Mouse kappa-opioid receptor mRNA differential transport in neurons.
Three kappa-opioid receptor (KOR) mRNA isoforms have been detected in different parts of the central nervous system. At the cellular level, three KOR mRNA isoforms are also differentially distributed in the axons and cell bodies of adult mouse trigeminal neurons, as well as in the processes and cell bodies of differentiated P19 neurons. To determine the molecular basis underlying differential distribution of KOR mRNA isoforms, a GFP-fused RNA binding domain, MS2, was generated and used to trace movement of KOR mRNA tagged with the MS2-binding sequence in living neurons of dorsal root ganglia and in differentiated P19 neurons. The 5'- and 3'-untranslated regions (UTRs) of KOR, either alone or in combination, are able to mediate transport of mRNAs to processes of P19 neurons and axons of dorsal root ganglia. The efficiency of mRNA transport mediated by each 5'-UTR of KOR varies among the three isoforms; isoform A is most efficient. This study demonstrates the biological activity of the UTRs of KOR mRNA isoforms in directing differential transport of mRNA in mammalian neurons.


Epidural tramadol for postoperative pain relief.
Forty-two surgical patients were given epidural tramadol for control of postoperative pain. They were randomly assigned to three groups: group 1 (n = 15), in which 25 mg of tramadol were given; group 2 (n = 13), in which 50 mg of tramadol were given; and group 3 (n = 14), in which 75 mg of tramadol were given. When the patients complained of wound pain, epidural tramadol was given. Heart rate, blood pressure, respiratory rate, oxygen saturation (SpO2), sedation scale, motor blockade, verbal rating scale, subjective grading, and visual analogue pain scale (VAPS) were measured and recorded before the tramadol administration, at 5 and 15 min, and at 1, 2, 4, and 8 h after the tramadol administration. Only 26.6% of the patients in group 1 had significant relief of pain. The rest of them needed at least one incremental dose of 25 mg of tramadol. The baseline VAPS of the patients in group 2 was 8.9 +/- 2.0. It became 5.46 +/- 3.0 (p greater than 0.05) 15 min after tramadol was given, and dropped further to 1.9 +/- 1.8 (p greater than 0.05) 2 h later. The average duration of pain relief was 12.0 +/- 5.9 h. In group 3, the initial VAPS was 8.14 +/- 1.9. It decreased to 4.28 +/- 1.8 (p greater than 0.05) 15 min, and further dropped to 1.7 +/- 0.9 (p greater than 0.05) 2 h following tramadol administration. The average duration of pain relief was 11.3 +/- 4.8 h. The common side effects of tramadol such as dizziness, nausea, and dry mouth, were most frequently found in group 3.(ABSTRACT TRUNCATED AT 250 WORDS)


Bioplastic Production from Microalgae: A Review.
Plastic waste production around the world is increasing, which leads to global plastic waste pollution. The need for an innovative solution to reduce this pollution is inevitable. Increased recycling of plastic waste alone is not a comprehensive solution. Furthermore, decreasing fossil-based plastic usage is an important aspect of sustainability. As an alternative to fossil-based plastics in the market, bio-based plastics are gaining in popularity. According to the studies conducted, products with similar performance characteristics can be obtained using biological feedstocks instead of fossil-based sources. In particular, bioplastic production from microalgae is a new opportunity to be explored and further improved. The aim of this study is to determine the current state of bioplastic production technologies from microalgae species and reveal possible optimization opportunities in the process and application areas. Therefore, the species used as resources for bioplastic production, the microalgae cultivation methods and bioplastic material production methods from microalgae were summarized.


Is leg muscle strength correlated with functional balance and mobility among inpatients in geriatric rehabilitation?
Determinants of functional balance and mobility have rarely been investigated in geriatric wards. This study examined if leg muscle strength correlates to functional balance and mobility among geriatric inpatients. Fifty inpatients, 29 women and 21 men (mean age 79.6 years) were included. Functional balance was assessed with the Berg Balance Scale (BBS) and mobility was assessed with the Physiotherapy Clinical Outcome Variable Scale (COVS). Strength in the leg extension muscles was measured as 1 Repetition Maximum (1RM) in a leg press and strength in the ankle muscles was measured with Medical Research Council grades (MRC, 0-5). The sum scores, and most of the single items, of the BBS and the COVS significantly correlated to 1RM/body weight, ankle dorsiflexion, and plantar flexion. In a stepwise multiple regression, ankle dorsiflexion and 1RM/body weight together accounted for 39% of the variance of the BBS and 41% of the variance of the COVS. Estimated values of the BBS and the COVS can be calculated from the equation. In clinical work, the knowledge about how leg muscle strength associates with balance and mobility may be useful in analyzing underlying causes of reduced balance and mobility function, and in planning rehabilitation programs.


A Nurse-Pharmacist Collaborative Approach to Reducing Financial Toxicity in Cancer Care.
Financial toxicity is well recognized as a sequela of surviving cancer. As the number of survivors is expected to increase, so are costs associated with cancer treatments. Using a nurse-pharmacist collaborative model, efforts between oncology pharmacists and nurses may inform real-world practice solutions to improve medication access. Increased medication access may reduce out-of-pocket expenses for patients with cancer.


[Comparative diagnosis of focal liver changes using computed tomographic and scintigraphic methods].
The value of scintigraphic methods for the diagnosis of focal lesions of the liver (IDA, colloids, blood pool) in comparison to dynamic sequential computer tomography (CT) has been examined in this study. We found CT to be diagnostic in typical cases. For example, focal nodular hyperplasia is characterized by a rapid, strong increase and subsequent decrease after application of contrast medium (71%), whereas hemangiomas show a delayed density increase mostly at the rim (20%). In the event of deviations from the typical pattern, scintigraphic methods have to be applied which then often yield a specific diagnosis, especially in hemangiomas, focal nodular hyperplasia, and adenomas (71%). Ultrasound findings indicating the possible presence of hemangiomas or focal nodular hyperplasia should lead to scintigraphic studies prior to CT, not only for reasons of economy.


Does the impact of anti-drinking and driving Public Service Announcements differ based on message type and viewer characteristics?
The purpose of this study was to inform future Public Service Announcement (PSA) development by examining the potential effectiveness of different types of anti-driving under the influence (DUI) PSAs for persons with different characteristics. PSAs utilizing empathy, fear, and informational approaches were shown to persons recruited from psychology courses (n = 137) and individuals that were mandated to treatment following a DUI offense (n = 17). The empathy approach was perceived to be the most effective and evoked the most negative affect, followed by fear and informational approaches. Less experience with DUI, lower sensation seeking, higher motivation to change, and higher perception of dangerousness of DUI all emerged as good predictors of higher perceived effectiveness of anti-DUI PSAs. Gender differences in perceived effectiveness were examined for fear and empathy PSAs, with inconclusive findings.


Epidemiology of Charcot-Marie-Tooth disease in the population of Belgrade, Serbia.
The aim of this study was to determine prevalence and 15-year survival in Charcot-Marie-Tooth disease (CMT). The study covers the period from 1 January 1988 to 31 December 2007 in the territory of Belgrade. Data on a number of CMT-affected persons and their basic demographic characteristics as well as data on the disease were collected from medical records. Data on the course and outcome of the disease were obtained through direct contact with patients, their families and their physicians. We registered 161 patients with CMT in the population of Belgrade. The most frequent type was CMT1. The crude prevalence of CMT disease in the Belgrade population on 31 December 2007 was 9.7/100,000 for all subtypes, 7.1/100,000 for CMT1, and 2.3/100,000 for CMT2. Gender-specific prevalence was 11.2/100,000 for males and 8.3/100,000 for females. The highest age-specific prevalence was registered in the oldest age group (75+ years; 19.1/100,000), and the lowest one in patients aged 5-14 years (5.0/100,000). The cumulative probability of 15-year survival for CMT patients in Belgrade was 85.6 ± 7.8% (44.9 ± 31.8% for males and 98.2 ± 1.8% for females). The prevalence of CMT found in Belgrade is similar to the prevalence registered in Southern European countries.


Trusted sources for COVID-19 testing and vaccination: lessons for future health communication.
Promoting COVID-19 vaccination (both the primary series and boosters) remains a priority among healthcare professionals and requires understanding the various sources people trust for acquiring COVID-19 information. From October 2021 to May 2022, we interviewed 150 people who called 2-1-1 helplines in Connecticut and North Carolina about their COVID-19 testing and vaccination experiences in order to (1) better understand where people obtain trusted COVID-19 health information and (2) identify how public health professionals can share emergency health information in the future. We used a mixed methods approach in which semi-structured qualitative interviews and survey data were collected in parallel and analyzed separately. Participants were mostly female (74.0%), Black (43.3%) or White (38.0%), and had a high school degree or higher (88.0%). Most had prior COVID-19 testing experience (88.0%) and were vaccinated (82.7%). A variety of information sources were rated as being very trustworthy including medical professionals and social service organizations. We found that repetition of information from multiple sources increased trust; however, perceived inconsistencies in recommendations over time eroded trust in health communication, especially from government-affiliated information sources. Observations such as seeing long lines for COVID-19 testing or vaccination became internalized trusted information. Public health professionals can leverage the reach and strong community ties of existing, reputable non-government organizations, such as physician groups, schools, and pharmacies, to distribute COVID-19 information about vaccination and testing.


Enhancement of charge transfer between graphene and donor-π-acceptor molecule for ultrahigh sensing performance.
In this work, we report the formation of a supramolecular assembly of graphene with a donor-π-acceptor (D-π-A) molecule to detect low concentration NO2. 5-Aminonaphthalene-1-sulfonic acid (ANS) was used herein to π-π stack with reduced graphene oxide (rGO), the resulting π-conjugated bridge being linked by a donor unit (-NH2) and an acceptor unit (-SO3H). The prepared ANS-rGO shows the highest response (Ra/Rg = 13.2 to 10 ppm NO2) so far among the reported organic molecule modified graphene materials, and excellent selectivity and reliable reversibility at room temperature. Furthermore, as revealed through the charge density difference calculation, it is the effective enhancement of charge transfer between ANS and graphene that should be responsible for the sharp improvement of NO2 gas response of the material. Thus, for the first time, we demonstrate that supramolecular assembly of a D-π-A molecule and graphene provides a facile and effective approach to fabrication of high performance graphene-based gas sensors.


