Ethnic Disparities in Oral Health Related Quality of Life among Adults in London, England.
To explore ethnic disparities in oral health related quality of life (OHQoL) among adults, and the role that socioeconomic factors play in that association. Data from 705 adults from a socially deprived, ethnically diverse metropolitan area of London (England) were analysed for this study. Ethnicity was self-assigned based on the 2001 UK Census categories. OHQoL was measured using the Oral Health Impact Profile (OHIP-14), which provides information on the prevalence, extent and intensity of oral impacts on quality of life in the previous 12 months. Ethnic disparities were assessed in logistic regression models for prevalence of oral impacts and negative binomial regression models for extent and intensity of oral impacts. The prevalence of oral impacts was 12.7% (95% CI: 10.2-15.1) and the mean OHIP-14 extent and severity scores were 0.27 (95% CI: 0.20-0.34) and 4.19 (95% CI: 3.74-4.64), respectively. Black adults showed greater and Asian adults lower prevalence, extent and severity of oral impacts than White adults. However, significant differences were only found for the extent of oral impacts; Black adults reporting more and Asian adults fewer OHIP-14 items affected than their White counterparts. After adjustments for socioeconomic factors, Asian adults had significantly fewer OHIP-14 items affected than White adults (rate ratio: 0.28; 95%CI: 0.08-0.94). This study found disparities in OHQoL between the three main ethnic groups in South East London. Asian adults had better and Black adults had similar OHQoL than White adults after accounting for demographic and social factors.


Serendipity or prepared mind? Recollections of the KOP translocation (1967) and of one form of Perrault syndrome.
The human X/autosome translocation, designated KOP, was discovered by Dr. Philip D. Pallister in Montana in 1967 in a young man with apparent Klinefelter syndrome. Collaboratively it was possible to elucidate the genetic nature of his unprecedented chromosome rearrangement and its developmental effects in mother and son. In retrospect, these clinical and genetic studies at the height of the somatic cell genetics era (Ruddle, Siniscalco, etc.) presented human genetics with a highly productive opportunity to begin gene mapping of autosomes and the X chromosome. The late Victor McKusick considered the discovery of the KOP translocation, as he determined personally in Montana, one of the major transforming events in human genetics. The Perrault syndrome evaluated in two families in Montana and one in Sicily for familial deafness, primary amenorrhea and neurologic impairment (progressive in some), turned out to be heterogeneous. In the "hands" of Dr. M.-C. King of Seattle four forms of Perrault syndrome have been identified. The autosomal recessive mutation present in the P family studied with Dr. Pallister in Helena, turned out to affect the mitochondrial histidyl tRNA synthetase gene present in prokaryotes, annelids, fungi and mammals, hence, must already have been present in LUCA some 3.8 billion years ago.


Physicians' Well-Being Linked To In-Basket Messages Generated By Algorithms In Electronic Health Records.
Despite concerns about physicians' workload associated with electronic health records (EHRs), little attention has been paid to the relationship between physicians' well-being and the in-basket messages physicians receive-specifically, their volume and sources. Analyses of EHR work performed by physicians in a multispecialty practice found that in-basket messages generated by the EHR system accounted for almost half (114) of the 243 weekly in-basket messages received per physician, on average-far exceeding the numbers received from their colleagues (53) and patients (30). In a survey, 36 percent of the physicians reported burnout symptoms, and 29 percent intended to reduce their clinical work time in the upcoming year. Receiving more than the average number of system-generated in-basket messages was associated with 40 percent higher probability of burnout and 38 percent higher probability of intending to reduce clinical work time. Physicians' perceptions of a positive work environment were associated with lower odds of burnout and intention to reduce clinical work time and with greater satisfaction with life. Female physicians had a higher risk of burnout and lower satisfaction with life, compared to males. Meaningful redesign of EHR in-basket workflow and a wellness-enhancing work environment are necessary to effectively improve physicians' well-being.


Excimer Laser Surgery: Biometrical Iris Eye Recognition with Cyclorotational Control Eye Tracker System.
A prospective comparative study assessing the importance of the intra-operative dynamic rotational tracking-especially in the treatment of astigmatisms in corneal refractive Excimer laser correction-concerning clinical outcomes is presented. The cyclotorsion from upright to supine position was measured using iris image comparison. The Group 1 of patients was additionally treated with cyclorotational control and Group 2 only with X-Y control. Significant differences were observed between the groups regarding the mean postoperative cylinder refraction (p < 0.05). The mean cyclotorsion can be calculated to 3.75° with a standard deviation of 3.1°. The total range of torsion was from -14.9° to +12.6°. Re-treatment rate was 2.2% in Group 1 and 8.2% in Group 2, which is highly significant (p < 0.01). The investigation confirms that the dynamic rotational tracking system used for LASIK results in highly predictable refraction quality with significantly less postoperative re-treatments.


Morphological observation of Y and T junctions in nanostructured boron nitride thin films.
Formations of Y and T nano junctions have been observed in boron nitride films deposited on silicon substrates by plasma chemical reaction of diborane (B2H6 diluted in hydrogen) and ammonia (NH3) gases using dual frequency (microwave/radio) plasma enhanced chemical vapor deposition technique without any intentional heating of the substrates. It has been observed that these nano junctions form at a critical feed gas ratio of ammonia and diborane. We have investigated the effect of gas feed ratio R (=NH3/B2H6) in the plasma reaction chamber, keeping all other deposition parameters constant, on the morphology of boron nitride films. The deposited films are characterized by SEM, AFM, TEM and Laser Raman. For gas feed ratio, R < 100, octahedron and cubic morphologies have been observed in BN films and on increasing R to >100, size of the crystallites reduces to nanometer level. In some of our BN samples deposited at a critical value of gas ratio (R = 400), uniform Y and T junctions having bamboo like morphologies, in nanometer level, have been observed, which we wish to emphasis here as an interesting and newer observation in boron nitride films deposited by the dual frequency PECVD technique. This change in morphology exhibited by varying gas feed ratio is mainly due to excess nitrogen ions in the plasma.


Adrenergic receptor-mediated regulation of cultured rabbit airway smooth muscle cell proliferation.
To evaluate the potential role of adrenergic receptors in regulating airway smooth muscle (ASM) cell proliferation, the mitogenic effects and mechanisms of action of selective alpha- and beta-adrenoceptor activation were investigated in cultured rabbit ASM cells. The alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, elicited significant dose-dependent (10(-10)-10(-4) M) stimulation of ASM cell mitogenesis, with mean +/- SE peak increases in ASM cell count amounting to 17.0 +/- 3.5 and 44.0 +/- 6.8% above unstimulated (control) levels, respectively. Similarly, the alpha 2-adrenoceptor agonist clonidine (10(-8)-10(-4)) also induced ASM cell proliferation, with a 41.1 +/- 5.5% peak increase in cell count above control. The promitogenic responses to alpha-adrenoceptor activation were blocked by pertussis toxin (PT; 100 ng/ml), which ADP-ribosylates G protein negatively coupled to adenylate cyclase activation. In additional studies, we found that 1) treatment with agents inducing intracellular adenosine 3',5'-cyclic monophosphate (cAMP) accumulation including the beta-adrenergic agonist, isoproterenol, the cAMP analogue, 8-(4-chlorophenylthio)-cAMP and forskolin, all produced significant dose-dependent inhibition of serum-stimulated ASM cell growth; 2) alpha-adrenoceptor activation inhibited isoproterenol-induced cAMP accumulation; and 3) the anti-proliferative effects of isoproterenol and PT were additive. Collectively, the above findings provide new evidence that adrenergic receptors exert an opposing duality of action in regulating ASM cell proliferation, wherein receptors which are negatively coupled (i.e., alpha-adrenergic) and those which are positively coupled (i.e., beta-adrenergic) to activation of the adenylate cyclase/cAMP signal-transduction pathway are promitogenic and growth inhibitory to ASM cells, respectively.


Time course of fiber outgrowth from fetal anterior hypothalamic heterografts.
Fetal anterior hypothalamic (AH) heterografts can restore circadian rhythmicity to animals rendered arrhythmic following ablation of the suprachiasmatic nucleus (SCN). Behavioral restoration of circadian activity typically begins between two and six weeks post-implantation. The time course of fiber outgrowth from fetal AH heterografts was examined to determine whether neuronal outgrowth from the implants precedes the typically observed effects of such implants upon circadian behavior. Fetal mouse or rat AH tissue containing the SCN was implanted into the third ventricle of SCN-lesioned hamsters. Using species-specific monoclonal antibodies generated against mouse or rat neuronal elements, fiber outgrowth into the host hypothalamus was examined at 2, 4, 7, 14, 30 and 45 days after implantation. Fibers were observed to have emerged from the implant at the earliest time point examined. Four days after surgery, individual fibers had extended up to 0.6 mm into the host neuropil. By 14 days post-implantation, outgrowth from the implant had formed a dense fiber plexus in the host hypothalamus. This observation demonstrates that neuronal integration of the implant with the host brain begins within 48 hours of implantation, and is extensively established well before a restoration of rhythmicity is typically observed. Thus, on the basis of the time course of fiber outgrowth, it is clear that neuronal contact between graft and host may mediate the observed restoration of circadian rhythmicity.


Infrared-infrared double resonance spectroscopy of cyanoacetylene in helium nanodroplets.
Infrared-infrared double resonance spectroscopy is used as a probe of the vibrational dynamics of cyanoacetylene in helium droplets. The nu1 C-H stretching vibration of cyanoacetylene is excited by an infrared laser and subsequent vibrational relaxation results in the evaporation of approximately 660 helium atoms from the droplet. A second probe laser is then used to excite the same C-H stretching vibration downstream of the pump, corresponding to a time delay of approximately 175 micros. The hole burned by the pump laser is narrower than the single resonance spectrum, owing to the fact that the latter is inhomogeneously broadened by the droplet size distribution. The line width of the hole is characteristic of another broadening source that depends strongly on droplet size.


