Motor and linguistic linking of space and time in the cerebellum.
Recent literature documented the presence of spatial-temporal interactions in the human brain. The aim of the present study was to verify whether representation of past and future is also mapped onto spatial representations and whether the cerebellum may be a neural substrate for linking space and time in the linguistic domain. We asked whether processing of the tense of a verb is influenced by the space where response takes place and by the semantics of the verb. Responses to past tense were facilitated in the left space while responses to future tense were facilitated in the right space. Repetitive transcranial magnetic stimulation (rTMS) of the right cerebellum selectively slowed down responses to future tense of action verbs; rTMS of both cerebellar hemispheres decreased accuracy of responses to past tense in the left space and to future tense in the right space for non-verbs, and to future tense in the right space for state verbs. The results suggest that representation of past and future is mapped onto spatial formats and that motor action could represent the link between spatial and temporal dimensions. Right cerebellar, left motor brain networks could be part of the prospective brain, whose primary function is to use past experiences to anticipate future events. Both cerebellar hemispheres could play a role in establishing the grammatical rules for verb conjugation.


High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker.
RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a recently identified human tumor-associated antigen expressed on various cancer cells. It is thought that tumor cells evade immune surveillance by expression of RCAS1, which induces apoptotic cell death in receptor-positive immune cells. The purpose of our study was to investigate the relation between RCAS1 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemical analysis for RCAS1 was performed on paraffin-embedded specimens of 80 patients (mean age, 62 years) who underwent surgical resection for pancreatic adenocarcinoma. Of the 80 specimens, 77 (96%) were positive for RCAS1. No significant correlation was found between RCAS1 expression and age, gender, depth of invasion, tumor diameter, surgical margin, lymphatic invasion, venous invasion or histopathological grading. Borderline correlations between RCAS1 expression were noted for lymph node metastasis and stage (p = 0.0608 and 0.0934, respectively). RCAS1 expression was very frequently observed and the survival of patients with high RCAS1 expression was significantly shorter than that of those with low expression (p = 0.0012). Multivariate analysis using the Cox regression model indicated that high RCAS1 expression was an independent prognostic factor (risk ratio, 3.090; p = 0.0090). These results suggested that RCAS1 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection.


Extracellular proteinase activity of Cryptococcus neoformans.
Extracellular proteinase activity was studied for eight strains of Cryptococcus neoformans var. neoformans and two strains of Cryptococcus neoformans var. gattii. Proteinase activity was measured by protein agar clearance, azoalbumin hydrolysis, gelatin liquefaction, and protein substrate polyacrylamide gel electrophoresis. All strains of C. neoformans produced extracellular proteolytic activity. Maximal extracellular proteinase activity in supernatants of C. neoformans cultures was associated with late logarithmic- and stationary-phase cultures. C. neoformans was able to utilize murine immunoglobulin G1, bovine immunoglobulin G, and human complement factor 5 for growth in media containing these proteins as the sole sources of carbon and nitrogen, suggesting a capacity to degrade immunologically important proteins. Protein substrate polyacrylamide gel electrophoresis revealed several bands with proteolytic activity at apparent molecular masses of 200, 100, and 50 kDa. The results confirm the existence of extracellular proteinase activity for C. neoformans.


Absence of t(14;18) major and minor breakpoints and of Bcl-2 protein overproduction in Reed-Sternberg cells of Hodgkin's disease.
The t(14;18) translocation, found in most human follicular non-Hodgkin's lymphomas (NHLs), juxtaposes the Bcl-2 oncogene at 18q21 with the immunoglobulin heavy chain locus at 14q32. As a result, the Bcl-2 protein is markedly overproduced. Most of the breakpoints on chromosome 18 cluster at one of two sites, the major breakpoint region (mbr) and the minor cluster region (mcr). Recently, others used the polymerase chain reaction (PCR) to detect the t(14;18) mbr in 32% of specimens diagnosed as Hodgkin's disease (HD). In an attempt to confirm and extend those observations the authors used PCR to assay for both the mbr and mcr in HD specimens diagnosed at their institution and examined the specimens for Bcl-2 overproduction. The authors subjected the DNAs from 28 well-characterized HD tumors of 26 patients to PCR analyses using primers specific for the t(14;18) mbr and mcr breakpoints. Based on various PCR controls, the authors ascertained that 26 of the 28 specimens contained amplifiable template DNA. Southern blotting of the amplification products showed that none of the 26 HD DNAs had detectable t(14;18) mbr or mcr breakpoints. By admixing small amounts of t(14;18)-bearing NHL DNA with HD DNA samples, the authors directly demonstrated that the sensitivity of the PCR assays was adequate for the molecular detection of t(14;18)-bearing cells at a frequency comparable to that of Reed-Sternberg cells and their variants in HD. Immunohistochemical studies employing a highly specific anti-Bcl-2 antiserum under conditions optimized to detect t(14;18)-mediated overexpression of the Bcl-2 gene showed that the Reed-Sternberg cells and variants in all 19 HD tumors examined were negative for Bcl-2 immunostaining. In conclusion, the PCR and immunohistochemical data provided evidence that the t(14;18) translocation was not involved in the pathogenesis of the HD cases.


Atg8: an autophagy-related ubiquitin-like protein family.
Autophagy-related (Atg) proteins are eukaryotic factors participating in various stages of the autophagic process. Thus far 34 Atgs have been identified in yeast, including the key autophagic protein Atg8. The Atg8 gene family encodes ubiquitin-like proteins that share a similar structure consisting of two amino-terminal α helices and a ubiquitin-like core. Atg8 family members are expressed in various tissues, where they participate in multiple cellular processes, such as intracellular membrane trafficking and autophagy. Their role in autophagy has been intensively studied. Atg8 proteins undergo a unique ubiquitin-like conjugation to phosphatidylethanolamine on the autophagic membrane, a process essential for autophagosome formation. Whereas yeast has a single Atg8 gene, many other eukaryotes contain multiple Atg8 orthologs. Atg8 genes of multicellular animals can be divided, by sequence similarities, into three subfamilies: microtubule-associated protein 1 light chain 3 (MAP1LC3 or LC3), γ-aminobutyric acid receptor-associated protein (GABARAP) and Golgi-associated ATPase enhancer of 16 kDa (GATE-16), which are present in sponges, cnidarians (such as sea anemones, corals and hydras) and bilateral animals. Although genes from all three subfamilies are found in vertebrates, some invertebrate lineages have lost the genes from one or two subfamilies. The amino terminus of Atg8 proteins varies between the subfamilies and has a regulatory role in their various functions. Here we discuss the evolution of Atg8 proteins and summarize the current view of their function in intracellular trafficking and autophagy from a structural perspective.


Novel therapeutic strategies using nanodrug delivery, stem cells and combination therapy for CNS trauma and neurodegenerative disorders.
The 10th Global College of Neuroprotection and Neuroregeneration Annual Conference in collaboration with the 6th International Association of Neurorestoratology VI Intercontinental Hotel, Bucharest, Romania, 4-7 April 2013 The 10th Global College of Neuroproetction and Neuroregeneration Annual Conference together with the International Association of Neurorestoratology VI was held in Bucharest under the auspicious of the Society for the Study of Neuroprotection and Neuroplasticity during 4-7 April 2013. The focus of these unified societies meeting was on neurorestoration, neuroprotection and neuroregeneration in various clinical neurodegenerative diseases; for example, Alzheimer's, Parkinson's, Huntington's disease, stroke and brain or spinal cord injuries. The main aim to enhance healthcare was suggested by the use of stem cells, nanodrug delivery of drugs and stem cells, use of multimodal drugs as well as a combination of different approaches. The meeting was attended by more than 500 delegates including researches, policy makers and healthcare professionals along with several representatives from drug industries from Europe and USA. It appears that future of neuroprotection could be achieved by the use of stem cells and nanodrug delivery in chronic neurological disorders.


Growth dynamics of the canine proximal tibial physis.
To determine growth of the proximal tibial physis in the Labrador Retriever, a breed of dog at risk for rupture of the cranial cruciate ligament (CCL). Male Labrador Retriever dogs (n=6). Tantalum markers (0.5 mm diameter) were implanted in the right proximal tibial epiphysis and metaphysis of each dog at 16 weeks of age. Lateral and craniocaudal radiographic projections of the tibia were made monthly and longitudinal growth was assessed from radiographs; a growth curve was generated from the data. Data from dogs that had undergone proximal tibial epiphysiodesis (PTE) was compared with the growth curve to demonstrate if the growth curve accurately predicted changes in the growth associated with this procedure. Growth rate of individual dogs decreased slowly and non-linearly over the 1st year of age. Growth from the proximal tibial physis is described. Growth of individual dogs described here follows the model of saltation and stasis. The growth curve generated predicted the change in tibial plateau angle (TPA) for two Labrador Retrievers that had PTE (± 1°).


Extremely enlarged right atrial appendage in paediatric idiopathic pulmonary hypertension.
We report an extremely rare case of a right atrial appendage aneurysm in idiopathic pulmonary arterial hypertension (PAH) identified at autopsy. The female patient was diagnosed with idiopathic PAH at the age of 7. Despite intensive treatment, she expired due to cardiac failure at the age of 18. At autopsy, initial thoracotomy revealed an extremely enlarged intrapericardial balloon-like chamber with characteristic horizontal stripes, which turned out to be a markedly dilated right atrial appendage. The histology of the lungs was compatible with idiopathic PAH. In cor pulmonale which may complicate PAH, the occurrence of a right atrial appendage aneurysm is extremely rare, although right ventricular dilatation is common. Improved prognosis and rare paediatric occurrence of idiopathic PAH may have disclosed the unprecedented flexibility and expandability of the atrial appendage in children.


