Magnetic Graphene-Based Sheets for Bacteria Capture and Destruction Using a High-Frequency Magnetic Field.
Magnetic reduced graphene oxide (MRGO) sheets were prepared by embedding Fe3O4 nanoparticles on polyvinylpyrrolidone (PVP) and poly(diallyldimethylammonium chloride) (PDDA)-modified graphene oxide (GO) sheets for bacteria capture and destruction under a high-frequency magnetic field (HFMF). The characteristics of MRGO sheets were evaluated systematically by transmission electron microscopy (TEM), scanning electron microscopy (SEM), zeta potential measurement, X-ray diffraction (XRD), vibrating sample magnetometry (VSM), and X-ray photoelectron spectroscopy (XPS). TEM observation revealed that magnetic nanoparticles (8-10 nm) were dispersed on MRGO sheets. VSM measurements confirmed the superparamagnetic characteristics of the MRGO sheets. Under HFMF exposure, the temperature of MRGO sheets increased from 25 to 42 °C. Furthermore, we investigated the capability of MRGO sheets to capture and destroy bacteria (Staphylococcus aureus). The results show that MRGO sheets could capture bacteria and kill them through an HFMF, showing a great potential in magnetic separation and antibacterial application.


Impact of the COVID-19 Pandemic on the Provision of Dialysis Service and Mortality in Veterans Receiving Maintenance Hemodialysis in the VA: An Interrupted Time-Series Analysis.
According to the US Renal Data System (USRDS), patients with end-stage kidney disease (ESKD) on maintenance dialysis had higher mortality during early COVID-19 pandemic. Less is known about the effect of the pandemic on the delivery of outpatient maintenance hemodialysis and its impact on death. We examined the effect of pandemic-related disruption on the delivery of dialysis treatment and mortality in patients with ESKD receiving maintenance hemodialysis in the Veterans Health Administration (VHA) facilities, the largest integrated national healthcare system in the USA. Using national VHA electronic health records data, we identified 7,302 Veterans with ESKD who received outpatient maintenance hemodialysis in VHA healthcare facilities during the COVID-19 pandemic (February 1, 2020, to December 31, 2021). We estimated the average change in the number of hemodialysis treatments received and deaths per 1,000 patients per month during the pandemic by conducting interrupted time-series analyses. We used seasonal autoregressive moving average (SARMA) models, in which February 2020 was used as the conditional intercept and months thereafter as conditional slope. The models were adjusted for seasonal variations and trends in rates during the pre-pandemic period (January 1, 2007, to January 31, 2020). The number (95% CI) of hemodialysis treatments received per 1,000 patients per month during the pre-pandemic and pandemic periods were 12,670 (12,525-12,796) and 12,865 (12,729-13,002), respectively. Respective all-cause mortality rates (95% CI) were 17.1 (16.7-17.5) and 19.6 (18.5-20.7) per 1,000 patients per month. Findings from SARMA models demonstrate that there was no reduction in the dialysis treatments delivered during the pandemic (rate ratio: 0.999; 95% CI: 0.998-1.001), but there was a 2.3% (95% CI: 1.5-3.1%) increase in mortality. During the pandemic, the non-COVID hospitalization rate was 146 (95% CI: 143-149) per 1,000 patients per month, which was lower than the pre-pandemic rate of 175 (95% CI: 173-176). In contrast, there was evidence of higher use of telephone encounters during the pandemic (3,023; 95% CI: 2,957-3,089), compared with the pre-pandemic rate (1,282; 95% CI: 1,241-1,324). We found no evidence that there was a disruption in the delivery of outpatient maintenance hemodialysis treatment in VHA facilities during the COVID-19 pandemic and that the modest rise in deaths during the pandemic is unlikely to be due to missed dialysis.


Dutch guidelines for physiotherapy in patients with stress urinary incontinence: an update.
Stress urinary incontinence (SUI) is the most common form of incontinence impacting on quality of life (QOL) and is associated with high financial, social, and emotional costs. The purpose of this study was to provide an update existing Dutch evidence-based clinical practice guidelines (CPGs) for physiotherapy management of patients with stress urinary incontinence (SUI) in order to support physiotherapists in decision making and improving efficacy and uniformity of care. A computerized literature search of relevant databases was performed to search for information regarding etiology, prognosis, and physiotherapy assessment and management in patients with SUI. Where no evidence was available, recommendations were based on consensus. Clinical application of CPGs and feasibility were reviewed. The diagnostic process consists of systematic history taking and physical examination supported by reliable and valid assessment tools to determine physiological potential for recovery. Therapy is related to different problem categories. SUI treatment is generally based on pelvic floor muscle exercises combined with patient education and counseling. An important strategy is to reduce prevalent SUI by reducing influencing risk factors. Scientific evidence supporting assessment and management of SUI is strong. The CPGs reflect the current state of knowledge of effective and tailor-made intervention in SUI patients.


[The Italian Group for the Study of Streptokinase in Myocardial Infarct: Analysis of intrahospital causes of death].
Aim of the present study was to analyse the causes of death of the patients admitted to the G.I.S.S.I. Study. Clinical records of the 1386 in-hospital deaths were centrally analysed by two independent clinicians, who were not aware of the performed treatment and based their classification criteria upon clinical and anatomic data. Death causes were classified as follows: cardiac failure, electromechanical dissociation, cardiac rupture, sudden death and extracardiac deaths. Cardiac failure was the most frequent cause of mortality, as 725 pts out of the 1386 (52%) died from this complication in the whole group. 392 pts were part of the control group (6.7%), while 333 had received SK (5.6%): the difference was significant. No difference was observed between treated patients and control group for what concerns the remaining causes of death. Mortality from cardiac failure was strikingly reduced in a few groups of patients: females (from 11.4 down to 8.7%); age less than 65 years (from 4.1 down to 3.2%); early treated pts (up to 3 hrs): from 6.3 down to 5.2%; anterior location of AMI (9.2 down to 7.4%); first AMI episode (from 5.9 down to 4.7%). Such a reduction was remarkable for patients who remained alive after the 7th day from onset of symptoms: cardiac failure was the cause of death in 65 out of 5385 treated patients, and in 100 out of 5333 control group patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Improving the apo-state detergent stability of NTS1 with CHESS for pharmacological and structural studies.
The largest single class of drug targets is the G protein-coupled receptor (GPCR) family. Modern high-throughput methods for drug discovery require working with pure protein, but this has been a challenge for GPCRs, and thus the success of screening campaigns targeting soluble, catalytic protein domains has not yet been realized for GPCRs. Therefore, most GPCR drug screening has been cell-based, whereas the strategy of choice for drug discovery against soluble proteins is HTS using purified proteins coupled to structure-based drug design. While recent developments are increasing the chances of obtaining GPCR crystal structures, the feasibility of screening directly against purified GPCRs in the unbound state (apo-state) remains low. GPCRs exhibit low stability in detergent micelles, especially in the apo-state, over the time periods required for performing large screens. Recent methods for generating detergent-stable GPCRs, however, offer the potential for researchers to manipulate GPCRs almost like soluble enzymes, opening up new avenues for drug discovery. Here we apply cellular high-throughput encapsulation, solubilization and screening (CHESS) to the neurotensin receptor 1 (NTS1) to generate a variant that is stable in the apo-state when solubilized in detergents. This high stability facilitated the crystal structure determination of this receptor and also allowed us to probe the pharmacology of detergent-solubilized, apo-state NTS1 using robotic ligand binding assays. NTS1 is a target for the development of novel antipsychotics, and thus CHESS-stabilized receptors represent exciting tools for drug discovery.


Cholesterol ester transfer protein, apolipoprotein E and lipoprotein lipase genotypes in patients with coronary artery disease in the Turkish population.
The aim of this study was to compare patients with coronary artery disease (CAD) to healthy objects, in order to explore a possible association between CAD and the variants in the gene encoding cholesterol ester transfer protein (CETP), apolipoprotein E (Apo E) and lipoprotein lipase (LPL). The relationship between CETP MspI, apo E and LPL PvuII gene polymorphisms and serum lipids were investigated in 173 patients with CAD and 111 healthy controls. The frequency of Apo epsilon4 (p < 0.05) and CETP M1 (p < 0.01) alleles were higher in the CAD group than in the control group. In the CAD group, those with the Msp M1 allele had higher levels of total cholesterol (TC) (p = 0026) and low-density lipoprotein cholesterol (LDL-C) than those with the Msp M2 allele. Subjects with an epsilon2 allele had the lowest levels of TC and LDL-C, while subjects with the epsilon4 allele had the highest. In the control group, CETP, the Msp M2 allele was associated with a higher level of high-density lipoprotein cholesterol (HDL-C) (p = 0.012) than the Msp M1 allele. The distributions of LPL genotype and allele did not differ between the CAD and control groups. The present study demonstrates that the CETP Msp1 and Apo E gene polymorphisms are associated with variations in lipids in patients with CAD and healthy controls in Turkish population.


Clinical observation of palatine tonsils with IgA nephropathy.
We have previously reported that clinical remission could be achieved by combination therapy consisting of steroid pulse therapy and tonsillectomy in patients with IgA nephropathy. However, there is no consensus as to the indications for tonsillectomy in IgA nephropathy (IgAN) patients. To clarify whether there is any correlation between characteristics of removed palatine tonsils and clinical remission rate, we evaluated the relationships between the remission rate of urinary abnormalities and characteristics of 186 IgAN patients (aged 11-65 years) with mild or moderate renal pathology and their tonsils. Remission of proteinuria was observed in 134 patients (72%) and remission of hematuria was observed in 111 patients (60%). There was no significant difference in remission rate of either proteinuria or hematuria in terms of the past history of recurrent tonsillitis, episodes of synpharyngitic gross hematuria, pus plugs in the tonsillar lacunae, size of tonsils, age and the results of tonsillar provocation tests. Our findings suggest that it is very difficult to predict the efficacy of tonsillectomy and steroid pulse therapy based on the gross appearance of tonsils, the tonsillar provocation test or clinical episodes of tonsillitis. Moreover, contraindication of tonsillectomy for aged IgAN patients is not always justified.


