The link between airway reflux and non-acid reflux in children: a review.
Airway reflux, a member of extra-esophageal reflux, has been linked to countless respiratory pathologies amongst children. The advent of novel instrumentation has enabled the discovery of non-acid reflux which was postulated as the main culprit of airway reflux. The objective of this review is to outline the association between non-acid reflux and airway reflux in children. A comprehensive review of recent literature on non-acid reflux and airway reflux in children was conducted. Studies ranged from January 2010 till November 2021 were searched over a period of a month: December 2021. A total of eleven studies were identified. All studies included in this review revealed a strong link between non-acid reflux and airway reflux in children. 6 of the included studies are prospective studies, 3 retrospective studies, 1 cross-section study, and type of study was not mentioned in 1 study. The most common reported respiratory manifestation of non-acid reflux in children was chronic cough (7 studies). Predominant non-acid reflux was noted in 4 studies. The total number of children in each study ranges from 21 to 150 patients. MII-pH study was carried out in all studies included as a diagnostic tool for reflux investigation. Non-acid reflux is the culprit behind airway reflux as well as other myriads of extra-esophageal manifestations in children. Multicentre international studies with a standardized protocol could improve scientific knowledge in managing non-acid reflux in airway reflux amongst children.


Superconductivity and phase transitions in Kagome compound Pd3P2S8from first-principles calculation.
Pd3P2S8is a semiconductor that contains Kagome lattices, which exhibits various physical phenomena. Structural searches of Pd3P2S8in the pressure range from 0 to 120 GPa have revealed two phases of the space groupP3‾m1(designated asP3‾m1-1 andP3‾m1-2) and two phases of the space groupC2/m(designated asC2/m-1 andC2/m-2), with all butC2/m-2 phase being dynamically stable. Electron-phonon calculations combined with Bardeen-Cooper-Schrieffer's argument have shown that both phases are superconductors. Notably, theP3‾m1-1 phase undergoes a semiconductor-to-superconductor transition, with superconducting critical temperature (Tc) increasing up to a maximum of 9.13 K at 70 GPa. BothC2/m-1 andP3‾m1-2 phases exhibit superconductivity at 0 GPa. Our calculations demonstrate several new superconducting phases of Pd3P2S8, providing a pathway and platform for exploring superconductivity in materials with Kagome lattices and expanding the options for studying such lattices.


Expression of chloride channel protein CLC-3 in patients with allergic rhinitis: effect of topical corticosteroid treatment.
To determine whether the chloride channel protein CLC-3 is upregulated in patients with allergic rhinitis (AR) and whether topical corticosteroid treatment decreases the expression of CLC-3. Histologic study. Academic research. Eighteen patients with AR were included in the study. Expression of CLC-3 was detected by immunohistochemistry and by reverse transcription-polymerase chain reaction before and at 4 weeks after treatment with the topical corticosteroid mometasone furoate. Strong CLC-3 expression was detected in epithelium and in submucosal glands. An increased presence of CLC-3 was demonstrated in nasal mucosa compared with that in normal nasal tissue. A statistically significant difference in CLC-3 gene expression level was found in nasal tissues before vs at 4 weeks after treatment with mometasone. CLC-3 may have a role in modulating the pathogenesis of AR. Decreased expression of CLC-3 may be the mechanism of action of corticosteroid treatment in controlling AR.


Carotid aneurism with acute dissection: an unusual case of IgG4-related diseases.
IgG4-related disease is a systemic disease that involves organs and vascular structures, in particular, the aorta. This is the first case that showed the carotid artery involvement with dissection evolution. In a 67-year-old man with speech impairment and right-hand clumsiness, a brain computed tomography revealed signs of acute ischemia in the left frontal lobe while an echo-color Doppler sonography of the cervical vessels showed a tight stenosis of left internal carotid artery with a large pseudoaneurysm. Histological findings performed on the surgical specimen disclosed IgG4-related disease. To the best of our knowledge, this is the first manifestation of IgG4-related disease with carotid artery dissection complicated by pseudoaneurysm. Even though unsuccessful since the patients died within 48 h, this case highlights the diverse facets of the IgG4-related disease representing a new complication with important clinical implications of such a diagnosis targeting immunosuppressive therapy particularly B-cell depletion.


Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma.
The study aimed to evaluate associations of relative leukocyte telomere length (LTL) and polymorphisms of telomere length-associated genes TERT (rs2736098), TERT-CLPTM1L (rs401681), TRF1 (rs1545827, rs10107605) and TNKS2 (rs10509637, rs10509639) in patients with laryngeal squamous cell carcinoma (LSCC). The study consisted of 300 patients with LSCC and 369 healthy control subjects. Genotyping and relative LTL measuring were carried out using qPCR. Relative LTL was statistically significantly shorter in the G3 (tumor differentiation grade) subgroup of patients with LSCC compared to the G1 and G2 subgroups. Significant differences were found in genotype distributions of TERT rs401681 and TNKS2 rs10509639 between the study groups. TERT rs401681 C/T and T/T genotypes were associated with approximately 30% decreased odds of LSCC development. LTL was shorter in the G3 subgroup compared to the G2 and G1 subgroups of LSCC patients. TERT rs401681 and its C/T and T/T genotypes were associated with decreased odds of overall LSCC development.


An inappropriate defibrillator shock during ventricular tachycardia.
Ventricular oversensing in patients with defibrillators is an infrequent but deleterious condition. We report a patient with a cardiac resynchronization-defibrillation device that presented with hyperkalemia and syncope. Device interrogation revealed ventricular double-counting within the QRS of a slow ventricular tachycardia, resulting detection of the slow ventricular tachycardia in the ventricular fibrillation zone, and delivery of an effective therapy, below device programmed detection rate. This case of defibrillator inappropriate detection emphasizes the relevance of device electrogram interrogation in order to minimize inappropriate therapies.


Effects of anipamil, a long acting analog of verapamil, in pigs subjected to myocardial ischemia.
In this study we examined the cardiovascular and possible antiarrhythmic actions of anipamil, a long acting analog of verapamil. Initial dose-response studies for anipamil (0.25-6.0 mg/kg, i.v.) in pentobarbitone-anesthetized pigs (n = 4) were conducted to determine the effects of the drug on EKG and hemodynamic measures. In this initial study anipamil was found to produce a dose-dependent reduction in blood pressure, left-ventricular pressure and its derivative (dP/dtmax), cardiac output, and increase in heart rate. These results were used as a basis from which to choose doses for a second study to assess antiarrhythmic actions of anipamil against arrhythmias induced by regional myocardial ischemia. The antiarrhythmic effects of the two doses were compared with verapamil when the latter was given at a dose producing cardiovascular effects mid-way between those produced by the two doses of anipamil. Anesthetized pigs were randomly assigned to receive one of three drug treatments, or vehicle control, prior to occlusion of the left-anterior descending coronary artery. Antiarrhythmic effectiveness of low (1.0 mg/kg + 0.10 mg/kg/min infusion, n = 8) and high (5.0 mg/kg + 0.50 mg/kg/min infusion, n = 12) dose anipamil was compared to that of verapamil (0.5 mg/kg + 0.60 mg/kg/min infusion, n = 8) in a vehicle controlled study (n = 15). Arrhythmic events (VPB, VT and VF incidence) were monitored and grouped according to their time of occurrence after occlusion. Thus phase 1a arrhythmias occurred 0-5 min after initiation of occlusion, phase 1b, 5-30 min, and phase 2, 0.5-4 hr after occlusion. This study showed that during phase 1a there was a low incidence of arrhythmias in all groups except the one receiving 5 mg/kg anipamil where the group incidence of VT was 58% as compared to 20% in controls (n = 15). Most ventricular arrhythmias occurred in all groups during phase 1b. In this phase verapamil abolished VF and reduced VT, as compared with controls. Anipamil (high and low doses) tended to reduce VT but not VF. In the period 0.5 to 4 hours post occlusion (phase 2) all three drug treatments were associated with fewer arrhythmias but this only reached statistical significance with verapamil. Thus verapamil was more efficacious than anipamil at providing antiarrhythmic protection against both early and late onset arrhythmias. Anipamil may have been proarrhythmic in the early phase of arrhythmias and only moderately antiarrhythmic, if at all, in the later phase.(ABSTRACT TRUNCATED AT 400 WORDS)


Metal-Organic Framework Thin Films as Platforms for Atomic Layer Deposition of Cobalt Ions To Enable Electrocatalytic Water Oxidation.
Thin films of the metal-organic framework (MOF) NU-1000 were grown on conducting glass substrates. The films uniformly cover the conducting glass substrates and are composed of free-standing sub-micrometer rods. Subsequently, atomic layer deposition (ALD) was utilized to deposit Co(2+) ions throughout the entire MOF film via self-limiting surface-mediated reaction chemistry. The Co ions bind at aqua and hydroxo sites lining the channels of NU-1000, resulting in three-dimensional arrays of separated Co ions in the MOF thin film. The Co-modified MOF thin films demonstrate promising electrocatalytic activity for water oxidation.


Suppressor of cytokine signaling 3 inhibits breast tumor kinase activation of STAT3.
Breast tumor kinase (Brk) was originally isolated from a human metastatic breast tumor, but also is found expressed in other epithelial tumors and in a subset of normal epithelia. Brk is a tyrosine kinase and its expression in breast carcinoma has been linked to tumor progression. The signal transducer and activator of transcription 3 (STAT3) is one of the substrate targets of Brk, and elevated tyrosine phosphorylation of STAT3 is known to contribute to oncogenesis. Conventional activation of STAT3 occurs in response to cytokine stimulation of Janus tyrosine kinases (JAK). One of the negative regulators discovered in cytokine signaling of the JAK-STAT pathway is the suppressor of cytokine signaling 3 (SOCS3). In this report we describe the finding that SOCS3 can also inhibit the unconventional target, Brk. Investigation of the mechanism by which SOCS3 inhibits Brk reveals the SOCS3 protein binds to Brk primarily via its SH2 domain, and its main inhibitory effect is mediated by the SOCS3 kinase inhibitory region (KIR). SOCS3 has only a modest effect on promoting Brk degradation, and this requires the C-terminal SOCS box domain. SOCS3 is the only known inhibitor of Brk, and knowledge of the mechanisms by which SOCS3 inhibits Brk may lead to methods that block Brk in cancer progression.


