The efficacy of balneotherapy, mud therapy and spa therapy in patients with osteoarthritis: an overview of reviews.
Osteoarthritis is a degenerative disease considered a leading cause of functional disability. Its treatment is based on a combination of pharmacological and non-pharmacological interventions, but the role of these latter is still debated. This overview of systematic reviews aimed at evaluating the short-term efficacy of different thermal modalities in patients with osteoarthritis. We searched PubMed, Scopus, CINHAL, Web of Science, ProQuest and the Cochrane Database of Systematic Reviews from inception until October 2020, with no language restrictions. We selected the following outcomes a priori: pain, stiffness and quality of life. Seventeen systematic reviews containing 27 unique relevant studies were included. The quality of the reviews ranged from low to critically low. Substantial variations in terms of interventions studied, comparison groups, population, outcomes and follow-up between the included SRs were found. From a re-analysis of primary data, emerged that balneotherapy was effective in reducing pain and improving stiffness and quality of life, mud therapy significantly reduced pain and stiffness, and spa therapy showed pain relief. However, the evidence supporting the efficacy of different thermal modalities could be seriously flawed due to methodological quality and sample size, to the presence of important treatment variations, and to the high level of heterogeneity and the absence of a double-blind design. There is some encouraging evidence that deserves clinicians' consideration, suggesting that thermal modalities are effective on a short-term basis for treating patients with AO.


The 3D-structure of a natural inhibitor of cell adhesion molecule expression.
The three-dimensional structure of cyclopeptolide HUN-7293, a naturally-occurring inhibitor of cell adhesion molecule expression, has been determined from nuclear magnetic resonance data recorded in solution and from X-ray diffraction analysis of single crystals. The backbone conformation of HUN-7293 is characterized by two cis-peptide bonds in both the solution and crystalline state. Differences between the solution and crystal structure are visible for the orientation of some side chains and the strength of two transannular hydrogen bonds. Such structural information helps to provide insight into the molecular architecture of HUN-7293 on the atomic level and opens the way for structure-based modifications of this novel inhibitor of cell adhesion molecule expression.


Acute onset of dizziness caused by a cavernous malformation lateral to the fourth ventricle: a case report.
Dizziness, diplopia, and nystagmus may be nonspecific symptoms and in part attributed to central causes. We report a case with brain stem lesion and discuss these nonspecific symptoms. A 13-year-old boy presented to our emergency department with a lasting dizziness for 1 week and diplopia for 5 days. New onset horizontal nystagmus was also noted during the physical examination. A cavernous malformation in the right middle cerebral peduncle lateral to the fourth ventricle was suspected by brain computed tomography and confirmed by magnetic resonance imaging. Without progression of the lesion, conservative treatment and regular follow-up were performed. This case report demonstrates the importance of primary physicians paying attention to children with dizziness, diplopia, and nystagmus for considering possible central nervous problems.


Study of the mandible under static constraints by holographic interferometry. New biomechanical deductions.
In order to try to determine the nature of the mechanical structure of the mandible, the authors have compared, with the help of holographic interferometry, the behavior of the fresh mandible of a corpse, of a representative iron angle, and of a block of carbon-carbon under static constraint. There are no similarities between the behavior of the human mandible and that of a polycrystalline steel. On the contrary, the behavior of the mandible and of the carbon-carbon block are very similar. It would be hasty to state that bones are a heterogeneous composite. We can only prove, in a first approach, that they behave similarly under identical experimental conditions. The authors also demonstrated that the mandible presents a "mechanical hysteresis" phenomenon. This means that, when subjected to a small strain, its shape changes, but this change tends to neutralize itself in part in the course of time.


ICAT inhibits glioblastoma cell proliferation by suppressing Wnt/β-catenin activity.
Inhibitor of β-catenin and T-cell factor (ICAT) is a key component of Wnt/β-catenin signaling. ICAT blocks the formation of the β-catenin/TCF complex and has been demonstrated to be involved in embryonic development and carcinogenesis. As an inhibitor of canonical Wnt signaling, ICAT was presumed to be a tumor-suppressor gene. However, the ICAT functions in human glioma remain unknown. In this study, we evaluated the expression of ICAT in 305 human glioma tissues and found that negative ICAT expression correlated with higher grade glioma and poor survival in patients with glioma. Then we transfected glioma cells with ICAT plasmid. Western blotting showed an increased ICAT protein expression level in glioma cells. MTT assay, flow cytometry and cell invasion assay were used to detect cell proliferation, cell cycle distribution, apoptosis and invasion. Our studies confirmed that ICAT inhibits glioma cell proliferation and invasion, and it induces cell apoptosis and cell cycle progression arrest. Besides, ICAT slowed down tumor growth in a glioblastoma xenograft model. Therefore, our study demonstrates that ICAT may serve as a tumor-suppressor in human glioma suggesting a promising direction for targeting therapy in glioma.


Energetics and kinetics of substrate analog-coupled staphylococcal nuclease folding revealed by a statistical mechanical approach.
Protein conformational changes associated with ligand binding, especially those involving intrinsically disordered proteins, are mediated by tightly coupled intra- and intermolecular events. Such reactions are often discussed in terms of two limiting kinetic mechanisms, conformational selection (CS), where folding precedes binding, and induced fit (IF), where binding precedes folding. It has been shown that coupled folding/binding reactions can proceed along both CS and IF pathways with the flux ratio depending on conditions such as ligand concentration. However, the structural and energetic basis of such complex reactions remains poorly understood. Therefore, we used experimental, theoretical, and computational approaches to explore structural and energetic aspects of the coupled-folding/binding reaction of staphylococcal nuclease in the presence of the substrate analog adenosine-3',5'-diphosphate. Optically monitored equilibrium and kinetic data, combined with a statistical mechanical model, gave deeper insight into the relative importance of specific and Coulombic protein-ligand interactions in governing the reaction mechanism. We also investigated structural aspects of the reaction at the residue level using NMR and all-atom replica-permutation molecular dynamics simulations. Both approaches yielded clear evidence for accumulation of a transient protein-ligand encounter complex early in the reaction under IF-dominant conditions. Quantitative analysis of the equilibrium/kinetic folding revealed that the ligand-dependent CS-to-IF shift resulted from stabilization of the compact transition state primarily by weakly ligand-dependent Coulombic interactions with smaller contributions from specific binding energies. At a more macroscopic level, the CS-to-IF shift was represented as a displacement of the reaction "route" on the free energy surface, which was consistent with a flux analysis.


Refinement and Pilot Testing of a Brief, Early Intervention for PTSD and Alcohol Use Following Sexual Assault.
Experiencing a sexual assault can have long-lasting negative consequences including development of posttraumatic stress disorder (PTSD) and alcohol misuse. Intervention provided in the initial weeks following assault can reduce the development of these chronic problems. This study describes the iterative treatment development process for refining a brief intervention targeting PTSD and alcohol misuse for women with recent sexual assault experiences. Experts, treatment providers, and patients provided feedback on the intervention materials and guided the refinement process. Based on principles of cognitive change, the final intervention consists of one in-person session and four coaching calls targeting beliefs about the assault and about drinking behavior. Initial feasibility and acceptability data are presented for patients enrolled in an open trial (N = 6). The intervention was rated as helpful, not distressing, and interesting by patients and all patients completed the entire treatment protocol. A large decrease in PTSD symptoms pre- to post-intervention was observed. A small effect on decreasing alcohol consequences also emerged, although drinks consumed per week showed a slight increase, not a decrease, over the course of the intervention. Applications of this intervention and next steps for testing efficacy are presented.


A turbidimetric assay of lipid transfer activity.
A novel method to assay insect plasma lipid transfer particle (LTP) activity has been developed that employs insect high density lipophorin (HDLp) and human low density lipoprotein (LDL) as donor/acceptor substrate particles. At a 3:1 or greater HDLp:LDL protein ratio, LTP-mediated net vectorial transfer of diacylglycerol from lipophorin to LDL produces destabilized LDL particles that aggregate, causing sample turbidity. Turbidity was measured spectrophotometrically as a function of absorbance at 340 nm. After an initial lag phase, lipoprotein sample turbidity increased as a function of reaction time and LTP concentration. Saturation was observed at longer times or higher LTP concentrations, indicating that a reaction end point had been reached. As the substrate HDLp concentration was increased relative to LDL, a saturable increase in LTP-induced lipoprotein sample turbidity was observed. When the LDL concentration was increased relative to HDLp, however, there was an initial production of turbidity but at higher concentrations the sample did not develop turbidity. Reaction progress was also dependent on temperature over the range 0-37 degrees C. Taken together the results are consistent with the concept that LTP-mediated diacylglycerol transfer from HDLp to LDL creates unstable product LDL particles that aggregate. The assay method is advantageous because it employs relatively abundant, natural lipoprotein substrates, does not require prelabeling of donor lipid particles with radioactive or fluorescent lipids, and does not require separation of donor and acceptor after incubation. This is the first description of a lipid transfer assay that can be measured spectrophotometrically.


Accuracy of Siri and Brozek equations in the percent body fat estimation in older adults.
To identify which equation, Siri or Brozek, based on the two compartment model, provides a more accurate conversion of body density (BD) in percent body fat (%BF) in a group of older adults. Cross-sectional study. Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto. 60 older adults, aged 60-92 years. Skinfold thickness was used to estimate BD through Visser et al. prediction equation. The conversion of BD to %BF was done with Siri (%BF-Siri) and Brozek (%BF-Brozek) formulas and these determined values were both compared to Dual-Energy X-ray Absorptiometry (%BF-DXA) evaluations. A strong correlation between the %BF-DXA value and %BF-Siri (r=0.91, p < 0.001) and %BF-Brozek (r=0.91, p < 0.001) was found, although %BF-Siri and %BF-Brozek overestimated %BF-DXA (p < 0.001). The comparison of the %BF-Siri and %BF-Brozek mean values also revealed significant differences (p < 0.001). The %BF-Brozek reflects a better agreement than the %BF-Siri with %BF-DXA with respectively a mean difference of -4.0 %BF (limits of agreement = -10.9 to 2.9%) and -5.7 %BF (-12.6 to 1.2). The Bland and Altman plots confirmed that %BF-Brozek reflects a better agreement with %BF-DXA. The results of the present study show that the use of Brozek equation may correspond to a more accurate alternative than Siri equation for the conversion of BD in %BF in older adults.


