Treating asthma as a neuroelectrical disorder.
The trend in asthma therapy for the last two decades has been based on the suppression of inflammation and bronchodilation via adrenergic agonism or cholinergic antagonism. These strategies help to control asthmatic symptoms but do not lead to a cure. Substantial populations of patients may still have poorly managed symptoms and suffer a decline in quality of life due to the disease. Reversible airflow obstruction and nonspecific airway reactivity are the key features of asthma. Inflammatory changes do not correlate always with symptoms in asthma patients. It is our opinion that the primary defect in asthma is cell membrane excitation-bronchoconstriction and reactivity-rather than inflammation. Our research, clinical experience and the accumulated evidence from medical literature strongly suggest that controlling other excitatory mechanisms such as voltage-gate sodium channel and glutamate receptors in the central nervous system and lung tissue could lead to more effective and safer strategies for asthma prevention and treatment.


Celiac Autoimmunity Is Associated With Lower Blood Pressure and Renal Risk in Type 1 Diabetes.
Though the long-term consequences of celiac disease (CD) in type 1 diabetes are unclear, CD has been associated with increased prevalence of end-stage renal disease (ESRD) independent of type 1 diabetes. We evaluated whether celiac autoimmunity is related to the cumulative incidence of microalbuminuria [albumin excretion rate (AER) 20 to 200 µg/min], macroalbuminuria (AER >200 µg/min), and ESRD. In the prospective follow-up of the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset type 1 diabetes, 618 participants were screened for tissue transglutaminase (tTG) antibodies with a clinical assay. Nephropathy outcomes were determined at 25 years of diabetes duration. Overall, the 33 subjects (5.3%) with strongly positive tTG levels (≥3 times the upper limit of normal) or a reported clinical history of CD had lower baseline blood pressure and lipid values. At 25 years of diabetes duration, a lower cumulative incidence of macroalbuminuria in strongly positive subjects compared with those with negative serology (3.6% vs 30.0%; P = 0.003) remained significant after adjustment for age, HbA1c, lipid measures, and blood pressure (adjusted P = 0.004). No considerable differences between these subjects and tTG-negative groups were found for microalbuminuria (40.0% vs 57.1%) or ESRD (0 vs 4.1%). These findings show that strongly positive celiac autoimmunity status in individuals with childhood-onset type 1 diabetes is associated with lower baseline blood pressure and cholesterol measurements as well as lower macroalbuminuria risk after 25 years of type 1 diabetes duration with no increase in the risk of microalbuminuria or ESRD.


Psychological implications of abortion: a longitudinal study on two cohorts of women who recur to elective and therapeutic abortion.
The aim of this work was to identify risk predictors of a negative psychological outcome among personal, situational and systemic characteristics of women who choose to interrupt a pregnancy by elective (e.g., not feeling ready for giving birth) or therapeutic means (e.g., fetal abnormalities). A prospective study on two cohorts were conducted and focused on a group of women: the first recurred to elective abortion (VTP) (n=20) and the second recurred to therapeutic abortion (TTP) (n=30). The psychological distress was measured before and after abortion through the administration of two psychometric tests: SCL-90-r and CES-D. Dependent samples t-test was used to evaluate the tendency of the two cohorts' mean scores before and after abortion; repeated measures analysis of variance (ANOVA) was used to analyze the variance of mean scores of subgroups isolated for variables of interest before and after abortion. After the termination of pregnancy, in VTP a significant decrease between t-0 and t-1 mean score (p<0.05) was observed in all SCL-90-r's global scores and subscales: GSI (p=0.036), PST (p=.031), PSDI (p=0.004), SOM (p=0.009), DEP (p=0.032), ANX (p=0.036) and even in CES-D score of DEP (p=0.017) and SOM (p=0.011) subscales. In TTP a relevant decrease was found in SCL-90's SOM (p=0.023) and ANX, (p=0.016) subscales and in CES-D total score (p=0.020), POS (p=0.014) and SOM (p=0.09)subscales. In VTP group presence of partner support and absence of relational problems resulted as protective factors from a worse outcome. The results of this study suggest that, following an induced abortion, women experienced a significant improvement in the mood state compared to the period before the event; poor partner support and relational problems related with the abortion emerged as risk factors for a significantly worse psychological outcome compared to other causes interruption of pregnancy.


American canine hepatozoonosis.
American canine hepatozoonosis (ACH) is a tick-borne disease that is spreading in the southeastern and south-central United States. Characterized by marked leukocytosis and periosteal bone proliferation, ACH is very debilitating and often fatal. Dogs acquire infection by ingesting nymphal or adult Gulf Coast ticks (Amblyomma maculatum) that, in a previous life stage, ingested the parasite in a blood meal taken from some vertebrate intermediate host. ACH is caused by the apicomplexan Hepatozoon americanum and has been differentiated from Old World canine hepatozoonosis caused by H. canis. Unlike H. canis, which is transmitted by the ubiquitous brown dog tick (Rhipicephalus sanguineus), H. americanum is essentially an accidental parasite of dogs, for which Gulf Coast ticks are not favored hosts. The geographic portrait of the disease parallels the known distribution of the Gulf Coast tick, which has expanded in recent years. Thus, the endemic cycle of H. americanum involves A. maculatum as definitive host and some vertebrate intermediate host(s) yet to be identified. Although coyotes (Canis latrans) are known to be infected, it is not known how important this host is in maintaining the endemic cycle. This review covers the biology of the parasite and of the tick that transmits it and contrasts ACH with classical canine hepatozoonosis. Clinical aspects of the disease are discussed, including diagnosis and treatment, and puzzling epidemiologic issues are examined. Brief consideration is given to the potential for ACH to be used as a model for study of angiogenesis and of hypertrophic osteoarthropathy.


Technology use and clinical outcomes in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes.
Technology use has been shown to improve diabetes control, but minority youths tend to have low rates of technology use and exhibit suboptimal glycemic control. We examined the impact of continuous glucose monitors (CGM) and continuous subcutaneous insulin infusion (CSII) on glycemic control in a racial-ethnic minority cohort of children and adolescents with type 1 diabetes (T1D). A cross-sectional study was conducted among 140 pediatric T1D patients seen at a multidisciplinary clinic. From January to November 2022, data on demographics and glycated hemoglobin (HbA1c) levels were collected. Patients were categorized as technology (CGM, CSII, or both) or non-technology users (finger stick meter (FS) and multiple daily injections (MDI)). The majority identified as Hispanic (79 %) and had public health insurance (71 %). Sixty-nine percent used technology. Compared with non-technology users, technology users had significantly lower mean HbA1c levels (9.60 vs. 8.40 %, respectively) (p=0.0024), though no group (CGM + CSII, CGM + MDI, FS + CSII, and FS + MDI) achieved a mean HbA1c level of <7.0 %. Regarding minority status, no significant differences in mean HbA1c levels existed between Hispanics and Blacks in the CGM + MDI and FS + CSII groups (p=0.2232 and p=0.9224, respectively). However, there was a significant difference in mean HbA1c levels between Hispanic and Black non-technology users (9.19 vs. 11.26 %, respectively) (p=0.0385). Technology users demonstrated better glycemic control than non-technology users. Further research is needed to investigate factors affecting glycemic control in minority youths with T1D.


A radiological study of morphology and growth in the human fetal colon.
A radiological study has been made of the colon in 64 human fetuses between 11 and 20 weeks gestation (64-160 mm crown rump (CR) length). A dynamic picture of colon development was obtained from analysis of the radiographs. The findings challenge textbook descriptions, but can be interpreted in terms of the ultimate morphology of the colon. According to the morphology of the proximal (pre-splenic) part of the colon, there are three types of colon. In Type 1 it lies transversely, in Type 2 it is oblique in direction, and Type 3 has a postnatal form with ascending and transverse elements. Although the Type 1 predominates in smaller fetuses and the type 3 is most common in larger fetuses, there is some overlap in their distribution. The ileocaecal junction does not descend, but actually slightly ascends as the fetus grows. The splenic flexure grows in a distinctly cranial direction, and at almost three times the rate of the ileocaecal junction. Thus, as the fetus develops, the ileocaecal junction and splenic flexure grow further apart, and this determines the change from a Type 1 to a Type 2 colon. The divergence of the ileocaecal junction and splenic flexure appears to be related to different rates of growth in the colon, the distal (post-splenic) part growing almost half as fast again as the proximal (pre-splenic) part. The more mature (Type 3) form of colon appears to result from conversion of the Type 2 following early adhesion between the proximal colon and the second part of the duodenum.


[Effects of Different Pretreatment Methods on the Phenylketonuria Screening Model by FTIR/ATR Spectroscopy].
To establish a phenylketonuria screening model by FTIR/ATR spectroscopy, and to compare the effects of different pretreatment methods, such as baseline correction, smoothing, derivation, Fourier deconvolution, on the model quality. A consensus partial least squares regression method (cPLS) was used to build the quantitative model of phenylalanine in dried blood spots. The effects of different pretreatment methods on the model performance were investigated, using the correlation coefficient (r), root mean square error of prediction (RMSEP), mean relative error (MRE) and predictive accuracy (Acc). The nine-point smoothing coupled with the first differential was found to perform the best. Compared with the model by the original spectra, its r, RMSEP, MRE and Acc were improved from 0. 822 7, 115. 8, 0. 395 and 94. 6 to 0. 889 9, 102. 2, 0. 286 and 100, respectively. With the advantages of fast speed, easy process, no reagents consumption and environmental protection, the present method is expected to become a simple and green technology for rapidly screening the neonatal phenylketonuria in a large population.


