Evaluation of the bacterial ocular surface microbiome in clinically normal cats before and after treatment with topical erythromycin.
The ocular surface microbiome of veterinary species has not been thoroughly characterized using next generation sequencing. Furthermore, alterations in the feline ocular surface microbiome over time or following topical antibiotic treatment are unknown. Aims of this study were to further characterize the ocular surface microbiome of healthy cats and to identify whether there are microbial community changes over time and following topical antibiotic use. Twenty-four eyes from twelve adult, research-bred, female spayed domestic shorthaired cats were evaluated. Erythromycin ophthalmic ointment (0.5%) was applied to the ocular surface of one randomly assigned eye per cat three times daily for 7 days, while the fellow eye served as an untreated control. The ocular surface was sampled by swabbing the inferior conjunctival fornix of both eyes prior to initiating treatment (day 0), after 1 week of treatment (day 7), and 4 weeks after concluding treatment (day 35). Genomic DNA was extracted from the swabs and sequenced using primers that target the V4 region of bacterial 16S rRNA genes. At baseline, the most common bacterial phyla identified were Proteobacteria (42.4%), Firmicutes (30.0%), Actinobacteria (15.6%), and Bacteroidetes (8.1%). The most abundant bacterial families sequenced were Corynebacteriaceae (7.8%), Helicobacteraceae (7.5%), Moraxellaceae (6.1%), and Comamonadaceae (5.6%). Alpha and beta diversity measurements were largely unchanged in both treatment and control eyes over time. However, univariate and linear discriminant analyses revealed significant and similar changes in the abundance of some bacterial taxa over time in both treatment and control eyes. Overall, the feline ocular surface microbiome remained stable over time and following topical antibiotic therapy.


Development of a Video Coding Scheme for Understanding Human-Computer Interaction and Clinical Decision Making.
The usability of healthcare information technology has become a major issue in health informatics. There have been many reports of systems that have been deemed unusable by end users such as clinicians and a growing body of usability studies have been reported in the literature. The issue of how to fruitfully analyze and code usability study data in a meaningful way that can lead to optimized and more efficient systems has remained to be fully detailed. In this paper we describe our work in developing and organizing a principled video coding scheme that builds from our previous work in a couple of areas. We include video coding categories we have developed for understanding problems and issues with human-computer interaction. In addition, we integrate this coding scheme with categories we have used to characterize human cognition, such as clinical reasoning and decision making, in isolation of technology use. The resultant new scheme thus incorporates coding categories that can used to evaluate both usability issues (applying categories from human-computer interaction) and human cognition, in order to assess the impact of technology on clinical reasoning and decision making.


Early Advanced Weight-Bearing After Periarticular Fractures: A Randomized Trial Comparing Antigravity Treadmill Therapy Versus Standard of Care.
In current clinical practice, weight-bearing is typically restricted for up to 12 weeks after definitive fixation of lower extremity periarticular fractures. However, muscle atrophy resulting from restricting weight-bearing has a deleterious effect on bone healing and overall limb function. Antigravity treadmill therapy may improve recovery by allowing patients to safely load the limb during therapy, thereby reducing the negative consequences of prolonged non-weight-bearing while avoiding complications associated with premature return to full weight-bearing. This article describes a multicenter randomized controlled trial comparing outcomes after a 10-week antigravity treadmill therapy program versus standard of care in adult patients with periarticular fractures of the knee and distal tibia. The primary hypothesis is that, compared with patients receiving standard of care, patients receiving antigravity treadmill therapy will report better function 6 months after definitive treatment.


[Endoscopic intubation of the trachea in emergencies].
The article presents the results of performing endoscopic intubation of the trachea under emergency situations in patients and victims of traumatic and pyo-inflammatory alterations of organs and tissue of the neck. The technique of the trachea intubation is described. It was noted that in such patients there appear serious problems during the intubation of the trachea by the method of direct laryngoscopy which are due to considerable disturbances of the anatomo-topographic interrelations of the organs, marked edema of the tissues and by the presence of the pathological content in the lumen of the oro- and laryngopharynx. The trachea intubation performed under the control of vision with the help of a bronchofibroscope allows to avoid additional traumatization of the tissue of the oro- and laryngopharynx, to rapidly introduce the endotracheal tube into the trachea without hypoxia, to perform sanitation of the oral cavity, pharynx and the tracheobronchial tree.


Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion.
Insights into the role of the astrocyte intermediate filament protein, glial fibrillary acidic protein (GFAP), have only recently emerged with reports on subtle abnormalities in GFAP-deficient mice, including the documentation of defective long-term maintenance of central nervous system myelination. Here, we extend these observations by examining the astroglial response in GFAP-/- mice with autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Clinically, the monophasic disease was more severe in GFAP-/- mice than in wild-type littermates despite increased remyelination in the former. More in keeping with the clinical course was the observation of an infiltrative EAE lesion in GFAP-/- mice. GFAP-/- astrocytes had a reduced cytoarchitectural stability as evidenced by less abundant and irregularly spaced hemidesmosomes. The blunt GFAP-/- astrocyte processes possessed intermediate filaments consisting mainly of vimentin, though to a lesser degree than in the wild-type. In contrast, in wild-type littermates, GFAP was most abundant and nestin occurred at lower levels. Taken together, the present study introduces the novel concepts that GFAP plays an important role in the control of clinical disease associated with formation of a clearly defined edge to the EAE lesion and that GFAP is operative in the regulation of the intermediate filament components in reactive fibrillary astrogliosis.


Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.
Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and shares homology with ancestral serine proteinase cascades that are involved in, for example, Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. In the present study, we show that the induction of coagulation by bacteria leads to immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via cross-linking of bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice developed severe signs of pathologic inflammation at the local site of infection, and fXIII treatment of wild-type animals dampened bacterial dissemination during early infection. Bacterial killing and cross-linking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis, supporting the concept that coagulation is part of the early innate immune system.


Connecting the Dots from Professional Development to Student Learning.
Following professional development (PD), implementation of contemporary topics into high school biology requires teachers to make critical decisions regarding integration of novel content into existing course scope and sequence. Often exciting topics, such as neuroscience, do not perfectly align with standards. Despite commitment to enacting what was learned in the PD, teachers must adapt novel content to their perceptions of good teaching, local context, prior knowledge of their students, and state and district expectations. How teachers decide to integrate curricula encountered from PD programs may affect student outcomes. This mixed-methods study examined the relationship between curricular application strategies following an inquiry-based neuroscience PD and student learning. Post-PD curricular implementation was measured qualitatively through analysis of teacher action plans and classroom observations and quantitatively using hierarchical linear modeling to determine the impact of implementation on student performance. Participation in neuroscience PD predicted improved student learning compared with control teachers. Of the two distinct curricular implementation strategies, enacting a full unit produced significantly greater student learning than integrating neuroscience activities into existing biology units. Insights from this analysis should inform teacher implementation of new curricula after PD on other contemporary biology topics.


Characteristics of low-nitrite pork emulsified-sausages with paprika oleoresin solution during refrigerated storage.
The objective of this study was to evaluate quality characteristics of low-nitrite emulsified-sausages (ESs, < 75 ppm) containing paprika oleoresin solution (POS) for replacing sodium nitrite (NaNO2). Pork ESs were prepared with four treatments (reference (REF), 150 ppm NaNO2; TRT1, 0 ppm NaNO2 + 0.1% POS; TRT2, 37.5 ppm NaNO2 + 0.1% POS; and TRT3, 75 ppm NaNO2 + 0.1% POS). The physicochemical and texture properties, microbial counts, residual nitrite and thiobarbituric acid reactant substances (TBARS) were measured during refrigerated storage of 35 days. Although TRT2 and TRT3 had lower levels of NaNO2, they had higher redness and yellowness than REF (p < 0.05). Microbial counts of total bacterial counts and Enterobacteriaceae of TRT2 and TRT3 were similar to those of REF (p > 0.05). Expressible moisture percentages (EM, %) of TRT2 and TRT3 were lower than those of REF (p < 0.05). TBARS values of TRT2 and TRT3 were not different from those of REF (p > 0.05). Among treatments, TRT1 had the highest TBARS values (p < 0.05). In conclusion, 0.1% POS in combination with 37.5 ppm NaNO2 would have quality characteristics similar to those of REF. Therefore, approximately 3/4 of the initial nitrite level could be replaced with 0.1% POS, and eventually developed healthier pork products.


Fiber-Content Measurement of Wool-Cashmere Blends Using Near-Infrared Spectroscopy.
Cashmere and wool are two protein fibers with analogous geometrical attributes, but distinct physical properties. Due to its scarcity and unique features, cashmere is a much more expensive fiber than wool. In the textile production, cashmere is often intentionally blended with fine wool in order to reduce the material cost. To identify the fiber contents of a wool-cashmere blend is important to quality control and product classification. The goal of this study is to develop a reliable method for estimating fiber contents in wool-cashmere blends based on near-infrared (NIR) spectroscopy. In this study, we prepared two sets of cashmere-wool blends by using either whole fibers or fiber snippets in 11 different blend ratios of the two fibers and collected the NIR spectra of all the 22 samples. Of the 11 samples in each set, six were used as a subset for calibration and five as a subset for validation. By referencing the NIR band assignment to chemical bonds in protein, we identified six characteristic wavelength bands where the NIR absorbance powers of the two fibers were significantly different. We then performed the chemometric analysis with two multilinear regression (MLR) equations to predict the cashmere content (CC) in a blended sample. The experiment with these samples demonstrated that the predicted CCs from the MLR models were consistent with the CCs given in the preparations of the two sample sets (whole fiber or snippet), and the errors of the predicted CCs could be limited to 0.5% if the testing was performed over at least 25 locations. The MLR models seem to be reliable and accurate enough for estimating the cashmere content in a wool-cashmere blend and have potential to be used for tackling the cashmere adulteration problem.