Recent Advances in Sustainable Antimicrobial Food Packaging: Insights into Release Mechanisms, Design Strategies, and Applications in the Food Industry.
In response to the issues of foodborne microbial contamination and carbon neutrality goals, sustainable antimicrobial food packaging (SAFP) composed of renewable or biodegradable biopolymer matrices with ecofriendly antimicrobial agents has emerged. SAFP offers longer effectiveness, wider coverage, more controllability, and better environmental performance. Analyzing SAFP information, including the release profile of each antimicrobial agent for each food, the interaction of each biomass matrix with each food, the material size, form, and preparation methods, and its service quality in real foods, is crucial. While encouraging reports exist, a comprehensive review summarizing these developments is lacking. Therefore, this review critically examines recent release-antimicrobial mechanisms, kinetics models, preparation methods, and key regulatory parameters for SAFPs based on slow- or controlled-release theory. Furthermore, it discusses fundamental physicochemical characteristics, effective concentrations, advantages, release approaches, and antimicrobial and preservative effects of various materials in food simulants or actual food. Lastly, inadequacies and future trends are explored, providing practical references to regulate the movement of active substances in different media, reduce the reliance on petrochemical-based materials, and advance food packaging and preservation technologies.


Molecular basis of activation and regulation of the phagocyte respiratory burst.
The molecular basis of activation and regulation of the phagocyte respiratory burst is discussed with particular reference to the role of inositol phospholipid hydrolysis, guanine nucleotide coupling proteins, and activation of protein kinase C.


The timing of computed tomography in acute stroke: a practice audit.
To compare the patterns of practice and diagnostic yields for early and late computed tomography (CT) in patients with acute stroke. Among the 191 consecutive patients with acute stroke admitted to a university teaching hospital from Sept. 1, 1989, to Sept. 1, 1993, charts were available for review for 185. In addition to the timing and results of CT in these patients, data were collected on the demographic features of the patient group and the presence of any cardiovascular risk factors or other features suggestive of a nonstroke cause for the neurologic deficit. Of the 185 patients for whom charts were available, 177 (95.7%) underwent CT. In 107 (60.4%) of the cases, scanning was performed early, within 24 hours of the onset of neurologic deficit, and only 25 (23.4%) of these scans demonstrated a lesion. Of the 70 initial scans obtained more than 24 hours after the deficit onset (delayed scanning), 41 (58%) revealed a diagnostic lesion (relative probability of finding a lesion with early vs delayed scanning, 0.40; 95% confidence interval 0.27 to 0.59; p < 0.0001, Fisher's exact test). Of the 107 patients who underwent early scanning, 45 (42.0%) underwent repeat CT, and previously unrecognized lesions were seen in 28 (62%) of these. Scanning was repeated in only 17 (24%) of the 70 patients who underwent delayed initial scanning (p = 0.02), and previously unrecognized lesions were seen in only 4 of these (24%). All lesions documented on repeat scans after initially nondiagnostic scanning were ischemic. Patients presenting with features thought to justify early CT were no more likely to undergo this intervention than those without such features (68% and 56% respectively, p = 0.11). Initial CT was often carried out within 24 hours of the onset of deficit in patients with suspected acute stroke at this institution, CT was a low-yield investigation, and scanning was frequently repeated. Although the literature suggests that clinical features can distinguish that subset of patients who should undergo urgent neuroimaging, prospective studies are needed to establish the indications for early CT in patients presenting with acute neurologic deficit.


Oral delivery of double-stranded RNAs induces mortality in nymphs and adults of the Asian citrus psyllid, Diaphorina citri.
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is one of the most important citrus pests. ACP is the vector of the phloem-limited bacteria Candidatus Liberibacter americanus and Candidatus Liberibacter asiaticus, the causal agents of the devastating citrus disease huanglongbing (HLB). The management of HLB is based on the use of healthy young plants, eradication of infected plants and chemical control of the vector. RNA interference (RNAi) has proven to be a promising tool to control pests and explore gene functions. Recently, studies have reported that target mRNA knockdown in many insects can be induced through feeding with double-stranded RNA (dsRNA). In the current study, we targeted the cathepsin D, chitin synthase and inhibitor of apoptosis genes of adult and nymph ACP by feeding artificial diets mixed with dsRNAs and Murraya paniculata leaves placed in dsRNAs solutions, respectively. Adult ACP mortality was positively correlated with the amount of dsRNA used. Both nymphs and adult ACP fed dsRNAs exhibited significantly increased mortality over time compared with that of the controls. Moreover, qRT-PCR analysis confirmed the dsRNA-mediated RNAi effects on target mRNAs. These results showed that RNAi can be a powerful tool for gene function studies in ACP and perhaps for HLB control.


Influence of the geometry of the screwdriver-screw connection on the reverse torque of UCLA screws.
The aim of this study was to evaluate the influence of the geometry of the screwdriver-screw connection on the reverse torque of UCLA screws after repeated cycles of tightening and loosening in an implant-supported prosthesis. Thirty sets of external hex titanium implants, UCLA abutments, and UCLA abutment screws were divided into 3 experimental groups (n = 10). In the square group, the implant and UCLA abutment system were mounted in an upright position using a screw with a square screwdriver-screw connection. In the hexagonal group, the implant and UCLA abutment system were mounted in an upright position using a screw with a hexagonal screwdriver-screw connection. In the hexalobular group, the implant and UCLA abutment system were mounted at 70° using a dynamic UCLA abutment and screw with a hexalobular screwdriver-screw connection. Ten alternating torque-reverse torque cycles were applied to each screw using a screwdriver fixed at the end of a digital torque meter. The screws with a square connection resulted in less loss of reverse torque than the other types. Screws with a hexagonal connection showed a statistically significant loss of torque initially but remained constant for the remaining cycles. For the screws with a hexalobular connection, the loss of torque was greater, and substantial deformation of the plastic in the microstructure was noted. The screwdriver-screw connection geometry had a direct influence on the reverse torque of UCLA screws, and the initial reverse torque of the abutment screws with a square connection was greater than that of the hexagonal and hexalobular designs.


[Multidisciplinary approach to the rehabilitation of patients with osteoporosis].
The article outlines the modern concept of rehabilitation of patients with osteoporosis (OP), the cornerstone of which is the use of a multidisciplinary approach. This approach involves not only the participation of specialists of various specializations and levels in the process of rehabilitation treatment, but the formation of a new functional unit - a multidisciplinary team, whose members actively interact with each other from the first days to the completion of the rehabilitation course at every stage of the course; they together make a rehabilitation diagnosis based on the International Classification of Functioning, Disability and Health (ICF); they formulate rehabilitation goals, evaluate rehabilitation potential, discuss and develop a rehabilitation program and evaluate its effectiveness by using modern scales, tests and questionnaires to assess the change in the condition of the patient"s life at all levels and the quality of life in general. Taking into account the principle of multidisciplinarity, approaches to preparation of rehabilitation programs for patients with OP are described using various methods: those of therapeutic gymnastics, mechanotherapy, physiotherapy, balneotherapy, occupational therapy, psychotherapy, drug treatment and orthosis. Particular attention in the process of rehabilitation of patients with OP is given to physical therapy and orthosis, which are aimed at reducing pain, improving coordination, posture, as well as reducing the risk of falls and fractures. The literature review presented in the article allows us to conclude that the use of a multidisciplinary approach in the rehabilitation of patients with OP makes it possible to significantly improve the quality of life of patients even with severe forms of the disease.


Diastereoselective synthesis of three-, five-, six-, and seven-membered rings from Fischer carbene complexes and 4-unsubstituted 1-amino-1,3-dienes.
Fischer carbene complexes react with 4-unsubstituted 1-amino-1,3-dienes to give different carbocyclization products depending on the nature of the carbene complex and on the substitution pattern of the aminodiene. Thus, the reaction of arylcarbene chromium complexes and 1-aminodienes diastereoselectively affords cyclopropane derivatives by means of a formal [2+1] carbocyclization reaction. In particular, pentacarbonyl[(2-furyl)(methoxy)methylene]chromium complex furnishes formal [4+1] carbocyclization products. Starting from beta-substituted alkenylcarbene complexes, formal [4+1] reactions occur and cyclopentenamine derivatives are diastereoselectively formed. However, when the alpha,beta-disubstituted alkenylcarbene complex pentacarbonyl[(5,6-dihydro-2H-pyran-2-yl)(methoxy)methylene]tungsten is used, the outcome of the reaction depends on the substitution on the carbon atom at the 3-position of the aminodiene, generating the [3+2] or [4+3]-cyclization products if the substituent is or is not a hydrogen atom, respectively. Finally, when the reaction is performed with alkynylcarbene complexes, benzaldehyde derivatives are obtained if the triple-bond substituent is a phenyl group or indene derivatives if the group is an alkenyl moiety.


Subcellular sites for synthesis of chondromucoprotein of cartilage.
Microsomes from embryonic cartilage have been subfractionated to yield smooth microsomes and rough microsomes. The in vitro enzymic activities involved in chondroitin sulfate biosynthesis have been assayed in these subfractions. The results demonstrate that all of the activities necessary for linkage to protein as well as for completion of the polysaccharide chain are present in both the rough and smooth fractions. Only in the case of the polymerization of N-acetylgalactosamine and glucuronic acid could enzyme assays be done independent of endogenous acceptor. This enzyme(s) was equally distributed between the rough and smooth fractions. The activities for the addition of xylose and galactose to protein were highest in the rough fraction while that for sulfation was highest in the smooth fraction. These findings suggest that polysaccharide chain-initiation occurs in the rough endoplasmic reticulum and that chain completion occurs in the smooth reticulum. This pattern is consistent with modern theories of synthesis, transfer, and export of extracellular macromolecules.


[Analysis of clinicopathological features of 68 cases of malignant pleural mesothelioma].
Objective: To analyze the clinicopathological characteristics of diffuse malignant pleural mesothelioma (MPM), and explore the diagnostic methods in order to improve the early diagnosis rate. Methods: In January 2019 to January 2022, the clinical features, auxiliary examination and immunohistochemical results of 68 cases of MPM were analyzed retrospectively. The pathogenic features, histopathological morphology and the expression of related antibodies including Calretinin (CR), D2-40 and WT-1 were summarized. Results: Among the 68 patients, 40 male (58.82%), 28 female (41.18%), male to female ratio was 1.43%, median age was 58 years old; 50% of patients in Dayao County, epithelial mesothelioma 59 cases (86.76%), occurred in right chest in 39 cases (57.35%), left chest in 25 cases (36.76%), and 4 cases in both sides (5.89%). The most common initial clinical manifestations were pleural effusion (95.59%), chest pain (36.75%), chest tightness and shortness of breath (30.88%). The main imaging findings were pleural effusion in 49 cases (98.00%) and pleural thickening in 46 cases (92.00%). MPM tumor cells often expressed Calretinin, CK5/6, WT1 and D2-40, while TTF-1, NapsinA and CEA, the main markers differentiated from lung adenocarcinoma were negative. Serum CYFRA21-1 and CEA have high value in differential diagnosis of benign and malignant pleural effusions. Conclusion: Diffuse MPM has diverse histological and cytological morphology, which needs to be differentiated from a variety of diseases. Correct diagnosis of diffuse MPM through immunohistochemistry requires the combined application of a group of Mesothelium related antibodies.


Clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy for pulmonary tuberculosis with Yin-deficiency and Fire-hyperactivity syndrome.
To evaluate the clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy in mitigating the symptoms of pulmonary tuberculosis and to measure the effect on the CD4+ CD25+ regulatory T cell (Treg) ratio. This randomized study enrolled patients with pulmonary tuberculosis and randomly assigned them to one of two treatment groups: an anti-tuberculosis treatment group and a combined treatment group. Bronchoalveolar lavage was performed before and 2 weeks after treatment. The ratio of CD4+ CD25+ Treg cells and the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-6 and IL-12 in peripheral blood and bronchoalveolar lavage fluid were measured. Symptoms were recorded before and after treatment. A total of 100 patients were enrolled and assigned to the anti-tuberculosis (n = 58) and combined treatment groups (n = 42). In the combined treatment group, Leicester Cough Questionnaire score, erythrocyte sedimentation rate, CD4+ CD25+ Treg cell ratio in bronchoalveolar lavage fluid, cytokine levels, chest pain score and sleep disorder score were significantly decreased compared with the anti-tuberculosis treatment group after treatment. The leukocyte count, haemoglobin level, platelet and alanine aminotransferase levels did not differ significantly between the two groups after treatment. The creatinine level in the combined treatment group was significantly lower than that in the anti-tuberculosis treatment group. Baihe Gujin decoction combined with anti-tuberculosis treatment can effectively alleviate the symptoms of pulmonary tuberculosis, enhance the host immune function and protect renal function.


A Novel Biosensing Approach: Improving SnS2 FET Sensitivity with a Tailored Supporter Molecule and Custom Substrate.
The exclusive features of two-dimensional (2D) semiconductors, such as high surface-to-volume ratios, tunable electronic properties, and biocompatibility, provide promising opportunities for developing highly sensitive biosensors. However, developing practical biosensors that can promptly detect low concentrations of target analytes remains a challenging task. Here, a field-effect-transistor comprising n-type transition metal dichalcogenide tin disulfide (SnS2 ) is developed over the hexagonal boron nitride (h-BN) for the detection of streptavidin protein (Strep.) as a target analyte. A self-designed receptor based on the pyrene-lysine conjugated with biotin (PLCB) is utilized to maintain the sensitivity of the SnS2 /h-BN FET because of the π-π stacking. The detection capabilities of SnS2 /h-BN FET are investigated using both Raman spectroscopy and electrical characterizations. The real-time electrical measurements exhibit that the SnS2 /h-BN FET is capable of detecting streptavidin at a remarkably low concentration of 0.5 pm, within 13.2 s. Additionally, the selectivity of the device is investigated by measuring its response against a Cow-like serum egg white protein (BSA), having a comparative molecular weight to that of the streptavidin. These results indicate a high sensitivity and rapid response of SnS2 /h-BN biosensor against the selective proteins, which can have significant implications in several fields including point-of-care diagnostics, drug discovery, and environmental monitoring.


No evidence on the effectiveness of oral splints for the management of temporomandibular joint dysfunction pain in both short and long-term follow-up systematic reviews and meta-analysis studies.
The aim of this study was to determine the efficacy of oral splints in reducing the intensity of pain in patients with temporomandibular joint dysfunction in both short and long-term treatment durations. Electronic databases, Cochrane Library, MEDLINE via PubMed, Web of Science, Egyptian Knowledge Bank, and EMBASE were searched for randomized controlled trials comparing different types of splints to non-occluding splints, behavioral therapy, pharmacotherapy, counseling, and no treatment. The risk of bias was assessed by using Cochrane risk of bias recommendations. Fixed and random effects were used to summarize the outcomes. The effect estimates were expressed as standardized mean differences (SMD) or risk ratios with a 95% confidence interval (CI). Subgroup analyses were carried out according to the treatment duration. Twenty-two studies met the inclusion criteria. A meta-analysis of short-term studies up to three months revealed no significant difference between the study groups. However, long-term studies exhibited a significant difference in pain reduction in favor of the control group. Total analysis revealed that the control group resulted in significant pain reduction (SMD 0.14, 95% CI 0.05-0.23, P=0.002, I2=0%). Oral splints are not effective in reducing pain intensity or improving function in patients with temporomandibular joint dysfunction.


Beryllium-ferritin: lymphocyte proliferation and macrophage apoptosis in chronic beryllium disease.
A beryllium (Be)-ferritin adduct containing 270 pm of Be stimulated proliferation of bronchoalveolar lavage (BAL) lymphocytes from subjects with chronic beryllium disease (CBD) at concentrations 5-6 logs lower than the amounts of beryllium sulfate (BeSO4) needed to induce proliferation. We observed increased apoptotic CBD BAL macrophages after exposure to both BeSO4 (50 +/- 6%, mean +/- SEM, P <0.05 versus unstimulated controls) and Be-ferritin (40 +/- 2%), whereas only 2.0 +/- 0.2% of BAL lymphocytes underwent activation-induced cell death. Be-ferritin also induced apoptosis in BAL macrophages from subjects with Be sensitization (25 +/- 3%) and in the H36.12j hybrid macrophage cell line (15 +/- 2%). Be-ferritin induced lung macrophage CD95 (Fas) expression and the activation of intracellular caspase-3, -8 and -9. Thus, lung macrophages take up Be-ferritin, delivering physiologically relevant levels of Be that promote Be antigen presentation and macrophage apoptosis. Be-ferritin thereby serves as a "Trojan Horse," triggering proliferation of Be-ferritin-specific CBD BAL T cells. We hypothesize that Be-ferritin exposure may result in persistent antigen exposure inducing Be-specific T cell clonal expansion and T cell helper type 1-type cytokine production and potentially explains the chronicity of CBD and its development years after environmental Be exposure has ceased.


Reconstruction of the heel pad by flexor digitorum brevis musculocutaneous flap transfer.
We strongly believe that rotational transfer of a musculocutaneous island flap composed of the flexor digitorum brevis muscle is the best procedure currently available for covering and reconstructing the weight-bearing area of the heel and its posterior area from the histologic and functional points of view. Further, since it requires only one operation, we are confident that it is the ideal method.


Serious mental illness and physical health problems: a discussion paper.
People with serious mental illness have higher morbidity and mortality rates of chronic diseases than the general population. This discussion paper explores the complex reasons for these disparities in health, such as limitations of health services, the effects of having a serious mental illness, health behaviours and the effects of psychotropic medication. Physical health can be enhanced by improved monitoring and lifestyle interventions initiated at the start of treatment. There are opportunities for mental health nurses to play a significant role in improving both the physical and mental health of people with serious mental illness.


Incremental benefit of cardiac resynchronisation therapy with versus without a defibrillator.
To determine the incremental value of implantable cardioverter defibrillators (ICD) in contemporary optimally treated patients with heart failure (HF) undergoing cardiac resynchronisation therapy (CRT). Consecutive patients with HF undergoing CRT-pacemaker (CRT-P) or CRT-defibrillator (CRT-D) implantation in a single tertiary care centre between October 2008 and August 2015 were retrospectively evaluated. For patients with a primary prevention indication of the CRT-D, no benefit of the ICD was defined as absence of appropriate therapy (device analysis) or lethal ventricular tachyarrhythmias (mode of death analysis) during follow-up. 687 patients (CRT-P/CRT-D; n=361/326) were followed for 38±22 months. CRT-P recipients were older (75.7±9.1 vs 71.8±9.3 years; p<0.001) and had a higher comorbidity burden. Five patients with CRT-P (1%) experienced episodes of sustained ventricular-tachycardia vs 64 (20%) patients with CRT-D (p<0.001). Remote tele-monitoring detected the episodes of sustained ventricular tachycardia in four patients with CRT-P, allowing for elective upgrade to CRT-D. All-cause mortality was higher in patients with CRT-P versus CRT-D (21% vs 12%, p=0.003), even after adjusting for baseline characteristics (HR 2.5; 95% CI 1.36 to 4.60; p=0.003). However, mode of death analysis revealed a predominant non-cardiac mode of death in CRT-P recipients (n=47 (71%) vs n=13 (38%) in CRT-D, p=0.002). Multivariate analysis revealed that age >80 years, New York Heart Association class IV, intolerance to beta-blockers and underlying non-ischaemic cardiomyopathy were independently associated with little incremental value of a primary prevention ICD on top of CRT. The majority of patients with contemporary HF as currently selected for CRT-P exhibit mainly non-cardiac-driven mortality. Weighing risk of ventricular-tachyarrhythmic death versus risk of all-cause mortality helps to address the incremental value of an ICD to CRT-P.


Quantitative analysis of diabetic macular ischemia using optical coherence tomography.
We described the optical coherence tomography (OCT) features of diabetic macular ischemia (DMI), and correlate these findings with visual acuity (VA). Clinical and imaging data were collected from 100 patients with type 2 diabetes. Qualitative grading of DMI severity was determined according to criteria defined by the Early Treatment Diabetic Retinopathy Study. Quantitative analysis of foveal avascular zone (FAZ), and OCT images were performed using custom software. In all eyes, the outer retina was thicker in eyes with DMI (167.4 ± 18.5 vs. 150.4 ± 31.4 μm, P = 0.04). However, subanalysis of eyes "without macular edema" revealed the converse; outer retinal thinning in eyes with DMI (223.1 ± 31.2 vs. 244.9 ± 37.2 μm, P = 0.007). A thinner retinal nerve fiber layer also was observed to correlate with increasing FAZ size (r = -0.231, P = 0.03), which strengthened in eyes "without macular edema" (r = -0.62, P = 0.001). In the choroid, quantification of its sublayers revealed a thicker Haller's large vessel layer in the presence of DMI (144.3 ± 51.0 vs. 103.5 ± 39.4 μm, P = 0.01). In eyes with DMI, a thicker retina was correlated with worsening VA (r = 0.52, P = 0.001). However, when eyes with macular edema were excluded, a thinner retina was associated with poor VA (r = -0.37, P = 0.004). In eyes with DMI, we observed thinning of the retinal nerve fiber layer, outer retina, and thickening of Haller's large vessel layer of the choroid. These parameters showed good correlation with VA and may serve as a useful tool for monitoring DMI in clinical practice or future clinical trials.


