Treatment of Lower Extremity Fractures in Chronic Spinal Cord Injury: A Systematic Review of the Literature.
To review the literature regarding outcomes of surgical and nonsurgical management of lower extremity (LE) fractures in chronic spinal cord injury (SCI). TYPE: Systematic review. Medline (PubMed), Embase, Cochrane Database of Systemic Reviews, Cochrane Central, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, International Clinical Trials Registry Platform, and International Standard Randomized Controlled Trials were searched from January 1, 1966, to March 1, 2019. Search was restricted to English language and adults (age ≥ 18 yr). Titles and abstracts were reviewed for relevance to study topics for inclusion. Case reports, reviews, non-SCI population studies, and studies examining fractures at the time of acute SCI were excluded. References of included articles from the original search and task force and external submissions yielded two additional articles that were included in the review after voting by task force members. Data extraction was performed by four task force members using a data extraction form, glossary, and instructions created in Microsoft Excel. Quality assessment was performed by three methodologists using prespecified criteria. Twenty-three articles were included. Use of surgery to treat LE fractures in chronic SCI has increased, though nonoperative management was still more frequently reported. Regardless of type of management, amputations, nonunion/malunion, and pressure injuries were among the most commonly reported complications. Functional and quality of life outcomes were less frequently reported. There is insufficient evidence to support operative versus nonoperative management as best practice for management of LE fracture of SCI. Existing literature was limited by small sample sizes, lack of randomization or matched study designs, significant heterogeneity in populations and treatment strategies studied, and variability in defining and reporting outcomes of interest. The field would benefit from future research to address study design issues and standardization of outcome reporting to facilitate comparison of outcomes of operative versus nonoperative management.


YBa2Cu3O7 nano superconducting quantum interference devices on MgO bicrystal substrates.
We report on nanopatterned YBa2Cu3O7-δ (YBCO) direct current superconducting quantum interference devices (SQUIDs) based on grain boundary Josephson junctions. The nanoSQUIDs are fabricated by epitaxial growth of 120 nm-thick films of the high-transition temperature cuprate superconductor YBCO via pulsed laser deposition on MgO bicrystal substrates with 24° misorientation angle, followed by sputtering of dAu = 65 nm thick Au. Nanopatterning is performed by Ga focused ion beam (FIB) milling. The SQUID performance is comparable to devices on SrTiO3 (STO), as demonstrated by electric transport and noise measurements at 4.2 K. MgO has orders of magnitude smaller dielectric permittivity than STO; i.e., one may avoid Au as a resistively shunting layer to reduce the intrinsic thermal flux noise of the nanoSQUIDs. However, we find that the Au layer is important for avoiding degradation during FIB milling. Hence, we compare devices with different dAu produced by thinning the Au layer via Ar ion milling after FIB patterning. We find that the reduction of dAu yields an increase in junction resistance, however at the expense of a reduction of the critical current and increase in SQUID inductance. This results in an estimated thermal flux noise that is almost independent of dAu. However, for two devices on MgO with 65 nm-thick Au, we find an order of magnitude lower low-frequency excess noise as compared to nanoSQUIDs on STO or those on MgO with reduced dAu. For one of those devices we obtain with bias-reversal readout ultra-low flux noise of ∼175 nΦ0 Hz-1/2 down to ∼10 Hz.


Numerical classification of sporoactinomycetes containing meso-diaminopimelic acid in the cell wall.
One hundred and thirty actinomycetes representing 19 genera and 50 species were compared in a numerical phenetic survey using 108 unit characters. Data were examined using the simple matching (SSM), Jaccard (SJ) and pattern (DP) coefficients and clustering was achieved using both the single and unweighted pair group average algorithms. Cluster composition was barely affected by the statistics used or by test error, estimated at 2.1%. Over 80% of the strains were assigned to 2 clusters containing between two and 25 organisms. Most of the clusters were distinct and homogeneous though two were divided into subclusters. Some of the clusters and subclusters were equated with the established taxa Actinomadura madurae, Actinomadura pelletieri, Dermatophilus congolensis, Geodermatophilus obscurus, Microbispora spp., Micromonospora spp., Micropolyspora brevicatena, Micropolyspora faeni, Nocardia spp., Nocardiopsis (Actinomadura) dassonvillei, Planobispora spp., Planomonospora spp., Saccharomonospora viridis, Streptomyces somaliensis, Thermoactinomyces candidus, Thermoactinomyces dichotomica, Thermoactinomyces sacchari, Thermoactinomyces vulgaris and "Thermomonospora fusca'. The numerical data, together with results from previous chemical and genetical studies, provide sufficient evidence for the transfer of Micropolyspora brevicatena to Nocardia as Nocardia brevicatena comb. nov.


The Role of Mast Cells in Bone Metabolism and Bone Disorders.
Mast cells (MCs) are important sensor and effector cells of the immune system that are involved in many physiological and pathological conditions. Increasing evidence suggests that they also play an important role in bone metabolism and bone disorders. MCs are located in the bone marrow and secrete a wide spectrum of mediators, which can be rapidly released upon activation of mature MCs following their differentiation in mucosal or connective tissues. Many of these mediators can exert osteocatabolic effects by promoting osteoclast formation [e.g., histamine, tumor necrosis factor (TNF), interleukin-6 (IL-6)] and/or by inhibiting osteoblast activity (e.g., IL-1, TNF). By contrast, MCs could potentially act in an osteoprotective manner by stimulating osteoblasts (e.g., transforming growth factor-β) or reducing osteoclastogenesis (e.g., IL-12, interferon-γ). Experimental studies investigating MC functions in physiological bone turnover using MC-deficient mouse lines give contradictory results, reporting delayed or increased bone turnover or no influence depending on the mouse model used. By contrast, the involvement of MCs in various pathological conditions affecting bone is evident. MCs may contribute to the pathogenesis of primary and secondary osteoporosis as well as inflammatory disorders, including rheumatoid arthritis and osteoarthritis, because increased numbers of MCs were found in patients suffering from these diseases. The clinical observations could be largely confirmed in experimental studies using MC-deficient mouse models, which also provide mechanistic insights. MCs also regulate bone healing after fracture by influencing the inflammatory response toward the fracture, vascularization, bone formation, and callus remodeling by osteoclasts. This review summarizes the current view and understanding of the role of MCs on bone in both physiological and pathological conditions.


Factors affecting the ongoing pregnancy rate in women with repeated implantation failure undergoing an endometrial receptivity array.
In this retrospective study, we analyzed factors influencing the ongoing pregnancy rate (PR) in women with repeated implantation failure (RIF) undergoing embryo transfer with endometrial receptivity array (ERA). Eighty-three consecutive personalized embryo transfers (pETs) with ERA, from 54 women with RIF, were selected from June 2020 to April 2022. Vitrified blastocyst transfer was timed based on ERA results. The ongoing PR per pET was 33.7%. Using ERA, the endometrium was identified as pre-receptive in 26 cycles, early receptive in 25 cycles, receptive in 31 cycles, and late receptive in one cycle. With cycles categorized into three receptivity phases (pre-receptive, early receptive, or receptive), no significant differences were found in the clinical PR (27.3%, 55.6%, and 40%, respectively) or ongoing PR (9.1%, 55.6%, and 40%, respectively) after a single blastocyst transfer. Similarly, no significant differences were observed in the clinical PR or ongoing PR after the transfer of two or more blastocysts. Among women with ongoing pregnancy relative to those without, age at first pET was significantly lower (35 years vs. 39 years, p=0.001), while blastocyst score (23 vs. 18, p=0.012) and the proportion of blastocyst scores >18 (71.4% vs. 38.9%, p=0.005) were significantly higher. In multiple logistic regression analysis, the woman's age (odds ratio [OR], 0.814; 95% confidence interval [CI], 0.706 to 0.940; p=0.005) and blastocyst score >18 (OR, 3.052; 95% CI, 1.075 to 8.665; p=0.036) were identified as significant factors influencing ongoing pregnancy. In pET with ERA, ongoing pregnancy was closely associated with woman's age and blastocyst quality.


Paget's disease of the scrotum: a case report and review of current literature.
A case of extramammary Paget's disease of the scrotum is presented. A patient was diagnosed by biopsy and treated for squamous cell carcinoma in situ of the scrotum. Following surgery, the tumor was found to be extramammary Paget's disease. Management consisted of treatment with 5-fluorouracil followed by wide local excision. The current literature is reviewed briefly.


Ultrasonographic findings in three cows with chronic ragwort (Senecio alpinus) poisoning.
Three cows with regwort (Senecio alpinus) poisoning were examined clinically, haematologically and ultrasonographically, and biopsy specimens of the liver were examined histologically. At the end of the study, the cows were euthanased and examined postmortem. The major clinical signs included severely disturbed general demeanour and behaviour, and severe diarrhoea. One cow was photosensitive. The activities of liver enzymes and the concentration of bilirubin were high in all of the cows. In two of the cows, ultrasonographic examination revealed a heavy accumulation of abdominal fluid, which was diagnosed as non-inflammatory ascites. In all the cows, the liver parenchyma was heterogeneous, and cows 1 and 2 had multiple echogenic foci 5 to 10 mm in diameter. In cow 3, the facies diaphragmatica of the liver appeared irregular in outline owing to the presence of nodules which were approximately 5 cm in diameter. The liver was also greatly enlarged and extended almost to the linea alba ventrally and beyond the reticulum cranially. All the cows had portal hypertension and the portal vein was dilated, resulting in oedema of the walls of the gall bladder, the small intestines and the omentum. The diameter of the caudal vena cava was reduced as a result of the impaired hepatic circulation. Histological examination of liver biopsy specimens revealed severe hepatic fibrosis in all the cows.


Rare case of pulmonary lymphomatoid granulomatosis in conjunction with tuberculosis: A case report.
Lymphomatoid granulomatosis is a very rare Epstein-Barr virus-driven lymphoproliferative disease. This disease has high mortality owing to its low incidence in conjunction with nonspecific presentations, which contribute to delays in diagnosis. An 87-year-old male had a week-long history of intermittent fever and general weakness. A chest radiograph showed multifocal patchy consolidations with nodular lesions. Open lung biopsy using video-assisted thoracic surgery resulted in a diagnosis of grade III lymphomatoid granulomatosis. Three days after surgery, Mycobacterium tuberculosis complex was identified from the culture of sputum samples collected at admission. Antituberculous treatment was commenced first. However, after 34 days of antituberculosis medication, the patient died owing to aggravated lymphomatoid granulomatosis. This case highlights the fact that rare diseases should also be considered in differential diagnosis, particularly with a common presentation such as multiple lung nodules. Furthermore, a diagnosis of pulmonary lymphomatoid granulomatosis was made after open lung biopsy. To our knowledge, this is the first case of lymphomatoid granulomatosis coexisting with active tuberculosis in the Republic of Korea, where tuberculosis is endemic.