Biosynthesis of (R)-3-hydroxybutyric acid from syngas-derived acetate in engineered Escherichia coli.
Acetate is a potential non-food carbon source for industrial production, coping with the shortage of food-based feedstocks. (R)-3-hydroxybutyric acid (R-3HB) can be used as an important chiral intermediate in the fine chemical and pharmaceutical industry. In this study, the R-3HB biosynthesis pathway was successfully constructed when genes of β-ketothiolase (phaA), acetoacetyl-CoA reductase (phaB) from Ralstonia eutropha, and propionyl-CoA transferases (pct) from Clostridium beijerinckii 8052 were introducedinto Escherichia coli. The effects of host E. coli strains, different propionyl-CoA transferases, and post-induction temperatures were investigated. The final concentration of R-3HB reached 0.86 g/L using acetate as the sole carbon source. Subsequently, a kind of culture broth containing the syngas-derived acetate was used to produce 1.02 g/L of R-3HB with a yield of 0.26 g/g. Inthis study, the engineered E. coli strain could efficiently utilize syngas-derived acetate to synthesize R-3HB.


Relationship of Retinal Vessel Caliber with Age-Related Macular Degeneration.
Evaluate the relationship between retinal vascular caliber and age-related macular degeneration (AMD) severity or progression. A retrospective secondary analysis of 1172 fundus photographs and clinical data from the prospective Age-Related Eye Disease Study (AREDS). Central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) were measured using the Parr-Hubbard-Knudtson formula. Univariate and multivariate regressions were used to determine the association of CRAE, CRVE, and AVR with age, sex, smoking status, presence of cilioretinal artery, and AMD severity at baseline and 5 years using the 9-step AMD severity score. Only CRAE and CRVE were higher in men (P < 0.001), current smokers (P < 0.001), and the eyes with a cilioretinal artery (P=0.009 - 0.043). AMD severity was greater in older patients (P=0.001), current smokers (P=0.012), the eyes without a cilioretinal artery (P=0.001), and lower AVR (P=0.034) on multivariate regression but was not influenced by CRAE or CRVE (P=0.240 - 0.500). Choroidal neovascularization (CNV) presence was associated with older age (P=0.003) and absence of a cilioretinal artery (P=0.009), while central geographic atrophy (CGA) was associated with narrower CRAE (P=0.002) and possibly AVR (P=0.046). None of the retinal vessel parameters were predictive of AMD severity score or new onset of CNV or CGA at 5 years. A lower arteriole-to-venule ratio may be associated with AMD severity, with narrower arterioles seen in the eyes with geographic atrophy, suggesting a role of the retinal vasculature in AMD pathophysiology. This trial is registered with ClinicalTrials.gov Identifier: NCT00000145.


Angina pectoris with normal coronary angiograms.
Of patients with angina pectoris who undergo cardiac catheterization, angiographically normal-appearing coronary arteries are found in a significant minority. Multiple etiologies have been proposed to explain chest pain in this setting, including psychiatric illness, esophageal motility disorders or acid reflux, and limited coronary flow response to stress. A fundamental abnormality in this patient population may be abnormal visceral pain perception. Evidence for and against various etiologies as well as a management strategy for the patient with chest pain are presented in this article, both with respect to the decision for performing cardiac catheterization and the management after demonstration of angiographically normal coronary arteries.


A Randomized Controlled Trial of Kinematically and Mechanically Aligned Total Knee Arthroplasties: Long-Term Follow-Up.
The optimal alignment technique for total knee arthroplasty (TKA) remains controversial. We previously reported 6-month and 2-year results of a randomized controlled trial comparing kinematically versus mechanically aligned TKA. In the present study, we report the mean 13-year (range, 12.6-14.4) follow-up results from this trial. The original cohort included 88 TKAs (44 kinematically aligned using patient-specific guides and 44 mechanically aligned using conventional instrumentation), performed from 2008 to 2009. After institutional review board approval, the health records of the original 88 patients were queried. Revisions, reoperations, and complications were recorded. There were 26 patients who died, leaving 62 patients for follow-up. Of these, 48 patients (77%) were successfully contacted via phone. Reoperations and complications were documented. Furthermore, a battery of patient-reported outcome measures (PROMs) (including Western Ontario and McMaster University Index, Oxford Knee Score, Knee Injury and Osteoarthritis Outcome Score Junior, Forgotten Joint Score, Modified-Single Assessment Numerical Evaluation, and patient satisfaction) were obtained. Of the original 88 patients in the study, 15 patients had at least one reoperation (17%) and 5 patients had undergone complete revision surgery (6%). There was no difference between the 2 alignment methods for major and minor reoperations (P = .66). The kinematically aligned total knees self-reported a nonstatistically significant (P = .16) improved satisfaction (96% versus 82%), but no difference in other PROMs compared to mechanically aligned TKAs. Kinematically aligned TKA demonstrates excellent mean 13-year results, comparable to mechanically aligned TKA with similar reoperations, complications, and PROMs.


COVID-Associated Cast-Forming Cholangiopathy: A Commentary on Disease Mechanism, Treatment, and Prognosis.
The complete impact of COVID-19 infection continues to develop since the onset of the COVID-19 pandemic. COVID-19 cholangiopathy has been recently described in a subset of patients who recovered from severe COVID-19 infection. The most common phenotype of patients suffering from COVID-19 cholangiopathy had severe infection requiring a stay in the intensive care unit, mechanical ventilation and vasopressor medications. Patients with COVID-cholangiopathy present with severe and prolonged cholestatic liver injury. In cases where biliary cast formation is identified, we defined the entity as "COVID-19 cast-forming cholangiopathy". This subset of COVID-19 cholangiopathy is not well understood and there are no standardized diagnosis or management to this date. The reported clinical outcomes are variable, from resolution of symptoms and liver test abnormalities to liver transplant and death. In this commentary, we discuss the proposed pathophysiology, diagnosis, management, and prognosis of this disease.


Pain-related cerebral potentials in patients with frontal or parietal lobe lesions.
The present study investigated the processing of painful electrical stimuli in patients with unilateral frontal or parietal lobe damage and matched control subjects. Patients with frontal lesions showed increased pain thresholds when the stimuli were administered contralateral to the lesion. While the peak-to-peak amplitudes of the N150/P250 components of the somatosensory potentials increased linearly with stimulus intensity in the control subjects, the responses in the frontal group did not change significantly between stimulation at pain and tolerance threshold. There was no evidence for altered pain processing in patients with parietal lobe lesions. The findings of the present study support the hypothesis of an involvement of the frontal cortex in pain perception in humans.


Efficacy of antimalarial agents to prevent the progression of discoid lupus erythematosus to systemic lupus erythematosus: A retrospective cross-sectional study.
Discoid Lupus Erythematosus (DLE) patients have the potential to developing Systemic Lupus Erythematosus (SLE) at a later time. The prescription of antimalarial agents might be beneficial to prevent this progression but the validated data is still lacking. Our study aimed to explore whether antimalarial agent could slow progression to SLE in DLE patients, adjusting for other potential confounders. We retrospectively studied 65 patients who were diagnosed as DLE and attended the outpatient clinic at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between January 1, 2017 and December 31, 2020. We reviewed medical records including history of DLE, SLE signs and symptoms, laboratory findings and treatment options. Over a total of 458.73 person years (PY), 19 patients (29.23%) eventually progressed to SLE within approximately 1 year. Of these, 15 patients had widespread lesions whereas only 4 patients presented with localized form. The prescription of antimalarial drug was associated with delayed SLE progression in our cohort. Other parameters such as generalized form (IRR 6.243 (95% CI 1.450-26.872); P = 0.014), joint involvement (IRR 5.005 (95% CI 1.931-12.969); P = 0.001) and LE specific skin lesions (IRR 3.799 (95% CI 1.220-11.825); P = 0.021) were considered as strong risk factors in SLE development. Our study suggested that an antimalarial drug could postpone the SLE development in DLE patients.


Intermuscular coherence as a biomarker of subthalamic nucleus deep brain stimulation efficacy in Parkinson's disease.
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD. EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated. Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01). Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement. We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS.


Lipolytic and antilipolytic effects of human growth hormone, its 20-kilodalton variant, a reduced and carboxymethylated derivative, and human placental lactogen on chicken adipose tissue in vitro.
The lipolytic and antilipolytic effects of human growth hormone (22K-hGH), its 20-kilodalton variant (20K-hGH), a reduced and S-carboxymethylated derivative (RCM-hGH), and human placental lactogen were examined using chicken adipose tissue explants in vitro. Lipolysis, as determined by glycerol release, was stimulated by 22K-hGH (biosynthetic and pituitary derived), 20K-hGH (pituitary derived), and RCM-hGH (modified biosynthetic). These growth hormone preparations also exhibited similar antilipolytic activity (i.e., transient inhibition of glucagon-induced lipolysis). However, unlike human growth hormone, human placental lactogen neither stimulated lipolysis nor inhibited glucagon-stimulated lipolysis. Some augmentation of glucagon-stimulated lipolysis was observed in the presence of human placental lactogen. These results indicate that the disulfide bridges (Cys53----Cys165; Cys182----Cys189) and amino acid residues 32-46 of hGH are not required for lipolytic or antilipolytic activities of human growth hormone on chicken adipose tissue.


Variables affecting productivity in food service systems of nursing homes.
Data were collected in food service systems of 14 nursing homes to measure and correlate 16 variables hypothesized to affect quantitative productivity, defined as minutes per meal equivalent. Analysis of data showed that as two variables--ratio of the number of employees to full-time equivalent positions and total labor hours--increased, minutes per meal equivalent increased; thus quantitative productivity decreased. As four variables--turnover of full-time employees and of all employees, ratio of number of residents to full-time equivalent worker, and total meal equivalents served--increased, minutes per meal equivalent decreased; thus quantitative productivity increased.


