Curcumin Inhibition of TGFβ signaling in bone metastatic breast cancer cells and the possible role of oxidative metabolites.
TGFβ signaling promotes progression of bone-metastatic (BMET) breast cancer (BCa) cells by driving tumor-associated osteolysis, a hallmark of BCa BMETs, thus allowing for tumor expansion within bone. Turmeric-derived bioactive curcumin, enriched in bone via local enzymatic deconjugation of inactive circulating curcumin-glucuronides, inhibits osteolysis and BMET progression in human xenograft BCa BMET models by blocking tumoral TGFβ signaling pathways mediating osteolysis. This is a unique antiosteolytic mechanism in contrast to current osteoclast-targeting therapeutics. Therefore, experiments were undertaken to elucidate the mechanism for curcumin inhibition of BCa TGFβ signaling and the application of this finding across multiple BCa cell lines forming TGFβ-dependent BMETs, including a possible role for bioactive curcumin metabolites in mediating these effects. Immunoblot analysis of TGFβ signaling proteins in bone tropic human (MDA-SA, MDA-1833, MDA-2287) and murine (4T1) BCa cells revealed uniform curcumin blockade of TGFβ-induced Smad activation due to down-regulation of plasma membrane associated TGFβR2 and cellular receptor Smad proteins that propagate Smad-mediated gene expression, resulting in downregulation of PTHrP expression, the osteolytic factor driving in vivo BMET progression. With the exception of early decreases in TGFβR2, inhibitory effects appeared to be mediated by oxidative metabolites of curcumin and involved inhibition of gene expression. Interestingly, while not contributing to changes in Smad-mediated TGFβ signaling, curcumin caused early activation of MAPK signaling in all cell lines, including JNK, an effect possibly involving interactions with TGFβR2 within lipid rafts. Treatment with curcumin or oxidizable analogs of curcumin may have clinical relevancy in the management of TGFβ-dependent BCa BMETs.


Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene.
The authors present three novel missense mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, the causative gene for hereditary inclusion body myopathy, in Japanese patients with distal myopathy with rimmed vacuoles. Seven out of nine patients had homozygous V572L mutation, one was a compound heterozygote with C303V and V572L mutations, and the remaining patient bore homozygous A631V mutation.


Buruli ulcer - A neglected tropical disease in the Barwon region of Victoria, Australia: An emerging public health threat with local and national ramifications.
Mycobacterium ulcerans (MU) is known to be endemic in heavily touristed coastal regions of Victoria and is the cause of Buruli ulcer (BU) disease. The incidence, severity and geographic spread of MU infection/BU disease is increasing, including metropolitan Victorian suburbs. While the specifics of disease transmission and effective prevention strategies remain uncertain, severe complications can be mitigated by health systems that provide vigilant population surveillance to underpin early recognition, early specialist involvement and definitive treatment for the individual. Current theories regarding disease transmission and 'best practice' (or best guess) prevention and mitigation measures are presented herein. Opportunities to improve the health system response to this emerging public health threat are identified. It is incumbent upon all healthcare providers, including ED clinicians, to contribute by familiarising themselves with the established and emerging areas of endemicity of MU infection and the array of BU clinical presentations.


Circulating immune complexes in patients with rheumatoid arthritis and the effect of penicillamine in vitro.
Protein precipitated from the sera of 15 patients with rheumatoid arthritis (RA) by increasing concentrations of polyethylene glycol 6000 (PEG) was compared with that from 20 normal controls. The wide range of precipitable protein obtained was only significantly different for the two groups when a 4% PEG concentration was used. To increase the discrimination of the procedure, the precipitated protein was measured for IgG, IgM, C3 and C4 using immunospecific antisera and laser nephelometry. The data obtained from each of these procedures did not increase the specificity of the technique as a means of distinguishing between patients and controls. As part of an investigation of the effect of penicillamine on immune complexes, penicillamine was incubated at 37 degrees C for 24 and 48 h with sera containing immune complexes from RA patients. When the immune complexes were precipitated with PEG, it was found that incubation, by itself, reduced the amount of PEG precipitable protein. The results of in vitro incubation with penicillamine were very variable.


Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema.
To identify the relative contribution of hydrostatic and permeability mechanisms to the development of human neurogenic pulmonary edema. Retrospective review of patients with neurogenic pulmonary edema who had pulmonary edema fluid analysis. University hospital ICU. Twelve patients with neurogenic pulmonary edema in whom the associated neurologic condition was subarachnoid hemorrhage (n = 8, 67%), postcraniotomy (n = 2), and stroke (n = 2). Protein concentration was measured from pulmonary edema fluid and plasma samples obtained shortly after the onset of clinical pulmonary edema. The mechanism of pulmonary edema was classified according to the initial alveolar edema fluid to plasma protein concentration ratio. A hydrostatic mechanism (ratio < or = 0.65) was observed in seven patients, none of whom had cardiac failure or intravascular volume overload. Five patients had evidence for increased permeability (ratio > 0.70). Patients with a hydrostatic mechanism had better initial oxygenation (mean +/- SD PaO2/FIO2 [fraction of inspired oxygen] = 233 +/- 132) compared with patients with increased permeability (PaO2/FIo2 = 80 +/- 42), and oxygenation improved more rapidly in the hydrostatic patients. Overall mortality (58%) was high, but it was related to unresolved neurologic deficits, not to respiratory failure. Many of our patients had a hydrostatic mechanism for neurogenic pulmonary edema. This is a novel observation in humans since prior clinical case reports have emphasized increased permeability as the usual mechanism for neurogenic pulmonary edema. These findings are consistent with pulmonary venoconstriction or transient elevation in left-sided cardiovascular pressures as contributing causes to the development of human neurogenic pulmonary edema.


Intradural Lumbar Disc Herniation From the Lateral Inner Surface of the Dura Without a Penetration Hole: A Case Report.
Intradural disc herniation (IDH) is usually diagnosed during surgery when a herniated mass is found to have penetrated the ventral dura. We experienced a case of IDH that entered the dura from the lateral side with no penetrating hole. A 61-year-old man presented to our institution with left leg pain of two months' duration. Plain x-ray imaging showed degeneration of the lumbar spine, and a magnetic resonance imaging (MRI) scan revealed a suspected tumor at the L3-L4 level. Two weeks later, the patient suffered from acute cauda equina syndrome. A gadolinium-enhanced MRI showed an enlarged lesion with no enhancement visible, and emergency surgery was performed. The lesion originated from the left side of the dura. Despite the white debris suggesting a herniated disc, no penetrating hole was found in the dura. Pathologically, the lesion was found to be an intervertebral disc and was diagnosed as an intradural lumbar disc herniation. The patient's neurological symptoms improved, but he did not recover his left ankle dorsiflexion. In a degenerated lumbar spine, IDH may not always originate from the ventral dura and may not be accompanied by a penetrating hole.


MRI texture analysis in predicting treatment response to neoadjuvant chemoradiotherapy in rectal cancer.
To evaluate the importance of MRI texture analysis in prediction and early assessment of treatment response before and early neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). This retrospective study comprised of 59 patients. The tumoral texture parameters were compared between pre- and early nCRT. Area Under receiver operating characteristic (ROC) Curves [AUCs] were used to compare the diagnostic performance of statistically significant difference parameters and logistic regression analysis predicted probabilities for discriminating responders and nonresponders. The Standard Deviation (SD), kurtosis and uniformity were statistically significantly difference between pre- and early nCRT (p = 0.0012, 0.0001, and < 0.0001, respectively). In pathological complete response (pCR) group, pre-uniformity and pre-Energy were significantly higher than that of nonresponders (p = 0.03 and p < 0.01, respectively), while the pre-entropy in nonresponder was reverse (p = 0.01). The diagnostic performance of pre-kurtosis and pre-Energy were higher in tumor regression grade (TRG) and pCR group (AUC = 0.67, 0.73, respectively). Logistic regression analysis showed that diagnostic performance for prediction responder and nonresponder did not significantly improve compared with to pre-uniformity, energy and entropy in pCR group (AUC = 0.76, p = 0.2794, 0.4222 and 0.3512, respectively). Texture parameters as imaging biomarkers have the potential to prediction and early assessment of tumoral treatment response to neoadjuvant chemoradiotherapy in patients with LARC.


Molecular orientation of enzymes attached to surfaces through defined chemical linkages at the solid-liquid interface.
The immobilization of enzymes on solid supports is widely used in many applications, including biosensors, antifouling coatings, food packaging materials, and biofuel cells. Enzymes tend to lose their activity when in contact with a support surface, a phenomenon that has been attributed to unfavorable orientation and (partial) unfolding. In this work, specific immobilization of 6-phospho-β-galactosidase (β-Gal) on a self-assembled monolayer (SAM) containing maleimide end groups and oligo(ethylene glycol) spacer segments was achieved through a unique cysteinyl residue. A systematic means to characterize the interfacial orientation of immobilized enzymes has been developed using a combination of sum frequency generation vibrational spectroscopy and attenuated total reflectance FTIR-spectroscopy. The possible orientations of the immobilized β-Gal were determined and found to be well-correlated with the tested activity of β-Gal. This study will impact the development of an increasingly wide range of devices that use surface-immobilized enzymes as integral components with improved functions, better sensitivity, enhanced stability, and longer shelf life.


Synthesis of 3-Substituted 2-Arylpyridines via Cu/Pd-Catalyzed Decarboxylative Cross-Coupling of Picolinic Acids with (Hetero)Aryl Halides.
A decarboxylative cross-coupling of 3-substituted picolinic acids with (hetero)aryl halides is presented. In the presence of catalytic Cu2O and Pd(1,5-cyclooctadiene)Cl2 with 2-dicyclohexylphosphino-2'-(N,N-dimethylamino)biphenyl as the ligand, both electron-rich and electron-deficient aryl bromides and chlorides as well as heteroaryl bromides were successfully coupled with various picolinate salts under mild conditions in yields up to 96%. This protocol provides an efficient entry to 2-(hetero)arylpyridines, an attractive substance class in drug discovery.


