Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.
Atherosclerosis, one of the life-threatening cardiovascular diseases (CVDs), has been demonstrated to be a chronic inflammatory disease, and inflammatory and immune processes are involved in the origin and development of the disease. Toll-like receptors (TLRs), a class of pattern recognition receptors that trigger innate immune responses by identifying pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), regulate numerous acute and chronic inflammatory diseases. Recent studies reveal that TLRs have a vital role in the occurrence and development of atherosclerosis, including the initiation of endothelial dysfunction, interaction of various immune cells, and activation of a number of other inflammatory pathways. We herein summarize some other inflammatory signaling pathways, protein molecules, and cellular responses associated with TLRs, such as NLRP3, Nrf2, PCSK9, autophagy, pyroptosis and necroptosis, which are also involved in the development of AS. Targeting TLRs and their regulated inflammatory events could be a promising new strategy for the treatment of atherosclerotic CVDs. Novel drugs that exert therapeutic effects on AS through TLRs and their related pathways are increasingly being developed. In this article, we comprehensively review the current knowledge of TLR signaling pathways in atherosclerosis and actively seek potential therapeutic strategies using TLRs as a breakthrough point in the prevention and therapy of atherosclerosis.


Association of amino acid imbalance with the severity of liver fibrosis and esophageal varices.
The relationships between the metabolic parameters and the endoscopic findings of esophageal varices have been poorly investigated. We investigated the association of the branched-chain amino acids to tyrosine ratio (BTR) with the severity of liver fibrosis and esophageal varices. We studied hepatitis C virus (HCV)-positive chronic liver disease patients who had undergone liver biopsy (n = 149). The relationship between the BTR values and the liver fibrotic stage was investigated. We also studied whether the BTR value was associated with the presence and bleeding risk of varices in patients with HCV-related compensated cirrhosis. The mean values of the BTR decreased with the progression of the fibrosis (METAVIR score: F0-1: 6.40 ± 1.19; F2: 5.85 ± 1.33; F3: 5.24 ± 0.97, F4: 4.78 ± 1.14). In the 58 patients with HCV-related compensated cirrhosis, the mean values of the BTR decreased with the severity of varices (patients without varices: 5.01 ± 1.15, patients with a low-risk varices: 4.42 ± 1.06, patients with a high-risk varices: 3.86 ± 1.02). The BTR value was significantly lower in the patients with varices than in those without varices (4.17 ± 1.07 vs. 5.01 ± 1.15, P < 0.01). The BTR value was also significantly lower in the patients with a high risk of hemorrhage than in those with a low risk (3.86 ± 1.02 vs. 4.78 ± 1.14, P < 0.01). Furthermore, the BTR value was the most significantly different parameter, with the smallest P-value among all the factors examined, including the platelet count and albumin level. A decreased BTR value was found to be associated with the progression of liver fibrosis and severity of varices.


Pre-exposure to the unconditioned or conditioned stimulus does not affect learned immunosuppression in rats.
In order to analyze the effects of pre-exposure to either the unconditioned (US) or conditioned stimulus (CS) on learned immunosuppression, we employed an established conditioned taste aversion (CTA) paradigm in rats. In our model, a sweet-tasting drinking solution (saccharin) serves as CS and injection of the immunosuppressive drug cyclosporine A (CsA) is used as US. The conditioned response is reflected by a pronounced CTA and diminished cytokine production by anti-CD3 stimulated splenic T cells. In the present study, experimental animals were exposed either to the US or the CS three times prior to the acquisition phase. On the behavioral level, we found a significantly diminished CTA when animals were pre-exposed to the US or the CS before acquisition. In contrast, US or CS pre-exposure did not affect the behaviorally conditioned suppression of interleukin (IL)-2 production. From the clinical perspective, our data may suggest that conditioning paradigms could be systemically integrated as supportive therapeutic interventions in patients that are already on immunosuppressive therapy or have had previous contact to the gustatory stimulus. Such supportive therapies to pharmacological regimens could not only help to reduce the amount of medication needed and, thus, unwanted toxic side effects, but may also maximize the therapeutic outcome.


The delivery of cancer chemotherapy by constant venous infusion. Ambulatory management of venous access and portable pump.
Fifty chemotherapy trials with 5-fluorouracil; mitomycin C; vinblastine; Adriamycin; and cis-platinol were initiated employing constant (24-hour) intravenous infusion for protracted periods (14-94 days). The use of the tunneled subclavian line for greater than 2200 patient days was associated with minimal complications and no instances of thrombosis or infection were observed. The use of an ambulatory infusion pump was associated with a pump efficiency of greater than 85% in 38 of 39 evaluable trials. Only four of 50 trials were associated with excess drug infusion and in no instance was a drug complication encountered. Constant infusion cancer chemotherapy is feasible, reliable, and safe. Objective tumor regression is observed but the superiority of this drug schedule over the standard intermittent bolus schedule is yet to be determined. Nonetheless, drug toxicity patterns are altered substantially and, in particular, gastrointestinal side effects of chemotherapeutic drugs may be eliminated without compromising cumulative dose.


Transcriptome Profiling of Anhidrotic Eccrine Sweat Glands Reveals that Olfactory Receptors on Eccrine Sweat Glands Regulate Perspiration in a Ligand-Dependent Manner.
Sweat maintains systemic homeostasis in humans. Although sweating disorders may cause multifaceted health problems, therapeutic options for sweat disorders have not yet been established. To gain new insight into the mechanism underlying the regulation of perspiration, we compared eccrine sweat gland transcriptomes from hidrotic and anhidrotic lesions from patients with anhidrosis and found out that olfactory receptors were expressed differentially in anhidrotic and hidrotic eccrine sweat glands. We then confirmed OR51A7 and OR51E2 expression in human eccrine sweat glands by in situ hybridization and immunohistochemistry. An alkaline phosphatase-TGFα shedding assay revealed that β-ionone activates G-proteins through OR51A7 or OR51E2. The effect of topically applied β-ionone on sweating was examined with the quantitative sudomotor axon reflex test, which showed that responses to β-ionone differed between sexes. Topical β-ionone attenuated female sweating and augmented male sweating. Taken together, this study suggests that olfactory receptors expressed in eccrine sweat glands may regulate sweating in response to odorous ligands on the basis of sex. These unexpected results indicate that olfactory receptors may modulate sweating and that olfactory receptor modulators may contribute to the management of sweat disorders.


Differences in the timing of implausibility detection for recipient and instrument prepositional phrases.
We conducted two word-by-word reading experiments to investigate the timing of implausibility detection for recipient and instrument prepositional phrases (PPs). These PPs differ in thematic role, relative frequency, and possibly in argument status. The results showed a difference in the timing of garden path effects such that the detection of implausible dative recipients (which are clearly arguments) was delayed relative to the detection of implausible instruments (which may not be arguments). They also demonstrated that commitments to syntactic structure were made at the preposition for both dative and instrument PPs. While these results refute delay models of parsing (e.g., Britt, 1994) and syntax-first accounts of PP-attachment (e.g., Frazier, 1978; Frazier & Clifton, 1996), they support constraint-based lexicalist models that enable verb bias and plausibility information to compete (Garnsey, Pearlmutter, Myers, & Lotocky, 1997).


Screening of Echinops ellenbeckii and Echinops longisetus for biological activities and chemical constituents.
Members of the genus Echinops in the family of Asteraceae are widely used in Ethiopian herbal medicine for the treatment of various diseases and illness such as migraine, diarrhea, heart pain, different forms of infections, intestinal worm infestation and hemorrhoid. Hydroalcoholic extracts of the root, flower head, leaf and stem of Echinops ellenbeckii O. Hoffm. and Echinops longisetus A. Rich were investigated for their chemical constituents and biological activities. The presence of alkaloids, saponins, phytosterols, polyphenols and carotenoids in the different parts of the plants was observed whilst anthraquinones were not detected. The leaf extracts of both plants and stem extract of E. longisetus showed strong inhibitory activity against cultures of Staphylococcus aureus. None of the extracts were found to be active against Gram-positive organisms. The flower extract of E. ellenbeckii showed strong inhibitory activity against Candida albicans. Root and flower extracts of the plants investigated showed lethal activity against earthworms. Moreover, the extracts of the roots of both plants showed molluscicidal activity against schistosome-transmitting snail hosts. The biological activities observed were dose dependent.


Immunologic responses to Candida albicans. III. Effects of passive transfer of lymphoid cells or serum on murine candidiasis.
Passive transfer of immune serum gave a significant degree of protection against deep seated candidiasis in mice. Repeated attempts to transfer resistance by the transfer of sensitized lymphoid cells gave negative results, even though cutaneous delayed hypersensitivity was transferred by the cells. The results suggest that cell-mediated immunity is not of primary importance in this model of murine candidiasis, and that humoral immunity contributes to protection.


Learning styles of first-year orthopedic surgical residents at 1 accredited institution.
This study represents 1 arm of a 5-year prospective study investigating the learning styles of orthopedic residents and their surgical educators. This project investigates the learning styles of the 2009-2010 year 1 orthopedic surgical residents. A cross-sectional survey using the Kolb Learning Style Inventory was completed by 13 first year orthopedic residents. Direct 1-to-1 interviews were completed with the primary investigator and each participant using the Kolb Learning Style Inventory and learning styles were determined. Converging learning style was the most common among the residents (53.8%). Residents demonstrated a high tendency toward the learning skill of abstract conceptualization combined with active experimentation, and a transition from action-oriented to more reflective learning style with age and postgraduate education. These results may be useful in creating strategies specific to each learning style that will be offered to residents to enhance future teaching and learning.