Lifespan of one nickel-titanium rotary file with reciprocating motion in curved root canals.
The purpose of this study was to examine the lifespan of one nickel-titanium (NiTi) rotary file when used in reciprocating motion and to compare the time required for its preparation of a curved root canal using both reciprocating and continuous motion. One hundred twenty curved canals from 60 extracted maxillary and mandibular molars were selected for measuring the mean number of uses. Each canal was prepared with reciprocating motion until the ProTaper F2 single file (Dentsply Maillefer, Ballaigues, Switzerland) reached the working length. One file was used until it was fractured. Another 60 canals were divided into two groups. 30 canals in the continuous rotation motion (CM) group were prepared using continuous rotation following the sequence of ProTaper files, whereas the canals in the reciprocating motion (RM) group (n = 30) were prepared with reciprocating motion with the sole use of the ProTaper F2. The total root canal preparation time was measured until the F2 file finally reached the working length in both groups. A total of 11 files were used in the preparation of 120 curved root canals. The average lifespan of one F2 file was 10.60 ± 4.35 canals with the longest lifespan of 21 canals. The total time for canal preparation was 46.42 ± 18.12 seconds and 21.15 ± 6.70 seconds in the CM and RM groups, respectively. There was a statistically significant difference between the groups (p < 0.01). Within the limitation of this study, one F2 file can be safely used to the working length of curved canals at least six times under reciprocating motion. Reciprocating preparation with only one F2 file was much faster than root canal instrumentation with continuous rotation.


A novel approach to the identification and quantitative elemental analysis of amyloid deposits--insights into the pathology of Alzheimer's disease.
There is considerable interest in the role of metals such as iron, copper, and zinc in amyloid plaque formation in Alzheimer's disease. However to convincingly establish their presence in plaques in vivo, a sensitive technique is required that is both quantitatively accurate and avoids isolation of plaques or staining/fixing brain tissue, since these processes introduce contaminants and redistribute elements within the tissue. Combining the three ion beam techniques of scanning transmission ion microscopy, Rutherford back scattering spectrometry and particle induced X-ray emission in conjunction with a high energy (MeV) proton microprobe we have imaged plaques in freeze-dried unstained brain sections from CRND-8 mice, and simultaneously quantified iron, copper, and zinc. Our results show increased metal concentrations within the amyloid plaques compared with the surrounding tissue: iron (85 ppm compared with 42 ppm), copper (16 ppm compared to 6 ppm), and zinc (87 ppm compared to 34 ppm).


Radial nerve cross-finger flap differential nerve contribution in thumb reconstruction.
Six patients with extensive palmar thumb pulp and soft tissue loss were treated with a staged transfer of radial nerve innervated flap tissues from the dorsum of the index finger. They were followed for a mean period of 3 years. This transfer of radial nerve innervated dorsal index finger tissues to the palmar surface of the thumb has been a successful method of innervation restoration. The ultimate sensibility of the reconstructed thumb seems to be a mixture of median and radial nerve sensibility. Sensory testing shows that after transfer, the ulnar side of the flap is more innervated from the radial nerve than the radial side. Our findings suggest that the presence of active sensory axons in the radial nerve innervated flap may play an inhibitory role in direct and/or functional neurotization of the transferred flap.


Anatomic vs Dome Patella: Is There a Difference Between Fixed- vs Mobile-Bearing Posterior-Stabilized Total Knee Arthroplasties?
It has been hypothesized that the patella, working in conjunction with both medial and lateral femoral condyles, can influence kinematic parameters such as posterior femoral rollback and axial rotation. The objective of this study is to determine the in vivo kinematics of subjects implanted with a fixed-bearing (FB) or mobile-bearing (MB) posterior-stabilized (PS) total knee arthroplasty (TKA), with a specific focus on evaluating the impact that Anatomic and Medialized Dome patellar components have on tibiofemoral kinematic patterns. Tibiofemoral kinematics were assessed for 40 subjects; 20 with an anatomic patella and 20 with a dome patella. Within these groups, 10 subjects received an FB PS TKA and 10 subjects received an MB PS TKA. All subjects were analyzed using fluoroscopy while performing a deep knee bend activity. Kinematics were collected during specific intervals to determine similarities and differences in regard to patella and bearing type. The greatest variation in kinematics was detected between the 2 Anatomic patellar groups. Specifically, the MB-Anatomic subjects experienced greater translation of the lateral condyle, the highest magnitude of axial rotation, and the highest range of motion compared to the FB-Anatomic subjects. Subjects with a Dome Patella displayed much variability among the average kinematics, with all parameters between FB and MB cohorts being similar. The findings in this study suggest that subjects with an Anatomic patellar component could have more normal kinematic patterns with an MB PS TKA as opposed to an FB PS TKA, while subjects with a Dome patella could achieve similar kinematics regardless of TKA type.


Plasma protein lipofuscin-like fluorophores in men with coronary artery disease treated with statins.
Lipid oxidation products react with protein to produce lipofuscin-like fluorophores (P-LLF) and modified apolipoprotein B that is an important element of the atherogenic properties of oxidized low-density lipoprotein (oxLDL). The aim of this study was to compare plasma concentrations of P-LLF between men with coronary artery disease (CAD) treated with statin drugs and healthy controls and to identify determinants of P-LLF. Plasma markers of protein modification including P-LLF and oxidized low-density lipoprotein-4E6 (oxLDL-4E6), low-density lipoprotein-conjugated dienes (LDL-CD), lipid peroxides, apolipoprotein B, and serum albumin were measured in 24 men with CAD who were receiving statin therapy and 20 healthy men in the same age range. Plasma P-LLF (+23%, p = 0.001) was significantly higher and plasma oxLDL-4E6 (-33%, p <0.001) and apolipoprotein B (apoB) (-30%, p <0.001) concentrations were significantly lower in men with CAD compared with controls. Plasma P-LLF concentration was correlated significantly with plasma apoB (r = -0.596, p <0.001), serum albumin (r = 0.518, p <0.001), and age (r = 0.390, p = 0.009) and these variables were independent predictors of P-LLF in the study population. Plasma P-LLF was no longer significantly higher in men with CAD when plasma apoB concentration was taken into account. Plasma P-LLF concentration is abnormally high and appears to be closely associated with lower levels of apoB in men with CAD receiving statin therapy. ApoB may be a preferential target of reactive aldehydic lipid oxidation products and a decrease in apoB may increase the quantity of these products available for condensation with albumin.


Prognostic significance of sustained monomorphic ventricular tachycardia induced by programmed ventricular stimulation using up to triple extrastimuli in survivors of acute myocardial infarction.
The prognostic significance of sustained monomorphic ventricular tachycardia (VT) induced by programmed ventricular stimulation using up to 3 extrastimuli was evaluated in 133 consecutive survivors of acute myocardial infarction (AMI) at a mean interval of 1.8 +/- 1.1 months after onset. This was compared with hemodynamic and angiographic abnormalities shown by cardiac catheterization and ventricular ectopic activity detected by Holter monitoring. Sustained monomorphic VT was induced in 25 (19%) patients, sustained polymorphic VT in 11 (8%) patients, nonsustained monomorphic VT (greater than or equal to 10 beats) in 12 patients (9%) and nonsustained polymorphic VT in 9 patients (7%). Multivariate logistic regression analysis of clinical, angiographic, hemodynamic and electrocardiographic variables showed that the presence of a left ventricular aneurysm (p = 0.005) and Lown grade 4B ventricular ectopic activity (p less than 0.001) were independent predictors of inducibility of sustained monomorphic VT. During a mean follow-up of 21 +/- 13 months, there were 8 (6%) sudden cardiac deaths and 3 (2.3%) spontaneous occurrences of life-threatening sustained VT. The 2-year probability of freedom from sudden cardiac death or sustained ventricular tachyarrhythmias was 53 +/- 13% for patients with inducible sustained monomorphic VT, 70 +/- 10% for those with a left ventricular ejection fraction less than 40% and 58 +/- 13% for those with Lown grade 4B ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Cytochrome c-551.5 (c7) from Desulfuromonas acetoxidans.
Cytochrome c-551.5 of the anaerobic sulfur-reducing bacterium Desulfuromonas acetoxidans has been purified to homogeneity and characterized. It elicits absorption bands at 551.5, 522.5 and 418 nm in the reduced form; the absorptivity ratio Aalpha(red)/A280nm(ox) equals 3.8 for the pure preparation. The molecular weight was estimated to be 9800 by gel filtration. Determination of the amion acid composition and analysis of the N-terminal amino acid sequence showed the cytochrome to be identical with the threehaem cytochrome c-551.5 (c7) isolated from the syntrophic mixed culture Chloropseudomonas ethylica strain 2K. The occurrence of multihaem cytochromes c in bacteria is discussed.


Treatment of High Surgical Risk Thoracoabdominal Aortic Aneurysms with Stent Graft and Multilayer Bare Stents Joint Technique: Mid-Long-Term Clinical Results.
This study aims to present the performance data on stent-graft and multilayer bare stents (MBS) joint technique in the treatment of high-risk thoracoabdominal aortic aneurysm (TAAA). From May 2012 to December 2015, 8 selective TAAA cases (ages 46-75 years) ineligible for surgical repair underwent the stent-graft and MBS joint procedure, and were closely followed up for a median of 32 months (range 14-58). Using computed tomography images, the aneurysm size, luminal blood flow diameter, and the covered visceral branches were analyzed. Technical success was achieved in all patients (100%, 8/8). Twenty-four visceral branches were covered by MBS in total. There was no complication or death during hospital stay. During follow-up period, no death or complication occurred. Aneurysm shrinkage (maximum diameter decrease ≥5 mm) was observed in 7 patients. No aneurysm expansion was observed. Total aneurysm sac thrombosis was observed in all patients. The majority of covered side branches (23/24) were successfully preserved. No visceral ischemia or bleeding complications was observed during follow-up. Total endovascular repair of TAAA using stent-graft and MBS joint technique may be a safe and effective alternative in high surgical risk patients. More approving clinical evidences about the safety and efficacy of this procedure are anticipated.


