Age as a predictive factor of mammographic breast density in Jamaican women.
We sought to determine the relationship between age, and other clinical characteristics such as parity, oestrogen use, dietary factors and menstrual history on breast density in Jamaican women. A retrospective study was done of 891 patients who attended the breast imaging unit. The clinical characteristics were extracted from the patient records. Mammograms were assessed independently by two radiologists who were blinded to the patient clinical characteristics. Breast densities were assigned using the American College of Radiology (ACR) classification. The concordance between the ACR classification of breast density between the two independent radiologists was 92% with k = 0.76 (SE = 0.02, P < 0.001). Women with low breast density were heavier (81.3 +/- 15.5 kg vs 68.4 +/- 14.3 kg, P < 0.0001, mean +/- standard deviation (SD)) and more obese (body mass index (BMI), 30.3 +/- 5.8 kg m(-2) vs 26.0 +/- 5.2 kg m(-2), P < 0.0001). Mammographic breast density decreased with age. The age adjusted odds ratios (ORs) for predictors significantly related to high breast density were parity, OR = 0.79 (95%CIratio0.71, 0.88), weight, OR = 0.92 (95% CIratio0.91, 0.95), BMI, OR = 0.83 (95% CIratio0.78, 0.89), menopause, OR = 0.51 (95% CIratio0.36, 0.74) and a history of previous breast surgery, OR 1.6 (95% CIratio1.1, 2.3). The rate decline of breast density with age in our population was influenced by parity and body composition.


EGF signaling activates proliferation and blocks apoptosis of mouse and human intestinal stem/progenitor cells in long-term monolayer cell culture.
The homeostatic renewal of the intestinal epithelium depends on regulation of proliferation and differentiation of stem/progenitor cells residing in a specific site, called the 'stem cell niche.' Thus, the reconstitution of the microenvironment of the stem cell niche may allow us to maintain intestinal stem/progenitor cells in culture for a longer period. Although epidermal growth factor (EGF) is conventionally used as a supplement of intestinal epithelial cell culture, little has been known regarding a role of EGF signaling in a stem/progenitor cell population. In this study, we attempted to clarify the role of EGF signaling in intestinal stem/progenitor cells, and to establish a culture system in which these cells could be maintained with normal differentiation potential. We first examined the expression pattern of EGF and its receptor, EGFR, and inhibited EGF signaling in mouse intestines. Next, we cultured intestinal cells isolated from mouse and human intestines in the presence of EGF and analyzed the function of EGF signaling in cultured cells. In both embryonic and adult mouse intestines, EGFR and EGF were expressed in immature epithelial cells and adjacent fibroblasts, respectively, and EGF signaling was essential to activate proliferation and inhibit apoptosis of intestinal stem/progenitor cells. Activation of EGF signaling also stimulated proliferation and suppressed apoptosis, both of which are necessary to maintain mouse and human intestinal epithelial cells in culture. Moreover, in these cultured epithelial cells, putative intestinal stem/progenitor cells persisted longer, and gave rise to different types of differentiated intestinal epithelial cells. We conclude that EGF signaling is indispensable for activation of proliferation and inhibition of unexpected cell death, not only in the intestinal stem cell niche, but also in culture of primitive intestinal epithelial cells.


Clinical outcome in four children with metachromatic leukodystrophy treated by bone marrow transplantation.
Four children with metachromatic leukodystrophy (MLD) underwent allogeneic bone marrow transplantation between 1988 and 1993. No effect on the natural course of the disease was observed in two children with late infantile and juvenile MLD. They had moderate neurological symptoms at the time of BMT and were followed for 7 and 6 years, respectively. The third child with the juvenile form of MLD was mildly to moderately affected when transplanted. She had lost some gross motor functions as well as speech and mental abilities at follow-up 3 years later. The fourth case, diagnosed biochemically and presymptomatically as late infantile MLD, had a subtle gait disturbance when grafted at 18 months of age. Demyelination, not observed before BMT, was visualized 1 year later on MRI. This boy's condition has continued to deteriorate 2 years after transplantation. We have adopted recent recommendations that BMT should be considered only in presymptomatic children with late infantile MLD or early in the course of juvenile MLD. In such children, still longer follow-up periods are necessary to evaluate the benefit of BMT.


Sleep-wake cycling in a neonate admitted to the NICU: a video-EEG case study during hypothermia treatment.
This retrospective case study describes the sleep-wake cycles of an infant in the neonatal intensive care unit. We analyzed video-electroencephalographic recording of the term infant monitored during treatment with therapeutic hypothermia for hypoxic-ischemic encephalopathy. The continuous video-electroencephalographic recording over a 4-day period also allowed us to describe the following dimensions of daily care in relation to the infant's sleep-wake states: (1) handling by professional and parent caregivers and (2) stress, pain, and analgesia. Physical contact constituted 17% to 36% of each 24-hour period. The infant's care was fragmented, with a mean of 3 to 4 physical contacts per hour. As a result, the structure of infant sleep was altered by the increased amount of awake and quiet sleep. The number of painful procedures ranged from 5 to 24 per day. Nurses were the main care providers. Parents had more contact after the infant was rewarmed. This case study suggests that neonatal intensive care unit infants are exposed to frequent handling and stress as well as altered sleep. The cumulative negative impact of frequent handling and sleep fragmentation may go unnoticed by caregivers focused on episodes of care. Continuous video-electroencephalographic monitoring is a useful tool for longitudinal evaluation of infant sleep and responses to caregiving in the neonatal intensive care unit.


Studies of the mechanism of spontaneous germline ecotropic provirus acquisition in mice.
SWR/J--RF/J hybrid mice spontaneously acquire new germline ecotropic proviruses at high frequency. We have performed ovarian transplantation and in situ hybridization studies to delineate the mechanism and developmental stage of germline provirus acquisition. In addition, we have developed a novel, efficient and simple method to introduce single copy proviruses into the mouse germline. The results reported here have direct implications for understanding how proviruses are acquired in the germline, for using murine leukemia viruses as insertional mutagens, and for using retroviral vectors to introduce foreign genes into the mouse germline.


Cowpea Physiological Responses to Terminal Drought-Comparison between Four Landraces and a Commercial Variety.
Cowpea (Vigna unguiculata) is a robust legume; nevertheless, yield is always affected by drought, especially when it occurs during reproductive growth and seed filling. Considered a key crop in the effort to attain food security, and a suitable crop for a scenario of climate change, modern disregard for cowpea landraces is particularly detrimental as it causes genetic variability loss, compromising breeding efforts. To contribute to the evaluation of the cowpea germplasm, four Portuguese landraces (L1, L2, L3, L4) were compared with a commercial variety (CV) to evaluate their physiological responses to terminal drought and their inter-variation on productivity, under semi-controlled conditions. Despite no differences in relative water content (RWC) between the CV and the landraces under water deficit (WD), differences in leaf water potential (Ψ) defined the CV as having an isohydric control of stomata in contrast with anisohydric control for landraces. There was an identical decrease in the photosynthetic rate for all plants under stress, caused by both stomatal and non-stomatal limitations, namely, damages at the level of photosystem II as indicated by fluorescence measurements. Instantaneous water use efficiency (iWUE) was improved with stress in L1 and L3. Maintenance of higher relative chlorophyll content for longer periods in the CV revealed a stay-green phenotype. The slim differences observed in terms of stomatal control, iWUE and progression of senescence between the CV and the landraces under WD led to quite important differences in terms of productivity, as inferred from improved yield (number of pods and number of grains per plant). This is a clear result of pragmatic on-farm selection. On one hand it shows that small differences in stomatal responses or water saving strategies under WD may lead to desirable outcomes and should therefore be considered during breeding. On the other hand, it suggests that other traits could be explored in view of drought adaptation. These results highlight the need to preserve and characterize as many genetic pools as possible within a species.


Novel factors modulating human β-cell proliferation.
β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.


Extracellular lipolytic enzyme activity of a newly isolated Debaryomyces hansenii.
A strain isolated from waste of a milk products plant and exhibited extracellular lipolytic activity was identified as Debaryomyces hansenii by 5.8S rRNA and 28S rRNA gene sequence analyses. Lipolytic activity was assayed spectrophotometrically by using p-nitrophenylpalmitate. Higher specific lipolytic activities were obtained in the presence of tristearin (0.68 U/mg prot), oleic acid (0.56 U/mg prot), and soybean oil (0.36 U/mg prot) than other triglycerides, fatty acids, and vegetable oils considered as carbon sources. Cheese whey appeared to be a good alternative to lipidic substances for lipolytic activity. Among various organic and inorganic nitrogen sources, soy flour was found to attain the lipolytic activity similar to that provided by universal yeast medium components. This work is the first report on the discussion of lipolytic activity enhancement by D. hansenii through modulating the cultivation medium. It also proposes low cost medium nutrients that could be of industrial value and could serve as basal nutrients for further optimization studies on the lipase production by D. hansenii.


High-dose isotretinoin treatment and the rate of retrial, relapse, and adverse effects in patients with acne vulgaris.
Isotretinoin is the most effective treatment for acne. The ideal dosing regimen is unknown. To determine the rates of relapse of acne vulgaris and retrial of isotretinoin after high cumulative-dose treatment and the changes to the adverse effect profile. A prospective, observational, intervention study was conducted from August 1, 2008, to August 31, 2010, in a single academic tertiary care center with multiple providers. A total of 180 patients with acne resistant to other treatments were enrolled. Of these, 116 participated in the 12-month follow-up survey, for a response rate of 64.4%. Patients received isotretinoin, with dosing based on the providers' judgment. Patients were divided into 2 groups on the basis of cumulative dosing (<220 mg/kg and ≥ 220 mg/kg). Relapse (treatment with a prescription topical or oral acne medication after a course of isotretinoin) or retrial (retreatment with isotretinoin) at 12-month follow-up and adverse effects experienced during and after 12 months of treatment. RESULTS The mean age of the participants was 19.3 years, 51.9% were female, and 74.1% were white. At 12 months' follow-up, 97.4% of the patients reported that their acne was improved. Overall, acne in 32.7% of patients in the study relapsed at 12 months, and 1.72% of the patients required a retrial. In the lower-dose treatment group (<220 mg/kg), the relapse rate was 47.4% (95% CI, 32.3%-63.0%) compared with 26.9% (95% CI, 18.3%-37.8%) in the high-dose group (P = .03). Almost 100% of the patients in both treatment groups developed cheilitis and xerosis during treatment. Retinoid dermatitis was significantly more common in the high-dose treatment group (53.8% vs 31.6%; P = .02). None of the other adverse effects was significantly different between the 2 groups. The dosing regimen used in the present study is considerably higher than that used in previous studies of isotretinoin. At 1 year after completion of isotretinoin treatment, we found that patients receiving 220 mg/kg or more had a significantly decreased risk of relapse. Rash was the only adverse effect that was significantly more common in the high-dose group during treatment. This study suggests that significantly higher doses of isotretinoin are effective for treating acne and decreasing relapse rates without increasing adverse effects.