Benzene in the blood and breath of normal people and occupationally exposed workers.
Benzene was measured in blood and alveolar air of 168 men, aged 20-58 years, subdivided into four groups: blood donors, hospital staff, chemical workers occupationally exposed to benzene, and chemical workers not occupationally exposed to benzene. The group of exposed workers was employed in work places with a mean environmental exposure to benzene of 1.62 mg/M3 (8 hr TWA). Non-exposed workers were employed elsewhere in the same plant, with an environmental exposure to benzene lower than 0.1 mg/M3. Blood and alveolar air samples were collected in the morning, before the start of the work shift for the chemical workers. The group of exposed workers was found to be significantly different from the other three groups, both for blood and alveolar benzene concentrations. The mean blood benzene concentration was 789 ng/l in the exposed workers, 307 ng/l in the non-exposed workers, 332 ng/l in the hospital staff, and 196 ng/l in the blood donors. Apart from the exposed workers, blood benzene concentration was significantly higher in smokers than in non-smokers. The mean alveolar benzene concentration was 92 ng/l in the exposed workers, 42 ng/l in the non-exposed workers, 22 ng/l in the hospital staff, and 11 ng/l in the blood donors. Alveolar benzene concentration was significantly higher in smokers than in non-smokers in the groups of the hospital staff and non-exposed workers, but not in the blood donors and exposed workers. In the three groups without occupational exposure considered altogether, the alveolar benzene concentration correlated significantly with environmental benzene concentration measured at the moment of the individual examinations, both in the smokers (r = .636; p less than .001) and non-smokers (r = .628; p less than .001). In the same three groups and in the exposed workers, alveolar benzene concentration showed a significant correlation with the blood benzene concentration.


Parental Experience of Prenatal Diagnosis of Lymphatic Malformation.
Lymphatic malformations are a developmental anomaly arising from a somatic mutation in the lymphatic endothelial cells. This study investigated parental experiences associated with prenatal diagnosis of LM. Parents of 5 children diagnosed prenatally with LM were recruited from the Vascular Anomalies Clinic at the Royal Childrens Hospital, Melbourne. Ten in-depth semistructured interviews were conducted with each parent separately to explore their experiences and views at the time of diagnosis and immediately after childbirth. Transcribed interviews were coded and thematically analyzed. Parents experienced prenatal diagnosis of LM as an unexpected and traumatic event. The lack of adequate information and clear care pathway created confusion and added to the difficulty of understanding the impact of LM on the unborn child and what to expect after the child was born. Parents used the internet as the primary source of additional information; however, some parents found that information distressing. Differences between mothers and fathers were noted in terms of roles that each parent played and their emotional responses during pregnancy and the prenatal diagnosis. Closer connection between obstetric centers and specialized treatment clinics are suggested to facilitate better understanding of the LM impact on the unborn child and available treatment options after birth.


Protection or peril? An analysis of firearm-related deaths in the home.
To study the epidemiology of deaths involving firearms kept in the home, we reviewed all the gunshot deaths that occurred in King County, Washington (population 1,270,000), from 1978 through 1983. The medical examiner's case files were supplemented by police records or interviews with investigating officers or both, to obtain specific information about the circumstances, the scene of the incident, the type of firearm involved, and the relationship of the suspect to the victim. A total of 743 firearm-related deaths occurred during this six-year period, 398 of which (54 percent) occurred in the residence where the firearm was kept. Only 2 of these 398 deaths (0.5 percent) involved an intruder shot during attempted entry. Seven persons (1.8 percent) were killed in self-defense. For every case of self-protection homicide involving a firearm kept in the home, there were 1.3 accidental deaths, 4.6 criminal homicides, and 37 suicides involving firearms. Hand-guns were used in 70.5 percent of these deaths. The advisability of keeping firearms in the home for protection must be questioned.


Learning Curve for Transoral Endoscopic Thyroid Lobectomy.
Objective To define the learning curve for transoral endoscopic thyroidectomy via the vestibular approach (TOETVA). Study Design Case series with planned data collection. Setting Tertiary care academic hospital. Subjects and Methods Included patients were those who met the 2015 American Thyroid Association guidelines for lobectomy and our group's previously documented indications for TOETVA. Operative time (incision to closure) was used as a surrogate for procedural proficiency and plotted as a function of case number to determine a learning curve. A simple moving average of operative time was then calculated, with the proficiency case defined as the case number where the slope of this curve changed. Demographic/characteristic data, outcomes, and complications were compared between the skill acquisition period (case 1 to proficiency case) and the proficiency period (remaining cases). A linear regression model was then used to calculate and compare the slopes of the skill acquisition and proficiency periods in the "operative time versus case number" plot. Results Thirty cases were attempted, with a procedural success rate of 29 of 30 (94%) and no incidence of permanent mental nerve or recurrent laryngeal nerve injury. The proficiency case was case 11. There was a statistically significant difference between the skill acquisition and proficiency periods in slopes of the linear regressions (-16.7 vs -0.3, respectively; P < .001) and median operative times (191 vs 119 minutes, P < .001). There was no difference in demographics, procedural success rate, or complication rate between the periods. Conclusions The learning curve for TOETVA was 11 cases for the surgeon evaluated in this series.


A new LMS algorithm for analysis of atrial fibrillation signals.
A biomedical signal can be defined by its extrinsic features (x-axis and y-axis shift and scale) and intrinsic features (shape after normalization of extrinsic features). In this study, an LMS algorithm utilizing the method of differential steepest descent is developed, and is tested by normalization of extrinsic features in complex fractionated atrial electrograms (CFAE). Equations for normalization of x-axis and y-axis shift and scale are first derived. The algorithm is implemented for real-time analysis of CFAE acquired during atrial fibrillation (AF). Data was acquired at a 977 Hz sampling rate from 10 paroxysmal and 10 persistent AF patients undergoing clinical electrophysiologic study and catheter ablation therapy. Over 24 trials, normalization characteristics using the new algorithm with four weights were compared to the Widrow-Hoff LMS algorithm with four tapped delays. The time for convergence, and the mean squared error (MSE) after convergence, were compared. The new LMS algorithm was also applied to lead aVF of the electrocardiogram in one patient with longstanding persistent AF, to enhance the F wave and to monitor extrinsic changes in signal shape. The average waveform over a 25 s interval was used as a prototypical reference signal for matching with the aVF lead. Based on the derivation equations, the y-shift and y-scale adjustments of the new LMS algorithm were shown to be equivalent to the scalar form of the Widrow-Hoff LMS algorithm. For x-shift and x-scale adjustments, rather than implementing a long tapped delay as in Widrow-Hoff LMS, the new method uses only two weights. After convergence, the MSE for matching paroxysmal CFAE averaged 0.46 ± 0.49 μV(2)/sample for the new LMS algorithm versus 0.72 ± 0.35 μV(2)/sample for Widrow-Hoff LMS. The MSE for matching persistent CFAE averaged 0.55 ± 0.95 μV(2)/sample for the new LMS algorithm versus 0.62 ± 0.55 μV(2)/sample for Widrow-Hoff LMS. There were no significant differences in estimation error for paroxysmal versus persistent data. From all trials, the mean convergence time was approximately 1 second for both algorithms. The new LMS algorithm was useful to enhance the electrocardiogram F wave by subtraction of an adaptively weighted prototypical reference signal from the aVF lead. The extrinsic weighting over 25 s demonstrated that time-varying functions such as patient respiration could be identified and monitored. A new LMS algorithm was derived and used for normalization of the extrinsic features in CFAE and for electrocardiogram monitoring. The weighting at convergence provides an estimate of the degree of similarity between two signals in terms of x-axis and y-axis shift and scale. The algorithm is computationally efficient with low estimation error. Based on the results, proposed applications include monitoring of extrinsic and intrinsic features of repetitive patterns in CFAE, enhancement of the electrocardiogram F wave and monitoring of time-varying signal properties, and to quantitatively characterize mechanistic differences in paroxysmal versus persistent AF.


[ECMO support in a child with cardiogenic shock due to Kingella Kingae endocarditis].
Endocarditis is a rare disease in children, especially in those without previous heart disease, and Kingella Kingae (KK) is rarely identified as the cause. Extracorporeal membrane oxyge nation (ECMO) is a support for both heart and respiratory failure. To report the first case of infectious endocarditis (IE) due to KK which required ECMO support secondary to refractory cardiogenic shock. 19-months-old previously healthy female patient, with a 2-day his tory of fever, and diagnosed with hand-foot-and-mouth disease. The patient developed refractory cardiogenic shock, multiorgan failure, acute respiratory distress syndrome, and deep hemodynamic compromise that required veno-arterial ECMO support. The echography showed an image compa tible with mitral valve vegetation, confirming IE with transthoracic echocardiography. Blood culture was positive for KK. She had an ischemic stroke and required two heart surgeries, the first one for the mass resection and the second one for mitral valve repair, which had a posterior ring pseudoa neurysm. The patient had a favorable evolution and was discharged 73 days after admission. At one year of follow-up, she had no cardiological symptoms, but a mild right brachial-crural hemiparesis persisted. This is the first reported case of IE due to KK that required extracorporeal life support. KK endocarditis is an uncommon pathology that can cause multiorgan failure, which can be successfully supported with ECMO.


