Uric acid spherulites in the reflector layer of firefly light organ.
In firefly light organs, reflector layer is a specialized tissue which is believed to play a key role for increasing the bioluminescence intensity through reflection. However, the nature of this unique tissue remains elusive. In this report, we investigated the role, fine structure and nature of the reflector layer in the light organ of adult Luciola cerata. Our results indicated that the reflector layer is capable of reflecting bioluminescence, and contains abundant uric acid. Electron microscopy (EM) demonstrated that the cytosol of the reflector layer's cells is filled with densely packed spherical granules, which should be the uric acid granules. These granules are highly regular in size (∼700 nm in diameter), and exhibit a radial internal structure. X-ray diffraction (XRD) analyses revealed that an intense single peak pattern with a d-spacing value of 0.320 nm is specifically detected in the light organ, and is highly similar to the diffraction peak pattern and d-spacing value of needle-formed crystals of monosodium urate monohydrate. However, the molar ratio evaluation of uric acid to various cations (K(+), Na(+), Ca(2+) and Mg(2+)) in the light organ deduced that only a few uric acid molecules were in the form of urate salts. Thus, non-salt uric acid should be the source of the diffraction signal detected in the light organ. In the light organ, the intense single peak diffraction signal might come from a unique needle-like uric acid form, which is different from other known structures of non-salt uric acid form. The finding of a radial structure in the granules of reflector layer implies that the spherical uric acid granules might be formed by the radial arrangement of needle-formed packing matter.


Making clinical decisions using a clinical practice guideline.
Clinical practice guidelines are statements developed from best evidence about clinically relevant appropriate care. A simulated patient case is presented to demonstrate how to use a CPG in decision-making in determining a clinical decision. Conceptualized knowledge management software templates are provided to explain a process by which best evidence is retrieved from a primary, centralized network database. Templates describe the process of converting a clinical question into a research question, retrieving best evidence, and performing data analysis for the outcome of individualizing and optimizing a clinical decision. Templates also describe the reciprocation of information to update CPGs by translational researchers who manage and build the primary, centralized network database.


Dihydropyrimidine dehydrogenase inhibition as a strategy for the oral administration of 5-fluorouracil: utility in the treatment of advanced colorectal cancer.
Dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism, has been a key target for the development of novel oral fluoropyrimidines. DPD-inhibiting oral fluoropyrimidines showing promise in early clinical studies included UFT (the 5-FU prodrug, tegafur, plus the DPD substrate, uracil), eniluracil (an irreversible DPD inhibitor that improves the oral bioavailability of 5-FU) and S-1 (tegafur plus a reversible DPD inhibitor, 5-chloro-2,4-dihydroxypyridine, and oxonic acid). However, results from phase II/III trials evaluating these agents as first-line therapy for metastatic colorectal cancer have been disappointing. Although DPD-inhibiting oral fluoropyrimidines have some activity in colorectal cancer and oral administration provides significant convenience advantages, the inferior efficacy of UFT/leucovorin and eniluracil/5-FU versus 5-FU/leucovorin in phase III trials does not support the use of these compounds. A feasible regimen for the phase III development of S-1 outside Japan has not been defined. Thus the DPD-inhibiting oral fluoropyrimidines have failed to fulfill their early promise: clinical data indicate that none of these compounds is likely to improve outcomes for patients with metastatic colorectal cancer.


Follicular dendritic cell sarcoma of oral cavity: report of 2 cases.
We report 2 cases of Follicular Dendritic Cell Sarcomas of Oral Cavity in two elderly patients. The patients presented with oral cavity tumors. Initial tru-cut biopsies in both cases revealed spindle cell neoplasms. One of them was of low grade malignancy and showed positivity for of Vimentin. Few cells showed positivity for keratin and were negative for S-100 protein, CD 34, CD 68, EMA, SMA, HMB-45. A possible diagnosis of low grade fibrohistiocytic tumor was made. He underwent Lt total maxillectomy. Three years later he presented back with regional nodal metastasis. The regional lymph nodes showed features of follicular dendritic cell sarcoma. The second case revealed high grade spindle cell neoplasm and showed positivity for vimentin and S100 protein and was negative for EMA, keratin, CD-34, desmin, muscle actin and HMB-45. He was offered initial radio-therapy followed by hemifacial resection. The histology along with immuno histochemistry favoured a diagnosis of follicular dendritic cell sarcoma. He presented with local recurrence two months later. Both the cases are discussed in detail.


Patterns and predictors of adherence to colorectal cancer screening recommendations in Alberta's Tomorrow Project participants stratified by risk.
Colorectal cancer (CRC) screening is an important modifiable behaviour for cancer control. Regular screening, following recommendations for the type, timing and frequency based on personal CRC risk, contributes to earlier detection and increases likelihood of successful treatment. To determine adherence to screening recommendations in a large provincial cohort of adults, participants in Alberta's Tomorrow Project (n = 9641) were stratified based on increasing level of CRC risk: age (Age-only), family history of CRC (FamilyHx), personal history of bowel conditions (PersonalHx), or both (Family/PersonalHx) using self-reported information from questionnaires. Provincial and national guidelines for timing and frequency of screening tests were used to determine if participants were up-to-date based on their CRC risk. Screening status was compared between enrollment (2000-2006) and follow-up (2008) to determine screening pattern over time. The majority of participants (77%) fell into the average risk Age-only strata. Only a third of this strata were up-to-date for screening at baseline, but the proportion increased across the higher risk strata, with > 90% of the highest risk Family/PersonalHx strata up-to-date at baseline. There was also a lower proportion (< 25%) of the Age-only group who were regular screeners over time compared to the higher risk strata, though age, higher income and uptake of other screening tests (e.g. mammography) were associated with a greater likelihood of regular screening in multinomial logistic regression. The low (< 50%) adherence to regular CRC screening in average and moderate risk strata highlights the need to further explore barriers to uptake of screening across different risk profiles.


Characterization of N-linked oligosaccharides attached to human renin expressed in COS cells.
To study the role of N-linked oligosaccharides attached to human renin, we generated three kinds of glycosylation-deficient renins in which one or both of two putative N-glycosylation sites was eliminated by amino acid replacement using site-directed mutagenesis. Examination of the three mutant renins (Asn-5 to Ala, Asn-75 to Ala, and both Asn-5 and -75 to Ala) expressed in COS cells demonstrated that both putative sites were certainly glycosylated with heterologous N-linked oligosaccharides. Moreover, the oligosaccharide chain attached at Asn-5 was different from that attached at Asn-75 in its molecular size. In addition, the secreted amount of the three mutant renins were different from one another, although the mutant and wild-type renins had practically the same specific activity. Our results suggest that the N-linked oligosaccharides have no effect on the enzymatic activity, but play an important role in stable secretion of human renin.


Discrimination of interaural temporal disparities conveyed by high-frequency sinusoidally amplitude-modulated tones and high-frequency transposed tones: effects of spectrally flanking noises.
Dreyer and Oxenham [(2008). "Effects of level and background noise on interaural time difference discrimination for transposed stimuli," J. Acoust. Soc. Am. 123, EL1-EL7] reported that spectrally flanking noise increased threshold interaural temporal disparities (ITDs) conveyed by high-frequency transposed tones but rendered them indiscriminable when they were conveyed by high-frequency sinusoidally amplitude-modulated (SAM) tones. This study extends those observations and evaluates the role of "off-frequency listening." Threshold ITDs were measured using 4-kHz-centered transposed or SAM tonal "targets." In "baseline" conditions, targets were presented without spectrally flanking noise. Additionally, targets were presented along with continuous diotic broadband Gaussian noise spectrally "notched" between 3.6 and 4.4 kHz. In another condition, only the high-pass segment of the notched noise was continuously present. In the final condition, only the low-pass segment was continuously present. Results indicate that (1) relative to baseline, adding notched noise resulted in similar relative increases of threshold ITDs for both SAM and transposed targets; (2) the presence of the high-pass segment of the notched noise resulted in greater relative increases in threshold ITDs over those obtained in baseline conditions for SAM tones as compared to transposed tones; (3) comparisons among all of the data were consistent with the interpretation that both on-frequency and off-frequency processing of envelope-based ITDs can be disrupted by the presence of a notched noise.


High-glucose concentrations change DNA methylation levels in human IVM oocytes.
What are the effects of high-glucose concentrations on DNA methylation of human oocytes? High-glucose concentrations altered DNA methylation levels of Peg3 and Adiponectin in human in vitro maturation oocytes. Maternal diabetes has a detrimental influence on oocyte quality including epigenetic modifications, as shown in non-human mammalian species. Immature metaphase I (MI) stage oocytes of good quality were retrieved from patients who had normal ovarian potential and who underwent ICSI in the Reproductive Medicine Center of People's Hospital of Zhengzhou University. MI oocytes were cultured in medium with different glucose concentrations (control, 10 mM and 15 mM) in vitro and 48 h later, oocytes with first polar body extrusion were collected to check the DNA methylation levels. MI oocytes underwent in vitro maturation (IVM) at 37°C with 5% mixed gas for 48 h. Then the mature oocytes were treated with bisulfite buffer. Target sequences were amplified using nested or half-nested PCR and the DNA methylation status was tested using combined bisulfite restriction analysis (COBRA) and bisulfite sequencing (BS). High-glucose concentrations significantly decreased the first polar body extrusion rate. Compared to controls, the DNA methylation levels of Peg3 in human IVM oocytes were significantly higher in 10 mM (P < 0.001) and 15 mM (P < 0.001) concentrations of glucose. But the DNA methylation level of H19 was not affected by high-glucose concentrations in human IVM oocytes. We also found that there was a decrease in DNA methylation levels in the promoter of adiponectin in human IVM oocytes between controls and oocytes exposed to 10 mM glucose (P = 0.028). N/A. It is not clear whether the alterations are beneficial or not for the embryo development and offspring health. The effects of high-glucose concentrations on the whole process of oocyte maturation are still not elucidated. Another issue is that the number of oocytes used in this study was limited. This is the first time that the effects of high-glucose concentration on DNA methylation of human oocytes have been elucidated. Our result indicates that in humans, the high risk of chronic diseases in offspring from diabetic mothers may originate from abnormal DNA modifications in oocytes. This work was supported by the fund of National Natural Science Foundation of China (81401198) and Doctor Foundation of Qingdao Agricultural University (1116008).The authors declare that there are no potential conflicts of interest relevant to this article.