Quantification of Bacterial Loads in Caenorhabditis elegans.
Caenorhabditis elegans is a ubiquitous free-living nematode that feeds on bacteria. The organism was introduced into a laboratory setting in the 1970s and has since gained popularity as a model to study host-bacteria interactions. One advantage of using C. elegans is that its intestine can be colonized by the bacteria on which it feeds. Quantifying the bacterial load within C. elegans is an important and easily obtainable metric when investigating host-bacteria interactions. Although quantification of bacteria harbored in C. elegans via whole-worm lysis is not a novel assay, there is great variation between existing methods. To lyse C. elegans, many protocols rely on the use of a hand-held homogenizer, which could introduce systematic error and subsequent variation between researchers performing the same experiment. Here, we describe a method of lysing the intestines of C. elegans to quantify the bacterial load within the intestine. Our method has been optimized for removing exogenous bacteria while maintaining worm paralysis, to ensure no bactericidal agents are swallowed, which could kill bacteria within the intestine and affect results. We utilize and compare the efficiency of two different homogenization tools: a battery-powered hand-held homogenizer, and a benchtop electric homogenizer, where the latter minimizes variability. Thus, our protocol has been optimized to reduce systematic error and decrease the potential for variability among experimenters. Graphic abstract: Simplified overview of the procedure used to quantify the bacterial load within C. elegans. The two different methods are herein described for worm lysis: "Option 1" is a hand-held homogenizer, and "Option 2" is a benchtop homogenizer.


Progesterone-binding proteins in plasma of guinea-pigs and other hystricomorph rodents.
Progesterone-binding plasma proteins (PBPP, progesterone-binding globulin, PBG, and corticosteroid binding globulin, CBG) have been measured in plasma of guinea-pigs, casiragua, cuis, degu and plains viscacha. During pregnancy PBPP increased to reach peak values between Days 20-25 and Days 50-term in guinea-pigs, immediately before parturition in casiragua, and in mid-gestation in cuis, degu and viscacha. The pattern of PBPP concentration during pregnancy was similar to that of plasma progesterone concentration, and the ratio of molar concentration of PBPP and progesterone was greater than 1 in all species. Plasma proteins were separated by chromatography on SP-Sephadex C-50, and from its chromatographic behaviour and progesterone-binding property evidence was obtained for an anionic, high-affinity PBG in the plasma of all the animals studied during gestation: Electrophoretic mobility of SP-Sephadex-purified PBG applied to 7% polyacrylamide gels differed between species, being highest for casiragua PBG and lowest for guinea-pig PBG. Binding capacities ranged from 0.5 to 4.8 X 10(-6) M, and association constants from 7.6 to 17.4 X 10(8) M-1. Ligand specificities differed between species and marked contrasts were found for certain steroid isomers. The average molecular weights measured by gel electrophoresis of PBG under denaturing conditions were similar in cuis, degu and viscacha and close to PBG I of guinea-pigs, while coypu PBG had a molecular weight of about one half, approximately 75000. It is concluded that PBG has been adopted in pregnancy as a progesterone-conserving mechanism in this suborder of rodents with long gestation periods relative to maternal body weight. Restricted homologies in the physico-chemical characteristics of PBG from various hystricomorph rodents suggest that interspecific differences in structure are considerable.


Glucose inhibits prostacyclin production by cultured aortic endothelial cells.
A reduction in production of prostacyclin (PGI2) by the cells in the vascular wall may play a role in the pathogenesis of atherosclerosis in diabetic patients. The present study was undertaken to evaluate the effect of glucose on PGI2 production by endothelial cells in vitro. It was shown that PGI2 production by cultured bovine aortic endothelial cells was significantly reduced in the presence of a high concentration of glucose (300 mg/dl) compared with physiological concentrations of glucose (100 mg/dl). In contrast, no reduction in PGI2 production was observed in cells cultured with equimolar mannitol, suggesting that glucose itself, rather than the effect of osmolality, inhibited PGI2 production by cultured endothelial cells. In addition, a high concentration of glucose also inhibited the proliferation of cultured endothelial cells.


Patient volumes and pre- and postdischarge postpartum infection: A retrospective cohort study.
To examine the association between hospital and clinician obstetric volume and postpartum infection risk in the pre- and postdischarge periods. We used data from the 2011 New York State Inpatient and Emergency Department Databases to fit generalized estimating equation models to examine the effect of hospital and clinician obstetric volume on infection before discharge and in the 30 days after discharge after delivery. Higher clinician volume was associated with lower predischarge infection risk (odds ratio [OR] for first vs third quartile was 0.84; 95% confidence interval [CI], 0.77-0.98). There was an uncertain trend toward higher predischarge infection risk in higher volume hospitals (OR for first vs third quartile was 1.36; 95% CI, 0.79-2.34). We found no associations between patient volumes and postdischarge infections; however, power was insufficient to rule out small associations. The joint association of hospital and clinician volumes with postdischarge infection appeared submultiplicative (product term OR = 0.95; 95% CI, 0.92-0.98). This study adds to the evidence that hospital obstetric volume is positively associated with predischarge postpartum infections, whereas clinician volume may be negatively associated with those predischarge infections. The associations between hospital obstetric volume and postdischarge infection appear to differ. These results underscore the importance of including postdischarge follow-up in hospital-based studies of postpartum infection.


Incorporation of isotopically labeled cocaine into human hair: race as a factor.
In order to evaluate race as a possible factor affecting the incorporation of drugs into human hair, 2 mg/kg deuterium-labeled cocaine (cocaine-d5) was administered intranasally to nine male non-Caucasian volunteers under controlled laboratory conditions. Sequential blood samples were collected for up to three days, and scalp hair samples were collected at 24 and 72 h after dosing and at monthly intervals for up to 12 months. The samples were then analyzed by gas chromatography-mass spectrometry for cocaine-d5 and benzoylegonine-d5 (BZE-d5). The amounts of cocaine-d5 found in the hair of these non-Caucasian subjects were compared with the amounts of cocaine-d5 found in the hair of Caucasian subjects who received the same cocaine dose under identical conditions as part of a study we reported previously. The non-Caucasians in the present study had approximately 2.7 times more cocaine-d5 in their hair than the Caucasian subjects in the earlier study. In five of the non-Caucasian subjects, cocaine-d5 could be detected in hair within 24 h after dosing. Curiously, we were unable to detect any cocaine-d5 in one of the non-Caucasian subject's hair at any time after dosing even though cocaine-d5 was in plasma at the expected levels. The results from these studies suggest there may be a racial bias in the incorporation of cocaine into human hair; however, the data are not conclusive because of the relatively small sample size.


Double-wall TiO2 nanotube arrays: enhanced photocatalytic activity and in situ TEM observations at high temperature.
By decreasing the water content in an NH4F and glycerol-water electrolyte, the transition from single-wall to double-wall TiO2 nanotube arrays was successfully achieved using an anodization method. The double-wall TiO2 nanotube structures exhibited better photocatalytic activity than the typical single-wall structures. After modification with platinum nanoparticles, the photocatalytic activity of both the single- and double-wall TiO2 nanotubes was improved further. In situ observations at the annealing temperature of the TiO2 nanotubes were performed using a transmission electron microscopy (TEM) system. A slower structural failure of the nanotubes was obtained with the introduction of oxygen gas into the TEM column compared with the structural changes observed under high-vacuum conditions without the introduction of oxygen gas. These behaviors suggest that oxygen injection is an important factor in stabilizing the TiO2 nanotubes during the in situ TEM annealing process. The high-magnification TEM images of the double-wall TiO2 nanotubes revealed that the sintering of the inner wall can draw a clear distinction between the inner and outer walls.


Dermatological complications of obesity.
Obesity is a health problem of considerable magnitude in the Western world. Dermatological changes have been reported in patients with obesity, including: acanthosis nigricans and skin tags (due to insulin resistance); hyperandrogenism; striae due to over extension; stasis pigmentation due to peripheral vascular disease; lymphedema; pathologies associated with augmented folds; morphologic changes in the foot anatomy due to excess load; and complications that may arise from hospitalization. Acanthosis nigricans plaques can be managed by improved control of hyperinsulinemia; the vitamin D3 analog calcipitriol has also been shown to be effective. Skin tags can be removed by snipping with curved scissors, by cryotherapy or by electrodesiccation. Hyperandrogenism, a result of increased production of endogenous androgens due to increased volumes of adipose tissue (which synthesizes testosterone) and hyperinsulinemia (which increases the production of ovarian androgens) needs to be carefully assessed to ensure disorders such as virilizing tumors and congenital adrenal hyperplasia are treated appropriately. Treatment of hyperandrogenism should be centred on controlling insulin levels; weight loss, oral contraceptive and antiandrogenic therapies are also possible treatment options. The etiology of striae distensae, also known as stretch marks, is yet to be defined and treatment options are unsatisfactory at present; striae rubra and alba have been treated with a pulsed dye laser with marginal success. The relationship between obesity and varicose veins is controversial; symptoms are best prevented by the use of elastic stockings. Itching and inflammation associated with stasis pigmentation, the result of red blood cells escaping into the tissues, can be treated with corticosteroids. Lymphedema is associated with dilatation of tissue channels, reduced tissue oxygenation and provides a culture medium for bacterial growth. Lymphedema treatment is directed towards reducing the limb girth and weight, and the prevention of infection. Intertrigo is caused by friction between skin surfaces, combined with moisture and warmth, resulting in infection. This infection, most commonly candidiasis, is best treated with topical antifungal agents; systemic antifungal therapy may be required in some patients. Excess load on the feet can result in morphological changes that require careful diagnosis; insoles may offer some symptom relief while control of obesity is achieved. Obesity-related dermatoses associated with hospitalization, such as pressure ulcers, diminished wound healing, dermatoses secondary to respiratory conditions, and incontinence, must all be carefully managed with an emphasis on prevention where possible. Recognition and control of the dermatological complications of obesity play an important role in diminishing the morbidity of obesity.