[Correlation between non-cyclic and pseudocyclic electron transport in pea chloroplasts: dependent on the concentration of ferredoxin].
The effects of ferredoxin concentrations on the correlation between pseudocyclic and non-cyclic electron transport in isolated pea chloroplasts with NADP+ as an electron acceptor was studied. The correlation of psuedocyclic and non-cyclic electron transport upon photoreduction of NADP+ in vitro can be regulated by ferredoxin concentration. At ferredoxin concentrations studied an addition of NADP+ to the system which makes possible electron transfer from ferredoxin to ferredoxin-NADP+-reductase increases the rate of overall electron transport across the chain. Unlike the pseudocyclic electron transport, photoreduction of NADP+ reaches its maximal saturation at relatively low (10-15 microM) concentrations of ferredoxin (Km = approximately 2-5 microM).


Surgical aspects of intestinal tuberculosis in children: our experience.
Tuberculosis (TB) is a major health problem in resource-constrained countries. Intestinal TB is especially notorious as a number of cases have to be dealt surgically, which too have morbidity and mortality. This study was conducted to identify various presentations of intestinal TB necessitating surgical intervention, their management, complications, and outcome in our hospital. This was a retrospective study carried out at the Department of Paediatric Surgery, The Children's Hospital and The Institute of Child Health Lahore, Pakistan, from December 2007 to January 2010. The information about the demography, clinical presentations, investigations, management performed, complications encountered, and outcome of patients with intestinal TB were reviewed. There were a total of 18 patients with intestinal TB who were managed surgically during this period. Five were male and 13 female patients (M : F 1 : 2.6). Mean age of presentation was 8.3 years. Clinical presentations were acute peritonitis in 7 patients, pneumoperitoneum in 5 patients, complete intestinal obstruction in 4 patients, pain in right iliac fossa in 2 patients, and irreducible inguinal hernia in 1 patient. Four patients had concurrent pulmonary TB. Surgical interventions included primary repair of perforation in one, repair of perforation with diversion ileostomy in 8, and merely peritoneal drainage (haemodynamically unstable patients) in 3 patients. The post-operative complications were high output ileostomy in 3, faecal fistula in 1, wound dehiscence in 3, wound infection 5, and prolonged ileus in 1 patient. In three patients stoma was reversed during the same admission. There was one expiry in our study. Acute peritonitis, intestinal obstruction and intestinal perforation are the main clinical presentations requiring surgical interventions. Optimal surgical strategy should be adopted to avoid such pitfalls in the management.


Nonnative SOD1 trimer is toxic to motor neurons in a model of amyotrophic lateral sclerosis.
Since the linking of mutations in the Cu,Zn superoxide dismutase gene (sod1) to amyotrophic lateral sclerosis (ALS) in 1993, researchers have sought the connection between SOD1 and motor neuron death. Disease-linked mutations tend to destabilize the native dimeric structure of SOD1, and plaques containing misfolded and aggregated SOD1 have been found in the motor neurons of patients with ALS. Despite advances in understanding of ALS disease progression and SOD1 folding and stability, cytotoxic species and mechanisms remain unknown, greatly impeding the search for and design of therapeutic interventions. Here, we definitively link cytotoxicity associated with SOD1 aggregation in ALS to a nonnative trimeric SOD1 species. We develop methodology for the incorporation of low-resolution experimental data into simulations toward the structural modeling of metastable, multidomain aggregation intermediates. We apply this methodology to derive the structure of a SOD1 trimer, which we validate in vitro and in hybridized motor neurons. We show that SOD1 mutants designed to promote trimerization increase cell death. Further, we demonstrate that the cytotoxicity of the designed mutants correlates with trimer stability, providing a direct link between the presence of misfolded oligomers and neuron death. Identification of cytotoxic species is the first and critical step in elucidating the molecular etiology of ALS, and the ability to manipulate formation of these species will provide an avenue for the development of future therapeutic strategies.


The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients.
The effect of selenium (Se) in reducing the toxicity of cisplatin in cancer patients was studied. Forty-one patients were randomized into group A (20 patients with Se administration in first cycle of chemotherapy as study cases and without Se in second cycle of chemotherapy as control) and group B (21 patients without Se in first cycle of chemotherapy and with Se in second cycle of chemotherapy). The 4000 micrograms per day of Se as Seleno-Kappacarrageenan were administered from 4 before to 4 d after chemotherapy for study cases. The serum Se increased from 70.4 +/- 22.86 to 157.04 +/- 60.23 ng/mL (P < 0.001) in patients received Se. The cisplatin dosage was iv administration in 60-80 mg/m2 on the first day. The results showed that the peripheral WBC counts on day 14 after initiation of chemotherapy in study cases was significantly higher than the controls (3.35 +/- 2.01 vs 2.31 +/- 1.38 [x10(9)L])/L, p < 0.05). On the other hand, the consumption of GCSF for the cases was significantly less than the controls (110.1 +/- 82.2 vs 723.6 +/- 192.6 IU, p < 0.05). The volumes of blood transfusion for the study group were also significantly less than the controls (0 vs 62 +/- 38 mL, p < 0.05). The nephrotoxicity of cisplatin was measured by urine enzymes (NAG, GGT, AAP, LAP, and ALP) were determined prior to and at 2, 24, 48, and 72 h after initiation of chemotherapy. The urine enzymes NAG, GGT, AAP, and ALP after chemotherapy for cases were significantly lower than the controls. No toxicity of Seleno-Kappacarrageenan was noted. The above results suggest that the Se can be used as an agent for reducing the nephrotoxicity and bone marrow suppression induced by cisplatin.


Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden.
Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42-7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called 'Carter effect' could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared environmental component was estimated to be 0.01 (0.00-0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported.


What do binge drinkers drink? Implications for alcohol control policy.
Although binge drinking (drinking five or more drinks on an occasion) is an important public health problem, little is known about which beverage types are consumed by binge drinkers. This knowledge could guide prevention efforts because beer, wine, and liquor are taxed, marketed, and distributed differently. Data from 14,150 adult binge drinkers who responded to the Behavioral Risk Factor Surveillance System binge-drinking module in 2003 and 2004 were analyzed. Information pertained to the amount of alcohol consumed during a binge drinker's most recent binge episode, including beverage-specific consumption. Overall, 74.4% of binge drinkers consumed beer exclusively or predominantly, and those who consumed at least some beer accounted for 80.5% of all binge alcohol consumption. By beverage type, beer accounted for 67.1%, liquor for 21.9%, and wine accounted for 10.9% of binge drinks consumed. Beer also accounted for most of the alcohol consumed by those at highest risk of causing or incurring alcohol-related harm, including people aged 18-20 years (67.0% of drinks were beer); those with three or more binge episodes per month (70.7%); those drinking eight or more drinks per binge episode (69.9%); those binging in public places (64.4%); and those who drove during or within 2 hours of binge drinking (67.1%). Beer accounted for two thirds of all alcohol consumed by binge drinkers and accounted for most alcohol consumed by those at greatest risk of causing or incurring alcohol-related harm. Lower excise taxes and relatively permissive sales and marketing practices for beer as compared with other beverage types may account for some of these findings. These findings suggest that equalizing alcohol control policies at more stringent levels would be an effective way to prevent excessive drinking.


[Clinical characteristics and prognosis of breast cancer patients with vascular invasion].
To analyze the clinicopathological features, parameters of molecular biology, survival rate, and prognostic factors in breast cancer patients with vascular invasion. The data of 262 breast cancer patients with vascular invasion surgically treated between January 1995 and December 2003 in our institution were retrospectively analyzed. Clinicopathological characteristics, parameters of molecular biology, disease free survival rate and overall survival rate were surveyed. Of all breast cancer patients registered in our institution during the same period, these 262 breast cancer patients with vascular invasion accounted for 5.3% with a median age of 43 years. The major pathological type was invasive ductal carcinoma (93.3%). The stages included stage I in 5% , stage II 31. 3% , stage III 58.8% , stage IV 1.1% , and unknown 3.8%. Immunohistochemical staining showed that ER positive in 67.7%, PR(+) 68.0%, p53(+) 54.2%, PCNA(+) 93.3%, c-erbB2( +++) 20.8% and c-erbB2(++) 16.9%. The 5-year and 10-year cumulative disease free survival and overall survival were 57.6% , 50.7% and 62.8%, 52.9% , respectively. The factors which were found to compromise disease free survival were the tumor size, lymph node status, stage, and radiotherapy in the univariate analysis, and for overall survival, were the tumor size, lymph node status, stage, location of vascular invasion and radiotherapy. The tumor size and radiotherapy were found to be independent prognostic factors for disease free survival and overall survival in the multivariate analysis. Breast cancers with vascular invasion have poor biological behavior though having been treated by surgery, radiotherapy and chemotherapy. The independent prognostic factors of such patients are tumor size and radiotherapy. Anti-angiogenesis and antilymphangiogenesis may gradually become promising target treatment for such patient.


Retrospective characterization of a vaccine-derived poliovirus type 1 isolate from sewage in Greece.
Retrospective molecular and phenotypic characterization of a vaccine-derived poliovirus (VDPV) type 1 isolate (7/b/97) isolated from sewage in Athens, Greece, in 1997 is reported. VP1 sequencing of this isolate revealed 1.87% divergence from the VP1 region of reference strain Sabin 1, while further genomic characterization of isolate 7/b/97 revealed a recombination event in the nonstructural part of the genome between a vaccine strain and a nonvaccine strain probably belonging to Enterovirus species C. Amino acid substitutions commonly found in previous studies were identified in the capsid coding region of the isolate, while most of the attenuation and temperature sensitivity determinants were reverted. The ultimate source of isolate 7/b/97 is unknown. The recovery of such a highly divergent derivative of a vaccine strain emphasizes the need for urgent implementation of environmental surveillance as a supportive procedure in the polio surveillance system even in countries with high rates of OPV coverage in order to prevent cases or even outbreaks of poliomyelitis that otherwise would be inevitable.


