Tele-ophthalmology as an aid tool for primary care physicians in the IDF, during the Covid-19 lockdown.
To describe tele-ophthalmology consultations for primary-physicians in the IDF during the Covid-19 lockdown. Retrospective cross-sectional study. Medical records of tele-ophthalmology consultations from March to June 2020 were reviewed. The study included 245 cases in which an ophthalmologist was consulted. In 62.0% cell-phone camera photographs were used. The mean age was 21.5 ± 6.4 years. The most common diagnoses were acute-conjunctivitis (8.6%); conjunctival-hyperemia (non-specific diagnosis, 8.2%); scleritis/episcleritis (7.3%); chronic allergic-conjunctivitis (7.3%); chalazion (7.3%) hordeolum (6.5%); acute allergic-conjunctivitis (4.5%). 37.6% of patients received primary physician-based treatment, 24.9% of patients received specialist-based treatment. 13.1% were referred to the ER. The consult prevented ER referral for 39.2% and changed the physician's treatment plan in 70.6% of cases. Foreign-body sensation complaints were more likely treated by a primary-physician (p = 0.015). Cases with suspected foreign-body diagnosis were referred more to the ER (p < 0.001). For most cases of eyelid complaints and diagnoses, primary physician care was sufficient (p < 0.001). Conjunctival complaints and diagnoses received significantly more ophthalmologist-based treatment (p < 0.001). Corneal disorders were significantly referred more to the ER (p = 0.001). Despite of possible ethical and legal problems and clinical limitations of this instrument, Tele-ophthalmology using objective aids such as smartphone photography can be an efficient tool in aiding the primary-physician, especially for patients with low access to ophthalmologists, with major impact on patient management.


Micro-optical Components for Bioimaging on Tissues, Cells and Subcellular Structures.
Bioimaging generally indicates imaging techniques that acquire biological information from living forms. Among different imaging techniques, optical microscopy plays a predominant role in observing tissues, cells and biomolecules. Along with the fast development of microtechnology, developing miniaturized and integrated optical imaging systems has become essential to provide new imaging solutions for point-of-care applications. In this review, we will introduce the basic micro-optical components and their fabrication technologies first, and further emphasize the development of integrated optical systems for in vitro and in vivo bioimaging, respectively. We will conclude by giving our perspectives on micro-optical components for bioimaging applications in the near future.


Selective anthelmintic therapy of horses in the Federal states of Bavaria (Germany) and Salzburg (Austria): an investigation into strongyle egg shedding consistency.
For 9 consecutive months (March-November 2008), faecal samples were collected monthly from 129 horses residing within 40 km of Salzburg, Austria. Samples were analysed quantitatively using a modified McMaster egg counting technique. Whenever a faecal egg count (FEC) result exceeded 250 eggs per gram (EPG), the horse was treated with pyrantel, ivermectin or moxidectin. In 52 of 129 horses (40.3%), no strongyle eggs were ever detected over the course of 9 months. In 39 horses (30.2%), strongyle eggs were detected in at least 1 sample, but the egg count never exceeded 250 EPG. The remaining 38 (29.5%) horses were treated at least once in response to a FEC that exceeded 250 EPG. As a result of this selective anthelmintic scheme, the total number of anthelmintic treatments was reduced to 54% of the number of treatments administered to the same horses in the previous year. Both the maximum and mean FEC dropped significantly after initiation of the study. A statistically significant, negative correlation was demonstrated between the maximum and mean FEC of a horse and its age. Pasture hygiene appeared to reduce FECs, but the effect was not statistically significant. The magnitude of the initial FEC was significantly correlated with the maximum FECs in the subsequent 8 months (p<0.01). The same relationship was observed for the maximum FEC of the first 2 samples. Furthermore, horses which required several anthelmintic treatments had a higher initial FEC and a greater maximum FEC in the first 2 samples than horses which received only one or no treatment. These results suggest that selective anthelmintic treatment accomplished a reduced pasture contamination with strongyle eggs, while simultaneously decreasing the number of anthelmintic treatments. Sustained implementation of a selective treatment strategy has the potential to reduce selection pressure for anthelmintic resistance. These results reported herein will assist equine practitioners in designing and monitoring sustainable anthelmintic treatment programs.


cAMP-dependent regulation of IKs single-channel kinetics.
The delayed potassium rectifier current, IKs , is composed of KCNQ1 and KCNE1 subunits and plays an important role in cardiac action potential repolarization. During β-adrenergic stimulation, 3'-5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) phosphorylates KCNQ1, producing an increase in IKs current and a shortening of the action potential. Here, using cell-attached macropatches and single-channel recordings, we investigate the microscopic mechanisms underlying the cAMP-dependent increase in IKs current. A membrane-permeable cAMP analog, 8-(4-chlorophenylthio)-cAMP (8-CPT-cAMP), causes a marked leftward shift of the conductance-voltage relation in macropatches, with or without an increase in current size. Single channels exhibit fewer silent sweeps, reduced first latency to opening (control, 1.61 ± 0.13 s; cAMP, 1.06 ± 0.11 s), and increased higher-subconductance-level occupancy in the presence of cAMP. The E160R/R237E and S209F KCNQ1 mutants, which show fixed and enhanced voltage sensor activation, respectively, largely abolish the effect of cAMP. The phosphomimetic KCNQ1 mutations, S27D and S27D/S92D, are much less and not at all responsive, respectively, to the effects of PKA phosphorylation (first latency of S27D + KCNE1 channels: control, 1.81 ± 0.1 s; 8-CPT-cAMP, 1.44 ± 0.1 s, P < 0.05; latency of S27D/S92D + KCNE1: control, 1.62 ± 0.1 s; cAMP, 1.43 ± 0.1 s, nonsignificant). Using total internal reflection fluorescence microscopy, we find no overall increase in surface expression of the channel during exposure to 8-CPT-cAMP. Our data suggest that the cAMP-dependent increase in IKs current is caused by an increase in the likelihood of channel opening, combined with faster openings and greater occupancy of higher subconductance levels, and is mediated by enhanced voltage sensor activation.


Diacylglycerol hydrolysis to arachidonic acid is necessary for insulin secretion from isolated pancreatic islets: sequential actions of diacylglycerol and monoacylglycerol lipases.
Arachidonic acid has been implicated as a second messenger in insulin secretion on the basis of (1) mobilization of intracellular Ca2+ from the endoplasmic reticulum of islets and (2) amplification of voltage-dependent Ca2+ entry. The insulin secretagogues D-glucose and the muscarinic agonist carbachol both increase unesterified arachidonic acid accumulation in isolated islets. We now show that diacylglycerol, a product of phospholipase C action, is a major source of free arachidonic acid in islets. Diacylglycerol hydrolysis in islets occurs through a two-step process. In the first step, the sn-1 bond of 1-stearoyl-2-arachidonyl-sn-glycerol is hydrolyzed by a diacylglycerol lipase, giving rise to 2-arachidonyl-sn-glycerol. Next, the sn-2 bond of 2-arachidonyl-sn-glycerol is hydrolyzed by a monoacylglycerol lipase, which is the rate-limiting step, releasing unesterified arachidonic acid. Both diacylglycerol lipase and monoacylglycerol lipase are highly enriched in the plasma membrane of beta-cells. Diacylglycerol lipase activity in islet homogenates is selectively inhibited in a dose-dependent manner by the compound RHC-80267, a specific diacylglycerol lipase inhibitor. RHC-80267 inhibits glucose- and carbachol-induced insulin release from intact islets in a dose-dependent manner that parallels its inhibition of diacylglycerol lipase activity. Importantly, RHC-80267, at concentrations that almost completely inhibit diacylglycerol lipase activity and glucose- and carbachol-induced insulin secretion by islets, markedly inhibits glucose- and carbachol-induced increases in islet arachidonic acid levels, as measured by gas chromatography with electron-capture detection of its pentafluorobenzyl esters. RHC-80267 did not significantly affect islet glucose oxidation, phospholipase C, monoacylglycerol lipase, or phospholipase A2. Since glucose and carbachol are known to stimulate phospholipase C, our observations indicate that diacylglycerol is an important source of arachidonic acid and other free fatty acids in islets. Furthermore, production of arachidonic acid from the hydrolysis of diacylglycerol is essential for glucose- and carbachol-induced insulin secretion.


Language Disorders due to Posterior System Strokes - An Ignored Dysfunction.
The anterior system is primarily responsible for the clinical picture in a patient that presents with clinical aphasia. However, recent reports have shown that injuries to posterior structures, the cerebellum in particular, may have a role in language processing. Herein, we will look first at the linguistic role of the cerebellum in light of the literature, then of the thalamus and some described clinical syndromes, and finally, specific syndromes resulting from occipital lobe lesions, all of which are supported by the posterior vascular system. The human brain is such a complex organization that in addition to the thalamus and occipital cortex, we can see the involvement of the cerebellum in high cognitive functions. Posterior system strokes may lead to clinical findings of cognitive deficits, including neurolinguistic components. Determining these defects in stroke patients may precipitate changes in current management strategies.


Cytomegalovirus immediate early genes upregulate interleukin-6 gene expression.
The immediate early genes (IE) of human cytomegalovirus (CMV) can be expressed in monocytic cells and are known to regulate viral and cellular genes. Interleukin-6 (IL-6) plays a central role in numerous inflammatory and immune processes. Interleukin-6 levels are increased in lung transplant patients clinically diagnosed with CMV pneumonitis. The regulation of IL-6 is dependent on various stimuli that include lipopolysaccharide (LPS), viruses, and other cytokines. These studies examined the ability of CMV IE gene products to modulate IL-6 production. THP-1 cells, a monocytic cell line, were transfected with the CMV IE genes. Interleukin-6 protein and IL-6 mRNA were measured in control and CMV immediate early transfected cells. Cotransfection of CMV IE genes and IL-6 chloramphenicol acetyl transferase (CAT) or IL-6 luciferase constructs were used to study IL-6 promoter activity. Interleukin-6 protein and mRNA production were significantly increased in cells transfected with the CMV IE genes and stimulated with LPS compared to LPS-stimulated control cells. Cytomegalovirus IE gene products significantly enhanced LPS stimulation of IL-6 promoter activity in both IL-6 CAT and IL-6 luciferase assays. A deletion construct that contains a NF-kappa B site but is missing the multiple response region demonstrated a continued increase in IL-6 luciferase activity in LPS-stimulated CMV transfected cells. Cytomegalovirus immediate early gene products significantly enhanced expression of IL-6 in LPS-stimulated cells. The increase in IL-6 luciferase activity occurs in the absence of the multiple response region, the area of the IL-6 promoter responsive to IL-1, TNF alpha, cyclic amp, and phorbol 12-myristate 13-acetate. The ability of CMV IE gene products to enhance IL-6 production may play an important role in immune inflammatory states associated with CMV infection.