Variations of gonadal veins: embryological prospective and clinical significance.
An adequate knowledge of anomalies of gonadal veins will help the radiologists and surgeons in recognition and protection of these veins which play major roles in thermo-regulation that is essential for the efficient functioning of testis on which the survival of the human species depends. The aim of this work is to present an analysis of the anatomical variations of gonadal veins. An effort has also been made to explicate the possible embryological model of development of such variants and to present the variable clinical aspects concerning them. Gonadal veins in 60 dissection room cadavers were examined for variations from the classic anatomic description. In the present study, out of 60 cases, male: female ratio was 2:1(40:20) in which no variation was found in ovarian veins. In the 18 (45%) cases, testicular veins showed variations which consist of duplication and atypical drainage. Variations of drainage of gonadal vein are due to error of embryological development in venous shift and alteration in anastomotic channel of post-cardinal, supra-cardinal and sub cardinal veins. The gonadal veins present numeric variations as well as variations in its site of drainage, which attributed to the various pathological conditions as varicocele and pelvic congestion syndrome, leading to infertility in patients. Hence, in -depth knowledge of these developmental anomalies of gonadal veins is important.


Update on clinical gene therapy for hemophilia.
In contrast to other diverse therapies for the X-linked bleeding disorder hemophilia that are currently in clinical development, gene therapy holds the promise of a lasting cure with a single drug administration. Near-to-complete correction of hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency) have now been achieved in patients by hepatic in vivo gene transfer. Adeno-associated viral vectors with different viral capsids that have been engineered to express high-level, and in some cases hyperactive, coagulation factors were employed. Patient data support that sustained endogenous production of clotting factor as a result of gene therapy eliminates the need for infusion of coagulation factors (or alternative drugs that promote coagulation), and may therefore ultimately also reduce treatment costs. However, mild liver toxicities have been observed in some patients receiving high vector doses. In some but not all instances, the toxicities correlated with a T-cell response directed against the viral capsid, prompting use of immune suppression. In addition, not all patients can be treated because of preexisting immunity to viral capsids. Nonetheless, studies in animal models of hemophilia suggest that the approach can also be used for immune tolerance induction to prevent or eliminate inhibitory antibodies against coagulation factors. These can form in traditional protein replacement therapy and represent a major complication of treatment. The current review provides a summary and update on advances in clinical gene therapies for hemophilia and its continued development.


NAVILAS Laser System Focal Laser Treatment for Diabetic Macular Edema - One Year Results of a Case Series.
To report one year outcomes of focal Navigated Retina Laser Therapy (NAVILAS) for diabetic macular edema (DME). Retrospective cohort series of 7 diabetic patients treated with NAVILAS focal laser. Statistical analysis included descriptive and continuous variables (Best-corrected logMAR Visual Acuity and time-domain optical coherence tomography (OCT) parameters) which were compared using a non-parametric procedure, the Friedman tests for repeated measures. A p-value of less than 0.05 was considered to denote statistical significance. diabetic patients (4 male; 3 female) with an average age of 60.8 years (range 48-85 years) were included. All treated eyes were phakic; patients had an average hemoglobin A1C of 9.1 (range 7.8-11.7) at baseline and 8.0 (range 7.4-8.4) at 12 months. Six of the 7 patients had intravitreal bevacizumab injections prior to focal laser treatment with 1 patient having had more than 1 prior injection (total 3). At 12 months, median logMAR improved from 0.695 (± interquartile range 0.574) to 0.477 (± 0.573, p <0.001). OCT median central foveal thickness decreased from 248 (± 112) to 220 µm (± 41, p <0.001); total macular volume decreased from 7.84 (± 0.8) to 7.44 mm3 (± 0.7, p = 0.117); and largest macular subfield thickness decreased from 354 (± 116) to 289 µm (± 42, p <0.001). All patients were treated without complications. Focal NAVILAS showed to be safe and effective in treating DME with improvement in visual acuity and macular edema on OCT over 12 months in this case series. In clinical practice, combined treatment with focal laser including NAVILAS and anti-vascular endothelial growth factor may provide long-term improvement in DME.


Organic aggregates formed by benthopleustophyte brown alga Acinetospora crinita (Acinetosporaceae, Ectocarpales).
This work presents the elemental, polysaccharide, and fatty acid compositions of benthic aggregates formed by the filamentous brown alga Acinetospora crinita, which are widely spread on the rocky bottoms of the Mediterranean Sea. The aggregates can be characterized as mineralized centers in which regeneration of nutrients and recycling of dissolved organic matter actively occur and favor the development of an abundant phytoplankton community. Analyses of the stable isotopes of C and N display their marine origin and could provide evidence of the processes that occur inside/outside of the aggregates. The monosaccharide compositions of Adriatic and Tyrrhenian mucilages produced by brown alga A. crinita were quite similar. In particular, the Adriatic sample compositions resembled the average composition of the Tyrrhenian high molecular weight exopolymers, and the observed differences could be ascribed to different degradation stages. The fatty acid patterns found for the aggregates were similar to those observed in the isolated A. crinita algae with variable contributions from embedded diatom species. The bacterial contribution to the fatty acid pool was quite low, most likely due to the known poor conditions for their heterotrophic growth.


Improved efficiency of daratumumab treatment of multiple myeloma adopting the subcutaneous route: A micro-costing analysis in three Italian hematology centers.
Daratumumab is a humanized monoclonal antibody approved for the treatment of adult patients with newly diagnosed or relapsed/refractory multiple myeloma (RRMM). Subcutaneous (SC) formulation proved to be non-inferior in comparison with intravenous (IV) administration route. This study aimed at assessing the economic and time impact associated with the use of SC versus IV daratumumab in patients with RRMM from the perspective of the hematology center. This was a 5-month multicenter time-and-motion cross-sectional micro-costing study conducted in three Italian hematology centers among adult patients diagnosed with RRMM with ongoing treatment with IV or SC daratumumab. Measurements were performed by an ad hoc App. Nineteen (20%) IV and 76 (80%) SC administration procedures were measured. Patients spent a mean of 4.85 ± 0.91 or 1.08 ± 0.56 h in the hematology center to receive IV or SC daratumumab, respectively. Healthcare professionals (HCPs) spent a mean of 49.38 ± 16.13 and 20.37 ± 7.88 min of active working time to manage IV and SC administrations, respectively. The infusion chair was occupied for a mean of 4.85 ± 0.91 and 0.99 ± 0.55 h during IV or SC administration, respectively. On average, considering the costs due to HCP and chair time, materials, and overhead costs, every IV and SC administration costed €80.33 and 34.90, respectively. In conclusion, as compared with IV administration, SC daratumumab was associated with 78%, 59%, 80% savings in terms of patient time, HCP active working time, and infusion chair, respectively, and 56.6% budget savings.


Effect of osmolarity on aldosterone production by rat adrenal glomerulosa cells.
The effect of osmotic changes on aldosterone production, [Ca2+]i and voltage-gated Ca2+ currents, was studied in cultured rat glomerulosa cells. Alteration of osmolarity by sucrose addition in the 250-330 mosM range did not influence aldosterone production per se, but it substantially affected K+-stimulated aldosterone production. Hyposmosis markedly increased the hormone response evoked by raising [K+] from 3.6 to 5 mM, whereas hyperosmosis had a mild decreasing effect. Cytoplasmic [Ca2+]i, measured in single glomerulosa cells, did not show detectable change in response to either hyposmotic or hyperosmotic exposure, but the [Ca2+]i signal evoked by elevation of [K+] to 5 mM was augmented in hyposmotic solution. The osmosensitivity of the transient (T)-type and long-lasting (L)-type voltage-gated Ca2+ currents was studied using the nystatin-perforated voltage-clamp technique. Lowering osmolarity to 250 mosM significantly increased the amplitude of the T-type current, and it had a transient augmenting effect on L-type current amplitude. Hyperosmotic solution (330 mosM) reduced L-type current amplitude but did not evoke significant change in T-type current. These results indicate that the responsiveness of rat glomerulosa cells to physiological elevation of [K+] is remarkably influenced by changes in osmolarity by means of modulating the function of voltage-gated Ca2+ channels.


The Dichotomy of Interleukin-9 Function in the Tumor Microenvironment.
Interleukin 9 (IL-9) is a cytokine with potent proinflammatory properties that plays a central role in pathologies such as allergic asthma, immunity to parasitic infection, and autoimmunity. More recently, IL-9 has garnered considerable attention in tumor immunity. Historically, IL-9 has been associated with a protumor function in hematological malignancies and an antitumor function in solid malignancies. However, recent discoveries of the dynamic role of IL-9 in cancer progression suggest that IL-9 can act as both a pro- or antitumor factor in various hematological and solid malignancies. This review summarizes IL-9-dependent control of tumor growth, regulation, and therapeutic applicability of IL-9 blockade and IL-9-producing cells in cancer.


A meta-analysis of studies of treatments for feline urine spraying.
Feline urine spraying inside the home is a common problem behaviour that owners seek advice for from veterinarians. Individual trials relating to a variety of interventions produce variable results, and to date, no consensus on the value of different treatments has emerged. This study therefore aimed to meta-analyse, current data from appropriate published clinical trials that evaluate treatments for feline urine spraying.Inclusion and exclusion criteria for study selection were predefined and methodological quality was assessed by two independent reviewers. Ten studies in nine publications that either evaluated pharmacotherapy or pheromonatherapy (the use of a synthetic analogue of the F3 facial fraction in the cat) were suitable for analysis. There was a significant (P<0.001) association between the use of any intervention and the number of cats that ceased or reduced urine spraying by at least 90%. Analysis by intervention type indicated that fluoxetine, clomipramine and pheromonatherapy may each assist in managing urine spraying beyond a placebo based intervention.This is the first time meta-analytical techniques have been used and reported to evaluate the efficacy of interventions used in veterinary behavioural medicine, and it has established confidence in the value of both conventional treatments (pharmacotherapy) and a more recently developed treatment modality (pheromonatherapy) as an adjunct to the management of this problem. It is suggested that future research into treatment efficacy for this problem uses the benchmark standard of randomised, controlled trials lasting for at least 8 weeks, with the outcome criteria of cessation of feline urine spraying or reduction by at least 90%.