SPECT thallium-201 combined with Toxoplasma serology for the presumptive diagnosis of focal central nervous system mass lesions in patients with AIDS.
To determine the utility of brain thallium-201 single photon emission computerized tomography (Tl-201 SPECT) combined with Toxoplasma serology for the diagnosis of focal CNS lesions in patients with AIDS. Sixty-one consecutive HIV-infected patients with focal CNS lesion(s) on head computed tomography (CT) or MRI scan who underwent brain Tl-201 SPECT and serum Toxoplasma serology were evaluated, retrospectively. Thallium-201 uptake ratios were calculated by comparing lesion activity to contralateral scalp activity. Diagnoses were made by a combination of histology, serology, PCR, and empirical response to therapy. Toxoplasma serologies (IgG IFA) were compared in the patients with central nervous system (CNS) toxoplasmosis and those without CNS toxoplasmosis. Fifty-six patients were evaluable and a definitive diagnosis was made in 38 patients: toxoplasmosis (17), lymphoma (14), PML (three), Aspergillus (one), tuberculoma (one), Cryptococcus (one), varicella-zoster virus (one). Patients with lymphoma had significantly higher lesion/contralateral scalp ratios compared to patients without lymphoma: 1.03 vs. 0.67, P < 0.05. Using a cut-off of 0.90 for the lesion/scalp uptake ratios (based on analysis of ROC curves) the sensitivity and specificity for the diagnosis of lymphoma were 86% and 83%, respectively. Serum Toxoplasma IgG titres were significantly higher in patients diagnosed with toxoplasmosis compared to those with a diagnosis other than toxoplasmosis, 1:5444 vs. 1:15, P < 0.05. Only one patient with confirmed toxoplasmosis had a Toxoplasma serology < 1:256, while no patients without toxoplasmosis (including all lymphoma patients) had serologies > 1:256. In a series of HIV-infected patients, Tl-201 SPECT was able to accurately differentiate primary brain lymphoma from other causes of focal CNS lesions in most patients; however, both false positive and false negative results occurred. By combining Tl-201 SPECT with serum Toxoplasma IgG, diagnostic accuracy was improved.


Adsorptive removal of Cd(II) and Pb(II) ions from aqueous solutions by using Turkish illitic clay.
The ability of Turkish illitic clay (TIC) in removal of Cd(II) and Pb(II) ions from aqueous solutions has been examined in a batch adsorption process with respect to several experimental conditions including initial solution pH, contact time, initial metal ions concentration, temperature, ionic strength, and TIC concentration, etc. The characterization of TIC was performed by using FTIR, XRD and XRF techniques. The maximum uptake of Cd(II) (11.25 mg g(-1)) and Pb(II) (238.98 mg g(-1)) was observed when used 1.0 g L(-1) of TIC suspension, 50 mg L(-1) of initial Cd(II) and 250 mg L(-1) of initial Pb(II) concentration at initial pH 4.0 and contact time of 240 min at room temperature. The experimental data were analyzed by the Langmuir, Freundlich, Temkin and Dubinin Radushkevich (D-R) isotherm models. The monolayer adsorption capacity of TIC was found to be 13.09 mg g(-1) and 53.76 mg g(-1) for Cd(II) and Pb(II) ions, respectively. The kinetics of the adsorption was tested using pseudo-first-order, pseudo-second-order, Elovich and intraparticle diffusion models. The results showed that the adsorption of Cd(II) and Pb(II) ions onto TIC proceeds according to the pseudo-second-order model. Thermodynamic parameters including the Gibbs free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) changes indicated that the present adsorption process was feasible, spontaneous and endothermic in the temperature range of 5-40 °C.


Age-related changes of skeletal muscle metabolic response to contraction are also sex-dependent.
Mitochondria adapt to increased energy demands during muscle contraction by acutely altering metabolite fluxes and substrate oxidation. With age, an impaired mitochondrial metabolic response may contribute to reduced exercise tolerance and decreased skeletal muscle mass, specific force, increased overall fatty depositions in the skeletal muscle, frailty and depressed energy maintenance. We hypothesized that elevated energy stress in mitochondria with age alters the capacity of mitochondria to utilize different substrates following muscle contraction. To test this hypothesis, we used in vivo electrical stimulation to simulate high-intensity intervals (HII) or low intensity steady-state (LISS) exercise in young (5-7 months) and aged (27-29 months) male and female mice to characterize effects of age and sex on mitochondrial substrate utilization in skeletal muscle following contraction. Mitochondrial respiration using glutamate decreased in aged males following HII and glutamate oxidation was inhibited following HII in both the contracted and non-stimulated muscle of aged female muscle. Analyses of the muscle metabolome of female mice indicated that changes in metabolic pathways induced by HII and LISS contractions in young muscle are absent in aged muscle. To test improved mitochondrial function on substrate utilization following HII, we treated aged females with elamipretide (ELAM), a mitochondrially-targeted peptide shown to improve mitochondrial bioenergetics and restore redox status in aged muscle. ELAM removed inhibition of glutamate oxidation and showed increased metabolic pathway changes following HII, suggesting rescuing redox status and improving bioenergetic function in mitochondria from aged muscle increases glutamate utilization and enhances the metabolic response to muscle contraction in aged muscle. KEY POINTS: Acute local contraction of gastrocnemius can systemically alter mitochondrial respiration in non-stimulated muscle. Age-related changes in mitochondrial respiration using glutamate or palmitoyl carnitine following contraction are sex-dependent. Respiration using glutamate after high-intensity contraction is inhibited in aged female muscle. Metabolite level and pathway changes following muscle contraction decrease with age in female mice. Treatment with the mitochondrially-targeted peptide elamipretide can partially rescue metabolite response to muscle contraction.


Effects of receipt of Social Security retirement benefits on older women's employment.
Labor force participation of women has declined since 1999; however, labor force participation of women 62+ has increased. The 2000-2006 waves of Health and Retirement Study (HRS) data, the initial years of the continuing upward trajectory, were used to test the effects of receipt of Social Security retirement benefits on older women's employment. The models tested: (a) the effect of receipt of Social Security retirement benefits on whether employed; and (b) for women receiving Social Security retirement benefits, the effect of age elected receipt of benefits on whether employed. Both models included the effects of human capital characteristics and income sources. Receipt of Social Security benefits, pension income, and current age reduced the likelihood of employment; while educational level, good to excellent health, and nonmarried marital status increased the likelihood of employment. The older the woman was when she elected Social Security benefits, the more likely she was to be employed.


White matter imaging helps dissociate tau from TDP-43 in frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) is most commonly associated with TAR-DNA binding protein (TDP-43) or tau pathology at autopsy, but there are no in vivo biomarkers reliably discriminating between sporadic cases. As disease-modifying treatments emerge, it is critical to accurately identify underlying pathology in living patients so that they can be entered into appropriate etiology-directed clinical trials. Patients with tau inclusions (FTLD-TAU) appear to have relatively greater white matter (WM) disease at autopsy than those patients with TDP-43 (FTLD-TDP). In this paper, we investigate the ability of white matter (WM) imaging to help discriminate between FTLD-TAU and FTLD-TDP during life using diffusion tensor imaging (DTI). Patients with autopsy-confirmed disease or a genetic mutation consistent with FTLD-TDP or FTLD-TAU underwent multimodal T1 volumetric MRI and diffusion weighted imaging scans. We quantified cortical thickness in GM and fractional anisotropy (FA) in WM. We performed Eigenanatomy, a statistically robust dimensionality reduction algorithm, and used leave-one-out cross-validation to predict underlying pathology. Neuropathological assessment of GM and WM disease burden was performed in the autopsy-cases to confirm our findings of an ante-mortem GM and WM dissociation in the neuroimaging cohort. ROC curve analyses evaluated classification accuracy in individual patients and revealed 96% sensitivity and 100% specificity for WM analyses. FTLD-TAU had significantly more WM degeneration and inclusion severity at autopsy relative to FTLD-TDP. These neuroimaging and neuropathological investigations provide converging evidence for greater WM burden associated with FTLD-TAU, and emphasise the role of WM neuroimaging for in vivo discrimination between FTLD-TAU and FTLD-TDP.


Nonverbatim captioning in Dutch television programs: a text linguistic approach.
In the Netherlands, as in most other European countries, closed captions for the deaf summarize texts rather than render them verbatim. Caption editors argue that in this way television viewers have enough time to both read the text and watch the program. They also claim that the meaning of the original message is properly conveyed. However, many deaf people demand verbatim subtitles so that they have full access to all original information. They claim that vital information is withheld from them as a result of the summarizing process. Linguistic research was conducted in order (a) to identify the type of information that is left out of captioned texts and (b) to determine the effects of nonverbatim captioning on the meaning of the text. The differences between spoken and captioned texts were analyzed on the basis of on a model of coherence relations in discourse. One prominent finding is that summarizing affects coherence relations, making them less explicit and altering the implied meaning.


Subtelomeric silencing of the MTL3 locus of Candida glabrata requires yKu70, yKu80, and Rif1 proteins.
Candida glabrata is a haploid opportunistic fungal pathogen that is phylogenetically related to Saccharomyces cerevisiae. Even though C. glabrata has no known sexual cycle, it contains, like S. cerevisiae, three mating type-like loci (MTL) called MTL1, MTL2, and MTL3, as well as most of the genes required for mating, meiosis, and sporulation. MTL1 is localized at an internal position on chromosome B and is thought to be the locus corresponding to the MAT locus in S. cerevisiae. MTL2 and MTL3 are localized close to two telomeres on different chromosomes (29.4 kb from Chr E-L and 10.5 kb from Chr B-L, respectively). By using URA3 reporter gene insertions at the three MTL loci, we found that in contrast to the case for S. cerevisiae, only MTL3 is subject to transcriptional silencing while MTL2 is transcriptionally active, and this is in agreement with previously reported data. We found that the silencing of MTL3 is nucleated primarily at the left telomere of chromosome B and spreads over 12 kb to MTL3, rather than nucleating at flanking, closely positioned cis-acting silencers, like those flanking HMR and HML of S. cerevisiae. Interestingly, the silencing of MTL3 absolutely requires the yKu70, yKu80, and Rif1 proteins, in sharp contrast to the silencing of the HM loci of S. cerevisiae. In addition, we found that several cell type-specific genes are expressed in C. glabrata regardless of the presence, or even absence, of mating type information at any of the MTL loci.


The cerebrospinal fluid immunoglobulin G index as a diagnostic aid in multiple sclerosis: a Bayesian approach.
Having determined immunoglobulin G (IgG) and albumin concentrations in 1100 cerebrospinal fluid and serum samples, we calculated the IgG index. Likelihood ratios for multiple sclerosis were calculated by using a training set consisting of 100 patients with definite multiple sclerosis and one consisting of 97 patients suffering from diseases from which multiple sclerosis must be differentiated. Predictive values for multiple sclerosis, given different values for the IgG index, are given in a graphical representation of Bayes' theorem. We conclude that this approach increases the diagnostic usefulness of the IgG index for the diagnosis of multiple sclerosis.