[Clinical characteristic and surgical treatments for the fresh thoracolumbar fracture-dislocation combined with paraspinal muscles, ligaments and intervertebral disc ruptures].
To analyze the clinical characteristics of fresh thoracolumbar fracture-dislocation combined with paraspinal muscles, ligaments and intervertebral disc ruptures and to discuss the surgical procedure for the fracture. The clinical materials of 15 patients who suffered from the disease mentioned above were retrospectively analyzed. The common physical examination findings were local bump in the dorsal or lumbar spine area and palpation of rupture ends of paraspinal muscles and ligaments. The common MRI manifestations were ruptures of anterior longitudinal ligament, intervertebral disc, paraspinal muscles, and spinous process ligaments. The common operative findings were similar to MRI findings. The fractured vertebrae in 5 patients who underwent posterior reduction and fixation with two-segments pedicle screw did not restore their shape, but 10 patients who underwent posterior three-segments pedicle screw reduction and fixation restored the shape of fractured vertebrae. The fresh thoracolumbar fracture-dislocation combined with paraspinal muscles, ligaments and intervertebral disc ruptures is a severe spine injury. Clinical physical examination and MRI appearance and intraoperative observation are important for the selection of operation procedure. The open reduction and internal fixation with pedicle screw-rod system, and intervertebral resection and fusion via posterior approach is a good procedure for the special thoracolumbar fracture.


[Chapter 4. Care, capabilities and disability: what ethics for an inclusive society].
The purpose of this contribution is to show the way in which confronting theories of justice and democracy with the question of disability constrains the former to reconsider their contractarian groundings and to build up a frame that takes into account the effective situation of the most vulnerable persons. In this perspective, the approach through capabilities, while it does appear as an advance in the taking into considerations the situation of these persons and their specific capacity, requires nevertheless a futher radicalization of this consideration and analysis, as well as, the construction of an ethical and political framework that could take account of the required conditions for an effective participation of the disabled persons in the definition of their individual and collective project.


The damage done: a study of injection drug use, injection related abscesses and needle exchange regulation.
This study investigated the impact of a needle exchange policy change on community health. Data were collected from a needle exchange program in Eureka, California, for clients who participated in the program between the weeks (n = 112) of January 1, 2002, and February 28, 2004. Analysis was done using an autoregressive integrated moving average (ARIMA), indicating that greater utilization of the needle exchange program, in terms of needles exchanged and number of visits, is related to fewer numbers of abscesses treated. Additionally, self-report data collected from former intravenous drug users (n = 62) demonstrated that more needles exchanged were related to fewer occurrences of abscesses. The limitations of this research are discussed.


Treatment options for patients with hormone receptor-positive, HER2-negative advanced-stage breast cancer: maintaining cyclin-dependent kinase 4/6 inhibitors beyond progression.
Breast cancer is the most commonly diagnosed cancer in women worldwide. Over the past decade, the treatment paradigm for patients with metastatic breast cancer (MBC) has taken an important shift towards better survival and improved quality of life (QOL), especially for those with hormone receptor (HR)-positive diseases which represent the majority of breast cancer subtypes. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in the upfront therapy of such patients has resulted in dramatic improvement in progression-free survival (PFS) and overall survival (OS), too. However, almost all patients would, sooner or later, develop disease progression and necessitate transition to different lines of treatment that may include chemotherapy. The idea of maintaining CDK4/6 inhibitors beyond disease progression seems attractive, as this approach has the potential to improve outcome in this setting despite the fact that the true benefit, in terms of survival, might not carry the same weight as it initially does. Researchers have been investigating potential mechanisms of resistance and identify possible biological markers for response after disease progression. Much of the available data is retrospective; however, few randomized clinical trials were recently published and few more are ongoing, addressing this point. In this paper, we intend to review the available published studies investigating the potential role for keeping CDK4/6 inhibitors in play beyond disease progression.


Langerhans' cell histiocytosis in an adult.
A woman with typical skin lesions of histiocytosis X is reported. Electron microscopic and immunohistochemical investigations revealed a large number of markedly long Birbeck Langerhans' cell granulae. During treatment with Interferon alpha -2b, the patient developed infarctus cerebri and died.


Transmodal Fabry-Pérot Resonance: Theory and Realization with Elastic Metamaterials.
We discovered a new transmodal Fabry-Pérot resonance where one elastic-wave mode is maximally transmitted to another. It occurs when the phase difference of two dissimilar modes through an anisotropic layer becomes odd multiples of π under the reflection-free and weak mode-coupling assumptions. Unlike the well-established Fabry-Pérot resonance, the transmodal resonance must involve two coupled elastic waves between longitudinal and shear modes. The investigation into the origin of wiggly transmodal transmission spectra suggests that efficient broadband mode conversion can be achieved if the media satisfy the structural stability condition to some degree. The new resonance mechanism, also experimentally characterized, opens up new possibilities for manipulating elastic wave modes as an effective alternative to generating shear-mode ultrasound.


Acute Oral Toxicity, Antioxidant Activity, and Molecular Docking Study of 2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4-chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide.
Several studies have been conducted on 4-H chromene compounds because of their intriguing pharmacological and biological properties. Various new natural compounds having a chromene foundation have been reported over the past 20 years. In the present study, we reported the acute oral toxicity, antioxidant activity, and molecular docking study of the most active 4H-chromene derivative2-(4-Bromo-phenoxy)-N-[6-chloro-4-(4-chlorophenyl)-3-cyano-4H-chromen-2-yl]-acetamide (A9). The acute oral toxicity was carried out as per OECD 423 guidelines. For investigating the antioxidant activity, various biochemical parameters in colon tissue like SOD, CAT, MDA, PC and GSH and also enzyme levels, such as ALT, AST, ALP, and LDH, were measured in this experiment. Acute oral toxicity study indicated that the A9 ligand was found to be safer in animals. Additionally, the A9 ligand had significant antioxidant properties at various doses and was not found to be harmful to the liver. Due to its stronger binding energy and the appropriate interactions that induce inhibition, the A9 ligand's antioxidant function was also validated by additional molecular docking research. This compound can be exploited as a lead molecule in further research.


The locust tegula: kinematic parameters and activity pattern during the wing stroke.
The tegula is a complex, knob-shaped sense organ associated with the base of the locust wing. Despite a detailed knowledge of its role in flight motor control, little is known about the relationship between the stroke parameters of the wing, movement of the tegula organ and the pattern of tegula activity. In this study, therefore, the kinematic parameters of the fore- and hindwings were investigated with respect to the tegula activity pattern during tethered flight. The following results were obtained. (i) The tegula moves through a complex three-dimensional trajectory during the wing stroke, involving inclination and rotation about its longitudinal axis. (ii) The kinematic parameters of tegula movement are phase-locked to the wing stroke and vary in conjunction with wing stroke parameters such as amplitude and cycle period. (iii) In accordance with these phase-locked kinematics, both the onset of tegula activity with respect to the downstroke (latency) and the discharge of the organ (burst duration and amplitude) vary in conjunction with downstroke movement and cycle period, resulting in an (almost) constant phase of tegula activation during the stroke cycle. (iv) The pattern of tegula activity during flight is largely independent of stroke amplitude. (v) The latency, burst duration and amplitude of tegula activity are strongly related to the angular velocity of the wing during the downstroke, with latency reaching a steady minimum value at higher angular velocities. The data suggest that the tegula encodes the timing and velocity of the downstroke and that it may be involved in the control of the stroke's angular velocity.


Ginsenoside Rh2 induces human hepatoma cell apoptosisvia bax/bak triggered cytochrome C release and caspase-9/caspase-8 activation.
Ginsenoside Rh2 (G-Rh2) has been shown to induce apoptotic cell death in a variety of cancer cells. However, the details of the signal transduction cascade involved in G-Rh2-induced cell death is unclear. In this manuscript we elucidate the molecular mechanism of G-Rh2-induced apoptosis in human hepatoma SK-HEP-1 cells by demonstrating that G-Rh2 causes rapid and dramatic translocation of both Bak and Bax, which subsequently triggers mitochondrial cytochrome c release and consequent caspase activation. Interestingly, siRNA-based gene inactivation of caspase-8 effectively delays caspase-9 activation and apoptosis induced by G-Rh2, indicating that caspase-8 also plays an important role in the G-Rh2-induced apoptosis program. Taken together, our results indicate that G-Rh2 employs a multi pro-apoptotic pathway to execute cancer cell death, suggesting a potential role for G-Rh2 as a powerful chemotherapeutic agent.


Psoriasis, Vitiligo, and Biologic Therapy: Case Report and Narrative Review.
Psoriasis and vitiligo are 2 multifactorial immune-mediated diseases, partially sharing pathogenetic underpinnings. Their coexistence in the same patient, although uncommon, is documented in the literature. Further, several cases of vitiligo induced by biological drugs in psoriatic patients are reported. However, improvements in psoriasis and pre-existing vitiligo after the introduction of biological therapy are also described. To date, anti-TNF-alpha is the most cited group of biological drugs that induce new-onset vitiligo or progression of pre-existence vitiligo in psoriatic patients. Even anti-IL-12/23 class would seem to induce vitiligo (as in our case) or even worse it. Anti-IL-17 drugs induce a progression of pre-existing vitiligo while, to date, no cases are reported in literature considering anti-IL-23 class.


Third-Year Medical Student Impressions of Resident Teaching in Simulated and Clinical Settings.
We sought to determine whether simulation-based medical education using Trauma Evaluation and Management® (TEAM®) training module contributes to a positive impression of resident and faculty teaching. Qualitative and quantitative data regarding medical students' experience of TEAM® training and their interaction with instructors were collected using anonymous surveys after the completion of the training module. A combination of yes or no responses, as well as classification of student confidence and perceptions on the utility of TEAM® training obtained using Likert-type scales, was evaluated. Qualitative data regarding student perceived strengths and weaknesses of this training and their perception of the quality of teaching were collected and analyzed. Most of the students felt the quality of teaching was better when compared with clinical settings, with 91 per cent of the respondents who provided additional feedback stating that residents were better teachers in the simulated setting. The application of TEAM® training in the surgical clerkship curriculum provides an environment to foster high-quality resident-led education.


