Unraveling the uptake mechanisms of mannan nanogel in bone-marrow-derived macrophages.
The mechanisms associated with the cellular internalization of nanomedicines must be carefully considered when designing drug- and vaccine-delivery systems. The cellular fate and effects of nanomedicines depend to a large extent on the cell uptake routes. A self-assembled mannan nanogel is developed as a vaccination platform for antigen and adjuvant delivery. The mannan nanogel uptake by murine bone-marrow-derived macrophages is found to be time-, concentration-, and energy-dependent, involving mannose-receptor-mediated phagocytosis and clathrin-mediated endocytosis. The nanogel is also visualized in the cytosol suggesting endolysosomal escape. These results indicate that mannan nanogel is a promising versatile carrier for intracellular delivery of vaccines or therapeutic agents.


Clinical experiences in conducting cognitive-behavioral therapy for social phobia.
Several authors have identified a disconnect between psychotherapy research, including research on cognitive behavioral therapy (CBT), and real-world psychotherapy practice. This disconnect has several negative consequences, potentially including less-than-optimal practice standards as well as a lack of input from practicing psychotherapists on how research can be improved and made more relevant in their day-to-day clinical work. As part of an ongoing effort to engage practicing psychotherapists in a feedback loop with psychotherapy researchers, this study reports the results of a survey of CBT therapists who have used CBT in the treatment of social phobia (SP). The survey was designed primarily to document how often certain potential problems, identified by expert researchers and CBT manuals, actually act as barriers to successful treatment when CBT is employed in nonresearch environments. The participants were 276 psychotherapists responding to email, online, and print advertisements completing the online survey. Participants varied considerably in psychotherapy experience, work environment, experience in using CBT for SP, and in some ways varied in their usual CBT techniques when treating SP. Among the most prominent barriers identified by many of the participants were patient motivation, comorbidity, logistical problems (especially with exposures), patient resistance, and severity and chronicity of SP symptoms. These findings may be useful for psychotherapy researchers as areas for potential study. The results may also suggest topics requiring clinical guidelines, innovations within CBT, and dissemination of successful techniques to address the barriers identified here.


Complicated Grief: Risk Factors, Interventions, and Resources for Oncology Nurses.
When a loved one dies of cancer, complicated grief (CG) may occur because of the trauma associated with family caregivers' perceptions of their loved one's suffering, either from advanced cancer or from side effects of cancer treatment. . This article provides an overview of CG and existing interventions for family caregivers who may be at risk for CG following the loss of a loved one and the implications for oncology nurses who provide emotional support and guidance. . Current evidence related to the treatment of CG and information to assist with identification of individuals at risk for CG are presented, as well as resources for oncology nurses who encounter individuals who are at high risk for, or who are experiencing, CG. . Although therapy interventions for CG have been shown to be effective forms of treatment, these therapies are not widely available and often require an extended treatment period to yield results. Oncology nurses can provide early interventions, such as referrals to supportive care services and mental health professionals to facilitate effective treatment.


Enzymic transfer of glucose and xylose from uridine diphosphate glucose and uridine diphosphate xylose to bilirubin by untreated and digitonin-activated preparations from rat liver.
1. Digitonin-treated and untreated homogenates, cell extracts and washed microsomal preparations from liver of Wistar R rats are capable of transferring sugar from UDP-glucose or UDP-xylose to bilirubin. No formation of bilirubin glycosides occurred with UDP-galactose or d-glucose, d-xylose or d-glucuronic acid as the sources of sugar. 2. Procedures to assay digitonin-activated and unactivated bilirubin UDP-glucosyltransferase and bilirubin UDP-xylosyltransferase were developed. 3. In digitonin-activated microsomal preparations the transferring enzymes had the following properties. Both enzyme activities were increased 2.5-fold by pretreatment with digitonin. They were optimum at pH6.6-7.2. Michaelis-Menten kinetics were followed with respect to UDP-glucose. In contrast, double-reciprocal plots of enzyme activity against the concentration of UDP-xylose showed two intersecting straight-line sections corresponding to concentration ranges where either bilirubin monoxyloside was formed (at low UDP-xylose concentrations) or where mixtures of both the mono- and di-xyloside were synthesized (at high UDP-xylose concentrations). Both enzyme activities were stimulated by Mg(2+); Ca(2+) was slightly less, and Mn(2+) slightly more, stimulatory than Mg(2+). Of the activities found in standard assay systems containing Mg(2+), 58-78% (substrate UDP-glucose) and 0-38% (substrate UDP-xylose) were independent of added bivalent metal ion. Double-reciprocal plots of the Mg(2+)-dependent activities against the concentration of added Mg(2+) were linear. 4. In comparative experiments the relative activities of liver homogenates obtained with UDP-glucuronic acid, UDP-glucose and UDP-xylose were 1:1.5:2.7 for untreated preparations and 1:0.29:0.44 after activation with digitonin. 5. Bilirubin UDP-glucuronyltransferase was protected against denaturation by human serum albumin, whereas bilirubin UDP-xylosyltransferase was not. 6. Digitonin-treated and untreated liver homogenates from Gunn rats were inactive in transferring sugar to bilirubin from UDP-glucuronic acid (in agreement with the work of others), UDP-glucose or UDP-xylose.


Successful management of natalizumab-associated progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient with multiple sclerosis.
To describe a case of successful clinical management of natalizumab-associated progressive multifocal leukoencephalopathy (PML) and immune reconstitution syndrome (IRIS) in a patient with multiple sclerosis. Case report. University hospital. A 41-year-old woman with relapsing-remitting multiple sclerosis developed PML after 29 natalizumab infusions. Immediate plasma exchange was combined for removal of natalizumab with application of mefloquine and mirtazapine to limit viral replication and oligodendrocyte infection. A subsequent IRIS was treated with glucocorticosteroids. After 3 months of treatment, cerebrospinal fluid tested negative for JC virus. There was a favorable outcome, and the Expanded Disability Status Scale score remained stable at 3.5 compared with before PML. In the setting of early diagnosis and consequent treatment, natalizumab-associated PML can be well managed in some cases. This situation differs from the course of PML in other conditions, eg, after the application of depleting monoclonal antibodies, in which irreversible cellular effects are associated with very high mortality.


Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide.
Flow-induced vasodilation is attenuated with old age in rat skeletal muscle arterioles. The purpose of this study was to determine whether diminished cyclooxygenase (COX) signaling contributes to the age-induced attenuation of flow-induced vasodilation in gastrocnemius muscle arterioles and to determine whether, and through which mechanism(s), exercise training restores this deficit in old rats. Fischer 344 rats (3 and 22 mo old) were assigned to a sedentary or exercise-trained group. First-order arterioles were isolated from the gastrocnemius muscles, cannulated, and pressurized to 70 cm H(2)O. Diameter changes were determined in response to graded increases in intraluminal flow in the presence and absence of nitric oxide synthase (NOS) inhibition [10(-5) M N(G)-nitro-L-arginine methyl ester (L-NAME)], COX inhibition (10(-5) M indomethacin), or combination NOS (10(-5) M L-NAME) plus COX (10(-5) M indomethacin) inhibition. Aging reduced flow-induced vasodilation in gastrocnemius muscle arterioles. Exercise training restored responsiveness to flow in arterioles of aged rats and enhanced flow-induced vasodilation in arterioles from young rats. L-NAME inhibition of flow-induced vasodilation was greater in arterioles from old rats compared with those from young rats and was increased after exercise training in arterioles from both young and old rats. Although the indomethacin-sensitive portion of flow-induced dilation was not altered by age or training, both COX-1 mRNA expression and PGI(2) production increased with training in arterioles from old rats. These data demonstrate that exercise training restores flow-induced vasodilation in gastrocnemius muscle arterioles from old rats and enhances flow-induced vasodilation in gastrocnemius muscle arterioles from young rats. In arterioles from both old and young rats, the exercise training-induced enhancement of flow-induced dilation occurs primarily through a NOS mechanism.


Chitosan-based bio(nano)platforms and hydrogels in breast cancer therapy: immunotherapy, phototherapy and stimuli-responsive devices.
Breast cancer is the most common and malignant tumor among women. Chitosan (CS)-based nanoparticles have been introduced into breast cancer therapy as a way to increase the targeted delivery of drugs and genes to the tumor site. CS nanostructures suppress tumorigenesis by enhancing both the targeted delivery of cargo (drug and gene) and its accumulation in tumor cells. The tumor cells internalize CS-based nanoparticles through endocytosis. Moreover, chitosan nanocarriers can also induce phototherapy-mediated tumor ablation. Smart and multifunctional types of CS nanoparticles, including pH-, light- and redox-responsive nanoparticles, can be used to improve the potential for breast cancer removal. In addition, the acceleration of immunotherapy by CS nanoparticles has also been achieved, and there is potential to develop CS-nanoparticle hydrogels that can be used to suppress tumorigenesis.


Actin in the green alga, Nitella.
Bundles of microfilaments very similar in appearance to actin are present in cytoplasmic suspensions obtained from Nitella flexilis. The microfilaments bind rabbit heavy meromyosin in arrowhead arrays similar to those produced on muscle actin. The arrowheads are removed with ATP. The results provide evidence that actin is present in green plants, probably in the form of microfilaments thought to be involved in cytoplasmic streaming.