Effects of lesions in the hypothalamic paraventricular, supraoptic and suprachiasmatic nuclei on vasopressin and oxytocin in rat brain and spinal cord.
The content of arginine vasopressin and oxytocin in various extrahypothalamic sites of the rat brain and spinal cord was determined by specific radioimmunoassays after lesions had been made in either the paraventricular (PVN), supraoptic (SON) or suprachiasmatic nuclei (SCN). In some animals all 3 nuclei were destroyed together. The PVN provided a considerable amount of the vasopressin innervation of the solitary tract nucleus, and most of that in the spinal cord. Oxytocin was removed from some areas after lesions of the PVN and, again, most of this peptide was lost from the spinal cord. Lesions of the SCN did not appear to be followed by significant quantitative changes in either hormone in any of the areas studied. Lesions of the SON resulted in loss of oxytocin, particularly in the periventricular grey and some other areas, suggesting that extrahypothalamic projections from this nucleus may be more important than was previously assumed. Lesions of all 3 nuclei which included destruction of accessory hypothalamic nuclei resulted in a much more widespread loss of vasopressin and oxytocin, but there was preservation of both peptides in the dorsal raphe nucleus and much of those present in the locus coeruleus. It is concluded that the contribution of the classical hypothalamic nuclei to the extrahypothalamic content of vasopressin and oxytocin in rat brain is less than was originally believed, and that there are areas of the brain such as the locus coeruleus and dorsal raphe nucleus in which the source of these peptides may be outside the hypothalamus.


New sustainable alternatives to reduce the production costs for surfactin 50 years after the discovery.
In 1968, Arima et al. discovered the heptapeptide, known as surfactin, which belongs to a family of lipopeptides. Known for its ability to reduce surface tension, it also has biological activities such as antimicrobial and antiviral. Its non-ribosomal synthesis mechanism was later discovered (1991). Lipopeptides represent an important class of surfactants, which can be applied in many industrial sectors such as food, pharmaceutical, agrochemicals, detergents, and cleaning products. Currently, 75% of the surfactants used in the various industrial sectors are from the petrochemical industry. Nevertheless, there are global current demands (green chemistry concept) to replace the petrochemical products with environmentally friendly products, such as surfactants by biosurfactants. The production biosurfactants still are costly. Thus, an alternative to reduce the production costs is using agro-industrial waste as a culture medium associated with an efficient and scalable purification process. This review puts a light on the agro-industrial residues used to produce surfactin and the techniques used for its recovery.


Age at first intercourse, number of partners and sexually transmitted infection prevalence among Danish, Norwegian and Swedish women: estimates and trends from nationally representative cross-sectional surveys of more than 100 000 women.
Sexual behavior at the population level impacts on public health. Recent representative sexual behavior data are lacking. Cross-sectional surveys in 2005 and 2012 on women age 18-45 years randomly selected from the general population in Denmark (n = 40 804), Norway (n = 30 331) and Sweden (n = 32 114). Median (interquartile range) age at first intercourse was 16 (15-18) years in Denmark, 17 (16-18) years in Norway, and 17 (15-18) years in Sweden. Women in the most recent birth cohort had sexual debut at the lowest age, and were most likely to have sexual debut before the legal age of consent. Proportions with debut age ≤14 years among women born 1989-1994 vs 1971-1976, odds ratio (95% confidence interval) were: 18.4% vs 10.9%, 1.95 (1.74-2.18) in Denmark, 12.9% vs 6.3%, 2.38 (2.01-2.82) in Norway, 17.8% vs 11.4%, 1.75 (1.55-1.98) in Sweden. Median (interquartile range) number of lifetime sexual partners was 6 (3-10) in Denmark, 5 (2-10) in Norway, and 6 (3-11) in Sweden. The proportion of women reporting >10 sexual partners was also highest in the most recent survey. The percentage with odds ratio (95% confidence interval) in 2012 vs 2005 surveys were: 24.9% vs 22.8%, 1.13 (1.07-1.18) for Denmark; 23.8% vs 19.8%, 1.27 (1.19-1.34) for Norway; and 28.3% vs 23.8%, 1.31 (1.24-1.38) for Sweden. Similarly, the proportion of women reporting ever having had a sexually transmitted infection among women age <30 years were: 29.4% vs 26.4%, 1.21 (1.13-1.31) in Denmark, 28.9% vs 25.0%, 1.20 (1.10-1.31) in Norway, and 29.4% vs 22.2%, 1.45 (1.33-1.58) in Sweden. Scandinavian women reported lower age at first intercourse in younger birth cohorts. Moreover, they reported more lifetime sexual partners and a higher prevalence of ever having a sexually transmitted infection in 2012 than in 2005. Our findings may inform the interpretation of trends in outcomes associated with sexual health, and public health policies.


Epigenetic regulation of flowering time in polyploids.
Polyploidy plays a significant role in the evolution of flowering plants. Understanding the effects of polyploidy on the epigenetic regulation of adaptive traits may resolve questions about the success of polyploids. One such trait, flowering time, has been the subject of several gene expression studies because it has one of the best characterized genetic networks and because polyploidy has a significant impact on generating variation in flowering time. Future research on the epigenetic consequences of polyploidy on flowering time should begin to examine natural variation in an ecological context, while continuing to make use of resynthesized polyploids.


The influence of iododeoxyuridine pretreatment of various cell cultures on adenovirus multiplication.
Treatment of cell cultures with iododeoxyuridine (IUdR) before virus inoculation may enhance the subsequent virus multiplication. This effect was studied in seven kinds of cell cultures with seven human adenoviruses from six subgenera. IUdR (50 micrograms/ml) was added 24 h after the seeding of cells, left for 2 days, and removed before virus inoculation. IUdR had no effect on cell proliferation. Viral cytopathic effect was enhanced in many instances by IUdR pretreatment. However, virus multiplication was enhanced weakly in only four cases [adenovirus 7 in Vero, African green monkey kidney, cynomolgus monkey kidney; adenovirus 4 (Ad4) in HeLa cells], and strongly only for Ad4 in Vero cells, which are semipermissive for Ad4. IUdR pretreatment of Vero cells shortened the replication cycle for Ad4 and increased sensitivity for minimal virus concentrations about 1000-fold. From immunofluorescence experiments it appears that more than one infectious particle is required to infect an untreated Vero cell.


Immune cells and cytokines in systemic lupus erythematosus: an update.
Systemic lupus erythematosus is characterized by overactive B cells that differentiate into autoantibody-forming cells, aberrant T cell function that provides help to B cells, and the production of pro-inflammatory cytokines. This article reviews recent studies unraveling the complex interplay between cytokines and lymphocytes in systemic lupus erythematosus. In systemic lupus erythematosus, T cells are characterized by heightened calcium responses early after activation of their surface receptor. Alterations of the T cell receptor/CD3 complex, namely the substitution of the FcepsilsonRgamma for the T cell receptor zeta chain, and increased mitochondrial potentials can account for this 'overexcitable' phenotype. At the same time, this heightened calcium signal leads to a block of the transcription of the IL-2 gene, a pivotal cytokine for the immune response. The end result is increased spontaneous apoptosis and decreased activation-induced cell death of T cells in systemic lupus erythematosus that in turn leads to enhanced help to B cells and potentially decreased regulatory function. The B cells, on the other hand, are shown to be directly activated by immune complexes by way of Toll-like receptors independently of T cells. Finally, recent studies have tried to elucidate the role of cytokines such as interferon-alpha in systemic lupus erythematosus and, following the paradigm of rheumatoid arthritis, to establish targets for treatment. The increased apoptosis and aberrant T cell activation coupled with nonspecific activation of B cells lead to the production of auto-antigen: auto-antibody complexes that are the hallmark of systemic lupus erythematosus. Future treatments aiming at correcting the intracellular and intercellular signaling abnormalities may prove effective in restoring immune tolerance in systemic lupus erythematosus.


Research on the effect of Dipsaci Radix before and after salt-processed on kidney yang deficiency syndrome rats and the preliminary mechanism study through the BMP-Smad signaling pathway.
Dipsaci Radix (DR) is the dry root of Dipsacus asper Wall. ex DC. The purpose of this study was to compare the effects of DR on rats before and after salt-processed with kidney yang deficiency syndrome (KYDS), and we selected the BMP-Smad signaling pathway to explore the mechanism of DR. The model of KYDS was established by subcutaneous injection of hydrocortisone, the crude DR (CDR) and salt-processed DR (SDR) were given the corresponding dose (2 g/kg, 4 g/kg, and 6 g/kg). The organ index and the contents of adrenocorticotropic hormone (ACTH), cortistatin (CORT), thyroid hormone (T4), tumor necrosis factor-alpha (TNF-α), testosterone (T), estradiol (E2), cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), Na+-K+-ATPase, and growth hormone (GH) in serum were measured to evaluate the intervention effect of DR on KYDS rats. The expression of Smad 1, Smad 4, Smad 5, Smad 8, and BMP 7 protein in kidney was determined by immunohistochemistry, quantitative PCR (qPCR) and Western blot analysis. The effects of DR on 5 expression factors in the BMP-Smad signaling pathway were studied. Constituents absorbed into blood were identified by UPLC-Q-TOF/MS. The results showed that compared with the model group, the thymus and kidney index, as well as the contents of ACTH, CORT, cAMP, GH, Na+-K+-ATPase, T, T4, and E2 were significantly increased in the CDR and SDR groups, and the contents of cGMP and TNF-α were significantly decreased. Compared with the CDR high dose group, ACTH, Na+-K+-ATPase, T, and T4 were significantly increased in the SDR high dose group. The results of immunohistochemistry, qPCR, and Western blot analysis showed that compared with the model group, the expression levels of Smad 1, Smad 4, Smad 5, Smad 8 and BMP 7 proteins in the kidney of DR groups were significantly increased. And SDR groups tended to be better than CDR groups. 8 constituents migrating to blood were identified. This study showed that both CDR and SDR could have a good therapeutic effect on KYDS, and SDR was better than CDR. This study chose the BMP-Smad signaling pathway to study the mechanism of DR in the treatment of KYDS and provided a scientific basis for the processing mechanism of salt-processed.