Quantitative analysis of microvascular changes in diffuse astrocytic neoplasms with increasing grade of malignancy.
Because glioblastoma multiforme (GBM) frequently shows striking, glomeruloid microvascular proliferation (MVP), this tumor has become a strong candidate for anti-angiogenic therapy. However, the efficacy of anti-angiogenic treatment may rather be determined by the extent of classic angiogenesis with the formation of delicate microvascular sprouts. Therefore, this study differentially quantifies the microvascular changes in supratentorial diffuse astrocytic neoplasms by computerized image analysis of histological sections in which the microvessels were highlighted by a combined anti-collagen IV/MIB-1 staining. Four microvascular parameters (number, area, perimeter, diameter), the cellularity of the glial tissue, and the MIB-1 labeling index were assessed in biopsies of astrocytoma (A, n = 13), anaplastic astrocytoma (AA, n = 14), and GBM (n = 20), and in normal cerebral cortex (n = 7) and white matter (n = 7). In As and AAs, the microvascular parameters were not significantly different from each other, and the microvascular changes were generally limited compared with WM and CX. In contrast, in GBMs the microvascular parameters were highly variable, and their overall mean value was significantly increased compared with As and AAs (ranging from 1.3x for vessel diameter to 3.3x for vessel area). Our study indicates that not only glomeruloid MVP, but also classic angiogenesis, occurs mainly and only locally in GBMs. Thus, this study provides evidence that As and AAs are not good candidates for anti-angiogenic therapy. The efficacy of such therapy for GBMs awaits further evaluation.


Kikuchi-Fujimoto Disease presenting with fever, lymphadenopathy and dysphagia.
Kikuchi Fujimoto Disease (KFD) can present with dysphasia, fever and lymphadenopathy. A young Bangladeshi girl presented with fever, cervical lymphadenopathy, dysphasia, weight loss and skin rash. Antitubercular drugs were given on clinical judgement, with no improvement after one month. Later, fine needle aspiration and histopathology of Lymph Node suggested KFD. Computerized Tomography (CT) scan of neck revealed enlarged retropharyngeal lymphnode (LN) causing pharyngeal narrowing. Oral Prednisolone was given showing improvement and no relapse was encountered. KFD may present with dysphasia uncommonly along with fever and lymphadenopathy. Awareness of this disorder by clinicians and pathologists will help prevent misdiagnosis and inappropriate treatment.


Seasonal influenza vaccination in healthcare personnel in Greece: 3-year report.
Influenza vaccination rates of healthcare personnel (HCP) have been largely unsatisfactory in Greece. In September 2016, the Ministry of Health established a Steering Committee in order to raise influenza vaccine uptake by HCP. Hereby, we present the results of the actions undertaken by the Steering Committee during the first 2 years of operation. From the 2015-2016 through the 2017-2018 influenza season, influenza vaccination rates among HCP rose from 10.9 to 24.9% in hospitals, and from 24.3 to 40.2% in primary healthcare centers (increases of 128 and 65%, respectively). Rewards were consistently associated with higher vaccine uptake rates among HCP. The following strategies were also significantly associated with increased vaccination rates: vaccination on-site, vaccination of the heads of the departments and promotion of a culture of safety and ethical duty in the workplace.


Therapeutic strategies for invasive fungal infections in neonatal and pediatric patients.
Invasive Candida and Aspergillus infections are the most commonly encountered fungal infections. They appear to be life threatening in the setting of profound immunosuppression, whereas cases that are resistant to antifungal therapy are occasionally encountered. Novel antifungal triazole and echinocandin agents appear to exhibit good activity as first-line or salvage therapy, whereas the use of amphotericin B formulations is particularly valuable in neonates. Significant differences in toxicity have been demonstrated among various antifungal agents with in vitro activity from available comparative data on fungal infections in children: however, no clear difference in treatment efficacy has been demonstrated. However, very little data are available about neonates. Host factors and responsible fungal species most frequently guide the choice of therapy.


[Inefficacy of diltiazem in restenosis prevention after coronary angioplasty].
To evaluate the efficacy of diltiazem in preventing restenosis after balloon angioplasty (PTCA). Eighty-nine patients who were undergone to successful PTCA, were divided them in 2 groups (G): A) 44 patients (50%) who received diltiazem (180 mg tid) immediately after PTCA and were kept on it for 6 months); B) 45 patients (50%) who received placebo. Fifty two lesions were dilated in GA and 54 in GB. Patients were excluded from analysis for several reasons, including: necessity of diltiazem or others calcium channel blockers use; heart failure, bradicardia, AV block of any degree, PTCA to chronic total occlusion, ostial lesions and AMI less than 30 days prior to PTCA. Patients were randomized to either the active drug or placebo in a double blind fashion. Restenosis was defined as a 50% lesion. Patients underwent late angiography either at 6 months or sooner if clinically indicated. Both G were similar to age > 70 years (A = 7% vs B = 4%-p = NS), sex (A = 13% vs B = 11%-p = NS), stable angina (A = 43% vs B = 51%), unstable angina (A = 57% vs B = 49%-p = NS) and single vessel (A = 91% vs B = 87%-p = NS) or multivessel (A = 9% vs B = 13%-p = NS) PTCA. We studied 39/44 (89%) patients in GA and 43/45 (96%) in GB (p = NS). We observed restenosis in 17/39 (43%) in GA and 16/43 (37%) in GB (p = NS). The restenosis rate per lesion was 39% in GA and 31% in GB (p = NS). Diltiazem was ineffective in the prevention of restenosis following PTCA.


The epidemiology of major joint contractures: a systematic review of the literature.
Current knowledge on the epidemiology of major joint contractures is limited. We systematically reviewed the literature to identify studies examining the epidemiology of joint contracture regardless of clinical condition. Epidemiologic measures of interest were prevalence, incidence, and prognostic risk factors. We used Medline to identify all epidemiologic studies of major joint contractures published from 1966 to March 2005. There was a high prevalence of major joint contractures. Most studies focused on one joint rather than including all relevant major contractures. However, most studies did provide a definition of a contracture or the measures used to assess contractures. Immobility is a highly prevalent disability in at-risk populations, and constitutes a tremendous burden to patients in nursing homes, hospitals, and the outpatient community. The lack of epidemiologic data is a major impediment to providing appropriate treatment.


Colour blindness and natural selection: studies in four nomadic tribal groups from Andhra Pradesh, India.
438 males and 369 females from four endogamous nomadic groups of the Yerukala viz. Suvvi, Badda, Uppu and Kunchapuri of Andhra Pradesh (India) were examined for red-green colour blindness using the 15th edition of Isihara's colour blindness chart. The absence of defective colour vision in the Badda Yerukala and very low frequencies among the other groups agree not only with the hypotheses of Post (1962) and Pickford (1963) concerning the operation of natural selection, but corroborates, too, the opinion of Malhotra (1978) that nomads by virtue of their life-style demand good colour vision.


Quality of life in patients with a perineal hernia.
Patients who develop a perineal hernia after abdominoperineal resection may experience discomfort during daily activities and urogenital dysfunction, but the impact on quality of life has never been formally assessed. Patients who underwent abdominoperineal resection for rectal cancer between 2014 and 2022 in two prospective multicenter trials were included. Primary outcome was defined as median overall scores or scores on functional and symptom scales of the following quality of life questionnaires: 5-level version of the 5-dimensional EuroQol, Short Form-36, and European Organization for Research and Treatment of Cancer QoL Questionnaire Colorectal cancer 29 and 30, Urogenital Distress Inventory-6, Incontinence Impact Questionnaire-7. Questionnaires were available in 27 patients with a perineal hernia and 62 patients without a perineal hernia. The 5-dimensional EuroQol score was significantly lower in patients with a perineal hernia (83 vs 87, p = 0.048), which implies a reduced level of functioning. The median scores of pain-specific domains were significantly worse in patients with a perineal hernia as measured by the SF-36 (78 vs. 90, p = 0.006), the EORTC-CR29 (17 vs. 11, p=<0.001) and EORTC-C30 (17 vs. 0, p = 0.019). Also, significantly worse physical (73 vs. 100, p = 0.049) and emotional (83 vs. 100, p = 0.048) functioning based on EORTC-C30 was observed among those patients. Minimally important differences were found for role, physical and social functioning of the SF-36 and EORTC-C30. The urological function did not differ between the groups. A symptomatic perineal hernia can significantly worsen quality of life on several domains, indicating the severity of this complication.


[A DNA bank for people subjected to occupational irradiation. Goals and prospects].
A DNA bank was created to preserve the genetic material of staff of the first Russian atomic plant, Production Association (PO) Mayak, who were exposed to chronic external gamma-irradiation at various doses in the early years of plant operation. Some of the workers experienced combined irradiation from external and internal (incorporated plutonium-239) sources. The unique genetic material of the subjects and their children can be used to study the remote consequences of irradiation by means of modern molecular-genetic techniques. At present, the bank contains the genetic material of 500 people. A database was constructed to include medical, demographic, professional, and dose characteristics of each individual and quantitative and qualitative parameters of each DNA preparation. The bank is continuously augmented with new DNA samples of the irradiated people and members of their families.


Gene expression analysis of cold and freeze stress in Baker's yeast.
We used mRNA differential display to assess yeast gene expression under cold or freeze shock stress conditions. We found both up- and down-regulation of genes, although repression was more common. We identified and sequenced several cold-induced genes exhibiting the largest differences. We confirmed, by Northern blotting, the specificity of the response for TPI1, which encodes triose-phosphate isomerase; ERG10, the gene for acetoacetyl coenzyme A thiolase; and IMH1, which encodes a protein implicated in protein transport. These genes also were induced under other stress conditions, suggesting that this cold response is mediated by a general stress mechanism. We determined the physiological significance of the cold-induced expression change of these genes in two baker's yeast strains with different sensitivities to freeze stress. The mRNA level of TPI1 and ERG10 genes was higher in freeze-stressed than in control samples of the tolerant strain. In contrast, both genes were repressed in frozen cells of the sensitive strain. Next, we examined the effects of ERG10 overexpression on cold and freeze-thaw tolerance. Growth of wild-type cells at 10 degrees C was not affected by high ERG10 expression. However, YEpERG10 transformant cells exhibited increased freezing tolerance. Consistent with this, cells of an erg10 mutant strain showed a clear phenotype of cold and freeze sensitivity. These results give support to the idea that a cause-and-effect relationship between differentially expressed genes and cryoresistance exists in Saccharomyces cerevisiae and open up the possibility of design strategies to improve the freeze tolerance of baker's yeast.