Fractionation of beta-Lactoglobulin from whey by mixed matrix membrane ion exchange chromatography.
Mixed matrix membranes (MMMs), which incorporate adsorptive particles during membrane casting, can be prepared simply and have performances that are competitive with other membrane chromatography materials. The application of MMM chromatography for fractionation of beta-Lactoglobulin from bovine whey is described in this article. MMM chromatography was prepared using ethylene vinyl alcohol polymer and lewatit anion exchange resin to form a flat sheet membrane. The membrane was characterized in terms of structure and its static and dynamic binding capacities were measured. The optimum binding for beta-Lactoglobulin was found to be at pH 6.0 using 20 mM sodium phosphate buffer. The MMM had a static binding capacity of 120 mg/g membrane (36 mg/mL membrane) and 90 mg/g membrane (27 mg/mL membrane) for beta-Lactoglobulin and alpha-Lactalbumin, respectively. In batch fractionation of whey, the MMM showed selective binding towards beta-Lactoglobulin compared to other proteins. The dynamic binding capacity of beta-Lactoglobulin in whey solution was about 80 mg/g membrane (24 mg beta-Lac/mL of MMM), which is promising for whey fractionation using this technology. This is the first reported application of MMM chromatography to a dairy feed stream.


RNA polyadenylation sites on the genomes of microorganisms, animals, and plants.
Pre-messenger RNA (mRNA) 3'-end cleavage and subsequent polyadenylation strongly regulate gene expression. In comparison with the upstream or downstream motifs, relatively little is known about the feature differences of polyadenylation [poly(A)] sites among major kingdoms. We suspect that the precise poly(A) sites are very selective, and we therefore mapped mRNA poly(A) sites on complete and nearly complete genomes using mRNA sequences available in the National Center for Biotechnology Information (NCBI) Nucleotide database. In this paper, we describe the mRNA nucleotide [i.e., the poly(A) tail attachment position] that is directly in attachment with the poly(A) tail and the pre-mRNA nucleotide [i.e., the poly(A) tail starting position] that corresponds to the first adenosine of the poly(A) tail in the 29 most-mapped species (2 fungi, 2 protists, 18 animals, and 7 plants). The most representative pre-mRNA dinucleotides covering these two positions were UA, CA, and GA in 17, 10, and 2 of the species, respectively. The pre-mRNA nucleotide at the poly(A) tail starting position was typically an adenosine [i.e., A-type poly(A) sites], sometimes a uridine, and occasionally a cytidine or guanosine. The order was U>C>G at the attachment position but A>>U>C≥G at the starting position. However, in comparison with the mRNA nucleotide composition (base composition), the poly(A) tail attachment position selected C over U in plants and both C and G over U in animals, in both A-type and non-A-type poly(A) sites. Animals, dicot plants, and monocot plants had clear differences in C/G ratios at the poly(A) tail attachment position of the non-A-type poly(A) sites. This study of poly(A) site evolution indicated that the two positions within poly(A) sites had distinct nucleotide compositions and were different among kingdoms.


Hair follicle stem cell marker nestin expression in regenerating hair follicles of patients with alopecia areata.
Cells that are nestin positive and keratin 15 (K15) negative are located in the hair follicle pluripotent stem cell (hfPS) area (hfPSA). The hfPSA is located within the root of the sebaceous glands, in a region just above the hair follicle bulge area. In the current study, we investigated the expression pattern of the stem cell marker nestin in the hair follicle cycling of patients with alopecia areata. In the normal human scalp, the majority of hair follicles are in the anagen phase of development. While it is often difficult to identify nestin expression in late anagen phases, nestin-expressing cells are easily identified in proliferating cells located in the hfPSA of the growing early and middle anagen phase hair follicles. In patients exhibiting alopecia areata, the middle anagen hair follicles with growing cells were found to be nestin positive and K15 negative. In contrast, the hair follicles undergoing degradation in alopecia areata patients demonstrated lymphocytic infiltration within the nestin- and K15-negative dermal papilla cells. Both the nestin-positive hfPSA and K15-positive hair follicle bulge areas were not damaged in all phases. In addition, the regenerating early anagen hair follicles demonstrated nestin-positive and K15-negative cells within the dermal papilla and in the area surrounding the hair bulb. These results suggest that the nestin-positive cells play an important role not only in the hfPSA, but also in the dermal papilla in the regenerating hair follicle.


Tetralogy of Fallot. The spectrum of severity in a regional study, 1981-1985.
The combined medical and surgical mortality rate for 125 infants with tetralogy of Fallot registered in the Baltimore-Washington Infant Study from 1981 to 1985 was 28% (mean age at follow-up for living infants, 40 months). Despite early diagnosis and successful early repair in many infants, significant risk factors for death included pulmonary atresia, major additional cardiac anomalies, major noncardiac malformations, low birth weight, and prematurity. There is a wide spectrum of severity, ranging from infants with isolated tetralogy and no risk factors who have an excellent prognosis to infants with three or more risk factors and a high probability of neonatal death. Further treatment advances will improve outcome in some, but not all, infants. A regional all-inclusive study of a specific cardiac defect can define research and treatment challenges not obvious from selected clinical series.


Clinical features and outcomes of 84 COVID-Positive hemodialysis patients in a resource poor setting from India.
With the declaration of severe acute respiratory syndrome novel coronavirus-2019 as pandemic by the World Health Organization on March 11, 2020, there has been a steady rise in number of cases. Chronic kidney disease and dialysis population are risk factors for increased severity of illness. Literature about the coronavirus disease 2019 (COVID-19) in dialysis population is scarce. Management of COVID-19 patients in resource poor setting in a developing country does vary compared to developed nations. Nonavailability of the advanced laboratory facility and the newer medicines forces the treating team to manage the patients with available investigations and drugs. We aimed at analysis of clinical characteristics and outcomes of 84 patients on maintenance hemodialysis (HD). Data of all COVID-positive patients on maintenance HD, who were referred to our center were collected. All patients were given HD on NIKISSO machines. Outcomes of all the admitted patients were analyzed. Maintenance HD group formed majority of the kidney referrals (54%). Age group that was commonly affected was >50 years. Factors associated with mortality were age, diabetes, thrombocytopenia, prolonged baseline activated partial thromboplastin time, admission hypoxemia, high qSOFA score. Institutional Ethics Committee approval has been obtained for the study. Methodology of the study was in accordance with the Declaration of Helsinki. Verbal consent was obtained from patients/ attendants. In the ongoing COVID pandemic, in a developing nation where resources are constrained, it is difficult to salvage the critically ill patients. With the drugs available and the changing strategies, treatment was given to all the patients admitted with bedside renal replacement therapies. Our mortality rate was high compared to other studies due to delay in referral, admission hypoxemia, and late initiation of steroids.


Diabetes services in Yugoslavia.
The Socialist Federal Republic of Yugoslavia lies in south east Europe between the Soviet block and the free enterprise countries of Western Europe. It was originally established as a confederation of independent Balkan states after the first world war; after the second world war it became an independent federation of the socialist republics of Bosnia, Herzegovnia, Montenegro, Croatia (including Dalmatia), Slovenia, and Serbia, together with the two small autonomous provinces of Kosovo and Vojvodina. In the subsequent 30 years the trend towards decentralised decision making and institutional self management has continued. Nevertheless, the federal authorities retain major control over economic decision making and policies. For example, they forbid anyone from owning more than two houses or 10 hectares of land, and no factory owner may employ more than 10 people. Capitalism in any other than this minor form is not allowed, and any businessman whose business expands must become involved in frustrating negotiations with the local government to set up a state industry. I recently visited Yugoslavia as a guest of the Institute for Diabetes, Endocrinology, and Metabolic Diseases and of the medical faculty of the University of Zagreb and visited various health care units which provide services for diabetics in Croatia. As well as Zagreb itself I visited units in Split on the Adriatic coast and at Varazdin, near the Hungarian border. Necessarily my observations are based on the diabetes services in Croatia, but although the other republics may have less developed services they follow similar principles.


Insulin resistance is an independent predictor of erectile dysfunction in patients with gout.
Gout is associated with metabolic disorders that are important risk factors for cardiovascular disease and erectile dysfunction (ED). We aimed to identify independent predictors of ED in patients with gout. From August 2014 to August 2015, male outpatients who were being treated for gout in our rheumatology clinic and healthy males without any history of inflammatory disease (control group) were studied. ED was assessed in participants using the five-item version of the International Index of Erectile Function questionnaire. Insulin resistance (IR) was estimated using the homeostatic model assessment (HOMA-IR). Logistic regression analysis was performed to determine the effect of variables on ED risk in all of the study subjects and in patients with gout. We analyzed 80 patients with gout and 70 healthy controls. The median age of patients with gout was 52 years and median disease duration was 120 months. Gout patients were more likely to have ED than controls (55.3% vs. 41.4%, p < 0.047). After adjustment for confounding factors, only HOMA-IR was significantly associated with ED (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.05 to 3.15). Gout patients with ED were more likely to be older (p < 0.001), have higher HOMA-IR (p = 0.048), and have lower glomerular filtration rate (p = 0.038) than those without ED. Multivariate logistic regression analysis showed that HOMAIR was an independent predictor for ED (OR, 1.62; 95% CI, 1.03 to 2.82) in gout patients. IR is an independent predictor of ED in patients with gout.


