The influence of pacing strategy on marathon world records.
The aim of this study was to analyse the influence of the pacing strategy adopted by elite marathon runners when setting every marathon world record in the last 50 years. We divided former marathon record holders into two groups: classic athletes (record holders between 1967 and 1988) and contemporaneous athletes (record holders between 1988 and 2018). The total distance of the marathon was divided into 8 sections of 5 km and 1 last section of 2.195 km, and the relative average speed of each section was calculated individually. On average athletes were slightly faster in the first half-marathon than in the second one, where they slowed down progressively (ES = 0.28, small effect). However, when comparing classic vs. contemporaneous athletes, we observed that classic athletes started significantly faster (p < .05, ES = 1.16, moderate effect), although after 25 km, their speed dropped dramatically and was significantly slower than in their contemporaneous counterparts (ES = 2.41, very large effect). This study shows that the pacing strategies of the best marathon runners in the world have changed over the last 50 years. Although a negative pace distribution has been proposed as the most efficient option, a pacing strategy characterised by very little speed changes across the whole race may be the way to go in the future.


Automatized responding and cognitive inertia in individuals with mental retardation.
The relation between cognitive rigidity and cognitive inertia was examined. Results showed that cognitive inertia was greater in individuals with mental retardation than in CA- but not MA-matched subjects without mental retardation. For individuals with mental retardation, cognitive inertia was positively correlated with CA. Results of comparisons of MA-matched individuals with and without mental retardation were not consistent with Kounin's (1941) theory. However, the current findings provided some support for Kounin's notion that there are age-related inherent structural differences that lead to greater rigidity in older adults.


International Guidelines for the Diagnosis and Management of Hyperinsulinism.
Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI, however; there have been almost no new therapeutic modalities since the development of diazoxide. Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in 'developed' countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use. This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited.


Obstruction due to rectal cuff after laparoscopy-assisted transanal endorectal pull-through for Hirschsprung's disease.
We report a case of persistent obstruction after laparoscopy-assisted transanal endorectal pullthrough for Hirschsprung's disease in a 4-week-old boy with biopsy-proven HD. Before pull-through, the posterior rectal cuff was split along its entire length cranially, starting from the dentate line. Initial recovery was uneventful; however, signs of obstruction developed 3 weeks postoperatively. Reoperation through a posterior sagittal approach confirmed a residual rectal cuff surrounding the neo-rectum circumferentially. The dorsal side of the residual rectal cuff was removed completely. At follow-up 5 years later, he defecates 2 to 4 times a day with occasional staining. We hypothesize that the persistent postoperative obstruction was caused by a long residual rectal cuff that spontaneously reapproximated and/or became folded during pull-through. Therefore, a shorter cuff with near-total posterior excision should be strongly considered during laparoscopy-assisted transanal endorectal pull-through for Hirschsprung's disease.


Serum creatinine during physiological perinatal dehydration may estimate individual nephron endowment.
It is well known that the nephron endowment of healthy subjects is highly variable and that individual nephron mass has potentially important implications both in health and disease. However, nephron count is technically impossible in living subjects. Based on the observation of an increase in serum creatinine (sCr) in otherwise healthy newborns with solitary kidney during the physiological perinatal dehydration, we hypothesized that perinatal sCr might be helpful in identifying healthy subjects with a reduced nephron mass. In the framework of a study on blood pressure in babies (NeoNeph), sCr of normal Caucasian neonates was determined 48-96 h after birth and their association with a family history of arterial hypertension (AH) was analyzed. SCr was determined in 182 normal newborns (90 males) at a mean of 61 ± 8 h after birth (range 46-82). Newborns with paternal AH had a higher mean sCr (0.97 + 0.28 mg/dL) then newborns without paternal AH (0.73 + 0.28 mg/dL; p = 0.006). No differences in mean sCr were found in relation with mother or grandparent's history of AH. The association between parental AH and high sCr during perinatal dehydration supports the hypothesis that the latter is a promising tool for identifying normal subjects with a reduced nephron mass with potential important implications in prevention and in understanding the individual outcome of renal and extrarenal diseases (including AH). What is Known: • Nephron endowment of healthy subjects is highly variable and individual nephron mass has potentially important implications both in health and disease however nephron count is not feasible in living subjects. What is New: • Serum creatinine during perinatal dehydration is a possible biomarker for identifying normal subjects with a reduced nephron mass.


[Percutaneous transcardiac intraluminal balloon angioplasty for reopening an arterial thrombosis after percutaneous arterial heart catheterization in a 19-month-old patient with tetralogy of Fallot].
Cardiac catheterization is a common cause of arterial thrombosis in children. Besides heparin therapy, fibrinolysis plays a major role in the therapeutic approaches to arterial thrombosis while surgery is rarely performed in pediatric patients. We report on a 19 month old patient with tetralogy of fallot, who developed thrombosis of the right femoral artery after a retrograde interventional cardiac catheterization. We performed an antegrade balloon angioplasty of his thrombosed femoral artery using a transvenous, transcardial approach via a ventricular septal defect. There were no complications. Doppler sonography showed no residual stenosis after 4 months.


Focal Segmental Glomerulosclerosis and Hyalinosis in a Patient with Spondyloarthritis: A Rare Renal Involvement Case Report.
During its course, spondyloarthritis (SpA) may be associated with extra-articular manifestations affecting several organs. Renal involvement is one of the most common extra-articular manifestations and is dominated by secondary amyloidosis (AA), immunoglobulin A (IgA) nephropathy, and urolithiasis. Other nephropathies such as Focal segmental glomerulosclerosis and hyalinosis (FSGS) are less common and are limited to few case reports. We report the case of a patient followed for axial SpA, who consulted, after being lost to follow-up for 3 years, for elevated blood pressure and edema of both lower limbs associated with an hydrocele and bilateral pleural effusion. Biological examinations showed hypoproteinemia, hypoalbuminemia, and proteinuria. In this context of nephrotic syndrome, the diagnosis of FSGS was confirmed by renal biopsy. Furthermore, the etiological investigation ruled out the causes of secondary FSGS. Renal involvement is a sign of severity in SpA. Its detection and management should be part of the overall management of SpA.


Urinary tract infections following radical cystectomy and urinary diversion: a review of 1133 patients.
To investigate the incidence and microbiology of urinary tract infection (UTI) within 90 days following radical cystectomy (RC) and urinary diversion. We reviewed 1133 patients who underwent RC for bladder cancer at our institution between 2003 and 2013; 815 patients (72%) underwent orthotopic diversion, 274 (24%) ileal conduit, and 44 (4%) continent cutaneous diversion. 90-day postoperative UTI incidence, culture results, antibiotic sensitivity/resistance and treatment were recorded through retrospective review. Fisher's exact test, Kruskal-Wallis test, and multivariable analysis were performed. A total of 151 urinary tract infections were recorded in 123 patients (11%) during the first 90 days postoperatively. 21/123 (17%) had multiple infections and 25 (20%) had urosepsis in this time span. Gram-negative rods were the most common etiology (54% of positive cultures). 52% of UTI episodes led to readmission. There was no significant difference in UTI rate, etiologic microbiology (Gram-negative rods, Gram-positive cocci, fungi), or antibiotic sensitivity and resistance patterns between diversion groups. Resistance to quinolones was evident in 87.5% of Gram-positive and 35% of Gram-negative bacteria. In multivariable analysis, Charlson Comorbidity Index > 2 was associated with higher 90-day UTI rate (OR = 1.8, 95% CI 1.1-2.9, p = 0.05) and Candida UTI (OR 5.6, 95% CI 1.6-26.5, p = 0.04). UTI is a common complication and cause of readmission following radical cystectomy and urinary diversion. These infections are commonly caused by Gram-negative rods. High comorbidity index is an independent risk factor for postoperative UTI, but diversion type is not.


The Central Role of Hypothermia and Hyperactivity in Anorexia Nervosa: A Hypothesis.
Typically, the development of anorexia nervosa (AN) is attributed to psycho-social causes. Several researchers have recently challenged this view and suggested that hypothermia and hyperactivity (HyAc) are central to AN. The following hypothesis will attempt to clarify their role in AN. Anorexia nervosa patients (ANs) have significantly lower core temperatures (Tcore) compared to healthy controls (HCs). This reduced temperature represents a reset Tcore that needs to be maintained. However, ANs cannot maintain this Tcore due primarily to a reduced basal metabolic rate (BMR); BMR usually supplies heat to sustain Tcore. Therefore, to generate the requisite heat, ANs revert to the behavioral-thermoregulatory strategy of HyAc. The majority of ANs (~89%) are reportedly HyAc. Surprisingly, engagement in HyAc is not motivated by a conscious awareness of low Tcore, but rather by the innocuous sensation of "cold- hands" frequently reported by ANs. That is, local hand-thermoreceptors signal the brain to initiate HyAc, which boosts perfusion of the hands and alters the sensation of "cold-discomfort" to one of "comfort." This "rewarding" consequence encourages repetition/habit formation. Simultaneously, hyperactivity increases the availability of heat to assist with the preservation of Tcore. Additionally, HyAc induces the synthesis of specific brain neuromodulators that suppress food intake and further promote HyAc; this outcome helps preserve low weight and perpetuates this vicious cycle. Based on this hypothesis and supported by rodent research, external heat availability should reduce the compulsion to be HyAc to thermoregulate. A reduction in HyAc should decrease the production of brain neuromodulators that suppress appetite. If verified, hopefully, this hypothesis will assist with the development of novel treatments to aid in the resolution of this intractable condition.


Quadrivalvular nonbacterial thrombotic endocarditis in a patient with clear cell cervical cancer.
Nonbacterial thrombotic endocarditis (NBTE) is a rare finding, which is mostly associated with malignant diseases leading to hypercoagulability. We report the case of a severe quadruple valve nonbacterial thrombotic endocarditis in a patient with clear cell cervical cancer.