Metatropic dysplasia: clinical and radiographic findings in 11 patients demonstrating long-term natural history.
We report on the largest long-term follow-up study in metatropic dysplasia incorporating data collected over a 37-year period. Case summaries from 11 patients are presented, ranging from 20 weeks of gestation to age 70 years, characterizing the natural history. All patients were seen through the Victorian Clinical Genetics Service and the Southern Cross Bone Dysplasia Centre. Our data lend little support for the current clinical classification of metatropic dysplasia and highlight a spectrum of severity in this rare condition, which we propose has an autosomal dominant inheritance pattern. Complications such as upper respiratory obstruction secondary to laryngo-tracheal dysfunction need to be carefully monitored for in infancy because this is a preventable cause of mortality. The progression of a thoracic kyphoscoliosis in this condition is often relentless and resistant to surgical treatment. Other causes of morbidity include cervical instability, hearing loss, and functional impairments resulting from degenerative joint deformity. Intellectual outcome in all surviving cases has been normal. Final adult heights ranged from 107 to 135 cm.


A valuable peroxidase activity from the novel species Nonomuraea gerenzanensis growing on alkali lignin.
Degradation of lignin constitutes a key step in processing biomass to become useful monomers but it remains challenging. Compared to fungi, bacteria are much less characterized with respect to their lignin metabolism, although it is reported that many soil bacteria, especially actinomycetes, attack and solubilize lignin. In this work, we screened 43 filamentous actinomycetes by assaying their activity on chemically different substrates including a soluble and semi-degraded lignin derivative (known as alkali lignin or Kraft lignin), and we discovered a novel and valuable peroxidase activity produced by the recently classified actinomycete Nonomuraea gerenzanensis. Compared to known fungal manganese and versatile peroxidases, the stability of N. gerenzanensis peroxidase activity at alkaline pHs and its thermostability are significantly higher. From a kinetic point of view, N. gerenzanensis peroxidase activity shows a Km for H2O2 similar to that of Phanerochaete chrysosporium and Bjerkandera enzymes and a lower affinity for Mn2+, whereas it differs from the six Pleurotus ostreatus manganese peroxidase isoenzymes described in the literature. Additionally, N. gerenzanensis peroxidase shows a remarkable dye-decolorizing activity that expands its substrate range and paves the way for an industrial use of this enzyme. These results confirm that by exploring new bacterial diversity, we may be able to discover and exploit alternative biological tools putatively involved in lignin modification and degradation.


Acoustic Radiation Force Impulse Elastography: A Useful Tool for Differential Diagnosis of Thyroid Nodules and Recommending Fine-Needle Aspiration: A Diagnostic Accuracy Study.
To investigate the diagnostic performance of combined use of conventional ultrasound (US) and elastography, including conventional strain elastography such as elasticity imaging (EI) and acoustic radiation force impulse (ARFI) elastography, and to evaluate their usefulness in recommending fine-needle aspiration (FNA).A total of 556 pathologically proven thyroid nodules were evaluated by US, EI, and ARFI examinations in this study. Three blinded readers scored the likelihood of malignancy for 4 datasets (ie, US alone, US and EI, US and virtual touch tissue imaging [VTI], and US and virtual touch tissue quantification [VTQ]). The diagnostic performances of 4 datasets in differentiating malignant from benign thyroid nodules were evaluated. The decision-making changes for FNA recommendation in the indeterminate nodules or the probably benign nodules on conventional US were evaluated after review of elastography.The diagnostic performance in terms of area under the ROC curve did not show any change after adding EI, VTI, or VTQ for analysis; and no differences were found among different readers; however, the specificity and positive predictive value (PPV) improved significantly after adding VTI or VTQ for analysis in the senior reader. For the indeterminate nodules on US that were pathologically benign, VTQ made correct decision-making changes from FNA biopsy to follow-up in a mean of 82.6% nodules, which was significantly higher than those achieved by EI (46.8%) and VTI (54.4%) (both P < 0.05). With regard to the probably benign nodules on US that were pathologically malignant, EI made the highest correct decision-making change from follow-up to FNA biopsy in a mean of 62.6% nodules (compared with 41.5% on VTQ, P < 0.05).The results indicated that ARFI increases the specificity and PPV in diagnosing thyroid nodules. US combined VTQ might be helpful in reducing unnecessary FNA for indeterminate nodules on US whereas US combined EI is useful to detect the false negative nodules that are probably benign on conventional US.


Verrucous carcinoma and squamous cell papilloma of the oral cavity: Report of two cases and review of literature.
Verrucous carcinoma (VC) of oral cavity is a rare variant of well-differentiated squamous cell carcinoma and squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass. There is a certain clinical similarity between squamous cell papilloma and VC. We presented a report of two cases which are VC and squamous cell papilloma that are showed the same clinical appearance but different pathological appearance, with a review of the literature.


Evaluating toxicologic end points to derive minimal risk levels for hazardous substances.
The Agency for Toxic Substances and Disease Registry (ATSDR) uses chemical-specific minimal risk levels (MRLs) to assist in evaluating public health risks associated with exposure to hazardous substances. MRLs are estimates of daily human exposure to a chemical that are likely to be without an appreciable risk of adverse noncancer health effects over a specified duration of exposure. MRLs serve as screening levels for health assessors to identify contaminants and potential health effects that may be of concern for populations living near hazardous waste sites and chemical releases. MRLs are derived from toxicologic data complied from a comprehensive literature search and are presented in ATSDR's toxicological profile for that substance. They are based on the most sensitive substance-induced end point considered to be of relevance to humans. MRLs for each substance are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) exposure durations, and for the oral and inhalation routes of exposure. In this paper, we present an overview of the approach used for evaluating the toxicologic end points in deriving the MRLs. Examples are given to illustrate the agency's efforts to achieve increased understanding, reduced uncertainty and improved public health guidance.


Steroid receptors in human spermatozoa.
The presence of steroid binding sites in (or on) human spermatozoa was first suggested in the late 1970s, by studies showing that some steroids were able to influence sperm function. Subsequently, several effects exerted on spermatozoa by biological fluids, such as follicular fluid, were found to be probably linked to the action of steroids, and among them progesterone. Since the effects of progesterone on spermatozoa were rapid, dose-dependent and not affected by progesterone conjugation with high molecular weight proteins unable to cross the plasma membrane, the existence of a novel class of non-genomic progesterone receptors was strongly suspected. This hypothesis was further supported by the observation that some of the effects of progesterone on human spermatozoa were not abolished by inhibitors of the classical progesterone nuclear receptors, nor mimicked by progesterone genomic receptor agonists. Recently, surface progesterone binding sites were directly identified on the membranes of human spermatozoa, and their mechanism of action partially characterized.


The twilight envelope: a user-centered approach to describing roadway illumination at night.
Visual recognition functions, such as acuity and contrast sensitivity, deteriorate rapidly over the declining luminances found during civil twilight. Thus civil twilight, a critical part of the transition between daylight and darkness, represents lighting conditions that may be useful to describe artificial illumination. Automotive headlamps project a three-dimensional beam that ranges from illumination levels comparable to daylight at the vehicle to the dark limit of civil twilight (3.3 1x) at some distance ahead. This twilight envelope is characterized as a distance beyond which foveal visual functions are severely impaired, and thus it provides a general, functional description of the useful extent of the headlamp beam. This user-centered approach to describing illumination is useful for characterizing visibility when driving at night or in other artificially lit environments. This paper discusses the twilight envelope approach and its application to intervehicle variations in headlamp systems. Actual or potential applications of this research include user-centered description of artificial illumination and driver/pedestrian safety education.


A Multiomics Approach to Identify Genes Associated with Childhood Asthma Risk and Morbidity.
Childhood asthma is a complex disease. In this study, we aim to identify genes associated with childhood asthma through a multiomics "vertical" approach that integrates multiple analytical steps using linear and logistic regression models. In a case-control study of childhood asthma in Puerto Ricans (n = 1,127), we used adjusted linear or logistic regression models to evaluate associations between several analytical steps of omics data, including genome-wide (GW) genotype data, GW methylation, GW expression profiling, cytokine levels, asthma-intermediate phenotypes, and asthma status. At each point, only the top genes/single-nucleotide polymorphisms/probes/cytokines were carried forward for subsequent analysis. In step 1, asthma modified the gene expression-protein level association for 1,645 genes; pathway analysis showed an enrichment of these genes in the cytokine signaling system (n = 269 genes). In steps 2-3, expression levels of 40 genes were associated with intermediate phenotypes (asthma onset age, forced expiratory volume in 1 second, exacerbations, eosinophil counts, and skin test reactivity); of those, methylation of seven genes was also associated with asthma. Of these seven candidate genes, IL5RA was also significant in analytical steps 4-8. We then measured plasma IL-5 receptor α levels, which were associated with asthma age of onset and moderate-severe exacerbations. In addition, in silico database analysis showed that several of our identified IL5RA single-nucleotide polymorphisms are associated with transcription factors related to asthma and atopy. This approach integrates several analytical steps and is able to identify biologically relevant asthma-related genes, such as IL5RA. It differs from other methods that rely on complex statistical models with various assumptions.


Keep meaning in conversational coordination.
Coordination is a widely employed term across recent quantitative and qualitative approaches to intersubjectivity, particularly approaches that give embodiment and enaction central explanatory roles. With a focus on linguistic and bodily coordination in conversational contexts, I review the operational meaning of coordination in recent empirical research and related theorizing of embodied intersubjectivity. This discussion articulates what must be involved in treating linguistic meaning as dynamic processes of coordination. The coordination approach presents languaging as a set of dynamic self-organizing processes and actions on multiple timescales and across multiple modalities that come about and work in certain domains (those jointly constructed in social, interactive, high-order sense-making). These processes go beyond meaning at the level that is available to first-person experience. I take one crucial consequence of this to be the ubiquitously moral nature of languaging with others. Languaging coordinates experience, among other levels of behavior and event. Ethical effort is called for by the automatic autonomy-influencing forces of languaging as coordination.