Is ABPM clinically useful after pediatric solid organ transplantation?
When ambulatory blood pressure monitoring (ABPM) is performed in populations with a high risk for secondary hypertension, such as solid organ transplant recipients, hypertension or abnormalities in circadian blood pressure variability are often discovered even in patients with normal office blood pressure (BP). To discuss whether ABPM should be routinely assessed in pediatric solid organ recipients, the available information on pathological findings, association of ABPM abnormalities with outcome parameters, and treatment options is reviewed. ABPM is a useful tool to optimize therapy in the large proportion of transplant recipients with confirmed hypertension. Whether the use of ABPM on a routine basis should be recommended for pediatric transplantation patients without office hypertension remains to be determined.


Polyrotaxane composed of poly-L-lactide and alpha-cyclodextrin exhibiting protease-triggered hydrolysis.
Biodegradable polyrotaxanes (PRXs) were synthesized from bis-amino-terminated poly(L-lactide) (PLLA) and alpha-cyclodextrin (alpha-CD), combined with capping by bulky end groups at the amino-termini of PLLA through enzymatically cleavable peptide linkages. The crystalline structure of the PRXs in the solid state was investigated by wide-angle X-ray diffraction (WAXRD), and the results suggested that PRX forms a column-type crystalline structure. Hydrolysis of ester bonds of the PLLA in PRX was prevented due to the supramolecular structure. However, in the presence of a protease (papain), the hydrolysis of PLLA in PRX was induced. The removal of the bulky end groups by the protease acted as a trigger for the release of alpha-CD and allowed hydrolysis of the PLLA ester bonds. Such unique hydrolysis behavior, that is, proteinase-triggered degradation of a polyester, was achieved by the combination of the supramolecular architecture, biodegradable PLLA, and enzymatically cleavable end groups.


Force-velocity characteristics of stomach muscle: a comparison between longitudinal and circular muscle strips.
The longitudinal and circular muscle preparations from guinea pig stomach were compared in their property of shortening. The highest shortening speed was attained only for about 1 sec for longitudinal muscle and about 2 sec for circular muscle from the onset of stimulation in the course of tetanic contraction. Dynamic constants calculated from a force-velocity curve were almost independent of the muscle length, being set near its optimum length. Mean dynamic constants of the longitudinal muscle were: Vmax: 0.205 L/sec, b: 0.056 L/sec, a/Po: 0.292 and that of the circular muscle were: Vmax: 0.576 L/sec, b: 0.056 L/sec, a/Po: 0.107. The difference in Vmax of these muscles are discussed along with the difference in ultrastructure of the contractile filaments.


Lattice imaging in low-angle and high-angle bright-field scanning transmission electron microscopy.
Atomic resolution low-angle bright-field (LABF) scanning transmission electron-microscope (STEM) images and high-angle bright-field (HABF) STEM images of [011]-orientated Si have been experimentally obtained together with high-angle annular dark-field (HAADF) STEM images. The contrast formation mechanisms of the LABF STEM and HABF STEM images are examined in comparison with HAADF STEM images. The HABF STEM images independent of defocus and thickness have spatial resolution comparable with HAADF STEM images, and are shown to be given as a simple convolution under the non-dispersion approximation of localized Bloch waves.


Mucocutaneous pseudoepitheliomatous hyperplasia: a review.
Pseudoepitheliomatous hyperplasia, also called pseudocarcinomatous hyperplasia because of its resemblance to well-differentiated squamous cell carcinoma, is a reactive epithelial proliferation that is characterized by prominent irregular hyperplasia of the epithelium with tongue-like epithelial projections into the dermis. This reactive pattern may involve cutaneous or mucosal surfaces and has been described in association with a wide variety of stimuli including infectious, neoplastic, inflammatory, and traumatic among others. In this review, we will discuss the pathophysiology of pseudoepitheliomatous hyperplasia, the histopathological findings that are helpful in its differentiation from squamous cell carcinoma, and the spectrum of conditions that may show this unique feature on microscopic examination.


Combining wearable sensor signals, machine learning and biomechanics to estimate tibial bone force and damage during running.
There are tremendous opportunities to advance science, clinical care, sports performance, and societal health if we are able to develop tools for monitoring musculoskeletal loading (e.g., forces on bones or muscles) outside the lab. While wearable sensors enable non-invasive monitoring of human movement in applied situations, current commercial wearables do not estimate tissue-level loading on structures inside the body. Here we explore the feasibility of using wearable sensors to estimate tibial bone force during running. First, we used lab-based data and musculoskeletal modeling to estimate tibial force for ten participants running across a range of speeds and slopes. Next, we converted lab-based data to signals feasibly measured with wearables (inertial measurement units on the foot and shank, and pressure-sensing insoles) and used these data to develop two multi-sensor algorithms for estimating peak tibial force: one physics-based and one machine learning. Additionally, to reflect current running wearables that utilize running impact metrics to infer musculoskeletal loading or injury risk, we estimated tibial force using a commonly measured impact metric, the ground reaction force vertical average loading rate (VALR). Using VALR to estimate peak tibial force resulted in a mean absolute percent error of 9.9%, which was no more accurate than a theoretical step counter that assumed the same peak force for every running stride. Our physics-based algorithm reduced error to 5.2%, and our machine learning algorithm reduced error to 2.6%. Further, to gain insights into how force estimation accuracy relates to overuse injury risk, we computed bone damage expected due to a given loading cycle. We found that modest errors in tibial force translated into large errors in bone damage estimates. For example, a 9.9% error in tibial force using VALR translated into 104% error in estimated bone damage. Encouragingly, the physics-based and machine learning algorithms reduced damage errors to 41% and 18%, respectively. This study highlights the exciting potential to combine wearables, musculoskeletal biomechanics and machine learning to develop more accurate tools for monitoring musculoskeletal loading in applied situations.


Development and evaluation of wound healing hydrogels based on a quinolone, hydroxypropyl methylcellulose and biodegradable microfibres.
Ofloxacin is a synthetic antibiotic of the fluoroquinolone class, with activity against gram-positive and gram-negative bacteria. Wound healing involves a complex interaction of cells and processes which can be improved using appropriate wound- dressing materials. The aim of the present study was to develop and evaluate wound healing hydrogels containing hydroxypropyl methylcellulose (HPMC), ofloxacin and biodegradable microfibres from surgical sutures. The hydrogels were formulated by air-drying mixtures of dilute dispersions of micronized sutures (polyglycolic acid, Vicryl® and catgut), ofloxacin and HPMC gel. The prepared hydrogels were evaluated for gel fraction, swelling capacity, breaking elongation, particle size and morphology, and chemical interactions. Furthermore, in vivo wound healing activities were studied in rats using excision wound model and histological examination. The percentage gel fraction was ≥50% in all the batches, the percentage swelling ratio was within the range of 531.8-1700% and the percentage breaking elongation was found to be in the range of 70-120%. The chemical interaction studies using Fourier Transform Infra Red (FTIR) spectroscopy showed that there was no interaction between the drug and excipients used. Ofloxacin-loaded hydrogels containing dilute microfibres of the sutures showed 95% wound size reduction after fourteen days. These formulations also caused high collagen deposition after twenty one days of wounding, with minimal scar formation. Ofloxacin hydrogels containing HPMC and micronized suture fibres can be applied for effective wound healing.


'It's a logistical nightmare!' Recommendations for optimising human papillomavirus school-based vaccination experience.
To date, no published studies examine procedural factors of the school-based human papillomavirus (HPV) vaccination program from the perspective of those involved. This study examines the factors that were perceived to impact optimal vaccination experience. Schools across Sydney were selected to reflect a range of vaccination coverage at the school level and different school types to ensure a range of experiences. Semi-structured focus groups were conducted with girls; and one-on-one interviews were undertaken with parents, teachers and nurses until saturation of data in all emergent themes was reached. Focus groups and interviews explored participants' experiences in school-based HPV vaccination. Transcripts were analysed, letting themes emerge. Themes related to participants' experience of the organisational, logistical and procedural aspects of the vaccination program and their perceptions of an optimal process were organised into two categories: (1) preparation for the vaccination program and (2) vaccination day strategies. In (1), themes emerged regarding commitment to the process from those involved, planning time and space for vaccinations, communication within and between agencies, and flexibility. In (2), themes included vaccinating the most anxious girls first, facilitating peer support, use of distraction techniques, minimising waiting time girls, and support staff. A range of views exists on what constitutes an optimal school-based program. Several findings were identified that should be considered in the development of guidelines for implementing school-based programs. Future research should evaluate how different approaches to acquiring parental consent, and the use of anxiety and fear reduction strategies impact experience and uptake in the school-based setting.


Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.
Among the many adipocyte-derived endocrine factors, we recently found an adipocyte-specific secretory protein, adiponectin, which was decreased in obesity. Although obesity is associated with increased cardiovascular mortality and morbidity, the molecular basis for the link between obesity and vascular disease has not been fully clarified. The present study investigated whether adiponectin could modulate endothelial function and relate to coronary disease. For the in vitro study, human aortic endothelial cells (HAECs) were preincubated for 18 hours with the indicated amount of adiponectin, then exposed to tumor necrosis factor-alpha (TNF-alpha) (10 U/mL) or vehicle for the times indicated. The adhesion of human monocytic cell line THP-1 cells to HAECs was determined by adhesion assay. The surface expression of vascular cell adhesion molecule-1 (VCAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), and intracellular adhesion molecule-1 (ICAM-1) was measured by cell ELISA. Physiological concentrations of adiponectin dose-dependently inhibited TNF-alpha-induced THP-1 adhesion and expression of VCAM-1, E-selectin, and ICAM-1 on HAECs. For the in vivo study, the concentrations of adiponectin in human plasma were determined by a sandwich ELISA system that we recently developed. Plasma adiponectin concentrations were significantly lower in patients with coronary artery disease than those in age- and body mass index-adjusted control subjects. These observations suggest that adiponectin modulates endothelial inflammatory response and that the measurement of plasma adiponectin levels may be helpful in assessment of CAD risk.