New mechanism for the ring-opening polymerization of lactones? Uranyl aryloxide-induced intermolecular catalysis.
The uranyl aryloxide [UO2(OAr)2(THF)2] (Ar = 2,6-(t)Bu2-C6H2) is an active catalyst for the ring-opening cyclo-oligomerization of ε-caprolactone and δ-valerolactone but not for β-butyrolactone, γ-butyrolactone, and rac-lactide. (1)H EXSY measurements give the thermodynamic parameters for exchange of monomer and coordinated THF, and rates of polymerization have been determined. A comprehensive theoretical examination of the mechanism is discussed. From both experiment and theory, the initiation step is intramolecular and in keeping with the accepted mechanism, while computational studies indicate that propagation can go via an intermolecular pathway, which is the first time this has been observed. The lack of polymerization for the inactive monomers has been investigated theoretically and C-H···π interactions stabilize the coordination of the less rigid monomers.


Preliminary efficacy and predictors of response to a remotely-delivered symptom self-management program for persistent symptoms after concussion.
More than a quarter of adults with concussion endure prolonged symptoms of >3 months. We developed the Concussion Education Self-Management program to help people manage persisting symptoms. Here, we assess feasibility, preliminary efficacy, and correlates of response. N = 80 adults participated in the program; ages ranged from 18 to 65 years and time post-injury ranged from 6 months to 18 years. Weekly sessions, delivered remotely and in groups, comprised education and strategies for management of cognitive, emotional, and physical symptoms. Primary outcome: Confidence to self-manage symptoms. Secondary outcomes: Quality of life; mood/anxiety/stress. Predictors of response: Self-reported cognitive, emotional and physical symptoms at intake. Pre- to post-program improvements were observed in confidence to self-manage, p < 0.03; quality of life, p < 0.001; depression, p < 0.001; anxiety, p < 0.001; and stress, p < 0.001. Considering confidence to self-manage, those with fewer cognitive and physical symptoms benefitted more (p's < 0.0005 and p < 0.01, respectively). This program shows promise for improving self-management of prolonged symptoms. Those with high symptom burden may need extra sessions to benefit. This is a cost-effective and scalable program that can reach people regardless of geographic location or impediments to travel.


Falls and fractures in patients chronically treated with antiepileptic drugs.
To evaluate fractures and falls in epilepsy patients taking antiepileptic drugs (AED) and to assess their awareness of AED-related bone health, falls, and fracture risk. A cross-sectional study was conducted in epilepsy patients taking AEDs and in nonepileptic non-AED users. Information on falls and fracture history was collected. A total of 150 AED users were compared with 506 non-AED users. Users had greater odds of fracture at spine (odds ratio [OR] 3.92; confidence interval [CI] 1.08-14.16; p = 0.037), clavicle (OR 3.75; CI 1.24-11.34; p = 0.019), and ankle sites (OR 2.34; CI 1.01-5.42; p = 0.048), increased odds for osteoporosis (OR 4.62; CI 1.40-15.30; p = 0.012), and fracture occasions (OR 2.64; CI 1.29-5.43; p = 0.008). We estimate that with every year of AED use the odds of fractures increase by 4%-6%, or 40% per decade for any fracture (OR 1.40; CI 1.02-1.91) and 60% for seizure-related fractures (OR 1.63; CI 1.10-2.37). Non-seizure-related fractures (69% of cumulative fractures) occurred more than seizure-related fractures during therapy. Female users, compared to female nonusers, had more non-seizure falls (31% vs 17%, p = 0.027) and multiple falls (18% vs 5%, p = 0.028) in the preceding year. Fewer than 30% of epilepsy patients knew of the association of AED use with increased risk for fractures, decreased bone mineral density, or falls. Epilepsy patients taking AEDs had a higher risk of fractures, which was highest in those with longer-term AED exposure. Female AED users had a higher prevalence of falls than matched nonusers. Awareness among epilepsy patients regarding risks of falling and fractures was low.


[A study of plasma atrial natriuretic peptide, antidiuretic hormone and cerebral vasospasms in patients with aneurysmal subarachnoid hemorrhage].
The relationship between plasma atrial natriuretic peptide (ANP) and antidiuretic hormone (ADH) both of which show high values after subarachnoid hemorrhage and cerebral vasospasm was studied. The subjects were 23 patients who were admitted because of aneurysmal subarachnoid hemorrhage during three years from March, 1989 to March, 1992 and in whom plasma ANP and ADH levels could be determined over time. Cerebral vasospasm was evaluated by the finding of cerebral angiography, clinical symptoms, and presence or not of low density areas on CT. Hyponatremia was defined as the serum sodium level of 130 mEq/l or less for two days or more. Angiographical vasospasm was found in 17 patients (85%), symptomatic vasospasm in 15 patients (65.2%), low density areas on CT in 9 patients (40.9%) and hyponatremia in 8 patients (34.8%). Symptomatic vasospasm was noted in 7 of the 8 patients (87.5%) with hyponatremia, low density areas on CT in 4 patients (50%), the detection rate being high. The plasma ANP and ADH levels were 76.7 +/- 32.1 pg/ml and 2.2 +/- 0.7 pg/ml respectively in the patients with symptomatic vasospasm against 38.3 +/- 21.3 pg/ml and 2.4 +/- 0.6 pg/ml respectively without symptomatic vasospasm, the plasma ANP level being significantly high in the patients with symptomatic vasospasm (p < 0.01). The plasma ANP and ADH were 71.2 +/- 33.8 pg/ml and 2.0 +/- 1.1 pg/ml respectively in the patients with low density areas on CT against 51.2 +/- 31.3 pg/ml and 1.8 +/- 0.5 pg/ml respectively without low density areas on CT.(ABSTRACT TRUNCATED AT 250 WORDS)


Cold-recombinant influenza A/California/10/78 (H1N1) virus vaccine (CR-37) in seronegative children: infectivity and efficacy against investigational challenge.
Forty-seven seronegative children were inoculated intranasally with influenza A/California/10/78 (H1N1) cold-recombinant vaccine (CR-37). Doses ranged from 10(3.2) to 10(7.2) TCID50 per child. The dose necessary to infect 50% of children (one HID50 ) was approximately 10(3.5) TCID50. Only two of eight children given 10(3.2) TCID50 became infected, and neither shed virus. The majority of children who were given 10(4.2), 10(5.2), 10(6.2), or 10(7.2) TCID50 of CR-37 became infected. Twenty-four of 39 children given greater than one HID50 of CR-37 shed vaccine virus. Overall, 31 of 39 became infected, as indicated by shedding of virus or antibody response or both. Although virus was shed for up to 12 days postinoculation, shedding of revertant virus was not detected. Six months after primary vaccination 26 children were challenged intranasally with 10(6.2) TCID50 of CR-37. Of 21 children previously infected with CR-37, only eight had further antibody increase, and none shed vaccine virus. In contrast, five of five (P less than .05) children not infected with CR-37 at the time of initial inoculation were infected with the challenge inoculum (as indicated by a fourfold rise in antibody titer) and three of five children shed vaccine virus. Previous infection with CR-37 conferred significant protection from challenge with a high dose of CR-37.


Overcoming bottlenecks in the membrane protein structural biology pipeline.
Membrane proteins account for a third of the eukaryotic proteome, but are greatly under-represented in the Protein Data Bank. Unfortunately, recent technological advances in X-ray crystallography and EM cannot account for the poor solubility and stability of membrane protein samples. A limitation of conventional detergent-based methods is that detergent molecules destabilize membrane proteins, leading to their aggregation. The use of orthologues, mutants and fusion tags has helped improve protein stability, but at the expense of not working with the sequence of interest. Novel detergents such as glucose neopentyl glycol (GNG), maltose neopentyl glycol (MNG) and calixarene-based detergents can improve protein stability without compromising their solubilizing properties. Styrene maleic acid lipid particles (SMALPs) focus on retaining the native lipid bilayer of a membrane protein during purification and biophysical analysis. Overcoming bottlenecks in the membrane protein structural biology pipeline, primarily by maintaining protein stability, will facilitate the elucidation of many more membrane protein structures in the near future.


A Patient with MSUD: Acute Management with Sodium Phenylacetate/Sodium Benzoate and Sodium Phenylbutyrate.
In treatment of metabolic imbalances caused by maple syrup urine disease (MSUD), peritoneal dialysis, and hemofiltration, pharmacological treatments for elimination of toxic metabolites can be used in addition to basic dietary modifications. Therapy with sodium phenylacetate/benzoate or sodium phenylbutyrate (NaPB) in urea-cycle disorder cases has been associated with a reduction in branched-chain amino acid (BCAA) concentrations when the patients are on adequate dietary protein intake. Moreover, NaPB in treatment of MSUD patients is also associated with reduction of BCAA levels in a limited number of cases. However, there are not enough studies in the literature about application and efficacy of this treatment. Our case report sets an example of an alternative treatment's efficacy when extracorporeal procedures are not available due to technical difficulties during attack period of the disease.


Dual tumor targeting with pH-sensitive and bioreducible polymer-complexed oncolytic adenovirus.
Oncolytic adenoviruses (Ads) have shown great promise in cancer gene therapy but their efficacy has been compromised by potent immunological, biochemical, and specific tumor-targeting limitations. To take full advantage of the innate cancer-specific killing potency of oncolytic Ads but also exploit the subtleties of the tumor microenvironment, we have generated a pH-sensitive and bio-reducible polymer (PPCBA)-coated oncolytic Ad. Ad-PPCBA complexes showed higher cellular uptake at pH 6.0 than pH 7.4 in both high and low coxsackie and adenovirus receptor-(CAR)-expressing cells, thereby demonstrating Ad-PPCBA's ability to target the low pH hypoxic tumor microenvironment and overcome CAR dependence for target cell uptake. Endocytic mechanism studies indicated that Ad-PPCBA internalization is mediated by macropinocytosis instead of the CAR-dependent endocytic pathway that internalizes naked Ad. VEGF-specific shRNA-expressing oncolytic Ad complexed with PPCBA (RdB/shVEGF-PPCBA) elicited much more potent suppression of U87 human brain cancer cell VEGF gene expression in vitro, and human breast cancer MCF7 cell/Matrigel plug vascularization in a mouse model, when cancer cells had been previously infected at pH 6.0 versus pH 7.4. Moreover, intratumorally and intravenously injected RdB/shVEGF-PPCBA nanocomplexes elicited significantly higher therapeutic efficacy than naked virus in U87-tumor mouse xenograft models, reducing IL-6, ALT, and AST serum levels. These data demonstrated PPCBA's biocompatibility and capability to shield the Ad surface to prevent innate immune response against Ad after both intratumoral and systemic administration. Taken together, these results demonstrate that smart, tumor-specific, oncolytic Ad-PPCBA complexes can be exploited to treat both primary and metastatic tumors.


