Clearance of osteocalcin in adults with end-stage renal disease undergoing CAPD.
Osteocalcin (OC) is a bone-specific protein whose blood concentration is a specific and sensitive marker of bone turnover. In adults undergoing continuous ambulatory peritoneal dialysis (CAPD), mean serum osteocalcin levels (S-OC) are lower than in similar patients on hemodialysis. We therefore measured the serum (S) and dialysate (D) levels of OC, estimated the peritoneal clearance (Cp) and mass transfer (MT) of OC and evaluated the relationship between S-OC levels and other serum biochemical parameters of bone metabolisms. Fourteen adult patients on CAPD were studied with a mean age of 46.3 +/- 13 years and a mean dialytic age on CAPD of 17.4 +/- 9.6 months. OC concentrations in (S) and (D) were 60.8 +/- 55.5 micrograms/l (normal range: 4.3-12.4 micrograms/l) and 6.9 +/- 6.2 micrograms/l, respectively. The Cp of OC was 1.08 +/- 0.3 ml/min and the MT of OC over 4-h dialysis exchange periods was 14.5 +/- 12.3 micrograms when using a dialysis solution containing 2.27% glucose. S-OC was significantly correlated with serum levels of alkaline phosphatase (r = 0.80), intact PTH (r = 0.82) and the MT of OC (r = 0.94). No significant correlations were found with serum levels of total calcium, phosphate, creatinine, total protein and dialytic age. These results suggest that the OC level in serum is influenced by both bone turnover and peritoneal clearance. Therefore, altered serum levels of OC should be interpreted always together with the peritoneal mass transfer of OC. Taking this into account, OC and intact PTH may be of value as markers of increased bone turnover secondary to renal osteodystrophy in CAPD.


Chiral N,N'-dioxide-Sc(NTf2)3 complex-catalyzed asymmetric bromoamination of chalones with N-bromosuccinimide as both bromine and amide source.
The catalytic asymmetric bromoamination of chalcones with N-bromosuccinimide as both bromine and amide source was realized by using a chiral N,N'-dioxide-Sc(NTf2)3 complex as an efficient catalyst. The corresponding chiral bromoamination products were obtained in high yields with high dr and good ee values (up to 92% yield, 93 : 7 dr and 97% ee) under mild reaction conditions.


Point prevalence surveys on healthcare acquired infections in medical and surgical wards of a teaching hospital in Rome.
Healthcare acquired infections (HAI) are an important cause of morbidity and mortality in hospitals worldwide. Aim of the study was to analyze nine years surveillance activity, carried out by point prevalence surveys from 2007 to 2015, in a 450-bed teaching hospital in Rome. Point prevalence surveys were carried out every year in the medical and surgical wards following the same methodology. In accordance with definitions used by the Centers for Disease Control, all infections occurred more than 48 hours after hospital admission were considered HAI, and included in the study. Baseline characteristics, clinical features, isolated pathogens (only for the period 2011-2015) and antimicrobial resistance were recorded. During the nine years point prevalence surveys a total 2,840 patients were enrolled. Overall 136 (4.79%) patients developed 180 (6.34%) HAI. The most frequent HAI were respiratory tract infections (RTI), which accounted for 35.0% of all HAI, followed by surgical site infections (SSI) 22.2%, urinary tract infections (UTI) 19.4%, bloodstream infections (BSI) 17.2%, and others 6.1%. HAI related to major invasive risk procedures were also evaluated. SSI/patients undergoing surgery 3.99%, UTI/ patients with urinary catheter 4.17% and BSI/patients with CVC 9.42%. Over one-half of all patients surveyed (1,532, 53.9%) were receiving antibiotics at the time of our study. Among them 892 (58.2%) for treatment, 641 (41.8%) for prophylaxis. In the latter group, 109 (17.0%) underwent extra-short term, 89 (13.9%) short term and 443 (69.1%) a long term prophylaxis. During the period 2011-2015 out of 110 HAI episodes 71 (64.5%) were confirmed microbiologically. In total 106 pathogens were isolates, Gram-negative bacteria (63.2%) were isolated more frequently than Gram-positive bacteria (28.3%). The overall HAI prevalence in our hospital was consistent with those reported in other studies in Italy. The study underlined the role of Gram-negative bacteria in HAI and the need for antimicrobial stewardship. It also provided useful baseline data for rational priorities in allocation of resources, for further infection control activities.


Misuse of emergent healthcare in contemporary Japan.
Medical care is obviously an important public service to ensure the health of a nation; however, medical resources are not always used appropriately. 'Convenience-store consultations' and inappropriate ambulance transportation represent instances of such improper use by contemporary Japanese citizens in recent years. This article illustrates two examples of misuse and discusses potential countermeasures by considering factors contributing to these behaviours. From both public and medical perspectives, these patient behaviours are problematic, causing potential harm to others, negative consequences to such patients themselves, exhaustion of healthcare staff, and breakdown of emergency medical services. Although citizens need to recognize the public nature and scarcity of medical care, the more immediate need may be to identify and to remove personal and social causes inducing such misuse. In addition, healthcare professionals should become more trustworthy. To combat these issues, one-sided penalties such as accusations or sanctions for patients who misuse the system cannot be justified in principle. If measures taken to prevent misuse are ineffective, imposing surcharges or restricting consultations may be considered official policy, but these are not acceptable for several reasons. For now, we conclude that we must rely on the spontaneous motivation of patients who engage in 'convenience-store consultations' and ambulance transportation instead of taking a taxi.


Metabolism of 5(6)Oxidoeicosatrienoic acid by ram seminal vesicles. Formation of two stereoisomers of 5-hydroxyprostaglandin I1.
Cytochrome P-450 can metabolize arachidonic (5,8,11,14-eicosatetraenoic) acid to four epoxides. One of them, cis-5(6)oxido-8,11,14-eicosatrienoic acid, has been reported to possess biological activity. To ascertain whether this epoxide could be a substrate for the enzyme fatty acid cyclooxygenase, synthetic 3H-labeled cis-5(6)-oxido-8,11,14-eicosatrienoic acid was incubated with microsomes of ram seminal vesicles and incubated with microsomes of ram seminal vesicles and the products were separated by reversed phase high performance liquid chromatography. The substrate was enzymatically transformed into products, which were more polar than 5,6-dihydroxy-8,11,14-eicosatrienoic acid. The biosynthesis was strongly inhibited by indomethacin or diclofenac sodium, two inhibitors of fatty acid cyclooxygenase. Two of the major metabolites could be identified by capillary gas chromatography-mass spectrometry as two stereoisomers of 5-hydroxyprostaglandin I1, viz. (5R,6R)-5-hydroxyprostaglandin I1 and (5S,6S)-5-hydroxyprostaglandin I1. The structures were established by comparison with the mass spectra of authentic material and by the retention time on capillary gas chromatography using deuterated internal standards. The two stereoisomers were presumably formed nonenzymatically from the intermediate 5(6)oxidoprostaglandin endoperoxides or from 5(6)oxidoprostaglandin F1 alpha during the isolation procedure.


Stochastic modeling of B lymphocyte terminal differentiation and its suppression by dioxin.
Upon antigen encounter, naïve B lymphocytes differentiate into antibody-secreting plasma cells. This humoral immune response is suppressed by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxin-like compounds, which belong to the family of aryl hydrocarbon receptor (AhR) agonists. To achieve a better understanding of the immunotoxicity of AhR agonists and their associated health risks, we have used computer simulations to study the behavior of the gene regulatory network underlying B cell terminal differentiation. The core of this network consists of two coupled double-negative feedback loops involving transcriptional repressors Bcl-6, Blimp-1, and Pax5. Bifurcation analysis indicates that the feedback network can constitute a bistable system with two mutually exclusive transcriptional profiles corresponding to naïve B cells and plasma cells. Although individual B cells switch to the plasma cell state in an all-or-none fashion when stimulated by the polyclonal activator lipopolysaccharide (LPS), stochastic fluctuations in gene expression make the switching event probabilistic, leading to heterogeneous differentiation response among individual B cells. Moreover, stochastic gene expression renders the dose-response behavior of a population of B cells substantially graded, a result that is consistent with experimental observations. The steepness of the dose response curve for the number of plasma cells formed vs. LPS dose, as evaluated by the apparent Hill coefficient, is found to be inversely correlated to the noise level in Blimp-1 gene expression. Simulations illustrate how, through AhR-mediated repression of the AP-1 protein, TCDD reduces the probability of LPS-stimulated B cell differentiation. Interestingly, stochastic simulations predict that TCDD may destabilize the plasma cell state, possibly leading to a reversal to the B cell phenotype. Our results suggest that stochasticity in gene expression, which renders a graded response at the cell population level, may have been exploited by the immune system to launch humoral immune response of a magnitude appropriately tuned to the antigen dose. In addition to suppressing the initiation of the humoral immune response, dioxin-like compounds may also disrupt the maintenance of the acquired immunity.


Immunodepression after major surgery in normal patients.
Multiple parameters of in vivo and in vitro immune function were measured serially before, during, and following nephrectomy in 12 normal renal transplant donors. All in vitro functions studied (total blood lymphocyte count, B-cell count, T-cell count, mitogen blastogenic response, and mixed leukocyte reactivity as both responder and stimulator) decreased on induction of anethesia and continued to fall during and after operation to reach a low point on the evening after nephrectomy. Depth of depression and rate of recovery varied with the individual function, but all were near normal by the fifth postoperative day. The in vivo delayed hypersensitivity response to cutaneously administered recall antigens declined more gradually and was still falling at the fifth postoperative day. Return of preoperative skin response was delayed, being complete for streptokinase/streptodornase (SK/SD) by 10 to 14 days but incomplete as long as 2 to 3 weeks for mumps and Candida antigens. Serum immunoglobulins did not change. These findings suggest incomplete correlation among the responses to the commonly used in vitro assays of cellular immunity and poor correlation with the in vivo tests. Although surgery and anesthesia results in measurable depression of immune response, clinically significant problems did not arise in these patients.