Granulocytic sarcoma of breast: an aleukemic presentation.
Granulocytic sarcoma is a rare extramedullary tumor composed of immature myeloid cells. It is usually associated with leukemia or other myeloproliferative disorders but can also occur without overt hematologic diseases. The breast is an uncommon site of presentation and requires a high index of suspicion for diagnosis. We report such a case in a 45-year-old female, who presented with nontender left breast lump of 6 months' duration. A peripheral smear and bone marrow examination at that time was normal. A lumpectomy was done. An H and E diagnosis of lobular carcinoma vs. non-Hodgkin's lymphoma was entertained. Immunostains, however, revealed myeloperoxidase, naphthol AS-D chloroacetate esterase and CD43 positivity, indicating a diagnosis of granulocytic sarcoma. It appears that early initiation of systemic AML-type chemotherapy is beneficial and may delay or avert the development of AML in bone marrow and blood. Eight months later, the patient presented with an orbital mass; bone marrow and peripheral smear involvement by AML.


Complexity of the consistency problem for certain Post classes.
The complexity of the consistency problem for several important classes of Boolean functions is analyzed. The classes of functions under investigation are those which are closed under function composition or superposition. Several of these so-called Post classes are considered within the context of machine learning with an application to breast cancer diagnosis. The considered Post classes furnish a user-selectable measure of reliability. It is shown that for realistic situations which may arise in practice, the consistency problem for these classes of functions is polynomial-time solvable.


The Belgian DNA Debate: An Online Deliberative Platform on the Ethical, Legal, and Social Issues of Genomics.
Genomics is increasingly being implemented in the society. To fully realise this implementation, citizens should be consulted about their perspectives on genomics and its associated ethical, legal, and social issues (ELSI) to enable them to co-create with experts a society-supported framework in genomics. A Belgian online DNA debate was organised, where 1,127 citizens contributed to its deliberative platform. Contributors expressed a dual attitude towards the societal use of genomic information throughout 5 main themes. Firstly, contributors considered DNA to have a significant but nondeterministic impact on identity. The second theme describes how genomic information may guide people's behaviour but has unfavourable effects such as psychological distress. The third theme covers the tension between a genomics-based responsibility and the rejection of genetic discrimination. The fourth theme depicts how genomic information may be useful for the common good and society at large but how, nevertheless, it should be people's free choice to use this information. In the fifth theme, contributors expressed both willingness to share their data and caution towards the harm and abuses this may engender. Finally, contributors formulated some recommendations for the responsible implementation of genomics. The attitude of contributors towards the societal use of genomic information and its ELSI aligns with a soft precautionary approach, in which prudence and the weighing of different values should result in protective measures against potential risks and harms. Further societal implementation of genomics should include these values and concerns.


Human beta-defensin 3 has immunosuppressive activity in vitro and in vivo.
Beta-defensins are antimicrobial peptides with an essential role in the innate immune response. In addition beta-defensins can also chemoattract cells involved in adaptive immunity. Until now, based on evidence from dendritic cell stimulation, human beta defensin-3 (hBD3) was considered pro-inflammatory. We present evidence here that hBD3 lacks pro-inflammatory activity in human and mouse primary Mphi. In addition, in the presence of LPS, hBD3 and the murine orthologue Defb14 (but not hBD2), effectively inhibit TNF-alpha and IL-6 accumulation implying an anti-inflammatory function. hBD3 also inhibits CD40/IFN-gamma stimulation of Mphi and in vivo, hBD3 significantly reduces the LPS-induced TNF-alpha level in serum. Recent work has revealed that hBD3 binds melanocortin receptors but we provide evidence that these are not involved in hBD3 immunomodulatory activity. This implies a dual role for hBD3 in antimicrobial activity and resolution of inflammation.


ECG artifacts and heart period variability: don't miss a beat!
The impact of artifacts on estimates of heart period variability were evaluated by modeling the effects of missed R-waves and spurious R-wave detections in actual and simulated heart period series. Results revealed that even a single artifact, occurring within a 128-s interbeat interval series, can impart substantial spurious variance into all commonly analyzed frequency bands, including that associated with respiratory sinus arrhythmia. In fact, the spurious variance introduced by a single artifact may be greater than that associated with true basal heart period variability and can far exceed typical effect sizes in psychophysiological studies. The effects of artifacts are not related to a specific analytical method and are apparent in both frequency and time domain analyses. Results emphasize the importance of artifact detection and resolution for studies of heart period variability.


Aortoenteric fistula 24 years after aortic endarterectomy.
Aortoenteric fistula is a well-recognized and potentially catastrophic complication of aortic surgery. It usually follows aortic graft placement and removal of the prosthesis. Extra-anatomic bypass is the treatment generally recommended. The authors report the case of a 74-year-old woman who presented with an aortoenteric fistula 24 years after aortic endarterectomy. The fistula was managed with an anatomically placed Dacron graft. The radiologic findings and approach to management of this uncommon problem are discussed.


The Interior Surfaces of Wooden Barrels Are an Additional Microbial Inoculation Source for Lambic Beer Production.
Traditional lambic beer production takes place through wort inoculation with environmental air and fermentation and maturation in wooden barrels. These wooden casks or foeders are possible additional inoculation sources of microorganisms for lambic worts. To date, however, these lambic barrels have been examined only with culture-dependent techniques, thereby missing a portion of the microorganisms present. Moreover, the effects of the cleaning procedures (involving high-pressure water and/or fumigation) and the barrel type on the microbial community structures of the interior surfaces of wooden lambic barrels were unclear. The culture-dependent plating and culture-independent amplicon sequencing of swab samples obtained from the interior surfaces of different wooden casks and foeders used for traditional lambic beer production in Belgium revealed that the microbial compositions of these surfaces differed statistically throughout the barrel-cleaning procedures applied. At the end of the cleaning procedures, amplicon sequencing still detected fermentation- and maturation-related microorganisms, although only a few colonies were still detectable using culture-dependent methods. It is possible that some of the surviving microorganisms were missed due to the presence of many of these cells in a viable but not culturable state and/or engrained deeper in the wood. These surviving microorganisms could act as an additional inoculation source, besides brewery air and brewery equipment, thereby helping to establish a stable microbial community in the wort to diminish batch-to-batch variations in fermentation profiles. Furthermore, the microbial compositions of the interior barrel surfaces differed statistically based on the barrel type, possibly reflecting different characteristics of the lambic barrels in terms of age, wood thickness, and wood porosity.IMPORTANCE Although the coolship step is generally regarded as the main contributor to the spontaneous inoculation by environmental air of fresh worts for lambic beer production, it is known that microorganisms often associate with specific surfaces present in a brewery. However, knowledge about the association of microorganisms with the interior surfaces of wooden lambic barrels is limited. To clarify the role of casks and foeders as additional microbial inoculation sources, it was important to determine the influence of the barrel characteristics and the cleaning procedures on the microbial communities of the interior barrel surfaces. Moreover, this helped to elucidate the complex spontaneous lambic beer fermentation and maturation process. It will allow further optimization of the lambic beer production process, as well as the wooden-barrel-cleaning procedures applied.


Expression of interferon regulatory factor family and its prognostic value in acute myeloid leukemia.
Aim: To elucidate the clinicopathological and prognostic values of interferon regulatory factor (IRF) family genes in acute myeloid leukemia (AML). Patients & methods: Differential expression analysis and survival analysis from several reliable databases were conducted and further validated using patients with AML. Results: The expression level of IRF1/2/4/5/7/8/9 in patients with AML was upregulated, while IRF3/6 expression was downregulated. High IRF1/7/9 expression indicated a worse overall survival rate. Conclusion: Overexpression of IRF1/7/9 may be associated with poor survival in patients with AML, suggesting that the IRF family may be a promising therapeutic target.


Current Experiences and Future Expectations for Physical Activity Participation: Perspectives of Young People with Physical Disabilities and Their Rehabilitation Clinicians.
Purpose: Researchers investigated current physical activity experiences of youth with physical disabilities and expectations for continued participation as they transition to adult services. Method: Youth (n = 6) and clinicians (n = 7) from a rehabilitation center participated in two separate focus groups. Researchers used inductive thematic analysis. Results: Four themes emerged among youth: "good for your health"; "motivation is key"; "social opportunities in safe environments"; "wanting to stay active." Among clinicians, five themes arose: "added therapeutic benefits with participation"; "development as individuals through physical activity"; "inclusive and supportive environments"; "parents as advocates"; "transitioning to adult services is important." Conclusions: Themes across focus groups were comparable. Participants expressed positive experiences for youth attending a dedicated adapted fitness center. To facilitate current and future physical activity in adulthood for youth with physical disabilities in integrated settings, the following are warranted: accessible buildings, trained staff, adapted equipment, and positive attitudes toward disability.


COVID-19 Vaccination Acceptance Among Healthcare Workers and Non-healthcare Workers in China: A Survey.
Background: The coronavirus pneumonia is still spreading around the world. Much progress has been made in vaccine development, and vaccination will become an inevitable trend in the fight against this pandemic. However, the public acceptance of COVID-19 vaccination still remains uncertain. Methods: An anonymous questionnaire was used in Wen Juan Xing survey platform. All the respondents were divided into healthcare workers and non-healthcare workers. Multinomial logistic regression analyses were performed to identify the key sociodemographic, cognitive, and attitude associations among the samples of healthcare workers and non-healthcare workers. Results: A total of 2,580 respondents completed the questionnaire, including 1,329 healthcare workers and 1,251 non-healthcare workers. This study showed that 76.98% of healthcare workers accepted the COVID-19 vaccine, 18.28% workers were hesitant, and 4.74% workers were resistant. Among the non-healthcare workers, 56.19% workers received the COVID-19 vaccine, 37.57% workers were hesitant, and 6.24% workers were resistant. Among the healthcare workers, compared with vaccine recipients, vaccine-hesitant individuals were more likely to be female (AOR = 1.52, 95% CI: 1.12-2.07); vaccine-resistant individuals were more likely to live in the suburbs (AOR = 2.81, 95% CI: 1.44-3.99) with an income of 10,000 RMB or greater (AOR = 2.00, 95% CI: 1.03-3.90). Among the non-healthcare workers, vaccine-hesitant individuals were more likely to be female (AOR = 1.66, 95% CI: 1.31-2.11); vaccine-resistant individuals were also more likely to be female (AOR = 1.87, 95% CI: 1.16-3.02) and older than 65 years (AOR = 4.96, 95% CI: 1.40-7.62). There are great differences between healthcare workers and non-healthcare workers in their cognition and attitude toward vaccines. Conclusions: Our study shows that healthcare workers are more willing to be vaccinated than non-healthcare workers. Current vaccine safety issues continue to be a major factor affecting public acceptance, and to expand vaccine coverage in response to the COVID-19 pandemic, appropriate vaccination strategies and immunization programs are essential, especially for non-healthcare workers.