Enhancement of coxsackievirus B4 virulence by indomethacin.
The safety of nonsteroidal anti-inflammatory agents in viral infections was assessed in a mouse model of coxsackievirus B4 neonatal myocarditis. Two-day-old mice were infected intraperitoneally with 10(4) TCID50 coxsackievirus B4 and then randomized to receive indomethacin or saline for 7 days. A number of them were killed on designated days. Mortality, viral titers, antibody, and interferon levels plus histopathologic changes in the heart were compared. Among treated animals, mortality was greater (22/45 vs 7/27; p = 0.07) and viral titers were higher on days 4 and 7 (p = 0.038 and 0.028, respectively). Interferon levels were lower on days 4 and 7 (p = 0.028 and 0.008, respectively), and histopathologic changes were more extensive on days 7 and 21 (p = 0.008 and 0.028, respectively). These findings show that indomethacin decreased interferon production, increased coxsackievirus4 titers, and enhanced the virulence of coxsackievirus B4. These results raise significant concerns about the safety of indiscriminate use of nonsteroidal anti-inflammatory agents during severe viral infections.


Release from polymeric prodrugs: linkages and their degradation.
Polymeric prodrugs have evolved into a very useful class of drug delivery agents. Numerous polymeric prodrugs have been prepared for applications ranging from passive drug targeting to controlled release. The mechanistic aspects of the release processes, however, have not been clearly delineated. This review highlights the salient features of the chemical reactions that are responsible for drug release from these systems. The mechanisms of release from polymeric prodrugs employing various chemical linkages, esters, carbonates, carbamates, C=N linkage and amides, are discussed.


SLC7A11 negatively associates with mismatch repair gene expression and endows glioblastoma cells sensitive to radiation under low glucose conditions.
The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.


Mutation of essential catalytic residues in pig citrate synthase.
Two amino acid residues, His274 and Asp375, were replaced singly in the active site of pig citrate synthase (PCS) with Gly274, Arg274, Gly375, Asn375, Glu375, and Gln375. The nonmutant protein and the mutant proteins were expressed in and purified from Escherichia coli, and the effects of these amino acid substitutions on the overall reaction rate and conformation of the PCS protein were studied by initial velocity and full time course kinetic analysis, behavior during affinity column chromatography, and monoclonal antibody reactivity. Native and mutant proteins purified similarly had a subunit molecular weight of 50,000 and were homologous when examined with 10 independent a-PCS monoclonal IgGs or with a polyclonal anti-PHCS serum. No activity was detected for Asn375 or Gln375. The kcats of the other purified mutant proteins, however, were decreased by about 10(3) compared to the nonmutant enzyme activity. The Km for oxalacetate was decreased 10-fold in the Glu375 protein and was reduced by half in Gly274 and Arg274 PCSs, while the Km for acetyl-CoA was decreased 2-3-fold in Gly274, Arg274, and Gln375 PCSs. A mechanism is proposed that electrostatically links His274 and Asp375.


Palladium-catalyzed decarboxylative cross-coupling reactions: a route for regioselective functionalization of coumarins.
A straightforward, regioselective, and step-economical ligand-free palladium-catalyzed decarboxylative functionalization of coumarin-3-carboxylic acids is devised. This protocol is compatible with a wide variety of electron-donating and -withdrawing substituents and allows for construction of various biologically important π-electron extended coumarins.


Electrically controlled nuclear spin polarization and relaxation by quantum-Hall states.
We study interactions between electrons and nuclear spins by using the resistance ( Rxx) peak which develops near the Landau-level filling factor nu = 2/3 as a probe. Temporarily tuning nu to a different value, nu(temp), with a gate demonstrates that the Rxx peak regenerates even after complete depletion ( nu(temp) = 0), while it rapidly relaxes on either side of nu(temp) = 1. This indicates that the nu = 2/3 domain morphology is memorized by the nuclear spins which can be rapidly depolarized by Skyrmions. An additional enhancement in the nuclear spin relaxation around nu = 1/2 and 3/2 suggests a Fermi sea of partially polarized composite fermions.


Allogeneic Skin Substitutes Versus Human Placental Membrane Products in the Management of Diabetic Foot Ulcers: A Narrative Comparative Evaluation of the Literature.
Outcomes following standard wound care (SWC) for diabetic foot ulcers (DFUs) remain suboptimal. Supplementing SWC with tissue engineered allogeneic cellular wound therapies represents an emerging treatment strategy. This review aimed to evaluate the efficacy and safety of allogeneic skin substitutes and human placental membrane allografts in the management of DFUs. Ovid MEDLINE and Embase databases were searched from inception to October 2017. Any randomized controlled trial (RCT) with an allogeneic skin substitute or placental membrane allograft intervention group was included. Our primary outcome measure was the proportion of completely healed ulcers. Secondary outcome measures included time to complete wound healing and local adverse event rates. Each study was assessed for risk of bias and the quality of evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Moderate quality evidence from 11 included RCTs demonstrated that both allogeneic cellular approaches improve the proportion of completely healed ulcers at 6 and 12 weeks. One RCT showed that a placental membrane allograft was superior to an allogeneic skin substitute, although this has yet to be repeated in other studies. The addition of allogeneic cellular wound products to SWC improves DFU outcomes. Further studies are required to conclusively establish if placental membrane allografts are superior to allogeneic skin substitutes.


Red Blood Cell Product Transfusion Thresholds and Clinical Outcomes.
To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay. An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders. This study included all adult patients discharged from 1 of 203 adult ICUs from 32 US health-care systems. The patients were from community hospitals, tertiary, and academic medical centers. Transfusion of allogenic packed RBCs or whole blood was prescribed at the discretion of the treating clinicians. We found that 15% of adult ICU patients are transfused RBC products, and most transfusions for hemodynamically stable patients are administered above the guideline-specified pretransfusion Hb threshold of 7 g/dL. Hemodynamically stable patients transfused below this threshold were significantly more likely to survive their ICU stay than those not transfused (odds ratio [OR] 0.59, 95% confidence interval [CI], 0.43-0.81; P = .001), and patients transfused at thresholds above 9 g/dL were less likely to survive their ICU stay than those not transfused. Patients of the acute blood loss group who were transfused appeared to benefit or were not harmed by transfusion. Conservative RBC product transfusion practices for groups that are targeted by guidelines are justified by outcomes observed in clinical practice. This study provides evidence for the liberal administration of RBC products to critically ill adults with acute blood loss based on association with lower risk of mortality.


Hope, happiness and home treatment: a study into patient satisfaction with being treated at home.
Aims and method This study investigates patient satisfaction and levels of hope after receiving treatment from a home treatment team. It studies whether distributing questionnaires during the last visit increases the response rate, and explores whether patient satisfaction and levels of hope are associated with particular elements of the care received. Results Patients who answered the questionnaire tended to be satisfied. When forms were distributed during the last visit, the response rate increased to at least 64%. People with negative views were more likely to return the form by post. Patient satisfaction and levels of hope were associated with most elements of received care, and the resolution of problems was predictive of both satisfaction and increased hope in logistic regression. Clinical implications The distribution of service evaluation questionnaires during the last visit increased the response rate considerably. This study suggests that in order to improve services, it is important to focus on whether patients think their problems have been resolved.


Enzymatic formation of angiotensins II and III in the hindlimb circulation of dogs.
Experiments were performed in 14 anesthetized dogs to (1) to determine if the reductions in hindlimb blood flow produced by [des-Asp1] angiotensin I were due to its local enzymatic (kininase II) conversion to angiotensin III and (2) to quantitate the extent of conversion of angiotensin I to angiotensin II and of [des-Asp1] angiotensin I to angiotensin III in the hindlimb circulation. Graded doses of these peptides were administered as bolus injections directly into the left external iliac artery while measuring flow in this artery electromagnetically. Dose-response relationships were determined before and during the inhibition of kininase II activity with captopril or antagonism of angiotensin receptor sites with [Ile7] angiotensin III. Captopril inhibited the vasoconstrictor responses to angiotensin I and [des-Asp1] angiotensin I, but did not affect the responses to angiotensins II or III, or norepinephrine. [Ile7] angiotensin III inhibited the vasoconstrictor responses to all four angiotensin peptides but did not alter the responses to norepinephrine. These findings indicate that the hindlimb vasoconstrictor responses to [des-Asp1] angiotensin I were due to the local formation of angiotensin III. The extent of conversion of [des-Asp1] angiotensin I to angiotensin III that occurred in one transit through the hindlimb arterial circulation was estimated to be 36.7%, which was not different from the estimated 36.4% conversion of angiotensin I to angiotensin II. We conclude that angiotensin I and [des-Asp1] angiotensin I are converted to their respective vasoactive forms (angiotensins II and III) to a similar extent in the hindlimb circulation via the action of kininase II.


Regulation of later neurogenic stages of adult-derived neural stem/progenitor cells by L-type Ca2+ channels.
In the adult hippocampus, new neurons are continuously generated and incorporated into the local circuitry in a manner dependent on the network activity. Depolarization evoked by neurotransmitters has been assumed to activate L-type Ca2+ channels (LTCC) which regulate the intracellular Ca2+ -dependent signaling cascades. The process of neurogenesis contains several stages such as proliferation, fate determination, selective death/survival and maturation. Here, we investigated which stage of neurogenesis is under the regulation of LTCC using a clonal line of neural stem/progenitor cells, PZ5, which was derived from adult rat hippocampus. Although undifferentiated PZ5 cells were type 1-like cells expressing both nestin and glial fibrillary acidic protein, they generated neuronal, astrocytic and oligodendrocytic populations in differentiation medium containing retinoic acid. Proliferation of undifferentiated PZ5 cells was dependent on neither the LTCC antagonist, nimodipine (Nimo) nor the LTCC agonists, Bay K 8644 (BayK) or FPL 64176 (FPL), whereas the fraction of neuronal population that expressed both βIII-tubulin and MAP2 was reduced by Nimo but increased by BayK or FPL. At an earlier period of differentiation (e.g., day 4), the fraction of PZ5 cells expressing HuC/D, pan-neuronal marker, was not affected either by the LTCC activation or inhibition. At a later period of differentiation (e.g., day 9), the fraction of dying neurons was decreased by LTCC activation and increased by LTCC inhibition. It is suggested that the LTCC activation facilitates the survival and maturation of immature neurons, and that its inhibition facilitates the neuronal death.