Influence of lime juice on the severity of sickle cell anemia.
The pain in sickle cell anemia (SCA) is often triggered by dehydration, acidosis, and fever that are usually due to malaria. Intake of lime juice was recently demonstrated to facilitate clearance of the malaria parasite. It was therefore sought to determine whether regular intake of lime juice will ameliorate crisis, especially recurrent bone pain. In this preliminary, open-labeled, randomized study, the effects of lime juice on the clinical and some laboratory characteristics of children with SCA were tested. Among the 113 children with SCA studied in two hospitals, the 58 receiving lime treatment had lower rates of significant painful episodes than the 55 without lime (37 versus 83 crises in 6 months, and 0.64±0.11 versus 1.51±0.34 average rates per child, p<0.001). Also, fewer subjects than the controls had significant painful episodes (50.0% versus 92.7%); febrile illness (46.6% versus 87.3%) and admission rate (3.4% versus 34.5%) (p<0.001). The mean hematocrit of the subjects (26.23±2.03%) at the end of the study was also higher, p<0.001. However, transfusion rate, presence of hepatomegaly, splenomegaly, and jaundice was similar. Treatment with lime did not cause any significant side-effect. Regular intake of lime juice may be of great therapeutic and nutritional relevance in children with SCA.


Lytic viral replication as a contributor to the detection of Epstein-Barr virus in breast cancer.
Epstein-Barr virus (EBV) has an accepted association with the epithelial malignancy nasopharyngeal carcinoma and has also been reported in other more controversial carcinoma settings. Evaluation of EBV association with epithelial carcinomas such as breast cancer would benefit from a better understanding of the outcome of EBV infection of these cells. Cell-free preparations of a green fluorescent protein-expressing virus, BX1, were used to infect breast cancer cell lines, which were then examined for EBV gene expression and viral genome copy number. Reverse transcription-PCR analyses revealed that the cells supported a mixture of latency II and lytic EBV gene expression. Lytic Zta and BMRF1 protein expression was detected by immunohistochemistry, and DNA PCR analyses estimated an EBV copy number of 300 to 600 genomes per infected cell. Evidence for lytic EBV expression was also found in breast tissue, where reverse transcription-PCR analyses detected lytic Zta transcripts in 7 of 10 breast carcinoma tissues and 4 of 10 normal tissues from the same patients. Scattered cells immunoreactive for Zta protein were also detectable in breast carcinoma. Quantitative real-time PCR analysis of EBV-positive breast carcinoma tissues suggested that less than 0.1% of the cells contained viral genomes. We suggest that sporadic lytic EBV infection may contribute to PCR-based detection of EBV in traditionally nonvirally associated epithelial malignancies.


Sleep: An Open-Source Python Software for Visualization, Analysis, and Staging of Sleep Data.
We introduce Sleep, a new Python open-source graphical user interface (GUI) dedicated to visualization, scoring and analyses of sleep data. Among its most prominent features are: (1) Dynamic display of polysomnographic data, spectrogram, hypnogram and topographic maps with several customizable parameters, (2) Implementation of several automatic detection of sleep features such as spindles, K-complexes, slow waves, and rapid eye movements (REM), (3) Implementation of practical signal processing tools such as re-referencing or filtering, and (4) Display of main descriptive statistics including publication-ready tables and figures. The software package supports loading and reading raw EEG data from standard file formats such as European Data Format, in addition to a range of commercial data formats. Most importantly, Sleep is built on top of the VisPy library, which provides GPU-based fast and high-level visualization. As a result, it is capable of efficiently handling and displaying large sleep datasets. Sleep is freely available (http://visbrain.org/sleep) and comes with sample datasets and an extensive documentation. Novel functionalities will continue to be added and open-science community efforts are expected to enhance the capacities of this module.


Inactivation of 6-phosphofructo-2-kinase during anaerobiosis in the marine whelk Busycon canaliculatum.
6-Phosphofructo-2-kinase (PFK-2) was analyzed in four organs of the anoxia-tolerant marine gastropod mollusk Busycon canaliculatum. Whelk PFK-2 resembled the nonhepatic enzyme from mammals with highest activity occurring in gill (22 pmol.min-1.g-1). Hepatopancreas PFK-2 was purified over 8,000-fold to a final specific activity of 11 mU/mg protein (at 20 degrees C) and gave a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was a dimer with a native molecular mass of 142 kDa and a subunit molecular mass of 67 kDa. The purified enzyme showed negligible fructose-2,6-bisphosphatase (FBPase-2) activity, although the activity ratio of PFK-2 to FBPase-2 was 0.625 in crude extracts. In response to environmental anoxia, the activity of PFK-2 dropped in all organs to 34-56% of the corresponding aerobic value (half-time was 2 h in gill), and the Michaelis constant for fructose 6-phosphate increased by 50% (to 92 microM in gill). These changes paralleled decreases in organ fructose 2,6-bisphosphate concentration and pyruvate kinase activity and contribute to the overall glycolytic rate depression induced by anoxia in this facultative anaerobe. In vitro treatment of the anoxic form of hepatopancreas PFK-2 with alkaline phosphatase increased enzyme activity, suggesting that the aerobic and anoxic enzyme forms are interconverted by reversible protein phosphorylation. However, the protein kinase involved in this process is not yet known; incubation of aerobic PFK-2 with Mg-ATP plus adenosine 3',5'-cyclic monophosphate-dependent protein kinase or protein kinase C did not alter enzyme activity.


The metallothionein gene, TaMT3, from Tamarix androssowii confers Cd2+ tolerance in tobacco.
Cadmium (Cd) is a nonessential microelement and low concentration Cd2+ has strong toxicity to plant growth. Plant metallothioneins, a class of low molecular, cystein(Cys)-rich and heavy-metal binding proteins, play an important role in both metal chaperoning and scavenging of reactive oxygen species (ROS) with their large number of cysteine residues and therefore, protect plants from oxidative damage. In this study, a metallothionein gene, TaMT3, isolated from Tamarix androssowii was transformed into tobacco (Nicotiana tobacum) through Agrobacterium-mediated leaf disc method, and correctly expressed under the control of 35S promoter. Under Cd2+ stress, the transgenic tobacco showed significant increases of superoxide dismutase (SOD) activity and chlorophyll concentration, but decreases of peroxidase (POD) activity and malondialdehyde (MDA) accumulation when compared to the non-transgenic tobacco. Vigorous growth of transgenic tobacco was observed at the early development stages, resulting in plant height and fresh weight were significantly larger than those of the non-transgenic tobacco under Cd2+ stress. These results demonstrated that the expression of the exogenous TaMT3 gene increased the ability of ROS cleaning-up, indicating a stronger tolerance to Cd2+ stress.


Distribution of native legumes (Leguminoseae) in frequently burned longleaf pine (Pinaceae)-wiregrass (Poaceae) ecosystems.
Legume species distribution and abundance and selected environmental variables were quantified across a complex gradient (varying in both water-holding capacity and fertility) for frequently burned longleaf pine (Pinus palustris)-wiregrass (Aristida stricta) ecosystems. Legumes were present in all months; however, abundance peaked in June and was minimal after killing frosts in October. Legume species were prominent in the flora (43 species encountered) ubiquitous (94% of 2-m(2) subplots had at least one legume species), and abundant (nearly 120 000 stems/ha). Although most species were widely distributed throughout the gradient, Lespedeza angustifolia was distinctly associated with the more hydric end of the gradient, while both Petalostemon pinnatum and Galactia microphylla were located in the more xeric extreme. The percentage variation in species that could be accounted for by environmental variation was low (27%). Of the variation that could be accounted for, a number of environmental variables were important, including soil moisture, pine basal area (i.e., light), and bivalent base cations (e.g., Ca(2+)). Although gradients in resource availability among sites did not affect the distribution of species or abundance of legumes strongly, variation in resources are likely to regulate N(2)-fixation rates of the various native legume species, and thereby affect ecological functions such as maintenance of N capital and productivity.


Problems of in vitro SPF measurements brought about by viscous fingering generated during sunscreen applications.
Up to date, no worldwide standard in vitro method has been established for the determination of the sun protection factor (SPF), since there are many problems in terms of its repeatability and reliability. Here, we have studied the problems on the in vitro SPF measurements brought about by the phenomenon called viscous fingering. A spatially periodic stripe pattern is usually formed spontaneously when a viscous fluid is applied onto a solid substrate. For the in vitro SPF measurements, the recommended amount of sunscreen is applied onto a substrate, and the intensity of the transmitted UV light through the sunscreen layer is evaluated. Our theoretical analysis indicated that the nonuniformity of the thickness of the sunscreen layer varied the net UV absorbance. Pseudo-sunscreen composites having no phase separation structures were prepared and applied on a quartz plate for the measurements of the UV absorbance. Two types of applicators, a block applicator and a 4-sided applicator were used. The flat surface was always obtained when the 4-sided applicator was used, while the spatially periodic stripe pattern was always generated spontaneously when the block applicator was used. The net UV absorbance of the layer on which the stripe pattern was formed was found to be lower than that of the flat layer having the same average thickness. Theoretical simulations quantitatively reproduced the variation of the net UV absorbance led by the change of the geometry of the layer. The results of this study propose the definite necessity of strict regulations on the coating method of sunscreens for the establishment of the in vitro SPF test method.