Anti-interleukin-6 (tocilizumab) therapy in Takayasu's arteritis: a real life experience.
Tumour necrosis factor inhibitors and anti-interleukin-6 (anti-IL-6) therapies are increasingly being used in Takayasu's arteritis (TA) patients who are unresponsive to corticosteroids ± conventional immunosuppressive agents. The aim of this study is to assess the efficacy and safety of anti-IL-6 (tocilizumab) therapy in refractory TA patients in real life. Fifteen TA patients (86.7% were female) who received at least 3 cycles of tocilizumab therapy were retrospectively assessed by clinical, laboratory, and radiological evaluations before and after tocilizumab therapy. The median (min-max) age of the patients at evaluation was 35 (20-58) years and the median disease duration from diagnosis was 24 (12-168) months. The median (min.-max.) duration of follow-up after tocilizumab was 15 (3-42) months. There was a significant decrease in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and patient global visual analogue scale (VAS) scores of patients after tocilizumab therapy. The median (min.-max.) ESR was 26 (5-119) vs. 3 (2-49) mm/h, P = 0.02; CRP was 39.8 (2.4-149.0) vs. 7.9 (0-92.9) mg/L, P = 0.017; and patient global VAS was 50 (0-90) vs. 30 (0-60), P = 0.027, respectively. In 8 patients, ESR and CRP levels were in the normal range in the last control. Imaging modality results after tocilizumab were available for 9 patients; 8 patients were radiologically stable and regression was seen in 1 patient. Comparable imaging modality results before and after tocilizumab were available for 5 patients; 4 patients were radiologically stable and regression was seen in 1 patient. Radiological findings were consistent with laboratory responses. Glucocorticoid dosages decreased from a mean dosage of 16.2 (9.1) mg/day at baseline to 7.1 (3.8) mg/day (P = 0.001) at the last follow-up visit. There was no increase in the steroid dosage in any of the patients. All patients tolerated tocilizumab well. Based on retrospective real life data, anti-IL-6 (tocilizumab) appears to be an effective and tolerable treatment option in refractory TA patients.


[Helicobacter pylori Eradication Therapy and Gastric Cancer Prevention].
Gastric cancer is the most common cancer in Korea and the fifth most common cancer globally. Helicobacter pylori (H. pylori) infection is considered the main etiologic agent for gastric cancer development. Most regional guidelines for H. pylori treatment recommend treating the organism to prevent gastric cancer in the high-risk group. However, evidence that such a strategy can also be applied to the general population, especially in terms of the preventive effect and safety, has not been adequately presented yet. Although a meta-analysis in the general population suggested effectiveness in decreasing gastric cancer incidence, individual studies should be critically reviewed to evaluate the soundness of the evidence. Recently published, long-term, Korean studies on metachronous gastric cancer prevention ended the controversies from previous short-term studies and confirmed the effectiveness. Currently, further prospective, large, randomized studies are ongoing in the general population and will provide more definitive, high-level evidence on this gastric cancer prevention strategy in the next decade.


SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset.
It was recently shown that the major allele of the SLC30A8 (zinc transporter 8, ZnT8) single nucleotide polymorphism (SNP) rs13266634 was associated with type 2 diabetes and with reduced insulin secretion in non-diabetic relatives. Because of its role in beta-cell function, we hypothesized that this candidate SNP may confer increased susceptibility for beta-cell destruction in type 1 diabetes. We analyzed SLC30A8 genotypes in 874 patients with type 1 diabetes and 1021 control subjects. No difference in allele and genotype frequencies of the SLC30A8 SNP rs13266634 was found between patients and controls. Analysis with respect to age at type 1 diabetes onset, however, showed that patients with a diabetes onset before age 5 years had an increased prevalence of the cytosine (C) allele (risk allele, 82%) and the homozygous CC genotype (65%) compared to patients who developed type 1 diabetes after age 5 years (67% and 49%; p < 0.01) and compared to controls (69% and 48%; p < 0.03). These data suggest that genetic susceptibility for beta-cell dysfunction in the presence of autoimmunity may lead to accelerated progression and early manifestation of the disease.


Mild cognitive impairment and mild dementia: a clinical perspective.
Mild cognitive impairment and mild dementia are common problems in the elderly. Primary care physicians are the first point of contact for most patients with these disorders and should be familiar with their diagnosis, prognosis, and management. Both mild cognitive impairment and mild dementia are characterized by objective evidence of cognitive impairment. The main distinctions between mild cognitive impairment and mild dementia are that in the latter, more than one cognitive domain is invariably involved and substantial interference with daily life is evident. The diagnosis of mild cognitive impairment and mild dementia is based mainly on the history and cognitive examination. The prognosis for mild cognitive impairment and mild dementia is an important motivation for diagnosis because in both, there is a heightened risk for further cognitive decline. The etiology of mild cognitive impairment and mild dementia can often be established through the clinical examination, although imaging and other laboratory tests may also contribute. Although Alzheimer disease is the most common cause of both, cerebrovascular disease and Lewy body disease make important contributions. Pharmacological treatments are of modest value in mild dementia due to Alzheimer disease, and there are no approved pharmacological treatments for mild cognitive impairment of any etiology. Nonetheless, new-onset cognitive impairment is a worrisome symptom to patients and families that demands answers and advice. If a patient is having difficulties managing medications, finances, or transportation independently, diagnosis and intervention are necessary to ensure the health and safety of the patient.


Probing the solvent dependent photophysics of fac-[Re(CO)3(dppz-X2)Cl] (dppz-X2 = 11,12-X2-dipyrido[3,2-a:2',3'-c]phenazine); X = CH3, H, F, Cl, CF3).
The results of electrochemical measurements, density-functional theory calculations, emission and time-resolved IR (TRIR) spectroscopic studies for fac-[ReCl(CO)3(dppz-X2)], (dppz = dipyrido[3,2-a:2',3'-c]phenazine; X = CH3, H, F, Cl, CF3) are reported. For all complexes the calculations show that the lowest unoccupied molecular orbital (LUMO) is a phenazine based orbital localized on the dppz ligand. We observe that three different excited states, IL pi pi*, metal-to-ligand charge-transfer (MLCT) (phen), and MLCT (phz), are formed depending upon the substituent on the dppz ligand and on the nature of the solvent. This means that both the energy and the nature of the photophysically active state(s) can be tuned by both chemical modification of dppz ligand and solvent properties. The excited-state dynamics in these systems is directly related to the mechanism of the "light switch effect", and ps-TRIR has allowed a deeper insight into this mechanism by being able to directly monitor the change in the population of the higher lying emissive phen-type (3)MLCT and IL pi pi* states and the dark (3)MLCT (phz) state depending on the different environmental factors.


Deep enteroscopy with standard endoscopes using a novel through-the-scope balloon.
A new on-demand enteroscopy (ODE) device has been designed to allow deep enteroscopy using a standard adult colonoscope with the aid of a novel through-the-scope balloon. The aims of the current study were to establish the feasibility, efficacy, and safety of ODE in performing anterograde and retrograde enteroscopy. A retrospective, single-center study of 28 consecutive deep ODE procedures (11 anterograde and 17 retrograde) was performed. Diagnostic yield, therapeutic yield, technical success, procedure time, depth of maximal insertion (DMI), time to DMI, and adverse events were recorded. The mean diagnostic and therapeutic yields were 45 % and 36 % for anterograde enteroscopy and 59 % and 47 % for retrograde enteroscopy, respectively. Technical success was achieved in 100 %. For anterograde enteroscopy, the mean total procedure time was 24 minutes, with a mean DMI of 1.2 m. For retrograde enteroscopy, the mean total procedure time was 31 minutes, with a mean DMI of 1.1 m. No adverse events were recorded. Deep enteroscopy using a novel through-the-scope balloon and standard endoscope appeared to be feasible and safe, with rapid procedures times.


Injection testosterone and adverse cardiovascular events: A case-crossover analysis.
Exogenous testosterone administration may affect blood clotting, polycythaemia, and may increase atherosclerosis, though any association with cardiovascular events is unclear. While the literature is inconclusive, some studies have suggested testosterone use may increase short-term risk of cardiovascular events and stroke, and injection testosterone may convey higher risks than other dosage forms. We sought to evaluate the short-term cardiovascular risk of receiving injection testosterone. We conducted a case-crossover analysis comparing injection testosterone exposure in the 7 days prior to an outcome event to referent windows in the past to estimate the acute association of cardiovascular outcomes with the receipt of testosterone injections. We identified adult male testosterone users hospitalized with myocardial infarction (MI), stroke or a composite of MI, stroke or unstable angina in US commercial claims (2000-2013) or Medicare (2007-2010) databases. We identified testosterone use for the patients from pharmacy dispensing claims or in-office procedure codes in the insurance billing data. We identified 2898 commercially insured men with events and recent testosterone use, and 339 from Medicare. Injected testosterone was associated with an increased risk of adverse events (composite outcome of myocardial infarction, stroke or unstable angina) in the immediate postinjection period for the older, Medicare population only: commercial insurance, odds ratios (OR) = 0.98 (95% confidence intervals [CI]: 0.86-1.12); Medicare, OR = 1.45 (1.07, 1.98). This association was either greatly attenuated or not present when evaluating receipt of any testosterone dosage forms (injection, gel, patch, implant): commercial insurance, OR = 1.01 (0.92, 1.11); Medicare, OR = 1.26 (95% CI: 0.98-1.63). Testosterone injections were uniquely associated with short-term risk of acute cardio- and cerebrovascular events in older adult men following injection receipt.


Analysis of lower limb asymmetries by isokinetic and vertical jump tests in soccer players.
Assessment of lower extremity bilateral asymmetries in soccer players is important for both injury prevention and performance. The purpose of this investigation was to compare isokinetic knee extensor assessment of asymmetry with a more specific countermovement jump (CMJ). Forty-six Brazilian male professional soccer players participated in this study. The maximal power, maximal force and impulse were determined during CMJ and the total work and peak torque at 60, 180, and 300°·s during isokinetic leg extension, separately for each leg. Factor analysis was performed for all investigated variables, and the diagnostic concordance between different criteria was analyzed by McNemar's χ test. The factor analysis showed that the isokinetic and CMJ tests were widely independent methods for the assessment of bilateral differences. Concordance of the diagnostic information could only be found between the maximal force during CMJ and the total work and peak torque at 180 and 300°·s during isokinetic leg extension. Impulse and maximal power during CMJ on a double force platform appear to be appropriate additional variables for the identification of bilateral differences. Therefore, it might be pertinent to perform, in addition to isokinetic assessment, a vertical jump test on a force platform to assure widespread and reliable diagnostic information.