Velvet Antler Peptides Reduce Scarring via Inhibiting the TGF-β Signaling Pathway During Wound Healing.
Scar formation generally occurs in cutaneous wound healing in mammals, mainly caused by myofibroblast aggregations, and currently with few effective treatment options. However, the pedicle wound (about 10 cm in diameter) of the deer can initiate regenerative healing, which has been found to be achieved via paracrine factors from the internal tissues of antlers. Enzymatically digested velvet antler peptides (EVAP) were prepared along with other types of antler extracts as the controls. The effects of EVAP on healing of full-thickness skin wounds were evaluated using rats in vivo, and on myofibroblast transdifferentiation tested using transforming growth factor-β1 (TGF-β1)-induced human dermal fibroblasts in vitro. EVAP significantly accelerated the wound healing rate, reduced scar formation, and improved the healing quality, including promoted angiogenesis, increased number of skin appendages (hair follicles and sebaceous glands) and improved the distribution pattern of collagen fibers (basket-wave like) in the healed tissue. Moreover, EVAP significantly down-regulated the expression levels of genes pro- scar formation (Col1a2 and TGF-β1), and up-regulated the expression levels of genes anti-scar formation (Col3a1 and TGF-β3), and suppressed the excessive transdifferentiation of myofibroblasts and the formation of collagen I in vivo and in vitro. Furthermore, we found these effects were highly likely achieved by inhibiting the TGF-β signaling pathway, evidenced by decreased expression levels of the related genes, including TGF-β1, Smad2, p-Smad2, α-SMA, and collagen I. EVAP may be a promising candidate to be developed as a clinic drug for regenerative wound healing.


Association of APOE With Primary Open-Angle Glaucoma Suggests a Protective Effect for APOE ε4.
Prior studies have demonstrated that microglial activation is involved in the pathogenesis of primary open-angle glaucoma (POAG). Here we sought to identify genetic associations between POAG and variants in APOE and TREM2, genes associated with Alzheimer disease (AD) that critically regulate microglial neurodegeneration-associated molecular signature. APOE genotypes were called using imputed data from the NEIGHBOR consortium (2120 POAG cases, 2262 controls) and a second cohort from the Massachusetts Eye and Ear Infirmary (MEEI; 486 cases, 344 controls). TREM2 coding variants were genotyped by means of the Illumina HumanExome BeadArray. The data set was analyzed for association with POAG overall, as well as the high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) subgroups, using logistic regression adjusting for age and sex. In the combined NEIGHBOR-MEEI data set, significant association was observed for APOE ε4 in POAG overall (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.74-0.94; P = 0.0022) and in both the HTG subgroup (OR, 0.81; 95% CI, 0.70-0.94; P = 0.0052) and NTG subgroup (OR, 0.71; 95% CI, 0.58-0.87; P = 0.0014). A rare TREM2 variant (A105V) was found only in HTG cases (3 of 2863 cases) and in none of the controls (P = 0.03). Three TREM2 rare variants associated with AD were not significantly associated with POAG (P > 0.05). We have found that the APOE ε4 allele is associated with a reduced risk of POAG. Interestingly, the same allele is adversely associated with AD, suggesting a mechanistic difference between neurodegenerative diseases of the eye and the brain. TREM2 variants associated with AD did not significantly contribute to POAG risk.


[Normal and pathologic sebaceous function. Research in a shallow milieu?].
Modern therapeutic approaches allow to control sebaceous secretion but knowledge about the sebaceous gland and its precise function within the pilosebaceous unit is still insufficient. Steroid hormones are the principal albeit not exclusive regulators of the sebaceous glands. Three phases may be distinguished in sebaceous physiology: secretion-production, stocking in the follicular reservoir, and excretion. Human "native" intracellular sebum, before secretion, is composed of squalene, waxes, and triglycerides. Once secreted, the sebum is colonised by various xenobiots whose development is controlled by several defensive humoral mechanisms and by the contact with ambient oxygen. Oxygen and micro-organisms transform "native" sebum, lysis of triglycerides to fatty acids being the most pronounced activity. Certain components of this complex mixture of molecules present in the sebum are clearly cytotoxic or irritant, provoking reactive follicular hyperkeratosis and comedone formation--the first step to acne. Some lipophilic organisms like Malassezia yeast may be highly antigenic and induce chronic inflammatory reactions like in seborrhoeic dermatitis. Demodex is an inrafollicular parasite feeding on sebum that frequently causes blepharitis. Sebum is also a vehicle transporting and transmitting several endogenous and exogenous molecules, including potential regulatory factors of hair follicles. Recent development of in vitro cultures of functional sebocytes should help to better understand several aspects of the sebaceous gland's biology.


Study on the adsorption of nitrogen and phosphorus from biogas slurry by NaCl-modified zeolite.
A NaCl-modified zeolite was used to simultaneously remove nitrogen and phosphate from biogas slurry. The effect of pH, contact time and dosage of absorbants on the removal efficiency of nitrogen and phosphate were studied. The results showed that the highest removal efficiency of NH4+-N (92.13%) and PO43--P (90.3%) were achieved at pH 8. While the zeolite doses ranged from 0.5 to 5 g/100 ml, NH4+-N and PO43--P removal efficiencies ranged from 5.19% to 94.94% and 72.16% to 91.63% respectively. The adsorption isotherms of N and P removal with NaCl-modified zeolite were well described by Langmuir models, suggesting the homogeneous sorption mechanisms. While through intra-particle diffusion model to analyze the influence of contact time, it showed that the adsorption process of NH4+-N and PO43--P followed the second step of intra-particle diffusion model. The surface diffusion adsorption step was very fast which was finished in a short time.


Multiscaled Neural Autoregressive Distributed Lag: A New Empirical Mode Decomposition Model for Nonlinear Time Series Forecasting.
Forecasting has always been the cornerstone of machine learning and statistics. Despite the great evolution of the time series theory, forecasters are still in the hunt for better models to make more accurate decisions. The huge advances in neural networks over the last years has led to the emergence of a new generation of effective models replacing classic econometric models. It is in this direction that we propose, in this paper, a new multiscaled Feedforward Neural Network (FNN), with the aim of forecasting multivariate time series. This new model, called Empirical Mode Decomposition (EMD)-based Neural ARDL, is inspired from the well-known Autoregressive Distributed Lag (ARDL) model being our proposal founded upon the concepts of nonlinearity, EMD-multiresolution and neural networks. These features give the model the ability to effectively capture many nonlinear patterns like the ones often present in econophysical time series, such as nonlinear trends, seasonal effects, long-range dependency, etc. The proposed algorithm can be summarized into the following four basic tasks: (i) EMD breaking-down multivariate time series into different resolution levels, (ii) feeding EMD components from the same levels into a number of feedforward neural ARDL models, (iii) from one level to the next, extrapolating the component corresponding to the response variable (scalar output) a number of steps ahead, and finally, (iv) recombining level-by-level forecasts into a single output. An optimal learning scheme is rigorously designed for efficiently training the new proposed architecture. The approach is finally tested and compared to a number of powerful benchmark models, where experiments are conducted on real-world data.


Celecoxib exhibits therapeutic potential in experimental model of hyperlipidaemia.
Hyperlipidaemia is a major risk factor for cardiovascular diseases, the leading cause of death globally. Celecoxib attenuated hypercholesterolaemia associated with CCl4-induced hepatic injury in rats without improving liver function in our previous study. This present study investigated the lipid lowering potential of celecoxib in normal rats fed with coconut oil subjected to five deep-frying episodes. Male Sprague Dawley rats were randomly assigned to groups (n = 6 rats/group) which received physiological saline (10 mL/kg), unheated coconut oil (UO, 10 mL/kg) or heated coconut oil (HO, 10 ml/kg) for 60 days. Groups that received HO were subsequently treated with either physiological saline, atorvastatin (25 mg/kg), celecoxib (5 mg/kg) or celecoxib (10 mg/kg) in the last fifteen days of the experiment. Rats were sacrificed 24 hours after last treatment and blood and tissue samples collected for analysis. HO consumption produced significant hyperlipidaemia and elevation in marker enzymes of hepatic function. Celecoxib ameliorated the hyperlipidaemia as shown by the significantly (P<0.05) lower total cholesterol, triglycerides, low and very low density lipoprotein in the celecoxib-treated rats when compared with HO-fed rats that received saline. Celecoxib also reduced (P<0.05) alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and liver weight of hyperlipidaemic rats. Similarly, hepatocellular damage with the hyperlipidaemia was significantly reversed by celecoxib. However, serum TNF-α and IL-6 did not change significantly between the various groups. Taken together, data from this study suggest that celecoxib may exert therapeutic benefit in hyperlipidaemia and its attendant consequences.


Bioelectrical impedance analysis of nutritional status in uremic patients on regular hemodialysis.
The body composition of uremic patients on regular hemodialysis (HD) therapy was studied using the bioelectrical impedance analysis (BIA) technique. The accuracy of BIA in estimating fluid loss during HD was also studied. Thirty-five uremic patients (28 men and 7 women), regularly treated by hemodialysis (HD), were enrolled. The uremic patients had lower serum albumin levels and a marginally lower arm muscle circumference (AMC; p = 0.06) than 107 age- and sex-matched normal control subjects (86 men and 21 women). Before HD, the uremic patients presented with a similar percentage of body fat (BF), fat-free mass (FFM) and total body water (TBW) as normal controls, but they possessed a lower percentage of TBW and FFM, and a higher percentage of BF after HD. When BIA was applied to estimate the fluid loss during HD, overestimation usually occurred. A good correlation between the body fluid loss estimated by the BIA method (BIAL) and that estimated by the body weighing method (BWL) was noted. An equation of BWL = 0.452 BIAL + 0.844 (n = 35, R = 0.85, SEE = 0.58, p less than 0.0001) was derived following linear regression analysis. The weight of BF estimated by BIA before and after HD demonstrated a good correlation (n = 35, R = 0.98, p less than 0.0001). In conclusion, uremic patients on regular HD therapy seem to have decreased serum albumin levels and decreased AMC in anthropometry. After HD, they possess a lower percentage of FFM and TBW than normal controls. The results suggest that accelerated protein catabolism is a common problem in uremic patients on regular HD therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term follow-up of concurrent radiotherapy and chemotherapy for locally advanced cervical cancer: 12-Year survival after radiochemotherapy.
Recently randomized trials show an overall survival advantage of 30% for cisplatin-based chemotherapy given concurrently with radiation therapy. Current data do not allow to conclude which drugs could be best combined with cisplatin. Here we report the very long-term results of a prospective phase II trial of concurrent radiochemotherapy in advanced cancer of the cervix. Psychological impact has been evaluated with long-term survivors. Patient with squamous cell carcinoma of the cervix FIGO stage IIB, III or IVA received a concomitant chemotherapy with cisplatin, fluorouracil and mitomycin C and radiotherapy. From June 1988 to September 1990, 22 of 23 patients were eligible. The overall response rate was 82%. All 22 patients treated showed acute hematological toxicity and two patients developed severe late bowel toxicity. Ten patients (45%) were alive after a median observation time of 145.5 months. Intolerance to certain food and vaginal changes due to radiotherapy remain problematic. The lack of improvement compared to cisplatin alone and late bowel toxicity do not support the use of mitomycin C in the combination of the concurrent treatment of chemoradiation. The psychological impact of this treatment should not be minimized. Most problems tend to diminish with time with the exception of intestinal side effects and vaginal changes.


