Gamma-glutamyl transpeptidase activity in superficial exfoliated cells during hamster buccal pouch carcinogenesis.
The study of gamma-glutamyl transpeptidase (GGT) activity in transformed tissues has conventionally involved the killing of an animal or excision of the lesion, preventing longitudinal study. Oral exfoliative cytology allows longitudinal examination; however, it has been shown to be an unreliable criterion of malignancy. GGT activity has been demonstrated histochemically to involve the full thickness of the epithelium, including the keratin layer during carcinogenesis of hamster buccal pouch epithelium. This study correlates the GGT-stained foci in tissue sections and the proportion of GGT-positive cells in a superficial smear during a 13-week regime of tri-weekly topical application of 7,12-dimethylbenz[a]-anthracene (DMBA) in mineral oil. GGT-positive cells were detected in smears 3 weeks after application of the carcinogen, coincident with GGT-positive foci in tissue sections involving the keratin layer. The proportion of GGT-positive cells in each experimental period increased during the first 7 weeks of the experiment and plateaued thereafter. The number of GGT-positive foci in tissue sections in each experimental period also increased during the experiment. GGT activity was not detected in either smears or tissue sections of untreated or mineral oil treated mucosa. The correlation between the proportion of GGT-positive cells in smears and GGT-positive foci in tissue sections suggest the possibility of studying the GGT activity in an experimentally induced lesion without its elimination. Furthermore, oral exfoliative cytology using GGT staining may be useful in detecting precancerous lesions clinically.


The molecular basis of lecithin:cholesterol acyltransferase deficiency syndromes: a comprehensive study of molecular and biochemical findings in 13 unrelated Italian families.
To better understand the role of lecithin:cholesterol acyltransferase (LCAT) in lipoprotein metabolism through the genetic and biochemical characterization of families carrying mutations in the LCAT gene. Thirteen families carrying 17 different mutations in the LCAT gene were identified by Lipid Clinics and Departments of Nephrology throughout Italy. DNA analysis of 82 family members identified 15 carriers of 2 mutant LCAT alleles, 11 with familial LCAT deficiency (FLD) and 4 with fish-eye disease (FED). Forty-four individuals carried 1 mutant LCAT allele, and 23 had a normal genotype. Plasma unesterified cholesterol, unesterified/total cholesterol ratio, triglycerides, very-low-density lipoprotein cholesterol, and pre-beta high-density lipoprotein (LDL) were elevated, and high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, LpA-I, LpA-I:A-II, cholesterol esterification rate, LCAT activity and concentration, and LDL and HDL3 particle size were reduced in a gene-dose-dependent manner in carriers of mutant LCAT alleles. No differences were found in the lipid/lipoprotein profile of FLD and FED cases, except for higher plasma unesterified cholesterol and unesterified/total cholesterol ratio in the former. In a large series of subjects carrying mutations in the LCAT gene, the inheritance of a mutated LCAT genotype causes a gene-dose-dependent alteration in the plasma lipid/lipoprotein profile, which is remarkably similar between subjects classified as FLD or FED.


Gender adjustment or stratification in discerning upper extremity musculoskeletal disorder risk?
The aim was to explore whether "adjustment" for gender masks important exposure differences between men and women in a study of rotator cuff syndrome (RCS) and carpal tunnel syndrome (CTS) and work exposures. This cross-sectional study of 733 subjects in 12 health care and manufacturing workplaces used detailed individual health and work exposure assessment methods. Multiple logistic regression analysis was used to compare gender stratified and adjusted models. Prevalence of RCS and CTS among women was 7.1% and 11.3% respectively, and among men 7.8% and 6.4%. In adjusted (gender, age, body mass index) multivariate analyses of RCS and CTS, gender was not statistically significantly different. For RCS, upper arm flexion >/=45 degrees and forceful pinch increased the odds in the gender-adjusted model (OR 2.66, 95% CI 1.26-5.59) but primarily among women in the stratified analysis (OR 6.68, 95% CI 1.81-24.66 versus OR 1.45, 95% CI 0.53-4.00). For CTS, wrist radial/ulnar deviation >/=4% time and lifting >/=4.5kg >3% time, the adjusted OR was higher for women (OR 4.85, 95% CI 2.12-11.11) and in the gender stratified analyses, the odds were increased for both genders (women OR 5.18, 95% CI 1.70-15.81 and men OR 3.63, 95% CI 1.08-12.18). Gender differences in response to physical work exposures may reflect gender segregation in work and potential differences in pinch and lifting capacity. Reduction in these exposures may reduce prevalence of upper extremity disorders for all workers.