Probing mutual interactions between Pseudomonas aeruginosa and Candida albicans in a biofabricated membrane-based microfluidic platform.
Microbes are typically found in multi-species (polymicrobial) communities. Cooperative and competitive interactions between species, mediated by diffusible factors and physical contact, leads to highly dynamic communities that undergo changes in composition diversity and size. Infections can be more severe or more difficult to treat when caused by multiple species. Interactions between species can improve the ability of one or more species to tolerate anti-microbial treatments and host defenses. Pseudomonas aeruginosa (Pa), a ubiquitous bacterium, and the opportunistic pathogenic yeast, Candida albicans (Ca), are frequently found together in cystic fibrosis lung infections and wound infections. While significant progress has been made in determining interactions between Pa and Ca, there are still important questions that remain unanswered. Here, we probe the mutual interactions between Pa and Ca in a custom-made microfluidic device using biopolymer chitosan membranes that support cross-species communication. By assembling microbes in physically separated, chemically communicating populations or bringing into direct interactions in a mixed culture, in situ polymicrobial growth and biofilm morphology were qualitatively characterized and quantified. Our work reveals new dynamic details of their mutual interactions including cooperation, competition, invasion, and biofilm formation. The membrane-based microfluidic platform can be further developed to understand the polymicrobial interactions within a controlled interactive microenvironment to improve microbial infection prevention and treatment.


Adult tinea capitis and tinea barbae in a tertiary Portuguese hospital: A 11-year audit.
Adult tinea capitis and tinea barbae are nowadays considered uncommon in developed countries. Despite their potential for morbidity and healthcare costs, few series have attempted to characterise these infectious disorders. We conducted a cross-sectional study to analyse the epidemiological, clinical and mycological characteristics of adult tinea capitis and tinea barbae of a large tertiary centre in Southern Europe. All adult patients with a mycological-confirmed tinea capitis or barbae over a 11-year period (January 2008 to December 2018) were considered for the analysis. Concerning tinea capitis, 860 culture-confirmed diagnoses were made during this 11-year period, of which only 15 (1.5%) occurred in adults (15 patients). A disproportionately high number of patients were female and immunocompromised. Microsporum audouinii (20%) and Trichophyton rubrum (20%) were the most common isolates. Half of the cases were initially misdiagnosed. Regarding tinea barbae, 7 cases were diagnosed over this time period. Overuse of topical steroids was widespread in this population. Trichophyton rubrum was the infectious agent in all cases. Initial misdiagnosis was very common (43%). Adult tinea capitis and tinea barbae can still be observed in contemporary practice and remain a public health concern, with the immunosuppressed patient being particularly affected. Initial misdiagnosis is a common occurrence. Anthropophilic fungi are now the most common aetiologic agents of these infections, and they will probably continue to do so as the large urban centres expand peripherally. Awareness for this diagnosis is necessary to prevent unwarranted morbidity and costs.


Assignment of six genes to bovine chromosomes 5 and 16 by fluorescence in situ hybridization, radiation hybrid mapping and genetic linkage analysis.
Several quantitative trait loci for beef carcass traits have been mapped to bovine chromosome 5. The objective of this study was to map six candidate genes for these traits by fluoresence in situ hybridization, genetic linkage analysis and radiation hybrid mapping. MYF5 and MYF6 were assigned to 5q13, WIF1 to 5q23 and MMP19 to 5q25. A paralog of MYF5 (putatively MYOG) was assigned to 16q12. A novel microsatellite placed MYF5 and MYF6 10.4 cM from BM6026 and 19.1 cM from BL23 on the genetic linkage map. MYF5 (62.6 cR), WNT10B (319.5 cR), WIF1 (500.8 cR) and MMP19 (701.2 cR) were also integrated into the 5000(Rad) radiation hybrid map.


Factors associated with dengue shock syndrome: a systematic review and meta-analysis.
The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not yet completely understood. Several factors are reportedly associated with DSS, a more severe form of dengue infection that reportedly causes 50 times higher mortality compared to that of dengue patients without DSS. However, the results from these reports remain inconclusive. To better understand the epidemiology, clinical manifestation, and pathogenesis of DSS for development of new therapy, we systematically reviewed and performed a meta-analysis of relevant studies that reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2) patients. PubMed, EMBASE, Scopus, Google Scholar, Dengue Bulletin, Cochrane Library, Virtual Health Library, and a manual search of reference lists of articles published before September 2010 were used to retrieve relevant studies. A meta-analysis using fixed- or random-effects models was used to calculate pooled odds ratios (OR) or event rate with corresponding 95% confidence intervals. Assessment of heterogeneity and publication bias, meta-regression analysis, subgroup analysis, sensitivity analysis, and analysis of factor-specific relationships were further performed. There were 198 studies constituting 203 data sets that met our eligibility criteria. Our meta-regression analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio over a period of 40 years in Southeast Asia, especially in Thailand. The meta-analysis revealed that age, female sex, neurological signs, nausea/vomiting, abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine transaminase and aspartate transaminase, thrombocytopenia, prothrombin time, activated partial thromboplastin time, fibrinogen level, primary/secondary infection, and dengue virus serotype-2 were significantly associated with DSS when pooling all original relevant studies. The results improve our knowledge of the pathogenesis of DSS by identifying the association between the epidemiology, clinical signs, and biomarkers involved in DSS.


Suppression of VEGF-induced angiogenesis and tumor growth by Eugenia jambolana, Musa paradisiaca, and Coccinia indica extracts.
Abnormal angiogenesis and evasion of apoptosis are hallmarks of cancer. Accordingly, anti-angiogenic and pro-apoptotic therapies are effective strategies for cancer treatment. Medicinal plants, namely, Eugenia jambolana Lam. (Myrtaceae), Musa paradisiaca L. (Musaceae), and Coccinia indica Wight & Arn. (Cucurbitaceae), have not been greatly investigated for their anticancer potential. We investigated the anti-angiogenic and pro-apoptotic efficacy of ethyl acetate (EA) and n-butanol (NB) extracts of E. jambolana (seeds), EA extracts of M. paradisiaca (roots) and C. indica (leaves) with respect to mammary neoplasia. Effect of extracts (2-200 μg/mL) on cytotoxicity and MCF-7, MDA-MB-231 and endothelial cell (EC) proliferation and in vitro angiogenesis were evaluated by MTT, 3[H]thymidine uptake and EC tube formation assays, respectively. In vivo tumour proliferation, VEGF secretion and angiogenesis were assessed using the Ehrlich ascites tumour (EAT) model followed by rat corneal micro-pocket and chicken chorioallantoic membrane (CAM) assays. Apoptosis induction was assessed by morphological and cell cycle analysis. EA extracts of E. jambolana and M. paradisiaca exhibited the highest cytotoxicity (IC50 25 and 60 μg/mL), inhibited cell proliferation (up to 81%), and tube formation (83% and 76%). In vivo treatment reduced body weight (50%); cell number (16.5- and 14.7-fold), secreted VEGF (∼90%), neoangiogenesis in rat cornea (2.5- and 1.5-fold) and CAM (3- and 1.6-fold) besides EAT cells accumulation in sub-G1 phase (20% and 18.38%), respectively. Considering the potent anti-angiogenic and pro-apoptotic properties, lead molecules from EA extracts of E. jambolana and M. paradisiaca can be developed into anticancer drugs.


Global text matching for information retrieval.
An approach is outlined for the retrieval of natural language texts in response to available search requests and for the recognition of content similarities between text excerpts. The proposed retrieval process is based on flexible text matching procedures carried out in a number of different text environments and is applicable to large text collections covering unrestricted subject matter. For unrestricted text environments this system appears to outperform other currently available methods.


Dosimetry of heavy ion exposure to human cells using nanoscopic imaging of double strand break repair protein clusters.
The human body is constantly exposed to ionizing radiation of different qualities. Especially the exposure to high-LET (linear energy transfer) particles increases due to new tumor therapy methods using e.g. carbon ions. Furthermore, upon radiation accidents, a mixture of radiation of different quality is adding up to human radiation exposure. Finally, long-term space missions such as the mission to mars pose great challenges to the dose assessment an astronaut was exposed to. Currently, DSB counting using γH2AX foci is used as an exact dosimetric measure for individuals. Due to the size of the γH2AX IRIF of ~ 0.6 µm, it is only possible to count DSB when they are separated by this distance. For high-LET particle exposure, the distance of the DSB is too small to be separated and the dose will be underestimated. In this study, we developed a method where it is possible to count DSB which are separated by a distance of ~ 140 nm. We counted the number of ionizing radiation-induced pDNA-PKcs (DNA-PKcs phosphorylated at T2609) foci (size = 140 nm ± 20 nm) in human HeLa cells using STED super-resolution microscopy that has an intrinsic resolution of 100 nm. Irradiation was performed at the ion microprobe SNAKE using high-LET 20 MeV lithium (LET = 116 keV/µm) and 27 MeV carbon ions (LET = 500 keV/µm). pDNA-PKcs foci label all DSB as proven by counterstaining with 53BP1 after low-LET γ-irradiation where separation of individual DSB is in most cases larger than the 53BP1 gross size of about 0.6 µm. Lithium ions produce (1.5 ± 0.1) IRIF/µm track length, for carbon ions (2.2 ± 0.2) IRIF/µm are counted. These values are enhanced by a factor of 2-3 compared to conventional foci counting of high-LET tracks. Comparison of the measurements to PARTRAC simulation data proof the consistency of results. We used these data to develop a measure for dosimetry of high-LET or mixed particle radiation exposure directly in the biological sample. We show that proper dosimetry for radiation up to a LET of 240 keV/µm is possible.


Inorganic liquid photovoltaic cell: tetravalent molybdenum in water.
An inorganic liquid photovoltaic cell is described. The cell is based on the reaction 2Mo(4+) <--> Mo(5+) + Mo(3+), with pentavalent molybdenum formed in the illuminated half-cell and trivalent molybdenum formed in the dark half-cell. In the photochemical reaction pentavalent molybdenum precipitates. Consequently, the cell has the capability of storing energy.