Betamethasone modulates the biological function of human polymorphonuclear leukocytes.
We have examined the influence of betamethasone (BT) on cyclic AMP (cAMP) metabolism and lysosomal enzyme release from highly purified (approximately equal to 99%) human polymorphonuclear leukocytes (PMNs). Preincubation (1-24 h) of human PMNs with BT (10(-9)-10(-5) M) had no effect on either cAMP content or on beta-glucuronidase release induced by formyl-containing tripeptide (f-met peptide). Preincubation (16-24 h) of PMNs with BT (10(-8)-10(-7) M) dose-dependently potentiated the cAMP accumulation caused by beta-agonists (isoproterenol), adenosine A2/Ra agonist (NECA), prostaglandin E1 (PGE1) and histamine in PMNs. Similarly, BT potentiated the inhibition of f-met peptide-induced beta-glucuronidase release from human PMNs caused by PGE1 (10(-6) M), histamine (2 X 10(-5) M), NECA (10(-4) M) and isoproterenol (10(-6) M).


Doctor-assisted suicide: What is the present legal position in South Africa?
In the recent case of Stransham-Ford v. the Minister of Justice and Correctional Services, the North Gauteng High Court held that a terminally ill patient who was experiencing intractable suffering was entitled to commit suicide with the assistance of his doctor and that the doctor's conduct would not be unlawful. The court was careful to state that it was not making a general rule about doctor-assisted suicide. The latter should be left to the Parliament, the Constitutional Court and 'future courts'. The judge dealt specifically with the facts of the case at hand. In order to understand the basis of the decision it is necessary to consider: (i) the facts of the case; (ii) the question of causation; (iii) the paradox of 'passive' and 'active' euthanasia; (iv) the test for unlawfulness in euthanasia cases; and (v) the meaning of doctor-assisted suicide. It is also necessary to clarify the present legal position regarding doctor-assisted suicide.


Large hydropower projects increase stress despite compensation efforts: Evidence from the Brazilian Amazon.
Large hydropower projects continue to be built in developing nations, despite their known negative impacts. Large-scale energy projects strain local infrastructure and reduce access to infrastructure for households that live near them. Here we investigate the link between large-scale hydropower projects and stress. Our results suggest that these projects create stress through two mechanisms: strains on community resources and through the process of displacement. We also ask how compensation and resettlement programs condition these relationships. Using data from the Madeira river basin in the Brazilian Amazon, we find that hydropower projects increase stress by reducing access to energy, water, sanitation and land. Compensation provided was not sufficient to moderate this effect.


Understanding Formal Caregiver Burden in Nursing Assistants in Nursing Homes: A Mixed Methods Approach.
The current study aimed to describe formal caregiver burden of nursing assistants in nursing homes. A descriptive, cross-sectional, convergent mixed methods approach identified attributes of formal caregiver burden using phenomenological interviews and established self-report measures. Themes included nursing assistants' experiences of stress, close relationships, extensive assistance of residents, balancing needs and routines, and feeling accomplished. Self-report measures demonstrated moderate stress, moderate caring behaviors, responsibility, and competence. MDS 3.0 results showed moderate cognitive impairment, minimal depressive symptoms, and decreased functional status of residents. The mixed methods synthesis confirmed the presence of five attributes of formal caregiver burden: perceived stress, caring for another, dependency of the older adult, responsibility, and competence. Burnout was not confirmed. Future investigation of attributes among a larger, diverse sample of nursing assistants, residents, and nursing homes will advance knowledge and inform research design and methods of interventions. [Research in Gerontological Nursing, 16(5), 231-240.].


Depression symptoms, sexual satisfaction and satisfaction with a relationship in individuals with type 2 diabetes and sexual dysfunctions.
The level of sexual satisfaction constitutes a significant factor affecting satisfaction with a relationship, particularly in the case of people with chronic diseases (like type 2 diabetes), sexual dysfunctions and depressive symptoms. The aim of the conducted research was to verify a moderating role of intensified depressive symptoms in relation to sexual satisfaction and relationship quality, as well as the relationship between these variables in the group of individuals with type 2 diabetes and sexual dysfunctions. We also examined which aspects of sexual satisfaction and relationship quality the participants were the most satisfied with. Finally, 93 persons (38 women) with type 2 diabetes and with at least one sexual dysfunction took part in the research. Three questionnaire methods were applied in the research: the Sternberg Triangular Love Scale, the Sexual Satisfaction Scale and the Beck Depression Inventory. . The results showed differences in the level of individual aspects of sexual satisfaction and components of satisfaction with a relationship. Intensified depressive symptoms turned out to be a moderator in the relationship between sexual satisfaction and relationship quality in the case of general and specific indicators. The higher the satisfaction with controlling sexual contacts in people with type 2 diabetes and high-intensity of depressive symptoms, the more satisfied they are with emotional and physical intimacy with a partner. People with low-intensity of depressive symptoms who assume their influence on sexual contacts with a partner to be low, are found to be more motivated to search for them.


Megakaryocytes and platelets in vascular disease.
Platelets are anucleate cells with no DNA. They are derived from their precursor, the megakaryocyte (MK), whose differentiation is characterized by nuclear polyploidization through a process called endomitosis. Changes in the MK-platelet-haemostasis axis may precede acute thrombotic events. Changes in MK ploidy distribution may be associated with the production of large platelets. Mean platelet volume (MPV) is an important biological variable as it is a determinant of platelet reactivity. Large platelets are denser and more active haemostatically. MPV is increased in patients after myocardial infarction (MI) and is a predictor of a further ischaemic event and death when measured after MI. It has been suggested that changes not only in platelets but also in the parental MK are associated with chronic and acute vascular events. The regulation of megakaryocytopoiesis depends on several haematopoietic factors such as thrombopoietin. An understanding of the signalling system that controls platelet number and size might give insight into a role of platelet production in thrombogenesis and atherogenesis.


Students´ perception of interprofessional education in the bachelor programme "Interprofessional Health Care" in Heidelberg, Germany: an exploratory case study.
Interprofessional education is receiving increased attention worldwide. This has led to the development of a bachelor programme "Interprofessional Health Care" at the University of Heidelberg, Germany beginning in the winter semester 2011. Aim of this study was to evaluate the students' perception of this innovative programme regarding interprofessional learning. An exploratory case study was conducted. A semi-structured guideline was developed and seven focus groups were performed with the students of the first three cohorts in 2012-2014. Data was transcribed and analyzed using content analysis leading to main categories, one of which was titled "interprofessional learning". This article presents the results focussing on the students' experiences regarding interprofessional education and learning during their first two semesters of the programme. Four main categories related to interprofessional learning were developed inductively. Students assessed "interprofessional learning" in general as positive and wished to encounter a more intense experience and collaboration with different health professions during their studies. Students reported to benefit from the programme due to a better understanding of other professions and their different perspectives. They described decreased hesitance to approach other health professions in every day practice. Results are in line with the four domains of the Interprofessional Core Competencies. All in all students at an early stage recognized the benefit of interprofessional learning for their studies and their everyday work in practice showing the way forward for the bachelor programme and encouraging more interprofessional encounters with students from other health care programmes.


In-hospital mortality of intermittent vs daily antitubercular regimen in patients with meningeal tuberculosis--a retrospective study.
The Revised National Tuberculosis Control Programme (RNTCP), the State-run Tuberculosis Control Initiative of the Government of India, recommends intermittent thrice a week Directly Observed Treatment Short course (DOTS) both during intensive phase and continuation phase for a total of nine months for tubercular meningitis. However, most recent guidelines recommend daily regimen. Assessment of the in-hospital mortality in patients with meningeal tuberculosis. We retrospectively analyzed the data of patients (n = 98) admitted with a diagnosis of meningeal tuberculosis from January 1st 2006 to December 31st 2009 in a tertiary care centre in South India. Thwaites index score of four or less was used for diagnosis of meningeal tuberculosis which is a weighted diagnostic index score for dichotomised clinical variables including age, blood white cell count, duration of illness, CSF total white cell count, and CSF neutrophil percentage. We compared in-hospital treatment outcome of patients on thrice weekly intermittent DOTS regimen with daily regimen patients. The inhospital mortality was same (27%) in the two treatment regimens (p 0.944). However, there was less incidence of hepatic dysfunction in the intermittent DOTS regimen, even though it was not statistically significant (p 0.148). In the short-term, both regimens have similar mortality outcomes and no statistically significant difference in hepatic dysfunction during the hospital stay.


Catalyst-free growth of nanocrystalline graphene/graphite patterns from photoresist.
Catalyst-free growth of a nanocrystalline few-layer graphene (or graphite) film from photoresist on variable substrates was demonstrated. The thickness of the film can be easily controlled from 1 nm to hundreds of nanometers. With this method, graphene/graphite patterns with different thicknesses have been designed for integrated electronics.


Falls and Frailty in Prostate Cancer Survivors: Current, Past, and Never Users of Androgen Deprivation Therapy.
To compare the prevalence of and association between falls and frailty of prostate cancer survivors (PCSs) who were current, past or never users of androgen deprivation therapy (ADT). Cross-sectional. Mail and electronic survey. PCSs (N = 280; mean age 72 ± 8). Cancer history, falls, and frailty status (robust, prefrail, frail) using traditionally defined and obese phenotypes. Current (37%) or past (34%) ADT users were more than twice as likely to have fallen in the previous year as never users (15%) (P = .002). ADT users had twice as many recurrent falls (P < .001) and more fall-related injuries than unexposed men (P = .01). Current (43%) or past (40%) ADT users were more likely to be classified as prefrail or frail than never users (15%) (P < .001), and the prevalence of combined obese frailty + prefrailty was even greater in current (59%) or past (62%) ADT users than never users (25%) (P < .001). Traditional and obese frailty significantly increased the likelihood of reporting falls in the previous year (odds ratio (OR) = 2.15, 95% CI = 1.18-3.94 and OR = 2.97, 95% CI = 1.62-5.58, respectively) and was also associated with greater risk of recurrent falls (OR = 3.10, 95% CI = 1.48-6.5 and OR = 3.99, 95% CI = 1.79-8.89, respectively). Current and past exposure to ADT is linked to higher risk of falls and frailty than no treatment. PCSs should be appropriately counseled on fall prevention strategies, and approaches to reduce frailty should be considered.