Phloem-derived γ-aminobutyric acid (GABA) is involved in upregulating nodule N2 fixation efficiency in the model legume Medicago truncatula.
Nitrogen fixation in legumes is downregulated through a whole plant N feedback mechanism, for example, when under stress. This mechanism is probably triggered by the impact of shoot-borne, phloem-delivered compounds. However, little is known about any whole-plant mechanism that might upregulate nitrogen fixation, for example, under N deficiency. We induced emerging N-deficiency through partial excision of nodules from Medicago truncatula plants. Subsequently, the activity and composition of the remaining nodules and shifts in concentration of free amides/amino acids in the phloem were monitored. Furthermore, we mimicked these shifts through artificial feeding of γ-aminobutyric acid (GABA) into the phloem of undisturbed plants. As a result of increased specific activity of nodules, N(2) fixation per plant recovered almost completely 4-5 d after excision. The concentration of amino acids, sugars and organic acids increased strongly in the upregulated nodules. A concomitant analysis of the phloem revealed a significant increase in GABA concentration. Comparable with the effect of nodule excision, artificial GABA feeding into the phloem resulted in an increased activity and higher concentration of amino acids and organic acids in nodules. It is concluded that GABA might be involved in upregulating nodule activity, possibly because of its constituting part of a putative amino acid cycle between bacteroids and the cytosol.


Cytokine production in response to endodontic infection in germ-free mice.
This study evaluated the cytokine profiles (type 1 or type 2) that are triggered by and modulate endodontic periapical infections in the root canal system of germ-free mice. Microorganisms isolated from two patients with pulpal necrosis were inoculated into two groups of experimental animals: group I (Gemella morbillorum) and group II (Bifidobacterium adolescentis, Fusobacterium nucleatum and Clostridium butyricum). In vitro, G. morbillorum induced type 1 cytokine synthesis, while the modulation processed in vivo seemed to have the opposite effect, with a reduction in the basal levels of IL-12 and IFN-gamma, IL-4-independent down-modulation. In vitro, microorganisms from group II, in poly-infection, induced a reduction of type 1 cytokine levels from day 10 to day 20, which seemed to be modulated via IL-4. In vivo, however, a predominance of the immune response to one species over the others occurred.


Identification of two IgD+ B cell populations in channel catfish, Ictalurus punctatus.
Channel catfish Ictalurus punctatus express two Ig isotypes: IgM and IgD. Although catfish IgM has been extensively studied at the functional and structural levels, much less is known about IgD. In this study, IgM(+)/IgD(+) and IgM(-)/IgD(+) catfish B cell populations were identified through the use of anti-IgM and anti-IgD mAbs. Catfish IgM(+)/IgD(+) B cells are small and agranular. In contrast, IgM(-)/IgD(+) B cells are larger and exhibit a plasmablast morphology. The use of cell sorting, flow cytometry, and RT-PCR demonstrated that IgD(+) B cell expression varies among individuals. For example, some catfish have <5% IgM(-)/IgD(+) B cells in their PBLs, whereas in others the IgM(-)/IgD(+) B cell population can represent as much as 72%. Furthermore, IgD expressed by IgM(-)/IgD(+) B cells preferentially associates with IgL σ. Comparatively, IgM(+)/IgD(+) B cells can express any of the four catfish IgL isotypes. Also, transfection studies show that IgD functions as a typical BCR, because Igδ-chains associate with CD79a and CD79b molecules, and all membrane IgD transcripts from sorted IgM(-)/IgD(+) B cells contain viable VDJ rearrangements, with no bias in family member usage. Interestingly, all secreted IgD transcripts from IgM(+)/IgD(+) and IgM(-)/IgD(+) B cells were V-less and began with a leader spliced to Cδ1. Importantly, transfection of catfish clonal B cells demonstrated that this leader mediated IgD secretion. Together, these findings imply that catfish IgM(-)/IgD(+) B cells likely expand in response to certain pathogens and that the catfish IgD Fc-region, as has been suggested for human IgD, may function as a pattern recognition molecule.


A novel invertebrate trophic factor related to invertebrate neurotrophins is involved in planarian body regional survival and asexual reproduction.
Trophic factors are a heterogeneous group of molecules that promote cell growth and survival. In freshwater planarians, the small secreted protein TCEN49 is linked to the regional maintenance of the planarian central body region. To investigate its function in vivo, we performed loss-of-function and gain-of-function experiments by RNA interference and by the implantation of microbeads soaked in TCEN49, respectively. We show that TCEN49 behaves as a trophic factor involved in central body region neuron survival. In planarian tail regenerates, tcen49 expression inhibition by double-stranded RNA interference causes extensive apoptosis in various cell types, including nerve cells. This phenotype is rescued by the implantation of microbeads soaked in TCEN49 after RNA interference. On the other hand, in organisms committed to asexual reproduction, both tcen49 mRNA and its protein are detected not only in the central body region but also in the posterior region, expanding from cells close to the ventral nerve chords. In some cases, the implantation of microbeads soaked in TCEN49 in the posterior body region drives organisms to reproduce asexually, and the inhibition of tcen49 expression obstructs this process, suggesting a link between the central nervous system, TCEN49, regional induction, and asexual reproduction. Finally, the distribution of TCEN49 cysteine and tyrosine residues also points to a common evolutionary origin for TCEN49 and molluscan neurotrophins.


Is there an association between sweetened beverages and adiposity?
Four mechanisms were reviewed to explain the possible association between sweetened beverages and increased overweight or obesity: excess caloric intake, glycemic index and glycemic load, lack of effect of liquid calories on satiety, and displacement of milk. The findings were inconsistent across studies. The strongest support was for the excess caloric intake hypothesis, but the findings were not conclusive. Assigning possible links between sweetened beverage consumption and adiposity requires research that compares and contrasts specific mechanisms, especially in populations at risk for obesity, while controlling for likely confounding variables.


The effects of intranasal oxytocin on black participants' responses to outgroup acceptance and rejection.
Social acceptance (vs. rejection) is assumed to have widespread positive effects on the recipient; however, ethnic/racial minorities often react negatively to social acceptance by White individuals. One possibility for such reactions might be their lack of trust in the genuineness of White individuals' positive evaluations. Here, we examined the role that oxytocin-a neuropeptide putatively linked to social processes-plays in modulating reactions to acceptance or rejection during interracial interactions. Black participants (N = 103) received intranasal oxytocin or placebo and interacted with a White, same-sex stranger who provided positive or negative social feedback. After positive feedback, participants given oxytocin (vs. placebo) tended to display approach-oriented cardiovascular responses of challenge (vs. threat), exhibited more cooperative behavior, and perceived the partner to have more favorable attitudes toward them after the interaction. Following negative feedback, oxytocin reduced anger suppression. Oxytocin did not modulate testosterone reactivity directly, but our exploratory analysis showed that the less participants suppressed anger during the interaction with their partner, the greater testosterone reactivity they displayed after the interaction. These results survived the correction for multiple testing with a false discovery rate (FDR) of 20%, but not with a rate of 10 or 5%. Discussion centers on the interplay between oxytocin and social context in shaping interracial interactions.


Regulation of GLUT-3 glucose transporter in the hippocampus of diabetic rats subjected to stress.
Previous studies from our laboratory have demonstrated that chronic stress produces molecular, morphological, and ultrastructural changes in the rat hippocampus that are accompanied by cognitive deficits. Glucocorticoid attenuation of glucose utilization is proposed to be one of the causative factors involved in stress-induced changes in the hippocampus, producing an energy-compromised environment that may make hippocampal neuronal populations more vulnerable to neurotoxic insults. Similarly, diabetes potentiates neuronal damage in acute neurotoxic events, such as ischemia and stroke. Accordingly, the current study examined the regulation of the neuron-specific glucose transporter, GLUT-3, in the hippocampus of streptozotocin-induced diabetic rats subjected to restraint stress. Diabetes leads to significant increases in GLUT-3 mRNA and protein expression in the hippocampus, increases that are not affected by stress. Collectively, these results suggest that streptozotocin-induced increases in GLUT-3 mRNA and protein expression in the hippocampus may represent a compensatory mechanism to increase glucose utilization during diabetes and also suggest that modulation of GLUT-3 expression is not responsible for glucocorticoid impairment of glucose utilization.


Laryngeal paraganglioma: an updated critical review.
Laryngeal paragangliomas are rare submucosal lesions that arise from paraganglion cells located in the false vocal fold and subglottic larynx. To date, 76 recognized cases have been reported in the world literature. Symptoms arise when the lesions become large enough to impair function. Supraglottic paragangliomas cause hoarseness and deglutition disorders, whereas subglottic tumors become symptomatic when they obstruct the airway. Evaluation of these tumors includes obtaining a complete history. Familial paragangliomas and hypertension should be sought but are rarely, if ever, associated with laryngeal paragangliomas. MRI can detect these lesions and permit characterization of the vascularity of the lesion. Adding 111In pentetreotide scanning can distinguish neuroendocrine tumors from other submucosal laryngeal lesions, making the preoperative diagnosis clearer and obviating the need for biopsy. The biggest dilemma regarding laryngeal paragangliomas is making the correct pathologic distinction between paraganglioma, typical carcinoid, atypical carcinoid and medullary thyroid cancer. Immunohistochemical markers, supplementing standard histopathologic evaluation, can distinguish paragangliomas from the aforementioned tumors. This distinction is critical as the prognosis for treated paragangliomas is excellent compared to that for other neuroendocrine neoplasms. Almost all alleged malignant paragangliomas of the larynx are in reality atypical carcinoid tumors that have been misdiagnosed. Treatment should always comprise excision. Thyrotomy has the best chance of achieving a sustained cure without damaging phonation or deglutition. Laser excision has been used successfully but there is no great experience with this modality. Surgery is preferable to radiation for paragangliomas in all locations but especially so in the larynx, due to issues such as swelling, airway protection and destruction of cartilage. With increased clinical suspicion and the use of modern imaging techniques, laryngeal paragangliomas should be routinely diagnosed and treated without loss of laryngeal functions.