Airway reactivity in the periphery of the lung in mongrel dogs. Male and female differences.
The present study was designed to compare acute responses of the lung periphery to locally administered histamine in male and female dogs. A fiberoptic bronchoscope was wedged in peripheral airways of anesthetized dogs. Increasing doses of histamine were directed through the bronchoscope. Measurements of collateral resistance (Rcoll) were used to monitor responses to histamine and lung inflation. Baseline measurements of Rcoll were similar for both sexes. The males responded to histamine with greater increases in Rcoll than the females did. After doses of histamine (1.5 x 10(-6) mg for males and 1.5 x 10(-4) mg for females), which produced similar increases in Rcoll, the effects of lung inflation and the time course of the responses were similar for the two sexes. We conclude that male dogs exhibit greater reactivity to histamine than female dogs do. If these results apply to humans, it is possible that increased reactivity in the lung periphery contributes to the development of chronic obstructive pulmonary disease in males.


A comparative study of Desktop, Fishtank, and Cave systems for the exploration of volume rendered confocal data sets.
We present a participant study that compares biological exploration tasks using volume renderings of laser confocal microscopy data across three environments which vary in level of immersion. For the tasks, data, and visualization approach used in our study, we found that subjects qualitatively preferred and quantitatively performed better in environments with greater levels of immersion. Subjects performed real-world biological data analysis tasks that emphasized understanding spatial relationships including characterizing the general features in a volume, identifying co-located features, and reporting geometric relationships such as whether clusters of cells were coplanar. After analyzing data in each environment, subjects were asked to choose which environment they wanted to analyze additional data sets in--subjects uniformly selected the Cave environment.


Reperfused myocardial infarction in mice: 3D mapping of late gadolinium enhancement and strain.
We developed mathematical modeling tools for mapping 3D infarct geometry from multislice late gadolinium enhancement data, allowing fusion with multislice MR tagging data, in mice with myocardial infarction. Five C57BL/6 mice were imaged at baseline, 1, 7 and 28 days after 60 min occlusion of the left anterior descending coronary artery. The 3D infarct geometry was mapped in material coordinates, and registered with 3D strain, showing permanent dysfunction in infarcted segments, intermediate function in the adjacent zone, and maintained function in the remote zone. 3D mapping of late enhancement and strain allows registration of multiple studies in a consistent framework.


The effects of the pre-treatment of intravenous nimodipine on Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, lipid peroxidation and early ultrastructural findings following middle cerebral artery occlusion in the rat.
Excessive calcium influx has been implicated in the pathophysiology of ischemic cerebral damage. The effects of nimodipine, a calcium antagonist, on the Na(+)-K+/MG+2 ATPase activity, Ca+2/Mg+2 ATPase, lipid peroxidation, and early ultrastructural findings were examined at the acute stage of ischemia in the rat brain. Ischemia was produced by permanent unilateral occlusion of the middle cerebral artery. In Group I, the rats which had no ischemia and not received medication were used for determining Na(+)-K+/Mg+2 ATPase, Ca+2/Mg+2 ATPase, the extent of lipid peroxidation by measuring the malondialdehyde content and normal ultrastructural findings. In Group II, the rats which had only subtemporal craniectomy without occlusion and received saline solution were used for determining the effect of the surgical procedure on the biochemical indices and ultrastructural findings. In Group III, the rats received saline solution following the occlusion in the same amount of nimodipine and in the same duration as used in Group IV. In Group IV, nimodipine pre-treatment 15 min before occlusion (microgram kg-1 min-1 over a 10 min period) was applied i.v. Na(+)-K+/Mg+2 ATPase and Ca+2/Mg+2 ATPase activities decreased significantly and promptly as early as 10 min and remained at a lower level than the contralateral hemisphere in the same group and at the normal level in Group I. Nimodipine pre-treatment immediately attenuated the inactivation of Na(+)-K+/Mg+2 ATPase (p < 0.05) but there was no change on Ca+2/Mg+2 ATPase activity (p < 0.05). Malondialdehyde content increased significantly in Group III following ischemia as early as 30 min. Nimodipine pre-treatment decreased the malondialdehyde level in Group IV (p < 0.05). This study supports the possibility that nimodipine pre-treatment effects the membrane stabilizing properties via inhibiting the lipid peroxidation and subsequently restoring some membrane bound and lipid dependent enzymes' activity such as Na(+)-K+/Mg+2 ATPase and the ultrastructural findings.


Encouraging Reflexivity in a Residency Leadership Development Program: Expanding Outside the Competency Approach.
While leadership development is increasingly a goal of academic medicine, it is typically framed as competency acquisition, which can limit its focus to a circumscribed set of social behaviors. This orientation may also reinforce the cultural characteristics of academic medicine that can make effective leadership difficult, rather than training leaders capable of examining and changing this culture. Expanding leadership development so it promotes social reflexivity presents a way to bolster some of the weaknesses of the competency paradigm. In 2013-2016, the University of Penn sylvania's Department of Anesthesiology and Critical Care (DACC) carried out a leadership development program for residents, which included seminars focused on developing particular leadership skills and annual capstone sessions facilitating discussion between residents and attending physicians about topics chosen by residents. The capstone sessions proved to be most impactful, serving as forums for open conversation about how these groups interact when engaged in social behaviors such as giving/receiving feedback, offering support after an adverse event, and teaching/learning in the clinic. The success of the capstone sessions led to a 2016 DACC-wide initiative to facilitate transparency among all professional roles (faculty, residents, nurse anesthetists, administrative staff) and encourage widespread reflexive examination about how the manner in which these groups interact encourages or impedes leadership and teamwork. Further work is necessary to describe how leadership program formats can be diversified to better encourage reflexivity. There is also a need to develop mechanisms for assessing outcomes of leadership programs that expand outside the competency-based system.


Volatiles for mycological quality grading of barley grains: determinations using gas chromatography-mass spectrometry and electronic nose.
The possibility of using an electronic nose or gas chromatography combined with mass spectrometry (GC-MS) to quantify ergosterol and colony forming units (CFU) of naturally contaminated barley samples was investigated. Each sample was split into three parts for (i) ergosterol and CFU analysis, (ii) measurements with the electronic nose and (iii) identification of volatiles collected on an adsorbent with a GC-MS system. Forty samples were selected after sensory analysis to obtain 10 samples with normal odour and 30 with some degree of off-odour. The data set of volatile compounds and the data collected from the electronic nose were evaluated by multivariate analyse techniques. SIMCA classification (soft independent modelling of class analogy) was used for objective evaluation of the usefulness of the data from the GC-MS or electronic nose measurements for classification of grain samples as normal or with off-odour. The main volatile compounds of grain with normal odour were 2-hexenal, benzaldehyde and nonanal, while 3-octanone, methylheptanone and trimethylbenzene were the main volatile compounds of grain with off-odours. Using data from the electronic nose three samples of 40 were misclassified, while data analysis of the volatile compounds detected with the GC-MS, led to six misclassified samples. Regression models (partial least-squares, PLS) were built to predict ergosterol- and CFU-levels with data from the GC-MS or electronic nose measurements. PLS models based on both GC-MS and electronic nose data could be used to predict the ergosterol levels with high accuracy and with low root mean square error of prediction (RMSEP). CFU values from naturally infected grain could not be predicted with the same degree of confidence.


You spin me round: MaFBx/Atrogin-1 feeds forward on FOXO transcription factors (like a record).
Poly-ubiquitin chains are post-translational modifications commonly used by the ubiquitin-proteasome system to mark proteins for degradation. The regulation of protein degradation plays an important role in regulating muscle cell size, a cellular process balanced by protein synthesis and catabolism. MaFBx/Atrogin-1, a muscle specific F-box protein, is a principle component of the SCF(atrogin-1) ubiquitin ligase complex that ubiquitinates and targets calcineurin for degradation, a key regulatory protein involved in pathologic hypertrophy. We have recently described a novel role for this ubiquitin ligase as a co-activator of the FOXO transcription factors through the catalysis of non-canonical poly-ubiquitin chain formation on FOXO proteins, an event that is sufficient to block Akt-dependent pathways involved in physiologic hypertrophy. In context with other reports describing the regulation and role of FOXO transcription factors, we present a working model for the role of atrogin-1 in both physiologic and pathologic hypertrophy.


Recent progress in nanotechnology for stem cell differentiation, labeling, tracking and therapy.
Stem cells offer great potential for regenerative medicine due to their excellent capability to differentiate into a specialized cell type of the human body. Recently, nanomaterial based scaffolds (e.g. graphene), biodegradable polymers (e.g. PLGA: poly-d,l-lactic-co-glycolic acid), and inorganic nanoparticles (NPs, e.g. metallic, magnetic, upconversion) have made considerable advances in controlling the differentiation of stem cells. Some of the notable advances include the development of a variety of NPs such as gold, silica, selenium and graphene quantum dots (QDs) for the controlled differentiation of stem cells - human mesenchymal stem cells (hMSCs), and magnetic core-shell NPs (e.g. ZnFe2O4-Au) for the control of neural stem cells (NSCs). Multimodal imaging (MR, optical, ultrasound, photoacoustic) of stem cells provides opportunities for probing the fate of implanted cells, thereby determining the therapeutic efficacy. Novel multifunctional NPs have been developed over the years, and probed using the aforementioned imaging techniques for stem cell research. This review article underscores the recent progress in nanotechnology for stem cell differentiation, labeling, tracking and therapy. Nano/biomaterial assisted stem cell therapies for bone, heart, and liver regeneration are also delineated.


Girdlestone resection arthroplasty following failed surgical procedures.
We retrospectively reviewed 43 patients who had undergone Girdlestone resection arthroplasty of the hip after failed total hip replacement or failed operations for hip trauma between 1990 and 2002. The indications were peri-prosthetic infection, aseptic loosening, recurrent dislocation and failed internal fixation for femoral neck fractures. Twenty-five patients died with an overall mortality of 58%. Out of 18 survivors, four patients had a prosthesis re-implanted and were excluded from the study. In 14 surviving patients followed-up for a mean of 44.5 months, the average age was 76 years. Adequate pain relief was achieved in 12 patients and infection was controlled in all. They all needed walking aids. The overall patient satisfaction was 10/14. We observed that patients who had had resection arthroplasty following failed operations for hip trauma had a higher mortality than those for failed total hip arthroplasty. Girdlestone arthroplasty is still a viable option to salvage irretrievably failed hips presenting technical difficulties in medically compromised patients. Limb shortening and the inevitable need for a walking aid should be clearly explained to patients during the consenting process in order to avoid unrealistic expectations.