Effectiveness of Vitamin C Solution in Reducing Adverse Reactions Caused by Painless Lugol Chromoendoscopy: A Multicenter Randomized Controlled Trial.
The purpose of this study was to evaluate the effectiveness of vitamin C solution (VCS) in reducing adverse reactions caused by painless Lugol chromoendoscopy. Lugol chromoendoscopy is an effective method for screening superficial esophageal squamous cell carcinoma, although Lugol iodine solution (LIS) causes mucosal irritation. In 4 hospitals in China, patients were randomized and divided into a distilled water (DW) group, an sodium thiosulfate solution (STS) group and a VCS group. Patients' esophageal mucosal surfaces were stained with either 1.2% or 0.5% LIS and then sprayed with DW, STS, or VCS at various concentrations. For the current randomized study, 1610 patients were enrolled in the 1.2% LIS group and 1355 patients were enrolled in the 0.5% LIS group. In addition, 150 patients were enrolled to assess the discoloration effect. The primary outcome for evaluation was the incidence of acute or late adverse reactions after Lugol iodine staining. The secondary outcome for evaluation was the discoloration effect on esophageal iodine-stained mucosa. VCS significantly reduced the occurrence of acute adverse reactions due to staining from 1.2% LIS. The effect of VCS was similar to that of STS but better than that of DW ( P <0.05). Regarding 0.5% LIS staining, VCS reduced the incidence of acute adverse reactions and heartburn within 1 week ( P <0.05). Both VCS and STS had similar effects. In addition, compared with spraying NS, VCS caused rapid decolorization of iodine-stained esophageal mucosa. After 120 seconds of deiodination, the color of the esophageal mucosa faded by 90%, which is similar to the results seen in the STS group. This contrasts with the results seen in the DW group, which showed fading by only 50.97% ( P <0.05). VCS can effectively reduce adverse reactions caused by different concentrations of LIS, indicating its important clinical application in the screening of superficial esophageal squamous cell carcinoma.


Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment.
The amyloidoses are a group of systemic diseases characterized by organ deposition of misfolded protein fragments of diverse origins. The natural history of the disease, involvement of other organs, and treatment options vary significantly based on the protein of origin. In AL amyloidosis, amyloid protein is derived from immunoglobulin light chains, and most often involves the kidneys and the heart. ATTR amyloidosis is categorized as mutant or wild-type depending on the genetic sequence of the transthyretin (TTR) protein produced by the liver. Wild-type ATTR amyloidosis mainly involves the heart, although the reported occurrence of bilateral carpal tunnel syndrome, spinal stenosis and biceps tendon rupture in these patients speaks to more generalized protein deposition. Mutant TTR is marked by cardiac and/or peripheral nervous system involvement. Cardiac involvement is associated with symptoms of heart failure, and dictates the clinical course of the disease. Cardiac amyloidosis can be diagnosed noninvasively by echocardiography, cardiac MRI, or nuclear scintigraphy. Endomyocardial biopsy may be needed in the case of equivocal imaging findings or discordant data. Treatment is aimed at relieving congestive symptoms and targeting the underlying amyloidogenic process. This includes anti-plasma cell therapy in AL amyloidosis, and stabilization of the TTR tetramer or inhibition of TTR protein production in ATTR amyloidosis. Cardiac transplantation can be considered in highly selected patients in tandem with therapy aimed at suppressing the amyloidogenic process, and appears associated with durable long-term survival.


Photoselective potassium-titanyl-phosphate laser vaporization of the benign obstructive prostate: observations on long-term outcomes.
We present long-term observations on photoselective vaporization of the prostate in a prospectively studied cohort of men with obstructive benign prostatic hyperplasia. Obstructive benign prostatic hyperplasia in 94 men was treated with transurethral near contact vaporization with potassium-titanyl-phosphate laser with the patient under general or spinal anesthesia. Baseline characteristics, perioperative data, postoperative outcomes and adverse events were recorded. Mean prostate volume was 45 ml (range 13 to 136). Mean lasing time was 47 minutes (range 10 to 99), and there was minimal blood loss and no evidence of fluid absorption. All 94 men were outpatients and all but 1 became catheter-free in less than 24 hours. Baseline mean American Urological Association symptom index score was 22, quality of life score 4.5, peak urinary flow rate 7.8 ml per second and post-void residual urine volume 197 ml. After surgery percentage changes from baseline in mean values of these parameters, reflecting significant (p <0.0001) improvement at 1, 2, 3 and 5 years, ranged from 83% to 88%, 86% to 90%, 170% to 252% and 76% to 89%, respectively. Complications were mild, and included transient dysuria (6%), delayed hematuria (3%), bladder neck contracture (2%) and 2-day retention (1%). No patient had incontinence or newly developed impotence, but up to 26% of the sexually active men experienced retrograde ejaculation. Postoperatively, low stage prostate cancer was detected in 5% of the patients. : Despite limitations our long-term experience and the literature suggest that significant improvements in symptomatic and urodynamic outcomes of photo-selective vaporization of the prostate are achievable and sustainable.


Minimally invasive spinal surgery for the management of symptomatic spinal metastasis.
Symptomatic metastatic spinal disease is on the increase. Minimally invasive spinal surgery has been associated with a lower complication profile when compared to traditional open methods; however there is paucity of literature evaluating the place of percutaneous pedicle screw fixation (PPSF) in the management of spinal metastases. The purpose of the study is to assess the efficacy of Minimally Invasive Spine Surgery (MISS) using PPSF with or without mini-decompression in the management of symptomatic spinal metastases. This is a single institution prospective study of 51 consecutive patients with metastatic spinal disease treated with PPSF. Patients presenting with pathological compression fractures and mechanical instability had PPSF, and those with radiological and/or clinical metastatic spinal cord compression (MSCC) underwent an additional mini-decompression. Data collected included patient demographics, Karnofsky's performance status (KPS), pain scores and neurology. Other data included number and location of involved levels, number of instrumented levels, blood loss, accuracy of screw placement and complications. Of the 51 patients, 49 could be successfully treated with MISS (26 females and 23 males). 26 patients (55%) required a mini-decompression. 27 patients (55%) had improvement in KPS by at least 10 points (p < 0.0005). Only 2 patients (4%) had a worsening of KPS, due to other coexisting problems. Six of the 13 patients improved their neurology by one Frankel grade following surgery and 95% reported improvement in pain. Mean blood loss was 92mls for the fixation only group and 222mls for those requiring mini-decompression, with no other differences between these two surgical groups. Screw positioning was excellent in 91%, with 98% having uncompromised bony hold. Only two patients required revision surgery for aseptic loosening. MISS using PPSF is a safe and reproducible technique that maintains or improves functional outcome in the vast majority of patients presenting with spinal metastases.


Description of Microgomphus farrelli sp. nov. (Odonata: Anisoptera: Gomphidae) based on adults of both sexes and larvae from Northern Thailand.
The new gomphid species, Microgomphus farrelli sp. nov., is described and illustrated on the basis of male and female adult specimens and larvae collected from Chiang Mai and Mae Hong Son province, Northern Thailand. It is compared with other species of the genus. Based on the larvae this species is most closely related to Microgomphus svihleri (Asahina, 1970), comb. nov., which is the senior and valid synonym of Microgomphus thailandicus Asahina, 1981, syn. nov.


The Edg family G protein-coupled receptors for lysophospholipids: their signaling properties and biological activities.
Sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA) are blood-borne lysophospholipids with a wide spectrum of biological activities, which include stimulation of cell growth, prevention of apoptosis, regulation of actin cytoskeleton, and modulation of cell shape, cell migration, and invasion. Activated platelets appear to be a major source of both S1P and LPA in blood. Despite the diversity of their biosynthetic origins, they are considered to share substantial structural similarity. Indeed, recent investigation has revealed that S1P and LPA act via a single family of G protein-coupled receptors designated as Edg. Thus, the Edg isoforms, Edg1 (also called S1P(1)), Edg5 (S1P(2)), Edg3 (S1P(3)), Edg6 (S1P(4)), and Edg8 (S1P(5)), are specific receptors for S1P (and SPC with a lower affinity), whereas Edg2 (LPA(1)), Edg4 (LPA(2)), and Edg7 (LPA(3)) serve as receptors specific for LPA. Each receptor isoform displays a unique tissue expression pattern and coupling to a distinct set of heterotrimeric G proteins, leading to the activation of an isoform-specific panel of multiple intracellular signaling pathways. Recent studies on knockout mice have unveiled non-redundant Edg receptor functions that are essential for normal development and vascular maturation. In addition, the Edg lysophospholipid signaling system may play a role in modulating cell motility under such pathological conditions as inflammation, tumor cell dissemination and vascular remodeling.


Neuropathological findings in Miller Fisher syndrome.
The neuropathological findings in a fatal case of Miller Fisher syndrome are described. The demyelinating peripheral neuropathy and normal appearance of the central nervous system that were observed support the inclusion of the syndrome within the spectrum of acute inflammatory polyneuropathy.


Pubic Osteomyelitis in a Combat Training Soldier: A Case Report.
Infectious osteomyelitis of the symphysis pubis, known as pubic osteomyelitis is a rare condition with potentially devastating consequences. To the best of our knowledge, this article is the first reported case of a military trainee presenting with pubic osteomyelitis. We present a unique case of a patient who simultaneously suffered a combination of local recurrent stress to the symphysis pubis area, and slow-healing multiple palm and finger lacerations which probably acted as distant ports of bacterial entry that concomitantly led to his illness. The patient went through a 6-month period of a complex diagnostic process and an antibiotic treatment with strict activity limitations, after which a full recovery was achieved. Although rare, when treating combat trainees or athletes whose daily life combines extensive physical training and potential ports of entry for bacteria, the treating physician should be aware of the potential for infectious osteomyelitis. Understanding the pathophysiology described would aid physicians when taking the patient history, and conducting an appropriate physical examination. The combination of a relevant history, pubic pain, high fever, and skin lacerations should alert the physician to the possibility of pubic osteomyelitis. When considering prevention, along with a well-designed training course for both soldiers in training camps and athletes, the significance of hygiene and treatment of superficial wounds or skin abrasions cannot be overemphasized.