Effect of soybean oil on atherogenic metabolic risks associated with estrogen deficiency in ovariectomized rats: dietary soybean oil modulate atherogenic risks in overiectomized rats.
The aim of the present study was to investigate the cardiac biomarker changes in experimental bilateral ovariectomized (OVX) rats in addition to evaluating the role of soybean oil-supplemented diet to attenuate these alterations. Female rats were divided into four groups and treated for 2 months as follows: groups 1 and 2 fed with standard diet with or without 15% soybean oil. Groups 3 and 4 were bilateral OVX and received the standard diet with or without 15% soybean oil. The results revealed that rats subjected to ovariectomy exhibited an inhibition in estrogen and high-density lipoprotein cholesterol levels and marked increase of lipid profile, low-density lipoprotein cholesterol, and VLDL-C accompanied with a marked elevation in atherogenic index, cardiac enzyme activity, tumor necrosis factor-α, and C-reactive protein. Signs of cardiovascular injury which included an increase in cardiac thiobarbituric acid-reactive substances were concomitantly noticed with a reduction in the reduced glutathione, total antioxidant capacity, and superoxide dismutase. However, supplementation of soybean oil resulted in the restoration of the changed lipid profile and improved cardiac biomarkers near to normal values as well as improved inflammatory and antioxidant status. It was concluded that consumption of soybean oil may have a role in retarding atherosclerosis and risk of cardiovascular disorders associated with estrogen deficiency in ovariectomy status.


Effects of six beta-blockers on the isolated guinea-pig trachea.
The effects of six beta-blocking agents (propranolol, metoprolol, atenolol, pindolol, medroxalol and labetalol) selected on the basis of their intrinsic sympathomimetic properties, membrane-stabilizing activities and selectivity for beta 1-adrenoceptors were investigated on the isolated guinea-pig trachea. Tracheal spirals were either allowed to remain under resting tension or were precontracted with histamine 2 X 10(-6) M or 2 X 10(-5) M. Pindolol, medroxalol and labetalol exerted a moderate relaxant effect on tracheal muscle. This effect was inhibited by propranolol, but not significantly modified by indomethacin. Propranolol and metoprolol exerted a moderate contracturant effect on the preparations. The effect was inhibited by indomethacin but not by FPL 55712. Atenolol had no effect on tracheal muscle. This in vitro study provided data concerning two properties of beta-blockers--intrinsic sympathomimetic and membrane-stabilizing activities--which are involved in the bronchomotor response to these drugs in vivo.


Lessons Learnt From a Greenfield Hangar-Based 1,000-Bedded Temporary Hospital in India.
During the COVID-19 pandemic, the total number of hospital beds in the National Capital Region (NCR) of Delhi was 54,321 (roughly 300 beds per one lakh population), which was inadequate for the patients. Therefore, the Indian government initiated the construction of a 1,000-bedded greenfield hangar-based hospital to bridge the healthcare gap. As a result, Intensive Care Unit (ICU) beds in the facility augmented the COVID-19 care ICU beds in the city by 11%. The authors were involved in the planning, developing, and initiating the functioning of 1,000-bedded Dedicated COVID-19 Hospital (DCH). The hospital was conceptualized, built, and operationalized in 12 days only. Lessons learned from this experience would be of benefit should similar situations arise in future. Coordinating structural designing early with the entire project team-from facility administrators and medical practitioners to architects, consultants, and contractors-can result in a structure that better matches the facility's long-term needs and often saves construction time and costs. This article enumerates various challenges faced and the way they were addressed. This hangar-based hospital can be rapidly constructed and deployed on a massive scale. While structural integrity is essential, the planning team was particularly aware of the patient-centric modality of healthcare. Many modifications were carried out in the structure based on patient inputs. Informal discussions with discharged patients and relatives revealed that the human-centric approach was the mainstay of the therapy.


One-pot synthesis of amino-alcohols using a de-novo transketolase and beta-alanine: pyruvate transaminase pathway in Escherichia coli.
Biocatalysis continues to emerge as a powerful technique for the efficient synthesis of optically pure pharmaceuticals that are difficult to access via conventional chemistry. The power of biocatalysis can be enhanced if two or more reactions can be achieved by a single whole cell biocatalyst containing a pathway designed de-novo to facilitate a required synthetic sequence. The enzymes transketolase (TK) and transaminase (TAm) respectively catalyze asymmetric carbon--carbon bond formation and amine group addition to suitable substrate molecules. The ability of a transaminase to accept the product of the transketolase reaction can allow the two catalysts to be employed in series to create chiral amino-alcohols from achiral substrates. As proof of principle, the beta-alanine: pyruvate aminotransferase (beta-A:P TAm) from Pseudomonas aeruginosa has been cloned, to create plasmid pQR428, for overexpression in E.coli strain BL21gold(DE3). Production of the beta-A:P TAm alongside the native transketolase (overexpressed from plasmid pQR411), in a single E.coli host, has created a novel biocatalyst capable of the synthesis of chiral amino alcohols via a synthetic two-step pathway. The feasibility of using the biocatalyst has been demonstrated by the formation of a single diastereoisomer of 2-amino-1,3,4-butanetriol (ABT) product, in up to 21% mol/mol yield, by the beta-A:P TAm, via transamination of L-erythrulose synthesized by TK, from achiral substrates glycolaldehyde (GA) and beta-hydroxypyruvate (beta-HPA). ABT synthesis was achieved in a one-pot process, using either whole cells of the dual plasmid strain or cell lysate, while the dual alcohol-amine functionality of ABT makes it an excellent synthon for many pharmaceutical syntheses.


Clinical benefit of component-resolved diagnosis in Japanese birch-allergic patients with a convincing history of apple or peach allergy.
In northern Japan, birch pollen is the major allergen in pollinosis, while oral allergy syndrome (OAS) is caused primarily by apple and peach, and is almost exclusively related to birch pollinosis. To clarify the clinical benefit of allergen-based component-resolved diagnosis (CRD) in Japanese birch-allergic patients with OAS, we present an analysis of IgE profiles in response to crude extracts and recombinant component-resolved allergen to birch pollen and Rosaceae fruits allergens. The sera of 30 patients with birch pollen-related OAS to apple or peach were analyzed for specific IgE reactivity to pathogenesis-related class 10 (PR-10) family (birch: rBet v 1, apple: rMal d 1, and peach: rPru p 1), profilin (birch: rBet v 2 and peach: rPru p 4), and lipid transfer protein (LTP) (apple: rMal d 3 and peach: rPru p 3) allergens, as well as to conventional crude, unfractionated extracts (birch: T3, apple: f49, and peach: f95) using the ImmunoCAP System™. Allergen-specific IgE values <0.35kUA/L were considered negative. Of the 30 sera CAP-positive for natural birch pollen extract, 28 (93.3%) exhibited specific IgE against Bet v1, and two (6.7%) contained specific IgE against Bet v2. Of the 26 sera of OAS to apple patients, only 17 were positive for specific IgE against f49 extract (65.4%); however, 24 were positive for specific IgE against rMal d 1 (92.3%). Similarly, only 17 of the 23 sera of OAS to peach patients contained specific IgE against the f95 extract (73.9%); however, 22 were positive for specific IgE against rPru p 1 (95.7%). Our data suggest that CRD constitutes a reliable tool for the diagnosis of birch pollen-related OAS.


Effect of fluticasone propionate-salmeterol therapy on seasonal changes in airway responsiveness and exhaled nitric oxide levels in patients with pollen-induced asthma.
There has been concern that in allergic asthmatic patients there might be an interactive effect on inflammation between regular salmeterol use and exposure to allergens, resulting in increased airway responsiveness. To determine the effects of salmeterol on allergen-induced changes in airway responsiveness and exhaled nitric oxide (ENO) levels in allergic asthmatic patients concomitantly taking inhaled corticosteroids. Forty-two asthmatic patients sensitized to pollen allergens were randomly allocated to treatment with fluticasone propionate-salmeterol (n=21) or fluticasone propionate alone (n=21). Spirometry, the methacholine provocation concentration causing a 20% decline in forced expiratory volume in 1 second (PC20), the adenosine 5'-monophosphate (AMP) PC20, and ENO levels were measured before and at the height of the pollen season after 6 weeks of treatment. Changes in the methacholine PC20, the AMP PC20, and ENO levels were not significantly different between treatment groups. No significant changes in the AMP PC20 were observed among the fluticasone propionate-salmeterol and fluticasone propionate groups during natural pollen exposure. However, a significant increase in the methacholine PC20 was observed in the fluticasone propionate-salmeterol group (P = .03) and in the fluticasone propionate group (P = .04); ENO concentrations decreased significantly in both groups during natural allergen exposure (P = .009 and .005). In patients with pollen-induced asthma, treatment with either fluticasone propionate or fluticasone propionate-salmeterol is associated with significant reductions in methacholine responsiveness and ENO concentrations, even during natural pollen exposure. Furthermore, at least in patients with mild asthma, natural allergen exposure and the regular use of fluticasone propionate-salmeterol are not associated with a greater increase in ENO levels and airway responsiveness than natural allergen exposure and fluticasone propionate use alone.


The association of pattern of maternal weight gain with length of gestation and risk of spontaneous preterm delivery.
Monitoring weight gain during pregnancy may be useful in detecting pregnancies that are at increased risk of early delivery. This study examines 7259 deliveries that occurred at the University of California, San Francisco's Moffitt Hospital from 1980 to 1990. Obese women, women with diabetes or hypertension during pregnancy, deliveries with congenital malformations and non-spontaneous preterm deliveries were excluded. Pattern of gain was assessed by fitting a quadratic curve to each woman's series of weight and date measurements, using simple regression techniques. The parameters from this curve were used to develop a variable for pattern of gain that reflects how much an individual's pattern of gain differs from a linear pattern of gain. Multivariable linear and logistic regression analyses indicate that patterns of gain that deviate greatly from the average pattern of gain (i.e. patterns that show a marked speeding up or slowing down of gain towards the end of pregnancy) are associated with significantly shorter gestational age and confer a significantly increased risk of spontaneous preterm delivery. The results suggest that monitoring weight gain during pregnancy is important, although more specific studies are needed to understand the mechanisms by which weight gain pattern relates to preterm delivery before appropriate interventions can be developed.