Development and validation of a patient-centered, meningioma-specific quality-of-life questionnaire.
Meningiomas can have significant impact on health-related quality of life (HRQOL). Patient-centered, disease-specific instruments for assessing HRQOL in these patients are lacking. To this end, the authors sought to develop and validate a meningioma-specific HRQOL questionnaire through a standardized, patient-centered questionnaire development methodology. The development of the questionnaire involved three main phases: item generation, item reduction, and validation. Item generation consisted of semistructured interviews with patients (n = 30), informal caregivers (n = 12), and healthcare providers (n = 8) to create a preliminary list of items. Item reduction with 60 patients was guided by the clinical impact method, multiple correspondence analysis, and hierarchical cluster analysis. The validation phase involved 162 patients and collected evidence on extreme-groups validity; concurrent validity with the SF-36, FACT-Br, and EQ-5D; and test-retest reliability. The questionnaire takes on average 11 minutes to complete. The meningioma-specific quality-of-life questionnaire (MQOL) consists of 70 items representing 9 domains. Cronbach's alpha for each domain ranged from 0.61 to 0.91. Concurrent validity testing demonstrated construct validity, while extreme-groups testing (p = 1.45E-11) confirmed the MQOL's ability to distinguish between different groups of patients. The MQOL is a validated, reliable, and feasible questionnaire designed specifically for evaluating QOL in meningioma patients. This disease-specific questionnaire will be fundamentally helpful in better understanding and capturing HRQOL in the meningioma patient population and can be used in both clinical and research settings.


[Tinnitus and implants].
The experience with cochlear implantation at Avicenne hospital prompted us to carry out a retrospective study on tinnitus in a population of operated patients. Improvement or disappearance of the symptoms was noted in all cases. These results, which partly match those found in the literature, are probably produced by rehabilitation inhibiting the "deafferentation" mechanisms in analogy with pain phenomena. In some precise cases, which are described, they led us to proposing implantation even though the main, if not sole, complaint of the patient was tinnitus.


Infant stress exposure produces persistent enhancement of fear learning across development.
In recent years, it has become increasingly clear that early life stress experiences persistently impact subsequent physiological, cognitive, and emotional responses. In cases of trauma, these early experiences can result in anxiety disorders such as phobias and posttraumatic stress disorder. In the present paper, we examined the effects of infant footshock stress exposure at postnatal day (PND) 17 on subsequent contextual fear conditioning at postnatal days 18 (Experiment 1), 24 (Experiment 2), or 90 (Experiment 3). In each experiment, PND17 footshock stress exposure enhanced later fear conditioning, indicating that the stress enhancement of fear learning (SEFL) persists throughout development. Memory for the original stress exposure context was gradually forgotten, with significant fear expression evident at PND20, and a complete lack of fear expression in that same context at PND90. These data suggest that the stress-enhancing component of infant fear learning is dissociable from the infant contextual fear memory per se. In other words, early life stress produces persistent effects on subsequent cognition that are independent of the memory for that early life event.


Cell cycle-dependent regulation of Greatwall kinase by protein phosphatase 1 and regulatory subunit 3B.
Greatwall (Gwl) kinase plays an essential role in the regulation of mitotic entry and progression. Mitotic activation of Gwl requires both cyclin-dependent kinase 1 (CDK1)-dependent phosphorylation and its autophosphorylation at an evolutionarily conserved serine residue near the carboxyl terminus (Ser-883 in Xenopus). In this study we show that Gwl associates with protein phosphatase 1 (PP1), particularly PP1γ, which mediates the dephosphorylation of Gwl Ser-883. Consistent with the mitotic activation of Gwl, its association with PP1 is disrupted in mitotic cells and egg extracts. During mitotic exit, PP1-dependent dephosphorylation of Gwl Ser-883 occurs prior to dephosphorylation of other mitotic substrates; replacing endogenous Gwl with a phosphomimetic S883E mutant blocks mitotic exit. Moreover, we identified PP1 regulatory subunit 3B (PPP1R3B) as a targeting subunit that can direct PP1 activity toward Gwl. PPP1R3B bridges PP1 and Gwl association and promotes Gwl Ser-883 dephosphorylation. Consistent with the cell cycle-dependent association of Gwl and PP1, Gwl and PPP1R3B dissociate in M phase. Interestingly, up-regulation of PPP1R3B facilitates mitotic exit and blocks mitotic entry. Thus, our study suggests PPP1R3B as a new cell cycle regulator that functions by governing Gwl dephosphorylation.


Amphotericin B lipid complex for neonatal invasive candidiasis.
This study describes the safety and efficacy of amphotericin B lipid complex (ABLC) in 11 neonates with systemic Candida infections. Nine of the 11 improved clinically, and eight of nine evaluable patients had a mycological cure with ABLC. Creatinine levels improved or did not significantly change in eight of the 11 patients.


Political depression? A big-data, multimethod investigation of Americans' emotional response to the Trump presidency.
Previous studies suggested that the 2016 presidential elections gave rise to pathological levels of election-related distress in liberal Americans; however, it has also been suggested that the public discourse and the professional discourse have increasingly overgeneralized concepts of trauma and psychopathology. In light of this, in the current research, we utilized an array of big data measures and asked whether a political loss in a participatory democracy can indeed lead to psychopathology. We observed that liberals report being more depressed when asked directly about the effects of the election; however, more indirect measures show a short-lived or nonexistent effect. We examined self-report measures of clinical depression with and without a reference to the election (Studies 1A & 1B), analyzed Twitter discourse and measured users' levels of depression using a machine-learning-based model (Study 2), conducted time-series analysis of depression-related search behavior on Google (Study 3), examined the proportion of antidepressants consumption in Medicaid data (Study 4), and analyzed daily surveys of hundreds of thousands of Americans (Study 5), and saw that at the aggregate level, empirical data reject the accounts of "Trump Depression." We discuss possible interpretations of the discrepancies between the direct and indirect measures. The current investigation demonstrates how big-data sources can provide an unprecedented view of the psychological consequences of political events and sheds light on the complex relationship between the political and the personal spheres. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


[Health of Brazilian elderly just before of the 21st century: current problems, forecasts and alternatives].
Current characteristics and perspectives of Brazilian demographic and epidemiological transition processes are analyzed. Results from the 1991, 1993, 1995 and 1996 censuses, new population projections and recent studies on socioeconomic and health profiles of elderly people of S. Paulo, Rio de Janeiro and Belo Horizonte are discussed. In 1995, estimated life expectancy at birth in Brazil was already over 67 years. The number of individuals aged 60 years and older--in 1995, 8.3%, of the total population--is expected to duplicate and probably stabilize by the year 2050. Yet lacking coverage and quality, health services are already burdened with degenerative diseases and mental disorders, frequent outpatient appointments, high hospital bed occupation and high costs. Functional impairment and self-reported diseases are related to poverty among the elderly. for whom social and health support are not properly provided. Support from informal caregivers becomes more difficult due to impoverishment, family size reduction and youth migration. Institutionalization remains a poor approach as scarcity of beds and inadequacy of staff preclude its utilization. To minimize the impact of population aging on health services, it is proposed that effective programs covering the control of degenerative diseases and the prevention of their complications should be implemented--for the elderly population too. The importance of physical exercise, screening for neoplastic diseases, immunization, prevention of fractures caused by falls and early diagnosis of depression and dementia is emphasized. Actions must be coordinated by primary health care units, oriented towards local needs. It is essential to maintain the elderly in adequate, productive activities, invest in young people's education and health and in social and medical support programs for the caregivers.


[The effects of haptenic presentation on B and T cell responses].
In this study the effect of haptenic presentation on the nature of immune response was investigated. Haptens (such as p-aminobenzoic acid, p-amino sulphanilic acid and p-aminoarsanilic acid) were coupled to an amino acid (tyrosine) alone, a protein (bovine serum albumine) a bacteria (M. tuberculosis) and injected to guinea pigs. Hapten specific humoral immune response was determined by either quantitative precipitin test or passive hemolysin test. Macrophage migration inhibition and skin tests were used for measurement of hapten specific cellular immunity. Hapten-tyrosine conjugates were found to be either non-immunogenic (PABA-Ti) or immunogenic only for T cells (PASA-Ti and PAAA-Ti). On the contrary, hapten-protein complexes induced anti-hapten antibodies, in the absence of cellular immunity to the hapten. Injection of hapten-bacteria conjugate in to animals caused a marked T cell responses to all haptens used, without or with minute amount of antibody. These results have suggested that it might be possible to direct an immune response towards a preferential humoral and cellular response by changing the way of presentation of a hapten.


Ascorbate/iron mediation of hydroxyl free radical damage to PBR322 plasmid DNA.
Plasmid PBR322 DNA has been exposed to hydroxyl free radicals generated from an ascorbate/Fe system. Hydroxyl free radical scavengers as well as the iron chelator desferroxamine and catalase inhibit the DNA nicking which occurs, but superoxide dismutase had no effect. The DNA nicking was temperature dependent, occurring more rapidly at higher temperatures. The rate of DNA nicking was accelerated by the addition of hydrogen peroxide. There was an early lag phase in DNA nicking, even though the rate of hydroxyl free radical generation, as assessed by salicylate hydroxylation, showed no lag phase. It is considered that the early hydroxyl free radical damage to DNA may be biologically very important in mutagenic and carcinogenic processes.


Cardiovascular genetic medicine: genomic assessment of prognosis and diagnosis in patients with cardiomyopathy and heart failure.
In the last half century, epidemiologic studies and basic science investigations revealed that hypertension (Kannel et al., Ann Intern Med 55:33-50, 1961), hyperlipidemia (Dawber et al., Am J Public Health Nations Health 49:1349-1356, 1959), diabetes (Kannel et al., Am J Cardiol 34(1):29-34, 1974), smoking (Dawber et al., Am J Public Health Nations Health 49:1349-1356, 1959), and inflammation (Rossmann et al., Exp Gerontol 43(3):229-237, 2008) posed increased risk for cardiovascular disease. These associations served both as risk factors and offered insight into disease pathophysiology. Currently, it is increasingly appreciated that polygenic factors may also play a role as etiologic or risk factors (Chakravarti and Little, Nature 421(6921):412-414, 2003; Dorn and Molkentin, Circulation 109(2):150-158, 2004). Recent technologic advances in genomic screening make the search for these factors possible, and robust technologies are now available for both entire genome screening for expression or single nucleotide polymorphisms. In this paper, we review the basic principles of gene expression and molecular signature analysis in the context of potential clinical applications of transcriptomics.