[Evaluation of a new immunochromatographic kit for enhanced detection of influenza B virus].
We have evaluated a new immunochromatographic kit, "KBM LineCheck Flu AB", which had been developed for enhanced detection of influenza B viruses. Five strains of influenza A and B viruses were tested for reactivity and detection limits of the kit. Compared with the detection limits of commercially available kit of QuickNavi-Flu, "KBM LineCheck Flu AB" showed a nearly equal reactivity to influenza A viruses, but quadruple reactivity to 2 influenza B viruses. Also, "KBM LineCheck Flu AB" exhibited high specificity when tested in 130 influenza-negative culture specimens derived from 24 adult volunteers. Furthermore, "KBM LineCheck Flu AB" was clinically evaluated by using 866 specimens, including 190 nasal swabs, 201 nasal aspirations, 262 self-blown nasal discharges, and 213 pharyngeal swabs. Compared with the results of QuickNavi-Flu for influenza A, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 92.0%, 95.0%, and 94.8%, respectively. Whereas, as to influenza B, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 96.3%, 98.5%, 96.2%, and 93.4%, respectively. Similarly, compared with the results of influenza A viral culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs was calculated to be 95.3%, 91.0%, 93.9%, and 92.5%, respectively. Regarding influenza B culture, the test efficiency for the nasal swabs, the nasal aspirations, self-blown nasal discharges, and pharyngeal swabs were calculated to be 95.8%, 97.5%, 95.1%, 91.5%, respectively. Overall, we concluded that the "KBM LineCheck Flu AB" is useful and suitable for diagnosis of influenza A and especially influenza B.


A new monitoring approach for sustainability assessment of subsurface utilities gasket materials against gasoline and chlorinated solvents: Field evaluation and model development.
Once installed, underground concrete pipes with rubber gaskets might be exposed to contaminated soil and groundwater. A pipe material monitoring capsule (PMMC) has been developed to evaluate volatile organic compounds (VOCs) breaking through three types of pipe gaskets; Neoprene, Buna-N, and Viton. The PMMCs were deployed in three contaminated sites: two with gasoline and one with chlorinated solvent (CS). A 3-D field-domain numerical model has been developed for each site to calibrate equivalent hydraulic parameters of each gasket material (ke, D) against benzene and PCE diffusion. The calibrated parameters were then used to compute the concentrations as well as rate of breakthrough of the two study contaminants. A protocol was developed for installing/retrieval of PMMCs to monitor PCE and benzene mass breaking through the gasket material with time. Employing PMMC, benzene concentrations breaking through the Neoprene and Buna-N after 4 months were approximately 70% and 60% respectively of the monitoring wells concentration. The corresponding value for PCE breakthrough after 4 months was 60% for both the Neoprene and Buna-N. Both gasket materials of Neoprene and Buna-N yielded similar performances, including higher rate of contaminant breakthrough compared to Viton. A nonlinear relationship of mass breaking through the gaskets of benzene and PCE with time was discerned from the modeling and field data.


Analysis of forage fiber and cell walls in ruminant nutrition.
Analysis of the fiber or cell wall present in forages is of major concern in ruminant nutrition because diets often contain large amounts of forage, and the fiber fraction affects both feed intake and animal performance. Traditional extractive, gravimetric methods such as crude fiber and neutral detergent fiber recover variable amounts of the plant cell wall, but they remain popular because of their ease of use and the large feed data bases available for these methods. More intensive chemical methods utilizing chromatography and spectrometric analysis provide greater detail on cell wall composition and structure, but they have been used little in ruminant nutrition. Lignin analysis has remained problematic because no definitive reference method exists. Recently attention has focused on the measurement of lignin composition and cell wall phenolic acids; however, these methods have yet to be widely adopted in ruminant nutrition. The detergent fiber methods have been semi-automated to increase sample handling capacity. Near-infrared spectroscopy is routinely used for prediction of fiber concentration in forages and has greatly increased the ease of obtaining fiber analysis of forage samples. Widespread adoption in ruminant nutrition of the more sophisticated methods of cell wall analysis is unlikely to occur until these methods can be demonstrated to improve diet formulation and prediction of animal performance.


Deletion of the cytochrome bc complex from Heliobacterium modesticaldum results in viable but non-phototrophic cells.
The heliobacteria, a family of anoxygenic phototrophs, possess the simplest known photosynthetic apparatus. Although they are photoheterotrophs in the light, the heliobacteria can also grow chemotrophically via pyruvate metabolism in the dark. In the heliobacteria, the cytochrome bc complex is responsible for oxidizing menaquinol and reducing cytochrome c553 in the electron flow cycle used for phototrophy. However, there is no known electron acceptor for the mobile cytochrome c553 other than the photochemical reaction center. We have, therefore, hypothesized that the cytochrome bc complex is necessary for phototrophy, but unnecessary for chemotrophic growth in the dark. We used a two-step method for CRISPR-based genome editing in Heliobacterium modesticaldum to delete the genes encoding the four major subunits of the cytochrome bc complex. Genotypic analysis verified the deletion of the petCBDA gene cluster encoding the catalytic components of the complex. Spectroscopic studies revealed that re-reduction of cytochrome c553 after flash-induced photo-oxidation was over 100 times slower in the ∆petCBDA mutant compared to the wild-type. Steady-state levels of oxidized P800 (the primary donor of the photochemical reaction center) were much higher in the ∆petCBDA mutant at every light level, consistent with a limitation in electron flow to the reaction center. The ∆petCBDA mutant was unable to grow phototrophically on acetate plus CO2 but could grow chemotrophically on pyruvate as a carbon source similar to the wild-type strain in the dark. The mutants could be complemented by reintroduction of the petCBDA gene cluster on a plasmid expressed from the clostridial eno promoter.


Treatment considerations in women with schizophrenia.
Schizophrenia is a challenging and complex psychiatric disorder. It is a chronic disorder of thought, affect, and cognition that significantly disturbs the individual's ability to function in society and develop interpersonal relationships. The clinical presentation can be extremely varied, with symptoms including delusional thinking, disorganized thoughts and speech, hallucinatory behavior, and negative symptoms (e.g., blunted affect, avolition, alogia, anhedonia). Approximately 1% of the population is affected by schizophrenia worldwide, and women may experience different symptoms, have a later age of onset, may respond to different treatments, and may be more concerned about specific side effects than men. Women with schizophrenia traditionally have been treated in the same way as men and have generally had poorer comprehensive medical care. With the introduction of many new antipsychotic medications in recent years, this review focuses on sex differences in schizophrenia, with an emphasis on differences in treatment and side effects. Additionally, it presents patient counseling issues in sexuality and health outcomes.


Is there a common water-activity limit for the three domains of life?
Archaea and Bacteria constitute a majority of life systems on Earth but have long been considered inferior to Eukarya in terms of solute tolerance. Whereas the most halophilic prokaryotes are known for an ability to multiply at saturated NaCl (water activity (a(w)) 0.755) some xerophilic fungi can germinate, usually at high-sugar concentrations, at values as low as 0.650-0.605 a(w). Here, we present evidence that halophilic prokayotes can grow down to water activities of <0.755 for Halanaerobium lacusrosei (0.748), Halobacterium strain 004.1 (0.728), Halobacterium sp. NRC-1 and Halococcus morrhuae (0.717), Haloquadratum walsbyi (0.709), Halococcus salifodinae (0.693), Halobacterium noricense (0.687), Natrinema pallidum (0.681) and haloarchaeal strains GN-2 and GN-5 (0.635 a(w)). Furthermore, extrapolation of growth curves (prone to giving conservative estimates) indicated theoretical minima down to 0.611 aw for extreme, obligately halophilic Archaea and Bacteria. These were compared with minima for the most solute-tolerant Bacteria in high-sugar (or other non-saline) media (Mycobacterium spp., Tetragenococcus halophilus, Saccharibacter floricola, Staphylococcus aureus and so on) and eukaryotic microbes in saline (Wallemia spp., Basipetospora halophila, Dunaliella spp. and so on) and high-sugar substrates (for example, Xeromyces bisporus, Zygosaccharomyces rouxii, Aspergillus and Eurotium spp.). We also manipulated the balance of chaotropic and kosmotropic stressors for the extreme, xerophilic fungi Aspergillus penicilloides and X. bisporus and, via this approach, their established water-activity limits for mycelial growth (∼0.65) were reduced to 0.640. Furthermore, extrapolations indicated theoretical limits of 0.632 and 0.636 a(w) for A. penicilloides and X. bisporus, respectively. Collectively, these findings suggest that there is a common water-activity limit that is determined by physicochemical constraints for the three domains of life.


