The role of non-coding RNAs in myocarditis: a narrative review.
Myocarditis is a heterogeneous disease that can lead to acute heart failure, dilated cardiomyopathy (DCM), and sudden death. However, the knowledge of the precise molecular mechanisms of myocarditis is fairly limited. In recent years, non-coding RNAs (ncRNAs) have been demonstrated to be involved in many physiological and pathological processes in myocarditis and to have the potential to be used as novel diagnostic and therapeutic strategies for myocarditis. This review summarizes the role of ncRNAs in myocarditis and discusses their potential as noninvasive biomarkers and therapeutic targets for myocarditis. Literature on ncRNAs and myocarditis published in PubMed was extensively reviewed for analysis and discussion. This review describes the roles of different ncRNAs in myocarditis and summarizes their potential in diagnosing and treating myocarditis. Multiple functions and mechanisms of ncRNAs in myocarditis have been uncovered. Current studies show that ncRNAs are widely involved in the occurrence and development of myocarditis caused by infection, autoimmunity, and the use of immune checkpoint inhibitors (ICIs) through their regulation of cell apoptosis, immune response, viral replication, and other aspects. Small-sample clinical studies have assessed the diagnostic value of ncRNAs. These results provide a new theoretical basis for diagnosing and treating myocarditis.


Understanding Aspects of Aluminum Exposure in Alzheimer's Disease Development.
Aluminum is a ubiquitously abundant nonessential element. Aluminum has been associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and dialysis encephalopathy. Many continue to regard aluminum as controversial although increasing evidence supports the implications of aluminum in the pathogenesis of AD. Aluminum causes the accumulation of tau protein and Aβ protein in the brain of experimental animals. Aluminum induces neuronal apoptosis in vivo and in vitro, either by endoplasmic stress from the unfolded protein response, by mitochondrial dysfunction, or a combination of them. Some, people who are exposed chronically to aluminum, either from through water and/or food, have not shown any AD pathology, apparently because their gastrointestinal barrier is more effective. This article is written keeping in mind mechanisms of action of aluminum neurotoxicity with respect to AD.


Variability in a dynamic postural task attests ample flexibility in balance control mechanisms.
When humans stand upright on a platform that sinusoidally translates in the anterior-posterior direction, the movements of upper and lower body segments are appropriately coordinated, in order to keep the body within its limits of stability. A significant fluctuation in this behaviour is evident across subjects and perturbation conditions. The inter- and intrasubject variability in the body segment kinematics, as occurs during repeated trials across different conditions, is quantitatively described here. Twenty normal subjects stood upright with eyes open (EO) or eyes closed (EC) on a platform moving to-and-fro in the horizontal plane for 30 s, at a frequency of 0.2 and 0.6 Hz, with a peak-to-peak amplitude of 6 cm. Each subject made two trial repetitions for each visual and frequency condition. The last 20 s of each trial was acquired. The displacement of markers fixed on the lateral malleolus, hip and head was sampled at a frequency of 50 Hz. An index of the 'average' displacement of each marker during the trial was the standard deviation (SD) of its anterior-posterior displacements, calculated across the acquired trial cycles. The cross-correlation (CC) between pairs of marker displacement traces gave an indication of the degree of coupling of the body segments. All subjects showed two basic modes of coping with the perturbation, depending on the availability of the visual input: with EO, they tended to stabilize the head in space; with EC, the head oscillated in the anterior-posterior direction more than hip and platform. Within this general behaviour, the values of the SD of horizontal displacement of head and hip marker traces varied within an ample range during different trials of the same perturbation condition. Even within a single trial there was an ample variability of the body segments' position. In spite of this, neither head nor hip ever bypassed the anterior or posterior limits of stability. Remarkably, the range of variability of the whole population of normal subjects, both across and within trials, was analogous to the range of variability of single subjects across numerous trials. This large variability notwithstanding, it appeared that the relationship of head to hip SD across trials was almost constant, independent of visual and perturbation frequency condition. The results show that there exist a large variety of dynamic postures, rather than one particular configuration, which assure stability. The findings also suggest a neural or biomechanical constraint underlying the operations of the equilibrium control strategy.


Influence of Inflammatory Pain and Dopamine on Synaptic Transmission in the Mouse ACC.
Dopamine (DA) inhibits excitatory synaptic transmission in the anterior cingulate cortex (ACC), a brain region involved in the sensory and affective processing of pain. However, the DA modulation of inhibitory synaptic transmission in the ACC and its alteration of the excitatory/inhibitory (E/I) balance remains relatively understudied. Using patch-clamp recordings, we demonstrate that neither DA applied directly to the tissue slice nor complete Freund's adjuvant (CFA) injected into the hind paw significantly impacted excitatory currents (eEPSCs) in the ACC, when recorded without pharmacological isolation. However, individual neurons exhibited varied responses to DA, with some showing inhibition, potentiation, or no response. The degree of eEPSC inhibition by DA was higher in naïve slices compared to that in the CFA condition. The baseline inhibitory currents (eIPSCs) were greater in the CFA-treated slices, and DA specifically inhibited eIPSCs in the CFA-treated, but not naïve group. DA and CFA treatment did not alter the balance between excitatory and inhibitory currents. Spontaneous synaptic activity revealed that DA reduced the frequency of the excitatory currents in CFA-treated mice and decreased the amplitude of the inhibitory currents, specifically in CFA-treated mice. However, the overall synaptic drive remained similar between the naïve and CFA-treated mice. Additionally, GABAergic currents were pharmacologically isolated and found to be robustly inhibited by DA through postsynaptic D2 receptors and G-protein activity. Overall, the study suggests that CFA-induced inflammation and DA do not significantly affect the balance between excitatory and inhibitory currents in ACC neurons, but activity-dependent changes may be observed in the DA modulation of presynaptic glutamate release in the presence of inflammation.


Dust mites living in human lungs--the cause of asthma?
Asthma does not have a clear cause and may represent a cluster of diseases. We propose that asthma in house dust mite sensitive patients may be caused by recurrent inhalation of live dust mites which are able to live for some time in the bronchioles of the lung. To provide themselves with a food source, the mites may purposefully excrete proteolytic enzymes, including Der p1, which increase epithelial shedding by freeing cells from the basement membrane. The mites then feed on the shed respiratory epithelial cells. Consequent loss of an intact respiratory epithelium exposes underlying tissues to dust mite protein and other allergens triggering sensitisation to these proteins. Later, repeated infestation provokes an allergic response which manifests itself as asthma attacks. The evidence for this hypothesis was tested against the Bradford-Hill criteria for causation; consistency, strength, temporal association and dose response. Potential areas for further research were also identified. The association between asthmatic symptoms and pulmonary acariasis was consistent across a number of studies. Determining the strength of the association and any dose response requires more work which is dependent on the development of better tests for the detection of mites in sputum. There was tentative evidence of a temporal association in the published studies identified. Biological plausibility and experimental evidence was available for pulmonary acariasis in primates and arsenic treatment was effective in humans. Better tests for mites in sputum are needed, as is work to assess more modern anti-acaricidal drugs in dust mite sensitive asthmatics.


"Quicker and sicker" under Medicare's prospective payment system for hospitals: new evidence on an old issue from a national longitudinal survey.
Medicare's prospective payment system for hospitals (PPS), introduced in the USA in 1983, replaced cost reimbursement with a system of fixed rates which created incentives for hospitals to control costs. Previous studies found that elderly patients were discharged from hospital "quicker and sicker" under PPS and concluded that families were coping at home. We analyse a national longitudinal survey, the first National Health and Nutrition Examination Survey and its Epidemiologic Followup Study, which includes data on more outcomes over a longer period than earlier studies. We find that the rate of admission to nursing homes from the community in the first weeks after a hospital discharge more than tripled under PPS, suggesting that families were not always able to cope. As another response to sicker patients, discharges directly to nursing homes from hospitals, which jumped initially under PPS, may have risen further when payment rates were tightened in the early 1990s. Hospital readmissions fell after the first few years. Our findings are strengthened by the fact that we control for patients' health using health information collected independently of hospital admission.


gamma delta T cells infiltrating sensory nerve biopsies from patients with inflammatory neuropathy.
Sensory nerve biopsy specimens from patients with Guillain Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and controls consisting of other neuropathies, were examined in order to characterise the nature and intensity of any inflammatory infiltrate. In order to establish whether gamma delta T cells were present in these infiltrates we examined the expression of alpha beta and gamma delta T cell receptors in the biopsy specimens from patients with inflammatory neuropathy. A section of each biopsy specimen was simultaneously cultured in order to attempt to establish T cell lines. T cell lines were established in 4 out of 7 patients with GBS of which 2 were gamma delta in phenotype. There was a significant correlation between the number of mononuclear cells detected by immunostaining within the biopsy specimens and the chance of successfully establishing a T cell line. Histological studies detected gamma delta T cell receptor in 2 out of the 7 patients with GBS, 14 out of the 20 with CIDP and in 5 out of the 13 controls (vasculitis 3, paraneoplastic 1, axonal neuropathy of uncertain cause 1). The presence of T cells of a gamma delta T cell receptor phenotype in nerve biopsy specimens from patients with inflammatory neuropathy is consistent with a possible pathogenetic role of a cellular immune response against non-protein antigens such as gangliosides.