Prevalence of Artificial Food Colors in Grocery Store Products Marketed to Children.
Artificial food colors (AFCs) in foods and beverages may be harmful to children. This study assesses the percentage of grocery store products marketed to children that contain AFCs, by category and company. The research team collected product and food-color information about 810 products in one grocery store in North Carolina in 2014. Overall, 350 products (43.2%) contained AFCs. The most common AFCs were Red 40 (29.8% of products), Blue 1 (24.2%), Yellow 5 (20.5%), and Yellow 6 (19.5%). Produce was the only category that did not have any AFCs. The highest percentage of products with AFCs was found in candies (96.3%), fruit-flavored snacks (94%), and drink mixes/powders (89.7%). Forty-one of the 66 companies marketed products containing AFCs. Given concerns about health effects of AFCs and high proportions of high-AFC categories, clinicians, parents, food companies, and the government can take steps to support children's healthy eating and development by reducing AFCs in children's diets.


[Using the FOCUS Family Intervention in Caring for a Patient-Spouse Dyad With Advanced Colorectal Cancer].
The care-related burdens of the spouses of advanced cancer patients often impact negatively on their physical health, emotional well-being, social functioning, and quality of life. Thus, dyad interventions have been created to meet the demands of advanced cancer patients and their spouses. However, the application of dyadic care in clinical settings is currently rather limited in Taiwan. The present case study involved a patient with advanced colorectal cancer and malignant bowel obstruction whose disease-related demands had eroded the patient's physical, psychological, and spiritual health. The patient's condition placed overwhelming stress on the spouse, jeopardizing the relationship of the dyad. This article elaborates the implementation of the FOCUS program with the goal of helping the dyad achieve better disease adjustment through family involvement, optimistic attitude, effective coping, better symptom management, and uncertainty reduction. Through this delineated experience, the authors hope to help healthcare providers achieve a higher quality of care while caring for patient-family dyads with colorectal cancer.


Obesity in African-Americans: The role of physiology.
The disproportionate obesity in African American (AA) women has a physiologic basis and can be explained by the interactive effects of insulin secretion, insulin clearance, insulin sensitivity and the glycaemic load of the diet. This review will present data supporting a physiologic basis for obesity propensity in obesity-prone AA women that resides in their unique metabolic/endocrine phenotype: high beta-cell responsiveness, low hepatic insulin extraction and relatively high insulin sensitivity, which together result in a high exposure of tissues and organs to insulin. When combined with a high-glycaemic (HG) diet (that stimulates insulin secretion), this underlying propensity to obesity becomes manifest, as ingested calories are diverted from energy production to storage. Our data indicate that both weight loss and weight loss maintenance are optimized with low-glycaemic (LG) vs HG diet in AA. Whether greater obesity in AA is mechanistically related to their greater prevalence of type 2 diabetes is debatable. This review provides data indicating that obesity is not strongly related to insulin resistance in AA. Rather, insulin resistance in AA is associated with relatively low adipose tissue in the leg, consistent with a genetic predisposition to impaired lipid storage. Greater bioenergetic efficiency has been reported in AA and, via resultant oxidative damage, could plausibly contribute to insulin resistance. In summary, it is proposed here that a subset of AA women are predisposed to obesity due to a specific metabolic/endocrine phenotype. However, greater diabetes risk in AA has an independent aetiology based on impaired lipid storage and mitochondrial efficiency/oxidative stress.


Management of plateau iris syndrome with cataract extraction and endoscopic cyclophotocoagulation.
Plateau iris configuration describes an anatomic abnormality in which large or anteriorly positioned pars plicata push the iris root forward, thereby narrowing the anterior chamber angle. Plateau iris syndrome (PIS) is diagnosed if the angle remains occludable, either spontaneously or pharmacologically, after iridotomy. PIS has traditionally been treated with chronic pilocarpine or laser peripheral iridoplasty. A series of 9 eyes of 6 patients with PIS, diagnosed by dark room provocative testing and ultrasound biomicroscopy (UBM) following iridotomy, underwent cataract extraction and endoscopic cyclophotocoagulation (ECP). The ciliary body was treated for a median of 180° (range of 120-360°). Post-ECP, the angles in areas treated with ECP were open with corresponding flattened ciliary processes on UBM, while the angles remained occludable in quadrants untreated by ECP despite lens extraction. The mean follow-up time post-ECP was 73.7 ± 34 months (range 11-122 months). The mean IOP was reduced from a baseline of 25.2 ± 10.9 mm Hg on 3.4 ± 1.0 IOP lowering medications to a mean IOP of 17.1 ± 5.3 mm Hg (p < 0.05) on 1.9 ± 1.5, (p < 0.01) medications at last visit. There were no cases of chronic inflammation, eye pain, decreased vision, retinal detachment, or hypotony. Lens extraction and ECP offers an alternative treatment option for patients with PIS, which may directly address the underlying anatomic abnormality leading to angle closure in PIS.


An interaural-correlation-based approach that accounts for a wide variety of binaural detection data.
Interaural cross-correlation-based models of binaural processing have accounted successfully for a wide variety of binaural phenomena, including binaural detection, binaural discrimination, and measures of extents of laterality based on interaural temporal disparities, interaural intensitive disparities, and their combination. This report focuses on quantitative accounts of data obtained from binaural detection experiments published over five decades. Particular emphasis is placed on stimulus contexts for which commonly used correlation-based approaches fail to provide adequate explanations of the data. One such context concerns binaural detection of signals masked by certain noises that are narrow-band and/or interaurally partially correlated. It is shown that a cross-correlation-based model that includes stages of peripheral auditory processing can, when coupled with an appropriate decision variable, account well for a wide variety of classic and recently published binaural detection data including those that have, heretofore, proven to be problematic.


Ablation of STAT3 in the B Cell Compartment Restricts Gammaherpesvirus Latency In Vivo.
A challenging property of gammaherpesviruses is their ability to establish lifelong persistence. The establishment of latency in B cells is thought to involve active virus engagement of host signaling pathways. Pathogenic effects of these viruses during latency or following reactivation can be devastating to the host. Many cancers, including those associated with members of the gammaherpesvirus family, Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, express elevated levels of active host signal transducer and activator of transcription-3 (STAT3). STAT3 is activated by tyrosine phosphorylation in response to many cytokines and can orchestrate effector responses that include proliferation, inflammation, metastasis, and developmental programming. However, the contribution of STAT3 to gammaherpesvirus pathogenesis remains to be completely understood. This is the first study to have identified STAT3 as a critical host determinant of the ability of gammaherpesvirus to establish long-term latency in an animal model of disease. Following an acute infection, murine gammaherpesvirus 68 (MHV68) established latency in resident B cells, but establishment of latency was dramatically reduced in animals with a B cell-specific STAT3 deletion. The lack of STAT3 in B cells did not impair germinal center responses for immunoglobulin (Ig) class switching in the spleen and did not reduce either total or virus-specific IgG titers. Although ablation of STAT3 in B cells did not have a global effect on these assays of B cell function, it had long-term consequences for the viral load of the host, since virus latency was reduced at 6 to 8 weeks postinfection. Our findings establish host STAT3 as a mediator of gammaherpesvirus persistence. The insidious ability of gammaherpesviruses to establish latent infections can have detrimental consequences for the host. Identification of host factors that promote viral latency is essential for understanding latency mechanisms and for therapeutic interventions. We provide the first evidence that STAT3 expression is needed for murine gammaherpesvirus 68 to establish latency in primary B cells during an active immune response to infection. STAT3 deletion in B cells does not impair adaptive immune control of the virus, but loss of STAT3 in B cells has a long-lasting impact on viral persistence. These results indicate a potential therapeutic benefit of STAT3 inhibitors for combating gammaherpesvirus latency and, thereby, associated pathologies.


Motor Rhythm Dissection From the Backward Circuit in C. elegans.
Motor rhythm is initiated and sustained by oscillatory neuronal activity. We recently discovered that the A-class excitatory motor neurons (MNs) (A-MNs) function as intrinsic oscillators. They drive backward locomotion by generating rhythmic postsynaptic currents (rPSCs) in body wall muscles. Molecular underpinning of the rPSCs, however, is not fully elucidated. We report here that there are three types of the rPSC patterns, namely the phasic, tonic, and long-lasting, each with distinct kinetics and channel-dependence. The Na+ leak channel is required for all rPSC patterns. The tonic rPSCs exhibit strong dependence on the high-voltage-gated Ca2+ channels. Three K+ channels, the BK-type Ca2+-activated K+ channel, Na+-activated K+ channel, and voltage-gated K+ channel (Kv4), primarily inhibit tonic and long-lasting rPSCs with varying degrees and preferences. The elaborate regulation of rPSCs by different channels, through increasing or decreasing the rPSCs frequency and/or charge, correlates with the changes in the reversal velocity for respective channel mutants. The molecular dissection of different A-MNs-rPSC components therefore reveals different mechanisms for multiplex motor rhythm.


GFP-based fluorescence assay for CAG repeat instability in cultured human cells.
Trinucleotide repeats can be highly unstable, mutating far more frequently than point mutations. Repeats typically mutate by addition or loss of units of the repeat. CAG repeat expansions in humans trigger neurological diseases that include myotonic dystrophy, Huntington disease, and several spinocerebellar ataxias. In human cells, diverse mechanisms promote CAG repeat instability, and in mice, the mechanisms of instability are varied and tissue-dependent. Dissection of mechanistic complexity and discovery of potential therapeutics necessitates quantitative and scalable screens for repeat mutation. We describe a GFP-based assay for screening modifiers of CAG repeat instability in human cells. The assay exploits an engineered intronic CAG repeat tract that interferes with expression of an inducible GFP minigene. Like the phenotypes of many trinucleotide repeat disorders, we find that GFP function is impaired by repeat expansion, in a length-dependent manner. The intensity of fluorescence varies inversely with repeat length, allowing estimates of repeat tract changes in live cells. We validate the assay using transcription through the repeat and engineered CAG-specific nucleases, which have previously been reported to induce CAG repeat instability. The assay is relatively fast and should be adaptable to large-scale screens of chemical and shRNA libraries.