Noninvasive detection of coronary artery disease using parametric spectral analysis methods.
The detection of coronary artery disease by noninvasive analysis of isolated diastolic heart sounds is considered. It is based on identifying features associated with turbulent blood flow in partially occluded coronary arteries. The application of two types of parametric spectral analysis-autoregressive methods and eigenvector methods-to identify the additional signal components is discussed. Results obtained with one eigenvector method, (the MUSIC method) for spectra obtained from an angioplasty patient and results obtained with the autoregressive model in a comparison study of ten diseased and five normal patients are presented and discussed.


Sudden death in athletes.
Sudden cardiac death in an athlete is a rare and heartrending event, often occurring in the absence of warning symptoms. The causes of sudden cardiac death in athletes are age dependent and demonstrate a degree of geographical variation. Pre-participation screening is recommended by both the European Society of Cardiology and the American Heart Association although there is no consensus regarding the utilisation of an electrocardiogram. This article will review the aetiology of sudden cardiac death and will present the evidence for pre-participation screening.


Combined experimental and statistical strategy for mass spectrometry based serum protein profiling for diagnosis of breast cancer: a case-control study.
Serum protein profiling by mass spectrometry is a promising method for early detection of cancer. We have implemented a combined strategy based on matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and statistical data analysis for serum protein profiling and applied it in a well-described breast cancer case-control study. A rigorous sample collection protocol ensured high quality specimen and reduced bias from preanalytical factors. Preoperative serum samples obtained from 48 breast cancer patients and 28 controls were used to generate MALDI MS protein profiles. A total of nine mass spectrometric protein profiles were obtained for each serum sample. A total of 533 common peaks were defined and represented a 'reference protein profile'. Among these 533 common peaks, we identified 72 peaks exhibiting statistically significant intensity differences ( p < 0.01) between cases and controls. A diagnostic rule based on these 72 mass values was constructed and exhibited a cross-validated sensitivity and specificity of approximately 85% for the detection of breast cancer. With this method, it was possible to distinguish early stage cancers from controls without major loss of sensitivity and specificity. We conclude that optimized serum sample handling and mass spectrometry data acquisition strategies in combination with statistical analysis provide a viable platform for serum protein profiling in cancer diagnosis.


Structural and functional role of cysteinyl residues in tobacco acetolactate synthase.
Acetolactate synthase (ALS) is the common enzyme in the biosynthesis of valine, leucine, and isoleucine. The role of four cysteinyl residues in tobacco ALS was determined using site-directed mutagenesis and cysteine-specific cleavage. The C411A mutation abolished the enzymatic activity, as well as the binding affinity for the cofactor FAD. The activation constant of C411S for FAD is approximately 50-fold higher than that of wALS. The C607S mutation did not significantly affect the kinetic parameters. The IC(50) values of C411S and C607S for ALS-inhibiting herbicides are not much different from those of wALS. Two mutants, C163S and C309S, are labile and readily degraded to peptide fragments. The treatment of wALS with 2-nitro-5-thiocyanobenzoic acid, specific for cleavage of the N-terminal side of cysteine, yielded three peptides of 37.0, 22. 0, and 7.0 kDa. This fragmentation pattern is consistent with that deduced from the amino acid sequence of tobacco ALS, assuming the disulfide bond between Cys163 and Cys309. These results suggest that Cys411 is involved in the binding of FAD and that the intrachain disulfide bond between Cys163 and Cys309 plays a key role in maintaining the correct conformation of tobacco ALS.


30-Day Morbidity and Mortality Outcomes of Prolonged Minimally Invasive Kidney Procedures Compared with Shorter Open Procedures: National Surgical Quality Improvement Program Analysis.
Prolonged operative time (ORT) is often considered a drawback to minimally invasive surgery (MIS) because of increased morbidity. Limited data exist comparing long laparoscopic ORT with similar or shorter open ORT. This study aims to identify ORT when a minimally invasive procedure becomes inferior to its open counterpart. Minimally invasive and open total and partial nephrectomies and nephroureterectomies were identified in the National Surgical Quality Improvement Program (NSQIP) from 2005 to 2012. Procedures were split into open and minimally invasive nephrectomy and then stratified into four ORT groups: 0 to 90 minutes, 91 minutes to 3 hours, 3 to 6 hours, and ≥ 6 hours. Thirty-day mortality and morbidity were analyzed. Univariate analysis was performed using chi-square and Fisher exact tests. Significant univariate results were then tested using stepwise logistic regression, controlling for demographics, comorbidities, and preoperative treatments. There were 14,813 patients identified. Both partial and total minimally invasive kidney procedures had significantly improved outcomes compared with open counterparts of similar ORT. In the total nephrectomy group, a minimally invasive approach had a lower rate of surgical site infections, sepsis, pneumonia, return to operating room, and overall length of stay when compared with open procedures of the same duration. Length of hospital stay decreased in MIS regardless of operative time, except when comparing minimally invasive cases longer than 6 hours with open cases less than 90 minutes. Transfusion rates also significantly decreased in minimally invasive total nephrectomy cases. In the partial nephrectomy group, similar outcomes were seen in terms of length of stay and infectious outcomes. Interestingly, transfusion risk was decreased in the open partial nephrectomy group when comparing cases less than 90 minutes with minimally invasive partial nephrectomies lasting 3 to 6 hours; otherwise there was no significant correlation with transfusion risk. Minimally invasive operations are less morbid than open operations of similar ORT. Longer and likely more complex laparoscopic procedures continue to provide a benefit to patients when compared with shorter and possibly less complex open procedures. These data should be considered during a surgeon's preoperative and operative decision-making.


Cutaneous melanoma in Swedish women: Occupational risks by anatomic site.
Few occupational studies have addressed melanoma in women. Accordingly, our aim was to identify occupations with higher risk of cutaneous melanoma, overall and by site, in Swedish female workers. All gainfully employed Swedish women were followed-up from 1971 to 1989, using Death/Cancer Registers. Occupational risk ratios adjusted for age, period, town size, and geographic zone were computed for each site. Risk patterns for different sites were then compared. High risks were observed among educators, bank tellers, dental nurses, librarians/archivists/curators, horticultural workers, and hatmakers/milliners. Telephone operators and textile workers had increased risk, mainly in the leg. Other occupation-specific site excesses were also found. Upper-limb risks were correlated with head/neck and thorax, though these two sites were not associated. Legs registered a special pattern, with a moderate correlation with upper limbs or thorax, and no correlation with head/neck. Some occupations with possible exposure to arsenic/mercury displayed increased risk. The generalized excess risk among hatmakers/milliners warrants further attention. The weak correlation between legs and other sites suggests site specificity in melanoma risk factors.


Health technology assessment in India: the potential for improved healthcare decision-making.
Health technology assessment (HTA) is a multidisciplinary approach that uses clinical effectiveness, cost-effectiveness, policy and ethical perspectives to provide evidence upon which rational decisions on the use of health technologies can be made. It can be used for a single stand-alone technology (e.g. a drug, a device), complex interventions (e.g. a rehabilitation service) and can also be applied to individual patient care and to public health. It is a tool for enabling the assessment and comparison of health technologies using the same metric of cost-effectiveness. This process benefits the patient, the health service, the healthcare payer and the technology producer as only technologies that are considered cost-effective are promoted for widespread use. This leads to greater use of effective technologies and greater health gain. The decision-making process in healthcare in India is complex owing to multiplicity of organizations with overlapping mandates. Often the decision-making is not evidence-based and there is no mechanism of bridging the gap between evidence and policy. Elsewhere, HTA is a frequently used tool in informing policy decisions in both resource-rich and resource-poor countries. Despite national organizations producing large volumes of research and clinical guidelines, India has not yet introduced a formal HTA programme. The incremental growth in healthcare products, services, innovation in affordable medical devices and a move towards universal healthcare, needs to be underpinned with an evidencebase which focuses on effectiveness, safety, affordability and acceptability to maximize the benefits that can be gained with a limited healthcare budget. Establishing HTA as a formal process in India, independent of healthcare providers, funders and technology producers, together with a framework for linking HTA to policy-making, would help ensure that the population gets better access to appropriate healthcare in the future.


[Minimally invasive surgical gastrostomy].
Description of a simple surgical gastrostomy technique fulfilling minimally-invasive surgery criteria and presentation of the results obtained with the same, compared with those of other surgical gastrostomies and percutaneous techniques. Patients from various wards in the Miguel Servet Teaching Hospital in Zaragoza, whether admitted or out-patients, all seen by the Hospital Nutrition Unit and where food-restricting gastrostomy is indicated. Prospective study including the first fifteen successive patients in whom a minimally-invasive surgical gastrostomy technique has been applied between January 1st, 2001, and June 30th, 2002, and in whom it was not possible, for a variety of reasons, to perform any kind of percutaneous gastrostomy. The technique was applied in the operating theatre, under local anaesthetic, using a Flexiflo 20 F gastrostomy probe and with antibiotic prophylaxis (Amoxicillin-Clavulanic Acid: 2 g i.v. pre-operatively). Patients were assessed as out-patients by the Nutrition and Surgery Unit after 10, 30 and 60 days. The procedure could be successfully completed in all cases. The mean time of the procedures duration was 45 minutes. In 5 patients, the procedure was performed without admission to hospital. The functionality of the device was 100% and it was effective from 10 days after the operation. Morbidity: 6.6%. Mortality after 60 days: 0%. This is a procedure which is safe, simple, economic and capable of being performed as an out-patient procedure, thus complying with the criteria for minimally-invasive techniques. It is complementary or an alternative to percutaneous techniques in selected cases or where these are impossible, have failed or are contraindicated.


Radiological patterns of pulmonary fungal infection in pediatric hematology and oncology patients.
To describe the radiological findings in pediatric patients with hematological or oncological diseases who also have an invasive fungal infection (IFI). This was a retrospective study of all patients with IFI admitted to a pediatric hematology and oncology hospital in Brazil between 2008 and 2014. Clinical and demographic data were collected. Chest computed tomography (CT) scans of the patients were reviewed by two independent radiologists. We evaluated the chest CT scans of 40 pediatric patients diagnosed with an IFI. Twenty-seven patients (67.5%) had nodules with the halo sign, seven (17.5%) had cavities, two (5.0%) had nodules without the halo sign, and seven (17.5%) had consolidation. The patients with the halo sign and cavities were older (123 vs. 77 months of age; p = 0.03) and had less severe disease (34% vs. 73%; p = 0.04). Ten patients had a proven IFI: with Aspergillus sp. (n = 4); with Candida sp. (n = 5); or with Fusarium sp. (n = 1). A diagnosis of IFI should be considered in children and adolescents with risk factors and abnormal CT scans, even if the imaging findings are nonspecific.