Surgical Management of Pediatric Vesicoureteral Reflux: A Comparative Study Between Endoscopic, Laparoscopic, and Open Surgery.
Our retrospective study compared the results of three surgical procedures for correction of pediatric vesicoureteral reflux (VUR): open Cohen, laparoscopic Lich-Gregoir reimplantation (LEVUR), and endoscopic subureteric injection (STING) procedure. We analyzed 90 patients (50 girls, 40 boys, average age 4.86 years) operated in two centers of pediatric surgery for VUR. Exclusion criteria were Grade 1 VUR, Grade 5 VUR with megaureters requiring ureteral tapering, secondary VUR, and patients already operated for VUR. Thirty patients underwent Cohen, 30 LEVUR, and 30 STING procedure. Follow-up included renal ultrasonography and voiding cystourethrography 6 months postoperatively. The statistical analysis was performed using χ(2) Pearson and Fisher tests. Operative time was shorter using STING either for unilateral or bilateral correction (P = .001). Hospitalization was statistically shorter using STING and LEVUR compared to Cohen (P = .001). The pain scores were worse after Cohen (P = .001). Analgesic requirements were higher after Cohen (P = .001). Reflux persistence was higher after STING (10 cases versus 5 Cohen and 4 LEVUR). Cohen presented more complications compared to LEVUR and STING (P = .001). Intraoperative costs were higher for STING procedure (P = .001), while hospitalization costs were significantly higher for Cohen procedure (P = .001). In children affected by VUR, open Cohen and LEVUR reported a higher success rate than STING procedure. However, Cohen procedure had a very long and painful hospital stay, more complications, more analgesic requirements compared to STING and LEVUR. Comparing the three techniques, it seems that LEVUR presents a high success rate similar to the Cohen procedure, but in addition, it presents the same advantages of STING procedure with no postoperative pain and a lower postoperative morbidity.


Diffusion of hard sphere fluids in disordered media: a molecular dynamics simulation study.
Molecular dynamic simulations are reported for the static and dynamic properties of hard sphere fluids in matrices (or media) composed of quenched hard spheres. The effect of fluid and matrix density, matrix structure, and fluid to matrix sphere size ratio on the static and dynamic properties is studied using discontinuous molecular dynamics. The matrix density has a stronger effect on the self-diffusion coefficient than the fluid density, especially at high matrix densities where the geometric constraints due to the quenched spheres are significant. When the ratio of the size of the fluid spheres to that of the matrix spheres is equal to or greater than one, the diffusion increases as the fluid density is increased, at constant total volume fraction. This trend is however reversed if the ratio is smaller than one. Different methods of generating the matrix have a very strong effect on the dynamic properties even though the static correlations are similar. An analysis of the single-chain structure factor of the particle trajectories shows a change in the particle diffusive behavior at different time scales, suggestive of a hopping mechanism, although normal diffusion is recovered at long times. At high matrix densities, there is considerable heterogeneity in the diffusion of the fluid particles. The simulations demonstrate that the correlations in the matrix play a significant role on the diffusion of fluid spheres. For example, the diffusion constant in matrices constructed by different methods can be an order of magnitude different even though the pair correlation functions are almost identical.


A Review of Population Pharmacokinetic Models of Posaconazole.
Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure. Articles published until May 2022 for PopPK analysis of posaconazole were searched in PubMed and EMBASE databases. Demographic characteristics, model characteristics, and results of PopPK analysis were extracted from the selected articles. In addition, the steady-state pharmacokinetic profiles of posaconazole were simulated at different covariate levels and dosing regimens. Out of the 13 studies included in our review, nine studies included adults, three included children, and one included both adults and children. All oral administration models were one-compartment models, and all intravenous administration models were two-compartment models. Body weight, proton pump inhibitors, and incidence of diarrhea were found to be important covariates. Clinically, the potential impact of factors such as patient physiopathologic characteristics and comorbid medications on posaconazole pharmacokinetics should be considered. Dose adjustment in combination with TDM or replacement with a tablet or intravenous formulation with higher exposure may be an effective way to ensure drug efficacy as well as to reduce fungal resistance. Meanwhile, published models require further external evaluation to examine extrapolation.


Probing the role of interfacial waters in protein-DNA recognition using a hybrid implicit/explicit solvation model.
When proteins bind to their DNA target sites, ordered water molecules are often present at the protein-DNA interface bridging protein and DNA through hydrogen bonds. What is the role of these ordered interfacial waters? Are they important determinants of the specificity of DNA sequence recognition, or do they act in binding in a primarily nonspecific manner, by improving packing of the interface, shielding unfavorable electrostatic interactions, and solvating unsatisfied polar groups that are inaccessible to bulk solvent? When modeling details of structure and binding preferences, can fully implicit solvent models be fruitfully applied to protein-DNA interfaces, or must the individualistic properties of these interfacial waters be accounted for? To address these questions, we have developed a hybrid implicit/explicit solvation model that specifically accounts for the locations and orientations of small numbers of DNA-bound water molecules, while treating the majority of the solvent implicitly. Comparing the performance of this model with that of its fully implicit counterpart, we find that explicit treatment of interfacial waters results in a modest but significant improvement in protein side-chain placement and DNA sequence recovery. Base-by-base comparison of the performance of the two models highlights DNA sequence positions whose recognition may be dependent on interfacial water. Our study offers large-scale statistical evidence for the role of ordered water for protein-DNA recognition, together with detailed examination of several well-characterized systems. In addition, our approach provides a template for modeling explicit water molecules at interfaces that should be extensible to other systems.


Notified viral hepatitis in Auckland.
One hundred and forty-nine patients notified in Auckland health district as suffering from hepatitis A or B during the period July 1978-June 1979 were investigated by health inspectors. The results were analysed by age, sex, ethnic group, potential source of infection and immunoglobulin prophylaxis of the contacts, and have increased the understanding of the epidemiology of these types of viral hepatitis in Auckland.


[Sexual assaults].
Examining a victim of sexual assault is a medico-legal emergency. It has to be performed within 72 h, in appropriate conditions. A recent laceration of the hymen does not necessarily indicate a rape, and conversely absence of trauma to a rape victim does not negate the validity of her claim to rape. A normal clinical examination does not exclude the possibility of a sexual abuse. Unlawful sexual intercourse is defined by a sexual penetration without valid consent. Specimen collection, to be considered as an evidence, must be sealed. Toxicological samples have to be performed to search a rape under influence.


The application of MALDI TOF MS in biopharmaceutical research.
The development and quality assessment of modern biopharmaceuticals, particularly protein and peptide drugs, requires an array of analytical techniques to assess the integrity of the bioactive molecule during formulation and administration. Mass spectrometry is one of these methods and is particularly suitable for determining chemical modifications of protein and peptide drugs. The emphasis of this review is the identification of covalent interactions between protein and peptide bioactives with polymeric pharmaceutical formulations using mass spectrometry with the main focus on matrix-assisted laser desorption/ionization (MALDI) coupled tandem time-of-flight (TOF/TOF) mass spectrometry (MS). The basics of MALDI TOF MS and collision-induced dissociation (CID)-based ion fragmentation will be explained and applications for qualitative characterization of protein and peptide drugs and their interactions with pharmaceutical polymers will be discussed using three case studies.


Revised Mechanism of Gold-Catalyzed Thioallylation of Propiolates.
Gold-catalyzed enantioselective thioallylation of propiolates proved effective in delivering highly enantio-enriched α-allyl-β-thioacrylates. In this work, we report a revised mechanism for this process based on the new mechanistic experiments and kinetic data in the presence of a competitive inhibitor. The employment of thioethers as nucleophiles inevitably involves their competitive binding to the only catalytic site of the Au(I) catalyst, which may inhibit the activity. We developed a modified Hammett plot in the presence of a dummy thioether inhibitor, which revealed a true kinetic profile, excluding the effect of inhibition. A revised mechanism suggested that the conjugate addition of thioethers to the Au(I)-activated alkynes is the turnover-limiting step, and the subsequent [3,3]-rearrangement occurs quickly, suggesting the efficacy of the sulfonium-based approach in accelerating Claisen rearrangement. In addition, the enantioselectivity was suggested to be determined during the sigmatropic rearrangement by discriminating the prochiral olefin faces of the allyl group in the σ-bound Au(I) complex.


Echocardiographic predictors of adverse short-term outcomes after heart surgery in patients with mitral regurgitation and pulmonary hypertension.
Pulmonary hypertension (PH) is a frequent occurrence and a negative prognostic indicator in patients with mitral regurgitation. Preoperative PH causes higher early and late mortality rates after heart surgery, adverse cardiac events, and postoperative systolic dysfunction in the left ventricle (LV). The research consisted of a retrospective study of a group of 171 consecutive patients with mitral regurgitation and preoperative PH who had undergone mitral valve surgery between January 2008 and October 2011. The PH diagnosis was based on echocardiographic evidence (systolic pulmonary artery pressure [sPAP] >35 mm Hg). The echocardiographic examination included assessment of the following: LV volume, LV ejection fraction (LVEF), sPAP, right ventricular end-diastolic diameter, right atrium area indexed to the body surface area, the ratio of the pulmonary acceleration time to the pulmonary ejection time (PAT/PET), tricuspid annular plane systolic excursion (TAPSE), determination of the severity of the associated tricuspid regurgitation, and presence of pericardial fluid. Surgical procedures consisted of mitral valve repair in 55% of the cases and mitral valve replacement in the remaining 45%. Concomitant coronary artery bypass grafting (CABG) surgery was carried out in 52 patients (30.41%), and De Vega tricuspid annuloplasty was performed in 29 patients (16.95%). The primary end point was perioperative mortality. The secondary end points included the following: pericardial, pleural, hepatic, or renal complications; the need for a new surgical procedure; postoperative mechanical ventilation >24 hours; length of stay in the intensive care unit; duration of postoperative inotropic support; need for an intra-aortic balloon pump; and need for pulmonary vasodilator drugs. The mortality rate was 2.34%. In the univariate analysis, the clinical and echocardiographic parameters associated with mortality were preoperative New York Heart Association (NYHA) class IV, the PAT/PET ratio, TAPSE, the indexed area of the right atrium, and concomitant CABG surgery. In the multivariate analysis, the indexed area of the right atrium and concomitant CABG surgery remained statistically significant. The multivariate analysis also showed the indexed area of the right atrium, LVEF, presence of pericardial fluid, preoperative NYHA class, and concomitant CABG surgery as statistically significant for the secondary end point. The receiver operating characteristic (ROC) curves identified an sPAP value >65 mm Hg to have the highest specificity and sensitivity for the risk of perioperative death in mitral regurgitation patients (area under the ROC curve [AUC], 0.782; P < .001) and identified an sPAP value of 60 mm Hg as the secondary end point (AUC, 0.82; P < .001). Severe PH (sPAP >60 mm Hg) is associated with a significant increase in the mortality rate; a longer stay in the intensive care unit; a mechanical ventilation duration >24 hours; lengthy inotropic support; renal, hepatic, and pericardial complications; and a need for endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and/or prostanoids, both in the general group and in patients with preserved systolic functioning of the left ventricle. PH is a strong short-term negative prognostic factor for patients with mitral regurgitation. The surgical procedure should be performed in the early stages of PH. Echocardiographic examination has useful, simple, and reproducible tools for classifying operative risks. An ischemic etiology and a need for concomitant CABG surgery are additional risk factors for patients with mitral regurgitation and PH.