Tailoring the interface using thiophene small molecules in TiO2/P3HT hybrid solar cells.
In this paper we focus on the effect of carboxylated thiophene small molecules as interface modifiers in TiO(2)/P3HT hybrid solar cells. Our results show that small differences in the chemical structure of these molecules, for example, the presence of the -CH(2)- group in the 2-thiopheneacetic acid (TAA), can greatly increase the TiO(2) surface wettability, improving the TiO(2)/polymer contact. This effect is important to enhance exciton splitting and charge separation.


Sox11 regulates mammary tumour-initiating and metastatic capacity in Brca1-deficient mouse mammary tumour cells.
Little is known about the role of Sox11 in the regulation of mammary progenitor cells. Sox11 is expressed by mammary bud epithelial cells during embryonic mammary gland development and is not detected in mammary epithelial cells after birth. As Sox11 is an oncofetal gene, we investigated the effects of reducing Sox11 levels in embryonic mammary progenitor cells and found that Sox11 regulates proliferative state, stem cell activity and lineage marker expression. We also investigated the effect of reducing Sox11 levels in two transplantable Brca1-deficient oestrogen receptor-negative mouse mammary tumour cell lines, to assess whether Sox11 regulates similar functions in tumour progenitor cells. When Sox11 levels were reduced in one Brca1-deficient mammary tumour cell line that expressed both epithelial and mesenchymal markers, similar effects on proliferation, stem cell activity and expression of lineage markers to those seen in the embryonic mammary progenitor cells were observed. Orthotopic grafting of mammary tumour cells with reduced Sox11 levels led to alterations in tumour-initiating capacity, latency, expression of lineage markers and metastatic burden. Our results support a model in which tumours expressing higher levels of Sox11 have more stem and tumour-initiating cells, and are less proliferative, whereas tumours expressing lower levels of Sox11 become more proliferative and capable of morphogenetic/metastatic growth, similar to what occurs during embryonic mammary developmental progression.


Protein signatures from blood plasma and urine suggest changes in vascular function and IL-12 signaling in elderly with a history of chronic diseases compared with an age-matched healthy cohort.
Key processes characterizing human aging are immunosenescence and inflammaging. The capacity of the immune system to adequately respond to external perturbations (e.g., pathogens, injuries, and biochemical irritants) and to repair somatic mutations that may cause cancers or cellular senescence declines. An important goal remains to identify genetic or biochemical, predictive biomarkers for healthy aging. We recruited two cohorts in the age range 70 to 82, one afflicted by chronic illnesses (non-healthy aging, NHA) and the other in good health (healthy aging, HA). NHA criteria included major cardiovascular, neurodegenerative, and chronic pulmonary diseases, diabetes, and cancers. Quantitative analysis of forty proinflammatory cytokines in blood plasma and more than 500 proteins in urine was performed to identify candidate biomarkers for and biological pathway implications of healthy aging. Nine cytokines revealed lower quantities in blood plasma for the NHA compared with the HA groups (fold change > 1.5; p value < 0.025) including IL-12p40 and IL-12p70. We note that, sampling at two timepoints, intra-individual cytokine abundance patterns clustered in 86% of all 60 cases, indicative of person-specific, highly controlled multi-cytokine signatures in blood plasma. Twenty-three urinary proteins were differentially abundant (HA versus NHA; fold change > 1.5; p value < 0.01). Among the proteins increased in abundance in the HA cohort were glycoprotein MUC18, ephrin type-B receptor 4, matrix remodeling-associated protein 8, angiopoietin-related protein 2, K-cadherin, and plasma protease C1 inhibitor. These proteins have been linked to the extracellular matrix, cell adhesion, and vascular remodeling and repair processes. In silico network analysis identified the regulation of coagulation, antimicrobial humoral immune responses, and the IL-12 signaling pathway as enriched GO terms. To validate links of these preliminary biomarkers and IL-12 signaling with healthy aging, clinical studies using larger cohorts and functional characterization of the genes/proteins in cellular models of aging need to be conducted.


Osteoporosis: A factor on residual limb pain in traumatic trans-tibial amputations.
Residual limb pain is defined as a painful sensation or feeling from the remaining part of the leg. Aggressive bone edge, bone spur formation, neuroma, abscess or bursitis are common causes of residual limb pain. On the other hand, regional osteoporosis on femur and tibia is an inevitable consequence in patients with lower limb amputations. The etiology of bone loss is uncertain but it is likely to be a local phenomenon in lower limb amputees. Altered gait pattern, decreased weight load, disuse atrophy and lack of muscular action at the limb seem to be important causal factors in the development of both local and generalized osteoporosis. The aims of this study are: (i) To determine if there is significant bone mineral density (BMD) difference at proximal tibias and femurs between intact and amputated limbs, (ii) to investigate the factors affecting bone loss in these areas and (iii) to investigate the possible relationship between residual limb pain and local bone loss. The 36 men who participated in this study had amputations due to land-mine injuries. Dual energy X-ray absorptiometry was used to determine BMD of the proximal femur and proximal tibia. The non-amputated limb was used as a control for the amputated side. BMD values on the amputated side were significantly lower than non-amputated side. In addition, BMD values on the amputated limbs with residual limb pain were significantly less than in those without residual limb pain. Insufficient mechanical loading leads to bone loss in patients with trans-tibial amputations. Furthermore, bone loss at tibia may be a cause of residual limb pain. However, this needs to be confirmed with more specific studies in the future.


Asymmetric Interfaces in Epitaxial Off-Stoichiometric Fe3+xSi1-x/Ge/Fe3+xSi1-x Hybrid Structures: Effect on Magnetic and Electric Transport Properties.
Three-layer iron-rich Fe3+xSi1-x/Ge/Fe3+xSi1-x (0.2 < x < 0.64) heterostructures on a Si(111) surface with Ge thicknesses of 4 nm and 7 nm were grown by molecular beam epitaxy. Systematic studies of the structural and morphological properties of the synthesized samples have shown that an increase in the Ge thickness causes a prolonged atomic diffusion through the interfaces, which significantly increases the lattice misfits in the Ge/Fe3+xSi1-x heterosystem due to the incorporation of Ge atoms into the Fe3+xSi1-x bottom layer. The resultant lowering of the total free energy caused by the development of the surface roughness results in a transition from an epitaxial to a polycrystalline growth of the upper Fe3+xSi1-x. The average lattice distortion and residual stress of the upper Fe3+xSi1-x were determined by electron diffraction and theoretical calculations to be equivalent to 0.2 GPa for the upper epitaxial layer with a volume misfit of -0.63% compared with a undistorted counterpart. The volume misfit follows the resultant interatomic misfit of |0.42|% with the bottom Ge layer, independently determined by atomic force microscopy. The variation in structural order and morphology significantly changes the magnetic properties of the upper Fe3+xSi1-x layer and leads to a subtle effect on the transport properties of the Ge layer. Both hysteresis loops and FMR spectra differ for the structures with 4 nm and 7 nm Ge layers. The FMR spectra exhibit two distinct absorption lines corresponding to two layers of ferromagnetic Fe3+xSi1-x films. At the same time, a third FMR line appears in the sample with the thicker Ge. The angular dependences of the resonance field of the FMR spectra measured in the plane of the film have a pronounced easy-axis type anisotropy, as well as an anisotropy corresponding to the cubic crystal symmetry of Fe3+xSi1-x, which implies the epitaxial orientation relationship of Fe3+xSi1-x (111)[0-11] || Ge(111)[1-10] || Fe3+xSi1-x (111)[0-11] || Si(111)[1-10]. Calculated from ferromagnetic resonance (FMR) data saturation magnetization exceeds 1000 kA/m. The temperature dependence of the electrical resistivity of a Ge layer with thicknesses of 4 nm and 7 nm is of semiconducting type, which is, however, determined by different transport mechanisms.


Acute serum amyloid A regulates cytoskeletal rearrangement, cell matrix interactions and promotes cell migration in rheumatoid arthritis.
Serum amyloid A (A-SAA) is an acute-phase protein with cytokine-like properties implicated in the pathogenesis of rheumatoid arthritis (RA), atherosclerosis, diabetes and Alzheimer's disease. This study characterises the mechanism of A-SAA-induced cytoskeletal rearrangement and migration in synovial fibroblasts and microvascular endothelial cells (human dermal endothelial cells; HDEC). Immunohistology and immunofluorescence were used to examine αvβ3 and β1-integrins, filamentous actin (F-actin) and focal adhesion expression in rheumatoid arthritis synovial tissue (RAST) and rheumatoid arthritis synovial fibroblast cells (RASFC). A-SAA-induced αvβ3 and β1-integrin binding was measured by adhesion assay. Cytoskeletal rearrangement and ρ-GTPase activation following A-SAA stimulation was examined using dual immunofluorescent staining for F-actin/vinculin staining, pull down assays and immunoblotting for Cdc42 and RhoA. Cell growth, invasion/migration, angiogenesis and actin formation were examined in the presence or absence of specific Rac1 and Cdc42 inhibitors (NSC23766 and 187-1). αvβ3, β1-integrin and F-actin predominantly localised to vascular endothelium and lining layer cells in RAST, compared with osteoarthritis and normal control synovial tissue. A-SAA significantly increased αvβ3 and β1 binding in RASFC. A-SAA induced cytoskeletal disassembly, loss of focal adhesions and filopodia formation in RASFC and HDEC. A-SAA significantly induced Cdc42 activation but failed to promote RhoA activation in HDEC and synovial fibroblast cells. Blockade of Rac-1 and Cdc42 inhibited A-SAA-induced cell growth, invasion/migration, actin cytoskeletal rearrangement and angiogenesis. These data show a novel mechanism for A-SAA-induced cell migrational events in RA mediated via cytoskeletal signalling pathways.


The effect of bean origin and temperature on grinding roasted coffee.
Coffee is prepared by the extraction of a complex array of organic molecules from the roasted bean, which has been ground into fine particulates. The extraction depends on temperature, water chemistry and also the accessible surface area of the coffee. Here we investigate whether variations in the production processes of single origin coffee beans affects the particle size distribution upon grinding. We find that the particle size distribution is independent of the bean origin and processing method. Furthermore, we elucidate the influence of bean temperature on particle size distribution, concluding that grinding cold results in a narrower particle size distribution, and reduced mean particle size. We anticipate these results will influence the production of coffee industrially, as well as contribute to how we store and use coffee daily.