Keratinocytes cultured from patients with Hailey-Hailey disease and Darier disease display distinct patterns of calcium regulation.
Hailey-Hailey disease (HHD) (OMIM 16960) and Darier disease (DD) (OMIM 124200) are dominantly inherited acantholytic skin diseases, respectively, caused by mutations in the genes encoding the Golgi secretory pathway Ca2+-ATPase (SPCA1, ATP2C1) and the sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2, ATP2A2) genes. To investigate calcium regulation in keratinocytes cultured from patients with HHD and DD by measuring intracellular calcium resting levels and the cellular responses to ATP and thapsigargin. The study was carried out using keratinocyte cultures established from four patients with HHD and four with DD. Calcium concentrations were measured with fluorescence ratio imaging using fura-2 loading. Control and HHD keratinocytes displayed approximately the same Ca2+ levels in resting phase, while DD keratinocytes showed elevated Ca2+ levels. Application of ATP caused less pronounced elevation of intracellular calcium concentration ([Ca2+]i) in both HHD and DD keratinocytes than in control cells. HHD keratinocytes did not lower their [Ca2+]i as efficiently as control keratinocytes after treatment with thapsigargin. In addition, DD keratinocytes were practically incapable of lowering their [Ca2+]i after treatment with thapsigargin. The results demonstrate that the defects in SPCA1 and SERCA2 calcium ATPases result in distinct patterns of calcium metabolism. This is also supported by the different clinical features of the diseases.


Paediatric heart transplantation during the COVID-19 pandemic in Iran: single-centre experience.
Transplant services were imposed to the multiple challenges of insufficient facilities and resources during the COVID-19 pandemic. Thus, each centre modified and altered its routine practice to maintain the service. We report our experience in Iran's single-centre paediatric heart transplantation unit during the 2 year pandemic in transplant rate and early transplant outcomes. We retrospectively reviewed all paediatric heart transplants performed at our centre between 19 February 2020 and February 2022. We studied the number and percentage of paediatric transplanted patients who developed COVID-19, in-hospital outcome, 30 day survival and left ventricular function during the first month of the follow-up visit. From February 2020 to February 2022, 59 transplants were performed compared with 62 patients from February 2018 to 2020. Compared with the year before the pandemic, the heart transplant rate was reduced by 34% in the first year of the pandemic; however, it bounced back in the second year with a 19% increase. The in-hospital mortality rate during the 2 year pandemic was (11.8%). One death occurred related to COVID-19 acute respiratory distress syndrome. The in-hospital COVID-19 infection rate was 11 patients (18%). In the 30 day follow-up, the overall 30 day survival rate was 88%, and the 30 day rejection rate was 10%. The mean left ventricular ejection fraction was (53.6 ± 4.9), the mean left ventricular global longitudinal strain was -16.9 ± 3.3, and the mean right ventricular global longitudinal strain was -17.0 ± 3.8 with no significant difference between patients with in-hospital COVID and other recipients (P = 0.1, P = 0.2 and P = 0.2). Throughout the pandemic, although we experienced a reduction in the transplant rate in the first year, with the increasing vaccination rate in health care and later in the general population, we continued to maintain our transplant rate by incorporating safety protocols and more resources.


Imaging and surgical approach for a schwannoma of the hand.
Schwannomas are benign encapsulated neoplasms of the peripheral nerve sheath. Clinical diagnosis is often difficult, and final diagnosis is usually based on histopathological findings. Imaging techniques, such as magnetic resonance imaging and ultrasonography, can be optimized to improve assessment prior to surgical treatment. The present case demonstrates that high-resolution sonography can be useful in assessing the underlying cause of median nerve pathology.


Neural substrates of intermanual transfer of a newly acquired motor skill.
In healthy humans, the two cerebral hemispheres show functional specialization to a degree unmatched in other animals, and such strong hemispheric specialization contributes to unimanual skill acquisition [1, 2]. When most humans learn a new motor skill with one hand, this process results in performance improvements in the opposite hand as well [3-6]. Despite the obvious adaptive advantage of such intermanual transfer, there is no direct evidence identifying the neural substrates of this form of skill acquisition [7-9]. Here, we used functional magnetic resonance imaging (fMRI) to study brain regions activated during intermanual transfer of a learned sequence of finger movements. First, we found that the supplementary motor area (SMA) has more activity when a skill has transferred well than when it has transferred poorly. Second, we found that fMRI activity in the ventrolateral posterior thalamic nucleus correlated with successful future intermanual transfer, whereas activity in the ventrolateral anterior thalamic nucleus correlated with past intermanual transfer. Third, we found that repetitive transcranial magnetic stimulation applied over the SMA blocked intermanual transfer without affecting skill acquisition. These findings provide direct evidence for an SMA-based mechanism that supports intermanual transfer of motor-skill learning.


Review of the scientific evidence to support environmental risk assessment of shale gas development in the UK.
Interest in the development of shale gas resources using hydraulic fracturing techniques is increasing worldwide despite concerns about the environmental risks associated with this activity. In the United Kingdom (UK), early attempts to hydraulically fracture a shale gas well resulted in a seismic event that led to the suspension of all hydraulic fracturing operations. In response to this occurrence, UK regulators have requested that future shale gas operations that use hydraulic fracturing should be accompanied by a high-level environmental risk assessment (ERA). Completion of an ERA can demonstrate competency, communicate understanding, and ultimately build trust that environmental risks are being managed properly, however, this assessment requires a scientific evidence base. In this paper we discuss how the ERA became a preferred assessment technique to understand the risks related to shale gas development in the UK, and how it can be used to communicate information between stakeholders. We also provide a review of the evidence base that describes the environmental risks related to shale gas operations, which could be used to support an ERA. Finally, we conclude with an update of the current environmental risks associated with shale gas development in the UK and present recommendations for further research.


[Inhalational exposure to rapidly eliminated substances: possibility and strategies for biological monitoring. A proposal for the use of biological limits equivalent to environmental limits].
Some advantages of biological compared with environmental monitoring and some preparatory steps and difficulties to be overcome during the planning of a biological monitoring program are firstly discussed. Then the biological compartments, their peculiarities and their use in the field of biological monitoring are described. The problem concerning the biological thresholds of the reference normal values and the biological limits corresponding to environmental limits (biological equivalent limits, BEL) is the next topic, followed by the description of the methods for measuring the BELs (in case of linear regression between biological and environmental values) and of the methods for the upper and lower confidence limits (UCL, LCL) of a biological value. They are to be used for a decision of compliance or noncompliance biological exposure. Finally some ways of using biological UCL-LCL and variation coefficients during cross-sectional and longitudinal studies (biological monitoring strategies) are shown.


Significance of barrier membrane on the reconstructive therapy of peri-implantitis: A randomized controlled trial.
The objective of this trial was to investigate the clinical and radiographic significance of using a mixture of mineralized and demineralized allografts in combination (M) or not (NM) with a resorbable cross-linked barrier membrane in the reconstructive therapy of peri-implantitis defects. A two-arm randomized clinical trial was performed in patients diagnosed with peri-implantitis that exhibited contained defects. Clinical parameters were recorded at baseline (T0 ), 6 months (T1 ), and 12 months (T2 ). Radiographic parameters were recorded at T0 and T2 . A composite criterion for disease resolution was defined a priori. A generalized linear model of repeated measures with generalized estimation equation statistical methods was used. Overall, 33 patients (nimplants = 48) completed the study. At T2 , mean disease resolution was 77.1%. The use of a barrier membrane did not enhance the probability of disease resolution at T2 (odds ratio [OR] = 1.55, p = 0.737). Conversely, the odds of disease resolution were statistically associated with the modified plaque index recorded at T0 (OR = 0.13, p = 0.006) and keratinized mucosa width (OR = 2.10, p = 0.035). Moreover, women exhibited greater odds to show disease resolution (OR = 5.56, p = 0.02). Reconstructive therapy by means of a mixture of mineralized and demineralized allografts is effective in clinically resolving peri-implantitis and in gaining radiographic marginal bone level. The addition of a barrier membrane to reconstructive therapy of peri-implantitis does not seem to enhance the outcomes of contained bone defects (NCT05282667).


Manipulation of epitope function by modification of peptide structure: a minireview.
We have explored various approaches to modify the immunrecognition of linear peptides representing sequential or continuous topographic B-cell or T-cell epitopes. For these studies, epitopes from herpes simplex virus (HSV) glycoprotein D (gD) and from mucin 1 and mucin 2 glycoproteins or T-cell epitopes from 16 kDa and 38 kDa proteins of Mycobacterium tuberculosis were selected. To increase antigenicity and immunogenicity we have prepared cyclic and chimaeric peptide variants as well as epitope peptides with altered flanking regions and epitope-carrier conjugates containing multiple epitope copies.


Metabolic linkages between zinc exposure and lung cancer risk: A nested case-control study.
Epidemiologic studies have suggested that elevated concentrations of zinc are associated with a decreased risk of lung cancer, but the underlying mechanisms remain to be investigated. The metabolites are highly sensitive to environmental stress, which will help to reveal the linkages between zinc exposure and lung cancer risk. We designed a nested case-control study including 101 incident lung cancer cases and 1:2 age- and sex-frequency-matched 202 healthy controls from the Dongfeng-Tongji (DFTJ) cohort. Their plasma level of zinc was determined by using inductively coupled plasma-mass spectrometry (ICP-MS) and plasma profiles of metabolites were detected by using an untargeted metabolomics approach. The generalized linear models (GLM) were applied to assess the associations of plasma zinc with metabolites, and the mediation effects of zinc-related metabolites on zinc-lung cancer association were further testified. The concentrations of 55 metabolites had linear dose-response relationships with plasma zinc at a false discovery rate (FDR) < 0.05, among which L-proline, phosphatidylcholine (PC, 34:2), phosphatidylethanolamine (PE, O-36:5), L-altrose, and sphingomyelin (SM, 40:3) showed different levels between lung cancer cases and healthy controls (fold change = 0.92, 0.95, 1.07, 0.90, and 1.08, respectively, and all P < 0.05). The plasma concentration of SM(40:3) was negatively associated with incident risk of lung cancer [OR(95%CI) = 0.71(0.55, 0.91), P = 0.007] and could mediate 41.7% of the association between zinc and lung cancer risk (P = 0.004). Moreover, compared to the traditional factors, addition of SM(40:3) exerted improved prediction performance for incident risk of lung cancer [AUC(95%CIs) = 0.714(0.654, 0.775) vs. 0.663(0.600, 0.727), P = 0.030]. Our findings revealed metabolic profiles with zinc exposure and provide new insight into the alternations of metabolites underpinning the links between zinc exposure and lung cancer development.