Psychophysiological factors in myofascial pain.
The interaction of the body and mind in stress syndromes; the input from the mind which influences the neurological functions regulating physiological responses; and the metabolic changes that result are discussed. Treatment direction is based on clinical experience and previously published theories. The synergistic effect of psychological and physiological treatment in stress syndromes is mandatory for permanent reduction of the negative feedback loop. Coordination of treatment by the physician and therapist is optimum.


Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man.
Elimination of the bacteriostatics tetracycline and doxycycline was compared in patients on long-term alcohol consumption to that in healthy controls. The half-life of doxycycline but not that of tetracycline was significantly shorter in alcoholics than in controls and in some patients the serum concentration of doxycycline decreased below the generally accepted minimum therapeutic concentration when dosed once daily. So, the dosing twice daily might be indicated especially if additional inducing drugs are used.


Second re-irradiation: a narrative review of the available clinical data.
Considerable controversy exists about the safety and efficacy of second re-irradiations (three courses of radiotherapy to overlapping volumes). Therefore, all published clinical studies were reviewed. Contemporary and historical articles were identified. Outcomes such as survival, local control, symptom improvement and side effects were extracted. Contemporary results were grouped by anatomical location of the re-irradiated region in the body. Most data were derived from central nervous system tumors, pelvic tumors and bone metastases. We could include nine contemporary, retrospective studies with 2-25 patients each. Nearly, all patients were treated with palliative intent. Most of the prescribed re-irradiation regimens were highly individualized and thus difficult to compare. Symptomatic responses were recorded in most patients. In palliatively treated patients with pelvic and bony target volumes, high-grade toxicity was uncommon. Despite of issues related to study size, length of follow-up and calculation of lifetime cumulative equivalent dose, the available data provide an initial framework for future studies and discussion of dose constraints. Selected dose-fractionation regimens may result in a satisfactory therapeutic ratio even after two previous courses of radiotherapy, if these were well tolerated.


A Clinicopathological and Dermoscopic Correlation of Seborrheic Keratosis.
Seborrheic keratosis (SK) is the most common benign epidermal tumor of the skin. Even though SK has been well characterized clinically, dermoscopically, and histopathologically, data regarding clinical dermoscopic and histopathological correlation of different types of SK are inadequate. We carried out this study to establish any correlation between the clinical, dermoscopic, and histopathological appearance of SK and its variants. This was a descriptive study. Patients with SK were evaluated with respect to age, sex, family history of similar lesions, site of lesions, and symptoms associated with the lesions. Dermoscopy was performed in all cases. Biopsies were taken from the lesions and assessed for histopathology. The most common age group affected by SK was 31-50 years (42%). A female preponderance of 76% was seen. Majority of our patients had a positive family history (62%), though Sun exposure was not seen to be a major factor. The most common clinical variant was common SK (CSK) (46%). The most common dermoscopic findings seen in CSK were comedo-like (CL) openings, fissures and ridges (FR), and milia-like (ML) cysts. Dermatosis papulosa nigra and pedunculated SK had characteristic FR and CL openings on dermoscopy. Stucco keratoses showed network-like (NL) structures and sharp demarcation. CL opening on dermoscopy corresponded to papillomatosis and pigmentation, ML cysts corresponded to horn cysts, FR corresponded to papillomatosis, and NL structures corresponded to an increase in basal layer pigmentation. This study emphasizes the use of dermoscopy in improving the diagnostic accuracy of SK. The correlation between the various histological and dermoscopic features is described.


Far red bioluminescence from two deep-sea fishes.
Spectral measurements of red bioluminescence were obtained from the deep-sea stomiatoid fishes Aristostomias scintillans (Gilbert) and Malacosteus niger (Ayres). Red luminescence from suborbital light organs extends to the near infrared, with peak emission at approximately 705 nanometers in the far red. These fishes also have postorbital light organs that emit blue luminescence with maxima between 470 and 480 nanometers. The red bioluminescence may be due to an energy transfer system and wavelength-selective filtering.