An approach to vehicle design: In-depth audit to understand the needs of older drivers.
The population of older people continues to increase around the world, and this trend is expected to continue; the population of older drivers is increasing accordingly. January 2012 figures from the DVLA in the UK stated that there were more than 15 million drivers aged over 60; more than 1 million drivers were aged over 80. There is a need for specific research tools to understand and capture how all users interact with features in the vehicle cabin e.g. controls and tasks, including the specific needs of the increasingly older driving population. This paper describes an in-depth audit that was conducted to understand how design of the vehicle cabin impacts on comfort, posture, usability, health and wellbeing in older drivers. The sample involved 47 drivers (38% female, 62% male). The age distribution was: 50-64 (n = 12), 65-79 (n = 20), and those 80 and over (n = 15). The methodology included tools to capture user experience in the vehicle cabin and functional performance tests relevant to specific driving tasks. It is shown that drivers' physical capabilities reduce with age and that there are associated difficulties in setting up an optimal driving position such that some controls cannot be operated as intended, and many adapt their driving cabins. The cabin set-up process consistently began with setting up the seat and finished with operation of the seat belt.


Developing Climate-Resilient Chickpea Involving Physiological and Molecular Approaches With a Focus on Temperature and Drought Stresses.
Chickpea is one of the most economically important food legumes, and a significant source of proteins. It is cultivated in more than 50 countries across Asia, Africa, Europe, Australia, North America, and South America. Chickpea production is limited by various abiotic stresses (cold, heat, drought, salt, etc.). Being a winter-season crop in northern south Asia and some parts of the Australia, chickpea faces low-temperature stress (0-15°C) during the reproductive stage that causes substantial loss of flowers, and thus pods, to inhibit its yield potential by 30-40%. The winter-sown chickpea in the Mediterranean, however, faces cold stress at vegetative stage. In late-sown environments, chickpea faces high-temperature stress during reproductive and pod filling stages, causing considerable yield losses. Both the low and the high temperatures reduce pollen viability, pollen germination on the stigma, and pollen tube growth resulting in poor pod set. Chickpea also experiences drought stress at various growth stages; terminal drought, along with heat stress at flowering and seed filling can reduce yields by 40-45%. In southern Australia and northern regions of south Asia, lack of chilling tolerance in cultivars delays flowering and pod set, and the crop is usually exposed to terminal drought. The incidences of temperature extremes (cold and heat) as well as inconsistent rainfall patterns are expected to increase in near future owing to climate change thereby necessitating the development of stress-tolerant and climate-resilient chickpea cultivars having region specific traits, which perform well under drought, heat, and/or low-temperature stress. Different approaches, such as genetic variability, genomic selection, molecular markers involving quantitative trait loci (QTLs), whole genome sequencing, and transcriptomics analysis have been exploited to improve chickpea production in extreme environments. Biotechnological tools have broadened our understanding of genetic basis as well as plants' responses to abiotic stresses in chickpea, and have opened opportunities to develop stress tolerant chickpea.


Success rate and safety of living donor kidney transplantation in ABO blood group incompatible relatives: A systematic review and meta-analysis.
Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis. ABO-incompatible (ABO-I) kidney transplantation relies on two principles: (i) removal of antibodies from a blood group; and (ii) inhibition of reappearance of blood group antibodies by intensifying the induction and maintenance of immunosuppression. This systematic review aimed to analyze the success and safety of ABO-I live-donor kidney transplantation. Databases, including Google Scholar, PubMed, Embase, Web of Science, and Medline were searched. Search duration was from the database establishment to December 2022. A thorough search was performed for relevant studies investigating the success and safety of ABO-I live-donor kidney transplantation. Two investigators independently extracted literature information and assessed the quality of the included studies. Heterogeneity test was performed using Cochrane's Q and chi-squared tests. All statistical analyses were performed using R software (version 4.2.1). The search for relevant literature in the five electronic databases yielded 1238 articles. Of the 1238 articles, only 15 were included. Meta-analysis of outcomes from five studies showed a survival rate of 0.93 (95% confidence interval [CI]: 0.88 to 0.97, P < 0.001) after ≥3 years, while outcomes from 12 studies revealed a short-term patient survival rate of 0.94 (95% CI: 0.92 to 0.96, P = 0.75). In contrast, long- and short-term graft survival rates were 0.89 (95% CI: 0.75 to 0.96, P < 0.001) and 0.94 (95% CI: 0.90 to 0.97, P < 0.001), respectively. Incidence rates of infectious, surgical, and medical complications were 0.31 (95% CI: 0.22 to 0.41, P < 0.001), 0.12 (95% CI: 0.05 to 0.25, P < 0.001), and 0.38 (95% CI: 0.17 to 0.66, P < 0.001), respectively. Good long- and short-term patient outcomes and graft survival rates were observed after ABO-I kidney transplantation. Similarly, the safety of performing kidney transplantations from living donors with ABO-I blood groups was established by the results of the current meta-analysis. Therefore, ABO-I live-donor kidney transplantations should be encouraged to reduce the time recipients spend on waiting lists and supplement the existing paired-exchange donor program.


Fibrin and Fibrinolysis in Cancer.
In 1878, Billroth discovered that tumor cells invest themselves in a fibrin thrombus, and he hypothesized that fibrin promotes tumor growth and invasion. Since then, many observations have supported this concept, showing that many hemostatic factors including fibrinogen, fibrin, and components of the fibrinolytic system have indeed a complex interaction with cancer growth and metastasis. Fibrin promotes cell migration by providing a matrix for tumor cell migration and by interactions with adhesive molecules and integrins. Fibrin-containing vascular endothelial growth factor promotes angiogenesis. Fibrin interacts with platelets and leukocytes, and promotes their respective carcinogenic properties. Fibrinolytic components exert different effects on tumors. Plasmin activates latent growth factors, and breaks down extracellular matrix (ECM), while urokinase plasminogen activator (uPA) and the uPA receptor (uPAR) form complexes with vitronectin and integrins to promote tumor cells to adhere to the ECM. This complex also binds the epidermal growth factor receptor on the tumor cell membrane, and signals the RAF-MEK-ERK pathway. The complex also binds to the G protein-coupled receptors leading to cell proliferation. Plasminogen activator inhibitor 1 (PAI-1) inhibits apoptosis, and increases tumor cell survival. PAI-1 also enhances cell senescence, leading to production of tumorigenic cytokines by the senescence secretome. The presence of uPA/uPAR and PAI-1 represents a strong biomarker for tumor aggressiveness and poor prognosis. Multiple attempts by blocking various carcinogenic steps have shown tumor-suppressing effects in experimental animals, but human responses are uncertain without clinical trials.


Using machine learning to predict ovarian cancer.
Ovarian cancer (OC) is one of the most common types of cancer in women. Accurately prediction of benign ovarian tumors (BOT) and OC has important practical value. Our dataset consists of 349 Chinese patients with 49 variables including demographics, blood routine test, general chemistry, and tumor markers. Machine learning Minimum Redundancy - Maximum Relevance (MRMR) feature selection method was applied on the 235 patients' data (89 BOT and 146 OC) to select the most relevant features, with which a simple decision tree model was constructed. The model was tested on the rest of 114 patients (89 BOT and 25 OC). The results were compared with the predictions produced by using the risk of ovarian malignancy algorithm (ROMA) and logistic regression model. Eight notable features were selected by MRMR, among which two were identified as the top features by the decision tree model: human epididymis protein 4 (HE4) and carcinoembryonic antigen (CEA). Particularly, CEA is a valuable marker for OC prediction in patients with low HE4. The model also yields better prediction result than ROMA. Machine learning approaches were able to accurately classify BOT and OC. Our goal is to derive a simple predictive model which also carries a good performance. Using our approach, we obtained a model that consists of just two biomarkers, HE4 and CEA. The model is simple to interpret and outperforms the existing OC prediction methods. It demonstrates that the machine learning approach has good potential in predictive modeling for the complex diseases.


Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: a role for mechanoreceptors.
Previous evidence suggests that the heart rate (HR) increase observed with isometric exercise is dependent on different afferent mechanisms to those eliciting the increase in blood pressure (BP). Central command and muscle metaboreceptors have been shown to contribute to this differential effect. However, in experimental animals passive stretch of the hindlimb increases HR suggesting that small fibre mechanoreceptors could also have a role. This has not been previously shown in humans and was investigated in this study. Healthy human volunteers were instrumented to record BP, ECG, respiration, EMG of rectus femoris and gastrocnemius and contraction force of triceps surae. Voluntary isometric contraction of triceps surae elicited a significant HR change in the first three respiratory cycles at 40 % of maximum voluntary contraction whereas BP did not change significantly until after 30 s. This suggests that different mechanisms are involved in the initiation of the cardiovascular changes. Sustained passive stretch of triceps surae for 1 min, by dorsiflexion of the foot, caused a significant (P < 0.05) increase in HR (5 +/- 2.6 beats min(-1)) with no significant change in BP. A time domain measure of cardiac vagal activity was reduced significantly during passive stretch from 69.7 +/- 12.9 to 49.6 +/- 8.9 ms. Rapid rhythmic passive stretch (0.5 Hz for 1 min) was without significant effect suggesting that large muscle proprioreceptors are not involved. We conclude that in man small fibre muscle mechanoreceptors responding to stretch, inhibit cardiac vagal activity and thus increase HR. These afferents could contribute to the initial cardiac acceleration in response to muscle contraction.


Silver-Catalyzed Dehydrogenative Synthesis of Carboxylic Acids from Primary Alcohols.
A simple silver-catalyzed protocol has been developed for the acceptorless dehydrogenation of primary alcohols into carboxylic acids and hydrogen gas. The procedure uses 2.5 % Ag2 CO3 and 2.5-3 equiv of KOH in refluxing mesitylene to afford the potassium carboxylate which is then converted into the acid with HCl. The reaction can be applied to a variety of benzylic and aliphatic primary alcohols with alkyl and ether substituents, and in some cases halide, olefin, and ester functionalities are also compatible with the reaction conditions. The dehydrogenation is believed to be catalyzed by silver nanoparticles that are formed in situ under the reaction conditions.