Lateral Knee Laxity Increases the Risk of Excessive Joint Line Obliquity after Medial Opening Wedge High Tibial Osteotomy.
Medial opening-wedge high tibial osteotomy (HTO) is a well-recognized treatment for patient with varus knee osteoarthritis. Joint line obliquity has recently been suggested to negatively impact clinical outcomes following HTO, but little is known about what factors lead to increased joint line obliquity. The purpose of the current study was 1) to evaluate whether increased preoperative lateral knee laxity, represented by the joint line convergence angle, results in increased joint line obliquity in a consecutive series of patients treated with HTO, and 2) to determine the effect of advanced arthritic changes on joint line obliquity. Increased joint line convergence angle would be associated with increased joint line obliquity. All HTOs performed at our center between 2010-2017 were retrospectively reviewed. Patients were excluded if pre- and postoperative standing alignment radiographs were not available. Varus-producing osteotomies were excluded. Patients were subdivided according to their preoperative joint line convergence angle (≤3° or >3°) and the degree of radiographic arthritic change. The primary outcome measure was the postoperative joint line obliquity. Categorical variables were compared using the paired samples t-test. Survival analysis was performed for failure and overall rate of reoperation. During the study period, 90 HTO were performed, and 38 patients (42 knees; M/F: 32/6; mean age: 41.6; mean follow-up: 4.72 years) met the inclusion criteria. The most common surgical indications were varus knee osteoarthritis (N=27, 64.3%) and osteochondritis dissecans (N=7, 8.2%). Patients with a preoperative joint line convergence angle >3° demonstrated significantly greater joint line obliquity postoperatively as compared to those with a joint line convergence angle ≤3° (6.4° ± 4.6° vs. 2.5° ± 5.7°, respectively; p = 0.02). Patients with advanced arthritic changes had significantly lower preoperative (-3° ± 3.4° vs. -5.6° ± 4.1°; p = 0.03) and greater postoperative (5.8° ± 4° vs. 2.2° ± 6.4°; p = 0.04) joint line obliquity as compared to those with minimal arthritic changes. There were 12 complications among the 42 procedures: one conversion to total knee replacement (TKR), one hardware failure (fixation revised), one infection, and 9 hardware removals. Overall survival using conversion to TKR was 96.23% (95% CI 0.92-1.0) at 10 years. Lateral knee laxity, as defined by a preoperative joint line convergence angle >3°, and advanced arthritic changes are associated with increased postoperative joint line obliquity following medial opening-wedge high tibial osteotomy. Soft-tissue adaptation should be accounted for in order to avoid excessive joint line obliquity following high tibial osteotomy, and the planned correction should be reduced by 25% in patients with a preoperative joint line convergence angle >3° when templating using standing alignment radiographs. IV.


Complete regression of primary cutaneous malignant melanoma.
While partial spontaneous histopathological regression is a common finding in invasive primary melanoma, proven complete regression is rare, with only 33 cases having been documented. None of the patients in these reported cases had a biopsy specimen taken from the original lesion, which would unequivocally prove the diagnosis of complete regressing melanoma. Over 4 years, we saw a 62-year-old white man who refused treatment of a biopsy specimen-proved superficial spreading melanoma (Breslow thickness, 0.7 mm) that eventually regressed completely. A biopsy specimen confirmed complete histopathological regression. There was no clinical evidence of regional or distant metastases throughout the 4 years. To our knowledge, this is the first documented case of a biopsy specimen-proved primary melanoma completely regressing. We present sequential photographic documentation and review the literature about this phenomenon. While the prevalence of such an event is unknown, evidence is presented that it may be more common than previously thought.


The normal parathyroid and the borderline with early hyperplasia: a light microscopic study.
The light microscopical appearance of the normal parathyroid gland based on an autopsy study of 138 glands from 38 adults without evidence of hyperparathyroidism, is described. It differs from earlier descriptions in that we found less adipose tissue in the glands of many normal adults than had been reported. This observation is in keeping with several other recent reports. Other features of the normal gland are also described. This study suggests that at times, a distinction between normal and early hyperplasia cannot be made, especially if the distinction is based solely on the amount of stromal adipose tissue present. Histological features which appear to indicate abnormality are cytological atypia, chief cell nodularity and diminished intracytoplasmic lipid. A gland which is equivocally enlarged but which has minimal stromal adipose tissue and one or more of the above features is most likely to be abnormal.


Comparison of the Poisoning Severity Score and National Poison Data System schemes for the severity assessment of animal poisonings: a pilot study.
To date, there are no publicly available schemes designed and evaluated specifically for severity assessment of animal poisonings. This poses challenges for the evaluation and comparison of animal poisoning exposure data. Our objective for this pilot study was to evaluate agreement between raters using the Poisoning Severity Score (PSS) and National Poison Data System (NPDS) medical outcome scheme for severity assessment of canine exposures reported to a multistate poison center (PC) and to identify issues regarding their use for severity assessment of animal poisonings. Agreement between both schemes was also assessed. The first 196 canine exposures reported to a multistate PC between 1 January and 31 August 2016 were selected and initial inquiry data from exposures was scored by four independent raters. Interrater agreement and agreement between the severity systems was calculated using weighted kappa (Κ) (Light's kappa). Reported clinical effects were also described. Interrater agreement for both the PSS (Κ 0.31; 95% CI 0.19, 0.43) and NPDS schemes (Κ 0.34; 95% CI 0.22, 0.44) was low. Agreement between the schemes was slight (Κ 0.05; 95% CI -0.08, 0.16) for pooled results from all four raters. For the PSS, 71.7% (n = 281) of ratings were minor, 23.0% (n = 90) moderate, and 5.4% (n = 21) severe. For the NPDS, 69.6% (n = 273) of ratings were minor, 27.0% (n = 106) moderate, and 3.3% (n = 13) severe. The top three reported clinical effects included vomiting (n = 86, 29.9%) drowsiness/lethargy (n = 38, 13.2%), and diarrhea (n = 24, 8.3%). This study shows considerable variability between raters using either the PSS or NPDS schemes for canine exposures severity assessment. The subjective nature of the schemes, the influence of intra- and interrater variation, and predominance of minor cases on the study findings should be taken into account when interpreting this data. Further evaluation of these schemes is warranted and could help inform their future use for animal poisoning severity assessment.


Prevalence of Frailty in Older Men and Women: Cross-Sectional Data from the Geelong Osteoporosis Study.
Few studies have investigated the prevalence of frailty in the Australian general population. This study determined the prevalence of frailty in a population-based sample of older adults and examined the relationship between frailty and comorbid conditions. Men (n = 347) and women (n = 360) aged ≥ 60 year from the Geelong Osteoporosis Study (GOS) were assessed between 2016-2019 and 2011-2014, respectively. Frailty was identified using a modified Fried frailty phenotype. Prevalence estimates were standardised to the 2011 Australian population. Kruskal-Wallis test and χ2 test were used to analyse data. For women, mean standardised prevalence estimates were 18.3% (14.1-22.5) for frail, 54.1% (47.3-60.8) pre-frail and 22.9% (18.9-26.8) robust. Corresponding estimates for men were 13.1% (9.8-16.3) frail, 47.8% (42.0-53.6) pre-frail and 27.3% (22.7-31.8) robust. Women who were frail were older, shorter, tended to have a higher body mass index (BMI) and used more medications compared to other groups. Compared to robust women, those who were frail were more likely to have cardio-metabolic (OR 3.5 (0.7-20.0)), pulmonary (OR 3.5 (1.5-8.4)) and musculoskeletal (OR 10.1 (2.1-48.0)) conditions. Frail men were older, had a higher BMI and were more likely to have musculoskeletal conditions (OR 5.8 (2.8-12.3)) and tended to be from a lower SES. No further associations were observed. This study reported the prevalence of frail and pre-frail individuals in a population-based sample of Australian men and women. Frailty was associated with musculoskeletal conditions for both men and women; however, associations with cardio-metabolic and pulmonary comorbidities were evident in women only.


Detection of extended-spectrum beta-lactamase in Pseudomonas aeruginosa.
The present study was designed to detect the extended-spectrum beta-lactamase (ESBL) production in Pseudomonas aeruginosa and to evaluate the susceptibility pattern. One hundred forty-eight isolates of P. aeruginosa were analyzed for the presence of ESBL enzyme by double disc synergy test. Antibiotic sensitivity pattern of ESBL-positive P. aeruginosa was determined. Of the 148 isolates tested, 30 (20.27%) were found to be positive. Maximum ESBL production was found in sputum and tracheostomy swabs (28.57%), followed by pus (24.13%), urine (19.04%), cerebrospinal fluid (CSF) and other sterile body fluids (15.38%) and blood (7.14%). All the ESBL-producing P. aeruginosa isolates were multi-drug-resistant. Isolates were 100% sensitive to imipenem. Ofloxacin was the second most (70%) effective drug. From this study, we conclude the presence of ESBL-positive P. aeruginosa in our hospital. This has important implications as carbapenems remain the only choice of treatment for infections caused by these organisms. The control measures include judicious use of antibiotics and implementation of appropriate infection control measures to control the spread of these strains in the hospital.


Modification of Cloward cervical retractor. Technical note.
A modification of a Cloward lateral cervical retractor with sharp blades is described. The purpose of the adaptation is to help prevent injuries to soft tissues of the neck and to facilitate placement during anterior cervical discectomy and fusion.