Proteins synthesized before and after fertilization in sea urchin eggs.
Acrylamide-gel patterns of proteins made before and during the first 30 minutes after fertilization were the same. The patterns of gels containing proteins from eggs whose rate of protein synthesis was stimulated reversibly by prior anaerobiosis or removal of carbon dioxide were also the same as that of the mature unfertilized egg. Changes were detected in the pattern of proteins synthesized in gastrulas as compared to proteins made in unfertilized eggs or zygotes.


Performance evaluation of case definitions of type 1 diabetes for health insurance claims data in Japan.
No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan. The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated. As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4). We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.


Suprachoroidal shunts.
This article reviews recent studies evaluating the efficacy and safety of ab externo and ab interno suprachoroidal shunts designed to augment uveoscleral outflow in patients with open angle glaucoma. The Gold Shunt and STARflo are placed into the suprachoroidal space via an ab externo approach, while the CyPass Micro-Stent and iStent Supra are inserted ab interno through a clear corneal incision. A small randomized clinical trial suggested similar efficacy among two different models of the Gold Shunt and the Ahmed glaucoma valve. The pivotal multicenter, randomized COMPASS trial showed that the CyPass Micro-Stent combined with cataract surgery is more effective than cataract surgery alone through 2 years. Study results suggest a favorable safety profile for each suprachoroidal device and intraocular pressure-lowering to the mid-to-high teens with an associated reduction in medication burden. Given the relative novelty of these procedures, it is currently unknown whether fibroblastic proliferation within the suprachoroidal space may limit their long-term success. Renewed interest in the suprachoroidal space has led to the development of new biocompatible glaucoma implants. Ab interno devices are easily combined with cataract surgery and preserve conjunctiva for future incisional glaucoma surgery. Additional data regarding the long-term efficacy and late complications of suprachoroidal shunts are needed.


Effectiveness of a Dyadic Buddy App for Smoking Cessation: Randomized Controlled Trial.
Tobacco smoking is one of the biggest public health threats. Smartphone apps offer new promising opportunities for supporting smoking cessation in real time. This randomized controlled trial investigated the effectiveness of an app that encourages individuals to quit smoking with the help of a social network member (buddy) in daily life. The objective of this study is to test the effectiveness of the SmokeFree buddy app compared with a control group with self-reported smoking abstinence and carbon monoxide (CO)-verified smoking abstinence as primary outcomes and self-reports of smoked cigarettes per day (CPD) as a secondary outcome. A total of 162 adults who smoked participated in this single-blind, two-arm, parallel-group, intensive longitudinal randomized controlled trial. Around a self-set quit date (ie, 7 days before the self-set quit date and 20 days after) and 6 months later, participants of the intervention and control groups reported on daily smoking abstinence and CPD in end-of-day diaries. Daily smoking abstinence was verified via daily exhaled CO assessments. This assessment was administered via an app displaying results of exhaled CO, thus addressing self-monitoring in both groups. In addition, participants in the intervention group used the SmokeFree buddy app, a multicomponent app that facilitates social support from a buddy of choice. A significant reduction in CPD from baseline to the 6-month follow-up was observed among participants in both groups. Multilevel analyses revealed no significant intervention effect on self-reported and CO-verified daily smoking abstinence at the quit date and 3 weeks later. However, CPD was lower at the quit date and 3 weeks later in the intervention group than in the control group. No significant differences between groups were found for any outcome measures 6 months after the quit date. Overall, low app engagement and low perceived usefulness were observed. Despite some encouraging short-term findings on the amount of smoking, the SmokeFree buddy app did not have beneficial effects on smoking abstinence over and above the self-monitoring control condition. Future studies should examine whether and what support processes can be effectively stimulated and how app use can be improved to better achieve this goal. ISRCTN Registry 11154315; https://www.isrctn.com/ISRCTN11154315. RR2-10.1186/s12889-019-7723-z.