School-Based Sleep Education Program for Children: A Cluster Randomized Controlled Trial.
Insufficient sleep contributes negatively to child developmental processes and neurocognitive abilities, which argues the need for implementing interventions to promote sleep health in children. In this study, we evaluated the effectiveness of a multimodal and multilevel school-based sleep education program in primary school children using a cluster randomized controlled design. Twelve schools were randomly assigned to either the sleep education or nonactive control groups. The sleep education group included a town hall seminar, small class teaching, leaflets, brochures, and a painting competition for children. Parents and teachers were invited to participate in a one-off sleep health workshop. Parental/caregiver-reported questionnaires were collected at baseline and 1-month follow-up. A total of 3769 children were included in the final analysis. There were no significant improvements observed in the sleep-wake patterns, daytime functioning, and insomnia symptoms between the two groups at follow-up, whereas the intervention group had significantly improved parental sleep knowledge than the controls (paternal: adjusted mean difference: 0.95 [95% confidence interval (CI): 0.18 to 1.71]; maternal: adjusted mean difference: 0.87 [95% CI: 0.17 to 1.57]). In addition, children receiving the intervention had a lower persistence rate of excessive beverage intake (adjusted odds ratio: 0.49 [95% CI: 0.33 to 0.73]), and experienced greater reductions in conduct problems (adjusted mean difference: 0.12 [95% CI: 0.01 to 0.24]) compared with the controls at 1-month of follow-up. Moreover, a marginally significant reduction for emotional problems in the intervention group was also observed (adjusted mean difference: 0.16 [95% CI: -0.00 to 0.32]). These findings demonstrated that school-based sleep education was effective in enhancing parental sleep knowledge and improving behavioral outcomes in children, but not sufficient in altering the children's sleep-wake patterns and sleep problems.


[Improvement of drug bioavailability using protease inhibitors].
Although many proteins and peptides were produced by gene-technology, their administration routes are limited to be i.v. route. To increase the clinical use of these products, oral dosage form is required. However, in the case of oral administration, proteins are degraded by digestive fluid having strong protease activity. To decrease the protease activity, protease inhibitors are administered concomitantly with proteins. Aprotinin, soybean trypsin inhibitors and gel-forming polymer such as Polycarbophil are representative protease inhibitors. Gel-forming polymers have both protease inhibiting activity and absorption enhancing effect on protein/peptides. The usefulness of these protease inhibitors have been suggested as an additive for the oral delivery of G-CSF and vasopressin derivatives.


Kienböck's disease. Results of treatment with ulnar lengthening.
Further experience with ulnar lengthening in the treatment of 22 patients with Kienböck's disease confirms the efficacy of this procedure as observed in a previous series of 20 patients. In this procedure, the joint compressive force is removed from the trabeculae of the convex portion of the body of the lunate that is weakened by avascular necrosis. Subchondral fractures were present in at least 13 of the 22 patients. The technique of ulnar osteotomy, with interposition bone graft supported by a slotted bone plate applied prior to completion of the osteotomy, seems well established. Three patients were lost to follow-up and one required a secondary lunate excision for continuing pain. The remainder of the patients were well satisfied with the procedure.


The phloem pathway: new issues and old debates.
The phloem is a central actor in plant development and nutrition, providing nutrients and energy to sink organs and integrating interorgan communication. A comprehensive picture of the molecules trafficking in phloem sap is being made available, with recent surveys of proteins, RNAs, sugars, and other metabolites, some of which are potentially acting as signals. In this review, we focus on recent breakthroughs on phloem transport and signalling. A case study was phloem loading of sucrose, acting both as a nutrient and as a signal, whose activity was shown to be tightly regulated. Recent advances also described actors of macromolecular trafficking in sieve elements, including chaperones and RNA binding proteins, involved potentially in the formation of ribonucleoprotein complexes. Likewise, long distance signalling appeared to integrate electrical potential waves, calcium bursts and potentially the generation of reactive oxygen species. The ubiquitin-proteasome system was also proposed to be on action in sieve elements for signalling and protein turnover. Surprisingly, several basic processes of phloem physiology are still under debate. Hence, the absence in phloem sap of reducing sugar species, such as hexoses, was recently challenged with observations based on an analysis of the sap from Ranunculaceae and Papaveraceae. The possibility that protein synthesis might occur in sieve elements was again questioned with the identification of components of the translational machinery in Pumpkin phloem sap. Altogether, these new findings strengthen the idea that phloem is playing a central role in interorgan nutrient exchanges and communication and demonstrate that the ways by which this is achieved can obey various patterns among species.


Inhibitory effect of a new orally active cedrol-loaded nanostructured lipid carrier on compound 48/80-induced mast cell degranulation and anaphylactic shock in mice.
Type I hypersensitivity is an allergic reaction characterized by the overactivity of the immune system provoked by normally harmless substances. Glucocorticoids, anti-histamines, or mast cell stabilizers are the choices of treatment for type I hypersensitivity. Even though these drugs have the anti-allergic effect, they can have several side effects in prolong use. Cedrol is the main bioactive compound of Cedrus atlantica with anti-tumor, anti-oxidative, and platelet-activating factor inhibiting properties. In this study, the preparation and anti-anaphylactic effect of cedrol-loaded nanostructured lipid carriers (NLCs) were evaluated. NLCs were prepared using Compritol® 888 ATO and triolein as lipid phase and vitamin E d-α-tocopherylpolyethyleneglycol 1000 succinate, soya lecithin, and sodium deoxycholate as nanoparticle stabilizers. The average diameter of cedrol-NLCs (CR-NLCs) was 71.2 nm (NLC-C1) and 91.93 nm (NLC-C2). The particle had negative zeta potential values of -31.9 mV (NLC-C1) and -44.5 mV (NLC-C2). Type I anaphylactoid reaction in the animal model is significantly reduced by cedrol and cedrol-NLC. This in vivo activity of cedrol resulted that cedrol suppressed compound 48/80-induced peritoneal mast cell degranulation and histamine release from mast cells. Furthermore, compound 48/80-evoked Ca2+ uptake into mast cells was reduced in a dose-dependent manner by cedrol and cedrol-NLC. Studies confirmed that the inhibition of type I anaphylactoid response in vivo in mice and compound 48/80-induced mast cell activation in vitro are greatly enhanced by the loading of cedrol into the NLCs. The safety of cedrol and CR-NLC was evaluated as selectivity index (SI) with prednisolone and cromolyn sodium as positive control. SI of CR-NLC-C2 was found to be 11.5-fold greater than both prednisolone and cromolyn sodium. Administration of CR-NLC 24 hours before the onset of anaphylaxis can prevent an anaphylactoid reaction. NLCs could be a promising vehicle for the oral delivery of cedrol to protect anaphylactic reactions.


Neurotoxins: Expanding Uses of Neuromodulators in Medicine--Headache.
Over the course of the past 17 years, since the initial discovery of the association between botulinum toxin-A (BT-A) and the reduction of headache symptoms, the use of this neurotoxin has greatly evolved. BT-A has emerged as an alternative to prophylactic pharmacological therapies in the prevention of chronic migraine headaches, with an excellent safety profile and proven efficacy, and is Food and Drug Administration-approved for on-label use since October 2010. The mechanism of BT-A involves its effect at the neuromuscular junction, inhibition of neuropeptide and neurotransmitter release in peripheral sensory neurons, and retrograde axonal transport allowing for its direct effect on inhibiting central sensitization. Through its diagnostic and therapeutic utility, BT-A has proven to be an integral part in the treatment of chronic headache disorders.


Efficacy, safety and tolerance of imidocarb dipropionate versus atovaquone or buparvaquone plus azithromycin used to treat sick dogs naturally infected with the Babesia microti-like piroplasm.
Piroplasmosis caused by the Babesia microti-like piroplasm (Bml) is increasingly being detected in dogs in Europe. Sick dogs show acute disease with severe anaemia associated with thrombocytopenia with a poor response to current available drugs. This study assesses the safety and tolerance of three treatments and compares their efficacy over a full year of follow up in dogs naturally infected with Bml. Fifty-nine dogs naturally infected with Bml were randomly assigned to a treatment group: imidocarb dipropionate (5 mg/kg SC, 2 doses 14 d apart) (IMI); atovaquone (13.3 mg/kg PO q 8 h, 10 d)/azithromycin (10 mg/kg PO q 24 h, 10 d) (ATO); or buparvaquone (5 mg/kg IM, 2 d apart)/azithromycin (same dosage) (BUP). Before and after treatment (days 15, 45, 90 and 360), all dogs underwent a physical exam, blood tests and parasite detection (blood cytology and PCR). Clinical efficacy was assessed by grading 24 clinical and 8 clinicopathological signs from low to high severity. Before treatment, most dogs had severe regenerative anaemia (88.13%) and thrombocytopenia (71.4%). On treatment Day 45, clinical signs were mostly reduced in all dogs, and by Day 90, practically all dogs under the ATO or BUP regimen were clinically healthy (76.4 and 88%, respectively). Highest percentage reductions in laboratory abnormalities (82.04%) were detected in animals treated with ATO. Over the year, clinical relapse of Bml was observed in 8 dogs (8/17) treated with IMI. However, on Day 360, these animals had recovered clinically, though clinicopathological abnormalities were still present in some of them. Parasitaemia was PCR-confirmed on Days 90 and 360 in 47.05 and 50% of dogs treated with ATO, 68 and 60.08% with BUP, and 94.1 and 73.3% with IMI, respectively. Even after 360 days, 13.3% of the dogs treated with IMI returned a positive blood cytology result. IMI showed the worse clinical and parasitological, efficacy such that its use to treat Bml infection in dogs is not recommended. The treatments ATO and BUP showed better efficacy, though they were still incapable to completely eliminate PCR-proven infection at the recommended dose. All three treatments showed good tolerance and safety with scarce adverse events observed.