A spectrophotometric study of the VO(2+)-glutathione interactions.
The interaction of the vanadyl (IV) cation with reduced glutathione (GSH) has been investigated by electronic absorption spectroscopy, at different metal-to-ligand ratios and pH values. The interaction depends strongly on the initial VO2+/GSH ratio. Starting with a tenfold GSH excess, coordination takes place through the two carboxylate groups of the ligand, generating (at pH = 7) a blue 1:2 VO2+/GSH complex; this stoichiometry could be confirmed by photometric titration experiments. Higher GSH concentrations produce a violet complex, which can also be obtained by addition of GSH to the blue species. Some measurements with the three component amino acids of GSH, as well as results obtained from the VO3-/GSH system, allowed a wider insight into the characteristics of this violet complex, in which the cation interacts with S and N atoms of the peptide.


A role for NF-kappa B subunits p50 and p65 in the inhibition of lipopolysaccharide-induced shock.
To evaluate the possibility that NF-kappaB subunits p50 and p65 have a role in limiting the systemic inflammatory response induced by endotoxin, we compared the susceptibility of wild-type (WT), p65+/-, p50-/-, and p50-/-p65+/- (3X) mice to LPS-induced shock. Interestingly, whereas p65+/- mice were no more sensitive than WT mice to LPS-induced shock, 3X mice were exquisitely sensitive to the toxic effects of LPS. Mice lacking p50 alone displayed an intermediate phenotype. Sensitivity to LPS was a property of the innate immune system and was characterized by elevated circulating levels of TNF in both p50-/- and 3X mice. The ability of LPS to induce shock depended upon TNF, and 3X mice were significantly more sensitive to the toxic effects of TNF than were p50-deficient mice. The expression of several LPS-inducible proinflammatory genes, including IFN-gamma, was significantly higher within the spleens of p50-/- mice than in the spleens of WT mice, and interestingly, the expression of IFN-gamma was augmented still further within the spleens of 3X mice. These results demonstrate that NF-kappaB subunits p50 and p65 have critical inhibitory functions during the systemic response to LPS and raise the possibility that these functions could be essential in preventing mortality associated with systemic inflammatory response syndromes.


Epidemiology of Parkinson's disease in Yonago City, Japan: comparison with a study carried out 12 years ago.
A study of the prevalence of Parkinson's disease (PD) was conducted in a Japanese city in 1992, and the data compared with those of a similar study performed in 1980. On the prevalence day, April 1, 1992, a total of 156 patients (46 males and 110 females) were found to be living in the investigated area, which had a population of 132,315. The prevalence per 100,000 population was 117.9 (72.8 in males and 159.1 in females), and the incidence during the period 1989 through 1992 was 15.0 per 100,000 population per year. The age- and sex-adjusted prevalence per 100,000 population was 99.5 in 1992 and 103.9 in 1980, as calculated using the 1990 Japanese population as the standard. The age-adjusted prevalence in the population under 60 years of age and the incidence in those under 55 years of age in 1992 were lower than in those under 55 in 1980. These results revealed that changes in the age structure of the population were the main contributors to the increased incidence of PD.


Neurospora crassa NAD(P)H-nitrite reductase. Studies on its composition and structure.
Neurospora crassa nitrite reductase (Mr = 290,000) catalyzes the NAD(P)H-dependent 6-electron reduction of nitrite to ammonia via flavin and siroheme prosthetic groups. Homogeneous N. crassa nitrite reductase has been prepared employing conventional purification methods followed by affinity chromatography on blue dextran-Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of homogeneous nitrite reductase reveals a single subunit band of Mr = 140,000. Isoelectric focusing of dissociated enzyme followed by sodium dodecyl sulfate-gel electrophoresis in the second dimension yields a single subunit spot with an isoelectric point at pH 6.8-6.9. Two-dimensional thin layer chromatography of acid-hydrolyzed nitrite reductase treated with 5-dimethylaminoaphthalene-1-sulfonyl chloride yields a single reactive NH2-terminal corresponding to glycine. An investigation of the prosthetic groups of nitrite reductase reveals little or no flavin associated with the purified protein, although exogenously added FAD is required for activity in vitro. An iron content of 9-10 Fe eq/mol suggests the presence of nonheme iron in addition to the siroheme moieties. Amino acid analysis yields 43 cysteinyl residues and sulfhydryl reagents react with 50 thiol eq/mol of nitrite reductase. The non-cysteinyl sulfur content, determined as 8.1 acid-labile sulfide eq/mol, is presumably associated with nonheme iron to form iron-sulfur centers. We conclude that N. crassa nitrite reductase is a homodimer of large molecular weight subunits housing an electron transfer complex of FAD, iron-sulfur centers, and siroheme to mediate the reduced pyridine nucleotide-dependent reduction of nitrite to ammonia.


Optimization and prospective evaluation of sensitive real-time PCR assays with an internal control for the diagnosis of melioidosis in Thailand.
Melioidosis is a serious infectious disease caused by Burkholderia pseudomallei, an environmental Gram-negative bacterium. Early detection of B. pseudomallei infection is crucial for successful antibiotic treatment and reducing mortality rates associated with melioidosis. Bacteria culture is currently used to identify B. pseudomallei in clinical samples, but the method is slow. Therefore, there is a need for more accurate and sensitive molecular-based diagnostic methods that can detect B. pseudomallei in all sample types, including samples from blood. We developed an optimal DNA extraction method for B. pseudomallei from plasma samples and used an internal control for real-time PCR. We evaluated six PCR target genes and identified the most effective target for the early detection of B. pseudomallei infection in patients. To prevent delays in the treatment of melioidosis that can lead to fatal outcomes, we recommend implementing this new approach for routine early detection of B. pseudomallei in clinical settings.


Mechanisms of interleukin 1beta-induced human airway smooth muscle hyporesponsiveness to histamine. Involvement of p38 MAPK NF-kappaB.
We have investigated the effect of IL-1beta on histamine H(1)-receptor (H(1)R)-mediated inositol phosphate (IP) accumulation in human airway smooth muscle cells (HASMC) and on histamine-induced contraction of human bronchial rings. Stimulation of HASMC for 24 h with IL-1beta resulted in significant loss of histamine-induced IP formation, which was associated with a reduction of histamine- induced contraction of IL-1beta-treated human bronchial rings. An inhibitor of NF-kappaB activation, pyrrolidine dithiocarbamate, and a p38 MAPK inhibitor, blocked the IL-1beta-induced H(1)R desensitization, whereas anisomycin, an SAPK/JNK and p38 MAPK activator, mimicked the effect of IL-1beta. IL-1beta has been demonstrated to induce cox-2 expression and PGE(2) synthesis. In our study, indomethacin a cox antagonist, completely inhibited the effect of IL-1beta on H(1)R, whereas exogenously added PGE(2) was able to desensitize H(1)R. Furthermore, H-89, a selective PKA inhibitor, antagonized the effect of IL-1beta. Here, we have demonstrated that IL-1beta desensitizes H(1)R, which involves the activation of p38 MAPK and NF-kappaB, leading to the expression of cox-2 and the synthesis of PGE(2). PGE(2) increases intracellular cAMP resulting in PKA activation, which phosphorylates and functionally uncouples H(1)R. Our results suggest that IL-1beta protects airway smooth muscle against histamine-induced contractile responses and that bronchial hyperreactivity to histamine is not associated with proinflammatory cytokine-induced enhancement in H(1)R signaling.


Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells.
Trypomastigotes, the highly motile infective forms of Trypanosoma cruzi, are capable of infecting several cell types. Invasion occurs either by direct recruitment and fusion of lysosomes at the plasma membrane, or through invagination of the plasma membrane followed by intracellular fusion with lysosomes. The lysosome-like parasitophorous vacuole is subsequently disrupted, releasing the parasites for replication in the cytosol. The role of this early residence within lysosomes in the intracellular cycle of T. cruzi has remained unclear. For several other cytosolic pathogens, survival inside host cells depends on an early escape from phagosomes before lysosomal fusion. Here, we show that when lysosome-mediated T. cruzi invasion is blocked through phosophoinositide 3-kinase inhibition, a significant fraction of the internalized parasites are not subsequently retained inside host cells for a productive infection. A direct correlation was observed between the lysosomal fusion rates after invasion and the intracellular retention of trypomastigotes. Thus, formation of a parasitophorous vacuole with lysosomal properties is essential for preventing these highly motile parasites from exiting host cells and for allowing completion of the intracellular life cycle.


Scalable Spray Drying Production of Amorphous V2 O5 -EGO 2D Heterostructured Xerogels for High-Rate and High-Capacity Aqueous Zinc Ion Batteries.
Rechargeable aqueous zinc-ion batteries (ZIBs) are promising in stationary grid energy storage due to their advantages in safety and cost-effectiveness, and the search for competent cathode materials is one core task in the development of ZIBs. Herein, the authors design a 2D heterostructure combining amorphous vanadium pentoxide and electrochemically produced graphene oxide (EGO) using a fast and scalable spray drying technique. The unique 2D heterostructured xerogel is achieved by controlling the concentration of EGO in the precursor solution. Driven by the improved electrochemical kinetics, the resultant xerogel can deliver an excellent rate capability (334 mAh g-1 at 5 A g-1 ) as well as a high specific capacity (462 mAh g-1 at 0.2 A g-1 ) as the cathode material in ZIB. It is also shown that the coin cell constructed based on spray-dried xerogel can output steady, high energy densities over a broad power density window. This work provides a scalable and cost-effective approach for making high performance electrode materials from cheap sources through existing industrialized materials processing.


Simulated annealing of binary holograms for the interconnection of single-mode structures.
The simulated annealing algorithm is applied to the design of binary holographic optical elements for the connection of single-mode structures. The system energy used with the simulated annealing algorithm is the absolute square of the overlap between the transmitted wave front and the modal characteristics of the receiving device; the system variables are the binary states of the hologram pixels. The plausibility of the obtained binary patterns is discussed for examples involving plane and spherical modal characteristics. The ability of the annealing process to avoid local minimum trapping is demonstrated.