Simultaneous evaluation of anti-EGFR-induced tumour and adverse skin effects in a microfluidic human 3D co-culture model.
Antibody therapies targeting the epithelial growth factor receptor (EGFR) are being increasingly applied in cancer therapy. However, increased tumour containment correlates proportionally with the severity of well-known adverse events in skin. The prediction of the latter is not currently possible in conventional in vitro systems and limited in existing laboratory animal models. Here we established a repeated dose "safficacy" test assay for the simultaneous generation of safety and efficacy data. Therefore, a commercially available multi-organ chip platform connecting two organ culture compartments was adapted for the microfluidic co-culture of human H292 lung cancer microtissues and human full-thickness skin equivalents. Repeated dose treatment of the anti-EGFR-antibody cetuximab showed an increased pro-apoptotic related gene expression in the tumour microtissues. Simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated, demonstrating crucial inhibitory effects on the physiological skin cell turnover. Furthermore, antibody exposure modulated the release of CXCL8 and CXCL10, reflecting the pattern changes seen in antibody-treated patients. The combination of a metastatic tumour environment with a miniaturized healthy organotypic human skin equivalent make this "safficacy" assay an ideal tool for evaluation of the therapeutic index of EGFR inhibitors and other promising oncology candidates.


Oxidation of LDL to a biologically active form by derivatives of nitric oxide and nitrite in the absence of superoxide. Dependence on pH and oxygen.
A key factor in atherogenesis is oxidation of LDL in the subendothelial space. In the normal vessel wall or in the thickened intima of diseased vessels, this space is rich in nitric oxide (NO.) released from endothelial cells, smooth muscle cells, and macrophages. To determine whether NO. has a role in LDL oxidation, we exposed human LDL to NO. under aerobic and anaerobic conditions and at acidic and neutral pH. Spectrophotometric detection of beta-carotene in the LDL was used as a marker for LDL oxidation. Depletion of beta-carotene was observed in LDL treated with NO. under aerobic conditions but not under anaerobic conditions. In contrast, treatment of LDL with sodium nitrite did not require oxygen for beta-carotene depletion, although depletion was increased when O2 was present. Furthermore, low pH greatly accelerated LDL oxidation by either NO. gas or by nitrite (NO2-). Depletion of beta-carotene corresponded with formation of conjugated dienes, increased susceptibility to further oxidation, and aggregation of apolipoprotein B-100, but did not increase electrophoretic mobility of LDL. Also, nitrite-oxidized LDL demonstrated biological properties similar to minimally oxidized LDL, including stimulation of monocyte adhesion and inhibition of lipopolysaccharide-induced neutrophil binding to endothelium. These results indicate that NO. under certain circumstances may contribute to oxidative modification of LDL and may have a role in atherogenesis.


Recent improvement of survival prognosis after pulmonary metastasectomy and advanced chemotherapy for patients with colorectal cancer.
New chemotherapeutic regimens (i.e. FOLFOX or FOLFIRI with molecular targeted drugs) have improved the prognosis of patients with unresectable or recurrent colorectal cancer. To estimate the prognostic impact of these chemotherapies, we examined the chronological change in survival rates of patients who underwent pulmonary metastasectomy for colorectal cancer metastasis. Using a large database, we conducted a retrospective, multi-institutional study to collect data of 1223 eligible patients from 26 institutions who had undergone pulmonary metastasectomy with curative intent. We divided those patients who underwent metastasectomy in different time periods according to the major trend of chemotherapy regimens for recurrent colorectal cancer: those who underwent metastasectomy between 1990 and 1999 ( N = 451, Group A), between 2000 and 2004 ( N = 433, Group B) or between 2005 and 2007 ( N = 339, Group C). Five-year overall survival rates after metastasectomy were 45% in Group A, 56% in Group B and 66% in Group C ( P < 0.0001) whereas rates after metastasectomy plus chemotherapy were 32% in Group A, 47% in Group B and 70% in Group C ( P = 0.0059). The prognosis of patients who underwent both metastasectomy and chemotherapy in Group C was significantly better than that of the other two groups. Overall survival of patients who did not receive chemotherapy was not significantly different between the groups. Survival rates of patients after pulmonary metastasectomy for colorectal cancer metastasis who underwent chemotherapy have increased over the years. It implies that newer chemotherapy regimens might have had a positive impact on these patients.


[Therapy of hyperhidrosis with tap water iontophoresis. Positive effect on healing time and lack of recurrence in hand-foot eczema].
Hyperhidrosis is due to an overfunction of eccrine glands (triggered by the autonomous nervous system) and may be a cofactor for palmoplantar eczema (dermatitis). Tapwater iontophoresis was used in 54 patients with hyperhidrosis manuum et pedum. After 10 applications directed by the dermatologist, 89% of patients noted an improvement in their hyperhidrosis. 20 patients suffering from palmoplantar eczema (dermatitis) who continued the treatment at home for at least 6 months were compared with a historical sex- and age-matched group of 20 eczema-patients without iontophoresis: The factors evaluated were the time needed for clearing and the relapse-free interval. Though iontophoresis-treated patients had a slightly faster clearing, this was statistically not significant (20 vs. 22.3 days; p > 0.05). However, the difference for relapse-free interval between the two groups was statistically highly significant (24.8 weeks vs. 8.35 weeks; p < 0.0001). Tapwater iontophoresis seems to be effective not only to control sweating. According to recently published data, galvanization seems to have a capsaicin-like effect as well. Our hypothesis is therefore, that galvanization with tapwater iontophoresis interrupts the neurogenic inflammation and prolongs the relapse-free interval in hyperhidrotic palmoplantar eczema (dermatitis).


Anatomy, Development, and Function of the Human Pelvis.
The pelvis is an anatomically complex and functionally informative bone that contributes directly to both human locomotion and obstetrics. Because of the pelvis' important role in obstetrics, it is one of the most sexually dimorphic bony elements of the human body. The complex intersection of pelvic dimorphism, locomotion, and obstetrics has been reenergized by exciting new research, and many papers in this special issue of the pelvis help provide clarity on the relationship between pelvic form (especially female) and locomotor function. Compared to the pelvis of our ape relatives, the human pelvis is uniquely shaped; it is superoinferiorly short and stout, and mediolaterally wide-critical adaptations for bipedalism that are already present in some form very early in the history of the hominin lineage. In this issue, 13 original research papers address the anatomy, development, variation, and function of the modern human pelvis, with implications for understanding the selection pressures that shaped and continue to shape this bone. This rich collection of scholarship moves our understanding of the pelvis forward, while raising dozens of new questions that we hope will serve as inspiration for colleagues and students (both current and future) puzzled by this fascinatingly complex bone. Anat Rec, 300:628-632, 2017. © 2017 Wiley Periodicals, Inc.


Nuclear localization of a novel protein, RGPR-p117, in cloned normal rat kidney proximal tubular epithelial cells.
A novel protein RGPR-p117 was discovered as a regucalcin gene promoter region-related protein that binds to the TTGGC motif. The role of RGPR-p117 in cell function is unknown. The nuclear localization of RGPR-p117 was investigated using cloned normal rat kidney proximal tubular epithelial NRK52E cells in vitro. RGPR-p117 mRNA was expressed in NRK52E cells, and its expression was stimulated by culture with parathyroid hormone (10(-7) M) or phorbol 12-myristate (10(-6) M). RGPR-p117 was found to localize in the cytoplasm and nucleus with immunocytochemical and Western blot analysis using HA-RGPR-p117/phCMV2-transfected NRK52E cells. Overexpression of HA-RGPR-p117 was found to have a significant stimulatory effect on regucalcin mRNA expression in NRK52E cells. This study demonstrates that RGPR-p117 is localized in the nucleus of kidney cells, and may be involved in gene expression.


Odontoid pannus formation in a patient with ankylosing spondylitis causing atlanto-axial instability.
Ankylosing spondylitis is one of the commonest inflammatory diseases of the axial skeleton and can be complicated by atlanto-axial instability. This serious and likely underestimated complication can be easily overlooked. However, there are clear features which can help alert suspicion to initiate the appropriate investigations with imaging that is very effective at diagnosing and assessing this complication. The authors report an unusual case where odontoid pannus formation, akin to that seen in rheumatoid arthritis, was the underlying cause.