Radiation treatment planning with an integrated positron emission and computer tomography (PET/CT): a feasibility study.
To investigate the usefulness of hardware coregistered PET/CT images for target volume definition. Thirty-nine patients presenting with various solid tumors were investigated. CT and a FDG-PET were obtained in treatment position in an integrated PET/CT scanner, and coregistered images were used for treatment planning. First, volume delineation was performed on the CT data. In a second step, the corresponding PET data were used as an overlay to the CT data to define the target volume. Delineation was done independently by two investigators. Coregistered PET/CT showed good fusion accuracy. The GTV increased by 25% or more because of PET in 17% of cases with head-and-neck (2/12) and lung cancer (1/6), and in 33% (7/21) in cancer of the pelvis. The GTV was reduced > or =25% in 33% of patients with head-and-neck cancer (4/12), in 67% with lung cancer (4/6), and 19% with cancer of the pelvis (4/21). Overall, in 56% (22/39) of cases, GTV delineation was changed significantly if information from metabolic imaging was used in the planning process. The modification of the GTV translated into altered PTV changes exceeding >20% in 46% (18/39) of cases. With PET, volume delineation variability between two independent oncologists decreased from a mean volume difference of 25.7 cm(3) to 9.2 cm(3) associated with a reduction of the standard deviation from 38.3 cm(3) to 13.3 cm(3) (p = 0.02). In 16% of cases, PET/CT revealed distant metastasies, changing the treatment strategy from curative to palliative. Integrated PET/CT for treatment planning for three-dimensional conformal radiation therapy improves the standardization of volume delineation compared with that of CT alone. PET/CT has the potential for reducing the risk for geographic misses, to minimize the dose of ionizing radiation applied to non-target organs, and to change the current practice to three-dimensional conformal radiation therapy planning by taking into account the metabolic and biologic features of cancer. The impact on treatment outcome remains to be demonstrated.


Detection of HBsAg, HBcAg, and HBV DNA in ovarian tissues from patients with HBV infection.
To investigate the presence of HBsAg, HBcAg, and HBV DNA in ovarian tissues from patients with HBV infection. HBsAg and HBcAg were examined in ovarian biopsy tissues from 26 patients with HBV infection by immunocytochemistry, and HBV DNA was detected in ovarian tissues by PCR. HBsAg and HBcAg were present with the same positive rate of 34.6% (9/26). The total positive rate was 46.2% (12/26). HBsAg and HBcAg were positive in 6 (23.1%) of the 26 patients. Brown positive particles were diffusely distributed in ovarian cells. The positive rate of HBV DNA was 58.3% (7/12). HBsAg, HBcAg, and HBV DNA can be detected in ovarian tissues from patients with HBV infection. The presence of HBsAg and HBcAg in ovarian tissues does not correlate with the HBV markers in serum.


Quantitative evaluation of spatial coherence of the electron beam from low temperature field emitters.
By using multiwalled carbon nanotubes as an element of a nanobiprism, we evaluated quantitatively the coherence of electrons emitted from tungsten tips at room temperature and 78 K, and found an enhancement of coherence at 78 K. The increase of the transverse coherence length of the electron beam agreed well with that of the inelastic mean free path of electrons in solids, demonstrating the direct relationship between the coherences of the electron beam and the original electronic states. On the basis of this experimental fact, we comment on the interpretation of recent Hanbury Brown-Twiss type experiments for electrons reported by Kiesel et al. [Nature (London) 418, 392 (2002)]].


Peptidergic sensory and parasympathetic fiber sprouting in the mucosa of the rat urinary bladder in a chronic model of cyclophosphamide-induced cystitis.
In this study, we used a well-established animal model to investigate changes in the peptidergic and parasympathetic innervation of the bladder following chronic bladder inflammation. Adult female Sprague-Dawley rats were injected with either 70 mg/kg cyclophosphamide diluted in saline, i.p., once every 3 days or saline. After 10 days, all animals were tested for urinary frequency and number of low volume voids, as well as symptoms of spontaneous pain. At the end of 12 days, all animals were perfused with histological fixatives and the urinary bladders processed for immunofluorescence using antibodies against calcitonin gene-related peptide and the vesicular acetylcholine transporter as markers, respectively, of peptidergic primary afferent fibers and parasympathetic efferent fibers. We show that animals treated with cyclophosphamide had inflamed bladders and displayed high urinary frequency as well as some indicators of spontaneous pain, such as piloerection and a rounded-back posture. Furthermore, they had a significant increase in the density of both parasympathetic and peptidergic sensory fibers in the bladder mucosa and an increase in peptidergic sensory fibers in the detrusor muscle. Based on these results, we suggest that peripheral sprouting of parasympathetic and peptidergic fibers could be a mechanism responsible for sensitization of the bladder, leading to urinary symptoms. Since we observed that the parasympathetic and peptidergic fibers often wrapped around one another and that their varicosities were very close, these two fiber populations may be interacting with each other to lead to and maintain sensitization. Future studies are required to establish the role of this fiber sprouting in bladder symptoms.


Shared attention for action selection and action monitoring in goal-directed reaching.
Dual-task studies have shown higher sensitivity for stimuli presented at the targets of upcoming actions. We examined whether attention is directed to action targets for the purpose of action selection, or if attention is directed to these locations because they are expected to provide feedback about movement outcomes. In our experiment, endpoint accuracy feedback was spatially separated from the action targets to determine whether attention would be allocated to (a) the action targets, (b) the expected source of feedback, or (c) to both locations. Participants reached towards a location indicated by an arrow while identifying a discrimination target that could appear in any one of eight possible locations. Discrimination target accuracy was used as a measure of attention allocation. Participants were unable to see their hand during reaching and were provided with a small monetary reward for each accurate movement. Discrimination target accuracy was best at action targets but was also enhanced at the spatially separated feedback locations. Separating feedback from the reaching targets did not diminish discrimination accuracy at the movement targets but did result in delayed movement initiation and reduced reaching accuracy, relative to when feedback was presented at the reaching target. The results suggest attention is required for both action planning and monitoring movement outcomes. Dividing attention between these functions negatively impacts action performance.


Yamanaka Factors in the Budding Tunicate Botryllus schlosseri Show a Shared Spatio-Temporal Expression Pattern in Chordates.
In vertebrates, the four transcription factors Sox2, c-Myc, Pou5f1 and Klf4 are involved in the differentiation of several tissues during vertebrate embryogenesis; moreover, they are normally co-expressed in embryonic stem cells and play roles in pluripotency, self-renewal, and maintenance of the undifferentiated state in adult cells. The in vitro forced co-expression of these factors, named Yamanaka factors (YFs), induces pluripotency in human or mouse fibroblasts. Botryllus schlosseri is a colonial tunicate undergoing continuous stem cell-mediated asexual development, providing a valuable model system for the study of pluripotency in the closest living relatives of vertebrates. In this study, we identified B. schlosseri orthologs of human Sox2 and c-Myc genes, as well as the closest homologs of the vertebrate-specific Pou5f1 gene, through an in-depth evolutionary analysis of the YF gene families in tunicates and other deuterostomes. Then, we studied the expression of these genes during the asexual cycle of B. schlosseri using in situ hybridization in order to investigate their possible involvement in tissue differentiation and in pluripotency maintenance. Our results show a shared spatio-temporal expression pattern consistent with the reported functions of these genes in invertebrate and vertebrate embryogenesis. Moreover, Myc, SoxB1 and Pou3 were expressed in candidate stem cells residing in their niches, while Pou2 was found expressed exclusively in the immature previtellogenic oocytes, both in gonads and circulating in the colonial vascular system. Our data suggest that Myc, SoxB1 and Pou3 may be individually involved in the differentiation of the same territories seen in other chordates, and that, together, they may play a role in stemness even in this colonial ascidian.


[Hyperlipoproteinemia in necrotizing pancreatitis].
Oxygen free radicals (OFR) generated during necrotizing acute pancreatitis (NAP) make an impact on cholesterol, phospholipids, and triglyceride metabolism. These compounds are poorly soluble in body fluids and form proteolipid complexes called lipoproteins. The aim of this study is to investigate the lipoprotein metabolism in accordance to NAP severity. Sixty patients with NAP were included to this study, 41 males and 19 females. Patients mean Ranson score exceeded 7 points. The severity of the disease and overall patient standing changes were monitored by means of APACHE II score. In all patients indications for surgery performed between 15th and 30th day of observation were signs of infection. All patients were divided into 2 groups. Group I included 42 patients, who survived the 30-day observation period. Group 2 was made of 18 patients who died. The total high density lipoproteins (HDL) and low density proteins (LDL) of lipoprotein fraction concentrations were measured on 1st, 5th, 10h, and 15th day of treatment. Concentrations of cholesterol, triglyceride, and phospholipids were measured in isolated fractions. HDL concentrations measured by means of cholesterol, triglyceride, and phospholipids levels decreased insignificantly in group 1, while in group 2 respective levels were significantly higher and increased along with patient deterioration. Lipoprotein levels showed correlation with patient APACHE II score. In the most severe NAP the decrease of high-density and increase of low-density lipoprotein fraction were observed. The assessment of lipoprotein metabolism derangement may be a useful prognostic factor in NAP.


Effect of polymer additives on heat transport in turbulent thermal convection.
In this Letter, we explore the possible effects of polymer additives on heat transport in turbulent thermal convective flows. Using both direct numerical simulations and shell-model calculations, we show that polymer additives can significantly enhance the heat transport in homogeneous turbulent thermal convection, which mimics the bulk of turbulent Rayleigh-Bénard convection. We also discuss the implication of our results for turbulent Rayleigh-Bénard convection, in which there are boundary layers in addition to the central bulk.


