Precipitation and discharge changes drive increases in Escherichia coli concentrations in an urban stream.
Determining the driving factors of E. coli dynamics and predicting future E. coli changes in urban aquatic systems are important for regulating water quality. In this study, data from 6985 measurements of E. coli from 1999 to 2019 in an urban waterway Pleasant Run in Indianapolis, Indiana (USA) were statistically analyzed by Mann-Kendall and multiple linear regression to assess the long-term trends in E. coli concentrations and to project E. coli concentrations under future climate change scenarios. E. coli concentrations monotonically increased over the last two decades, with the value increasing from 111 Most Probable Number (MPN)/100 mL in 1999 to 911 MPN/100 mL in 2019. E. coli concentrations have exceeded the Indiana standard of 235 MPN/100 mL since 1998. E. coli showed peak concentration in summer and higher concentration in sites with combined sewer overflows (CSOs) relative to those without. Precipitation had both direct and indirect impacts on E. coli concentrations meditated by stream discharge. Multiple linear regression results showed that annual precipitation and discharge accounted for 60 % of E. coli concentration variability. Based on the observed precipitation-discharge-E. coli concentration relationship, the projected results showed that, in the highest emission representative concentration pathways (RCP) 8.5 climate scenario, E. coli concentrations in the 2020s, 2050s, and 2080s will be 1350 ± 563 MPN/100 mL, 1386 ± 528 MPN/100 mL, and 1443 ± 479 MPN/100 mL, respectively. This study illustrates that climate change can impact E. coli concentrations by altering temperature, precipitation patterns, and stream flow in an urban stream and predicts an undesired future situation under a high CO2 emission scenario.


Macrophage-mediated natrual cytotoxicity against various target cells in vitro. I. Macrophages from diverse anatomical sites and different strains of rats and mice.
Adherent, predominantly phagocytic, mononuclear cells expressing spontaneous cytotoxic activity against diverse target cells in vitro were present in various tissues of different strains of rats and mice. Cells with such natural killer capacity were thus everywhere readily available for mobilization and activation. The inherent spontaneous killer capacity of adherent mononuclear phagocytes can be abrogated by silica particles in vitro, and can be considerably enhanced by appropriate stimuli in vivo. Spontaneous cytolysis mediated by unstimulated mononuclear phagocytes was consistently manifested only after a lag phase of 12-20 h and was quite nonspecific; there was no cogent correlation between susceptibility to lysis and transformation.


Occurrence of chondroitin sulfate E in glycosaminoglycan isolated from the body wall of sea cucumber Stichopus japonicus.
Glycosaminoglycan was isolated from the body wall of sea cucumber Stichopus japonicus by a method consisting of enzymatic digestion, gel filtration, and ion-exchange chromatography. One gram of sea cucumber glycosaminoglycan was composed of 2.50 mmol of sulfate, 0.47 mmol of N-acetylgalactosamine (GalNAc), 0.53 mmol of glucuronic acid (GlcA), 1.73 mmol of fucose, and a small amount of peptide. When mildly hydrolyzed with 0.1 N H2SO4, this glycosaminoglycan released two products, one consisting of fucose plus sulfate and the other of fucose only. Partially hydrolyzed glycosaminoglycan thus obtained was composed of sulfate, GalNAc, GlcA, and fucose at a molar ratio of 3:2:2:1. Partially hydrolyzed glycosaminoglycan was easily digested with chondroitinase AC II. In ion-exchange chromatography, the digest exhibited four sharp peaks whose retention times agreed with those of unsaturated 0-(delta Di-0S), mono-(delta Di-4S and delta Di-6S), and di-(delta Di-SE) sulfated disaccharide, respectively. The disaccharide unit of sea cucumber glycosaminoglycan was composed of 22.4% chondroitin sulfate E, 11.2% chondroitin, 10.4% chondroitin 4-sulfate, and 56.0% chondroitin 6-sulfate.


Advances in optical counting and imaging of micro/nano single-entity reactors for biomolecular analysis.
Ultrasensitive detection of biomarkers is of paramount importance in various fields. Superior to the conventional ensemble measurement-based assays, single-entity assays, especially single-entity detection-based digital assays, not only can reach ultrahigh sensitivity, but also possess the potential to examine the heterogeneities among the individual target molecules within a population. In this review, we summarized the current biomolecular analysis methods that based on optical counting and imaging of the micro/nano-sized single entities that act as the individual reactors (e.g., micro-/nanoparticles, microemulsions, and microwells). We categorize the corresponding techniques as analog and digital single-entity assays and provide detailed information such as the design principles, the analytical performance, and their implementation in biomarker analysis in this work. We have also set critical comments on each technique from these aspects. At last, we reflect on the advantages and limitations of the optical single-entity counting and imaging methods for biomolecular assay and highlight future opportunities in this field.


Effect of vitamin D3 administration on the serum calcium and inorganic phosphate levels of the freshwater catfish, Heteropneustes fossilis, maintained in artificial fresh water, calcium-rich fresh water, and calcium-deficient fresh water.
Freshwater catfish, Heteropneustes fossilis, were injected daily intraperitoneally either with vehicle (0.05 ml of 95% ethanol/100 g body wt) or vitamin D3 (50 I.U./100 g body wt) and maintained in artificial fresh water, calcium-rich fresh water, or calcium-deficient fresh water for 10 days. The specimens were sacrificed on Days 1, 3, 5, and 10 after initiation of the experiment. The blood samples were collected on these intervals and serum calcium and inorganic phosphate levels were analyzed. Vitamin D3 induced hypercalcemia and hyperphosphatemia in the freshwater catfish, H. fossilis. These effects of vitamin D3 are not dependent upon the calcium concentration of the different ambient media used in this study.


Has the prevalence of problematic social media use increased over the past seven years and since the start of the COVID-19 pandemic? A meta-analysis of the studies published since the development of the Bergen social media addiction scale.
Problematic Social Media Use (PSMU) has been defined as the lack of regulation of one's use of social media associated with negative outcomes in everyday functioning. Previous meta-analyses reported PSMU prevalence before the beginning of the COVID-19 pandemic and based the estimates on the cut-off scores, which are debatable in the current fields. The present meta-analysis aims to explore whether PSMU, as assessed by the most used self-report scale (i.e., the Bergen Social Media Addiction Scale; BSMAS), increased across the world (i) since the first published study on this topic (i.e., in the last seven years), (ii) since the beginning of the COVID-19 pandemic, and (iii) depending on age, gender and the income level of the countries. The meta-analysis involved 139 independent samples with 133,955 respondents from 32 countries spanning seven world regions. The results show that PSMU: (i) is significantly higher in low-income countries (LIC); (ii) did not increase in the last 7 years overall and after the beginning of the COVID-19 pandemic, except for LIC; (iii) did not vary depending on age and gender. The higher prevalence of PSMU reported during the COVID-19 pandemic by some single studies may have been a transient phenomenon to cope with physical distances in some countries, whilst, in others, an overall increase of PSMU occurred. High levels of PSMU in LIC might be explained based on socio-cultural differences between countries, but also with the higher prevalence of mental disorders in LIC since PSMU might be a symptom of other, more primary psychiatric disorders.


Determination of the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl) piperazine (IP/66) in rat and human plasma by high-performance liquid chromatography and isotope dilution mass spectrometry.
In connection with pharmacokinetic studies on the antihypertensive drug 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine (IP/66) (I), appropriate high-performance liquid chromatographic (HPLC) and gas chromatographic-mass spectrometric isotope dilution (GC-MS-ID) methods for its determination in rat and human plasma, respectively, were developed. In both techniques, deproteinized and basified plasma samples were extracted and purified by adsorption on an Extrelut-1 column, then the drug was eluted with dichloromethane. Quantitative HPLC analysis was performed on a C8 reversed-phase column. The mobile phase was phosphate buffer (0.02 M, pH 2.8)-acetonitrile (65:35), with UV detection at 208 nm. The internal standard was 1-[2-butoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxyphenyl)piperazine, a homologue of I. The inter-assay coefficient of variation (C.V.) was 9.9% for a drug level of 2 micrograms/ml. Quantitative GC-MS-ID analysis was performed with a DB-17 fused-silica capillary column using the selected-ion monitoring technique. The deuterated form of I, 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-2'-trideuteromethoxyphenyl)pipe razine, utilized as internal standard, was synthesized. The inter-assay C.V. was 7.36% for a drug level of 1 ng/ml.


Pain control following posterior spine fusion: patient-controlled continuous epidural catheter infusion method yields better post-operative analgesia control compared to intravenous patient controlled analgesia method. A retrospective case series.
Pain management following posterior spinal fusion surgeries is a challenging topic. Continuous epidural analgesia (CEA) technique has been invented to resolve some deleterious effects related with conventional intravenous patient-controlled analgesia (IV-PCA) method. However, studies for effectiveness and safety of CEA are scarce in adult population. Our aim was to compare effectiveness and safety of patient-controlled CEA with conventional IV-PCA method in adult patient population. Chart review of patients, scheduled for elective posterior spine fusion to treat spinal stenosis, degenerative disc disease, spondylolisthesis or spinal instability from May 2012 to March 2015, was performed. Patients with spinal infection, cancer, inflammatory disease, and ASA higher than class III, allergy to analgesic medications were excluded from the study. One hundred and nine patients were enrolled into the study. 80 out of 109 patients (40 in CEA group, 40 in IV-PCA group) were matched for age, gender, BMI, type of surgery, level of fusions. Visual Analog Scale scores (VAS) and Ramsay Sedation Scale (RSS) scores were evaluated following surgeries until post-operative 24th hour. There were 58 female patients (72.5 %). The mean age of the patients was 59.85 years (range 24-82 years). When VAS and RSS scores were compared between the groups, there were statistically significant differences between the groups in respect of VAS scores at every time point following surgery (lower in CEA group), whereas there was no significant difference between the groups in respect of RSS scores. More additional analgesia medication was needed in IV-PCA group (16 vs. 5 patients), which was significantly higher than CEA group (p = 0.029). Patient-controlled CEA method is as safe as IV-PCA method and is even more effective than that in controlling immediate post-operative pain in patients treated with posterior spinal fusion.