Probing effects of molecular conformation on the electronic and charge transport properties in two- and three-dimensional small molecule hole-transporting materials: a theoretical investigation.
Thiophene/benzene-fused π-conjugated systems are normally employed as the core units of two- and three-dimensionally expanded small molecule hole-transporting materials (HTMs) to improve their electronic and charge transport properties, whereas comparison studies between two-dimensional and three-dimensional core conformations are less reported. To further find useful clues for the design of highly-efficient small molecule HTMs and to find new core units, in this work, four HTM molecules are designed by employing triphenylene, benzotrithiophene, triptycene, and thiophenetriptycene as the core units, and simulated with density functional theory combined with the Marcus hopping model. Our results show that all the considered HTMs display appropriate molecular energy levels, less optical absorption in the visible light region and large Stokes shifts, and high hole mobilities (9.80 × 10-2 cm2 V-1 s-1). Compared with the two-dimensional core structures, the three-dimensional cores exhibit evident superiorities with the same chemical components. Meanwhile, we also find that the quasi-degenerate HOMO energy levels will be helpful to enlarge the transfer integrals between adjacent molecules, and further to promote the hole transport in HTMs. By considering the various elements simultaneously, these investigated HTMs (S-1-S-4) with thiophene- and benzene-fused cores can be expected as potential promising candidates to help create more efficient solar cells.


Is Geometric Frustration-Induced Disorder a Recipe for High Ionic Conductivity?
Ionic conductivity is ubiquitous to many industrially important applications such as fuel cells, batteries, sensors, and catalysis. Tunable conductivity in these systems is therefore key to their commercial viability. Here, we show that geometric frustration can be exploited as a vehicle for conductivity tuning. In particular, we imposed geometric frustration upon a prototypical system, CaF2, by ball milling it with BaF2, to create nanostructured Ba1-xCaxF2 solid solutions and increased its ionic conductivity by over 5 orders of magnitude. By mirroring each experiment with MD simulation, including "simulating synthesis", we reveal that geometric frustration confers, on a system at ambient temperature, structural and dynamical attributes that are typically associated with heating a material above its superionic transition temperature. These include structural disorder, excess volume, pseudovacancy arrays, and collective transport mechanisms; we show that the excess volume correlates with ionic conductivity for the Ba1-xCaxF2 system. We also present evidence that geometric frustration-induced conductivity is a general phenomenon, which may help explain the high ionic conductivity in doped fluorite-structured oxides such as ceria and zirconia, with application for solid oxide fuel cells. A review on geometric frustration [ Nature 2015 , 521 , 303 ] remarks that classical crystallography is inadequate to describe systems with correlated disorder, but that correlated disorder has clear crystallographic signatures. Here, we identify two possible crystallographic signatures of geometric frustration: excess volume and correlated "snake-like" ionic transport; the latter infers correlated disorder. In particular, as one ion in the chain moves, all the other (correlated) ions in the chain move simultaneously. Critically, our simulations reveal snake-like chains, over 40 Å in length, which indicates long-range correlation in our disordered systems. Similarly, collective transport in glassy materials is well documented [for example, J. Chem. Phys. 2013 , 138 , 12A538 ]. Possible crystallographic nomenclatures, to be used to describe long-range order in disordered systems, may include, for example, the shape, length, and branching of the "snake" arrays. Such characterizations may ultimately provide insight and differences between long-range order in disordered, amorphous, or liquid states and processes such as ionic conductivity, melting, and crystallization.


Characterization of beta-lapachone and methylated beta-cyclodextrin solid-state systems.
The purpose of this research was to explore the utility of beta cyclodextrin (betaCD) and beta cyclodextrin derivatives (hydroxypropyl-beta-cyclodextrin [HPbetaCD], sulfobutylether-beta-CD [SBbetaCD], and a randomly methylated-beta-CD [RMbetaCD]) to form inclusion complexes with the antitumoral drug, beta-lapachone (betaLAP), in order to overcome the problem of its poor water solubility. RMbetaCD presented the highest efficiency for betaLAP solubilization and was selected to develop solid-state binary systems. Differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier transform infrared (FTIR) and optical and scanning electron microscopy results suggest the formation of inclusion complexes by both freeze-drying and kneading techniques with a dramatic improvement in drug dissolution efficiency at 20-minute dissolution efficiency (DE(20-minute) 67.15% and 88.22%, respectively) against the drug (DE(20-minute) 27.11%) or the betaCD/drug physical mixture (DE(20-minute) 27.22%). However, the kneading method gives a highly crystalline material that together with the adequate drug dissolution profile make it the best procedure in obtaining inclusion complexes of RMbetaCD/betaLAP convenient for different applications of betaLAP.


Effects of selected pharmaceuticals on riverine biofilm communities.
Although pharmaceutical and therapeutic products are widely found in the natural environment, there is limited understanding of their ecological effects. Here we used rotating annular bioreactors to assess the impact of 10 microg.L(-1) of the selected pharmaceuticals ibuprofen, carbamazepine, furosemide, and caffeine on riverine biofilms. After 8 weeks of development, community structure was assessed using in situ microscopic analyses, fluor-conjugated lectin binding, standard plate counts, fluorescent in situ hybridization, carbon utilization spectra, and stable carbon isotope analyses. The biofilm communities varied markedly in architecture although only caffeine treated biofilms were significantly thicker. Cyanobacteria were suppressed by all 4 compounds, whereas the nitrogen containing caffeine, furosemide, and carbamazepine increased algal biomass. Ibuprofen and carbamazepine reduced bacterial biomass, while caffeine and furosemide increased it. Exopolymer content and composition of the biofilms was also influenced. Significant positive and negative effects were observed in carbon utilization spectra. In situ hybridization analyses indicated all treatments significantly decreased the gamma-proteobacterial populations and increased beta-proteobacteria. Ibuprofen in particular increased the alpha-proteobacteria, beta-proteobacteria, cytophaga-flavobacteria, and SRB385 probe positive populations. Caffeine and carbamazepine additions resulted in significant increases in the high GC354c and low GC69a probe positive cells. Live-dead analyses of the biofilms indicated that all treatments influenced the ratio of live-to-dead cells with controls having a ratio of 2.4, carbamazepine and ibuprofen being 3.2 and 3.5, respectively, and furosemide and caffeine being 1.9 and 1.7, respectively. Stable isotope analyses of the biofilms indicated delta 13C values shifted to more negative values relative to control biofilms. This shift may be consistent with proportional loss of cyanobacteria and relative increase in algal biomass rather than incorporation of pharmaceutical carbon into microbial biofilm. Thus, at 10 microg.L(-1) levels pharmaceuticals exhibit both nutrient-like and toxic effects on riverine microbial communities.


Reducing Influenza Virus Transmission: The Potential Value of Antiviral Treatment.
Prompt antiviral treatment has the potential to reduce influenza virus transmission to close contacts, but rigorous data on the magnitude of treatment effects on transmission are limited. Animal model data indicate that rapid reductions in viral replication after antiviral treatment reduce the risk of transmission. Observational and clinical trial data with oseltamivir and other neuraminidase inhibitors indicate that prompt treatment of household index patients seems to reduce the risk of illness in contacts, although the magnitude of the reported effects has varied widely across studies. In addition, the potential risk of transmitting drug-resistant variants exists with all approved classes of influenza antivirals. A controlled trial examining baloxavir treatment efficacy to reduce transmission, including the risk of transmitting virus with reduced baloxavir susceptibility, is currently in progress. If reduced transmission risk is confirmed, modeling studies indicate that early treatment could have major epidemiologic benefits in seasonal and pandemic influenza.


Captive rage.
Providing dental care for the sexual abuse survivor requires a mixture of technical and interpersonal skills. It is often necessary to counteract the effects of long term dental neglect complicated by the psychological aspects of the oral cavity. Feelings of loss of control of an important psychologically and sexually charged area must be dealt with effectively. Dentists must be flexible in their approach to the patient, yet never compromise the standard of care. Examination of case histories provides illustrations and examples.


Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease.
Blood-brain barrier disruption occurs in the early stages of Alzheimer's disease. Recent studies indicate a link between blood-brain barrier dysfunction and cognitive decline and might accelerate Alzheimer's disease progression. Astrocytes are the most abundant glial cells in the central nervous system with important roles in the structural and functional maintenance of the blood-brain barrier. For example, astrocytic coverage around endothelial cells with perivascular endfeet and secretion of homeostatic soluble factors are two major underlying mechanisms of astrocytic physiological functions. Astrocyte activation is often observed in Alzheimer's disease patients, with astrocytes expressing a high level of glial fibrillary acid protein detected around amyloid-beta plaque with the elevated phagocytic ability for amyloid-beta. Structural alterations in Alzheimer's disease astrocytes including swollen endfeet, somata shrinkage and possess loss contribute to disruption in vascular integrity at capillary and arterioles levels. In addition, Alzheimer's disease astrocytes are skewed into proinflammatory and oxidative profiles with increased secretions of vasoactive mediators inducing endothelial junction disruption and immune cell infiltration. In this review, we summarize the findings of existing literature on the relevance of astrocyte alteration in response to amyloid pathology in the context of blood-brain barrier dysfunction. First, we briefly describe the physiological roles of astrocytes in blood-brain barrier maintenance. Then, we review the clinical evidence of astrocyte pathology in Alzheimer's disease patients and the preclinical evidence in animal and cellular models. We further discuss the structural changes of blood-brain barrier that correlates with Alzheimer's disease astrocyte. Finally, we evaluate the roles of soluble factors secreted by Alzheimer's disease astrocytes, providing potential molecular mechanisms underlying blood-brain barrier modulation. We conclude with a perspective on investigating the therapeutic potential of targeting astrocytes for blood-brain barrier protection in Alzheimer's disease.


Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.
The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known. To characterize the role of IL-26 in antibacterial host defense of human lungs. Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro. Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells. This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.


Effect of ionic strength of buffer on the measurement of erythrocyte electrophoretic mobility.
Measurement of the electrophoretic mobility (EM) of biological cells provides information on the electrical properties of the cell surface. Different research groups have used different electrophoretic techniques. It is well known that the osmolality of the buffer used during an experiment exerts a major impact on EM, particularly in biological cells. In previous experiments either high or low ionic strength electrophoresis buffers were used with an arbitrary preference. The aim of this study is to investigate which buffer is more useful for EM measurements, and hence to give greater insight into the results of such experiments. Blood was drawn from healthy volunteers. Two different buffers were prepared: low ionic and high ionic. Twenty molarity steps were prepared by mixing the buffers in different ratios. Measurements were made using a Zetasizer. Our data confirmed that the EM fell as ionic strength increased. However, the relationship was biphasic: the first ten points were linear with a steep negative slope and the second set also linear but with a much smaller slope. EM studies usually have one of two extreme aims: either to compare the inherent surface electrical properties of cells from different sources at the same ionic strength, or to study the influence of different ionic environments on the surface electrical properties of cells from the source. Our data suggest that in the first instance it is better to work at high ionic strength. In the second, low ionic strength is preferable.