Percutaneous ultrasound-guided versus bronchoscopy-guided dilatational tracheostomy after median sternotomy: A case-control study.
In this study, we aimed to compare ultrasoundguided versus bronchoscopy-guided percutaneous dilatational tracheostomy outcomes in critically ill adult patients undergoing a median sternotomy. Between January 2015 and December 2020, a total of 54 patients (17 males, 37 females; mean age: 54.9±13.1 years; range, 39 to 77 years) who underwent elective ultrasound- or bronchoscopy-guided percutaneous dilatational tracheostomy after a median sternotomy were included. We compared the ultrasound-guided group (n=25) with the bronchoscopy-guided group (n=29) regarding all-cause mortality and complications. Safety assessments included major and minor bleeding, procedural hypoxic or hypotensive event, cardiac dysrhythmias, tracheal injury, damage to adjacent structures, and requirement of conversion to open surgical tracheostomy. No tracheostomy procedure-related death was observed in either group. The median time for tracheostomy was 13 (range, 8 to 17) min in the ultrasound-guided group and 10 (range, 7 to 15) min in the bronchoscopy-guided group (p=0.387). There was no need for conversion between the two methods or conversion to surgical tracheostomy for any patient. The overall complication rates did not significantly differ between the groups (p=0.15). Ultrasound-guided percutaneous dilatational tracheostomy can be safely performed in patients undergoing sternotomy. Complication rates of the procedure are similar to those guided with bronchoscopy.


Visual motion priors differ for infants and mothers.
Visual motion direction ambiguities due to edge-aperture interaction might be resolved by speed priors, but scant empirical data support this hypothesis. We measured optic flow and gaze positions of walking mothers and the infants they carried. Empirically derived motion priors for infants are vertically elongated and shifted upward relative to mothers. Skewed normal distributions fitted to estimated retinal speeds peak at values above 20°/sec.


Total synthesis of alkaloids using both chemical and biochemical methods.
Covering: 2000 to 2019Rapid access to genomic data has facilitated the identification of the biosynthetic enzyme genes of alkaloid natural products and elucidation of their biosynthetic pathways. Enzymes for the rapid construction of molecular scaffolds and versatile modifications during the late-stage biosynthesis of complex molecular skeletons constitute unique features of biosynthetic machineries. For example, enzymes involved in an alkaloid biosynthesis. In this review, we discuss three types of useful enzymes and enzymatic reactions that have been found in the biosynthetic studies of several alkaloids, and discuss their applications for the total synthesis of natural alkaloids and their derivatives. The selected examples include a single non-ribosomal peptide synthetase SfmC that catalyzes key Pictet-Spengler reactions, which construct a characteristic tetrahydroisoquinoline skeleton in antitumor antibiotics such as saframycin, prenylation-oxidative modification enzymes involved in the biosynthesis of fungal tremorgenic mycotoxins such as penitrem as well as versatile Diels-Alderases recently discovered in the biosynthesis of plant monoterpene indole alkaloids of iboga and aspidosperma type.


Nocturnal home hemodialysis in children: Advantages, implementation, and barriers.
Chronic kidney disease and end-stage renal disease (ESRD) in children are major health concerns worldwide with increasing incidence and prevalence. Renal replacement therapies and kidney transplants have remarkably improved the management of patients with ESRD in both adult and pediatric populations. Kidney transplant has the best patient outcomes, but many a time it has a considerable waiting period. In the meantime, the majority of patients with pediatric ESRD are dependent on dialysis. The conventionally utilized hemodialysis regimen is the three times weekly, in-center hemodialysis. Many studies have demonstrated the unfavorable long-term morbidity associated with the conventional regimen. Intensified dialysis programs, which include extended nocturnal hemodialysis or short daily hemodialysis, are being increasingly advocated over the past two decades. In addition to having much better clinical outcomes as compared with the conventional regimen, the flexibility to provide dialysis at home serves as a great incentive. PubMed/Medline, Embase and Cochrane databases for literature on nocturnal home hemodialysis in children with ESRD were extensively searched. Contrary to the noticeable literature available on adult home hemodialysis, a small number of studies exist in the pediatric population. In this review, the benefits, implementation and associated barriers of nocturnal home hemodialysis in children were addressed.


Visual improvement following continuous positive airway pressure therapy in diabetic subjects with clinically significant macular oedema and obstructive sleep apnoea: proof of principle study.
Diabetic retinopathy and diabetic macular oedema are more prevalent in patients with coexistent obstructive sleep apnoea (OSA). We assessed if treatment of OSA with continuous positive airway pressure (CPAP) might improve visual acuity (VA). A total of 35 patients with clinically significant macular oedema (CSMO) and OSA [oxygen desaturation index (ODI) ≥10 or apnoea-hypopnoea index (AHI) ≥15] were identified and agreed to be studied. VA (expressed as the logarithm of the minimum angle of resolution, logMAR), macular thickness, fundal photographs, glycosylated haemoglobin (HbA1c) and rhodopsin mRNA were measured twice at baseline and at 3 and 6 months post-CPAP. Fluorescein angiography and the Epworth Sleepiness Scale (ESS) were obtained once at baseline and at 6 months. Three patients withdrew before the first trial visit. Thus, a total of 32 patients (17 males) entered the study, and 4 subsequently withdrew; thus 28 completed 6 months of follow-up. Baseline characteristics of the subjects were as follows [mean (SD or inter-quartile range)]: age 66.2 (7.1) years, body mass index 31.7 (6.3), HbA1c 7.4% (1.44) [57.1 (15.7) mmol/mol], AHI 16.5 (11-25), ODI 16.0 (12-25), ESS 6.5 (4.0-12.0) and duration of diabetes 9.5 years (5.0-16.5). Participants were divided into 13 high and 15 low CPAP compliers (≥ and <2.5 h/night over the 6 months, respectively). At 6 months, the adjusted treatment effect on VA of high compliance versus low compliance was 0.11 (95% confidence interval 0.21 to -0.002; p = 0.047), equivalent to a one-line improvement on the logMAR chart. There was no significant improvement in macular oedema or fundal photographs. This hypothesis-generating, uncontrolled study suggests that ≥2.5 h/night CPAP usage over 6 months in individuals with CSMO and OSA may be associated with improvement in VA. This provides justification for a randomised controlled trial of CPAP therapy in such patients.


3D printing of biologics-what has been accomplished to date?
Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.


Erythema dyschromicum perstans.
A 39-year-old Hispanic man presented with widespread, symmetric, hyperpigmented, brown-gray-blue, oval-to-circular, discrete and coalescing patches on the upper extremities, trunk, neck and face, many with an associated annular erythematous border. Histopathologic features showed an interface dermatitis, thin lichenoid and superficial perivascular infiltrates, and dermal melanophages. These changes were consistent with a diagnosis of erythema dyschromicum perstans (EDP). The etiology of EDP is unknown, but many associations have been described. The rim of erythema that appears during the inflammatory phase of the disorder distinguishes it from other disorders of hyperpigmentation. There is no consistently effective treatment for EDP. We highlight the use of narrow-band UV B phototherapy in the treatment of this disorder, which has shown good success in our patient thus far.


Cholera control in an inaccessible district in Tanzania: importance of temporary rural centres.
The fourth ever recorded outbreak of cholera on Tanzania mainland started on 2.10.77 in Twasalie village which is a delta island in the Utete district on the Indian Ocean coastal line. Poor communication and inadequate health facilities in the district delayed detection and reporting of the outbreak for four weeks leading to wide dissemination of the disease. Socio-cultural and religious practices by residents of the district especially the procedure of burying the dead played a key role in enhancing spread of the infection. The outbreak was controlled by establishing 16 multipurpose cholera centres in the district. Whereas 55% of the 69 patients with the disease before control measures were introduced died, the mortality rate was reduced to 1.6% out of the 184 severely ill patients admitted to treatment centres.


Gene Networks and Pathways Involved in LPS-Induced Proliferative Response of Bovine Endometrial Epithelial Cells.
Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria involved in the pathogenic processes leading to mastitis and metritis in animals such as dairy cattle. LPS causes cell proliferation associated with endometrium inflammation. Former in vitro studies have demonstrated that LPS induces an intense stimulation of the proliferation of a pure population of bovine endometrial epithelial cells. In a follow-up transcriptomic study based on RNA-sequencing data obtained after 24 h exposure of primary bovine endometrial epithelial cells to 0, 2, and 8 μg/mL LPS, 752 and 727 differentially expressed genes (DEGs) were detected between the controls and LPS-treated samples that encode proteins known to be associated with either proliferation or apoptosis, respectively. The present bioinformatic analysis was performed to decipher the gene networks involved to obtain a deeper understanding of the mechanisms underlying the proliferative and apoptosis processes. Our findings have revealed 116 putative transcription factors (TFs) and the most significant number of interactions between these TFs and DEGs belong to NFKβ1, TP53, STAT1, and HIF1A. Moreover, our results provide novel insights into the early signaling and metabolic pathways in bovine endometrial epithelial cells associated with the innate immune response and cell proliferation to Escherichia coli-LPS infection. The results further indicated that LPS challenge elicited a strong transcriptomic response, leading to potent activation of pro-inflammatory pathways that are associated with a marked endometrial cancer, Toll-like receptor, NFKβ, AKT, apoptosis, and MAPK signaling pathways. This effect may provide a mechanistic explanation for the relationship between LPS and cell proliferation.