Combination therapy with miR34a and doxorubicin synergistically inhibits Dox-resistant breast cancer progression via down-regulation of Snail through suppressing Notch/NF-κB and RAS/RAF/MEK/ERK signaling pathway.
Resistance to breast cancer (BCa) chemotherapy severely hampers the patient's prognosis. MicroRNAs provide a potential therapeutic prospect for BCa. In this study, the reversal function of microRNA34a (miR34a) on doxorubicin (Dox) resistance of BCa and the possible mechanism was investigated. We found that the relative level of miR34a was significantly decreased in Dox-resistant breast cancer cell MCF-7 (MCF-7/A) compared with Dox-sensitive MCF-7 cells. Transfection with miR34a significantly suppressed the invasion, migration, adhesion of MCF-7/A cells without inhibiting their growth obviously. The combination of miR34a and Dox could significantly inhibit the proliferation, migration, invasion and induce the apoptosis of MCF-7/A cells. The synergistic effect of this combination on resistant MCF-7/A cells has no obvious relation with the expressions of classical drug-resistant proteins P-GP, MRP and GST-π, while closely related with the down-regulation on TOP2A and BCRP. Moreover, we found both protein and mRNA expression of Snail were significantly up-regulated in MCF-7/A cells in comparison with MCF-7 cells. Transfection with small interfering RNA (siRNA) of Snail could inhibit the invasion, migration and adhesion of drug-resistant MCF-7/A cells, while high-expression of Snail could remarkably promote the invasion, migration and adhesion of MCF-7 cells, which might be related with regulation of N-cadherin and E-cadherin. Transfection with miR34a in MCF-7/A cells induced a decrease of Snail expression. The potential binding sites of miR34a with 3' UTR of Snail were predicted by miRDB target prediction software, which was confirmed by luciferase reporter gene method. Results showed that the relative activity of luciferase was reduced in MCF-7/A cells after co-transfection of miR34a and wild type (wt)-Snail, while did not change by co-transfection with miR34a and 3' UTR mutant type (mut) Snail. Combination of miR34a and Dox induced a stronger decrease of Snail in MCF-7/A cells in comparison to miR34a or Dox treatment alone. What' more, for the first time, we also found miR34a combined with Dox could obviously inhibit the expression of Snail through suppressing Notch/NF-κB and RAS/RAF/MEK/ERK pathway in MCF-7/A cells. In vivo study indicated that combination of miR34a and Dox significantly slowed down tumor growth in MCF-7/A nude mouse xenograft model compared with Dox alone, which was manifested by the down-regulation of Snail and pro-apoptosis effect in tumor xenografts. These results together underline the relevance of miR34a-driven regulation of Snail in drug resistance and co-administration of miR34a and Dox may produce an effective therapy outcome in the future in clinic.


Use of Alkylarsonium Directing Agents for the Synthesis and Study of Zeolites.
Expanding the previously known family of -onium (ammonium, phosphonium, and sulfonium) organic structure-directing agents (OSDAs) for the synthesis of zeolite MFI, a new member, the arsonium cation, is used for the first time. The new group of tetraalkylarsonium cations has allowed the synthesis of the zeolite ZSM-5 with several different chemical compositions, opening a route for the synthesis of zeolites with a new series of OSDA. Moreover, the use of As replacing N in the OSDA allows the introduction of probe atoms that facilitate the study of these molecules by powder X-ray diffraction (PXRD), solid-state nuclear magnetic resonance (MAS NMR), and X-ray absorption spectroscopy (XAS). Finally, the influence of trivalent elements such as B, Al, or Ga isomorphically replacing Si atoms in the framework structure and its interaction with the As species has been studied. The suitability of the tetraalkylarsonium cation for carrying out the crystallization of zeolites is demonstrated along with the benefit of the presence of As atoms in the occluded OSDA, which allows its advanced characterization as well as the study of its evolution during OSDA removal by thermal treatments.


Predictive factors of operability after neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer: a single-center retrospective study.
Recently neoadjuvant chemotherapy (NAC) for pancreatic cancer has been shown to be superior to upfront surgery, but it remains a matter of debate for resectable cases. In clinical practice, some resectable cases may become unresectable after NAC. This study aimed to reveal the outcomes after NAC and to clarify the characteristics of unresected cases. The medical records of 142 patients who underwent NAC between 2016 and 2020 were retrospectively reviewed. Patient characteristics, effectiveness of NAC, and outcomes were compared between the surgical group and non-surgical group (NSG). Furthermore, the risk of recurrence limited to in the patients who received NAC with gemcitabine plus nab-paclitaxel, which were mostly administered in this cohort, following R0/R1 resection was assessed. The overall and R0 resection rates after NAC were 89.1% and 79.7%, respectively. The neutrophil to lymphocyte ratio (NLR) > 2.78 (p = 0.0120) and anatomical borderline resectable pancreatic cancer (p = 0.0044) revealed a statistically significantly correlation with the NSG. On the other hand, NAC week < 8 (p = 0.0285), radiological response, stable disease or progression disease (p = 0.0212), and pathological stage > IIA (P = 0.0003) were significantly associated with recurrence. The tumor response rate was approximately 26.1%, and three patients with ≥ 30% reduction of primary tumor lost excision opportunities because of metastasis, interstitial pneumonia, and vascular invasion. This study shows incomplete tumor shrinkage benefits, but pre-NAC NLR is a predictive factor for predicting operability after NAC. The NLR can be easily calculated by normal blood test, and can be considered as a suitable marker of operability.


A systematic review and meta-analysis on the co-infection of Helicobacter pylori with intestinal parasites: public health issue or neglected correlation?
The current study was conducted to assess the prevalence and odds ratio (OR) of co-infection of Helicobacter pylori (H. pylori) and intestinal parasites (IPs). English databases were searched. A total of 18 studies including 14 studies with cross-sectional design (a total of 3739 participants) and 4 studies with case-control design (397 patients and 320 controls) met the eligibility criteria. The pooled prevalence of H. pylori, intestinal parasite infections (IPIs), and their co-infections in different populations were 48.3% (95% CI, 34.1-62.8%), 15.4% (95% CI, 10-22.8%), and 11% (95% CI, 6.7-17.6%), respectively. The co-infection of H. pylori and Giardia was 7.6% (95% CI, 4.9-11.7%). Although statistically not significant, the risk of co-infection of H. pylori and IPIs was higher in case group compared to control group (OR, 1.59; 95% CI, 0.77-3.25). The overlaps between H. pylori and IPIs in countries with lower human development index (HDI) and income levels were high.


Predicting the need for mechanical ventilation in acute exacerbations of chronic obstructive pulmonary disease: comparing the CURB-65 and BAP-65 scores.
Clinicians lack a validated tool for risk stratification for need for mechanical ventilation (MV) in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). We sought to compare 2 risk scores, BAP-65 and CURB-65, at predicting a need for MV in AECOPDs. We analyzed 34,478 AECOPD admissions to 195 US hospitals (2007). We compared the rates of MV at admission and at any point during hospitalization based on the respective BAP-65 and CURB-65 scores. We compared the accuracy of the 2 scores via the area under the receiver operating characteristic curves. The overall MV rate at admission was 7.9%, and the rate of MV any time equaled 9.3%. Use of MV increased with escalating BAP-65 and CURB-65 scores. The area under the receiver operating characteristic curve for BAP-65 was higher than that for CURB-65 for both early MV, 0.81 (95% confidence interval [CI], 0.80-0.82) vs 0.76 (95% CI, 0.75-0.77), P < .0001, and MV any time, 0.78 (95% CI, 0.77-0.79) vs 0.74 (95% CI, 0.73-0.75), P < .0001. BAP-65 identifies patients with AECOPD at high risk for need of MV more accurately than does CURB-65. BAP-65 may represent a useful tool for initial MV risk stratification in AECOPD.


Spinning-disk confocal microscopy: present technology and future trends.
Live-cell imaging requires not only high temporal resolution but also illumination powers low enough to minimize photodamage. Traditional single-point laser scanning confocal microscopy (LSCM) is generally limited by both the relatively slow speed at which it can acquire optical sections by serial raster scanning (a few Hz) and the higher potential for phototoxicity. These limitations have driven the development of rapid, parallel forms of confocal microscopy, the most popular of which is the spinning-disk confocal microscope (SDCM). Here, we briefly introduce the SDCM technique, discuss its strengths and weaknesses against LSCM, and update the reader on some recent developments in SDCM technology that improve its performance and expand its utility for life science research now and in the future.


The exocyst complex is required for developmental and regenerative neurite growth in vivo.
The exocyst complex is an important regulator of intracellular trafficking and tethers secretory vesicles to the plasma membrane. Understanding of its role in neuron outgrowth remains incomplete, and previous studies have come to different conclusions about its importance for axon and dendrite growth, particularly in vivo. To investigate exocyst function in vivo we used Drosophila sensory neurons as a model system. To bypass early developmental requirements in other cell types, we used neuron-specific RNAi to target seven exocyst subunits. Initial neuronal development proceeded normally in these backgrounds, however, we considered this could be due to residual exocyst function. To probe neuronal growth capacity at later times after RNAi initiation, we used laser microsurgery to remove axons or dendrites and prompt regrowth. Exocyst subunit RNAi reduced axon regeneration, although new axons could be specified. In control neurons, a vesicle trafficking marker often concentrated in the new axon, but this pattern was disrupted in Sec6 RNAi neurons. Dendrite regeneration was also severely reduced by exocyst RNAi, even though the trafficking marker did not accumulate in a strongly polarized manner during normal dendrite regeneration. The requirement for the exocyst was not limited to injury contexts as exocyst subunit RNAi eliminated dendrite regrowth after developmental pruning. We conclude that the exocyst is required for injury-induced and developmental neurite outgrowth, but that residual protein function can easily mask this requirement.


A severe neurocognitive phenotype caused by biallelic CHD3 variants in two siblings.
CHD3 heterozygous variants are associated with Snijders Blok-Campeau syndrome (SBCS) which consists of intellectual disability (ID), macrocephaly, and dysmorphic facies. Most reported variants are missense or loss of function clustered within the ATPase/helicase domain of the protein. We report a severe neurocognitive phenotype caused by biallelic CHD3 variants in two siblings, each inherited from a mildly affected parent. Male and female siblings were referred to the Genetics Clinic due to severe ID and profound dysmorphism. The parents are first cousins of Iranian descent with borderline intellectual abilities. Exome sequencing was performed for the affected female and her parents. A single homozygous candidate variant in the CHD3 gene was detected in the proband: c.5384_5389dup. p.Arg1796_Phe1797insTrpArg, resulting in an in-frame insertion of 2 amino acids located outside the ATPase/helicase domain at the C-terminal region of CHD3-encoding residues. This variant is classified as likely pathogenic according to ACMG guidelines. The variant was detected in a heterozygous state in each parent. Both affected siblings were homozygous, while their unaffected brother did not carry the variant. Biallelic CHD3 variants cause a severe neurodevelopmental syndrome that is distinguishable from SBCS. We assume that the variant type (in-frame insertion) and location may enable CHD3 biallelic variants.