Cancer-Cell-Specific Mitochondria-Targeted Drug Delivery by Dual-Ligand-Functionalized Nanodiamonds Circumvent Drug Resistance.
We demonstrate a nanotechnology approach for the development of cancer-cell-specific subcellular organelle-targeted drug nanocarriers based on photostable nanodiamonds (ND) functionalized with folic acid and mitochondrial localizing sequence (MLS) peptides. We showed that these multifunctional NDs not only distinguish between cancer cells and normal cells, and transport the loaded drugs across the plasma membrane of cancer cells, but also selectively deliver them to mitochondria and induce significant cytotoxicity and cell death compared with free Dox localized in lysosomes. Importantly, the cellular uptake of Dox was dramatically increased in a resistant model of MCF-7 cells, which contributed to the significant circumvention of P-glycoprotein-mediated drug resistance. Our work provides a novel method of designing nanodiamond-based carriers for targeted delivery and for circumventing drug resistance in doxorubicin-resistant human breast adenocarcinoma cancer cells.


Thymopentin in the treatment of severe alopecia areata.
Since alopecia areata might be due to an aberrant T-cell-mediated immunity, the purpose of our study was to compare the results obtained with Thymopentin to those of topical sensitizing therapies, such as squaric acid dibutylester or diphencyprone. Statistical analysis showed no differences between the results obtained with these two therapies. Therefore, Thymopentin can be considered to be a new therapeutic agent which, like the classic topical drugs squaric acid dibutylester or diphencyprone, has immunoreactive properties and might provide some hope to patients with severe alopecia areata.


Prior exercise and antioxidant supplementation: effect on oxidative stress and muscle injury.
Both acute bouts of prior exercise (preconditioning) and antioxidant nutrients have been used in an attempt to attenuate muscle injury or oxidative stress in response to resistance exercise. However, most studies have focused on untrained participants rather than on athletes. The purpose of this work was to determine the independent and combined effects of antioxidant supplementation (vitamin C + mixed tocopherols/tocotrienols) and prior eccentric exercise in attenuating markers of skeletal muscle injury and oxidative stress in resistance trained men. Thirty-six men were randomly assigned to: no prior exercise + placebo; no prior exercise + antioxidant; prior exercise + placebo; prior exercise + antioxidant. Markers of muscle/cell injury (muscle performance, muscle soreness, C-reactive protein, and creatine kinase activity), as well as oxidative stress (blood protein carbonyls and peroxides), were measured before and through 48 hours of exercise recovery. No group by time interactions were noted for any variable (P > 0.05). Time main effects were noted for creatine kinase activity, muscle soreness, maximal isometric force and peak velocity (P < 0.0001). Protein carbonyls and peroxides were relatively unaffected by exercise. There appears to be no independent or combined effect of a prior bout of eccentric exercise or antioxidant supplementation as used here on markers of muscle injury in resistance trained men. Moreover, eccentric exercise as used in the present study results in minimal blood oxidative stress in resistance trained men. Hence, antioxidant supplementation for the purpose of minimizing blood oxidative stress in relation to eccentric exercise appears unnecessary in this population.


Increase of lower esophageal sphincter pressure after osteopathic intervention on the diaphragm in patients with gastroesophageal reflux.
The treatment of gastroesophageal reflux disease may be clinical or surgical. The clinical consists basically of the use of drugs; however, there are new techniques to complement this treatment, osteopathic intervention in the diaphragmatic muscle is one these. The objective of the study is to compare pressure values in the examination of esophageal manometry of the lower esophageal sphincter (LES) before and immediately after osteopathic intervention in the diaphragm muscle. Thirty-eight patients with gastroesophageal reflux disease - 16 submitted to sham technique and 22 submitted osteopathic technique - were randomly selected. The average respiratory pressure (ARP) and the maximum expiratory pressure (MEP) of the LES were measured by manometry before and after osteopathic technique at the point of highest pressure. Statistical analysis was performed using the Student's t-test and Mann-Whitney, and magnitude of the technique proposed was measured using the Cohen's index. Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham technique for the following measures of LES pressure: ARP with P= 0.027. The MEP had no statistical difference (P= 0.146). The values of Cohen d for the same measures were: ARP with d= 0.80 and MEP d= 0.52. Osteopathic manipulative technique produces a positive increment in the LES region soon after its performance.


Adrenomedullin protects from experimental arthritis by down-regulating inflammation and Th1 response and inducing regulatory T cells.
Rheumatoid arthritis is a chronic autoimmune disease of unknown etiology characterized by chronic inflammation in the joints and subsequent destruction of the cartilage and bone. The present study proposes a new strategy for the treatment of arthritis: the administration of the immunomodulatory neuropeptide adrenomedullin. Treatment with adrenomedullin significantly reduced incidence and severity of collagen-induced arthritis, an experimental model of rheumatoid arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of adrenomedullin was associated with a striking reduction of the two deleterious components of the disease, ie, the Th1-driven autoimmune and inflammatory responses. Adrenomedullin also induced the generation and/or activation of efficient CD4+ CD25+ regulatory T cells in arthritis with capacity to suppress autoreactive response and restore immune tolerance, which could play a pivotal role in the therapeutic effect of adrenomedullin on experimental arthritis contributing to the restoration of immune tolerance.


LigaSure AtiasTM Instrument.
It is the objective of this article to describe the features and applications of the LigaSure™ vessel sealing system and the new laparoscopic LigaSure Atlas™ instrument with both vessel sealing and tissue dividing capabilities. This new technique works by fusing the collagen and elastine in vessel walls to create a permanent seal. The fusion mechanism results in strong burst strength characteristics as compared to standard bipolar and ultrasonic coagulating instruments. This new energy-based source continually monitors the clinical effect on the tissue and provides greater tissue sealing with minimal damage to surrounding tissue. Studies have shown that the automated LigaSure™ device is safe, efficient, and easy to use and reduces intraoperative blood loss and operative time in many surgical procedures.


Skin-Permeable Nano-Lithocholic Lipidoid Efficiently Alleviates Psoriasis-like Chronic Skin Inflammations.
Long-term application of topical therapeutics for psoriasis has a plethora of side effects. Additionally, skin-permeating agents used in their formulations for deeper dermal delivery damage the skin. To address these limitations, we developed novel lithocholic acid analogues that could form lipid nanoparticles (nano-LCs) spontaneously in the aqueous milieu, permeate through the skin, penetrate the deeper dermal layers, and exert anti-inflammatory effects against psoriasis-like chronic skin inflammations. Prior findings demonstrated that lithocholic acid acts as a vitamin D receptor agonist without affecting the Ca+2 metabolism and also as an antagonist for ephrin type-A receptor 2 (EphA2). Taking cues from the previous findings, lithocholic acid derivatives with twin alkyl chains (LC6, LC8, LC10, and LC-12) were synthesized, nanoparticles (nano-LCs) were prepared, and they were evaluated for their skin permeability and anti-inflammatory properties. Among these nano-LCs, nano-LC10 demonstrated superior anti-inflammatory properties and inhibition of keratinocyte proliferation in various cell-based evaluations. Furthermore, the therapeutic efficiency of nano-LC10 was evaluated in an imiquimod-induced psoriasis-like mouse model and demonstrated comparable efficiency with the standard topical formulation, Sorvate, in reducing skin inflammations. Nano-LC10 also reduced systemic inflammation, organ toxicity, and also proinflammatory serum cytokine levels. Overall, nano-lithocholic lipidoid (nano-LC10) can be a potential novel class of therapeutics for topical application in treating psoriasis.


Development and internal validation of an in vitro-in vivo correlation for a hydrophilic metoprolol tartrate extended release tablet formulation.
To develop and validate internally an in vitro-in vivo correlation (IVIVC) for a hydrophilic matrix extended release metoprolol tablet. In vitro dissolution of the metoprolol tablets was examined using the following methods: Apparatus II, pH 1.2 & 6.8 at 50 rpm and Apparatus I, pH 6.8, at 100 and 150 rpm. Seven healthy subjects received three metoprolol formulations (100 mg): slow, moderate, fast releasing and an oral solution (50 mg). Serial blood samples were collected over 48 hours and analyzed by a validated HPLC assay using fluorescence detection. The f2 metric (similarity factor) was used to analyze the dissolution data. Correlation models were developed using pooled fraction dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the formulations. Predicted metoprolol concentrations were obtained by convolution of the in vivo dissolution rates. Prediction errors were estimated for Cmax and AUC to determine the validity of the correlation. Apparatus I operated at 150 rpm, and pH of 6.8 was found to be the most discriminating dissolution method. There was a significant linear relationship between FRD and FRA when using either two or three of the formulations. An average percent prediction error for Cmax and AUC for all formulations of less than 10% was found for all IVIVC models. The relatively low prediction errors for Cmax and AUC observed strongly suggest that the metoprolol IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies.


Growth of pleomorphic Trypanosoma brucei rhodesiense in irradiated inbred mice.
It was shown that irradiation (650 rad) of 7 inbred strains of mice did not block the ability of Trypanosoma brucei rhodesiense to transform from the long slender (LS) to the short stumpy (SS) form or alter the plateau in parasitemia. In addition, it was observed that significant differences in parasitemia levels, in the rate of transformation from the LS to the SS form, as well as in the survival times occurred between the irradiated C3HeB/FeJ and several of the other strains. These differences in the nonspecific ability to control parasitemia appeared to be characteristic for each inbred strain of mice. The resistant strains generally had lower parasitemia than the susceptible strains. However, it was also shown that there is not a one-to-one correlation between the innate ability of a mouse strain to control its initial parasitemia, and the strain's ability to clear the parasitemia or increase its survival time. It was therefore concluded that the hypothesis which states that the ability of an animal to increase nonspecifically the rate of transformation, and therefore to lower the parasitemia, allowing intact animals to respond immunologically and survive longer is either incorrect or incomplete. The results further show that the ability of mice to clear their initial parasitemia by an antibody response is not necessarily correlated with their survival time. Therefore, this study suggests that factors other than an antibody response and the nonspecific control of parasitemia are important in resistance.


The Leishmaniasis East Africa Platform (LEAP): strengthening clinical trial capacity in resource-limited countries to deliver new treatments for visceral leishmaniasis.
Visceral leishmaniasis is a neglected tropical disease endemic in East Africa where improved patient-adapted treatments are needed. The Leishmaniasis East Africa Platform (LEAP) was created in 2003 to strengthen clinical research capacity, serve as a base for training, and evaluate and facilitate implementation of new treatments. Major infrastructure upgrades and personnel training have been carried out. A short course of Sodium Stibogluconate and Paramomycin (SSG&PM) was evaluated and is now first-line treatment in the region; alternative treatments have also been assessed. LEAP can serve as a successful model of collaboration between different partners and countries when conducting clinical research in endemic countries to international standards.