Are patients satisfied after peripheral nerve blockade? Results from an International Registry of Regional Anesthesia.
Peripheral nerve blockade (PNB) is associated with superior outcomes compared with opioids; however, little is known regarding patients' perceptions of the care they have received. Patient satisfaction is emerging as an important indicator of quality of health care, and identifying deficiencies in discrete aspects of satisfaction may allow targeted interventions to improve quality. In this study, we analyze data relevant to patient satisfaction from the International Registry of Regional Anesthesia. The primary objective of this analysis was to report the results of a patient-satisfaction questionnaire and to determine predictors associated with unwillingness to have PNB repeated in the case of future surgery. The questionnaire used in this study was derived from this registry's results and from previously validated questionnaires and addressed 3 domains of importance, namely, provision of information, pain, and interaction with the anesthesiologist. The 11-item written, multidimensional questionnaire was given to patients within 2 days postoperatively. The primary outcome was willingness to have PNB repeated in the event of future similar surgery. Data related to 9969 surgical procedures were collected between July 1, 2011, and March 31, 2013. The survey response rate was 61.6%. Most respondents-94.6% (95% confidence interval, 94.0%-95.1%)--stated that they were willing to have a repeat PNB. Ninety percent of respondents were satisfied or completely satisfied with the information provided about the nerve block, as well as the anesthesiologist-patient interaction. Patients who were dissatisfied with either of these domains (ie, information provision or professional interaction) were less willing to undergo repeat PNB, as were patients who reported significant pain during the nerve block procedure. A high proportion of survey respondents were willing to undergo repeat PNB in case of future surgery and were satisfied with their anesthetic care. Targeted interventions to improve quality of PNB should be aimed at improving comfort, information provision, and physician-patient interaction.


Evanescent field sensors with periodically segmented waveguides.
An evanescent field-sensing configuration, based on a periodically segmented waveguide, is proposed and analyzed. It has advantages over existing configurations that relate to its simple realization (in single-step lithography). The sensitivity and operating point can be controlled easily with geometric parameters alone, which facilitates realization of more complex sensing arrays.


Pulsed estrogen therapy in prevention of postmenopausal osteoporosis. A 2-year randomized, double blind, placebo-controlled study.
The aim of this study was to evaluate the efficacy of pulsed estrogen therapy (intranasal 17beta-estradiol) in the prevention of postmenopausal bone loss. A total of 386 women (40-65 years old), less than 5 years past menopause, were randomized to intranasal placebo, 17beta-estradiol 150 micro g, or 300 micro g daily for 2 years. Women with an intact uterus received micronised progesterone 200 mg per day, 14 days of each 28-day cycle. Women randomised to placebo-treatment received placebo progesterone. The primary endpoints were changes in BMD at the spine (L2-L4) and femoral neck. Secondary endpoints were changes in bone turnover markers: serum osteocalcin (sOC) as a marker of bone formation and urinary C-terminal telopeptides (uCTX) as a marker of bone resorption. BMD increased at all measured sites in women receiving active treatment in a dose-related manner, the difference compared to placebo being 5.2% and 6.7% at the spine, and 3.2% and 4.7 % at the hip, respectively, with 150 microg and 300 microg ( P<0.001). On the other hand, a decrease versus baseline of -3.2% and -3.3% at the spine and hip, respectively, was observed in women receiving placebo ( P<0.001). In the patients with at least one risk factor for osteoporotic fracture, the difference between placebo and 150 microg or 300 micro g was even higher at the spine (5.4% and 7.4%, respectively), and at the femoral neck (4.0% and 5.2%, respectively). Correspondingly, uCTX decreased from baseline by 39% and 46 %, and sOC by 22% and 27%, in the 150 micro g group and 300 micro g group (all P<0.001 versus placebo). A strong correlation was found between variations of bone turnover markers after 1 year and BMD after 2 years, emphasizing that bone markers can predict BMD response during hormonal treatment. Acceptability and general tolerance were good. This study demonstrates that pulsed estrogen therapy at the dose of 150 microg and 300-microg per day prevents bone loss in a dose-dependant manner at each site studied, and normalizes bone turnover markers to premenopausal levels.


Effect of motilin on the lower oesophageal sphincter.
The effect of motilin on lower oesophageal sphincter (LES) pressure has been studied in unanesthetised specially trained dogs using an infusion manometric technique. Motilin produced significant rises in resting pressure and contractions of the LES after doses ranging from 0-009 mug/kg to 0-05 mug/kg. Doses greater than 0-05 mug/kg resulted in repetitive high amplitude contractions. Atropine 30 mug/kg completely abolished the effect of the lower doses of motilin. Higher doses of motilin in atropinised dogs still caused a small rise in baseline pressure and contractile activity still appeared. Hexamethonium 2 mg/kg resulted in both a diminished rise in LES pressure and the disappearance of contractions after motilin. Hexamethonium and atropine together completely abolished the LES response to motilin. We conclude that motilin increases LES pressure by acting on preganglionic cholinergic neurones to release acetylcholine which excites other cholinergic neurones supplying the circular muscle of the LES.


Pelvic morphology differs in rotation and obliquity between developmental dysplasia of the hip and retroversion.
Developmental dysplasia of the hip (DDH) and acetabular retroversion represent distinct acetabular pathomorphologies. Both are associated with alterations in pelvic morphology. In cases where direct radiographic assessment of the acetabulum is difficult or impossible or in mixed cases of DDH and retroversion, additional indirect pelvimetric parameters would help identify the major underlying structural abnormality. We asked: How does DDH and retroversion differ with respect to rotation and coronal obliquity as measured by the pelvic width index, anterior inferior iliac spine (AIIS) sign, ilioischial angle, and obturator index? And what is the predictive value of each variable in detecting acetabular retroversion? We reviewed AP pelvis radiographs for 51 dysplastic and 51 retroverted hips. Dysplasia was diagnosed based on a lateral center-edge angle of less than 20° and an acetabular index of greater than 14°. Retroversion was diagnosed based on a lateral center-edge angle of greater than 25° and concomitant presence of the crossover/ischial spine/posterior wall signs. We calculated sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve for each variable used to diagnose acetabular retroversion. We found a lower pelvic width index, higher prevalence of the AIIS sign, higher ilioischial angle, and lower obturator index in acetabular retroversion. The entire innominate bone is internally rotated in DDH and externally rotated in retroversion. The areas under the ROC curve were 0.969 (pelvic width index), 0.776 (AIIS sign), 0.971 (ilioischial angle), and 0.925 (obturator index). Pelvic morphology is associated with acetabular pathomorphology. Our measurements, except the AIIS sign, are indirect indicators of acetabular retroversion. The data suggest they can be used when the acetabular rim is not clearly visible and retroversion is not obvious. Level III, diagnostic study. See Guidelines for Authors for a complete description of levels of evidence.


Insights into the solvent-assisted degradation of organophosphorus compounds by a Zr-based metal-organic framework.
The degradation of a chemical warfare agent simulant using a catalytically active Zr-based metal-organic framework (MOF) as a function of different solvent systems was investigated. Complementary molecular modelling studies indicate that the differences in the degradation rates are related to the increasing size in the nucleophile, which hinders the rotation of the product molecule during degradation. Methanol was identified as an appropriate solvent for non-aqueous degradation applications and demonstrated to support the MOF-based destruction of both sarin and soman.


Sex differences in patients with mesial temporal lobe epilepsy.
Possible sex differences in the pattern of interictal hypometabolism were investigated, and also seizure spread in patients with mesial temporal lobe epilepsy (n=48) and hippocampal sclerosis (MTLE). Male patients (n=21) more often had a frontal lobe hypometabolism ipsilateral to the seizure onset (p<0.0001) and a spread of epileptiform activity to this region (p=0.001). By contrast, female patients more often exhibited hypometabolism (p=0.0052) and an ictal spread to the contralateral temporal lobe (p=0.0097). These findings suggest sex differences in spatial distribution of brain dysfunction in MTLE, perhaps reflecting sexual dimorphism in regional cerebral connectivity.


Weaning anorexia may contribute to local inflammation in the piglet small intestine.
Compromising alterations in villus-crypt structure are common in pigs postweaning. Possible contributions of local inflammatory reactions to villus-crypt alterations during the weaning transition have not been described. This study evaluated local inflammatory responses and their relationship with morphological changes in the intestine in 21-d-old pigs (n = 112) killed either at weaning (Day 0) or 0.5, 1, 2, 4 or 7 d after weaning to either milk- or soy-based pelleted diets. Cumulative intake averaged <100 g during the first 2 d postweaning, regardless of diet. During this period of weaning anorexia, inflammatory T-cell numbers and local expression of the matrix metalloproteinase stromelysin increased while jejunal villus height, crypt depth and major histocompatibility complex (MHC) class I RNA expression decreased. Upon resumption of feed intake by the fourth d postweaning, villus height and crypt depth, CD8(+) T cell numbers, MHC class I RNA expression and local expression of stromelysin returned to Day 0 values. Together the results indicate that inadequate feed intake during the immediate postweaning period may contribute to intestinal inflammation and thereby compromise villus-crypt structure and function.


A small set of conserved genes, including sp5 and Hox, are activated by Wnt signaling in the posterior of planarians and acoels.
Wnt signaling regulates primary body axis formation across the Metazoa, with high Wnt signaling specifying posterior identity. Whether a common Wnt-driven transcriptional program accomplishes this broad role is poorly understood. We identified genes acutely affected after Wnt signaling inhibition in the posterior of two regenerative species, the planarian Schmidtea mediterranea and the acoel Hofstenia miamia, which are separated by >550 million years of evolution. Wnt signaling was found to maintain positional information in muscle and regional gene expression in multiple differentiated cell types. sp5, Hox genes, and Wnt pathway components are down-regulated rapidly after β-catenin RNAi in both species. Brachyury, a vertebrate Wnt target, also displays Wnt-dependent expression in Hofstenia. sp5 inhibits trunk gene expression in the tail of planarians and acoels, promoting separate tail-trunk body domains. A planarian posterior Hox gene, Post-2d, promotes normal tail regeneration. We propose that common regulation of a small gene set-Hox, sp5, and Brachyury-might underlie the widespread utilization of Wnt signaling in primary axis patterning across the Bilateria.