Comparison Between Rapid Intraoperative and Central Laboratory Parathormone Dosage in 12 Kidney Transplant Candidates.
The rapid intraoperative parathormone (PTH) and at central laboratory PTH dosage gives similar results. The central laboratory provides results in longer times and higher costs. Intraoperative measurement can reduce time and costs during parathyroidectomy. Twelve patients undergoing parathyroidectomy for hyperparathyroidism renal transplant candidates were included. Diagnosis was made by laboratory tests (serum calcium, PTH) and imaging techniques (ultrasonography and scintigraphy). All patients presented PTH levels of >400 pg/mL (the limit value to be maintained in list for kidney transplantation) and resistant to medical therapy. For each patient, 2 blood samples were collected before surgery at anesthesia induction for PTH testing intraoperative (rapid assay) and central laboratory, and 10 minutes after the removal of each gland. The times from collection-processing to communication to the surgeon of the results were compared for both the methods. It was considered successful the abatement of PTH of ≥70% at rapid intraoperative testing and consequently surgical intervention stopped before communication of central laboratory PTH testing. The average time of reporting the test results of the central laboratory was 41.5 minutes (SD ± 9), whereas with the rapid intraoperative PTH (ioPTH) testing the average time was 9.9 minutes (SD ± 2.02). An average of 33.6 minutes of the duration per intervention (SD ± 10.27) were virtually saved with the use of ioPTH testing. The 2 values of the Pearson correlation (ρ) of 0.99 obtained (for baseline) and 0.975 (for the 10-minute) lead us to conclude that there is an excellent correlation between the series of data. Rapid ioPTH testing, owing to its accuracy, permits a dramatic reduction of operating time for patients with secondary hyperparathyroidism that need to be treated before inclusion on the waiting list.


Carcinogenicity in mice of some fatty acid methyl esters. 2. Peroral and subcutaneous application.
Two fatty acid methyl esters, methyl oleate and methyl 12-oxo-trans-10-octadecenoate, have been tested for carcinogenicty by oral and subcutaneous administration in ST/a mice of both sexes. A positive effect of methyl oleate could not be assessed, while the results pointed to a promoter effect of methyl oxo-octadecenoate. Given in the diet, this compound increased the incidence and number of forestomach papillomas within 83 weeks after initiation by 4-nitroguinoline 1-oxide. Repeated injections of methyl oxo-octadecenoate in the inguinal area resulted in 2 local sarcomas in a group of 20 females which had previously received skin initiation by 7, 12-dimethylbenz [alpha] anthracene in the neck. In no other animal group did sarcomas appear at this location within the observation period of 2 years. An influence by the injected methyl esters on the initiated skin carcinogenesis was possibly, but weakly, present. The need for more extensive experiments is stressed, especially with a view to the possible carcinogenic hazards involved in dietary intake of oxygen-containing derivatives of oleic acid.


Working hours, coping skills, and psychological health in Japanese daytime workers.
This study examined the relationship between coping skills, working hours, and psychological health among Japanese daytime workers. Self-administered questionnaires were mailed to a randomly selected sample of 2,000 workers who were members of a pre-recruited market research panel. A total of 1,821 participants responded (response rate=91.1%). Participants completed a questionnaire regarding working hours, coping skills, and psychological health (negative emotions, fatigue, and concentration/activity levels). Analyses of covariance were conducted to determine the relations of number of working hours, coping skills, and their interactions to psychological health with control for sex, age, drinking, job type, and employment type. Results revealed that working hours were significantly associated with fatigue and concentration/activity levels. High levels of instrumental support and positive reframing were significantly associated with low levels of negative emotions, fatigue, and concentration/activity levels. High levels of self-blame, denial, substance use, venting, self-distraction, religion, and behavioral disengagement were significantly associated with high levels of negative emotions, fatigue, and concentration/activity levels. This study suggests that improving coping skills such as using instrumental support or positive reframing may reduce the adverse health effects of long working hours.


Inhibitory effects of 5-hydroxy polymethoxyflavones on colon cancer cells.
Hydroxylated polymethoxyflavones (PMFs) are a class of novel flavonoid compounds mainly found in citrus plants. We studied the effects of three major 5-hydroxy PMFs, namely: 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone, 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone, and 5-hydroxy-6,7,8,4'-tetramethoxyflavone, on human colon cancer HCT116 and HT29 cells. Their effects were compared with those produced by their permethoxylated counterparts, namely: nobiletin, 3,5,6,7,8,3',4'-heptamethoxylflavone, and tangeretin. 5-Hydroxy PMFs showed much stronger inhibitory effects on the growth of the colon cancer cells in comparison with their permethoxylated counterparts, suggesting the pivotal role of hydroxyl group at 5-position in the enhanced inhibitory activity by 5-hydroxy PMFs. Flow cytometry analysis demonstrated that three 5-hydroxy PMFs produced different effects on the cell cycle and apoptosis, which may suggest that three 5-hydroxy PMFs act through different mechanisms. For example, 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone caused cell cycle arrest at G2/M phase in HT29 cells, while 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone led to significant G0/G1 phase arrest. In contrast, 5-hydroxy-6,7,8,4'-tetramethoxyflavone increased sub-G0/G1 cell population, which has been confirmed to be due to enhanced apoptosis. Our results further demonstrated that the inhibitory effects of 5-hydroxy PMFs were associated with their ability in modulating key signaling proteins related to cell proliferation and apoptosis, such as p21(Cip1/Waf1), CDK-2, CDK-4, phosphor-Rb, Mcl-1, caspases 3 and 8, and poly ADP ribose polymerase (PARP).


Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE).
Despite a broad and efficient pharmacological antihypertensive armamentarium, blood pressure (BP) control is suboptimal and heterogeneous throughout Europe. Recent representative data from Switzerland are limited. The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerland in accordance with current guidelines. The influence of risk factors, target organ damage and medication on BP levels and control was also evaluated. A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerland. 281 randomly selected physicians provided data on 5 consecutive hypertensive patients attending their practices for BP follow-up. Data were anonymously collected on demographics, comorbidities and current medication, and BP was recorded. Subsequent modification of pharmacological antihypertensive therapy was assessed. Data from 1376 patients were available. Mean age was 65 ± 12 years, 53.9% were male subjects. 26.4% had complicated hypertension. Overall, BP control (<140/90 mm Hg for uncomplicated and <130/80 mm Hg for complicated hypertension) was achieved in 48.9%. Compared to patients with complicated hypertension, BP control was better in patients with uncomplicated hypertension (59.4% vs. 19.2%, p <0.001). As a monotherapy the most prescribed drug class were angiotensin receptor blockers (ARB, 41%), followed by angiotensin converting enzyme (ACE) inhibitors (21.5%), betablockers (20.8%) and calcium channel blockers (CCB, 10.8%). The most prescribed drug combinations were ARB + diuretic (30.1%) and ACE inhibitors + diuretic (15.3%). 46% were receiving a fixed drug combination. In only 32.7% of patients with uncontrolled hypertension was a change in drug therapy made. This representative survey on treated adult hypertensive patients shows that, compared to earlier reports, the control rate of hypertension has improved in Switzerland for uncomplicated but not for complicated, particularly diabetes-associated hypertension. ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy, whereas diuretics and ARBs were the most used for combination therapy.


Characterization of miniature pig kidney cells and their resistance to chlamydial infection.
A miniature pig kidney cell line has been established from porcine fetuses taken aseptically by hysterectomy and maintained for more than 50 passages in Eagle's minimal essential medium containing 10% heat-inactivated newborn calf serum. Cell transfers were performed each week. Primary and serially passaged cells were found to be highly refractory to infection by Chlamydia trachomatis strains TW-3, Bour, and LGV 440L and Chlamydia psittaci strains meningopneumonitis and 6BC and insusceptible to poliovirus type 1. The cells were susceptible to vesicular stomatitis virus and herpes simplex type 1 virus. Identity of the cells was established by cytotoxicity, isozyme, and cytogenetic studies.


Urinary proteomics before and after extracorporeal circulation in patients with and without acute kidney injury.
Acute kidney injury is a well-known complication with high morbidity and mortality after cardiopulmonary bypass. Cardiopulmonary bypass-associated acute kidney injury is still poorly understood. Thirty-six patients undergoing elective cardiopulmonary bypass were enrolled. Spot urine samples before and after cardiopulmonary bypass were collected. Acute kidney injury was defined according to the RIFLE classification. To identify differentially regulated proteins after cardiopulmonary bypass, we first analyzed the urinary proteome before and after cardiopulmonary bypass. To identify differentially regulated proteins in acute kidney injury, we next compared the urinary proteome obtained on the first postoperative day between patients with and without acute kidney injury. Difference fluorescence gel electrophoresis was used to compare protein profiles and mass spectrometry to identify individual proteins. After cardiopulmonary bypass, inflammation-associated (zinc-alpha-2-glycoprotein, leucine-rich alpha-2-glycoprotein, mannan-binding lectin serine protease 2, basement membrane-specific heparan sulfate proteoglycan, and immunoglobulin kappa) or tubular dysfunction-associated (retinol-binding protein, adrenomedullin-binding protein, and uromodulin) proteins were differentially regulated. Acute kidney injury developed in 6 of 36 patients. A modified urinary albumin was increased, and zinc-alpha-2-glycoprotein and a fragment of adrenomedullin-binding protein were decreased in patients with acute kidney injury. Decreased excretion of zinc-alpha-2-glycoprotein in patients with acute kidney injury was confirmed by Western blot and enzyme-linked immunosorbent assay in an independent cohort of 22 patients with and 46 patients without acute kidney injury. Cardiopulmonary bypass leads to increased urinary excretion of inflammatory proteins and markers of tubular injury. Zinc-alpha-2-glycoprotein is a potentially useful predictive marker for acute kidney injury after cardiopulmonary bypass surgery.


Analysis of varicella-zoster virus DNAs of clinical isolates by endonuclease HpaI.
The DNAs of 20 strains of varicella-zoster virus (VZV) isolated from epidemiologically unrelated individuals, and of 15 strains isolated from vesicles of vaccinees with varicella or zoster after vaccination, were compared by restriction enzyme cleavage using HpaI. Differences were found in the sizes of the HpaI-F, -G and -K fragments of the wild strains. The gel migration patterns of the HpaI-F and -G fragments, but not of the HpaI-K fragment, were polymorphic in the different strains isolated from the vaccinees. The effects of serial passages in vitro and in humans on the genome stability of VZV were investigated by HpaI analysis. The DNA profiles of the HpaI-K fragments from six isolates recovered from room-mates infected in a single outbreak were identical, but the mobilities of their HpaI-F and -G fragments varied. The DNA profiles of the Oka vaccine virus after 10 and 85 passages in human embryo cells differed only in the HpaI-F fragment. The profiles of these fragments in DNA derived from two isolates obtained at different times from a vaccinee with varicella followed by zoster were compared with those of the Oka (parental) and Oka (vaccine) strains, and identical results were obtained for the two viruses. In addition, the same DNA profiles of HpaI fragments were obtained from three sequential isolates from one person and also from two isolates from another with varicella and zoster. Thus, it was concluded that: three variable fragments (HpaI-K, -F and -G) were not changed in the DNAs of isolates derived from the same patient; HpaI-K was stable both on passage in vitro and after human transmission in the case of the same outbreak, but was different among all wild-type strains isolated in epidemiologically unrelated outbreaks; HpaI-F was very unstable both on passage in vitro and in human infections by either vaccine or wild-type strains; HpaI-G was not influenced by passage in vitro but varied among wild-type strains. Using physical maps of VZV DNA established by others, three variable regions on the viral genome were identified. One was located near the 0.16 coordinate, which is covered by HpaI-K (variable region I, VRI). Another was represented by HpaI-F (VRII), the most unstable fragment, and mapped at about the 0.35 coordinate. The third was VRIII near the right terminus, covered by HpaI-G.