A Telemedicine Service as Partial Replacement of Face-to-Face Physical Rehabilitation: The Relevance of Use.
Different kinds of telemedicine services have made their entry into healthcare. In this article we focus on a telerehabilitation service for physical exercise, designed and implemented as partial replacement of a 3-day outpatient rehabilitation program for chronic disease patients. The aim of this article is to examine the use pattern of this telerehabilitation service by chronic disease patients and to examine the association between actual use and clinical benefit experienced by these patients. Chronic lower back pain (CLBP) patients and pulmonary disease (PD) patients referred to the physical outpatient rehabilitation programs were asked to participate in and to use the telerehabilitation service. The actual use was expressed as frequency and duration of use, and the measurement of clinical benefit focused on complaints and physical functioning. Sixty-two patients finished the outpatient rehabilitation using the telerehabilitation service. During the weeks of home rehabilitation the majority of the patients used the service. On average the service was used one or two times a week for a total of 35-38 min for both pathologies, with this value being lower than the time that was replaced. Frequency of use was significantly associated with the change in physical functioning outcome for both pathologies (CLBP, r=0.41, p=0.02; PD, r=0.55, p=0.003). Chronic disease patients used a telerehabilitation service as partial replacement of their face-to-face rehabilitation program, and more frequent use was positively related to higher clinical benefit.


A Large State Medicaid Outpatient Advanced Imaging Utilization Management Program: Substantial Savings Without the Need for Denials.
A decade of rapidly rising outpatient advanced imaging utilization ended toward the end of the past decade, with slow growth since. This has been attributed to repetitive reimbursement cuts, medical radiation exposure concerns, increasing deductibles and patient copayments, and the influence of radiology benefit management companies. State Medicaid programs have been reluctant to institute radiology benefit management preauthorization programs since the time burden for obtaining test approval could cause providers to drop out. Also, these patients may lack the knowledge to appeal denials, and medically necessary tests could be denied with adverse outcomes. Little data exist demonstrating the efficacy of such programs in decreasing utilization and cost. We report a 2-year experience with an outpatient advanced imaging prior notification program for a large state Medicaid fee-for-service population. The program did not allow any denials, but nevertheless the data reveal a large, durable decrease in advanced imaging utilization and cost.


Chromatography of medicinal plants and Chinese traditional medicines.
Applications of chromatographic techniques to medicinal plants and Chinese traditional medicines are outlined in this review. Areas involved are quantitation of active principles or index or principal components; quality evaluation of crude drugs; identification, characterization and preparative isolation of new compounds for medical use from plants; analysis of pharmaceutical preparations of plant origin and pharmacokinetic and pharmacological studies of herbal drugs and their preparations.


Microdosimetry of pulsed radiation fields employing the variance method.
The relationship between dose mean lineal energy and relative variance has been exploited previously to derive yD from the calculated variance in current measurements in steady and uniform radiation fields. Recently Kellerer and Rossi made the observation that utilization of two detectors can make the variance technique practicable in time-varying fields. We report here the first measurements of yD for 10 MeV X rays and 9 and 18 MeV electrons from a pulsed linear accelerator using the variance method. Two independent analog-to-digital converters were used to obtain data from two spherical proportional counters in synchrony with the beam pulse. The method is described in detail and results are reported for site diameters of 1/2, 1, and 2 microns. Data for an accurate determination of yD can be obtained with this technique in less than 1 min, making possible an essentially "on line" determination of yD or zD in a clinical situation.


Wheat FKBP73 functions in vitro as a molecular chaperone independently of its peptidyl prolyl cis-trans isomerase activity.
Peptidyl-prolyl cis-trans isomerases (PPIases) catalyse protein folding by accelerating the slow step of cis-trans isomerisation of peptidyl-prolyl bonds. Wheat (Triticum aestivum L.) FKBP73 (wFKBP73) is a peptidyl-prolyl cis-trans isomerase belonging to the FK506-binding protein (FKBP) family. It comprises three FKBP12-like domains, tetratricopeptide repeats and a calmodulin-binding domain (CaMbd). In vitro studies indicated that wFKBP73 possesses PPIase activity, binds calmodulin and forms a heterocomplex with mammalian p23 and wheat Hsp90 in wheat-germ lysate. To further study the role of wFKBP73 we have analysed its chaperone properties. Using the thermal unfolding and aggregation of citrate synthase (CS) as a model system, we have shown that the plant wFKBP73 exhibits chaperone activity, being able to suppress CS aggregation independently of its PPIase activity. The wFKBP73 interacts transiently with non-native CS and slows down its inactivation kinetics, whereas the mammalian homologue, hFKBP52 binds tightly to CS and does not affect its rate of inactivation. Hence, the first plant FKBP shown to function as a molecular chaperone has a mode of action different from that of the mammalian FKBP52.


High-field/high-pressure ESR.
We present a historical review of high-pressure ESR systems with emphasis on our recent development of a high-pressure, high-field, multi-frequency ESR system. Until 2000, the X-band system was almost established using a resonator filled with dielectric materials or a combination of the anvil cell and dielectric resonators. Recent developments have shifted from that in the low-frequency region, such as X-band, to that in multi-frequency region. High-pressure, high-field, multi-frequency ESR systems are classified into two types. First are the systems that use a vector network analyzer or a quasi-optical bridge, which have high sensitivity but a limited frequency region; the second are like our system, which has a very broad frequency region covering the THz region, but lower sensitivity. We will demonstrate the usefulness of our high-pressure ESR system, in addition to its experimental limitations. We also discuss the recent progress of our system and future plans.


Metyrapone: a management option for ectopic ACTH syndrome in small cell lung cancer treated with intravenous etoposide.
Small cell lung cancer (SCLC) with ectopic adrenocorticotropic hormone (ACTH) syndrome and resultant hypercortisolism carries a poor prognosis with a short median survival and high incidence of infective complications. The combination of etoposide with either carboplatin or cisplatin is the current standard chemotherapy used for the management of SCLC. Etoposide is metabolised by cytochrome P450 3A4. Ketoconazole is an imidazole derivative possessing antifungal properties and also causes inhibition of adrenal corticosteroid and androgen production. There is an additional increased risk of toxicity due to a potential interaction between etoposide and ketoconazole, which is a strong inhibitor of cytochrome P450 3A4, and theoretically can lead to greater myelosuppression. Metyrapone can be a safe alternative in such settings.


Liver preservation with UW solution. I. Evidence that hydroxyethyl starch is not essential.
Preservation of rat livers by simple ice-storage has been demonstrated after 24 hr using the University of Wisconsin (UW) solution. Equally good preservation could be obtained by substituting hydroxyethyl starch (HES) from another source or by omission of HES from the UW formulation. Survival, early and late function, and morphology at the end of a 3-month follow-up period were essentially similar for all three test groups. It is concluded that HES is not required for optimum preservation of the rat liver in this treatment model.


Effects of thiopental on tension development, action potential, and exchange of calcium and potassium in rabbit ventricular myocardium.
Thiopental in concentrations of 28 and 227 mumoles/liter reduced the tension developed by isolated rabbit ventricular myocardium by 50 and 80%, respectively. The effect was rapid, reversible, and independent of heart rate. Thiopental (227 mumoles/liter) inhibited influx and efflux of potassium to the same extent, so that no net gain or loss occurred. Calcium influx and efflux were also reduced, but calcium was not displaced from the myocardium in association with the decline of tension. The maximum rate of depolarization of the action potential and the time to 50% repolarization were decreased, but resting membrane potential, amplitude, and time to 90% depolarization were unchanged. The negative inotropic effect of thiopental appears to be due to reduced availability of calcium to the myofibrils.


Pedunculopontine nucleus area oscillations during stance, stepping and freezing in Parkinson's disease.
The pedunculopontine area (PPNa) including the pedunculopontine and cuneiform nuclei, belongs to the mesencephalic locomotor region. Little is known about the oscillatory mechanisms underlying the function of this region in postural and gait control. We examined the modulations of the oscillatory activity of the PPNa and cortex during stepping, a surrogate of gait, and stance in seven Parkinson's disease patients who received bilateral PPNa implantation for disabling freezing of gait (FOG). In the days following the surgery, we recorded behavioural data together with the local field potentials of the PPNa during sitting, standing and stepping-in-place, under two dopaminergic medication conditions (OFF and ON levodopa). Our results showed that OFF levodopa, all subjects had FOG during step-in-place trials, while ON levodopa, stepping was effective (mean duration of FOG decreasing from 61.7±36.1% to 7.3±10.1% of trial duration). ON levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity. PPNa activity was not modulated during quiet standing and sitting. Our results confirm the role of the PPNa in the regulation of gait and suggest that, in Parkinson disease, gait difficulties could be related to an imbalance between low and higher frequencies.


[Oriental biliary lithiasis. Retrospective study of 690 patients treated surgically over 8 years at Hospital 108 in Hanoi (Vietnam)].
The purpose of this study was to review the unique features distinguishing Oriental from Western gallbladder disease based on a series of 690 patient who underwent surgical treatment at hospital 108 in Hanoi. Oriental cholangiohepatitis often affects in young patients with no gender predilection. The disease originates mainly in canaliculi and leads to blockage or obstruction of the main bile duct inside and outside the liver. Onset has been related to nutritional, infectious, and parasitic factors. Ascariasis may play a determinant role. Because of these unique features, surgical treatment is usually focused on the main bile duct and depends on the size, number, and effects of gallstones. The authors recall that excision of liver tissue may be unavoidable in some cases due to the severity and consequences of lithiasis.