Seasonality in marine ecosystems: Peruvian seabirds, anchovy, and oceanographic conditions.
In fluctuating environments, matching breeding timing to periods of high resource availability is crucial for the fitness of many vertebrate species, and may have major consequences on population health. Yet, our understanding of the proximate environmental cues driving seasonal breeding is limited. This is particularly the case in marine ecosystems, where key environmental factors and prey abundance and availability are seldom quantified. The Northern Humboldt Current System (NHCS) is a highly productive, low-latitude ecosystem of moderate seasonality. In this ecosystem, three tropical seabird species (the Guanay Cormorant Phalacrocorax bougainvillii, the Peruvian Booby Sula variegata, and the Peruvian Pelican Pelecanus thagus) live in sympatry and prey almost exclusively on anchovy, Engraulis ringens. From January 2003 to December 2012, we monitored 31 breeding sites along the Peruvian coast to investigate the breeding cycle of these species. We tested for relationships between breeding timing, oceanographic conditions, and prey availability using occupancy models. We found that all three seabird species exhibited seasonal breeding patterns, with marked interspecific differences. Whereas breeding mainly started during the austral winter/early spring and ended in summer/early fall, this pattern was stronger in boobies and pelicans than in cormorants. Breeding onset mainly occurred when upwelling was intense but ecosystem productivity was below its annual maxima, and when anchovy were less available and in poor physiological condition. Conversely, the abundance and availability of anchovy improved during chick rearing and peaked around the time of fledging. These results suggest that breeding timing is adjusted so that fledging may occur under optimal environmental conditions, rather than being constrained by nutritional requirements during egg laying. Adjusting breeding time so that fledglings meet optimal conditions at independence is unique compared with other upwelling ecosystems and could be explained by the relatively high abundances of anchovy occurring throughout the year in the NHCS.


Obstacle Avoidance and Target Acquisition for Robot Navigation Using a Mixed Signal Analog/Digital Neuromorphic Processing System.
Neuromorphic hardware emulates dynamics of biological neural networks in electronic circuits offering an alternative to the von Neumann computing architecture that is low-power, inherently parallel, and event-driven. This hardware allows to implement neural-network based robotic controllers in an energy-efficient way with low latency, but requires solving the problem of device variability, characteristic for analog electronic circuits. In this work, we interfaced a mixed-signal analog-digital neuromorphic processor ROLLS to a neuromorphic dynamic vision sensor (DVS) mounted on a robotic vehicle and developed an autonomous neuromorphic agent that is able to perform neurally inspired obstacle-avoidance and target acquisition. We developed a neural network architecture that can cope with device variability and verified its robustness in different environmental situations, e.g., moving obstacles, moving target, clutter, and poor light conditions. We demonstrate how this network, combined with the properties of the DVS, allows the robot to avoid obstacles using a simple biologically-inspired dynamics. We also show how a Dynamic Neural Field for target acquisition can be implemented in spiking neuromorphic hardware. This work demonstrates an implementation of working obstacle avoidance and target acquisition using mixed signal analog/digital neuromorphic hardware.


Health technology, quality and safety in a learning health system.
Health technology quality and safety is an important issue for health informatics (i.e. digital health) professionals. Health technologies have been used to (1) collect data that can be analyzed to improve the quality and safety of healthcare activities and (2) re-engineer and/or automate error-prone processes. Health technologies are also able to introduce new types of errors (i.e. technology-induced errors) and have been implicated in propagating errors across digital health ecosystems. To develop a learning health system, health technologies need to be considered in terms of how they can improve the quality and safety of health activities traditionally carried out by humans (patients and health professionals) and also how the technology's quality and safety can be improved. This article outlines how this can be done by integrating evidence from health informatics research into practice using a learning health systems approach.


Interleukin-15 alters hippocampal synaptic transmission and impairs episodic memory formation in mice.
Cytokines are potent immunomodulators exerting pleiotropic effects in the central nervous system (CNS). They influence neuronal functions and circuit activities with effects on memory processes and behaviors. Here, we unravel a neuromodulatory activity of interleukin-15 (IL-15) in mouse brain. Acute exposure of hippocampal slices to IL-15 enhances gamma-aminobutyricacid (GABA) release and reduces glutamatergic currents, while chronic treatment with IL-15 increases the frequency of hippocampal miniature inhibitory synaptic transmission and impairs memory formation in the novel object recognition (NOR) test. Moreover, we describe that serotonin is involved in mediating the hippocampal effects of IL-15, because a selective 5-HT3A receptor antagonist prevents the effects on inhibitory neurotransmission and ameliorates mice performance in the NOR test. These findings provide new insights into the modulatory activities of cytokines in the CNS, with implications on behavior.


Calcitriol enhances pyrazinamide treatment of murine tuberculosis.
Tuberculosis is a leading cause of morbidity and mortality in humans worldwide. There is an urgent need for new and effective drugs to treat tuberculosis and shorten the duration of tuberculosis therapy. 1, 25-dihydroxy vitamin D3 (1,25 (OH)2D3) has been reported to have a synergistic effect with pyrazinamide (PZA) in killing tubercle bacilli in vitro. The addition of 1,25 (OH)2D3 to standard tuberculosis treatment should benefit patients if the adjunctive drug has a synergistic effect in vivo. Thus, in this study, calcitriol (bioactive 1,25 (OH)2D3) was administered to mice undergoing treatment for Mycobacterium tuberculosis (M.tb) infection with PZA, a first-line anti-tuberculosis drug, to determine whether vitamin D3 enhances the therapeutic effect. C57BL/6 female mice were infected with the M.tb H37Rv strain through aerosol exposure. Calcitriol and PZA, either alone or in combination, were orally administered to the M.tb infected mice. The effect of calcitriol on PZA activity was determined by evaluating the bacterial burden and analyzing the histopathological lesions in the lungs and spleen. To investigate the expression of inflammatory cytokines and anti-microbial peptide genes, we determined the transcriptional levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), mouse β-defensin-2 (mBD2), and cathelicidin LL-37 through real-time quantitative polymerase chain reaction. The protein levels of IFN-γ were detected by enzyme-linked immunosorbent assay. Differences between groups were analyzed with independent samples t-test or one-way analysis of variance. Calcitriol alone had little effect on tuberculosis infection, whereas PZA, compared with saline control treatment, decreased the bacterial burden (spleens: PZA vs. saline, 4.82 ± 0.22 vs. 5.22 ± 0.40 Log10 colony-forming units [CFU]/gram, t = 2.13, P < 0.05; lungs: PZA vs. saline, 5.55 ± 0.15 vs. 6.83 ± 0.46 Log10 CFU/gram, t = 6.56, P < 0.01) and pathological lesions in the lungs. Simultaneous administration of calcitriol with PZA, compared with PZA alone, decreased the bacterial load (spleen: calcitriol + PZA vs. PZA, 4.37 ± 0.13 vs. 4.82 ± 0.22 Log10 CFU/gram, t = 4.36, P < 0.01; lung: calcitriol + PZA vs. PZA, 5.03 ± 0.32 vs. 5.55 ± 0.15 Log10 CFU/gram, t = 3.58, P < 0.01) and attenuated the lung lesions (gross pathological score: calcitriol + PZA vs. PZA, 3.25 ± 0.50 vs. 2.50 ± 0.58, t = 1.96, P < 0.05; affected area of total lung area: calcitriol + PZA vs. PZA, 30.75% ± 6.50% vs. 21.55% ± 2.99%, t = 2.66, P < 0.05). Further studies demonstrated calcitriol significantly increased the expression of anti-inflammatory cytokine IL-4 but suppressed production of the pro-inflammatory cytokine IFN-γ (IL-4: calcitriol vs. saline, 5.69 ± 0.50 vs. 2.80 ± 0.56 fold of control, t = 6.74, P < 0.01; IFN-γ: calcitriol vs. saline, 1.36 ± 0.11 vs. 4.13 ± 0.83 fold of control, t = 5.77, P < 0.01). In addition, calcitriol alone or in combination with PZA significantly enhanced the transcriptional level of anti-microbial peptides (cathelicidin LL-37: calcitriol vs. saline, 10.59 ± 1.03 vs. 2.80 ± 0.90 fold of control, t = 9.85, P < 0.01; mBD2: calcitriol vs. saline, 7.92 ± 0.62 vs. 1.79 ± 0.45 fold of control, t = 13.82, P < 0.01), whereas PZA exerted a negative effect on anti-microbial peptide gene expression. Calcitriol as adjunctive treatment can result in beneficial treatment outcomes in M.tb infection by suppressing the inflammatory response and up-regulating the expression of anti-microbial peptides. These results indicate the feasibility of using calcitriol adjunctively with standard chemotherapy for the treatment of M.tb infection.


[Adenoid cystic carcinoma of the larynx].
Adenoid cystic carcinoma of the larynx is rare. Only 7 cases have been treated in our hospital from 1959 to 1986, which comprised 0.7% of all laryngeal malignancies in the same period. Of the 7 cases, there were 5 males and 2 females with the average age of 47. The symptoms at the time of diagnosis varied according to the size and location of the tumor. Three lesions were considered as supraglottic and one as subglottic. Six cases were treated by surgery and one by radiotherapy alone. The most common site of distant metastasis was the lung. The average survival was long even in those with pulmonary metastasis.


Associations between liver histological changes and hepatic monooxygenase activities in vitro in diabetic patients.
The associations between liver histological changes and hepatic cytochrome P-450 content (P-450) and the activities of aryl hydrocarbon hydroxylase (AHH) and 7-ethoxycoumarin O-de-ethylase (ECD) have been investigated in 30 diabetics undergoing diagnostic liver biopsy. There were more than 10-fold interindividual variations in P-450 contents and AHH and ECD activities in the diabetics. P-450 content decreased with increasing severity of liver histological changes, whereas AHH and ECD activities were significantly reduced only in biopsies with severe histological changes. However, despite differential effects of liver disorders on P-450 and AHH and ECD activities there were highly significant correlations between these three parameters with each other.


Legal issues in the delivery of alternative medicine.
As use of alternative therapies grows, there appears to be heightened concern among health care professionals about the liability implications of delivering these therapies. Little is known about malpractice law in this area. We begin by reviewing the type and frequency of claims brought against alternative medicine practitioners and by analyzing the standard of care to which these practitioners are held when sued. Next we turn to the standard of care question as it relates to physicians (MDs/DOs) who incorporate alternative therapies into their practices. Few cases have addressed this question to date. We argue, however, that when courts decide cases at the intersection between conventional and alternative medicine, they may judge conduct according to standards enunciated by: 1) alternative medicine practitioners who regularly deliver the treatment at issue, 2) physicians who have established similar practices, or 3) conventional practitioners. This latter possibility should be taken seriously; it raises troubling questions for physicians at the outset of the negligence inquiry. Available case law highlights the importance of ensuring that patients are fully informed about any alternative therapies they elect to receive, as well as any conventional treatments they may be foregoing, and that patients expressly consent to treatment in light of this information, preferably in writing.