Inhalant use initiation among U.S. adolescents: evidence from the National Survey of Parents and Youth using discrete-time survival analysis.
The purpose of this paper is to identify factors associated with initiation to inhalant use among adolescents aged 9 to 18. The data are from the National Survey of Parents and Youth, a longitudinal household survey. Baseline surveys for adolescents and parents were conducted between November 1999 and June 2001 and then annually for three subsequent rounds. The outcome measure is an indicator of a respondent's first use of inhalants. Discrete-time survival analysis was used to model the hazard of initiation. The hazard of inhalant initiation peaks at about 14 years of age (slightly younger than smoking and marijuana initiation). African Americans were less likely than Whites to initiate inhalant use, and higher family income was protective against inhalant initiation. The findings suggest that parenting is associated with initiation of inhalant use: parental drug use was a risk factor for inhalant initiation, and a measure of parental monitoring was protective. The study results also suggest a strong relationship between inhalant use and other problem behaviors and sensation seeking. These results highlight the need to intervene early for youth at risk of or just beginning to engage in risky behaviors including inhalant use.


Longstanding skin ulcers due to Mycobacterium tuberculosis in a healthy man.
Cutaneous tuberculosis, a rare form of extrapulmonary tuberculosis, has a wide variety of clinical presentations and continues to be one of the most important dermatological diseases in developing countries.The sites of predilection are neck, supraclavicular region, axilla, and groin. Single or multiple cutaneous and subcutaneous nodules first appear and breakdown later resulting in undermined ulcers with a purulent discharge, sinuses, and disfiguring scars. We report a multifocal case of scrofuloderma in a 47-year-old immunocompetent man treated successfully with four antituberculotic drugs, albeit lately due to the loss of awareness to the disease.


[A new method of ex vivo whole blood perfusion of isolated mammalian organs, exemplified by the kidney of swine].
A new method for the ex vivo perfusion of organs from large mammals is described. Gas exchange and dialysis are carried out simultaneously with a low-flux polysulfon dialysis module. The dialysate (e.g. Tyrode solution) is aerated with a mixture of oxygen and carbon dioxide to ensure gas exchange with the blood. Dialysis is carried out in a closed thermostatically controlled system. Monitoring of ultrafiltration is maintained by continuously weighing the blood reservoir and adjusting an afferent and efferent blood pump. Initial results obtained with isolated pig kidneys demonstrate the suitability of the new method for use as a model for the replacement of animal experiments. Theoretically, clinical application in the area of in vivo regional organ perfusion may also be possible.


Measured creatinine clearance from timed urine collections substantially overestimates glomerular filtration rate in patients with liver cirrhosis: a systematic review and individual patient meta-analysis.
Accurate glomerular filtration rate (GFR) assessment in patients with liver cirrhosis is important for prognostication, chronic kidney disease staging, drug dosing and identifying combined liver-kidney transplantation candidates. The objective of this study was to review the accuracy of measured creatinine clearance (MCrCl) from timed urine collections for estimating true GFR. A systematic review and individual patient meta-analysis was performed. MEDLINE, old MEDLINE, Index Medicus and Cochrane library bibliographic databases and conference proceedings were searched up to June 2004. Reference lists of relevant studies were searched and experts were contacted. Comparative diagnostic studies describing stable adult patients with cirrhosis categorized according to the Child-Pugh classification were included if a gold standard GFR measurement was performed within 3 days of MCrCl. Individual patient data were abstracted from graphs of primary articles to allow a pooled analysis of agreement between renal measures. Seven studies of 193 patients from 1974 to 2002 were summarized. MCrCl overestimated inulin clearance (CIn) by a mean of +13 ml/min/1.73 m2 and the limits of agreement (mean of the differences+/-2 SD) were +60 ml/min/1.73 m2 and -34 ml/min/1.73 m2. This overestimation was highest in patients with lower GFR. The mean clearance ratios [95% confidence interval (CI)] between MCrCl and CIn in the high (> or =60 ml/min/1.73 m2) and low (<60 ml/min/1.73 m2) GFR subgroups were 1.18 (1.12-1.23) and 1.49 (1.33-1.66), respectively (P<0.0001). Fourteen percent of patients with a MCrCl > or =60 ml/min/1.73 m2 had a CIn of <30 ml/min/1.73 m2. For patients with liver cirrhosis, MCrCl from timed urine collections consistently overestimates the true GFR. For patients requiring complete clinical evaluation, GFR assessment by CIn is justified.


MedFusionGAN: multimodal medical image fusion using an unsupervised deep generative adversarial network.
This study proposed an end-to-end unsupervised medical fusion generative adversarial network, MedFusionGAN, to fuse computed tomography (CT) and high-resolution isotropic 3D T1-Gd Magnetic resonance imaging (MRI) image sequences to generate an image with CT bone structure and MRI soft tissue contrast to improve target delineation and to reduce the radiotherapy planning time. We used a publicly available multicenter medical dataset (GLIS-RT, 230 patients) from the Cancer Imaging Archive. To improve the models generalization, we consider different imaging protocols and patients with various brain tumor types, including metastases. The proposed MedFusionGAN consisted of one generator network and one discriminator network trained in an adversarial scenario. Content, style, and L1 losses were used for training the generator to preserve the texture and structure information of the MRI and CT images. The MedFusionGAN successfully generates fused images with MRI soft-tissue and CT bone contrast. The results of the MedFusionGAN were quantitatively and qualitatively compared with seven traditional and eight deep learning (DL) state-of-the-art methods. Qualitatively, our method fused the source images with the highest spatial resolution without adding the image artifacts. We reported nine quantitative metrics to quantify the preservation of structural similarity, contrast, distortion level, and image edges in fused images. Our method outperformed both traditional and DL methods on six out of nine metrics. And it got the second performance rank for three and two quantitative metrics when compared with traditional and DL methods, respectively. To compare soft-tissue contrast, intensity profile along tumor and tumor contours of the fusion methods were evaluated. MedFusionGAN provides a more consistent, better intensity profile, and a better segmentation performance. The proposed end-to-end unsupervised method successfully fused MRI and CT images. The fused image could improve targets and OARs delineation, which is an important aspect of radiotherapy treatment planning.


Evaluation of outpatient experience with vitreoretinal surgery.
The experience of 55 consecutive individuals undergoing outpatient vitreoretinal surgery was evaluated. Objective variables, including preoperative and intraoperative information, subjective postoperative pain, and discomfort were measured with a previously validated 100 mm visual analogue scale. Patients also ranked the overall experience. Average pain and discomfort scores in the recovery room were 21.8 and 22.6 and overnight were 26.7 and 30.4 (scale 0 to 100), respectively. Eighty eight per cent of subjects were satisfied with the experience. Elevated pain and discomfort scores were statistically correlated with scleral buckling, prolonged surgical or recovery room time, requirement for parenteral pain medications, and high intraocular pressure on the first postoperative visit. None of the patients needed further hospital treatment. This study suggests that vitreoretinal surgery in an appropriately selected population does not require routine inpatient care.


Urinary phthalate metabolites among workers in plastic greenhouses in western China.
Agricultural plastic greenhouse (PG) production can extend the growing season of crops to satisfy domestic consumption in countries such as China. Workers in PGs have potential higher phthalate exposure risks than the general population as phthalate accumulation has been observed in greenhouse soil, air, and crops. To date, biomonitoring tests of phthalates for the working population have not been carried out. To address this shortage, we conducted a pilot study in Shaanxi Province, China, among 35 healthy PG workers by follow-up recording their seasonal dietary habits and work activities and urine sample collection and measurement between 2018 and 2019. The objectives were to uncover the association between phthalate metabolites and the population characteristics, seasonal and diurnal variations and causes, and to estimate exposure risks and contributions of exposure pathways from PG production systems. A total of 13 phthalate metabolite concentrations (Σ13 phthalate metabolites) ranged from 102 to 781 (5th-95th) ng/mL (median: 300 ng/mL). Mono-n-butyl phthalate (MNBP) made up 51.3% of Σ13 phthalate metabolites, followed by the sum of four di-2-ethylhexyl phthalate (DEHP) metabolites (24.2%), mono-2-isobutyl phthalate (MIBP) (13.4%), and mono-ethyl phthalate (MEP) (9.8%). The concentrations of MNBP and MIBP in summer were significantly higher than the levels in winter (p < 0.0001). A total of 62.3% of the PG worker population was shown to have exposure risks, and the proportion was as high as 79.4% in summer. Phthalate exposure of the workers from PG production systems constituted over 20% of the total creatinine-based daily intake, and consuming vegetables and fruit planted in PGs and inhalation in PGs were the two largest exposure pathways. Our findings demonstrate that it is important to protect workers in PGs from phthalate exposure risks, and phasing out the use of plastic materials containing phthalates in PGs is imperative, to guarantee food safety in PGs.


A comparative study of structure and function of the longitudinal muscle of the anal canal and the internal anal sphincter in pigs.
This study aims to compare the physiology of the longitudinal muscle of the anal canal with the internal anal sphincter in pigs. Histology and in vitro studies were performed to compare the effect of neural responses induced by electric stimulation and through nicotinic, purinergic, and serotoninergic receptors. The longitudinal muscle and the internal anal sphincter are constituted exclusively by smooth muscle. Strips from the internal anal sphincter a) developed myogenic tone; b) responded to electric stimulation with an "on" relaxation antagonized by nitric oxide synthase inhibitors and purinergic P2Y1 antagonists, and with an "off" contraction antagonized by atropine and phentolamine; and c) responded to stimulation of nicotinic receptors with a relaxation antagonized by nitrergic and purinergic P2Y1 antagonists, responded to stimulation of serotoninergic 5-hydroxytryptamine 3 receptors with a contraction, and relaxed to carbachol and purinergic P2X agonists. Strips from the longitudinal muscle a) did not develop tone, b) responded to electric stimulation with an "on" contraction antagonized by atropine, and c) did not respond to stimulation of nicotinic or serotoninergic 5-hydroxytryptamine 3 receptors, and carbachol and purinergic P2X agonists induced a contraction. The motility of the internal anal sphincter includes myogenic tone, relaxation mediated by nitric oxide and purinergic P2Y1 receptors, and contraction mediated by cholinergic motor neurons and sympathetic fibers. The motility of the longitudinal muscle is limited to a contraction mediated by cholinergic neurons, suggesting that longitudinal muscle contracts during relaxation of the internal sphincter, shortening the anal canal. Nicotinic, muscarinic, and serotoninergic receptors might be therapeutic targets for anal motor disorders.