Prognostic value of flow cytometry in surgically treated primary gastric lymphoma.
To investigate whether flow cytometry could help to define the optimal therapeutic strategy of primary gastric lymphomas. Retrospective study of 46 patients having primary gastric lymphoma--according to Dawson criteria--in Ann Arbor stage IE and IIE, who were surgically treated. From selected paraffin-embedded tissue blocks of the tumor, DNA content was studied by flow cytometry (FC). Other pathological tumor features were analysed by hematoxiline-eosine and Giemsa stains as well as immunohistochemical study; any possible influence on postoperative survival was investigated through statistical analysis. The DNA ploidy pattern was diploid in 40 cases (87%) and aneuploid (hyperdiploid) in 6 (13%). Postoperative survival probability (PSP) was 62.7% at 5 years. Statistical analysis showed significant prognostic value for Ann Arbor classification--with higher PSP for stage IE (p = 0.009)--and FC parameters: diploid tumors had higher PSP than aneuploid tumors. Also tumors having S-phase (p = 0.044) or G2-M phase values (p = 0.023) under the respective mean values had higher PSP. No influence on PSP was found for wall invasion, Helicobacter pylori infection, Isaacson's histologic type or resection margin involvement. No significant relationship was appreciated between Isaacson's histologic type and DNA ploidy patterns. FC could be useful in assessing gastric lymphoma prognosis.


Research on the Behavior Evolution of Interest Groups in Book Reverse Logistics.
With the gradual expansion of the book logistics market and the year-on-year increase in book publications, the incidence of book reverse logistics continues to increase, and the problem of book companies' inventory backlog has become increasingly prominent. To effectively alleviate the current backlog of book returns and exchanges, this paper constructs a two-party game model of "book publisher-book retailer," analyzes the evolution process of book publishers and book retailers' participation strategies and the influence of parameter changes on stable strategies through theoretical analysis and numerical simulation, and draws the following conclusions. (1) Whether book publishers and book retailers choose to participate in the reverse logistics optimization of book returns and exchanges is closely related to their benefits and costs, and it also depends on whether the other party participates in the reverse logistics optimization of books. (2) When the cost of participating in book reverse logistics reaches a certain condition, the probability of both parties participating in the optimization is the greatest.


Anti-TNF therapy reduces serum levels of chemerin in rheumatoid arthritis: a new mechanism by which anti-TNF might reduce inflammation.
Chemerin is a specific chemoattractant for macrophages and dendritic cells (DC). In addition, it can rapidly stimulate macrophage adhesion to extracellular matrix proteins and adhesion molecules and is able to activate fibroblast-like synoviocytes (FLS), suggesting a role in the pathogenesis of rheumatoid arthritis (RA). Chemerin is also an adipocytokine that has been related to the inflammatory state of endothelial cells and as such could be involved in the changes in endothelial cells in RA and perhaps increased cardiovascular morbidity. We investigated whether anti-Tumor Necrosis Factor (TNF) treatment affects chemerin levels. 49 patients with active RA (disease activity score evaluated in 28 joints (DAS28) ≥3.2) were started on adalimumab therapy. Blood was drawn from patients while fasting at baseline and 16 weeks after initiation of treatment. Chemerin serum levels were measured by ELISA and related to disease activity, mediators of inflammation and known risk factors for cardiovascular disease. Adalimumab therapy reduced chemerin serum levels, which was correlated with the reduction in DAS28 (r = 0.37, p = 0.009). In addition, the decrease in chemerin serum levels after anti-TNF treatment was associated with the decrease in serum levels of IL-6 (r = 0.39, p = 0.033) and macrophage migration inhibitory factor (MIF) (r = 0.31, p = 0.049). Baseline chemerin serum levels were not related to traditional risk factors for atherosclerosis, except perhaps for smoking (p = 0.07). This exploratory study shows that adalimumab therapy lowers chemerin levels, which is associated with the reduction in disease activity parameters, and inflammatory mediators IL-6 and MIF. This suggests a possible involvement of chemerin in the migration/retention of macrophages in the synovium. TRIAL REGISTRATION NEDERLANDS TRIAL REGISTER: NTR 857.


Catheter ablation of symptomatic idiopathic ventricular arrhythmias : A five-year single-centre experience.
This study was designed to gain insight into the patient characteristics, results and possible complications of ablation procedures for symptomatic idiopathic premature ventricular complexes (PVC) and idiopathic ventricular tachycardia (VT). Data were collected from all patients who underwent radiofrequency catheter ablation for symptomatic PVCs and idiopathic VT in the Catharina Hospital between 1 January 2011 and 31 December 2015. The procedural endpoint was elimination or non-inducibility of the clinical arrhythmia. Successful sustained ablation was defined as the persistent elimination of at least 80% of the PVCs or the absence of VTs at follow-up. In case of suspected PVC-induced cardiomyopathy, the systolic left ventricular function was reassessed 3 months post procedure. Our cohort consisted of 131 patients who underwent one or more ablation procedures; 99 because of symptomatic premature ventricular complexes, 32 because of idiopathic VT. In total 147 procedures were performed. The procedural ablation success rate was 89%. Successful sustained ablation rate was 82%. Eighteen (13.2%) patients had suspected PVC-induced cardiomyopathy. In 15 of them (83%), successful sustained ablation was achieved and the left ventricular ejection fraction improved from a mean of 39% (±8.8) to 55.4% (±8.1). Most arrhythmias originated from the right ventricular outflow tract (60%) or aortic cusps (13%). Complications included three tamponades. Catheter ablation therapy for idiopathic ventricular arrhythmias is very effective with a sustained success rate of 82%. In patients with PVC-induced cardiomyopathy, it leads to improvement of systolic left ventricular function. However, risk for complications is not negligible, even in experienced hands.


Tuning octopolar NLO chromophores: synthesis and spectroscopic characterization of persubstituted 1,3,5-tris(ethynylphenyl)benzenes.
The synthesis of a series of octopolar 1,3,5-tris(ethynylphenyl)benzenes via Sonogashira coupling is described, varying the substituents on both the central benzene core as well as the acetylenic periphery. In particular, systems bearing an electron-rich core and an electron-poor periphery are obtained that display advanced optical properties. The linear (by UV-vis and fluorescence spectroscopy) and second-order nonlinear optical properties are studied, the latter by hyper-Rayleigh scattering (HRS) (Hendrickx, E.; Clays, K.; Persoons, A. Acc. Chem. Res. 1998, 31, 675-683). The influence of different core and periphery substitution is revealed by the optical properties and confirms the possibility of fine-tuning those. Because of the presence of (one-photon) fluorescence for all compounds, femtosecond hyper-Rayleigh scattering has been applied (Olbrechts, G.; Strobbe, R.; Clays, K.; Persoons, A. Rev. Sci. Instrum. 1998, 69, 2233-2241). The implementation of the deconvolution in the frequency domain allows for a demodulation and a phase shift between immediate (nonlinear) scattering and time-delayed (multiphoton) fluorescence for high modulation frequencies (Wostyn, K.; Binnemans, K.; Clays, K.; Persoons, A. Rev. Sci. Instrum. 2001, 72, 3215-3220). In accordance with the linear optical properties, the second-order NLO properties can also be tuned by varying the core and peripheric substitutents.


Colchicine Depolymerizes Microtubules, Increases Junctophilin-2, and Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension.
Pulmonary arterial hypertension (PAH) is a lethal disease characterized by obstructive pulmonary vascular remodeling and right ventricular (RV) dysfunction. Although RV function predicts outcomes in PAH, mechanisms of RV dysfunction are poorly understood, and RV-targeted therapies are lacking. We hypothesized that in PAH, abnormal microtubular structure in RV cardiomyocytes impairs RV function by reducing junctophilin-2 (JPH2) expression, resulting in t-tubule derangements. Conversely, we assessed whether colchicine, a microtubule-depolymerizing agent, could increase JPH2 expression and enhance RV function in monocrotaline-induced PAH. Immunoblots, confocal microscopy, echocardiography, cardiac catheterization, and treadmill testing were used to examine colchicine's (0.5 mg/kg 3 times/week) effects on pulmonary hemodynamics, RV function, and functional capacity. Rats were treated with saline (n=28) or colchicine (n=24) for 3 weeks, beginning 1 week after monocrotaline (60 mg/kg, subcutaneous). In the monocrotaline RV, but not the left ventricle, microtubule density is increased, and JPH2 expression is reduced, with loss of t-tubule localization and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves t-tubule morphology in RV cardiomyocytes. Colchicine therapy diminishes RV hypertrophy, improves RV function, and enhances RV-pulmonary artery coupling. Colchicine reduces small pulmonary arteriolar thickness and improves pulmonary hemodynamics. Finally, colchicine increases exercise capacity. Monocrotaline-induced PAH causes RV-specific derangement of microtubules marked by reduction in JPH2 and t-tubule disarray. Colchicine reduces microtubule density, increases JPH2 expression, and improves both t-tubule architecture and RV function. Colchicine also reduces adverse pulmonary vascular remodeling. These results provide biological plausibility for a clinical trial to repurpose colchicine as a RV-directed therapy for PAH.


Estimating caffeine intake from energy drinks and dietary supplements in the United States.
No consistent definition exists for energy products in the United States. These products have been marketed and sold as beverages (conventional foods), energy shots (dietary supplements), and in pill or tablet form. Recently, the number of available products has surged, and formulations have changed to include caffeine. To help characterize the use of caffeine-containing energy products in the United States, three sources of data were analyzed: sales data, data from federal sources, and reports from the Drug Abuse Warning Network. These data indicate that sales of caffeine-containing energy products and emergency room visits involving their consumption appear to be increasing over time. Data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 indicate that 2.7% [standard error (SE) 0.2%] of the US population ≥1 year of age used a caffeine-containing energy product, providing approximately 150-200 mg/day of caffeine per day in addition to caffeine from traditional sources like coffee, tea, and colas. The highest usage of these products was among males between the ages of 19 and 30 years (7.6%, SE 1.0). Although the prevalence of caffeine-containing energy product use remains low overall in the US population, certain subgroups appear to be using these products in larger amounts. Several challenges remain in determining the level of caffeine exposure from and accurate usage patterns of caffeine-containing energy products.