The effect of magnetron pulsing on the structure and properties of tribological Cr-Al-N coatings.
The paper will discuss the effect of pulsing single or two unbalanced magnetrons in a closed magnetic field configuration on the structure and properties of tribological Cr-Al-N coatings. Nanocrystalline Cr-Al-N coatings were reactively deposited from Cr and Al elemental targets using two unbalanced magnetrons, which were powered in both dc, pulsing only Al target and asynchronously pulsing both Cr and Al targets at 100 kHz and 50% duty cycle conditions. The ion energy distributions of these deposition and pulsing conditions were characterized using a Hiden Electrostatic QuadruPole Plasma Analyzer. It was found that pulsing two magnetrons asynchronously at 100 kHz and 50% duty cycle produced higher ion energies and significant increased ion fluxes than pulsing none or pulsing only one (Al) target. The structure and properties of Cr-Al-N coatings synthesized under different dc and pulsing conditions were investigated using X-ray diffraction, scanning electron microscopy, nanoindentation and ball-on-disk wear test, and were correlated with the effects of ion energies and ion flux regimes observed in the plasma diagnostics. The advantages of using pulsed magnetron sputtering producing different energetic ion regimes to enhance the ion bombardment on the growing films and therefore achieving the improved density, refinement of grain size and properties are illustrated.


Identification and characterization of DEDDL, a human-specific isoform of DEDD.
Death effector domain (DED) containing molecules are usually involved in the intracellular apoptosis cascade as executioners or regulators. One of these molecules, DEDD, was identified as a final target of the CD95 signaling pathway by which it would be transferred into the nucleolus to inhibit RNA polymerase I-dependent transcription. Here we describe a longer isoform of DEDD, DEDDL, produced by alternatively splicing, as an immune cell-specific DED-containing molecule. It is only expressed in human T lymphocytes and dendritic cells (DCs), and the mRNA expression in DCs was elevated upon inductive maturation. In cell lines MCF-7 and Jurkat, the overexpression of DEDDL could induce apoptosis more potently than that of DEDD. That DEDDL could bind FADD and cFLIP more potently than DEDD in vivo was revealed by cotransfection and immunoprecipitation. This may explain why DEDDL is a more potent apoptosis inducer, because DED-containing proteins usually induce apoptosis through DED binding. Finally, why DEDD and DEDDL are unstable in the overexpression and other studies may be explained by the finding that they are potential substrates of active caspases.


Structural Basis of Small-Molecule Aggregate Induced Inhibition of a Protein-Protein Interaction.
A prevalent observation in high-throughput screening and drug discovery programs is the inhibition of protein function by small-molecule compound aggregation. Here, we present the X-ray structural description of aggregation-based inhibition of a protein-protein interaction involving tumor necrosis factor α (TNFα). An ordered conglomerate of an aggregating small-molecule inhibitor (JNJ525) induces a quaternary structure switch of TNFα that inhibits the protein-protein interaction between TNFα and TNFα receptors. SPD-304 may employ a similar mechanism of inhibition.


[Effect of stress and intesity of mobile phone using on the health and subjective symptoms in GSM workers].
There are no available data on the health consequences that may result from the synergistic effects of electromagnetic fields (EMF) and stress. Understanding the mechanisms of the simultaneous exposure will make it possible to develop procedures to minimize adverse health effects in professionals using mobile phones. A questionnaire survey was conducted in 600 randomly selected people to obtain data on their health status and the prevalence of subjective symptoms related to the mobile phones using. Among them, there were 208 GSM Network employees, to whom the Perceived Stress Scale and Assessment of Stress at Work Questionnaire were sent. Eighty-nine completed questionnaires were returned (response rate - 42.8%). The mean age of respondents was 30.3 years (standard deviation (SD) = 7.7), time of occupational use of mobile phone - 4.1 years (SD = 1.7), the level of occupational stress - 95.3 (SD = 19.1). A significant percentage of people (62.8%) complained of the frequent difficulties in coping with problems of everyday life, and 57.4% had a fairly frequent problems with managing their own affairs. Significant differences in the life stress were detected between groups with different time of phone use (p = 0.03), and in occupational stress level, significant differences were noted between the 2 groups differing in the length of the conversation (p = 0.05). The risk of headache, associated (odds ratio (OR) = 4.2, p = 0.008) or not associated (OR = 2.97, p = 0.04) with calls on mobile phone, adjusted for stress, was significantly higher in people speaking via mobile more than 60 min/day than in those talking less. The study indicates that both stressors acting at the same time (EMF from cell phone and stress) adversely affect the well-being of workers and increase the risk of subjective symptoms. Med Pr 2017;68(5):617-628.


Intramuscular methylprednisolone is superior to pulse oral methylprednisolone during the induction phase of chrysotherapy.
In a randomized double-blinded placebo-controlled trial, 41 patients with RA starting on i.m. sodium aurothiomalate (SAT) therapy were randomized to receive three doses of either 500 mg methylprednisolone (MP) orally and a placebo injection or 120 mg of i.m. depot methylprednisolone acetate (MPA) and oral placebo tablets at 4-weekly intervals. Disease activity was assessed by visual analogue scale (VAS) of pain, grip strength (GS), tender joint count (JC), and Health Assessment Questionnaire (HAQ). Laboratory assessment was by haemoglobin concentration (Hb) and ESR. A composite index of Disease Activity score (IDA) was constructed using all six measurements. The group receiving i.m. MPA showed greater improvement when compared with the group receiving oral MPA. These changes were statistically significant (P < 0.05) for ESR (weeks 2, 6, 8, 10, 12), VAS (week 4, 6, 8), JC (weeks 2, 4, 6, 8, 10) and HAQ (weeks 2, 8, 10). Statistically significantly (P < 0.05) greater improvement in Hb was seen throughout all time points in favour of the group treated with i.m. MPA. Using the IDA score to summarize the results, patients treated with i.m. MPA had better disease remission from weeks 2-12. In all measures, except Hb, no statistically significant difference between the two groups was seen by 16 weeks. We conclude that 120 mg i.m. depot MPA is more effective at inducing improvement in disease activity than 500 mg of oral MPA in RA patients starting on SAT therapy.


Enhancing fine retinal vessel segmentation: Morphological reconstruction and double thresholds filtering strategy.
Eye diseases such as diabetic retinopathy are progressive with various changes in the retinal vessels, and it is difficult to analyze the disease for future treatment. There are many computerized algorithms implemented for retinal vessel segmentation, but the tiny vessels drop off, impacting the performance of the overall algorithms. This research work contains the new image processing techniques such as enhancement filters, coherence filters and binary thresholding techniques to handle the different color retinal fundus image problems to achieve a vessel image that is well-segmented, and the proposed algorithm has improved performance over existing work. Our developed technique incorporates morphological techniques to address the center light reflex issue. Additionally, to effectively resolve the problem of insufficient and varying contrast, our developed technique employs homomorphic methods and Wiener filtering. Coherent filters are used to address the coherence issue of the retina vessels, and then a double thresholding technique is applied with image reconstruction to achieve a correctly segmented vessel image. The results of our developed technique were evaluated using the STARE and DRIVE datasets and it achieves an accuracy of about 0.96 and a sensitivity of 0.81. The performance obtained from our proposed method proved the capability of the method which can be used by ophthalmology experts to diagnose ocular abnormalities and recommended for further treatment.


Orthodontic Intervention to Impacted and Transposed Lower Canines.
Impacted and transposed teeth cause serious difficulties in tooth eruption and movement as well as esthetic and functional outcomes. Proper treatment planning including good biomechanical control is essential in order to avoid side effects during traction and aligning of the impacted and/or transposed teeth. The purpose of the present study was to present a successfully treated female patient having transposed and impacted lower canines by means of a modified lingual arch and fixed orthodontic appliance. A female patient aged 13 years and 9 months presented to the orthodontic department with a chief compliant of bilateral spacing and missing teeth in mandibular dentition. After leveling and creating sufficient space in the mandibular arch for the canines, a modified lingual arch was cemented to the mandibular first molars. The lingual arch had two hooks extending to the distobuccal areas of the canine spaces. Elastic chains were applied between the hooks on the lingual arch and the ligatures tied to the attachments on the canine crowns. The light forces generated by elastic materials caused impacted canines to erupt and tend towards their own spaces in the dental arch. As a result, impacted and transposed lower canines were properly positioned in their spaces, and the treatment results were stable during the retention period.


Elevated numbers of gamma-delta (gamma delta+) T lymphocytes in children with immune thrombocytopenic purpura.
Immune thrombocytopenic purpura (ITP) in childhood is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Although generally considered to involve autoreactive B lymphocytes which produce antiplatelet antibodies, there is increasing evidence that T lymphocytes also play an important role in this autoimmune process. We studied 11 children with acute ITP and 19 children with chronic ITP and observed elevated numbers of TCR gamma delta+ T lymphocytes in several patients. In the three children with the highest elevations (TCR gamma delta+/CD3+ percentage ranging from 37.8 to 48.1% at initial evaluation), the expanded cell population exclusively expressed the surface V delta 2/V gamma 9 heterodimer and had enhanced in vitro proliferation to mycobacterial extracts and IL-2. Analysis of the nucleotide sequences used by these TCR gamma delta+ cells demonstrated a diverse set of VDDJC gene rearrangements, indicating polyclonal expansion of cells reminiscent of a superantigen response. There was a close correlation between the number of TCR gamma delta+ T lymphocytes and the degree of thrombocytopenia in each patient. TCR gamma delta+ T lymphocytes may be important in the pathogenesis of immune-mediated platelet destruction in some children with ITP.


Inversion of melatonin circadian rhythm in chronic alcoholic patients during withdrawal: preliminary study on seven patients.
The inversion of melatonin circadian rhythm secretion in some alcoholics during both intake and acute withdrawal has been widely reported. In the same way, what happens to this inversion when these patients are in long-term withdrawal is not known. To document this abnormality in alcoholics after withdrawal we investigated melatonin secretion observed during chronic alcoholization and after withdrawal. We measured the urinary 6-sulfatoxymelatonin (6SM) (6SM/creatinine ratio), main metabolite of the hormone, in two fractions, one diurnal and the other nocturnal, in seven alcohol-dependent patients presenting with this abnormality during alcoholization at two times: in acute withdrawal phase (under benzodiazepines) and 15 days after beginning of withdrawal (free of any psychotropic treatment). Our results show that this reversed rhythm of melatonin secretion as seen by the diurnal excretion of 6SM (6SM/creatinine ratio) persists during acute withdrawal in more than half of the patients and is still present 15 days after withdrawal in three patients. It is remarkable that the inversion of the melatonin rhythms gets corrected in four out of seven patients after withdrawal. But, the circadian disorganization of melatonin secretion in three patients could underline a desynchronization in some alcoholic patients and may indicate more widespread circadian temporal structure disturbances in these patients.