Odorant intensity as a determinant for olfactory conditioning in honeybees: roles in discrimination, overshadowing and memory consolidation.
Stimulus intensity is an important determinant for perception, learning and behaviour. We studied the effects of odorant concentration on classical conditioning involving odorants and odorant-mechanosensory compounds using the proboscis-extension reflex in the honeybee. Our results show that high concentrations of odorant (a) support better discrimination in a feature-positive task using rewarded odorant-mechanosensory compounds versus unrewarded mechanosensory stimuli, (b) have a stronger capacity to overshadow learning of a simultaneously trained mechanosensory stimulus, and (c) induce better memory consolidation. Furthermore, honeybees were trained discriminatively to two different concentrations of one odorant. Honeybees are not able to solve this task when presented with rewarded low versus unrewarded high concentrations. Taken together, our results suggest that high concentrations of odorant support stronger associations (are more 'salient') than low concentrations. Our results, however, do not indicate that honeybees can treat two different concentrations of one odorant as qualitatively different stimuli. These findings fill a gap in what is known about honeybee olfactory learning and are a first step in relating behaviour to recent advances in the physiological analysis of coding for odorant concentration in honeybees.


Salmon caviar-induced anaphylactic shock.
Foods, particularly shellfish and nuts, are commonly implicated as causes of anaphylaxis. Salmon caviar, to our knowledge, is an exceedingly rare cause of anaphylactic shock. This study describes a patient who experienced anaphylactic shock on her initial ingestion of caviar. Skin testing and inhibition assays using the enzyme-linked immunosorbent assay were performed. On the percutaneous test, the patient had a 7 x 9 mm/15 x 55 mm wheal/ erythema reaction to caviar liquid. Caviar liquid caused 68, 73, and 73% inhibition of immunoglobulin E (IgE) binding at concentrations of 0.01, 0.1, and 1.0 mg/mL in an enzyme-linked immunosorbent assay, respectively. There was no evidence for IgE antibodies that could be demonstrated to bind to the caviar eggs. Despite using both metoprolol and lisinopril, the patient responded promptly to subcutaneous epinephrine. This report indicates that an IgE-mediated response occurred after caviar ingestion. Although she experienced anaphylactic shock, the patient recovered quickly after epinephrine administration despite routine use of a 3-adrenergic blocker and angiotensin-converting enzyme inhibitor.


Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells: evidence against direct drug extrusion from the plasma membrane.
P-glycoprotein (Pgp), a plasma membrane protein overexpressed in multidrug-resistant tumor cells, is an ATPase thought to actively export cytotoxic drugs. It has been proposed that Pgp transports drugs directly from the lipid bilayer to the external medium ("vacuum cleaner" hypothesis). A possible mechanism for this model is that the Pgp is a flippase--i.e., it catalyzes the translocation of hydrophobic substrates from the inner to the outer leaflet of the cell membrane. Two immediate predictions of the vacuum cleaner and flippase hypotheses are that the apparent unidirectional influx of substrate should be less in Pgp-expressing than in Pgp-lacking cells and that this difference should be abolished by inhibition of the Pgp. We used Chinese hamster fibroblasts with different levels of Pgp expression to measure true unidirectional fluxes of rhodamine 123 (R123), a Pgp-transported fluorescent dye that accumulates in mitochondria (hence, its cytosolic concentration remains low at short times after external addition). The unidirectional efflux of R123 was proportional to the level of Pgp expression and was reduced by Pgp inhibitors. The unidirectional influx of R123 was the same in sensitive and resistant cells--i.e., independent of the level of Pgp expression and insensitive to inhibitors of R123 efflux. From these results, we rule out the vacuum cleaner and flippase hypotheses and conclude that Pgp extracts the actively transported substrates from the cytosol and not from the plasma membrane.


HYBRIDIZATION OF RAPIDLY LABELED NUCLEAR RIBONUCLEIC ACIDS.
RNA, prepared from strain L fibroblasts which were incubated for 30 minutes in radioactive cytidine, was examined by quantitative DNA-RNA hybridization tests, autoradiography, and sedimentation analysis. About 60 percent of the radioactive RNA consists of 38 to 45S molecules located in the nucleoli and capable, under certain circumstances, of forming hybrids with DNA. Unlabeled 28S and 18S ribosomal RNA can compete with these components for DNA sites, indicating that the conversion of nucleolar RNA to ribosomal RNA occurs in such a way that base sequences are preserved. The polydisperse components associated with the chromatin region contain base sequences different from ribosomal and 4S RNA, and consequently have a uniquely high specific activity. These components are the only detectable hybridizing species in unfractionated preparations of RNA.