Methicillin Resistant Staphylococcus aureus among HIV Infected Pediatric Patients in Northwest Ethiopia: Carriage Rates and Antibiotic Co-Resistance Profiles.
MRSA infections are becoming more prevalent throughout the HIV community. MRSA infections are a challenge to both physicians and patients due to limited choice of therapeutic options and increased cost of care. This study was aimed to determine the prevalence of colonization and co-resistance patterns of MRSA species among HIV positive pediatric patients in the Amhara National Regional State, Northwest Ethiopia. Culture swabs were collected from the anterior nares, the skin and the perineum of 400 participants. In vitro antimicrobial susceptibility testing was done on Muller Hinton Agar by the Kirby-Bauer disk diffusion method, using 30 μg cefoxitin (OXOID, ENGLAND) according to the recommendations of the Clinical and Laboratory Standards Institute. Methicillin sensitivity/resistance was tested using cefoxitin. Data was analyzed by descriptive statistics and logistic regression model using Epi Info 7. S. aureus was detected in 206 participants (51.5%). The prevalence of MRSA colonization in this study was 16.8%. Colonization by S. aureus was associated with male gender (OR = 0.5869; 95% CI: 0.3812-0.9036; p-value = 0.0155), history of antibiotic use over the previous 3 months (OR = 2.3126; 95% CI: 1.0707-4.9948; p-value = 0.0329) and having CD4 T-cell counts of more than 350 x 10(6) cells / L (OR = 0.5739; 95% CI = 0.3343-0.9851; p-value = 0.0440). Colonization by MRSA was not associated with any one of the variables. Concomitant resistance of the MRSA to clindamycin, chloramphenicol, co-trimoxazole, ceftriaxone, erythromycin and tetracycline was 7.6%, 6%, 5.25%, 20.9%, 23.9% and 72.1%, respectively. High rates of colonization by pathogenic MRSA strains is observed among HIV positive pediatric patients in the Amhara National Regional state.


Functional analysis of the thioredoxin domain in Porphyromonas gingivalis HBP35.
Periodontitis is one of the most common oral diseases in humans. This caused by infection by the oral bacterium Porphyromonas gingivalis. Our strategy to prevent this infection is to establish a passive immunization system in which endogenous antibodies can be applied directly to neutralize virulent factors associated with this bacterium. We focused our attention on the P. gingivalis 35 kDa surface protein, or HBP35, since this protein is involved not only in the coaggregation with oral miroflora but also in hemin binding. In addition, nucleotide sequencing of the gene, hbp35, coding for this protein revealed the presence of a catalytic center for thioredoxin, and we further attempted to characterized the protein by amino acid substitution. A total of four Cys residues were substituted for Ser residues by combining the simple method for site-directed mutagenesis and the heterodimer system, an approach designed to construct chimeric plasmids readily. Native and mutagenized hbp35 were introduced into the Eschericha coli dsbA mutant strain, JCB 572, defective in both alkaline phosphatase and motile activities due to inefficient disulfide bond formation. Transformant harboring the native hbp35 could complement the dsbA mutation, suggesting a role of disulfide bond formation of this protein in P. gingivalis cells. Possible roles of the Cys residues in complementation are discussed.


Effects of vancomycin linoleic acid nanoparticles on male reproductive indices of Sprague-Dawley rats.
The management of bacterial infections, especially trains of methicillin-resistant Staphylococcus aureus observe in health care settings, has markedly improved with the introduction of established drugs but using newer nano-based formulations. This study investigates the effects of vancomycin-linoleic acid nanoparticles on testicular tissue in an experimental animal model. Twenty-five adult male Sprague-Dawley rats maintained at the Animal House of the Biomedical Resources Unit were assigned to five groups namely E - solid lipid nanoparticles; F - vancomycin solid lipid nanoparticle; G - linoleic acid nanoparticle; H - vancomycin linoleic acid; and A - control. Perturbations in seminal fluid parameters showed a reduced sperm count in groups F & G which was statistically significant (p < .05) but motility and morphology were not significant when compared to controls (A). Reduced testosterone levels were found in groups E, F and H but were not statistically significant (p > .05). There was also increased luteinizing hormone (LH) and decreased in follicular stimulating hormone (FSH) levels was statistically significant (p < .05). Hypoplasia, tubular atrophy and shrinkage were observed in histologic sections of the treated groups with basement membrane thickening. Vancomycin solid lipid nanoparticle and its constituents SLN and LA disrupted testicular morphometry and the hormonal milieu sufficient to potentially induce altered reproductive function.


Enhancement of spontaneous killer cytotoxicity by soluble factor.
Two-stage stimulation of SK activity of normal human peripheral blood lymphocytes by soluble factors was demonstrated. The first stage was initiated by factors present in supernatant derived from normal B-LCL cultures. Only cell lines which could induce SK activity in culture in an MLR-type reaction had the capacity to produce the active factor. Supernatant factor required adherent cells to cause SK augmentation. The interaction of adherent cells plus supernatant factor resulted in the production of a second soluble factor which stimulated an increase in SK activity in responding lymphocyte populations. This second stage involved a different soluble factor which acted directly on the non-SK, Fc-negative lymphocyte population, and within 3 hr. Data obtained using antisera to interferon (IF) indicated that IF is a component of the second soluble factor, and not of the supernatant factor derived from the B-LCL.


Tenecteplase in ischemic stroke offers improved recanalization: Analysis of 2 trials.
To test whether patients with complete vessel occlusion show greater recanalization at 24 hours and have improved clinical outcomes at 24 hours and 90 days when treated with tenecteplase compared to alteplase. Pooled clinical and imaging data from 2 phase 2 randomized trials comparing tenecteplase with alteplase allowed CT angiography (CTA) scans to be assessed centrally for occlusion status at baseline and at 24 hours post thrombolysis using the modified thrombolysis in cerebral infarction (TICI) scale. Twenty-four-hour poststroke NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores were also compared between treatment groups using linear regression to generate odds ratios (ORs). From 146 pooled patients, 69 had a TICI 0/1 occlusion overall at baseline. Tenecteplase-treated patients with a complete vessel occlusion had greater complete recanalization rates at 24 hours (71% for tenecteplase vs 43% for alteplase, p < 0.001). Patients with a TICI 0/1 occlusion who were treated with tenecteplase also showed greater early clinical improvement (median NIHSS change with tenecteplase was 9, interquartile range [IQR] 6, alteplase 1, IQR 1, p = 0.001) and higher rates of favorable 90-day outcomes (mRS 0-1 of tenecteplase compared with alteplase, OR 4.82, 95% confidence interval 1.02-7.84, p = 0.05). Tenecteplase may offer greater recanalization efficacy compared to alteplase, possibly exaggerated in patients with complete vessel occlusions on baseline CTA.


RT-PCR topography of chronic psoriasis skin based on analysis of T-cell receptor B variable region gene usage.
Psoriasis is a hyperproliferative inflammatory disease and 70% of patients develop a chronic plaque form. The pathogenesis of psoriasis is not known but evidence exists that T cells play a crucial role. The T cell V-gene receptor repertoire from psoriasis skin (different layers) was compared with peripheral blood T cells by employing RNA polymerase chain reaction (PCR) amplification. T cell receptor (TCR) BV 5.1, 11, 12, 13.1 and 16 were utilized to a significantly higher degree in areas close to the basal layers when compared to CD4+, CD8+ or unfractionated blood T cells from the same patients, whereas only BV11 and 13.1 genes of T cells from deeper layers of the dermis showed such a skewed usage. No biased usage of TCRBV genes was observed in superficial layers or in whole skin. Furthermore, T cell receptor junctional diversity analysed by high resolution gel electrophoresis showed skin psoriatic T cells to be poly- or oligoclonal. In conclusion, we show that TCRBV gene usage from different layers of psoriatic skin has a different pattern compared with the corresponding gene usage in circulating peripheral blood T cells. This pattern may implicate possible skin-associated antigen or superantigens activating a limited number of T cells in areas of skin close to basal layers, which in turn could promote keratinocyte proliferation.


Impaired lipid metabolism in aged mice as revealed by fasting-induced expression of apolipoprotein mRNAs in the liver and changes in serum lipids.
Changes in apolipoprotein (Apo) metabolism can cause an increased incidence of diseases such as cardiovascular disorders and diabetes with advancing age. Limited reports are available on this topic, however. To investigate age-related changes in mobilization of stored lipid, we studied the effects of fasting on the gene expression of Apos in the liver as well as serum triglyceride (TG) and cholesterol levels in the serum. Using young (6- to 8-month-old) and old (24- to 28-month-old) fasted and re-fed mice, Northern blots of hepatic mRNAs for Apos A-I, A-IV, C-II, C-III, and liver-type fatty acid-binding protein and HPLC analyses of serum lipids were conducted. Fasting induced 4- and 20-fold increases in the mRNA of Apo C-II and A-IV, respectively, in young mice while only 1.1- and 7-fold increases, respectively, were detected in old mice. In contrast, the Apo C-III gene expression was significantly reduced by fasting in the young mice but the reduction was small in the old. In view of the stimulating effect of Apo C-II and A-IV and the inhibiting effect of C-III on lipoprotein lipase (LPL), these findings suggest that the fasting-induced activation of LPL may be considerably decreased in old mice. The amount of TG in very low-density lipoprotein (VLDL), a major form of the transport of TG to peripheral tissues, was significantly greater in the young than in the old mice. Despite possible activation of LPL by fasting, the amount of TG in VLDL, a major form of the transport of TG to peripheral tissues, was significantly greater in the young mice than in the old. It is indicated that the synthesis of VLDL in the liver is high in the young but low in the old mice, which also may be true for the rate of transport of TG. The present findings suggest that mobilization of lipids is impaired in old animals due to decreased gene expression of Apos, possibly leading in the long run to excessive lipid accumulation in tissues such as the liver, adipose tissues and blood vessels even in normal feeding, and resulting in an increased incidence of age-related diseases.