Comparison of quantitative and semi-quantitative sampling methodologies for biomonitoring of Mediterranean streams using benthic macroinvertebrates: a case study from Greece.
In Greece, the implementation of the Water Framework Directive for rivers is based mainly on benthic macroinvertebrates and uses a semi-quantitative method with a D-frame net, which is certified by the International Organization for Standardization. Before the official adoption of this method, a quantitative shovel sampler ("Cretan shovel") was used in southern Greece (Crete), which has been implemented for almost three decades due to the specific river habitats found in Crete (e.g., seasonal flow, narrow riverbeds, and coarse substrates). In this study, we compared community metrics, diversity indices, feeding groups, locomotion types, and ecological quality derived from data collected using timed semi-quantitative kick samples and quantitative shovel samples collected from the same sites simultaneously. In total, 20 samples from the north and south of Greece were collected. The majority of community metrics, diversity indices, and traits were comparable between samplers. However, there were statistically significant differences in the relative abundance of Ephemeroptera, Plecoptera, and Trichoptera, passive filterers' and the (semi) sessil groups, and Pielou's index. Most differences in the ecological quality between the kick and shovel samples were observed in 50% of the sites in northern Greece because the shovel is less effective at capturing motile zoobenthos. The ecological quality assessment in Crete by the Cretan shovel is comparable with the D-frame net in 75% of the samples. Thus, the Cretan shovel could efficiently sample the Cretan streams, which are characterized by coarse, narrow, turbulent, and hydrologically fluctuating river habitats. Such comparisons could improve sampling effectiveness and make additional data available to assess ecological quality.


Introductory notes regarding a European Medical Risk Related History questionnaire (EMMRH) designed for use in dental practice.
The Medical Risk Related History (MRRH) has been in use for several years in the Netherlands. Since 1994 the MRRH system has been subject to research in nine European countries. Legal and ethical demands in all participating countries have been listed, and a national epidemiological analysis of pathology interfering with dental treatment has been undertaken for every participant.


Substance P and related tachykinins induce receptor-mediated hydrolysis of polyphosphoinositides in the rat anterior pituitary.
In the present study characterization of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PIP2-PLC) activity and receptor-mediated hydrolysis of PIP2 in rat anterior pituitary membranes were investigated. Incubation of the membrane fraction of anterior pituitary homogenate with [3H]inositol-labeled PIP2 in the presence of calcium increased the concentration of the water-soluble degradation product inositol trisphosphate (IP3) in a time-dependent manner. PIP2-PLC in the rat anterior pituitary had a pH optimum at 5.5 and a requirement for cations. Ca2+ and Mg2+ could activate the enzyme. Activity was maximal at a total magnesium concentration of 1 mM and at a free Ca2+ concentration of 100 microM. The addition of the detergent Triton X-100 (0.05% w/v) to the membrane fraction resulted in a 50% decrease of PIP2-PLC activity, whereas the presence of sodium deoxycholate (1 mg/ml) in the membrane fraction increased the PIP2-PLC activity by 100%. The tachykinins substance P, 8-Tyr-substance P, physalaemin, neurokinin A, eledoisin, kassinin and neurokinin B induced receptor-mediated breakdown of [3H]inositol-labeled PIP2 in the membrane fraction in a concentration-dependent manner, but with different potencies. The tachykinins displayed the following rank order of potencies: substance P greater than 8-Tyr-substance P greater than physalaemin greater than neurokinin A greater than eledoisin greater than kassinin greater than neurokinin B, which is consistent with the involvement of a NK-1 receptor. Combined treatment of anterior pituitary membranes by substance P and thyrotropin-releasing hormone (TRH) resulted in an additional increase in PIP2-PLC activity compared to stimulation with TRH alone.


Clk-1 deficiency induces apoptosis associated with mitochondrial dysfunction in mouse embryos.
Clk-1 gene encodes demethoxyubiquinone hydroxylase that catalyzes the production of coenzyme Q (CoQ) in mitochondria. Clk-1-deficient mice that lack CoQ fail to survive beyond the embryonic day 10.5 (E10.5). However, the relationship between the clk-1-deficiency and embryonic lethality remains unclear. We show in this study that TUNEL-positive cells are frequently observed in whole bodies of clk-1-deficient mouse embryos at E10.5. In addition, dissociated cells from the embryos exhibited characteristic features of apoptosis, such as externalization of phosphatidylserine on the plasma membrane, caspase-3 activation, and the release of cytochrome c from mitochondria into the cytoplasm, as the first sign of mitochondria-mediated apoptosis. In embryonic cells, the mitochondrial functions such as maintenance of the mitochondrial membrane potential and intracellular ATP level were impaired. Since exogenous CoQ10 rescued the mitochondrial dysfunction and suppressed apoptosis in clk-1-deficient cells, we propose that clk-1-deficiency induces apoptosis associated with mitochondrial dysfunction due to a lack of CoQ, which may lead to embryonic lethality in mice around E10.5.


Slow Magnetization Relaxation in a Family of Triangular {CoIII 2 LnIII } Clusters: The Effect of Diamagnetic CoIII Ions on the LnIII Magnetic Dynamics.
The first use of the Schiff base chelate N-naphthalidene-o-aminophenol (naphH2 ) in Co/Ln chemistry has afforded a family of isostructural [CoIII 2 LnIII (OMe)2 (naph)2 (O2 CMe)3 (MeOH)2 ] (Ln=Tb, Dy and Er) complexes, revealing a rare {CoIII 2 Ln(μ3 -OMe)}8+ triangular core composed of two diamagnetic CoIII ions and a 4f-ion with slightly distorted square antiprismatic geometry. Alternating current (ac) magnetic susceptibility studies revealed that {Co2 Dy}, and its magnetic diluted analogue {Co2 Dy0.05 Y0.95 }, behave as mononuclear single-molecule magnets (SMMs) with similar energy barriers for the magnetization reversal, Ueff , of ~85-90 K. SMM properties were also detected for {Co2 Er}, with the compound exhibiting a Ueff of 18.7 K under an applied magnetic field of 800 Oe. To interpret the experimental magnetic results, ab initio CASSCF/RASSI-SO and DFT calculations were performed as a means of exploring the single-ion characteristics of LnIII ions and comprehend the role of the diamagnetic CoIII ions in the magnetization relaxation of the three heterometallic compounds.


Reconstitution of Mammalian Mitochondrial Translation System Capable of Long Polypeptide Synthesis.
Mammalian mitochondria have their own dedicated protein synthesis system, which produces 13 essential subunits of the oxidative phosphorylation complexes. Here, we describe the in vitro reconstitution of the mammalian mitochondrial translation system, utilizing purified recombinant mitochondrial translation factors, 55S ribosomes from pig liver mitochondria, and a heterologous yeast tRNA mixture. The system is capable of translating leaderless mRNAs encoding model proteins, such as nanoluciferase with a molecular weight of 19 kDa, and is readily applicable for in vitro evaluations of mRNAs and nascent peptide chain sequences, as well as factors and small molecules that affect mitochondrial translation.


Environmentally benign antifouling activity and toxic properties of bioactive metabolites from mangrove Excoecaria agallocha L.
This study was aimed to investigate the antifouling (AF) potentials and toxic properties of methanol extract from leaves of mangrove Excoecaria agallocha. Antimicrofouling activity results inferred that this extract strongly inhibited fouling bacterial and microalgal growth. This extract had also inhibited the settlement of brown mussel Perna indica and larvae of barnacle Balanus amphitrite. Further, EC50 < LC50 and therapeutic ratio > 1 together propagated non-toxic nature of the extract. Mollusk foot adherence assay result showed complete inhibition of foot spreading and loss of attachment of common rocky fouler Patella vulgata to the substrata. Field assay results affirmed that this extract effectively deterred settlement of biofoulers. Purification and GC-MS analysis of bioassay-guided active spot evidenced presence of three major compounds (> 85%) responsible for the promising AF activity. The identified lead compounds subjected to an estimation (BIOWIN™) program developed by United States Environmental Protection Agency (USEPA) predicts that they are biodegradable in nature. Graphical abstract.


Biodistribution of tritiated benzoporphyrin derivative (3H-BPD-MA), a new potent photosensitizer, in normal and tumor-bearing mice.
The biodistribution of a new and very potent photosensitizer, benzoporphyrin derivative-monoacid, ring A (BPD-MA), was determined in normal and P815 (mastocytoma) or M1 (rhabdomyosarcoma) tumor-bearing DBA/2J mice. A dose of 80 micrograms of 3H-BPD-MA was determined at 3, 24, 48, 72, 96 and 168 h post injection. The following tissues were tested: blood, brain, heart, intestine, kidney, lung, liver, muscle, skin, stomach, spleen, thymus and tumor. The biodistribution of 3H-BPD-MA in normal and tumor-bearing mice was comparable overall. 3H-BPD-MA localized in tumors better than in other tissues except kidney, liver and spleen. The tumor to tissue ratios were in the range 1.5-3 at 24 h post injection and increased further during the next 72 h. The highest levels of 3H-BPD-MA were observed in all tissues at 3 h post injection and decreased rapidly during the first 24 h. After 24 h the clearance from tissues was rather slow. The preliminary clearance data obtained in a group of five normal mice indicated that the majority of the injected dose (60%) cleared from the body via the bile and feces, while only about 4% cleared via kidneys and urine. Studies in which 3H-BPD-MA was extracted from tumor, kidney and liver 3 and 24 h after injection showed that, at 3 h, all the photosensitizing activity in tumor was retained. At 24 h only 39% of the activity was retained and considerably less active material was present in liver and kidney.


A modified device to facilitate flow measurements during voiding cystometry studies in infants.
Urodynamic studies (UDS) in infants are traditionally hampered by technique and flow collection; both are difficult and have not yet been standardized. A very simple device has been developed to collect urine during the voiding phase in UDS. It is based on a urine-collection adhesive bag, which is connected to a tube that conducts the urine to a flowmeter. Eleven infants (4-23 months) were selected and a complete UDS was performed on all of them. A diagnosis was obtained for all of the infants. This device is easily available in every pediatric clinic; it is also disposable and inexpensive. It enables UDS in infants to be complete and achievable.