[Specific features of normal vaginal microflora in girls of preschool age].
The study of the vaginal microbial cenosis in 20 healthy girls aged 3-7 years did not confirm the notion on the dominating role of cocci (including epidermal staphylococci). The associations of 2-5 different microorganisms represented by more than 20 species in an amount of 4-6 Ig PFC/g of discharge were established. In the overwhelming majority of the examinees (84.2%) the microbial associations of the vagina were found to contain bifidobacteria. Gram positive cocci (staphylococci and streptococci) took the 2nd and 3rd places in the isolation rates and were detected in vaginal associations in 78.9% of the girls. Staphylococci were represented by 5 coagulase-negative staphylococcal species with S. simulans and S. epidermidis prevailing. Hemolytic streptococci variants alpha and beta were isolated in the proportion of 2:1. The latter belonged to serogroups C and F. No S. aureus, Lactobacillus sp., streptococci of groups A and B, yeast-like fungi were detected. Genital mycoplasms (M. hominis) could rarely be found in the vaginal discharge of the girls aged 3-7 years (5.3%). No resident and transitory components could be isolated from the normal vaginal microflora and no quantitative domination of any bacterial species (genus) was shown. The concentrations of all organisms in this association were moderate or low.


X-ray microanalysis of calcium binding sites in Paramecium with special reference to exocytosis.
In Paramecium cells Ca++-stimulated triggering of the exocytosis of secretory vesicles ("trichocysts") was achieved by ionophores X-537 A or A 23187. Under triggering conditions electron dense deposits were present in some "resting" trichocysts and regularly in discharging trichocysts; upon subsequent fixation deposits occurred on the trichocyst membrane (on the inner side or within the membrane) and on the "inner lamellar sheath" from where deposits seemed to "radiate" into the secretory materials. Similar results were obtained with glutardialdehyde fixation alone which also triggers exocytosis but only at low concentrations. Element analysis by energy dispersive x-ray microanalysis ascertained the presence of Ca and P in deposits occurring in trichocysts. Those "resting" trichocysts which were devoid of deposits did not contain Ca or P enriched. Hence, an abrupt Ca++-influx into individual trichocysts just before exocytosis seems to be involved in the triggering mechanism, possible in combination with the sudden activation of an ATPase system localized at those sites of the trichocysts which primarily contain the deposits. When paramecia were treated only with Ca++ and then fixed with OsO4 plus oxalate or merely with glutardialdehyde, electron scattering deposits were formed also on the inner side of the cell membrane and within the ciliary shaft (but rarely in trichocysts). Deposits obtained on cilia (including "ciliary granule plaques") also contained Ca, P and S. Cells contain osmiophilic "calcium-storing vacuoles" which were selectively rich in Ca and S but devoid of P.


Using a competency based approach in nurse education.
This article examines the development of the competency based approach to assessment in practice within pre-registration nursing. An historical perspective to the approach is given, including brief descriptions of the different models that have been used in nurse training and how these relate to the current system of nurse education. The approach is examined in relation to government, professional and educational requirements. Implications for practice are discussed, taking into consideration staffing levels, training and availability of mentors and assessors, and the impact these have on nurse training.


Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats.
Inflammation is a hallmark of several disease states ranging from neurodegeneration to sepsis but is also implicated in physiological processes like ageing. Non-resolving inflammation and prolonged neuroinflammation are unclear processes implicated in several conditions, including ageing. In this study we studied the long-term effects of endotoxemia, as systemic lipopolysaccharide (LPS) injection, focusing on the role of astrocyte activation and cytokine release in the brain of aged rats. A single dose of LPS (2 mg/kg) or 0.9% saline was injected intraperitoneally in aged rats. Levels of pro-inflammatory cytokines (TNFα and IL-1β) and NF-κB p65 activation were measured systemically and in hippocampal tissue. Astrocytes and cytokines release in the CNS were detected via double immunofluorescence staining at different time-points up to day 30. Serum levels of TNFα and IL-1β were significantly increased acutely after 30 minutes (p<0.001) and up to 6 hours (p<0.001) following LPS-injection. Centrally, LPS-treated rats showed up-regulated mRNA expression and protein levels of pro-inflammatory cytokines in the hippocampus. These changes associated with astrogliosis in the hippocampus dentate gyrus (DG), IL-1β immunoreactivity and elevated NF-κB p65 expression up to day 30 post LPS exposure. Overall, these data demonstrate that LPS induces prolonged neuroinflammation and astrocyte activation in the hippocampus of aged rats. Hippocampal NF-κB p65 and excessive astrocytes-derived IL-1β release may play a pivotal role in regulating long-lasting neuroinflammation.


Myelin-mediated inhibition of oligodendrocyte precursor differentiation can be overcome by pharmacological modulation of Fyn-RhoA and protein kinase C signalling.
Failure of oligodendrocyte precursor cell (OPC) differentiation contributes significantly to failed myelin sheath regeneration (remyelination) in chronic demyelinating diseases. Although the reasons for this failure are not completely understood, several lines of evidence point to factors present following demyelination that specifically inhibit differentiation of cells capable of generating remyelinating oligodendrocytes. We have previously demonstrated that myelin debris generated by demyelination inhibits remyelination by inhibiting OPC differentiation and that the inhibitory effects are associated with myelin proteins. In the present study, we narrow down the spectrum of potential protein candidates by proteomic analysis of inhibitory protein fractions prepared by CM and HighQ column chromatography followed by BN/SDS/SDS-PAGE gel separation using Nano-HPLC-ESI-Q-TOF mass spectrometry. We show that the inhibitory effects on OPC differentiation mediated by myelin are regulated by Fyn-RhoA-ROCK signalling as well as by modulation of protein kinase C (PKC) signalling. We demonstrate that pharmacological or siRNA-mediated inhibition of RhoA-ROCK-II and/or PKC signalling can induce OPC differentiation in the presence of myelin. Our results, which provide a mechanistic link between myelin, a mediator of OPC differentiation inhibition associated with demyelinating pathologies and specific signalling pathways amenable to pharmacological manipulation, are therefore of significant potential value for future strategies aimed at enhancing CNS remyelination.


Geometric morphometric study and cluster analysis of late Byzantine and modern human crania.
Inter-population variation of cranial morphology, which plays an important role in human evolution studies and biological research, can be studied morphologically and metrically. Geometric morphometry compares body forms using specific landmarks determined by anatomical prominences. The aim of this study was to identify cranial shape differences between the crania of Byzantium period humans and modern humans. Variability in cranial shape was examined using the geometric morphometric technique based on landmark coordinates. Landmark coordinate data were collected from two-dimensional digital photogrammetry and were analyzed using generalized Procrustes analysis, hierarchical clustering and thin-plate spline analysis.


A rationalization of the solvent effect on the Diels-Alder reaction in ionic liquids using multiparameter linear solvation energy relationships.
The Diels-Alder reaction between cyclopentadiene and three dienophiles (acrolein, methyl acrylate and acrylonitrile) having different hydrogen bond acceptor abilities has been carried out in several ionic liquids and molecular solvents in order to obtain information about the factors affecting reactivity and selectivity. The solvent effects on these reactions are examined using multiparameter linear solvation energy relationships. The collected data provide evidence that the solvent effects are a function of both the solvent and the solute. For a solvent effect to be seen, the solute must have a complimentary character; selectivities and rates are determined by the solvent hydrogen bond donation ability (alpha) in the reactions of acrolein and methyl acrylate, but not of acrylonitrile.


Protection of digital health information: Examining guidance from the physician regulatory colleges in Canada.
The use of information and communication technology (ICT) has tremendous potential to enhance communication among physicians, leading to improvements in service delivery. However, the protection of health information in digital/electronic format is an ongoing concern. The purpose of this study was to examine guidance for the protection of health information when using ICT from all 10 of Canada's provincial regulatory colleges for physicians and to discuss the potential policy and service delivery implications. A search of the regulatory college websites was conducted, followed by a document analysis (content and thematic). The college website search identified 522 documents; 12 of these documents (from 8 of the 10 colleges) met the study criteria. These documents were notable for the considerable variation in the scope and detail of guidance provided across the colleges. While the federal-provincial division of powers in Canada enables different jurisdictional approaches to health service delivery and, thus, opportunities for policy learning, this governing structure may also contribute to a lack of incentive for collaboration, leading to an absence of standardised guidance for health information protection when using ICT. This, in turn, may result in unequal and inequitable protection of health information across the provinces. Therefore, a macro-level approach to policy development in this area may hold the greatest promise for enhancing the protection of health information and doing so in a more standardised manner in countries with federal systems of governance.