Multiple routes of porcine circovirus type 2 transmission to piglets in the presence of maternal immunity.
Porcine circovirus 2 (PCV2), the cause of porcine circovirus-associated disease (PCVAD), is widespread in swine farms throughout the United States with vaccine controlling disease, but not eliminating infection. We examined the PCV2 virological and immunological status of sows, pre-suckling piglets, and the farrowing environment of sow farms to determine PCV2 exposure risks, transmission dynamics, and immunological impacts at the time of farrowing. PCV2 was widely distributed in animals and the farrowing environment of 6 midwestern US sow farms irrespective of sow vaccination status. High levels of PCV2 capsid-specific antibodies were observed in sow serum and colostrum and had no apparent effect on PCV2 transmission to and infection in piglets. In 281 pre-suckling piglets from 59 sows, PCV2 DNA was detected in 63% of serum samples and on 93% of axillary skin swabs. PCV2 was present in one or more samples from 58 of 59 sows and in the farrowing environment. Isolated infectious virus samples from sows, presuckling piglets, and the environment were shown by sequencing to be genetically similar from all farms. In conclusion, piglets are readily infected with PCV2 in utero and are under constant challenge by PCV2 through contact with infected sows and a contaminated farrowing environment. However, maternal immunity did not affect PCV2 transmission to piglets or the viral load in sows. These findings illustrate the importance of maternal infection, despite robust anti-PCV2 immunity, in early infection of newborn piglets, and the need to develop appropriate infection models for elucidation of mechanisms of protective immunity.


Protein-Templated Reactions Using DNA-Antibody Conjugates.
DNA-templated chemical reactions have found wide applications in drug discovery, programmed multistep synthesis, nucleic acid detection, and targeted drug delivery. The control of these reactions has, however, been limited to nucleic acid hybridization as a means to direct the proximity between reactants. In this work a system capable of translating protein-protein binding events into a DNA-templated reaction which leads to the covalent formation of a product is introduced. Protein-templated reactions by employing two DNA-antibody conjugates that are both able to recognize the same target protein and to colocalize a pair of reactant DNA strands able to undergo a click reaction are achieved. Two individual systems, each responsive to human serum albumin (HSA) and human IgG, are engineered and it is demonstrated that, while no reaction occurs in the absence of proteins, both protein-templated reactions can occur simultaneously in the same solution without any inter-system crosstalk.


Identification of Glis1, a novel Gli-related, Kruppel-like zinc finger protein containing transactivation and repressor functions.
In this study, we describe the identification and characterization of a novel Krüppel-like protein named Gli-similar 1 (Glis1). The Glis1 gene encodes an 84.3-kDa proline-rich protein. Its five tandem zinc finger motifs exhibit highest homology with those of members of the Gli and Zic subfamilies of Krüppel-like proteins. Glis1 was mapped to mouse chromosome 4C6. Northern blot analysis showed that expression of the 3.3-kb Glis1 mRNA is most abundant in placenta and adult kidney and expressed at lower levels in testis. Whole mount in situ hybridization on mouse embryos demonstrated that Glis1 is expressed in a temporal and spatial manner during development; expression was most prominent in several defined structures of mesodermal lineage, including craniofacial regions, branchial arches, somites, vibrissal and hair follicles, limb buds, and myotomes. Confocal microscopic analysis showed that Glis1 is localized to the nucleus. The zinc finger region plays an important role in the nuclear localization of Glis1. Electrophoretic mobility shift assays demonstrated that Glis1 is able to bind oligonucleotides containing the Gli-binding site consensus sequence GACCACCCAC. Although monohybrid analysis showed that in several cell types Glis1 was unable to induce transcription of a reporter, deletion mutant analysis revealed the presence of a strong activation function at the carboxyl terminus of Glis1. The activation through this activation function was totally suppressed by a repressor domain at its amino terminus. Constitutively active Ca(2+)-dependent calmodulin kinase IV enhanced Glis1-mediated transcriptional activation about 4-fold and may be mediated by phosphorylation/activation of a co-activator. Our results suggest that Glis1 may play a critical role in the control of gene expression during specific stages of embryonic development.


Effect of avermectin residues in sheep dung on mating of the Australian sheep blowfly Lucilia cuprina.
Male and female Lucilia cuprina adults were separated after emergence and then fed either dung excreted from sheep after an oral treatment with ivermectin (Ivomec) or non-treated sheep dung. Fresh dung (non-treated or ivermectin-treated) was collected daily and fed to adults for 6 days after drenching. After this feeding period, males and females from each feeding treatment were paired and all aspects of mating behaviour recorded. Feeding on avermectin residues by adults had a significant effect on two components of mating: (1) males fed on ivermectin-treated dung directed less mating attempts at females compared with males fed on non-treated dung; (2) mating duration by males fed on ivermectin-treated dung was longer compared with males fed on non-treated dung. There was no significant difference in the level of sexual receptivity (percentage mating) between females fed on either ivermectin-treated dung or non-treated dung, although subsequent oviposition by females fed ivermectin-treated dung was significantly delayed. Both female and male mortality was significantly greater when feeding on ivermectin-treated dung compared with non-treated dung. The effects on mating, when coupled with the deleterious effects on ovarian development and adult mortality, demonstrate the potential for avermectin usage in a control strategy against L. cuprina.


[Depression in the structure of schizophrenia: clinical and biochemical characteristics].
Was to investigate clinical and biochemical correlates of depression in the structure of schizophrenia to improve its diagnosis and differential diagnosis and to deepen understanding of mechanisms of schizophrenia development. Material and Methods. Forty-two inpatients at the stabilization stage of paranoid schizophrenia, aged 29.5±5.9 years, of whom 64.3% were women, were examined. The duration of the disease was 5.6±6.3 years. We used clinical and psychopathological methods, clinical scales (PANSS, SANS, BACS, Calgary Scale), catamnestic and clinic-laboratory methods (determination of brain-derived neurotrophic factor BDNF, proinflammatory cytokine interleukin-6, C-reactive protein). Results. At the stabilization stage, depression in patients with paranoid schizophrenia occurred in 19% of cases, more frequently in women. Female patients were more severely depressed, which was associated with an increased concentration of C-reactive protein, while negative symptoms predominated in male patients as compared to females. The presence of depression correlates with a lower severity of psychopathological, primarily positive symptoms and with a greater severity of neurocognitive deficit in schizophrenic patients. BDNF level directly correlates with the severity of positive and negative symptoms, and the level of interleukin 6 at the stage of remission formation does not differ from that in healthy individuals. C-reactive protein levels are associated with the characteristics of the course of schizophrenia.


miR-34a knockout attenuates cognitive deficits in APP/PS1 mice through inhibition of the amyloidogenic processing of APP.
The noncoding miRNA-34a (miR-34a) is involved in Alzheimer's disease (AD) pathologenesis and shows potential for application as a biomarker for early diagnosis and intervention. Here, we established miR-34a knockout mice in an APP/PS1 background (APP/PS1-miR-34a KO mice) by crossbreeding miR-34a-/- mice with APP/PS1 mice. We then investigated cognitive impairment and related pathologies. The results showed that the level of miR-34a was increased at about 6months in APP/PS1 mice, consistent with the increase in amyloid β (Aβ), and cognitive function was significantly improved in mice when miR-34a was knocked out in 9-month-old and 12-month-old mice, indicating that miR-34a is a potential candidate for determining the progression of AD. Furthermore, we assessed the processing of amyloid precursor protein (APP) and the results suggest that cognitive improvement by miR-34a knock out was mainly triggered by depression of γ-secretase activity, without affecting β- and α-secretase activities, indicating that miR-34a plays an important role in AD pathology, mainly by inhibiting the amyloidogenic processing of APP, without altering the non-amyloidogenic processing of APP.


Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel.
Voltage-gated sodium (Na(v)) channels are essential for the rapid depolarization of nerve and muscle, and are important drug targets. Determination of the structures of Na(v) channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Na(v) channels, exemplified by the Na(+)-selective channel of bacteria (NaChBac), provides a useful model system for structure-function analysis. Here we report the crystal structure of Na(v)Rh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114 (Rickettsiales sp. HIMB114; denoted Rh), at 3.05 Å resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr 178 and Leu 179 constitute an inner site within the selectivity filter where a hydrated Ca(2+) resides in the crystal structure. The outer mouth of the Na(+) selectivity filter, defined by Ser 181 and Glu 183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation in which all the gating charges are exposed to the extracellular environment. We propose that Na(v)Rh is in an 'inactivated' conformation. Comparison of Na(v)Rh with Na(v)Ab reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.


Experimental investigation on composites incorporating rice husk nanoparticles for environmental noise management.
Environmental noise characteristics are determined by factors besides its source. One such factor is reverberation time, which in city canyons tends to be high due to the reflective characteristics of materials commonly used in building facades. Incorporating sound absorbing materials into building facades can help improve urban environments. This research evaluates different facade materials (concrete mix, mortar mix, vinyl spackling, and epoxy resin) incorporated with rice husk nanoparticles (NPs). Rice husk, in addition to presenting good properties for acoustic absorption, is one of the main agricultural wastes worldwide. Additionally, the characteristic of rice husk nanoparticles is correlated with milling time (longer grinding times enhance production of rice husk NPs). Sound absorption coefficients levels increase for compounds with a greater amount of rice husk NPs.


Next-Generation Sequencing for Infectious Disease Diagnosis and Management: A Report of the Association for Molecular Pathology.
Next-generation sequencing (NGS) technologies are increasingly being used for diagnosis and monitoring of infectious diseases. Herein, we review the application of NGS in clinical microbiology, focusing on genotypic resistance testing, direct detection of unknown disease-associated pathogens in clinical specimens, investigation of microbial population diversity in the human host, and strain typing. We have organized the review into three main sections: i) applications in clinical virology, ii) applications in clinical bacteriology, mycobacteriology, and mycology, and iii) validation, quality control, and maintenance of proficiency. Although NGS holds enormous promise for clinical infectious disease testing, many challenges remain, including automation, standardizing technical protocols and bioinformatics pipelines, improving reference databases, establishing proficiency testing and quality control measures, and reducing cost and turnaround time, all of which would be necessary for widespread adoption of NGS in clinical microbiology laboratories.