Temporal trends of infant and birth outcomes in Minamata after severe methylmercury exposure.
Severe methylmercury poisoning occurred in Minamata and neighboring communities in Japan during the 1950s and 1960s, causing what is known as Minamata disease. Although an increase in stillbirths and a reduced male proportion at birth (i.e., reduced sex ratio) have been reported, no studies have evaluated the impact of exposure on an entire set of infant and birth outcomes. We therefore evaluated the temporal trends of these outcomes in the Minamata area from 1950 to 1974. We focused on the spontaneous/artificial stillbirth rate, crude fertility rate, male proportion at birth, male proportion among stillbirths, and infant mortality. We obtained the number of stillbirths, live births, and infant deaths in Minamata City and Kumamoto Prefecture (as a reference) from 1950 to 1974. After plotting annual figures for each outcome, we divided the study period into five intervals and compared them between Minamata City and Kumamoto Prefecture using the chi-squared test. We observed a slightly increased spontaneous stillbirth rate and decreased artificial stillbirth rate in Minamata City, followed by a reduced crude fertility rate. The crude fertility rates in Minamata City during the period 1955-1965 were significantly lower compared with those in Kumamoto Prefecture (p < 0.001). An increase in the male proportion among stillbirths was observed, corresponding to a reduction in the proportion of males at birth in the late 1950s. The impact on infant mortality was equivocal. These descriptive analyses demonstrate a severe regional impact of methylmercury exposure on a series of birth outcomes in the Minamata area.


Fatalities caused by nonvenomous animals: a ten-year summary from Sweden.
All 58 deaths caused by nonvenomous animals in Sweden 1975-1984 were scrutinized. In 38 cases horses were involved, in 16 cattle and in one case each a moose, a lion, a dog and a ram. In the horse-related fatalities, the most common cause of accident was that the horse bolted or reared, causing the rider to fall off the horse or the cart or sulky. Falls were thus associated with 22 horse-related deaths. In cattle-related accidents, all fatalities where the cause of accident was known occurred due to aggressive behaviour of the animal. In horse-related accidents, head injuries dominated, while in cattle-related accidents head and chest injuries were equally common. It is suggested that wearing a proper helmet is the most important safety measure in horse-related activities. In cattle-related activities, the herding of untethered bulls together with cows is particularly dangerous and should be avoided.


Percutaneous Minimally Invasive Thermal Ablation of Musculoskeletal Lesions: Usefulness of PET-Computed Tomography.
This article discusses the role of PET-computed tomography in percutaneous minimally invasive ablation of osseous metastases including diagnosis and preprocedural factors related to patient selection and procedure planning, intraprocedural imaging guidance, and posttreatment imaging assessment.


Genetic Variants of CYP4F2 Associated with Ischemic Stroke Susceptibility in the Han Population from Southern China.
The pathophysiological mechanism of ischemic stroke is complex. Traditional risk factors cannot fully or only partially explain the occurrence and development of IS. Genetic factors are getting more and more attention. Our study aimed to explore the association between CYP4F2 gene polymorphism and susceptibility to IS. A total of 1322 volunteers were enrolled to perform an association analysis through SNPStats online software. Using FPRP (false-positive report probability) to detect whether the result is a noteworthy finding. The interaction of SNP-SNP in IS risk was assessed by multi-factor dimensionality reduction. Statistical analysis of this study was mainly completed by SPSS 22.0 software. Mutant allele "A" (OR = 1.24) and genotype "AA" (OR = 1.49) or "GA" (OR = 1.26) of CYP4F2-rs2108622 are risk genetic factors for IS. Rs2108622 is significantly associated with an increased risk of IS among subjects who are females, aging >60 years old, with BMI ≥24 kg/m2, and smoking or drinking volunteers. CYP4F2-rs3093106 and -rs3093105 are associated with susceptibility to IS among smoking, drinking subjects, or IS patients complicated with hypertension. CYP4F2-rs2108622, -rs3093106, and -rs3093105 are associated with an increased risk of IS.


Druggable Allosteric Sites in β-Propeller Lectins.
Carbohydrate-binding proteins (lectins) are auspicious targets in drug discovery to combat antimicrobial resistance; however, their non-carbohydrate drug-like inhibitors are still unavailable. Here, we present a druggable pocket in a β-propeller lectin BambL from Burkholderia ambifaria as a potential target for allosteric inhibitors. This site was identified employing 19 F NMR fragment screening and a computational pocket prediction algorithm SiteMap. The structure-activity relationship study revealed the most promising fragment with a dissociation constant of 0.3±0.1 mM and a ligand efficiency of 0.3 kcal mol-1 HA-1 that affected the orthosteric site. This effect was substantiated by site-directed mutagenesis in the orthosteric and secondary pockets. Future drug-discovery campaigns that aim to develop small molecule inhibitors can benefit from allosteric sites in lectins as a new therapeutic approach against antibiotic-resistant pathogens.


Sucralfate for posttonsillectomy analgesia.
Pain is one of the most troublesome complications of tonsillectomy. The pain appears as throat pain, otalgia, or both, and continues until mucosal recovery on the tonsillar fossae is complete. Some surgical and hemostasis techniques may increase pain. Analgesics, antibiotics, steroids, and local and topical anesthetics are used to relieve posttonsillectomy pain, but none has the desired effectiveness. The pain reliever must not increase bleeding and must have minimal side effects. Sucralfate, a basic amino salt of sucrose octasulfate, binds to the matrix protein of a peptic ulcer and produces a protective barrier. Tonsillectomy leaves two large ulcerous wounds, and sucralfate may bind those wounds as it does peptic ulcers. In this controlled study, the efficacy of sucralfate on posttonsillectomy throat pain, otalgia, analgesic requirement, degree of strength, bleeding, body temperature, and mucosal recovery is investigated in 80 patients. Sucralfate is found to significantly reduce throat pain and analgesic requirement after surgery.


Research trends on digital flexor tendon: A bibliometric analysis based on CiteSpace.
A host of experts have shown interest in the digital flexor tendon. However, few have conducted a bibliometric analysis of this field. This study aimed to carry out comprehensive and practical research on the academic status and the development trend in this area. All papers regarding digital flexor tendons announced from 1991 to 2022 were retrieved and downloaded from the Web of Science Core Collection. CiteSpace was utilized to analyze the information on publication output, journals, authors, countries, institutions and keywords. A total of 3100 publications met the inclusion criteria, which were made up of articles and reviews. The publications and cite frequency increased rapidly per year (t = 10.652, P < 0.001; t = 19.716, P < 0.001). Journal of Hand Surgery American Volume had the largest number of studies (307 publications). Amadio PC was identified as the most prolific author, and Dyson SJ (336 citations) was the most cited author. The United States had the highest publications (35.39%), followed by England. Though Australia ranked tenth, which had the greatest impact (centrality = 0.43). This study collected 20 clusters and 25 citation bursts on the basis of keywords. This study recommends that international cooperation and linkages among authors, countries and institutions should be strengthened. Ultrasound, tenosynovitis, platelet-rich plasma, and 3-loop pulley suture have been the focus of current research. The surgical and non-surgical treatment of digital flexor tendon injury would be future frontiers.


Control of cancer pain in veterinary patients.
Control of cancer pain is within the capabilities of most veterinarians and is achievable in most animal patients that have cancer with techniques that are currently available. Great satisfaction can be derived from not only treating the pet's cancer but its pain. Incorporating pain management into oncology practice is good for the well-being of the pet, the owner, the staff, the veterinarians, and the practice.


A mathematical model for the dynamics and control of malaria in Nigeria.
Malaria is a life-threatening disease endemic in many African countries especially Nigeria. A mathematical model is used to study the dynamics of malaria in Nigeria. The model incorporates drug resistance, treatment, and the use of mosquito nets as preventive strategies. By fitting the model to data on the incidence of malaria in Nigeria, important parameters associated with the disease dynamics are estimated. Using these estimated parameters, the basic reproduction number is calculated, future dynamics simulated, and those parameters with a large impact on Nigerian malaria determined. Overall, the results indicate that the disease is likely to remain endemic in Nigeria unless better control measures are focused on the dominant resistant strain, treatment is improved and the use of mosquito nets become widespread.


Colonic variceal bleeding in a child.
A 5-year-old girl with biliary atresia is described who developed lower gastrointestinal bleeding from colonic varices. Vasopressin infusions temporarily controlled the bleeding. Following a right hemicolectomy the bleeding has not recurred.


Ancrod decreases the frequency of cyclic flow variations and causes thrombolysis following acute coronary thrombosis.
The potential use of ancrod, a purified isolate from the venom of the Malaysian pit viper, Agkistrodon rhodostoma, in decreasing the frequency of cyclic flow variations in severely stenosed canine coronary arteries and causing thrombolysis of an acute coronary thrombus induced by a copper coil was evaluated. Open-chest, anesthetized dogs were used. Ancrod was given intravenously (8 U/kg) over 1 hour and caused a significant reduction in the frequency of cyclic flow variations (5.8 +/- 0.7 to 3.6 +/- 0.8 cyclic flow variations per 30 minutes, p less than 0.05), whereas control animals failed to decrease the frequency of their cyclic flow variations over the same time period (5.3 +/- 0.3 to 5.0 +/- 0.4 cyclic flow variations per 30-minute period). Twenty-seven dogs had a coronary thrombus induced by a copper coil positioned directly in a major coronary artery; of these, four died of ventricular fibrillation prior to treatment, eight received an infusion of saline and showed no thrombolysis over 5 hours, and three died of ventricular fibrillation during the initial part of an intravenous infusion of ancrod. The remaining 12 dogs received ancrod intravenously (16 U/kg); six demonstrated lysis of the coronary thrombus (mean time to lysis, 65 +/- 20 minutes). The concentrations of ancrod used in these studies produced a severe decrease in systemic fibrinogen concentration and a significant decrease in the inhibitor of plasminogen activator levels. Thus, ancrod decreases the frequency of cyclic flow variations in stenosed canine coronary arteries and may cause coronary thrombolysis in approximately 50% of animals within 65 +/- 20 minutes of its intravenous administration.