The endonuclease Ankle1 requires its LEM and GIY-YIG motifs for DNA cleavage in vivo.
The LEM domain (for lamina-associated polypeptide, emerin, MAN1 domain) defines a group of nuclear proteins that bind chromatin through interaction of the LEM motif with the conserved DNA crosslinking protein, barrier-to-autointegration factor (BAF). Here, we describe a LEM protein annotated in databases as 'Ankyrin repeat and LEM domain-containing protein 1' (Ankle1). We show that Ankle1 is conserved in metazoans and contains a unique C-terminal GIY-YIG motif that confers endonuclease activity in vitro and in vivo. In mammals, Ankle1 is predominantly expressed in hematopoietic tissues. Although most characterized LEM proteins are components of the inner nuclear membrane, ectopic Ankle1 shuttles between cytoplasm and nucleus. Ankle1 enriched in the nucleoplasm induces DNA cleavage and DNA damage response. This activity requires both the catalytic C-terminal GIY-YIG domain and the LEM motif, which binds chromatin via BAF. Hence, Ankle1 is an unusual LEM protein with a GIY-YIG-type endonuclease activity in higher eukaryotes.


Elements of a unique bacteriorhodopsin neural network architecture.
A rapidly reprogrammable neural network architecture with the possibility for a large synapse matrix is presented. The concept is based on the use of bacteriorhodopsin as a molecular computational element with electrooptical characteristics that are associated with a series of intermediates that are photochemically initiated. One of these states has been stabilized by several orders of magnitude with specific environmental conditions, and this allows the concentration of intermediates to be readily affected without the need for continuous holding illuminations. Thus, the photoelectrical characteristics at each synapse can readily be modulated, and a scheme has been devised to read the synaptic matrix without erasing the impressed synaptic strengths. Electrical measurements are presented to test specific aspects of the overall neural network implementation, and the results of these measurements are encouraging for the development of such a distinctive neural network device.


Paracrine regulation of epithelial progesterone receptor by estradiol in the mouse female reproductive tract.
Regulation of progesterone receptor (PR) by estradiol-17beta (E(2)) in mouse uterine and vaginal epithelia was studied. In ovariectomized mice, PR expression was low in both vaginal stroma and epithelium, but high in uterine epithelium. E(2) induced PR in vaginal epithelium and stroma, but down-regulated PR in uterine epithelium. Analysis of estrogen receptor alpha (ERalpha) knockout (ERKO) mice showed that ERalpha is essential for E(2)-induced PR expression in both vaginal epithelium and stroma, and for E(2)-induced down-regulation, but not constitutive expression of PR in uterine epithelium. Regulation of PR by E(2) was studied in vaginal and uterine tissue recombinants made with epithelium and stroma from wild-type and ERKO mice. In the vaginal tissue recombinants, PR was induced by E(2) only in wild-type epithelium and/or stroma. Hence, in vagina, E(2) induces PR directly via ERalpha within the tissue. Conversely, E(2) down-regulated epithelial PR only in uterine tissue recombinants constructed with wild-type stroma. Therefore, down-regulation of uterine epithelial PR by E(2) requires stromal, but not epithelial, ERalpha. In vitro, isolated uterine epithelial cells retained a high PR level with or without E(2), which is consistent with an indirect regulation of uterine epithelial PR in vivo. Thus, E(2) down-regulates PR in uterine epithelium through paracrine mechanisms mediated by stromal ERalpha.