[Professor FANG Jianqiao's clinical experience in the treatment of primary cervical dystonia].
Professor FANG Jianqiao's clinical experience in the treatment of primary cervical dystonia based on the syndrome differentiation of TCM was explored preliminarily. Based on the disease identification of western medicine and the syndrome differentiation of TCM, in combination with the differentiations of meridians and collaterals of acupuncture, Professor FANG proposes the three-dimensional system of diagnosis and treatment of acupuncture, named "disease differentiation, TCM syndrome differentiation and meridian differentiation". Regarding the diagnosis and treatment of primary cervical dystonia, the physical examination of nerve system, TCM syndrome differentiation and meridian differentiation are equally important. It is pointed out that the key pathogenesis of the disease is qi and blood obstruction and the malnutrition in the muscle regions of meridians. Hence, the treating principle is proposed as eliminating the exogenous pathogens, regulating qi and blood and unblocking the muscle regions of meridians. Professor FANG also stresses that the affected sites and the factors of dystonia should be considered in acupuncture treatment. The local points are mainly those adjacent to the responsible muscles with the motor disturbance in the neck region. "Xinshe" point (Extra) is taken as the empirical point. The distal points are selected in accordance with the three-dimensional system of diagnosis and treatment. At the same time, the percutaneous acupoint electric stimulation is applied to the starting and ending points or the conjunctive points of the affected muscles, acting on regulating qi, nourishing blood and promoting the circulation in meridians and collaterals.


[Comparative analysis between cardiopulmonary exercise testing and echocardiography in patients of heart failure with normal ejection fraction].
To assess the clinical and predictive value of cardiopulmonary exercise testing (CPET) used in heart failure with normal left ventricular ejection fraction (HFNEF). A total of 49 HFNEF patients of (New York Heart Association) NYHA class II were randomly selected from September 2010 to July 2012. The parameters of CPET and ultrasonic cardiogram (UCG) were collected at Day 3 post-admission. Person's and partial correlations were used to perform to compare CPET and UCG. Pearson's correlation revealed that mitral peak velocity of early filling/early diastolic mitral annular velocity (E/E', 10.14 ± 2.05) was significantly correlated with peak oxygen uptake (VO₂ peak, (24.15 ± 8.31) ml×kg⁻¹×min⁻¹, r = -0.287, P = 0.046), carbon dioxide production (VCO₂, (1.63 ± 0.51) L/min, r = -0.429, P = 0.002), partial pressure of end-tidal carbon dioxide (PET CO₂, (39.50 ± 7.77) mm Hg, r = -0.282, P = 0.050) and minute ventilation/carbon dioxide production (VE/VCO₂, 31.69 ± 5.32, r = 0.411, P = 0.003). Early diastolic mitral annular velocity (E', (6.46 ± 1.60) cm/s) was relevant to VO₂ peak (r = 0.351, P = 0.013), VCO(2) (r = 0.452, P = 0.001), PET CO₂ (r = 0.310, P = 0.030), VE/VCO₂ (r = -0.434, P = 0.002) and respiratory exchange ratio (RER, 1.18 ± 0.13, r = 0.350, P = 0.014). After adjustment, VCO₂ was correlated with E/E' (r = -0.369, P = 0.019) and E' (r = 0.393, P = 0.010). VE/VCO₂ was relevant to E/E' (r = 0.414, P = 0.006) and E' (r = -0.334, P = 0.031). For HFNFE patients, CPET has high values of assessment and prognosis.


Third-order theory and aspheric spectacle lens design.
Third-order equations are developed giving sagittal and tangential power errors corresponding to the eye rotating to look through the periphery of a spectacle lens. The equations are applicable for conicoid aspherical surfaces. From these, other equations are derived for elimination of oblique astigmatism and mean oblique error. Graphical examples show how aspherizing either lens surface affects the lens bendings required to eliminate oblique astigmatism.


Conservative Measures for Managing Constipation in Patients Living With a Colostomy.
The purpose of this study was to determine the effect of a conservative regimen for the treatment of constipation in persons living with a colostomy. Prospective, noncontrolled, single-center study. The study sample comprised 35 patients with a colostomy who were diagnosed with constipation. Subjects with morphologic changes causing constipation such as stomal stenosis and neoplastic and inflammatory changes were excluded. The study was conducted in the Proctology and Stoma Outpatient Clinic at Poznan University of Medical Sciences. Patients at our Stoma Outpatient Clinic underwent baseline evaluation, and those with symptoms of constipation (prolonged periods between bowel movements, passage of pasty or hardened fecal effluent, and associated symptoms such as abdominal discomfort or bloating, flatulence, and pain with passage of effluent into the stoma) received individualized dietary recommendations that typically included an increase in dietary fiber and fluid intake, along with increased fluid intake. The outcomes of dietary changes were evaluated during a follow-up visit 3 months later. If dietary changes alone did not improve constipation symptoms, we prescribed a psyllium-based bulk-forming agent, an osmotic stool softener, and a probiotic, with or without a prokinetic agent such as metoclopramide taken 3 times daily. Dietary interventions alone were deemed successful in 60% of study subjects (n = 21); the remaining 14 patients required additional treatment. Dietary modifications alone relieved constipation in more than half of a group of 35 patients with constipation. We therefore recommend a trial of dietary modifications prior to the initiation of pharmacotherapy in patients with a colostomy.


Secondary task and risky driving behavior: a test of the mediating effect of situation awareness.
A theoretical model is developed by using a contingency perspective to hypothesize the relationship between a secondary task and risky driving behavior. It is conjectured that the relationship between the two variables is mediated by situation awareness (SA). An experiment is designed and administered to provide empirical evidence. Thirty Indonesian students as subjects were required to carry out a driving assignment in a simulated environment. Empirical evidence suggests that SA provides a partial mediation effect towards the relationship between a secondary task and risky driving behavior. It is also found that a secondary task has a significant effect on risky driving behavior. The secondary task also becomes a significant explanation of SA. In addition, working memory capacity, experience and gender are found to have no significant impact towards SA.


Heritable connective tissue disorders in cervical artery dissections: a prospective study.
We prospectively evaluated 15 consecutive patients with spontaneous cervical artery dissections. Three patients (20%) had a heritable connective tissue disorder, each with a unique phenotype. None of these patients met the criteria of any of the named syndromes, and collagen and fibrillin analyses were normal. Heritable connective tissue disorders are common among patients with spontaneous cervical artery dissections, but, despite intensive investigations, the type of disorder usually cannot be identified. The underlying arteriopathy in cervical artery dissections is likely to be heterogeneous.


A comparison of the effects of intravenous serotonin and dextran on the levels of factor XII, prekallikrein and plasminogen in rat plasma.
It was previously observed that serotonin injected intravenously into the rat caused significant reductions in the prekallikrein activator (PKA) and the benzoyl arginine ethyl ester (BAEe)-esterase activities induced in rat plasma by acetone/kaolin activation. In the present work it was demonstrated that serotonin was unable to exert these effects in vitro, in plasma or in whole blood. The assay of PKA and Baee-esterase activities after gel filtration on Sephadex G-100 of acetone-activated plasma from rats treated with serotonin 0.10 mg/kg revealed reduced fragmentation of factor XII, and reduced levels of kallikrein and of an additional BAEe-esterase. Serotonin also lowered the plasminogen level. The serotonin-induced reductions of PKA and BAEe-esterase were inhibited by pretreatment of the rats with epsilon-aminocaproic acid. Evidence was provided that serotonin did not lower the plasma level of factor XII of the coagulation system, but the level of a factor of significance for the activation of factor XII. All the above-mentioned serotonin effects were fundamentally similar to the corresponding effects caused by dextran. It is concluded that the effects of dextran on the plasma parameters mentioned are mediated by the release of endogenous serotonin.


Fabrication and characteristics of GaN-based light-emitting diodes with a reduced graphene oxide current-spreading layer.
A reduced graphene oxide (GO) layer was produced on undoped and n-type GaN, and its effect on the current- and heat-spreading properties of GaN-based light-emitting diodes (LEDs) was studied. The reduced GO inserted between metal electrode and GaN semiconductor acted as a conducting layer and enhanced lateral current flow in the device. Especially, introduction of the reduced GO layer on the n-type GaN improved the electrical performance of the device, relative to that of conventional LEDs, due to a decrease in the series resistance of the device. The enhanced current-spreading was further of benefit, giving the device a higher light output power and a lower junction temperature at high injection currents. These results therefore indicate that reduced GO can be a suitable current and heat-spreading layer for GaN-based LEDs.


B cell antigen receptor-induced Rac1 activation and Rac1-dependent spreading are impaired in transitional immature B cells due to levels of membrane cholesterol.
The BCR-triggered responses of mature and transitional immature B cells differ at both the biochemical and functional level. In this study, we show that in mature B cells, BCR signaling triggers Vav phosphorylation and Rac1 activation. Furthermore, we demonstrate that although downstream actin-dependent BCR capping is independent of Rac1 activation, actin-dependent membrane ruffling and cell spreading are Rac1-dependent processes. In contrast, BCR-induced Vav phosphorylation and Rac1 activation is impaired in transitional immature B cells, resulting in defects in actin polymerization-dependent spreading and membrane ruffling while Rac1-independent BCR capping remains intact. Because transitional immature murine B cells maintain lower steady-state levels of plasma membrane cholesterol, we augmented their levels to that of mature B cells and found that BCR-induced Rac1 activation and Rac1-dependent membrane ruffling and cell spreading were restored. These studies provide a direct link between B cell cholesterol levels and downstream cellular signaling processes.