Men's determinant factors on antenatal care involvement and childbirth place preference in Indonesia: An analysis of the 2012 Indonesia Demographic and Health Survey (IDHS).
This study aimed to describe the determinant factors of men's involvement in antenatal care and childbirth place preference in Indonesia. Secondary data from the 2012 Indonesia Demographic and Health Survey was used to identify factors determining men's presence during antenatal care and childbirth place preference. All factors were analyzed utilizing bivariate and multivariate logistic regression. Men living in urban areas, having a sufficient economy, having higher educational levels, and having more interaction with mass media were more likely present during the antenatal care of their wives. Men in Sulawesi and Maluku showed lower involvement in accompanying wives during antenatal care than those in Papua. In terms of delivery place preference, men in age 15-19 and 35-49 years, living in urban areas, having a more stable economy, reading newspapers or magazines as well as watching television at least once a week, and living in Java and Nusa Tenggara, were more likely having wife giving birth in healthcare facilities. Type of residence, economic situations, lower educational level, and fewer interactions with mass media and electronics are essential barriers to men's involvement in wives' antenatal care visits and childbirth place preference in Indonesia. Particular attention should be put to Sulawesi and Maluku to enforce the men and women as those islands underutilized antenatal care services and health facilities for childbirth.


Onlay island flap urethroplasty: variation on a theme.
The onlay island flap urethroplasty is useful in patients with distal, mid shaft and proximal hypospadias who have a well developed urethral plate and exhibit little or no curvature after release of chordee. The technique described has 2 main features: 1) use of the entire inner prepuce of the foreskin facilitates its mobilization and protects the vascular pedicle, and 2) additional soft tissue coverage is gained by removing the excess preputial mucosa not used for the neourethra. This extra soft tissue covering of the suture lines should prevent fistula formation. During the last 4 1/2 years the onlay island flap has been used for repair of hypospadias in 61 patients. The complication rate (6%) is low and compares favorably with other techniques. Further refinements in the onlay flap hypospadias repair should decrease the complication rate and widen its applicability.


Non-classical antifolates. Part 2: synthesis, biological evaluation, and molecular modeling study of some new 2,6-substituted-quinazolin-4-ones.
A new series of 2,6-substituted-quinazolin-4-ones was designed, synthesized, and evaluated for their in vitro DHFR inhibition, antimicrobial, and antitumor activities. Compounds 22, 33-37, 39-43, and 45 proved to be active DHFR inhibitors with IC(50) range of 0.4-1.0microM. Compound 18 showed broad-spectrum antimicrobial activity comparable to the known antibiotic gentamicin. Compounds 34 and 36 showed antitumor activity at GI(50) (MG-MID) concentrations of 11.2, and 24.2microM, respectively. Molecular modeling study including flexible alignment; electrostatic, hydrophobic mappings; and pharmacophore prediction were performed. A main featured pharmacophore model was developed which justifies the importance of the main pharmacophoric groups as well as of their relative distances. The substitution pattern and spatial considerations of the pi-systems in regard to the quinazoline nucleus proved critical for biological activity.


Asymmetry Optimization for 10 THz OPC Transmission over the C + L Bands Using Distributed Raman Amplification.
An optimized design for a broadband Raman optical amplifier in standard single-mode fiber covering the C and L bands is presented, to be used in combination with wideband optical phase conjugation (OPC) nonlinearity compensation. The use of two Raman pumps and fiber Bragg grating reflectors at different wavelengths for the transmitted (C band) and conjugated (L band) WDM channels is proposed to extend bandwidth beyond the limits imposed by single-wavelength pumping, for a total 10 THz. Optimization of pump and reflector wavelength, as well as pump powers, allows us to achieve low asymmetry across the whole transmission band for optimal nonlinearity compensation. System performance is simulated to estimate OSNR, gain flatness and nonlinear Kerr distortion.


Tartrate-resistant acid phosphate activity as osteoclastic marker: sensitivity of cytochemical assessment and serum assay in comparison with standardized osteoclast histomorphometry.
Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.


Genome-wide association study for grain mineral content in a Brazilian common bean diversity panel.
QTNs significantly associated to nine mineral content in grains of common bean were identified. The accumulation of favorable alleles was associated with a gradually increasing nutrient content in the grain. Biofortification is one of the strategies developed to address malnutrition in developing countries, the aim of which is to improve the nutritional content of crops. The common bean (Phaseolus vulgaris L.), a staple food in several African and Latin American countries, has excellent nutritional attributes and is considered a strong candidate for biofortification. The objective of this study was to identify genomic regions associated with nutritional content in common bean grains using 178 Mesoamerican accessions belonging to a Brazilian Diversity Panel (BDP) and 25,011 good-quality single nucleotide polymorphisms. The BDP was phenotyped in three environments for nine nutrients (phosphorus, potassium, calcium, magnesium, copper, manganese, sulfur, zinc, and iron) using four genome-wide association multi-locus methods. To obtain more accurate results, only quantitative trait nucleotides (QTNs) that showed repeatability (i.e., those detected at least twice using different methods or environments) were considered. Forty-eight QTNs detected for the nine minerals showed repeatability and were considered reliable. Pleiotropic QTNs and overlapping genomic regions surrounding the QTNs were identified, demonstrating the possible association between the deposition mechanisms of different nutrients in grains. The accumulation of favorable alleles in the same accession was associated with a gradually increasing nutrient content in the grain. The BDP proved to be a valuable source for association studies. The investigation of different methods and environments showed the reliability of markers associated with minerals. The loci identified in this study will potentially contribute to the improvement of Mesoamerican common beans, particularly carioca and black beans, the main groups consumed in Brazil.


Work, training and social sensibilities: analysis from the experiences of fit-fluencers.
The article aims to reflect on the transformations that have taken place in the "world of work", based on their connections with the way in which subjects "train themselves". In the interstices between "work time" and "leisure/training time", some important characteristics of current body politics (the ways in which societies accept the distribution and use of bodies and their energies) become visible. Specifically, we explore here the emerging phenomenon of "fit-influencers", contemporary referents of the "virtual" scene (social networks) through the promotion of sports and eating routines. In this sense, our corpus of analysis has been constructed from an ethnographic work located in Argentina, from which narratives that these actors present in social networks (Virtual Ethnography), and in situations of in-depth interviews, are recovered. These narratives allow us to understand the social sensibilities associated with these practices, enabling us to link the emergence and expansion of fit-influencers with a process of renewal of the "spirit of capitalism" (sensu Weber), which would translate into an updating of the "political economy of morality" (Scribano in ¡Disfrútalo! Una aproximación a la economía política de la moral desde el consumo, Elalephcom, Ciudad Autónoma de Buenos Aires, 2015). To be clearer, "political economy of morality" refers to a series of mechanisms of social domination and exploitation of bodily energies, which are legitimised as moral principles associated with enjoyment through consumption. The final reflections we present are oriented towards thinking about how the new "digital gurus" of routines and "homemade" prescriptions become guarantors of the organisation of work, by establishing parameters for the management of bodies and emotions that are associated to a "renewed" order of accumulation.


Design concepts for DNA-encoded library synthesis.
An approach of building block (BB) inclusivity and atom efficient library schemes deliver the quality and diversity of DNA-encoded libraries best suited for small molecule drug discovery. In this Perspective, we offer key learnings in DEL design from a decade's worth of DEL-driven screening.


Mass-spectrometry-based proteomics reveals mitochondrial supercomplexome plasticity.
Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based quantification, often limited to a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combine native electrophoresis and mass spectrometry to determine the supercomplexome of skeletal muscle from sedentary and exercise-trained mice. We quantify 422 mitochondrial proteins within 10 supercomplex bands in which we show the debated presence of complexes II and V. Exercise-induced mitochondrial biogenesis results in non-stoichiometric changes in subunits and incorporation into supercomplexes. We uncover the dynamics of supercomplex-related assembly proteins and mtDNA-encoded subunits after exercise. Furthermore, exercise affects the complexing of Lactb, an obesity-associated mitochondrial protein, and ubiquinone biosynthesis proteins. Knockdown of ubiquinone biosynthesis proteins leads to alterations in mitochondrial respiration. Our approach can be applied to broad biological systems. In this instance, comprehensively analyzing respiratory supercomplexes illuminates previously undetectable complexity in mitochondrial plasticity.


Use of anthropometric measurements in assessing risk for coronary heart disease: a useful tool in worksite health screening?
The study examined the association between the anthropometric measurements body mass index (BMI), waist/hip ratio (WHR), and waist/thigh ratio (WTR) and cardiovascular risk factors, and assessed whether a combination of BMI and WHR could be used in routine screening of risk for cardiovascular arteriosclerotic disease at worksites. The data were obtained from a cross-sectional survey designed to assess the nutritional situation, with special reference to cardiovascular risk factors. The study population comprised 372 healthy men working on platforms in the North Sea. Serum cholesterol, triglyceride, fibrinogen, and blood pressure were positively related to the anthropometric variables, while high-density lipoprotein (HDL) was inversely related with them. The relations remained after adjusting for possible confounders, such as age, smoking, physical activity, and an indicator of dietary fat intake. In stepwise multiple linear regression models, BMI, WHR, and WTR were positively related to serum cholesterol, triglycerides, fibrinogen, diastolic blood pressure, and systolic blood pressure, and inversely related to HDL. When controlling for the anthropometric variables WHR and WTR, BMI was not independently related to fibrinogen and risk score. WHR and WTR were not independently related to systolic and diastolic blood pressure, and WTR was in addition not related to triglycerides when controlling for BMI. Overall, the anthropometric variables BMI and WHR were considered the best predictors for CAD risk when taking several risk factors into consideration. A joint variable between BMI and WHR, called "body score", constituted the four categories lean, lean android, overweight gynoid, and overweight ovoid. This body score was positively associated with levels of serum lipids, fibrinogen, and blood pressure, and inversely associated with HDL. In stepwise multiple linear regression models, controlling for possible confounding variables, body score was positively related to CAD risk. Dividing the risk score into tertiles, about 51% of the lean were in the first, while 46% of the overweight ovoid were in the third tertile. Those classified as lean android or overweight gynoid had about the same distribution, namely between 31% and 39% in each tertile if the two categories were combined. These data support the hypothesis that BMI, WHR, and WTR are independent predictors for risk factors for CAD among oil workers, and that combinations of BMI and WHR are strong enough predictors to be useful in routine screening for CAD risk at worksites. Based on these findings, supported by data from the literature, a matrix aimed at screening for follow-up at worksites is proposed.