Modulation of granulocyte responses in three-spined sticklebacks Gasterosteus aculeatus infected with the tapeworm Schistocephalus solidus.
Leukocytes isolated from the head kidney and peripheral blood of 3-spined sticklebacks Gasterosteus aculeatus L. were analysed by means of flow cytometry during infection with the tapeworm Schistocephalus solidus (Müller, 1776). Although parasites increased their body weight continuously throughout the observation period (98 d), proportions of granulocytes increased in blood and head kidney only up to Day 63 post-infection (p.i.). Thereafter, declining proportions of granulocytes were observed in both organs. Thus the relative decrease in granulocyte number was not correlated to a decline in the parasitic load of the fish. To investigate a possible modulatory impact of S. solidus on granulocyte function, head kidney leukocytes were isolated at times before Day 63 p.i. and tested in vitro for their capacity to produce reactive oxygen species (ROS). Head kidney leukocytes from S. solidus-infected fish, analysed immediately after isolation (ex vivo, Day 40 p.i.), exhibited a higher ROS production when stimulated with phorbol myristate acetate (PMA), than leukocytes from naive, sham-treated control fish and fish that had resisted or cleared the infection (exposed but not infected). The latter showed an increased spontaneous ROS production that was not correlated to the numbers of granulocytes present in the head kidney isolates. In infected sticklebacks, spontaneous and PMA-induced ROS production was significantly correlated with numbers of granulocytes present in the head kidney isolates, suggesting that elevated ROS production was due to higher numbers of responding cells rather than an increased capacity of single cells. In vitro, after cultivation for 4 d in the presence of pokeweed mitogen (PWM) or extracts from S. solidus, head kidney leukocytes from control fish showed an increased ROS production and phagocytic activity compared with non-stimulated control cultures. In contrast, head kidney leukocytes from infected fish isolated on Days 48 and 44 p.i., failed to respond to S. solidus antigens in vitro. During S. solidus infection, granulocyte mobilisation resulted in elevated numbers of these cells in head kidneys, but the lack of an in vitro response to S. solidus antigens indicates an in vivo priming of granulocytes by the parasite. These observations may reflect the ability of S. solidus to impair the host's immune response once the parasite is developing in the body cavity of G. aculeatus.


Use of short tandem repeat fingerprinting to validate sample origins in hepatitis C virus molecular epidemiology studies.
Sequence analysis is used to define the molecular epidemiology and evolution of the hepatitis C virus. Whilst most studies have shown that individual patients harbour viruses that are derived from a limited number of highly related strains, some recent reports have shown that some patients can be co-infected with very distinct variants whose frequency can fluctuate greatly. Whilst co-infection with highly divergent strains is possible, an alternative explanation is that such data represent contamination or sample mix-up. In this study, we have shown that DNA fingerprinting techniques can accurately assess sample provenance and differentiate between samples that are truly exhibiting mixed infection from those that harbour distinct virus populations due to sample mix-up. We have argued that this approach should be adopted routinely in virus sequence analyses to validate sample provenance.


The ability of trained nurses to detect lumps in a test set of silicone breast models.
Screening for breast carcinoma is a Healthy People 2000 objective and physical examination is an important component of the screening process. However, many women do not have access to a high quality breast examination. To help address this problem for Native American women, the authors developed the Nurses Providing Annual Cancer Screening (NPACS) training program, a week-long training session conducted at the nurses' clinical site. The goal of the current study was to demonstrate that, after receiving training, the nurses can detect masses in breast models at acceptably high rates. Thirty-four nurses who had completed the NPACS training program performed examinations of a test set of six silicone breast models. True-positive and false-positive rates of lump detection were calculated. The nurses were able to detect more lumps in the simulated breasts than both untrained and trained physicians tested in previous trials using the same methodology. On the average, nurses found 76% of the 18 lumps in the 6 breast models. However, their rate of false-positive detections also was somewhat higher. Although the modal number of false-positive detections for both physicians and nurses was 0, the median number of false-positive detections was 0 for the physicians and 1.0 for the nurses. In the current study, trained nurses were able to detect masses in breast models at high rates. This observation suggests that widespread training of nurses to perform screening breast examinations might be considered as a response to the breast carcinoma screening needs of adult women.


[Treatment of blood circulation disorders with a hemoactive-vasoactive drug].
The therapeutic activity of Fludilat in circulatory disorders was evaluated in 9 women and 11 men, with ages between 41 and 75 years. Three suffered atherosclerosis and 17 diabetic vascular disease. Elimination of the symptom was obtained in intermittent claudication in 71 per cent of the patients who suffered it, in 67 per cent in case of feeling of coldness, in 46 per cent in paraesthesias, in 73 per cent in feeling of heaviness and in 6 per cent in trophic changes. In the remaining patients there was a significative reduction in the intensity of the symptoms, except in trophic changes. This result are considered as excellents. The general result of the treatment was satisfactory. There was no significacative change in the blood pressure and no side effects were reported. A better response of the atherosclerotic patients was obtained. We found no influence of age, sex and blood pressure on the results. The study corroborates the efficacy of Fludilat in the treatment of circulatory disorders and its excellent tolerance.


Characterization of the alkoxide-based sol-gel derived La9.33Si6O26 powder and ceramic.
In this study, we report on the acid-catalysed synthesis of La(9.33)Si(6)O(26) from lanthanum nitrate or acetate and silicon ethoxide (TEOS) in the ethanol solvent, upon the transition from liquid to amorphous and crystalline phases. The similarity of the Fourier transform infrared spectra of the lanthanum-salt solutions and lanthanum-silicon sols indicates that the lanthanum environment is not changed in the reaction of the La-salt with TEOS. In the nitric-acid catalysed synthesis, the hydrolysis reaction was almost instantaneous, as a consequence of a higher amount of water in this system, which contributed to a high level of chemical heterogeneity in the product. The acetic acid-based synthesis ensured a good mixing of the reagents at the nanometre level, which gave rise to the formation of the pure La(9.33)Si(6)O(26) powder upon heating at 900 °C, and single phase ceramics with 94 % relative density after sintering at 1400 °C for 3 h in air, which is 200 °C lower temperature then usually reported for the apatite material.


A multi-fluid model for microstructure formation in polymer membranes.
We develop a multi-fluid model for a ternary polymer solution using the Rayleighian formalism of Doi and Onuki, and give an efficient pseudo-spectral method for solving both the diffusion and momentum equations that result. Subsequently, we find that the numerical simulation is capable of describing systems at the micron length-scale and easily reaches millisecond time-scales. In addition, we characterize the model thermodynamics and kinetics including the (i) phase behavior, (ii) structure of the interfaces, (iii) mutual diffusion coefficients, (iv) bulk spinodal decomposition kinetics with and without hydrodynamics and (v) spinodal decomposition in the presence of an interface with a non-solvent bath. We obtain good qualitative agreement with the expected thermodynamic and kinetic behavior. We also show that a linear stability analysis of the diffusion equation quantitatively predicts the fastest growing mode obtained from simulation and gives insight into the phase separation process relevant for the evolution of microstructure in phase-separating ternary polymer solutions.


The role of recombination, niche-specific gene pools and flexible genomes in the ecological speciation of bacteria.
Bacteria diversify into genetic clusters analogous to those observed in sexual eukaryotes, but the definition of bacterial species is an ongoing problem. Recent work has focused on adaptation to distinct ecological niches as the main driver of clustering, but there remains debate about the role of recombination in that process. One view is that homologous recombination occurs too rarely for gene flow to constrain divergent selection. Another view is that homologous recombination is frequent enough in many bacterial populations that barriers to gene flow are needed to permit divergence. Niche-specific gene pools have been proposed as a general mechanism to limit gene flow. We use theoretical models to evaluate additional hypotheses that evolving genetic architecture, specifically the effect sizes of genes and gene gain and loss, can limit gene flow between diverging populations. Our model predicts that (a) in the presence of gene flow and recombination, ecological divergence is concentrated in few loci of large effect and (b) high rates of gene flow plus recombination promote gene loss and favor the evolution of niche-specific genes. The results show that changing genetic architecture and gene loss can facilitate ecological divergence, even without niche-specific gene pools. We discuss these results in the context of recent studies of sympatric divergence in microbes.


MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells.
The MITF transcription factor and the RAS/RAF/MEK/ERK pathway are two interconnected main players in melanoma. Understanding how MITF activity is regulated represents a key question since its dynamic modulation is involved in the phenotypic plasticity of melanoma cells and their resistance to therapy. By investigating the role of ARAF in NRAS-driven mouse melanoma through mass spectrometry experiments followed by a functional siRNA-based screen, we unexpectedly identified MITF as a direct ARAF partner. Interestingly, this interaction is conserved among the RAF protein kinase family since BRAF/MITF and CRAF/MITF complexes were also observed in the cytosol of NRAS-mutated mouse melanoma cells. The interaction occurs through the kinase domain of RAF proteins. Importantly, endogenous BRAF/MITF complexes were also detected in BRAF-mutated human melanoma cells. RAF/MITF complexes modulate MITF nuclear localization by inducing an accumulation of MITF in the cytoplasm, thus negatively controlling its transcriptional activity. Taken together, our study highlights a new level of regulation between two major mediators of melanoma progression, MITF and the MAPK/ERK pathway, which appears more complex than previously anticipated.


UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan.
Capecitabine and irinotecan are commonly used in the treatment of metastatic colorectal cancer (CRC). We hypothesized that germline polymorphisms within genes related to drug target (thymidylate synthase) or metabolizing enzymes (UDP-glucuronosyltransferase, UGT) would impact response and toxicity to the combination of capecitabine plus irinotecan (CPT-11). Sixty-seven patients with measurable CRC were treated with irinotecan i.v. (100 or 125 mg/m(2)) on days 1 and 8 and capecitabine orally (900 or 1,000 mg/m(2), twice daily) on days 2 through 15 of each 3-week cycle. Genomic DNA was extracted from peripheral blood and genotyped using Pyrosequencing, GeneScan, and direct sequencing (Big Dye terminator) technologies. The overall objective response rate was 45% with 21 patients (31%) exhibiting grade 3 or 4 diarrhea and 3 patients (4.5%) demonstrating grade 3 or 4 neutropenia in the first two cycles. Low enzyme activity UGT1A7 genotypes, UGT1A7*2/*2 (six patients) and UGT1A7*3/*3 (seven patients), were significantly associated with antitumor response (p = 0.013) and lack of severe gastrointestinal toxicity (p = 0.003). In addition, the UGT1A9 -118 (dT)(9/9) genotype was significantly associated with reduced toxicity (p = 0.002) and increased response (p = 0.047). There were no statistically significant associations between UGT1A1, UGT1A6, or thymidylate synthase genotypes and toxicity or tumor response. These data strongly suggest that UGT1A7 and/or UGT1A9 genotypes may be predictors of response and toxicity in CRC patients treated with capecitabine plus irinotecan. Specifically, patients with genotypes conferring low UGT1A7 activity and/or the UGT1A9 (dT)(9/9) genotype may be particularly likely to exhibit greater antitumor response with little toxicity.


Helminth development stages isolated from cattle faeces and herbage in pastures of rural areas in Imo State, Nigeria.
Examination of faecal and herbal samples from pastures of 6 villages in various parts of Imo State exhibited a preponderance of helminth eggs and infective larva. The percentage of the various genera present was assessed. These genera include: Oesophagostomum, Trichostrongylus, Cooperia, Strongyloides, Neoascaris, Haemonchus, Trichuris (nematodes), Fasciola, Cotylophoron, Paramphistomum (trematodes), Moniezia (cestodes). The results of investigation showed that the abundance of these developmental stages was seasonal, that there was no significant difference between pastures from different localities, and that there was a significant difference within samples due to the varying degree of accessibility.


Quality improvement activities of local health departments during the 2008-2010 economic recession.
A review of the work of researchers in the field of quality reveals a connection between the use of quality improvement (QI) concepts and improved financial performance. The disconnect between the expanding role of public health and the levels of per capita spending to support this role suggests that local health departments with a change in funding might benefit by employing QI to increase service delivery efficiency. To examine the relationship between changes in local health department (LHD) total revenue during the 2008-2010 economic recession and changes in LHD quality improvement activities during the same period. A matched-pairs study assessed change in revenue and associated change in QI activities at two points of time, 2008 and 2010. The study was completed in 2013. A proportional odds regression model estimated the adjusted ORs, measuring the association between change in QI activities and total revenue change, controlling for demographics, leadership QI training, and accreditation intention. Neither changes in revenue nor changes in expenses predicted change in QI activities in LHDs. Enhanced QI activities were found in LHDs led by a director with a master's degree, led by directors trained in QI, or those serving medium-sized (50,000-499,000) jurisdictions. This study revealed that neither changes in revenue nor changes in LHD expenses predict enhanced QI activities. Rather, improvements appear to be more related to characteristics of local health department leaders, which suggests areas to focus on for future efforts in public health services improvement.


Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains.
Fatty acid-binding proteins (FABPs) are candidate molecules for vaccines against several parasitic platyhelminths. A FABP from the cestode Echinococcus granulosus (EgDf1) was expressed in Salmonella vaccine strains as a C-terminal fusion to fragment C of tetanus toxin (TetC) by using expression vector pTECH. The fusion protein was equally expressed in several attenuated vaccine strains derived from bacteria with different genetic backgrounds and different attenuating mutations. Single-dose immunization experiments with the aroA Salmonella typhimurium strain SL3261 carrying the pTECH-EgDf1 construct were conducted with mice, using both the intravenous and the oral routes. Surprisingly, the antibody response to EgDf1 and the antigen-specific cytokine production in spleen cells were stronger in mice immunized orally. Furthermore, immune mouse sera strongly reacted with fixed sections of the worm's larval stage. Analysis of the isotype distribution of the specific anti-EgDf1 antibodies showed similar production of immunoglobulin G1 (IgG1) and IgG2a together with specific IgA antibodies. In addition, stimulation of spleen cells from mice immunized with the different constructs with either Salmonella lysate, TetC, or EgDf1 showed that, together with Th1-related cytokines (gamma interferon and interleukin 2 [IL-2]), significant levels of a Th2 cytokine (IL-5) were produced specifically, indicating a Th2 component to the response to the Salmonella carrier and to the recombinant antigens. Salmonellae expressing the TetC-rEgDfl fusion are currently under evaluation as potential vaccines against E. granulosus.


Influence of macro- and microvascular comorbidity on time to insulin initiation in type 2 diabetes patients: a retrospective database analysis in Germany, France, and UK.
To investigate if micro- and macrovascular co-morbidity has an influence on the time to insulin initiation in type 2 diabetes patients. Longitudinal data from general practices in Germany, France and UK (Disease Analyzer) from 1995 to 2009 were analyzed, including 44,440 patients in Germany, 10,148 patients in France, and 25,499 patients in UK with newly diagnosed diabetes (index date). Cox regression was used to investigate the association of newly diagnosed micro- and macrovascular complications (ICD-10) on the time to insulin initiation adjusting for age, sex, antidiabetic therapy, and co-morbidity (hypertension, lipid disorders). Insulin treatment was started in 9747 (22%) patients in Germany within 10 years after index date (France: n=702, 7%; UK: 3936, 14%). In all three countries, occurrence of microvascular complications was significantly associated with a higher likelihood to have insulin initiated (hazard ratio (HR), 95%CI: neuropathy: Germany 1.6; 1.5-1.8; France: 2.1; 1.1-3.9; UK: 1.5; 1.3-1.9; nephropathy: Germany 1.4; 1.3-1.6; France: 2.7; 1.4-3.8; UK: 1.2; 1.1-1.3). Among macrovascular complications, only coronary heart disease was related to insulin initiation in all three countries (Germany 1.2; 1.1-1.3; France: 1.5; 1.2-2.0; UK: 1.5; 1.3-1.7). A more rapid progression to insulin therapy was found in patients with microvascular complications.


Targeting mesenchymal stem cell therapy for severe pneumonia patients.
Pneumonia is the inflammation of the lungs and it is the world's leading cause of death for children under 5 years of age. The latest coronavirus disease 2019 (COVID-19) virus is a prominent culprit to severe pneumonia. With the pandemic running rampant for the past year, more than 1590000 deaths has occurred worldwide up to December 2020 and are substantially attributable to severe pneumonia and induced cytokine storm. Effective therapeutic approaches in addition to the vaccines and drugs under development are hence greatly sought after. Therapies harnessing stem cells and their derivatives have been established by basic research for their versatile capacity to specifically inhibit inflammation due to pneumonia and prevent alveolar/pulmonary fibrosis while enhancing antibacterial/antiviral immunity, thus significantly alleviating the severe clinical conditions of pneumonia. In recent clinical trials, mesenchymal stem cells have shown effectiveness in reducing COVID-19-associated pneumonia morbidity and mortality; positioning these cells as worthy candidates for combating one of the greatest challenges of our time and shedding light on their prospects as a next-generation therapy to counter future challenges.


Non-apoptotic role of BID in inflammation and innate immunity.
Innate immunity is a fundamental defence response that depends on evolutionarily conserved pattern recognition receptors for sensing infections or danger signals. Nucleotide-binding and oligomerization domain (NOD) proteins are cytosolic pattern-recognition receptors of paramount importance in the intestine, and their dysregulation is associated with inflammatory bowel disease. They sense peptidoglycans from commensal microorganisms and pathogens and coordinate signalling events that culminate in the induction of inflammation and anti-microbial responses. However, the signalling mechanisms involved in this process are not fully understood. Here, using genome-wide RNA interference, we identify candidate genes that modulate the NOD1 inflammatory response in intestinal epithelial cells. Our results reveal a significant crosstalk between innate immunity and apoptosis and identify BID, a BCL2 family protein, as a critical component of the inflammatory response. Colonocytes depleted of BID or macrophages from Bid(-/-) mice are markedly defective in cytokine production in response to NOD activation. Furthermore, Bid(-/-) mice are unresponsive to local or systemic exposure to NOD agonists or their protective effect in experimental colitis. Mechanistically, BID interacts with NOD1, NOD2 and the IκB kinase (IKK) complex, impacting NF-κB and extracellular signal-regulated kinase (ERK) signalling. Our results define a novel role of BID in inflammation and immunity independent of its apoptotic function, furthering the mounting evidence of evolutionary conservation between the mechanisms of apoptosis and immunity.


Quality of life, social support and self-efficacy in women after a miscarriage.
Pregnancy loss is typically experienced as a traumatic, critical event, which may lead to secondary psychological health disorders. Its burden involves both the experience of loss and related medical issues, which are associated with pain, hospitalization, limitation in one's social roles, decreased sense of security, and changes in one's perceived quality of life. The purpose of the present study was to evaluate levels of quality of life (QoL), social support and self-efficacy among women who had suffered a miscarriage. The study was performed using a diagnostic survey method with questionnaires administered to 610 patients hospitalized due to spontaneous pregnancy loss in hospitals in Lublin (Poland). The instruments used were: the Berlin Social Support Scales (BSSS), the Generalized Self-Efficacy Scale (GSES), the WHOQoL-BREF questionnaire, and a standardized interview questionnaire. Respondents rated their overall quality of life (3.90 points) higher than their overall perceived health (3.66). In terms of social support, the highest scores were noted for perceived available instrumental support (M = 3.78), perceived available emotional support (M = 3.68) and actually received support (M = 3.60). The mean generalized self-efficacy score among the women after pregnancy loss was 30.29. Respondents' QoL was significantly correlated with multiple social support subscales and self-efficacy (p < 0.05). Women after a miscarriage perceive their overall quality of life as better than their overall health, while reporting the poorest QoL in the psychological domain. They also have a high level of self-efficacy. Regarding the types of social support, perceived available support, both instrumental and emotional, and actually received support was rated highly. Social support and self-efficacy contributed to better perceived QoL among the respondents.