Tunable and Dynamic Optofluidic Microlens Arrays Based on Droplets.
Microlens arrays (MLAs) are acquiring a key role in the micro-optical system, which have been widely applied in the fields of imaging processing, light extraction, biochemical sensing, and display technology. Compared with solid MLAs, liquid MLAs have received extensive attention due to their natural smooth interface and adjustability. However, manufacturing tunable liquid MLAs with ideal structures is still a key challenge for current technologies. In this paper, a novel and simple optofluidic method is demonstrated, enabling the tunable focusing and high-quality imaging of liquid MLAs. Tunable droplets are fabricated and self-assembled into arrays as the MLAs, which can be easily adjusted to focus, form images, and display different focal lengths. Tuning of MLAs' focusing properties (range from 550 to 5370 μm) is demonstrated by changing the refractive index (RI) of the droplets with a fixed size of 200 μm, which can be changed by adjusting the flow rates of the two branch streams. Also, the corresponding numerical apertures of the MLAs range from 0.026 to 0.26. Furthermore, the MLAs' functionality for microparticle imaging applications is also illustrated. Combining the MLAs with a 4× objective, microparticle imaging is magnified two times, and the resolution has also been improved on the original basis. Besides, both the size and RI of the MLAs in an optofluidic chip can be further adjusted to detect samples at different positions. These MLAs have the merits of high optical performance, a simple fabrication procedure, easy integration, and good tunability. Thus, it shows promising opportunities for many applications, such as adaptive imaging and sensing.


Molecular characterization, expression, and immunological response analysis of the TWEAK and APRIL genes in grass carp, Ctenopharyngodon idella.
TWEAK and APRIL are important members of the TNF superfamily, which play a crucial role in several diseases. Here, we describe the identification of grass carp (Ctenopharyngodon idella) homologs of TWEAK and APRIL (designated gcTWEAK and gcAPRIL, respectively) and their response to Aeromonas hydrophila and Aquareovirus infection. The gcTWEAK cDNA sequence contains 2273 bases with an open reading frame of 753 bases encoding 250-amino acid residues. The gcTWEAK protein contains a predicted transmembrane domain, a putative furin protease cleavage site, 3 conserved cysteine residues, and a typical TNF homology domain. The gcAPRIL cDNA sequence contains 1408 bases with an open reading frame of 747 bases encoding 248-amino acid residues. The gcAPRIL protein contains a predicted transmembrane domain, a putative furin protease cleavage site, 2 conserved cysteine residues, and a typical TNF homology domain corresponding to other, known APRIL homologs. Reverse transcription-polymerase chain reaction analysis shows that both gcTWEAK and gcAPRIL transcripts are predominantly expressed in the skin, spleen, and head kidney, and they are significantly upregulated in most immune tissues by A. hydrophila and Aquareovirus infections. Our results demonstrate that liver is the most responsive tissue against bacterial infection, whereas gill is the most responsive tissue against viral infection. The association of increased gcTWEAK and gcAPRIL expression after bacterial and viral infections suggests that they play a potentially important role in the immune system of fish.


FT-IR microspectroscopic imaging of flax (Linum usitatissimum L.) stems.
Fourier transform infrared (FT-IR) microspectroscopy was used to image and subsequently produce maps of the distribution chemical components in flax stem tissue. Cross-sections of two flax cultivars, Ariane and Natasja, were examined. The infrared maps produced were keyed to the visible images of the samples, thus permitting superimposition of chemical composition onto anatomical structure. The functional group frequencies utilized to produce chemical maps were based on their diagnostic capability for indicating each component to the exclusion of others in the matrix, by comparison of the spectra of "pure" components. Waxes were best indicated by a sharp shoulder at 2850 cm(-1) and appeared primarily in the cuticular and epidermal tissues. Pectins gave a band ca. 1615 cm(-1) for the Ca2+ salt form that was primarily detected in tissue surrounding the fiber bundles. Cellulose was the strongest contributor to the band located at ca. 1335 cm(-1) that showed its greatest intensity in the fiber cells. Aromatic compounds were indicated most readily by the band at 1510 cm(-1) and were located primarily in the core tissue. Acetyl groups, likely associated with hemicellulosic polysaccharides, were indicated by a band centered at 1250 cm(-1) and found within the fibers and core tissue.


Metastatic basal cell carcinoma.
A case of basal cell carcinoma which metastasized to an axillary lymph node is presented. There were no histological features that enabled either the presumed primary lesion or the metastasis to be distinguished from the usual non-metastasizing basal cell carcinoma. Evidence is presented that metastasis is considerably less freguent in Queensland that is reported in an overseas series.


Mitochondrial transplantation attenuates traumatic neuropathic pain, neuroinflammation, and apoptosis in rats with nerve root ligation.
Traumatic neuropathic pain (TNP) is caused by traumatic damage to the somatosensory system and induces the presentation of allodynia and hyperalgesia. Mitochondrial dysfunction, neuroinflammation, and apoptosis are hallmarks in the pathogenesis of TNP. Recently, mitochondria-based therapy has emerged as a potential therapeutic intervention for diseases related to mitochondrial dysfunction. However, the therapeutic effectiveness of mitochondrial transplantation (MT) on TNP has rarely been investigated. Here, we validated the efficacy of MT in treating TNP. Both in vivo and in vitro TNP models by conducting an L5 spinal nerve ligation in rats and exposing the primary dorsal root ganglion (DRG) neurons to capsaicin, respectively, were applied in this study. The MT was operated by administrating 100 µg of soleus-derived allogeneic mitochondria into the ipsilateral L5 DRG in vivo and the culture medium in vitro. Results showed that the viable transplanted mitochondria migrated into the rats' spinal cord and sciatic nerve. MT alleviated the nerve ligation-induced mechanical and thermal pain hypersensitivity. The nerve ligation-induced glial activation and the expression of pro-inflammatory cytokines and apoptotic markers in the spinal cord were also repressed by MT. Consistently, exogenous mitochondria reversed the capsaicin-induced reduction of mitochondrial membrane potential and expression of pro-inflammatory cytokines and apoptotic markers in the primary DRG neurons in vitro. Our findings suggest that MT mitigates the spinal nerve ligation-induced apoptosis and neuroinflammation, potentially playing a role in providing neuroprotection against TNP.


Endovascular treatment of descending thoracic aneurysms.
Current strategies for repair of descending thoracic aortic aneurysms consist of open repair with surgical graft replacement or thoracic endovascular aortic repair. We review and update our overall experience in aortic thoracic diseases and specifically analyzed our outcomes with thoracic endovascular aortic repair in patients with descending thoracic aortic aneurysms. From 1993 to present a total of 1144 patients were treated in our Center for pathology involving the thoracic aorta. Since 1998, 322 patients underwent thoracic endovascular aortic repair, and among this group, in 188 cases the descending aorta was involved. In 74% of patients treated for a descending thoracic aortic lesion, a degenerative aneurysm was observed. In patients with descending thoracic aortic aneurysms receiving thoracic endovascular aortic repair, our technical success rate, i.e. deployment of endograft with complete exclusion of the lesion/minimal endoleak, was 99.5% (one case required emergent open conversion) with a perioperative mortality of 2.6% (five patients). The rate of spinal cord ischemia, manifesting either as paraplegia or paraparesis, was 4.7%. Delayed onset spinal cord ischemia ameliorated with adequate arterial pressure and cerebrospinal fluid drainage. Our experience of selected patients undergoing thoracic endovascular aortic repair of descending thoracic aorta aneurysms is satisfactory with very low mortality and morbidity. A large use of thoracic endovascular aortic repair is foreseen in the next future.


Resistance of Wood Wool Cement Board to the Attack of Philippine Termites.
The resistance of yemane (Gmelina arborea Roxb.)-based wood wool cement board (WWCB) against Philippine termites was evaluated under laboratory and field conditions. Tests were conducted following the FPRDI standard procedures in determining the resistance of WWCB against subterranean and drywood termites. Results of the laboratory tests showed that WWCB was resistant to both Microcerotermes losbañosensis Oshima and Cryptotermes dudleyi Banks. Under field conditions, WWCB was highly resistant to subterranean termites. There was no remarkable termite damage except for the normal nibbling or initial termite feeding on the board during the 8-year exposure period.


[The molecular mechanism of apical hook development in dicot plant].
After the seeds of the dicot model plant Arabidopsis germinate in the soil, the tip of the hypocotyl will form a specialized structure called apical hooks to protect the cotyledons and shoot apical meristems from the mechanical damage during the soil emerging process. The development process of the apical hook is divided into three stages: the apical hook formation, maintenance, and opening. In recent decades, studies have shown that different kinds of plant hormones and environmental signals play a vital role in the development of the apical hook. As the downstream of a variety of signals, the asymmetric distribution of auxin and the signal transduction pathways play a decisive role in the development of the apical hook. However, the detailed mechanism of the asymmetric signal transduction pathway of the cells on both sides of the apical hook is still unclear. In this review, we summarize the molecular mechanisms of the development of apical hook and further refine the role of auxin in the development of apical hook, and prospect for future research directions in this field.


Associations of walking and resistance training with chronic low back pain in older adults: A cross-sectional analysis of Korean National Health and Nutrition Examination Survey data.
Physical activities, such as resistance training and walking, are known to be effective against chronic low back pain (CLBP). However, few studies have examined the associations of walking and resistance training with CLBP in the general older population. Therefore, this study analyzed these relationships in the older Korean population (aged ≥65 years), with the goal of determining which exercise is better for CLBP.This cross-sectional study analyzed Korean National Health and Nutrition Examination Survey data for the period 2012 to 2015. The Korean National Health and Nutrition Examination Survey, which provides representative data for the Korean population, uses a clustered, multistage, random sampling method with stratification based on geographic area, age, and sex. Three multiple logistic regression models were generated in this study to determine the associations of walking and resistance training with CLBP.A total of 5233 participants were enrolled, 3641 (69.6%) of whom were free from CLBP; the remaining 1592 (30.4%) had CLBP. 78.4% and 64.8% of the non-CLBP and CLBP group patients, respectively, walked at least once a week. Also, 23.5% and 11.6% of the participants in the non-CLBP and CLBP groups, respectively, engaged in resistance training at least once a week. In the multiple logistic regression analysis, which was adjusted for all potential confounders, walking was significantly associated with a lower risk of CLBP (1-2d/wk: odds ratio [OR] = 0.65, P = .002; 3-4d/wk: OR = 0.69, P = .004; ≥5 d/wk: OR = 0.57, P < .001). However, resistance training showed no association with the risk of CLBP.In this cross-sectional study, walking was associated with a lower risk of CLBP. In particular, walking >5days per week had the maximum benefit in a lower risk of CLBP. Therefore, clinicians can consider recommending walking to patients with CLBP for optimal pain improvement.