[Immunomodulation using an epidermal cytokine (ETAF)].
Tissue cultures of freshly isolated murine and human keratinocytes as well as transformed keratinocyte cell lines secret a cytokine, epidermal cell derived thymocyte activating factor (ETAF), which augments in vitro lymphoproliferative responses. Keratinocytes produce increased levels of ETAF activity after exposure to a variety of cell damaging agents such as silica, endotoxin, phorbol esters, hydroxyurea, mechanical disruption and UV-irradiation. Biochemical studies showed that ETAF is a heat- and pH-stable low molecular weight (15K) protein which is produced in low amounts and active at low (10(-10)-10(-15) M) concentration. The most important biological property of ETAF is an antigen non specific stimulation of the immunological system. ETAF in conjunction with the antigen presenting function of Langerhans cells results in an activation of T-lymphocytes and increased production of lymphokines such as Interleukin 2, which is responsible for the activation of T- and B-lymphocytes. In addition ETAF is chemotactic for polymorphonuclear leukocytes, monocytes and natural killer cells and is directly mitogenic for fibroblasts. When injected into mice ETAF induces production of acute phase proteins such as Serum Amyloid A. Furthermore ETAF may act as an endogenous pyrogen and induce fever. According to its biochemical characteristics and biological properties ETAF can not be separated from the macrophage derived Interleukin 1(IL 1), suggesting that both ETAF and IL 1 are identical. These findings indicate that production of IL 1-like molecules is not confined to cells of the immunological system and ETAF production by keratinocytes may have important implications in the pathogenesis of inflammatory as well as neoplastic skin diseases.


Quantitative analysis of platelets aggregates in 3D by digital holographic microscopy.
Platelet spreading and retraction play a pivotal role in the platelet plugging and the thrombus formation. In routine laboratory, platelet function tests include exhaustive information about the role of the different receptors present at the platelet surface without information on the 3D structure of platelet aggregates. In this work, we develop, a method in Digital Holographic Microscopy (DHM) to characterize the platelet and aggregate 3D shapes using the quantitative phase contrast imaging. This novel method is suited to the study of platelets physiology in clinical practice as well as the development of new drugs.


Effect of surface curvature on critical adsorption.
We studied critical adsorption on curved surfaces by utilizing spherical nanoparticles immersed in a critical binary liquid mixture of 2,6 lutidine+water. The temperature dependence of the adsorbed film thickness and excess adsorption was determined from fluorescence correlation spectroscopy measurements of the enlarged effective hydrodynamic radius of the particles. Our results indicated that the adsorbed film thickness is of the order of correlation length associated with concentration fluctuations. The excess adsorption per unit area increases following a power law in reduced temperature with an exponent of -1, which is the mean-field value for the bulk susceptibility exponent. This has been confirmed with silica particles of two different radii, 10 and 25 nm. The results were also compared with the theoretical mean-field scaling function.


Structural equation modeling the "control of gut overgrowth" in the prevention of ICU-acquired Gram-negative infection.
Conceptually, the "control of gut overgrowth" (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis.


Developments in drug delivery of bioactive alkaloids derived from traditional Chinese medicine.
The bioactive alkaloids (e.g. vincristine, hydroxycamptothecin, ligustrazine, and so on) from traditional Chinese medicine (TCM) have exerted potent efficacies (e.g. anti-tumor, anti-inflammation, immunosuppression, etc.). However, a series of undesirable physicochemical properties (like low solubility and weak stability) and baneful pharmacokinetic (PK) profiles (e.g. low bioavailability, short half time, rapid clearance, etc.) have severely restricted their applications in clinic. In addition, some side effects (like cumulative toxicities caused by high-frequency administration and their own toxicities) have recently been reported and also confined their clinical uses. Therefore, developments in drug delivery of such alkaloids are of significance in improving their drug-like properties and, thus, treatment efficiencies in clinic. Strategies, including (i) specific delivery via liposomes; (ii) sustained delivery via nanoparticles, gels, and emulsions; and (iii) transdermal delivery via ethosomes, solid lipid nanoparticles, and penetrating enhancers, have been reported to improve the pharmacokinetic and physicochemical characters of problematic TCM alkaloids, decline their adverse effects, and thus, boost their curative efficacies. In this review, the recent reports in this field were comprehensively summarized with the aim of providing an informative reference for relevant readers.


Oscillometric carotid to femoral pulse wave velocity estimated with the Vicorder device.
Carotid to femoral pulse wave velocity (PWV) is associated with an increase in cardiovascular morbidity and all-cause mortality. Noninvasive approach has made this method applicable for the examination of larger populations. This study aimed to obtain reference values of PWV measured with the Vicorder device. PWV was obtained using the oscillometric Vicorder in 318 healthy, normotensive patients (165 women, 28.7±17.6 years, range 6-83 years). A plethysmographic sensor was placed over the right carotid region to pick up the carotid pulse wave and a blood pressure cuff was placed around the upper thigh to trace the femoral pulse wave. Path length was defined as the distance from the suprasternal notch to the top of the thigh cuff. Mean PWV was 6.1±1.4 m/s and significantly increased with age (r=.842; P<.0001). PWV was associated with mean arterial pressure (r=.546; P<.0001) and body mass index (r=.396; P<.0001). In a multiple linear regression model, age, mean arterial pressure, and body height emerged as independent markers for PWV. This study established reference values for carotid to femoral PWV derived by oscillometric measures that can now be used for risk stratification.


Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review.
Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.


Spectrum of Febrile Thrombocytopenia in the Pediatric Population (1-18 Years) Admitted in a Tertiary Care Center.
Aim Thrombocytopenia is a common manifestation of various infections. Thrombocytopenia associated with fever helps to narrow down the differential diagnosis and management of fever. It also helps to know the various complications of thrombocytopenia, its management, and the outcome of the patient. This study aimed to evaluate the clinical profile and determine etiology and complications in patients with fever and thrombocytopenia in pediatric populations. Methods One hundred and fifteen patients of both sexes aged 1-18 years with fever and found to have thrombocytopenia (platelet count < 1.5 lakhs) between June 1, 2018 and March 31, 2019 were included in this study. Results Infection was the common cause of febrile thrombocytopenia and dengue fever was the most common infection. Bleeding manifestations were seen in 9.6 % of patients. Petechiae/purpura was the commonest bleeding manifestation followed by gum and nose bleeding. Common bleeding manifestations were seen in patients with a platelet count below 50,000 and the majority of them did not require platelet transfusion. Good recovery was noted in 96.5% of patients while 2.6% had mortality. Conclusions An infection, particularly dengue, was the common most cause of fever with thrombocytopenia. In the majority of patients, thrombocytopenia was transient and asymptomatic. Bleeding was present in the majority of patients with platelets less than 10,000 and 20,000 to 50,000. The most common bleeding manifestation was petechial rashes over the skin. Platelet transfusion was not required in most of the cases. On treating the specific cause, a drastic improvement in the platelet count was noted during discharge and further follow-up. Immunization is highly recommended for vaccine-preventable diseases.


The Who, When, Why, and How of PET Amyloid Imaging in Management of Alzheimer's Disease-Review of Literature and Interesting Images.
Amyloid imaging using positron emission tomography (PET) has an emerging role in the management of Alzheimer's disease (AD). The basis of this imaging is grounded on the fact that the hallmark of AD is the histological detection of beta amyloid plaques (Aβ) at post mortem autopsy. Currently, there are three FDA approved amyloid radiotracers used in clinical practice. This review aims to take the readers through the array of various indications for performing amyloid PET imaging in the management of AD, particularly using 18F-labelled radiopharmaceuticals. We elaborate on PET amyloid scan interpretation techniques, their limitations and potential improved specificity provided by interpretation done in tandem with genetic data such as apolipiprotein E (APO) 4 carrier status in sporadic cases and molecular information (e.g., cerebral spinal fluid (CSF) amyloid levels). We also describe the quantification methods such as the standard uptake value ratio (SUVr) method that utilizes various cutoff points for improved accuracy of diagnosing AD, such as a threshold of 1.122 (area under the curve 0.894), which has a sensitivity of 92.3% and specificity of 90.5%, whereas the cutoff points may be higher in APOE ε4 carriers (1.489) compared to non-carriers (1.313). Additionally, recommendations for future developments in this field are also provided.


Catalytic Reductive Amination of Aldehydes and Ketones With Nitro Compounds: New Light on an Old Reaction.
Reductive amination of carbonyl compounds with primary amines is a well-established synthetic methodology for the selective production of unsymmetrically substituted secondary and tertiary amines. From the industrial and green chemistry perspective, it is attractive to combine reductive amination with the synthesis of primary amines in a single one-pot catalytic process. In this regard, nitro compounds, which are readily available and inexpensive feedstocks, received much attention as convenient precursors to primary amines in such processes. Although the direct reductive coupling of nitro compounds with aldehydes/ketones to give secondary and tertiary amines has been known since the 1940's, due to the development of highly efficient and selective non-noble metal-based catalysts a breakthrough in this area was made in the last decade. In this short overview, recent progress in the methodology of the reductive amination with nitro compounds is summarized together with applications to the synthesis of bioactive amines and heterocycles. Remaining challenges in this field are also analyzed.


Clinicopathological, dermoscopic, and ultrastructural observation of annular secondary syphilis on the penis.
Annular syphilis may range from mildly raised lesions with scaly borders to verrucous plaques. Localized annular syphilis on the genitalia has been rarely reported in HIV-negative cases. This paper reports a case of annular secondary syphilis on the penis. Dermoscopy showed peripheral dotted and short linear vessels and white scaling with a relatively clear central area in an erythematous annular plaque. Histopathology revealed mild hyperkeratosis, parakeratosis, psoriasiform acanthosis, and focal basal vacuolar degeneration with lichenoid, perivascular, and periadnexal infiltrate of lymphohistiocytes and plasma cells in the superficial dermis. Silver stain showed several spirochetes in the lower epidermis and superficial dermis. Electron microscopy revealed a few intercellular and intracytoplasmic spirochetes in the basal epidermis and free spirochetes in the papillary dermis. Rapid plasma reagin and Treponema pallidum particle agglutination assays were positive. The lesions disappeared after intramuscular benzathine penicillin, with no relapse at six-month follow-up.