Engineering control circuits for molecular robots using synthetic biology.
The integration of molecular robots and synthetic biology allows for the creation of sophisticated behaviors at the molecular level. Similar to the synergy between bioelectronics and soft robotics, synthetic biology provides control circuitry for molecular robots. By encoding perception-action modules within synthetic circuits, molecular machines can advance beyond repeating tasks to the incorporation of complex behaviors. In particular, cell-free synthetic biology provides biomolecular circuitry independent of living cells. This research update reviews the current progress in using synthetic biology as perception-action control modules in robots from molecular robots to macroscale robots. Additionally, it highlights recent developments in molecular robotics and cell-free synthetic biology and suggests their combined use as a necessity for future molecular robot development.


Plasma lipid changes and medroxyprogesterone acetate.
Progestogens may have profound effects on lipid metabolism. Effects are generally dose-related and are more pronounced with 19-nor testosterone derivatives. Progestogens suppress circulating levels of high-density lipoprotein cholesterol (HDL-C) and increase circulating low-density lipoprotein cholesterol. Therefore, over a long period of time, the risk of atherosclerosis may increase. Although contraceptive use of depot medroxyprogesterone acetate (DMPA) reduced HDL-C levels by 15-20%, the levels generally remain within the normal range. Progestogens such as DMPA usually do not have any influence on fasting triglyceride levels. Some progestogens produce changes in the composition of phospholipids, but not DMPA. Progestogen effects on lipid metabolism are different from estrogen effects alone or estrogen-progestogen combinations. Increased risk of cardiovascular disease in longterm DMPA users is probably very small, but may become more significant when coupled with high risk factors. 10 years ago, most of the undesirable metabolic changes associated with the use of oral contraceptives were attributed to the estrogen component. 2 recent findings illustrate that certain progestogens can create metabolic havoc. 1) There is a strong association between depressed circulating levels of HDL-C and risk of serious cardiovascular disesase. 2) Certain progestogens are capable of substantially depressing the circulating levels of HDL-C, whereas estrogen actually elevates HDL-C. This does not prove that progestogens cause cardiovascular disease, but this possibility should be considered.


Temperature- and Rate-Dependent Pathways in Formation of Metastable Silicon Phases under Rapid Decompression.
High-pressure metallic β-Sn silicon (Si-II), depending on temperature, decompression rate, stress, etc., may transform to diverse metastable forms with promising semiconducting properties under decompression. However, the underlying mechanisms governing the different transformation paths are not well understood. Here, two distinctive pathways, viz., a thermally activated crystal-crystal transition and a mechanically driven amorphization, were characterized under rapid decompression of Si-II at various temperatures using in situ time-resolved x-ray diffraction. Under slow decompression, Si-II transforms to a crystalline bc8/r8 phase in the pressure range of 4.3-9.2 GPa through a thermally activated process where the overdepressurization and the onset transition strain are strongly dependent on decompression rate and temperature. In comparison, Si-II collapses structurally to an amorphous form at around 4.3 GPa when the volume expansion approaches a critical strain via rapid decompression beyond a threshold rate. The occurrence of the critical strain indicates a limit of the structural metastability of Si-II, which separates the thermally activated and mechanically driven transition processes. The results show the coupled effect of decompression rate, activation barrier, and thermal energy on the adopted transformation paths, providing atomistic insight into the competition between equilibrium and nonequilibrium pathways and the resulting metastable phases.


Timing of the Brunhes-Matuyama transition constrained by U-series disequilibrium.
U-series disequilibrium measurements carried out on thermogenic travertine samples from a 12.6 m-long core and a 10 m-thick section from southeastern Morocco yielded finite ages ranging from 500 ka to the present-day, as well as two clusters determined to be older than 500 ka. The calculation of initial 234U/238U activity ratios in all samples younger than 500 ka shows high, reasonably constant values, with an average of 5.172 ± 0.520 (one standard deviation). Assuming that this value prevailed for periods older than 500 ka, we derived ages of up to approximately 1.2 Ma using the initial 234U excess decay. Our results indicate that the two older clusters have ages of 776 ± 14 ka for samples from between 8 and 10.1 m and 1173 ± 22 ka for deeper samples respectively. The palaeomagnetic record of the core shows normal polarity inclinations from the surface to around 9 m followed by reverse polarity inclination and antipodal declinations. The inversion is attributed to the Brunhes-Matuyama transition. 234U excess ages for the interval corresponding to the part of the core where the polarity inversion occurred are in the range of 735 ± 51 to 794 ± 54 ka, with an arithmetic mean value of 776 ± 14 ka for the B-M transition. This age is in good agreement with that determined previously using other dating methods.


CNS Organoid Surpasses Cell-Laden Microgel Assembly to Promote Spinal Cord Injury Repair.
The choice of therapeutic agents remains an unsolved issue in the repair of spinal cord injury. In this work, various agents and configurations were investigated and compared for their performance in promoting nerve regeneration, including bead assembly and bulk gel of collagen and Matrigel, under acellular and cell-laden conditions, and cerebral organoid (CO) as the in vitro preorganized agent. First, in Matrigel-based agents and the CO transplantations, the recipient animal gained more axon regeneration and the higher Basso, Beattie, and Bresnahan (BBB) scoring than the grafted collagen gels. Second, new nerves more uniformly infiltrated into the transplants in bead form assembly than the molded chunks. Third, the materials loaded the neural progenitor cells (NPCs) or the CO implantation groups received more regenerated nerve fibers than their acellular counterparts, suggesting the necessity to transplant exogenous cells for large trauma (e.g., a 5 mm long spinal cord transect). In addition, the activated microglial cells might benefit from neural regeneration after receiving CO transplantation in the recipient animals. The organoid augmentation may suggest that in vitro maturation of a microtissue complex is necessary before transplantation and proposes organoids as the premium therapeutic agents for nerve regeneration.


Topical Adrenaline (1: 1000) for the Management of Severe Tarsal Conjunctival Chemosis.
Severe, refractory tarsal conjunctival chemosis developed in a severely autistic 9-year-old boy with a history of allergic conjunctival chemosis. The child was initially treated with topical and oral antihistamines, topical steroids, lubricants, and topical phenylephrine 10% with worsening of condition until complete eyelid eversion secondary to gross conjunctival chemosis with total obstruction of vision in the affected eye. Subsequently, he was successfully treated with topical adrenaline (1:1000) with rapid and lasting effect. The authors suggest that topical (1:1000) adrenaline is an effective therapy when other conservative therapies fail and can be useful in avoiding examination under general anesthetic and invasive intervention. Such a case has not been previously reported in the literature.


Fast Li ion dynamics in the solid electrolyte Li7 P3 S11 as probed by (6,7) Li NMR spin-lattice relaxation.
The development of safe and long-lasting all-solid-state batteries with high energy density requires a thorough characterization of ion dynamics in solid electrolytes. Commonly, conductivity spectroscopy is used to study ion transport; much less frequently, however, atomic-scale methods such as nuclear magnetic resonance (NMR) are employed. Here, we studied long-range as well as short-range Li ion dynamics in the glass-ceramic Li7 P3 S11 . Li(+) diffusivity was probed by using a combination of different NMR techniques; the results are compared with those obtained from electrical conductivity measurements. Our NMR relaxometry data clearly reveal a very high Li(+) diffusivity, which is reflected in a so-called diffusion-induced (6) Li NMR spin-lattice relaxation peak showing up at temperatures as low as 313 K. At this temperature, the mean residence time between two successful Li jumps is in the order of 3×10(8) s(-1) , which corresponds to a Li(+) ion conductivity in the order of 10(-4) to 10(-3) S cm(-1) . Such a value is in perfect agreement with expectations for the crystalline but metastable glass ceramic Li7 P3 S11 . In contrast to conductivity measurements, NMR analysis reveals a range of activation energies with values ranging from 0.17 to 0.26 eV, characterizing Li diffusivity in the bulk. In our case, through-going Li ion transport, when probed by using macroscopic conductivity spectroscopy, however, seems to be influenced by blocking grain boundaries including, for example, amorphous regions surrounding the Li7 P3 S11 crystallites. As a result of this, long-range ion transport as seen by impedance spectroscopy is governed by an activation energy of approximately 0.38 eV. The findings emphasize how surface and grain boundary effects can drastically affect long-range ionic conduction. If we are to succeed in solid-state battery technology, such effects have to be brought under control by, for example, sophisticated densification or through the preparation of samples that are free of any amorphous regions that block fast ion transport.


Do physical diagnostic tests accurately detect meniscal tears?
Numerous physical tests have been described but their diagnostic accuracy is often questioned. Karachalios et al. described the new 'Thessaly test' and concluded that it could be safely used as a first line screening test for the selection of patients who need arthroscopic meniscal surgery. Our objective was to study the role of physical diagnostic tests in screening for meniscal tears and to validate the diagnostic accuracy of the Thessaly test. We examined 109 patients (80 male, 29 female; average age: 39 years; range: 16-56) who were presented with a history suggestive of a meniscal tear. Joint line tenderness, McMurray's test, and the Thessaly test were assessed by an independent investigator blinded to any imaging data in all patients. MRI and subsequent arthroscopy results were then collated. Our study showed a much lower diagnostic accuracy for the Thessaly test (61% for medial meniscus and 80% for lateral meniscus). It is comparable to McMurray's test (57% for medial meniscus and 77% for lateral meniscus). The Joint line tenderness test has a far superior diagnostic accuracy (81% for medial meniscus and 90% for lateral meniscus). However, combining the joint line tenderness test with McMurray's test or the joint line tenderness test with Thessaly test further increased the accuracy of physical diagnosis of meniscal tears. Magnetic resonance imaging (MRI) detected 96% of meniscal tears. Physical tests may not always be diagnostic of meniscal tears. MRI and arthroscopy may be essential in dubious clinical presentations and especially where more than one pathology is suspected. Our study showed that the Thessaly test in isolation was not useful for the detection of meniscal tears but it helps to increase diagnostic certainty when combined with other standard tests.