Long-Term In Vivo Monitoring of Adult-Derived Human Liver Stem/Progenitor Cells by Bioluminescence Imaging, Positron Emission Tomography, and Contrast-Enhanced Computed Tomography.
Adult-derived human liver stem/progenitor cells (ADHLSCs) have the potential to alleviate liver injury. However, the optimal delivery route and long-term biodistribution of ADHLSCs remain unclear. In this article, we used a triple fusion reporter system to determine the kinetic differences in the biodistribution of ADHLSCs following intrasplenic (IS) and intrahepatic (IH) administration in severe combined immunodeficiency/beige mice. ADHLSCs were transduced with a lentiviral vector expressing a triple fusion reporter comprising renilla luciferase, monomeric red fluorescent protein, and truncated HSV-1 thymidine kinase. The stability and duration of the transgenes, and the effects of transduction on the cell properties were evaluated in vitro. The acute retention and long-term engraftment in vivo were revealed by positron emission tomography and bioluminescence imaging (BLI), respectively, followed by histochemical analysis. We showed that ADHLSCs can be safely transduced with the triple fusion reporter. Radiolabeled ADHLSCs showed acute cell retention at the sites of injection. The IH group showed a confined BLI signal at the injection site, while the IS group displayed a dispersed distribution at the upper abdominal liver area, and a more intense signal. In conclusion, ADHLSCs could be monitored by BLI for up to 4 weeks with a spread out biodistribution following IS injection.


Early versus delayed emergency department presentation following mild Traumatic Brain Injury and the presence of symptom at 1, 4 and 12 weeks in children.
We evaluated the association between timing of presentation and postconcussive symptoms (PCS) at 1, 4 and 12 weeks after injury. This was a secondary analysis of a prospective cohort study conducted in nine Canadian paediatric EDs in 2013-2015 (5P study). Participants were children who suffered a head injury within the preceding 48 hours and met Zurich consensus concussion diagnostic criteria. The exposure was the time between head injury and ED presentation. The primary outcome was the presence of PCS at 1 week defined by the presence of at least three symptoms on the Post-Concussion Symptom Inventory (PCSI). Secondary outcomes evaluated PCS at 4 and 12 weeks. Multivariable logistic regression analyses were adjusted for ED PCSI and other potential confounders. There were 3041 patients with a concussion in which timing of the injury was known. 2287 (75%) participants sought care in the first 12 hours, 388 (13%) 12-24 hours after trauma and 366 (12%) between 24 and 48 hours. Compared with children who sought care >24 hours after trauma, children who sought care in the first 12 hours had a significantly lower incidence of PCS at 1 week (OR: 0.55 (95% CI 0.41 to 0.75)) and 4 weeks (OR: 0.74 (95% CI 0.56 to 0.99)) but not at 12 weeks (OR: 0.88 (95% CI 0.63 to 1.23)). Patients who present early after a concussion appear to have a shorter duration of PCS than those presenting more than 12 hours later. Patients/families should be informed of the higher probability of PCS in children with delayed presentation.


Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot Study.
Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.


Foldable structures and the natural design of pollen grains.
Upon release from the anther, pollen grains of angiosperm flowers are exposed to a dry environment and dehydrate. To survive this process, pollen grains possess a variety of physiological and structural adaptations. Perhaps the most striking of these adaptations is the ability of the pollen wall to fold onto itself to prevent further desiccation. Roger P. Wodehouse coined the term harmomegathy for this folding process in recognition of the critical role it plays in the survival of the pollen grain. There is still, however, no quantitative theory that explains how the structure of the pollen wall contributes to harmomegathy. Here we demonstrate that simple geometrical and mechanical principles explain how wall structure guides pollen grains toward distinct folding pathways. We found that the presence of axially elongated apertures of high compliance is critical for achieving a predictable and reversible folding pattern. Moreover, the intricate sculpturing of the wall assists pollen closure by preventing mirror buckling of the surface. These results constitute quantitative structure-function relationships for pollen harmomegathy and provide a framework to elucidate the functional significance of the very diverse pollen morphologies observed in angiosperms.


Membrane-associated antigens of herpes simplex virus.
A brief overview is presented concerning the membrane-associated antigens of herpes simplex viruses (HSV). Aspects discussed include certain properties and functional roles of the HSV-specific glycoproteins. In addition, recent findings of an association between certain immediate-early proteins of HSV-1 and the tegument of virions as well as the plasma membrane of virus-infected cells are discussed.


Liver response to diet and estrogen in white Leghorn and Rhode Island Red chickens.
Experiments were conducted to compare the response of Rhode Island Reds (RIR) and White Leghorns (WL) to estradiol (E2) administration and diets of different composition. In growing chickens injected with E2 for 7 days, RIR accumulated significantly more hepatic lipid and had significantly less plasma lipid than WL. Both RIR and WL, injected for 4 days with E2, had lower hepatic lipids when fed a diet containing fish meal, alfalfa meal, and torula yeast (FAY) than when fed a corn-soybean meal diet (CS). Plasma glutamic oxaloacetic transaminase activity was significantly lower for RIR. Feeding a FAY diet to laying hens significantly reduced hepatic lipids in WL but not in RIR. Implantation of tubes containing E2 in RIR-laying hens resulted in a significant body weight loss and 25% mortality, while a similar treatment in WL-laying hens caused no body weight loss or mortality. Injecting both RIR and WL-laying hens with E2 caused a marked body weight loss and high mortality in both breeds although WL were less severely affected. The results show that breeds of chickens respond differently to both E2 administration and changes in diet composition.


Ultrasound-guided transvaginal ovarian needle drilling for clomiphene-resistant polycystic ovarian syndrome in subfertile women.
Ovulatory disturbance is a key diagnostic feature of polycystic ovarian syndrome (PCOS), leading to infertility and correspondingly heavy disease burden. Many therapeutic strategies have been used to induce ovulation for women with PCOS who are infertile. Ultrasound-guided transvaginal ovarian needle drilling (UTND) is a novel surgical method used to induce ovulation for women with clomiphene-resistant PCOS at the outpatients clinic. Nevertheless, the quality in most of the studies seemed low, and the safety and efficacy of UTND is still uncertain. To evaluate the efficacy and safety of UTND for subfertile women with clomiphene-resistant PCOS. We searched the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, and six other databases to November 2018. We checked conference abstracts from the 2018 ESHRE, reference lists, and clinical trials registries. We contacted experts and specialists in the field. We included randomised controlled trials (RCTs) comparing UTND to laparoscopic ovarian drilling (LOD), and UTND combined with gonadotropins to gonadotropins alone for women of reproductive age with clomiphene-resistant PCOS and infertility. Two review authors independently screened appropriate trials for inclusion, assessed methodological quality and risk of bias, and extracted data. The primary outcomes were live birth rate and incidence of surgical complications (bleeding and infection). We included ovarian hyperstimulation syndrome (OHSS) as a secondary outcome. Meta-analyses could only be conducted for the secondary outcomes pregnancy rate and ovulation rate in the comparison of UTND versus LOD using a random-effect model. We calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous data. We assessed the overall quality of the evidence by applying GRADE criteria. We included five trials involving 639 clomiphene-resistant women with PCOS. Three studies compared UTND with LOD, and two compared UTND combined with gonadotropins with gonadotropins alone. The evidence was of low to very low quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency resulting from heterogeneity, imprecision induced by limited sample size, and lack of reporting of clinically relevant outcomes such as live birth and surgical complications.UTND versus LODNo studies reported on the main outcome live birth. One study reported on surgical complications; however, the evidence for this outcome was of very low quality because it was based on one study with small sample size and there were no events in either arm. Thus, we are uncertain whether there is any difference in surgical complications between UTND and LOD.We are also uncertain whether there is any difference in pregnancy rate when comparing UTND with LOD (OR 0.54, 95% CI 0.28 to 1.03; I2 = 56%; 3 RCTs, n = 473; very-low quality evidence). UTND may lead to a slight decrease in ovulation rate when compared to LOD (OR 0.66, 95% CI 0.45 to 0.97; I2 = 0%; 3 RCTs, n = 473; low-quality evidence). This suggests that among clomiphene-resistant women with PCOS using LOD with an expected ovulation rate of 69.5%, the ovulation rate among women using UTND may be between 50.6% and 68.8%No studies reported on the outcomes OHSS and multiple pregnancy. There was also insufficient evidence to reach a conclusion regarding miscarriage as there was only one study of very low quality.UTND combined with gonadotropins versus gonadotropins aloneNo studies reported on the main outcomes live birth and incidence of surgical complications. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, we are uncertain whether there is any difference in these outcomes for women with clomiphene-resistant PCOS using UTND combined with gonadotropins as compared with gonadotropins. Based on very low-quality evidence, It is uncertain whether there is any difference in pregnancy rate, incidence of surgical complications, and miscarriage rate between UTND and LOD in women with clomiphene-resistant PCOS. UTND may lead to a slight decrease in ovulation rate when compared to LOD. No studies reported on the outcomes live birth rate, incidence of OHSS, and multiple pregnancy rate. No studies reported on the main outcomes live birth and surgical complications for the comparison UTND combined with gonadotrophins versus gonadotrophins alone. The evidence for the outcomes OHSS, pregnancy, ovulation, miscarriage, and multiple pregnancy in this comparison was of very low quality. Thus, it is unclear if there is a difference in any of the outcomes between UTND combined with gonadotrophins versus gonadotrophins alone.


Effects of long-term release GnRH agonist "deslorelin" on testicular HSP expression, accessory sex glands and testicular functions in adult male rats.
The objective of the present was to determine the effect of long-term release GnRH agonists "deslorelin" on suppression and restoration of testicular and accessory sex glands functions, and expression of HSP in testes of adult male rats. A group of twenty-eight male rats and fifty-six female rats were kept for eleven months. The male rats were subdivided into treatment (n = 18; deslorelin, an analogue of GnRH, 4.7 mg, S.C; six months) and control (n = 10; untreated), and the adult female rats were introduced with either treatment or control male rats at the 2nd, 6th and 11th months post implant insertion. At 6th month of deslorelin implants insertion, six male rats from treatment and five rats from control group were sacrificed. The remaining (twelve treatment and five control) male rats were sacrificed at 11 months. The testicular dimension were measured monthly in both treatment and control rats. The blood samples were collected for testosterone and HSP70 antibody, whereas, the testes and accessory glands were isolated for histological examination at each sacrificial time. The results showed that testicular dimension were significantly lesser in treatment group until 9 months post treatment. HSP70 protein expression was negligible at 6 months in treatment group but its intensity increased in spermatids 11 months of treatment similar to control group. Significantly lower testosterone concentrations with poor semen quality, and smaller litter size were observed in treatment group. The histological picture of accessory sex glands and seminiferous tubules shown a variable integrity in treatment group than control at 6 months implant insertion. In conclusion, the subcutaneous application of 4.7 mg of the GnRH-analogue deslorelin represents a practicable, like in the female rats, method to suppress testicular, accessory sex glands functions, testicular HSP expression and fertility in male rats. Moreover, the suppressive effects of deslorelin, continued until 11th months after removal of the implant.