Disposable terbium (III) salicylate complex imprinted membrane using solid phase surface fluorescence method for fast separation and detection of salicylic acid in pharmaceuticals and human urine.
In this work, a simple, low cost, selective and sensitive complex imprinted membrane (CIM) for solid-phase fluorescent detection was developed with terbium (III) salicylate as complex template. Terbium-sensitized luminescence was employed for monitoring salicylic acid (SA) based on the fluorescence enhancement effect of benzoic acid derivatives on lanthanide ion Tb (III). The resulting CIM showed good fluorescent response and high selectivity towards SA with Tb as pivot in protic solvents, while demonstrating better analytical performance than the controlled membranes. The optimized adsorption time was 10 min, indicating rapid kinetics of the imprinted membrane. The linear response of CIM to SA was from 0.20 to 10mg/L with limit of detection (LOD) of 0.040 mg/L. The prepared CIM was successfully applied to the analysis of salicylic acid in pharmaceuticals and spiked human urine with recoveries of 80.6%-88.1%. The analytical results of the proposed method were in good agreement with those obtained by high performance liquid chromatography (HPLC) method, indicating that the developed membrane has acceptable practicability for fast determination of SA in real samples.


The outcome of initial endoscopic treatment in the management of concomitant vesicoureteral reflux and ureteropelvic junction obstruction.
To report the results of a single-center experience with the endoscopic injection of Deflux as the initial minimally invasive approach in patients with vesicoureteral reflux (VUR) and coexisting obstruction at the ureteropelvic junction (UPJO) level who presented with VUR. Between May 2004 and July 2011, 2810 children with a diagnosis of VUR were referred to our center; 143 (5%) had concomitant UPJO. On the basis of the study inclusion criteria, 76 were included. All patients received antibiotic therapy. VUR and UPJO resolved in 50 children without the need for further intervention, and 26 underwent endoscopic Deflux injection by applying the hydrodistention autologous blood injection technique (HABIT). All patients received antibiotic prophylaxis until resolution of VUR was confirmed on voiding cystourethrogram (VCUG). Patients underwent follow-up visits at 1, 6, and 12 months postoperatively. At a mean follow up of 20.0 ± 1.6 months, 20 of those with concomitancy showed resolution of VUR and the coexisting UPJO after the first injection (success rate, 76.9%), and 2 resolved after the second injection, leading to an overall success rate of 84.6%. Finally, 3 patients required further ureteral reimplantation, and 3 underwent pyeloplasty for correction of UPJO by applying miniature pyeloplasty technique. Differential renal function was preserved in all patients. Performing an initial endoscopic injection of Deflux in the management of concomitant VUR and UPJO provides promising results in terms of spontaneous resolution of obstruction at the UPJ level and complete resolution or decrease in hydronephrosis.


Lipid-lowering therapy: Guidelines to precision medicine.
Dyslipidemia is correlated with a series of health problems, such as obesity, insulin resistance, and the development of cardiovascular disease (CVD). Currently, accumulating evidence sheds light on the fact that β-hydroxy β-methylglutaryl-CoA reductase inhibitors, named statins, could lower circulating lipid-density lipoprotein cholesterol (LDL-C) and represent a revolution for the prevention of metabolic disorder diseases. In addition, statins remain the cornerstone of LDL-C-lowering treatments, together with ezetimibe and bile acid sequestrants, which are used either in combination with statins or as monotherapies in the case of statin intolerance or side effects. On the other hand, other medicines that reduce circulating LDL-C have also been researched, including inhibitors of protein convertase subtilisin/kexin type 9 (PCSK9). More recently, PCSK9 inhibitors have been approved for the secondary prevention of CVD and for the atherogenic dyslipidemia therapy. Here, we summarize the latest guidelines for the management of dyslipidemia and its relation to CVD, focusing on LDL-C-lowering medicines that are either available in daily clinical practice or under investigation. In addition, we also discuss the "who, when, and how" with respect to treating patients with dyslipidemia according to LDL-C reduction as an individualized clinical precision medicine.


Sarcopenia in community-dwelling persons over 60 years of age from a northern spanish city: relationship between diagnostic criteria and association with the functional performance.
Sarcopenia is a recognized problem in older people. Currently, its diagnosis goes beyond a simple loss of muscle mass. The aim of this study was to determine the frequency of sarcopenia, defined by the European Working Group on Sarcopenia in Older People (EWGSOP), in independent persons over 60 years of age from a northern Spanish city. In addition, this study compared the diagnostic criteria for sarcopenia and assessed the differences in functional performance according to them. A cross-sectional study was carried out on 258 members of community centers of both genders. Body composition was assessed with dual-energy X-ray absorptiometry. Appendicular lean mass index (App LMI), hand grip strength (HGS), and 8 foot up-and-go test (8f-UG) were used to diagnose sarcopenia. The frequency of sarcopenia was 2.4% (n=6). In women, the App LMI was correlated with HGS (r= 0.164, p<0.05) and 8f–UG (r= -0.167, p<0.05), while in men, the App LMI was correlated with HGS (r=0.241, p<0.05) but not with 8f–UG (r= -0.173, p=0.117). The subjects with low HGS and low performance in the 8f–UG presented lower values in other functional outcomes than people with low App LMI (p<0.05). Using the EWGSOP definition, the frequency of sarcopenia was low in a group of individuals over 60 years of age from a northern Spanish city. In clinical practice, greater emphasis should be placed on the decrease in muscle strength and functional performance rather than on low muscle mass alone.


Horizontal distribution of surface microplastic concentrations and water-column microplastic inventories in the Chukchi Sea, western Arctic Ocean.
The recent influx of microplastics into the Arctic Ocean may increase environmental stress on the western Arctic marine ecosystem, which is experiencing significant sea-ice loss due to global warming. Quantitative data on microplastics in the western Arctic Ocean are very limited, and the microplastic budget of the water column is completely unknown. To fill in gaps in our knowledge of Arctic microplastics, we observed surface concentrations (number of particles per unit volume of seawater) of meso- and microplastics using a neuston net, and we observed wind speeds and significant wave heights in the Chukchi Sea, Bering Strait, and Bering Sea. From these observations, we estimated the total number (particle inventory) and mass (mass inventory) of microplastics in the entire water column by taking into account the effect of vertical mixing. The particle inventory of microplastics in the Chukchi Sea ranged from 0 to 18,815 pieces km-2 with a mean and standard deviation of 5236 ± 6127 pieces km-2. The mass inventory ranged from 0 to 445 g km-2 with a mean and standard deviation of 124 ± 145 g km-2. Mean particle inventories for the Chukchi Sea were one-thirtieth of those for the Arctic Ocean on the Atlantic side and less than one-tenth of the average for the global ocean, suggesting that the Chukchi Sea is less polluted. However, the annual flux of microplastics from the Pacific Ocean into the Chukchi Sea, estimated from microplastic concentrations in the Bering Strait, was about 5.5 times greater than the total amount of microplastic in the entire Chukchi Sea water. This suggests that microplastic inflows from the Pacific Ocean are accumulating in large amounts in reservoirs other than the Chukchi Sea water (e.g., sea ice and seafloor sediments) or in the downstream regions of the Pacific-origin water.


[Comparative study of arthroscopic and open meniscus surgery].
In this paper we compared two groups of 80 patients each with meniscal tears. One group was treated by Arthrotomie and partial meniscectomie and the other group by an arthroscopic procedure also with partial meniscectomie. All patients were seen at a follow up between six and 18 months postoperatively. According to the Gaudernak scale we found in both groups 98% of very good and good results. The duration of hospitalisation and sickleave was reduced by 50% after the arthroscopic operation, which showed a significant difference.


Successful localization of parathyroid adenomas by magnetic resonance imaging.
Exploration of the neck for primary hyperparathyroidism is facilitated if the parathyroid glands can be localized preoperatively. Magnetic resonance imaging is a noninvasive and relatively safe procedure that is capable of distinguishing and differentiating small soft-tissue structures. Ten patients with primary hyperparathyroidism underwent preoperative diagnostic magnetic resonance imaging followed by cervical exploration. In 9 of these patients (90 percent), imaging correctly predicted the location of a single enlarged parathyroid gland, and in one patient the findings were misleading. All 10 patients proved to have single adenomas in orthotopic locations. Based on this early experience, magnetic resonance imaging appears to be a promising technique for preoperative localization of an enlarged parathyroid gland.


Endometrial resection/vaporization: a patient-friendly first-option treatment for menorrhagia in rural areas.
Hysterectomy, a major surgical procedure, is often an unacceptable procedure for many patients from rural areas who attend small rural hospitals. Near total endometrial resection/vaporization is a more acceptable procedure which can control menorrhagia. This procedure can be carried out with standard urology instruments.


Benzodioxane-Benzamides as Antibacterial Agents: Computational and SAR Studies to Evaluate the Influence of the 7-Substitution in FtsZ Interaction.
FtsZ is a crucial prokaryotic protein involved in bacterial cell replication. It recently arose as a promising target in the search for antimicrobial agents able to fight antimicrobial resistance. In this work, going on with our structure-activity relationship (SAR) study, we developed variously 7-substituted 1,4-benzodioxane compounds, linked to the 2,6-difluorobenzamide by a methylenoxy bridge. Compounds exhibit promising antibacterial activities not only against multidrug-resistant Staphylococcus aureus, but also on mutated Escherichia coli strains, thus enlarging their spectrum of action toward Gram-negative bacteria as well. Computational studies elucidated, through a validated FtsZ binding protocol, the structural features of new promising derivatives as FtsZ inhibitors.


Predictors of eustachian tube dysfunction improvement and normalization after endoscopic sinus surgery.
Studies have demonstrated improvement in Eustachian tube dysfunction (ETD) symptomatology after functional endoscopic sinus surgery (FESS); however, factors associated with ETD symptom alteration have not been elucidated. This study evaluated factors associated with improvement and normalization of ETD symptoms after FESS. A case-control study was performed of FESS patients who had clinically significant ETD symptoms based on the Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7 ≥ 2.1) without middle ear effusion (MEE) preoperatively. Study patients were identified as those with a normalized ETDQ-7 at 2 months postoperatively. Controls were patients whose ETDQ-7 did not normalize at 2 months. Demographics, surgery characteristics, chronic rhinosinusitis phenotype, Lund-Mackay score, temporomandibular joint dysfunction (TMJD), preoperative ETDQ-7 and SNOT-22 scores, and tympanograms were analyzed. Univariate and multivariate analyses were performed comparing study cases and controls. Data were collected on 165 patients, with 46% patients having clinically significant preoperative ETD and 60 patients meeting final study inclusion/exclusion criteria. FESS was associated with both SNOT-22 and ETDQ-7 improvement (P < 0.001). Nasal polyposis was associated with a higher probability of ETDQ-7 normalization (OR 4.429, P = 0.035). Factors associated with failure of ETDQ-7 normalization included TMJD (OR 0.086, P < 0.001, 95% CI 0.019-0.391) and high preoperative ETDQ-7 (OR 0.140, P = 0.006, 95% CI 0.032-0.613). In patients with clinically significant ETD symptoms without MEE, FESS was associated with ETDQ-7 improvement. Nasal polyposis was associated with an increased probability of normalization of ETD symptoms postoperatively, whereas TMJD had a negative association. 3b Laryngoscope, 2019.