Occurrence and variability of mycotoxigenicFusarium species associated to wheat and maize in the South West of Spain.
The contamination of cereals with mycotoxins produced by species ofFusarium is an important risk to human and animal health. The toxigenic profile is different depending on theFusarium species considered and, in some species, differences can also be observed at intraspecific level. Information about the distribution and variability of the mycotoxigenicFusarium species allow prediction of the toxins that may occur and to devise control strategies. In this work, the occurrence of mycotoxigenicFusarium species associated to cereals was analysed in a wide sample of durum wheat fields (Triticum durum Desf.) and maize from the South West of Spain (Andalucía).F. equiseti, F. graminearum andF. culmorum were the most frequentFusarium species detected in wheat fields followed byF. sambucinum andF. avenaceum, whereas in the case of maize,F. verticillioides andF. proliferatum were the onlyFusarium species present. The relationships of the Spanish isolates from theF. equiseti, F. avenaceum andF. sambucinum species were analysed by nucleotide sequence comparison of a partial region of the Elongation Factor 1 alpha (EF-1α) with other sequences available in data bases. The results indicated thatF. avenaceum andF. equiseti showed high variability and that the SpanishF. equiseti isolates seemed to belong toF. equiseti type II.


Complementary and alternative treatments for late-life depression, anxiety, and sleep disturbance: a review of randomized controlled trials.
We reviewed randomized controlled trials of complementary and alternative medicine (CAM) treatments for depression, anxiety, and sleep disturbance in nondemented older adults. We searched PubMed (1966-September 2006) and PsycINFO (1984-September 2006) databases using combinations of terms including depression, anxiety, and sleep; older adult/elderly; randomized controlled trial; and a list of 56 terms related to CAM. Of the 855 studies identified by database searches, 29 met our inclusion criteria: sample size >or= 30, treatment duration >or= 2 weeks, and publication in English. Four additional articles from manual bibliography searches met inclusion criteria, totaling 33 studies. We reviewed identified articles for methodological quality using a modified Scale for Assessing Scientific Quality of Investigations (SASQI). We categorized a study as positive if the CAM therapy proved significantly more effective than an inactive control (or as effective as active control) on at least 1 primary psychological outcome. Positive and negative studies were compared on the following characteristics: CAM treatment category, symptom(s) assessed, country where the study was conducted, sample size, treatment duration, and mean sample age. 67% of the 33 studies reviewed were positive. Positive studies had lower SASQI scores for methodology than negative studies. Mind-body and body-based therapies had somewhat higher rates of positive results than energy- or biologically-based therapies. Most studies had substantial methodological limitations. A few well-conducted studies suggested therapeutic potential for certain CAM interventions in older adults (e.g., mind-body interventions for sleep disturbances and acupressure for sleep and anxiety). More rigorous research is needed, and suggestions for future research are summarized.


Sandwich-Based Antibody Arrays for Protein Detection.
Sandwich-based antibody arrays enable the detection of multiple proteins simultaneously, thus offering a time- and cost-effective alternative to single-plex platforms. The protein of interest is "sandwiched" between an antibody that captures it to the array and a second antibody that is used for detection. Here we describe a 1-day procedure to process samples, such as serum or cell lysates, with a quantitative sandwich-based antibody array on a glass substrate using fluorescence.


The behavior of the human erythrocyte as an imperfect osmometer: a hypothesis.
The human erythrocyte does not behave as a perfect osmometer that is its volume does not change as predicted with the change of the tonicity of the medium, as if there was a fraction of the cell water not participating in the osmotic exchange. A mechanism of control of the erythrocyte shape has been previously proposed in which Band 3 (AE1), the protein anion exchanger of Cl(-) and HCO(3)(-), plays a central role. Specifically, decrease and increase of the ratio of its outward-facing conformation and inward-facing conformation (Band 3(o)/Band 3(i)) contract and relax the membrane skeleton, thus favoring echinocytosis and stomatocytosis, respectively. The equilibrium Band 3(o)/Band 3(i) ratio is determined by the Donnan equilibrium ratio of anions and protons, increasing with it (r=Cl(i)(-)/Cl(o)(-)=HCO 3(i)(-)/HCO 3(o)(-)=H(o)(+)/H(i)(+)). The Donnan ratio is influenced by the erythrocyte transport and metabolic activities. The volume change of the human erythrocyte alters the skeleton conformation as it is accompanied by a change of the membrane curvature. Thus, the mechanism could be a hypothesis for explaining the behavior of the human erythrocyte as an imperfect osmometer since the Donnan ratio controls the Band 3(o)/Band 3(i) ratio which controls the volume by a control of the degree of contraction or relaxation of the skeleton. Predictions made by the hypothesis on the Ponder's coefficient R' values in the presence of sucrose or Band 3 substrates slowly transported as well as on the participation of Band 3 in the osmotic hemolysis appear to be corroborated by previous observations. If the hypothesis was valid, it would follow that there is a pressure gradient across the erythrocyte membrane. The equilibrium volume is antagonistically determined by the Donnan ratio per se and Band 3. Band 3, rather than the ratio of surface-to-volume, primarily controls the osmotic hemolysis.


Stimulation of muscle growth by clenbuterol: lack of effect on muscle protein biosynthesis.
1. Young rats were offered to appetite a semi-synthetic diet either alone or containing the beta 2-selective agonist clenbuterol (4-amino-alpha[t-butylamino)methyl]-3,5-dichlorobenzyl alcohol). 2. In female rats (starting weight 116g) the presence of the drug at daily doses greater than 10 micrograms/kg body-weight per d increased the growth of skeletal and cardiac muscle but had no stimulatory effect on the growth of the liver, gastrointestinal tract and kidney. 3. Male rats (starting weight 53 g) received clenbuterol at a daily oral dose of 200 micrograms/kg body-weight per d. Animals were slaughtered after 0, 4, 8, 11, 18, 21 and 25 d of treatment. At 4, 11, 21 and 25 d muscle protein synthesis was measured by the method of Garlick et al. (1980). Although clenbuterol increased the rate of protein and RNA accretion in gastrocnemius and soleus muscles, protein synthesis was not increased. 4. The results suggested that the drug had a rapid, perhaps direct, inhibitory effect on protein degradation. It is concluded that the growth-promoting effect of clenbuterol may be specific to muscle and that the drug may act in a novel manner which circumvents the physiological mechanisms responsible for the control of muscle growth.


Chronic Ankle Instability - Mechanical vs. Functional.
Chronic ankle instability arises from three interacting contributing factors: mechanical ankle instability, functional ankle instability, and perceived ankle instability. To decide on the most appropriate individual recommendation for therapeutic options, it is necessary to assess which of the two main aetiologies - functional vs. mechanical - is dominant in causing the perceived impairment. It is essential to perform a thorough analysis and diagnosis, even though quantifying mechanical ankle instability is still a challenge in the clinical approach to this common pathology. When diagnosing mechanical instability, the most established procedure is physical examination, although this unfortunately does not allow the deficit to be quantified. Additional options include stress-ultrasound, 3D stress-MRI (3SAM), ankle arthrometry, marker-based 3D motion analysis, and diagnostic ankle arthroscopy. Of these the latter is considered the gold standard, even though it is an invasive procedure, it may not be performed for diagnostic reasons only, and it also does not allow the mechanical instability to be quantified. For diagnosing functional instability there are non-instrumented tests such as the Star Excursion Balance Test or Y-Balance Test, posturography/stabilometry, and gait and running analysis, possibly combined with EMG acquisition and isokinetic strength testing.To date, the standard of care is conservative management of ankle instability, and the therapy should include sensorimotor training, strength training of the periarticular muscles, balance training, and gait and running exercises on different surfaces. However, it is increasingly clear that a certain degree of mechanical instability cannot be compensated for by functional training. Thus, it is the goal of differential diagnostics to identify those patients and guide them to mechanical therapy, including ankle bracing, taping, and surgical ligament reconstruction.


Coronary risk prediction in adults (the Framingham Heart Study)
The Framingham Heart Study, an ongoing prospective study of adult men and women, has shown that certain risk factors can be used to predict the development of coronary artery disease. These factors include age, gender, total cholesterol level, high density lipoprotein cholesterol level, systolic blood pressure, cigarette smoking, glucose intolerance and cardiac enlargement (left ventricular hypertrophy on electrocardiogram or enlarged heart on chest x-ray). Calculators and computers can be easily programmed using a multivariate logistic function that allows calculation of the conditional probability of cardiovascular events. These determinations, based on experience with 5,209 men and women participating in the Framingham study, estimate coronary artery disease risk over variable periods of follow-up. Modeled incidence rates range from less than 1% to greater than 80% over an arbitrarily selected 6-year interval; however, they are typically less than 10%, and rarely exceed 45% in men and 25% in women.


CD4+ cell count and HIV load as predictors of size of anal warts over time in HIV-infected women.
Little is known about the associations between CD4(+) cell counts, human immunodeficiency virus (HIV) load, and human papillomavirus "low-risk" types in noncancerous clinical outcomes. This study examined whether CD4(+) count and HIV load predict the size of the largest anal warts in 976 HIV-infected women in an ongoing cohort. A linear mixed model was used to determine the association between size of anal wart and CD4(+) count and HIV load. The incidence of anal warts was 4.15 cases per 100 person-years (95% confidence interval [CI], 3.83-4.77) and 1.30 cases per 100 person-years (95% CI, 1.00-1.58) in HIV-infected and HIV-uninfected women, respectively. There appeared to be an inverse association between size of the largest anal warts and CD4(+) count at baseline; however, this was not statistically significant. There was no association between size of the largest anal warts and CD4(+) count or HIV load over time. There was no evidence for an association between size of the largest anal warts and CD4(+) count or HIV load over time. Further exploration on the role of immune response on the development of anal warts is warranted in a larger study.


RNAi knockdown of transcription factor Pu.1 in the differentiation of mouse embryonic stem cells.
Murine embryonic stem (mES) cells are pluripotent cells derived from the inner cell mass of the preimplantation blastocyst. These cells are primitive and undifferentiated and have the potential to become a wide variety of specialized cell types. Mouse ES cells can be regarded as a versatile biological tool that has led to major advances in our understanding of cell and developmental biology. To study specific gene function in early developmental events, gene knockout approaches have been traditionally used, however, this is a time-consuming and expensive approach. Recently, we have shown that small interfering RNA is an effective strategy to knockdown target gene expression, during ES cell differentiation, and consequently, one can alter cell fates in ES-derived differentiated cells. This method will be useful to test the function of a wide variety of gene products using the ES cell differentiation system.