[Bracelet localisation of chickenpox: a case of atypical varicella].
We report on a 3-year-old child with bracelet localisation of chickenpox. Varicella with unusual clinical aspects and course is known as atypical varicella; it is characterized by its unique clinical features, unusual distribution, or a prolonged course. In case of atypical varicella, clinical diagnosis can be difficult. Pre-existing factors have been reported such as immunocompromised status, sun exposition, local injury and pre-existing rash.


Yersinia pestis and Yersinia pseudotuberculosis infection: a regulatory RNA perspective.
Yersinia pestis, responsible for causing fulminant plague, has evolved clonally from the enteric pathogen, Y. pseudotuberculosis, which in contrast, causes a relatively benign enteric illness. An ~97% nucleotide identity over 75% of their shared protein coding genes is maintained between these two pathogens, leaving much conjecture regarding the molecular determinants responsible for producing these vastly different disease etiologies, host preferences and transmission routes. One idea is that coordinated production of distinct factors required for host adaptation and virulence in response to specific environmental cues could contribute to the distinct pathogenicity distinguishing these two species. Small non-coding RNAs that direct posttranscriptional regulation have recently been identified as key molecules that may provide such timeous expression of appropriate disease enabling factors. Here the burgeoning field of small non-coding regulatory RNAs in Yersinia pathogenesis is reviewed from the viewpoint of adaptive colonization, virulence and divergent evolution of these pathogens.


Improved plant bioconcentration modeling of pesticides: The role of periderm dynamics.
There is a continuous need to advance pesticide plant uptake models in support of improving pest control and reducing human exposure to pesticide residues. The periderm of harvested root and tuber crops may affect pesticide uptake, but is usually not considered in plant uptake models. To quantify the influence of the periderm on pesticide uptake from soil into potatoes, we propose a model that includes an explicit periderm compartment in the soil-plant mass balance for pesticides. Our model shows that the potato periderm acts as an active barrier to the uptake of lipophilic pesticides with high KOW , while it lets more lipophobic pesticides accumulate in the medulla (pulp). We estimated bioconcentration factors (BCFs) for over 700 pesticides and proposed parameterizations for including the effects of the periderm into a full plant uptake modeling framework. A sensitivity analysis shows that both the degradation half-life inside the tuber and the lipophilicity drive the contributions of other aspects to the variability of BCFs, while highlighting distinct dynamics in the periderm and medulla compartments. Finally, we compare model estimates with measured data, showing that predictions agree with field observations for current-use pesticides and some legacy pesticides frequently found in potatoes. Considering the periderm improves the accuracy of quantifying pesticide uptake and bioconcentration in potatoes as input for optimizing pest control and minimizing human exposure to pesticide residues in edible crops.


The National Policy for Comprehensive Health of Lesbians, Gays, Bisexuals and Transgender (LGBT) and access to the Sex Reassignment Process in the Brazilian Unified Health System (SUS): progress and challenges.
This study aimed to analyze how the Brazilian Ministry of Health (MS) is implementing the Sex Reassignment Process (SRP) in the Unified Health System (SUS), through research of public domain official documents, systematization of surgery's quantitative data and analysis of meeting reports of the LGBT Health Technical Committee (CTSLGBT) of the MS. We conducted exploratory research combining quantitative and qualitative methods, using as methodological basis the normative proposal of health programs and systems evaluation study. The study resulted in the total data calculation of sex reassignment surgeries performed by the SUS (2008-2016), which highlight no deaths and unequal regional access; and in the monitoring of the implementation of actions of the National LGBT Health Policy by a specific committee appointed by the MS. Despite considerable progress, challenges remain. Currently, the most threatening hurdle is the possibility of a setback imposed by conservative sectors from the Executive and Legislative branches. Therefore, the visibility of achievements is a decisive step toward maintaining and enhancing SRP in the SUS.


Ventricular arrhythmia in unrepaired and repaired tetralogy of Fallot. Relation to age, timing of repair, and haemodynamic status.
Ventricular arrhythmias are common after repair of tetralogy of Fallot and are associated with late sudden death. This study examined the relation of ventricular arrhythmia during normal daily activities to the timing of repair, duration of follow up, and postoperative haemodynamic status. Forty eight hour ambulatory electrocardiographic monitoring was performed in 145 patients: 60 (aged 3 months to 46 years) had not yet undergone repair and 85 were followed from four to 22 (mean 14.6) years after repair. Cardiac catheterisation was performed in 47 (55%) one to 22 (mean 8.9) years after repair. Twelve (20%) of the uncorrected group had ventricular arrhythmia. The incidence increased significantly with age from 0% in patients aged less than 8 years to 58% in those aged greater than or equal to 16 years. In the corrected group 44% had ventricular arrhythmia. The incidence of arrhythmia was associated with older age at repair but not with postoperative haemodynamic status, duration of follow up, or era of surgery. It is concluded that ventricular arrhythmia is common in older patients with tetralogy of Fallot before repair and that during long term follow up of patients after repair the incidence of ventricular arrhythmia is influenced by the timing of surgery rather that the duration of postoperative follow up, era of surgery, or the haemodynamic result.


[Influence of anxiety in diverse cutaneous diseases].
The objective of the current study is to determine the levels of anxiety in patients with dermatological diseases compared to healthy subjects and the degree of anxiety in the different cutaneous diseases. It is a descriptive study of a case series where 152 patients are selected, 20 of whom are healthy controls and the other 132 are patients that attend a Dermatology clinic. The patients are divided into 5 groups based on the cutaneous disorder for which they attend the clinic: chronic urticaria, acute urticaria, plaque psoriasis, atopic dermatitis, and a miscellaneous group (includes several diagnoses such as seborrheic keratosis, follow-up of multiple nevi, carcinomas...) where, a priori, anxiety does not influence these disorders. Spielberger State-Trait Anxiety Inventory (STAI) is administered to the participating subjects and the differences in State Anxiety Inventory (SAI) and Trait Anxiety Inventory (TAI) for the different groups are analyzed. Patients were asked to report any stressful event in the six months prior to the appearance of the disease that might have been a trigger, and they were also asked about history of psychiatric disorders or atopy. We observed significant differences in the means obtained in SAI and TAI in healthy subjects compared to patients. We obtained higher mean scores in SAI in patients diagnosed of atopic dermatitis, that were significant when compared with patients with chronic urticaria or other diseases. Forty-eight percent of patients with psoriasis and 38.89 % of patients with atopic dermatitis report a stressful event in the past six months compared to 11.54% of patients from the group with miscellaneous diseases and, additionally, patients with psoriasis and atopic dermatitis have the highest mean scores in the anxiety tests. Twenty-one percent of the 132 patients with cutaneous diseases report a history of psychiatric disorders, showing statistically significant higher mean scores in STAI. The findings show the comorbidity of psychiatric disorders in patients with chronic cutaneous diseases and the high levels of state and trait anxiety, mainly in patients with psoriasis and atopic dermatitis.


Use of permacol in parietal and general surgery: a bibliographic review.
The use of synthetic meshes on infected incisional hernias often fails and is therefore contraindicated. Biological meshes offer a novel solution. Among them, Permacol requires a bibliographic analysis of its efficacy and tolerance. A bibliographic analysis was carried out on the efficacy and tolerance of Permacol in parietal and general surgery. A total of 22 publications described the use of Permacol in digestive surgery. The advantages of Permacol would be usability in contaminated surgical fields, biocompatibility, no erosion of intestinal wall, and less risk of adhesions. The main drawback of Permacol is its high cost. Even so, Permacol can play an important part in the short-term management of complex or contaminated abdominal wall defects. The lack of long-term studies and the high cost of the implant call for a medical cost-effectiveness assessment to determine the indications for Permacol in parietal and general surgery.


Meth A fibrosarcoma cells express two transforming mutant p53 species.
Expression plasmids directing the synthesis of various forms of the p53 cellular tumor antigen were compared with respect to their biological activities. All plasmids encoding wild type p53, derived from two different cDNA libraries, had absolutely no detectable activity when assayed for transformation of primary rat embryo fibroblasts in collaboration with Ha-ras. In contrast, p53 variants carrying point mutations in the protein coding region exhibited at least some transforming activity. Most notably, this was true for both types of mutant p53 cDNA clones isolated from Meth A cells. The data indicate that these cells, derived from a chemically-induced tumor, carry two independently mutated p53 alleles, each encoding a transformationally activated protein. This may imply that the mutations in the p53 gene played a role in the development of the Meth A tumor. Finally, cells overexpressing a transfected mutant p53 exhibit a physical complex between this exogenous p53 and its endogenous counterpart, possibly resulting in the stabilization of the latter.


Growth of elaborate microbial pinnacles in Lake Vanda, Antarctica.
Microbial pinnacles in ice-covered Lake Vanda, McMurdo Dry Valleys, Antarctica, extend from the base of the ice to more than 50 m water depth. The distribution of microbial communities, their photosynthetic potential, and pinnacle morphology affects the local accumulation of biomass, which in turn shapes pinnacle morphology. This feedback, plus environmental stability, promotes the growth of elaborate microbial structures. In Lake Vanda, all mats sampled from greater than 10 m water depth contained pinnacles with a gradation in size from <1-mm-tall tufts to pinnacles that were centimeters tall. Small pinnacles were cuspate, whereas larger ones had variable morphology. The largest pinnacles were up to ~30 cm tall and had cylindrical bases and cuspate tops. Pinnacle biomass was dominated by cyanobacteria from the morphological and genomic groups Leptolyngbya, Phormidium, and Tychonema. The photosynthetic potential of these cyanobacterial communities was high to depths of several millimeters into the mat based on PAM fluorometry, and sufficient light for photosynthesis penetrated ~5 mm into pinnacles. The distribution of photosynthetic potential and its correlation to pinnacle morphology suggests a working model for pinnacle growth. First, small tufts initiate from random irregularities in prostrate mat. Some tufts grow into pinnacles over the course of ~3 years. As pinnacles increase in size and age, their interiors become colonized by a more diverse community of cyanobacteria with high photosynthetic potential. Biomass accumulation within this subsurface community causes pinnacles to swell, expanding laminae thickness and creating distinctive cylindrical bases and cuspate tops. This change in shape suggests that pinnacle morphology emerges from a specific distribution of biomass accumulation that depends on multiple microbial communities fixing carbon in different parts of pinnacles. Similarly, complex patterns of biomass accumulation may be reflected in the morphology of elaborate ancient stromatolites.