Anti-fibrosis effect of BMP-7 peptide functionalization on cobalt chromium alloy.
Orthopedic metallic prosthetic implants are commonly made of cobalt chromium (CoCr) alloys. However, such metal-based implants are susceptible to fibrous capsule formation on the implant surface after implantation. At the bone-implant interface, this capsule can prevent implant integration, resulting in loosening and failure. Minimizing the development of such a capsule on the CoCr surface would improve direct bone-implant bonding leading to long-term implant functionality. We evaluated the anti-fibrosis effect of bone morphogenic protein-7 (BMP-7) peptide covalently bonded to CoCr alloy. This peptide, a biomimetic derivation of the knuckle epitope of BMP-7, was conjugated at the N-terminus with a cysteine amino acid. X-ray photoelectron spectroscopy (XPS) and probe binding assay were used to evaluate different stages of grafting and surface functionalization using polydopamine coating. Cellular functions were studied using fibroblast attachment, cell proliferation, and MTT assays. Fibroblasts were grown on functionalized and pristine CoCr substrates, and the efficacy of BMP-7 peptide on anti-fibrosis was analyzed via gene expression and protein expression of fibrosis markers ACTA2, Collagen 1A1, and fibronectin. The peptide functionalized substrates showed significant reduction of fibrosis markers expression after 1 week of incubation compared to controls. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. These findings may contribute to the improvement of CoCr implants in orthopedic surgery applications.


Focusing property of autofocusing Bessel beams.
We introduce what we believe to be a new family of abruptly autofocusing waves named autofocusing Bessel beams (ABBs). Since the beams only strongly influence the area near the focus, it holds promise for medical laser treatment and optical tweezers. By the angular spectrum method, ABBs are proved to be a class solution for the Helmholtz equation. The focal length is well-defined and easily tuned in our mathematical description. Under the finite energy limitation, the abruptly autofocusing and vortex characteristics of Gaussian-modulated ABBs are studied. Interestingly, we found a kind of abruptly autofocusing waves focusing twice on the propagation axis, which is formed by an ABB passing through a focusing lens. Dual-focus ABBs make it possible for a single laser to manipulate two particles on the propagation axis simultaneously. In the experiment, the autofocusing of ABBs and the dual focus of ABBs passing through a focusing lens are observed. This article provides a theoretical model and experimental protocol for studying abruptly autofocusing waves.


Social regulation of the brain-pituitary-gonadal axis.
Reproduction in vertebrates is regulated by the hypothalamic-pituitary-gonadal axis via neural and hormonal feedback. This axis is also subject to exogenous influences, particularly social signals. In the African cichlid fish Haplochromis burtoni, gonadal development in males is socially regulated. A small fraction of the males, which are brightly colored, maintain territories and aggressively dominate inconspicuously colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are significantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorial through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin-releasing hormone-containing cells project to the pituitary and are ultimately responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuron-endocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a similar form of physiological regulation.


A three-dimensional finite element model for the mechanics of cell-cell interactions.
Technical challenges, including significant ones associated with cell rearrangement, have hampered the development of three-dimensional finite element models for the mechanics of embryonic cells. These challenges have been overcome by a new formulation in which the contents of each cell, assumed to have a viscosity mu, are modeled using a system of orthogonal dashpots. This approach overcomes a stiffening artifact that affects more traditional models, in which space-filling viscous elements are used to model the cytoplasm. Cells are assumed to be polyhedral in geometry, and each n-sided polygonal face is subdivided into n triangles with a common node at the face center so that it needs not remain flat. A constant tension gamma is assumed to act along each cell-cell interface, and cell rearrangements occur through one of two complementary topological transformations. The formulation predicts mechanical interactions between pairs of similar or dissimilar cells that are consistent with experiments, two-dimensional simulations, contact angle theory, and intracellular pressure calculations. Simulations of the partial engulfment of one tissue type by another show that the formulation is able to model aggregates of several hundred cells without difficulty. Simulations carried out using this formulation suggest new experimental approaches for measuring cell surface tensions and interfacial tensions. The formulation holds promise as a tool for gaining insight into the mechanics of isolated or aggregated embryonic cells and for the design and interpretation of experiments that involve them.


Electrochemistry and electrocatalytic activities of superoxide dismutases at gold electrodes modified with a self-assembled monolayer.
In this article, the electrochemical properties and electrocatalytic activity of three kinds of superoxide dismutases (SODs), that is, bovine erythrocyte copper-zinc superoxide dismutase (Cu/Zn-SOD), iron superoxide dismutase from Escherichia coli (Fe-SOD), and manganese superoxide dismutase from E. coli (Mn-SOD), in the SOD family were studied. It was revealed that the direct electron transfer of the three kinds of SODs could be efficiently promoted by a self-assembled monolayer (SAM) of 3-mercaptopropionic acid (MPA) confined on a gold electrode. The electrochemical properties of the SODs at the MPA-SAM electrode vary with the sort of SOD with respect to the formal potential, reversibility of electrode reactions, kinetic parameters, and pH dependence, suggesting different mechanisms for the electrode reactions of the individual SODs. A combination of the facilitated direct electron transfer and the bifunctional enzymatic catalytic activities of the SODs via a redox cycle of their active metals substantially offered a flexible electrochemical route to determination of O(2)(*)(-) where O(2)(*)(-) can be sensed with the SOD-based biosensors in both anodic and cathodic polarizations. Such an intrinsic feature of the SOD-based biosensors successfully enabled a sensitive determination scheme for O(2)(*)(-) free from the interference from some coexisting electroactive species, such as ascorbic acid (AA) and uric acid (UA). Further potential applications for in vivo determination of O(2)(*)(-) is also suggested.


[Glucagon metabolism in the in vitro recycling perfused rat liver].
A kinetic study of different processes of hepatic glucagon metabolism has been performed using the model of recycling perfused rat liver. Glucagon was eliminated in a concentration dependent fashion from the circulation. The initial rates of hepatic glucagon extraction were rather small, and did not exceed 2.8 +/- 0.2% of the initial glucagon mass flow of 9.6 +/- 0.0 ng/min. The major portion of glucagon was eliminated within the first 10 min of perfusion. Both binding and internalization of glucagon were the dominating processes in this phase. After 10 min of perfusion, an acceleration of glucagon degradation was observed leading to the release of cleavage products into the perfusate. The physiological role of glucagon degradation and its possible relation to the termination of the hepatic glucagon action is still unknown. The present results suggest that the liver seems not to be of primary importance for systemic glucagon degradation.


Continuous analysis of dissolved gaseous mercury and mercury volatilization in the upper St. Lawrence River: exploring temporal relationships and UV attenuation.
The formation and volatilization of dissolved gaseous mercury (DGM) is an important mechanism by which freshwaters may naturally reduce their mercury burden. Continuous analysis of surface water for diurnal trends in DGM concentration (ranging from 0 to 60.4 pg L(-1); n=613), mercury volatilization (ranging from 0.2 to 1.1 ng m(-2) h(-1); n=584), and a suite of physical and chemical measurements were performed during a 68 h period in the St. Lawrence River near Cornwall (Ontario, Canada) to examine the temporal relationships governing mercury volatilization. No lag-time was observed between net radiation and OGM concentrations (highest cross-correlation of 0.817), thus supporting previous research indicating faster photoreduction kinetics in rivers as compared to lakes. A significant lag-time (55-145 min; maximum correlation = 0.625) was observed between DGM formation and mercury volatilization, which is similar to surface water Eddy diffusion times of 42-132 min previously measured in the St. Lawrence River. A depth-integrated DGM model was developed using the diffuse integrated vertical attenuation coefficients for UVA and UVB (K(dI UVA) = 1.45 m(-1) K(dI UVB)= 3.20 m(-1)) Low attenuation of solar radiation was attributed to low concentrations of dissolved organic carbon (mean = 2.58 mg L(-1) and particulate organic carbon (mean = 0.58 mg L(-1) in the St. Lawrence River. The depth-integrated DGM model developed found that the top 0.3 m of the water column accounted for only 26% of the total depth-integrated DGM. A comparison with volatilization data indicated that a large portion (76% or 10.5 ng m(-2) of the maximum depth-integrated DGM (13.8 ng m(-2))is volatilized over a 24 h period. Therefore, at least 50% of all DGM volatilized was produced at depths below 0.3 m. These results highlight the importance of solar attenuation in regulating DGM formation with depth. The results also demonstrate both the fast formation of DGM in rivers and the importance of understanding DGM dynamics with depth as opposed to surface waters.