Understanding immunosenescence and its impact on vaccination of older adults.
Older adults are more susceptible to viral and bacterial infection, and experience higher incidence and severity of infectious diseases. Although vaccination is the most logical solution in preventing infectious diseases, primary vaccine responses in individuals aged ≥65 years-old fail to generate complete protection. This is presumably attributed to immunosenescence, a term that describes functional differences associated with the immune system and natural age advancement. Both the innate and adaptive immune systems experience age-related impairments that contribute to insufficient protection following vaccination. This review addresses current knowledge of age-related changes that affect vaccine responsiveness; including the deficits in innate cell functions, dampened humoral and cell-mediated immune responses, current vaccination schedules for older adults, and concludes with potential strategies for improving vaccine efficacy specifically for this age group. Due to an age-related decline in immunity and poor vaccine responses, infectious diseases remain a burden among the aged population.


C1 lateral mass screw placement via the posterior arch: a technique comparison and anatomic analysis.
Instrumentation of C1 is becoming increasingly common. Starting points initially described for C1 lateral mass screws at the lateral mass/posterior arch junction are technically challenging. Recently, a number of techniques have evolved advocating varying starting points and trajectories. Despite being technically easier, there are new safety concerns. Insufficient evidence exists for optimal C1 lateral mass screw placement with starting points in the posterior arch. To determine anatomic variability of the C1 lateral mass and posterior ring and to compare safety and feasibility of C1 lateral mass screw placement techniques via the posterior arch. Descriptive anatomy for surgical technique. One hundred thin-cut cervical spine computed tomography scans were acquired and formatted for virtual surgery. Four different described techniques were used for virtual placement of C1 lateral mass screws. Success was defined as avoidance of critical structures including the transverse foramen, vertebral groove, and spinal dura. Anatomic variability of the C1 vertebra and safe zones for screw placement were also clarified. Overall screw placement success for the four techniques was 50% (Resnick), 92% (Tan et al.), 58% (Ma et al.), and 85% (Christensen et al.). Average posterior arch height was 6.7±2.1 mm, and vertebral groove height 4.9±1.1 mm was the most limiting dimension to safe screw placement. A safe zone for screw placement was found in 100% of cases (200 screws), 17.0±1.1 mm from midline and a width of 12.6±1.7 mm. Posterior tubercle morphology was variable. C1 lateral mass screws could be virtually placed bilaterally in each of 100 clinical cases without violating critical structures. However, none of the previously described approaches worked in every case because of significant anatomic variability. The vertical starting point was particularly critical, and vertebral groove height was the most limiting variable. Although a reliable safe zone could be found in every case, preoperative planning is essential to avoid critical structures.


Primed lymphoid cell tolerance. II. In vivo tolerization of highly tolerogen-sensitive hapten-primed, potentially IgG-producing B cells.
The relative ease of tolerizing IgM-bearing versus IgG-bearing B cells was investigated. Previous work had shown that IgG-bearing trinitrophenyl (TNP)-specific B cells from mice primed and boosted with TNP-keyhole limpet hemocyanin (TNP-KLH) are highly susceptible to tolerization in vitro by TNP presented on an unrelated carrier. TNP-OVA was used as tolerogen, as it may represent a more general class of tolerogens than those which are nonmetabolizable or immunoglobulin containing. This study showed that highly primed B cells are tolerizable in vivo using TNP-OVA, with the IgG response to TNP-KLH easier to tolerize than the IgM response. To determine if the ease of tolerization of the IgG response in vivo was due to intrinsic differences in B-cell precursors of the IgM and IgG responses, tolerance was performed in vitro with B cells of defined surface isotypes. A T-independent antigen, TNP-endotoxin, was employed to minimize T-cell effects. At least 10 times as much TNP-OVA was required to tolerize B cells bearing the IgM surface isotype than those with the IgG surface isotype. Thus, the ease of inhibition of the IgG response as compared to the IgM response in vivo by preexposure to TNP-OVA may be at least partially explained by inherent differences in IgM and IgG B-cell precursors.


Nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase of Neurospora.
Neurospora NADP-specific glutamate dehydrogenase that was treated with iodoacetate, iodoacetamide, or N-ethylmaleimide to block the thiol groups was cleaved with cyanogen bromide. Of the expected 10 peptides, based on a methionine content of 9 residues, 8 were obtained in pure form and 2 were handled as a mixture. The fragments ranged in size from 9 to 109 residues. In addition, there were isolated 6 peptides, produced by anomalous cleavage at the carboxyl groups of tryptophan residues, and two by hydrolysis of an aspartyl-proline bond. Preliminary separation of these peptides was accomplished by gel filtration followed by either ion-exchange chromatography of the larger peptides or by paper chromatography and paper electrophoresis of the smaller fragments. Ordering of the CNBr fragments in sequence was based upon sequences of tryptic and chymotryptic peptides obtained in another laboratory. The complete sequence of the protein is presented. The amino acid sequences of the bovine and chicken liver glutamate dehydrogenases previously determined show considerable homology with the NADP-specific enzyme of Neurospora in the NH2-terminal half of the molecule; this includes the region of the specifically reactive lysine residue and the portion of the sequence that has been implicated in coenzyme binding. Particularly striking is the fact that most of the residues conserved among the three homologous proteins would be expected to be important for conformational, rather than catalytic, effects. This implies that the conformation of the Neurospora enzyme must be similar in parts of its structure to the vertebrate enzymes but undoubtedly differs in some regards.


Heparin-functionalized polymer graft surface eluting MK2 inhibitory peptide to improve hemocompatibility and anti-neointimal activity.
The leading cause of synthetic graft failure includes thrombotic occlusion and intimal hyperplasia at the site of vascular anastomosis. Herein, we report a co-immobilization strategy of heparin and potent anti-neointimal drug (Mitogen Activated Protein Kinase II inhibitory peptide; MK2i) by using a tyrosinase-catalyzed oxidative reaction for preventing thrombotic occlusion and neointimal formation of synthetic vascular grafts. The binding of heparin-tyramine polymer (HT) onto the polycarprolactone (PCL) surface enhanced blood compatibility with significantly reduced protein absorption (64.7% decrease) and platelet adhesion (85.6% decrease) compared to bare PCL surface. When loading MK2i, 1) the HT depot surface gained high MK2i-loading efficiency through charge-charge interaction, and 2) this depot platform enabled long-term, controlled release over 4weeks (92-272μg/mL of MK2i). The released MK2i showed significant inhibitory effects on VSMC migration through down-regulated phosphorylation of target proteins (HSP27 and CREB) associated with intimal hyperplasia. In addition, it was found that the released MK2i infiltrated into the tissue with a cumulative manner in ex vivo human saphenous vein (HSV) model. This present study demonstrates that enzymatically HT-coated surface modification is an effective strategy to induce long-term MK2i release as well as hemocompatibility, thereby improving anti-neointimal activity of synthetic vascular grafts.


Aptamer based recognition of cancer cells: Recent progress and challenges in bioanalysis.
Rapid and accurate monitoring of cancer cells with high sensitivity is essential for a successful cancer treatment. As high-affinity nucleic acid ligands, aptamers can improve the properties of detection methods by conjugating with intracellular or extracellular cancer biomarkers. Despite the advances in the early detection and treatment of cancer cells, lacking effective early detection tools is one of the causes of a high mortality rate. Aptasensors, which are based on the specificity of aptamer-target recognition, with transduction for analytical purposes have received particular attention due to their high sensitivity and selectivity, simple instrumentation, as well as low production cost. In this review, some selective and sensitive methods were summarized based on advanced nanomaterials towards aptasensing of cancer cells, such as blood, breast, cervical, colon, gastric, liver, and lung cancer cells. This review summarizes advances from 2010 to June 2020 in the development of aptasensors for cancer cell detection. Various aptasensing strategies are assessed according to their potential for reaching relevant limits of sensitivity, specificity, and degrees of multiplexing. Furthermore, we address the remaining challenges and opportunities to integrate aptasensing platforms into point-of-care solutions. Finally, the advantages and limitations of aptamer-based aptasensing strategies were reviewed.


Regulatory functions of the lambda repressor reside in the amino-terminal domain.
The repressor of bacteriophage lambda is a protein containing two domains of approximately equal size. Fragments containing the amino-terminal domain of repressor bind specifically to lambda operator DNA and mediate positive and negative control of lambda transcription both in vitro and in vivo.


Effect of Physalis peruviana L. on cadmium-induced testicular toxicity in rats.
Cadmium (Cd) stimulates the production of reactive oxygen species and causes tissue damage. We investigated here the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced testes toxicity in rats. Twenty-eight Wistar albino rats were used. They were divided into four groups (n=7). Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg body weight (bwt) of cadmium chloride for 5 days. Group 3 was orally treated with 200 mg/kg bwt of methanolic extract of physalis (MEPh). Group 4 was pretreated with MEPh before cadmium for 5 days. Changes in body and testes weights were determined. Oxidative stress markers, antioxidant enzymes, and testosterone level were measured. Histopathological changes of testes were examined, and the immunohistochemical staining for the proapoptotic (caspase-3) protein was performed. The injection of cadmium caused a significant decrease in body weight, while a significant increase in testes weight and testes weight index was observed. Pretreatment with MEPh was associated with significant reduction in the toxic effects of Cd as shown by reduced testicular levels of malondialdehyde, nitric oxide, and caspase-3 expression and increased glutathione content, and the activities of superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and testosterone were also increased. Testicular histopathology showed that Cd produced an extensive germ cell apoptosis, and the pretreatment of MEPh in Cd-treated rats significantly reduced Cd-induced testicular damage. On the basis of the above results, it can be hypothesized that P. peruviana L. has a protective effect against cadmium-induced testicular oxidative stress and apoptosis in the rat.


Relationship of electronic medical knowledge resource use and practice characteristics with Internal Medicine Maintenance of Certification Examination scores.
Maintenance of certification examination performance is associated with quality of care. We aimed to examine relationships between electronic medical knowledge resource use, practice characteristics and examination scores among physicians recertifying in internal medicine. We conducted a cross-sectional study of 3,958 United States physicians who took the Internal Medicine Maintenance of Certification Examination (IM-MOCE) between January 1, 2006 and December 31, 2008, and who held individual licenses to one or both of two large electronic knowledge resource programs. We examined associations between physicians' IM-MOCE scores and their days of electronic resource use, practice type (private practice, residency teaching clinic, inpatient, nursing home), practice model (single or multi-specialty), sex, age, and medical school location. In the 365 days prior to the IM-MOCE, physicians used electronic resources on a mean (SD, range) of 20.3 (36.5, 0-265) days. In multivariate analyses, the number of days of resource use was independently associated with increased IM-MOCE scores (0.07-point increase per day of use, p = 0.02). Increased age was associated with decreased IM-MOCE scores (1.8-point decrease per year of age, p < 0.001). Relative to physicians working in private practice settings, physicians working in residency teaching clinics and hospital inpatient practices had higher IM-MOCE scores by 29.1 and 20.0 points, respectively (both p < 0.001). Frequent use of electronic resources was associated with modestly enhanced IM-MOCE performance. Physicians involved in residency education clinics and hospital inpatient practices had higher IM-MOCE scores than physicians working in private practice settings.