Current Use of Oral Anticoagulants and Prognostic Analysis in Patients with Atrial Fibrillation Undergoing Coronary Stenting.
It is currently believed that triple oral antithrombotic therapy in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI) should be recommended if there are no contraindications. However, selecting triple therapy for AF patients undergoing PCI is still challenging when bleeding risk is considered. This study aimed to investigate the current use of oral anticoagulants (Vitamin K antagonists [VKA]) and perform prognostic analysis in real-world patients with AF undergoing coronary stenting. A total of 276 consecutive coronary artery disease (CAD) patients with or without AF undergoing coronary stenting were retrospectively evaluated and analyzed. The univariate and multivariate analyses were conducted to explore the current use of VKA and prognosis of patients with AF undergoing coronary stenting. The primary end-point was composite of all-cause death, nonfatal recurrent myocardial infarction, stroke, serious bleeding events, unplanned repeat revascularization, and worsening heart failure at 12-month follow-up after coronary stenting. AF patients undergoing coronary stenting have more clinical concomitant diseases. Only 9.0% AF patients after coronary stenting received triple antithrombotic therapy (VKA, aspirin, and clopidogrel) at discharge. AF was independently associated with increased risk of the 12-month composite end-points (relative risk = 5.732, 95% confidence interval 1.786-18.396, P = 0.003). In real-life AF patients undergoing coronary stenting, guideline-recommended VKA was less used. AF patients had adjusted worse prognosis during 12-month follow-up after discharge. It is of utmost importance to improve the current status of oral anticoagulants use.


The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty.
Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. A total of 60 patients, aged 37-81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.


[Ecological/hygienic and toxicological evaluation of combustion products of aviation kerosene and liquefied natural gas].
Products of kerosene combustion in the present-day aeroengines contain more than 200 compounds of incomplete combustion, partial oxidation, and thermal decomposition of fuel and oil. Most of these are strong toxicants for humans. Increase of temperature in the turbine engine combustion chamber led to production of very toxic nitrogen oxides. In search for the ecologically safe and less toxic alternative attention of fuel engineers was drawn to liquefied natural gas which compares well and even excels kerosene in ecological, economic and many other respects.


p27Kip1 promotes invadopodia turnover and invasion through the regulation of the PAK1/Cortactin pathway.
p27Kip1 (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity. p27 promotes the interaction of Cortactin with PAK1. In turn, PAK1 promotes invadopodia turnover by phosphorylating Cortactin, and expression of Cortactin mutants for PAK-targeted sites abolishes p27's effect on invadopodia dynamics. Thus, in absence of p27, cells exhibit increased invadopodia stability due to impaired PAK1-Cortactin interaction, but their invasive capacity is reduced compared to wild-type cells. Overall, we find that p27 directly promotes cell invasion by facilitating invadopodia turnover via the Rac1/PAK1/Cortactin pathway.


[Clinical study on treatment of chronic hepatitis B by kurarinone combined with interferon alpha-1b].
To study the clinical effect of combination of kurarinone (KR) and interferon a-lb (IFNalpha-1b) in treating chronic hepatitis B. One hundred and forty-six patients with chronic hepatitis B were randomized into four groups. Under the basic conventional treatment, additional KR combined IFNa-lb was given to Group A, IFNa-lb to Group B and KR to Group C while none was given to Group D. The therapeutic course for them was 6 months and succeeded with 6 months of follow-up. Changes in liver histology, expression of transforming growth factor beta (TGF-beta) in liver tissue, and serum levels of TGF-beta, hyaluronic acid (HA), laminin (LN), collagen type IV (IVC), precollagen III (PCIII), as well as the negative conversion rate of HBeAg and HBV DNA, and normalization rate of alanine transaminase (ALT) before and after treatment were observed by immuno chemical method, RIA and ELISA. After treatment, in Group A, the scores of liver fibrosis and all the above-mentioned indexes significantly lowered, as compared with those in Group B and C, the difference was significant (P<0.05 or P<0.01). The negative conversion rate of TGF-beta in liver tissue was in accordance with the dynamic change of liver fibrosis. Comparison between Group B and C in those aspects showed insignificant difference (P >0.05). KR combined with IFNalpha-1b shows better effect in treating chronic hepatitis B than that of using either of the two alone.


Engineering of stable and fast-folding sequences of model proteins.
The statistical mechanics of protein folding implies that the best-folding proteins are those that have the native conformation as a pronounced energy minimum. We show that this can be obtained by proper selection of protein sequences and suggest a simple practical way to find these sequences. The statistical mechanics of these proteins with optimized native structure is discussed. These concepts are tested with a simple lattice model of a protein with full enumeration of compact conformations. Selected sequences are shown to have a native state that is very stable and kinetically accessible.


[Tracheal injury is a rare but potentially critical complication to intubation].
Tracheal rupture is a rare but potentially lethal injury. There are several causes; traumatic, neck surgery, tracheal dilatation and association to intubation. We describe a case of tracheal injury where the patient developed subcutaneous emphysema while coughing in the recovery room. Our patient did initially not complain of any breathing difficulties but after further coughing the emphysema increased and the patient became dyspnoeic. Emergent CT-imaging showed a tracheal injury and our patient was transport to ENT for stent therapy. It is important to recall the risk for tracheal injury. Subcutaneous emphysema and breathing difficulties with debut following extubation should raise the suspicion.


Nanoparticles in allergen immunotherapy.
Allergen immunotherapy is the only recognized causal treatment for allergic disease that modulates the immune system toward a tolerogenic or desensitized state. Allergens or their derivative preparations are formulated with adjuvants of different origin and having diverse immunological functions, such as prolonged tissue release and specific immunomodulatory properties. In the last 2 decades, thanks to developments in the field of nanotechnology, more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique and versatile properties which can be employed to develop drug carriers with safer profiles, better stability in physiological conditions and immunomodulatory properties. Nanoparticles can have an adjuvant effect per se or also when they are packed in structures whose physical-chemical properties can be handled in a way that also influences its release dynamics. In particular, it has been suggested that nanoparticle preparations can be put in complexes or loaded with allergens or allergenic extracts, opening the way to innovative paradigms. In this review, we analyze allergen/nanoparticle properties in terms of cytotoxicity, stability and immunogenic reaction in in-vitro and animal systems.


C9orf72: At the intersection of lysosome cell biology and neurodegenerative disease.
The discovery that expansion of a hexanucleotide repeat within a noncoding region of the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia raised questions about C9orf72 protein function and potential disease relevance. The major predicted structural feature of the C9orf72 protein is a DENN (differentially expressed in normal and neoplastic cells) domain. As DENN domains are best characterized for regulation of specific Rab GTPases, it has been proposed that C9orf72 may also act through regulation of a GTPase target. Recent genetic and cell biological studies furthermore indicate that the C9orf72 protein functions at lysosomes as part of a larger complex that also contains the Smith-Magenis chromosome region 8 (SMCR8) and WD repeat-containing protein 41 (WDR41) proteins. An important role for C9orf72 at lysosomes is supported by defects in lysosome morphology and mTOR complex 1 (mTORC1) signaling arising from C9orf72 KO in diverse model systems. Collectively, these new findings define a C9orf72-containing protein complex and a lysosomal site of action as central to C9orf72 function and provide a foundation for the elucidation of direct physiological targets for C9orf72. Further elucidation of mechanisms whereby C9orf72 regulates lysosome function will help to determine how the reductions in C9orf72 expression levels that accompany hexanucleotide repeat expansions contribute to disease pathology.


[Ureteral stenosis of a kidney transplant: a rare cause. Percutaneous nephroscopy of the transplant: an uncommon indication].
The authors report a case of a ureteral stenosis of a transplanted kidney. The cause was a compression by the spermatic cord. The treatment was surgical, with a ureteroureterostomy with pyelostomy tube intubating the anastomosis. A bit of the drain remained in the renal pelvis; it was removed by percutaneous nephroscopy.


Social Determinants of Sexual Behavior and Awareness of Sexually Transmitted Infections (STI) Among Low-Income HIV+ or STI At-Risk Hispanic Residents Receiving Care at the U.S.-Mexico Border.
U.S.-Mexico border communities are uniquely vulnerable to sexually transmitted infection (STI) transmission given the economic and social challenges these communities face. This study examines how marginalized statuses of U.S. border residents are associated with STI awareness and sexual behaviors. We surveyed low-income residents receiving STI testing and/or HIV/AIDS care in the lower Rio Grande Valley of southernmost Texas. Respondents aged 18+ took a self-administered survey available in English or Spanish in a clinic waiting room (N = 282). Approximately 52% of respondents reported being HIV+, and 32% of respondents reported having a prior STI other than HIV. Although most respondents had heard of HPV (72%), awareness of the HPV vaccine was low across all subgroups (28%), including women (< 35%), reflecting previous findings that border residents are less knowledgeable about the HPV vaccine. Almost half of respondents reported always using a condom (45%), which is higher than elsewhere in the U.S. Male and non-Hispanic respondents had higher estimated prevalence ratios (PR) of lifetime partners [PR 1.39 (95% confidence interval 1.43-3.68), PR 1.88 (1.04-3.41), respectively] and sexual partners met online [PR 3.73 (1.00-14.06), PR 19.98 (5.70-70.10), respectively]. Sexual minority, non-Hispanic, and male respondents had higher adjusted odds ratios (AOR) of utilizing the internet to find sexual partners than their peers [AOR 2.45 (1.60-3.87), AOR 1.52 (1.11-2.07), AOR 1.97 (1.20-3.24), respectively], placing them at greater STI-transmission risk. We found diversity in dimensions of STI awareness and sexual behaviors in our sample. Results can help tailor public health interventions to the unique STI risks of marginalized groups in border communities.