The effects of combinatorial treatments with stress inducing molecules on growth of E. coli colonies.
Stress inducing molecules affect both the mean behavior of bacterial growth and also variations in the growth. While the mechanisms that cause changes in the mean behavior are well understood, little is known about changes in the variation of the population. A true understanding of how organisms respond to stress must include an understanding of the mechanisms and purposes of changes in variation and the distribution not directly related to changes in the mean of the population. We have explored the results of combinatorial treatments using EDTA, copper sulfate, hydrogen peroxide, and hydrochloric acid as stress inducing molecules on bacterial colony formation and area on LB-agar plates. Three different combinations of X-gal and IPTG were used to create different background conditions. Some treatments alter the variation and/or the distribution of the area without having a significant effect on the mean, others affect the mean without altering the distribution, and yet others affect distribution and the mean.


Towards REPO4 nanocrystal-doped optical fibers for distributed sensing applications.
Rayleigh scattering enhanced nanoparticle-doped optical fibers, for distributed sensing applications, is a new technology that offers unique advantages to optical fiber community. However, the existing fabrication technology, based on in situ grown alkaline earth nanoparticles, is restricted to few compositions and exhibit a great dependence on many experimental conditions. Moreover, there is still several uncertainties about the effect of drawing process on the nanoparticle characteristics and its influence on the scattering enhancement and the induced optical loss. In this work, we shed light on all these issues that prevent the progress in the field and demonstrate the suitability of doping optical fibers with YPO4 nanocrystals for developing tunable Rayleigh scattering enhanced nanoparticle-doped optical fibers. An exhaustive 3D microstructural study reveals that their features are closely linked to the fiber drawing process, which allow the size and shape engineering at the nanoscale. In particular, the YPO4 nanocrystals preserve their features to a large extent when the optical fibers are drawn below 1950 °C, which allows obtaining homogeneous nanocrystal features and optical performance. Fabricated fibers exhibit a tunable enhanced backscattering in the range of 15.3-54.3 dB, with respect to a SMF-28 fiber, and two-way optical losses in the range 0.3-160.7 dB/m, revealed by Optical Backscatter Reflectometry (OBR) measurements. This allows sensing lengths from 0.3 m up to more than 58 m. The present work suggests a bright future of YPO4 nanocrystals for distributed sensing field and open a new gate towards the incorporation of other rare-earth orthophosphate (REPO4) nanocrystals with pre-defined characteristics that will overcome the limitations of the current in situ grown alkaline earth-based technology.


Syntheses and biological activities of azido ubiquinone derivatives.
A general method for the synthesis of azido-ubiquinone derivatives has been developed directly by substituting one hydrogen atom on the benzoquinone ring with an azido group under weakly acidic conditions. The reaction takes several hours and the yield is generally low. The azido-ubiquinone was purified by preparative thin layer chromatography, and identified by NMR, IR and mass spectra. All the synthesized azido-ubiquinone derivatives show partial activity in mediating biological electron transfer in the dark, and show partial or complete inhibition upon photolysis.


The MNI data-sharing and processing ecosystem.
Neuroimaging has been facing a data deluge characterized by the exponential growth of both raw and processed data. As a result, mining the massive quantities of digital data collected in these studies offers unprecedented opportunities and has become paramount for today's research. As the neuroimaging community enters the world of "Big Data", there has been a concerted push for enhanced sharing initiatives, whether within a multisite study, across studies, or federated and shared publicly. This article will focus on the database and processing ecosystem developed at the Montreal Neurological Institute (MNI) to support multicenter data acquisition both nationally and internationally, create database repositories, facilitate data-sharing initiatives, and leverage existing software toolkits for large-scale data processing.


The insulin degrading enzyme activates ubiquitin and promotes the formation of K48 and K63 diubiquitin.
We report an ATP-dependent ubiquitin conjugation with IDE which, in turn, promotes Ub-Ub linkages in tube tests. We propose a novel function for IDE as a non-canonical ubiquitin activating enzyme.


Effects of indapamide on endothelium-dependent relaxations in isolated canine femoral arteries.
Indapamide is an effective antihypertensive agent in humans and in experimental hypertensive animals. The aim of the present study was to investigate whether indapamide affects endothelium-dependent and independent relaxations in canine femoral arteries. Rings (with or without endothelium) were contracted with prostaglandin F2 alpha (2 X 10(-6) mol/liter) before the addition, in a cumulative fashion, of relaxing agents. Indapamide (10(-7) to 10(-4) mol/liter) had no direct effect on unstimulated or prostaglandin-stimulated preparations; it did not alter relaxations of preparations with endothelium induced by acetylcholine, bradykinin, adenosine diphosphate or the calcium ionophore A23187. Similarly, it did not affect relaxations induced by sodium nitroprusside, prostacyclin or forskolin in preparations with or without endothelium. Indomethacin shifted the concentration-response curve to bradykinin to the right and did not alter that to the other relaxing drugs. The reduced relaxation to bradykinin was reversed in a concentration-dependent manner by indapamide (10(-7) to 10(-5) mol/liter). In the presence of indomethacin, indapamide shifted the concentration response curve to prostacyclin (in rings with endothelium) and to forskolin (in rings with and without endothelium) to the left. Thus, indapamide does not directly affect endothelium-dependent and independent relaxations. However, when prostanoid production is impaired, indapamide facilitates the release of endothelium-derived relaxing factor(s), and to a lesser extent, the direct action on vascular smooth muscle of prostanoids (prostacyclin) released from the endothelium.


Investigating the properties of bio-chemical networks of artificial organisms with opposing behaviours.
Organisms, be it singled-celled organisms or multi-cellular organisms, are constantly faced with opposing objectives requiring different sets of behaviours. These behaviours can be classified into two, predatory behaviours or anti-prey behaviours, with one set of behaviours causing an opposite effect to the other. A healthy organism aims to achieve its equilibrium state or to be in homeostasis. Homeostasis is achieved when a balance between the two opposing behaviours is created and maintained. This raises some questions: is there an innate mechanism that encodes for these categories of behaviours? Is there also an innate mechanism(s) that resolves conflicts and allows switching between these two opposing behaviours? If we consider artificial organisms as single-celled organisms, how do the organisms' gene regulatory network, metabolic network and/or signalling network (their biochemical networks) maintain homeostasis of the organisms? This paper investigates the properties of the networks of best evolved artificial organisms, in order to help answer these questions, and guide the evolutionary development of controllers for artificial systems.


Post-migration screening for active tuberculosis in Victoria, Australia.
Tuberculosis (TB) screening clinic. To determine TB prevalence at entry, screening yield and incidence in immigrants on a TB health undertaking (TBU) who were selected for post-migration screening due to an abnormal chest radiograph (CXR) in Victoria, Australia, in the years 1996-2006. Rates of notified TB calculated from linkage of a screening programme database with the Victorian TB database. Prevalence at entry (cases notified between arrival in Australia and 6 months after the screening registration date) was 505 per 100,000 population; yield at entry (prevalent cases detected by the screening programme) was 420/100,000, and incidence (cases notified between 6 and 12 months after screening registration date) was 160/100,000 person-years. Persons issued a TBU after applying from within Australia (on-shore) had a prevalence of 1876/100,000, seven-fold higher than those issued a TBU outside Australia (off-shore, 254/100,000). The combination of an abnormal CXR and a tuberculin skin test ≥ 15 mm carried a prevalence of notified TB of 2907/100,000. Selective post-migration screening can achieve a high yield of notified TB.


Structural views of quinone oxidoreductase from Mycobacterium tuberculosis reveal large conformational changes induced by the co-factor.
Energy generation, synthesis of biomass and detoxification of synthetic compounds are driven by electron transfer in all living organisms. Soluble quinone oxidoreductases (QORs) catalyze transfer of electrons from NADPH to substrates. The open reading frame Rv1454c of Mycobacterium tuberculosis (Mtb) encodes a NADPH-dependent QOR that is known to catalyze one-electron reduction of quinones to produce semiquinones. Here, we report the crystal structures of the apo-enzyme of MtbQOR and its binary complex with NADPH determined at 1.80 and 1.85 Å resolutions, respectively. The enzyme is bi-modular. Domain I binds the substrate, while domain II folds into a typical Rossmann fold for tethering NADPH. Binding of NADPH induces conformational changes. Among the known structures of QORs, MtbQOR exhibits the largest conformational change. Movement of Phe41 to stack against Ala244 results in partial closure of the active site. Comparison of the structure with homologs suggests a conserved topology. However, differences are observed in the region around the site of hydride transfer, highlighting differences in substrate specificities amongst the homologs. Unliganded as well as NADPH-bound MtbQOR crystallized as a dimer. Dimerization is mediated by homotypic intermolecular interactions involving main chain Cα as well as side-chain atoms of residues. The results of analytical ultracentrifugation analysis revealed that MtbQOR exists as a dimer in solution. Enzymatic assays indicate that MtbQOR prefers 9,10-phenanthrenequinone over 1,4-benzoquinone as a substrate. The ability to reduce quinones probably assists Mtb in detoxification of a range of harmful chemicals encountered in the host during invasion. The coordinates and structure factors for apo- and NADPH-bound MtbQOR have been deposited in the Protein Data Bank under accession codes 4RVS and 4RVU, respectively.


PDE4 regulates tissue plasminogen activator expression of human brain microvascular endothelial cells.
Factors regulating brain tissue plasminogen activator (tPA) are pertinent for stroke. Recent observations have suggested a role for the phosphodiesterase-4 (PDE4) pathway in stroke pathogenesis, via an uncertain mechanism. We studied PDE4 regulation of tPA expression by human brain microvascular endothelial cells in a variety of conditions, including an in vitro model of ischemia. We analyzed tPA antigen and mRNA of human brain microvascular endothelial cells (HBECs) during normoxia and oxygen-glucose deprivation (OGD) following inhibition of PDE4 and PDE4D, using HBEC monocultures and co-cultures with astrocytes and pericytes, and analyzed relevant signal transduction pathways. PDE4 inhibitor rolipram enhanced OGD effects on endothelial tPA release in endothelial monocultures and co-cultures with astrocytes; there was a 54±10% (p<0.001) reduction of tPA release in astrocyte-endothelial co-cultures under OGD. PDE4D siRNA reduced endothelial tPA mRNA to 40-55% of control (p<0.05). Use of Epac inducer mimicked, while use of Epac siRNA inhibited, these effects. Inhibition of PDE4 and PDE4D reduced expression of tPA by HBEC via Epac pathway.