Association between smoking and mortality: Khon Kaen cohort study, Thailand.
Despite anti-smoking campaigns, smoking prevalence among Thai males aged 30 or older is high, at around 50%. The purpose of this study was to determine the relationship between smoking and mortality in a rural Thai community. Subjects enrolled into the Khon Kaen cohort study between 1990 and 2001 were followed up for their vital status until 16th March 2012. The death resource was from the Bureau of Policy and Strategy, Ministry of Interior, Thailand. A Cox proportional hazards model was used to analyse the association between smoking and death, controlling for age, education level and alcohol drinking, and confidence intervals were calculated using the floating risk method. The study recruited 5,962 male subjects, of whom 1,396 died during a median 13.5 years of follow-up. Current smokers were more likely to die than never smokers after controlling for age, education level and alcohol drinking (HR, 95%CI: 1.41, 1.32- 1.51), and the excess mortality was greatest for lung cancer (HR, 95%CI: 3.51, 2.65-4.66). However, there was no increased risk with increasing dose of tobacco, and no difference in risk between smokers of yamuan (hand- rolled cigarettes) and manufactured tobacco. Mortality from cancer, particularly lung cancer, and from all causes combined is dependent on smoking status among men in rural Thailand, but the relative risks are lower than have been reported from studies in high income countries, where the tobacco epidemic is more established.


Effect of employee worktime control on health: a prospective cohort study.
To investigate the health effects of employee worktime control. Prospective cohort study among 4218 permanent full time municipal employees linking questionnaire data from 1997 and 2000 with sickness absence records from 1997 and 2001. Worktime control was considered high for the highest tertile in both 1997 and 2000, low for the lowest tertile for both years, and intermediate for all other combinations. Self rated health status, psychological distress, and medically certified periods of sickness absence were used as the health outcomes. Adjustments were made for age, baseline health status, occupational status, marital status, dependent children, and behavioural health risks. In the follow up, women with a low level of worktime control had a 1.9 times (95% CI 1.4 to 2.5) higher odds ratio for poor self rated health, a 1.4 times (95% CI 1.1 to 1.8) higher odds ratio for psychological distress, and a 1.5 times (95% CI 1.3 to 1.7) higher risk of medically certified sickness absences than women with a high level of worktime control. The health effects of worktime control were particularly evident among women with families. Among men, worktime control was not associated with self rated health or distress, but it predicted sickness absences in two subgroups: those with dependent children and those with manual occupations. A low level of worktime control increases the risk of future health problems. The risk is highest among women, especially those with families, and among manual workers. The results suggest that worktime control can help workers integrate their work and private lives successfully.


Test--retest reliability of the StepWatch Activity Monitor outputs in individuals with chronic stroke.
To examine the test-retest reliability of the StepWatch Activity Monitor outputs over two periods, a week apart, in participants with stroke. Test-retest reliability study over monitoring periods of one, two and three days. Participant's usual environment. Forty participants more than six months post stroke. StepWatch outputs: total step count, number of steps at high medium and low stepping rates, sustained activity indices, peak activity index. The intraclass correlation coefficients were high for all StepWatch outputs and all monitoring periods but were highest for the three-day monitoring period (0.930-0.989) and lowest for the one-day monitoring period (0.830-0.950). The coefficient of variation ranged from 6.7% to 48.7% over the monitoring periods, with higher variation shown for shorter monitoring periods. The most reliable four outputs had 95% limits of agreement between three-day periods that were less than 40%. These were total step count (+/-37.8%), highest step rate in 1 minute (+/-23.0%), highest step rate in 5 minutes (+/-38.6%) and peak activity index (+/-29.8%). The highest step rate in 1 minute was the only StepWatch output that had 95% limits of agreement less than 40% for the two-day (+/-31.2%) and one-day (+/-36.7%) monitoring periods. Total step count, highest step rate in 1 minute, highest step rate in 5 minutes and peak activity index have good test-retest reliability over a three-day monitoring period, with lower reliability shown by the other StepWatch outputs. In general, monitoring over one or two days is less reliable.


Ganitumab (AMG 479) inhibits IGF-II-dependent ovarian cancer growth and potentiates platinum-based chemotherapy.
Insulin-like growth factor 1 receptor (IGF-IR) has been implicated in the pathogenesis of ovarian cancer. Ganitumab is an investigational, fully human monoclonal antibody against IGF-IR. Here, we explore the therapeutic potential of ganitumab for the treatment of ovarian cancer. The effects of ganitumab were tested in vitro against a panel of 23 established ovarian cancer cell lines. The ability of ganitumab to inhibit IGF-I-, IGF-II-, and insulin-mediated signaling was examined in vitro and in tumor xenografts using ovarian cancer models displaying IGF-IR/PI3K/AKT pathway activation by two distinct mechanisms, PTEN loss and IGF-II overexpression. Drug interactions between ganitumab and cisplatin, carboplatin, or paclitaxel were studied in vitro and in vivo. In vitro, growth inhibition varied significantly among individual ovarian cancer cell lines. IGF-II mRNA and phospho-IGF-IR protein expression were quantitatively correlated with response to ganitumab, and PTEN mutations conferred resistance to ganitumab. Ganitumab potently inhibited baseline and IGF-I-, IGF-II-, and insulin-induced IGF-IR and IGF-IR/insulin hybrid receptor signaling in vitro and in vivo. Synergistic and additive drug interactions were seen for ganitumab and carboplatin or paclitaxel in vitro. Furthermore, ganitumab significantly increased the efficacy of cisplatin in ovarian cancer xenograft models in vivo. These observations provide a biologic rationale to test ganitumab as a single agent or in combination with carboplatin/cisplatin and paclitaxel in patients with ovarian cancer. Moreover, assessment of tumor expression of IGF-II, phospho-IGF-IR, or PTEN status may help select patients with ovarian cancer who are most likely to benefit from ganitumab. Clin Cancer Res; 20(11); 2947-58. ©2014 AACR.


Reliability and criterion validity of handheld dynamometry for measuring trunk muscle strength in people with and without chronic non-specific low back pain.
Evaluating trunk strength is an important aspect of the physical examination of people with low back pain (LBP). Thus, reliable, valid, and easily applied measurement tools are needed to quantify trunk muscle strength and monitor changes in response to interventions. To determine within-day and between-day test re-test reliability and criterion validity of a handheld dynamometer (HHD) to evaluate maximum isometric trunk strength in people with chronic LBP and asymptomatic individuals. Reliability and criterion validity study. Twenty adult participants with chronic, non-specific LBP and 35 asymptomatic individuals participated. Isometric trunk flexion, extension, and rotation strength were evaluated with the HHD (Active force 2) and the within-day and between-day reliability were determined with intraclass correlation coefficients (ICC2,1) and the standard error of the measurements (SEM), minimal detectable change (MDC), and the limits of agreement (LOA) using Bland-Altman plots. Criterion validity was evaluated using Pearson correlation coefficients to compare HHD measurements to isokinetic dynamometry for both isometric trunk flexion and extension strength. Good to excellent within-day and between-day reliability was observed for people with LBP and asymptomatic individuals with (ICC2,1) of 0.73-0.93 and 0.62-0.92 respectively. A moderate to strong correlation was found between measurements with the HHD and the isokinetic dynamometer with a correlation of r = 0.68-0.78 and r = 0.56-0.59 for people with LBP and asymptomatic participants respectively. A HHD is a reliable, valid, and clinically applicable tool for the measurement of trunk strength in adults with and without chronic LBP.


Imaging key wrist ligaments: what the surgeon needs the radiologist to know.
Although much attention is paid to the scapholunate ligament, lunotriquetral ligament, and the triangular fibrocartilage complex, additional intrinsic and extrinsic ligaments in the wrist play an important part in carpal stability. With improved MRI techniques, the radiologist can increasingly visualize these ligaments. The anatomy, MRI appearance, and clinical significance of the scapholunate ligament, lunotriquetral ligament, triangular fibrocartilage complex, carpal metacarpal ligaments, and volar and dorsal extrinsic ligaments are reviewed.


Environmental stress and Umbilicaria lichens: the effect of high temperature pretreatments.
The heat sensitivity of net CO2 exchange in four Umbilicaria species has been examined. Plants were exposed to pulses of heat from 2 to 24 h, were exposed either air-dry or saturated with water, and then were examined repeatedly under stress-free conditions to see if the responses were stable over many days or weeks. The initial responses found were maintained in all cases up to one month implying that the effects were not reversible. Hydrated plants were much more sensitive than dry plants, but in both cases the sensitivity increased with exposure time. All species showed basically the same critical temperatures thus suggesting that selection in the field was not operating on the basis of differential heat sensitivity. This idea was supported both by observations of thallus temperatures in the field during periods of hot weather, and by observations of thallus temperatures exposed to controlled high temperatures. Both approaches suggested that temperatures high enough to induce heat stress in the field, do not occur.


Predicting Perinatal Outcome from Prenatal Ultrasound Characteristics in Pregnancies Complicated by Gastroschisis.
The objective of the study was to establish the predictive value of prenatal ultrasound markers for complex gastroschisis (GS) in the first 10 days of life. In this retrospective cohort study over 11 years (2000-2011) of 117 GS cases, the following prenatal ultrasound signs were analyzed at the last second- and third-trimester ultrasounds: intrauterine growth restriction, intra-abdominal bowel dilatation (IABD) adjusted for gestational age, extra-abdominal bowel dilatation (EABD) ≥25 mm, stomach dilatation, stomach herniation, perturbed mesenteric circulation, absence of bowel lumen and echogenic dilated bowel loops (EDBL). Among 114 live births, 16 newborns had complex GS (14.0%). Death was seen in 16 cases (13.7%): 3 intrauterine fetal deaths, 9 complex GS and 4 simple GS. Second-trimester markers had limited predictive value. Third-trimester IABD, EABD, EDBL, absence of intestinal lumen and perturbed mesenteric circulation were statistically associated with complex GS and death. IABD was able to predict complex GS with a sensitivity of 50%, a specificity of 91%, a positive predictive value of 47% and a negative predictive value of 92%. Third-trimester IABD adjusted for gestational age appears to be the prenatal ultrasound marker most strongly associated with adverse outcome in GS.