The epiphyseal scar: changing perceptions in relation to skeletal age estimation.
It is imperative that all methods applied in skeletal age estimation and the criteria on which they are based have a strong evidential basis. The relationship between the persistence of epiphyseal scars and chronological age, however, has remained largely untested. To assess the relationships between the level of persistence of the epiphyseal scar and chronological age, biological sex and side of the body in relation to the interpretation of epiphyseal scars in methods of skeletal age estimation. A sample of radiographic images was obtained from the Tayside NHS Trust, Ninewells Hospital, Dundee, UK. This included images of four anatomical regions from living female and male individuals aged between 20-50 years. Some remnant of an epiphyseal scar was found in 78-99% of individuals examined in this study. The level of persistence of epiphyseal scars was also found to vary between anatomical regions. The overall relationship between chronological age and the level of persistence or obliteration of the epiphyseal scar was found to be of insufficient strength to support a causative link. It is, therefore, necessary that caution is employed in their interpretation in relation to skeletal age estimation practices.


Effects of an injectable trace mineral supplement on first-service conception rate of dairy cows.
A total of 825 dairy cows from a commercial dairy farm in central California were used to evaluate effects of one or 2 doses of an injectable trace mineral supplement containing 20 mg/mL of zinc, 20 mg/mL of manganese, 5 mg/mL of selenium, and 10 mg/mL of copper on first-service conception rate. Cows were randomly allocated into treatment or control group to either a single dose (experiment 1) or a double dose (experiment 2) of injected supplement. Allocation was based on days in lactation for experiment 1 and the length of gestation periods for experiment 2. In experiment 1, cows 38 to 45 d in lactation (n = 190) received a single dose of 5 mL of injected supplement. Similar cows were used as controls (n = 227). In experiment 2, cows and pregnant heifers received an initial injection of 5 mL of the mineral supplement from 2 to 3 wk precalving (n = 186). An equal dose was repeated 38 to 45 d in lactation. A similar group of cows and pregnant heifers served as controls for experiment 2 (n = 222). Health and reproductive events postcalving were recorded. In experiment 1, the odds of first-service conception were not significantly different for cows receiving a one-dose regimen of minerals compared with untreated control cows; conception rates were 26.8 and 27.5% for experiment 1 treatment and control groups, respectively. In experiment 1, the odds of first-service conception were significantly lower (odds ratio = 0.66) for cows and heifers given the 2-dose regimen of minerals compared with untreated controls; overall conception rates were 21.5 and 31.5% for experiment 2 treatment and control groups, respectively. In this intensively managed dairy herd, a single dose of injected trace minerals before breeding had no beneficial effects on first-service conception rate. However, dairy cows receiving a dose of trace minerals before calving and another dose before breeding had lower conception at first service.


Examining characteristics of congregation members willing to attend health promotion in African American churches.
Although churches are an important partner for improving health within the African American community, it is not known how congregants are best reached by health promotion activities and thus how best to target members in recruitment. This study examined how characteristics of churches and congregants' beliefs and interests in faith-based health promotion related to their willingness to attend church-based health promotion activities. We surveyed adult congregants (n = 1,204) of 11 predominately African American churches in North Carolina. Surveys collected data within four domains: demographics (age, sex, education), behavioral (church attendance, respondent food choices, and physical activity), cognitive (church-based health promotion belief, Bible-based healthy living interest, healthy living resource interest), or environmental (family health, church travel distance, church health ministry activity, church members' food choices). Analyses used a dichotomous outcome, interest in attending programs offered by the health ministry. Domain-specific models were constructed. Logistic generalized estimating equations adjusted for clustering. Of the 1,204 congregants, 72% were female, 57% were 50 years or older, 84% had a high school education or more, and 77% had a chronic health condition. In bivariate analyses and in models adjusting for all four domains, cognitive factors had the highest odds of willingness to attend. Congregants' belief in the church's role in health promotion and their desire to learn about healthy behaviors highlight the role of the African American church as a partner in addressing health disparities and the need to capitalize on this expectation through stronger partnerships between medical and faith communities.


Photostability of natural orange-red and yellow fungal pigments in liquid food model systems.
The variation in the photostability among the currently authorized natural pigments limits their application span to a certain type of food system, and more robust alternatives are being sought after to overcome this problem. In the present study, the photostability of an orange-red and a yellow fungal pigment extract produced by ascomycetous fungi belonging to the genera Penicillium and Epicoccum , respectively, were studied in a soft drink model medium and in citrate buffer at low and neutral pH. The quantitative and qualitative color change pattern of the fungal pigment extracts indicated an enhanced photostability of fungal pigment extracts compared to the commercially available natural colorants Monascus Red and turmeric used as controls. Yellow components of the orange-red fungal pigment extract were more photostable than the red components. Chemistry of the photodegradation of the orange-red pigment extract was studied by high-performance liquid chromatography-diode array detection-mass spectrometry (HPLC-DAD-MS), and a light-induced formation of a structural analogue of sequoiamonascin C, a Monascus -like polyketide pigment discovered in the extract of Penicillium aculeatum IBT 14263 on yeast extract sucrose (YES) medium, was confirmed in the soft drink medium at pH 7.


In vitro toxicology of respirable Montserrat volcanic ash.
In July 1995 the Soufriere Hills volcano on the island of Montserrat began to erupt. Preliminary reports showed that the ash contained a substantial respirable component and a large percentage of the toxic silica polymorph, cristobalite. In this study the cytotoxicity of three respirable Montserrat volcanic ash (MVA) samples was investigated: M1 from a single explosive event, M2 accumulated ash predominantly derived from pyroclastic flows, and M3 from a single pyroclastic flow. These were compared with the relatively inert dust TiO(2) and the known toxic quartz dust, DQ12. Surface area of the particles was measured with the Brunauer, Emmet, and Teller (BET) adsorption method and cristobalite content of MVA was determined by x ray diffraction (XRD). After exposure to particles, the metabolic competence of the epithelial cell line A549 was assessed to determine cytotoxic effects. The ability of the particles to induce sheep blood erythrocyte haemolysis was used to assess surface reactivity. Treatment with either MVA, quartz, or titanium dioxide decreased A549 epithelial cell metabolic competence as measured by ability to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). On addition of mannitol, the cytotoxic effect was significantly less with M1, quartz, and TiO(2). All MVA samples induced a dose dependent increase in haemolysis, which, although less than the haemolysis induced by quartz, was significantly greater than that induced by TiO(2). Addition of mannitol and superoxide dismutase (SOD) significantly reduced the haemolytic activity only of M1, but not M2 or M3, the samples derived from predominantly pyroclastic flow events. Neither the cristobalite content nor the surface area of the MVA samples correlated with observed in vitro reactivity. A role for reactive oxygen species could only be shown in the cytotoxicity of M1, which was the only sample derived from a purely explosive event. These results suggest that in general the bioreactivity of MVA samples in vitro is low compared with pure quartz, but that the bioreactivity and mechanisms of biological interaction may vary according to the ash source.


Sodium transport during the natriuresis of volume expansion; a study using peripheral blood leucocytes.
1. Leucocyte sodium transport was investigated as a possible assay for the small molecular weight natriuretic material isolated from the urine of normal subjects who had undergone volume expansion by saline infusion. 2. This fraction (fraction four or FIV), inhibitory to sodium transport in several other assays, was also found to inhibit leucocyte sodium transport. 3. FIV isolated from the urine of five normal subjects undergoing the natriuresis of mineralocorticoid 'escape' was also found to be inhibitory to leucocyte sodium transport. 4. Leucocytes isolated from the blood of the same subjects during mineralocorticoid escape showed decreased sodium transport.


Von Willebrand factor:antigen and ADAMTS-13 level, but not soluble P-selectin, are risk factors for the first asymptomatic deep vein thrombosis in cancer patients undergoing chemotherapy.
There is a high incidence of deep vein thrombosis (DVT) among cancer patients undergoing chemotherapy. Chemotherapy-induced vascular endothelial cell activation (VECA) is characterized by increased plasma levels of von Willebrand factor (vWF) and soluble P-selectin (sP-selectin), leading to the activation of endothelial cells and signaling cascades. The biological role of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS-13) is to control the activity of vWF and consequently the risk of thrombosis. The objective of this study was to investigate the roles of sP-selectin, vWF, and ADAMTS-13 as risk factors for the first episode of DVT in cancer patients undergoing chemotherapy. This prospective cohort study was conducted at Dr. Kariadi Hospital, Indonesia, on 40 cancer patients. Prechemotherapy (baseline) and postchemotherapy sP-selectin, vWF antigen (vWF:Ag), and ADAMTS-13 plasma levels were determined with ELISAs before and 3 months after chemotherapy. The clinical characteristics of the patients, cancer type, cancer stage, chemotherapy regimen, ABO blood type, D-dimer level and Khorana risk score were also analyzed using logistic regression. Patients were observed for the possibility of developing DVT during chemotherapy. DVT was confirmed in 5 patients (12.5%) after a period of 3 months. In patients with DVT, sP-selectin and vWF were significantly higher while ADAMTS-13 was lower than in their counterparts. The levels of baseline vWF:Ag and ADAMTS-13, with cut-off points ≥ 2.35 IU/mL and ≤ 1.03 IU/mL, respectively, were found to independently predict the incidence of DVT. In the multivariate logistic regression analysis, the relative risk (RR) for DVT in patients with high vWF:Ag was 3.80 (95% CI 1.15-12.48, p = 0.028), and that for patients with low ADAMTS-13 was 2.67 (95% CI 1.22-23.82, p = 0.005). The vWF:Ag/ADAMTS-13 ratio and both vWF:Ag and ADAMTS-13 dynamics during treatment were also able to differentiate those with prospective DVT. However, sP-selectin and other covariates showed no statistical significance. We found that prechemotherapy plasma levels of vWF:Ag ≥ 2.35 IU/mL and ADAMTS-13 ≤ 1.03 IU/mL are independent risk factors for DVT incidence among cancer patients.