Optimal processing of photoreceptor signals is required to maximize behavioural sensitivity.
The sensitivity of receptor cells places a fundamental limit upon the sensitivity of sensory systems. For example, the signal-to-noise ratio of sensory receptors has been suggested to limit absolute thresholds in the visual and auditory systems. However, the necessity of optimally processing sensory receptor signals for behaviour to approach this limit has received less attention. We investigated the behavioural consequences of increasing the signal-to-noise ratio of the rod photoreceptor single-photon response in a transgenic mouse, the GCAPs-/- knockout. The loss of fast Ca2+ feedback to cGMP synthesis in phototransduction for GCAPs-/- mice increases the magnitude of the rod single-photon response and dark noise, with the increase in size of the single-photon response outweighing the increase in noise. Surprisingly, despite the increased rod signal-to-noise ratio, behavioural performance for GCAPs-/- mice was diminished near absolute visual threshold. We demonstrate in electrophysiological recordings that the diminished performance compared to wild-type mice is explained by poorly tuned postsynaptic processing of the rod single-photon response at the rod bipolar cell. In particular, the level of postsynaptic saturation in GCAPs-/- rod bipolar cells is not sufficient to eliminate rod noise, and degrades the single-photon response signal-to-noise ratio. Thus, it is critical for retinal processing to be optimally tuned near absolute threshold; otherwise the visual system fails to utilize fully the signals present in the rods.


Outcome and reproductive function after chemotherapy for ovarian dysgerminoma.
To review the outcome for all patients with ovarian dysgerminoma treated at the M.D. Anderson Cancer Center who received bleomycin, etoposide, and cisplatin (BEP) and to assess the menstrual and reproductive function of those who received conservative treatment. Clinical information was abstracted from the medical record. Patients completed a detailed questionnaire about menstrual and reproductive function; those who did not return the questionnaire were interviewed by telephone. Twenty-six patients were identified as having been treated with BEP chemotherapy for pure ovarian dysgerminoma from January 1984 to January 1998. Their median age was 19.5 years (range, 7 to 32 years). Sixteen patients underwent fertility-sparing surgery in the form of unilateral salpingo-oophorectomy. At a median follow-up time of 89 months, 25 (96%) of the 26 patients remained continuously disease-free. One patient apparently developed a second primary dysgerminoma in her remaining ovary after BEP and was clinically disease-free after further treatment. Of the 16 patients who underwent fertility-sparing surgery, one was lost to follow-up when she was pregnant, and one was still premenarchal. Of the remaining 14 patients, 10 (71%) maintained their normal menstrual function during and after chemotherapy, and 13 (93%) had returned to their prechemotherapy menstrual pattern at the time of the questionnaire. Five pregnancies have occurred thus far, and two patients have had difficulty conceiving. Most patients with metastatic dysgerminoma can expect cure with maintenance of normal reproductive function when treated with conservative surgery and BEP chemotherapy.


The factors that have an impact on the development of brain metastasis in the patients with breast cancer.
To evaluate the factors that have an impact on the development of brain metastasis in patients with breast cancer. Among the patients who were followed-up and treated for breast cancer between January 2000 and January 2010, the ones with brain metastasis were included to the analysis. Metastatic breast cancer patients without brain metastasis, which had similar duration of follow-up and median age were included as the control group. Both group were compared for prognostic and predictive factors in terms of relationship between with or without brain metastasis and survival. There were a total of 63 female patients with metastatic breast cancer who had brain metastasis and the researchers enrolled the same number of female patients as the control group. In the univariate analysis, as a significant finding, it was found that, the patients with breast cancer who had brain metastasis had vascular invasion positivity, human epidermal growth factor receptor-2 (HER-2) positivity, a rare detection of invasive lobular carcinoma component in the tumor, estrogen receptor negativity, and no bone and liver metastasis and they did not receive chemotherapy due to several reasons after the detection of metastasis in any organ. In the multivariate analysis, HER-2 positivity, no bone and liver metastasis and not receiving chemotherapy due to several reasons after the detection of metastasis in any organ were detected as significant findings. As the prognostic and predictive factors showing the development of brain metastasis in breast cancer patients may be identified, follow-up also including the brain is important in order to take preventive measures.


A rapid method for the determination of brominated flame retardant concentrations in plastics and textiles entering the waste stream.
Due to new European legislation, products going to waste are subject to 'low persistent organic pollutant concentration limits'. Concentrations of restricted brominated flame retardants in waste products must be determined. A rapid extraction and clean-up method was developed for determination of brominated flame retardants in various plastics and textiles. The optimised method used vortexing and ultrasonication in dichloromethane followed by sulfuric acid clean-up to determine target compounds. Poly-brominated diphenyl ethers were determined by gas chromatography with mass spectrometry and hexabromocyclododecane by liquid chromatography with tandem mass spectrometry. Good recoveries of target analytes were obtained after three extraction cycles. The method was validated using poly-propylene and poly-ethylene certified reference materials as well as previously characterised textiles, expanded and extruded poly-styrene samples. Measured concentrations of target compounds showed good agreement with the certified values indicating good accuracy and precision. Clean extracts provided low noise levels resulting in low limits of quantification (0.8-1.5 ng/g for poly-brominated diphenyl ethers and 0.3 ng/g for α-, β- and γ-hexabromocyclododecane). The developed method was applied successfully to real consumer products entering the waste stream and it provided various advantages over traditional methods, including reduced analysis time, solvent consumption, minimal sample contamination and high sample throughput, which is crucial to comply with the implemented legislation.


Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA.
The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVdelta3 (the live attenuated vaccine strain derived from SIVmac239), or SIVdelta3+ (a pathogenic progeny virus that had evolved from SIVdelta3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVdelta3, and SIVdelta3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression.


Study of hopping transport in long oligothiophenes and oligoselenophenes: dependence of reorganization energy on chain length.
Internal reorganization energies for self-exchange hole-transfer process were calculated at the B3LYP/6-31G(d) level of theory for a series of oligothiophenes and oligoselenophenes up to the 50-mers. This is the first study of reorganization energy in very long pi-conjugated systems. We observed a linear correlation between reorganization energy and the reciprocal chain length for these long pi-conjugated heterocyclic oligomers, which can be explained by the changes in bond length that occur between the neutral and cation radical species and by the charge distribution in the cation radicals. In contrast to the saturation behavior observed for the HOMO-LUMO gaps of long pi-conjugated heterocyclic oligomers, the reorganization energy does not show saturation behavior for any length of the oligomers in this study, even up to the 50-mers. Interestingly, the reorganization energy approaches zero for infinite numbers of oligomer units (at the B3LYP/6-31G(d) level of theory), that is, for polythiophene and polyselenophene. The absolute values of the reorganization energies of oligoselenophenes, and the changes that occur in those energies with chain length, are similar to those found for oligothiophenes.


Characterization of mouse models of Mycobacterium avium complex infection and evaluation of drug combinations.
The Mycobacterium avium complex is the most common cause of nontuberculous mycobacterial lung disease worldwide; yet, an optimal treatment regimen for M. avium complex infection has not been established. Clarithromycin is accepted as the cornerstone drug for treatment of M. avium lung disease; however, good model systems, especially animal models, are needed to evaluate the most effective companion drugs. We performed a series of experiments to evaluate and use different mouse models (comparing BALB/c, C57BL/6, nude, and beige mice) of M. avium infection and to assess the anti-M. avium activity of single and combination drug regimens, in vitro, ex vivo, and in mice. In vitro, clarithromycin and moxifloxacin were most active against M. avium, and no antagonism was observed between these two drugs. Nude mice were more susceptible to M. avium infection than the other mouse strains tested, but the impact of treatment was most clearly seen in M. avium-infected BALB/c mice. The combination of clarithromycin-ethambutol-rifampin was more effective in all infected mice than moxifloxacin-ethambutol-rifampin; the addition of moxifloxacin to the clarithromycin-containing regimen did not increase treatment efficacy. Clarithromycin-containing regimens are the most effective for M. avium infection; substitution of moxifloxacin for clarithromycin had a negative impact on treatment efficacy.


Anetodermic variant of a periorbital pilomatricoma.
Pilomatricoma usually presents as a solitary hard nodule located deep in the dermis. However, a variant termed anetodermic is often seen in the elderly. Instead of a hard nodule, a rapidly growing bullous lesion is seen. The authors report a 60-year-old man who presented with an erythematous bullous lesion at the left medial canthus. The lesion started as a small 3-mm papule and grew significantly to a 12-mm lesion in 5 weeks. Histopathologically, the tumor was composed of basophilic and keratinized shadow cells typical of pilomatricoma. Anetodermic changes could also be seen, represented by intralesional hemorrhage, dilated blood and lymphatic vessels, and disruption of dermal collagen fibers. The anetodermic variant of pilomatricoma was described in 1943 and accounts for only 2% of cases. Compression of vessels by the neoplastic process and peritumoral inflammatory infiltration are the proposed pathogenic mechanisms underlying the atypical findings.