Beta-lactamase determinants and molecular typing of carbapenem-resistant classic and hypervirulent Klebsiella pneumoniae clinical isolates from southwest of Iran.
This study investigated the molecular epidemiology of carbapenem-resistant classic Klebsiella pneumoniae (CR-cKp) and carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolates in southwestern Iran. From 2019 to 2021, 136 (88.9%) cKp and 17 (11.1%) hvKp isolates were identified using biochemical tests and polymerase chain reaction (PCR). Antibiotic resistance, beta-lactamases, and clonal relatedness of carbapenem-resistant isolates were investigated using disk diffusion, PCR, and enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR), respectively. The different markers of hvKp isolates were as follows: string test (35.3%, n = 6/17), magA (11.8%, n = 2/17), rmpA (11.8%, n = 2/17), rmpA2 (52.9%, n = 9/17), iucA (52.9%, n = 9/17), and peg344 (35.3%, n = 6/17). Also, 55.1% (n = 75/136) of cKp and 47.1% (n = 8/17) of hvKp isolates were CR-cKp and CR-hvKp, respectively. All CR-hvKp (100.0%, n = 8) isolates were MDR. Colistin, tetracycline, and tigecycline were the most effective antibiotics. The occurrence of beta-lactamase genes in 75 CR-cKp and 8 CR-hvKp isolates was as follows: bla NDM (41.3, 25.0%), bla IMP (4.0, 0.0%), bla VIM (8.0, 0.0%), bla GES (14.7, 25.0%), bla OXA-48-like (20.0, 0.0%), bla CTX-M (26.7, 12.5%), bla SHV (24.0, 12.5%), bla TEM (10.7, 0.0%), bla FOX (6.7, 0.0%), bla DHA (6.7, 0.0%), bla CMY (5.3, 0.0%), bla LAT (12.0, 0.0%), and bla ACT (8.0, 0.0%). ERIC-PCR showed a high diversity among isolates. In this study, the occurrence of MDR CR-hvKp isolates harboring bla NDM and bla GES was detected for the first time in southwestern Iran. To prevent the spread of CR-hvKp and reduce selection pressure, long-term surveillance and more effective treatment strategies should be implemented.


Face perception and within-category discrimination in prosopagnosia.
Prosopagnosics are impaired at face recognition, but unimpaired, or relatively less impaired, at common object recognition. It has been suggested that this dissociation results simply from the greater difficulty of face recognition compared to object recognition, or from the greater need to discriminate visually similar members of a single category in face recognition compared to object recognition. We tested these hypotheses using the performance of normal subjects in an 'old/new' recognition paradigm to establish the true relative difficulty of face and object recognition, and required both normal subjects and a prosopagnosic subject to discriminate both faces and visually similar exemplars of nonface object categories. In two different experiments, the prosopagnosic patient performed disproportionately poorly with faces. These results disconfirm the hypotheses described above, and imply that prosopagnosia is an impairment of a specialized form of visual recognition that is necessary for face recognition and is not necessary, or less necessary, for the recognition of common objects.


Pediatric and Adolescent Gynecology in Europe: Clinical Services, Standards of Care, and Training.
To identify current clinical services and training available across Europe within pediatric and adolescent gynecology (PAG) and establish the extent to which PAG services meet current European Board and College of Obstetrics and Gynecology (EBCOG) standards. Quantitative and qualitative questionnaire. European countries that are members of the EBCOG and the European Association of Pediatric and Adolescent Gynecology. Thirty-six countries that were approached beginning in September 2013; data were obtained from 27 countries. Questionnaires with 28 stems were sent to clinical leaders in 36 European countries. National society, national standards, legislation for female genital mutilation, protocols for transition to adult services, human papilloma virus vaccination programs, sex and contraception education, safeguarding, clinical leads for PAG, delivery of PAG services, and training available for PAG. Of 36 countries, 27 responded. Seventy-seven percent had a national PAG society but only 44% had national standards in PAG. There was agreement that PAG cases should be multidisciplinary but not all have clinical networks in place to facilitate this. Human papilloma virus programs are available in some European countries and not all have legislation against female genital mutilation. A significant proportion of cases continue to be seen in adult gynecology clinics as opposed to designated PAG clinics with only 41% with processes to transfer patients into adult care. In this article we provide a framework to explore areas for improvement within PAG services and training across Europe. The EBCOG standards of care are not being adhered to in many countries because processes and clinical networks are not in place to facilitate them.


Considering pharmacokinetic and mechanistic information in cancer risk assessments for environmental contaminants: examples with vinyl chloride and trichloroethylene.
Risk assessments for vinyl chloride (VC) and trichloroethylene (TCE) are presented as examples of approaches for incorporating chemical-specific pharmacokinetic and mechanistic information into a more scientifically plausible cancer risk assessment. For VC, the evidence regarding mode of action includes direct reaction of a metabolite with DNA, resulting in DNA adducts and mistranscription, and cross-species target-tissue correspondence of a rare tumor type. Risk estimates for human exposure to VC predicted with a physiologically-based pharmacokinetic (PBPK) model and the linearized multistage (LMS) model were lower than those currently used in environmental decision-making by a factor of 30 to 50, and were more consistent with human epidemiological data. For TCE, there is evidence of increased cell proliferation due to receptor interaction or cytotoxicity in every instance in which tumors are observed, and the tumors typically represent an increase in the incidence of a commonly observed, species-specific lesion. Virtually safe exposure estimates for human exposure to TCE predicted with a PBPK model and a margin of exposure (MOE) approach were higher than those obtained by the conventional LMS approach by roughly a factor of 100. The MOE approach is recommended as an alternative to the LMS approach for chemicals with a carcinogenic mode of action which entails increased cell proliferation, leading to the expectation of a highly nonlinear cancer dose-response.


Postmenopausal women with vasomotor symptoms have increased urinary excretion of calcitonin gene-related peptide.
To establish whether 24 h urinary excretion of the potent vasodilator calcitonin gene-related peptide (CGRP) was higher in postmenopausal women with vasomotor symptoms compared to the level in women without symptoms. We also wanted to establish whether urinary excretion of CGRP changed during the menstrual cycle in women of fertile age. Thirteen postmenopausal women with and 13 women without vasomotor symptoms were included. Urine was collected over 24 h and CGRP excretion was measured utilizing radio-immunoassay technique. Twenty-four hour CGRP excretion was also measured in ten fertile women with regular cycles in early follicular, preovulatory and midluteal phase. Twenty-four hour urinary excretion of CGRP was significantly higher in women with vasomotor symptoms compared to non-flushing women (median 7.16 vs 5.15 pmol/24 h; P = 0.028). CGRP concentrations were stable throughout the ovulatory cycles. The 24 h urinary excretion of CGRP is higher in women with vasomotor symptoms than in women without these symptoms. CGRP may be the mediator of vasodilator signals originating from the thermoregulatory center.


Large Solitary Fibrous Tumor (SFT) of the penis- a case report and review of literature.
Solitary fibrous tumors (SFTs) are very rare spindle cell neoplasms of mesenchymal origin with largely benign course of disease. Genital SFT's can be managed providing excellent functional and psychological outcomes by timely intervention. We report the largest and possibly the second only reported case of penile SFT in a 34 year male presenting with a gradually increasing perineal mass with clinically normal appearing phallus. MRI revealed a 9.8 × 3.2 cm soft tissue mass arising from left corpora cavernosae, the mass was excised en-bloc via a perineal approach under spinal anaesthesia. Histopathology revealed spindle cell tumor embedded in myxohyaline stroma along with hyalinized vascular channels demonstrating IHC positivity for CD34 and STAT6. The patient is disease free post 2 years of resection with no sexual or urinary dysfunctions. Genital SFTs, although rare, should be considered in the differential diagnosis of well-circumscribed, painless, slow growing solid masses and histopathologists must be vigilant of its malignant characteristics.


Mutagenic activities of fecapentaene derivatives in the Ames/Salmonella test system.
The direct mutagenic activities of a pair of naturally-occurring and several synthetic fecapentaenes were measured in the Ames/Salmonella test system. We found that strain TA100 with preincubation was the most sensitive procedure for the naturally-occurring fecapentaene-12 (FP-12). Its natural analog, FP-14, and the synthetic isomer, cis-FP-12, yielded similar mutagenic activities to FP-12 in the range of 1000-2000 TA100 revertants per microgram of compound. The synthetic analogs of FP-12 and FP-14, MFP-12 and MFP-14, wherein the glycerol moiety was replaced by methoxy, exhibited consistently higher mutagenic activities than their parent fecapentaenes (MFP-12 was about 20 times more potent than FP-12; MFP-14 was about twice the potency of FP-14). The standard rat liver metabolizing system (S9) reduced the activities of all the fecapentaenes in a dose-related manner.


The effect of myotonic dystrophy transcript levels and location on muscle differentiation.
In myotonic dystrophy type I (DM1), nuclear retention of mutant DMPK transcripts compromises muscle cell differentiation. Although several reports have identified molecular defects in myogenesis, it remains still unclear how exactly the retention of the mutant transcripts induces this defect. We have recently created a novel cellular model in which the mutant DMPK 3' UTR transcripts were released to the cytoplasm of myoblasts by using the WPRE genetic element. As a result, muscle cell differentiation was repaired. In this paper, this cellular model was further exploited to investigate the effect of the levels and location of the mutant transcripts on muscle differentiation. Results show that the levels of these transcripts were proportional to the inhibition of both the initial fusion of myoblasts and the maturity of myotubes. Moreover, the cytoplasmic export of the mutant RNAs to the cytoplasm caused less inhibition only in the initial fusion of myoblasts.


Critical appraisal of surgical revascularization for critical limb ischemia.
Peripheral artery disease is growing in global prevalence and is estimated to afflict between 8 and 12 million Americans. Its most severe form, critical limb ischemia (CLI), is associated with high rates of limb loss, morbidity, and mortality. Revascularization is the cornerstone of limb preservation in CLI, and has traditionally been accomplished with open surgical bypass. Advances in catheter-based technologies, coupled with their broad dissemination among specialists, have led to major shifts in practice patterns in CLI. There is scant high-quality evidence to guide surgical decision making in this arena, and market forces have exerted profound influences. Despite this, available data suggest that the expected outcomes for both endovascular and open surgery in CLI are strongly dependent on definable patient factors such as anatomic distribution of disease, vein quality, and comorbidities. Optimal patient selection is paramount for maximizing benefit with each technique. This review summarizes some of the existing data and suggests a selective approach to revascularization in CLI, which continues to rely on vein bypass surgery as a primary option in appropriately selected patients.