Clostridium difficile associated diarrhoea in hospitalised patients: onset in the community and hospital and role of flexible sigmoidoscopy.
Clostridium difficile associated diarrhoea (CDAD) is a hospital acquired infection in which optimal methods for diagnosis and the scale of the problem in the community remain to be determined. In hospitalised patients with CDAD, we aimed to (i) study patients in whom the onset of diarrhoea was in the community and (ii) investigate the role of bedside flexible sigmoidoscopy in diagnosis. Patients with CDAD (onset in hospital or community) were studied prospectively. In those with diarrhoea of unknown aetiology, flexible sigmoidoscopy was compared with stool assay for C difficile cytotoxin. Of 136 patients with CDAD (which was associated with antibiotic exposure in 96%), diarrhoea started in the community in 38 (28%; majority in own home) and while an inpatient in 98 (72%). The majority with CDAD onset in the community had been hospitalised over the preceding 12 months (86.8% v 57.1% in the hospital onset group; p<0.001). In 56 patients with pseudomembranous colitis at sigmoidoscopy, the stool C difficile cytotoxin test was negative in 29 (52%) but toxigenic C difficile was isolated from all of nine stool samples cultured. Of patients with pseudomembranous colitis, 30.4% relapsed over the subsequent 57.7(4.2) days. In a significant proportion of hospitalised patients with CDAD, diarrhoea started in the community. However, the majority of these had been hospital inpatients previously when they may have acquired C difficile, with the subsequent onset of diarrhoea in the community following exposure to antibiotics. Flexible sigmoidoscopy is superior to the stool C difficile cytotoxin test in a subgroup of patients with pseudomembranous colitis. Sigmoidoscopy should therefore be considered in all hospitalised patients with diarrhoea in whom the stool test for C difficile cytotoxin and enteric pathogens is negative.


Implementation of Digital Image Analysis in Assessment of Ki67 Index in Breast Cancer.
The clinical utility of the proliferation marker Ki67 in breast cancer treatment and prognosis is an active area of research. Studies have suggested that differences in pre-analytic and analytic factors contribute to low analytical validity of the assay, with scoring methods accounting for a large proportion of this variability. Use of standard scoring methods is limited, in part due to the time intensive nature of such reporting protocols. Therefore, use of digital image analysis tools may help to both standardize reporting and improve workflow. In this study, digital image analysis was utilized to quantify Ki67 indices in 280 breast biopsy and resection specimens during routine clinical practice. The supervised Ki67 indices were then assessed for agreement with a manual count of 500 tumor cells. Agreement was excellent, with an intraclass correlation coefficient of 0.96 for the pathologist-supervised analysis. This study illustrates an example of a rapid, accurate workflow for implementation of digital image analysis in Ki67 scoring in breast cancer.


Red blood cell surface adhesion molecules: their possible roles in normal human physiology and disease.
Human erythrocytes express a relatively large number of known adhesion receptors, despite the fact that red blood cells (RBCs) are generally considered to be nonadhesive for endothelial cell surfaces. Some of these adhesion receptors are expressed by many other tissues, while others have more limited tissue distribution. Some adhesion receptors, including CD36 and VLA-4, are only expressed by immature erythroid cells, while others are present on mature erythrocytes. The structure and function of these proteins is reviewed here. LW, CD36, CD58, and CD147 have been shown in other tissues to mediate cell-cell interaction. Other receptors, such as CD44, VLA-4, and B-CAM/LU, can mediate adhesion to components of extracellular matrix. In addition, their roles in normal erythropolesis, as well as in the pathophysiology of human disease, are summarized. The most convincing evidence for a pathophysiologic role for any of these receptors on erythrocytes comes from studies of cells from patients homozygous for hemoglobin S, as RBC adhesion is thought to contribute to vaso-occlusion. Thus, receptors such as B-CAM/LU may become targets for future therapy aimed at preventing or ameliorating this thrombotic process.


Detection of hepatitis B virus in bone allografts from donors with occult hepatitis B infection.
The implementation of nucleic acid testing in donor screening has improved the safety of tissue allografts. Although infectious disease transmission can be considered a rare event, the detection of occult hepatitis B infection remains challenging. The studies concerning this risk are mainly based on testing blood specimens. This work shows the correlation between results of samples obtained from donor blood and the corresponding tissue washing solution. Hepatitis B virus deoxyribonucleic acid was detected both in bone allografts from donors with serological profiles associated to active hepatitis B infection and occult hepatitis B infection. These results suggest that hepatitis B virus seems to concentrate in bone marrow even when a low viral load is present in peripheral blood. Even detection at molecular level is not enough to avoid the risk of hepatitis B virus transmission and a multiparametrical evaluation is required in tissue donor screening. The role of clinicians in recognition and reporting of allograft-associated infections is a major concern for the acquisition of experience to be applied in risk control of disease transmission.


Applying the partitioned multiobjective risk method (PMRM) to portfolio selection.
The analysis of risk-return tradeoffs and their practical applications to portfolio analysis paved the way for Modern Portfolio Theory (MPT), which won Harry Markowitz a 1992 Nobel Prize in Economics. A typical approach in measuring a portfolio's expected return is based on the historical returns of the assets included in a portfolio. On the other hand, portfolio risk is usually measured using volatility, which is derived from the historical variance-covariance relationships among the portfolio assets. This article focuses on assessing portfolio risk, with emphasis on extreme risks. To date, volatility is a major measure of risk owing to its simplicity and validity for relatively small asset price fluctuations. Volatility is a justified measure for stable market performance, but it is weak in addressing portfolio risk under aberrant market fluctuations. Extreme market crashes such as that on October 19, 1987 ("Black Monday") and catastrophic events such as the terrorist attack of September 11, 2001 that led to a four-day suspension of trading on the New York Stock Exchange (NYSE) are a few examples where measuring risk via volatility can lead to inaccurate predictions. Thus, there is a need for a more robust metric of risk. By invoking the principles of the extreme-risk-analysis method through the partitioned multiobjective risk method (PMRM), this article contributes to the modeling of extreme risks in portfolio performance. A measure of an extreme portfolio risk, denoted by f(4), is defined as the conditional expectation for a lower-tail region of the distribution of the possible portfolio returns. This article presents a multiobjective problem formulation consisting of optimizing expected return and f(4), whose solution is determined using Evolver-a software that implements a genetic algorithm. Under business-as-usual market scenarios, the results of the proposed PMRM portfolio selection model are found to be compatible with those of the volatility-based model. However, under extremely unfavorable market conditions, results indicate that f(4) can be a more valid measure of risk than volatility.


Rats discriminate individual cats by their odor: possible involvement of the accessory olfactory system.
Social behavior in mammals often relies upon the discrimination of same-species individuals via olfactory processing of unique chemosensory signatures. The ability to identify individuals from a different species by their odor (heterospecific discrimination) is less well documented. Here we used a habituation-dishabituation paradigm to demonstrate that rats can discriminate individual cats by their odor. Rats were repeatedly exposed to a collar previously worn by a domestic cat. Strong initial defensive responses (hiding in a small box and vigilant "head out" behavior from the box entrance) habituated with repeated exposure to the same collar. Brain activation following repeated presentation of the same odor - as indexed by c-Fos expression - also habituated in accessory olfactory regions (mitral and granular layers of the posterior accessory olfactory bulb and posteroventral medial amygdala), as well as regions involved in defensive behavior, including the ventromedial and dorsal premammillary hypothalamic nuclei, basolateral amygdala and periaqueductal grey. When a collar taken from a different cat was presented to habituated rats, defensive responses (hiding, vigilance, suppression of grooming) were dishabituated, and c-Fos expression was reinstated in the accessory olfactory system and in defense-related hypothalamic, amygdaloid and brainstem nuclei. Results indicate that rats may process and store details of the chemosensory signatures of individual predators using the accessory olfactory system.


The effect of selective head-neck cooling on physiological and cognitive functions in healthy volunteers.
In general, brain temperatures are elevated during physical sporting activities; therefore, reducing brain temperature shortly after a sports-related concussion (SRC) could be a promising intervention technique. The main objective of this study was to examine the effects of head and neck cooling on physiological and cognitive function in normal healthy volunteers. Twelve healthy volunteers underwent two different sessions of combined head and neck cooling, one session with a cold pack and one session with a room temperature pack. Physiological measurements included: systolic/diastolic blood pressure, pulse oximetry, heart rate, and sublingual and tympanic temperature. Cognitive assessment included: processing speed, executive function, and working memory tasks. Physiological measurements were taken pre-, mid- and post-cooling, while cognitive assessments were done before and after cooling. The order of the sessions was randomized. There was a significant decrease in tympanic temperature across both sessions; however more cooling occurred when the cold pack was in the device. There was no significant decrease in sublingual temperature across either session. The observed heart rates, pulse oximetry, systolic and diastolic blood pressure during the sessions were all within range of a normal healthy adult. Cognitive assessment remained stable across each session for both pre- and post-cooling. We propose that optimizing brain temperature management after brain injury using head and neck cooling technology may represent a sensible, practical, and effective strategy to potentially enhance recovery and perhaps minimize the subsequent short and long term consequences from SRC.