Spontaneous dissections of cervicocephalic arteries in childhood and adolescence.
Among 263 consecutive patients with spontaneous cervicocephalic arterial dissections evaluated at the Mayo Clinic, 18 (6.8%) were 18 years of age or younger (mean age, 12 years). The dissection involved the cervical arteries in 11 patients and the intracranial arteries in seven. Extracranially, the internal carotid artery was involved in eight patients, the vertebral artery in two, and both arteries in one. Intracranially, only the anterior circulation was affected. All the patients had cerebral or retinal ischemic symptoms, usually preceded by headache. Death occurred in a 13-year-old boy with intracranial arterial dissection and coarctation of the aorta. For the 17 remaining patients, the follow-up period ranged from 1 to 21 years. A complete or good clinical recovery occurred in 10 of the 11 patients with cervical arterial dissection but in only four of the seven with dissection of intracranial arteries. Recurrent arterial dissection occurred in two patients with cervical arterial dissections and in one patients with intracranial arterial dissection.


Which type of tourism short video content inspires potential tourists to travel.
While user-generated short videos have become very common in tourism marketing, how they affect potential tourists' decisions has not been discussed academically. Based on the customer inspiration theory, this study explored the effects of different tourism short video contents on potential tourists' travel intentions, as well as the mediating effect of customer inspiration and the moderating effect of consumption orientation through three experiments. The following conclusions were drawn. (1) Tourism short videos significantly increased potential tourists' customer inspiration and travel intention; (2) The customer inspirations ("inspired-by" and "inspired-to") chain-mediated the relationship between tourism short videos and potential tourists' travel intentions; (3) Consumption orientation positively moderated the chained mediation effect above, and the chained mediation effect of tourism short videos on the travel intentions of tourists with hedonistic motivations through inspire-by and inspire-to is stronger than that of tourists with utilitarian motivations. The above findings could help expand the perspective of tourism short video research and provide suggestions for tourism business managers to apply short video content to marketing.


Evaluation of Adsorption and Permeation Behaviors in Hydrated Nafion Membranes with Degradation.
In the operation of proton exchange membrane fuel cells, its ionomeric-polymer membrane is easily attacked by free radicals, resulting in the degradation of performance. In this work, the chemical degradation effect of hydrated Nafion membranes on gas adsorption, diffusion, and permeation behaviors is evaluated by molecular dynamics and Monte Carlo simulation. The correlation of pore ratio, free volume, hydrophilic/hydrophobic interface as well as the connectivity of the hydrophilic domain of Nafion membranes with gas transport characteristics are revealed. The results demonstrate that large free volume, high large pore ratio, smooth hydrophilic/hydrophobic interface, and good connectivity of the hydrophilic domain are favorable for adsorption, diffusion, and permeability processes. The C-S bond and C-O-C bond attack of membranes can increase the gas adsorption amount, which becomes weak after the tertiary carbon is attacked.


ER complex proteins are required for rhodopsin biosynthesis and photoreceptor survival in Drosophila and mice.
Defective rhodopsin homeostasis is one of the major causes of retinal degeneration, including the disease Retinitis pigmentosa. To identify cellular factors required for the biosynthesis of rhodopsin, we performed a genome-wide genetic screen in Drosophila for mutants with reduced levels of rhodopsin. We isolated loss-of-function alleles in endoplasmic reticulum membrane protein complex 3 (emc3), emc5, and emc6, each of which exhibited defective phototransduction and photoreceptor cell degeneration. EMC3, EMC5, and EMC6 were essential for rhodopsin synthesis independent of the ER associated degradation (ERAD) pathway, which eliminates misfolded proteins. We generated null mutations for all EMC subunits, and further demonstrated that different EMC subunits play roles in different cellular functions. Conditional knockout of the Emc3 gene in mice led to mislocalization of rhodopsin protein and death of cone and rod photoreceptor cells. These data indicate conserved roles for EMC subunits in maintaining rhodopsin homeostasis and photoreceptor function, and suggest that retinal degeneration may also be caused by defects in early biosynthesis of rhodopsin.


Influence of Fermentation with Different Lactic Acid Bacteria and in Vitro Digestion on the Biotransformation of Phenolic Compounds in Fermented Pomegranate Juices.
This study describes the effect of fermentation and the impact of simulated gastrointestinal digestion (SGD) of four fermented pomegranate juices with different lactic acid bacteria (LAB) on the biotransformation of phenolic compounds. The changes of the antioxidant capacity (AOC) and of LAB growth and survival in different fermented juices were also studied. Two new phenolic derivatives (catechin and α-punicalagin) were identified only in fermented juices. During SGD, the AOC increased together with the phenolic derivatives concentration mainly in the juices fermented with Lactobacillus. These derivatives were formed due to the LAB metabolism of the ellagitannins, epicatechin, and catechin after fermentation and during SGD. The FRAP assay performance might be associated with the degradation and biotransformation of catechin. The fermented pomegranate juices with these LAB increased the bioaccessibility of phenolic compounds, ensuring the survival of LAB after SGD, suggesting a possible prebiotic effect of phenolic compounds on LAB.


Predictive markers of depression in hypertension.
Hypertension and depression, as 2 major public health issues, are closely related. For patients having hypertension, in particular, depression is a risk factor for mortality and jeopardizes their wellbeing. The aim of the study is to apply support vector machine (SVM) learning to blood tests and vital signs to classify patients having hypertension complicated by depression and patients having hypertension alone for the identification of novel markers.Data on patients having both hypertension and depression (n = 147) and patients having hypertension alone (n = 147) were obtained from electronic medical records of admissions containing the records on blood tests and vital signs. Using SVM, we distinguished patients having both hypertension and depression from gender- and age-matched patients having hypertension alone.SVM-based classification achieved 73.5% accuracy by 10-fold cross-validation between patients having both hypertension and depression and those having hypertension alone. Twelve features were selected to compose the optimal feature sets, including body temperature (T), glucose (GLU), creatine kinase (CK), albumin (ALB), hydroxybutyrate dehydrogenase (HBDH), blood urea nitrogen (BUN), uric Acid (UA), creatinine (Crea), cholesterol (TC), total protein (TP), pulse (P), and respiration (R).SVM can be used to distinguish patients having both hypertension and depression from those having hypertension alone. A significant association was identified between depression and blood tests and vital signs. This approach can be helpful for clinical diagnosis of depression, but further studies are needed to verify the role of these candidate markers for depression diagnosis.


3D domain swapping: as domains continue to swap.
Three-dimensional (3D) domain swapping creates a bond between two or more protein molecules as they exchange their identical domains. Since the term '3D domain swapping' was first used to describe the dimeric structure of diphtheria toxin, the database of domain-swapped proteins has greatly expanded. Analyses of the now about 40 structurally characterized cases of domain-swapped proteins reveal that most swapped domains are at either the N or C terminus and that the swapped domains are diverse in their primary and secondary structures. In addition to tabulating domain-swapped proteins, we describe in detail several examples of 3D domain swapping which show the swapping of more than one domain in a protein, the structural evidence for 3D domain swapping in amyloid proteins, and the flexibility of hinge loops. We also discuss the physiological relevance of 3D domain swapping and a possible mechanism for 3D domain swapping. The present state of knowledge leads us to suggest that 3D domain swapping can occur under appropriate conditions in any protein with an unconstrained terminus. As domains continue to swap, this review attempts not only a summary of the known domain-swapped proteins, but also a framework for understanding future findings of 3D domain swapping.


Design of a ruthenium(III) immobilized affinity material based on a β-cyclodextrin-functionalized poly(glycidyl methacrylate-ethylene dimethacrylate) monolith for the enrichment of hippuric acid.
Immobilized metal affinity chromatography has drawn great attention as a widespread separation and purification approach. In this work, ruthenium was firstly introduced into the preparation of immobilized metal affinity chromatography considering its affinity to N,O-donor ligands. A β-cyclodextrin-functionalized poly(glycidyl methacrylate-ethylene dimethacrylate) monolith was designed and employed as the supporting material in immobilized metal affinity chromatography. Thiosemicarbazide was introduced into the synthesis process, which not only acted as a bridge between β-cyclodextrin and glycidyl methacrylate, but also chelated with ruthenium because of its mixed hard-soft donor characteristics. The developed monolithic ruthenium(III)-immobilized metal affinity chromatography column was utilized for the adsorption and separation of hippuric acid, a biological indicator of toluene exposure. To achieve high extraction capacity, the parameters affecting the extraction efficiency were investigated with an orthogonal experiment design, L9 (34 ). Under the optimized conditions, the enrichment factor of hippuric acid was 16.7-fold. The method reproducibility was investigated in terms of intra- and interday precisions with relative standard deviations lower than 8.7 and 9.5%, respectively. In addition, ruthenium(III)-immobilized metal affinity chromatography material could be used for up to 80 extractions without an apparent change in extraction recovery.


Molecular imaging of oxidized collagen quantifies pulmonary and hepatic fibrogenesis.
Fibrosis results from the dysregulation of tissue repair mechanisms affecting major organ systems, leading to chronic extracellular matrix buildup, and progressive, often fatal, organ failure. Current diagnosis relies on invasive biopsies. Noninvasive methods today cannot distinguish actively progressive fibrogenesis from stable scar, and thus are insensitive for monitoring disease activity or therapeutic responses. Collagen oxidation is a universal signature of active fibrogenesis that precedes collagen crosslinking. Biochemically targeting oxidized lysine residues formed by the action of lysyl oxidase on collagen with a small-molecule gadolinium chelate enables targeted molecular magnetic resonance imaging. This noninvasive direct biochemical elucidation of the fibrotic microenvironment specifically and robustly detected and staged pulmonary and hepatic fibrosis progression, and monitored therapeutic response in animal models. Furthermore, this paradigm is translatable and generally applicable to diverse fibroproliferative disorders.