Transureteral lithotripsy in pediatric practice.
The present study reviews ureteroscopy intervention for the treatment of ureteral stones in pediatric patients in the last 6 years at three institutions in Iran. Sixty-six ureteroscopies were performed in 66 prepubertal patients (mean age 9 years; range 2-15 years) with a male/female ratio of 31/35. Ultrasonography, plain film, or intravenous urography was performed in all cases. The mean stone size was 8 mm (range 5-15 mm). All the interventions were performed under general anesthesia with semirigid ureteroscopes of 8F to 11.5F. The stone was located in the left ureter in 32 patients and in the right in 34 patients. Stones were located in the distal ureter in 59 patients, in the midureter in 5, and in the proximal ureter in 2. Before ureteroscopy, ureteral dilatation with a balloon was done to 12F if necessary. If the calculus could not be removed with the basket (stone.8 mm), lithotripsy using ultrasonic, electrohydraulic (EHL), or pneumatic equipment was performed. Ureteroscopy with an 11.5F, 9F, 8.5F, or 8F ureteroscope were performed in 26, 14, 5, and 21 patients, respectively, and ureteral dilatation was necessary in 23, 0, 0, and 2 cases, respectively. We were unable to introduce the ureteroscope into the ureter in three patients (two boys with an 11.5F ureteroscope and one girl with an 8.5F ureteroscope) with distal ureteral stones. The stones moved to the kidney in four patients. Stone management was with basketing alone in 14, EHL in 3, ultrasonic lithotripsy in 8, and ballistic lithotripsy in 34 patients. The stone-free rate was 88% (58 patients) at 48 hours postprocedure. The complication rate was 23% and included renal colic (1), gross hematuria (11), and pyelonephritis (3). No patient had obvious perforation or stricture of the ureter at 3-month follow-up. Our series demonstrates the high success rate that can be achieved with ureteroscopic removal of ureteral calculi in children. Ureteroscopic treatment, especially with a small-caliber ureteroscope, should be considered the first choice for treatment of calculi in the distal ureter in children.


Diabetes and Auditory-Vestibular Pathology.
The relationship between diabetes mellitus (DM) and the auditory/vestibular system has been investigated for more than a century. Most population-based investigations of hearing loss in persons with diabetes (PWD) have revealed a slow progressive, bilateral, high-frequency sensorineural hearing loss. Despite the growing research literature on the pathophysiology of DM-related hearing loss using various animal models and other human studies, knowledge of specific mechanism of the degenerative changes of the inner ear and/or auditory nerve is far from full elucidation. Recent investigations of the mechanisms underlying the association between hearing loss and DM suggest complex combined contributions of hyperglycemia, oxidative stress resulting in cochlear microangiopathy, and auditory neuropathy. An even lesser understood complication of DM is the effect on the vestibular system. Here we provide an overview of animal and human evidence of pathophysiological changes created by DM and its effects on auditory-vestibular anatomy and function.


Association of per- and polyfluoroalkyl substance exposure with metabolic syndrome and its components in adults and adolescents.
Per- and polyfluoroalkyl substances (PFAS) are widespread contaminants, but few studies have explored the relationship between PFAS and levels of metabolic syndrome (MetS) in the population. The available evidence of an association is also conflicting. We selected adults and adolescents with complete PFAS data from the National Health and Nutrition Examination Survey conducted between 2003 and 2018. We analyzed the association between PFAS and MetS using multivariate logistic regression models and evaluated potential nonlinear relationships with restricted cubic spline models. Additionally, we employed weighted quantile sum (WQS) regressions to uncover the multiple exposure effects and relative weights of each PFAS. Finally, we conducted a series of sensitivity analyses to test the robustness of our findings. In this population-based study, we analyzed data from a total of 4,973 adults, aged 20-85 years, and 1,381 adolescents, aged 12-19 years. Using fully adjusted multivariate logistic regression models, we found that serum levels of perfluorodecanoate (PFDA) [0.65 (0.50, 0.85)] and total PFAS [0.92 (0.85, 0.99)] were negatively associated with the prevalence of MetS in adults. Similarly, in adolescents, we observed negative correlations between the prevalence of MetS and levels of PFDA [0.55 (0.38, 0.80)], perfluorooctanoic acid (PFOA) [0.62 (0.39, 1.00)], perfluorooctane sulfonic acid (PFOS) [0.59 (0.36, 0.96)], and total PFAS [0.61 (0.37, 0.99)]. Additionally, our study identified statistically significant negative associations between serum levels of PFAS and certain components of MetS, primarily elevated fasting glucose and lower high-density lipoprotein cholesterol. Our study found that PFAS was associated with a lower prevalence of MetS in both adults and adolescents, offering new insights into the relationship between PFAS and metabolic health. Interestingly, however, we observed conflicting findings across the components of MetS. Specifically, we observed that PFAS had a negative correlation with some metrics and a positive correlation with others. These conflicting results point to a complex interplay between PFAS and various metrics of metabolic health.


Curative effect of transcatheter arterial chemoembolization combined with radiofrequency ablation in treating hepatic cell carcinoma and its effect on serum markers.
Hepatic cell carcinoma (HCC) is more common in clinical practice, and has high malignant degree. This study aims to analyze the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating hepatic cell carcinoma (HCC) and its effect on serum markers. A total of 106 cases of patients with hepatic cell carcinoma treated in our hospital were randomly divided into two groups: observation group and control group. Patients in the observation group (53 cases) received transcatheter arterial chemoembolization combined with radiofrequency ablation therapy, while subjects in the control group (53 cases) received transcatheter arterial chemoembolization therapy. Differences in the overall effect, indicators of inflammation and oxidative stress, tumor activity-related indicators and tumor recurrence-related indicators between these two groups were compared. At one and two weeks after treatment, the number of cases of CR and PR in the observation group was higher than that in the control group, the number of cases of SD was not different from that in the control group, and the number of cases of PD was lower than that in the control group. At two weeks after treatment, differences in serum MDA, SOD, GSH, CRP, TNF-α and ESR between the two groups were significant. However, serum EC, VEGF, MMP, AFP, CA199 and GGT content was significantly lower in the observation group than that in the control group. Transcatheter arterial chemoembolization combined with radiofrequency ablation therapy can effectively control the growth of liver cancer lesions, reduce the levels of tumor-related serum markers, and inhibit the activity of tumor cells.


[An epileptic syndrome in infantile cerebral palsy].
The results of examination of 102 patients with infantile cerebral paralysis (ICP) with epileptic syndrome (ES) at the age from 3 months to 14 years are presented. Epileptic fits predominated in patients with hemiparetic form of ICP (40.8%) and spastic diplegia (32.4%). ES manifestations were observed in ICP during the first 3 years of life (more than 80% of cases). The peculiarities of ES clinical course were revealed. There were determined the main types of seizures in patients with ICP which depended on age of their manifestation, as well as their further transformation and prognosis. Computer tomographic and EEG-correlations were established in different forms of ICP. They permitted to revealed pathogenetic mechanisms of ES development in patients with ICP and to determine therapeutic policy and prognosis of the disease.


Fast-dissolving sublingual films of terbutaline sulfate: formulation and in vitro/in vivo evaluation.
Terbutaline sulfate fast dissolving sublingual films were prepared using seven drug compatible film formers in different combinations and proportions. The film polymers are maltodextrin, Na alginate, Carpabol 430, xanthan gum, HPMC E5, PVP K-25, and Na CMC. Propylene glycol and sorbitol were used as plasticizers and mannitol as filler. The optimum polymer concentrations and the plasticizer amount were selected on the basis of flexibility, tensile strength, and stickiness of the films. The prepared films were evaluated for their tensile strength, thickness uniformity, disintegration time (in vitro and in vivo), in vitro dissolution, and moisture content. Polymer type rather than total polymer concentration or plasticizer amount showed a significant effect on the tested film properties. A randomized, single dose, crossover study was conducted in four healthy volunteers to compare the pharmacokinetic profile of terbutaline sulfate from the prepared films and the conventional oral tablets. The film formula of choice gave a significantly faster drug absorption rate and recorded a relative bioavailability of 204.08%. Sublingual films could be promising as a convenient delivery system for terbutaline sulfate in patients with swallowing problems. The improved extent of absorption (higher AUC(0-24)) indicates success in improving drug bioavailability, and the faster absorption rate could be promising for the management of acute episodes of asthma.


Effects of chromophore orientation and molecule conformation on surface-enhanced Raman scattering studied with alkanoic acids and colloidal silver nanoparticles.
Experimental studies have been carried out to gain a better understanding of the effects of chromophore orientation and molecular conformation on surface-enhanced Raman scattering (SERS) based on metal nanostructures. A series of alkanoic acids that contain a phenyl ring separated by methylene groups from the carboxylic acid, including phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, and 6-phenylhexanoic acid, was investigated as model molecules with colloidal silver nanoparticles as SERS substrates. As the number of methylene groups increases, the molecules display an interesting zigzag intensity pattern of the phenyl ring bending mode around 1000 cm(-1) as well as a trend of appearance and disappearance of either the degenerate ring breathing mode or C[Double Bond]O vibrational mode near 1585 and 1630 cm(-1), respectively. Molecules containing an odd number of methylene units display a higher ring bending intensity and degenerate ring breathing mode and are suggested to have a trans conformation on the particle surface. Molecules with an even number of methylene units show a C[Double Bond]O vibrational mode and weaker ring bending in their SERS spectra and are suggested to have a gauche conformation on the silver nanoparticle surface. The different conformation is attributed to the varying interactions of the carboxylic group or the phenyl ring pi electrons with the silver surface. The SERS intensity was found to change little as the length between the phenyl ring and the carboxylic group was increased by adding CH(2) spacers. This is possibly because the effective distance between the phenyl ring and the silver surface does not change much with increasing number of CH(2) spacers as a result of changes in molecular conformation and variations in the phenyl ring orientation with CH(2) addition. The insight gained from this study is important for understanding SERS of complex molecules for which chromophore orientation and molecular conformation must be taken into careful consideration.


Thermionic microwave gun for terahertz and synchrotron light sources.
Conventional thermionic microwave and radio frequency (RF) guns can offer high average beam current, which is important for synchrotron light and terahertz (THz) radiation source facilities, as well as for industrial applications. For example, the Advanced Photon Source at Argonne National Laboratory is a national synchrotron-radiation light source research facility that utilizes thermionic RF guns. However, these existing thermionic guns are bulky, difficult to handle and install, easily detuned, very sensitive to thermal expansion, and due for a major upgrade and replacement. In this paper, we present the design of a new, more stable, and reliable gun with optimized electromagnetic performance, improved thermal engineering, and a more robust cathode mounting technique, which is a critical step to improve the performance of existing and future light sources, industrial accelerators, and electron beam-driven THz sources. We will also present a fabricated gun prototype and show results of high-power and beam tests.