Delivery at Catholic hospitals and postpartum contraception use, five US states, 2015-2018.
To evaluate whether the prevalence of postpartum contraceptive use was lower among people who delivered at a Catholic hospital compared to a non-Catholic hospital. We linked 2015-2018 Pregnancy Risk Assessment Monitoring System (PRAMS) survey data from five states to hospital information from the corresponding birth certificate file. People with a live birth self-reported their use of contraception methods on the PRAMS survey at 2-6 months postpartum, which we coded into two dichotomous (yes vs. no) outcomes for use of female sterilization and highly-effective contraception (female/male sterilization, intrauterine device, implant, injectable, oral contraception, patch, or ring). We conducted multilevel log-binomial regression to examine the relationship between birth hospital type and postpartum contraception use adjusting for confounders. Prevalence of female sterilization for people who delivered at a Catholic hospital was 51% lower than that of their counterparts delivering at a non-Catholic hospital (adjusted prevalence ratio: 0.49; 95% confidence interval: 0.37-0.65). We found lower use of postpartum female sterilization, but no difference in highly effective contraception overall, for people who delivered at a Catholic hospital compared to a non-Catholic hospital.


Role of Helicobacter pylori serology in evaluating treatment success.
Duodenal ulcer recurrence and gastritis are reduced with successful Helicobacter pylori treatment. Serology is accurate in the diagnosis of H. pylori, but its value in determining eradication is unproved. To evaluate the usefulness of serology in monitoring treatment, we measured serial serum antibodies in three patient groups: eradication success (N = 57), eradication failure (N = 19), and untreated patients (N = 24). Eradication was determined by Warthin Starry staining of antral biopsies and repeat 13C breath tests at six weeks. Subsequent 13C breath tests were then performed at three-month intervals to monitor eradication. IgG antibody concentrations to H. pylori were determined by a commercially available ELISA kit. Serology concentrations remained constant throughout the study period in the untreated patients. IgG concentrations decreased slightly in the treatment failure group at six weeks but thereafter remained at baseline values. In the eradicated group, serum IgG concentrations decreased 26% by three months, 43% by six months and 55% at nine and 12 months (P < 0.001). A 20% reduction in IgG concentrations by six months was associated with successful treatment (sensitivity 86% and specificity 88%). We conclude that serology is a potentially useful way to monitor H. pylori treatment success.


Pharmacological characterization of the human vasopressin receptor subtypes stably expressed in Chinese hamster ovary cells.
Three subtypes of human (h) arginine vasopressin (AVP) receptors, hV1A, hV1B and hV2, were stably expressed in Chinese hamster ovary (CHO) cells and characterized by [3H]-AVP binding studies. In addition, the coupling of the expressed receptor protein to a variety of signal transduction pathways was investigated. Scatchard analysis of saturation isotherms for the specific binding of [3H]-AVP to membranes, prepared from CHO cells transfected with hV1A, hV1B and hV2 receptors, yielded an apparent equilibrium dissociation constant (Kd) of 0.39, 0.25 and 1.21 nM and a maximum receptor density (Bmax) of 1580 fmol mg(-1) protein, 5230 fmol mg(-1) protein and 7020 fmol mg(-1) protein, respectively. Hill coefficients did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Pharmacological characterization of the transfected human AVP receptors was undertaken by measuring the relative ability of nonpeptide AVP receptor antagonists, YM087, OPC-21268, OPC-31260, SR 49059 and SR 121463A, to inhibit binding of [3H]-AVP. At hV1A receptors, the relative order of potency was SR49059>YM087>OPC-31260>SR 121463A> >OPC-21268 and at hV2 receptors, YM087=SR 121463A>OPC-31260>SR 49059> >OPC-21268. In contrast, the relative order of potency, at hV1B receptors, was SR 49059> >SR 121463A=YM087=OPC-31260=OPC-21268. In CHO cells expressing either hV1A or hV1B receptors, AVP caused a concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) with an EC50 value of 1.13 nM and 0.90 nM, respectively. In contrast, stimulation of CHO cells expressing hV2 receptors resulted in an accumulation of cyclic AMP with an EC50 value of 2.22 nM. The potency order of antagonists in inhibiting AVP-induced [Ca2+]i or cyclic AMP response was similar to that observed in radioligand binding assays. In conclusion, we have characterized the pharmacology of human cloned V1A, V1B and V2 receptors and used these to determine the affinity, selectivity and potency of nonpeptide AVP receptor antagonists. Thus they may prove to be a valuable tool in further examination of the physiological and pathophysiological roles of AVP.


[Investigations on the effect of acupuncture on affective and sensory components of pain in patients with different stages of chronic pain].
The aim of the study was to investigate the effects of acupuncture on the affective and sensory experience of pain in chronic pain patients. Furthermore, the study tried to estimate the therapeutical benefit of acupuncture in relation to the stage of chronic pain according to the Mainz pain staging system for chronic pain (MPSS). Patients with chronic pain syndromes who received acupuncture treatment answered a standardized pain questionnaire before and after treatment. The questionnaire included the visual-analogue-scale for the intensity of pain, the pain perception scale for the assessment of affective and sensory components of pain perception, and addressed the patients to the three stages of chronic pain (MPSS). From April 1997 to October 1999, patients (n = 165) suffering from chronic headache and facial pain syndromes (23%), spine associated pain syndromes (48%) or other pain conditions (29%) were subsequently included. Treatment with acupuncture showed a more pronounced reduction of the affective assessment than of the sensory assessment of pain. These effects were particularly pronounced in patients assigned to stage 3 of chronic pain (MPSS). Acupuncture in patients with high-stage chronic pain syndromes preferentially influences the affective dimension of pain perception. For the estimation of the overall clinical outcome of acupuncture treatment, a differentiation between affective and sensory components of pain is recommended.


Correlating intraepithelial papillary capillary loops of vocal cord leukoplakia with histopathology.
The pathology of vocal fold leukoplakia (VFL) was hard to predict before surgery. To investigate the correlation of intraepithelial papillary capillary loops (IPCLs) with the malignant transformation in VFL. The IPCLs in 90 patients were classified according to 2019 Ni classification. Type I-III represented to non- to moderate dysplasia in pathology being viewed as 'benign leukoplasia', type IV-VI represented to severe dysplasia/cancer in situ, cancerization being viewed as 'malignant leukoplasia'. The corresponding relationship of IPCLs with pathology was calculated. Forty-one cases were classified as type I-III, the consistency of type I-III with pathology was 61.0%, with 100.0% of type I, 47.1% of type II and 30.0% of type III. 49 cases were classified as type IV-VI, all were 'malignant leukoplasia', the consistency of type IV-VI and pathology was 100.0%. The accuracy of type I-III, IV-VI to predict pathology were 61.0, 100.0%. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of Ni classification corresponding to 'benign/malignant leukoplasia' was 75.8, 100.0, 82.2, 100.0, 60.0%, respectively. IPCLs of type IV-VI in vocal cord leukoplasia had a close correlation with pathology. The degree of dysplasia was underestimated in type II and type III.


Significance of avian linker histone (H1) polymorphic variation.
Most of avian histone H1 non-allelic subtypes, i.e. eight out of nine, show polymorphic heterogeneity manifested by the presence of two or three allelic variants formed as a result of amino acid deletion and substitution. In addition, some of histone H1 non-allelic subtypes exhibit various allelic complements in different bird species leading to the widening of a whole pool of histone H1 polymorphic variation. A wide range of histone H1 heterogeneity may indicate that the polymorphic variants can individually modulate some histone H1-dependent cellular processes by showing allele-specific influence on chromatin organization and function. Although, the exact way of avian histone H1 allelic variants' activity is not known, their structural separateness inferred from biochemical experiments and relationship with some characteristics of organism functioning disclosed in the genetic studies seem to confirm their importance. The aim of this review is to characterize the molecular origin of histone H1 polymorphisms and draw attention to the link between the histone H1 polymorphic variants and avian organismal features related to the physiological effects of bird individuals' living in the natural and breeding populations.


Dynamic pulmonary MRI using motion-state weighted motion-compensation (MostMoCo) reconstruction with ultrashort TE: A structural and functional study.
To improve the quality of structural images and the quantification of ventilation in free-breathing dynamic pulmonary MRI. A 3D radial ultrashort TE (UTE) sequence with superior-inferior navigators was used to acquire pulmonary data during free breathing. All acquired data were binned into different motion states according to the respiratory signal extracted from superior-inferior navigators. Motion-resolved images were reconstructed using eXtra-Dimensional (XD) UTE reconstruction. The initial motion fields were generated by registering images at each motion state to other motion states in motion-resolved images. A motion-state weighted motion-compensation (MostMoCo) reconstruction algorithm was proposed to reconstruct the dynamic UTE images. This technique, termed as MostMoCo-UTE, was compared with XD-UTE and iterative motion-compensation (iMoCo) on a porcine lung and 10 subjects. MostMoCo reconstruction provides higher peak SNR (37.0 vs. 35.4 and 34.2) and structural similarity (0.964 vs. 0.931 and 0.947) compared to XD-UTE and iMoCo in the porcine lung experiment. Higher apparent SNR and contrast-to-noise ratio are achieved using MostMoCo in the human experiment. MostMoCo reconstruction better preserves the temporal variations of signal intensity of parenchyma compared to iMoCo, shows reduced random noise and improved sharpness of anatomical structures compared to XD-UTE. In the porcine lung experiment, the quantification of ventilation using MostMoCo images is more accurate than that using XD-UTE and iMoCo images. The proposed MostMoCo-UTE provides improved quality of structural images and quantification of ventilation for free-breathing pulmonary MRI. It has the potential for the detection of structural and functional disorders of the lung in clinical settings.


Status gelasticus after temporal lobectomy: ictal FDG-PET findings and the question of dual pathology involving hypothalamic hamartomas.
To present the first ictal fluorodeoxyglucose-positron emission tomography (FDG-PET) evidence of the hypothalamic origin of gelastic seizures in a patient with a hypothalamic hamartoma (HH) and to raise the issue of true dual pathology related to this entity. Ictal FDG-PET was acquired during an episode of status gelasticus with preserved consciousness, in a patient previously operated on for complex partial seizures (CPSs) due to a temporal lobe epileptogenic cyst. Ictal hypermetabolism was localized to the region of the HH during the status gelasticus. CPSs had been completely eliminated after temporal lobe surgery. Ictal FDG-PET independently confirmed that gelastic seizures in patients with HH do originate in the diencephalic lesion. An HH may coexist with another epileptogenic lesion, in a context of dual pathology.