Treatment of pneumothorax as a complication of long-term central venous port placement in oncology patients. An observational study.
Background and purpose.In percutaneous placement of central venous catheters an inadvertent, direct lesion of the lung parenchyma can occur. This is a cause of iatrogenic pneumothorax, whose incidence is approximately 1 to 4%, largely dependent on the experience of the operator, the site of venipuncture and proba-bly the technique employed. Initial treatment currently ranges from observation alone to formal tube-thoracostomy. In an attempt to define the best initial treatment, if any, we reviewed our personal series and contributions from the literature. As a result we have produced a flow-chart proposing a rational treatment of this frequent complication. Patients and Methods.One thousand four hundred twenty-one ports were placed in patients at the Department of Surgery of the European Institute of Oncology in Milan through an infraclavicular standardized percutaneous subclavian approach. They were placed during the 60-month period from January 1, 1996 to December 31, 2000 for long-term chemotherapy treatment of solid tumours. Chest upright X-rays were obtained post-operatively in all cases to check the correct position of the catheter tip and the presence of pneumothorax. Results.Twenty-two patients out of 1421 (1.54%) experienced a radiologically-proven pneumothorax, ranging from 5 to 70% of the affected pleural space. Sixteen patients out of 22 (72.7%) with minor portions of affected pleural space received simple observation. In these patients the most common finding was an uncomplicated tachycardia (more than 100 beats/min); 8 of them did not complain of any symptoms. Six patients (27.2%) un-derwent an additional procedure (3 tube-thoracostomies and 3 aspirations of the pleural space), claiming symptoms of chest pain and various degrees of dyspnea. Tube thoracostomy was mainly adopted at the beginning of our experience, and in patients with a severe degree of pleural involvement (55 to 70% of the pleural space). Aspiration, instead, was used more recently and in patients with varying degrees of pleural space involved, ranging from 40 to 60%. Conclusions.Looking at our own series and literature data, patients with iatrogenic pneumothorax following central venous cannulation who do not have a severe underlying pulmonary disease can be reassured, at the time of diagnosis, that surgery is usually unnecessary and tube thoracostomy is rarely needed. Simple aspiration of the pleural air by means of a central venous catheter inserted percutaneously into the pleural space under local anesthesia should be considered, even if the amount of affected pleural space is more than 50%, before opting for a formal tube-thoracostomy using small-bore tubes.


Activating HRAS mutation in a case of inverted ductal papilloma of the salivary gland.
Inverted ductal papilloma (IDP) is one of the least common benign papillary/cystic neoplasms of the salivary duct system, being characterized histologically by florid hyperplasia of duct-type epithelial cells into a cystic lumen near the orifice with occasional endophytic growth of the surface squamous epithelium along the terminus of the affected excretory duct. Given its rarity, the exact etiology of IDP remains to be defined. We herein present the first evidence of oncogenic HRAS mutation in a case of oral IDP. This finding, together with the frequent and specific BRAF mutations in sialadenoma papilliferum reported in the recent literature, supports an active role of the MAP-kinase cascade in the pathogenesis of benign papillary neoplasms of terminal duct origin.


Adherence to a Mediterranean diet and onset of disability in older persons.
Higher adherence to a Mediterranean-type diet is linked to lower risk of mortality, cardiovascular disease and Alzheimer's disease while its association with disability has never been assessed. The aim of the study was to investigate the relation between adherence to a Mediterranean diet (MeDi) and disability in activities of daily living. The study sample consisted of 1,410 individuals from Bordeaux, France, included in 2001-2002 in the Three-City Study and re-examined at least once over 5 years. Adherence to a MeDi (scored as 0-9) was computed from a food frequency questionnaire and 24H recall. Disability in Basic and Instrumental ADL (B-IADL) was evaluated on the Lawton-Brody and Katz scales. Statistical analyses were stratified by gender and adjusted for potential confounders. No association between MeDi adherence and baseline disability in B-IADL was highlighted in men or in women in multivariate models. Risk of onset of disability in B-IADL over time was not significantly associated with MeDi adherence in men. In women, MeDi adherence was inversely associated with the risk of incident disability in B-IADL (HR = 0.90, 95% Confidence Interval 0.82-0.98 for 1 point of the score). Women with the highest MeDi adherence (score 6-8) had a 50% (22-68%) relative risk reduction of incident disability in B-IADL over time than women in the lowest MeDi category (score 0-3). In addition to its well-documented beneficial effects on health, adherence to a Mediterranean-type diet could contribute to slow down the disablement process in women.


Some relationships between sex, marriage and mood.
Although sexual dysfunction, marital difficulty and depression or other mood disturbance coexist in clinical populations, not infrequently detailed information is lacking about many aspects of relationships between problems in these areas. Methods of measuring sexuality, marital relations and depression are discussed. A pilot study of clinic patients is described and the results obtained using a marital pathology scale, a sexual functioning scale and the Beck Depression Inventory discussed. A small pilot study conducted in general practice indicated the likelihood of an enormous incidence of difficulties with 16.5% of patients admitting a present relationship problem and 15.6% a present sexual one.


Cell-cycle-dependent colonization of mouse spermatogonial stem cells after transplantation into seminiferous tubules.
Spermatogonial stem cells (SSCs) migrate to the niche upon introduction into the seminiferous tubules of the testis of infertile animals. However, only 5-10% of the transplanted cells colonize recipient testes. In this study, we analyzed the impact of cell cycle on spermatogonial transplantation. We used fluorescent ubiquitination-based cell cycle indicator transgenic mice to examine the influence of cell cycle on SSC activity of mouse germline stem (GS) cells, a population of cultured spermatogonia enriched for SSCs. GS cells in the G1 phase are more efficient than those in the S/G2-M phase in colonizing the seminiferous tubules of adult mice. Cells in the G1 phase not only showed higher expression levels of GFRA1, a component of the GDNF self-renewal factor receptor, but also adhered more efficiently to laminin-coated plates. Furthermore, this cell cycle-dependency was not observed when cells were transplanted into immature pup recipients, which do not have the blood-testis barrier (BTB) between Sertoli cells, suggesting that cells in the G1 phase may passage through the BTB more readily than cells in the S/G2-M phase. Thus cell cycle status is an important factor in regulating SSC migration to the niche.


Lipid Abundance in Zebrafish Embryos Is Regulated by Complementary Actions of the Endocannabinoid System and Retinoic Acid Pathway.
The endocannabinoid system (ECS) and retinoic acid (RA) signaling have been associated with influencing lipid metabolism. We hypothesized that modulation of these pathways could modify lipid abundance in developing vertebrates and that these pathways could have a combinatorial effect on lipid levels. Zebrafish embryos were exposed to chemical treatments altering the activity of the ECS and RA pathway. Embryos were stained with the neutral lipid dye Oil-Red-O (ORO) and underwent whole-mount in situ hybridization (WISH). Mouse 3T3-L1 fibroblasts were differentiated under exposure to RA-modulating chemicals and subsequently stained with ORO and analyzed for gene expression by qRT-PCR. ECS activation and RA exposure increased lipid abundance and the expression of lipoprotein lipase. In addition, RA treatment increased expression of CCAAT/enhancer-binding protein alpha. Both ECS receptors and RA receptor subtypes were separately involved in modulating lipid abundance. Finally, increased ECS or RA activity ameliorated the reduced lipid abundance caused by peroxisome proliferator-activated receptor gamma (PPARγ) inhibition. Therefore, the ECS and RA pathway influence lipid abundance in zebrafish embryos and have an additive effect when treated simultaneously. Furthermore, we demonstrated that these pathways act downstream or independently of PPARγ to influence lipid levels. Our study shows for the first time that the RA and ECS pathways have additive function in lipid abundance during vertebrate development.


The formation of paranodal spirals at the ends of CNS myelin sheaths requires the planar polarity protein Vangl2.
During axonal ensheathment, noncompact myelin channels formed at lateral edges of the myelinating process become arranged into tight paranodal spirals that resemble loops when cut in cross section. These adhere to the axon, concentrating voltage-dependent sodium channels at nodes of Ranvier and patterning the surrounding axon into distinct molecular domains. The signals responsible for forming and maintaining the complex structure of paranodal myelin are poorly understood. Here, we test the hypothesis that the planar cell polarity determinant Vangl2 organizes paranodal myelin. We show that Vangl2 is concentrated at paranodes and that, following conditional knockout of Vangl2 in oligodendrocytes, the paranodal spiral loosens, accompanied by disruption to the microtubule cytoskeleton and mislocalization of autotypic adhesion molecules between loops within the spiral. Adhesion of the spiral to the axon is unaffected. This results in disruptions to axonal patterning at nodes of Ranvier, paranodal axon diameter and conduction velocity. When taken together with our previous work showing that loss of the apico-basal polarity protein Scribble has the opposite phenotype-loss of axonal adhesion but no effect on loop-loop autotypic adhesion-our results identify a novel mechanism by which polarity proteins control the shape of nodes of Ranvier and regulate conduction in the CNS.


Examining cultural competence in health care: implications for social workers.
This article examines and unpacks the "black box" of cultural competence in health interventions with racial and ethnic minority populations. The analysis builds on several recent reviews of evidence-based efforts to reduce health disparities, with a focus on how cultural competence is defined and operationalized. It finds that the use of multiple similar and indistinct terms related to cultural competence, as well as the lack of a mutually agreeable definition for cultural competence itself, has resulted in an imprecise concept that is often invoked but rarely defined and only marginally empirically validated as an effective health intervention. This article affirms the centrality of cultural competence as an essential values-based component of optimal social work practice, while also suggesting future directions for operationalizing, measuring, and testing cultural competence to build an evidence base on whether and how it works to reduce health disparities.


Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and locomotor behavior in larval zebrafish (Danio rerio).
Quercetin is a natural product that is sold as a supplement in health food stores. While there are reported benefits for this flavonoid as a dietary supplement due to antioxidant properties, the full scope of its biological interactions has not been fully addressed. To learn more about the mechanisms of action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and 10μg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to 10μg/L did not induce significant mortality in developing fish, but did increase prevalence of an upward-curved dorsal plane in hatched larvae. To determine whether this developmental defect was potentially related to mitochondrial bioenergetics during development, we measured oxygen consumption rate in whole embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP-linked respiration were decreased at 1 and 10μg/L quercetin, and maximal respiration was decreased at 10μg/L quercetin, suggesting that quercetin impairs mitochondrial bioenergetics. This is proposed to be related to the deformities observed during development. Due to the fact that ATP production was affected by quercetin, larval behaviors related to locomotion were investigated, as well as transcriptional responses of six myogenesis transcripts. Quercetin at 10μg/L significantly reduced the swimming velocity of zebrafish larvae. The expression levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also altered by quercetin. Mstna, an inhibitory factor for myogenesis, was significantly increased at 1μg/L quercetin exposure, while myoD, a stimulatory factor for myogenesis, was significantly increased at 10μg/L quercetin exposure. There were no changes in transcripts related to apoptosis (bcl2, bax, casp3, casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish exposed to each dose, supporting an oxidative stress response. Our data support the hypothesis that quercetin may affect locomotion and induce deformities in zebrafish larvae by diminishing ATP production and by altering the expression of transcripts related to muscle formation and activity.


Development of a Shock-Wave Catheter Ablation System for Ventricular Tachyarrhythmias: Validation Study in Pigs In Vivo.
Background Although radiofrequency catheter ablation is the current state-of-the-art treatment for ventricular tachyarrhythmias, it has limited success for several reasons, including insufficient lesion depth, prolonged inflammation with subsequent recurrence, and thromboembolisms due to myoendocardial thermal injury. Because shock waves can be applied to deep lesions without heat, we have been developing a shock-wave catheter ablation ( SWCA ) system to overcome these fundamental limitations of radiofrequency catheter ablation. In this study, we evaluated the efficacy and safety of our SWCA system for clinical application to treat ventricular tachyarrhythmia. Methods and Results In 33 pigs, we examined SWCA in vivo for the following 4 protocols. First, in an epicardial substrate model (n=8), endocardial SWCA significantly decreased the sensing threshold (pre- versus postablation: 11.4±3.8 versus 6.8±3.6 mV ; P<0.05) and increased the pacing threshold (pre- versus postablation: 1.6±0.8 versus 2.0±1.1 V; P<0.05), whereas endocardial radiofrequency catheter ablation failed to do so. Second, in a myocardial infarction model (n=3), epicardial SWCA of the border zone of the infarcted lesion was as effective as ablation of the normal myocardium. Third, in a coronary artery application model (n=10), direct application of shock waves to the epicardial coronary arteries caused no adverse effects in either the acute or chronic phase. Fourth, with an epicardial approach (n=8), we found that 90 shots per site provided an ideal therapeutic condition to create deep lesions with less superficial damage. Conclusions These results indicate that our new SWCA system is effective and safe for treatment of ventricular tachyarrhythmias with deep arrhythmogenic substrates.


[Post therapeutic female pelvis MR imaging].
Thanks to a superior resolution and contrast, MRI allows recognizing the post therapeutic modifications of female pelvis, often very subtle and nonvisible by the other imaging modalities. The main surgical or medical therapies in the female pelvis will be described as well as the normal post therapeutic anatomical aspects. The main complications and failures will be mentioned and informed. Finally the keys that will allow to understand these complications and failures will be boarded.


Keloid: A case report and review of pathophysiology and differences between keloid and hypertrophic scars.
Keloids extend beyond the borders of the original wound invading normal skin. Usually appear as firm nodules, often pruritic and painful, and generally do not regress spontaneously. Most often occur on the chest, shoulders, upper back, back of the neck, and earlobes. The aim of the paper is to discuss a case of keloid, review the pathophysiology and also to highlight the differences between keloid and hypertrophic scars. A 26-year-old female complains of swelling on ear lobe since 3 years. Swelling was firm, non-tender, dumbell-shaped with central wooden stick still present, measuring 3 cm in diameter medial to the inferior part of the helix. A clinical diagnosis of keloid was given. Histopathological sections showed hyperorthokeratinized stratified squamous epithelium with deep dermal sclerosis showing large dense bundle of glassy collagen diagnostic of Keloid. Special stain like Van Gieson's was used to identify collagen bundles. The sections were also subjected to immunohistochemical markers such as α-SMA (alpha Smooth muscle actin), Desmin, and S-100. Despite decades of research, the pathophysiology of keloids remains incompletely understood. Recent studies indicate that TGF-β (Transforming growth factor beta) and PDGF (Platelet-derived growth factor) play an integral role in the formation of keloids. In future, development of selective inhibitors of TGF-β might produce new therapeutic tools with enhanced efficacy and specificity for the treatment of keloids. Patients with a previous history of keloid or other risk-factors should avoid body piercing and elective cosmetic procedures. Keloid scars should be sent for histopathology in order to avoid missing potentially malignant conditions particularly those showing unusual features.


Study on barrier mechanism and application of silico-alkaline sol-modified bentonite cutoff wall materials to lead pollution in lead-zinc tailings pond.
In this paper, the barrier mechanism of silico-alkaline sol-modified bentonite as cutoff wall materials for lead ions in lead‑zinc tailings ponds was investigated. Mechanical property tests, adsorption capacity tests, and permeability tests were conducted to assess the performance of the materials. The results indicated that the addition of silico-alkaline sol at a proportion of 20% by weight of bentonite improved the mechanical strength, anti-seepage ability, and adsorption capacity of the materials towards lead ions. The modification process of bentonite using silico-alkaline sol was confirmed through XED analysis. It was observed that silico-alkaline sol particles adsorbed onto the end face of montmorillonite crystal layer, altering its charge properties. This modification enhanced the adsorption capacity of bentonite towards metal cations. The interaction between the cutoff walls and lead ions was primarily governed by ion exchange. Through the utilization of CT and the finite element method (FEM), demonstrated the exiguity of connected flow lines in the vertical direction within the cutoff walls. Furthermore, column tests revealed that lead ions permeating through the cutoff walls gradually transformed into residuals and were immobilized within the wall. Visual Modflow analysis confirmed the effective application of the cutoff wall in remediating contaminated sites and the potential for practical implementation.


Impact of two different patient decision aids in prosthodontic consultations: a prospective randomized controlled study.
Different approaches to prosthodontic consultation, all involving a strong focus on shared decision-making, were analyzed from the perspective of patients by inter-group comparisons. No patient decision aid (PDA) was used in the control group, a paper-based PDA in test group 1, and a software-based PDA in test group 2. Seventy-five patients were prospectively randomized to the control group or a test group. All patients then rated the consultation on a questionnaire, six key items of which were analyzed, along with the time spent on each consultation. Overall satisfaction was highest in test group 2, with a significant difference from the control group (p = 0.015). Test group 2 showed the most favorable ratings for all six questionnaire items, which invariably was significant compared to the control group (p = 0.032). Test group 1 significantly differed from test group 2 based on two items (consultation was adequately intelligible: p = 0.011; consultation was adequately comprehensive: p = 0.034) but not from the control group based on any item (p = 0.070). Within the limitations of this study, the use of a software-based PDA, in particular, can be recommended based on patient satisfaction and was associated with the shortest sessions for consultation. Patients are routinely faced with a wealth of information in dental offices and may be overwhelmed especially by prosthetic treatment options and decision requirements. Our findings shed some light on the nature of aids that may truly be helpful in the process of shared decision-making. ClinicalTrials.gov.Identifier: ISRCTN11472465.


Differentiating trait pain from state pain: a window into brain mechanisms underlying how we experience and cope with pain.
Across various biological and psychological attributes, individuals have a set point around which they can fluctuate transiently into various states. However, if one remains in a different state other than their set point for a considerable period (eg, induced by a disease), this different state can be considered to be a new set point that also has associated surrounding states. This concept is instructive for understanding chronic pain, where an individual's set point may maladaptively shift such that they become stuck at a new set point of pain (trait pain), from which pain can fluctuate on different timescales (ie, pain states). Here, we discuss the importance of considering trait and state pains in neuroimaging studies of brain structure and function to gain an understanding of not only an individual's current pain state but also more broadly to their trait pain, which may be more reflective of their general condition.


Telomeres shorten in response to oxidative stress in mouse skeletal muscle fibers.
Aging phenotypes are dictated by myriad cellular changes including telomere shortening. In most tissues, telomere shortening is accelerated during replication if unrepaired oxidative damage to telomere sequences is present. However, the effect of reactive oxygen species exposure on skeletal muscle telomeres is unknown. We sought to determine if oxidative stress shortens telomeres in isolated adult rodent skeletal muscle fibers. Flexor digitorum brevis muscles were dissected from male mice (C57BL/6, long telomere and CAST/Ei, wild-derived, short telomere) and dissociated into single fibers. Fibers were cultured at an oxygen tension of 2%-5% for 5 days in control, hydrogen peroxide (oxidant), or a combination of N-acetylcysteine (antioxidant) and oxidant containing media. Telomere length, telomerase enzyme activity, and protein content of TRF1 and TRF2 were subsequently measured. In both strains, oxidative stress resulted in significant telomere shortening in isolated skeletal muscle fibers, likely by different mechanisms. Telomerase activity was not altered by oxidative stress treatment but was significantly different between strains, with greater telomerase activity in long-telomere-bearing C57BL/6 mice. These results provide important insights into mechanisms by which oxidative stress could shorten skeletal muscle telomeres.