Treatment of Acute Osteomyelitis with Once-Weekly Oritavancin: A Two-Year, Multicenter, Retrospective Study.
Acute osteomyelitis is typically caused by Gram-positive pathogens, commonly antibiotic-resistant Staphylococcus species. Standard antibiotic treatment is challenging due to required multiple daily doses, therapeutic drug monitoring, and parenteral administration for at least 4 weeks. Oritavancin is a long-acting lipoglycopeptide antibiotic approved as a single 1200 mg dose for the treatment of adult patients with acute bacterial skin and skin structure infections. To characterize the real-world use, efficacy, and safety of oritavancin in adult patients with acute osteomyelitis. This was a 2-year, multicenter, retrospective, descriptive study of patients treated for acute osteomyelitis with weekly doses of oritavancin. End of therapy evaluation (ETE) was defined as evaluation at 7-10 days after the last dose of oritavancin, and post-therapy assessment (PTE) was at 3 months and 6 months. At ETE and PTE, patients were interviewed via telephone for clinical outcomes, using a standard questionnaire. Electronic medical record review was also conducted. 134 patients were treated with oritavancin for acute osteomyelitis across 20 different Metro Infectious Disease Consultants infusion centers in six states. Of total positive cultures, 71.9% (92/128) were methicillin-resistant Staphylococcus aureus (MRSA) from deep wounds, bone, or joint culture; an additional nine (6.7%) of 134 patients presented with concomitant MRSA bacteremia. Oritavancin was administered via intravenous catheter; patients received an initial treatment of 1200 mg and then 800 mg weekly thereafter for a total number of doses of four (n = 118) or five (n = 16). 118 patients (88.1%) of the baseline 134 patients achieved clinical success at the ETE timepoint. 130 patients were available for PTE at 3 months and 6 months. Overall, relapse or persistent infection was diagnosed in 13/134 (9.7%) patients. Nine (6.7%) of 134 patients were admitted to the hospital during the follow-up period but none for osteomyelitis. Adverse events were reported in five (3.7%) patients including hypoglycemia-related symptoms (three patients), tachycardia (one patient), and tachycardia with chest pain (one patient). None of these patients were hospitalized due to adverse events, and all patients eventually finished their treatment regimens. This is the largest real-world clinical study of adult patients treated with oritavancin for acute osteomyelitis. Use of oritavancin for acute osteomyelitis infection resulted in a high rate of positive clinical outcomes and a low incidence of adverse events, thereby providing potential for a convenient, effective, and safe therapeutic option. Future prospective and comparative studies are needed to validate these findings.


Research disruption during PhD studies and its impact on mental health: Implications for research and university policy.
Research policy observers are increasingly concerned about the impact of the disruption caused by the Covid-19 pandemic on university research. Yet we know little about the effect of this disruption, specifically on PhD students, their mental health, and their research progress. This study drew from survey responses of UK PhD students during the Covid-19 pandemic. We explored evidence of depression and coping behaviour (N = 1780), and assessed factors relating to demographics, PhD characteristics, Covid-19-associated personal circumstances, and significant life events that could explain PhD student depression during the research disruption (N = 1433). The majority of the study population (86%) reported a negative effect on their research progress during the pandemic. Results based on eight mental health symptoms (PHQ-8) showed that three in four PhD students experienced significant depression. Live-in children and lack of funding were among the most significant factors associated with developing depression. Engaging in approach coping behaviours (i.e., those alleviating the problem directly) related to lower levels of depression. By assessing the impact of research disruption on the UK PhD researcher community, our findings indicate policies to manage short-term risks but also build resilience in academic communities against current and future disruptions.


Over-expression of F5H in COMT-deficient Arabidopsis leads to enrichment of an unusual lignin and disruption of pollen wall formation.
The presence of the phenylpropanoid polymer lignin in plant cell walls impedes breakdown of polysaccharides to the fermentable sugars that are used in biofuel production. Genetically modified plants with altered lignin properties hold great promise to improve biomass degradability. Here, we describe the generation of a new type of lignin enriched in 5-hydroxy-guaiacyl units by over-expressing ferulate 5-hydroxylase in a line of Arabidopsis lacking caffeic acid O-methyltransferase. The lignin modification strategy had a profound impact on plant growth and development and cell-wall properties, and resulted in male sterility due to complete disruption of formation of the pollen wall. The modified plants showed significantly improved cell-wall enzymatic saccharification efficiency without a reduction in post-harvest biomass yield despite the alterations in the overall growth morphology. This study demonstrated the plasticity of lignin polymerization in terms of incorporation of unusual monomers that chemically resemble conventional monomers, and also revealed the link between the biosynthetic pathways of lignin and the pollen wall-forming sporopollenin.


Isolation and physiological characterization of Streptococcus milleri strains from human dental plaque.
Of 271 Gram-positive, catalase-negative, chain-forming cocci isolated from crevicular and supragingival plaques of 22 adults, 71 stains were clustered as Streptococcus milleri by testing 23 physiological characters. Most of the oral S. milleri strains were nonhaemolytic and formed minute smooth colonies on glucose and sucrose agar plates, while some of the clinical strains were alpha-haemolytic, forming rough colonies on Carlsson's MC agar plate as well as carrying the Lancefield group antigens C, F or G. The strains were divided into two biotypes, and further into six subtypes by their abilities to ferment maltose, salicin and/or lactose. Distribution of the varieties according to the haemolytic, colonial and serological properties among the oral isolates generally corresponded to the tentative biological types of S. milleri.


A practical approach for diagnosis and treatment of central venous stenosis and occlusion.
Treating symptomatic central venous stenosis and occlusion is a challenge for those caring for patients with end stage renal disease. With the increase incidence and decrease mortality of end stage renal disease, there are more patients presenting for vascular access procedures. Although there has been a significant increase in the prevalence of fistulae in the United States over the last several years, many of these patients require central venous catheters during the fistula maturation process. The use of these catheters, along with the increase in the diameters of many of these catheters over the last several years, has likely played a significant role in the development of symptomatic central venous stenosis and occlusion. In this article the origin or central venous stenosis and occlusion will be reviewed along with a practical approach on how to best manage this disease process.


A cohort study to evaluate cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients attending orthopedic department of a tertiary care hospital.
Cyclooxygenase-2 inhibitors (COX-2-Is) have recently been concerned in the occurrence of adverse cardiovascular (CV) events. Rofecoxib and valdecoxib has been withdrawn from the market, but celecoxib, etoricoxib and parecoxib continues to be used. Other nonsteroidal anti-inflammatory drugs (NSAIDs) may also increase the risk of CV events. However, clinical trial databases for COX-2-Is had created lots of controversies regarding cardiovascular safety of selective and nonselective cyclooxygenase inhibitors (COX-Is). This study was, conducted to assess and compare the CV risk of COX-Is in arthritic patients over a period of time. In this prospective cohort study adult arthritics of either sex those were freshly diagnosed or taking COX-Is for < 3 months; were included. Patients were grouped into nonselective and selective COX-2-I groups with reference to treatment they received. The CV risk factors like blood pressure (BP), blood sugar level (BSL), lipid profile, body mass index (BMI) were assessed and compared; demography of CV risk factors was also studied. Data obtained was analysed using Student's 't'-test of OpenEpi statistical software. Study clearly revealed that all NSAIDs exhibit variable CV risk; however, selective COX-2-Is found to exhibit more CV risk. BMI, BP and lipid profile; the potential CV risk factors, showed significant impairment in selective COX-2-Is group; P < 0.01, P < 0.001 and P < 0.05, respectively, compared to baseline and P < 0.05 vs. nonselective COX-Is for BMI. This study portrays the potential CV risk of selective COX-2-Is; confirms and re-evaluate the results of earlier studies in this regard.


Sustaining immunity during starvation in bivalve mollusc: A costly affair.
Complete or partial depletion of resource in a freshwater habitat is a common phenomenon. As a consequence, aquatic fauna including bivalve molluscs may be exposed to dietary stress on a seasonal basis. Haemocyte based innate immune profile of the freshwater mollusc Lamellidens marginalis (Bivalvia: Eulamellibranchiata) was evaluated under starvation induced stress for a maximum period of 32 days in a controlled laboratory condition. During starvation, the bivalve haemocytes maintained a homeostasis in phagocytic efficacy and nitric oxide generation ability with respect to the control. The mollusc maintained a significantly high protein content in its haemolymph and tissues under the nutritional stress with respect to the control. The dietary stress had no significant impact on the activity of digestive tissue derived α-amylase till sixteenth day but by 32 days the enzyme activity went down significantly. The histopathological profile revealed that the bivalve was adapted to maintain a steady immune profile by incurring degeneration of its own tissue structure. The total haemocyte count surged significantly till 16 days but differed insignificantly with respect to the control at 32 days implying probable haematopoietic exhaustion. The study reflects the instinctive urge of the bivalve to maintain immune physiology at heavy metabolic cost under nutrient limited condition.


Limited Predictive Utility of Admissions Scores and Objective Structured Clinical Examinations for APPE Performance.
To examine the relationship between admissions, objective structured clinical examination (OSCE), and advanced pharmacy practice experience (APPE) scores. Admissions, OSCE, and APPE scores were collected for students who graduated from the doctor of pharmacy (PharmD) program in spring of 2012 and spring of 2013 (n=289). Pearson correlation was used to examine relationships between variables, and independent t test was used to compare mean scores between groups. All relationships among admissions data (undergraduate grade point average, composite PCAT scores, and interview scores) and OSCE and APPE scores were weak, with the strongest association found between the final OSCE and ambulatory care APPEs. Students with low scores on the final OSCE performed lower than others on the acute care, ambulatory care, and community APPEs. This study highlights the complexities of assessing student development of noncognitive professional skills over the course of a curriculum.


Charcot-Marie-Tooth disease with giant axons: a clinicopathological and genetic entity.
The authors report an Italian family with autosomal-dominant Charcot-Marie-Tooth disease (CMT) in which there were giant axons in the sural nerve biopsy. Linkage to the known CMT2 loci (CMT2A, CMT2B, CMT2D, CMT2F) and mutations in the known CMT2 genes (Cx32, MPZ, NEFL), GAN, NEFM, and CMT1A duplication/HNPP deletion were excluded. This family with CMT and giant axons has a pathologic and genetic entity distinct from classic CMT.