Potentiation of excitatory transmission in substantia gelatinosa neurons of rat spinal cord by inhibition of estrogen receptor alpha.
It has been shown that estrogen is synthesized in the spinal dorsal horn and plays a role in modulating pain transmission. One of the estrogen receptor (ER) subtypes, estrogen receptor alpha (ERα), is expressed in the spinal laminae I-V, including substantia gelatinosa (SG, lamina II). However, it is unclear how ERs are involved in the modulation of nociceptive transmission. In the present study, a selective ERα antagonist, methyl-piperidino-pyrazole (MPP), was used to test the potential functional roles of spinal ERα in the nociceptive transmission. Using the whole-cell patch-clamp technique, we examined the effects of MPP on SG neurons in the dorsal root-attached spinal cord slice prepared from adult rats. We found that MPP increased glutamatergic excitatory postsynaptic currents (EPSCs) evoked by the stimulation of either Aδ- or C-afferent fibers. Further studies showed that MPP treatment dose-dependently increased spontaneous EPSCs frequency in SG neurons, while not affecting the amplitude. In addition, the PKC was involved in the MPP-induced enhancement of synaptic transmission. These results suggest that the selective ERα antagonist MPP pre-synaptically facilitates the excitatory synaptic transmission to SG neurons. The nociceptive transmission evoked by Aδ- and C-fiber stimulation could be potentiated by blocking ERα in the spinal neurons. Thus, the spinal estrogen may negatively regulate the nociceptive transmission through the activation of ERα.


A qualitative study to explore health professionals' experience of treating gout: understanding perceived barriers to effective gout management.
INTRODUCTION The management of gout is challenging and mainly occurs in primary care. This study aims to explore the experience of treating gout among primary care clinicians and understand the perceived barriers to effective therapy. METHODS Fourteen health professionals from primary care practices in South Auckland were recruited. Each participated in a semi-structured interview exploring their experience of treating and managing gout patients were analysed thematically. FINDINGS Participants described the large burden of gout in their communities and the importance of the clinician-patient relationship in gout management. Four themes summarise the perceived barriers to effective urate lowering therapy (ULT); unique gout factors, eg its intermittent nature and potential for stigmatisation; systemic barriers to optimal treatment, or barriers that emerge from working within a certain organisation; uncertainty about ownership, or who should carry responsibility for overcoming barriers to optimal treatment; and cultural barriers to optimal treatment. CONCLUSION Clinicians in primary practice perceive gout management to be mainly acute rather than preventive care. Patients may be stigmatised and management difficult particularly when diet is emphasised over ULT. Practice nurses are a group potentially available and willing to assist in educating patients. These findings may be helpful in planning for and improving healthcare in gout. KEYWORDS Gout; general practice; uric acid; primary health care; allopurinol; primary prevention.


Treatment of fatigue and sleep disorders in cancer patients.
Sleep disorders are highly prevalent among cancer patients. These disorders can include disorders of sleep onset or maintenance or disorders of excessive sleepiness. A broad differential diagnosis is required to adequately treat these disorders. This review discusses current diagnoses and treatment associated with sleep difficulties that may be seen in cancer patients. With appropriate diagnosis and treatment, the prognosis is good for sleep improvement and improvements in quality of life.


Malignant orbital teratoma in a neonate: A clinicopathological case report.
Teratoma of the orbit is rare; very few cases have been published in literature. A case of orbital teratoma in a neonate is presented where the proptosis was massive enough to obscure the eyeball. Clinically, the diagnosis of teratoma was considered. As there was no possibility of salvaging the eye, exenteration of the orbit was done. Orbital teratomas are generally benign. Histopathological examination revealed the features of malignant teratoma.


Pulmonary mechanics in diffuse fibrosing alveolitis.
The mechanical and the diffusing lung properties have been measured in 19 cases of diffuse fibrosing alveolitis of unknown etiology (proved by histology in 17 cases). The characteristic findings are: a) a striking reduction of DLCO in all the cases; b) a marked reduction of the static and dynamic compliance, in correlation with the reduction of vital capacity; c) an increase in P1max in correlation with the decrease of FRC; d) an increase of the elastic recoil when it is considered at various percentages of the predicted lung volume, but in some cases a normal shape of the V-P curve if the measured lung volume is taken into account; e) a reduction of the maximum expiratory flows suggesting bronchiolar stenosis; f) alterations of DL more marked than those of CL suggesting that DL is a more sensitive test.


Mitral valve abnormalities in patients with right ventricular pressure overload. Analysis by real time cross sectional echocardiography.
Abnormalities of the mitral valve in patients with pulmonary stenosis, tetralogy of Fallot, and pulmonary hypertension with right ventricular pressure overload were studied by real time cross sectional echocardiography. Dislocation of the anterior and posterior mitral leaflets at the coaptation zone in systole was present in 16 of 46 cases: nine of 11 (82%) cases of pulmonary hypertension, four of 20 (20%) cases of tetralogy of Fallot, and three of 15 (20%) cases of pulmonary stenosis. The incidence was highest in patients with pulmonary hypertension. In eight of the 16 patients with mitral valve lesions, mitral regurgitation was seen on left ventriculograms or cross sectional Doppler echocardiograms. The dislocation was located near the posteromedial commissure of the anterior mitral leaflet in all cases. These findings are similar to the mitral valve abnormalities seen in patients with secundum atrial septal defect, and therefore may be due to a common cause. No relation could be found between the left ventricular deformity index and the incidence of dislocation of the mitral leaflets. Thus, the reason why this mitral valve abnormality occurs in conditions with right ventricular pressure overload could not be established.


Energy saving control strategies for Haliscomenobacter hydrossis filamentous sludge bulking in the A/O process treating real low carbon/nitrogen domestic wastewater.
The control strategies of energy saving for filamentous sludge bulking were investigated in the A/O process under low dissolved oxygen (DO) with low carbon/nitrogen (C/N) ratio, and the dominant filamentous bacteria were identified by using fluorescent in situ hybridization. Initially, the sludge volume index reached nearly 500 mL/g and serious bulking occurred when the DO value was 0.5 mg/L, with Haliscomenobacter hydrossis as the major filamentous bacteria in the bulking sludge. Later on, the compartment number increased in the aerobic zone, increasing by this way DO, to control serious bulking. Increasing DO to 1 mg/L based on the increase of compartment number in the aerobic zone was the favorable controlling method, which solved the sludge loss, improved the effluent quality to the national discharge standard and allowed for energy costs saving. As a result, the effective control method for H. hydrossis filamentous sludge bulking provided the economical, convenient and longstanding method for most municipal wastewater treatment plants treating real low C/N domestic wastewater.


Reproducibility of the multiple inert gas elimination technique.
Although measurement errors in the multiple inert gas elimination technique have a coefficient of variation of approximately 3%, small biological fluctuations in ventilation, blood flow, or other variables must contribute additional variance to this method of assessing ventilation-perfusion (VA/Q) mismatch. To determine overall variance of computed indices of VA/Q mismatch, an analysis of variance was carried out using a total of 400 duplicate pairs of inert gas samples obtained from canine (N = 118) and human (N = 282) studies in the past 2 years. In both sets VA/Q mismatch ranged from minimal (2nd moment of ventilation and blood flow distributions, log SDV and log SDQ, respectively approximately equal to 0.3 each) to severe (log SDV and log SDQ approximately equal to 2.0). Differences between duplicate log SD values were computed and found to be a constant fraction of the mean log SD of each duplicate pair, averaging 13% for both canine and human ventilation and blood flow data. The resultant coefficient of variation for a single measurement of log SD about its mean averaged 8.6% for all data combined. This analysis demonstrates excellent reproducibility of these dispersion indices over a wide range of conditions, and if the mean of duplicate values is used, thus reducing variability by square root 2 to 6.1%, log SD can be estimated with an approximately 95% confidence limit of +/- 12%.


Evaluation of the impact of UGT polymorphism on the pharmacokinetics and pharmacodynamics of the novel PPAR agonist sipoglitazar.
Sipoglitazar is a peroxisome proliferator-activated receptor α, δ, and γ agonist. During phase I, a wide distribution of clearance between individuals was observed. Hypothesized to result from a polymorphism in the uridine 5'-diphospate-glucuronosyltransferase (UGT)2B15 enzyme, pharmacogenetic samples were collected from each individual for genotyping UGT2B15 in a subsequent phase I trial in healthy subjects (n = 524) and in 2 phase II trials in type 2 diabetes subjects (n = 627), total genotype frequency was as follows: *1/*1 (22%), *1/*2 (51%), and *2/*2 (27%). The impact of genotype on exposure was assessed using a pharmacokinetic modeling approach; the influence of genotype on efficacy was evaluated using 12-week HbA1c change from baseline. Model analysis demonstrated UGT2B15 genotype accounted significantly for the variability in sipoglitazar clearance; however, a small fraction of subjects had a clearance that could not be explained entirely by genotype. HbA1c drop increased with daily drug dose. When stratified by both dose and genotype, HbA1c drop was larger in the UGT2B15*2/*2 compared with UGT2B15*1/*1 and UGT2B15*1/*2 genotypes (P < .05). In summary, UGT2B15 genotype is a strong predictor for sipoglitazar clearance; a greater clinical response observed in the UGT2B15*2/*2 genotype appears to confirm this. However, overlap in individual rates of clearance across genotypes remains after accounting for genotype.