Owners' view of their pets' emotions, intellect, and mutual relationship: Cats and dogs compared.
Companion animals have established special relationships with humans, as demonstrated by many studies describing their abilities and bonds to communicate with humans. In this questionnaire-based study, we explored owners' views of pets in terms of their emotional and intellectual functions and their relationship with owners, and compared the results between cat owners and dog owners. We found that although both types of owners most often regarded their pets as "family members," this tendency was weaker in cat owners. Cat owners also scored significantly lower than dog owners for some emotions and intellect they thought their pets might have. Additionally, cat owners who regard their cats as family members tend to attribute "compassion" to their cats more strongly than cat owners who regard their pets as non-family. This study revealed that some aspects of cat owners' views of their pets differ from those of dog owners. These finding may help us to better understand our heterospecific companions and establish good relationships with them.


Increased healthcare facility use in veterans surviving sepsis hospitalization.
We sought to measure inpatient healthcare utilization among U.S. Veteran Affairs beneficiaries surviving sepsis hospitalization, and to examine how post-sepsis utilization varies by select patient characteristics. Retrospective cohort study of 26,561 Veterans who survived sepsis hospitalization in 2009. Using difference-in-differences analysis, we compared changes in healthcare utilization in one year before and one year after sepsis hospitalization by Veteran age, illness severity, and recent nursing facility use. Median days in a healthcare facility increased from 5 to 10. Veterans with recent nursing facility use spent a median 65days (or 86% of days alive) in a healthcare facility in the year after sepsis. Older age, greater illness severity, and recent nursing home use were each associated with spending more days, and a greater proportion of days alive, in a healthcare facility during the year after sepsis. However, none of these characteristics was associated with a greater rise in utilization after sepsis. Veterans surviving sepsis experience high rates of post-sepsis mortality and significant increases in healthcare facility use. Recent nursing facility use is strongly predictive of greater post-sepsis healthcare utilization.


In situ identification of inflammatory cells in malignant, non-lymphoid human tumours.
Inflammatory cells (the term is considered to include lymphocytes, plasma cells, macrophages, mast cells and PMN) were identified and quantitated in sections from human carcinomas. Two types of cellular infiltrates are described. In the stroma surrounding the cancer tissue (peritumoural) and, to a lesser degree, also within the malignant tissue (intratumoural), lymphocytes, plasma cells, macrophages and mast cells dominated, whilst numerous polymorph nucleated cells (PMN) and aggregates of macrophages characterized central tumour necroses. The demonstration of both T-lymphocytes and macrophages in and around the cancer tissue supports the view that a local immune reaction is initiated by the tumour, and the consistent finding of IgG, IgA and IgM plasma cells at the borders of the carcinomas, indicates that plasma cells are also part of an immune response at the tumour site. This view is further supported by the demonstration of an increased proportion of IgG containing plasma cells in the stroma of colon tumours, compared with normal mucosa.


Cellular defense in critically ill surgical patients.
Cell-mediated immunity was examined using 4 recall antigens in 102 critically ill surgical patients treated in an ICU. There were 4 (14%) deaths in 28 patients with positive reactions (R), compared to 33 (45%) deaths in 74 nonreactors (NR) (p less than .01). Thirty-seven of the patients were admitted after trauma, and mortality in this group was not significantly different between R and NR patients. Repeat testing in 40 NR patients who remained in the ICU for more than 7 days showed that 30 remained NR (70% mortality) and 10 became R (20% mortality, p less than .001). Peripheral blood lymphocytes from the patients showed a reduced response to concanavalin A, but a normal response to phytohemagglutinin and pokeweed mitogen. Mononuclear cells and granulocytes both showed a small increase in chemotactic response to casein, suggesting that the reduced response to skin testing may be partly due to defective T-cell function, rather than impaired phagocyte chemotaxis.


[Assessment of Soil Fluorine Pollution in Jinhua Fluorite Ore Areas].
The contents of. soil total fluorine (TF) and water-soluble fluorine (WF) were measured in fluorite ore areas located in Jinhua City. The single factor index, geoaccumulation index and health risk assessment were used to evaluate fluorine pollution in soil in four fluorite ore areas and one non-ore area, respectively. The results showed that the TF contents in soils were 28. 36-56 052. 39 mg.kg-1 with an arithmetic mean value of 8 325.90 mg.kg-1, a geometric mean of 1 555. 94 mg.kg-1, and a median of 812. 98 mg.kg-1. The variation coefficient of TF was 172. 07% . The soil WF contents ranged from 0. 83 to 74. 63 mg.kg-1 with an arithmetic mean value of 16. 94 mg.kg-1, a geometric mean of 10. 59 mg.kg-1, and a median of 10. 17 mg.kg-1. The variation coefficient of WF was 100. 10%. The soil TF and WF contents were far higher than the national average level of the local fluorine epidemic occurrence area. The fluoride pollution in soil was significantly affected by human factors. Soil fluorine pollution in Yangjia, Lengshuikeng and Huajie fluorite ore areas was the most serious, followed by Daren fluorite ore area, and in non-ore area there was almost no fluorine pollution. Oral ingestion of soils was the main exposure route. Sensitivity analysis of model parameters showed that children's weight exerted the largest influence over hazard quotient. Furthermore, a significant positive correlation was found among the three kinds of evaluation methods.


Formation Mechanisms of Iodine-Ammonia Clusters in Polluted Coastal Areas Unveiled by Thermodynamics and Kinetic Simulations.
It has been revealed that iodine species play important roles in atmospheric new particle formations (NPFs) in pristine coastal areas. However, it is unclear whether other atmospheric species, such as NH3, for which the levels in coastal areas of China are >2.5 × 1010 molecules·cm-3 are involved in the NPFs of iodine species, although NH3 has been proved to promote particle formation of H2SO4. Via high-level quantum chemical calculations and atmospheric cluster dynamic code simulations, this study unveiled new mechanisms of nucleation, in which NH3 mediates the formation of iodine particles by assisting hydrolysis of I2O5 or reacting with HIO3. The simulated formation rates of iodine-ammonia clusters via the new mechanisms are much higher than those simulated via sequential addition of HIO3 with subsequent release of H2O, under the condition that NH3 concentrations are higher than 1010 molecules·cm-3. The new mechanisms can well explain the observed cluster formation rates at a coastal site in Zhejiang of China. The findings not only expand the current understandings of the role of NH3 in NPFs but also highlight the importance of monitoring and evaluating NPFs via the iodine-ammonia cluster pathway in the coastal areas of China and other regions worldwide.


Does JCAHO require one nurse executive?
Rumors have been flying that the Joint Commission is going to eliminate the requirement for a single nurse executive as required by standard NR. 1 in the Comprehensive Accreditation Manual for Hospitals (CAMH). This column clarifies the JCAHO's intent in this regard.


Proliferative fibromatosis in avian skeletal muscle caused by cloned recombinant avian leukosis viruses.
Two molecular recombinants (EU-8 and K-3) constructed from ring-necked pheasant virus and UR2AV, the helper virus associated with avian sarcoma virus UR2, caused a high incidence of a hitherto unreported pathological condition in chick skeletal muscle. A disease spectrum was observed in which muscle was infiltrated by proliferating fibroblasts and caused white streaks, white diffuse areas, or well-defined elongated tumors. Fibroblast proliferation was progressive, and the gross presentation depended on the rapidity and extent of proliferation. There was evidence of anaplasia but not frankly malignant disease or metastases. The disease was produced at a high frequency when 10-day-old embryos were infected. Breast muscle (pectoralis major and minor) was affected with variable severity in all birds, thigh muscles were affected occasionally, while other thoracic, external abdominal, and wing muscles were affected very rarely. Progression of proliferative muscle lesions was demonstrated by sequential necropsies and microscopic examination of muscle samples. The disease appeared before 2 weeks of age, and thin white streaks with minimal cellular proliferation were the earliest lesions observed. Elongated, spindle-shaped tumors were the most advanced form of proliferation observed. The advanced lesions showed cellular anaplasia and signs of rapid growth, and appeared most commonly at 6 weeks of age or later. Histologically, mild proliferation correlated with normal appearing fibroblasts producing collagen. Severe proliferation correlated with anaplastic, rapidly dividing cells producing little collagen and a high mitotic index. A decrease in the virus dose resulted in less severe fibromatosis, but at least one chicken infected with a low virus dose showed severe disease. When 10- or 35-day-old hatched chicks were injected in the breast muscle with EU-8 or K-3, a low incidence of lymphoid leukosis was observed, but no fibromatosis resulted during an observation period of 27 weeks. Infectious virus was extracted from the fibromatosis in the breast muscle, and extracted virus caused the same disease when injected in 10-day-old embryos. No transforming activity was observed on normal chick embryo fibroblast monolayers. Cell cultures were established from areas in the breast muscle affected by fibromatosis, and from discrete tumors. These cells did not show any signs of transformation in culture. Supernatants obtained from these cell cultures caused fibromatosis when injected into 10-day-old embryos, but did not transform normal chick embryo fibroblasts.


Gestation dependant changes in angiogenic factors and their associations with fetal growth measures in normotensive pregnancy.
Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight. Ninety two pregnant women were followed at three different time points: 16-20 weeks, 26-30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits. Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight. Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16-20 weeks) may be predictive of birth weight in healthy term pregnancies.