Cross beam scintillations in non-Kolmogorov medium.
For the collimated and focused cross beams, the on-axis scintillation index is evaluated when these beams propagate in weak non-Kolmogorov turbulence. In the limiting cases, our solution correctly reduces to the known Gaussian beam scintillations in Kolmogorov turbulence. For both the collimated and the focused cross beams, large power law exponent of the non-Kolmogorov turbulence is found to result in larger scintillations. Evaluating at a fixed power law exponent, the scintillation index of the collimated (focused) cross beam is higher (lower) than the collimated (focused) Gaussian beam scintillation index. When the asymmetry of the collimated (focused) cross beam increases, the scintillations increase (decrease). At a given cross beam configuration, change in the turbulence parameters varies the scintillations in the same manner for all power law exponent values.


Pseudolipoma of Glisson's capsule. Report of six cases and review of the literature.
We report six cases of pseudolipoma of Glisson's capsule. The patients ranged from 53 to 83 years old (mean 67.7 years), and all were men. Pseudolipoma of Glisson's capsule was detected by imaging studies before operation in two cases, and noted incidentally in the remaining four. Computed tomography demonstrated a subcapsular low-density nodule with or without a high-density spot. All but one patient had a history of abdominal operation. Grossly, the pseudolipoma was a solitary encapsulated nodule on the surface of the anterior aspect in five, and posteroinferior to the right lobe in one. The pseudolipomas ranged from 0.5 to 2 cm in diameter, were white to yellowish-white and elastic-firm. Histologically, the nodules had a dense fibrous capsule and contained necrotic mature fat tissue. In addition, three showed focal calcification. Blood vessels were rarely found within the capsule. These findings strongly suggest that history of abdominal operation, advanced age, sex, and poor blood supply to the nodule are causal to their development. Although only 18 cases have been reported previously, our six cases during but a 3-year period suggests that it may not be as rare as believed.


How does service workers' behavior affect their health? Service climate as a moderator in the service behavior-health relationships.
To address the question of whether providing high-quality service deteriorates or benefits workers' health, a contingency model was tested that focused on service climate as a moderator. This interacts with service behavior to affect workers' perceptions of emotional exhaustion, hence their physical and mental health. Findings of this study with 328 nurses from 66 nursing units indicated that congruent conditions of service climate and behaviors benefited workers' health, whereas incongruent conditions affected it adversely. The findings are discussed in light of stress, and emotion-work perspectives.


Fecal microbiota transplantation for treatment of refractory or recurrent Clostridioides difficile infection in Taiwan: a cost-effectiveness analysis.
Compared to antibiotic treatment, fecal microbiota transplantation (FMT) is a more effective treatment for refractory or recurrent CDI (rCDI). Patients with inflammatory bowel disease (IBD) have a higher incidence of CDI and worse outcomes. There has been no study from Asia to evaluate the cost-effectiveness of FMT for overall rCDI patients and rCDI patients with IBD. We applied a Markov model with deterministic and probabilistic sensitivity analyses to evaluate the cost and effectiveness of different treatments for rCDI patients with a time horizon of 1 year from the payer's perspective. We compared the cost and clinical outcomes of FMT through colonoscopy to two antibiotics (vancomycin and fidaxomicin) using data from Chang Gung Memorial Hospital, Taoyuan, Taiwan. Compared to vancomycin, FMT was cost-effective in overall rCDI patients as well as IBD patients with rCDI [USD 39356 (NT$1,101,971.98)/quality-adjusted life year (QALY) gained in overall patients; USD65490 (NT$1,833,719.14)/QALY gained in IBD patients]. Compared to fidaxomicin, FMT was only cost-effective in overall rCDI patients [USD20255 (NT$567,133.45)/QALY gained] but slightly increased QALY (0.0018 QALY gained) in IBD patients with rCDI. FMT is cost-effective, compared to vancomycin or fidaxomicin, for the treatment of rCDI in most scenarios from the payers' perspective in Taiwan.


Colonization of plant roots and enhanced atrazine degradation by a strain of Arthrobacter ureafaciens.
Our previous research found that culturable atrazine degraders associated with maize roots were dominated by genetically similar strains of Arthrobacter ureafaciens, suggesting their rhizosphere competence. The present study aimed to assess the root-colonizing capacity of strain A. ureafaciens DnL1-1 and to evaluate consequent root-associated degradation of atrazine. A soil-sand assay and pot experiments provided evidence that A. ureafaciens DnL1-1 competitively colonized roots of maize, wheat, and alfalfa following seed inoculation. Atrazine was not absolutely required but promoted colonization of plant roots by the bacterium. In association with plants, A. ureafaciens DnL1-1 enhanced the degradation of atrazine and strongly reduced accumulation of its dealkylated metabolites. Our results show that after low-level inoculation of seeds, the bacterium A. ureafaciens DnL1-1 can establish root populations sufficient for the rapid degradation of atrazine in soil that makes it a promising bioremediation agent which can be easily applied to large areas of polluted soil. Application of the root-colonizing, atrazine-degrading Arthrobacter bacteria as seed inoculants may be a reliable remediation strategy for soils contaminated with chlorinated s-triazines and their degradation products.


Digital mediation of candidacy in maternity care: Managing boundaries between physiology and pathology.
This paper brings together scholarship across sociology, media and communication, and human computer interaction to explore the intersection of digital health and the maternity care system. We draw on data (including interviews, focus groups, observations, and analyses of digital media content) from 19 studies involving over 400 women to explore women's experiences of using different forms of digital support such as the Internet, mobile technologies (apps and text messaging), social media, and remote monitoring devices in their reproductive journeys. We use a best fit approach to analysis, mapping our findings to the candidacy framework and notions of trajectory work to understand how women engage in digital health practices to negotiate boundaries between physiology and pathology and to enter dialogue with maternity services during conception, pregnancy and the postnatal period. We propose an integrated revised conceptual framework which explicates intersections between digital and care practices, and micro-level negotiations between women and professionals in the maternal health context. Our revised framework retains the dimensions of candidacy, but it introduces a precursor to the identification of candidacy in the form of 'understanding normality'. It identifies distinct forms of digital work (e.g. information work, navigation work, machine work) which operate across the candidacy dimensions that women (and partners at times) engage in to negotiate legitimacy when entering into encounters with the maternity care system. Operating conditions (norms around expert motherhood; neoliberal discourses around health optimisation, risk and responsibilisation) provide a broader macro-level context, influencing the micro-level dialogic processes between women and healthcare professionals. Our synthesis highlights digital mediation as a useful filter to understand care systems, distribution of lay/professional responsibilities, relational practices and the (dis)enablement of candidacy.


Charge Assisted S/Se Chalcogen Bonds in SAM Riboswitches: A Combined PDB and ab Initio Study.
In this study, we provide experimental (Protein Data Bank (PDB) inspection) and theoretical (RI-MP2/def2-TZVP level of theory) evidence of the involvement of charge assisted chalcogen bonding (ChB) interactions in the recognition and folding mechanisms of S-adenosylmethionine (SAM) riboswitches. Concretely, an initial PDB search revealed several examples where ChBs between S-adenosyl methionine (SAM)/adenosyl selenomethionine (EEM) molecules and uracil (U) bases belonging to RNA take place. While these interactions are usually described as a merely Coulombic attraction between the positively charged S/Se group and RNA, theoretical calculations indicated that the σ holes of S and Se are involved. Moreover, computational models shed light on the strength and directionality properties of the interaction, which was also further characterized from a charge-density perspective using Bader's "Atoms in Molecules" (AIM) theory, Non-Covalent Interaction plot (NCIplot) visual index, and Natural Bonding Orbital (NBO) analyses. As far as our knowledge extends, this is the first time that ChBs in SAM-RNA complexes have been systematically analyzed, and we believe the results might be useful for scientists working in the field of RNA engineering and chemical biology as well as to increase the visibility of the interaction among the biological community.


Low rate of high-level athletes maintained a return to pre-injury sports two years after arthroscopic treatment for femoroacetabular impingement syndrome.
The aim was to investigate the rate of athletes still active at their pre-injury sports level two years after arthroscopic treatment for femoroacetabular impingement syndrome (FAIS), and examine this between different sports and gender, and its correlation to patient-reported outcome measures (PROMs). High-level athletes planned for arthroscopic treatment for FAIS were included prospectively in a Swedish hip arthroscopy registry between 2011 and 2017, and 717 met the inclusion criteria. Self-reported sporting activity was recorded preoperatively. The subjects answered PROMs, including the HSAS, iHOT-12 and HAGOS pre- and postoperatively. A total of 551 athletes (median age 26, interquartile range 20-34 years; 23% women) had completed follow-up PROMs, at mean 23.4 ± 7.2 months postoperatively. In total, 135 (24.5%) were active at their pre-injury level of sports at follow-up (RTSpre). Athletes ≤30 years at time of surgery (n = 366; median age 22 years) had higher rate of RTSpre (31.4%) compared with athletes > 30 years (n = 185; median age 40 years) (10.8%; p < 0.001). All athletes had improvements in iHOT-12 and HAGOS, two years postoperatively (p < 0.001), while RTSpre athletes reported significantly better PROMs, pre- and postoperatively, and had greater improvements two years postoperatively, compared with athletes not active at pre-injury level. Only 25% of all high-level athletes and 31% of athletes ≤30 years were still active at their pre-injury sports level two years after arthroscopic treatment for FAIS. Athletes still active had significantly and clinically greater improvement regarding hip symptoms, function and quality of life, as compared with athletes not active at pre-injury level, two years postoperatively.