Decreased and increased expression of the subunit CHL I diminishes Mg chelatase activity and reduces chlorophyll synthesis in transgenic tobacco plants.
The chelation of Fe2+ and Mg2+ ions forms protoheme IX and Mg-protoporphyrin IX, respectively, and the latter is an intermediate in chlorophyll synthesis. Active magnesium protoporphyrin IX chelatase (Mg-chelatase) is an enzyme complex consisting of three different subunits. To investigate the function of the CHL I subunit of Mg-chelatase and the effects of modified Mg-chelatase activity on the tetrapyrrole biosynthetic pathway, we characterized N. tabacum transformants carrying gene constructs with the Chl I cDNA sequence in antisense and sense orientation under the control of the CaMV 35S promoter. Both elevated and diminished levels of Chl I mRNA and Chl I protein led to reduced Mg-chelatase activities, reflecting a perturbation of the assembly of the enzyme complex. The transformed plants did not accumulate the substrate of Mg-chelatase, protoporphyrin IX, but the leaves contained less chlorophyll and possessed increased chlorophyll a/b ratios, as well as a deficiency of light-harvesting chlorophyll binding proteins of photosystems I and II. The expression and activity of several tetrapyrrolic enzymes were reduced in parallel to lower the Mg-chelatase activity. Consistent with the lower chlorophyll contents, the rate-limiting synthesis of 5-aminolevulinate was also decreased in the transgenic lines analyzed. The consequence of reduced Mg-chelatase on early and late steps of chlorophyll synthesis, and on the organization of light harvesting complexes is discussed.


Multi-Polarization Reconfigurable Antenna for Wireless Biomedical System.
This paper presents a multi-polarization reconfigurable antenna with four dipole radiators for biomedical applications in body-centric wireless communication system (BWCS). The proposed multi-dipole antenna with switchable 0°, +45°, 90° and -45° linear polarizations is able to overcome the polarization mismatching and multi-path distortion in complex wireless channels as in BWCS. To realize this reconfigurable feature for the first time among all the reported antenna designs, we assembled four dipoles together with 45° rotated sequential arrangements. These dipoles are excited by the same feeding source provided by a ground tapered Balun. A metallic reflector is placed below the dipoles to generate a broadside radiation. By introducing eight PIN diodes as RF switches between the excitation source and the four dipoles, we can control a specific dipole to operate. As the results, 0°, +45°, 90° and -45° linear polarizations can be switched correspondingly to different operating dipoles. Experimental results agree with the simulation and show that the proposed antenna well works in all polarization modes with desirable electrical characteristics. The antenna has a wide impedance bandwidth of 34% from 2.2 to 3.1 GHz (for the reflection coefficient ≤ -10 dB) and exhibits a stable cardioid-shaped radiation pattern across the operating bandwidth with a peak gain of 5.2 dBi. To validate the effectiveness of the multi-dipole antenna for biomedical applications, we also designed a meandered PIFA as the implantable antenna. Finally, the communication link measurement shows that our proposed antenna is able to minimize the polarization mismatching and maintains the optimal communication link thanks to its polarization reconfigurability.


Cytogenetic evidence for gene amplification in mouse skin carcinogenesis.
Using our recently developed methodology for cytogenetic evaluation of solid tumors, we analyzed the occurrence of double minutes (DM) in chemically induced mouse skin carcinomas and papillomas. These studies revealed that DM were observed in 10% of the squamous cell carcinomas and in none of the papillomas screened. In addition, we analyzed four cell lines derived from mouse skin papillomas and one spontaneously transformed mouse epidermal cell line. The presence of DM was a consistent feature in all the studied cell lines. In the papilloma cell lines, the degree that DM occurred correlated with the cell line's capacity to form malignant tumors in immunosuppressed mice. DM were also observed in direct chromosomal preparations from tumors induced by one of the papilloma cell lines. Homogeneously staining regions were also present in metaphases from the spontaneously transformed cell line. We have shown here, for the first time, DM and homogeneously staining regions in mouse skin tumors and transformed cells derived from mouse skin. Since DM and homogeneously staining regions are the cytogenetic equivalents of gene amplification, which is a mechanism of increased expression of normal or altered gene products, these findings may play a relevant role in mouse epidermal carcinogenesis.


Emergency management of diverticulitis.
The most common indications for emergency operative intervention in the treatment of sigmoid diverticulitis are peritonitis and failure of medical therapy. Primary resection and diversion (Hartmann's procedure) followed by delayed colostomy closure is the current standard of emergency surgical care. Guidelines for best operative strategy, however, remain controversial and continue to evolve based on recent comparative reviews of surgical outcomes. Primary resection and anastomosis with or without proximal diversion and laparoscopic lavage are alternatives to Hartmann's procedure that may provide an improved outcome in properly selected patients. Ongoing changes in the historical paradigm of the surgical approach to this disease mandate the need for large multicentered prospective randomized trials to determine the best surgical strategy under emergent conditions for the treatment of diverticulitis. The current literature is reviewed with suggestions for a management algorithm.


An ancestral MADS-box gene duplication occurred before the divergence of plants and animals.
Changes in genes encoding transcriptional regulators can alter development and are important components of the molecular mechanisms of morphological evolution. MADS-box genes encode transcriptional regulators of diverse and important biological functions. In plants, MADS-box genes regulate flower, fruit, leaf, and root development. Recent sequencing efforts in Arabidopsis have allowed a nearly complete sampling of the MADS-box gene family from a single plant, something that was lacking in previous phylogenetic studies. To test the long-suspected parallel between the evolution of the MADS-box gene family and the evolution of plant form, a polarized gene phylogeny is necessary. Here we suggest that a gene duplication ancestral to the divergence of plants and animals gave rise to two main lineages of MADS-box genes: TypeI and TypeII. We locate the root of the eukaryotic MADS-box gene family between these two lineages. A novel monophyletic group of plant MADS domains (AGL34 like) seems to be more closely related to previously identified animal SRF-like MADS domains to form TypeI lineage. Most other plant sequences form a clear monophyletic group with animal MEF2-like domains to form TypeII lineage. Only plant TypeII members have a K domain that is downstream of the MADS domain in most plant members previously identified. This suggests that the K domain evolved after the duplication that gave rise to the two lineages. Finally, a group of intermediate plant sequences could be the result of recombination events. These analyses may guide the search for MADS-box sequences in basal eukaryotes and the phylogenetic placement of new genes from other plant species.


Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.
Developmental transcription factors important in early neuron specification and differentiation often remain expressed in the adult brain. However, how these transcription factors function to mantain appropriate neuronal identities in adult neurons and how transcription factor dysregulation may contribute to disease remain largely unknown. The transcription factor Nurr1 has been associated with Parkinson's disease and is essential for the development of ventral midbrain dopamine (DA) neurons. We used conditional Nurr1 gene-targeted mice in which Nurr1 is ablated selectively in mature DA neurons by treatment with tamoxifen. We show that Nurr1 ablation results in a progressive pathology associated with reduced striatal DA, impaired motor behaviors, and dystrophic axons and dendrites. We used laser-microdissected DA neurons for RNA extraction and next-generation mRNA sequencing to identify Nurr1-regulated genes. This analysis revealed that Nurr1 functions mainly in transcriptional activation to regulate a battery of genes expressed in DA neurons. Importantly, nuclear-encoded mitochondrial genes were identified as the major functional category of Nurr1-regulated target genes. These studies indicate that Nurr1 has a key function in sustaining high respiratory function in these cells, and that Nurr1 ablation in mice recapitulates early features of Parkinson's disease.


Surgical outcome and complications of total laparoscopic hysterectomy for very large myomatous uteri in relation to uterine weight: a prospective study in a continuous series of 461 procedures.
To analyze whether a large uterine size was associated with increased rate of intraoperative and postoperative surgical complications in patients who underwent total laparoscopic hysterectomy (TLH) for myomatous uteri. We examined prospectively data from 461 consecutive TLHs performed by a single surgeon between August 2004 and August 2014 at the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and at the Department of Gynecologic Oncology, Businco Hospital, Cagliari, Italy. Demographic and surgical data were stratified by uterine weight (range 90-5500 g) into four groups: <300 g; from 300 to 500 g; from 500 to 800 g; and >800 g. Outcomes examined included blood loss, operative time, intraoperative and postoperative complications, and duration of hospital stay. A linear regression analysis was performed to identify whether uterine weight was an independent predictor affecting these outcomes. In addition, BMI, previous surgery with adhesiolysis, and endometriosis were tested as a predictor of surgical complications and outcomes. No significant difference was found in intraoperative and postoperative complications, as well as hospital stay, by uterine weight. Increased uterine size was significantly associated with longer operative time and increased blood loss. Beside uterine weight, prior surgery was predictive of postoperative complications. In contrast, higher BMI was not associated with increased complication rate. Independent predictors of longer operative time included previous surgery, endometriosis, and BMI. Our results showed that in experienced hands, TLH is feasible and safe also in presence of very large uteri. TLH results in a few complications and short hospital stay regardless of uterine weight.


Phosphatation of zeolite H-ZSM-5: a combined microscopy and spectroscopy study.
A variety of phosphated zeolite H-ZSM-5 samples are investigated by using a combination of Fourier transfer infrared (FTIR) spectroscopy, single pulse (27)Al, (29)Si, (31)P, (1)H-(31)P cross polarization (CP), (27)Al-(31)P CP, and (27)Al 3Q magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, scanning transmission X-ray microscopy (STXM) and N2 physisorption. This approach leads to insights into the physicochemical processes that take place during phosphatation. Direct phosphatation of H-ZSM-5 promotes zeolite aggregation, as phosphorus does not penetrate deep into the zeolite material and is mostly found on and close to the outer surface of the zeolite, acting as a glue. Phosphatation of pre-steamed H-ZSM-5 gives rise to the formation of a crystalline tridymite AlPO4 phase, which is found in the mesopores of dealuminated H-ZSM-5. Framework aluminum species interacting with phosphorus are not affected by hydrothermal treatment. Dealuminated H-ZSM-5, containing AlPO4 , retains relatively more framework Al atoms and acid sites during hydrothermal treatment than directly phosphated H-ZSM-5.