A content analysis of oral health messages in Australian mass media.
Social analysis regarding oral health and oral health promotion are almost non-existent in the Australian context. The usefulness of such exploration lies in framing and informing research methodologies and health promotion initiatives, and can improve our understanding of oral health behaviours and their social contexts. We conducted a systematic content analysis of a random sample of popular Australian magazines, newspapers and television shows from May to September 2012. Our sample included the top three best-selling magazines, six weekly newspapers, one from each available Australian state, and the four highest ranked Australian prime time television shows and their associated commercials. Data comprised 72 hours of prime time television and 14,628 pages of hardcopy media. Seventy-one oral health related media 'incidents' were counted during a five-month period. Only 1.5% of incidents referenced fluoride and only two made dietary references. Women were represented almost six times more than men and the majority of oral health related incidents conveyed no social context (63%). Oral health messages conveyed in Australian media fail to provide a social context for preventive or health-promoting behaviours. In light of increased levels of oral disease and retention of natural teeth, more community based oral health promotion and support for oral health literacy would be prudent in the Australian context.


MRI volumetric analysis of breast fibroglandular tissue to assess risk of the spared nipple in BRCA1 and BRCA2 mutation carriers.
Prophylactic nipple-areolar complex (NAC)-sparing mastectomy (NSM) in BRCA1/2 mutation carriers is controversial over concern regarding residual fibroglandular tissue (FGT) with malignant potential. The objective of this study was to model the volume of FGT in the NAC at a standard retroareolar margin (5 mm) and examine the change in this amount with a greater retroareolar margin or areola-sparing technique. A segmentation protocol was applied to breast MRIs from 105 BRCA1/2 patients to quantify volumes of FGT for total breast and NAC. The proportion of FGT in the NAC relative to the breast was calculated as the primary outcome and was compared for 5 mm versus 10 mm retroareolar depths. The proportion of FGT in the areola was compared with the NAC. At 5 mm retroareolar thickness, residual NAC FGT comprised 1.3 % of the total breast FGT. This amount was not significantly greater than the proportion in the areola (p = 0.3, d = 0.1). Increasing the retroareolar thickness to 10 mm led to a statistically and possibly clinically significant increase in the amount of NAC FGT (p < 0.001, d = 1.1). The proportion of FGT remaining in the spared NAC with a 5 mm margin is extremely small, suggesting that leaving the entire NAC would create very little added risk. Doubling the retroareolar margin may translate into a clinically meaningful increase. Overall, our findings support the safety of the current trend toward increased rates of prophylactic NSM performed in this high-risk population.


Epidemiology and genetic epidemiology of the liver function test proteins.
The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI). To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins--including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP)--using the classical twin model. Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach. Our results show that (1) variation in all the LFTs has a significant heritable basis (h(2) ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c(2) ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use. Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.


Development of mucoadhesive buccal films from rice for pharmaceutical delivery systems.
The aim of this work was to investigate the suitable rice varieties for developing pharmaceutical buccal films. Two rice varieties with extreme difference in amylose content were used. Rice powders were chemically modified to yield the carboxymethyl rice prior to film preparation. Scanning electron microscope (SEM) and X-ray diffractometer (XRD) were used to investigate the solid structure of rice powders. The results indicated that amylose content in the rice grains played the effects on the morphology and crystalline structure of the modified rice powders as well as the film properties. The modified rice powders of low amylose content showed halo pattern XRD whereas some crystalline peaks could be observed from the high amylose content modified rice powders. Adding of glycerin caused the films better properties of more transparency and getting rid of air bubbles. High amylose rice films showed more transparency and higher mucoadhesive property and was considered to be suitable for incorporating the drug. Adding of surfactant caused the increase in tensile strength and decrease in elongation of the rice films. The most suitable surfactant for diclofenac buccal rice film is Tween 20. This study demonstrates that rice grains are the promising natural source for pharmaceutical film forming agent. Suitable pharmaceutical buccal films could be developed from the rice with high amylose content.


Preparation, Physicochemical Characterization and Oxidative Stability of Omega-3 Fish Oil/α-Tocopherol-co-Loaded Nanostructured Lipidic Carriers.
Purpose: This study aimed to improve the pharmacokinetic behavior of polyunsaturated fatty acids (PUFAs) oxidation to enhance oxidative stability for inhibiting formation of toxic hydroperoxides, develops off-flavors and shortens shelf-life. Methods: Nanostructured lipid carrier (NLC) co-encapsulating omega-3 fish oil and α-tocopherol was successfully prepared by melt blending and hot sonication method to enhance the oxidative stability of the fish oil. Encapsulation efficiency (EE) and in vitro release, the oxidative stability of prepared nanoparticles (NPs) were measured using detection of peroxide value (PV) and thiobarbituric acid (TBA) during 40 days. Results: Electron microscopy and particle size analysis showed dispersed and homogenous NPs with an average diameter of 119 nm. Sustained oil release at a physiologic pH, and longterm stability in terms of the size, zeta, and dispersity of NPs was achieved after 75 days of storage. The omega-3 fish oil co-encapsulated with α-tocopherol in the NLC possessed better oxidative stability compared with the all other formulations. Also, it was found that the NLC as an encapsulation method was more successful to inhibit the formation of the primary oxidation products than the secondary oxidation products. Conclusion: Generally, these findings indicated that co-encapsulation of fish oil and α-tocopherol within the NLC can be a suitable delivery system in order to enrich foodstuffs, in particular clear beverages.


Cisplatin-resistant cells in malignant pleural mesothelioma cell lines show ALDH(high)CD44(+) phenotype and sphere-forming capacity.
Conventional chemotherapy in malignant pleural mesothelioma (MPM) has minimal impact on patient survival due to the supposed chemoresistance of cancer stem cells (CSCs). We sought to identify a sub-population of chemoresistant cells by using putative CSC markers, aldehyde dehydrogenase (ALDH) and CD44 in three MPM cell lines; H28, H2052 and Meso4. The Aldefluor assay was used to measure ALDH activity and sort ALDH(high) and ALDH(low) cells. Drug-resistance was evaluated by cell viability, anchorage-independent sphere formation, flow-cytometry and qRT-PCR analyses. The ALDH(high) - and ALDH(low) -sorted fractions were able to demonstrate phenotypic heterogeneity and generate spheres, the latter being less efficient, and both showed an association with CD44. Cis- diamminedichloroplatinum (II) (cisplatin) treatment failed to reduce ALDH activity and conferred only a short-term inhibition of sphere generation in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Induction of drug sensitivity by an ALDH inhibitor, diethylaminobenzaldehyde (DEAB) resulted in significant reductions in cell viability but not a complete elimination of the sphere-forming cells, suggestive of the presence of a drug-resistant subpopulation. At the transcript level, the cisplatin + DEAB-resistant cells showed upregulated mRNA expression levels for ALDH1A2, ALDH1A3 isozymes and CD44 indicating the involvement of these markers in conferring chemoresistance in both ALDH(high) and ALDH(low) fractions of the three MPM cell lines. Our study shows that ALDH(high) CD44(+) cells are implicated in conveying tolerance to cisplatin in the three MPM cell lines. The combined use of CD44 and ALDH widens the window for identification and targeting of a drug-resistant population which may improve the current treatment modalities in mesothelioma.


Mutant analysis of the Shal (Kv4) voltage-gated fast transient K+ channel in Caenorhabditis elegans.
Shal (Kv4) alpha-subunits are the most conserved among the family of voltage-gated potassium channels. Previous work has shown that the Shal potassium channel subfamily underlies the predominant fast transient outward current in Drosophila neurons (Tsunoda, S., and Salkoff, L. (1995) J. Neurosci. 15, 1741-1754) and the fast transient outward current in mouse heart muscle (Guo, W., Jung, W. E., Marionneau, C., Aimond, F., Xu, H., Yamada, K. A., Schwarz, T. L., Demolombe, S., and Nerbonne, J. M. (2005) Circ. Res. 97, 1342-1350). We show that Shal channels also play a role as the predominant transient outward current in Caenorhabditis elegans muscle. Green fluorescent protein promoter experiments also revealed SHL-1 expression in a subset of neurons as well as in C. elegans body wall muscle and in male-specific diagonal muscles. The shl-1 (ok1168) null mutant removed all fast transient outward current from muscle cells. SHL-1 currents strongly resembled Shal currents in other species except that they were active in a more depolarized voltage range. We also determined that the remaining delayed-rectifier current in cultured myocytes was carried by the Shaker ortholog SHK-1. In shl-1 (ok1168) mutants there was a significant compensatory increase in the SHK-1 current. Male shl-1 (ok1168) animals exhibited reduced mating efficiency resulting from an apparent difficulty in locating the hermaphrodite vulva. SHL-1 channels are apparently important in fine-tuning complex behaviors, such as mating, that play a crucial role in the survival and propagation of the species.