RFID technology in health environment opportunities and challenges for modern cancer care.
Cancers are significant contributors to the mortality and health care expenditures. Cancer can be reduced and monitored by new information technology. Radio frequency identification or RFID is a wireless identification technology. The use of this technology can be employed for identifying and tracking clinical staff, patients, supplies, medications and equipments. RFID can trace and manage chemotherapy drugs. There are different types of RFID. Implantable RFID allowing a chip to be embedded under the skin and that store the cancer patient's identifier. These are concerns about applications of RFID. Privacy, security and legal issues are key problems. This paper describes capabilities, benefits and confidentiality aspects in radio frequency identification systems and solutions for overcoming challenges.


Interfacility transfers of noncritically ill children to academic pediatric emergency departments.
We aimed to characterize the demographics, diagnoses, and management of transferred patients who were directly discharged from the emergency department (ED) or admitted less than 24 hours. We conducted a retrospective, cross-sectional study of patients classified as interfacility ED transfers over a 12-month period in the Pediatric Health Information System database, an administrative database of 42 tertiary care pediatric US hospitals. The primary study outcomes were ED resource utilization at the receiving facility with a focus on children who were discharged directly from the ED or admitted less than 24 hours. Overall, 24,905 interfacility transfers were identified, accounting for 1.3% of the ED volume of these academic pediatric centers. Of these, 24.7% were discharged directly from the ED and 17.0% were admitted for less than 24 hours. Among those directly discharged from the ED, the 3 most common complaints were orthopedic problems, nonsurgical abdominal pain, and viral gastroenteritis; 20.7% received no medical or procedural intervention. Among those admitted for less than 24 hours, the 3 most common complaints were orthopedic problems, traumatic head injury, and gastrointestinal conditions. A significant proportion of interfacility transfers to academic pediatric EDs is discharged directly from the ED or is admitted for less than a day. These patients and their clinical outcomes provide insight into the educational needs and medical capabilities of referring hospitals and clinicians.


Secular trends of reduced visual acuity from 1985 to 2010 and disease burden projection for 2020 and 2030 among primary and secondary school students in China.
Understanding the burden and trends of reduced visual acuity (VA), a proxy measure for myopia, is essential to guide future health care and clinical management in China. To describe the secular trends from 1985 to 2010, correlate the prevalence of reduced VA among children and adolescents with population density, and project the burden of reduced VA in China in 2020 and 2030. The National Survey on the Constitution and Health of Chinese Students conducted from 1985 to 2010, including 6 repeated surveys with a 3-stage clustering sampling strategy. Mainland China. Primary and secondary school students 7 to 18 years of age were randomly selected from 30 of 31 mainland provinces, excluding Tibet. Unaided distance VA was measured using a retroilluminated logMAR chart with tumbling-E optotypes. World Population Prospects data (the 2012 revision from the Population Division of the Department of Economic and Social Affairs of the United Nations) were used to project the number of people affected by reduced VA in 2020 and 2030. This analysis included 725 423, 142 655, 206 601, 219 663, 234 377, and 215 308 students in 1985, 1991, 1995, 2000, 2005, and 2010, respectively. The overall prevalence of reduced VA was 28.6% (95% CI, 28.4%-28.7%) in 1985, 38.6% (95% CI, 38.3%-38.8%) in 1991, 41.0% (95% CI, 40.8%-41.2%) in 1995, 38.5% (95% CI, 38.3%-38.7%) in 2000, 49.5% (95% CI, 49.3%-49.7%) in 2005, and 56.8% (95% CI, 56.6%-57.0%) in 2010. Girls were more susceptible than boys to having reduced VA (odds ratio, 1.38 [95% CI, 1.35-1.40]), and reduced VA was more prevalent in urban areas than in rural areas (odds ratio, 1.84 [95% CI, 1.81-1.87]). Reduced VA was not significantly associated with population density (P = .11). The projected numbers of cases with reduced VA are about 152.4 million (95% CI, 151.9-152.9 million) in 2020, increasing to 180.4 million (95% CI, 179.8-181.2 million) in 2030 among students who are 7 to 18 years of age in mainland China. There was an increasing trend of reduced VA in both urban and rural areas from 1985 to 2010 in China. Although reduced unaided distance VA is not equal to visual impairment, these summary data are helpful in designing strategies for eye care and health services in China, which may also have public health implications for other developing countries whose economies are growing rapidly.


Detection of Rickettsia spp. in ticks (Acari: Ixodidae) of domestic animals in Colombia.
Rickettsiosis are emerging or re-emerging diseases, with a worldwide distribution associated to transmission by arthropod vectors. Rickettsia species belong to the spotted fever group (SFG) and are transmitted by hard ticks (Acari: Ixodidae) that may act as vectors and reservoirs. This study carried out a molecular detection of Rickettsia from 7 species of the family Ixodidae collected from domestic hosts by PCR amplification of fragments of the citrate synthase "gltA" gene and outer membrane protein "ompA" gene. Of the 204 samples analyzed, 11.3% (23) were positive for rickettsial infection. Three Rickettsia species belonging to the SFG were found, constituting the first reports of Rickettsia rickettsii in 2 departments of Colombia. Furthermore, we confirmed the first occurrence of Candidatus Rickettsia andeanae in Colombia, a species with an unknown pathogenic role in humans. These results raise awareness regarding the need to increase epidemiological control measures, as well as to consider new endemic regions in Colombia for Rocky Mountain spotted fever (RMSF).


Ruptured common femoral artery aneurysm or abdominal aortic aneurysm?
We encountered a patient with a large retroperitoneal hematoma due to rupture of a common femoral artery aneurysm. A 77-year-old man was transferred to our hospital with left groin pain and shock. Computed tomography demonstrated a large retroperitoneal hematoma involving the left iliofemoral segment with extravasation of contrast into the left groin from a ruptured left common femoral artery aneurysm. The patient also had an abdominal aortic aneurysm. Reconstruction of the common femoral artery with a graft was performed successfully. The patient had an uneventful postoperative course and subsequently underwent Y-graft replacement of the abdominal aortic aneurysm.


Black Lives Matter and the spatial imaginaries of urban political resistance.
Scholars have often characterized the city as the epicenter of social inequality. The city has largely been argued to be the product of capitalistic endeavors resulting in deep pockets of conflicting class interests and racial tensions. However, any attempt to understand the city as a function of a broader urban process must consider the ways in which class and racial struggles constitutively restructure power dynamics that are lived out among people and places. In this article, I briefly engage Black Loves Matter (BLM) and their policy efforts to think about the ways in which Black people create imaginaries about their own urban futures.


[Site of action of analgesics: the peripheral site of action of these drugs].
This review describes: recent findings about the peripheral site of action and mechanism of the algesic action of narcotic and nonnarcotic analgesics. Special attention was given to the stimulatory or inhibitory actions of opiates and opioid peptides on the polymodal receptor of the sensory afferent fibers. Bradykinin, a pain producing substance, augmented the production of opioid peptides, for example, methionine and leucine enkephalins in in vitro and in vivo experiments. It was demonstrated that a pharmacological feed back reaction, the antinociceptive response, took place in the peripheral site of the primary afferent fibers.


Anorectal transplantation in human cadavers: mock anorectal allotransplantation.
Anorectal transplantation is a method for patients who have lost their anorectal function or suffer from congenital anorectal dysfunction to recover this function, and this has been investigated in experimental animal models using pigs, dogs, and rats. In this study, we performed an examination of anorectal transplantation in human cadavers to investigate whether this procedure could be performed in patients. A 77-year-old woman cadaver 1 was used as the donor and a 98-year-old woman cadaver 2 was used as the recipient. Initially, abdominoperineal excision of the anus and rectum (the Miles' operation) was performed on the recipient. Next, an anorectal graft containing the pudendal nerve (PN), pudendal artery (PA), pudendal vein (PV), inferior mesenteric artery (IMA), and inferior mesenteric vein (IMV) was harvested from the donor. The donor graft was transplanted into the recipient by intestinal anastomosis and microneurovascular anastomoses orthotopically. The diameters of the PN (right/left), IMA, and IMV were 2.5 mm/2.5 mm, 2.0 mm, and 1.5 mm, respectively, in cadaver 1, and 2.0 mm/2.0 mm, 2.0 mm, and 2.0 mm, respectively, in cadaver 2. The length of the PN, PA, PV, IMA, and IMV in the graft was sufficient to allow proper anastomosis. This preliminary study indicated that human anorectal transplantation was possible anatomically and technically. We anticipate our study will aid in the potential future application of this procedure to human patients.


Teachers' attitudes toward testing practices.
The purpose of this research was to investigate how teachers' attitudes toward testing practices affect the way teachers prepare and administer standardized tests. Classroom teachers (N = 186) from Georgia took the testing practices instrument developed to measure the three variables (behavior, attitude, and pressure) examined in this study. Attitudes were negatively correlated with behavior; teachers who felt that the testing practices were dishonest were less likely to engage in them. Pressure to increase standardized test scores was positively correlated with behavior; the greater the perceived pressure (subjective norms) to increase test scores, the greater the likelihood that teachers had engaged in more test preparation activities. The data also suggest that the amount of test preparation was greater in the lower grades than in the upper grades and that teachers in schools with more low-socioeconomic-status (SES) students tended to engage in more test preparation activities than their colleagues in higher SES schools.