Metabolic engineering of Synechococcus sp. PCC 7002 to produce poly-3-hydroxybutyrate and poly-3-hydroxybutyrate-co-4-hydroxybutyrate.
Cyanobacteria are an important group of photoautotrophic bacteria that have been engineered and used to produce a wide range of biomaterials and biofuels, which are usually derived from important intermediates of the central metabolic pathways. In this study, the production of poly-3-hydroxybutyrate and poly-3-hydroxybutyrate-co-4-hydroxybutyrate in cyanobacteria was studied, and metabolic engineering strategies to improve the yields were also investigated. The genes involved in the biosynthetic pathway for poly-3-hydroxybutyrate from Chlorogloeopsis fritschii PCC 9212 were introduced into Synechococcus sp. PCC 7002, and the resulting strain was able to accumulate 2.77% of total cell dry weight as poly-3-hydroxybutyrate. When the ccmR gene was deleted in this strain, the yield of poly-3-hydroxybutyrate increased to 3.97% of total cell dry weight. A biosynthetic pathway for the production of 4-hydroxybutyryl-CoA was also constructed and introduced into the poly-3-hydroxybutyrate-producing strain. The resulting strain was able to produce ~4.5% of total cell dry weight as poly-3-hydroxybutyrate-co-4-hydroxybutyrate, in which 4-hydroxybutyrate accounted for ~12% of the co-polymer. These results demonstrate that poly-3-hydroxybutyrate-co-4-hydroxybutyrate can be produced in cyanobacteria and confirm that succinic semialdehyde is an important TCA cycle metabolite in cyanobacteria. This study also demonstrates the potential for future metabolic engineering in cyanobacteria that is based on recently discovered metabolites.


Augmentation ileocystoplasty in a case of eosinophilic cystitis.
Eosinophilic cystitis (EC) is a rare form of bladder inflammation characterized by massive eosinophilic infiltration of the bladder wall. The most frequent signs and symptoms are pollakiuria, urgency, macroscopic haematuria and hypogastric pain: the involvement of the ureters may cause hydronephrosis and renal failure. Eosinophilia and eosinophiluria are present in 35% and in 50% of the cases respectively. EC may evolve towards sclerosis up to the anatomoclinical picture of small retracted bladder, which requires to be differentiated from tubercular cystitis, interstitial cystitis and cancer. Imaging techniques are not definitely diagnostic. Diagnosis can be reached only by biopsy with the microscopic demonstration of eosinofilic infiltration of the whole bladder wall in the early and acute stages, while fibrosis with poor cellularity predominates in the chronic stages. Etiology is unknown and the hypothesis of an allergic origin is unproved even though remissions or recoveries induced by steroidal therapy have been reported. Surgical therapy of EC, as in our observation, is absolutely required to correct urgency and incontinence and to prevent renal failure when the urinary upper tract has been primarily or secondarily involved.


Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.
GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism. Fifteen children with GLUT1 deficiency syndrome were enrolled prospectively for a 2.0 - 5.5-year follow-up of the effectiveness of a 3 : 1 LCT ketogenic diet. Eight patients enrolled were described previously, seven patients were novel. Four novel heterozygous GLUT1 mutations were identified. 10/15 patients remained seizure-free on the ketogenic diet in monotherapy. In 2/15 patients seizures recurred after 2(1/2) years despite adequate ketosis, but were controlled by add-on ethosuximide. In one patient seizures were reduced without complete seizure control. No serious adverse effects occurred and parental satisfaction with the diet was good. 2/15 patients discontinued the diet. GLUT1 deficiency syndrome represents a complex childhood encephalopathy that can be treated effectively by means of a ketogenic diet. The response to the diet did not correlate to clinical, biochemical, or genetic features of the disease. In contrast to previous reports, our results indicate that epilepsy is not always completely controlled by a ketogenic diet and can recur in a subset of patients.


Comparison Between Extracorporeal Shock Wave Therapy and Intra-articular Hyaluronic Acid Injections in the Treatment of First Carpometacarpal Joint Osteoarthritis.
To compare extracorporeal shockwave therapy (ESWT) with hyaluronic acid (HA) intra-articular injections in terms of pain relief, improvement in hand function, and strength in subjects with first carpometacarpal (CMC) joint osteoarthritis. Fifty-eight patients received either focused ESWT or HA injection once a week for 3 consecutive weeks. In the ESWT group, 2,400 consecutive pulses were performed during each treatment session using a frequency of 4 Hz and an energy flux density of 0.09 mJ/mm2. The HA group underwent one cycle of three injections of 0.5 cm3 HA. The main outcome measures were pain and hand function as measured by the visual analogue scale (VAS) and Duruoz Hand Index (DHI), respectively. The secondary outcomes were grip and pinch strength. Each assessment was performed at baseline, at the end of treatment, and at 3- and 6-month follow-up visits. According to VAS and DHI scores, a significant change in test performance was observed over time in both groups (p<0.001), with a greater average improvement in painful symptomatology at the 6-month follow-up in the ESWT group. A significant improvement in strength was observed in both groups, but the ESWT group showed better results on the pinch test starting immediately at the end of treatment. The use of ESWT in patients with first CMC joint osteoarthritis leads to a reduction in pain, an improvement in pinch test performance that persists for at least 6 months, and a decrease in hand disability up to the 6-month follow-up visit.


ANG II induces c-Jun NH2-terminal kinase activation and proliferation of human mesangial cells via redox-sensitive transactivation of the EGFR.
We previously showed that ANG II induces mesangial cell (MC) proliferation via the JNK-activator protein-1 pathway. The present study attempted to determine the upstream mediators of JNK activation, with emphasis on reactive oxygen species (ROS) and the epidermal growth factor (EGF) receptor (EGFR). In cultured human MCs (HMCs), as early as 3 min, ANG II time dependently increased intracellular ROS production, which was sensitive to 10 microM diphenyleneiodonium sulfate and 500 microM apocynin, two structurally distinct NADPH oxidase inhibitors. In contrast, inhibitors of other oxidant-producing enzymes, including the mitochondrial complex I inhibitor rotenone, the xanthine oxidase inhibitor allopurinol, the cyclooxygenase inhibitor indomethacin, the lipoxygenase inhibitor nordihydroguiaretic acid, the cytochrome P-450 oxygenase inhibitor ketoconazole, and the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester, were without effect. ANG II-induced ROS generation was inhibited by the angiotensin type 1 receptor antagonist losartan (10 muM) but not the angiotensin type 2 receptor antagonist PD-123319 (10 microM). ANG II induced translocation of p47(phox) and p67(phox) from the cytosol to the membrane. The antioxidants almost abolished the ANG II mitogenic response, as assessed by [(3)H]thymidine incorporation and cell number, associated with a remarkable blockade of the activation of EGFR (90% inhibition) and JNK (83% inhibition). The EGFR inhibitor AG-1478 was able to mimic the effect of antioxidants, in that it inhibited the mitogenic response and the JNK activation following ANG II treatment. Together, these data suggest that the ROS-EGFR-JNK pathway is involved in transducing the proliferative effect of ANG II in cultured HMCs.


Anti-Aspergillus Activities of the Respiratory Epithelium in Health and Disease.
Respiratory epithelia fulfil multiple roles beyond that of gaseous exchange, also acting as primary custodians of lung sterility and inflammatory homeostasis. Inhaled fungal spores pose a continual antigenic, and potentially pathogenic, challenge to lung integrity against which the human respiratory mucosa has developed various tolerance and defence strategies. However, respiratory disease and immune dysfunction frequently render the human lung susceptible to fungal diseases, the most common of which are the aspergilloses, a group of syndromes caused by inhaled spores of Aspergillus fumigatus. Inhaled Aspergillus spores enter into a multiplicity of interactions with respiratory epithelia, the mechanistic bases of which are only just becoming recognized as important drivers of disease, as well as possible therapeutic targets. In this mini-review we examine current understanding of Aspergillus-epithelial interactions and, based upon the very latest developments in the field, we explore two apparently opposing schools of thought which view epithelial uptake of Aspergillus spores as either a curative or disease-exacerbating event.


PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues.
PD-1, an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. We tested the role of PD-1:PD-1 ligand (PD-L) interactions in cross-presentation and the generation and control of CD8(+) responses against self-Ag. Ag-naive PD-1(-/-) OVA-specific OT-I CD8(+) T cells exhibited exacerbated responses to cross-presented Ag in mice expressing soluble OVA under the control of the rat insulin promoter (RIP-ova(high)). Following adoptive transfer into RIP-ova(high) recipients, PD-1(-/-) OT-I T cells expanded in the pancreatic lymph node. In contrast to wild-type OT-I cells, PD-1(-/-) OT-I T cells secreted IFN-gamma and migrated into the pancreas, ultimately causing diabetes. Loss of PD-1 affected CD8(+) cells intrinsically, and did not significantly alter the responses of wild-type OT-I T cells adoptively transferred into the same RIP-ova(high) recipient mouse. PD-1:PD-L interactions also limited CD8(+) effector cells, and PD-L1 expression on parenchymal tissues protected against effector OT-I T cell attack. Finally, we found that the loss of PD-1 on effector OT-I cells lowers the threshold for Ag recognition in peripheral tissues. These findings indicate two checkpoints where PD-1 attenuates self-reactive T cell responses: presentation of self-Ag to naive self-reactive T cells by dendritic cells in the draining lymph node and reactivation of pathogenic self-reactive T cells in the target organ.


A practical approach to ocular pain for the non-ophthalmologist.
Pain involving the eye has numerous etiologies and is a feared challenge of many clinicians. Between a fear of the patient losing vision and a lack of familiarity with the ophthalmic equipment necessary to diagnose the problem, working up eye pain can be a daunting task. While the ophthalmologist can be indispensable in challenging cases of eye pain, this article will help clarify the unique clinical features of each etiology that can help clinicians narrow down the differential and arrive at a diagnosis.


Velopharyngeal insufficiency in the facio-auriculo-vertebral malformation complex.
Twenty-two patients with the Facio-Auriculo-Vertebral Malformation Complex (hemifacial microsomia) were examined with multi-view videofluoroscopy and nasopharyngoscopy at rest and during speech. Fifty-five per cent of the subjects had velopharyngeal insufficiency (VPI) and hypernasal speech. Only two of these 12 subjects had cleft palate. VPI was related to structural and physiological asymmetry of the pharynx. No relationship was found between the severity of facial malformation and the presence of VPI.