New species and a new record of the mite family Scutacaridae (Acari: Heterostigmata) from alpine New Zealand.
Seven new species of the mite family Scutacaridae (Acari: Pygmephoroidea) are described from the alpine zone (1600-1900 m a.s.l.) of the Central Otago region of the South Island of New Zealand: Diversipes laticaudatus sp. nov., Scutacarus isotrichus sp. nov., S. incisus sp. nov., S. spinisetus sp. nov., S. cornutus sp. nov., S. novaezealandicus sp. nov., and S. crassus sp. nov. In addition, Imparipes woodi Mahunka, 1974 is recorded from the New Zealand for the first time and redescribed.


Possible involvement of primary motor cortex in mentally simulated movement: a functional magnetic resonance imaging study.
The role of the primary motor cortex (M1) during mental simulation of movement is open to debate. In the present study, functional magnetic resonance imaging (fMRI) signals were measured in normal right-handed subjects during actual and mental execution of a finger-to-thumb opposition task with either the right or the left hand. There were no significant differences between the two hands with either execution or simulation. A significant involvement of contralateral M1 (30% of the activity found during execution) was detected in four of six subjects. Premotor cortex (PM) and the rostral part of the posterior SMA were activated bilaterally during motor imagery. These findings support the hypothesis that motor imagery involves virtually all stages of motor control.


Development of an Innovative Quantification Assay Based on Aptamer Sandwich and Isothermal Dumbbell Exponential Amplification.
Detecting blood biomarkers such as proteins with high sensitivity and specificity is of the utmost importance for early and reliable disease diagnosis. As molecular probes, aptamers are raising increasing interest for biosensor applications as an alternative to antibodies, which are used in classical enzyme-linked immuno-sorbent assays (ELISA). We have developed a sensitive and antibody-free molecular quantification assay that combines the specificity of aptamers and the sensitivity of the loop-mediated isothermal amplification (LAMP). For the proof-of-concept, we consider two types of biomarkers: (i) a model of oligonucleotide mimicking nucleic acid targets and (ii) the thrombin involved in the complex coagulation cascade as a model protein for which two relevant aptamers form a stable sandwich. The assay protocol is based on a few successive steps, similar to sandwich ELISA. First, aptamer-coated magnetic beads are added to the sample to specifically capture the targets. Then, the sandwich complex is formed by adding the second aptamer. This secondary aptamer is integrated in a larger oligonucleotide dumbbell sequence designed for LAMP detection using only two primers. After a proper rinsing step, the isothermal dumbbell exponential amplification is performed to detect and quantify a low amount of targets (limit of detection ∼ 1 pM for the oligonucleotide and ∼100 pM for thrombin). This study demonstrates that our innovative aptamero-LAMP assay could be relevant for the detection of different types of biomarkers and their quantification at physiological levels. This may also pave the way for antibody-free molecular assays.


Molecular cloning of prohormone convertase 1 from the atrial gland of Aplysia.
We have screened an Aplysia atrial gland cDNA library using a prohormone convertase (PC)1 probe prepared by polymerase chain reaction (PCR) and have isolated an Aplysia PC1-related full-length 3.6-kb cDNA clone. The cDNA sequence (3,565 bp) encoded a putative preproendoprotease (APC1) of 703 amino acid residues that showed considerable sequence identity with other eukaryotic PC1s, and indicated a high degree of sequence identity with an Aplysia nervous system PC sequence (aPC1B). Northern blot analysis of atrial gland RNA identified two APC1 transcripts of 3.9 kb and 5.0 kb. APC1 is a candidate PC that may play an important role in the processing of egg-laying hormone (ELH)-related precursors in atrial gland secretory cells and represents one of the first examples of PC1 expression in an exocrine tissue.


A tandem-lens epifluorescence macroscope: hundred-fold brightness advantage for wide-field imaging.
The design of a macroscope constructed with photography lenses is described and several applications are demonstrated. The macroscope incorporates epi-illumination, a 0.4 numerical aperture, and a 40 mm working distance for imaging wide fields in the range of 1.5-20 mm in diameter. At magnifications of 1X to 2.5X, fluorescence images acquired with the macroscope were 100-700 times brighter than those obtained with commercial microscope objectives at similar magnifications. In several biological applications, the improved light collection efficiency (20-fold, typical) not only minimized bleaching effects, but, in concert with improved illumination throughput (15-fold, typical), significantly enhanced object visibility as well. Reduced phototoxicity and increased signal-to-noise ratios were observed in the in vivo real-time optical imaging of cortical activity using voltage-sensitive dyes. Furthermore, the macroscope has a depth of field which is 5-10 times thinner than that of a conventional low-power microscope. This shallow depth of field has facilitated the imaging of cortical architecture based on activity-dependent intrinsic cortical signals in the living primate brain. In these reflection measurements large artifacts from the surface blood vessels, which were observed with conventional lenses, were eliminated with the macroscope.


Distribution of 22 cytokine gene polymorphisms in the healthy Czech population.
Cytokine gene polymorphisms (CGP) have been implicated in the pathogenesis of immune-mediated diseases including transplant complications via their effect on cytokine production and regulation. This study aimed to determine population frequencies of selected cytokine single nucleotide polymorphisms in the healthy Czech population and compare them with the data from other selected European populations. CGP were genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) using the Heidelberg kit in 120 unrelated Czech healthy individuals. Chi-squared analysis was used to test for a deviation from Hardy-Weinberg equilibrium. Allelic and genotype frequencies and carriage rates were determined for 22 CGP located within 13 cytokine genes in total. The frequencies observed in this study were similar to those available from the other two geographically close Central European centres, but they differed for several CGP from the data reported in south European populations. The data on the distribution of 22 CGP in the healthy Czech population reported here may be utilized to investigate possible associations of CGP with diseases or transplantation outcome.


Increased expression of nucleoside diphosphate kinase/nm23 and c-Ha-ras mRNA is associated with spontaneous lung metastasis in rat-transplantable osteosarcomas.
The relationship between expression of nucleoside diphosphate kinase (NDP kinase)/nm23, c-Ha-ras, and c-myc genes and metastatic potential was assessed in rat-transplantable osteosarcoma lines, derived from spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcomas in Fischer 344/NS1c rats. These osteosarcomas possess metastatic potential and highly metastatic lines spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions were respectively established by selectively transplanting lung metastatic lesions. Northern blot analysis revealed that the levels of NDP kinase/nm23 and c-Ha-ras gene expression were increased in line with metastatic ability; thus transcript levels were remarkably greater in both spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions highly metastatic lines than in their respective low metastatic spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcoma counterparts. c-myc mRNA expression was observed in all tumor lines, without any correlation with metastatic ability. Southern blot analysis did not show evidence of gross rearrangement or amplification of NDP kinase/nm23, c-Ha-ras, or c-myc genes suggesting regulation of their gene expression at the transcriptional and/or posttranscriptional level. These results indicate that NDP kinase/nm23 and c-Ha-ras might be cooperatively involved in a positive manner in signal transduction processes, especially involving G-protein reactions, responsible for metastasis of rat-transplantable osteosarcomas.


A new approach of denoising the regular and chaotic signals using Empirical Mode Decomposition: comparison and application.
The Empirical Mode Decomposition has been used to present a new approach for denoising of regular and chaotic time series originating from the nonlinear systems. The proposed filtering approach is based on the frequency distribution of different Intrinsic Mode Functions (IMFs). It provides complete frequency and noise strength information present in the data set. The actual frequencies in an experimental data set are distributed among different IMFs which are subsequently disentangled through the algorithm resulting into filtered as well as noise components. The filtered signal is produced only after a suppression (hard threshold) of noise components. The noise strength present in the data set is produced by the identified noisy IMFs. This innovative approach has been tested for linear, nonlinear, and chaotic types of calculated data sets with various levels of simulated noise strengths and results have been compared with the existing methods. The validity of the present approach is confirmed by experimentally observed astrophysical data as well as data from a neutron detector. A sharp improvement in the signal strength has been observed with the proposed method in comparison to the existing methods.


Spin-momentum correlations in quasielastic electron scattering from deuterium.
The spin-momentum correlation parameter A(V)(ed) was measured for the 2H-->(e-->,e'p)n reaction for missing momenta up to 350 MeV/c at Q2 = 0.21 (GeV/c)(2) for quasielastic scattering of polarized electrons from vector-polarized deuterium. The data give detailed information about the deuteron spin structure and are in good agreement with the results of microscopic calculations based on realistic nucleon-nucleon potentials and including various spin-dependent reaction mechanism effects. The experiment reveals in a most direct manner the effects of the D state in the deuteron ground-state wave function and shows the importance of isobar configurations for this reaction.


Combined Effects of Noise and Reverberation on Sound Localization for Listeners With Normal Hearing and Bilateral Cochlear Implants.
This study examined the individual and combined effects of noise and reverberation on the ability of listeners with normal hearing (NH) and with bilateral cochlear implants (BCIs) to localize speech. Six adults with BCIs and 10 with NH participated. All subjects completed a virtual localization test in quiet and at 0-, -4-, and -8-dB signal-to-noise ratios (SNRs) in simulated anechoic and reverberant (0.2-, 0.6-, and 0.9-s RT60) environments. BCI users were also tested at +8- and +4-dB SNR. A 3-word phrase was presented at 70 dB SPL from 9 simulated locations in the frontal horizontal plane (±90°), with the noise source at 0°. BCIs users had significantly poorer localization than listeners with NH in all conditions. BCI users' performance started to decrease at a higher SNR (+4 dB) and shorter RT60 (0.2 s) than listeners with NH (-4 dB and 0.6 s). The combination of noise and reverberation began to degrade localization of BCI users at a higher SNR and a shorter RT60 than listeners with NH. The clear effect of noise and reverberation on the performance of BCI users provides information that should be useful for refining cochlear implant processing strategies and developing cochlear implant rehabilitation plans to optimize binaural benefit for BCI users in everyday listening situations.


Crystal structure of the RRM domain of poly(A)-specific ribonuclease reveals a novel m(7)G-cap-binding mode.
Poly(A)-specific ribonuclease (PARN) is a processive 3'-exoribonuclease involved in the decay of eukaryotic mRNAs. Interestingly, PARN interacts not only with the 3' end of the mRNA but also with its 5' end as PARN contains an RRM domain that specifically binds both the poly(A) tail and the 7-methylguanosine (m(7)G) cap. The interaction of PARN with the 5' cap of mRNAs stimulates the deadenylation activity and enhances the processivity of this reaction. We have determined the crystal structure of the PARN-RRM domain with a bound m(7)G triphosphate nucleotide, revealing a novel binding mode for the m(7)G cap. The structure of the m(7)G binding pocket is located outside of the canonical RNA-binding surface of the RRM domain and differs significantly from that of other m(7)G-cap-binding proteins. The crystal structure also shows a remarkable conformational flexibility of the RRM domain, leading to a perfect exchange of two alpha-helices with an adjacent protein molecule in the crystal lattice.