The pathogenesis of obstetric APS: a 2023 update.
The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the persistent presence of antibodies directed against phospholipids and phospholipid-binding proteins that are associated with thrombosis and pregnancy-related morbidity. The latter includes fetal deaths, premature birth and maternal complications. In the early 1990s, a distinct set of autoantibodies, termed collectively antiphospholipid antibodies (aPL), were identified as the causative agents of this disorder. Subsequently histological analyses of the placenta from APS pregnancies revealed various abnormalities, including inflammation at maternal-fetal interface and poor placentation manifested by reduced trophoblast invasion and limited uterine spiral artery remodeling. Further preclinical investigations identified the molecular targets of aPL and the downstream intracellular pathways of key placental cell types. While these discoveries suggest potential therapeutics for this disorder, definitive clinical trials have not been completed. This concise review focuses on the recent developments in the field of basic and translational research pursuing novel mechanisms underlying obstetric APS.


Imaging exams of bone lesions in patients with diffuse cutaneous leishmaniasis (DCL).
We studied bone lesion alterations in three patients with diffuse cutaneous leishmaniasis (DCL) by imaging exams (radiography and scintigraphy) and histopathology. Two patients had bone lesions of distal extremities of hands and feet, and one infiltrating plaques in the skin. The study was conducted at three specialized centers (Presidente Dutra Hospital/Nucleus of Tropical Pathology, UFMA-MA; Gonçalo Moniz Research Center-FIOCRUZ-BA; Laboratory of Pathology of Infectious Diseases (LIM-50), University of São Paulo, SP). Three-phase bone scintigraphy demonstrated high sensitivity and specificity for bone lesions, showing increased uptake of the radiopharmaceutical at sites of active lesions. In contrast, radiography demonstrated lytic lesions, cortical destruction and local osteopenia of the bone extremeties in two patients. Histopathological analysis showed sequestration with presence of amastigote forms of Leishmania (osteomyelitis), mononuclear cells and macrophages containing amastigote forms of Leishmania in one patient. These preliminary data indicate that imaging exams (radiography and scintigraphy) are important in the evaluation of bone lesions in diffuse cutaneous leishmaniasis and should be included in the routine histopathological diagnosis of the disease and follow-up of bone lesions.


Inhibitory effect of FK506 and cyclosporine A on the growth and invasion of human liver cancer cells.
The prognosis of liver transplantation for liver cancer is determined by recurrence in the liver graft. In this study, the effects of immunosuppressors, FK506 and cyclosporine A (CsA) on the migration of liver cancer cells were investigated. The effects of FK506 at concentrations of 1-100 ng/mL and CsA at 1-1000 ng/mL on the growth of poorly and well differentiated human hepatocellular carcinoma cell lines, HLE and HuH-7, respectively, were examined. After treatment of these cells with FK506 and CsA, the growth of these cells, their cytotoxicities and invasion assay on the Matrigel basement membrane invasion chamber were evaluated. In addition, the effects of FK506 and CsA on the changes in the production of a soluble intercellular adhesion molecule-1 (sICAM-1) of these cells were measured. FK506 and CsA at concentrations of 1-10 ng/mL inhibited the growth of both HLE and HuH-7 and those immunosuppressors at concentrations over 100 ng/mL exhibited cytotoxicity on these cells. FK506 at concentration of 1 ng/mL significantly inhibited the invasion of poorly differentiated HLE, but not well differentiated HuH-7, after treatment for 2-5 days in culture (p<0.05), but FK 506 at 10 ng/mL showed less inhibitory efficient. CsA at concentrations of 1-10 ng/mL, however, did not inhibit or transiently inhibited the invasion of both cell lines. The production of ICAM-1 in HLE and HuH-7 was suppressed by FK506 at concentrations of 1-10 ng/mL after treatment for 3-5 days but the effect was not significant in the initial phase at days 1-2 and the last phase at days 5-6. FK506, but not CsA, at a clinical dose of 1 ng/mL significantly inhibited the invasion of the poorly-differentiated HLE, but not HuH-7 and also inhibited the production of sICAM-1 in HLE.


Plasmid profiles of value in differentiating Salmonella muenster isolates.
Strains of Salmonella muenster displaying identical antibiotic susceptibility and bacteriophage reaction patterns were found to differ in their complements of plasmid DNA. Plasmid profiles were used to separate 40 isolates from diverse sources into four distinct groups, one of which contained 30 strains without plasmids.


Low-density lipoprotein subfractions and the prevalence of silent lacunar infarction in subjects with essential hypertension.
Recent lipid research has focused on low-density lipoprotein (LDL) subfractions as new markers for cardiovascular risk. However, the clinical significance of measurement of LDL subfractions in subjects with essential hypertension is yet to be established. We studied the association between the prevalence of silent lacunar infarction (SLI) and LDL subfractions in patients with essential hypertension. We performed brain MRI to detect SLI and measured LDL subfractions in 100 asymptomatic non-diabetic middle-aged subjects with essential hypertension (mean age, 62 years). We fractionated LDL into three parts, LDL-1, LDL-2, and LDL-3, with LDL-3 being the oxidized subfraction. Of the 100 study subjects, 24 (24%) had one or more SLIs, while the remaining 76 (76%) were considered as a non-SLI group. The LDL-3 levels were significantly higher in the SLI group than in the non-SLI group (8.3 +/- 4.4 mg/dl vs. 6.3 +/- 2.0 mg/dl, p = 0.006). Multiple logistic regression analysis showed that LDL-3 levels alone were an independent predictor of SLI (odds ratio [OR]: 1.380; 95% confidence interval [CI]: 1.113-1.663; p = 0.003). When subjects were divided into quartiles based on LDL-3 levels, the prevalence of SLI was significantly higher in the highest LDL-3 level group than in the lowest LDL-3 level group (p = 0.0036). The present study suggests that LDL-3 levels are associated with the prevalence of SLI in subjects with essential hypertension.


The Valproic Acid Derivative Valpromide Inhibits Pseudorabies Virus Infection in Swine Epithelial and Mouse Neuroblastoma Cell Lines.
Pseudorabies virus (PRV) infection of swine can produce Aujeszky's disease, which causes neurological, respiratory, and reproductive symptoms, leading to significant economic losses in the swine industry. Although humans are not the natural hosts of PRV, cases of human encephalitis and endophthalmitis caused by PRV infection have been reported between animals and workers. Currently, a lack of specific treatments and the emergence of new PRV strains against which existing vaccines do not protect makes the search for effective antiviral drugs essential. As an alternative to traditional nucleoside analogues such as acyclovir (ACV), we studied the antiviral effect of valpromide (VPD), a compound derived from valproic acid, against PRV infection in the PK15 swine cell line and the neuroblastoma cell line Neuro-2a. First, the cytotoxicity of ACV and VPD in cells was compared, demonstrating that neither compound was cytotoxic at a specific concentration range after 24 h exposure. Furthermore, the lack of direct virucidal effect of VPD outside of an infected cell environment was demonstrated. Finally, VPD was shown to have an antiviral effect on the viral production of two strains of pseudorabies virus (wild type NIA-3 and recombinant PRV-XGF) at the concentrations ranging from 0.5 to 1.5 mM, suggesting that VPD could be a suitable alternative to nucleoside analogues as an antiherpetic drug against Aujeszky's disease.


Management of transient bone osteoporosis: a systematic review.
Transient bone osteoporosis (TBO) is characterized by persistent pain, loss of function, no history of trauma and magnetic resonance image (MRI) findings of bone marrow edema. PubMed, Google scholar, EMABSE and Web of Science were accessed in February 2023. No time constrains were used for the search. TBO is rare and misunderstood, typically affecting women during the third trimester of pregnancy or middle-aged men, leading to functional disability for 4-8 weeks followed by self-resolution of the symptoms. Given the limited evidence in the current literature, consensus on optimal management is lacking. This systematic review investigates current management of TBO. A conservative approach leads to the resolution of symptoms and MRI findings at midterm follow-up. Administration of bisphosphonates might alleviate pain and accelerate both clinical and imaging recovery.


Drosophila dLMO-PA isoform acts as an early activator of achaete/scute proneural expression.
The Drosophila bHLH proneural factors Achaete (Ac) and Scute (Sc) are expressed in clusters of cells (proneural clusters), providing the cells with the potential to develop a neural fate. Mediodorsal proneural patterning is mediated through the GATA transcription factor Pannier (Pnr) that activates ac/sc directly through binding to the dorsocentral (DC) enhancer of ac/sc. Besides, the Gfi transcription factor Senseless (Sens), a target of Ac/Sc, synergizes with ac/sc in the presumptive sensory organ precursors (SOPs). Here we investigate, through new genetic tools, the function of dLMO, the Drosophila LIM only transcription factor that was already known to control wing development. We show that dLMO gene encodes two isoforms, dLMO-RA and dLMO-RB. dLMO null and dLMO-RA(-) deletions have similar phenotypes, lacking thoracic and wing margin sensory organs (SO), while dLMO-RB(-) deletion has normal SOs. At early stages, dLMO-RA is expressed in proneural clusters, however later it is excluded from the SOPs. We found that dLMO functions as a Pnr coactivator to promote ac/sc expression. In the late SOPs, where dLMO-PA is not expressed, Pnr participates to the Sens-dependent regulation of ac/sc. Taken together these results suggest that dLMO-PA is the major isoform that is required for early activation of ac/sc expression.


Combined Arthroscopic Scapulothoracic Bursectomy, Partial Scapulectomy, and Pectoralis Minor Release for the Treatment of Snapping Scapular Syndrome.
Snapping scapula syndrome (SSS) is a source of pain and discomfort in patients. It is not uncommon for patients who present with SSS to have some degree of scapular dysfunction, especially with the tightness of the pectoralis minor (PM) muscle. In this Technical Note, we demonstrate our preferred technique for arthroscopic scapulothoracic bursectomy and partial scapulectomy with concomitant pectoralis minor release for the treatment of symptomatic SSS and PM tightness. In the treatment of these patients, PM release is beneficial because arthroscopic scapulothoracic bursectomy or partial scapulectomy alone may result in residual scapular dyskinesis.