Surgical approaches to the brain stem.
During the last decade there has been a remarkable increase in the interest of neurosurgeons in surgical approaches along the base of the skull. A plethora of different approaches, most of which involve a slight variation of a previously described approach, have been reported in the recent literature, frequently with proprietary claims of originality. This increased confidence of the neurosurgeon in approaching lesions along the base is due to our renewed interest in the anatomy of the skull base and our willingness to collaborate with some of our colleagues in otorhinolaryngology who have concentrated their surgical anatomic studies in this area for years. It is clear that the neurosurgeon who currently undertakes surgery of complex lesions involving the base of the skull, the brain stem and the associated cranial nerves and arteries must have a thorough understanding of this anatomy and frequently must engage the help of an ear-nose-and-throat colleague to enhance his or her own expertise with these complex cases. The emerging principle is that whenever possible, exposure should be obtained through carefully planned bone removal along the base rather than through brain retraction. It needs to be emphasized, however, that most of the complex approaches alluded to in the preceding sections are necessary only when the surgeon is dealing with extrinsic lesions, neoplastic or vascular, that only secondarily affect the brain stem itself. Almost all intrinsic lesions of the brain stem can be accessed through one of the more traditional approaches with which all neurosurgeons should be fully familiarized. When the lesion involves or points toward the floor of the fourth ventricle, a standard suboccipital approach through the vermis suffices. Lesions presenting in the cerebellopontine angle or the lateral pons may be safely approached through a standard retromastoid craniectomy. A more direct (perpendicular) access can be obtained by a standard subtemporal-transtentorial approach when the lesion is high and lateral, by a combined subtemporal-suboccipital approach when the lesion extends more inferiorly, and by a combined subtemporal-presigmoid approach for the more anteriorly located lesions. Anterior or anterolateral lesions of the highest aspect of the pons or of the mesencephalon can be readily accessed by the pterional-anterior temporal approach or by a standard subtemporal approach. Dorsal mesencephalic lesions require a supracerebellar/infratentorial approach or, when they extend more inferiorly, an occipital transtentorial approach. When the ventral aspect of the lower brain stem is involved, the lateral suboccipital approach works well.(ABSTRACT TRUNCATED AT 400 WORDS)


Heterogeneity in ADHD: Neurocognitive predictors of peer, family, and academic functioning.
Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in peer, family, and academic functioning. Although impairment is required for diagnosis, children with ADHD vary significantly in the areas in which they demonstrate clinically significant impairment. However, relatively little is known about the mechanisms and processes underlying these individual differences. The current study examined neurocognitive predictors of heterogeneity in peer, family, and academic functioning in a well-defined sample of 44 children with ADHD aged 8-13 years (M = 10.31, SD = 1.42; 31 boys, 13 girls; 81% Caucasian). Reliable change analysis indicated that 98% of the sample demonstrated objectively-defined impairment on at least one assessed outcome measure; 65% were impaired in two or all three areas of functioning. ADHD children with quantifiable deficits in academic success and family functioning performed worse on tests of working memory (d = 0.68 to 1.09), whereas children with impaired parent-reported social functioning demonstrated slower processing speed (d = 0.53). Dimensional analyses identified additional predictors of peer, family, and academic functioning. Working memory abilities were associated with individual differences in all three functional domains, processing speed predicted social functioning, and inhibitory control predicted family functioning. These results add to a growing literature implicating neurocognitive abilities not only in explaining behavioral differences between ADHD and non-ADHD groups, but also in the substantial heterogeneity in ecologically-valid functional outcomes associated with the disorder.


Correction: Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative.
Correction for 'Impact of metal binding on the antitumor activity and cellular imaging of a metal chelator cationic imidazopyridine derivative' by Mithun Roy et al., Dalton Trans., 2011, 40, 4855-4864.


Additive prognostic value of the SYNTAX score over GRACE, TIMI, ZWOLLE, CADILLAC and PAMI risk scores in patients with acute ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention.
This study evaluated additive prognostic value of the SYNTAX score over GRACE, TIMI, ZWOLLE, CADILLAC and PAMI risk scores in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). All six scores were calculated in 209 consecutive STEMI patients undergoing pPCI. Primary end-point was the major adverse cardiovascular event (MACE--composite of cardiovascular mortality, non-fatal myocardial infarction and stroke); secondary end point was cardiovascular mortality. Patients were stratified according to the SYNTAX score tertiles (≤12; between 12 and 19.5; >19.5). The median follow-up was 20 months. Rates of MACE and cardiovascular mortality were highest in the upper tertile of the SYNTAX score (p < 0.001 and p = 0.003, respectively). SYNTAX score was independent multivariable predictor of MACE and cardiovascular mortality when added to GRACE, TIMI, ZWOLLE, and PAMI risk scores. However, the SYNTAX score did not improve the Cox regression models of MACE and cardiovascular mortality when added to the CADILLAC score. The SYNTAX score has predictive value for MACE and cardiovascular mortality in patients with STEMI undergoing primary PCI. Furthermore, SYNTAX score improves prognostic performance of well-established GRACE, TIMI, ZWOLLE and PAMI clinical scores, but not the CADILLAC risk score. Therefore, long-term survival in patients after STEMI depends less on detailed angiographical characterization of coronary lesions, but more on clinical characteristics, myocardial function and basic angiographic findings as provided by the CADILLAC score.


Microwave variable waveguide attenuator.
A new type of cutoff attenuator is presented. The attenuator works in the X-band in conditions of almost perfect matching. This means that the phase of the wave, which propagates inside the guide, does not suffer sensible variation in the passage between X- and K(u)-bands. Moreover, the attenuator works directly in the X-band, avoiding the passage between waveguide and cable, thus eliminating spurious effects due to this (double) passage. Experimental results of attenuation and dephasing using a prototype are also presented.


Safety and Postoperative Outcomes of Regional versus Global Ischemia for Partial Nephrectomy: A Systematic Review and Meta-Analysis.
To analyze current evidence comparing the safety and outcomes of regional and global ischemia for partial nephrectomy (PN). A systematic search of the PubMed and Web of Science databases was conducted in May 2014 to identify studies comparing the safety and outcomes of regional and global ischemia for PN. A systematic review and meta-analysis was also performed. Six retrospective observational studies were selected for the analysis, including 363 patients who underwent PN (162 regional ischemia and 201 global ischemia cases). Operation times were not statistically different [weighted mean difference (WMD) = 20.35 min, 95% CI: -0.28-40.97, p = 0.05], but estimated blood loss was significantly higher in the regional ischemia group (WMD = 52.04 ml, 95% CI: 14.30-89.78, p = 0.007) than in the global ischemia group. Complication rates [odds ratio (OR) = 1.16; 95% CI: 0.63-2.15, p = 0.63] and blood transfusion rates (OR = 1.85; 95% CI: 0.86-4.01, p = 0.12) of the two groups were not significantly different. The regional ischemia group showed better postoperative renal function (WMD = 4.23 ml/min, 95% CI: 2.61-5.85, p < 0.00001) than the global ischemia group, and all cases in the regional ischemia group showed negative margins. Regional ischemia is as safe to perform as global ischemia, and the former leads to better postoperative renal functions than the latter. These findings support the application of regional ischemia for PN.


An adhesion variant of the MG-63 osteosarcoma cell line displays an osteoblast-like phenotype.
MG-63 human osteosarcoma cells were selected for attachment and growth in increasing concentrations of a synthetic peptide containing the cell attachment-promoting Arg-Gly-Asp (RGD) sequence derived from the cell-binding region of fibronectin. Cells capable of attachment and growth in 5 mM concentrations of a peptide having the sequence Gly-Arg-Gly-Asp-Ser-Pro overproduce the cell surface receptor for fibronectin. No increase in fibronectin receptor gene copy number was detected by Southern blot analysis. The peptide-resistant MG-63.3A cells look very different from the MG-63 cells and resemble osteocytes. The resistant cells also grow more slowly than MG-63 cells. The enhanced expression of the fibronectin receptor on the resistant cells indicates that cells can regulate the amount of this receptor on their surface in response to environmental factors and that this may affect the phenotypic properties of the cell. MG-63.3A cells differ from MG-63 cells in their ability to form a calcified matrix in vitro and in their increased synthesis of type I collagen. The MG-63.3A cells synthesize 50-100-fold less prostaglandin E2, a mediator of bone resorption, than MG-63 cells. There is an overall down-regulation of chondroitin sulphate proteoglycans in MG-63.3A cells. These results are consistent with the hypothesis that such proteoglycans interfere with calcium phosphate deposition and with the observation that chondroitin sulphate is increased in a wide variety of neoplasms but is absent or in small amounts in normal tissue. We conclude that MG-63.3A cells represent a more differentiated cell type with osteoblast-like properties.


Understanding the thermostability and activity of Bacillus subtilis lipase mutants: insights from molecular dynamics simulations.
Improving the thermostability of industrial enzymes is an important protein engineering challenge. Point mutations, induced to increase thermostability, affect the structure and dynamics of the target protein in several ways and thus can also affect its activity. There appears to be no general rules for improving the thermostabilty of enzymes without adversely affecting their enzymatic activity. We report MD simulations, of wild type Bacillus subtilis lipase (WT) and its six progressively thermostable mutants (2M, 3M, 4M, 6M, 9M, and 12M), performed at different temperatures, to address this issue. Less thermostable mutants (LTMs), 2M to 6M, show WT-like dynamics at all simulation temperatures. However, the two more thermostable mutants (MTMs) show the required flexibility at appropriate temperature ranges and maintain conformational stability at high temperature. They show a deep and rugged free-energy landscape, confining them within a near-native conformational space by conserving noncovalent interactions, and thus protecting them from possible aggregation. In contrast, the LTMs having marginally higher thermostabilities than WT show greater probabilities of accessing non-native conformations, which, due to aggregation, have reduced possibilities of reverting to their respective native states under refolding conditions. Our analysis indicates the possibility of nonadditive effects of point mutations on the conformational stability of LTMs.