Atlantoaxial Instability Treated with Posterior Atlantoaxial Fixation in Two Siblings with Dyggve-Melchior-Clausen Syndrome.
To discuss the rare association of atlantoaxial instability in patients with the Dyggve-Melchior-Clausen syndrome, a rare autosomal recessive disease characterized by progressive spondyloepimetaphyseal dysplasia and mild to severe mental retardation. We report an uncommon association of two siblings with Dyggve-Melchior-Clausen syndrome, odontoid hypoplasia and atlantoaxial instability. Both the patients were treated with Goel?s atlantoaxial fixation procedure. The patients had a remarkable neurological recovery following the stabilization procedure. Atlantoaxial instability is a potentially life-threatening condition in patients with this syndrome and should be treated early with atlantoaxial stabilization. Recognition and treatment of atlantoaxial instability in patients with Dyggve-Melchior- Clausen syndrome can give gratifying results.


Catalytic phosphorylation using a bifunctional imidazole derived nucleophilic catalyst.
A bifunctional catalyst containing a polyether backbone and a nucleophilic imidazole moiety has been prepared that demonstrates cooperative catalysis in the presence of added group 1 and 2 salts for the phosphorylation of alcohols.


[Loading of the tibiotalar joint and Chopart's joint following subtalar arthrodesis: dynamic cadaver study of 5 specimens].
Little has been known until now about biomechanical intra-articular changes in the condition of adjacent joints following subtalar arthrodeses. We tested 5 cadaver specimens in a dynamic axially loaded foot model under computer-regulated load application on 9 extrinsic tendons of the foot regarding changes in load under native conditions and following an anatomically fixed subtalar arthrodesis. We saw an averaged native force transmission in the talonavicular joint of 87 N, increasing post-arthrodesis to 92 N. In the calcaneocuboid joint we measured an increase from 72 N to 74 N. For peak pressure, the increase was from native 3152 kPa to 3286 kPa in the talonavicular joint and in the calcaneocuboid joint we recorded a reduction from 3282 kPa to 3277 kPa. The effects are not striking from a statistical viewpoint. However, we observed a reduction in force from native 103 N to 90 N and in peak pressure from 4778 kPa to 4261 kPa in the ankle. When the ankle was divided into discrete zones in the sagittal and frontal planes there was no evidence of load displacement. Our measurements show that anatomically fixed arthrodeses of the talocalcanear joint do not lead to any striking increase in loads on adjacent joints. Any adjacent segment degeneration following subtalar arthrodeses may be the result of changes in joint kinematics or non-anatomically reconstructed hindfoot positions.


Socio-demographic and environmental determinants of under-five child mortality in Ethiopia: using Ethiopian demographic and Health 2019 survey.
The under-five mortality rate is a reliable indicator of a country's general level of development and the wellbeing of its children. Life expectancy is a good indicator of a population's standard of living. To identify Socio-demographic and Environmental determinants of under-five child mortality in Ethiopia. A national representative cross sectional study and a quantitative study were conducted among 5753 households selected based on 2019 Mini-Ethiopian Demographic and Health Survey (EDHS-2019) data. The analysis was done using STATA version 14 statistical software. Bivariate and multivariate analyses were used. To assess the determinants of under-five child mortality in multivariate analysis, p values less than 0.05 were considered statistically significant, and odds ratios with 95% CI (confidence interval) were used. A total of 5,753 children were included in the study. Sex of the head of the household being female (AOR = 2:350, 95% CI: 1.310, 4.215), the U5CM for being their mother were currently married (AOR = 2:094, 95% CI: 1.076, 4.072), The odds of U5CM was less by 80% (AOR = 1.797, 95% CI: 1.159-2.782) with the number of under-five children at the household born 2-4th order as compared to those children born on the first order. For the mothers visit anti natal care four and above visit (AOR = 1:803, 95% CI: 1.032, 3.149), for the way of delivery (AOR = 0:478, 95% CI: 0.233, 0.982). Multivariate logistic analysis reflected that way of delivery, mothers had being currently marred, sex of the head of the household and number of antenatal care visit were found to be significant predictors of under-five child mortality. So, government policy, nongovernmental organizations, and all concerned bodies should be focused on the major determinants of under-five child mortality and put in a lot more effort to reduce under-five child mortality.


Erratum to: A prospective observational study comparing a physiological scoring system with time-based discharge criteria in pediatric ambulatory surgical patients.
Erratum to: Can J Anesth/J Can Anesth DOI 10.1007/s12630-015-0428-6. In the published version, the first phrase of the introduction was incorrect and should read as follows: Since the inception of the postanesthesia care unit (PACU) in 1923, the question of when it is safe to discharge a patient has remained contentious. The publisher apologizes most sincerely for this typesetting error.


Hypoxic erythrocytes spark lung leukocyte adhesion.
Erythrocytes are generally expected to passively transit microvascular beds, carrying oxygen but not delivering ROS. In contrast, Kiefmann and colleagues report in this issue of Blood that, in hypoxic lungs, erythrocytes release ROS, activate endothelium, and trigger leukocyte accumulation.


Studies on biology and genomic characterization of a caulimo-like virus associated with a leaf distortion disease of Lamium maculatum.
A virus associated with leaf distortion of Lamium maculatum had features characteristic of caulimoviruses. The viral genome (Genbank accession number: EU554423) is 7,713 bp in size, with six open reading frames similar in size and organization to those of known caulimoviruses. Phylogenetic analyses based on the conserved ORF V polyprotein coding region indicated that the Lamium virus is a possible new member of the genus Caulimovirus. The virus was not transmitted by mechanical or graft inoculation, or by Myzus persicae. Because proof of pathogenicity remains to be demonstrated, the virus was named provisionally Lamuim leaf distortion-associated virus (LLDAV).


Application of time-dependent sessile drop contact angles on compacts to characterise the surface energetics of sulfathiazole crystals.
The time-dependent wetting of sulfathiazole compacts with sessile water drops was evaluated using video microscopy. The influence of sulfathiazole crystalline form, particle size, pre-saturation with water, humidity and compaction pressure on the droplet spreading kinetics and contact angles are reported. The rate and extent of droplet spreading decreased for compact surfaces of high microscopic roughness; this was determined by atomic force microscopy (AFM). Pre-saturation of powder compacts with water (pre-saturated with sulfathiazole) enhanced droplet spreading and enabled pseudo-equilibrium contact angles to be determined for up to 10 min. Sessile-drop contact angles on both sulfathiazole powder compacts and single crystals are compared with particle contact angles determined by liquid penetration. This study has led to an improved understanding of the influence of physical heterogeneities and the face-specific surface chemistry of individual crystals on the wetting characteristics of pharmaceutical compacts.


Influence of stent properties on the alteration of cerebral intra-aneurysmal haemodynamics: flow quantification in elastic sidewall aneurysm models.
Stent implantation across the neck of cerebral aneurysms may induce intra-aneurysmal flow reduction, and consequently saccular thrombosis and vessel wall repair. To analyse the influence of different stent parameters on such flow reduction, we studied the flow changes in vascular models, induced by a series of stents. Two different neck-sized elastic sidewall aneurysm models were connected to a circulatory loop. Twenty different stents were introduced in both models to analyse the effect of their parameters, such as porosity, filament diameter and permeability. Flow patterns were visualized by using glass particles and laser sheet translumination. The digitally recorded data were transferred for computer analysis. The changes of the vortex velocity for each stent model combination were investigated and statistically evaluated. Intra-aneurysmal flow analysis showed dispersion of the vortices of a variable degree, and velocity reduction of 30% mean in model 1 and 49% mean in model 2. By statistical analysis three groups of stents ('best', 'medium', 'worst') were identified, according to their haemodynamic efficacy. No correlations were observed between the haemodynamic performance of the stents and the porosity, filament diameter and permeability values separately. The stent effects were on average more important in the large-necked than in the small-necked aneurysm model. Stent implantation induces intra-aneurysmal loss of vortex coherence and flow reduction. The analysed stent parameters show complex interrelationship, including also stent 'design'. The difference in the haemodynamic efficacy of the individual stents between the two models raises the question of 'stent positioning effects'.


Effects of a microbial muramidase on the growth performance, intestinal permeability, nutrient digestibility, and welfare of broiler chickens.
The objective of these studies was to evaluate the inclusion of a microbial muramidase (MUR) in the diets of broiler chickens on the growth performance, intestinal permeability (IP), total blood carotenoid content, apparent ileal digestibility (AID), and foot pad dermatitis (FPD). In Experiment 1, a total of 1,000 one-day-old chicks were placed in floor-pens with reused litter, and randomly distributed into 4 treatments with 10 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 15,000; 25,000 or 35,000 LSU (F)/kg of MUR. Feed intake (FI), body weight gain (BWG), and feed conversion ratio (FCR) were evaluated at d 21 and 43. Intestinal permeability was evaluated on d 35 by FITC-d, and FPD and AID on d 43. In Experiment 2, a total of 800 one-day-old chicks were placed in floor-pens with fresh litter, and randomly distributed into 4 treatments with 8 replicates each. Treatments were a basal diet (control), or basal diet supplemented with 25,000 or 35,000 LSU (F)/kg of MUR, and a fourth group where the basal diet was supplemented with enramycin. The birds were induced to a mild intestinal challenge. Feed intake, BWG, and FCR were evaluated on d 21 and d 42, and total blood concentration of carotenoids was evaluated on d 28. In experiment 1, 35,000 LSU (F)/kg of MUR promoted the best FCR (P < 0.05). Muramidase supplementation linearly increased the AID of dry matter, ash, and fat (P < 0.01), and regardless of the dose, MUR decreased the IP (P < 0.05). In Experiment 2, the supplementation of 35,000 LSU (F)/kg of MUR improved BWG and FCR in the entire cycle (1-42 d) and increased the concentration of carotenoids in the blood on d 28 compared to the control group (P < 0.05). These studies show that MUR improves growth performance of broilers by improving intestinal permeability, digestibility of dry matter, ash and fat, absorption of carotenoids, and reducing FPD.