Hypochondriacal attitudes and beliefs, attitudes towards complementary and alternative medicine and modern health worries predict patient satisfaction.
To investigate how hypochondriacal attitudes and beliefs, attitudes towards complementary and alternative medicine (CAM) and modern health worries (MHWs) related to patient satisfaction with their general practitioner. Participants completed a five-part questionnaire anonymously which measured satisfaction with one's doctor, hypochondriacal beliefs, attitudes to CAM, MHWs and personality. England. Included 215 adults from a variety of cultural backgrounds. The Illness Attitudes Scales measuring the attitudes, fears and beliefs associated with hypochondriasis; Worry about Illness; Concerns about Pain, Health Habits, Hypochondriacal beliefs; Thanatophobia, Disease phobia, Bodily preoccupations; Treatment experience and Effects of symptoms. Correlations (around r = .10 to .25) and Regressions (R square from .06 to .09) showed demographic and personality variables only modestly related to patient satisfaction. Hypochondriasis, CAM and MHWs were associated with greater patient dissatisfaction as predicted with the former as the most powerful correlate. The study indicates the different needs of potential patients in a typical medical consultation. It is important to ascertain patients' health beliefs and practices with regard to medical history, attitudes to CAM and MHWs to increase consultation satisfaction.


Design and Development of Graphene Oxide Nanoparticle/Chitosan Hybrids Showing pH-Sensitive Surface Charge-Reversible Ability for Efficient Intracellular Doxorubicin Delivery.
A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π-π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug delivery system with positive surface charge by taking advantage of the pH difference between physiological conditions and the tumor microenvironment to enhance the cellular uptake. Then, the pH-dependent site-specific drug release was realized. The in vitro investigations confirmed that these promising GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various merits including excellent encapsulation efficiency, high stability under physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable intracellular chemotherapeutic agent release profiles, proving its capability as an intelligent anticancer agent nanocarrier with enhanced therapeutic effects. This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character may be used as a significant drug delivery system for cancer treatment.


Comparable fitness and transmissibility between oseltamivir-resistant pandemic 2009 and seasonal H1N1 influenza viruses with the H275Y neuraminidase mutation.
Limited antiviral compounds are available for the control of influenza, and the emergence of resistant variants would further narrow the options for defense. The H275Y neuraminidase (NA) mutation, which confers resistance to oseltamivir carboxylate, has been identified among the seasonal H1N1 and 2009 pandemic influenza viruses; however, those H275Y resistant variants demonstrated distinct epidemiological outcomes in humans. Specifically, dominance of the H275Y variant over the oseltamivir-sensitive viruses was only reported for a seasonal H1N1 variant during 2008-2009. Here, we systematically analyze the effect of the H275Y NA mutation on viral fitness and transmissibility of A(H1N1)pdm09 and seasonal H1N1 influenza viruses. The NA genes from A(H1N1)pdm09 A/California/04/09 (CA04), seasonal H1N1 A/New Caledonia/20/1999 (NewCal), and A/Brisbane/59/2007 (Brisbane) were individually introduced into the genetic background of CA04. The H275Y mutation led to reduced NA enzyme activity, an increased K(m) for 3'-sialylactose or 6'-sialylactose, and decreased infectivity in mucin-secreting human airway epithelial cells compared to the oseltamivir-sensitive wild-type counterparts. Attenuated pathogenicity in both RG-CA04(NA-H275Y) and RG-CA04 × Brisbane(NA-H275Y) viruses was observed in ferrets compared to RG-CA04 virus, although the transmissibility was minimally affected. In parallel experiments using recombinant Brisbane viruses differing by hemagglutinin and NA, comparable direct contact and respiratory droplet transmissibilities were observed among RG-NewCal(HA,NA), RG-NewCal(HA,NA-H275Y), RG-Brisbane(HA,NA-H275Y), and RG-NewCal(HA) × Brisbane(NA-H275Y) viruses. Our results demonstrate that, despite the H275Y mutation leading to a minor reduction in viral fitness, the transmission potentials of three different antigenic strains carrying this mutation were comparable in the naïve ferret model.


Fetal alcohol syndrome. Experience with 41 patients.
Forty-one patients with the fetal alcohol syndrome, including 11 whose cases were previously reported, were studied. These children have a pattern of defects including prenatal and postnatal growth deficiency, small head size with mental subnormality, and facial abnormalities allowing for recognition of the disorder in infancy. The same pattern of abnormalities has been independently reported from France in a series of 127 offspring of chronic alcoholics.


Enzymatic acylation of blackcurrant (Ribes nigrum) anthocyanins and evaluation of lipophilic properties and antioxidant capacity of derivatives.
Anthocyanin-rich fractions isolated from blackcurrant (Ribes nigrum L.) including delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside were enzymatically acylated with lauric acid. All the four anthocyanins were successfully monoacylated, and their relative proportions did not affect the conversion yield. The acylation occurred at the 6″-OH position of the glucosides and at the rhamnose 4‴-OH of the rutinosides. The rutinoside moieties of the anthocyanins were successfully acylated for the first time, and the corresponding acylation sites were verified by NMR analysis. The acylation enhanced the lipophilicity. The hydrophilic anthocyanin rutinosides were more lipophilic after acylation. Introducing lauric acid into the anthocyanins significantly improved the thermostability and capacity to inhibit lipid peroxidation and maintained UV-vis absorbance and antioxidant activity. This research provides important insights into acylation of mixed anthocyanins with different glycosyl moieties.


Neoadjuvant chemotherapy in breast cancer significantly reduces number of yielded lymph nodes by axillary dissection.
Neoadjuvant chemotherapy (NC) is an established therapy in breast cancer, able to downstage positive axillary lymph nodes, but might hamper their detectibility. Even if clinical observations suggest lower lymph node yield (LNY) after NC, data are inconclusive and it is unclear whether NC dependent parameters influence detection rates by axillary lymph node dissection (ALND). We analyzed retrospectively the LNY in 182 patients with ALND after NC and 351 patients with primary ALND. Impact of surgery or pathological examination and specific histomorphological alterations were evaluated. Outcome analyses regarding recurrence rates, disease free (DFS) and overall survival (OS) were performed. Axillary LNY was significantly lower in the NC in comparison to the primary surgery group (median 13 vs. 16; p < 0.0001). The likelihood of incomplete axillary staging was four times higher in the NC group (14.8% vs. 3.4%, p < 0.0001). Multivariate analyses excluded any influence by surgeon or pathologist. However, the chemotherapy dependent histological feature lymphoid depletion was an independent predictive factor for a lower LNY. Outcome analyses revealed no significant impact of the LNY on local and regional recurrence rates as well as DFS and OS, respectively. NC significantly reduces the LNY by ALND and has profound effects on the histomorphological appearance of lymph nodes. The current recommendations for a minimum removal of 10 lymph nodes by ALND are clearly compromised by the clinically already established concept of NC. The LNY of less than 10 by ALND after NC might not be indicative for an insufficient axillary staging.


Investigation of the Effects of Speech Signal Length on Vocal Disorder Sorting Done Via Dynamic Pattern Modeling.
Development of a noninvasive method for separating different vocal fold diseases is an important issue concerning vocal analysis. Due to the time variations along a pathologic vocal signal, application of dynamic pattern modeling tools is expected to help in the detection of defects that occur in the speech production mechanism. In the present study, the hidden Markov model, which is a state space model, is employed to sort some of the vocal diseases. Moreover, this research mainly investigates the effects of the processed vocal signal lengths on the mentioned sorting task. To this end, the signal lengths of 1, 3, and 5 seconds of different disorders are used. The experimental results show that some pathologic conditions in vocal folds such as cyst, false vocal cord, and mass are more evident in continued voice production, and the recognition accuracies gained via dynamic modeling of pathologic voice signals with more lengths are considerably improved.


Giant lymphedema of the penis and scrotum: a case report.
Lymphedema of the penis and scrotum is a rare entity characterized by enlargement of the skin and subcutaneous tissue of the genital region due to lymphatic drainage impairment. This clinical condition is more frequent in tropical countries due to a higher incidence of filariasis, which, in turn, is the main etiology. We describe the case of a 33-year-old man with large lymphedema of the scrotum and penis due to an acute and chronic inflammatory process, foreign body granuloma, and marked hyalinization. Four consecutive surgical interventions were necessary to remove the great part of the affected tissue, which enabled satisfactory results and improved the patient's quality of life.


Characterization of cell fusion in an experimental mouse model of endometriosis†.
Cell fusion is involved in the development of some adult organs, is implicated in the pathogenesis of specific types of cancer, and is known to participate in repair/regeneration processes mediated by bone-marrow-derived cells (BMDCs). Endometriosis is a disease characterized by growth of functional endometrial tissue outside of the uterine cavity. Endometriosis shares some molecular properties with cancer and BMDCs home to endometriosis lesions in a mouse model. Our objective was to determine if cell fusion can occur in endometriosis and establish whether bone-marrow-derived cells participate in cell fusion events in lesions. We employed a Cre-Lox system to identify cell fusion events in a mouse model of endometriosis. Fused cells were detected in endometriotic lesions, albeit at a low frequency (∼1 in 400 cells), localized to the stromal compartment, and displayed restricted proliferation. Using 5-fluorouracil-based nongonadotoxic bone marrow transplantation model, we demonstrate that bone marrow cells represent a principal cell source for fusion events in lesions. Cell fusion progeny uniformly lacked expression of selected markers of hematopoietic, endothelial, and epithelial markers, though they expressed the mesenchymal/stromal markers Sca-1 and CD29. This study is the first to describe the phenomenon of cell fusion in endometriosis and points to a mesenchymal population derived from cell fusion events with limited proliferative activity, properties previously attributed to endometrial stem cells. Their putative role in the pathogenesis of the disease remains to be elucidated.


α-Methylbenzylamine Functionalized Crown-Ether-Appended Calix[4]arene Phase Transfer Catalyst for Enantioselective Henry Reaction.
In this letter, we designed a highly selective α-methylbenzylamine functionalized crown-ether-appended calix[4]arene derived phase transfer catalyst for asymmetric nitroaldol reaction to provide the desired nitroaldol adducts in high yields (up to 99 % yield) with good to excellent enantioselectivities (up to 99.8 % ee).