An intriguing case of regular RR and QRS alternans during idiopathic left posterior fascicle ventricular tachycardia.
This study represents a case of idiopathic left posterior fascicle ventricular tachycardia (LPF-VT), which is intriguing due to regular alternation of short-long RR intervals and QRS morphology. Transthoracic echocardiogram analysis did not detect any structural heart disease. A baseline electrophysiological study was performed. Intracardiac recording during tachycardia showed V-A dissociation, confirming the final diagnosis of idiopathic LPF-VT. No regularity in the monomorphic VT was recorded. Previous relevant studies suggested that a single focus with two exits in distal branches of the left posterior fascicle or two different foci localized in the Purkinje-myocardial network of the left posterior fascicle can clarify the mechanisms. Our team proposed an additional explanation that combines the physiological refractory period with the Ashman phenomenon in individual reentrant LPF-VT circuit.


Neonatal exposure to D,L-2-amino-3-phosphonopropionate (D,L-AP3) produces lesions in the eye and optic nerve of adult rats.
Metabotropic glutamate receptors are a recently described receptor class with emerging importance in synaptic plasticity and brain development. Activation of metabotropic glutamate receptors results in several cellular secondary messenger events that are especially important during postnatal development. This study characterized the effects of D,L-2-amino-3-phosphonopropionate (D,L-AP3), an aspartic acid analog with agonist and antagonist activity at the metabotropic receptor, on the postnatal development of the rat eye and optic nerve. Sprague-Dawley rat pups were treated daily (i.p.) with saline or 500 mg/kg D,L-AP3 on postnatal days (PND) 4-10 or 10-14. After making clinical and ophthalmoscopic examinations, rats were necropsied between 65 and 70 days of age and light microscopic evaluations were made of eyes and optic nerves. Between postnatal days 10-20, all treated rats exhibited motor tremors, circling, and head tilt. Ophthalmoscopic lesions were more severe in rats treated on days 4-10 than days 10-14 and included decreased retinal vasculature, cataracts, and retinal dysplasia, hypoplasia, and detachment. All rats treated on days 4-10 had severe optic nerve atrophy/hypoplasia grossly and severe retinal atrophy, retinal detachment, and cataracts histologically. Seven of eight rats treated on days 10-14 had qualitatively similar but less severe lesions. Overall, rats treated with D,L-AP3 on PND 4-10 had earlier and more severe retinal and optic nerve lesions when compared to rats treated on PND 10-14. These data characterize the morphologic effects in adult rats exposed to D,L-AP3 as neonates and suggest a possible role for the metabotropic receptor in the postnatal development of retina and optic nerve.


Breast recurrence and survival related to primary tumor location in patients undergoing conservative surgery and radiation for early-stage breast cancer.
Between 1977 and 1986, 886 pts with Stage I and II breast cancer underwent excisional biopsy, axillary dissection and radiation. Median follow-up was 5 years (range 2 months-13 years). The patients were divided into four groups according to the primary tumor location: 1) outer (495 patients), 2) inner (202 patients), 3) central (119 patients), and 4) subareolar (70 patients). Subareolar tumors were defined as those immediately beneath the nipple-areolar complex or within 2 cm of the areolar margin. The comparability of the groups was assed in terms of clinical T stage, patient age, histology, final pathologic margin status, estrogen and progesterone receptor status, pathologic nodal status, and use of adjuvant chemotherapy. There were no significant differences among the four groups in the distribution of these factors except for the pathologic nodal status (outer 38% positive nodes, inner 24%, central 23%, subareolar 31%) p = .0004. There were no significant differences in 5 year actuarial overall survival (91% vs 86% vs 92% vs 91%, p = .34), relapse-free (75% vs 74% vs 80% vs 79%, p = .77), or NED survival (82% vs 78% vs 87% vs 84%, p = .29) for the four groups. A separate analysis for pathologic node negative and node positive patients revealed similar findings. For node-negative patients, the 5 year actuarial overall survival was 93% vs 88% vs 94% vs 91% (p = .20), the relapse-free survival was 78% vs 76% vs 82% vs 79% (p = .49), and the NED survival was 86% vs 81% vs 88% vs 86% (p = .46). For node-positive patients, the 5 year actuarial overall survival was 87% vs 82% vs 84% vs 90% (p = .59), relapse-free survival was 69% vs 66% vs 77% vs 80% (p = .78), and NED survival was 75% vs 68% vs 85% vs 80% (p = .66). Patterns of first failure were also not significantly different among the four groups: local only first failure (7% vs 4% vs 5% vs 8%, p = .49), any local first failure, i.e., +/- simultaneous distant metastases (8% vs 5% vs 5% vs 9%, p = .61), regional only (2% vs 1% 1% vs 0%, p = .65), any regional (4% vs 3% vs 3% vs 3%), or distant metastases (11% vs 17% vs 9% vs 10%, p = .16). A separate analysis of node negative and node positive patients revealed similar findings.(ABSTRACT TRUNCATED AT 400 WORDS)


MiRNAs in tuberculosis: Their decisive role in the fate of TB.
Tuberculosis (TB) is one of the most lethal global infectious diseases. Despite the availability of much higher levels of technology in health and medicine, tuberculosis still remains a serious global health problem. Mycobacterium tuberculosis has the capacity for prolonged survival inside macrophages by exploiting host metabolic and energy pathways and perturbing autophagy and apoptosis of infected cells. The mechanism(s) underlying this process are not completely understood but evidence suggests that mycobacteria subvert the host miRNA network to enable mycobacterial survival. We present here a comprehensive review on the role of miRNAs in TB immune escape mechanisms and the potential for miRNA-based TB therapeutics. Further validation studies are required to (i) elucidate the precise effect of TB on host miRNAs, (ii) determine the inhibition of mycobacterial burden using miRNA-based therapies and (iii) identify novel miRNA biomarkers that may prove useful in TB diagnosis and treatment monitoring.


The vessels of the stria vascularis: quantitative comparison of three rodent species.
The stria vascularis (SV) was quantitatively compared in three species commonly used in auditory research: guinea pig, mouse and gerbil. Measurements were obtained for surface area, cross-sectional area, length, width and thickness of SV. Surface area and length were proportional to the overall size of the cochlea in each species, but there was no significant difference between species in mean cross-sectional area. In guinea pig and mouse, there was no significant difference in thickness (endolymphatic surface to spiral ligament) and a similar pattern was observed for width (Reissner's membrane to spiral prominence): the width of SV increased from the apical end to a point 80% of the distance from the apex, then decreased to the basal end of SV. The thickness of gerbil SV was significantly less (P less than 0.001) and there was less of a gradient in width as compared to guinea pig and mouse. The vessels of SV were compared in terms of vascular density (vessels per unit area), rbc density (red blood cells per unit area), R/V (rbc density/vascular density), inter-vessel spacing and vessel diameter. Highly significant (P less than 0.001) differences between species were found in vascular density, RBC density and vessel diameter, but there were no differences between species for R/V or inter-vessel spacing. The results of this study may reflect differences in the metabolic requirements of SV among different species.


Salvage of the modified nucleoside ribothymidine in cultured hamster embryo cells.
RNA turnover in hamster embryo cells results in the release of ribothymidine, a methylated nucleoside formed only on intact RNA. [methyl-3H]Methionine ribothymidine polyphosphates and deoxyribothymidine polyphosphates are found in approximately equivalent amounts in the acid-soluble pool of hamster embryo cells. This observation is consistent with prior unexplained observations, in intact animals, that the methyl group of S-adenosyl methionine can be used for deoxythymidine synthesis, This is the only modified ribonucleoside known to be salvaged through pathways in normal cells. Several possible pathways for salvage were investigated.


Effect of season and supplementation on percentage live sperm and sperm abnormalities in Horro (Zebu) bulls in sub-humid environment in Ethiopia.
A total of 32 Horro (Bos indicus) bulls, with an average initial body weight and age of approximately 211 kg and 6 years were evaluated. The bulls were divided into two treatment groups. One group was given a supplementary concentrate at a rate of 1.5 kg/day and the second group served as the control and received no supplementation. The observation period lasted for 50 weeks. Semen was collected every two weeks by mean of electrical stimulation with the aid of an electro-ejaculator. The percentage of abnormal sperm (total abnormalities, head, midpiece and tail) remained lower in the supplemented group than in the non-supplemented group. The percentage of live sperm tended to be higher in the supplemented group throughout the 50-week trial period. Until week 17 of the trial there were no significant differences; however, starting at week 18 there were significant differences between the two treatment groups except for week 26. Thereafter, significant differences were recorded until week 38; from week 40 no significant differences were observed between the two groups in respect of percentage of live sperm (except for week 48). Season (week) during which the semen samples were collected had no significant effect on the percentage of abnormal sperm in both treatment groups (supplemented and non-supplemented). At the start of the trial the nutritionally supplemented group had a higher occurrence of sperm abnormalities (11.4% +/- 1.1%) compared to 8.3% +/- 1.3% in the control group. Thereafter, sperm abnormalities declined rapidly in the supplemented group (except for week 50). The sperm abnormalities for the non-supplemented group showed a tendency to increase during the entire observation period.


Reversal of fortune: Rad5 to the rescue.
In a recent issue of Molecular Cell, Blastyák et al. (2007) show that the yeast Rad5 protein can promote error-free template switching and replication past a DNA lesion via a novel DNA unwinding reaction that also pairs nascent and parental strands.


Distribution of serotonin 5-HT1C receptor mRNA in adult rat brain.
Based on in situ hybridization histochemistry (ISHH), we describe the anatomical distribution of the serotonin 5-HT1C receptor mRNA. In addition to the very high levels in epithelial cells of the choroid plexus, 5-HT1C receptor mRNA is found throughout the limbic system, in catecholaminergic cells and in serotonergic neurons. Receptor transcripts are also present in the hypothalamus, numerous motor nuclei and the subthalamus. Our results correlate well with serotonin (5-HT) innervation and receptor binding. Receptor mRNA is present in many brain structures in addition to regions previously shown to have 5-HT1C receptor binding. The distribution of this receptor mRNA suggests that the 5-HT1C receptor may mediate a number of the central effects of 5-HT.


Large scale modification of biomolecules using immobilized sortase A from Staphylococcus aureus.
Recently, sortase A (SrtA) from Staphyloccus aureus moved into the focus of bioscience because of its ability to incorporate site specific modifications into proteins. The enzyme was mostly used to modify target proteins in an analytical scale, to study biomolecules in their cellular context. In this study, we show the applicability of SrtA mediated ligation for site specific modification of proteins in a large scale. Therefore, the reaction was first optimized using peptides and subsequently new reaction conditions were applied for the large scale biotinylation of interleukin-8. Furthermore, we established C-terminal immobilization of the SrtA on a PEG based resin and could demonstrate maintaining enzymatic activity. Immobilized SrtA significantly facilitates previous ligation protocols as the enzyme can be easily recycled. Also, the removal of excess reaction solution and the whole washing process is significantly accelerated, as centrifugation or filtration techniques can be applied instead of time-consuming chromatography steps.