Comparative safety of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma: a systematic review and network meta-analysis.
Objective: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) approved for use as monotherapy or combination therapy for the first-line treatment of adult patients with metastatic clear cell renal cell carcinoma (RCC). Methods: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvatinib + pembrolizumab, axitinib + avelumab, and axitinib + pembrolizumab in previously untreated adult patients with metastatic clear cell RCC. Eligible studies were identified by two reviewers in MEDLINE (via PubMed), EMBASE, and Cochrane Library. The risk of bias for RCTs was assessed using the Cochrane Collaboration tool. The P score was used to determine the treatment ranking. The mean probability of an event along with the relative measures of the NMA was considered with the treatment rankings. Results: A total of 13 RCTs were included in the systematic review and NMA. Sorafenib and tivozanib used as monotherapy were the best treatment options. Sorafenib achieved the highest P score for treatment discontinuation due to adverse events (AEs), fatigue, nausea, vomiting of any grade, and hypertension of any grade or grade ≥3. Tivozanib achieved the highest P score for AEs, grade ≥3 AEs, dose modifications due to AEs, and grade ≥3 diarrhea. Sunitinib was the best treatment option in terms of diarrhea and dysphonia of any grade, while cabozantinib, pazopanib, and axitinib + pembrolizumab-in terms of grade ≥3 fatigue, nausea, and vomiting. TKIs used in combination were shown to have a poorer safety profile than those used as monotherapy. Lenvatinib + pembrolizumab was considered the worst option in terms of any AEs, grade ≥3 AEs, treatment discontinuation due to AEs, dose modifications due to AEs, fatigue of any grade, nausea, vomiting, and grade ≥3 nausea. Axitinib + avelumab was the worst treatment option in terms of dysphonia, grade ≥3 diarrhea, and hypertension, while cabozantinib + nivolumab was the worst option in terms of grade ≥3 vomiting. Interestingly, among the other safety endpoints, cabozantinib monotherapy had the lowest P score for diarrhea and hypertension of any grade. Conclusion: The general safety profile, including common AEs, is better when TKIs are used as monotherapy vs. in combination with immunological agents. To confirm these findings, further research is needed, including large RCTs.


Simultaneous Identification of Potential Pathogenicity Factors of Mycoplasma agalactiae in the Natural Ovine Host by Negative Selection.
Mycoplasmas possess complex pathogenicity determinants that are largely unknown at the molecular level. Mycoplasma agalactiae serves as a useful model to study the molecular basis of mycoplasma pathogenicity. The generation and in vivo screening of a transposon mutant library of M. agalactiae were employed to unravel its host colonization factors. Tn4001mod mutants were sequenced using a novel sequencing method, and functionally heterogeneous pools containing 15 to 19 selected mutants were screened simultaneously through two successive cycles of sheep intramammary infections. A PCR-based negative selection method was employed to identify mutants that failed to colonize the udders and draining lymph nodes in the animals. A total of 14 different mutants found to be absent from ≥ 95% of samples were identified and subsequently verified via a second round of stringent confirmatory screening where 100% absence was considered attenuation. Using this criterion, seven mutants with insertions in genes MAG1050, MAG2540, MAG3390, uhpT, eutD, adhT, and MAG4460 were not recovered from any of the infected animals. Among the attenuated mutants, many contain disruptions in hypothetical genes, implying their previously unknown role in M. agalactiae pathogenicity. These data indicate the putative role of functionally different genes, including hypothetical ones, in the pathogenesis of M. agalactiae. Defining the precise functions of the identified genes is anticipated to increase our understanding of M. agalactiae infections and to develop successful intervention strategies against it.


A very rare case of polysplenia syndrome with congenital diffuse pulmonary arteriovenous fistulas.
A five-year-old girl patient was admitted with cyanosis and dyspnea, which started from birth. She had small telangiectatic lesions on her face and cerebral arteriovenous malformation, but no family history of hereditary hemorrhagic telangiectasia. Contrast echocardiography and pulmonary angiography demonstrated diffuse pulmonary arteriovenous fistulas. The patient was diagnosed as polysplenia syndrome characterized with left atrial isomerism, interrupted inferior vena cava, azygous continuation to the superior vena cava, and hepatic veins draining to the right atrium. In contrast to the other polysplenia syndrome cases, in this patient, pulmonary arteriovenous fistulas were not associated with cavopulmonary anastomoses or liver disease.


Enforcing surveillance of antimicrobial resistance and antibiotic use to drive stewardship: experience in a paediatric setting.
Antibiotic Stewardship (AS) interventions in paediatrics are still not standardized regarding methodology, metrics, and outcomes. We report the results of an AS intervention in the paediatric area based on education and guideline provision via an electronic App. The AS intervention was conducted in 2021 through observation, education, audit and feedback and provision of an electronic App (Firstline.org) to support antibiotic prescription based on local susceptibility data. The primary outcome was the antibiotic consumption in the 12-months following the intervention (year 2022) compared to a historical 12-month control (year 2019) via an interrupted time series analysis. Secondary outcomes were appropriateness of therapy, length-of-stay, 30-day readmission, transfers to the paediatric intensive care unit, in-hospital mortality, and prevalence of antimicrobial resistance (AMR). During the post-intervention phase, 29 cross-sectional audits and feedback were conducted including 467 patients. Prescriptions were appropriate according to the guidelines in 85.7% of cases, with a stable trend over time. A significant decrease of antibiotic consumption was measured in terms of Defined Daily Doses per 1000 Patient Days (-222.13; p<0.001) and Days of Therapy per 1000 Patient Days (-452.49; p <0.001) in the post-intervention period with a clear inversion of the Access to Watch ratio (from 0.7 to 1.7). Length of stay, in-hospital mortality, ICU transfers, and incidence of AMR infections remained stable, while 30-day readmission decreased from 4.9 per 100 admissions to 2.8 per 100 admissions (p <0.001). The intervention was associated with a significant reduction in antimicrobial consumption and an increase in the appropriateness of prescriptions. Electronic tools can be of value in promoting adherence to guidelines and ensuring the sustainability of results.


Phytochemical screening and evaluation of Monechma ciliatum (black mahlab) seed extracts as antimicrobial agents.
Tribes in Nubia Mountains regions of Sudan used Monechma ciliatum seeds for common cold and other chest allergic conditions as a traditional medicine. The aim of this paper is to validate this traditional practice scientifically. Monechma ciliatum seeds were screened for major phytochemical groups using standard methods. Different extracts were bioassayed in- vitro for their bioactivity to inhibit the growth of pathogenic bacteria and fungi. Phytochemical screening results showed the presence of flavonoids, tannins, triterpens, and anthraquinones. Staphylococcus aureus was found to be sensitive to both water extract with zones of inhibition 22 - 26 mm at concentrations of 50 and 100mg/ml and ethanol extract 17 mm at concentration of 100 mg/ml. The growth of Klebsiella pneumoniae was inhibited by ethanol extract with zones of inhibition equal to 16, 26, and 33 mm at concentrations of 50, 100, and 150 mg/ml, respectively. Pseudomonas aeruginosa was insensitive to all extracts used. Similarly, all used fungi were found to be insensitive to extracts used. The minimum inhibitory concentrations of the extracts against microorganisms were ranged from 12.5 to 25 mg/ml. The findings of the current study support the traditional uses of the plant's seed in the therapy of respiratory tract infections caused by Staphylococcus aureus and Klebsiella pneumoniae.


A role for CCAAT/enhancer binding protein beta-liver-enriched inhibitory protein in mammary epithelial cell proliferation.
The transcription factor, CCAAT/enhancer binding protein beta (C/EBPbeta), regulates the expression of genes involved in proliferation and terminal differentiation. Dimerization of the dominant-negative C/EBPbeta-liver-enriched inhibitory protein (LIP) isoform with the C/EBPbeta-liver-enriched activating protein (LAP) isoform inhibits the transcriptional activation of genes involved in differentiation. Consequently, an increase in LIP levels may inhibit terminal differentiation and lead to proliferation. C/EBPbeta-LIP and LAP are crucial for mammary gland development (G. W. Robinson et al., Genes Dev., 12: 1907-1916, 1998; T. N. Seagroves et al., Genes Dev., 12: 1917-1928, 1998) and are also overexpressed in breast cancer (B. Raught et al., Cancer Res., 56: 4382-4386. 1996; C. A. Zahnow et al., J. Natl. Cancer Inst., 89: 1887-1891, 1997); however, little is known about how these isoforms differentially regulate cell cycle progression. To address this question, C/EBPbeta-LIP was overexpressed in both the mammary glands of transgenic mice and in cultured TM3 mammary epithelial cells. Here we report that the involuted mammary glands from transgenic mice overexpressing C/EBPbeta-LIP contain both focal and diffuse alveolar hyperplasia and, less frequently, contain mammary intraepithelial neoplasias (high grade) and invasive and noninvasive carcinomas. Likewise, cultured TM3 cells, stably expressing C/EBPbeta-LIP, showed an increase in proliferation and foci formation attributable to a reentry into S-phase during cellular confluence. These results demonstrate that C/EBPbeta-LIP can induce epithelial proliferation and the formation of mammary hyperplasias and suggest that a C/EBPbeta-LIP-initiated growth cascade may be susceptible to additional oncogenic hits, which could result in the initiation and progression of neoplasia.


The Mll-Een knockin fusion gene enhances proliferation of myeloid progenitors derived from mouse embryonic stem cells and causes myeloid leukaemia in chimeric mice.
Rearrangement of the mixed lineage leukaemia (MLL) gene with extra eleven nineteen (EEN) was previously identified in an infant with acute myeloid leukaemia. Using homologous recombination, we have created a mouse equivalent of the human MLL-EEN allele and showed that when Mll(Een/+) embryonic stem (ES) cells were induced to differentiate in vitro into haemopoietic cells, there was increased proliferation of myeloid progenitors with self-renewal property. We also generated Mll(Een/+) chimeric mice, which developed leukaemia displaying enlarged livers, spleens, thymuses and lymph nodes owing to infiltration of Mll(Een/+)-expressing leukemic cells. Immunophenotyping of cells from enlarged organs and bone marrow (BM) of the Mll(Een/+) chimeras revealed an accumulation of Mac-1+/Gr-1- immature myeloid cells and a reduction in normal B- and T-cell populations. We observed differential regulation of Hox genes between myeloid cells derived from Mll(Een/+) ES cells and mouse BM leukemic cells which suggested different waves of Hox expression may be activated by MLL fusion proteins for initiation (in ES cells) and maintenance (in leukemic cells) of the disease. We believe studies of MLL fusion proteins in ES cells combined with in vivo animal models offer new approaches to the dissection of molecular events in multistep pathogenesis of leukaemia.