Children within the juvenile justice system in Nigeria: psychopathology and psychosocial needs.
Many children in Nigeria face a life of poverty, family instability, inadequate educational opportunities and poor physical and mental health which hinder their ability to develop into healthy adults, live an improved quality of life or fulfil their life aspirations. These factors have also been associated with juvenile delinquency and need for institutional care. As a step toward providing comprehensive services for incarcerated children in Nigeria, this study aimed to identify the psychosocial needs as well as types of psychopathology among a group of incarcerated children at the Ibadan remand home. A cross-sectional survey of children and adolescents at the Ibadan remand home was carried out using a semi-structured questionnaire. A total of 59 children were assessed over a one year period. Majority (90%) were in need of care and protection. All (100%) had significant psychosocial needs presenting as difficulty with their primary support, economic, social environment, or educational systems. Majority (97%) also demonstrated significant psychopathology and anxiety, suicidal and depressive symptoms were the most commonly elicited. Incarcerated children in this study showed significant mental health needs which need to be addressed as a matter of urgency. This should be carried out through the collaborative efforts of mental health professionals with various stakeholders in child care.


A Transcription and Translation Protocol for Sensitive Cross-Cultural Team Research.
Assurance of transcript accuracy and quality in interview-based qualitative research is foundational for data accuracy and study validity. Based on our experience in a cross-cultural ethnographic study of women's pelvic organ prolapse, we provide practical guidance to set up step-by-step interview transcription and translation protocols for team-based research on sensitive topics. Beginning with team decisions about level of detail in transcription, completeness, and accuracy, we operationalize the process of securing vendors to deliver the required quality of transcription and translation. We also share rubrics for assessing transcript quality and the team protocol for managing transcripts (assuring consistency of format, insertion of metadata, anonymization, and file labeling conventions) and procuring an acceptable initial translation of Spanish-language interviews. Accurate, complete, and systematically constructed transcripts in both source and target languages respond to the call for more transparency and reproducibility of scientific methods.


Pathology Training for Cancer Diagnosis in Africa.
In response to requests for training in cancer pathology, two virtual training courses were organized: one in English for participants in Nigeria and another in French for participants in Francophone Africa. Each course had weekly 90-minute sessions covering essential topics in cancer pathology led by global experts. Two research questions were investigated for both courses: (1) did the participants improve their knowledge of the topics covered during the course, and (2) did the course participants appreciate the virtual training format? The Nigeria course enrolled 85 participants from 26 Nigerian states; the Francophone Africa course enrolled 425 participants from 18 African countries. In the pre-post technical assessment, participants increased their scores on average by 3.4% (P > .05) in the Nigeria course and by 13.1% (P < .001) in the Francophone Africa course. On the postcourse survey, 95.8% of Nigerian respondents and 96.1% of Francophone African respondents reported being satisfied or very satisfied with the virtual format. Virtual training is a promising tool to improve cancer diagnosis in Africa, as the experience of the courses illustrates that participants appreciate the virtual format. Continued training is required to reinforce skills and enable participants to appropriately apply new knowledge to their daily practice.


Colchicine for the prevention of recurrent pericarditis.
The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, which occur in 15-32% of cases. It was recently found that viral infection has a major role, but in many cases the cause is unknown. The optimal method for prevention has not been fully established; accepted modalities include non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Based on the proven efficacy of colchicine in familial Mediterranean fever, several small and large-scale international clinical trials have shown the beneficial effect of colchicine therapy in preventing recurrent pericarditis. Indeed, colchicine-treated patients consistently display significantly fewer recurrences, longer symptom-free periods, and even when attacks occur they are weaker and shorter in nature. It was also found that pretreatment with corticosteroids substantially attenuates the efficacy of colchicine, as evidenced by significantly more recurrence episodes and longer therapy periods. Colchicine is a safe and effective modality for the treatment and prevention of recurrent pericarditis, especially as an adjunct to other modalities, since it provides a sustained benefit superior to all current modalities. The safety profile seems superior to other drugs such as corticosteroids and immunosuppressive drugs.


Synthesis of peptides by the solid-phase method. 6. Neurotensin, fragments, and analogues.
Neurotensin (NT) and 24 related compounds, including fragments or analogues modified at the C-terminal end of the parent molecule, have been prepared by the solid-phase method. After purification by cation-exchange chromatography, the compounds were characterized by thin-layer chromatography, amino acid analysis, elemental analysis, and high-pressure liquid chromatography. The stimulating effects of the peptides were evaluated in rat stomach strips, in isolated spontaneously beating atria of guinea pigs, and in the coronaries of perfused rat hearts. The differences between the biological activities of these compounds are discussed.


Posttransplant Intramuscular Injection of PLX-R18 Mesenchymal-Like Adherent Stromal Cells Improves Human Hematopoietic Engraftment in A Murine Transplant Model.
Late-term complications of hematopoietic cell transplantation (HCT) are numerous and include incomplete engraftment. One possible mechanism of incomplete engraftment after HCT is cytokine-mediated suppression or dysfunction of the bone marrow microenvironment. Mesenchymal stromal cells (MSCs) elaborate cytokines that nurture or stimulate the marrow microenvironment by several mechanisms. We hypothesize that the administration of exogenous MSCs may modulate the bone marrow milieu and improve peripheral blood count recovery in the setting of incomplete engraftment. In the current study, we demonstrated that posttransplant intramuscular administration of human placental derived mesenchymal-like adherent stromal cells [PLacental eXpanded (PLX)-R18] harvested from a three-dimensional in vitro culture system improved posttransplant engraftment of human immune compartment in an immune-deficient murine transplantation model. As measured by the percentage of CD45+ cell recovery, we observed improvement in the peripheral blood counts at weeks 6 (8.4 vs. 24.1%, p < 0.001) and 8 (7.3 vs. 13.1%, p < 0.05) and in the bone marrow at week 8 (28 vs. 40.0%, p < 0.01) in the PLX-R18 cohort. As measured by percentage of CD19+ cell recovery, there was improvement at weeks 6 (12.6 vs. 3.8%) and 8 (10.1 vs. 4.1%). These results suggest that PLX-R18 may have a therapeutic role in improving incomplete engraftment after HCT.


[Partial abolition of seasonal variations of testicular weight in rams by decreasing the photoperiod].
Under moderate latitudes all breeds of rams undergo seasonal variations in testicular weight with a maximum during summer under decreasing daylength ([1]-[4]). Similarly, in rams submitted to a 6-month artificial light regime [5] or to an alternation of long (16L:8D) and short (8L:16D) days [6] an increase in testicular weight occurred following a decrease in daylength and vice versa. However this effect is transitory, a phenomenon which can be referred as photorefractoriness. In the present study the influence of the period of the light cycle on variation in testicular weight in the ram was investigated. 4 groups of 6 adults Ile-de-France rams were submitted to artificial light cycles where the daylength varied between 8-16 hrs. and the period (T) was 6, 4, 3, or 2 months respectively (Groups T6, T4, T3, and T2). Testicular volume was measured fortnightly using an orchidometer, Variations in testicular volume were submitted to harmonic regression analysis following the model y(t)=mu + a sin(2(pi t/tau) + phi). Cyclic changes in testicular volume were seen with each light cycle, at least in groups T6, T4, and T3 (Fig.). Analysis (Table) showed that: (1) the coefficient of determination R2 was high in the groups (2) mean testicular volume has increased from 258 to 294 cm3 when the period of the light cycle decreased from 6 to 2 months; (3) conversely, the amplitude decreased from 66.5 to 26.5 cm3 as the period decreased; (4) maximal testicular volumes (mean plus amplitude) were similar in all groups (range: T4, 312,5-T6,324 cm3) while minima (mean less amplitude) differed significantly (P<0.000,1) between groups (range: T6 and T4 about 190, T2 267.5 cm3) and (50 th computed periods of testicular volumes cycles were almost identical to the imposed light cycles.(ABSTRACT TRUNCATED AT 250 WORDS)


Tyrosine nitration by peroxynitrite formed from nitric oxide and superoxide generated by xanthine oxidase.
Peroxynitrite (ONOO(-)) is a potent nitrating and oxidizing agent that is formed by a rapid reaction of nitric oxide (NO) with superoxide anion (O(2)). It appears to be involved in the pathophysiology of many inflammatory and neurodegenerative diseases. It has recently been reported (Pfeiffer, S., and Mayer, B. (1998) J. Biol. Chem. 273, 27280-27285) that ONOO(-) generated at neutral pH from NO and O(2) (NO/O(2)) was substantially less efficient than preformed ONOO(-) at nitrating tyrosine. Here we re-evaluated tyrosine nitration by NO/O(2) with a shorter incubation period and a more sensitive electrochemical detection system. Appreciable amounts of nitrotyrosine were produced by ONOO(-) formed in situ (2.9 micrometer for 5 min; 10 nm/s) by NO/O(2) flux obtained from propylamine NONOate (CH(3)N[N(O)NO](-) (CH(2))(3)NH(2)(+)CH(3)) and xanthine oxidase using pterin as a substrate in phosphate buffer (pH 7.0) containing 0.1 mm l-tyrosine. The yield of nitrotyrosine by this NO/O(2) flux was approximately 70% of that produced by the same flux of preformed ONOO(-) (2.9 micrometer/5 min). When hypoxanthine was used as a substrate, tyrosine nitration by NO/O(2) was largely eliminated because of the inhibitory effect of uric acid produced during the oxidation of hypoxanthine. Tyrosine nitration caused by NO/O(2) was inhibited by the ONOO(-) scavenger ebselen and was enhanced 2-fold by NaHCO(3), as would be expected, because CO(2) promotes tyrosine nitration. The profile of nitrotyrosine and dityrosine formation produced by NO/O(2) flux (2.9 micrometer/5 min) was consistent with that produced by preformed ONOO(-). Tyrosine nitration predominated compared with dityrosine formation caused by a low nanomolar flux of ONOO(-) at physiological concentrations of free tyrosine (<0.5 mm). In conclusion, our results show that NO generated with O(2) nitrates tyrosine with a reactivity and efficacy similar to those of chemically synthesized ONOO(-), indicating that ONOO(-) can be a significant source of tyrosine nitration in physiological and pathological events in vivo.


pH-Responsive copolymer assemblies for controlled release of doxorubicin.
pH-Responsive drug carriers have the potential to provide selective drug release at therapeutic targets including tumors and in acidic intracellular vesicles such as endosomes and lysosomes. We have developed a new approach to the design of acid-sensitive micelles by incorporating hydrophobic acetal groups on the core block of a micelle-forming block copolymer. Hydrolysis of the acetals at mildly acidic pH is designed to reveal polar groups on the core-forming block, thus changing its solubility and disrupting the micelle, triggering drug release. The anticancer drug doxorubicin (DOX) was encapsulated in these pH-sensitive micelles, and the acetal hydrolysis rates and DOX release rates were determined in the pH range of 4.0 to 7.4 and were compared to those of control systems. The micelle disruption was investigated by dynamic light scattering. The in vitro toxicities of the empty and DOX-loaded micelles were determined, and the intracellular fate of the encapsulated DOX was compared to free DOX using fluorescence confocal microscopy.