Three-dimensional intrauterine sonography in the early first-trimester of human pregnancy: preliminary study.
Our purpose was to visualize normal embryonal surface anatomic structures using three-dimensional (3D) intrauterine sonography with a 20 MHz flexible catheter-based high-resolution real-time miniature transducer in the early first trimester of pregnancy. A total of 15 women about to undergo therapeutic abortion at 7-9.9 weeks gestational age were studied by means of 3D intrauterine sonography with a specially developed catheter-based high-resolution real-time miniature (2.4 mm in outer diameter) ultrasound transducer (20 MHz). This imaging system can provide conventional 2D intrauterine sonographic images and can also generate within seconds high-quality 3D images in the surface and transparent mode. At week 8, prominent forehead was evident, and upper and lower limbs and midgut herniation were clearly depicted. At week 9, fingers and toes were depicted as small digital rays, and the sacral tail protruded caudally. The midline cranial ectodermal cleft was also identified. At week 10, embryonic face and fingers were clearly shown. 3D intrauterine sonography provides a novel means for visualizing of surface anatomic structures of the human embryo in utero. These results suggest that 3D intrauterine sonography can become an important modality in future embryological research and in detection of embryonic developmental disorders in the early first-trimester pregnancy.


Amyand's hernia containing an appendiceal goblet cell carcinoid tumour.
Amyand's hernia is a rare occurrence where the appendix is trapped within an inguinal hernia. Appendicitis within the hernia is even rarer. However, the presence of an appendiceal neoplasm in an inguinal hernia is almost unheard of with only two cases reported in the literature. We present an extremely rare case of an inflamed appendix within an Amyand's hernia, which was found to be a goblet cell type carcinoid tumour requiring further oncological resection and treatment.


Anomalous acoustic reflection on a sliding interface or a shear band.
We study the reflection of an acoustic plane wave from a steadily sliding planar interface with velocity-strengthening friction or a shear band in a confined granular medium. The corresponding acoustic impedance is utterly different from that of the static interface. In particular, the system being open, the energy of an in-plane polarized wave is no longer conserved, the work of the external pulling force being partitioned between frictional dissipation and gain (of either sign) of coherent acoustic energy. Large values of the friction coefficient favor energy gain, while velocity strengthening tends to suppress it. An interface with infinite elastic contrast (one rigid medium) and v-independent (Coulomb) friction exhibits spontaneous acoustic emission, as already shown by Nosonovsky and Adams [Int. J. Eng. Sci. 39, 1257 (2001)]. But this pathology is cured by a moderately large V strengthening of friction, or, for systems with not too large friction coefficients, by any finite elastic contrast. We show that (i) positive gain should be observable for rough-on-flat multicontact interfaces and (ii) a sliding shear band in a granular medium should give rise to sizable reflection, which opens a promising possibility for the detection of shear localization.


Shilnikov problem in Filippov dynamical systems.
In this paper, we introduce the concept of sliding Shilnikov orbits for 3D Filippov systems. In short, such an orbit is a piecewise smooth closed curve, composed by Filippov trajectories, which slides on the switching surface and connects a Filippov equilibrium to itself, namely, a pseudo-saddle-focus. A version of Shilnikov's theorem is provided for such systems. Particularly, we show that sliding Shilnikov orbits occur in generic one-parameter families of Filippov systems and that arbitrarily close to a sliding Shilnikov orbit there exist countably infinitely many sliding periodic orbits. Here, no additional Shilnikov-like assumption is needed in order to get this last result. In addition, we show the existence of sliding Shilnikov orbits in discontinuous piecewise linear differential systems. As far as we know, the examples of Fillippov systems provided in this paper are the first to exhibit such a sliding phenomenon.


A Novel Luminescence-Based Serum Bactericidal Assay for Vibrio cholerae Reduces Assay Variation, Is Time- and Cost-Effective, and Directly Measures Continuous Titer Values.
Cholera remains a significant public health burden worldwide, and better methods for monitoring cholera incidence would enhance the effectiveness of public health interventions. The serum bactericidal assay (SBA) has been used extensively for Vibrio cholerae vaccine assessments and serosurveillance. Current SBA approaches for V. cholerae rely on colony enumeration or optical density (OD600nm) readings to measure viable bacteria following complement-mediated lysis. These methods provide titer values that are constrained to discrete dilution values and rely on bacterial outgrowth, which is time consuming and prone to variation. Detection of bacterial proteins following complement-mediated lysis presents a faster and potentially less variable alternative approach independent of bacterial outgrowth. Here, we present an SBA that measures luciferase luminescence driven by lysis-released adenylate kinase. This approach is faster and less variable than growth-dependent SBAs and directly measures continuous titer values. This novel SBA method can potentially be applied to other bacteria of interest.


Enhancement of Oral Tolerance Induction in DO11.10 Mice by Lactobacillus gasseri OLL2809 via Increase of Effector Regulatory T Cells.
Food allergy is a serious problem for infants and young children. Induction of antigen-specific oral tolerance is one therapeutic strategy. Enhancement of oral tolerance induction by diet is a promising strategy to prevent food allergy in infants. Thus, in this study, we evaluate the effect of probiotic Lactobacillus gasseri OLL2809 (LG2809) on oral tolerance induction in a mouse model. The degree of oral tolerance induction was evaluated by measuring the proliferation and level of IL-2 production of splenic CD4+ T cells from DO11.10 mice fed ovalbumin (OVA) alone or OVA with LG2809. Oral administration of LG2809 significantly decreased the rate of proliferation and IL-2 production by CD4+ T cells from OVA-fed mice. LG2809 increased a ratio of CD4+ T-cell population, producing high levels of IL-10 and having strong suppressive activity. Moreover, LG2809 increased a ratio of plasmacytoid dendritic cells (pDCs) among the lamina propria (LP) in small intestine. When used as antigen presenting cells to naïve CD4+ T cells from DO11.10 mice, LP cells from BALB/c mice fed LG2809 induced higher IL-10 production and stronger suppressive activity than those from non-treated mice. These results suggest that oral administration of LG2809 increases the population of pDCs in the LP, resulting in the enhancement of oral tolerance induction by increasing the ratio of effector regulatory T cells. LG2809 could, therefore, act as a potent immunomodulator to prevent food allergies by promoting oral tolerance.


Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer's disease and diabetes.
Epidemiological evidence suggests an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD), in that one disease increases the risk of the other. T2DM and AD share several molecular processes which underlie the tissue degeneration in either disease. Disturbances in insulin signaling may be the link between the two conditions. Drugs originally developed for T2DM are currently being considered as possible novel agents in the treatment of AD. This review discusses the potential role of glucagon-like peptide -1 (GLP-1) treatment in AD. GLP-1 receptors are expressed in areas of the brain important to memory and learning, and GLP-1 has growth-factor-like properties similar to insulin. A key neuropathological feature of AD is the accumulation of amyloid-beta (Aβ). In preclinical studies, GLP-1 and longer lasting analogues have been shown to have both neuroprotective and neurotrophic effects, and to protect synaptic activity in the brain from Aβ toxicity. A convincing amount of evidence has shown a beneficial effect of GLP-1 agonist treatment on cognitive function, memory and learning in experimental models of AD. GLP-1 analogues may therefore be the new therapeutic agent of choice for intervention in AD.


High frequency of ETFDH c.250G>A mutation in Taiwanese patients with late-onset lipid storage myopathy.
Lipid storage myopathies (LSMs) are characterized pathologically by the accumulation of lipid droplets in muscle fibers due to impaired cellular lipid metabolism. The purpose of this study was to determine etiologies and genetic mutations associated with LSMs in ethnic Han Taiwanese. The usefulness of the blood acylcarnitine (AC) profile for diagnosing LSMs in adult patients was also investigated. Nine patients were diagnosed with late-onset LSMs following a review of muscle biopsies and medical records and were recruited retrospectively. Genetic studies were performed to detect mutations in the SLC22A5 for primary carnitine deficiency, PNPLA2 for neutral lipid storage disease with myopathy, ABHD5 for neutral lipid storage disease with ichthyosis, ETFDH for multiple acyl-CoA dehydrogenation deficiency (MADD), and CPT2 for carnitine palmitoyltransferase II deficiency. Blood AC levels were measured by tandem mass spectrometry. The mutation c.250G>A in ETFDH was detected in seven (78%) patients, six of whom were homozygous for the variant. Patients with ETFDH mutations had elevated blood levels of ACs ranging from C8 to C16 species, a pattern consistent with MADD. ETFDH c.250G>A mutation is common in Taiwanese patients with late-onset LSMs. The blood AC profile is a sensitive biochemical marker for diagnosing MADD arising from ETFDH mutations in adults.


Platelet genetic testing by next-generation sequencing: A practical update.
Inherited platelet disorders (IPDs) are a heterogeneous group of disorders characterized by normal or reduced platelet counts, bleeding diatheses of varying severities, and the presence (syndromic) or absence (non-syndromic) of involvement of other organs. Due to the lack of highly specific platelet function tests and overlapping clinical and laboratory features, diagnosing the underlying cause of IPDs remains challenging. In recent years, genetic testing via next-generation sequencing (NGS) technologies to rapidly analyze multiple genes has gradually emerged as an important part of the laboratory investigation of patients with IPDs. A systemic clinical and laboratory testing approach and thorough phenotype and genotype correlation studies of both patients and their family members are crucial for accurate diagnoses of IPDs.


Strategies for the Management of Aggressive Invasive Plant Species.
Current control methods for invasive alien plants (IAPs) have acceptable short-term outcomes but have proven to be unfeasible or unaffordable in the long-term or for large invaded areas. For these reasons, there is an urgent need to develop sustainable approaches to control or restrict the spread of aggressive IAPs. The use of waste derived from IAP control actions could contribute to motivating the long-term management and preservation of local biodiversity while promoting some economic returns for stakeholders. However, this strategy may raise some concerns that should be carefully addressed before its implementation. In this article, we summarize the most common methods to control IAPs, explaining their viability and limitations. We also compile the potential applications of IAP residues and discuss the risks and opportunities associated with this strategy.