Immune abnormalities in myelodysplastic syndromes.
The immune states of 52 patients with myelodysplastic syndromes classified according to the FAB criteria were studied. Serum electrophoresis and immunoelectrophoresis, direct Coombs test, and tests for organ and non-organ specific antibodies were performed. Twenty six patients had immunoglobulin abnormalities: six (11.5%) had monoclonal gammopathy; 17 (32.6%) had polyclonal increases in serum immunoglobulin; while in three (5.8%) immunoglobulin concentrations were decreased. The distribution of immunoglobulin abnormalities among the five myelodysplastic syndrome subtypes was fairly uniform. Results of direct Coombs test were negative in all cases. Organ specific antibodies were not detected in any of the patients tested, although two patients were found positive for antinuclear antibodies. The presence of immunoglobulin abnormalities indicates an involvement of the lymphoplasmatic system in myelodysplastic syndromes.


Massive suprachoroidal hemorrhage with central retinal apposition. A clinical and echographic study.
We reviewed the charts of 18 patients diagnosed with a massive suprachoroidal hemorrhage (MSCH) with central retinal apposition (kissing configuration). Four cases occurred intraoperatively (expulsive), eight after a surgical procedure (delayed), and six associated with blunt or perforating injury (traumatic). In this study, echography was used to monitor the course of MSCH; the mean time for clot lysis was 14 days, and the mean duration of central retinal apposition was 15 days. The expulsive MSCHs were all allowed to resolve spontaneously, with good initial visual outcome in three of the four eyes in which they occurred. In the delayed MSCH group, the majority of patients attained their prehemorrhage visual acuity, with or without early surgical intervention. In the traumatic MSCH group, retinal detachment was a constant complication in all patients. All six patients in the traumatic MSCH group had a poor visual outcome, despite early surgical intervention in five patients. The results of this study suggest that not all MSCHs need to be drained surgically and that, when surgical drainage is indicated, echography may be a useful adjunct in determining the optimal time of drainage.


Generating (Factual?) Narrative Summaries of RCTs: Experiments with Neural Multi-Document Summarization.
We consider the problem of automatically generating a narrative biomedical evidence summary from multiple trial reports. We evaluate modern neural models for abstractive summarization of relevant article abstracts from systematic reviews previously conducted by members of the Cochrane collaboration, using the authors conclusions section of the review abstract as our target. We enlist medical professionals to evaluate generated summaries, and we find that summarization systems yield consistently fluent and relevant synopses, but these often contain factual inaccuracies. We propose new approaches that capitalize on domain-specific models to inform summarization, e.g., by explicitly demarcating snippets of inputs that convey key findings, and emphasizing the reports of large and high-quality trials. We find that these strategies modestly improve the factual accuracy of generated summaries. Finally, we propose a new method for automatically evaluating the factuality of generated narrative evidence syntheses using models that infer the directionality of reported findings.


An invariability-area relationship sheds new light on the spatial scaling of ecological stability.
The spatial scaling of stability is key to understanding ecological sustainability across scales and the sensitivity of ecosystems to habitat destruction. Here we propose the invariability-area relationship (IAR) as a novel approach to investigate the spatial scaling of stability. The shape and slope of IAR are largely determined by patterns of spatial synchrony across scales. When synchrony decays exponentially with distance, IARs exhibit three phases, characterized by steeper increases in invariability at both small and large scales. Such triphasic IARs are observed for primary productivity from plot to continental scales. When synchrony decays as a power law with distance, IARs are quasilinear on a log-log scale. Such quasilinear IARs are observed for North American bird biomass at both species and community levels. The IAR provides a quantitative tool to predict the effects of habitat loss on population and ecosystem stability and to detect regime shifts in spatial ecological systems, which are goals of relevance to conservation and policy.


Interferon alpha for the adjuvant treatment of cutaneous melanoma.
Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates of treatment efficacy. Eighteen RCTs enrolling a total of 10,499 participants were eligible for the review. The results from 17 of 18 of these RCTs, published between 1995 and 2011, were suitable for meta-analysis and allowed us to quantify the therapeutic efficacy of interferon in terms of disease-free survival (17 trials) and overall survival (15 trials). Adjuvant interferon was associated with significantly improved disease-free survival (HR (hazard ratio) = 0.83; 95% CI (confidence interval) 0.78 to 0.87, P value < 0.00001) and overall survival (HR = 0.91; 95% CI 0.85 to 0.97; P value = 0.003). We detected no significant between-study heterogeneity (disease-free survival: I² statistic = 16%, Q-test P value = 0.27; overall survival: I² statistic = 6%; Q-test P value = 0.38).Considering that the 5-year overall survival rate for TNM stage II-III cutaneous melanoma is 60%, the number needed to treat (NNT) is 35 participants (95% CI = 21 to 108 participants) in order to prevent 1 death. The results of subgroup analysis failed to answer the question of whether some treatment features (i.e. dosage, duration) might have an impact on interferon efficacy or whether some participant subgroups (i.e. with or without lymph node positivity) might benefit differently from interferon adjuvant treatment.Grade 3 and 4 toxicity was observed in a minority of participants: In some trials, no-one had fever or fatigue of Grade 3 severity, but in other trials, up to 8% had fever and up to 23% had fatigue of Grade 3 severity. Less than 1% of participants had fever and fatigue of Grade 4 severity. Although it impaired quality of life, toxicity disappeared after treatment discontinuation. The results of this meta-analysis support the therapeutic efficacy of adjuvant interferon alpha for the treatment of people with high-risk (AJCC TNM stage II-III) cutaneous melanoma in terms of both disease-free survival and, though to a lower extent, overall survival. Interferon is also valid as a reference treatment in RCTs investigating new therapeutic agents for the adjuvant treatment of this participant population. Further investigation is required to select people who are most likely to benefit from this treatment.


[The treatment of ureteral lithiasis with a pulsed dye laser].
Pulsed dye laser lithotripsy has shown to be an effective and safe procedure for treatment of ureteral calculi. We report our experience. A total of 1000 patients were treated with pulsed dye laser between January 1990 and February 1996. In 450 patients the procedure was performed under general or regional anaesthesia; the remaining 550 patients were treated with the aid of a mild sedation. In the mild sedation group a total of 417 out of 550 patients (75.8%) had their calculi completely cleared (85.6% of effectiveness in women with pelvic lithiasis). Different facts caused the treatment to fail in the remaining patients: severe pain, vagal reaction and technical difficulties. In the anesthesia group the procedure was effective in 346 cases (76.9%). Laser failed to clear calculi in 104 patients in this group due to technical impossibility and persistence of ureteral fragments. Additional treatment options in order to achieve resolution of the calculi were: ESWL, both ESWL and laser, Dormia basket, Zeiss stent, three-prong grasping forceps, ureterolithotomy and nephrectomy. Morbidity was higher in the group treated under anesthesia, being haematuria the most frequent adverse effect. We believe that ureteroscopy and laser lithotripsy is an effective, safe and low morbidity procedure for the treatment of ureteral calculi in women with distal calculi. It is often suitable to perform it with mild sedation with the subsequent benefit for both the patient and health care system regarding to cost-effectiveness balance.


[The exploration of the lived experiences of schizophrenic patients and family members facing the fear of illness hereditary].
Schizophrenia negatively affects both patients and their families. What are the effects of this incurable, potentially hereditary disease on daily life? Related research shows that schizophrenics tend to experience 'uncertainty' in daily life. Discussions on 'uncertainty' experienced in daily life in the context of concerns regarding hereditary illness remain scarce in Taiwan. This research was designed to gather important data on schizophrenic patients and their family members related to their uncertainties about disease heredity. Participants were recruited from the psychiatric unit and outpatient services department at two hospitals in Hsinchu County. Research subjects included a total of six schizophrenics and six family members. The three topics deduced from data analysis included: 1. marriage / family difficulties rooted in feelings of suffering and torture related to the psychosis and uncertainties regarding disease heredity; 2. evolution from doubt to trust as patients gradual accept choices and make decisions related to disease heredity; and 3. dealing with disease heredity again after having made a successful transition (i.e. persistence to maintain family ties). Both patients and family members experienced worry and fear due to uncertainty about the hereditary condition of the disease. Some experienced emotional responses such as anxiety and helplessness. Research results are expected to help nursing personnel understand the multiple effects and impacts of uncertainty toward illness heredity experienced by the patients and their families in order to provide better consultation and medical care quality under differing circumstances depending on the individual characteristics of patients and their families.


Evaluation of the anti-inflammatory properties of Dodonaea polyandra, a Kaanju traditional medicine.
Extracts of the medicinal plant species Dodonaea polyandra were investigated as part of a collegial research partnership between Northern Kaanju traditional owners represented by Chuulangun Aboriginal Corporation (centred on the Wenlock and Pascoe Rivers, Cape York Peninsula, Queensland, Australia) and university-based researchers. D. polyandra, known as "Uncha" in Kaanju language, is used in Northern Kaanju Traditional Medicine for relief from pain associated with toothache and related ailments. The species has a restricted distribution in Cape York Peninsula and there has been no previous Western scientific investigation of its pharmacology or chemistry. The current study investigates the anti-inflammatory effects of several extracts from D. polyandra. Phytochemical screening was conducted using TLC. Anti-inflammatory effects of leaf extracts were determined using an acute mouse ear oedema model induced by croton oil and 12-o-tetradecanoylphorbol-13-acetate (TPA) chemical irritants. Flavonoid and terpenoid secondary compounds were detected in leaf extracts of D. polyandra. Non-polar hexane and methylene chloride/methanol extracts showed potent inhibition of inflammation in TPA-induced mouse ear oedema by 72.12 and 79.81%, respectively, after 24 h at 0.4 mg/ear. In a mouse model of acute inflammation, this study revealed that leaf extracts of D. polyandra possess significant anti-inflammatory potential. These results contribute to a Western scientific understanding of the ethnopharmacological use of the plant in Northern Kaanju Medicine for reducing tooth-related pain.