Forest response to increasing typhoon activity on the Korean peninsula: evidence from oak tree-rings.
The globally observed trend of changing intensity of tropical cyclones over the past few decades emphasizes the need for a better understanding of the effects of such disturbance events in natural and inhabited areas. On the Korean Peninsula, typhoon intensity has increased over the past 100 years as evidenced by instrumental data recorded from 1904 until present. We examined how the increase in three weather characteristics (maximum hourly and daily precipitation, and maximum wind speed) during the typhoon activity affected old-growth oak forests. Quercus mongolica is a dominant species in the Korean mountains and the growth releases from 220 individuals from three sites along a latitudinal gradient (33-38°N) of decreasing typhoon activity were studied. Growth releases indicate tree-stand disturbance and improved light conditions for surviving trees. The trends in release events corresponded to spatiotemporal gradients in maximum wind speed and precipitation. A high positive correlation was found between the maximum values of typhoon characteristics and the proportion of trees showing release. A higher proportion of disturbed trees was found in the middle and southern parts of the Korean peninsula where typhoons are most intense. This shows that the releases are associated with typhoons and also indicates the differential impact of typhoons on the forests. Finally, we present a record of the changing proportion of trees showing release based on tree-rings for the period 1770-1979. The reconstruction revealed no trend during the period 1770-1879, while the rate of forest disturbances increased rapidly from 1880 to 1979. Our results suggest that if typhoon intensity rises, as is projected by some climatic models, the number of forest disturbance events will increase thus altering the disturbance regime and ecosystem processes.


Action ethical dilemmas in surgery: an interview study of practicing surgeons.
The aim of this study was to describe the kinds of ethical dilemmas surgeons face during practice. Five male and five female surgeons at a University hospital in Norway were interviewed as part of a comprehensive investigation into the narratives of physicians and nurses about ethically difficult situations in surgical units. The transcribed interview texts were subjected to a phenomenological-hermeneutic interpretation. No gender differences were found in the kinds of ethical dilemmas identified among male and female surgeons. The main finding was that surgeons experienced ethical dilemmas in deciding the right treatment in different situations. The dilemmas included starting or withholding treatment, continuing or withdrawing treatment, overtreatment, respecting the patients and meeting patients' expectations. The main focus in the narratives was on ethical dilemmas concerning the patients' well-being, treatment and care. The surgeons narrated about whether they should act according to their own convictions or according to the opinions of principal colleagues or colleagues from other departments. Handling incompetent colleagues was also seen as an ethical dilemma. Prioritization of limited resources and following social laws and regulations represented ethical dilemmas when they contradicted what the surgeons considered was in the patients' best interests. The surgeons seemed confident in their professional role although the many ethical dilemmas they experienced in trying to meet the expectations of patients, colleagues and society also made them professionally and personally vulnerable.


Proteus mirabilis fimbriae: identification, isolation, and characterization of a new ambient-temperature fimbria.
Urinary tract infections involving Proteus mirabilis may lead to complications including bladder and kidney stones, acute pyelonephritis, and bacteremia. This bacterium produces a number of fimbriae, two of which, MR/P fimbria and P. mirabilis fimbria, have been shown to contribute to the ability of this pathogen to colonize the bladder and kidney. We have now purified and characterized a previously undescribed fimbria of P. mirabilis, named ambient-temperature fimbria (ATF). Electron microscopy of a pure preparation and immunogold labeling of cells demonstrated that ATF was fimbrial in nature. The major fimbrial subunit of ATF has an apparent molecular weight of 24,000. The N-terminal amino acid sequence, E-X-T-G-T-P-A-P-T-E-V-T-V-D-G-G-T-I-D-F, did not show significant similarity to that of any previously described fimbrial protein. ATF was expressed by all eight P. mirabilis strains examined. Culture conditions affected expression of ATF, with optimal expression observed in static broth cultures at 23 degrees C. This fimbria was not produced by cells grown at 42 degrees C or on solid medium. Expression of ATF did not correlate with mannose-resistant/Proteus-like (MR/P) or mannose-resistant/Klebsiella-like (MR/K) hemagglutination and represents a novel fimbria of P. mirabilis.