Eltrombopag in patients with chronic liver disease.
Thrombocytopenia may represent a barrier to optimal management of chronic liver disease patients undergoing invasive procedures, or who need to be treated with interferon-based antiviral therapy. Eltrombopag is a thrombopoietic drug that acts upon binding thrombopoietin receptor and stimulates megakaryocytopoiesis and platelet production. A summary of the preclinical studies and of studies carried out in patients with chronic liver disease with eltrombopag are presented in this paper. Data are based on abstracts from journal articles and international conferences found in a PubMed search of literature published up to November 2012. Eltrombopag has shown to be capable of reducing the need for platelet transfusion in thrombocytopenic patients with advanced liver disease undergoing invasive procedures and help increase the sustained virological response rate to interferon-based antiviral therapy in patients with chronic hepatitis C who were poor candidates to treatment because of thrombocytopenia. In chronic liver disease patients, the possible benefits of eltrombopag administration should be accurately weighed against the adverse events profile of the drug due to possible concerns regarding the occurrence of thromboembolic events and the potential for decompensation of chronic liver disease.


Fetal neural transplantation: placing the ethical debate within the context of society's use of human material.
In this paper I wish to place the debate about the use of fetal tissue, as in fetal neural transplantation, within the context of society's use of, and dependence upon, human material for many teaching, research, and therapeutic purposes. I shall argue that such an emphasis is required if we are to be consistent in our approach to the ethical dimensions of the fetal neural transplantation debate. What will emerge is the ambivalence of society's ethical attitudes and also the diversity of perspectives in most debates involving the use of human material.


Primary amebic meningoencephalitis: a review of the clinical literature.
Primary amebic meningoencephalitis (PAM) is a rapidly progressive and potentially fatal infection frequently contracted by swimming in bodies of warm fresh water. The etiological agent in most reported cases of PAM is the ameboflagellate Naegleria fowleri. Infection with this organism closely mimics and is often mistaken for a bacterial or a viral pyogenic meningitis. Recovery is rare and depends on rapid diagnosis and treatment. Physicians treating individuals who present with an acute pyogenic meningitis should consider the diagnosis of PAM, particularly if the patient has a recent history of swimming in warm fresh water. We review the recent literature for cases of PAM and the discuss ecology of N. fowleri and the clinical presentation, diagnosis, and treatment of PAM.


Patients' desires and expectations for medical care in primary care clinics.
To explore whether patients' desires for and expectations of medical care differ between the United States and Canada, we surveyed 652 patients and 105 physicians at primary care sites in Michigan and Ontario. Patient desires were similar at both sites, but expectations were higher in Michigan. Michigan physicians gave higher estimates of patient desire than physicians in Ontario. Physicians at both sites, however, similarly underestimated patients' desires. These between-site differences in expectation may reflect differences both in general cultural factors and in patient exposure to different clinical policies within the medical systems.


An assessment of selective cerebral perfusion via the innominate artery in aortic arch replacement.
Maintaining an adequate cerebral oxygen supply is a serious problem in aortic arch surgery. Deep hypothermic circulatory arrest is the most common method used for cerebral protection, but guarantees only a time-limited safety period. Based on experimental investigations, we applied selective cerebral perfusion via the innominate artery alone with only moderate hypothermia (28 degrees C) and without circulatory arrest in 25 consecutive patients undergoing surgical treatment of an aneurysm (n = 10) or acute type-A dissection (n = 15) involving the aortic valve and arch. In every case a test perfusion was carried out to assess whether the cerebral perfusion achieved would be adequate for the whole operation. In no case was the perfusion inadequate. As a new perioperative monitoring system, we used computer-aided topographical electroencephalometry (CATEEM). There were 18 male and 7 female patients, their age was 47.0 +/- 15.1 years (mean +/- SD). Mean time periods were 155.1 +/- 37.3 min for aortic cross-clamping, and 69.3 +/- 35 min for selective cerebral perfusion. Postoperatively, two patients (8%) revealed a temporary left-sided hemiparesis, and 4 patients (16%) died within 30 days. The overall mortality rate was 16% in a follow-up period of 24.2 +/- 9.5 months. In this small group the CATEEM monitoring enabled an intraoperative selection of patients with sufficient bihemispheric collateral circulation and therefore suitable for simple innominate artery perfusion.


Applications of the Cambridge Structural Database to molecular inorganic chemistry.
Applications of the data in the Cambridge Structural Database (CSD) to knowledge acquisition and fundamental research in molecular inorganic chemistry are reviewed. Various classes of application are identified, including the derivation of typical molecular dimensions and their variability and transferability, the derivation and testing of theories of molecular structure and bonding, the identification of reaction paths and related conformational analyses based on the structure correlation hypothesis, and the identification of common and presumably energetically favourable intermolecular interactions. In many of these areas, the availability of plentiful structural data from the CSD is set against the emergence of high-quality computational data on the geometry and energy of inorganic complexes.


High-resolution genetic mapping and physical map construction for the fertility restorer Rfm1 locus in barley.
High-resolution genetic linkage mapping and BAC physical mapping narrowed the fertility restorer locus Rfm1 in barley to a sub-centimorgan genetic interval and a 208-kb physical interval. Rfm1 restores the fertility of msm1 and msm2 male-sterile cytoplasms in barley. The fertility restoration gene is located on the short arm of chromosome 6H (6HS), and we pursued a positional cloning of this gene. Starting from a previous result that has delimited Rfm1 within a 10.8 cM region on 6HS, we developed novel CAPS and SSR markers tightly linked to the gene in barley using the sequence information from the syntenic region of rice and barley genome assemblies. Next, we performed fine mapping of the Rfm1 locus. To isolate recombinants, we surveyed 3,638 F2 plants derived from a cross between the CMS strain and the Rf strain with adjacent markers (NAS2090 and NAS1080). This analysis identified 175 recombinant plants from the F2 population to build a high-resolution map with nine markers tightly linked to the Rfm1 locus. Rfm1 was located within the 0.14 cM region delimited by two markers (NAS9113 and NAS9200). Using these flanking markers as well as marker cosegregating with Rfm1 (NAS9133), we screened the BAC libraries of the cultivar Morex, an rfm1 carrier. We isolated 11 BAC clones and constructed a BAC physical map using their fingerprints. Finally, we delimited the Rfm1 locus encompassing the rfm1 allele on a 208-kb contig composed of three minimally overlapping BAC clones. This precise localization of the Rfm1 locus in the barley genome is expected to greatly accelerate the future map-based cloning of the Rfm1 gene by sequence analysis and its genetic transformation for the complementation of cytoplasmic male-sterile plants.


Changes in PgR and Ki-67 in residual tumour and outcome of breast cancer patients treated with neoadjuvant chemotherapy.
Limited data are available on the prognostic value of changes in the biological features of residual tumours following neoadjuvant therapies in breast cancer patients. We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neoadjuvant chemotherapy at the European Institute of Oncology (IEO), Milan, Italy, between 1999 and 2011. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation, including ER, PgR, HER2 protein and Ki-67 expression carried out at the IEO both at diagnostic core biopsy and at final surgery. We identified a total of 904 patients. The 5% of patients who were ER positive at diagnostic biopsy had ER-negative residual tumour at final surgery. For PgR expression, 67% of the patients, whose tumours had a PgR >20% at diagnostic biopsy had a PgR <20% at final surgery. The Ki-67 expression changed from >20% to <20% in 40% of the patients. At the multivariate analysis, the decrease of PgR-immunoreactive cells correlated with improved outcome in terms of disease-free survival (DFS) [hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.54-1.00, P 0.046]. In addition, the decrease of Ki-67 expression to <20% of the cells at final surgery was found to be associated with better outcome both in terms of DFS (HR 0.52; 95% CI 0.40-0.68 P < 0.0001) and overall survival (HR 0.45; 95% CI 0.32-0.64, P < 0.0001). The decrease of PgR and Ki-67 expression after preoperative chemotherapy has a prognostic role in breast cancer patients with residual disease.


Let's not contribute to disparities: the best methods for teaching clinicians how to overcome language barriers to health care.
Clinicians should be educated about how language barriers contribute to disparities for patients with limited English proficiency (LEP). However, educators must avoid developing educational interventions that increase health disparities for LEP patients. For example, studies suggest that teaching "Medical Spanish" or related courses may actually contribute to health care disparities if clinicians begin using these non-English language skills inappropriately with patients. We discuss the risks and benefits of teaching specific cultural competence skills and make evidence-based recommendations for the teaching content and methods for educational interventions focused on overcoming language barriers in health care. At minimum, we suggest such interventions include: (1) the role of language barriers in health disparities, (2) means of overcoming language barriers, (3) how to work with interpreters, (4) identifying and fixing problems in interpreted encounters, and (5) appropriate and safe use of one's own limited non-English language skills.


Novel Seimatosporium Species from Grapevine in Northern California and Their Interactions with Fungal Pathogens Involved in the Trunk-Disease Complex.
Seimatosporium spp. and closely related "pestalotioid fungi" have been isolated from vineyards worldwide, but their ecological status in grapevine wood is unclear. To determine their involvement in the grapevine trunk-disease complex, we tested the pathogenicity of Californian isolates obtained from vines with general symptoms of Botryosphaeria, Eutypa, and Phomopsis diebacks. Multilocus phylogenetic analyses revealed three species: Seimatosporium vitis and two newly described and typified species, S. luteosporum sp. nov. and S. vitifusiforme sp. nov. Inoculations to woody stems of potted grapevines of both isolates of S. vitis and one isolate of S. vitifusiforme, but not S. luteosporum, were associated with significantly larger lesions than those of noninoculated controls. Coinoculations with trunk pathogens (Cryptovalsa ampelina, Diaporthe ambigua, Diatrypella verruciformis, Diplodia seriata, and Eutypa lata), coisolated from the same wood cankers in the field, brought about increased lesion lengths for S. vitifusiforme paired with D. seriata, and S. luteosporum paired with Diaporthe ambigua. In contrast, there were no differences in lesion lengths of S. vitis and Diatrypella verruciformis or S. vitis and E. lata, inoculated alone or together. Our findings suggest that Seimatosporium spp. are involved in the grapevine trunk-disease complex, and their virulence may depend on or affect that of trunk pathogens.