Low Heart Rate Variability in a 2-Minute Electrocardiogram Recording Is Associated with an Increased Risk of Sudden Cardiac Death in the General Population: The Atherosclerosis Risk in Communities Study.
Low heart rate variability (HRV) has been linked to increased total mortality in the general population; however, the relationship between low HRV and sudden cardiac death (SCD) is less well-characterized. The goal of this study was to evaluate the relationship between low HRV and SCD in a community-based cohort. Our cohort consisted of 12,543 participants from the Atherosclerosis Risk in Communities (ARIC) study. HRV measures were derived from 2-minute electrocardiogram recordings obtained during the baseline exam (1987-89). Time domain measurements included the standard deviation of all normal RR intervals (SDNN) and the root mean squared successive difference (r-MSSD). Frequency domain measurements included low frequency power (LF) and high frequency (HF) power. During a median follow-up of 13 years, 215 SCDs were identified from physician adjudication of all coronary heart disease deaths through 2001. In multivariable adjusted Cox proportional hazards models, each standard deviation decrement in SDNN, LF, and HF were associated with 24%, 27% and 16% increase in SCD risk, respectively. Low HRV is independently associated with increased risk of SCD in the general population.


Changes in the plasma activities of protein C and protein S during pregnancy.
The objective of the study was to determine the changes in the plasma activities of protein C and protein S that occur during normal pregnancy In this prospective cross-sectional study, plasma activities of protein C and protein S were measured in 32 normal pregnant women in the first, second and third trimester and 6 weeks after delivery There was a significant fall in protein C and protein S activities during normal pregnancy compared with the post-puerperal period. The activities of protein C and protein S also gradually decreased throughout pregnancy (p < 0.01). Increasing plasma volume during normal pregnancy and its dilutional effect might play some role in the low activities of protein S observed. The normal falls in protein S and protein C activities make it difficult to diagnose protein S and C deficiency during pregnancy. Based on our findings, if a woman has a thromboembolic event during pregnancy, testing for a definitive diagnosis of protein C or protein S deficiency or functional failure should be delayed until at least 6 weeks postpartum.


Bivalve metallothionein as a biomarker of aquatic ecosystem pollution by trace metals: limits and perspectives.
Owing to their induction by metals metallothioneins (MTs) have been proposed as biomarkers of the metallic contamination of the environment. On the other hand, bivalves are regarded as very convenient bioindicators of the aquatic ecosystems and an extensive literature has been dedicated to their response to metals. Among studies supporting the involvement of MTs in metal detoxification some discrepancy appears due to inter- and intra-specific variations, or to heterogeneous exposure conditions. A lesser number of papers are dealing with the use of metallothionein levels as biomarkers, and sometimes they evidence that natural factors influencing metallothionein synthesis have to be taken into account before final conclusions can been drawn. Moreover, there is still a large number of non-intercalibrated protocols used to quantify amounts of metallothioneins in organisms. As comparisons are necessary to assess the relative abundance of metallothioneins in a studied species, more work has to be completed before such comparisons could be validated. In the present paper we wish to establish the limits of the use of mollusc metallothioneins as a biomarker of aquatic ecosystem contamination by trace metals, using published and recent data as support for our conclusions and perspectives.


Self-perceived risk of HIV infection and attitudes about preexposure prophylaxis among sexually transmitted disease clinic attendees in South Carolina.
Several domestic and international trials of the use of preexposure prophylaxis (PrEP) for HIV prevention are ongoing among groups at high risk for HIV infection. The objective of this cross-sectional study was to assess self-perceived risk of HIV infection and attitudes about PrEP among 405 sexually transmitted disease (STD) clinic attendees in South Carolina. Self-percieved risk of HIV infection and attitudes about PrEP were assessed using three questions from a self-administered survey. Ordinal logistic regression and logistic regression were used to evaluate differences in risk perception for HIV infection and attitudes about the use of PrEP among risk groups. Compared to heterosexual participants, homosexual participants were significantly more likely to have knowledge of PrEP (odds ratio [OR]=6.7, 95% confidence interval [CI]: 1.70-26.1). Compared to those participants who had 1 sexual partner in the past 3 months, individuals who had 2 to 4 sexual partners in the past 3 months were approximately 2.35 times as likely to have a lower level of agreement with the statement "I believe I am at risk of getting HIV" (p=0.0003). Compared to female participants, respondents who were male were approximately 2.8 times as likely to have a lower level of agreement with the statement "If I had to it would be very difficult for me (or my partner) to both use condoms and take daily pills to prevent HIV infection" (p<0.0001). These results suggest the need for the creation of PrEP implementation programs that are tailored to self-perceived risk perception, age, and gender.


MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion.
Metastasis remains a significant challenge in treating cancer. A better understanding of the molecular mechanisms underlying metastasis is needed to develop more effective treatments. Here, we show that human breast tumor biomarker miR-30c regulates invasion by targeting the cytoskeleton network genes encoding twinfilin 1 (TWF1) and vimentin (VIM). Both VIM and TWF1 have been shown to regulate epithelial-to-mesenchymal transition. Similar to TWF1, VIM also regulates F-actin formation, a key component of cellular transition to a more invasive mesenchymal phenotype. To further characterize the role of the TWF1 pathway in breast cancer, we found that IL-11 is an important target of TWF1 that regulates breast cancer cell invasion and STAT3 phosphorylation. The miR-30c-VIM/TWF1 signaling cascade is also associated with clinical outcome in breast cancer patients.


[Bioethical views of Abu Bakr Al-Razi (Rhazes)].
Abu Bakr Muhammad ibn Zakariya ar-Razi, who is known in Europe as Razes, was born in 865 year in Ree city. A lot of his books were translated in Latin; his books have served as guidance for physicians during centuries. However, "the book about spiritual medicine" is the most popular. In this book in details presented ethical views of the scientist. The book discusses about the significance improving spiritual quality of person. In his meaning of "spiritual medicine" is seen a synonym to the notion-"medical ethics".


Neurovascular compression syndrome of the brain stem with opsoclonus-myoclonus syndrome combined with vestibular paroxysmia and autonomic symptoms.
We describe a rare case of neurovascular compression syndrome (NVCS) of the brain stem and opsoclonus-myoclonus syndrome (OMS) complicated with vestibular paroxysmia (VP) and autonomic symptoms. Moreover, we discuss the case with respect to the available information in medical literature. A 36-year-old man with vertigo and nausea had difficulty standing, and was transported by an ambulance to our hospital. He had VP, opsoclonus, cervical myoclonus, anxiety, and restless legs syndrome. Magnetic resonance imaging at hospitalization showed that the dolichoectatic vertebral artery was in contact with the postero-lateral side of the pontomedullary junction. He was diagnosed with NVCS of the brain stem (most likely of the input to the vestibular nucleus) associated with contact with the dolichoectatic vertebral artery. Combination therapy using multiple antiepileptic drugs, such as low-dose carbamazepine, clonazepam, and lacosamide, improved his clinical symptoms. He was finally able to walk and was discharged on day 42 after admission. He is being routinely followed-up since then. Further research is needed to confirm the validity of the combination therapy.


Pelvic Exenteration for Advanced Nonrectal Pelvic Malignancy.
To determine factors associated with outcomes following pelvic exenteration for advanced nonrectal pelvic malignancy. The PelvEx Collaborative provides large volume data from specialist centers to ascertain factors associated with improved outcomes. Consecutive patients who underwent pelvic exenteration for nonrectal pelvic malignancy between 2006 and 2017 were identified from 22 tertiary centers. Patient demographics, neoadjuvant therapy, histopathological assessment, length of stay, 30-day major complication/mortality rate were recorded.The primary endpoints were factors associated with survival. The secondary endpoints included the difference in margin rates across the cohorts, impact of neoadjuvant treatment on survival, associated morbidity, and mortality. One thousand two hundred ninety-three patients were identified. 40.4% (n = 523) had gynecological malignancies (endometrial, ovarian, cervical, and vaginal), 35.7% (n = 462) urological (bladder), 18.1% (n = 234) anal, and 5.7% had sarcoma (n = 74).The median age across the cohort was 63 years (range, 23-85). The median 30-day mortality rate was 1.7%, with the highest rates occurring following exenteration for recurrent sarcoma or locally advanced cervical cancer (3.3% each). The median length of hospital stay was 17.5 days. 34.5% of patients experienced a major complication, with highest rate occurring in those having salvage surgery for anal cancer.Multivariable analysis showed R0 resection was the main factor associated with long-term survival. The 3-year overall-survival rate for R0 resection was 48% for endometrial malignancy, 40.6% for ovarian, 49.4% for cervical, 43.8% for vaginal, 59% for bladder, 48.3% for anal, and 48.1% for sarcoma. Pelvic exenteration remains an important treatment in selected patients with advanced or recurrent nonrectal pelvic malignancy. The range in 3-year overall survival following R0 resection (40%-59%) reflects the diversity of tumor types.


Effectiveness and tolerability of dietary supplementation with a combination of omega-3 polyunsaturated fatty acids and antioxidants in the treatment of dry eye symptoms: results of a prospective study.
We assessed the effectiveness and tolerability of a dietary supplement based on the combination of omega-3 essential fatty acids and antioxidants on dry eye-related symptoms. A total of 905 patients (72% women, median age 60 years) with dry eye syndrome and using artificial tears to relieve symptoms participated in an open-label prospective intervention study. They were recruited during a routine ophthalmological appointment. Patients were instructed to take three capsules/day of the nutraceutical formulation (Brudysec® 1.5 g) for 12 weeks. Dry eye symptoms (categorized as 0, none; 1, mild; 2, moderate; and 3, severe) included scratchy and stinging sensation in the eyes, eye redness, grittiness, painful eyes, tired eyes, grating sensation, and blurry vision. The mean intensity of dry eye symptoms varied from 1.1 (± standard deviation [SD] 0.9) for painful eyes to 2.0 (0.9) for grittiness, with a mean value of 11.9 (4.8) for all symptoms together. At week 12, all individual symptoms improved significantly (P<0.001). The mean value for all symptoms together decreased from a mean value of 11.9 (± SD 4.8) at baseline to 6.8 (± SD 4.5) after 12 weeks of treatment (P<0.001). There was a decrease in the percentage of patients in which dry eye symptoms predominated nearly all the time (53.5% versus 34.1%). A total of 68.1% of patients reported better tolerance to contact lenses after treatment. The mean number of daily instillations of artificial tears also decreased significantly (3.8 [± SD 1.6] versus 3.3 [± SD 1.6], P<0.001). A total of 634 patients (70.1%) did not report any adverse events. In the remaining patients with adverse events, the most frequent was fish-tasting regurgitation in 13.5% of cases, followed by nausea in 4.9%, diarrhea in 1.3%, and vomiting in 0.3%. Dietary supplementation with a combination of omega-3 essential fatty acids and antioxidants was an effective treatment for dry eye.