Evaluation of the VTEC-Screen "Seiken" test for detection of different types of Shiga toxin (verotoxin)-producing Escherichia coli (STEC) in human stool samples.
An immunoassay for in vitro detection of Shiga (Vero) toxins Stx1 and Stx2 (VTEC-Screen "Seiken") was compared with the verocell toxicity test (VCA) and an stx-gene specific PCR for detection of Shiga toxin-producing E. coli (STEC) from 234 human stool samples selectively enriched on sorbitol-MacConkey (SMAC) agar. Culturable STEC were isolated from 59 (25.2%) of the 234 stool specimens and were found to be distributed over 20 different O-serogroups. Fifty-three (89.8%) of the 59 STEC-positive samples were identified with the VTEC-Screen compared to 55 (93.2%) with the PCR and 58 (98.3%) with the VCA. A possible false positive reaction with the VTEC-Screen was obtained with one sample and five samples showed aspecific reactions with both the test- and the control latex. The VTEC-Screen detected all samples which contained Stx1 producing strains (77.9% of STEC-positive samples) but was negative with six samples (10.2%) which contained Stx2 and/or Stx2 variant producers, although secondary enrichment of on brain-heart infusion agar detected three of these to improve the detection rate to 94.9%. Examination of reference strains encoding different genotypes of stx(1) and stx(2) indicated that certain variants of Stx2 reacted poorly (Stx2d-Ount, Stx2e and Stx2ev) or not at all with the VTEC-Screen. Overall, however, the test was found to be accurate, rapid and easy to perform, thus being suitable for the routine screening of clinical stool specimens for STEC.


Challenging the distribution shift: statically-induced direction illusion implicates differential processing of object-relative and non-object-relative motion.
The direction illusion is the phenomenal exaggeration of the angle between the drift directions, typically, of two superimposed sets of random dots. The direction illusion is commonly attributed to mutual inhibition between direction-selective cell populations (distribution-shift model). A second explanation attributes the direction illusion to the differential processing of relative and non-relative motion components (differential processing model). Our first experiment demonstrates that, as predicted by the differential processing model, a static line can invoke a misperception of direction in a single set of dots--a phenomenon we refer to as the statically-induced direction illusion. In a second experiment, we find that the orientation of a static line can also influence the size of the conventional direction illusion. A third experiment eliminates the possibility that these results can be explained by the presence of motion streaks. While the results of these experiments are in agreement with the predictions made by the differential processing model, they pose serious problems for the distribution-shift account of shifts in perceived direction.


Emerging hubs in phantom perception connectomics.
Brain networks are small-world networks typically characterized by the presence of hubs, i.e. nodes that have significantly greater number of links in comparison to other nodes in the network. These hubs act as short cuts in the network and promote long-distance connectivity. Long-distance connections increase the efficiency of information transfer but also increase the cost of the network. Brain disorders are associated with an altered brain connectome which reflects either as a complete change in the network topology, as in, the replacement of hubs or as an alteration in the connectivity between the hubs while retaining network structure. The current study compares the network topology of binary and weighted networks in tinnitus patients and healthy controls by studying the hubs of the two networks in different oscillatory bands. The EEG of 311 tinnitus patients and 256 control subjects are recorded, pre-processed and source-localized using sLORETA. The hubs of the different binary and weighted networks are identified using different measures of network centrality. The results suggest that the tinnitus and control networks are distinct in all the frequency bands but substantially overlap in the gamma frequency band. The differences in network topology in the tinnitus and control groups in the delta, theta and the higher beta bands are driven by a change in hubs as well as network connectivity; in the alpha band by changes in hubs alone and in the gamma band by changes in network connectivity. Thus the brain seems to employ different frequency band-dependent adaptive mechanisms trying to compensate for auditory deafferentation.


Helminth parasite communities in anuran amphibians of Kalesar Wildlife Sanctuary (Haryana), India.
Helminth parasite fauna in anuran amphibia were investigated during the general faunistic surveys of Kalesar Wildlife Sanctuary, situated in Haryana state. Three species of amphibian hosts were found to harbour 12 genera of helminth parasites. The prevalence, intensity and abundance were studied. Euphlyctis cyanophlyctis harboured maximum parasite species followed by Fejervarya limnocharis and Duttaphrynus melanostictus. In E. cyanophlyctis, among nematode parasites, the genus Camallanus was most prevalent followed by Cosmocerca and Cosmocercoides, whereas, Rhabdias and Aplectana were the least prevalent genera. Among trematode parasites, Ganeo was the most prevalent genus and least was Diplodiscus. Acanthocephalus was recovered only once and no cestode infection was found. In F. limnocharis, the most prevalent nematode genus was Oxysomatium, followed by Cosmocerca and the only trematode recorded was Ganeo, whereas, cestode Proteocephalus was also recovered once. In D. melanostictus, only two nematode genera were recovered of which Oxysomatium was dominant followed by Cosmocerca. The helminth parasite community in anuran amphibia of Kalesar WLS comprised 52.9% of nematodes, 46.2% of trematodes, 0.58% cestodes and 0.29% acanthocephala.


Disease control priorities for neglected tropical diseases: lessons from priority ranking based on the quality of evidence, cost effectiveness, severity of disease, catastrophic health expenditures, and loss of productivity.
In the context of limited health care budgets in countries where Neglected Tropical Diseases (NTDs) are endemic, scaling up disease control interventions entails the setting of priorities. However, solutions based solely on cost-effectiveness analyses may lead to biased and insufficiently justified priorities. The objectives of this paper are to 1) demonstrate how a range of equity concerns can be used to identify feasible priority setting criteria, 2) show how these criteria can be fed into a multi-criteria decision-making matrix, and 3) discuss the conditions under which this decision-making procedure should be carried out in a real-world decision-making context. This paper draws on elements from theories of decision analysis and ethical theories of fair resource allocation. We explore six typical NTD interventions by employing a modified multi-criteria decision analysis model with predefined criteria, drawn from a priority setting guide under development by the WHO. To identify relevant evidence for the six chosen interventions, we searched the PubMed and Cochrane databases. Our in vitro multi-criteria decision analysis suggested that case management for visceral leishmaniasis should be given a higher priority than mass campaigns to prevent soil-transmitted helminthic infections. This seems to contradict current health care priorities and recommendations in the literature. We also consider procedural conditions that should be met in a contextualised decision-making process and we stress the limitations of this study exercise. By exploring how several criteria relevant to the multi-facetted characteristics of NTDs can be taken into account simultaneously, we are able to suggest how improved priority settings among NTDs can be realised.


The psychiatric consultant in professional team sports.
The role of the sport psychiatrist consulting to a professional sports team is complex, challenging, and varied. Sport psychiatrists enhance the psychosocial development of the athlete by removing obstacles to growth and by facilitating lines of communication that support exchange of information, sharing of feelings, and the development of solid winning relationships on the team and throughout the organization. The consultant psychiatrist often provides input both to players and to management, however; these dual responsibilities raise ethical concerns and often require the services of additional treating psychiatrists and other mental health professionals.


Metronidazole as a radiosensitizer and high-dose radiation in advanced vulvovaginal malignancies, a pilot study.
Advanced vulvovaginal cancers have a survival of less than 25% in 5 years when treated with radiotherapy alone. The radiosensitizer metronidazole was used with unconventional radiation fractions in 10 patients. Local control was achieved in 9 out of 10 patients treated. Five of 10 patients have remained free of disease 9-30 months postdiagnosis. Two patients died with metastatic disease, but with local control. In only 1 patient did this approach fail to control local disease. The outcome of these 10 patients represents a significant improvement over conventional radiation. A randomized prospective study has been started on the basis of this pilot study.


Studies of introital colonization in women with recurrent urinary infections. I. The role of vaginal pH.
The pH of the vaginal introitus was compared to quantitative cultures of the introital mucosa (Escherichia coli, Proteus mirabilis and Streptococcus faecalis) in 800 samples. Introital carriage of more than 100 bacteria per ml. was significantly greater at pH of more than 4.4 (p less than 0.005) when compared to mucosal pH of less than or equal to 4.4.


Method development and validation for analysis of phenolic compounds in fatty complex matrices using enhanced matrix removal (EMR) lipid cleanup and UHPLC-QqQ-MS/MS.
Reliable analysis of phenolic compounds in fatty matrices is a challenging task. In this work, a robust analytical method was developed and validated for 55 phenolic compounds employing QuEChERS (quick, efficient, cheap, easy, rugged and safe) and Enhanced Matrix Removal (EMR)-lipid cleanup in 96-well plates for sample preparation, coupled with ultra-high performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS). Seven high-fat matrices of pork brain, belly and liver; horse serum, beef, salmon and avocado were explored for method validation and led to promising stepwise recoveries of extraction, clean-up, drying-reconstitution of most analytes ranging from 75% to 113%, and with an accuracy of 78%∼117%, except for six catechin-analogues. The matrix removal efficiency of EMR was determined using UHPLC-quadruple time of flight (QTOF)-MS, and results indicated that 56%∼77% of co-extractives were removed. This method would be readily extended to wide range of applications demanding high-throughput and sensitive analysis of phenolic compounds in fatty samples.


The effectiveness of two infant hearing screening programmes in New Zealand.
Early detection of congenital hearing loss is vital. A neonatal hearing screening programme and a 9 month at risk hearing screening programme are analysed. Neither contributed significantly to the detection of deaf infants, though 9 month at risk screening can be worthwhile if well administered. Age of detection data for deaf preschoolers in New Zealand are presented.


