability estimates for 6 concurrent self-report measures and conducted convergent validity analyses using latent variable modeling with scores on the MRAI-21 and concurrent measures. Results showed that scores on all instruments had adequate estimates of reliability and revealed a unique network of correlates for each of the MRAI-21 scale scores. Findings suggest that revenge can be measured as a multidimensional construct within the context of suicide; future directions and clinical implications are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Crossbridges in insect flight muscles of the blowfly (Sarcophaga bullata).
Crossbridges in quick-frozen deep-etched blowfly flight muscles (from Sarcophaga bullata) were compared with those observed in the traditional waterbug preparation (Lethocerus) and found to be indistinguishable. Hence, blowfly was chosen as a fresher more accessible tissue for determining the effect of various fixatives and nucleotides on crossbridge structure. In rigor control, crossbridges were most regular in muscles that were stabilized before freezing by prefixation in glutaraldehyde followed by 'hardening' with neutralized tannic acid, so all nucleotide treatments were terminated by such fixation. MgATP (5 mM) converted the rigor pattern of crossbridges into a random array of disconnected thick filament projections. Lower levels of ATP (0.1 mM) caused a variable but generally lesser degree of crossbridge disconnection, as did 5 mM ADP (probably because it slowly converted to ATP inside the muscle fibres). Vanadate (1-2 mM) potentiated muscle relaxation in the latter two nucleotide treatments (i.e. produced a greater degree of crossbridge disconnection). Thus, differences in overall crossbridge abundance were readily apparent in chemically fixed muscles. Structural details within individual crossbridges were less well preserved, however. Chemical prefixation tended to collapse the muscle lattice, add a surface film to the filaments and thus obscure crossbridge details. Rigorous control of fixative pH largely prevented these problems and permitted recognition of the fact that in Sarcophaga flight muscle, as in Lethocerus muscle in rigor, the S1 'heads' of crossbridges attach to the thin filaments in the expected 'arrowhead' configuration.


Differential phosphorylation of translation initiation regulators 4EBP1, S6k1, and Erk 1/2 following inhibition of alcohol metabolism in mouse heart.
Acute alcohol intoxication leads to an inhibition of protein synthesis in heart that results in part through altered phosphorylation of protein factors controlling mRNA translation initiation. The purpose of the present set of experiments was designed to examine the effects of inhibitors of ethanol metabolism on the phosphorylation of 4E-binding protein (4EBP1) and S6k1(Thr(389)), two factors regulating mRNA translation initiation. Phosphorylation of 4E-BP1, S6k1(Thr(389)), and Erk 1/2 was reduced 2 h following IP injection of alcohol. Pretreatment with 4-methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase (ADH), did not attenuate the ethanol-induced decrease in phosphorylation of 4EBP1 and S6k1(Thr(389)). In contrast, 4-MP prevented the decrease in Erk 1/2 phosphorylation observed with acute ethanol intoxication. Pretreatment with cyanamide, an inhibitor of aldehyde dehydrogenase, did not attenuate the ethanol-induced decrease in phosphorylation S6k1(Thr(389)), but partially prevented the ethanol-induced lowering of 4EBP1 phosphorylation. The studies indicate that modulation of ethanol metabolism through inhibition of ADH or aldehyde dehydrogenase leads to preferential modulation of the phosphorylation of distinct myocardial signaling systems involved in regulating protein synthesis.


Inhibition of Ras attenuates the course of experimental autoimmune neuritis.
EAN induced in Lewis rats by immunization with peripheral bovine myelin was treated by the Ras inhibitor farnesylthiosalicylate (FTS). Treatment from day 0 with FTS (5 mg/kg intraperitoneally twice daily) attenuated peak clinical scores (mean+/-S.E., 2.5+/-0.5 compared to 4.1+/-0.5 in saline treated controls, p=0.018, t-test) but not recovery. Treatment from day 10 with FTS attenuated peak disability (2.5+/-0.6, p=0.032 compared to saline treated controls) and improved recovery (0.84+/-0.42, untreated controls 2.4+/-0.6, p=0.028 by repeated measures ANOVA). Effects were confirmed by rotarod and nerve conduction studies. An inactive analogue, geranylthiosalicylate, had no clinical effect. Inhibition of Ras is of potential use in the treatment of inflammatory neuropathies.