Post-translational modification of peptide messengers in the gut.
Recombinant DNA technology has enabled valuable information to be obtained on the precursors of gastrointestinal regulatory peptides. A number of precursors such as progastrin and proCCK contain a single recognized biologically active sequence, while others contain multiple active sequences. Some of the latter group such as proenkephalin contain repeated copies of a single peptide sequence, some such as proVIP and proglucagon contain related, but not identical, biologically active peptides, and others such as proopiomelanocortin contain unrelated active sequences. However, while cDNA sequencing studies reveal the potential secretory products available within precursors, they provide no information on the actual cleavages and prosthetic modifications that occur. Some prediction of processing events can be made from the occurrence of consensus sequences of amino acids, but confirmation is possible only by isolation and characterization of the products of the post-translational processing. This is of particular physiological significance because in many instances processing occurs in a cell-specific manner, such that a single precursor may give rise to several products with a range of biological activities. For this reason it is important that studies of post-translational processing keep pace with the ever increasing number of precursor sequences deduced by recombinant DNA technology.


The Ecology and Evolution of Microbial Defense Systems in Escherichia coli.
Microbes produce an extraordinary array of microbial defense systems. These include broad-spectrum classical antibiotics critical to human health concerns; metabolic by-products, such as the lactic acids produced by lactobacilli; lytic agents, such as lysozymes found in many foods; and numerous types of protein exotoxins and bacteriocins. The abundance and diversity of this biological arsenal are clear. Lactic acid production is a defining trait of lactic acid bacteria. Bacteriocins are found in almost every bacterial species examined to date, and within a species, tens or even hundreds of different kinds of bacteriocins are produced. Halobacteria universally produce their own version of bacteriocins, the halocins. Streptomycetes commonly produce broad-spectrum antibiotics. It is clear that microbes invest considerable energy in the production and elaboration of antimicrobial mechanisms. What is less clear is how such diversity arose and what roles these biological weapons play in microbial communities. One family of microbial defense systems, the bacteriocins, has served as a model for exploring evolutionary and ecological questions. In this review, current knowledge of how the extraordinary range of bacteriocin diversity arose and is maintained in one species of bacteria, Escherichia coli, is assessed and the role these toxins play in mediating microbial dynamics is discussed.


Myocardial infarction 1979-1988 in Denmark: secular trends in age-related incidence, in-hospital mortality and complications.
All admissions to a coronary care unit (CCU) in Copenhagen County were prospectively registered over a 10-year period, from 1979 to 1988, i.e. after the introduction of CCUs but before the era of intervention with thrombolytic or prophylactic medical treatment. The catchment area remained nearly constant throughout the study period; all patients with MI were admitted to the CCU regardless of age and concomitant diseases, and treatment and discharge policy of the department was unchanged. A total of 4176 MI admissions were registered. During the study period, the age-specific incidence of MI decreased in males above 50 years of age, but was virtually unchanged in females, increasing the proportion of women in the MI population from 26 to 33%. In-hospital and 30-day mortality was unchanged. The occurrence of atrial fibrillation during the admission increased significantly (from 11 to 18%), while the incidence of ventricular fibrillation, heart failure and pulmonary oedema was unchanged.


Hyperuricemia as a Protective Factor for Mild Cognitive Impairment in Non-Obese Elderly.
Mild cognitive impairment (MCI) is regarded as incipient dementia. Patients with MCI have increased risk of later progressing to dementia. Blood uric acid (UA) is an important non-enzymatic antioxidant in peripheral circulation, and plays an unconfirmed protective role in MCI. Furthermore, obesity-induced inflammation, which affects UA metabolism and MCI onset, might regulate such protective role. Thus, the aim of the study was to determine the relationship of UA to MCI and the potential effect from inflammation. The study consisted of 933 MCI patients diagnosed by neuropsychological scales and 933 controls with normal cognitive function. All subjects were ≥ 60 years old. There were 378 obese subjects in MCI group and 410 obese subjects in control group. A relationship between lower serum UA levels and higher risk of MCI was found in all MCI patients and non-obese MCI patients (OR: 0.78, 95% CI: 0.72 ~ 0.86; OR: 0.66, 95% CI: 0.55 ~ 0.78), but not in obese MCI patients (OR: 0.94, 95% CI: 0.81 ~ 1.12). Serum UA and hypersensitive C reactive protein (hs-CRP) levels were higher in obese MCI patients than in non-obese MCI patients (P < 0.001 and P < 0.001). Serum UA levels showed a positive linear correlation with serum hs-CRP levels in obese MCI patients (r = 0.284, P < 0.001), but not in non-obese MCI patients (r = 0.030, P = 0.481). In conclusion, we show the significant association between lower serum UA levels and higher risk of MCI in non-obese subjects. Obesity-induced inflammation may weaken such relationship.


A new pyruvate oxidase biosensor based on 3-mercaptopropionic acid/6-aminocaproic acid modified gold electrode.
In the biosensor construction, 3-mercaptopropionic acid (3-MPA) and 6-aminocaproic acid (6-ACA) were used for forming self-assembled monolayer (SAM) on a gold disc electrode and pyruvate oxidase was immobilized on the modified electrode surface by using glutaraldehyde. Biosensor response is linearly related to pyruvate concentration at 2.5-50 μM, detection limit is 1.87 μM and response time of the biosensor is 6 s for differential pulse voltammograms. From the repeatability studies (n = 6) for 30.0 μM pyruvate revealed that the average value ([Formula: see text]), standard deviation (S.D) and coefficient of variation (CV %) were calculated to be 31.02 μM, ± 0.1914 μM and 0.62%, respectively.


[Knowledge of endocrine disease pictures from the viewpoint of the pathologist].
Endocrinology is an independent discipline based on biochemistry and pathochemistry, but we cannot know any endocrine disease entity without making pathomorphological research. In these days professional pathologists cannot define any new endocrine disease entity by the means of the macroscopical examination, but they may contribute to the micromorphological confirmation of many syndromes using the results and methods of histochemistry, topochemistry, immunofluorescence and isotopic diagnostics. In order to give an acceptable explanation they have to integrate the ultrastructural picture with the classic cytologic picture. This the unity of the functional and morphological aspects can prove to be especially lucrative in the research of endocrinology.


Effectiveness of Digital Physiotherapy Practice Compared to Usual Care in Long COVID Patients: A Systematic Review.
Long COVID syndrome has been recognized as a public health problem. Digital physiotherapy practice is an alternative that can better meet the needs of patients. The aim of this review was to synthesize the evidence of digital physiotherapy practice in Long COVID patients. A systematic review was carried out until December 2022. The review was complemented by an assessment of the risk of bias and methodological quality. A narrative synthesis of results was conducted, including subgroup analyses by intervention and clinical outcomes. Six articles, including 540 participants, were selected. Five articles were considered of high enough methodological quality. Parallel-group, single-blind, randomized controlled trials were the most commonly used research design. Tele-supervised home-based exercise training was the most commonly used intervention. Great heterogeneity in clinical outcomes and measurement tools was found. A subgroup analysis showed that digital physiotherapy is effective in improving clinical outcomes. Significant differences in favor of digital interventions over usual care were reported. Nevertheless, discrepancies regarding effectiveness were found. Improvements in clinical outcomes with digital physiotherapy were found to be at least non-inferior to usual care. This review provides new evidence that digital physiotherapy practice is an appropriate intervention for Long COVID patients, despite the inherent limitations of the review. Registration: CRD42022379004.


Cytotoxic Activity of Isoniazid Derivative in Human Breast Cancer Cells.
Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N'-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. ITHB4 demonstrated a lower IC50 compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC50, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G2/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.


Topical Application of M89PF Containing Vichy Mineralising Water and Probiotic Fractions Prevents Cutaneous Damage Induced by Exposure to UV and O3.
Exposure of the skin to ultraviolet radiation (UV) or ozone (O3) results in stressed skin, leading to the alteration of the skin physical barrier and defence functions. In this work, the preventive benefit of a dermocosmetic, M89PF, containing Vichy mineralising water, probiotic fractions, antioxidant vitamins and hyaluronic acid, in the alteration of skin physical barrier and skin defence functions after exposure to O3 and UV, alone or combined, was assessed. Untreated and treated (M89PF) skin explants were exposed to O3, to UV rays or to O3+UV. Immunofluorescence was performed for skin barrier, oxidative stress, and inflammatory markers after one and four days of exposure to the pollutants. M89PF significantly (p≤0.05) prevented the decrease of the expression level of different skin barrier markers, and significantly (p≤0.05) prevented the induction of OxInflammatory markers and inflammasome components by UV, O3, or both combined. M89PF prevents skin barrier damage, as well as oxidative stress and inflammatory markers induced by exposome factors, such as UV, O3, or both combined.


Endodontic complications following periodontal and prosthetic treatment of patients with advanced periodontal disease.
A retrospective analysis was carried out to determine the frequency and onset of endodontic complications occurring in 52 patients treated for advanced periodontal disease. Comparisons were made between teeth which, following periodontal treatment, were used as abutments in fixed prosthetic reconstructions and nonabutment teeth. The study included 672 teeth with initially vital pulps (255 abutment teeth and 417 nonabutment teeth). The observation period varied from 4 to 13 years with a mean of 8.7 years. Pulpal necrosis including periapical lesions developed with a significantly higher frequency in abutment teeth than in nonabutment teeth (15% vs. 3%). The majority of these lesions did not appear until several years following the completion of active treatment. Conceivable reasons for the development of pulpal necrosis in teeth subjected to combined periodontal and prosthetic treatment are discussed.