Replating of bioreactor expanded human bone marrow results in extended growth of primitive and mature cells.
The capability to expand human bone marrow mononuclear cells (BM MNC) in high density perfusion culture chambers (bioreactors) has recently been developed. In these bioreactors, total cell colony-forming unit-granulocyte/macrophage (CFU-GM), and long-term culture-initiating cell (LTC-IC) numbers increase significantly over a 14-day period. However, cell growth ceases after the 14-day period, possibly due to cell density limitations. Because of the remaining presence of early cells, it should be feasible to replate the cells and obtain continued expansion. In this study, we demonstrate that bioreactors generate cells, which upon replating into secondary bioreactors, lead to continued cell, CFU-GM, and LTC-IC(8) (measured after 8 weeks of secondary culture) expansion. A two-stage protocol, involving the replating of cells on days 9 to 12 of culture into new bioreators at the original seeding density, yielded greater than 50-fold cell expansion from BM MNC in 25 days. CFU-GM were expanded inhibitory factor (LIF) had no significant effect on total cells, CFU-GM, or LTC-IC(5) in this system. We conclude that two-stage bioreactor cultures are capable of supporting extended growth of human BM MNC, CFU-GM, and LTC-IC(8). The continued expansion of these primitive cells in the second stage of culture suggests that primitive cells with significant proliferative potential were generated in this system, and previous data on LTC-IC(5) expansion has now been extended to LTC-IC(8) expansion. Further optimization of culture conditions is likely to improve on the results obtained here, thus making perfusion bioreactor culture correspondingly more attractive for expanding BM MNC for BM transplantation.


Outcomes of anterior levator resection in congenital blepharoptosis.
To identify any consistent factors which may predict over- or undercorrection of congenital blepharoptosis treated by anterior levator resection. A retrospective case note review of 100 consecutive patients undergoing anterior levator resection for congenital blepharoptosis was performed to identify: (1) the amount of ptosis and degree of levator function present pre-operatively and (2) the surgical outcome. For unilateral ptosis, a successful result was defined as a lid level within 1 mm of the fellow lid following a single operation. Seventy-six per cent of all unilateral cases had a successful outcome at 6 weeks following surgery, falling slightly to 74% by 6 months. The most common complications at 6 months were undercorrection (19%) and overcorrection (7%). All patients undercorrected at 6 months had a pre-operative levator function in the range of 4-10 mm with a mean of 6.4 mm, whereas all those overcorrected at 6 months had a levator function in the range 9-15 mm with a mean of 12.2 mm. In the whole population, the degree of levator function was a predictor of increased risk of overcorrection, with a trend towards predicting undercorrection as well. In this series of patients, pre-operative levator function was found to be the most significant predictor of surgical outcome for anterior levator resection.


Efficacy of intramuscular penicillin in the eradication of group B streptococcal colonization at delivery.
Due to rapid deliveries and human error, not all group B streptococcal positive mothers will receive adequate prophylactic antibiotic treatment in labor. We sought to determine if long acting intramuscular penicillin given after a positive culture result would be efficacious in eradicating group B streptococcal colonization at the time of delivery. Patients positive for group B streptococci at 35-37 weeks were randomized to receive 2.4 million units of intramuscular benzathine penicillin G suspension (Bicillin L-A) versus no treatment. Study patients were recultured at the time of admission to labor and delivery prior to receiving prophylactic antibiotics according to CDC guidelines. A total of 53 patients were enrolled. A small but significant decrease in the rate of group B streptococcal colonization was observed in the treatment group (14/27, 52%) versus the control group (20/23, 87%), p=0.03. The large number of persistent carriers suggests that 2.4 million units of intramuscular benzathine penicillin G suspension (Bicillin L-A) is insufficient as sole therapy. However, the decline in group B streptococcal carriers might lessen the risk of failed or insufficient intrapartum treatment. Intramuscular benzathine penicillin G suspension (Bicillin L-A) may be useful as an adjunctive treatment for patients at risk for rapid delivery, before adequate intrapartum prophylaxis can be given.


Denoising the hob vibration signal using improved complete ensemble empirical mode decomposition with adaptive noise and noise quantization strategies.
A novel denoising method combining complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and noise quantization strategies is proposed to solve the problem of the noise of the hob vibration signals disturbing the condition monitoring and feature extraction. The vibration signal is decomposed into several intrinsic mode functions (IMFs) and a residual based on CEEMDAN first. Considering that statistical indicators such as correlation coefficient and kurtosis are not effective in the presence of non-Gaussian noises and modulation because they primarily focus on the signal statistical distribution while ignoring the characteristics of the mechanism, a novel index based on the autocorrelation function analysis called periodic modulation for noise assessment (PMNA) is proposed to quantify the noise of IMFs. Further, IMFs are rearranged in the decreasing order of PMNA. A novel threshold joint with IMFs noise assessment (TJINA) varying with the combination of PMNA and the rearranged IMF retrieval is designed, which has advantages in the local smoothness and small fluctuation. On that basis, IMFs are divided into noise domain and signal domain, IMFs in the noise domain are denoised with TJINA and soft threshold function strategies. The proposed method is applied to the simulated signals with different input signal to noise ratios (SNRin) and two measured gear hobbing vibration signals. The comparison with some state-of-the-art approaches and the ablation experiment reveals that the proposed method performs better in enhancing the effective components and eliminating noise.


Continuous and simultaneous monitoring of EEG spectra and brainstem auditory and somatosensory evoked potentials in the intensive care unit and the operating room.
Individual monitoring of EEG and evoked potentials is gradually becoming standard in neurosurgery: compressed power spectra during carotid endarterectomy, brainstem auditory evoked potentials (BAEP) during posterior fossa surgery, and somatosensory evoked potentials (SEP) mainly during spinal cord surgery. In this paper, a new technique is described in which EEG, BAEP, and SEP are recorded and evaluated simultaneously and continuously. This allows a better survey of different neuronal structures and systems in the brain and brainstem. First results from intraoperative and intensive care patient monitoring are reported.


Early detection of spoilage moulds in bread using volatile production patterns and quantitative enzyme assays.
Early detection of spoilage fungi (two Eurotium spp., a Penicillium chrysogenum species) in bread analogues over periods of 72 h at 25 degrees C and 0.95 water activity was evaluated using volatile production patterns, hydrolytic enzyme production, and changes in fungal populations. Using an electronic nose system it was possible to differentiate between uninoculated controls and samples contaminated with P. chrysogenum within 28 h. After 40-48 h it was possible to differentiate between the Eurotium spp., P. chrysogenum and the control using Principal Component Analysis (PCA). Cluster analyses could differentiate between the control, P. chrysogenum and the Eurotium spp. after 40 h. Of seven hydrolytic enzymes examined after 48 h, the specific activities of three were significantly different from uninoculated control bread. There were also differences between the mould species in production of three enzymes. Penicillium chrysogenum populations increased fastest, from about 10(3) cfu g(-1) to 10(6)-10(7) cfu g(-1) after 72 h. For the Eurotium spp. this increase was slower. Overall, this study suggests, for the first time, that an electronic nose system using a surface polymer sensor array is able to detect qualitative changes in volatile production patterns for the early detection of the activity of spoilage moulds in bakery products. Potential exists for application of such systems for microbial quality assurance in intermediate moisture food products.


Modelling journalists' coping strategies for occupational hazards in their coverage of protests against police brutality (ENDSARS protests) in Nigeria.
Although journalism practice exposes media workers to different levels of occupational hazards, research on the coping strategies is limited. This study made an effort to extend literature in this direction by providing a model that explains the coping strategies of Nigerian journalists who covered the 2020 ENDSARS protests in Nigeria. The researchers surveyed a total of 470 journalists who were sampled through a respondent-driven chain referral sampling technique. It was found that journalists who covered the protests faced occupational hazards such as physical attacks, disgrace, threats, trauma, anxiety as well as fear. The coping strategies were found to include seeking social support, selective appearance, self-censorship as well as self-motivation. It was further found that perceived behavioural control significantly moderates the implementation of coping strategies. The researchers explored the implications of these results on theory, practice and scholarship.


Sublabial approach to the nasal and nasopharyngeal cavities.
A sublabial transnasal degloving approach to the mid-face, nasal cavity, septum, paranasal sinuses, and nasopharynx is described. This approach provides adequate exposure and ample facility for management of tumors in these areas. The pterygomaxillary space and infratemporal fossa ard readily accessible for hemostasis and management of tumor extensions. Children, adolescents, and women with benign and low-grade malignant tumors of these areas are the ideal candidates for this procedure. Twenty-six patients have been managed in this fashion, with no major complication. The cosmetic results have been excellent. This approach to the mid-third of the face, nasal, paranasal, and nasopharyngeal cavities should receive more attention and use.


A systematic review of cannabidiol trials in neurodevelopmental disorders.
Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations. This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE. Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency. Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders. Prospero registration number: CRD42021267839.


MiR-631/ZAP70: A novel axis in the migration and invasion of prostate cancer cells.
MicroRNAs (miRNAs) are short, endogenous non-coding RNA molecules involved in cancer initiation and progression. Using transwell migration and invasion assays, we found that miR-631 inhibited the migration and invasion of prostate cancer (PCa) cells. Bioinformatic algorithms indicated the 3'-untranslated region (3'-UTR) of zeta-associated protein 70 (ZAP70) has a putative binding site for miR-631. We found that miR-631 can bind to the 3'-UTR of ZAP70 and decrease its expression. Further studies confirmed that ZAP70 facilitates PCa cell migration and invasion. Interestingly, using gain- and loss-of function experiments, we found that ZAP70 is a major target of miR-631 and largely mediates its activity. In addition, we further discovered that miR-631 was downregulated and ZAP70 was overexpressed in PCa cell lines and PCa tissues. A concordant inverse correlation between miR-631 and ZAP70 was also found in PCa tissues. In all, our study demonstrates that miR-631 decreases PCa cell migration and invasion by dampening ZAP70 expression.


An N-terminal truncated form of Orp150 is a cytoplasmic ligand for the anti-proliferative mushroom Agaricus bisporus lectin and is required for nuclear localization sequence-dependent nuclear protein import.
Nuclear localization sequence-dependent nuclear protein import is essential for maintaining cell function and can be selectively blocked in epithelial cells by mushroom (Agaricus bisporus) lectin. Here we report that a major intracellular ligand for this lectin is an N-terminally truncated form of oxygen-regulated protein 150 (Orp150), which lacks the endoplasmic reticulum translocation signal peptide of full-length Orp150. This cytoplasmic form of Orp150 expresses the lectin carbohydrate ligand (sialyl-2,3-galactosyl-beta1,3-N-acetylgalactosamine-alpha) and is shown to be essential for nuclear localization sequence-dependent nuclear protein import.