The Effect of Adding Magnesium Sulfate to Lidocaine Compared with Paracetamol in Prevention of Acute Pain in Hand Surgery Patients Under Intravenous Regional Anesthesia (IVRA).
This study was done to compare the analgesic effects of "magnesium plus lidocaine", "paracetamol plus lidocaine", and "placebo plus lidocaine" on block characteristics for intravenous regional anesthesia (IVRA) in patients undergoing upper extremity orthopedic surgery. In a double-blind, placebo-controlled randomized clinical trial, 90 patients were selected and entered randomly into three study groups after applying the inclusion and exclusion criteria. Time to start of the sensory and motor block were measured separately and also the duration of these two block types were measured. Post-op pain assessment was measured using a numeric rating scale. Venous samples were checked and compared regarding blood gas and pH measurements. The time from drug injection to sensory block onset was the shortest in the magnesium plus lidocaine group; the time from drug injection to the time of motor block onset was the shortest in the lidocaine plus magnesium group; the duration of the motor block was the longest in the lidocaine plus magnesium group. Addition of magnesium lidocaine in patients undergoing upper extremity orthopedic operations using IVRA decreases significantly the time gap between drug administration and the start of the block; also, this drug combination increases the IVRA block length, while paracetamol does not have such a significant effect.


Structural studies of induced antibodies with defined idiotypic specificities. IV. The heavy chains of anti-streptococcal group A carbohydrate antibodies from Sprague-Dawley rats carrying a cross-reacting idiotype.
The heavy (H) chains of three anti-streptococcal group A carbohydrate antibodies (anti-SACHO) of restricted heterogeneity, elicited in inbred Sprague-Dawley rats, were subjected to 40 cycles of automated Edman degradation. All three antibody H-chain preparations had an identical amino acid sequence and were classified as a variant of the VHIII subgroup of immunoglobulin H chains. A comparison of the H-chain sequence of these antibodies with that of pooled rat gamma chains suggests that a very minor population of H chains (closely related to the VHIII subgroup) has been 'recruited' as a consequence of this immunization. This observation further supports the notion that 'framework' and 'specificity' or 'hypervariable regions' are closely linked.


Magnesium homeostasis following chemotherapy with cisplatin: a prospective study.
Retrospective studies suggest that cisplatin chemotherapy regularly leads to hypomagnesemia and occasionally hypocalcemia. The hypomagnesemia has been attributed to renal magnesium wasting. We examined prospectively the incidence of hypomagnesemia, magnesuria, and hypocalcemia in 17 patients receiving chemotherapy with cisplatin. Hypomagnesemia was found in 53% to 88% of patients, depending on the definition of hypomagnesemia. All displayed inappropriate renal excretion of magnesium. Hypocalcemia occurred in one of the 17 prospectively studied patients (5.8%) and in three additional retrospective patients. Hypocalcemic patients demonstrated lower serum magnesium values, higher fractional magnesium excretion, and evidence for reduced intestinal magnesium absorption. We conclude that hypomagnesemia, renal magnesium wasting, and hypocalcemia occur frequently among patients receiving cisplatin. Hypocalcemia occurs in those patients who have the severest renal magnesium wasting, the severest hypomagnesemia, and inadequate intestinal magnesium absorption.


Silencing TTK expression inhibits the proliferation and progression of prostate cancer.
The main objective of our study was to explore changes in the expression levels of differentially expressed genes associated with prostate cancer progression and to design a series of experiments to verify the function of differentially expressed genes. The transcriptome datas of 499 cases of prostate cancer patients was downloaded from TCGA database. Differential genes associated with Gleason score were selected and filtered out by p < 0.05 and spearman coefficient >0.3. KEGG signaling pathway was enriched by differentially expressed genes, and TTK was selected as the research object. The expression of TTK was tested in prostate cancer tissues and prostate cancer cell lines. The changes of biological behavior of prostate cancer cell lines were verified after TTK was knocked out by siRNA and tumorigenic effect of TTK was verified by shRNA in vivo experiments. The expression of TTK was positively correlated with Gleason score of prostate cancer, and the expression of protein and mRNA in metastatic prostate cancer cell lines was higher than that in non-metastatic prostate cancer cell lines. Vitro biological experiments showed that TTK gene knockout could inhibit the proliferation, invasion and migration of PC3 and DU145 cells, and promote cell apoptosis. In vivo experiments showed that TTK knockout inhibited tumorigenesis in mice. It was found that the expression of CDK2 and CCNE1 decreased after TTK was knocked out. Our results suggest that TTK is a gene associated with malignancy of PCa and could be a novel therapeutic target for clinical application.


Trends in malnutrition among children in India: growing inequalities across different economic groups.
This paper examines the trends and patterns of economic inequalities with respect to child malnutrition by wealth status of population across major regions and states of India. Data from three rounds of National Family and Health Survey (NFHS) conducted during 1992-2006 were analyzed. The proportion of underweight children (measure of both acute and chronic malnutrition) has been used as a dependent variable. The wealth index is used as proxy for economic status of the population, and was estimated through principal component analysis by employing a set of variables representing durable asset ownership, access to utilities and infrastructure, and housing characteristics of respondents for all the three survey rounds. Bivariate analyses, poor-rich ratio and concentration indices were used to understand the trends in economic inequalities with respect to child malnutrition. Pooled logistic regression models were fitted to estimate the adjusted effect of economic status on the likelihood of child malnutrition over time. Results indicate sluggish change coupled with concomitant rise in economic inequalities with respect to child malnutrition in India during 1992-2006. The burden of malnutrition was disproportionately concentrated among poor children. In addition, average decline in malnutrition concealed large economic disparities across space and time.


Creatine kinase regulation by reversible phosphorylation in frog muscle.
Creatine kinase (CK) was analyzed from skeletal muscle of wood frogs, Rana sylvatica, a species that survives natural whole body freezing during the winter months. Muscle CK activity increased by 35% and apparent K(m) creatine decreased by 29% when frogs froze. Immunoblotting analysis showed that this activity increase was not due to a change in total CK protein. Frog muscle CK was regulated by reversible protein phosphorylation; in vitro incubations with (32)P-ATP under conditions that facilitated the actions of various protein kinases (PKA, PKG, PKC, CaMK or AMPK) resulted in immunoprecipitation of (32)P-labeled CK. Furthermore, incubations that stimulated CaMK or AMPK altered CK kinetics. Incubation under conditions that facilitated protein phosphatases (PP2B or PP2C) reversed these effects. Phosphorylation of CK increased activity, whereas dephosphorylation decreased activity. Ion-exchange chromatography revealed that two forms of CK with different phosphorylation states were present in muscle; low versus high phosphate forms dominated in muscle of control versus frozen frogs, respectively. However, CK from control versus frozen frogs showed no differences in susceptibility to urea denaturation or sensitivity to limited proteolysis by thermolysin. The increased activity, increased substrate affinity and altered phosphorylation state of CK in skeletal muscle from frozen frogs argues for altered regulation of CK under energy stress in ischemic frozen muscle.


Blood pressure and heart rate response evoked by p-hydroxyamphetamine and by p-hydroxynorephedrine II. A quantitative assessment of the role of amphetamine metabolites in acute responses evoked by d-amphetamine.
At postganglionic sympathetic sites, p-hydroxyamphetamine is neither a receptor agonist nor a receptor antagonist; in addition the drug does not act presynaptically to antagonize or synergize d-amphetamine. p-Hydroxyamphetamine is an indirectly acting sympathomimetic amine with a potency approximately twice that of d-amphetamine. In the rat, a large fraction (approximately 0.5) of d-amphetamine is biotransformed to p-hydroxyamphetamine. However, the rate of biotransformation to p-hydroxyamphetamine (approximately 0.0099 . min-1) is slow compared to the rate of elimination of p-hydroxyamphetamine (0.049 . min-1). As a result, plasma levels of d-amphetamine exceed those of p-hydroxyamphetamine. The kinetic data suggest that: 1) p-hydroxyamphetamine plays little role in immediate responses to single injections of d-amphetamine; 2) p-hydroxyamphetamine is not involved in tachyphylactic responses to repeated injections of d-amphetamine; and 3) p-hydroxynorephedrine plays no role in immediate or tachyphylactic responses to d-amphetamine.


Adding a "GRADE" to the quality appraisal of rheumatoid arthritis guidelines identifies limitations beyond AGREE-II.
To assess how well treatment recommendations for rheumatoid arthritis (RA) address Grading of Recommendations Assessment, Development and Evaluation (GRADE) steps and determine whether these steps can be adequately appraised using Appraisal of Guidelines Research & Evaluation II (AGREE-II). We systematically reviewed English-language treatment recommendations for the pharmacologic management of RA since 2000, assessed how well GRADE steps were addressed, rated AGREE-II quality, and compared the findings. GRADE steps were poorly addressed by the 44 included guidelines. Few guidelines discussed study limitations and/or risk of bias (23%), inconsistency (50%), indirectness (39%), imprecision (23%), or potential for publication bias (0%). Observational evidence was cited in 96% but rarely evaluated systematically. Only one guideline considered evidence on patients' preferences for health outcomes, and few provided an explicit justification for the strength of evidence or recommendation. The five GRADE steps that overlapped with AGREE-II questions were addressed more frequently (by 54-100% of guidelines) than the 13 GRADE steps not directly assessed by AGREE-II (0-50%). Among the nine guidelines rated as "Recommended for use" by AGREE-II, 8 of 13 GRADE steps were not addressed consistently by any guideline. GRADE's steps are poorly addressed by RA recommendations. AGREE-II provides a broad assessment of quality but lacks sufficient granularity to assess how well a guideline addresses GRADE's steps.