The psychopathic "label" and effects on punishment outcomes: A meta-analysis.
The current study, using a meta-analytic approach and moderation analysis, examines 22 studies reporting how psychopathic "labeling" influences perceptions on 3 punishment outcomes (dangerousness, treatment amenability, and legal sentence/sanction) for 2 types of experimental studies utilizing vignettes: (a) studies in which a defendant with a psychopathic "label" is compared to a defendant with no mental health diagnosis (psychopathic label vs. no label) and (b) studies in which a defendant with a psychopathic "label" is compared to a defendant with a different psychiatric diagnosis (psychopathic label vs. other psychiatric label). Results show statistically significant or marginally significant (p < .10) summary effect sizes, albeit of different strengths, for the three punishment outcomes studied (legal sentence/sanction: d = 0.17; dangerousness: d = 0.58; and treatment amenability: d = -0.30) for studies comparing a psychopathic label versus no label. Conversely, all summary effects sizes for the three punishment outcomes in studies comparing a psychopathic label versus other psychiatric label were both weak and nonsignificant (legal sentence/sanction: d = 0.09; dangerousness: d = 0.14; and treatment amenability: d = 0.02). This suggests a significant general labeling effect, but not a specific labeling effect, for psychopathy in these studies. Further, these results suggest that the lay public, but not those in the criminal justice system, may subscribe to both general and specific labeling effects for psychopathy when it comes to punishment. This has potential implications for jury sentencing in both capital and, in select states, noncapital cases. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Tissue quantification with acoustic radiation force impulse imaging: Measurement repeatability and normal values in the healthy liver.
The purpose of this study was to describe the most reliable measurement procedure for acoustic radiation force impulse technology and to define the normal wave velocity values in a healthy liver. Twenty healthy volunteers underwent acoustic radiation force impulse imaging tissue quantification and were enrolled in this prospective study. All patients were examined by two independent operators at the same time. Twenty-four measurements per subject were obtained. Intraoperator and interoperator evaluations were performed. Statistical comparison of all mean data was performed with Student's t test. A value of p < 0.05 was considered significant. A comparative analysis was performed, and interclass correlation coefficients were calculated. The operators obtained 960 measurements. A statistically significant difference was found between the mean shear wave velocity values obtained by one operator deep in the right lobe of the liver and the values obtained on the surface of the right lobe (1.56 vs 1.90 m/s) and between the mean values obtained deep in the right lobe and those obtained deep in the left lobe (1.56 vs 1.84 m/s). The other operator had similar results. The distribution of all mean values obtained by both operators deep in the right hepatic lobe exhibited less dispersion (95% CI, 1.391-1.725) than those obtained on the surface (95% CI, 1.664-2.136). In 77.5% of cases, the shear wave speeds were between 1 and 2 m/s. No statistically significant difference was found in the comparisons performed on the right hepatic lobe by the two operators. The interclass correlation coefficient calculated for measurements deep in the right lobe was 0.87 (p < 0.0001). Acoustic radiation force impulse imaging quantification of hepatic tissue is more reproducible when applied to the deeper portion of the right lobe of the liver.


Perianal extramammary Paget's disease.
Perianal extramammary Paget's disease is a rare disorder of unknown aetiology and is frequently associated with malignancy. Since Sir James Paget's original description, extramammary Paget's disease has been surrounded by controversy, speculation and much interest on the part of surgeons, pathologists and dermatologists. This case report draws attention to this rare condition, which should be considered in the differential diagnosis of perianal disorders. The physician must maintain a high index of suspicion, especially in cases with characteristic lesions unresponsive to conventional dermatological therapy. The importance of awareness of the condition is stressed and the diagnosis and treatment are commented upon. Treatment and prognosis depend on the presence of an underlying invasive carcinoma. An adequate initial evaluation and long-term follow up are necessary to identify recurrence and development of other malignancies.


Visual Outcomes of Adding Erythropoietin to Methylprednisolone for Treatment of Retrobulbar Optic Neuritis.
To compare the short-term visual function results and safety of erythropoietin as an add-on to the standard corticosteroid therapy in retrobulbar optic neuritis (RON). In this prospective pilot study, adult patients with isolated RON with less than 10 days of onset were enrolled. Patients were consecutively assigned to standard intravenous methylprednisolone treatment either in combination with intravenous erythropoietin (20,000 units/day for three days) (group-1) or intravenous methylprednisolone alone (group-2). Primary outcome measure was best-corrected visual acuity (BCVA), which was assessed up to 120 days from the day the treatment was begun. Systemic evaluations were performed during and after treatment. Sixty-two patients with RON (mean age = 26.6 ± 5.77 years; range = 18-40 years) were enrolled into the study (group-1, n = 35; group-2, n = 27). BCVA three months after the treatment was 0.19 ± 0.55 logMAR and 0.11 ± 0.32 logMAR in group-1 and group-2, respectively (95% CI: - 0.61 - 0.16; P = 0.62). Change in BCVA after three months was 2.84 ± 3.49 logMAR in group-1 and 2.46 ± 1.40 logMAR in group-2 (95% CI: - 0.93 - 1.91; P = 0.57). Pace of recovery was not significantly different between the groups. No complications were detected among patients. Intravenous erythropoietin as an add-on did not significantly improve the visual outcome in terms of visual acuity, visual field, and contrast sensitivity compared to traditional intravenous corticosteroid. This pilot study supports the safety profile of intravenous human recombinant erythropoietin, and it may help formulate future investigations with a larger sample size.


[Congenital hemangioma arising of internal orbitary edge. Importance of ENT exploration and treatment options].
Hemangiomas are the most common tumors in children. It id reported the case of 11 months girl with congenital hemangioma at internal orbitary edge. ENT exploration is essential to rule out the affectation of nose and paranasal sinuses as well as other associated similar injuries in head and neck. As complementary tests we asked for CT and IRM to delimit the tumoration whose classic treatment are oral corticoids in high doses. Surgery usually is reserved for refractory cases to the medical therapy although the present exposition is changing due to different factors that we expose in the final discussion.


The "Acute" Stone Clinic Effect: Improving Healthcare Delivery by Reorganizing Clinical Resources.
To determine the time to specialist urologic consultation and definitive management after establishing a subspecialist administered acute stone clinic (ASC) for adults with symptomatic upper tract stones in a publically funded universal healthcare system. We retrospectively reviewed 337 adult referrals for stone management. Three distinct 9-week periods were assessed. Group 1 patients were seen/treated by their individual urologist before inception of a general urology emergency clinic (pre-EC). Group 2 patients were seen in a pooled EC and Group 3 patients were seen in the ASC. A total of 337 patients (75, pre-EC; 91, EC; 171, ASC) were reviewed. Mean time to consultation for pre-EC, EC, and ASC cohorts was 29, 7, and 7 days, respectively (p < 0.05), whereas loss to follow-up decreased from 13% to 5% (p < 0.05). On average, the number of patients seen per week increased from 9 to 20. Mean time to stone surgery from date of referral was 75 days pre-EC, 43 days EC, and 25 days ASC (p < 0.05). The percentage of patients undergoing surgery was between 59% and 63% per cohort; however, the number of patients increased from 5 to 11 per week. By reorganizing clinical resources, a dedicated ASC was able to increase patient capacity, reduce time to urologist consultation and reduce surgical wait times.


Comparative studies of embryo metabolism in early pregnancy.
Embryo metabolism during early pregnancy has been investigated, mainly in the mouse and rabbit, using a variety of catabolic and anabolic parameters. The rate of metabolic activity of the conceptus continues to increase markedly with the approach of implantation. However, in species in which the embryo enters a period of delayed implantation the diapause is associated with relative metabolic quiescence. Mouse, rabbit, ovine and bovine preimplantation embryos can be cultured in a simple defined medium. Under such conditions energy substrates in the medium represent a major source of carbon for anabolism. Glucose carbon is incorporated into macromolecules during in-vitro culture of cleaving mouse embryos and implanting and diapausing mouse blastocysts. In particular, both acid-soluble glycogen and desmoglycogen are rapidly synthesized from glucose presumably to act as a source of energy at implantation. The pattern of glucose accumulation by cleaving sheep embryos and embryonic discs and early somites excised from sheep and cattle embryos between Days 14 and 18 or pregnancy is basically similar to that in the mouse except that very little glycogen is synthesized by ruminant embryos. During embryonic diapause in the tammar wallaby there is a cessation of cell division and glucose uptake appears to be relatively low. After removal of pouch young in the breeding season to reactivate embryo development, glucose accumulation by the tammar blastocyst increases. The increase is related to the start of blastocyst expansion. Furthermore, the pattern of glucose metabolism in the reactivated wallaby blastocyst is similar to that in ruminant species, approximately 30% of the glucose carbon being incorporated into macromolecules such as protein, lipid and nucleic acid but with little synthesis of glycogen.


The G protein-coupled receptor GPR30 inhibits human urothelial cell proliferation.
We have previously shown that estrogen stimulates cell proliferation in both normal and transformed urothelial cells mainly through activation of the two primary estrogen receptors (ERs), ERalpha and ERbeta. A growing body of evidence suggests that estrogen also initiates nongenomic effects that cannot be explained by activation of primary ERs. In the present study, we observed that urothelial cells express high amounts of GPR30, a G protein-coupled receptor recently identified as a candidate for membrane-associated estrogen binding. Membrane- impermeable bovine serum albumin-conjugated 17beta-estradiol and the specific GPR30 agonist G-1 both inhibited urothelial cell proliferation in a concentration-dependent manner. Transient overexpression of GPR30 inhibited 17beta-estradiol (E2)-induced cell proliferation. Decreased GPR30 expression caused by specific small interfering RNA increased E2-induced cell proliferation. These results indicate that membrane-associated inhibitory effects of E2 on cell proliferation correlate with abundance of GPR30. Although E2 induced a significant increase in caspase-3/7 activity, G-1 did not, suggesting that the GPR30-mediated inhibitory effect on cell proliferation was not caused by apoptosis. Furthermore, we found that G-1 failed to induce c-fos, c-jun, and cyclin D1 expression, and GPR30 overexpression abolished E2-induced c-fos, c-jun, and cyclin D1 expression. However, inactivation of GPR30 by small interfering RNA increased c-fos, c-jun, and cyclin D1 expression. These results suggest that GPR30-mediated inhibition of urothelial cell proliferation is the result of decreased cyclin D1 by down-regulation of activation protein-1 signaling.


Mast cell-derived prostaglandin D2 inhibits colitis and colitis-associated colon cancer in mice.
Compared with prostaglandin E2, which has an established role in cancer, the role of the COX metabolite prostaglandin D2 (PGD2) in chronic inflammation leading to tumorigenesis is uncertain. In this study, we investigated the role of PGD2 in colitis and colitis-associated colon cancer (CAC) using genetically modified mice and an established model of inflammatory colon carcinogenesis. Systemic genetic deficiency in hematopoietic PGD synthase (H-PGDS) aggravated colitis and accelerated tumor formation in a manner associated with increased TNFα expression. Treatment with a TNFα receptor antagonist attenuated colitis regardless of genotype. Histologic analysis revealed that infiltrated mast cells strongly expressed H-PGDS in inflamed colons. Mast cell-specific H-PGDS deficiency also aggravated colitis and accelerated CAC. In contrast, treatment with a PGD2 receptor agonist inhibited colitis and CAC. Together, our results identified mast cell-derived PGD2 as an inhibitor of colitis and CAC, with implications for its potential use in preventing or treating colon cancer.