Preliminary results of a new sanitation program for the eradication of enzootic bovine leukosis.
The program under discussion is based on results obtained during transmission studies in which specific antibodies were detected in the immunodiffusion test earlier than antigen in peripheral blood leukocytes. Furthermore, it could be demonstrated that seroconversion does not seem to occur later than 3 months after transmission of the infectious agent. The results obtained in 11 herds are presented. The program is as follows: when the result of the immunodiffusion test becomes available all positive animals above 6 months of age are immediately removed from the herd. The remaining animals are checked at intervals of 3 months and sero-positives are always instantly removed. In pursuing the program a number of herds have obviously reachend 2 years old.


Ball-milled PET plastic char as an electron shuttle accelerated anaerobic degradation of 2,4,6-trichlorophenol in water environment.
1The combination of carbonaceous materials and microbial degradation is an attractive measure in improving the removal efficiency of organic pollutants in water environment. In this study, the anaerobic dechlorination in a coupled system of ball-milled plastic chars (BMPCs) and the microbial consortium were investigated. The anaerobic microorganism cultured from raw sludge (CAM) contributed to the dechlorination of the 2,4,6-trichlorophenol (2,4,6-TCP) into 4-chlorophenol (4-CP) as the final product via ortho-dechlorination in all testing groups. The dechlorination rate was accelerated in different BMBC plus CAM groups than that in only CAM group (0.048 d-1), of which, it was greater in BMPC-500 plus CAM group (0.375 d-1) than that in BMPC-700 plus CAM group (0.171 d-1). The electron exchange capacity (EEC) of BMPCs decreased with the increase of pyrolysis temperature (0.053 mmol e-/g for BMPC-500 and 0.037 mmol e-/g for BMPC-700), which directly affected anaerobic dechlorination. Direct interspecies electron transfer (DIET) of BMPCs also boosted the biogas yield by 1.5 times compared to that without BMPCs. Microbial community analysis illustrated that BMPCs helped to enrich the putative dechlorinating bacteria. The abundance of Clostridium_aenus_stricto_12, as a dominant dechlorinator, significantly increased from 0.02 % to 11.3 % (without BMPCs), 39.76 % (BMPC-500) and 9.3 % (BMPC-700), and followed by, Prevotella and Megaspheara, which was reported to take part in anaerobic dechlorination and digestion as H2 producers, also increased in the presence of BMPC. This study contributes to the realization of 2,4,6-TCP in-situ reduction technology and provides a scientific reference for anaerobic dechlorination by cultured anaerobes combined with BMPCs.


Attaining interprofessional competencies by connecting oral health to overall health.
The purpose of this study was to evaluate the effectiveness of an annual oral-systemic health interprofessional education (IPE) clinical simulation and case study experience with nurse practitioner/midwifery (NP/MW), dental (DDS), medical (MD), and pharmacy (PharmD) students. The Interprofessional Collaborative Competency Attainment Scale (ICCAS) was used to measure students' self-reported attainment of interprofessional competencies before and after the IPE experience. Pre- and post-test surveys were completed by NP/MW, DDS, MD, and PharmD student cohorts from 2017 to 2019. Students also had the opportunity to provide qualitative feedback about their experience at post-test. Data were collected from IPE faculty facilitators to assess their perception of the value of the Teaching Oral-Systemic Health (TOSH) program. Student ICCAS results demonstrated statistically significant improvement in self-reported interprofessional competencies among all types of students across all 3 years (P < 0.001); qualitative student comments reflected positive experiences with the TOSH program. Survey data from IPE faculty facilitators supported the value of the IPE experience for all students. The findings demonstrate the effectiveness of the TOSH program in using oral-systemic health as a clinical exemplar to develop interprofessional competencies. The 2017-2019 data reinforce the credibility of scaling the TOSH model for developing interprofessional competencies with students from different health professions.


Malignant Superficial Mesenchymal Tumors in Children.
Malignant superficial mesenchymal tumors are a very diverse group of neoplasms with few clinical and radiological discriminatory factors. Hence, some of these cancers are rarely suspected based on clinical and radiological grounds, others may be easily misdiagnosed, and the histological analysis of a biopsy or resection is central in the diagnostic process. In children, the age at presentation is a major element of the differential diagnosis. Some tumors have a very distinct epidemiology, while others may be seen at any age. More recently, the advances in molecular biology have greatly improved the diagnosis of mesenchymal tumors and new entities are still being described. In the present review, we provide an overview of the diversity of malignant superficial mesenchymal tumors in children, including new and/or rare entities. We discuss the important diagnostic features, be they clinical, histological, or molecular. Special attention was given to the genetic features of these tumors, particularly when they were helpful for the diagnosis or treatment.


Combined Healthy Behaviors and Healthcare Services Use in Older Adults.
Data on the combined impact of healthy behaviors on healthcare use in older adults are limited. Study with community-dwelling individuals aged ≥60 years from the Spanish Seniors-ENRICA cohort, recruited in 2008-2010, followed through 2012-2013, and analyzed in 2016 (N=2,021). At baseline, the following healthy behaviors were self-reported: three traditional (never smoking, being physically active, having a healthy diet) and three emerging (sleeping 7-8 hours/day, sitting <8 hours/day, not living alone). Outcomes were self-reported polypharmacy (five or more drugs per day), primary care physician visits (one or more per month), medical specialist visits (more than one per year), and hospitalization (one or more in the last year). The associations between baseline healthy behaviors and healthcare services used in 2012-2013 were summarized with ORs and 95% CIs from multiple logistic regression, adjusting for demographics, lifestyles, comorbidities, and baseline health services used. Most single healthy behaviors were associated with lower use of most health services. Compared with participants with zero or one healthy behavior, those with five or six healthy behaviors showed lower risk of polypharmacy (OR=0.46, 95% CI=0.24, 0.85, p-trend=0.001), visits to the primary care physician (OR=0.50, 95% CI=0.26, 0.96, p-trend=0.013), and hospitalization (OR=0.50, 95% CI=0.24, 1.01, p-trend=0.016). No association was found with visits to the medical specialist. The combination of five to six healthy behaviors in older adults is associated with half the risk of polypharmacy and using several healthcare services. In an era of constrained resources in most countries, this information may help inform health policy to control healthcare spending in the future.


Air-displacement plethysmography for the measurement of body composition in children aged 6-48 months.
Air-displacement plethysmography (ADP) is an age-appropriate method for measuring relative fat mass (%FM) in children; however, the accuracy of this method has not been evaluated in children aged 5 y or younger. Mean %FM values measured by ADP (17.9 ± 8.0%) and by total body water (TBW) (23.7 ± 6.3%) were significantly different (P < 0.001). Regression analysis of %FM by ADP vs. TBW provided a line of best fit with a slope of 0.089, r(2) = 0.013, and standard error of the estimate (SEE) = 6.3% FM (P = 0.40). The error was related to child weight and %FM, but not to behaviors (movement or vocalizations) occurring during the test sequence. A large portion of the error was attributable to imprecision in measuring small volumes. As currently designed, ADP is not an accurate method for measuring %FM in young children. Further investigation of the sources of variability will provide insight into ways of improving the accuracy of this technology for this population. This study examined the accuracy of an ADP system modified for young children (BOD POD; Life Measurement, Concord, CA) by comparing %FM results from ADP with those obtained from TBW by deuterium (D(2)O) dilution (reference method) in 72 children aged 6-48 mo.


Human factors engineering approaches to patient identification armband design.
The task of patient identification is performed many times each day by nurses and other members of the care team. Armbands are used for both direct verification and barcode scanning during patient identification. Armbands and information layout are critical to reducing patient identification errors and dangerous workarounds. We report the effort at two large, integrated healthcare systems that employed human factors engineering approaches to the information layout design of new patient identification armbands. The different methods used illustrate potential pathways to obtain standardized armbands across healthcare systems that incorporate human factors principles. By extension, how the designs have been adopted provides examples of how to incorporate human factors engineering into key clinical processes.


Protein acetylation-mediated cross regulation of acetic acid and ethanol synthesis in the gas-fermenting Clostridium ljungdahlii.
The autotrophic acetogen Clostridium ljungdahlii has emerged as a major candidate in the biological conversion of one-carbon gases (CO2/CO) to bulk chemicals and fuels. Nevertheless, the regulatory pathways and downstream metabolic changes responsible for product formation and distribution in this bacterium remain minimally explored. Protein lysine acetylation (PLA), a prevalent posttranslational modification, controls numerous crucial cellular functions. Herein, we revealed a novel cross-regulatory mechanism that uses both the PLA system and transcription factors to regulate the carbon flow distribution for product formation in C. ljungdahlii. The dominant acetylation/deacetylation system (At2/Dat1) in C. ljungdahlii was found to regulate the ratio of two major products, acetic acid and ethanol. Subsequent genetic and biochemical analyses revealed that the activities of Pta and AdhE1, two crucial enzymes responsible for acetic acid and ethanol synthesis, respectively, were greatly affected by their levels of PLA. We found that the acetylation statuses of Pta and AdhE1 underwent significant dynamic changes during the fermentation process, leading to differential synthesis of acetic acid and ethanol. Furthermore, the crucial redox-sensing protein Rex was shown to be regulated by PLA, which subsequently altered its transcriptional regulation on genes responsible for acetic acid and ethanol formation and distribution. Based on our understanding of this cross-regulatory module, we optimized the ethanol synthetic pathway by modifying the acetylation status (deacetylation-mimicked mutations of crucial lysine residues) of the related key enzyme, achieving significantly increased titer and yield of ethanol, an important chemical and fuel, by C. ljungdahlii in gas fermentation.


Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity.
Surgical treatment of low-grade gliomas (LGGs) aims to maximise the amount of tumour tissue resected, while minimising the risk of functional sequelae. In this review I address the issue of how to reconcile these two conflicting goals. First, I review the natural history of LGG-growth, invasion, and anaplastic transformation. Second, I discuss the contribution of new techniques, such as functional mapping, to our understanding of brain reorganisation in response to progressive growth of LGG. Third, I consider the clinical implications of interactions between tumour progression and brain plasticity. In particular, I show how longitudinal studies (preoperative, intraoperative, and postoperative) could allow us to optimise the surgical risk-to-benefit ratios. I will also discuss controversial issues such as defining surgical indications for LGGs, predicting the risk of postoperative deficit, aspects of operative surgical neuro-oncology (eg, preoperative planning and preservation of functional areas and tracts), and postoperative functional recovery.


Rapid electroplating of insulators.
Electrochemical techniques for depositing metal films and coatings have a long history. Such techniques essentially fall into two categories, with different advantages and disadvantages. The first, and oldest, makes use of spontaneous redox reactions to deposit a metal from solution, and can be used on both insulating and metallic substrates. But the deposition conditions of these processes are difficult to control in situ, in part because of the variety of salts and additives present in the solution. The second approach-electroplating-uses an electric current to reduce metal ions in solution, and offers control over the quantity (and, to some extent, grain size) of deposited metal. But application of this technique has hitherto been restricted to conducting substrates. Here we describe an electroplating technique that permits coating of insulating substrates with metals having controlled grain size, thickness and growth speed. The basis of our approach is the progressive outward growth of the metal from an electrode in contact with the substrate, with the cell geometry chosen so that the electron current providing the reduction passes through the growing deposit. Such an approach would normally form dendritic or powdery deposits, but we identify a range of conditions in which uniform films rapidly form.


Impact of Magnetic Resonance Imaging (MRI) Findings on Management of Symptomatic Patients Following Radiofrequency Ablation (RFA) of Osteoid Osteoma (OO).
To assess the impact of MRI findings on management of symptomatic patients following RFA of OO. Retrospective review of 43 patients with RFA for OO between June 2010 and June 2017 was performed. Patient, nidus and ablation data were reviewed. Pre- and 6-8 weeks post-procedural MRI (n=32) were compared for coverage of nidus by ablation zone, bone marrow edema, nidus hyperintensity and other findings. Baseline pain levels and analgesic use were compared with post-procedural follow-up visit at 6-8 weeks. Three groups of clinical and MRI outcomes of complete (CR), partial (PR) and no response (NR) were defined. A weighted-kappa statistic was used to assess for agreement. Clinical responses were CR in 34/43 (79.1%, 95%CI: 64.0-90.0%), PR in 8/43 (18.6%) and NR in 1/43 (2.3%) patients. All 19/32 patients with MRI CR experienced clinical CR. One patient with MRI NR had clinical NR. All 7/32 patients with clinical PR had MRI PR. All 4/43 complications were in MRI PR or NR groups. Substantial agreement was observed between MRI and clinical outcomes (kappa:0.69, 95%CI:0.45-0.95). MRI helped determine etiologies in all symptomatic patients and their management (n=8). MRI is recommended for symptomatic patients after ablation.


Punicalagin Attenuates Palmitate-Induced Lipid Droplet Content by Simultaneously Improving Autophagy in Hepatocytes.
Several studies show that excessive lipid intake can cause hepatic steatosis. To investigate lipotoxicity on cellular level, palmitate (PA) is often used to highly increase lipid droplets (LDs). One way to remove LDs is autophagy, while it is controversially discussed if autophagy is also affected by PA. It is aimed to investigate whether PA-induced LD accumulation can impair autophagy and punicalagin, a natural autophagy inducer from pomegranate, can improve it. To verify the role of autophagy in LD degradation, HepG2 cells are treated with PA and analyzed for LD and perilipin 2 content in presence of autophagy inducer Torin 1 and inhibitor 3-Methyladenine. PA alone seems to initially induce autophagy-related proteins but impairs autophagic-flux in a time-dependent manner, considering 6 and 24 h PA. To examine whether punicalagin can prevent autophagy impairment, cells are cotreated for 24 h with PA and punicalagin. Results show that punicalagin preserves expression of autophagy-related proteins and autophagic flux, while simultaneously decreasing LDs and perilipin 2. Data provide new insights into the role of PA-induced excessive LD content on autophagy and suggest autophagy-inducing properties of punicalagin, indicating that punicalagin can be a health-beneficial compound for future research on lipotoxicity in liver.


Mechanisms of transplacental transport and barrier of polybrominated diphenyl ethers: A comprehensive human, Sprague-Dawley rat, BeWo cell and molecular docking study.
Although studies have reported that polybrominated diphenyl ethers (PBDEs) can transfer from mothers to fetuses, the underlying transplacental transport and barrier mechanisms are still unclear. Therefore, we conducted a series of comprehensive experiments in humans, Sprague-Dawley rats, and a BeWo cell monolayer model, as well as a molecular docking study. PBDEs in mothers can transfer to fetuses with a ratio of approximately 0.46, suggesting that the placenta could not efficiently acts as a barrier to PBDE transplacental transport. Similar results were observed in pregnant rats, although varying times were required for different congeners to reach a steady-state in fetuses. The transport ratios at pregnancy day 14 in rats were generally higher than those at pregnancy day 18, which demonstrated that the barrier capacity of immature placentas was lower than that of mature placentas. None concentration-dependent transplacental transport was observed in BeWo cells with efflux ratios of 1.73-2.32, which suggested passive diffusion mechanisms govern the influx of PBDEs through placenta. The accumulated ratios of PBDEs and the inhibitor assay indicated that the effluent channel of P-glycoprotein was partially inhibited by PBDEs. Using molecular docking studies, three pocket sites were identified for different congeners in P-glycoprotein, which demonstrated that the inhibition of P-glycoprotein efflux pump through the pocket sites.


Pain-related fear predicts reduced spinal motion following experimental back injury.
The current study examined the prospective relationship between pain-related fear and altered motor behavior, as well as perceived interference, among 51 healthy participants following induction of delayed-onset muscle soreness (DOMS) to the trunk extensor muscles. Healthy participants without history of back pain completed standardized reaches to high and low targets at self-paced and rapid speeds before and after induction of acute low back pain using a DOMS paradigm. Pain-related fear was assessed prior to DOMS induction. Three-dimensional joint motions of the thoracic spine, lumbar spine, and hip were recorded using an electromagnetic tracking device. DOMS-induced differences between high- and low-fear participants were observed for lumbar spine flexion, but not for thoracic or hip flexion. Pain-related fear scores were not predictive of lumbar flexion during baseline, but predicted reduced lumbar flexion during self- and fast-paced trials to low target locations once DOMS was induced. Pain-related fear was likewise predictive of perceived interference in life activities following DOMS induction. The findings suggest that initially pain-free individuals with high pain-related fear adopt avoidant spinal strategies during common reaching movements shortly after injury is sustained, which may comprise a risk factor for future pain and disability.


The effect of dexamethasone-induced immunosuppression on the development of faecal antibody and recovery from and resistance to rotavirus infection.
Rotavirus-naive and rotavirus-immune gnotobiotic calves were treated with high doses of dexamethasone (DX) to suppress the immune system. Calves were then infected with a virulent rotavirus inoculum, J-160, to investigate the role of immune responses both in recovery from primary rotavirus infection and in resistance to secondary rotavirus infection. Treatment of calves with DX markedly suppressed in vitro responsiveness of peripheral blood lymphocytes to mitogens within 48 h of the start of DX treatment. Suppression was similar in rotavirus-naive and rotavirus-immune calves. In contrast, the effect of DX treatment on specific antibody responses differed depending on when DX treatment started in relation to rotavirus infection. When DX treatment commenced prior to primary rotavirus infection both systemic and local specific antibody responses were inhibited. These calves, in which mitogen and antibody responses were suppressed, exhibited greater clinical signs than did control calves after infection with virulent rotavirus, but virus excretion was affected in only one of the two calves. When DX treatment was started after primary rotavirus infection but before secondary infection, systemic and local antibody responses to the primary infection and to the challenge infection were not affected. These calves resisted challenge with virulent virus as did DX-untreated rotavirus-immune calves, even though mitogen responses were suppressed. We conclude that in a primary rotavirus infection, virus excretion ceased when both antibody and mitogen responses were suppressed. Resistance to secondary rotavirus infection occurred when mitogen responsiveness was suppressed, but when antibody levels were normal. Thus, no evidence was obtained that fully functional cell-mediated immune mechanisms are essential for resistance to rotavirus infection. Evidence was provided for the ability of parenteral treatment with DX to suppress mucosal as well as systemic antibody responses.


Data availability and feasibility of various techniques to predict response to volume expansion in critically ill patients.
The accuracy of various techniques to predict response to volume expansion in shock has been studied, but less well known is how feasible these techniques are in the ICU. This is a prospective observation single-center study of inpatients from a mixed profile ICU who received volume expansion. At time of volume expansion, we determined whether a particular technique to predict response was feasible, according to rules developed from available literature and nurse assessment. We studied 214 volume expansions in 97 patients. The most feasible technique was central venous pressure (50%), followed by vena cava collapsibility, (47%) passive leg raise (42%), and stroke volume variation (22%). Aortic velocity variation, and pulse pressure variation, and were rarely feasible (1% each). In 37% of volume expansions, no technique that we assessed was feasible. Techniques to predict response to volume expansion are infeasible in many patients in shock.


Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial.
Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways. To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advanced (metastatic or fatal) cancer and an examination possible effect modification by body mass index. VITAL is a randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial of vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d). This multicenter clinical trial was conducted in the United States; participants included men aged 50 years or older and women aged 55 years or older who were free of cancer and cardiovascular disease at baseline. Randomization took place from November 2011 through March 2014, and study medication ended on December 31, 2017. Data for this secondary analysis were analyzed from November 1, 2011, to December 31, 2017. Vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (1 g/d) supplements. For the present analysis, the primary outcome was a composite incidence of metastatic and fatal invasive total cancer, because the main VITAL study showed a possible reduction in fatal cancer with vitamin D supplementation and effect modification by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) for total cancer incidence reduction for individuals with normal BMI, but not for individuals with overweight or obesity. Secondary analyses included examination of BMI (<25, 25 to < 30, and ≥30) as effect modifiers of the observed associations. Among 25 871 randomized VITAL participants (51% female; mean [SD] age, 67.1 [7.1] years), 1617 were diagnosed with invasive cancer over a median intervention period of 5.3 years (range, 3.8-6.1 years). As previously reported, no significant differences for cancer incidence by treatment arm were observed. However, a significant reduction in advanced cancers (metastatic or fatal) was found for those randomized to vitamin D compared with placebo (226 of 12 927 assigned to vitamin D [1.7%] and 274 of 12 944 assigned to placebo [2.1%]; HR, 0.83 [95% CI, 0.69-0.99]; P = .04). When stratified by BMI, there was a significant reduction for the vitamin D arm in incident metastatic or fatal cancer among those with normal BMI (BMI<25: HR, 0.62 [95% CI, 0.45-0.86]) but not among those with overweight or obesity (BMI 25-<30: HR, 0.89 [95% CI, 0.68-1.17]; BMI≥30: HR, 1.05 [95% CI, 0.74-1.49]) (P = .03 for interaction by BMI). In this randomized clinical trial, supplementation with vitamin D reduced the incidence of advanced (metastatic or fatal) cancer in the overall cohort, with the strongest risk reduction seen in individuals with normal weight. ClinicalTrials.gov Identifier: NCT01169259.


Prognostic value of interleukin-1 receptor antagonist in patients undergoing percutaneous coronary intervention.
Elevated plasma levels of inflammatory markers, such as C-reactive protein (CRP), have been associated with adverse outcome in selected patients with coronary artery disease (CAD) treated with coronary angioplasty or stenting. The aim of this study was to evaluate the predictive value of preprocedural interleukin-1 receptor antagonist (IL-1Ra) plasma levels for long-term major adverse cardiac events (MACE) in a series of unselected patients with symptomatic CAD treated with percutaneous coronary intervention (PCI). Seventy-three consecutive patients (62 men, aged 62 +/- 9 years) undergoing PCI were enrolled in a prospective follow-up study. IL-1Ra and CRP plasma levels were measured before the procedure; 36 patients (49%) had unstable angina pectoris on admission, 37 (51%) had chronic stable angina pectoris, and 30 (41%) had multivessel CAD, 15 of whom underwent multivessel PCI. Success was achieved in all 73 patients, with coronary stenting performed in 63 (86%). Follow-up clinical assessment included occurrence of MACE at 3, 6, 12, and 18 months. Logistic regression analysis, performed to determine independent predictors of MACE, identified IL-1Ra levels in the upper quartile as the only independent predictive factor of MACE at 18 months (19% in the fourth quartile vs 0% in the first quartile; p = 0.032). Patients with high preprocedural CRP levels (fourth quartile) had a nonsignificant increased risk of MACE (p = 0.09). Thus, preprocedural IL-1Ra plasma levels appear to be a valuable independent predictive factor of MACE in unselected patients undergoing PCI.


The efficiency of the DoctorVox voice therapy technique in conversion dysphonia and aphonia.
The main purpose of this study was to retrospectively evaluate the efficiency of DoctorVox voice therapy in psychogenic dysphonia or aphonia patients, and to share the mid- to long-term results of the method. The study was carried out on patients who underwent DoctorVox voice therapy for psychogenic dysphonia or aphonia between January 2015 and September 2019. The evaluation methods used were: the Voice Handicap Index-10; the grade, roughness, breathiness, asthenia and strain ('GRBAS') scale; and videolaryngostroboscopy recordings. The mean Voice Handicap Index-10 values of the patients were 30.91 ± 2.97 before treatment, 8.14 ± 3.82 after treatment, and 3.36 ± 1.78 in the final follow-up examination. The grade, roughness, breathiness, asthenia and strain scale scores were: 9 ± 0.67 pre-treatment, 0.78 ± 0.80 post-treatment, and 0.57 ± 0.64 at the final follow up. DoctorVox voice therapy seems to be an efficient treatment method for psychogenic dysphonia or aphonia; it helps develop phonatory muscle functions, using multidimensional biofeedback mechanisms, and increases the patients' therapy adherence.


Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition.
To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. Cross-sectional study. Five hospitals, Western Sweden. Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. The 7-item GDS according to Broekman et al. (), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80-1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.


Apolipoprotein E polymorphism and lipoproteins in insulin-treated diabetes mellitus.
Apolipoprotein E (apo E), a component of VLDL, HDL and chylomicron remnants, is inherited at a single genetic locus with 3 common alleles (epsilon 2, epsilon 3 and epsilon 4). epsilon 2 homozygosity is found in 0-2% of healthy populations, but in 75-100% of subjects with type III hyperlipoproteinaemia, in whom an increased prevalence of glucose intolerance has previously been reported. The lipoprotein abnormality associated with diabetes mellitus has features in common with type III hyperlipoproteinaemia and both conditions lead to accelerated atherogenesis with a similar anatomical distribution. We have therefore examined the frequency of apo E genotypes in 120 subjects with insulin-treated diabetes mellitus (ITDM) and 107 healthy controls, and examined the effect of apo E polymorphism on lipoproteins in the diabetic group. As in the general population, the apo E phenotype in ITDM was a significant determinant of the total serum and LDL cholesterol concentrations which were lowest in patients possessing the epsilon 2 allele, intermediate in those homozygous for epsilon 3 and highest in those with an epsilon 4 allele. The observed gene frequencies of epsilon 2 (0.091), epsilon 3 (0.780) and epsilon 4 (0.130) were similar to those of the healthy control group and those in the general population. However, there was an unexpected increase (P less than 0.0002) in epsilon 2 homozygosity of 6.7% compared to a prevalence of 0.8% predicted both from the Hardy-Weinberg equilibrium and the 0.9% prevalence observed in the healthy control group. This suggests either that epsilon 2 homozygosity increases susceptibility to the development of ITDM or that the two conditions are genetically linked.(ABSTRACT TRUNCATED AT 250 WORDS)


The ESS for evolutionary matrix games under time constraints and its relationship with the asymptotically stable rest point of the replicator dynamics.
Recently we interpreted the notion of ESS for matrix games under time constraints and investigated the corresponding state in the polymorphic situation. Now we give two further static (monomorphic) characterizations which are the appropriate analogues of those known for classical evolutionary matrix games. Namely, it is verified that an ESS can be described as a neighbourhood invader strategy independently of the dimension of the strategy space in our non-linear situation too, that is, a strategy is an ESS if and only if it is able to invade and completely replace any monomorphic population which totally consists of individuals following a strategy close to the ESS. With the neighbourhood invader property at hand, we establish a dynamic characterization under the replicator dynamics in two dimensions which corresponds to the strong stability concept for classical evolutionary matrix games. Besides, in some special cases, we also prove the stability of the corresponding rest point in higher dimensions.


Carcinoma of the tonsillar region. Aspects on treatment modalities with reference to a study on patients treated by irradiation.
Irradiation is the most common form of treatment of tonsillar region carcinomas in Scandinavia. During recent years, encouraging results have been reported when surgery has been performed. Therefore, an effort was made to compare different treatment principles on the basis of a study on patients treated by irradiation. This retrospective study comprised 37 patients over a 20-year period. The relative 5-year survival was 33%. Most of the patients died in the next two years after diagnosis. Seventy-three percent of the patients initially had signs of regional metastasis. Hardly 20% of these were still alive after 5 years, while patients without evidence of metastasis had a 5-year survival of 50%. Neither the size, nor the histopathological features of the primary tumor seemed to affect the incidence of regional metastasis. The duration of symptoms before diagnosis, however, seemed to influence prognosis. Surgical consideration alone, or in combination with irradiation, should be made in cases with large primary tumor with regional lymph node involvement. In other cases, however, there was no evidence suggesting surgery as a better form of therapy than irradiation alone.


Chemical and photochemical degradation of polybrominated diphenyl ethers in liquid systems - A review.
Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants which have received a great deal of attention due to their persistence, potential to bioaccumulate and possible toxic effects. PBDEs have been globally detected in humans, wildlife and environment, highlighting the urgency of looking for effective removal technologies to mitigate their spread and accumulation in the environment. Among all environmental compartments, the water has raised particular attention. This paper aims to provide information about the suitability of the main degradation processes investigated to date (photolysis, zerovalent iron and TiO2 photocatalysis) for the degradation of PBDEs in water matrices. The most relevant criteria behind the design of a system for such purpose are discussed in detail for each individual process. The comparative analysis suggests that the oxidative degradation by TiO2 is the most appropriated technology to treat waters contaminated with PBDEs because higher debromination and mineralization degrees are achieved, preventing the formation/accumulation of lower brominated PBDE congeners and promoting the cracking of aromatic cores.


The visual representations of words and style in text: an adaptation study.
While the nature of face representations in the human perceptual system has been extensively studied using adaptation, there has been little investigation using this technique of the neural basis of another parallel class of high-level objects, words. We used the perceptual-bias technique to determine if aftereffects could be generated for either the word content or stylistic properties of textual stimuli, and if these aftereffects showed invariance for the non-adapted dimension. In a first experiment, we examined adaptation for word versus handwriting style. In a second experiment we contrasted adaptation for words with adaptation for computer font. The third experiment performed a similar study of aftereffects for words and case. In all three experiments we consistently found adaptation for words, which were not diminished by changing the style between the adapting and probe stimuli: hence word aftereffects are invariant for handwriting, font and case. Aftereffects were negligible for style. Additional analyses showed that discriminative ability was better for word than for style content. These results confirm that the neural representations of words can be probed with the adaptation technique and suggest that adaptation accesses word representations at an abstract level, where the identity of a word is invariant for stylistic properties.