Source connectivity patterns in the default mode network differ between elderly golf-novices and non-golfers.
Learning to play golf has high demands on attention and therefore may counteract age-related changes of functional brain networks. This cross-sectional study compared source connectivity in the Default Mode Network (DMN) between elderly golf novices and non-golfers. Four-minute resting-state electroencephalography (128 channels) from 22 elderly people (mean age 67 ± 4.3 years, 55% females) were recorded after completing a 22-week golf learning program or after having continued with normal life. Source connectivity was assessed after co-registration of EEG data with native MRI within pre-defined portions of the DMN in the beta band (14-25 Hz). Non-golfers had significantly higher source connectivity values in the anterior DMN compared to non-golfers. Exploratory correlation analyses did not indicate an association to cognitive performance in either group. Inverse correlations between a marker of external attention with source connectivity of the anterior DMN may suggest a trend in the golf group only, but have to be replicated in future studies. Clinical relevance of these findings remains to be elucidated, but the observed difference in the anterior DMN may provide a starting point to further investigate if and how learning golf may have an impact on physiological age-related cognitive changes.


Mechanisms of platelet dysfunction and response to DDAVP in patients with congenital platelet function defects. A double-blind placebo-controlled trial.
To examine the impact of the underlying defective platelet mechanism on the response to 1-desamino-8-D-arginine vasopressin (DDAVP, Desmopressin), we studied the effect of intravenous infusion of 0.3 microgram/kg of DDAVP in a randomized double blind placebo-controlled trial with cross-over in 18 carefully characterized patients with congenital platelet defects (CPD) and BT > or = 9 min. Eleven patients had normal dense granule stores and normal thromboxane A2 (TxA2) production (Group I), 3 patients had normal granule stores but impaired TxA2 production (Group II), and 4 had delta-storage pool deficiency (Group III). DDAVP shortened BT at 50 min (DDAVP 14.6 +/- 2.2 vs placebo 19.6 +/- 2.3 min; n = 18; mean +/- SE; p = 0.003) and 4 h (17.0 +/- 2.2 vs 19.6 +/- 2.1 min, p = 0.055), and raised plasma FVIIIC and von Willebrand factor (vWF). At 50 min DDAVP shortened BT by > or = 5 min in 8 of 11 Group I patients (mean 9.7 +/- 1.3 vs 16.3 +/- 2.8 min; p < 0.008), 1 of 3 Group II patients (11.9 +/- 3.9 vs 17.7 +/- 6.6; p = NS) and none of Group III patients (mean 30 min both arms). Ten patients (Group I or II) were managed successfully during surgical procedures with DDAVP alone. We conclude that DDAVP shortens BT in majority of CPD patients with normal dense granule stores and suggest that BT response may be dependent on the underlying platelet defect. DDAVP is a useful modality in management of selected patients, particularly those with normal dense granule stores.


Vascular endothelial growth factor/kinase insult domain receptor (KDR)/fetal liver kinase 1 (FLK1)-mediated skin-epithelial progenitor cells reprogramming.
Vascular endothelial growth factor (VEGF) is an angiogenic protein that has effects on damaged neurons. We investigated VEGF function and found that it effectively induces the transition of skin-derived epithelial progenitor cells (EPCs) to more primitive stem cells. This change was accompanied by the epigenetic reprogramming of many genes. Among these genes are several stem-cell-associated transcription factors, such as Rex1, Oct4, Nanog, and Sox2. The VEGF-induced reprogramming of EPCs occurred through the FLK1 receptor and Janus kinase (JAK)/signal transducer- and activator of transcription 3 (STAT3) phosphorylation. When we engrafted VEGF-sensitized EPCs into sites of brain trauma, both engrafted VEGF/EPCs and endogenous cells showed functionally active neurogenesis and potent immunomodulatory function. These results indicate that VEGF actively induces the reprogramming of EPCs to become more primitive stem cells that display active cell growth, neurogenesis, migration, and survival behaviors, which may lead to a novel therapeutic strategy for central nervous system disorders.


Are sexual dissatisfaction and sexual abuse associated with obesity? A population-based study.
To investigate whether there is any association between obesity and sexual satisfaction and sexual abuse in a normal population. A representative sample of 2810 subjects from a population study was interviewed about sexual satisfaction, sexual abuse, and life satisfaction. The answers from normal weight, overweight, and obese participants were compared. Univariate and multivariate analyses were performed. Data were presented separately for two age groups, 18 to 49 and 50 to 74 years, and gender. The older group of obese men reported a greater decrease of sexual desire compared with 5 years prior than normal weight men [odds ratios (OR), 2.44; 95% confidence interval (CI), 1.4 to 4.3]. The older group of overweight men reported involuntary participation in sexual activities more often than normal weight men (OR, 2.06; 95% CI, 1.1 to 3.8). Although older overweight and obese women were diagnosed with a lingering disease (defined as >1 month) more often than normal weight women (overweight: OR, 2.41; 95% CI, 1.3 to 4.4; obese: OR, 4.45; 95% CI, 1.7 to 11.5), there was no difference between BMI groups in satisfaction with physical health. Overweight and obese groups seem to be heterogeneous with respect to sexual satisfaction and experiences of sexual abuse. No significant differences were detected between BMI groups, which does not exclude the possibility of significant differences between BMI groups among patients seeking medical attention.


The distribution of 13 killer-cell immunoglobulin-like receptor loci in UK blood donors from three ethnic groups.
Killer-cell immunoglobulin-like receptors (KIRs) can inhibit the killing activity of natural killer (NK) cells if they interact with their ligand, class I HLA. Using a modified polymerase chain reaction-sequence-specific primers (PCR-SSP) method for typing KIRs using genomic DNA, we compared KIR frequencies in three ethnic populations drawn from UK blood donors. We found a significantly lower frequency of the inhibitory KIRs KIR2DS1 and 3DS1 in Afro-Caribbean blood donors. Despite this, there was a (non-significant) increase in the B haplotype in Afro-Caribbean and Indian Asian donors. Some donors from each group tested negative for all non-inhibitory KIRs. In addition, we describe several new KIR profiles. Analysis of linkage disequilibrium was consistent with previously published findings.


Association between long interpregnancy intervals and cesarean delivery due to arrest disorders.
It is hypothesized that pregnancy causes time-limited physiologic adaptations of the reproductive system, such as increased blood flow to the uterus. With long interpregnancy intervals, those adaptations may regress, and maternal physiologic characteristics may revert to those of primigravid women. Therefore, it is plausible that long interpregnancy interval is associated with cesarean delivery, especially due to arrest disorders (failed induction of labor, arrest of dilation, or arrest of descent). To examine the association between interpregnancy interval and cesarean delivery due to arrest disorders in multiparous women without a history of cesarean delivery. This was a retrospective cohort study of all women who had more than 1 singleton pregnancy at 23 weeks' gestation or greater at MedStar Washington Hospital Center from January 2009 to June 2018. We defined the interpregnancy interval as the duration from the birth of the preceding offspring to the date of conception of the index offspring. We a priori decided to categorize women based on the interpregnancy interval (less than 18 months, 18-59 months, and 60 months or greater). Our primary outcome was cesarean delivery due to arrest disorders. We also examined overall cesarean delivery and cesarean delivery due to nonreassuring fetal heart tracing. Multivariable logistic regression was performed to calculate adjusted odds ratios and 95% confidence intervals, controlling for predefined covariates. Of 2741 women, 1143 (41.7%), 1369 (49.9%), and 229 (8.4%) had an interpregnancy interval of less than 18 months, 18-59 months, and 60 months or more, respectively. After adjusting for confounders, an interpregnancy interval of 60 months or more compared to an interpregnancy interval of 18-59 months was associated with increased odds of cesarean delivery due to arrest disorders (4.8% vs 1.3%; adjusted odds ratio, 3.06; 95% confidence interval, 1.34-6.97) and cesarean delivery due to arrest of dilation (3.1% vs 0.7%; adjusted odds ratio, 3.24; 95% confidence interval, 1.10-9.59). An interpregnancy interval of less than 18 months compared to an interpregnancy interval of 18-59 months was associated with decreased odds of cesarean delivery due to nonreassuring fetal heart tracing (2.4% vs 4.1%; adjusted odds ratio, 0.55; 95% confidence interval, 0.32-0.92). An interpregnancy interval of 60 months or greater compared to an interpregnancy interval of 18-59 months was associated with increased odds of cesarean delivery due to arrest disorders. Beneficial effects on postpartum adaptations in the reproductive system may regress as interpregnancy interval increases.


Thromboelastography does not reduce transfusion requirements in liver transplantation: A propensity score-matched study.
To compare total blood product requirements in liver transplantation (LT) assisted by thromboelastography (TEG) or conventional coagulation tests (CCTs). Retrospective observational study. A tertiary care referral center for LT. Adult patients undergoing LT from deceased donor. Hemostasis was monitored by TEG or CCTs and corresponding transfusion algorithms were adopted. Number and types of blood products (red blood cells, RBC; fresh-frozen plasma, FFP; platelets, PLT) transfused from the beginning of surgery until the admission to the intensive care unit. We compared data retrospectively collected in 226 LTs, grouped according to the type of hemostasis monitoring (90 with TEG and 136 with CCTs, respectively). Confounding variables affecting transfusion needs (recipient age, sex, previous hepatocellular carcinoma surgery, Model for End Stage Liver Disease - MELD, baseline hemoglobin, fibrinogen, creatinine, veno-venous by pass, and trans-jugular intrahepatic portosystemic shunt) were managed by propensity score match (PSM). The preliminary analysis showed that patients in the TEG group received fewer total blood products (RBC + FFP + PLT; p = 0.001, FFP (p = 0.001), and RBC (p = 0.001). After PSM, 89 CCT patients were selected and matched to the 90 TEG patients. CCT and TEG matched patients received similar amount of total blood products. In a subgroup of 39 patients in the top MELD quartile (MELD ≥25), the TEG use resulted in lower consumption of FFP units and total blood products. Nevertheless, due to the low number of patients, any meaningful conclusion could be achieved in this subgroup. In our experience, TEG-guided transfusion in LT does not reduce the intraoperative blood product consumption. Further studies are warranted to assess an advantage for TEG in either the entire LT population or the high-MELD subgroup of patients.