Additively Manufactured Zirconia for Dental Applications.
We aimed to assess the crystallography, microstructure and flexural strength of zirconia-based ceramics made by stereolithography (SLA). Two additively manufactured 3 mol% yttria-stabilized tetragonal zirconia polycrystals (3Y-TZP: LithaCon 3Y 230, Lithoz; 3D Mix zirconia, 3DCeram Sinto) and one alumina-toughened zirconia (ATZ: 3D Mix ATZ, 3DCeram Sinto) were compared to subtractively manufactured 3Y-TZP (control: LAVA Plus, 3M Oral Care). Crystallographic analysis was conducted by X-ray diffraction. Top surfaces and cross-sections of the subsurface microstructure were characterized using scanning electron microscopy (SEM). Biaxial flexural strength was statistically compared using Weibull analysis. The additively and subtractively manufactured zirconia grades revealed a similar phase composition. The residual porosity of the SLA 3Y-TZPs and ATZ was comparable to that of subtractively manufactured 3Y-TZP. Weibull analysis revealed that the additively manufactured LithaCon 3Y 230 (Lithoz) had a significantly lower biaxial flexural strength than 3D Mix ATZ (3D Ceram Sinto). The biaxial flexural strength of the subtractively manufactured LAVA Plus (3M Oral Care) was in between those of the additively manufactured 3Y-TZPs, with the additively manufactured ATZ significantly outperforming the subtractively manufactured 3Y-TZP. Additively manufactured 3Y-TZP showed comparable crystallography, microstructure and flexural strength as the subtractively manufactured zirconia, thus potentially being a good option for dental implants.


Optimization of Mass Flow in the Synthesis of Ferromagnetic Carbon Nanotubes in Chemical Vapor Deposition System.
Carbon nanotubes have unique properties, which make it possible to be applied in a variety of sensing applications. Moreover, by controlling the synthesis chemistry process, it is possible for carbon nanotubes to either fill or attach to its surface metal particles, e.g., iron. In an industrial scale, the yield and purity of the final product is very important. This work describes the chemical vapor deposition (CVD) method of carbon iron nanocontainers with maximum nanoparticles to impurities ratio. As one of the main parameters, the mass flow of gases was considered. To investigate the quality of the product, the scanning electron microscopy and thermogravimetric methods were used. Results for different process conditions were presented and discussed. The low gas velocity and high temperatures may affect the catalyst decomposition and ionization. The optimum flow and temperature in the reactor were determined.


Systematic back muscle exercise after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients: a randomized controlled trial.
To analyze the clinical significance of postoperative back muscle exercises after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients. Clinical randomized controlled trials of parallel group nonpharmacologic study. Patients practised back muscle exercises in the spinal surgery department, rehabilitation department and at their residences. Osteoporotic compression fracture patients who had undergone percutaneous vertebroplasty and processed sufficient muscle strength to participate in the training were studied. Patients were randomized into two groups, which were titled A and B. General postoperation therapy, including antiosteoporotic medications and education, was offered to all patients. Group B patients received additional systematic back muscle exercise. Both Oswestry Disability Index (ODI) and visual analogue scale (VAS) were recorded preoperatively and postoperatively at three-day, one-month, six-month, one-year and two-year follow-up. From January 2006 to January 2009, a total of 82 patients were assessed for eligibility, 60 patients were enrolled and randomized into two groups. Forty-two (70%) patients (20 of 30 in Group A and 22 of 30 in Group B) were successfully followed-up for two years. Systematic back muscle exercises resulted in a significant advantage in both measurements. The ODI of Group B was significantly better than Group A at the six-month, one-year and two-year follow-ups (P < 0.05). The pain level of Group B was significantly lower than in Group A at the one- and two-year follow-ups (P < 0.05). At the end of our study, the mean (SD) of the ODI in Groups A and B were 39.1 (9.14) and 23.4 (5.62); the mean (SD) of the VAS in Groups A and B were 3.4 (1.15) and 2.1 (0.84), respectively. Our findings suggest that the benefit of the exercises required at least six months to be observed; however, the favourable effects could last for two years. Therefore, systematic back muscle exercise should be recommended as one of the treatment guidelines for postpercutaneous vertebroplasty patients.


A molar pregnancy detected by following beta-human chorionic gonadotropin levels after a first trimester loss.
This case report summarizes the sequence of events that led to the detection of a molar pregnancy missed by ultrasound and initial pathology examinations. This patient illustrates that following serial quantitative beta-human chorionic gonadotropin (B-hCG) levels after spontaneous, therapeutic, and elective abortions will help detect potentially life-threatening molar and ectopic pregnancies. Further research is needed to determine the optimal frequency of B-hCG testing. For now, maternity care providers can follow the American College of Obstetrics and Gynecology recommendation that abnormal bleeding for more than 6 weeks after any pregnancy should be evaluated with B-hCG testing. Earlier testing may be considered.


Wnt and Notch signaling pathways in calcium phosphate-enhanced osteogenic differentiation: A pilot study.
Calcium phosphate (CaP) ceramics are being increasingly used to repair critical bone defect for biocompatibility, biosafety, porous structure and osteoinduction. Wnt and Notch signaling pathways are conservative and classic signaling pathways regulating osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs). In this study, we evaluated the expression of Wnt, Notch signal pathways and osteogenic related genes of BMSCs with and without Wnt pathway inhibitor DKK1 on CaP ceramics in vitro by real-time RT-PCR. Also, we evaluated new bone formation after implantation of CaP ceramics in vivo. The in vitro culture displayed the expression of Wnt, Notch signaling pathways and osteogenic related genes was increased at first and then declined. After adding DKK1 to the culture, the expression was decreased. The in vivo implantation showed significant bone formation on CaP ceramics. These findings reveal that Wnt and Notch signaling pathways play important roles in the CaP-enhanced osteogenic differentiation but the mechanism of synergistic effect needs to be further explored. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 149-160, 2019.


Parental Resources, Schooling Achievements, and Gender Schooling Gaps: Evidence of Change over 25 years in Rural Guatemala.
We use village census data and linear regression models to examine changes between 1975 and 2002 in the associations of parental resources with boys' and girls' schooling in four rural Guatemalan villages. Levels of schooling in 1975 were universally low for children 7-17 years. Large increases in schooling achievements occurred between 1975 and 2002. By 2002, schooling levels were comparable for younger boys and girls (7-12 years, N = 3,525) and favored older boys compared to older girls (13-17 years, N = 2,440) by about 0.5 grades. The associations of household standard of living and maternal schooling with schooling among girls diminished over time and became more comparable with these associations among boys, and the associations of household standard of living with schooling among older boys declined and became more comparable with these associations among girls. Thus, as increased social investments reduce the costs of schooling or increase the supply and quality of schooling to families, the magnitudes of the associations between parental resources and children's schooling decline and become more gender equitable at all ages. However, our results show that older boys may benefit more than older girls from social investments in schooling. These changes suggest potential needs to monitor gender gaps in schooling retention among older children, to insure gender equitable access to social investments in schooling, and to encourage parents to invest in schooling as joint measures to achieve greater schooling achievements of girls and boys.


In utero and lactational treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs mammary gland differentiation but does not block the response to exogenous estrogen in the postpubertal female rat.
These experiments tested whether in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters mammary gland differentiation, estrogen receptor alpha (ERalpha) expression levels, or the response to estrogen in the female postpubertal rat mammary gland. Pregnant Holtzman rats were administered a single oral dose of 1 microg/kg TCDD or vehicle on gestation-day 15. Exposed and non-exposed female offspring were weaned on postnatal day 21 and ovariectomized at 9 weeks of age. Two weeks later, both TCDD and control animals were divided into 3 groups, receiving treatment with placebo, 0.025, or 0.1 mg 17beta-estradiol pellet implants. After 48 h, mammary tissue was removed for analysis following euthanasia. TCDD-exposed mammary glands demonstrated impaired differentiation as measured by the distribution of terminal ductal structures and increased expression levels of ERalpha. The response to exogenous estrogen was tested in TCDD-exposed animals and compared to control non-exposed animals. Estrogen stimulation of the TCDD-exposed glands induced progesterone receptor expression and mammary gland differentiation as measured by a shift in distribution from terminal end buds and terminal ducts to Types I and II lobules. Control glands were better differentiated at baseline and did not exhibit any significant changes in the distribution of terminal ductal structures following estrogen stimulation. The increase in progesterone receptor-expression levels by exogenous estrogen in control glands was similar to the TCDD-exposed glands. These experiments demonstrate that in utero and lactational exposures to TCDD impair mammary gland differentiation but that TCDD-exposed mammary glands retain the ability to differentiate in response to estrogen.


Separation of mounting-inducing pheromones of vaginal mucus from estrual heifers.
There is evidence that mucus of the female bovine genital tract contains pheromones that induce physiological and behavioral responses in other animals. To study these pheromones, vaginal mucus was collected from heifers either at estrus or during diestrus. The mucus was then applied to the hindquarters of the same animal during diestrus or to the hindquarters of herdmates during diestrus. The behaviors of the treated animal and its herdmates were then observed. To attempt to isolate the mounting-inducing substance, mucus was dialyzed or separated on ion-exchange resins. Diestrous heifers to which their own estrual mucus has been applied were nearly always mounted by herdmates (P less than .01). But, heifers to which another's estrous mucus had been applied were not mounted. This suggests that vaginal mucus contains not only estrus-related pheromones, but also individual distinctive odors. The dialyzable fraction of vaginal mucus and the neutral fraction, prepared by ion-exchange chromatography of the dialyzable solution of vaginal mucus, had a mounting-inducing activity on the herdmates, as did the application of an animal's own vaginal mucus. These findings suggest that mounting-inducing pheromones are relatively low molecular weight, neutral substances.