Word order denotes relevance differences: The case of conjoined phrases with lexical gender.
This work explores the order of linguistic references to the two genders (e.g., men and women vs. women and men). It argues that a gender is more likely to be mentioned first when it is perceived to have higher relevance in a context rather than lower relevance, and audiences assign stronger relevance to a party when the party is mentioned first rather than second. Studies 1-3 document the current prevalence of male-first conjoined phrases in the public (but not family) domain and link the pattern to historical changes in women's public presence over the 20th century. Study 4 shows that contextual relevance cues affect the odds of first mention, such that people are more likely to refer to a woman before a man, when the two are in a primary school classroom rather than a corporate office. At the same time, Studies 4 and 5 find that people often choose to reproduce collectively preferred word order patterns (e.g., men and women). Studies 6 and 7 show that these choices matter because people assign more relevance to a party when it comes first rather than second in a conjoined phrase. Overall, this work offers theoretical grounding and empirical evidence for word order as a means of expressing and perpetuating gender stereotypes. (PsycINFO Database Record


Description and comparison of documentation of nursing assessment between paper-based and electronic systems in Australian aged care homes.
To describe nursing assessment documentation practices in aged care organizations and to evaluate the quality of electronic versus paper-based documentation of nursing assessment. This was a retrospective nursing documentation audit study. Study samples were 2299 paper-based and 6997 electronic resident assessment forms contained in 159 paper-based and 249 electronic resident nursing records, respectively, from three aged care organizations. The practice of nursing assessment documentation in participating aged care homes was described. Three attributes of quality of nursing assessment documentation were evaluated: format and structure, process, and content by seven measures: quantity, completeness, timeliness comprehensiveness, frequencies of documentation specific to care domains and data items, and whether assessment forms were signed and dated. Varying practice in documentation of nursing assessment was found among different aged care organizations and homes. Electronic resident records contained higher numbers and more comprehensive resident assessment forms than paper-based records. The frequency of documentation was higher in electronic than in paper-based records in relation to most care domains. There was no difference between the two types of documentation systems on other aspects of nursing assessment documentation (overall completeness and timeliness, variation of frequencies among different care domains, and item completion in personal hygiene assessment forms). Electronic nursing documentation systems could improve the quality of documentation structure and format, process and content in the aspects of quantity, comprehensiveness and signing and dating of assessment forms. Further studies are needed to understand the factors leading to the variations of practice and the limitations of nursing assessment documentation and to evaluate documentation quality from a clinical perspective.


Swept field laser confocal microscopy for enhanced spatial and temporal resolution in live-cell imaging.
Confocal fluorescence microscopy is a broadly used imaging technique that enhances the signal-to-noise ratio by removing out of focal plane fluorescence. Confocal microscopes come with a variety of modifications depending on the particular experimental goals. Microscopes, illumination pathways, and light collection were originally focused upon obtaining the highest resolution image possible, typically on fixed tissue. More recently, live-cell confocal imaging has gained importance. Since measured signals are often rapid or transient, thus requiring higher sampling rates, specializations are included to enhance spatial and temporal resolution while maintaining tissue viability. Thus, a balance between image quality, temporal resolution, and tissue viability is needed. A subtype of confocal imaging, termed swept field confocal (SFC) microscopy, can image live cells at high rates while maintaining confocality. SFC systems can use a pinhole array to obtain high spatial resolution, similar to spinning disc systems. In addition, SFC imaging can achieve faster rates by using a slit to sweep the light across the entire image plane, thus requiring a single scan to generate an image. Coupled to a high-speed charge-coupled device camera and a laser illumination source, images can be obtained at greater than 1,000 frames per second while maintaining confocality.


Croizat's form-making, RNA networks, and biogeography.
Advances in technology have increased our knowledge of the processes that effect genomic changes and of the roles of RNA networks in biocommunication, functionality, and evolution of genomes. Natural genetic engineering and genomic inscription occur at all levels of life: cell cycles, development, and evolution. This has implications for phylogenetic studies and for biogeography, particularly given the general acceptance of using molecular clocks as arbiters between vicariance and dispersal explanations in biogeography. Léon Croizat's development of panbiogeography and his explanation for the distribution patterns of organisms are based on concepts of dispersal, differential form-making, and ancestor that differ from concepts of descent used broadly in phylogenetic and biogeographic studies. Croizat's differential form-making is consistent with the extensive roles ascribed to RNAs in development and evolution and recent discoveries of genome studies. Evolutionary-developmental biology (evo-devo), including epigenetics, and the role of RNAs should be incorporated into biogeography.


Towards better prediction of xenobiotic genotoxicity: CometChip technology coupled with a 3D model of HepaRG human liver cells.
Toxicology is facing a major change in the way toxicity testing is conducted by moving away from animal experimentation towards animal-free methods. To improve the in vitro genotoxicity assessment of chemical and physical compounds, there is an urgent need to accelerate the development of 3D cell models in high-throughput DNA damage detection platforms. Among the alternative methods, hepatic cell lines are a relevant in vitro model for studying the functions of the liver. 3D HepaRG spheroids show improved hepatocyte differentiation, longevity, and functionality compared with 2D HepaRG cultures and are therefore a relevant model for predicting in vivo responses. Recently, the comet assay was developed on 3D HepaRG cells. However, this approach is still low throughput and does not meet the challenge of evaluating the toxicity and risk to humans of tens of thousands of compounds. In this study, we evaluated the performance of the high-throughput in vitro CometChip assay on 2D and 3D HepaRG cells. HepaRG cells were exposed for 48 h to several compounds (methyl methanesulfonate, etoposide, benzo[a]pyrene, cyclophosphamide, 7,12-dimethylbenz[a]anthracene, 2-acetylaminofluorene, and acrylamide) known to have different genotoxic modes of action. The resulting dose responses were quantified using benchmark dose modelling. DNA damage was observed for all compounds except 2-AAF in 2D HepaRG cells and etoposide in 3D HepaRG cells. Results indicate that the platform is capable of reliably identifying genotoxicants in 3D HepaRG cells, and provide further insights regarding specific responses of 2D and 3D models.


A family of similarity measures between two strings.
We present a class of similarity measures for quantitatively comparing two strings, that is, two linearly ordered sets of elements. The strings can be of different lengths, the elements come from a single alphabet, and an element may appear any number of times. The limiting values of each measure are 0, when two completely different strings are compared, and 1, when the two strings are identical. Applications of similarity measures are numerous in nonnumerical computations, such as in heuristic search processes in associative networks, in pattern recognition and classification, in game playing programs, and in music and text analysis. We offer a number of feasible measures from among which some are discarded on plausibility grounds. One can select the measure most adequate for one's needs on the basis of a few characteristic examples of strings compared and by considering the specific requirements of the application at hand.


[Apropos of using patient isolation in psychiatry: point of view of nurses].
Seclusion continues to be used in the care of acutely disturbed psychiatric patients despite often emotionally charged debate about its appropriateness within mental health services. Powerful legal and moral arguments about the use of seclusion emphasize an urgent need to critically examine its role in the care of mentally ill people. This paper examines the use of seclusion on psychiatric departments in the management of acutely disturbed patients: 36 psychiatric nurses working in 6 departments in a specialized hospital (the CHS de la Savoie, in Chambery) were interviewed in relation to their perceptions of the role of seclusion. Data were analysed using grounded theory methodology revealing the core conceptual category "controlling" and two sub-categories "watching out for" and "watching over". Seclusion was found to be used as an adjunctive treatment in the care of individuals considered to be "out of control". Clinicians expressed comfort with the use of seclusion, citing a strict protocol that provided parameters for its use. While expert therapeutic interventions were described by clinicians, they are contextualized within a framework of power and control--a framework that stands in stark contrast to contemporary philosophies of nursing care, providing impetus for a reconsideration of the use of constraining practices in the care of mentally ill people.


Evidence for supraspinal nervous control of external anal sphincter motility in the cat.
The aim of this study was to investigate the role of noradrenergic descending nervous pathways in external anal sphincter motility. For this purpose, the effects of intravenously injected adrenoceptor antagonist and agonist on the tonic electrical activity of this sphincter were studied in anesthetized cats. The effects of stimulating the region of the locus coeruleus and the effects of intravenous, intracerebroventricular and intrathecal injection of the above drugs on the electromyographic responses of this muscle to pudendal nerve stimulation were also investigated. The tonic sphincteric activity and the reflex response triggered by electrically stimulating pudendal afferent nerve fibers were inhibited by alpha1-adrenoceptor antagonist nicergoline and enhanced by alpha1-adrenoceptor agonist phenylephrine. Stimulation of the locus coeruleus area either inhibited or enhanced the reflex responses. Intracerebroventricular and intrathecal injection of the alpha2-adrenoceptor agonists, morphine and leu-enkephalin decreased the amplitude of these reflex responses. All the effects of opioids were blocked by naloxone and by spinalization performed at the cervical and lumbar levels. The direct response elicited by stimulating the sphincteric motor axons was not affected either by these drugs or by the brainstem stimulation. These results suggests the existence of a pontine neuronal network controlling the motility of the external anal sphincter via noradrenergic and opioid neurons.