Recognition and lysis of target cells by cytotoxic T lymphocytes.
A single cytotoxic T lymphocyte (CTL) is capable of performing the two most fundamental functions of an immune response, recognition and elimination of foreign antigens. It is now clear that in a CTL these two functions are linked via the antigen-specific, heterodimeric receptor. We review here some experimental approaches that justify this conclusion and provide the means for further examination of the mechanisms by which CTLs lyse their target cells. When antireceptor antibodies serving as antigen substitutes are attached to various cells, they trigger the lytic activity of particular CTLs, which results in lysis of the antibody-modified cell. In the process, a novel serine esterase, which is located within cytolytic granules of the CTL, is released. The presence of this enzyme and a complement-like protein, perforin, in granules of a CTL has led to the suggestion that CTLs and complement have similar cytolytic mechanisms. However, the resistance of some CTLs to lysis by other CTLs, but not to lysis by antibody-activated complement, suggests fundamental differences between cytolytic mechanisms of CTLs and complement.


Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer.
Pancreatic cancer is one of the highest causes of mortality throughout the world; thus, it requires an effective treatment strategy. Some chemotherapeutic agents used in the clinics or under clinical trials are hydrophobic and have poor aqueous solubility; consequently, they also have minimal systemic bioavailability. Nanoparticle-based drug delivery tactics have the potential for overcoming these limitations and enhancing their therapeutic efficacy. Herein, a glutathione (GSH)-sensitive micelle (PAH-SS-PLGA) was synthesized for the combined delivery of alpha-tocopheryl succinate (TOS) and curcumin to improve its therapeutic efficacy. The chemical structures of PAH-SS-PLGA were analyzed using Proton Nuclear Magnetic Resonance (1H-NMR) and Fourier Transform Infrared (FTIR) spectroscopy, whereas the particle size, zeta potential, and surface morphology were observed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro drug release results revealed that more TOS and curcumin were released in the presence of GSH (5 mM) than the physiological pH value. Fluorescence microscopy images revealed that nanoformulated curcumin/rhodamine was uptaken by PAN02 pancreatic cancer cells. In vitro cytotoxicity assays showed higher cytotoxicity for nanoformulated TOS and/or curcumin than free TOS and/or curcumin. In addition, higher cytotoxicity was observed for combination drugs than free drugs alone. Most interestingly, at all tested concentrations of nanoformulated drugs (PAH-SS-PLGA, TOS, and curcumin), the calculated combination index (CI) value was less than one, which shows that TOS and curcumin have a synergistic effect on cellular proliferation inhibition. Overall, synthesized co-polymers are the best carriers for combination drugs, TOS, and curcumin, because they enhance the therapeutic efficacy and improve pancreatic cancer treatments.


Becoming part of an upwards spiral: Meanings of being person-centred in nursing homes.
Previous research suggests that person-centred care is positive for people living in nursing homes, but less is known on what motivates people working in nursing homes to be person-centred. Previous research has focused on person-centred care in relation to people in need of care, which may lead to a risk of viewing person-centred care as a means to achieve quality of care, and not as a means in itself. Therefore, this study aimed to illuminate meanings of being person-centred as narrated by people working in nursing homes. A total of 23 persons working in a nursing home in rural Australia participated in group and individual interviews, conducted and interpreted in respect to a phenomenological hermeneutic approach. The thematic structure as emerging from structural analyses of the text indicated that being person-centred involved a joint effort to think differently on what you do and why you do it interpreted as; Doing what you know and feel is the right thing to do, Being a person with and for another person, and Striving to do and be better together. The comprehensive understanding of these findings was that being person-centred means becoming part of an upwards spiral of doing person-centred actions and being person-centred to become even more person-centred and to feel a sense of belonging to a person-centred culture. Denoting the importance of being more of a person in one's professional role, this study highlights health aspects of being person-centred from the perspective of people working in nursing homes, and complements previous research that describes the impact of person-centred care on people in need of care. The findings could be applied to facilitate person-centred care in nursing home contexts, and to develop prevention strategies to diminish negative impacts on person-centred doing, being, becoming and belonging.


Evolution in health and medicine Sackler colloquium: Evolution and public health.
Evolution and its elements of natural selection, population migration, genetic drift, and founder effects have shaped the world in which we practice public health. Human cultures and technologies have modified life on this planet and have coevolved with myriad other species, including microorganisms; plant and animal sources of food; invertebrate vectors of disease; and intermediate hosts among birds, mammals, and nonhuman primates. Molecular mechanisms of differential resistance or susceptibility to infectious agents or diets have evolved and are being discovered with modern methods. Some of these evolutionary relations require a perspective of tens of thousands of years, whereas other changes are observable in real time. The implications and applications of evolutionary understanding are important to our current programs and policies for infectious disease surveillance, gene-environment interactions, and health disparities globally.


Splicing factor SRSF1 negatively regulates alternative splicing of MDM2 under damage.
Genotoxic stress induces alternative splicing of the oncogene MDM2 generating MDM2-ALT1, an isoform attributed with tumorigenic properties. However, the mechanisms underlying this event remain unclear. Here we explore MDM2 splicing regulation by utilizing a novel minigene that mimics endogenous MDM2 splicing in response to UV and cisplatinum-induced DNA damage. We report that exon 11 is necessary and sufficient for the damage-specific alternative splicing of the MDM2 minigene and that the splicing factor SRSF1 binds exon 11 at evolutionarily conserved sites. Interestingly, mutations disrupting this interaction proved sufficient to abolish the stress-induced alternative splicing of the MDM2 minigene. Furthermore, SRSF1 overexpression promoted exclusion of exon 11, while its siRNA-mediated knockdown prevented the stress-induced alternative splicing of endogenous MDM2. Additionally, we observed elevated SRSF1 levels under stress and in tumors correlating with the expression of MDM2-ALT1. Notably, we demonstrate that MDM2-ALT1 splicing can be blocked by targeting SRSF1 sites on exon 11 using antisense oligonucleotides. These results present conclusive evidence supporting a negative role for SRSF1 in MDM2 alternative splicing. Importantly, we define for the first time, a clear-cut mechanism for the regulation of damage-induced MDM2 splicing and present potential strategies for manipulating MDM2 expression via splicing modulation.


The effects of pre-pregnancy obesity on fetal cardiac functions.
Obesity is a substantial public health problem with a rapidly increasing prevalence in numerous industrialized nations. The objective of this study was to evaluate the effects of maternal pre-pregnancy obesity on fetal cardiac functions. We studied 55 fetuses of obese mothers and 44 fetuses of healthy mothers at 26-38 weeks of gestation. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. The two groups were similar in terms of maternal age, gravidity, parity, gestational age, estimated birth weight, serum lipids, and systolic-diastolic blood pressure. Fetal heart rate, diameters of the aortic and pulmonary valve annulus, aortic and pulmonary peak systolic velocities, ventricular systolic function, and cardiothoracic ratio were similar in the two groups. Pulsed-wave Doppler-derived E/A ratios in the mitral and tricuspid valves were similar in the two groups. The deceleration time of early mitral inflow was prolonged in the fetuses of the obese mothers. In the interventricular septum, left ventricle posterior wall, and right ventricle free wall, the E a and A a were higher, and E a/A a ratios were significantly lower in the study group than in the control group. The E/E a ratio was higher in the obese group than in the control group. The isovolumic relaxation time and the right and left ventricle myocardial performance indices were higher in the fetuses of the obese mothers than in the fetuses of the healthy mothers. We believe that maternal obesity has an important influence on fetal cardiac diastolic functions.


Loss of p27Kip1 from cyclin E/cyclin-dependent kinase (CDK) 2 but not from cyclin D1/CDK4 complexes in cells transformed by polyamine biosynthetic enzymes.
Cancer cells are known to display up-regulation of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), the key enzymes in the biosynthesis of polyamines that are essential for cellular proliferation. We have shown previously that overexpression of ODC or AdoMetDC alone can induce tumorigenic transformation of rodent fibroblasts. Because the subversion of normal cell cycle control is thought to be a crucial event in cancer development, we examined ODC- and AdoMetDC-transformed fibroblasts for alterations in the cell cycle components. The level of cyclin D1 and cyclin D1-dependent kinase and total cyclin-dependent kinase (CDK) 4 activities were elevated in the ODC transformants and particularly in the AdoMetDC transformants. Cyclin E content was not elevated, but a moderate increase in cyclin E-dependent kinase activity was seen in both cells. Total CDK2 activity was increased only in the ODC-transformed cells. The amount of the p27Kip1 CDK inhibitor was greatly decreased in both transformants. Nevertheless, p27Kip1 was present in the active cyclin D1/CDK4 complexes in the cells but absent from the cyclin E/CDK2 complexes. Restoration of p27Kip1 expression in the ODC- and AdoMetDC-transformed cells by transfection resulted in growth inhibition, but not in morphological reversion. An elevation in the level of hyperphosphorylated retinoblastoma protein was observed mainly in the ODC-transformed cells. These results suggest that the expression of ODC or AdoMetDC may affect cell cycle regulation in many ways. However, the largest common effect, which is therefore potentially relevant to some aspects of transformation, appears to be the constitutive down-regulation of p27Kip1 and its loss from the cyclin/CDK2 complexes.


Retraction: Sophocleous, M. (2012). On understanding and predicting groundwater response time. Ground Water, 50: 528–540. doi: 10.1111/j.1745-6584.2011.00876.x.
The above article, published online on October 24, 2011 on Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the author's sponsoring institution, the journal Editor in Chief, Franklin W. Schwartz, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation by the Kansas Geological Survey (a research and service division of the University of Kansas), which identified unattributed areas of overlap with a number of other publications.