Modulation of Voltage-Gating and Hysteresis of Lysenin Channels by Cu2+ Ions.
The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting single-step conformational changes and transitions to stable closed or sub-conducting states. However, the influence on voltage regulation of Cu2+ ions, capable of completely closing the lysenin channels in a two-step process, was not sufficiently addressed. In this respect, we employed electrophysiology approaches to investigate the response of lysenin channels to variable voltage stimuli in the presence of small concentrations of Cu2+ ions. Our experimental results showed that the hysteretic behavior, recorded in response to variable voltage ramps, is accentuated in the presence of Cu2+ ions. Using simultaneous AC/DC stimulation, we were able to determine that Cu2+ prevents the reopening of channels previously closed by depolarizing potentials and the channels remain in the closed state even in the absence of a transmembrane voltage. In addition, we showed that Cu2+ addition reinstates the voltage gating and hysteretic behavior of lysenin channels reconstituted in neutral lipid membranes in which lysenin channels lose their voltage-regulating properties. In the presence of Cu2+ ions, lysenin not only regained the voltage gating but also behaved like a long-term molecular memory controlled by electrical potentials.


Local impacts on road networks and access to critical locations during extreme floods.
Floods affected more than 2 billion people worldwide from 1998 to 2017 and their occurrence is expected to increase due to climate warming, population growth and rapid urbanization. Recent approaches for understanding the resilience of transportation networks when facing floods mostly use the framework of percolation but we show here on a realistic high-resolution flood simulation that it is inadequate. Indeed, the giant connected component is not relevant and instead, we propose to partition the road network in terms of accessibility of local towns and define new measures that characterize the impact of the flooding event. Our analysis allows to identify cities that will be pivotal during the flooding by providing to a large number of individuals critical services such as hospitalization services, food supply, etc. This approach is particularly relevant for practical risk management and will help decision makers for allocating resources in space and time.


Blowup as a driving mechanism of turbulence in shell models.
Since Kolmogorov proposed his phenomenological theory of hydrodynamic turbulence in 1941, the description of the mechanism leading to the energy cascade and anomalous scaling remains an open problem in fluid mechanics. Soon after, in 1949, Onsager noticed that the scaling properties in the inertial range imply nondifferentiability of the velocity field in the limit of vanishing viscosity. This observation suggests that the turbulence mechanism may be related to a finite-time singularity (blowup) of incompressible Euler equations. However, the existence of such blowup is still an open problem too. In this paper, we show that the blowup indeed represents the driving mechanism of the inertial range for a simplified (shell) model of turbulence. Here, blowups generate coherent structures (instantons), which travel through the inertial range in finite time and are described by universal self-similar statistics. The anomaly (deviation of scaling exponents of velocity moments from the Kolmogorov theory) is related analytically to the process of instanton creation using the large deviation principle. The results are confirmed by numerical simulations.


Bony labyrinth morphology clarifies the origin and evolution of deer.
Deer are an iconic group of large mammals that originated in the Early Miocene of Eurasia (ca. 19 Ma). While there is some consensus on key relationships among their members, on the basis of molecular- or morphology-based analyses, or combined approaches, many questions remain, and the bony labyrinth has shown considerable potential for the phylogenetics of this and other groups. Here we examine its shape in 29 species of living and fossil deer using 3D geometric morphometrics and cladistics. We clarify several issues of the origin and evolution of cervids. Our results give new age estimates at different nodes of the tree and provide for the first time a clear distinction of stem and crown Cervidae. We unambiguously attribute the fossil Euprox furcatus (13.8 Ma) to crown Cervidae, pushing back the origin of crown deer to (at least) 4 Ma. Furthermore, we show that Capreolinae are more variable in bony labyrinth shape than Cervinae and confirm for the first time the monophyly of the Old World Capreolinae (including the Chinese water deer Hydropotes) based on morphological characters only. Finally, we provide evidence to support the sister group relationship of Megaloceros giganteus with the fallow deer Dama.


Lipodystrophy among HIV-infected children and adolescents on highly active antiretroviral therapy in Uganda: a cross sectional study.
With widespread use of antiretroviral therapy (ART) and prolonged survival of HIV-infected children, toxicities like lipodystrophy are becoming more evident. Little is known about lipodystrophy in children in Uganda yet there is increased use of ART. The aim of this study was to determine the prevalence and factors associated with fat redistribution and metabolic abnormalities among HIV-infected children on highly active antiretroviral therapy (HAART) in Uganda. A cross-sectional study of 364 HIV positive children aged between 2 and 18 years on ART were enrolled after consent and assent as appropriate. Sociodemographic, clinical and immunological data were collected and recorded in a questionnaire. Fat redistribution was assessed clinically for physical findings of lipohypertrophy and lipoatrophy. A fasting blood sample was taken for lipid profile and blood glucose analysis. Lipodystrophy was defined as presence of abnormal fat redistribution or metabolic abnormalities or both. The proportion of children with fat redistribution and metabolic abnormalities was calculated. We conducted multivariate analysis for factors associated with lipodystrophy among children with lipodystrophic features and those without. The median age of the participants was eight years (range 2 to 18), with 43% of these aged ≥ 10 years and a male to female ratio of 1.1:1. Majority (65%) had advanced HIV (WHO Stage III/IV) at ART initiation with a mean duration on ART of 3.8 years (± 1.2). The prevalence of fat redistribution and hyperlipidemia was 27.0% and 34.0%, respectively. None of the children had hyperglycaemia. Among the children with hyperlipidemia, 16.8% exhibited hypercholesterolemia and 83% had hypertriglyceridemia. Only 29% of children with fat redistribution had hyperlipidemia. We found significant association between fat redistribution and Tanner stages 2 to 5 OR=2.3 (95%CI 1.3 to 3.8), age ≥ 5 years OR=3.9 (95%CI 1.5 to 9.9) and d4T exposure OR=3.4 (95%CI 2.0 to 5.8). A Tanner stage 2 to 5 was independently associated with hyperlipidemia. No significant association was observed with HIV clinical stage and any of the anthropometric measurements. The prevalence of lipodystrophy is high among HIV-infected children on ART with a likelihood of developing fat redistribution and metabolic abnormalities increased during puberty.


[Isolation of micro-organisms of the species Listeria from raw milk intended for human consumption].
Refrigerated mixtures of raw milk provided by a dairy which was supplied by farms from west and central Spain were tested for the presence of Listeria microorganisms. A total of 95 samples were taken at regular intervals over a 16-month period. Listeria grayi was isolated from 89.5% of the samples, Listeria monocytogenes s. str. from 45.3%, Listeria innocua from 15.8%, Listeria welshimeri from 3.1%, and Listeria seeligeri from 1.05%. Listeria ivanovii, Listeria murrayi, and Listeria denitrificans were not isolated.


Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet.
The introduction of all-trans retinoic acid (ATRA) and, more recently, arsenic trioxide (ATO) into the therapy of acute promyelocytic leukemia (APL) has revolutionized the management and outcome of this disease. Several treatment strategies using these agents, usually in combination with chemotherapy, but also without or with minimal use of cytotoxic agents, have provided excellent therapeutic results. Cure of APL patients, however, is also dependent on peculiar aspects related to the management and supportive measures that are crucial to counteract life-threatening complications associated with the disease biology and molecularly targeted treatment. The European LeukemiaNet recently appointed an international panel of experts to develop evidence- and expert opinion-based guidelines on the diagnosis and management of APL. Together with providing current indications on genetic diagnosis, modern risk-adapted front-line therapy and salvage treatment, the review contains specific recommendations for the identification and management of most important complications such as the bleeding disorder, APL differentiation syndrome, QT prolongation and other ATRA- and ATO-related toxicities, as well as for molecular assessment of response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women.


Capillary descent.
A superhydrophobic capillary tube immersed in water and brought in contact with the bath surface will be invaded by air, owing to its aerophilicity. We discuss this phenomenon where the ingredients of classical capillary rise are inverted, which leads to noticeable dynamical features. (1) The main regime of air invasion is linear in time, due to the viscous resistance of water. (2) Menisci in tubes with millimetre-size radii strongly oscillate before reaching their equilibrium depth, a consequence of inertia. On the whole, capillary descent provides a broad variety of dynamics where capillary effects, viscous friction and liquid inertia all play a role.


Sleeping sickness in the historical focus of forested Guinea: update using a geographically based method.
In 2017, 1447 new cases of Human African Trypanosomiasis (HAT) were reported, which reflects considerable progress towards the World Health Organisation's target of eliminating HAT as a public health problem by 2020. However, current epidemiological data are still lacking for a number of areas, including historical HAT foci. In order to update the HAT situation in the historical focus of forested Guinea, we implemented a geographically based methodology: Identification of Villages at Risk (IVR). The methodology is based on three sequential steps: Desk-based IVR (IVR-D), which selects villages at risk of HAT on the basis of HAT archives and geographical items; Field-based IVR (IVR-F), which consists in collecting additional epidemiological and geographical information in the field in villages at risk; and to be Medically surveyed IVR (IVR-M), a field data analysis through a Geographic Information System (GIS), to compile a list of the villages most at risk of HAT, suitable to guide active screening and passive surveillance. In an area of 2385 km2 with 1420,530 inhabitants distributed in 1884 settlements, 14 villages with a population of 11,236 inhabitants were identified as most at risk of HAT and selected for active screening. Although no HAT cases could be confirmed, subjects that had come into contact with Trypanosoma brucei gambiense were identified and two sentinel sites were chosen to implement passive surveillance. IVR, which could be applied to any gambiense areas where the situation needs to be clarified, could help to reach the objective of HAT elimination.


[The effect of platelet-rich fibrin on biologic characteristics of osteoblasts].
To investigate the effect of platelet-rich fibrin on biologic characteristics of osteoblasts. Osteoblasts were cultured with or without a PRF membrane. The cell proliferation was detected by MTT. The alkaline phosphatase (ALP) stain and the positive expression of collagen type I, osteoprotegerin and RANKL were measured. The data was statistically analyzed with SPSS17.0 software package. PRF promoted cell proliferation and increased expression of ALP, collagen typeI and OPG significantly, but there was no significant impact on expression of RANKL. PRF promotes osteoblasts proliferation, differentiation and OPG expression. PRF is involved in bone remodeling via regulating expression of OPG and RANKL.