Complement in atherosclerosis: friend or foe?
Atherosclerosis is a chronic inflammatory disease and the complement system plays a central role in innate immunity. Increasing evidence exists that the complement system is activated within atherosclerotic plaques. However, the role of complement in atherogenesis is not fully understood. Whereas complement activation by the classic and lectin pathway may be protective by removing apoptotic cells and cell debris from atherosclerotic plaques, activation of the complement cascade by the alternative pathway and beyond the C3 convertase with formation of anaphylatoxins and the terminal complement complex may be proatherogenic and may play a role in plaque destabilization leading to its rupture and the onset of acute cardiovascular events. In this review article we present evidence for complement activation within atherosclerotic plaques and we discuss recent data derived from experimental animal models that suggest a dual role of complement in the development of the disease. In addition, we summarize the role of complement components as biomarkers for cardiovascular disease.


Clinical review of attenuation-corrected cardiac SPECT.
Rather than the introduction of a heralded technologic advancement in cardiac SPECT imaging challenging the accuracy of PET perfusion imaging, the commercial introduction of attenuation correction has been met with at least as many negative as positive reports. Some studies have reported significant improvements in specificity or specificity and sensitivity, especially for high-risk patterns of coronary artery disease; others have reported no improvement or a decrease in accuracy resulting from the introduction of troublesome artifacts. Although this review has attempted to emphasize the positive aspects of attenuation-corrected cardiac SPECT perfusion imaging and the potential for improved patient care it may provide, several negative reports continue to appear. Still there has been sufficient positive data reported to suggest that with fully developed, accurate, and robust correction methods, significant gains in SPECT assessments of the presence and extent of CHD, patient risk, and myocardial viability can be anticipated. Ultimately attenuation correction for cardiac SPECT should have a positive impact on the management of patients with coronary artery disease with important savings in lives and health care dollars.


Self-reported knowledge and approaches toward complementary and alternative medicine among physicians dealing with allergic diseases.
Considering the popularity of Complementary and Alternative Medicine (CAM) in allergic patients, physicians involved in allergic patients' care need to be aware of CAM. To assess self-reported knowledge, attitude and approach to CAM of physicians who deal with allergic patients, a total of 500 structured questionnaires were distributed to physicians who participated in "Turkish National Society of Allergy and Clinical Immunology Congress-2009". For the questionnaires handed out, 242 (48.4%) physicians (median age 36.0 years, range 25-64 years) responded; 22.4% were fellows in training and 48.5% were residents. The main specialties were pediatrics (49.3%), and pulmonology (36.8%); half were either specialists or training in allergy and one-quarter (25.6%) referred patients to CAM. Asthma (42.1%) and chronic urticaria (28.9%) were the most common CAM referral diseases. Referred therapies were herbal (10.3%) and diet-based medicine (7.4%). The differences between physicians in terms of age, gender, experience in medicine, and specialty/allergy subspecialty were not statistically significant (p = 0.01). Affiliation to a university hospital was significantly associated with no CAM referral vs. affiliation in a state/private hospital or private practice. Academic degree and reported level of knowledge negatively/positively affected attitudes toward CAM, respectively. More than half of the respondents (68.8%) reported lack of or insufficient information about CAM, while 58.7% of physicians desired CAM education. This first report on physicians involved in allergic patients' care shows that they are reluctant to refer for CAM therapies. A minority believes that they have enough knowledge, and most are interested in continuing medical education on CAM. Considering physicians' interest and tendency to communicate significantly with their patients about CAM when they feel that they have sufficient knowledge and popularity of CAM among patients, training possibilities should be created to improve physicians' education in this field.


Quercetin improves pancreatic cancer chemo-sensitivity by regulating oxidative-inflammatory networks.
Chemotherapy is the main method for controlling pancreatic cancer metastasis but the prevalent chemotherapy resistance limits its utilization. The response of oxidation and inflammation often promotes pancreatic cancer progression and chemo-resistance. It is critical to explore the potential natural products with few side effects to control inflammatory responses and understand the related mechanisms. Quercetin is a flavonoid widely found in numerous vegetables, fruits, and foods and is thought to have antioxidant and anti-inflammatory properties, which may be associated with improvement of chemotherapy sensitivity during pancreatic cancer treatment. Quercetin may sensitize pancreatic cancer cells to the chemotherapeutic agents, including bromodomain and extraterminal domain inhibitors (BETI), daunorubicin, gemcitabine, sulforaphane, doxorubicin, and tumor necrosis factor-related signaling apoptosis-inducing ligand (TRAIL). Meanwhile, during the chemo-resistance therapy, many signaling molecules are involved with toll-like receptor 4 (TLR4)-mediated oxidative and inflammatory pathway. The effects of quercetin on other oxidative and inflammatory pathways were also explored. Quercetin may exert antitumor activity during the prevention of pancreatic cancer progression by regulating oxidative and inflammatory networks, which can promote immune escape of cancer cells by inducing immunosuppressive cytokines. Studying these patterns will help us to better understand the functional role of quercetin in the improvement of pancreatic cancer chemo-sensitivity. PRACTICAL APPLICATIONS: Chemotherapy is the major way for treating pancreatic cancer metastasis but the prevalent chemotherapy resistance caused by oxidative and inflammatory responses limits its utilization. It is necessary to explore the potential natural products with few side effects to prevent the oxidative and inflammatory responses. Quercetin is a flavonoid widely found in numerous vegetables, fruits, and foods and is thought to have antioxidant and anti-inflammatory properties, which may be associated with improvement of chemotherapy sensitivity of pancreatic cancer treatment by sensitizing pancreatic cancer cells to various chemotherapeutic agents via the regulation of oxidative and inflammatory networks. Studying these patterns will help us to better understand the functional role of quercetin in the improvement of pancreatic cancer chemo-sensitivity.


Cyclic strain and motion control produce opposite oxidative responses in two human endothelial cell types.
The phenotype of endothelial cells (ECs) is specific to the vascular bed from which they originate. To examine how mechanical forces alter the phenotype of different ECs, we compared the effects of cyclic strain and motion control on reactive oxygen species (ROS) production and metabolism and cell adhesion molecule expression in human umbilical vein endothelial cells (HUVEC) vs. human aortic endothelial cells (HAEC). HUVEC and HAEC were subjected to cyclic strain (10% or 20%, 1 Hz), to a motion control that simulated fluid agitation over the cells without strain, or to static conditions for 24 h. We measured H(2)O(2) production with dichlorodihydrofluorescein acetate and superoxide with dihydroethidium fluorescence changes; superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities spectrophotometrically; and vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 protein expression with Western blot analyses. HUVEC under cyclic strain showed 1) higher intracellular H(2)O(2) levels, 2) increased SOD, catalase, and GPx activities, and 3) greater VCAM-1 and ICAM-1 protein expression, compared with motion control or static conditions. However, in HAEC, motion control induced higher levels of ROS, enzyme activities associated with ROS defense, and VCAM-1 and ICAM-1 expression than cyclic strain. The opposite responses obtained with these two human EC types may reflect their vessels of origin, in that HAEC are subjected to higher cyclic strain deformations in vivo than HUVEC.


A case of ovarian paragonimiasis mimicking ovarian carcinoma.
The purpose of this report is to describe ovarian paragonimiasis, a rare form of lung fluke infestation, mimicking ovarian cancer. A 47-year-old Thai woman presented with a pelvic mass. Imaging suggested ovarian cancer with pulmonary and hepatic metastases. She was scheduled for complete surgical staging. However, a frozen section revealed Paragonimus eggs in the enlarged ovarian mass. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed instead of complete staging. All other lesions were also proven later to be Paragonimus infestation. Postoperative treatment with antiparasitic drugs resulted in dramatic improvement, with nearly complete resolution of all lesions at 4 months of follow-up. This is an unusual case of ovarian paragonimiasis mimicking ovarian cancer, which is instructive and informative for differential diagnoses of pelvic masses.


Concomitant autoantibodies in newly diagnosed diabetic children with transient celiac serology or proven celiac disease.
We previously demonstrated that children with Type 1 Diabetes Mellitus (T1DM) may have transiently elevated tissue transglutaminase antibodies (TTG) on a gluten-containing diet. This study aimed to examine if the presence of autoantibodies in newly diagnosed T1DM differs between patients with celiac disease and those with transient celiac serology. Forty children were identified who had been diagnosed with T1DM between 2003 and 2009 and who had elevated serum IgA-TTG antibody levels at diagnosis. Blood samples were collected for measurement of insulin (IA-2A) antibodies, islet cell antigen (ICA) antibodies, glutamic acid decarboxylase (GAD) antibodies, thyroglobulin (TgAb) antibodies, and thyroid peroxidase (TPO) antibodies. Children diagnosed with celiac disease (CD; group 1, n=23) and children in whom TTG antibody levels spontaneously normalized over time (group 2, n=17) were compared. No significant differences in positivity rates between groups 1 and 2 were found for any of the autoantibodies tested. The respective findings were as follows: IA-2A 50% and 47.1% (p=0.855); ICA 77.3% and 76.5% (p=0.953); GAD 27.3% and 52.9% (p=0.102). Thyroid antibodies were found positive in a limited number of patients: TgAb 4.5% and 11.8%; TPO 4.5% and 11.8%. In addition, antibody titer levels did not differ significantly for all autoantibodies. Difference in occurrence of clinical or subclinical thyroid disease did not reach significance (4.3% vs. 29.4%; p=0.07). Age was positively correlated with the presence of thyroglobulin and thyroid peroxidase antibodies, and negatively correlated with the presence of insulin antibody. Neither the number of concomitant autoantibodies nor their titers in newly diagnosed T1DM differed between patients with proven CD and those with transient TTG serology.