Shear stress investigation across mechanical heart valve.
The particle image velocimetry technique was used to study the shear field across a transparent mechanical heart valve model in one cardiac cycle. Shear stress was continuously increased until peak systole and high turbulent stress was observed at the orifice of the central channel and also around the occluder trailing tips. The peak Reynolds shear stress was up to 500 N/m at peak systole, which was higher than the normal threshold for hemolysis.


Metaplastic Carcinoma of Breast with Extensive Chondroid Differentiation: A Case Report with Review of Literature.
Metaplastic carcinoma of breast (MBC) is a rare and aggressive type of invasive breast cancer. As it encompasses a variety of distinct histopathologic designations, diagnostic challenges abound. We present a case report of metaplastic carcinoma with extensive chondroid differentiation. This case merits presentation because of its rarity and difficulty to diagnose, especially if the tumour is composed mainly of sarcomatous elements. Standard chemotherapy regimes are ineffective against MBC. The prognosis of MBC is poor in comparison to classical invasive breast cancer. Data focusing on MBC is limited due to its rare incidence.


Some aspects of the public health importance of measurement of growth.
Growth is a fundamental process of life which in complex animals is influenced by genetic constitution, nurture and nutrition. Increase in size is accompanied by process of development and both growth and development are closely linked with time--the age of the individual. This paper considers ways in which simple measurements of different aspects of the growth of children have contributed, and are continuing to contribute, to our understanding of the origins of disease. The results of these measurements can help those involved in the care of children to identify individuals at risk of disturbances of growth and the possibility of the development of diseases associated with them. It can also help instigate preventative measures that may help children to develop more fruitful and longer disease-free lives.


Effect of metal ions on photoluminescence, charge transport, magnetic and catalytic properties of all-inorganic colloidal nanocrystals and nanocrystal solids.
Colloidal semiconductor nanocrystals (NCs) provide convenient "building blocks" for solution-processed solar cells, light-emitting devices, photocatalytic systems, etc. The use of inorganic ligands for colloidal NCs dramatically improved inter-NC charge transport, enabling fast progress in NC-based devices. Typical inorganic ligands (e.g., Sn(2)S(6)(4-), S(2-)) are represented by negatively charged ions that bind covalently to electrophilic metal surface sites. The binding of inorganic charged species to the NC surface provides electrostatic stabilization of NC colloids in polar solvents without introducing insulating barriers between NCs. In this work we show that cationic species needed for electrostatic balance of NC surface charges can also be employed for engineering almost every property of all-inorganic NCs and NC solids, including photoluminescence efficiency, electron mobility, doping, magnetic susceptibility, and electrocatalytic performance. We used a suite of experimental techniques to elucidate the impact of various metal ions on the characteristics of all-inorganic NCs and developed strategies for engineering and optimizing NC-based materials.


The bronchial tree and lobular division of the crab-eating monkey (Macaca fascicularis) lung.
The lungs of 70 crab-eating monkeys were examined. The crab-eating monkey has the dorsal, lateral, ventral and medial bronchiole systems on both sides. According to the bronchial ramification, the right lung consists of the upper, middle, lower, and accessory lobes, whereas the left lung consists of a middle lobe which is bilobed and a lower lobe. These findings were based on the comparative anatomy of the bronchial tree and blood vessels of the mammalian lung.


Signatures of local adaptation in lowland and highland teosintes from whole-genome sequencing of pooled samples.
Spatially varying selection triggers differential adaptation of local populations. Here, we mined the determinants of local adaptation at the genomewide scale in the two closest maize wild relatives, the teosintes Zea mays ssp parviglumis and ssp. mexicana. We sequenced 120 individuals from six populations: two lowland, two intermediate and two highland populations sampled along two altitudinal gradients. We detected 8 479 581 single nucleotide polymorphisms (SNPs) covered in the six populations with an average sequencing depth per site per population ranging from 17.0× to 32.2×. Population diversity varied from 0.10 to 0.15, and linkage disequilibrium decayed very rapidly. We combined two differentiation-based methods, and correlation of allele frequencies with environmental variables to detect outlier SNPs. Outlier SNPs displayed significant clustering. From clusters, we identified 47 candidate regions. We further modified a haplotype-based method to incorporate genotype uncertainties in haplotype calling, and applied it to candidate regions. We retrieved evidence for selection at the haplotype level in 53% of our candidate regions, and in 70% of the cases the same haplotype was selected in the two lowland or the two highland populations. We recovered a candidate region located within a previously characterized inversion on chromosome 1. We found evidence of a soft sweep at a locus involved in leaf macrohair variation. Finally, our results revealed frequent colocalization between our candidate regions and loci involved in the variation of traits associated with plant-soil interactions such as root morphology, aluminium and low phosphorus tolerance. Soil therefore appears to be a major driver of local adaptation in teosintes.


Construction and visible-light-photocatalysis of a novel ternary heterostructure BiOI/(001)TiO2/Ti3C2.
Constructing effective heterojunctions between semiconductors and appropriate cocatalysts and exposing highly active crystal facets have been considered an effective approach to obtain efficient photocatalysts. Herein, a novel BiOI/(001)TiO2/Ti3C2 (BTT) hybrid was for the first time synthesized by in situ growing (001)TiO2 nanosheets on a 2D MXene nanomaterial (Ti3C2) and subsequent deposition of flower-like nanoflake BiOI on the obtained (001)TiO2/Ti3C2 hybrid. The BTT hybrid exhibited excellent photocatalytic performance for degradation of Rhodamine B under visible light irradiation, with the highest degradation rate being 6.26, 1.72, and 1.35 times of that of a pure BiOI, BiOI/TiO2 hybrid, and BiOI/Ti3C2 hybrid, respectively. The staggeringly enhanced photoactivity of BTT was attributed to the separation of photogenerated carriers by a multiple charge transfer channels because of the formed p-n and Schottky double junctions. This study demonstrates that (001)TiO2/Ti3C2 obtained by simple hydrothermal oxidation of Ti3C2 can be a good cocatalyst for fabricating excellent visible-light-driven photocatalyst.


meso-meso-Linked corrole dimers with modified cores: synthesis, characterization, and properties.
The synthesis and characterization of the first examples of core-modified corrole dimers linked through the meso positions are described. The dimers are obtained by a simple Ag(I)- or Fe(III)-catalyzed coupling reaction in near-quantitative yields. The corroles obtained are metalated with metal ions, such as Cu(II) and Ni(II). The electronic-absorption spectral studies reveal weak electronic interaction between the two subunits and the exciton coupling observed for the free-base corrole dimer (1717 cm(-1)) is lower than that for the corresponding protonated derivative (4081 cm(-1)). The solution-state structure derived from (1)H and two-dimensional NMR spectral studies reveals a noncoplanar arrangement of two corrole units. Geometry optimization at the B3LYP-631G level also confirms the noncoplanar arrangement of corroles with a dihedral angle of 64.8 degrees between two corrole planes. The electron paramagnetic resonance (EPR) and magnetic characterization studies on the paramagnetic copper-metalated dimer indicate that both copper ions behave as independent spins without any noticeable interaction. Results of fluorescence studies reveal a bathochromic shift of about 60 nm upon dimerization. The first hyperpolarizability (beta) measured by using the hyper Rayleigh scattering (HRS) method reveals doubling of the beta values on progressing from monomer to dimer, attributed to enhanced pi conjugation. The use of copper dimers in the photocleavage of DNA is also explored. It is shown that the bimetallic copper dimer selectively cleaves the nucleic acids without affecting the proteins, suggesting a possible application of the copper complex in the removal of nucleic acid contaminants from protein extracts through a simple photolytic pathway.


Substituting human chorionic gonadotropin by gonadotropin-releasing hormone agonist to trigger final follicular maturation, during controlled ovarian hyperstimulation, results in less systemic inflammation.
To investigate the degree of systemic inflammation, as reflected by serum C-reactive protein (CRP) levels, associated with controlled ovarian hyperstimulation (COH) with human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone (GnRH) agonist for the induction of final follicular maturation. Prospective, observational study. An in vitro fertilization (IVF) unit of an academic medical center. Twenty-four women undergoing COH and IVF with the flexible GnRH antagonist protocol were prospectively assigned to receive hCG or GnRH agonist for the induction of final follicular maturation. Blood was drawn three times during COH for measurement of sex-steroid and CRP levels: the day on which adequate suppression was obtained (Day-0); the day of or prior to administration of hCG (Day-hCG); and (3) the day of ovum pick-up (Day-OPU). Levels were compared among the three time points in the two groups. No between-group differences were observed in terms of patient age, gonadotropin dosage, duration of stimulation or number of oocytes retrieved. Serum CRP levels were significantly higher on Day-OPU than on Day-hCG and Day-0, but the difference was significant only in the hCG group (p<0.03 for both). The percentage change in CRP levels after hCG administration (Day-OPU vs. Day-hCG) (96%) was higher than that after GnRH administration (23%). Administration of GnRH agonist in patients undergoing COH for IVF yields a lesser degree of systemic inflammation, as reflected by CRP levels, than hCG.