Tunable Chiral Second-Order Nonlinear Optical Chromophores Based on Helquat Dications.
Fourteen new dipolar cations have been synthesized, containing methoxy or tertiary amino electron donor groups attached to helquat (Hq) acceptors. These Hq derivatives have been characterized as their TfO- salts by using various techniques including NMR and electronic absorption spectroscopies. UV-vis spectra show intense, relatively low energy absorptions with λmax ≈ 400-600 nm, attributable to intramolecular charge-transfer (ICT) excitations. Single-crystal X-ray structures have been solved for two of the chromophores, one as its PF6- salt, revealing centrosymmetric packing arrangements (space groups Pbca and P1̅). Molecular quadratic nonlinear optical (NLO) responses have been determined directly by using hyper-Rayleigh scattering (HRS) with a 800 nm laser, and indirectly via Stark (electroabsorption) spectroscopy for the low energy absorption bands. The obtained static first hyperpolarizabilities β0 range from moderate to large: (9-140) × 10-30 esu from HRS in MeCN and (44-580) × 10-30 esu from the Stark data in PrCN. The magnitude of β0 increases upon either extending the π-conjugation length or replacing a methoxy with a tertiary amino electron donor substituent. Density functional theory (DFT) and time-dependent DFT calculations on selected tertiary amino chromophores confirm that the low energy absorptions have ICT character. Relatively good agreement between the simulated and experimental UV-vis absorption spectra is achieved by using the CAM-B3LYP functional with the 6-311G(d) basis set. The βtot values predicted by using DFT at the same level of theory are large ((472-1443) × 10-30 esu in MeCN). Both the theoretical and experimental results show that para-conjugation between Hq and electron donor fragments is optimal, and enlarging the Hq unit is inconsequential with respect to the molecular quadratic NLO response.


ChemmineR: a compound mining framework for R.
Software applications for structural similarity searching and clustering of small molecules play an important role in drug discovery and chemical genomics. Here, we present the first open-source compound mining framework for the popular statistical programming environment R. The integration with a powerful statistical environment maximizes the flexibility, expandability and programmability of the provided analysis functions. We discuss the algorithms and compound mining utilities provided by the R package ChemmineR. It contains functions for structural similarity searching, clustering of compound libraries with a wide spectrum of classification algorithms and various utilities for managing complex compound data. It also offers a wide range of visualization functions for compound clusters and chemical structures. The package is well integrated with the online ChemMine environment and allows bidirectional communications between the two services. ChemmineR is freely available as an R package from the ChemMine project site: http://bioweb.ucr.edu/ChemMineV2/chemminer


Hereditary hemochromatosis. Detecting and correcting iron overload.
Hereditary hemochromatosis is a common genetic disorder. A large number of homozygous patients with early disease are asymptomatic, but with early diagnosis and treatment, their life expectancy is normal. The best screening test is determination of the percent saturation of transferrin or the transferrin index. Liver biopsy with measurement of hepatic iron concentration is required for definitive diagnosis. Once the diagnosis is confirmed, treatment by phlebotomy at regular intervals is straightforward.


Characterization of three myotonia-associated mutations of the CLCN1 chloride channel gene via heterologous expression.
Two novel mutations of the human CLCN1 chloride channel gene, c.592C>G (p.L198V) and c.2255A>G (p.K752R), are described, occurring coincidentally in the one myotonic patient. These individual mutations and a construct with both mutations in the one cDNA were transcribed and expressed in Xenopus oocytes where channel gating parameters were extracted from chloride currents recorded under voltage clamp. We found that the p.L198V mutation has its major effects on the common (or slow) gate of the chloride channel, as do other dominant ClC-1 mutations, and may therefore be causative of the patient's symptoms (when co-expressed with wild-type human ClC-1, the p.L198V mutation exerts a dominant negative effect on common gating) but the p.K752R mutation appears to be innocuous and may be a benign polymorphism. A third mutant, the recently described c.2795C>T (p.P932L), was expressed in HEK 293 cells. Despite the severity of the disease associated with this mutation, chloride currents in cells expressing p.P932L were not significantly different from those of cells expressing wild-type ClC-1.


Ultrastructure of the Ewing's sarcoma family of tumors.
Specimens of 47 tumors diagnosed by routine light microscopy as Ewing's sarcoma of bone, and 5 similar soft tissue tumors (extraskeletal Ewing's sarcomas), were examined by transmission electron microscopy. Immunohistochemical stains were performed on all the tumors, and pre-therapy and post-therapy specimens from 5 of the patients were compared. Cell and nuclear areas were assessed in 41 cases by cytomorphometry by using low-magnification electron micrographs. DNA ploidy was determined by static cytometry on 51 of the tumors. None of the methods revealed differences between the bone and soft tissue tumors. The ultrastructural spectrum extended imperceptibly from the typical forms to markedly irregular variants, and was much broader than could be anticipated from the light microscopy. Neural features were observed but they were not common. Comparison of the Ewing's sarcomas with a group of other small round cell tumors (rhabdomyosarcoma, neuroblastoma, small cell carcinoma) using the same techniques showed that they have similar cell and nuclear areas despite the obvious differences in their immunophenotypes and ultrastructure. The collective findings are in keeping with the currently favored view that Ewing's sarcoma and peripheral primitive neuro-ectodermal tumor are the extremes in a morphologic continuum within which neural differentiation ranges from absent to prominent.


Leptin levels, leptin receptor gene polymorphisms, and energy metabolism in women.
Resting metabolic rate (RMR) is mainly determined by fat-free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes. RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose-induced thermogenesis was measured over 3 hours. In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat-free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02). These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.


Adrenergic-cholinergic dual function in cultured sympathetic neurons of the rat.
Sympathetic principal neurons, dissociated from the superior cervical ganglia of newborn rats and put into culture, exhibit plasticity with respect to the choice between noradrenaline (norepinephrine) and acetylcholine as transmitter. The neurons shift from an initial, immature adrenergic state to a cholinergic state in certain culture conditions, e.g in co-culture with a variety of non-neuronal cells or after exposure to a medium conditioned by such cells. To study the transition directly, we have grown single neurons in "microcultures" with cardiac myocytes, which provide a sensitive assay for the transmitters secreted by the neurons. We have shown previously that during the transition from adrenergic to cholinergic status such neurons secrete both transmitters and have terminals of mixed fine structure (dual function). We describe here experiments in which identified neurons were serially assayed over periods of 9-45 days. Partial transitions were observed, always in the direction adrenergic to cholinergic function, and one complete transition was observed from apparently purely adrenergic function to dual function and then to apparently purely cholinergic function. We also report observation of adrenergic-cholinergic dual function, in preliminary single and serial assays, in sympathetic principal neurons from the superior cervical ganglia of adult rats.


Catalytic spectrum of the penicillin-binding protein 4 of Pseudomonas aeruginosa, a nexus for the induction of β-lactam antibiotic resistance.
Pseudomonas aeruginosa is an opportunistic Gram-negative bacterial pathogen. A primary contributor to its ability to resist β-lactam antibiotics is the expression, following detection of the β-lactam, of the AmpC β-lactamase. As AmpC expression is directly linked to the recycling of the peptidoglycan of the bacterial cell wall, an important question is the identity of the signaling molecule(s) in this relationship. One mechanism used by clinical strains to elevate AmpC expression is loss of function of penicillin-binding protein 4 (PBP4). As the mechanism of the β-lactams is PBP inactivation, this result implies that the loss of the catalytic function of PBP4 ultimately leads to induction of antibiotic resistance. PBP4 is a bifunctional enzyme having both dd-carboxypeptidase and endopeptidase activities. Substrates for both the dd-carboxypeptidase and the 4,3-endopeptidase activities were prepared by multistep synthesis, and their turnover competence with respect to PBP4 was evaluated. The endopeptidase activity is specific to hydrolysis of 4,3-cross-linked peptidoglycan. PBP4 catalyzes both reactions equally well. When P. aeruginosa is grown in the presence of a strong inducer of AmpC, the quantities of both the stem pentapeptide (the substrate for the dd-carboxypeptidase activity) and the 4,3-cross-linked peptidoglycan (the substrate for the 4,3-endopeptidase activity) increase. In the presence of β-lactam antibiotics these altered cell-wall segments enter into the muropeptide recycling pathway, the conduit connecting the sensing event in the periplasm and the unleashing of resistance mechanisms in the cytoplasm.


Extracapsular extension of pN2 lymph node metastases is not prognostically significant in surgically resected patients with non-small cell lung cancer.
In patients with non-small cell lung cancer (NSCLC) the pathologic lymph node status N2 is a heterogeneous entity, with different degrees of lymph node involvement representing different prognoses. It is speculated whether extra capsular nodal extension may help to define a subgroup with implications on long-term survival. We retrospectively identified 118 patients with non-small cell lung cancer (65 men, 53 women), who were treated between 2013 and 2018 and found to have pathologic N2 lymph node involvement. In all patients lung resection with systematic mediastinal and hilar lymph node dissection was performed with curative intent. In N2 lymph node metastases capsules of affected lymph nodes were examined microscopically as to whether extracapsular extension was present. 51 patients (43 %) had extracapsular extension (ENE). Most of these patients (n=35) only had ENE in a single lymph node (69 %). The overall 5-year survival rate was 24.6 % and progression-free survival rate 17.8 %. In the multivariate analysis OS was worse for patients with multiple affected pN2 stations, concurrent N1 metastases, increasing age, and larger tumor size. For the percentage of lymph nodes affected with ENE (of total examined) only a non-significant trend towards worse OS could be observed (p=0.06). Although we could not demonstrate significant prognostic differences between N2 extra capsular nodal involvement within our patient population, other analyses may yield different results. However, clinicians should continue performing thorough lymph nodes dissections in order to achieve local complete resection even in patients with extra capsular tumor spread.


Modelling noninvasively measured cerebral signals during a hypoxemia challenge: steps towards individualised modelling.
Noninvasive approaches to measuring cerebral circulation and metabolism are crucial to furthering our understanding of brain function. These approaches also have considerable potential for clinical use "at the bedside". However, a highly nontrivial task and precondition if such methods are to be used routinely is the robust physiological interpretation of the data. In this paper, we explore the ability of a previously developed model of brain circulation and metabolism to explain and predict quantitatively the responses of physiological signals. The five signals all noninvasively-measured during hypoxemia in healthy volunteers include four signals measured using near-infrared spectroscopy along with middle cerebral artery blood flow measured using transcranial Doppler flowmetry. We show that optimising the model using partial data from an individual can increase its predictive power thus aiding the interpretation of NIRS signals in individuals. At the same time such optimisation can also help refine model parametrisation and provide confidence intervals on model parameters. Discrepancies between model and data which persist despite model optimisation are used to flag up important questions concerning the underlying physiology, and the reliability and physiological meaning of the signals.