The Relationship between the Fear of Covid-19, Depression, and Spiritual Well-Being in Pregnant Women.
The purpose of this study was to explore the relationship between pregnant women's fear of coronavirus (COVID-19), depression, and spiritual well-being. This cross-sectional research was carried out with 336 pregnant women living in a city in the Eastern Anatolia region of Turkey between the 1st of March and 30th of March 2021. For data collection, the scales of the Fear of COVID-19, the Beck Depression Inventory, and the Spiritual Well-being were administered to the participants. The pregnant women's fear of COVID-19 was found to be at a moderate level, their depression was at a mild level, and their spiritual well-being was above the moderate level. It was found that there was a significant negative correlation between the spiritual well-being levels of pregnant women and their fear of COVID-19 and depression. Moreover, it was also found that there was a significant positive correlation between pregnant women's levels of fear of COVID-19 and depression (p < 0.001). It is recommended that relevant spiritual care practices can be disseminated and implemented effectively to reduce pregnant women's fear and depression during the pandemic. In addition, when providing care to pregnant women, health professionals can adopt a holistic approach to increase pregnant women's spiritual well-being.


Electrochemical cholesterylation of sugars with cholesteryl diphenylphosphate.
Electrochemical cholesterylation of various sugars with cholesteryl diphenylphosphate was studied. The reaction afforded mono-, di-, tri-, and tetra-cholesterylated products using equivalent amounts of the reagent. The reactions turned out to be completely stereoselective with respect to both sugar and steroid but only partially regioselective - primary and anomeric hydroxyl groups in sugars were the most reactive ones while no substantial differences in reactivity was found for different secondary hydroxyl groups.


Effect of a papain-based gel for chemomechanical caries removal on dentin shear bond strength.
The aim of this study was to assess the shear bond strength of an adhesive restorative system on sound and demineralized dentin after the use of a papain-based agent. Forty human dentin slabs were randomly distributed into 4 groups: (1) sound dentin slabs that received an application of papain-based gel (N=10); (2) sound dentin slabs that did not receive a papain-based gel application (N=10); (3) demineralized slabs that received an application of the agent (N=10); and (4) demineralized slabs that did not receive an application of the agent (N=10). After manual excavation and use of the chemomechanical agent, the slabs were restored with a total etch adhesive system and microhybrid resin composite. The test specimens were individually stored in a damp environment for 7 days, and the shear bond strength test was performed using a universal test machine at a speed of 0.5 mm/min. The fragments were observed under a stereoscopic microscope to assess the fracture mode. Fracture mode assessment showed adhesive and cohesive type fractures in resin for all the groups. The analysis of variance and the Tukey test showed that there were no differences in the shear bond strength means among the groups (P>.05). The use of a papain-based gel to remove dental caries did not interfere in the bond strength of restorative materials to dentin.


Expression of thymosin beta4 mRNA by activated microglia in the denervated hippocampus.
Thymosin beta4 is a major actin-sequestering molecule. Here, we report a prominent upregulation of thymosin beta4 in the hippocampus following entorhinal deafferentation. Northern blotting displayed a transient increase of thymosin beta4 mRNA in the deafferented hippocampus by 1.8, 2.3, 1.3 and 1.1-fold of controls, respectively, at 1, 3, 7 and 15 days post-lesion. In-situ hybridization confirmed that the induction of thymosin beta4 mRNA specifically occurred in the entorhinally denervated zones of the hippocampus. The double labeling of in-situ hybridization for thymosin beta4 mRNA with isolectin B4 cytochemistry showed that isolectin B4-positive microglial cells are responsible for deafferentation-induced thymosin beta4 mRNA expression. The results suggest that thymosin beta4 may participate in the process of microglial activation, which is the earliest event in lesion-induced plasticity.


Women-with-midwives-with-women: a model of interdependence.
To develop a research-based conceptual model of midwifery practice. Qualitative using grounded theory. Midwifery practice in New Zealand and Scotland. 250 midwives and 219 clients from the two countries. Data from the participants provided the contextual background as well as the major categories. Forming the background were the concepts of: beliefs, colleagues, culture, experience, expertise, education, environment, friends, families, intuition, knowledge and professionalism. The major categories of the model which emerged from the data were: attending and presencing, supplementing and complementing, reflection and reflexivity. These are discussed as pairs while the basic social process (core category) of reciprocity embraces the whole midwife-client relationship. This model offers the beginnings of documentary evidence of the essence of the midwife-client relationship and may go some way towards the creation of a written body of midwifery knowledge. It has potential applicability for both midwifery education and practice.