Similarity-Driven Fine-Tuning Methods for Regularization Parameter Optimization in PET Image Reconstruction.
We present an adaptive method for fine-tuning hyperparameters in edge-preserving regularization for PET image reconstruction. For edge-preserving regularization, in addition to the smoothing parameter that balances data fidelity and regularization, one or more control parameters are typically incorporated to adjust the sensitivity of edge preservation by modifying the shape of the penalty function. Although there have been efforts to develop automated methods for tuning the hyperparameters in regularized PET reconstruction, the majority of these methods primarily focus on the smoothing parameter. However, it is challenging to obtain high-quality images without appropriately selecting the control parameters that adjust the edge preservation sensitivity. In this work, we propose a method to precisely tune the hyperparameters, which are initially set with a fixed value for the entire image, either manually or using an automated approach. Our core strategy involves adaptively adjusting the control parameter at each pixel, taking into account the degree of patch similarities calculated from the previous iteration within the pixel's neighborhood that is being updated. This approach allows our new method to integrate with a wide range of existing parameter-tuning techniques for edge-preserving regularization. Experimental results demonstrate that our proposed method effectively enhances the overall reconstruction accuracy across multiple image quality metrics, including peak signal-to-noise ratio, structural similarity, visual information fidelity, mean absolute error, root-mean-square error, and mean percentage error.


"Xilala is only treated with a good hand": a study on the treatment of malnutrition in Mozambique.
In Mozambique old and new evils of body and spirit intertwine, thus allowing particular contours to modern life. Traditional diseases are reconfigured along the lines of a new thinking, and what Western medicine calls malnutrition is defined as xilala by the local traditional thinking. This study aimed to understand the point of view of both caregivers (mothers and grandmothers) of children participating in a Nutritional Rehabilitation Program and ethnomedicine experts, who find themselves entangled in a complex set of relationships through which different forms to comprehend body, health, and disease circulate. The supplement, as an object, has a life of its own and takes on new meanings when it leaves the hospital. When its use happens at home, it acquires a particularity: it becomes food. Thus, it ceases to be something inert and impersonal, which is a feature of standard medicine of the health institution. The local view centered on ethnomedicine is based on the certainty that a situation affecting a child cannot have a healing outcome if not by traditional medicine. Biomedical rationality erected from the confluence of the biological and technical sciences with their scientific postulates does not constitute the authorized discourse in this context.


Dendritic cells and adipose tissue.
Visceral adipose tissue inflammation in obesity is an established risk factor for metabolic syndrome, which can include insulin resistance, type 2 diabetes, hypertension and cardiovascular diseases. With obesity and related metabolic disorders reaching epidemic proportions globally, an understanding of the mechanisms of adipose tissue inflammation is crucial. Within the immune cell cohort, dendritic cells (DC) play a key role in balancing tolerance and immunity. Despite decades of research into the characterization of DC in lymphoid and non-lymphoid organs, their role in adipose tissue function is poorly understood. There is now an increasing interest in identification and characterization of DC in adipose tissue and understanding their function in regulating tissue metabolic homeostasis. This review provides an overview of the study of DC in adipose tissue, focusing on possible mechanisms by which DC may contribute to adipose tissue homeostasis.


Application of a single-flicker online SSVEP BCI for spatial navigation.
A promising approach for brain-computer interfaces (BCIs) employs the steady-state visual evoked potential (SSVEP) for extracting control information. Main advantages of these SSVEP BCIs are a simple and low-cost setup, little effort to adjust the system parameters to the user and comparatively high information transfer rates (ITR). However, traditional frequency-coded SSVEP BCIs require the user to gaze directly at the selected flicker stimulus, which is liable to cause fatigue or even photic epileptic seizures. The spatially coded SSVEP BCI we present in this article addresses this issue. It uses a single flicker stimulus that appears always in the extrafoveal field of view, yet it allows the user to control four control channels. We demonstrate the embedding of this novel SSVEP stimulation paradigm in the user interface of an online BCI for navigating a 2-dimensional computer game. Offline analysis of the training data reveals an average classification accuracy of 96.9±1.64%, corresponding to an information transfer rate of 30.1±1.8 bits/min. In online mode, the average classification accuracy reached 87.9±11.4%, which resulted in an ITR of 23.8±6.75 bits/min. We did not observe a strong relation between a subject's offline and online performance. Analysis of the online performance over time shows that users can reliably control the new BCI paradigm with stable performance over at least 30 minutes of continuous operation.


[Diagnostic accuracy of FP-CIT SPECT in patients with parkinsonism].
To determine the diagnostic accuracy of FP-CIT SPECT in entities with and without presynaptic involvement of the nigral-striatal dopaminergic pathway in a large group of patients with movement disorders, evaluating the usefulness of quantitative analysis. A group of 183 consecutive patients clinically diagnosed as either having or not having degenerative Parkinsonism. These results were then contrasted with those of FP-CIT SPECT to determine the diagnostic accuracy of the procedure. The specific binding index was evaluated with ROC curves. FP-CIT SPECT was highly accurate in the diagnosis of neurodegenerative Parkinsonism (sensitivity: 95 %, specificity: 90 %). Most of the false positive results arose in patients with vascular Parkinsonism and the false negative results in patients with Parkinson disease. ROC curve analysis of semiquantitative evaluation had a sensitivity of 83 % and specificity of 82 % with an optimal cut-off of 1.44. The area under the curve was not significantly different between patients </= 60 and > 60 years (0.899 vs 0.884) of age. FP-CIT SPECT has a high degree of diagnostic accuracy for striatal dopaminergic involvement. No significant changes in diagnostic accuracy were seen with respect to patient age.


Hyper IgE (Job's) syndrome: a primary immune deficiency with oral manifestations.
Autosomal dominant hyper IgE (HIES or Job's) syndrome is a rare primary immune deficiency characterized by eczema, recurrent skin and lung infections, extremely elevated serum IgE, and a variety of connective tissue and skeletal abnormalities. Individuals with HIES share a characteristic facial appearance and many oral manifestations including retained primary dentition, a high arched palate, variations of the oral mucosa and gingiva, and recurrent oral candidiasis. Mutations in STAT3 account for the majority, if not all, of the cases of autosomal dominant HIES, but the pathogenesis of the many varied features remains poorly understood. In this review, we discuss the clinical phenotype of HIES including immunologic and non-immunologic features, the genetics of HIES, and treatment.


Protective Effects of Curcumin on Manganese-Induced BV-2 Microglial Cell Death.
Curcumin, a bioactive component in tumeric, has been shown to exert antioxidant, anti-inflammatory, anticarcinogenic, hepatoprotective, and neuroprotective effects, but the effects of curcumin against manganese (Mn)-mediated neurotoxicity have not been studied. This study examined the protective effects of curcumin on Mn-induced cytotoxicity in BV-2 microglial cells. Curcumin (0.1-10 µM) dose-dependently prevented Mn (250 µM)-induced cell death. Mn-induced mitochondria-related apoptotic characteristics, such as caspase-3 and -9 activation, cytochrome c release, Bax increase, and Bcl-2 decrease, were significantly suppressed by curcumin. In addition, curcumin significantly increased intracellular glutathione (GSH) and moderately potentiated superoxide dismutase (SOD), both which were diminished by Mn treatment. Curcumin pretreatment effectively suppressed Mn-induced upregulation of malondialdehyde (MDA), total reactive oxygen species (ROS). Moreover, curcumin markedly inhibited the Mn-induced mitochondrial membrane potential (MMP) loss. Furthermore, curcumin was able to induce heme oxygenase (HO)-1 expression. Curcumin-mediated inhibition of ROS, down-regulation of caspases, restoration of MMP, and recovery of cell viability were partially reversed by HO-1 inhibitor (SnPP). These results suggest the first evidence that curcumin can prevent Mn-induced microglial cell death through the induction of HO-1 and regulation of oxidative stress, mitochondrial dysfunction, and apoptotic events.


PRUNE1 (located on chromosome 1q21.3) promotes multiple myeloma with 1q21 Gain by enhancing the links between purine and mitochondrion.
Patients with multiple myeloma (MM) with chromosome 1q21 Gain (1q21+) are clinically and biologically heterogeneous. 1q21+ in the real world actually reflects the prognosis for gain/amplification of the CKS1B gene. In this study, we found that the copy number of prune exopolyphosphatase 1 (PRUNE1), located on chromosome 1q21.3, could further stratify the prognosis of MM patients with 1q21+. Using selected reaction monitoring/multiple reaction monitoring (SRM/MRM) analysis, liquid chromatography-tandem mass spectrometry (LC-MS/MS), transmission electron microscopy (TEM), confocal fluorescence microscopy, calculation of adenosine triphosphate (ATP), intracellular reactive oxygen species (ROS) and mitochondrial oxygen consumption rates (OCRs), we demonstrated for the first time that PRUNE1 promotes the proliferation and invasion of MM cells by stimulating purine metabolism, purine synthesis enzymes and mitochondrial functions, enhancing links between purinosomes and mitochondria. SOX11 was identified as a transcription factor for PRUNE1. Through integrated analysis of the transcriptome and proteome, CD73 was determined to be the downstream target of PRUNE1. Furthermore, it has been determined that dipyridamole can effectively suppress the proliferation of MM cells with high-expression levels of PRUNE1 in vitro and in vivo. These findings provide insights into disease-causing mechanisms and new therapeutic targets for MM patients with 1q21+.


Separating cognitive and motor processes in the behaving mouse.
The cognitive processes supporting complex animal behavior are closely associated with ubiquitous movements responsible for our posture, facial expressions, ability to actively sample our sensory environments, and other central processes. These movements are strongly related to neural activity across much of the brain, making it challenging to dissociate the neural dynamics that support cognitive processes from those supporting movements when they are highly correlated in time. Of critical importance is whether the dynamics supporting cognitive processes and related movements are separable, or if they are both driven by common neural mechanisms. Here, we demonstrate how the separability of cognitive and motor processes can be assessed, and, when separable, how each component can be isolated. We establish a novel two-context behavioral task in mice that involves multiple cognitive processes and show that commonly observed dynamics taken to support cognitive processes are strongly contaminated by movements. When cognitive and motor components are isolated using our analytical approach, we find that they exhibit distinct dynamical trajectories. Further, properly accounting for movement revealed that separate populations of cells encode cognitive and motor variables, in contrast to the 'mixed selectivity' reported by prior work. Accurately isolating the dynamics associated with particular cognitive and motor processes will be essential for developing conceptual and computational models of neural circuit function and evaluating the function of the cell types of which neural circuits are composed.