What influences dental students' attitudes regarding the treatment of older adults? A scoping review.
The aim of this study is to investigate the literature to evaluate dental students' attitudes regarding the treatment of older adults. A scoping review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses/PRISMA guidelines to identify articles from four electronic databases: MEDLINE via the PubMed interface, Embase, Cumulative Index to Nursing and Allied Health Literature, and AgeLine. Gray literature searches were also performed in Scopus, Web of Science, and ProQuest Dissertations and Theses-Health and Medicine. Eleven articles were assessed. The majority (72, 72%) were published between 2011 and 2020, evidencing various contexts of dental students, such as different countries and cultures, and levels of education. The most commonly used tool/instrument to survey dental students' attitudes was the Aging Semantic Differential Scale. Student age, race, and marital status did not seem to interfere with dental students' attitudes regarding the treatment of older adults. Dental students tend to have a positive attitude toward older people. In this context, female students, students who interact with older people, and clinical students have more positive attitudes than male and nonclinical students.


The differential effects of twitch potentiators on charge movements in frog skeletal muscle.
The effects of twitch potentiators at physiologically effective concentrations on intramembrane charge movements were examined in voltage-clamped frog skeletal muscle in the presence and absence of tetracaine. Caffeine, even at high concentrations (2.5 mM) did not alter the potential dependence of either tetracaine-sensitive or tetracaine-resistant portions of non-linear charge through a voltage range that included the mechanical threshold. Perchlorate (8 mM) altered the form and shifted the potential dependence of the non-linear charge by about -25 mV in the hyperpolarizing direction, but did not alter the total available charge. Comparing charge movements in the presence and absence of 4 mM-tetracaine demonstrated that perchlorate shifted the threshold and voltage dependence of the delayed ('q gamma') transients but had no action on the steady-state tetracaine-resistant charge. Thiocyanate (10 mM) shifted the voltage dependence of charge movements by about 20 mV in the hyperpolarizing direction. Experiments employing 4 mM-tetracaine demonstrated that this was the result of effects on both tetracaine-sensitive and tetracaine-resistant charge movements. On the basis of their effects on contractile activation reported on earlier occasions, these differential effects of twitch potentiators are explicable in terms of tetracaine-sensitive and tetracaine-resistant charge components being causally separate and not requiring a direct participation of tetracaine-resistant charge in contractile activation.


Effects of supervised exercise therapy in patients receiving radiotherapy for breast cancer.
Postoperative radiotherapy for breast cancer has a number of associated complications. This study examined whether supervised moderate-intensity exercise could mitigate the complications that occur during radiotherapy. Forty women were randomized before radiotherapy after various operations for breast cancer. Seventeen patients who were assigned to the exercise group performed supervised moderate-intensity exercise therapy for 50 min 3 times per week for 5 weeks. Twenty-three patients in the control group were asked to perform self-shoulder stretching exercise. The World Health Organization Quality of Life-BREF (WHOQOL-BREF), brief fatigue inventory (BFI), range of motion (ROM) of the shoulder, and pain score were assessed before and after radiotherapy. There were no significant differences noted at baseline between groups. In the exercise group, there was an increase in the WHOQOL-BREF and shoulder ROM and decrease in BFI and pain score after radiotherapy. On the other hand, patients in the control group showed decrease in the WHOQOL-BREF and shoulder ROM and increase in BFI and pain score after radiotherapy. There were statistically significant differences in the changes in the WHOQOL, BFI, shoulder ROM, and pain score between the groups. Patients receiving radiotherapy for breast cancer may benefit in physical and psychological aspects from supervised moderate-intensity exercise therapy.


Asymmetric and Upper Body Parkinsonism in Patients with Idiopathic Normal-Pressure Hydrocephalus.
Our aims were to analyze the characteristics of parkinsonian features and to characterize changes in parkinsonian motor symptoms before and after the cerebrospinal fluid tap test (CSFTT) in idiopathic normal-pressure hydrocephalus (INPH) patients. INPH subjects were selected in consecutive order from a prospectively enrolled INPH registry. Fifty-five INPH patients (37 males) having a positive response to the CSFTT constituted the final sample for analysis. The mean age was 73.7±4.7 years. The pre-tap mean Unified Parkinson's Disease Rating Scale motor (UPDRS-III) score was 24.5±10.2. There was no significant difference between the upper and lower body UPDRS-III scores (p=0.174). The parkinsonian signs were asymmetrical in 32 of 55 patients (58.2%). At baseline, the Timed Up and Go Test and 10-meter walking test scores were positively correlated with the total motor score, global bradykinesia score, global rigidity score, upper body score, lower body score, and postural instability/gait difficulties score of UPDRS-III. After the CSFTT, the total motor score, global bradykinesia score, upper body score, and lower body score of UPDRS-III significantly improved (p<0.01). There was a significant decrease in the number of patients with asymmetric parkinsonism (p<0.05). In the differential diagnosis of elderly patients presenting with asymmetric and upper body parkinsonism, we need to consider a diagnosis of INPH. The association between gait function and parkinsonism severity suggests the involvement of similar circuits producing gait and parkinsonian symptoms in INPH.


Adult rats exposed to early-life social isolation exhibit increased anxiety and conditioned fear behavior, and altered hormonal stress responses.
Social isolation of rodents during development is thought to be a relevant model of early-life chronic stress. We investigated the effects of early-life social isolation on later adult fear and anxiety behavior, and on corticosterone stress responses, in male rats. On postnatal day 21, male rats were either housed in isolation or in groups of 3 for a 3 week period, after which, all rats were group-reared for an additional 2 weeks. After the 5-week treatment, adult rats were examined for conditioned fear, open field anxiety-like behavior, social interaction behavior and corticosterone responses to restraint stress. Isolates exhibited increased anxiety-like behaviors in a brightly-lit open field during the first 10 min of the test period compared to group-reared rats. Isolation-reared rats also showed increased fear behavior and reduced social contact in a social interaction test, and a transient increase in fear behavior to a conditioned stimulus that predicted foot-shock. Isolation-reared rats showed similar restraint-induced increases in plasma corticosterone as group-reared controls, but plasma corticosterone levels 2 h after restraint were significantly lower than pre-stress levels in isolates. Overall, this study shows that isolation restricted to an early part of development increases anxiety-like and fear behaviors in adulthood, and also results in depressed levels of plasma corticosterone following restraint stress.


Initial results of efficacy and safety of Sofosbuvir among Pakistani Population: A real life trial - Hepatitis Eradication Accuracy Trial of Sofosbuvir (HEATS).
The uridine nucleotide analogue sofosbuvir is a selective inhibitor of hepatitis C virus (HCV) NS5B polymerase approved for the treatment of chronic HCV infection with genotypes 1 - 4. The objective of the study was to evaluate the interim results of efficacy and safety of regimens containing Sofosbuvir (Zoval) among Pakistani population with the rapid virologic response (RVR2/4 weeks) with HCV infections. This is a multicenter open label prospective observational study. Patients suffering from chronic Hepatitis C infection received Sofosbuvir (Zoval) 400 mg plus ribavirin (with or without peg interferon) for 12/24 weeks. The interim results of this study were rapid virological response on week 4. Data was analyzed using SPSS version 21 for descriptive statistics. A total of 573 patients with HCV infection were included in the study. The mean age of patients was 46.07 ± 11.41 years. Out of 573 patients 535 (93.3%) were treatment naive, 26 (4.5%) were relapser, 7 (1.2%) were non-responders and 5 (1.0%) were partial responders. A rapid virologic response was reported in 563(98.2%) of patients with HCV infection after four weeks of treatment. The treatment was generally well tolerated. Sofosbuvir (Zoval) is effective and well tolerated in combination with ribavirin in HCV infected patients.


Transitional cell carcinoma of the urinary tract associated with vulvar Paget's disease: a report of two cases.
Two cases of the urothelial cancers associated with extramammary Paget's disease are reported. In one patient, vulvar Paget's disease was discovered 6 years after complete resection of a ureteral tumor. In another patient, vulvar and vaginal Paget's disease developed during a period of repeated transurethral surgery leading up to the final total cystectomy for recurrent bladder carcinoma. Since genital Paget's disease is frequently accompanied by internal malignancies, a skin biopsy is mandatory when an eczematous lesion has been persistent in the genital region of patients with genitourinary cancers.


Measurement of glomerular filtration rate during flight in a migratory bird using a single bolus injection of FITC-inulin.
During migration, passerine birds typically complete a series of multi-hour flights, each followed by a period of stopover. During flight, rates of respiratory water loss are high, yet these birds show no signs of dehydration after flights. During stopover, birds become hyperphagic to replenish fat reserves, often consuming food with high water content, such as fruit. Thus migratory birds seem to face an osmoregulatory challenge; they must reduce water losses during flight but retain the ability to excrete large quantities of water while maintaining osmotic balance at stopover. Our goal was to measure glomerular filtration rate (GFR) and fractional water reabsorption (FWR) of a migratory bird in free flight, at rest, and during feeding to assess the role of the kidney in maintaining water balance during migration. We used FITC-inulin and one- and two-phase exponential decay models to first validate a technique and then measure GFR in the Swainson's thrush, a small (∼30 g) songbird. Single-phase exponential decay models and the modified slope intercept method overestimated GFR by 26% compared with two-phase exponential decay models. We found no differences in GFR among fed, resting and flying birds, but FWR was significantly higher in resting and flying birds relative to feeding birds. There was no effect of the rate of respiratory water loss on GFR or FWR in flight. These data support the idea that birds in flight do not dramatically alter GFR but rely on increased FWR to minimize excretory water losses.


Towards an endoscopic intra-uterine treatment for congenital diaphragmatic hernia.
Congenital Diaphragmatic Hernia (CDH) is a simple defect in the diaphragm that however can lead to severe or lethal pulmonary hypoplasia. Fetuses with their liver herniating into the thorax and with a small lung volume as reflected by a lung-to-head ratio below < 1.0, have virtually no chance to survive despite most modern postnatal care. They are therefore theoretical candidates for in utero therapy. There is a large experimental basis supporting tracheal occlusion (TO) as a method to trigger lung growth, although the optimal time and duration of TO remains to be defined in humans. Animal studies have also shown that TO can be performed completely endoscopically, by means of in utero tracheoscopy and endoluminal balloon placement. TO was therefore applied by leading fetal surgery centers. Initial results with tracheal clipping via hysterotomy were discouraging, but more recently fetoscopic clipping was associated with a nearly 70% survival. The time has now come to achieve TO by means of percutaneous fetoscopic balloon plugging. This will make the intervention more acceptable in a European setting, where open fetal surgery never took off.