Psychological aspects of in vitro fertilization: a gender comparison.
This paper reports findings from a study investigating gender differences on the General Health Questionnaire (GHQ) and questionnaire ratings of the impact of in vitro fertilization (IVF), stressful aspects of treatment and reaction to a failed IVF attempt. The participants were 101 men and 117 women who were consecutive referrals to an IVF clinic. In line with previous research, women in comparison to men, rated IVF as having more impact upon emotional state. Scores on the GHQ were also consistent with greater emotional distress for women than men in relation to infertility diagnosis and treatment. With regard to the impact of IVF on the couple's sexual and marital relationship there were few gender differences, although both men and women felt that there was a greater likelihood that IVF had decreased the female partner's desire for sex. Both men and women agreed that a negative outcome and waiting for results were the most stressful aspects of IVF and, although the mean differences were again small, women reported experiencing more stress than men at a number of stages of treatment. Women were also more likely than men to endorse negative reactions in relation to IVF failure. The results are discussed in relation to counselling issues.


Scientific aesthetics: three steps forward.
Leder and Nadal (2014, this issue) examine the current state of scientific aesthetics through the lens of a prescient psychological model proposed 10 years ago. These retrospective points to several future directions of which I touch on three: the nature of aesthetic emotions, the time course of emotions in aesthetic episodes, and the relationship of art and evolution.


Symptoms, symptom distress and health-related quality of life in patients with polycythaemia vera or essential thrombocythaemia during treatment with interferon-alpha.
Sixteen patients with polycythaemia vera or essential thrombocythaemia were treated with interferon-alpha in order to normalize elevated platelets. Patients were followed for 6 months and the frequency and intensity of symptoms and side effects were recorded before and during the study period by the patients and by the doctor. Health-related quality of life was also assessed. The most frequently reported pretreatment symptoms were fatigue, headache and muscle pain. The intensity of fatigue initially increased during treatment and there was no relief of any of the three most frequent symptoms during the treatment period. Common interferon-related symptoms such as fever and chills were most frequently reported after one week. After one month of treatment, symptoms related to the gastrointestinal tract reached a peak. Two patients discontinued treatment during the study period. Another patient suffered severe depression after the study period when still on interferon. There was no difference between the frequency of symptoms recorded by the doctor and that reported by the patients.


New Insights toward Colorectal Cancer Chemotherapy Using Natural Bioactive Compounds.
Combination therapy consists in the simultaneous administration of a conventional chemotherapy drug (or sometimes, a radiotherapy protocol) together with one or more natural bioactives (usually from plant or fungal origin) of small molecular weight. This combination of anticancer drugs may be applied to cell cultures of tumor cells, or to an animal model for a cancer type (or its xenograft), or to a clinical trial in patients. In this review, we summarize current knowledge describing diverse synergistic effects on colorectal cancer cell cultures, animal models, and clinical trials of various natural bioactives (stilbenes, flavonoids, terpenes, curcumin, and other structural families), which may be important with respect to diminish final doses of the chemotherapy drug, although maintaining its biological effect. This is important as these approaches may help reduce side effects in patients under conventional chemotherapy. Also, these molecules may exerts their synergistic effects via different cell cycle pathways, including different ones to those responsible of resistance phenotypes: transcription factors, membrane receptors, adhesion and structural molecules, cell cycle regulatory components, and apoptosis pathways.


Multiple sclerosis and the TNFRSF1A R92Q mutation: clinical characteristics of 21 cases.
Tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited autoinflammatory disorder resulting from mutations in the TNFRSF1A gene, which encodes the p55 receptor for tumor necrosis factor alpha. We recently identified the R92Q mutation encoded by exon 4 in six patients with multiple sclerosis (MS) who reported at least two symptoms suggestive of TRAPS. The current study presents the characteristics of a larger cohort of MS patients carrying this mutation. Clinical and laboratory parameters, including human leukocyte antigen (HLA)-DR15 status, were evaluated, and genetic testing was performed. Whenever possible, family members were also invited for interview and mutation analysis. Twenty TNFRSF1A R92Q carriers had MS according to the McDonald criteria, and 1 had clinically isolated syndrome. The majority of patients had typical onset and features of MS. Nine patients carried an HLA-DR15 haplotype. All individuals showed TRAPS-compatible symptoms, which consisted mainly of myalgias, arthralgias, headache, severe fatigue, and skin rashes; were milder than usually described; and appeared mainly in adulthood. Most patients experienced severe side effects during immunomodulatory therapy for MS. Seventeen family members carried the identical mutation, and 15 of them reported symptoms suggestive of TRAPS. In most cases with multiple sclerosis (MS) and coexisting tumor necrosis factor receptor 1-associated periodic syndrome (TRAPS), features of MS were quite typical, whereas TRAPS presented mostly without the fever episodes observed in childhood. The penetrance of the R92Q mutation in affected family members was higher than reported. We recommend careful observation of MS patients with coexisting TRAPS with regard to unexpected side effects of immunomodulatory therapies.


Solid-State NMR Study of the Cicada Wing.
Wings of flying insects are part of the cuticle which forms the exoskeleton. The primary molecular components of cuticle are protein, chitin, and lipid. How these components interact with one another to form the exoskeleton is not completely understood. The difficulty in characterizing the cuticle arises because it is insoluble and noncrystalline. These properties severely limit the experimental tools that can be used for molecular characterization. Solid-state nuclear magnetic resonance experiments have been used in the past to characterize the exoskeleton of beetles and have found that chitin and protein make comparable contributions to the molecular matrix. However, little work has been done to characterize the components of the wing, which includes vein and membrane. In this work, solid-state NMR was used to characterize the wing of the 17-year cycle cicada (Magicicada cassini) that appeared in northern West Virginia during the summer of 2016. The NMR results show noticeable differences between the molecular components of the vein and membrane.


Micromarkers: miRNAs in cancer diagnosis and prognosis.
Molecular diagnostics in cancer should provide the highest specificity and sensitivity in classification, prognostic stratification and early detection. miRNAs could contribute to hitting the mark, or at least to come nearer, by virtue of their cancer-specific expression and stability. Indeed, different to other RNA classes, miRNAs can be detected and quantified not only in frozen tissues, but also in formalin-fixed paraffin-embedded tissues, as well as serum/plasma samples. Thus, miRNA studies have quickly moved from research on the molecular basis of cancer to areas of clinical application. This review summarizes the potential role of miRNAs as molecular markers for cancer classification, prognostic stratification and drug-response prediction. It also summarizes their potential as circulating markers and cancer-predisposing genes. If we consider that studies on miRNAs in cancer therapy have already given important contributions, miRNAs have an impact in all cancer areas. Whether this will translate into clinical applications is still too early to say. However, in the diagnostic field, miRNAs may already represent an improvement over presently available approaches; for example, their expression profile is effective in the identification of tissue of origin of metastasis. In addition, circulating miRNAs are expected to provide improved specificity and/or sensitivity over presently available markers.


Analysis of polypeptide expression in benign and malignant human breast lesions.
Results of two-dimensional electrophoresis (2-DE) analyses of human breast carcinoma are described. Tumor cells were extracted and purified from breast carcinomas with different proliferative indeces and degrees of genomic stability. Cells purified from fibroadenoma tissue served as controls for benign cells. The following results were observed: (i) Analysis of samples from different areas of the same tumor showed a high degree of similarity in the pattern of polypeptide expression. Similarly, analysis of two tumors and their metastases revealed similar 2-DE profiles. (ii) In contrast, large variations were observed between different lesions with comparable histological characteristics. Larger differences in polypeptide expression were observed between potentially highly malignant carcinomas compared to comparisons of less malignant lesions. These differences were in the same order of magnitude as those observed comparing a breast carcinoma to a lung carcinoma. (iii) The levels of all cytokeratin forms resolved (CK7, CK8, CK15, and CK18) were significantly lower in carcinomas compared to fibroadenomas. (iv) The levels of high molecular weight tropomyosins (1-3) were lower in carcinomas compared to fibroadenomas. The expression of tropomyosin-1 was found to be 1.7-fold higher in primary tumors with metastatic spread to axillar lymph nodes compared to primary tumors with no evidence of metastasis (p < 0.05). (v) The expression of proliferating cell nuclear antigen (PCNA) and some members of the stress protein family (pHSP60, HSP90, and calreticulin) were higher in carcinomas. We conclude that malignant progression of breast carcinomas results in large heterogeneity in polypeptide expression between different tumors, but that some common themes such as decreased expression of cytokeratin and tropomyosin polypeptides can be discerned.


[A rare hyperthyroid syndrome].
The exophthalmos, myxedema, acropachy (EMA) syndrome is a rare extrathyroid syndrome, interesting about 1% of the patients affected by extrathyroid complications of Graves' disease. The ratio female/male is 3.4:1 and this case report is very rare. The patient, a 52-year-old man, presented a serious ophthalmopathy with pretibial myxedema, acropachy with joint pain. The triad manifested itself after some ophthalmopathy treatments, i.e. total thyroidectomy, steroidal retrobulbar therapy and radiotherapy. The patient received T4 therapy and the thyroid function status was normal. The appearance of the EMA syndrome coincided with the fast worsening of the ophthalmopathy. This case report confirms previous observations regarding the chronological sequence of presentations of extrathyroidal manifestations of autoimmune thyroid disease. The thyroid disease develops first, followed by ophthalmopathy, then dermopathy, and finally, acropachy. The thyroid acropachy shows some differences between pulmonary and paraneoplastic osteoarthropathy, due to the presence of thyroid dermopathy and ophtalmopathy (EMA) and to the different subperiosteal proliferation. Steroidal therapy improved the ophthalmopathy, the pretibial myxedema and the acropachy. The improvement obtained has been faster as regards the exophtalmos and myxedema, slower as regards the acropachy, but of the same importance. In conclusion, acropachy is the latest manifestation of EMA and coincides with the worsening of ophthalmopathy. The traditional steroidal therapy is effective to improve the syndrome.