Effects of vascular endothelial growth factor on ischemic spinal cord injury caused by aortic cross-clamping in rabbits.
Spinal cord injury remains a devastating complication of thoracic and thoracoabdominal aortic operations. We aim to investigate neuro-protective role of vascular endothelial growth factor (VEGF) administered to rabbits after occlusion against ischemia-reperfusion (I/R) injury. Occlusion of the abdominal aorta was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. The abdominal aortas of New Zealand White albino rabbits were occluded for 30 min. Experimental groups were as follows: control group (sham operation group, n = 7), I/R group (n = 9) undergoing occlusion but receiving no pharmacologic intervention, and VEGF-treated group (n = 7) receiving 0.8 microg/kg VEGF intravenously after occlusion. Neurological status was assessed at 6, 24, and 48 h after the operation. All animals were killed at 48 h after the operation. Spinal cords were harvested for histopathologic and biochemical analyses. According to Tarlov's scale, neurological status of the rabbits at postoperative h 48 was better in the VEGF-treated group compared to the I/R group (P < 0.05). Decreased tissue and serum malondialdehyde levels and increased tissue and serum glutathione levels were observed in VEGF-treated group (P < 0.05). In the same group tissue and serum nitrate levels were decreased (P < 0.05). Histopathologic analyses demonstrated typical morphological changes characteristic of necrosis in the I/R group. VEGF attenuated ischemia-induced necrosis. This is the first study that shows the effects of VEGF administered after occlusion on induced oxidative damage to injured spinal cords. VEGF administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.


DOCK2 deficiency mitigates HFD-induced obesity by reducing adipose tissue inflammation and increasing energy expenditure.
Obesity is the major risk factor for type 2 diabetes, cardiovascular disorders, and many other diseases. Adipose tissue inflammation is frequently associated with obesity and contributes to the morbidity and mortality. Dedicator of cytokinesis 2 (DOCK2) is involved in several inflammatory diseases, but its role in obesity remains unknown. To explore the function of DOCK2 in obesity and insulin resistance, WT and DOCK2-deficient (DOCK2-/-) mice were given chow or high-fat diet (HFD) for 12 weeks followed by metabolic, biochemical, and histologic analyses. DOCK2 was robustly induced in adipose tissues of WT mice given HFD. DOCK2-/- mice with HFD showed decreased body weight gain and improved metabolic homeostasis and insulin resistance compared with WT mice. DOCK2 deficiency also attenuated adipose tissue and systemic inflammation accompanied by reduced macrophage infiltration. Moreover, DOCK2-/- mice exhibited increased expression of metabolic genes in adipose tissues with greater energy expenditure. Mechanistically, DOCK2 appeared to regulate brown adipocyte differentiation because increased preadipocyte differentiation to brown adipocytes in interscapular and inguinal fat was observed in DOCK2-/- mice, as compared with WT. These data indicated that DOCK2 deficiency protects mice from HFD-induced obesity, at least in part, by stimulating brown adipocyte differentiation. Therefore, targeting DOCK2 may be a potential therapeutic strategy for treating obesity-associated diseases.


Mammalian sperm energy resources management and survival during conservation in refrigeration.
The present review has as its main aim to present an overview regarding the mechanisms utilized by mammalian sperm to manage its intracellular energy levels. This management will strongly influence the sperm's ability to maintain its overall function during its entire life span. Thus, the precise knowledge of these mechanisms will be of the utmost interest to optimize the systems utilized to conserve mammalian sperm for a medium-to-long time-lapse. Briefly, utilization of hexoses as energy substrates by mammalian sperm is very finely regulated from the very first step of its metabolization. Furthermore, the equilibrium among the separate, monosaccharide metabolization pathways in mammalian sperm depends on many factors. This prevents the possibility to draw a general vision of sperm energy utilization, which explains the results of all mammalian species in all points of the sperm life-cycle. To complicate the matter further, there are separate energy phenotypes among mammalian spermatozoa. The precise knowledge of these phenotypes is of the greatest importance in order to optimize the design of new extenders for sperm conservation in refrigerated conditions. Moreover, sugars can act on sperm not only as passive metabolic substrates, but also as direct function activators through mechanisms like specific changes in the tyrosine phosphorylation status of distinct proteins. Finally, mammalian sperm utilizes non-glucidic substrates like citrate and lactate to obtain energy in a regular form. This utilization is also finely regulated and of importance to maintain overall sperm function. This implies that the exact proportion of glucidic and non-glucidic energy substrates could be very important to optimize the survival ability of these cells in conservation.


Neuroimaging in 205 consecutive Children Diagnosed with Central Precocious Puberty in Denmark.
A brain magnetic resonance image (MRI) is considered part of routine evaluation in children diagnosed with central precocious puberty (CPP) to rule out intracranial pathology. We evaluated the occurrence of pathological findings on neuroimaging among children diagnosed with CPP. A retrospective study based on an evaluation of 1544 children referred with early signs of puberty from 2009-2019. Of these, 205 children (29 boys) with confirmed CPP had a brain MRI performed, and we report MRI results, pubertal stage, bone age, and hormonal analyses. All abnormal MRI results were re-evaluated by a trained neuroradiologist. A new intracranial pathology was found by brain MRI in 6 out of 205 patients aged 1.5 to 6.1 years. The occurrence of intracranial pathology was 3/162 (1.8%) and 3/24 (12.5 %) in girls and boys respectively. Organic causes of precocious puberty are more frequent in boys with CPP than in girls. No cases of organic CPP were seen above age 6.1 years of age. The age cut off value for routine brain MRI could be lowered to seven or perhaps even six years of age for girls, except in rapidly progressing puberty or presence of neurological symptoms. In our study of children with central precocious puberty (CPP), intracranial pathology is a rare cause and occurs only in younger children. It supports the general trend, that younger children are at higher risk of having organic causes to CPP and supports the clinical practice, that only high-risk patients with CPP should undergo routine brain MRI.


Spatial distribution and temporal change of carbon storage in timber biomass of two different forest management units.
Forests make up large ecosystems and can play an important role in mitigating the emissions of CO2, the most important greenhouse gas. However, they are sources of atmospheric carbon when they are disturbed by human or natural causes. Storage of carbon through expansion and adaptive management of forest ecosystems can assist in reducing carbon concentrations in atmosphere. This study proposes a methodology to produce spatially explicit estimates of the carbon storages (aboveground plus belowground) depending on land use/cover changes in two different forest ecosystems during various periods. Carbon storages for each forest ecosystem were projected according to inventory data, and carbon storages were mapped in a geographic information system (GIS). Results showed that total carbon stored in above and belowground of both forest ecosystems increased from one period to other because of especially increase of productive forest areas and decline of degraded forest areas as well as protection of spruce forests subject to insect attacks.


Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).
Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.


Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease.
In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrPTSE) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrPTSE MVAG), showing that PrPTSE MVAG is composed of multiple conformers with biochemical properties distinct from those of PrPTSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MVAG to bank voles and gene-targeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrPTSE deposition patterns, and PrPTSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MVAGIMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two different major conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combinations of pathological prion protein types with codon 129 genotypes results in the identification of 3 or 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding of the pathogenesis of the disease and of possible mechanisms of prion transmission.


Pest Control Potential of Social Wasps in Small Farms and Urban Gardens.
In environments undergoing constant transformation due to human action, such as deforestation and urbanization, the emergence of pests has become a challenge for agriculture and human welfare. In Brazil, over a thousand tonnes of pesticides are used annually, causing serious environmental damage such as the decline of insect populations. It is necessary to search for control alternatives in order to reduce the environmental impact caused by insecticides. This review aims to describe the use of social wasps as agents of biological control, focusing on the perspectives of their use in small farms and urban gardens, and to discuss the benefits of using this method. Studies have shown that 90-95% of the prey captured by wasps in small crops is made of leaf-eating caterpillars. In urban gardens, wasps diversify their prey, among which potential disease vectors, such as dipterans, stand out. We outline techniques for managing social wasp colonies in small farm and urban garden settings, including the use of artificial shelters. Among the advantages of using wasps as control agents, we highlight the practicality of the method, the low operational cost, the absence of prey resistance and the decrease of the use of insecticides.


Where is the Dialectic in the Community-Diversity Dialectic?
Agent-based modeling has provided some interesting investigations of the hypothesis that there is a dialectical relationship between sense of community and diversity. A close look at those models strongly suggests that only models in which the attributes of agents are fixed completely support that hypothesis. Models which acknowledge that diversity is contextually defined, and thus changeable, suggest that there is no inherent dialectical relationship between the two values. Rather, it is the context of the setting, the way in which the setting is socially constructed, that determines whether a strong sense of community can exist in highly diverse settings.


A comparison of embedded validity indicators from the Stroop Color and Word Test among adults referred for clinical evaluation of suspected or confirmed attention-deficit/hyperactivity disorder.
This study investigated the utility of four Stroop Color and Word Test (SCWT) indices, including the raw score and T score for the word reading (WR) and color naming (CN) trials, as embedded performance validity tests (PVTs) within a sample referred for evaluation of suspected or known attention-deficit/hyperactivity disorder (ADHD). Data were analyzed from a final sample of 317 patients consecutively referred for ADHD evaluation, which was divided into groups with invalid (n = 43; 14%) and valid neuropsychological test performance (n = 274; 86%). A subset of the valid group with confirmed ADHD diagnoses (n = 226; 71%) were also analyzed separately. Classification accuracy for the overall valid sample was in the acceptable range (AUCs = .757-.794), with optimal cut scores of WR raw ≤75 (54% sensitivity/90% specificity), WR T score ≤ 28 (54% sensitivity/88% specificity), CN raw ≤57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). Classification accuracy was also in the acceptable range for the ADHD-confirmed subgroup (AUCs = .750-.790), with optimal cut scores of WR Raw ≤ 75 (54% sensitivity/89% specificity), WR T score ≤ 28 (54% sensitivity/87% specificity), CN Raw ≤ 57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). These findings indicate that embedded PVTs derived from the SCWT, particularly those derived from the WR trial, are effective measures for determining validity status in samples with suspected or confirmed ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii.
Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.