Bell's palsy. Nonrecurrent v recurrent and unilateral v bilateral.
Bell's palsy was classified into five categories--unilateral nonrecurrent , unilateral recurrent, simultaneous bilateral, alternating bilateral, and recurrent bilateral type--based on the clinical statistical study of two large series of patients with Bell's palsy treated at different locations in Japan. One series consisted of 1,217 patients and the other of 1,197 for a total of 2,414 patients in this study. The incidence of each type and the age and sex distributions were similar in the two groups. Clinical features of each type are described. The results imply that more specific causative factors trigger the recurrences and the simultaneous bilateral attacks.


Effects of different factors on the friction and wear mechanical properties of titanium alloy materials with cortical bones at near service conditions.
The artificial joint is one of the most effective methods to treat joint injuries. The service performance of artificial joints is gradually weakened because of the wear of artificial joints in actual service. In order to obtain the potential failure mechanism of the artificial joint in actual service, the study was carried out with the multiple factors that affect the service performance of the artificial joint. The experimental study was carried out on the change rule of mechanical behavior of the contact interface between the artificial joint of titanium alloy and cortical bone. The multi-factor is compression load, contact load, friction velocity, and lubrication environment, respectively. The results indicate that the friction coefficient, wear mass, and wear coefficient of Ti-6A1-4V titanium alloy decreased with the increasing of the compression load. The friction rate and the friction coefficient of Ti-6A1-4V titanium alloy decreased with the increasing of the contact load. The wear mass and friction coefficient of Ti-6A1-4V titanium alloy increased with the increasing of contact load. The lubrication effect is better with the increasing of lubricant concentration. Based on the observation of the SEM, the wear type influenced by compression load and friction rate is mainly abrasive wear and oxidation wear. The wear type influenced by contact load is mainly abrasive wear and adhesive wear. The wear type influenced by lubricants is mainly oxidation wear. When wear mass and wear coefficient are used as the criteria for evaluating friction and wear, the order of influential factors to friction and wear of Ti-6Al-4V titanium alloy plate is friction rate, compression load, contact load, and lubricant concentration. This research can provide a theoretical reference for the optimal manufacture of the artificial joint of titanium alloy and optimal rules of safe service conditions.


Marxism, social psychology, and the sociology of mental health.
The political activism of the 1960s brought with it activism in the mental health field, broadly defined as antipsychiatry. Included in this social phenomenon are R.D. Laing and his colleagues, mental patients' rights activists, movements against psycho-technological abuses such as psychosurgery, Marxist and radical critiques of mainstream psychiatric practices, and feminist therapy. Some aspects of this broad movement have been influenced or even directed by Marxist perspectives. When Marxist influences have not predominated, antipsychiatric points of view still have much affinity with Marxism. This broad-based criticism of mental health practices and ideologies not only influences the mental health field, but also affects general Marxist social theory, adding to traditional Marxism a concern with feminist issues and the politics of personal and family life. This article explores the progress made by these antipsychiatric perspectives, and examines their limitations as well. Four schools of thought in Marxist psychology--Freudo-Marxism, orthodox-economist Marxism, see Marxist medical model, and "ideology-critique"--are explored to see how they can contribute to the further production of Marxist psychological theory and practice.


Review of Biosimilar Trials and Data on Adalimumab in Rheumatoid Arthritis.
Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the evidence from bio-originator trials in rheumatoid arthritis (RA) to provide context for a critical review of biosimilar trial data. Currently, three adalimumab biosimilars are approved in Europe and/or the USA: Amgen's ABP 501 (AMJEVITA/Solymbic), Boehringer Ingelheim's BI 695501 (Cyltezo) and Samsung Bioepis's SB5 (Imraldi). All three agents met their pre-specified equivalence criteria. Subtle differences in adverse events and clinical responses between the reference and biosimilar products were noted. The introduction of adalimumab biosimilars will offer exciting opportunities in improving treatment access and increasing treatment options for RA and other licensed indications. Real-world data will further provide assurances on efficacy as well as safety.


Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules.
Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.


COVID-19 in Cabo Verde: an assessment of the first six months of the pandemic in the country.
COVID-19, or the new coronavirus, has spread globally since its emergence in December 2019, bringing enormous global health and socioeconomic challenges. Egypt confirmed the first case of COVID-19 in Africa on February 14, 2020, while Cabo Verde confirmed the first case on March 19, 2020. Contrary to forecasts that the virus would swiftly spread throughout Africa, which would soon become the infection's epicenter, the evolution of the pandemic on the continent over the investigated time period has been slower than expected. This study aims to comprehend the progression and consequences of the COVID-19 pandemic in Cabo Verde during its first six months of existence. After the first confirmed case of the new coronavirus, on March 19, 2020, the government of Cabo Verde closed its international borders. Consequently, a state of emergency was declared with stringent restrictions on the movement of persons and goods. Additionally, facilities for the isolation of sick individuals, including field hospitals, had been established. To aid the most vulnerable, public and private organisations had organized fundraising drives. Despite the use of mitigation techniques, the pandemic in Cabo Verde has caused severe socioeconomic harm. It is crucial to preserve and strengthen active surveillance, infection control, and risk communication methods. Social protection policies and economic incentives have the potential to boost infection control strategies.


Immunoinformatics as a Tool for New Antifungal Vaccines.
Immunoinformatics aids in screening for vaccine candidates, which can be experimentally tested for their efficacy. This chapter describes methods to use immunoinformatics to screen fungal vaccines candidates. Surface-localized molecules called adhesins could elicit immune response and serve as efficient vaccine candidates. The screening process is patterned on two steps, namely, a First Layer screen mostly used for value addition and prioritization based on characteristics of known antigens and a Second Layer highly focussed on core immunoinformatics analysis involving the binding and interactions of the molecules of the immune system. Together they offer a comprehensive objective evaluation of vaccine candidates selection in silico for fungal pathogens.


The pharmacodynamics of 5-hydroxytryptamine uptake and metabolism by the isolated perfused rabbit lung.
We have investigated the dynamics for the removal of 5-hydroxytryptamine (5-HT) from the circulation using the isolated perfused rabbit lung. 5-HT was removed from the circulation at a constant rate and metabolized completely to 5-hydroxyindoleacetic acid which effluxed from the lung into the circulation. Two methods were developed to determine the constant rate of removal of 5-HT: (1) the constant rate is equal to the difference between the 5-HT concentration flowing into the lung and the 5-HT concentration in the effluent times the flow rate and (2) extrapolation of the rate of appearance of radioactivity in the effluent to zero time. With these methods, we have confirmed the 5-HT is removed by the lung by a carrier-mediated Na+-dependent transport system. Studies of transport systems in perfused organs required an adequate supply of the chemical to the lung. Supply rates less than removal rate will result in erroneous measurements of the constant removal rate. The relationships between the rate of removal, perfusate concentration and perfusion rate were analyzed.


The Dietary Supplement and Health Education Act and supplements: dietary and nutritional supplements need no more regulations.
The Dietary Supplement and Health Education Act (DSHEA) of 1994 was intended to ensure consumer access to safe dietary supplements, e.g., herbs, minerals, and vitamins. It granted the Food and Drug Administration (FDA) considerable enforcement authority to regulate dietary supplement industry. This article discusses relevant components of the DSHEA, explains the division of regulatory responsibilities between the FDA and the Federal Trade Commission (FTC), and refutes the often cited allegation that the herb and dietary supplement industry are unregulated.


[Color Doppler echography in the diagnosis of nonspecific granulomatous prostatis: personal experience].
Non-specific granulomatous prostatitis (NSGP) is a rare but important pathology of the prostate because it often is confused with prostatic cancer. In fact, NSGP, presents at digital rectal examination as an area of increased consistency and painful, and at endorectal ultrasonography as an hypoechoic area with inhomogeneous echo structure. The frequent elevation of Prostatic-Specific Antigen (PSA) serum level vanish, moreover, its role of a differential factor. Since 1994 we used Echo-color doppler (ECD) in the evaluation of prostate cancer with satisfying results. The aim of our work is to value the route of ECD in the diagnosis of NSGP, and in the differential diagnosis with prostate cancer, actually only bioptic . Since January 1994 we observed 9 cases of NSGP; 7 patients with prostatic symptomatology and 2 with PSA serum level between 4 and 10 ng/ml. In all patients we performed endorectal US who showed, in 7 cases, nodular hypoechoic areas in the peripheral or central zone of the prostate, and in 2 cases the presence of evident BPH. In 5/7 cases with hypoechoic areas, ECD-US showed an increase of color intensity intra-perinodular. In 2 patients with BPH no marked color enhancement was observed. The diagnosis of NSGP has been done after needle biopsy in the 7 patients with suspect nodular areas, and in the 2 patients with BPH, after histological examination secondary to open prostatectomy. Our experience shows that ECD-US scanning picture in NSGP is superimposable with the prostatic cancer one. In fact the anatomical presupposition on the grounds of the "positivity" in ECD-US, focal hypervascularization, is present in ECD scanning pictures of both pathologies. In conclusion, ECD doesn't give an advantage in the differential diagnosis between NSGP and prostate cancer that actually remains only bioptic .


Dynamic pituitary testing in a female with Kallman's syndrome and associated cardiac anomaly.
A patient with Kallman's syndrome and an anomalous right aortic arch is described. Dynamic pituitary testing was carried out revealing no significant response of prolactin to chlorpromazine stimulation or water loading suppression. A normal response of growth hormone to insulin induced hypoglycemia was observed. These data are interpreted as indicating a primary hypothalamic abnormality in Kallman's syndrome. In addition, this is the first report of the association of a cardiovascular abnormality with Kallman's syndrome.


Advances in the diagnosis and management of neurocysticercosis.
Neurocysticercosis is the most common cause of late-onset epilepsy in developing countries. The larval stage of Taenia solium is the causative agent of the disease. Recent advances in neuroimaging and serologic diagnostic techniques have led to increased recognition of its importance, but its pathogenesis is just beginning to be clarified. Experts now agree that the clinical manifestations, pathogenic mechanisms and optimal treatment vary with the number of parasites, their location and the degree of host inflammation. Symptomatic therapy (i.e., antiepileptic medications and, when indicated, surgery) is critically important but there are also important roles for antiparasitic and anti-inflammatory drugs. Neurocysticercosis is a potentially eradicable disease but this is probably unlikely to be achieved in the short term.