Failure of 5-aminosalicylic acid enemas to improve chronic radiation proctitis.
Radiation proctitis is a well-known complication of abdominal and pelvic radiation. Conventional medical and surgical treatment often is disappointing. 5-Aminosalicylic acid (5-ASA) is the active component in sulfasalazine and is effective in the treatment of distal ulcerative colitis. Four patients with radiation proctitis were treated with 4 g 5-ASA by enema nightly for two to six months. Patients were seen monthly, interviewed, and a sigmoidoscopic exam performed. No change was seen in the degree of mucosal inflammation on follow-up sigmoidoscopic exams. Three patients noted no change in their symptoms of bleeding, pain, or tenesmus. One patient noted initial improvement, but this was not sustained. 5-ASA enemas do not appear to be effective in the treatment of radiation proctitis.


Renal injury associated with intravenous pyelography in nondiabetic and diabetic patients.
We studied 23 patients with renal functional deterioration after intravenous pyelography; 16 were nondiabetic. Nondiabetic patients at risk are often elderly and have preexisting renal disease. The course of acute renal failure is fairly characteristic; most patient recover, but some do not. Estimates suggest that the syndrome is not uncommon in susceptible nondiabetic subjects. Pyelography cannot be considered absolutely safe for this group, and alternative diagnostic procedures or caution with contrast dosage and patient preparation may be wise.


Artifacts associated with 2-mercaptoethanol upon high resolution two-dimensional electrophoresis.
The presence of 2-mercaptoethanol in the protein denaturing solution used to prepare samples for high resolution two-dimensional electrophoresis can result in artifacts when the two-dimensional patterns are detected by silver staining. These are (i) spots of discrete isoelectric point and electrophoretic mobility, (ii) horizontal bands of the same electrophoretic mobility as the spots (corresponding predominantly to molecular weights of 54,000 and 68,000), and (iii) vertical streaks of variable length and intensity. Although the nature and source of artifacts have not been positively identified the evidence suggests that they are probably not inherent in the 2-mercaptoethanol itself but rather released by the latter from some component common to both the first- and second-dimension constituents of the electrophoretic system.


Positron emission tomography detection of breast cancer metastasis to the uterus.
We report the case of a patient presenting with moderate elevation of the tumor marker cancer antigen 15.3 during breast cancer follow-up. After a negative standard metastatic work-up, a positron emission tomography scan identified a localized central pelvic zone of uptake. Hysterectomy was performed, and pathology revealed a breast cancer metastasis within a previously known uterine leiomyoma. Positron emission tomography allowed assessment of soft tissues. With high sensitivity and specificity, positron emission tomography can be used to localize breast cancer metastases suspected by the presence of elevated serum tumor marker but not detected on standard metastatic workup.


Predictors of Lymph Node Metastasis in Surgically Resected T1 Esophageal Cancer.
The application of endoscopic therapies for early cancers of the esophagus is limited by the possible presence of regional lymph node metastases. Our objective was to determine the prevalence and predictors of lymph node metastases in patients with pT1 carcinoma of the esophagus and the gastric cardia. The National Cancer Institute's Surveillance Epidemiology and End Results Database (2004 to 2010) was used to identify all patients with pT1 carcinomas who underwent primary surgical resection for squamous cell carcinoma (SCC) or adenocarcinoma (EAC) of the esophagus and of the esophagogastric junction (AEG). Prevalence of lymph node metastases was assessed, and survival in all types of cancer was calculated. Multivariate logistic regression was used to identify factors predicting positive lymph node status. There were 1,225 patients (84% male), with a mean age of 64 ± 10 years, and 90% were white. Intramucosal disease was present in 44% of patients, and submucosal invasion (T1b) was present in 692 (56%). Prevalence of lymph node metastases in EAC, SCC, and AEG was 6.4%, 6.9%, and 9.5% for pT1a tumors and 19.6%, 20%, and 22.9% for pT1b tumors, respectively. In patients with more than 23 lymph nodes removed during resection, prevalence of lymph node metastases in EAC, SCC, and AEG was 8.1%, 25%, and 7.4% for pT1a tumors and 27.8%, 33.3%, and 22% for pT1b tumors, respectively. Positive lymph node status was associated with worse overall 5-year survival in EAC (N0 vs N+: 78% vs 52%) and AEG (N0 vs N+: 83% vs 44%) but did not have a significant effect on the long-term survival of patients with SCC. Infiltration of the submucosa, tumor size exceeding 10 mm, and poor tumor differentiation were independently associated with the risk of nodal disease. Prevalence of lymph node metastasis negative for these three risk factors was only 4.8%. Prevalence of lymph node metastasis in early esophageal cancer is high in patients with T1 cancer. Inadequate lymphadenectomy underestimates lymph node status. Endoscopic treatment can be considered only in a select group of patients with early esophageal cancer.


Evaluation of community mental health services: comparison of a primary care mental health team and an extended day hospital service.
Alongside mental health policies emphasising the need to focus on people experiencing serious, long-term problems, recent general healthcare policy is leading to the development in the UK of a primary care-led National Health Service. While most primary care-led mental health initiatives have focused on supporting general practitioners (GPs) in managing milder depression and anxiety, this article describes an evaluation comparing primary care-based and secondary care-based services for people with serious long-term problems. A survey of service users was carried out at three points in time using three measures: the Camberwell Assessment of Need, the Verona Satisfaction with Services Scales and the Lancashire Quality of Life Profile. Staff views were sought at two time intervals and carers' views were obtained towards the end of the 2-year study period. The results indicate that both services reduced overall needs and the users' need for information. The primary care service also reduced the need for help with psychotic symptoms whereas the secondary care service reduced users' need for help with benefits and occupation. There were no major differences in terms of satisfaction or quality of life. Primary care-based services therefore appear to have the potential to be as effective as more traditional secondary care services. However, a more comprehensive range of services is required to address the whole spectrum of needs, a conclusion supported by the views of staff and carers.


Radiomics nomogram: A noninvasive tool for preoperative evaluation of the invasiveness of pulmonary adenocarcinomas manifesting as ground-glass nodules.
In this study, we aimed to establish a radiomics nomogram that noninvasively evaluates the invasiveness of pulmonary adenocarcinomas manifesting as ground-glass nodules (GGNs). Computed tomography (CT) images of 509 patients manifesting as GGNs were collected: 70% of cases were included in the training cohort and 30% in the validation cohort. The Max-Relevance and Min-Redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm were used to select the radiomics features and construct a radiomics signature. Univariate and multivariate logistic regression were used to select the invasiveness-related clinical and CT morphological predictors. Age, smoking history, long diameter, and average CT value were retained as independent predictors of GGN invasiveness. A radiomics nomogram was established by integrating clinical and CT morphological features with the radiomics signature. The radiomics nomogram showed good predictive ability in the training set (area under the curve [AUC], 0.940; 95% confidence interval [CI], 0.916-0.964) and validation set (AUC, 0.946; 95% CI, 0.907-0.986). This radiomics nomogram may serve as a noninvasive and accurate predictive tool to determine the invasiveness of GGNs prior to surgery and assist clinicians in creating personalized treatment strategies.


An in vitro test for measuring cytotoxicity of mercuric chloride to human kidney epithelial cells by specific enzyme release.
Mercuric compound toxicity is well documented in animals and man for practically all organs. The recent development of cell culture techniques appeared as a novel fruitful tool in toxicology, especially in renal toxicology. Heavy metal induced renal cell alterations can be evaluated by membrane permeability damages.The present study evaluates mercuric chloride nephrotoxic effect in human kidney epithelial cells by measuring the release of two specific nephrotoxicity marker enzymes, Gamma Glutamyl Transferase (GGT) and Alkaline Phosphatase (ALP) in the culture medium. Cultured kidney epithelial cells were exposed to different HgCl(2) concentrations (5, 10, 20, and 50 μg). Cultures were examined after 6 and 24 hours exposure. A good correlation between mercury dose and toxic effect, and exposure time and toxic effect was found. Enzymes were significantly released into the culture medium for 5 μg and 10 μg HgCl(2)/ml after 6 hours exposure; and after 24 hours exposure, enzymes were released for 5 μg/ml only.It appears that the specific tubular enzyme release in the culture medium is a good in vitro test for quantification of specific tubular damage.


Total and caspase-cleaved cytokeratin 18 in chronic cholecystitis: a prospective study.
Cell death mode has been studied in cancer, autoimmune, and neurodegenerative diseases. In this study, apoptosis and necrosis are investigated for the first time in patients with chronic calculous cholecystitis. Thirty five (35) patients (27 women and 8 men, aged 55.65 +/- 13.48 years) with symptomatic chronic calculous cholecystitis underwent laparoscopic cholecystectomy. The early specific apoptotic tendency (caspase-cleaved cytokeratin 18) was studied in these patients with M30 Apoptosense ELISA and the total cytokerarin 18 (both derived from apoptosis and necrosis) with M65 ELISA. The ratio M30/M65 (caspase-cleaved to total cytokeratin 18) was also computed. According to the histopathological examination, the patients were divided in two groups: group A included patients with chronic inactive cholecystitis (n = 10), and group B those with chronic active cholecystitis (n = 25). The concentrations of caspase-cleaved cytokerarin 18 (CK18), and especially those of total CK18, were higher in bile samples than in serum samples. In group B, there were significant differences between serum and bile samples regarding both caspase-cleaved CK18 and total CK18. Cells staining positive for caspase-cleaved CK18 were present in the epithelial cells of the mucosa of the gallbladder. CK18 is expressed in the gallbladder epithelial cells. The concentrations of both caspase-cleaved CK18 and total CK18 were higher in bile samples than in serum samples. The levels of total CK18, as well as caspase-cleaved CK18, do not seem to differ between active and inactive chronic cholecystitis.


[Growth and oxygenium-consum of the larvae of Hyderma bovis (De Geer) (Diptera, Hypodermatidae)].
At the end of their migration larvae of Hypoderma bovis have reached about 42% of their final length, but only 10% of their final body-weight. Oxygenium-consum/mg body-weight decreased during the larval development: a larva of 50 mg weight needs 800 mm3/mg·h, one of 1500 mg weight only 100 mm3/mg·h. Third instar larvae have a much higher oxygenium-consum after moulting than second instar larvae have just before. The relation of oxygenium-consum/body-weight differs in the two larval stages. Respiration depends on the temperature, its maximum is between 32°C and 37°C. Young animals have a higher maximum than old ones.