The pheromone production of female Plodia interpunctella is inhibited by tyraminergic antagonists.
Several compounds were found to suppress the calling behavior and in vitro pheromone biosynthesis of the Indian meal moth, Plodia interpunctella. The compounds were screened by means of a calling-behavior bioassay with female P. interpunctella. Five derivatives with activities in the nanomolar range were identified, in order of decreasing pheromonostatic activity: 4-hydroxybenzaldehyde semicarbazone (42) > 5-(4-methoxyphenyl)-1,3-oxazole (38) > 5-[4-(tert-butyl)phenyl]-1,3-oxazole (40) > 5-(3-methoxyphenyl)-1,3-oxazole (35) > 5-(4-cyanophenyl)-1,3-oxazole (36). These compounds also showed in vitro inhibitory activity in intracellular de novo pheromone biosynthesis, as determined with isolated pheromone-gland preparations that incorporated [1-(14)C]sodium acetate in the presence of the so-called pheromone-biosynthesis-activating neuropeptide (PBAN). The non-additive effect of the inhibitor with antagonist (yohimbine) for the tyramine (TA) receptor suggests that it could be a tyraminergic antagonist. Three-dimensional (3D) computer models were built from a set of compounds. Among the common-featured models generated by the program Catalyst/HipHop, aromatic-ring (AR) and H-bond-acceptor-lipophilic (HBAl) features were considered to be essential for inhibitory activity in the calling behavior and in vitro pheromone biosynthesis. Active compounds, including yohimbine, mapped well onto all the AR and HBAl features of the hypothesis. Less-active compounds were shown to be unable to achieve an energetically favorable conformation, consistent with our 3D common-feature pharmacophore models. The present hypothesis demonstrates that calling behavior and PBAN-stimulated incorporation of radioactivity are inhibited by tyraminergic antagonists.


Do memory aids help everyday memory? A controlled trial of a Memory Aids Service.
There is a growing body of knowledge about the use of compensatory memory aids in memory rehabilitation, but relatively few controlled trials on how to train the use of such aids. This study investigated the effects of systematic training in the use of compensatory memory aids on everyday memory functioning within a Memory Aids Service. In a controlled clinical trial, a comparison was made between treatment participants and waiting list controls. Participants had everyday memory problems secondary to progressive or non-progressive neurological conditions. Following baseline assessment and goal setting, treatment participants underwent three training sessions, in which memory aids were matched to goals, across a six week period, with a follow-up assessment 12 weeks later. Outcome was measured by a goal attainment diary, neuropsychological test performance, psychosocial questionnaires and a problem solving inventory. There was a significant treatment effect of training on the goal attainment diary but only at 12 weeks follow-up. A post-hoc analysis indicated that treatment was effective for participants with a non-progressive condition but not for participants with a progressive condition. We conclude that a Memory Aids Service can be beneficial for patients with a non-progressive neurological condition, and make suggestions that might inform future applications of memory aids with those who have a progressive neurological disorder.


Electrochemical detection of carbamate pesticides at conductive diamond electrodes.
Conductive boron-doped diamond thin-film electrodes were used for the electrochemical detection of selected N-methylcarbamate pesticides (carbaryl, carbofuran, methyl 2-benzimidazolecarbamate, bendiocarb) after liquid chromatographic separation. Two kinds of detection methods were adopted in this study. In the first method, a direct detection of underivatized pesticides was carried out at an operating potential of 1.45 V versus Ag/AgCl, which resulted in the detection limits of 5-20 ng/mL (or 5-20 ppb) with S/N = 2 due to the low background current and wide potential window of the diamond electrode. In the second method, the detection limits were improved by subjecting the pesticide samples to alkaline hydrolysis in a separate step prior to injection. The phenolic derivatives obtained by alkaline hydrolysis oxidize at a relatively lower potential (0.9 V vs Ag/AgCl), which increases the sensitivity drastically. The advantage of the diamond electrode for the detection of phenolic derivatives is that it offers excellent stability in comparison to other electrodes. This method gives the detection limits of 0.6-1 ng/mL (or 0.6-1 ppb), which are well below the maximum residue levels allowed for carbaryl, carbofuran, and bendiocarb. While the lowest detection limits (LOD) obtained by the direct detection of pesticides are comparable to the those reported by the well-established HPLC-fluorescence, the LODs of the alkaline hydrolysis method are found to be even lower than the reported limits. On-line reactivation of the diamond electrode surface was shown to be possible by an anodic treatment of the electrode at approximately 3 V for 30 min in case of electrode fouling, which may occur after a prolonged use. Such a treatment damages the glassy carbon (GC) and metal electrodes, while the diamond electrode remains stable. These results suggest that the diamond electrode is superior to the other previously used electrodes such as GC and Kelgraf type for highly sensitive and stable detection of carbamate pesticides.


Circulating Microvesicles Regulate Treg and Th17 Differentiation in Human Autoimmune Thyroid Disorders.
Microvesicles (MVs) are emerging as important contributors to the development of inflammatory and autoimmune diseases. MVs can mediate immune modulation carrying genetic information, including microRNAs that can be transferred between cells. We determined the plasma levels of annexin-V+ MVs derived from different immune cells and platelets in patients with autoimmune thyroid diseases (AITDs) and in healthy controls. T lymphocyte polarization assays were performed in the presence of MVs to evaluate their effect in T regulatory and T helper 17 cells differentiation. microRNA content into plasma MVs and their corresponding mRNA targets were evaluated by RT-PCR. The percentage of platelet-derived MVs (CD41a+) was significantly increased in plasma samples from AITD patients compared with healthy controls. In contrast, patients with AITD showed a lower percentage of leukocyte and endothelial cell-derived MVs compared with controls. In addition, functional assays showed that MVs from AITD patients inhibited the in vitro differentiation of Foxp3+ T regulatory cells (11.35% vs 4.40%, P = .01) and induced the expression of interferon-γ by CD4+ lymphocytes (10.91% vs 13.99%, P = .01) as well as the differentiation of T helper 17 pathogenic (IL-17+interferon-γ+) cells (1.98% vs 5.13%, P = .03). Furthermore, in AITD patients, whereas miR-146a and miR-155 were increased in circulating MVs, their targets IL-8 and SMAD4 were decreased in peripheral blood mononuclear cells. Our data indicate that circulating MVs seem to have a relevant role in the modulation of the inflammatory response observed in AITD.


Radioimmunoassay for human alpha 1 -fetoprotein.
A method of radioimmunoassay has been developed for the quantitation of alpha(1)-fetoprotein in human serum. The assay requires 20 mul of serum, can be completed in 8 hr, and can reproducibly detect concentrations of 20 ng of alpha(1)-fetoprotein per ml of serum. Hence, the method is about 500-fold more sensitive for the detection of alpha(1)-fetoprotein than the Ouchterlony teohnique currently in general use. The procedure is of potential clinical value as an aid in the diagnosis of cancer and a number of noncancerous hepatic diseases.


Clinical use of systemic antifungal agents.
The chemistry, pharmacology, pharmacokinetics, clinical uses, adverse effects, and drug interactions of amphotericin B, flucytosine, ketoconazole, and miconazole are reviewed. Amphotericin B, a heptaene compound with poor water solubility, disrupts the fungal cell wall by binding to ergosterol. Ketoconazole and miconazole, imidazole derivatives, are poorly water soluble and inhibit the synthesis of ergosterol. Flucytosine is a readily water-soluble, fluorinated pyrimidine agent that may be metabolized to fluorouracil. The pharmacokinetics of amphotericin B is unique and has not yet been clearly defined. After oral administration, absorption of flucytosine from the gastrointestinal tract is rapid and nearly complete. In adults, oral administration of ketoconazole produces peak concentrations of drug one to two hours after the dose. Miconazole is administered only intravenously and distributes well into most tissues. Amphotericin B remains the drug of choice for most systemic mycoses. Dosing of amphotericin B is often empiric and patient specific. Flucytosine is rarely used alone; the combination of flucytosine and amphotericin B exerts synergistic killing of many fungi. Ketoconazole is effective for treating many chronic fungal infections. Miconazole is seldom used because of the availability of agents that are equally effective, less toxic, or both. Nephrotoxicity can occur with amphotericin B therapy, while flucytosine is associated with gastrointestinal and hematologic toxicities. Ketoconazole is much less toxic than any of the other agents, while miconazole has a high incidence of adverse effects. In addition to the need for more effective and less toxic agents, research is needed to clearly define the pharmacokinetics and pharmacodynamics of currently available antifungal drugs.


Clinical validity of the Mattis Dementia Rating Scale-2 in Parkinson disease with MCI and dementia.
The utility of the Mattis Dementia Rating Scale 2 (MDRS-2) in screening for dementia in Parkinson disease (PD) is well documented. However, little is known about its sensitivity to mild cognitive impairment in PD (PD-MCI). This study sought to document the validity of the MDRS-2 for diagnoses of PD-MCI and dementia in PD (PDD). Twenty-two healthy controls (HCs), 22 PD-MCI, and 16 PDD were compared on each MDRS-2 subscales and MDRS-2 total standard scores. Patients with PDD performed significantly worse than the other groups (all Ps < .05) on the MDRS-2 total and on all subscales, except attention. PD-MCI had significant lower scores than HCs on the MDRS-2 total and on initiation/perseveration and memory subscales. The optimal cutoff score for PD-MCI diagnosis was ≤ 140/144 and ≤ 132/144 for PDD. These findings suggest that MDRS-2 is a useful tool to identify dementia but that there might be a ceiling effect in the MDRS-2 cutoff score to diagnose MCI in PD.


Metallothionein: the multipurpose protein.
Metallothioneins (MTs) are intracellular, low molecular, low molecular weight, cysteine-rich proteins. Ubiquitous in eukaryotes, MTs have unique structural characteristics to give potent metal-binding and redox capabilities. A primary role has not been identified, and remains elusive, as further functions continue to be discovered. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs and inflammatory mediators. In teh gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration and/or redox control. Use of mice with altered gene expression has enhance our understanding of the multifaceted role of MT, emphasised in this review.