Serotonergic stimulation of the rat hypothalamo-pituitary-adrenal axis: interaction between 5-HT1A and 5-HT2A receptors.
Acute stimulation of the hypothalamo-pituitary-adrenal (HPA) axis by selective serotonin reuptake inhibitors (SSRIs) is mediated by several postsynaptic 5-HT receptor subtypes. Activation of 5-HT(1A) and 5-HT(2A) receptors increases plasma corticosterone levels, and it is likely that these receptor subtypes are central to mediating the effects of SSRIs. To study the interaction of these receptors, rats were administered with the 5-HT(1A/7) agonist 8-OH-DPAT (0.05 to 1.25 mg/kg), the 5-HT(2A/C) agonist DOI (0.25 to 5 mg/kg), or a mixture of both compounds, and trunk blood was taken 60 min later. The two compounds given in combination produced a lower increase in corticosterone than DOI does alone. DOI and 8-OH-DPAT also produced a marked induction of c-Fos in the paraventricular nucleus (PVN), but the induction was not different if the two compounds were given together. These data show that the two serotonin receptor subtypes affect the HPA axis via a central target. In conclusion, 5-HT(1A) and 5-HT(2A) receptors regulate corticotrophin-releasing hormone (CRH) neurons via distinct but strongly interacting pathways, probably converging on the same neurons in the hypothalamus.


In vitro and in vivo methods to study bacterial colonization of hydrogel dermal fillers.
Preclinical in vitro and in vivo methods to study bacterial interactions with dermal fillers and infection pathogenesis are lacking. In this work, first in vitro methods to assess protein biofouling and effective pore size of commercial dermal fillers, including degradable hyaluronic acid (HA)-based fillers and other semi-degradable or permanent fillers (non-HA), were developed. The results were then related to Staphylococcus aureus (S. aureus) adhesion rates in vitro. HA fillers had less protein sorption than non-HA fillers and overall had smaller effective pore sizes. The properties correlated with levels of bacterial adhesion, where the control glass surface had the most rapid increase in bacterial cell adhesion, with a slope of 0.29 cm-2 min-1 , three unique non-HA fillers had intermediate adhesion with slopes of 0.11 and 0.06 cm-2 min-1 , and three unique HA fillers had the least adhesion with slopes of 0.02, 0.02, and 0.01 cm-2 min-1 . S. aureus had greater motility on the HA fillers than on non-HA fillers. Next, a mouse model for dermal filler biofilm and infection was developed. Mice were inoculated with a controlled amount of bioluminescent bacteria (Xen36 S. aureus) and polyacrylamide hydrogels of different stiffness were injected. In vivo bioluminescence was monitored longitudinally for 35 days to ensure that lasting colonization was established. The inoculum was optimized to achieve adequate bioluminescent signal, and bacterial bioburden over time and inter-animal variability in bioburden were determined. These in vitro and in vivo approaches can be used for future studies of antimicrobial interventions for dermal fillers.


Structure determination of the three disulfide bond isomers of alpha-conotoxin GI: a model for the role of disulfide bonds in structural stability.
The three possible disulfide bonded isomers of alpha-conotoxin GI have been selectively synthesised and their structures determined by 1H NMR spectroscopy. alpha-Conotoxin GI derives from the venom of Conus geographus and is a useful neuropharmacological tool as it selectively binds to the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel involved in nerve signal transmission. The peptide has the sequence ECCNPACGRHYSC-NH2, and the three disulfide bonded isomers are referred to as GI(2-7;3-13), GI(2-13;3-7) and GI(2-3;7-13). The NMR structure for the native isomer GI(2-7;3-13) is of excellent quality, with a backbone pairwise RMSD of 0.16 A for a family of 35 structures, and comprises primarily a distorted 310 helix between residues 5 to 11. The two non-native isomers exhibit multiple conformers in solution, with the major populated forms being different in structure both from each other and from the native form. Structure-activity relationships for the native GI(2-7;3-13) as well as the role of the disulfide bonds on folding and stability of the three isomers are examined. It is concluded that the disulfide bonds in alpha-conotoxin GI play a crucial part in determining both the structure and stability of the peptide. A trend for increased conformational heterogeneity was observed in the order of GI(2-7;3-13)<GI(2-13;3-7)<GI(2-3;7-13). It was found that the peptide bond joining Cys2 to Cys3 in GI(2-3;7-13) is predominantly trans, rather than cis as theoretically predicted. These structural data are used to interpret the varying nAChR binding of the non-native forms.A model for the binding of native GI(2-7;3-13) to the mammalian nAChR is proposed, with an alpha-subunit binding face made up of Cys2, Asn4, Pro5, Ala6 and Cys7 and a selectivity face, comprised of Arg9 and His10. These two faces orient the molecule between the alpha and delta subunits of the receptor. The structure of the CCNPAC sequence of the native GI(2-7;3-13) is compared to the structure of the identical sequence from the toxic domain of heat-stable enterotoxins, which forms part of the receptor binding region of the enterotoxins, but which has a different disulfide connectivity.


Pain in Guillain-Barré syndrome.
The clinical features of pain were prospectively analyzed in 29 consecutive patients with Guillain-Barré syndrome (GBS). Sixteen (55%) had characteristic pain early in the illness described as similar to the muscular discomfort following exercise ("charley horse"). Pain preceded weakness by one to five days in four patients. The anterior and posterior aspects of the thighs, the buttocks, and the low part of the back were most frequently affected. Pain was frequently worse at night. Specific clinical signs or electrophysiologic abnormalities were not associated with pain, but serum creatine kinase level was elevated in ten of 13 patients with pain and only one of eight without pain. A review of previously reported pathologic material in five patients with GBS failed to disclose a relation between inflammation of dorsal root ganglia and pain. These results suggest that alterations in muscle related to neurogenic changes may cause the typical pain of GBS.


Trends in cesarean rates for first births and repeat cesarean rates for low-risk women: United States, 1990-2003.
This report presents trends in cesarean rates for first births and repeat cesarean rates for low-risk women, in relation to the Healthy People 2010 (HP 2010) objectives. Data for the U.S. showing trends by maternal age and race and Hispanic origin are presented. Cesarean rates were computed based on the information reported on birth certificates. With a decrease between 1990 and 1996 and an increase between 1996 and 2003, the trend in the cesarean rate for low-risk women having a first birth paralleled trends in the primary (regardless of parity) and total cesarean rates. During 1996-2003 the cesarean rate for low-risk women having a first birth has consistently been at least 13 percent lower than the rate for all women having a first birth. For 2003 the cesarean rate for all primiparous women was 27.1 percent; for low-risk women the rate was 23.6 percent. The trend in the repeat cesarean rate for low-risk women was similar to the trend in the repeat rate for all women, i.e., a decrease from 1990 to 1996 and an increase from 1996 to 2003. The repeat cesarean rate for low-risk women has consistently been slightly lower than the rate for all women. For 2003 the repeat rate for all women was 89.4; the rate for low-risk women was 88.7. These trends were found for low-risk women of all ages and racial or ethnic groups. Therefore, low-risk women giving birth for the first time who have a cesarean delivery are more likely to have a subsequent cesarean delivery.


Discriminating Tissue Stiffness with a Haptic Catheter: Feeling the Inside of the Beating Heart.
Catheter devices allow physicians to access the inside of the human body easily and painlessly through natural orifices and vessels. Although catheters allow for the delivery of fluids and drugs, the deployment of devices, and the acquisition of the measurements, they do not allow clinicians to assess the physical properties of tissue inside the body due to the tissue motion and transmission limitations of the catheter devices, including compliance, friction, and backlash. The goal of this research is to increase the tactile information available to physicians during catheter procedures by providing haptic feedback during palpation procedures. To accomplish this goal, we have developed the first motion compensated actuated catheter system that enables haptic perception of fast moving tissue structures. The actuated catheter is instrumented with a distal tip force sensor and a force feedback interface that allows users to adjust the position of the catheter while experiencing the forces on the catheter tip. The efficacy of this device and interface is evaluated through a psychophyisical study comparing how accurately users can differentiate various materials attached to a cardiac motion simulator using the haptic device and a conventional manual catheter. The results demonstrate that haptics improves a user's ability to differentiate material properties and decreases the total number of errors by 50% over the manual catheter system.


Arithmetic Optimization with RetinaNet Model for Motor Imagery Classification on Brain Computer Interface.
Brain Computer Interface (BCI) technology commonly used to enable communication for the person with movement disability. It allows the person to communicate and control assistive robots by the use of electroencephalogram (EEG) or other brain signals. Though several approaches have been available in the literature for learning EEG signal feature, the deep learning (DL) models need to further explore for generating novel representation of EEG features and accomplish enhanced outcomes for MI classification. With this motivation, this study designs an arithmetic optimization with RetinaNet based deep learning model for MI classification (AORNDL-MIC) technique on BCIs. The proposed AORNDL-MIC technique initially exploits Multiscale Principal Component Analysis (MSPCA) approach for the EEG signal denoising and Continuous Wavelet Transform (CWT) is exploited for the transformation of 1D-EEG signal into 2D time-frequency amplitude representation, which enables to utilize the DL model via transfer learning approach. In addition, the DL based RetinaNet is applied for extracting of feature vectors from the EEG signal which are then classified with the help of ID3 classifier. In order to optimize the classification efficiency of the AORNDL-MIC technique, arithmetical optimization algorithm (AOA) is employed for hyperparameter tuning of the RetinaNet. The experimental analysis of the AORNDL-MIC algorithm on the benchmark data sets reported its promising performance over the recent state of art methodologies.


Dissection and Staining of Drosophila Pupal Ovaries.
Unlike adult Drosophila ovaries, pupal ovaries are relatively difficult to access and examine due to their small size, translucence, and encasing within a pupal case. The challenge of dissecting pupal ovaries also lies in their physical location within the pupa: the ovaries are surrounded by fat body cells inside the pupal abdomen, and these fat cells must be removed to allow for proper antibody staining. To overcome these challenges, this protocol utilizes customized Pasteur pipets to extract fat body cells from the pupal abdomen. Moreover, a chambered coverglass is used in place of a microcentrifuge tube during the staining process to improve visibility of the pupae. However, despite these and other advantages of the tools used in this protocol, successful execution of these techniques may still involve several days of practice due to the small size of pupal ovaries. The techniques outlined in this protocol could be applied to time course experiments in which ovaries are analyzed at various stages of pupal development.