Alterations in Functional Connectivity During Different Phases of the Triggered Migraine Attack.
To understand the changes in functional connectivity between brain areas of potential importance in migraine during different phases of the attack. Migraine is a symptomatically heterogeneous disorder. Understanding the possible changes in brain function and, therefore, neurobiology during different phases of the migraine attack is important in developing disease biomarkers and advancing therapeutics. Randomized, double-blind, placebo-controlled, multi-visit experimental study. Subjects aged 18-50 years with migraine with and without aura (≤22 headache days per month) were recruited from across the UK using advertising, from both population and hospital clinic samples (n = 53). Consented subjects were randomized to a 0.5 µg/kg/min nitroglycerin infusion or to placebo over 20 minutes across different study visits, during the period February 2015-July 2017.* All subjects were exposed to a nitroglycerin infusion at least on 1 occasion at screening.** For those subjects who consented to participate in imaging visits (n = 25), structural T1, T2 and FLAIR sequences and resting state blood oxygen level dependant contrast (rsBOLD) time series, using a multiecho EPI sequence, were conducted over 30-40 minutes at baseline and rsBOLD during premonitory symptoms and migraine headache on a 3T General Electric MR750 MRI scanner. For the placebo visit, the imaging was conducted at the same times following infusion in the absence of symptoms. Montreal Neurological Institute (MNI) coordinates were used to characterize identified brain areas of connectivity change. Using repeated measures ANOVA models with time (visit number) and trigger substance (nitroglycerin/placebo) as factors, significant positive functional coupling was found between the thalami bilaterally and the right precuneus and cuneus regions during the nitroglycerin-triggered premonitory phase (T = 3.23, peak connectivity change at [-6, -68, 40] for left thalamus, P = 0.012 and [-4, -68, 40] for right thalamus, P = 0.019). The nitroglycerin-triggered premonitory phase was associated with a change in the direction of connectivity from positive to negative between the pons and the limbic lobe (T = 3.47, peak connectivity change at [2, 8, 50], P < 0.001). The headache phase of the nitroglycerin-triggered migraine attack was associated with ongoing negative functional coupling between the pons and the cingulate and frontal cortices, and positive functional coupling between the pons and the cerebellar tonsils and medulla (T = 3.47, peak connectivity change at [-8, -52, -58], P = 0.007). Understanding the functional reorganization between subcortical and cortical brain areas in different phases of the migraine attack provides novel insights into the abnormal sensory processing and integration during migraine, as well as functional correlation with clinical symptoms displayed during each phase. [*Correction added on July 22, 2020 after first online publication: This sentence was revised from, "Consented subjects had a 0.5 μg/kg/min nitroglycerin infusion…".] [**Correction added on July 22, 2020 after first online publication: This sentence was revised from, "… at least on 1 occasion at screening."].


Titration of the binding sites for the oligomycin-sensitivity conferring protein in beef heart submitochondrial particles.
The binding parameters of the oligomycin-sensitivity conferring protein (OSCP) in inside-out particles from beef heart mitochondria have been tested by means of two assays, the oligomycin-sensitive ATP-Pi exchange, and the oligomycin-sensitive ATP hydrolysis. The total number of OSCP binding sites in A particles was equal to 220 pmol/mg particle protein. Each mole of ATPase active site was able to bind 1.1 +/- 0.5 mol OSCP with Kd 1.7 nM.


The Beck Depression Inventory and General Health Questionnaire as measures of depression in the general population: a validation study using the Composite International Diagnostic Interview as the gold standard.
The Beck Depression Inventory (BDI) and the General Health Questionnaire (GHQ) are commonly used in population studies as measures of depression. We examined in a population sample the validity of four scales for depressive symptoms, the GHQ-12, the 21- and 13-item versions of the BDI, and a new 6-item version of the BDI developed for this study. A total of 5561 participants in the "Health 2000" survey (30-79 years) completed the four scales and were assessed with the Composite International Diagnostic Interview (CIDI), which was used as the validation criterion. We selected items for the BDI-6 through an exploratory factor analysis for the BDI-21. The accuracy of the scales, including the BDI-6, was satisfactory (c-statistics 0.88-0.92 for depression within the past 2 weeks and 0.80-0.83 within the past 12 months) and slightly better for men (0.92-0.96 and 0.85-0.87) than for women (0.86-0.88 and 0.78-0.79). Higher scores in all the scales were associated with more severe depression and more recent depressive episodes. This study suggests that various versions of the BDI and the GHQ-12 are useful in detecting depressive disorders in the general population. Even the 6-item version of the BDI showed acceptable criterion validity, although replication in an independent dataset is needed to confirm its validity.


Degradation of pesticide wastewater with simultaneous resource recovery via ozonation coupled with anaerobic biochemical technology.
The effective treatment of pesticide wastewater with high organic content, complex composition and high-toxicity has attracted enormous attention of researchers. This work proposes a new idea for removing the pesticide wastewater with simultaneous resource recovery, which is different from the traditional view of mineralization of pesticide wastewater via composite technology. This novel strategy involved a sequential three-step treatment: (a) acidic Ozonation process, to remove the venomous aromatic heterocyclic compounds; (b) hydrolysis and ozonation in alkaline conditions, enhancing the biodegradability of pesticide wastewater, mainly due to the dehalogenation, elimination of C=C bonds and production of low molecular-weight carboxylate anions; (c) the final step is anaerobic biological reactions. Based on the characterizations, this two-stage acidic-alkaline ozonation can efficiently degraded the virulence of pesticide wastewater and enhance its biodegradability from 0.08 to 0.32. The final anaerobic biochemical treatment can stably remove the residuals and convert the low molecular-weight organics into CH4, achieving the resource recovery. This work explored the pH-dependent of ozonized degradation of pesticide wastewater and gives a new perspective of wastewater treatment.


MuLV IN mutants responsive to HDAC inhibitors enhance transcription from unintegrated retroviral DNA.
For Moloney murine leukemia virus (M-MuLV), sustained viral infections require expression from an integrated provirus. For many applications, non-integrating retroviral vectors have been utilized to avoid the unwanted effects of integration, however, the level of expression from unintegrated DNA is significantly less than that of integrated provirus. We find that unintegrated DNA expression can be increased in the presence of HDAC inhibitors, such as TSA, when applied in combination with integrase (IN) mutations. These mutants include an active site mutation as well as catalytically active INs bearing mutations of K376 in the MuLV C-terminal domain of IN. MuLV IN K376 is homologous to K266 in HIV-1 IN, a known substrate for acetylation. The MuLV IN protein is acetylated by p300 in vitro, however, the effect of HDAC inhibitors on gene expression from unintegrated DNA is not dependent on the acetylation state of MuLV IN K376.


On disturbance of homeostasis in organ-cultured tissue.
The intact membranous rat mesentery was cultured in Eagle's minimum essential medium containing no serum or only low concentrations of serum. The procedure is in some important respects superior to previous organ culture techniques. To estimate the extent of disturbance of homeostasis of the tissue in culture, the spontaneous mast-cell histamine release was quantitated after preculture preparation of the specimens and after different intervals in culture. Also, the proliferation of fibroblasts and mesothelial cells that predominate in the mesentery was assessed at 48 h by cytofluorometric quantitation of DNA in single-tissue cells. Spontaneous histamine release was time dependent during cultivation, amounting to ca. 50% at 48 h, and was affected by the medium used for moistening the tissue before cultivation. Culturing also brought about great spontaneous increase in the proliferation of fibroblasts and mesothelial cells, the rate being related to the concentration of serum. Addition of the mast-cell secretagogues 48/80 or polymyxin B at 1 h caused rapid release of 50 to 60% of the histamine and was followed by augmented proliferation in the serum-containing media. The spontaneous increase of cell proliferation in tissue culture may be causally related to mast-cell secretion. Further studies are needed to define factors influencing the spontaneous mast-cell secretion and the mast-cell-dependent mitogenesis in normal tissue cells.


Vitamin D binding protein is required to utilize skin-generated vitamin D.
Vitamin D is produced in the skin following exposure to sunlight. Ultraviolet (UV) B (UVB, 280-310 nm) results in isomerization of 7-dehydrocholesterol to previtamin D that spontaneously isomerizes to vitamin D. This pool of skin-derived vitamin D is the major source of vitamin D for animals. However, the mechanisms by which it becomes available remain undefined. It has been assumed that cutaneous vitamin D is transported into the circulation by vitamin D binding protein (DBP), but experimental evidence is lacking. To determine whether cutaneous vitamin D is transported by DBP, we utilized DBP-/- mice that were made vitamin D-deficient. These animals lack measurable 25(OH)D in blood and are hypocalcemic. As controls, DBP+/+ animals were vitamin D depleted and made equally hypocalcemic. UV irradiation of DBP+/+ animals restored serum calcium and serum 25(OH)D while the same treatment of DBP-/- animals failed to show either a serum calcium or 25(OH)D response despite having normal vitamin D production in skin. Intravenous injection of small amounts of recombinant DBP to the vitamin D-deficient DBP-/- mice restored the response to UV light. These results demonstrate a requirement for DBP to utilize cutaneously produced vitamin D.


Synthesis, biological evaluation and molecular docking studies of novel thiopyrimidine analogue as apoptotic agent with potential anticancer activity.
This study synthesizes novel 6-amino-5-cyano-4-aryl-2-mercapto pyrimidines and condensed pyrimidines analogues in order to investigate their potential activity as anticancer agents. The compounds were synthesized via one-pot condensation of p-nitrobenzaldehyde or p-anisaldehyde with malononitrile and thiourea to prepare 6-amino-5-cyano-4-aryl-2-mercaptopyrimidines series (1-9a,b). The pyrimidine analogues were biologically screened In-vitro in HepG2 and MCF-7 compared to normal WI-38. Compound 8a showed higher antiproliferative activity to MCF-7 cells with sensitivity and minimal cytotoxic effect (IC50 53.3 µM- HepG2, 12.9 µM- MCF-7 and >100 µM- WI-38). Compound 8a was able to induce 40% of total antioxidants and 60% following treatment with 50 µM of H2O2 for 3hrs as external source of oxidative stress in MCF-7. 8a was able to significantly induce early stage apoptosis of 74.37% MCF-7 and cell cycle arrest with cells accumulation in subG0-G1 phase to 69.42% and reduction of cells in G2M phase to 3.6% and high apoptotic index. Compound 8a induced over-expression of Fas receptor and Cyto C genes. Molecular docking studies suggested that 8a can bind to both phosphodiesterase 4B and 4D binding pockets and inhibit their action through network of hydrophobic interactions in Q-P pockets with preferential selectivity to PDE4B through invariant Glu443. The chemical profile and the biological results suggest that 8a can be a promising anticancer agent.