Does the weight loss efficacy of alternate day fasting differ according to sex and menopausal status?
This study examined if the weight loss and metabolic benefits of alternate day fasting (ADF) varies according to sex and menopausal status in adults with obesity. This secondary analysis pooled the data of men and women (n = 75) who participated in three 12-week ADF studies (500 kcal fast day; alternated with an ad libitum intake feast day). Body weight decreased in premenopausal women (-4.6 ± 3.2%), postmenopausal women (-6.5 ± 3.2%) and men (-6.2 ± 4.4%) (main effect of time, P < 0.001), with no difference between groups (no group × time interaction). Energy intake on fast days was higher than prescribed in all groups (∼400-500 excess kcal consumed), with no differences between groups. Fat mass, lean mass, fasting insulin, and insulin resistance, and blood pressure decreased similarly in all groups (main effect of time, P < 0.05 for all comparisons). LDL cholesterol decreased more in postmenopausal versus premenopausal women (group × time interaction, P = 0.01). Fasting glucose, HDL cholesterol, and triglycerides remained unchanged in all groups. These findings suggest that the weight loss and metabolic benefits of ADF do not generally vary according to sex or menopausal status in adults with obesity. Clinicaltrials.gov, NCT00960505; NCT03528317.


A Deployable In Vivo EPR Tooth Dosimeter for Triage After a Radiation Event Involving Large Populations.
In order to meet the potential need for emergency large-scale retrospective radiation biodosimetry following an accident or attack, we have developed instrumentation and methodology for in vivo electron paramagnetic resonance spectroscopy to quantify concentrations of radiation-induced radicals within intact teeth. This technique has several very desirable characteristics for triage, including independence from confounding biologic factors, a non-invasive measurement procedure, the capability to make measurements at any time after the event, suitability for use by non-expert operators at the site of an event, and the ability to provide immediate estimates of individual doses. Throughout development there has been a particular focus on the need for a deployable system, including instrumental requirements for transport and field use, the need for high throughput, and use by minimally trained operators.Numerous measurements have been performed using this system in clinical and other non-laboratory settings, including in vivo measurements with unexposed populations as well as patients undergoing radiation therapies. The collection and analyses of sets of three serially-acquired spectra with independent placements of the resonator, in a data collection process lasting approximately five minutes, provides dose estimates with standard errors of prediction of approximately 1 Gy. As an example, measurements were performed on incisor teeth of subjects who had either received no irradiation or 2 Gy total body irradiation for prior bone marrow transplantation; this exercise provided a direct and challenging test of our capability to identify subjects who would be in need of acute medical care.


Protein arginine methyltransferase 3: A crucial regulator in metabolic reprogramming and gene expression in cancers.
Post-translational modification (PTM) of proteins increases proteome diversity, which is critical for maintaining cellular homeostasis. The importance of protein methylation in the regulation of diverse biological processes has been highlighted in the past decades. Methylation of the arginine residue on proteins is catalyzed by members of the protein arginine methyltransferase (PRMT) family. PRMTs play indispensable roles in various pathways that regulate cancer development, progression, and drug response. In this review, we discuss the role of PRMT3, a member of the PRMT family, in controlling oncogenic processes. Additionally, the effects of PRMT3 on the methylation of regulatory proteins involved in transcription, post-transcriptional control, ribosomal maturation, translation, biological synthesis, and metabolic signaling are summarized. Moreover, recent progresses in the development of PRMT3 inhibitors are introduced. Overall, this review highlights the importance of PRMT3 in tumorigenesis and discusses the underlying mechanisms by which PRMT3 modulates cellular metabolism and gene expression. These results also provide a molecular basis for therapeutic modalities by targeting PRMT3.


A randomized double-blind 12-week study of quetiapine, risperidone or fluphenazine on sexual functioning in people with schizophrenia.
Sexual dysfunction is common in people suffering from schizophrenia and is reported by patients to be a significant reason for medication nonadherence. This report contains data for 27 people with schizophrenia who participated in a randomized double-blind 12-week trial of risperidone (4 mg/day), quetiapine (400 mg/day) or fluphenazine (12.5 mg/day). At baseline and endpoint, subjects were rated on the Changes in Sexual Function Questionnaire (CSFQ), the Prolactin-Related Adverse Event Questionnaire (PRAEQ) and had prolactin levels drawn. Endpoint prolactin levels were 50.6 +/- 40.4, 24.4 +/- 18.5, and 8.2 +/- 4.4 mg/dl for risperidone (N = 12), fluphenazine (N = 9) and quetiapine (N=6), respectively (F = 7.5,df = 2, p = 0.005, controlling for sex). Orgasm quality/ability improved significantly for quetiapine as compared to fluphenazine and risperidone (F = 4.41, df = 2, p = 0.033). Seventy-eight percent of patients on fluphenazine reported sexual dysfunction whereas did only 42 and 50% of those on risperidone and quetiapine. Forty percent of quetiapine patients reported they felt better about their sexuality as compared to previous treatment, as did 55% on risperidone. Conversely, only 13% of fluphenazine subjects reported any improvement. Hormonal problems (menstrual problems, gynecomastia, galactorrhea) were predominately observed in risperidone-treated subjects. Overall, quetiapine was associated with a normalization of prolactin levels and had the greatest benefits among these drugs regarding sexual functioning.