Use of base-modified duplex-stabilizing deoxynucleoside 5'-triphosphates to enhance the hybridization properties of primers and probes in detection polymerase chain reaction.
Several base-modified duplex-stabilizing deoxyribonucleoside 5'-triphosphates (dNTPs) have been evaluated as agents for enhancing the hybridization properties of primers and probes in real-time polymerase chain reaction (PCR). It was shown that pyrimidines substituted at the 5-position with bromine or iodine atoms and methyl or propynyl groups are incorporated into PCR amplicons by Taq DNA polymerase as efficiently as natural dNTPs. The dNTP of 2-aminoadenosine was incorporated somewhat less efficiently than dATP but still supported PCR. Incorporation of these modified nucleotides into the amplified DNA represents a simple and inexpensive way to stabilize duplexes of primers and probes and is particularly effective in improving the amplification and detection of A/T-rich sequences. This technology permits the use of higher PCR annealing temperatures or alternatively a reduction in the length of the oligonucleotide components. Examples of successful application in TaqMan and Scorpion real-time detection assays are provided. Limits of the approach are identified and discussed. For example, application of the 5-bromo and 5-iodo derivatives may be limited to relatively G/C-rich DNA targets and, in particular, to those lacking long runs of adenylate and/or thymidylate. Simultaneous use of base-modified analogues of dATP and dTTP should be avoided in PCR due to "overstabilization" of the amplicon.


Systematic Review of Exercise for Caregiver-Care Recipient Dyads: What Is Best for Spousal Caregivers-Exercising Together or Not at All?
Though exercise for care recipients receives considerable emphasis, few dyadic studies focus on caregivers. This systematic review identified dyadic exercise interventions, which measured outcomes for older adult caregivers. Studies that met inclusion criteria were examined to better understand whether caregivers derived greater benefit from exercising with care recipients, or not exercising at all. PRISMA guidelines were followed to identify quantitative studies of dyadic exercise interventions in which caregivers enrolled with care recipients, and either coparticipated in exercise; or while their care recipients exercised independently, caregivers received a separate, nonexercise intervention or usual care (UC). To be included, studies had to measure physical or psychosocial outcomes for caregivers. Study quality was assessed via the Downs and Black checklist. Eleven studies met inclusion criteria. In six, the dyad exercised; in five, care recipients exercised while caregivers received a separate program, or UC. Results suggest that caregivers may improve both psychosocial and physical health when exercising together with care recipients. Caregivers who did not exercise but received a separate, nonexercise intervention, such as support, education, or respite, showed psychosocial benefits. Those who received UC were less likely to derive physical or psychosocial benefits. Included studies were fair to good quality with moderate to high risk of bias. Often examined secondarily, caregivers are overlooked for participation in interventions with care recipients. This analysis suggests that caregivers may benefit from dyadic interventions in which they either exercise together with their care recipients or receive a separate nonexercise intervention or respite.


Determination of Adsorption Equations for Chloro Derivatives of Aniline on Halloysite Adsorbents Using Inverse Liquid Chromatography.
Chloro derivatives of aniline are commonly used in the production of dyes, pharmaceuticals, and agricultural agents. They are toxic compounds with a large accumulation ability and low natural biodegradability. Halloysite is known as an efficient adsorbent of toxic compounds, such as phenols or herbicides, from wastewater. Inverse LC was applied to measure the adsorption of aniline and 2-chloroaniline (2-CA), 3-chloroaniline (3-CA), and 4-chloroaniline (4-CA) on halloysite adsorbents. A peak division (PD) method was used to determine a Langmuir equation in accordance with the adsorption measurement results. The values of adsorption equilibrium constants and enthalpy were determined and compared by breakthrough curve and PD methods. The physical sense of the calculated adsorption enthalpy values was checked by applying Boudart's entropy criteria. Of note, adsorption enthalpy values for halloysite adsorbents decreased in the following order: aniline > 4-CA > 2-CA > 3-CA.


Pharmacological benefits of Acacia against metabolic diseases: intestinal-level bioactivities and favorable modulation of gut microbiota.
Obesity-associated chronic metabolic disease is a leading contributor to mortality globally. Plants belonging to the genera Acacia are routinely used for the treatment of diverse metabolic diseases under different ethnomedicinal practices around the globe. The current review centres around the pharmacological evidence of intestinal-level mechanisms for metabolic health benefits by Acacia spp. Acacia spp. increase the proportions of gut commensals (Bifidobacterium and Lactobacillus) and reduces the population of opportunistic pathobionts (Escherichia coli and Clostridium). Acacia gum that is rich in fibre, can also be a source of prebiotics to improve gut health. The intestinal-level anti-inflammatory activities of Acacia are likely to contribute to improvements in gut barrier function that would prevent gut-to-systemic endotoxin translocation and limit "low-grade" inflammation associated with metabolic diseases. This comprehensive review for the first time has emphasised the intestinal-level benefits of Acacia spp. which could be instrumental in limiting the burden of metabolic disease.


Disparities in Athletic Trainer Staffing in Secondary School Sport: Implications for Concussion Identification.
First, to assess whether teams at schools with an athletic trainer (AT) on staff had a higher number of diagnosed concussions than teams without medical personnel present. Second, to assess whether the variability in employment of a certified AT by Washington state high schools is patterned by socioeconomic and demographic characteristics. Cross-sectional survey. Washington state public high schools. Stratified random sample of football and soccer coaches (n = 270 teams, 144 schools). Presence of an AT and school characteristics (percentage of students qualifying for free or reduced price lunch, rural location, enrollment). Football and boys' soccer teams at schools with an AT had a significantly greater number of athletes with diagnosed concussions compared to teams at schools without an AT (P < 0.05). There was no difference in number of athletes with diagnosed concussions by AT staffing for girls' soccer. Schools with an AT on staff were significantly more likely than schools without an AT to be in an urban location (P < 0.001), to have an enrollment of 1000 students or more (P < 0.001), and to have a smaller proportion of students eligible for school lunch (P = 0.005). The present study provides empirical support for the benefit of ATs in diagnosing concussions in high school sport and underscores the challenges to AT staffing in lower resource settings. These findings cause us to critically reflect on the threshold for medical oversight in contact and collision sport from the perspective of risk prevention, and the extent to which disparities in this medical oversight are acceptable in the public school setting. Strategies for increasing AT staffing in high school sports settings should be explored given their demonstrated benefit in diagnosing concussions.


[Pancreatic pseudocyst. Review of 22 cases].
The management of 22 children with pseudocyst of the pancreas presenting over a 15-year period at three pediatric Hospitals is reviewed. The mean age of patients was 7 years being more common in boys (17:5). Ninety one per cent were due to trauma, while in 9% the cause was unknown. Vomiting (81.8%), abdominal pain (77.2%), a mass (72.7%), fever (31.8%) and anorexia (31.8%) were the most frequent findings. The diagnosis was confirmed by finding hyperamylasemia (elevated in 72.7% of cases), by barium meal and ultrasound. Operative treatment included external drainage in 4 children, cystgastrostomy in 9, cystjejunostomy in 6, and excision in 1. One patient was successfully managed nonoperatively and another had spontaneous gastric drainage. There were no deaths or significative complications in this series.


Comparison of immunofluorescence, Western blotting, and cross-adsorption assays for diagnosis of African tick bite fever.
In testing paired serum samples from 40 consecutive cases of African tick bite fever, we detected diagnostic antibodies against spotted fever group rickettsiae in 45% of the patients by immunofluorescence assay (IFA) and in 100% of the patients by Western blotting (WB) (P < 0.01). A specific diagnosis of Rickettsia africae infection could be established in 15% of the patients by IFA and in 73% of the patients by a combination of WB and cross-adsorption assays (P < 0.01).


Salient object detection using coarse-to-fine processing.
In this paper, we propose a salient object detection algorithm that considers both background and foreground cues. It integrates both coarse salient region extraction and a top-down background weight map measure via boundary label propagation into a unified optimization framework to acquire a refined salient map. The coarse saliency map is additionally fused by three prior components: a local contrast map with greater alignment to physiological law, a global focus prior map, and a global color prior map. During the formation of the background weight map, we first construct an affinity matrix and select nodes existing on the border as labels to represent the background. Then we perform a propagation to generate the regional background weight map. Our proposed model was verified on four benchmark datasets, and the experimental results demonstrate that our method has excellent performance.


The Role of Beetroot Extract in Overcoming Chemoresistance of Neoadjuvant Adriamycin Cyclophosphamide Regimen by Targeting Immune Response in Tumor Microenvironment: A Preclinical Study in Mammary Adenocarcinoma Rats.
This study aims to determine the role of beetroot extract in overcoming the chemoresistance of Neoadjuvant Adriamycin Cyclophosphamide (NAC) regimens with a target immune response in the tumour microenvironment at the pre-clinical stage. This study was conducted on rats with 7,12-Dimethyl Benz (α) Anthracene (DMBA) induced mammary adenocarcinoma. Adriamycin Cyclophosphamide was given in 4 cycles, whereas beetroot extract was administered three times each cycle. Observations of CD8 T cells and Myeloid Derivative Suppressive Cells (MDSC) expression levels and pathological responses were carried out on tumour tissue taken at the end of the observation. Supplementation of beetroot extract to NAC could significantly increase CD8 T cells and decrease MDSC in the tumour microenvironment. The addition of beetroot extract gave a better pathological response. Beetroot extract enhances the immune response in the tumor microenvironment so that it has the potential to overcome chemoresistance in NAC.<br />.


Phosphine-Catalyzed α-Umpolung-Aldol Reaction for the Synthesis of Benzo[ b]azapin-3-ones.
A novel phosphine-catalyzed intermolecular cyclization between 2-sulfonamidobenzaldehyes and ynones is reported. This methodology serves as a conduit for the construction of benzo[ b]azepin-3-ones in good to excellent yields under mild conditions. The resulting 2-benzylidene moieties are formed exclusively in the E-configuration. Mechanistically, this unusual annulation occurs through a phosphine-catalyzed α-umpolung addition, followed by an aldol reaction. One of the benzo[ b]azepin-3-one products was converted to the core structure of 3-amino-[ a]benzazepin-2-one-1-alkanoic acids, many of which function as angiotensin-converting enzyme inhibitors.


Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis.
MicroRNAs (miRNAs) are present in human plasma and known as a non-invasive biomarker for cancer detection. Our study was designed to identify plasma miRNAs specific for rheumatoid arthritis (RA) by a comprehensive array approach. We performed a systematic, array-based miRNA analysis on plasma samples from three RA patients and three healthy controls (HCs). Plasma miRNAs with more than four times change or with significant (P<0.05) change in expression, or detectable only in RA plasma, were confirmed with plasma from eight RA patients and eight HCs using real-time quantitative PCR. Consistently detectable miRNAs that were significantly different between RA patients and HCs were chosen for further validation with 102 RA patients and 104 HCs. The area under curves (AUC) were calculated after plotting the receiver operating characteristic (ROC) curves. To determine if these miRNAs are specific for RA, the concentrations of these miRNAs were analyzed in 24 patients with osteoarthritis (OA), and 11 patients with systemic lupus erythematosus (SLE). The array analysis and the subsequent confirmation in larger patient cohort identified significant alterations in plasma levels of seven miRNAs. The highest AUC was found for miR-125a-5p, followed in order by miR-24 and miR-26a. Multivariable logistic regression analysis showed that miR-24, miR-30a-5p, and miR-125a-5p were crucial factors for making detection model of RA and provided a formula for Estimated Probability of RA by plasma MiRNA (ePRAM), employing miR-24, miR-30a-5p and miR-125a-5p, which showed increased diagnostic accuracy (AUC: 0.89). The level of miR-24, miR-125a-5p, and ePRAM in OA and SLE patients were lower than that in RA. There was no significant difference in detection for anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients. These results suggest that the plasma concentrations of miR-24 and miR-125a-5p, and ePRAM are potential diagnostic markers of RA even if patients were ACPA-negative.


Mechanisms of tubulo-interstitial injury in progressive renal diseases.
A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point out that the systemic hypertension which accompanies most forms of chronic renal disease could impact adversely upon the vasodilated interstitial vascular compartment which, together with a component of primary capillary injury related to the disease process, could cause progressive obliteration of particular capillaries. This would initiate a process of chronic tubular ischaemia ultimately leading to tubular atrophy. Since tubular cells have been shown to produce an array of cytokines and growth factors which modulate fibroblast proliferation, extracellular matrix production and chemo-attracts for infiltrating cells, it is further proposed that it is the tubular injury which initiates the deleterious cascade of events. Tubular injury may be aggravated by the filtration of potentially 'noxious' molecules through the diseased glomerulus and by infiltrating cells. As the vascular bed into which glomerular blood flow empties is progressively obliterated, glomerular function declines and renal failure advances in relation to the degree of tubulo-interstitial fibrosis.


The complete chloroplast genome sequence of Anthurium andraeanum Linden (Araceae; Pothoideae).
The chloroplast genome of Anthurium andraeanum Linden 1877 was assembled and analyzed in this study. The genome size is 162,560 bp, of which contains a large single-copy (LSC) region with 88,814 bp, a small single-copy (SSC) region with 22,856 bp, and two inverted repeat regions (IRA and IRB) with 25,445 bp, respectively. The plastome contains 124 genes, including 80 protein-coding genes, 37 tRNAs, six rRNAs and one pseudogene. Phylogenetic analysis indicated that A. andraeanum is a member of Pothoideae and sister to A. huixtlense.


Time-dependent inhibition of glucose 6-phosphatase by 3-mercaptopicolinic acid.
3-Mercaptopicolinate (3-MP) inhibits D-glucose-6-phosphate (G6P) phosphohydrolase activity of the glucose-6-phosphatase system (Bode et al. (1993) Biochem. Cell Biol. 71, 113-121). We therefore attempted to maximize the inhibition by varying the physical state of microsomes, the concentration of 3-MP, and the time of preliminary incubation of 3-MP with the enzyme. The inhibition was irreversible and time- and inhibitor-concentration-dependent, with G6P phosphohydrolase activity of intact rat liver microsomes, but there was no inhibition with detergent-treated microsomes. The effectiveness of 3-MP as a time-dependent inhibitor of glucose 6-phosphatase was demonstrated in situ by measuring glycogenolysis in isolated, perfused livers from fed rats. We first exposed the livers to 2 mM 3-MP for 40 min, and then assessed the inhibitory effects on glycogenolysis. It was lowered by 50%. These observations establish that 3-MP at the mM level may be useful as an experimental probe in the study of the role(s) of G6P in the regulation of glycogenolysis as well as glycogenesis. Further, they validate the use of much lower (microM) concentrations of 3-MP to block gluconeogenesis (at the phosphoenolpyruvate carboxykinase step) without interfering with glucose 6-phosphatase. We also explored the mechanism of 3-MP inhibition. The time-dependent inhibition of carbamoyl-phosphate:glucose phosphotransferase activity with microsomes incubated with 1 mM 3-MP for 60 or 90 min and then assayed with 1 mM carbamoyl phosphate and 180 mM glucose was modest compared with inhibition of G6P phosphohydrolase. When G6P production by carbamoyl-phosphate:glucose phosphotransferase was reduced by decreasing glucose concentration to 60 mM, no inhibition by 3-MP was discernible. There was no inhibition of inorganic pyrophosphatase activity. These studies support the model of time-dependent, irreversible reaction of 3-MP with the G6P translocase component of the glucose-6-phosphatase system.


Nighttime Driving in Older Adults: Effects of Glare and Association With Mesopic Visual Function.
To examine the associations between nighttime driving performance of older drivers and photopic, mesopic, and glare-based tests of visual function. Participants included 26 older drivers (71.8 ± 6.3 years), with minimal or no eye disease, but who reported vision-related nighttime driving difficulties. Nighttime driving performance was assessed on a closed-road circuit, which included intermittent glare. An overall driving performance score was calculated based on detection of signs, pedestrians, wooden animals and road markings, lane-keeping, and avoidance of low contrast hazards. Visual function tests included photopic and mesopic visual acuity (VA) and contrast sensitivity (CS). Tests of glare (Berkeley Glare and Aston Halometer) and mesopic motion sensitivity were also assessed. Regression analyses were used to explore the associations between these vision measures and nighttime driving performance. The overall driving performance score was significantly reduced by intermittent glare (P = 0.002); notably, pedestrian detection decreased by 38% in the presence of intermittent glare (P < 0.001). Overall driving scores were most strongly associated with motion sensitivity (P = 0.001) and mesopic high contrast VA (P = 0.002), rather than photopic or glare-based tests. Motion sensitivity accounted for more than twice the variation in driving performance compared to photopic high contrast VA (29% vs. 14%). Glare reduced several aspects of nighttime driving performance. Mesopic tests of visual function, including motion sensitivity and mesopic high contrast VA, were more strongly associated with nighttime driving performance than photopic high-contrast VA. These results highlight the potential importance of nonstandard vision tests for assessing older drivers' visual capacity to drive at night.


Caveolin-1(-/-)- and caveolin-2(-/-)-deficient mice both display numerous skeletal muscle abnormalities, with tubular aggregate formation.
Here, we examine the role of "non-muscle" caveolins (Cav-1 and Cav-2) in skeletal muscle biology. Our results indicate that skeletal muscle fibers from male Cav-1(-/-) and Cav-2(-/-) mice show striking abnormalities, such as tubular aggregates, mitochondrial proliferation/aggregation, and increased numbers of M-cadherin-positive satellite cells. Notably, these skeletal muscle defects were more pronounced with increasing age. Because Cav-2-deficient mice displayed normal expression levels of Cav-1, whereas Cav-1-null mice exhibited an almost complete deficiency in Cav-2, these skeletal muscle abnormalities seem to be due to loss of Cav-2. Thus, Cav-2(-/-) mice represent a novel animal model-and the first genetically well-defined mouse model-that can be used to study the pathogenesis of tubular aggregate formation, which remains a poorly understood age-related skeletal muscle abnormality. Finally, because Cav-1 and Cav-2 were not expressed within mature skeletal myofibers, our results indicate that development of these abnormalities probably originates in stem/precursor cells, such as satellite cells or myoblasts. Consistent with this hypothesis, skeletal muscle isolated from male Cav-3(-/-) mice did not show any of these abnormalities. As such, this is the first study linking stem cells with the genesis of these intriguing muscle defects.


Antifungal Potential of Copper(II), Manganese(II) and Silver(I) 1,10-Phenanthroline Chelates Against Multidrug-Resistant Fungal Species Forming the Candida haemulonii Complex: Impact on the Planktonic and Biofilm Lifestyles.
Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii, which form the C. haemulonii complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti-Candida potential of metal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of C. haemulonii species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of each C. haemulonii species complex were used and the effect of the metal chelates on viability was determined utilizing the CLSI standard protocol and on biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was evaluated by the MTT assay, employing lung epithelial cells. The majority of the metal chelates were capable of interfering with the viability of planktonic-growing cells of all the fungal isolates. The silver complexes were the most effective drugs (overall geometric mean of the minimum inhibitory concentration (GM-MIC) ranged from 0.26 to 2.16 μM), followed by the manganese (overall GM-MIC ranged from 0.87 to 10.71 μM) and copper (overall GM-MIC ranged from 3.37 to >72 μM) chelates. The manganese chelates (CC50 values ranged from 234.51 to >512 μM) were the least toxic to the mammalian cells, followed by the silver (CC50 values ranged from 2.07 to 13.63 μM) and copper (CC50 values ranged from 0.53 to 3.86 μM) compounds. When tested against mature biofilms, the chelates were less active, with MICs ranging from 2- to 33-fold higher levels when compared to the planktonic MIC counterparts. Importantly, manganese(II), copper(II), and silver(I) phen chelates are relatively cheap and easy to synthesize and they offer significant antifungal chemotherapeutic potential for the treatment of highly resistant pathogens.


Controlled synthesis and characterization of the elusive thiolated Ag55 cluster.
A stable, Ag55 cluster protected with 4-(tert-butyl)benzyl mercaptan (BBSH) was synthesized which exhibits two prominent absorption bands with maxima at 2.25 and 2.81 eV. A molecular ion peak at m/z 11 500 ± 20 in matrix assisted laser desorption ionization mass spectrum (MALDI MS), assigned to Ag55(BBS)31 was observed. Electrospray ionization (ESI MS) shows a prominent trication along with higher charged species. An analogous Ag55(PET)31 (PET = 2-phenylethanethiol, in the thiolate form) was also synthesized under optimized conditions which proves the amenability of this cluster and the synthetic methodology to other ligands.