[Effect of callosotomy on frequency characteristics of neuronal activity in the parastriate cortex].
In acute experiments on anesthetized cats, neuronal activity in the parastriate cortex was studied. Character of distribution of the firing rate mean frequency and the total energy of firing during mono- and binocular stimulation prior to (89 neurons) and after (67 neurons) callosotomy, were estimated. The spontaneous neuronal activity prior to callosotomy was found to be much higher than after it. The light stimulation in intact corpus callosum enlarged the range of frequencies of the neuronal activity. During the stimulation, activity of the majority of neurons was focused in a narrow frequency range, i.e. the synchronization occurred. The total energy of neuronal reactions in intact corpus callosum was higher than after callosotomy. The relative reactivity of the neurons was increased after callosotomy.


Defining and redefining the nephron progenitor population.
It has long been appreciated that the mammalian kidney arises via reciprocal interactions between an epithelial ureteric epithelium and the surrounding metanephric mesenchyme. More recently, lineage tracing has confirmed that the portion of the metanephric mesenchyme closest to the advancing ureteric tips, the cap mesenchyme, represents the progenitor population for the nephron epithelia. This Six2(+)Cited1(+) population undergoes self-renewal throughout nephrogenesis while retaining the potential to epithelialize. In contrast, the Foxd1(+) portion of the metanephric mesenchyme shows no epithelial potential, developing instead into the interstitial, perivascular, and possibly endothelial elements of the kidney. The cap mesenchyme rests within a nephrogenic niche, surrounded by the stroma and the ureteric tip. While the role of Wnt signaling in nephron induction is known, there remains a lack of clarity over the intrinsic and extrinsic regulation of cap mesenchyme specification, self-renewal, and nephron potential. It is also not known what regulates cessation of nephrogenesis, but there is no nephron generation in response to injury during the postnatal period. In this review, we will examine what is and is not known about this nephron progenitor population and discuss how an increased understanding of the regulation of this population may better explain the observed variation in final nephron number and potentially facilitate the reinitiation or prolongation of nephron formation.


Nonligamentous problems of the athlete's knee.
Acute and chronic nonligamentous problems of the athlete's knee are outlined, emphasizing diagnosis and treatment. Most such problems can be managed by the family physician or general practitioner, and recommendations are made for the referral of more complex problems.


[Therapeutic efficacies of neticonazole (SS717) cream and solution in experimental cutaneous Candida albicans infection of guinea pigs].
The therapeutic efficacies of 1% neticonazole (SS717) cream and solution on experimental cutaneous Candida albicans infection produced in prednisolone-treated guinea pigs were compared with those of 1% bifonazole (BFZ). Active preparations or blank vehicles were applied once daily for 3 consecutive days starting 5 days postinfection. Therapeutic effects were assessed on the basis of viable counts recovered from the infected loci 9 days postinfection. In animals treated with SS 717 or BFZ cream, a significant mycological improvement was observed when compared to untreated controls. A significant therapeutic efficacy of a SS717 cream compared to cream vehicle was also noted, while there was no significant difference in the recovery of Candida between the untreated control group and the cream vehicle-treated groups. The mycological result of the SS717 solution treated group was significantly superior to those of the untreated control group, the solution vehicle-treated group and the BFZ solution-treated group. The treatment with a solution vehicle or a BFZ solution appeared to lower, though not to a significant level, viable counts at the infected loci. These results led us to the conclusion that both SS717 cream and solution preparations exhibited significantly superior activity to that of BFZ in experimental cutaneous candidasis of guinea pigs.


'I'm over the moon!': patient-perceived outcomes of hepatitis C treatment.
Understanding patient-perceived outcomes is crucial for assessing the effectiveness and acceptability of hepatitis C virus (HCV) treatment. This study aimed to explore patient-perceived outcomes of receiving direct-acting antivirals (DAAs). This study was a part of a mixed-methods case study of the Prince Charles Hospital program for improving access to HCV treatment in community settings. Data were collected using semi-structured interviews with nine patients who were in different stages of their treatment for HCV. The participants were recruited using purposive sampling. All interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Patients emphasised 'having more energy' when reporting improvements in their physical health following treatment. They also reported a newly developed sense of freedom and hope. Improved physical and mental health empowered them to start a healthy lifestyle and to practise self-protection from the risk of re-infection. Patients highlighted their desire to help other patients to receive treatment, which was connected to their experience of the services that they received and their perceived health outcomes. Patients expect and experience various outcomes that are related to the physical, psychological and social aspects of living with, and being cured of HCV. Emphasis on the short-term outcomes of receiving HCV treatment may improve HCV treatment uptake and adherence rates.


What makes silica toxic?
Published data suggest that particle charge could be related to its toxicity. Respirable particles containing silica were therefore collected in foundries and their charge measured. These particles carried high levels of positive charge that were related to low humidity. Incubating these particles with pulmonary macrophages from mice produced detectable activities of collagenase, a precursor of silicosis. These experiments confirm that the toxicity of silica particles is likely to be because of the positive charge they carry.


Discriminatory power of typing schemes based on Simpson's index of diversity for Neisseria gonorrhoeae.
Simpson's index of diversity was used to produce a single numerical value to compare the abilities of single or combined typing schemes to discriminate between unrelated isolates. This calculation was used to compare the discriminating power of auxotype and serovar determination and plasmid content analysis, either singly or in combination, for Neisseria gonorrhoeae isolates having different antimicrobial susceptibilities (i.e., antibiotic-susceptible isolates and those that produce penicillinase, carry plasmid-mediated resistance to tetracycline, have chromosomally mediated penicillin resistance, or both produce penicillinase and carry plasmid-mediated resistance to tetracycline). Plasmid content analysis and auxotype determination produced the lowest level of discrimination, while a combination of auxotype and serovar typing schemes generally provided higher levels of discrimination. Addition of plasmid content analysis to auxotype and serovar typing provided additional discrimination only with penicillinase-producing isolates. For isolates that carried plasmid-mediated resistance to tetracycline, isolates that were tetracycline resistant, isolates that both produced penicillinase and carried plasmid-mediated resistance to tetracycline, or isolates that had chromosomally mediated penicillin resistance, none of the typing methods produced high discriminatory indices, indicating that these isolates are probably derived from relatively few clones.


Redetermination of bis-(acetyl-acetonato-κ(2) O,O')(1,10-phenanthroline-κ(2) N,N')manganese(II).
In the crystal structure of the title compound, [Mn(C5H7O2)2(C12H8N2)], the Mn(2+) cation is coordinated by one bidentate 1,10-phenanthroline ligand and two acetyl-acetonate anions within a slightly distorted N2O4 octa-hedron. The asymmetric unit consists of one Mn(2+) cation situated on a twofold rotation axis, one half of a 1,10-phenanthroline ligand and one acetyl-acetonate anion. In comparison with the previous determination based on visually estimated intensities recorded on precession photographs, the current redetermination with image-plate data reveals bond lengths and angles with much higher precision.


[Hereditary ectopia lentis].
If not due to trauma, ectopia lentis is usually caused genetically. It is a main symptom of several syndromal disorders such as Marfan syndrome or homocystinuria. Also other connective tissue disorders convey an elevated risk for ectopia lentis. Isolated ectopia lentis is frequently caused by genetic alterations as well, most commonly due to mutations in ADAMTSL4. Depending on the molecular basis, the consequences for the management of patients may differ significantly: On the one hand, possible accompanying symptoms may require a specific surveillance and treatment. Also, the risk for other family members to develop ectopia lentis or accompanying symptoms can only be determined if the genetic cause and thus inheritance pattern are known. This review describes the different types and genetic causes of syndromal and isolated ectopia lentis as well as possible consequences for the patients; also it presents a sensible algorithm for the molecular diagnostic approach.


Combination of Calcium Hydroxylapatite Diluted With Normal Saline and Microfocused Ultrasound With Visualization for Skin Tightening.
Background/Objectives: Treatment options for the correction of age-related changes in skin include the use of energy-based devices and dermal fillers. In this study, we evaluate the clinical efficacy and tolerability of microfocused ultrasound with visualization (MFU-V) and injectable calcium hydroxylapatite (CaHA) filler diluted with normal saline, for the correction of age-related changes and to assess patients' satisfaction with this combination therapy. Methods: This was a randomized, split-face, comparative clinical study and immunohistochemical analysis in 20 subjects with indications for lower face, neck and décolleté lifting. Over five visits, CaHA diluted with normal saline (1:2) was injected subdermally in the lower third of the face, neck and décolleté, and lower abdominal quadrant. MFU-V was performed on the lower third of the face, neck, and décolleté, and the right lower abdominal quadrant. Results: Upon baseline examination, the age-related changes were quantified as follows: marionette lines score 2.47 ± 0.8, jawline contour score 2.2 ± 0.7 and neck score 2.1 ± 0.7 points; and after 15 months, they changed to 1.8 ± 0.7 (P≤0.00003), 1.89 ± 0.56 (P≤0.005), and 1.7 ± 0.6 (P≤0.005) points, respectively. The procedures were well tolerated, and subject satisfaction was high. Conclusions: The injections of CaHA in combination with MFU-V treatment stimulated neoangiogenesis, led to the increased synthetic activity of cells, a marked increase in collagen and elastin fibers, and remodeling of both the superficial and deep layers of the dermis. An improvement in the severity of age-related changes was observed in all areas studied. J Drugs Dermatol. 2020;19(4):405-411. doi:10.36849/JDD.2020.4625.