[Detection of virulence genes in aminoglycoside susceptible and resistant Enterococcus faecalis].
Enterococcus spp. is an important cause of nosocomial infections A number of virulence factors that may enhance its ability to colonize have been described. Enterococcus is capable of acquiring resistance genes, including high-level resistance (HLR) to aminoglycoside antibiotics. to investigate the prevalence of genes encoding virulence factors in aminoglycosides susceptible and resistant E. faecalis. A total of 80 E. faecalis isolates from clinical (n: 52) and poultry samples (n: 28) were included in this study. Bacterial identification was performed by biochemical tests and phenotypificationwas done using the Phene-PlateTM system. Susceptibility to different antimicrobial agents was determined by the agar dilution method. Virulence genes aceI, agg, gelE and efaA were detected by multiplex PCR. All isolates were susceptible to vancomycin and ampicillin. HLR to gentamicin (13.5%) and streptomycin (9.6%) was detected only in clinical isolates. The phenotyping revealed a great diversity of PhP-types, but only one clone with 7 strains of similar characteristics was found. The efaA gen was detected in 100% of the isolates. aceI gene was present in 94.2% and 75%, agg gene in 73.1%, and 67.9%, and gelE gene in 57.5% and 28.6% of the clinical and chicken isolates, respectively. Only 6 strains with HLR to aminoglycosides, belonging to the same phenotype, had the aceI, agg, gelE and efaA genes. E. faecalis with virulence genes and HLR to aminoglycosides were isolated from clinical and chicken samples in Antofagasta. More studies will be necessary to establish an association.


Evaluation and optimization of antibiotic usage in upper respiratory tract infections in children at a tertiary care outpatient department: A clinical audit.
Inappropriate antibiotic (ab)use contributes to antimicrobial resistance. Upper respiratory tract infection (URTI) is the most common reason for antibiotic prescription in an outpatient department (OPD). Several factors influence the high and unjustified antibiotic use in a common ailment. A clinical audit was performed to assess antibiotic prescription rate (APR) for URTI in the pediatric OPD against the available benchmark. The prescription pattern was assessed, and interventions were formulated to improve prescription behavior. Data of all children attending OPD and fulfilling the criteria for URTI group were collected from the online hospital management system and analyzed. Interventions, in the form of discussions, presentations, posters, and guidelines (Indian Ministry of Health Guidelines for URTI) regarding etiology of URTI, and indications for antibiotic prescription were implemented. Data were monitored and feedback to consultants was given. The baseline APR was 14.7%. There was wide variation in APR (4.1%-53.1%) among consultants. Three consultants had a rate of 53.1%, 29.7%, and 28.6%, which was very high. Postintervention, the average APR decreased to 8.7%, a reduction of 40.8%. There was a reduction in APR among consultants with high APR as well. There was reduction in the use of azithromycin, a drug recommended for patients with penicillin allergy, from 21.2% to 14.4% (32.1% reduction). Amoxycillin plus clavulanic acid combination and amoxicillin alone continued to be the most prescribed antibiotics. Interventions through clinical audit were useful in reducing APR. The APR of 8.7% achieved in this study postintervention can be used as a benchmark by other institutions to assess APR in children with URTI.


GABA-responses of CA3 neurones at epileptogenic threshold concentrations of convulsants.
Epileptogenic actions of convulsants are often attributed to weakened inhibitory synaptic mechanisms. This assumption was tested by studying GABA-induced postsynaptic membrane potential (MP) changes of CA3 neurones (guinea-pig) before and during exposure to bicuculline methoiodide (BMI), pentylenetetrazol (PTZ), penicillin (PEN) and caffeine (CAF). Under control conditions GABA ejections elicited polyphasic MP fluctuations (components I-III). After adding BMI, PTZ, PEN or CAF, early hyperpolarizations (component I) did not change at epileptogenic threshold concentrations. These convulsants, however, exerted differential effects on the depolarizing component II, but only threshold concentrations of penicillin strongly reduced the amplitude of this component. Simultaneously, component III was slightly accentuated. These findings indicate that changes of GABA responses are not an essential prerequisite for the generation of paroxysmal depolarizations.


Exploring Barriers to Vitamin A Supplementation Uptake and Program Implementation Among Children Aged 6-59 Months in Ethiopia: A Qualitative Approach.
Background: Children in Ethiopia do not receive the recommended dose of vitamin A supplementation (VAS). Objective: This study aimed to explore the barriers to VAS uptake and program implementation among children aged 6-59 months in Ethiopia. Methods: Data were collected qualitatively using focus group discussions and in-depth interviews. The data were audio-recorded, transcribed, and inductively coded. The results were displayed using thematic analysis and the well-spoken verbatim of the respondents. Results: The barriers to VAS uptake were low parental awareness of the program and low interest or motivation, low promotion of the program among health professionals, an excessive workload for health extension workers, and low professional attention to VAS compared to other health services. Conclusion: Both client-side and supply-side issues posed significant obstacles to the uptake of VAS. It is important to educate mothers about VAS. Health workers should receive refresher training to raise their level of concern about VAS's importance and its schedule. It's crucial to initiate outreach programs for remote communities. The departmentalization of health extension packages will improve service and access.


Psychological intervention - a critical element of rehabilitation in chronic pulmonary diseases.
Chronic pulmonary diseases represent a segment of pathology with an increasing prevalence worldwide, this requiring joint efforts from specialists in this field to (a) identify those factors insufficiently explored so far, but critical for their evolution and (b) address them via new therapies. This study aims to explore the existing data regarding the psychological factors involved in the dynamics of chronic pulmonary diseases and the main possibilities of psychological intervention, as a distinct part of pulmonary rehabilitation (PR). 49 articles published on this topic in peer-reviewed journals between 1979 and 2010, indexed in PubMed, ProQuest and EBSCO databases, were examined for evidence. Among psychological factors considered important by study authors were the following: 1) the deficient instruction of the patient, 2) decreased treatment motivation, 3) a marginal social role, 4) a disadaptive cognitive style and 5) psychiatric comorbidity (especially anxiety and depression). Efficient interventions were, for physicians, 1) patient education and 2) designing a personalized self-management plan, and for the clinical psychologists, 1) cognitive-behavioral therapy, 2) biofeedback, 3) family therapy, 4) relaxation and 5) hypnosis. Despite the undeniable effect of these methods in selected cases, the high heterogeneity of designs and personal affiliations of researchers do not allow new generalizations about their efficacy or their routine implementation into PR. Further research including larger samples, more uniform designs, construction of consensual international standards regarding the objectives of PR, and assessments done by experts from multiple study domains could contribute to a better understanding of the role psychological interventions could play in PR.


An Improved Multi-Objective Programming with Augmented ε-Constraint Method for Hazardous Waste Location-Routing Problems.
Hazardous waste location-routing problems are of importance due to the potential risk for nearby residents and the environment. In this paper, an improved mathematical formulation is developed based upon a multi-objective mixed integer programming approach. The model aims at assisting decision makers in selecting locations for different facilities including treatment plants, recycling plants and disposal sites, providing appropriate technologies for hazardous waste treatment, and routing transportation. In the model, two critical factors are taken into account: system operating costs and risk imposed on local residents, and a compensation factor is introduced to the risk objective function in order to account for the fact that the risk level imposed by one type of hazardous waste or treatment technology may significantly vary from that of other types. Besides, the policy instruments for promoting waste recycling are considered, and their influence on the costs and risk of hazardous waste management is also discussed. The model is coded and calculated in Lingo optimization solver, and the augmented ε-constraint method is employed to generate the Pareto optimal curve of the multi-objective optimization problem. The trade-off between different objectives is illustrated in the numerical experiment.


[Development of beta-lactamase inhibitors].
The proportion of beta-lactamase producing bacteria in each species of clinical isolates is high (over 90%) in these years. According to the survey of bacterial resistance in 1995, higher proportion of resistant bacterial species against ampicillin, piperacillin (PIPC), cefazolin, cefotiam was observed. To overcome the bacterial resistance against these beta-lactam antibiotics, we have made a development of beta-lactamase inhibitor and its combination antibiotic. New beta-lactamase inhibitor, tazobactam (TAZ) showed strong inhibitory activity against various kinds of beta-lactamases including cephalosporinases. The combination antibiotic, TAZ/PIPC(TAZ combined with PIPC by 1 to 4) showed stronger antibacterial activity than PIPC against beta-lactamase producing stains. And also the activity of TAZ/PIPC was superior to PIPC in the mixed bacterial infection model in mouse. The in vitro and in vivo frequency of emergence of resistant bacteria from Enterobacteriacae treated with TAZ/PIPC was lower than that of PIPC or ceftazidime (CAZ). By these data, combined antibiotics with beta-lactamase inhibitor was effective to resolve the problems of bacterial resistances caused by beta-lactamases.


The pituitary-thyroid axis in adults with phenylketonuria.
Serum thyroxine and triiodothyronine levels in 15 adult phenylketonuric patients on an unrestricted diet were normal despite reduced circulating tyrosine levels. Serum thyrotropin levels were normal in the basal state or in response to thyrotropin-releasing hormone in selected patients tested. These results support and extend previous observations of normal thyroid function in phenylketonuria.


Differential requirement for phospholipase D/Spo14 and its novel interactor Sma1 for regulation of exocytotic vesicle fusion in yeast meiosis.
During sporulation and meiosis of budding yeast a developmental program determines the formation of the new plasma membranes of the spores. This process of prospore membrane (PSM) formation leads to the formation of meiotic daughter cells, the spores, within the lumen of the mother cell. It is initiated at the spindle pole bodies during meiosis II. Spore formation, but not meiotic cell cycle progression, requires the function of phospholipase D (PLD/Spo14). Here we show that PLD/Spo14 forms a complex with Sma1, a meiotically expressed protein essential for spore formation. Detailed analysis revealed that both proteins are required for early steps of prospore membrane assembly but with distinct defects in the respective mutants. In the Deltaspo14 mutant the initiation of PSM formation is blocked and aggregated vesicles of homogenous size are detected at the spindle pole bodies. In contrast, initiation of PSM formation does occur in the Deltasma1 mutant, but the enlargement of the membrane is impaired. During PSM growth both Spo14 and Sma1 localize to the membrane, and localization of Spo14 is independent of Sma1. Biochemical analysis revealed that Sma1 is not necessary for PLD activity per se and that PLD present in a complex with Sma1 is highly active. Together, our results suggest that yeast PLD is involved in two distinct but essential steps during the regulated vesicle fusion necessary for the assembly of the membranous encapsulations of the spores.