Anxiety, depression, and their comorbidity among Chinese college students during the COVID-19 lockdown in the post-epidemic era: an online cross-sectional survey.
The coronavirus disease 2019 (COVID-19) pandemic continues to affect the mental health of college students in the post-epidemic era. We assessed the status and related factors of college students who are vulnerable to anxiety and depression during the COVID-19 lockdown. This cross-sectional study was conducted two weeks after the beginning of the COVID-19 lockdown, from November 6, 2022, to December 2, 2022, with 1176 valid samples using convenience sampling. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to measure levels of anxiety and depression in college students. Factors related to anxiety, depression, and their comorbidity were analyzed using binary logistic regression. The prevalence of anxiety, depression, and their comorbidity were 27.04%, 34.10%, and 25.60%, respectively. There was a higher risk of anxiety, depression, and their comorbidity among those who were currently living in rural areas. Compared with individuals with low monthly living expenses, those with higher monthly living expenses were less prone to anxiety, depression, and their comorbidity. High prevalence of anxiety, depression, and their comorbidity were detected among college students during the COVID-19 lockdown. These were most common among college students who were senior students, had abnormal body mass index (BMI), were rural area residents, did study arts and humanities, were one-child in the family, and had low monthly living expenses and poor academic performance. Intervention practitioners and policymakers should formulate individualized prevention and intervention measures during the COVID-19 lockdown in the post-epidemic and possible future pandemics for college students.


Conditional versus non-conditional incentives to maximise return of participant completed questionnaires in clinical trials: a cluster randomised study within a trial.
High participant retention enhances the validity of clinical trials. A monetary incentive can increase retention, but it is not known if when it is provided and if it is conditional matters. We aimed to determine whether there was a difference in the number of follow-up trial questionnaires returned when a monetary (gift voucher) incentive was given to participants at recruitment (non-conditional), compared to informing participants at recruitment that the incentive would be given only once their 14-day daily diary (questionnaire) had been returned (conditional). A cluster randomised study within a trial embedded within the Antivirals for influenza-Like Illness, An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) Trial. Matched site pairs (GP practices) were randomised using computer-generated random numbers, to either a non-conditional or conditional monetary voucher incentive (only once their 14-day daily diary (questionnaire) had been returned. Sites were matched on previous recruitment levels and practice list size. Analyses were conducted according to randomised groups irrespective of compliance with a two-sided 5% level statistical significance level. The main analysis of the primary outcome (site proportion of diaries returned) was linear regression accounting for site pair (using cluster-robust variance). Additional weighted, paired and non-parametric sensitivity analyses were conducted. Secondary outcomes were the site average number of completed pages, time to return diary, and cost related to the incentive (administration and postage). Of the 42 randomised sites (21 for each intervention), only 28 recruited at least one participant with only 10 practice pairs recruiting participants at both constituent sites. Raw diaries return proportions were 0.58 (127/220) and 0.73 (91/125) for non-conditional and conditional incentive groups. Regression analysis adjusted for site pair showed no significant difference in returns, - 0.09, (95% CI, - 0.29, 0.10, p = 0.34); when weighted, there was still no clear difference: 0.15 (95% CI, - 0.02, 0.31, p = 0.07). There was no clear statistical evidence of a difference in time taken to return questionnaires, nor the proportion of pages completed, by the intervention group in the main analyses (all p > 0.05). The conditional incentive was approximately £23 cheaper per diary returned based upon observed data. There was no clear evidence of a statistically significant difference in the proportion of participant-completed diaries returned between conditional or non-conditional incentive groups. The time to questionnaire return and completeness of the returned questionnaires were similar in both groups. There was substantial statistical uncertainty in the findings. Some of the sensitivity analyses suggested that a meaningful benefit of a conditional incentive of a magnitude that would be meaningful was plausible. The conditional approach costs less in cash terms.


Drug survival of biologic therapies for palmoplantar pustulosis: A nationwide study.
Biological therapies have established efficacy in psoriasis vulgaris. However, palmoplantar pustulosis (PPP) has proven difficult to treat, and data on drug survival in these patients remain scarce. To investigate drug survival of biological treatments in a nationwide cohort of patients with PPP. We included all patients treated for PPP with a biologic from a prospective Danish nationwide registry between 2007 and 2019. Descriptive statistics were reported. Drug survival was calculated for all patients and specified for the most frequently used biologics. Drug survival was reported as median time to discontinuation. Kaplan-Meier plots were used to visualize drug survival. Trajectories of Dermatology Life Quality Index (DLQI) scores were plotted by interpolating between the different visits with a dermatologist for each treatment course. We identified 85 individual patients who received biological therapy for PPP across 194 treatment courses during follow-up. Of the included treatment courses, 151 (77.8%) were discontinued. The most frequent cause of discontinuation was ineffective response to treatment (54.3%), while 18.5% of courses were discontinued due to adverse events. The median drug survival across all therapies for PPP was 9.3 (Inter quartile range (IQR), 3.9-25.6) months. Ustekinumab demonstrated the longest median time to discontinuation of 14.6 (IQR, 9.1-51.8) months. The proportion of bio-naive patients in treatment at 12 months were according to drug 47.9% for adalimumab, 64.3% for ustekinumab and 40.0% for secukinumab. For bio-experienced, it was 58.2% adalimumab, 54.5% for ustekinumab and 51.4% for secukinumab. The treatment of PPP poses significant challenges, with limited drug survival observed across all therapies regardless of prior experience with biologics. Ustekinumab demonstrated the longest median drug survival. Notably, patients discontinuing therapy due to inefficacy exhibited higher DLQI scores, highlighting the importance of personalized treatment selection and timely consideration of therapy changes when inefficacy is established.


Coral Reefs at the Northernmost Tip of Borneo: An Assessment of Scleractinian Species Richness Patterns and Benthic Reef Assemblages.
The coral reefs at the northernmost tip of Sabah, Borneo will be established under a marine protected area: the Tun Mustapha Park (TMP) by the end of 2015. This area is a passage where the Sulu Sea meets the South China Sea and it is situated at the border of the area of maximum marine biodiversity, the Coral Triangle. The TMP includes fringing and patch reefs established on a relatively shallow sea floor. Surveys were carried out to examine features of the coral reefs in terms of scleractinian species richness, and benthic reef assemblages following the Reef Check substrate categories, with emphasis on hard coral cover. Variation in scleractinian diversity was based on the species composition of coral families Fungiidae (n = 39), Agariciidae (n = 30) and Euphylliidae (n = 15). The number of coral species was highest at reefs with a larger depth gradient i.e. at the periphery of the study area and in the deep South Banggi Channel. Average live hard coral cover across the sites was 49%. Only 7% of the examined reefs had > 75% hard coral cover, while the majority of the reef sites were rated fair (51%) and good (38%). Sites with low coral cover and high rubble fragments are evidence of blast fishing, although the observed damage appeared old. Depth was a dominant factor in influencing the coral species composition and benthic reef communities in the TMP. Besides filling in the information gaps regarding species richness and benthic cover for reef areas that were previously without any data, the results of this study together with information that is already available on the coral reefs of TMP will be used to make informed decisions on zoning plans for conservation priorities in the proposed park.


Anions induce conformational changes and influence the activity and photoaffinity-labelling by 8-azido-ATP of isolated cytochrome c oxidase.
The biphasic effect of anions on the activity of isolated bovine heart cytochrome c oxidase is paralleled by changes in the visible oxidized spectra, indicating the different conformational changes in the enzyme induced by bromide, chloride, sulphate, phosphate, ADP and ATP. Photoaffinity-labelling of most subunits of the isolated enzyme by low concentrations of 8-azido-[gamma-32P]ATP is strongly increased by ATP, ADP and unlabelled 8-azido-ATP in an unspecific manner. With the reconstituted enzyme less subunits are labelled and this labelling is only little affected by nucleotides. The data suggest a highly dynamic structure for isolated bovine heart cytochrome c oxidase.


Improving levels of service through enhanced distribution techniques at Newark Beth Israel Medical Center.
In an effort to reduce cost and improve service, Materiels Management Distribution Services, in cooperation with a prime vendor, created a distribution method unique to the needs of Newark Beth Israel Medical Center. The project combined the vendor's expertise and ability to "deliver direct" to an internal hospital location by product group with the distribution staff's ability to complete the process and deliver the merchandise to the final destination in an expedited manner. This article provides a contract template that can be adapted for other collaborative efforts and highlights the components of a successful program: electronic data interchange, verification of usage and par, reconfiguration of space, direct pallet delivery, and some basic indicators of success.


Dermatomyositis in a human immunodeficiency virus infected person.
It is interesting to study an autoimmune condition like dermatomyositis (DM) in the setting of immunosuppression due to human immunodeficiency virus (HIV) infection. An HIV seropositive female aged 30 years, presented with a nonitchy rash over the face, breathlessness, diarrhoea and difficulty in raising her hands above her head. A heliotrope rash around the eyes, Gottron's papules and proximal muscle weakness were found to be present. C reactive protein, erythrocyte sedimentation rate and lactate dehydrogenase levels were raised, but creatinine phosphokinase and anti-nuclear antibody profile were normal. Her HIV serostatus was confirmed by Western blotting, keeping in mind the potential for false positive HIV serology in an autoimmune disorder. Her CD4 count was 379 cells/mm3. An X-ray of the chest showed bilateral pleural effusion with raised pleural fluid adenosine deaminase levels. Clinical findings and laboratory investigations favored the diagnosis of DM and HIV infection with tuberculous effusion in an HIV seropositive patient. She was treated with antibiotics, four-drug anti-tubercular treatment, systemic steroids and later, antiretroviral treatment. Chances of a false positive antibody test for HIV should be considered in a patient having an autoimmune disease such as DM.


Giant pseudoaneurysm of the splenic artery.
Visceral artery pseudoaneurysms are uncommon. They most commonly affect the splenic artery and are secondary to chronic pancreatitis. Giant pseudoaneurysms (5 cm or larger in size) are rare and, until now, only 19 cases have been reported. A 47-year-old chronic alcoholic and diabetic male presented with upper abdominal pain of 1-month duration without any other significant complaint. Computed tomography was performed which revealed features of chronic pancreatitis along with a splenic artery pseudoaneurysm measuring 7x4 cm in size. As the disease was confined to the body and tail of the pancreas, the patient underwent a distal pancreatectomy and splenectomy along with resection of the pseudoaneurysm with an uneventful postoperative course. Splenic artery pseudoaneurysms, especially the giant variety, are uncommon. As they are most commonly secondary to chronic pancreatitis, they are better managed surgically which resolves the pseudoaneurysm as well as its underlying cause (i.e. chronic pancreatitis).