Acute coronary embolism: angiographic diagnosis and treatment with primary angioplasty.
Acute coronary embolism is rarely diagnosed and it may explain why normal coronary arteries are found after or even before an acute coronary event in patients with thromboembolic risk factors. Emergency coronary angiography was performed in three patients with prior normal coronary arteries and an acute myocardial infarction, followed by primary angioplasty with low-pressure balloon inflations plus stenting and combined antiaggregation with aspirin, clopidogrel, and abciximab to disrupt the thrombi and protect distal circulation from microemboli. Angiographic success was achieved in 100%, and 6-month follow-up has been uneventful on oral anticoagulation and antiaggregation.


Cardiac Phase and Flow Compensation Effects on REnal Flow and Microstructure AnisotroPy MRI in Healthy Human Kidney.
Renal diffusion-weighted imaging (DWI) involves microstructure and microcirculation, quantified with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM), and hybrid models. A better understanding of their contrast may increase specificity. To measure modulation of DWI with cardiac phase and flow-compensated (FC) diffusion gradient waveforms. Prospective. Six healthy volunteers (ages: 22-48 years, five females), water phantom. 3-T, prototype DWI sequence with 2D echo-planar imaging, and bipolar (BP) or FC gradients. 2D Half-Fourier Single-shot Turbo-spin-Echo (HASTE). Multiple-phase 2D spoiled gradient-echo phase contrast (PC) MRI. BP and FC water signal decays were qualitatively compared. Renal arteries and velocities were visualized on PC-MRI. Systolic (peak velocity), diastolic (end stable velocity), and pre-systolic (before peak velocity) phases were identified. Following mutual information-based retrospective self-registration of DWI within each kidney, and Marchenko-Pastur Principal Component Analysis (MPPCA) denoising, combined IVIM-DTI analysis estimated mean diffusivity (MD), fractional anisotropy (FA), and eigenvalues (λi) from tissue diffusivity (Dt ), perfusion fraction (fp ), and pseudodiffusivity (Dp , Dp,axial , Dp,radial ), for each tissue (cortex/medulla, segmented on b0/FA respectively), phase, and waveform (BP, FC). Monte Carlo water diffusion simulations aided data interpretation. Mixed model regression probed differences between tissue types and pulse sequences. Univariate general linear model analysis probed variations among cardiac phases. Spearman correlations were measured between diffusion metrics and renal artery velocities. Statistical significance level was set at P < 0.05. Water BP and FC signal decays showed no differences. Significant pulse sequence dependence occurred for λ1 , λ3 , FA, Dp , fp , Dp,axial , Dp,radial in cortex and medulla, and medullary λ2 . Significant cortex/medulla differences occurred with BP for all metrics except MD (systole [P = 0.224]; diastole [P = 0.556]). Significant phase dependence occurred for Dp , Dp,axial , Dp,radial for BP and medullary λ1 , λ2 , λ3 , MD for FC. FA correlated significantly with velocity. Monte Carlo simulations indicated medullary measurements were consistent with a 34 μm tubule diameter. Cardiac gating and flow compensation modulate of measurements of renal diffusion. 2 TECHNICAL EFFICACY STAGE: 2.


Temperature fluctuations in a changing climate: an ensemble-based experimental approach.
There is an ongoing debate in the literature about whether the present global warming is increasing local and global temperature variability. The central methodological issues of this debate relate to the proper treatment of normalised temperature anomalies and trends in the studied time series which may be difficult to separate from time-evolving fluctuations. Some argue that temperature variability is indeed increasing globally, whereas others conclude it is decreasing or remains practically unchanged. Meanwhile, a consensus appears to emerge that local variability in certain regions (e.g. Western Europe and North America) has indeed been increasing in the past 40 years. Here we investigate the nature of connections between external forcing and climate variability conceptually by using a laboratory-scale minimal model of mid-latitude atmospheric thermal convection subject to continuously decreasing 'equator-to-pole' temperature contrast ΔT, mimicking climate change. The analysis of temperature records from an ensemble of experimental runs ('realisations') all driven by identical time-dependent external forcing reveals that the collective variability of the ensemble and that of individual realisations may be markedly different - a property to be considered when interpreting climate records.


Open dorsal metacarpophalangeal dislocations of the index, long, and ring fingers.
An open dorsal dislocation of the metacarpophalangeal joints of the index, long, and ring fingers was treated satisfactorily by early reduction.