A comparison of dental caries and tooth loss for Iowa prisoners with other prison populations and dentate U.S. adults.
When one compares National Health and Nutrition Examination Survey III (NHANES III) data to previous national surveys it appears that oral health in the United States has improved. The purpose of this study was to determine if this trend holds for prisoners in Iowa, specifically in regard to number of decayed teeth, number of decayed surfaces, and number of missing teeth. This original research is a report of cross-sectional data regarding untreated decay and missing teeth. A representative sample of inmates newly admitted to the Iowa Medical Classification Center (IMCC) between June and December 1998 was selected. Oral health data were collected from records obtained as the result of dental treatment screening examinations conducted by the IMCC staff dental hygienist. Demographic data were obtained from questionnaires. The oral health status of this Iowa inmate population was compared with the status of previously studied samples of inmates throughout the nation using descriptive and parametric statistics and with dentate, noninstitutionalized U.S. adults using descriptive, non-parametric, and parametric statistics. Of the 174 study participants, 149 were male and 25 were female. On average, male inmates had 7.09 decayed teeth, 15.3 surfaces of decay, and 4.07 missing teeth. The female inmates averaged 5.56 teeth with untreated decay, 14.4 surfaces of decay, and 5.12 missing teeth. Findings showed that male Iowa inmates have more untreated decay than previously studied samples of inmates throughout the nation. IMCC Caucasian male inmates had 1.6 to 7.8 times as many untreated decayed teeth as previous inmates, while African American inmates showed 1.2 to 3.4 times as many untreated decayed teeth. The Iowa male inmates had fewer missing teeth than most of the inmate comparison groups. Compared with dentate, noninstitutionalized U.S. adults, the IMCC inmates, male and female combined, had 8.4 times the amount of untreated decay but similar numbers of missing teeth. Newly admitted male and female inmates were disparate from the general dentate U.S. adult population in terms of untreated decay. This also was found for IMCC male inmates compared to previous studies of male inmates. Inmates of both genders at IMCC did not appear to be disparate with the comparison population with regard to number of missing teeth.


[The debate about the right to die].
The Right to Die is a debatable issue and some basic notions need to be clarified to discuss it. Death needs to be recognized as part of human life. The goal of medicine is to avoid pain and alleviate suffering, to prevent premature death and when this is not possible, to let it occur peacefully. The concept of euthanasia is unclear, which increases the confusion on end-of-life topics. The term euthanasia should be used only when referring to medical acts performed to produce the patient's death, with the intention of terminating his/her suffering. It is what is usually called "active" euthanasia, which can be voluntary or involuntary. It is essential to understand the difference between producing and allowing death. This will permit timely decisions about limiting or withdrawing treatments, that can be disproportionate or that are only prolonging suffering. Limiting treatments does not mean to abandon the patient but rather to redefine his needs, such as pain treatment, prevention of complications, and relief of suffering. The ethic rationale for these decisions is the respect to the dignity of human life, and the estimation of proportionality or futility of each treatment. The physician's duty with the patient at the end of his life is to assist him in dying according to his values and to minimize his distress.


Generation of perfect polarization vortices using combined gratings in a single spatial light modulator.
Perfect polarization vortices (PPVs) are a type of vector beam with a diameter independent of the polarization order. In this paper, an experimental method is proposed to generate PPVs with an anisotropic polarization distribution. First, a specially designed hologram is generated on a liquid-crystal spatial light modulator (SLM) to obtain Bessel-Gaussian (BG) beams. Second, the BG beams are transformed into PPVs in the Bessel region by an interferometer, which includes a polarized beam splitter, two reflectors, and several lenses. In our experiment, PPVs with adjustable polarization orders and diameters are obtained by generating various combined holograms on the SLM.


A Case Report of Axillary Hibernoma: US, CT, MR, and Histopathologic Findings.
Hibernoma is a rare benign tumor of brown adipose tissue. Herein, we report a case of axillary hibernoma in a 53-year-old female and discuss the various radiologic findings. The US revealed a 4.5-cm well-defined oval heterogenous hyperechoic mass in the right axilla with anterior displacement of the axillary vessels. Non-enhanced chest CT showed a 5.0-cm well defined, oval, and low-attenuated mass. MRI demonstrated a 5.5-cm mass with heterogeneous intermediate-to-high signal intensity on T1-and T2-weighted images and irregular enhancement at the peripheral portion. The patient underwent an US-guided core needle biopsy and the final diagnosis was hibernoma.


Including a Three-Party Meeting Using the Demand and Ability Protocol in an Interdisciplinary Pain Rehabilitation Programme for a Successful Return to Work Process.
The Demand and Ability Protocol (DAP) is used in three-party meetings involving an employee, an employer, and a representative from the rehabilitation team. The aim of this study is to investigate the inclusion of an intervention using the DAP in an interdisciplinary pain rehabilitation programme (IPRP) compared to usual care. This non-randomised controlled trial included patients assigned to an IPRP in Sweden. The intervention group received a DAP intervention targeting their work situation in addition to the usual care provided by the IPRP. The control group received IPRP only. Outcome measures were collected from the Swedish Quality Registry for Pain Rehabilitation. Results demonstrated improvements in both groups regarding self-reported anxiety, depression and EQ5D. Sleep was improved in the intervention group but not in the control group. No statistical differences in outcomes were observed between the groups. In conclusion, adding the DAP intervention to IPRP seemed to have the potential to improve sleep among the patients, which may indicate an overall improvement regarding health outcomes from a longer perspective. The results were less clear, however, regarding the work-related outcomes of sickness absence and workability.


Association of dyslipidemia with single nucleotide polymorphisms of the cholesteryl ester transfer protein gene and cardiovascular disease risk factors in a highly admixed population.
Cardiovascular diseases (CVD) are major causes of mortality worldwide, leading to premature deaths, loss of quality of life, and extensive socioeconomic impacts. Alterations in normal plasma lipid concentrations comprise important risk factors associated with CVD due to mechanisms involved in the pathophysiology of atherosclerosis. Genetic markers such as single nucleotide polymorphisms (SNPs) are known to be associated with lipid metabolism, including variants in the cholesteryl ester transfer protein (CETP) gene. Thus, the study's objective was to assess the relationship among lipid profile, socioeconomic and demographic characteristics, health status, inflammatory biomarkers, and CETP genetic variants in individuals living in a highly admixed population. The study comprises an analysis of observational cross-sectional data representative at the population level from a highly admixed population, encompassing 901 individuals from three age groups (adolescents, adults, and older adults). Socioeconomic, demographic, health, and lifestyle characteristics were collected using semi-structured questionnaires. In addition, biochemical markers and lipid profiles were obtained from individuals' blood samples. After DNA extraction, genotyping, and quality control according to Affymetrix's guidelines, information on 15 SNPs in the CETP gene was available for 707 individuals. Lipid profile and CVD risk factors were evaluated by principal component analysis (PCA), and associations between lipid traits and those factors were assessed through multiple linear regression and logistic regression. There were low linear correlations between lipid profile and other individuals' characteristics. Two principal components were responsible for 80.8 % of the total variance, and there were minor differences in lipid profiles among individuals in different age groups. Non-HDL-c, total cholesterol, and LDL-c had the highest loadings in the first PC, and triacylglycerols, VLDL-c and HDL-c were responsible for a major part of the loading in the second PC;, whilst HDL-c and LDL-c/HDL-c ratio were significant in the third PC. In addition, there were minor differences between groups of individuals with or without dyslipidemia regarding inflammatory biomarkers (IL-1β, IL- 6, IL-10, TNF-α, CRP, and MCP-1). Being overweight, insulin resistance, and lifestyle characteristics (calories from solid fat, added sugar, alcohol and sodium, leisure physical activity, and smoking) were strong predictors of lipid traits, especially HDL-c and dyslipidemia (p < 0.05). The CETP SNPs rs7499892 and rs12691052, rs291044, and rs80180245 were significantly associated with HDL-c (p < 0.05), and their inclusion in the multiple linear regression model increased its accuracy (adjusted R2 rose from 0.12 to 0.18). This study identified correlations between lipid traits and other CVD risk factors. In addition, similar lipid and inflammatory profiles across age groups in the population suggested that adolescents might already present a significant risk for developing cardiovascular diseases in the population. The risk can be primarily attributed to decreased HDL-c concentrations, which appear to be influenced by genetic factors, as evidenced by associations between SNPs in the CETP gene and HDL-c concentrations, as well as potential gene-diet interactions. Our findings underscore the significant impact of genetic and lifestyle factors on lipid profile within admixed populations in developing countries.


Molecular mechanism for activation and regulation of matrix metalloproteinases during bacterial infections and respiratory inflammation.
Matrix metalloproteinases (MMPs) are critical mediators of tissue remodeling. Inappropriate regulation of MMPs causes many pathological events, including microbial invasion and inflammatory tissue damage. Some of the bacterial exoproteinases can effectively activate pro-MMPs (inactive zymogens) via limited proteolysis around their autoinhibitory domains. In addition, overproduction of nitric oxide (NO) may contribute to respiratory inflammation via the formation of reactive nitrogen species (RNS). Several studies have identified regulatory properties of NO/RNS on biomolecules due to functional modification of their cysteine residues. In fact, NO/RNS can mediate activation and expression of MMPs, because RNS can interact with a cysteine switch in the autoinhibitory domain, thus converting proMMPs into their active forms without proteolysis. Many studies have indicated that NO/RNS can participate in expression of various genes that affect immune-inflammatory responses, including MMPs. Although NO in some cases upregulates MMPs, S -nitrosothiols downregulate MMP-9 expression by suppressing the NF-kappaB pathway. While microbial proteinases cause excessive activation of MMPs and contribute to microbial pathogenesis, NO/RNS may modulate expression and activation of MMPs as well as various inflammatory mediators, depending on the redox status at sites of inflammation. Therefore, appropriate regulation of MMPs may be of potential therapeutic value for various infections and inflammatory lung diseases.