Predictors of functional disability in mild cognitive impairment and dementia.
Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible predictors. The aim of this study was to identify predictors of functional disability in patients with MCI and dementia. Cross-sectional cohort study. Data from patients who visited a memory clinic between 2011 and 2015 were evaluated. The Disability Assessment for Dementia (DAD) was used to assess functional disability. Patients diagnosed with MCI or dementia and with a DAD score available were included. This led to the inclusion of 474 patients. Univariate analyses with a broad range of variables were performed to detect factors that had a significant relationship to the DAD score. Age, gender and variables with a p-value of 0.1 or lower in the univariate analyses were taken into a multivariable analysis. This multiple linear regression analysis was performed to determine which variables were independently associated with the DAD score. Our multivariable model explained 42% of the variance in the DAD score. Independent predictors of the DAD score were age (B=0.03, 95%CI=0.002-0.05), gender (B=-0.43, 95%CI=-0.78 to -0.07), score on the Clinical Dementia Rating scale (CDR) (B=1.53, 95%CI=1.07-1.99 for CDR 1, B=2.93, 95%CI=2.28-3.58 for CDR 2, B=3.96, 95%CI=2.65-5.27 for CDR 3) and level of physical activity (B=0.56, 95%CI=0.05-1.07). Older age, male gender, higher CDR score and lower levels of physical activity are independent predictors of functional disability in MCI and dementia.


Efficacy of free flap reconstruction of the head and neck in patients 90 years and older.
To determine the efficacy of free flap reconstruction in patients 90 years and older. Retrospective medical chart review. Academic medical center. Patients 90 years and older who underwent a free flap reconstruction from 2002 through 2011 were identified. Clinical, demographic, and procedural data were recorded. Complications of surgery were either medical or flap related. Long-term follow-up was recorded to determine late flap complications, donor site morbidity, and functional outcomes. Of 847 free flaps, 10 (1.2%) were performed in patients 90 years and older, with a median follow-up time of 8.5 months. Four medical complications (40%) occurred (1 case of pneumonia and 3 cases of arrhythmia). There were no mortalities. Two recipient site complications (20%) occurred (1 infection and 1 fistula). The flap failure rate was 0%. One late complication developed 7 months postoperatively involving infection and nonunion of the mandibular reconstruction. There was donor site morbidity in 1 patient. Functional status returned to baseline in 8 patients (80%) at the last follow-up visit. Medical and flap-related complications in patients 90 years and older are consistent with rates previously reported in elderly patients. Furthermore, patients 90 years and older can tolerate free flap reconstruction with favorable long-term outcomes.


Towards a four-dimensional analysis of meteorological data.
Rapid advances in the gathering of meteorological data and the design of atmospheric models are making the conventional two-dimensional analysis inadequate. This article describes some progress towards a four-dimensional analysis system.


A predominantly articular cartilage-associated gene, SCRG1, is induced by glucocorticoid and stimulates chondrogenesis in vitro.
Cartilage tissue engineering using multipotential human mesenchymal stem cells (hMSCs) is a promising approach to develop treatment for degenerative joint diseases. A key requirement is that the engineered tissues maintain their hyaline articular cartilage phenotype and not proceed towards hypertrophy. It is noteworthy that osteoarthritic articular cartilage frequently contains limited regions of reparative cartilage, suggesting the presence of bioactive factors with regenerative activity. Based on this idea, we recently performed cDNA microarray analysis to identify genes that are strongly expressed only in articular cartilage and encode secreted gene products. One of the genes that met our criteria was SCRG1. This study aims to analyze SCRG1 function in cartilage development using an in vitro mesenchymal chondrogenesis system. Full-length SCRG1 cDNA was subcloned into pcDNA5 vector, and transfected into hMSCs and murine C3H10T1/2 mesenchymal cells, placed in pellet cultures and micromass cultures, respectively. The cultures were analyzed by reverse transcription-polymerase chain reaction for the expression of SCRG1 and cartilage marker genes, and by histological staining for cartilage phenotype. Induction of SCRG1 expression was seen during in vitro chondrogenesis, and was dependent on dexamethasone (DEX) known to promote chondrogenesis. Immunohistochemistry revealed that SCRG1 protein was localized to the extracellular matrix. Forced expression of SCRG1 in hMSCs suppressed their proliferation, and stimulated chondrogenesis in C3H10T1/2 cells, confirmed by reduced collagen type I and elevated collagen type IIB expression. These results suggest that SCRG1 is involved in cell growth suppression and differentiation during DEX-dependent chondrogenesis. SCRG1 may be of utility in gene-mediated cartilage tissue engineering.


Novel fluorinated derivative of curcumin negatively regulates thioredoxin-interacting protein expression in retinal pigment epithelial and macrophage cells.
Thioredoxin-interacting protein (TXNIP) has multiple disease-associated functions including inducing oxidative stress by inhibiting the anti-oxidant and thiol reducing activity of thioredoxin (TRX), reducing cellular glucose transport, and is a component of the activated inflammasome complex. Increased expression of TXNIP is encountered in diabetic conditions of high glucose. Curcumin and chemical derivatives have multiple therapeutic properties as anti-inflammatories, anti-oxidants, amyloid aggregation inhibitors and modulate a number of cellular signaling pathways. Using a fluorinated-derivative of curcumin (designated Shiga-Y6), we showed significant inhibition of TXNIP mRNA and protein expression, and induction of TRX mRNA and protein in ARPE-19 retinal pigment epithelial cells and THP-1-derived macrophages, while the non-fluorinated structural equivalent (Shiga-Y52) and native curcumin did not show these same effects. Shiga-Y6 was effective in reducing high glucose, endoplasmic reticulum stress-induced TXNIP in ARPE-19 cells, and reducing lipopolysaccharide and endoplasmic stress-induced proinflammatory gene expression in THP-1 macrophages. Moreover, TXNIP-knockdown experiments showed that the anti-inflammatory effect of Shiga-Y6 in LPS-stimulated THP-1 macrophages was TXNIP-independent.


The effect of an antibacterial drug on urinary calcium, magnesium and phosphorus excretion in patients with neurogenic bladder.
The effect of the simultaneous administration of hexamine mandelate and methionine on the urinary excretion of calcium, magnesium and phosphate is reported in 3 groups of paraplegic patients. Long-term therapy with G 500 increases bone loss in paralysed patients, and is contra-indicated when there is infection of the urinary tract by urea-splitting organisms.


Isolated mitral valve repair in patients with depressed left ventricular function.
The utility of mitral valve repair (MV repair) has been well documented in patients with normal left ventricular function. Few studies, however, have specifically examined outcomes of isolated MV repair in patients with decreased left ventricular function. The purpose of the present study is to review a modern experience with isolated MV repair in patients with depressed left ventricular function and to examine intermediate outcomes. A retrospective review of patients who underwent MV repair from 1996 to 2003 was performed to identify consecutive patients who had isolated MV repair. Preoperative studies were reviewed to further identify patients with an ejection fraction less than 0.45. Clinical operative data were collected from the medical record, and survival was determined with the Social Security Death Index. Further end points of reoperation and transplantation were also noted. A total of 101 patients were identified with a mean follow-up of 1,124 days. Mean ejection fraction and age was 0.34 +/- 0.09 and 56 +/- 14 years, respectively. Thirty-day mortality was 2.9%. One- and 5-year survival was 94% +/- 2% and 70% +/- 6%, respectively. There was no statistically significant difference in actuarial survival for functional versus primary mitral disease, or for ejection fraction less than 0.35 versus greater than 0.35. Six patients required transplantation. Five-year freedom from reoperation, transplantation, and death was 61% +/- 11% and 54% +/- 8% for patients with primary and secondary mitral valve disease, respectively (p = 0.279). Minimally invasive MV repair was performed in 57 patients with a mean ejection fraction of 0.369 +/- 0.07 and a 30-day mortality of 1.7%. In patients with isolated MV regurgitation and depressed left ventricular function, MV repair can be achieved with low operative mortality, but there remains a persistent risk of death, reoperation, or transplantation irrespective of valve disease. Minimally invasive MV repair was safe in this group.


CRISPR Critters and CRISPR Cracks.
This essay focuses on possible nonhuman applications of CRISPR/Cas9 that are likely to be widely overlooked because they are unexpected and, in some cases, perhaps even "frivolous." We look at five uses for "CRISPR Critters": wild de-extinction, domestic de-extinction, personal whim, art, and novel forms of disease prevention. We then discuss the current regulatory framework and its possible limitations in those contexts. We end with questions about some deeper issues raised by the increased human control over life on earth offered by genome editing.


Effects of the menstrual cycle on injection pain due to rocuronium.
To investigate the effect of the menstrual cycle on rocuronium injection pain. Prospective, randomized, double-blinded study. Academic medical center. 80 ASA physical status 1 and 2 women scheduled for elective surgery with general anesthesia. Patients were divided into two groups according to their time in the menstrual cycle. Forty patients at days 8 to 12 of the menstrual cycle were considered to be at the follicular phase (Group F), and 40 patients at days 20 to 24 of the menstrual cycle were considered to be at the luteal phase (Group L).Withdrawal movements were recorded. Overall frequency of withdrawal movements was significantly higher in Group L than Group F (P < 0.001). The mean withdrawal movement score was 1.77 ± 0.76 in Group L and 0.52 ± 0.67 in Group F. Menstrual cycle phases affect the severity of rocuronium injection pain. Women exhibit greater pain sensitivity from rocuronium injection in the luteal phase than the follicular phase.


Multiple neural circuits mediating airway sensations: Recent advances in the neurobiology of the urge-to-cough.
The respiratory system is densely innervated by sensory neurons arising from the jugular (superior) and nodose (inferior) vagal ganglia. However, a distinction exists between jugular and nodose neurons as these ganglia developmentally originate from the neural crest and the epibranchial placodes, respectively. This different embryological origin underpins an important source of heterogeneity in vagal afferent biology, and may extend to include fundamentally different central neural circuits that are in receipt of jugular versus nodose afferent inputs. Indeed, recent studies using viral tract tracing and human brain imaging support the notion that airway sensors contribute inputs to multiple central circuits. Understanding the neural pathways arising from the airways and lungs may provide novel insights into aberrant sensations, such as the urge-to-cough, characteristic of respiratory disease.


In vivo scintigraphic imaging of proteoglycans.
In this chapter, we present the methods developed in our lab for the scintigraphic imaging and direct quantitative evaluation of proteoglycan (PG) distribution in vivo. These methods relate to (1) the synthesis and radiolabeling of the NTP 15-5 with (99m)Tc, (2) preclinical scintigraphic imaging using laboratory animals, and (3) quantitative analysis of scintigraphic images.