The PrEDICT-DGE score as a simple preoperative screening tool identifies patients at increased risk for delayed gastric emptying after pancreaticoduodenectomy.
Morbidity after Pancreaticoduodenectomy (PD) has remained unchanged over the past decade. Delayed Gastric Emptying (DGE) is a major contributor with significant impact on healthcare-costs, quality of life and, for malignancies, even survival. We sought to develop a scoring system to aid in easy preoperative identification of patients at risk for DGE. The ACS-NSQIP dataset from 2014 to 2018 was queried for patients undergoing PD with Whipple or pylorus preserving reconstruction. 15,154 patients were analyzed using multivariable logistic regression to identify risk factors for DGE, which were incorporated into a prediction model. Subgroup analysis of patients without SSI or fistula (primary DGE) was performed. We identified 9 factors independently associated with DGE to compile the PrEDICT-DGE score: Procedures (Concurrent adhesiolysis, feeding jejunostomy, vascular reconstruction with vein graft), Elderly (Age>70), Ductal stent (Lack of biliary stent), Invagination (Pancreatic reconstruction technique), COPD, Tobacco use, Disease, systemic (ASA>2), Gender (Male) and Erythrocytes (preoperative RBC-transfusion). PrEDICT-DGE scoring strongly correlated with actual DGE rates (R2 = 0.95) and predicted patients at low, intermediate, and high risk. Subgroup analysis of patients with primary DGE, retained all predictive factors, except for age>70 (p = 0.07) and ASA(p = 0.30). PrEDICT-DGE scoring accurately identifies patients at high risk for DGE and can help guide perioperative management.


Chronic urticaria in patients with autoimmune thyroiditis: significance of severity of thyroid gland inflammation.
There is a clear association between autoimmune thyroiditis (AT) and chronic urticaria/angioedema (CUA). However, not all patients with AT demonstrate urticaria. The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP) was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not. Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1) and 28 patients without urticaria (Group 2) were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained. All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively) (P=0.358). Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012). Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282). In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015) was associated with the remission of urticaria. In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.


Dual-process theory of racial isolation, legal cynicism, and reported crime.
Why is neighborhood racial composition linked so strongly to police-reported crime? Common explanations include over-policing and negative interactions with police, but police reports of crime are heavily dependent on resident 911 calls. Using Sampson's concept of legal cynicism and Vaisey's dual-process theory, we theorize that racial concentration and isolation consciously and nonconsciously influence neighborhood variation in 911 calls for protection and prevention. The data we analyze are consistent with this thesis. Independent of police reports of crime, we find that neighborhood racial segregation in 1990 and the legal cynicism about crime prevention and protection it engenders have lasting effects on 911 calls more than a decade later, in 2006-2008. Our theory explains this persistent predictive influence through continuity and change in intervening factors. A source of cumulative continuity, the intensification of neighborhood racial concentration and isolation between 1990 and 2000, predicts 911 calls. Likewise, sources of change-heightened neighborhood incarceration and home foreclosures during the financial crisis in 2006-2008-also predict these calls. Our findings are consistent with legal cynicism theory's focus on neighborhood disadvantage, racial isolation, and concerns about police protection and crime prevention; they correspond less with the emphasis of procedural justice theory on police legitimacy.


GCN-5/PGC-1α signaling is activated and associated with metabolism in cyclin E1-driven ovarian cancer.
We previously found Cyclin E1-driven high grade serous ovarian cancer (HGSOC) showed metabolic shift. In this study, we aimed to elucidate signaling pathway therein. In silico reproduction of TCGA ovarian cancer dataset and pathway analysis were performed. Candidate metabolic pathway was validated using in vitro and in vivo assays. We found CCNE1-amplified HGSOC showed significant metabolic alteration besides canonical cell cycle control. Using CCNE1-amplified OVCAR-3 and A2780 OvCa cells, we found that knockdown of CDK2 and GCN5 resulted in decreased G6PC and increased PGC-1α level, and that both genetic and pharmaceutical (MB-3) inhibition of GCN5 resulted in significant decrease in acetylation of PGC-1α. Silencing of CDK2 also resulted in significant decrease in acetylation of both PGC-1α and Rb. GCN5-KD significantly decreased glucose uptake, increased lactate production and decreased SDH activity. Western blots showed hierarchy of the elements indicating Cyclin E1-CDK2/GCN5/PGC-1α regulatory axis from up- to down- stream. Inhibitory effect of Dinaciclib was similar to that of GCN5 silencing, whereas combination therapy further inhibited cell proliferation significantly. Similar findings were noted also in cell cycle arrest, apoptosis, invasion, migration and colony formation assays. Xenograft experiments showed that GCN5-KD alone did not alter tumor growth yet combination therapy of Dinaciclib and GCN5-KD conferred significant inhibition of tumor growth compared with either therapy alone with no toxicity observed. GCN-5/PGC-1α signaling is activated and associated with metabolism in Cyclin E1-driven HGSOC. Targeting GCN5 hold promise to augment current CDK2-targeting strategy and further studies are warranted for clinical translation.


Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.
Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.


An analysis of the polypeptide composition of bovine heart mitochondrial NADH-ubiquinone oxidoreductase by two-dimensional polyacrylamide-gel electrophoresis.
Purified preparations of Complex I (NADH-ubiquinone oxidoreductase) from bovine heart mitochondria may be resolved into 26 polypeptides by two-dimensional analysis combining isoelectric focusing and polyacrylamide-gel electrophoresis in sodium dodecyl sulphate. Similar analyses of the fragments obtained from chaotropic resolution of the enzyme show that each of these fragments contains a distinct and non-overlapping set of polypeptides. Evidence that the polypeptides seen in the intact enzyme are true constituents comes from analyses of immunoprecipitates obtained by allowing Complex I or solubilized submitochondrial particles to react with antisera directed against the whole enzyme and a subfragment of the enzyme.


[Dentists about dental anxiety and the treatment of anxious patients; a pilot study].
Dentists' attitudes towards dental anxiety and management of anxious patients were objects of a pilot study. Dentists from The Netherlands participated in a group discussion. Results show that dentists understand dental anxiety in their patients. However, upon closer consideration the picture they give of themselves in this respect appears to be too positive. The role of the dental assistant is generally considered to be very important.


Insulin-like growth factor 1 prevents diastolic and systolic dysfunction associated with cardiomyopathy and preserves adrenergic sensitivity.
Insulin-like growth factor 1 (IGF-1)-dependent signalling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here, we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Rats were perfused with isoproterenol via osmotic pump (1 mg kg(-1) per day) and treated with 2 mg kg(-1) IGF-1 (2 mg kg(-1) per day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analysed for fibrosis and apoptosis, and relevant biochemical signalling cascades were assessed. After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax) and structural remodelling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signalling and activated Akt are selectively upregulated in Iso+IGF-1-treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups; however, tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies.


Intra- and Inter-subject Variability in EEG-Based Sensorimotor Brain Computer Interface: A Review.
Brain computer interfaces (BCI) for the rehabilitation of motor impairments exploit sensorimotor rhythms (SMR) in the electroencephalogram (EEG). However, the neurophysiological processes underpinning the SMR often vary over time and across subjects. Inherent intra- and inter-subject variability causes covariate shift in data distributions that impede the transferability of model parameters amongst sessions/subjects. Transfer learning includes machine learning-based methods to compensate for inter-subject and inter-session (intra-subject) variability manifested in EEG-derived feature distributions as a covariate shift for BCI. Besides transfer learning approaches, recent studies have explored psychological and neurophysiological predictors as well as inter-subject associativity assessment, which may augment transfer learning in EEG-based BCI. Here, we highlight the importance of measuring inter-session/subject performance predictors for generalized BCI frameworks for both normal and motor-impaired people, reducing the necessity for tedious and annoying calibration sessions and BCI training.


Comparative study of influenza virus replication in MDCK cells and in primary cells derived from adenoids and airway epithelium.
Although clinical trials with human subjects are essential for determination of safety, infectivity, and immunogenicity, it is desirable to know in advance the infectiousness of potential candidate live attenuated influenza vaccine strains for human use. We compared the replication kinetics of wild-type and live attenuated influenza viruses, including H1N1, H3N2, H9N2, and B strains, in Madin-Darby canine kidney (MDCK) cells, primary epithelial cells derived from human adenoids, and human bronchial epithelium (NHBE cells). Our data showed that despite the fact that all tissue culture models lack a functional adaptive immune system, differentiated cultures of human epithelium exhibited the greatest restriction for all H1N1, H3N2, and B vaccine viruses studied among three cell types tested and the best correlation with their levels of attenuation seen in clinical trials with humans. In contrast, the data obtained with MDCK cells were the least predictive of restricted viral replication of live attenuated vaccine viruses in humans. We were able to detect a statistically significant difference between the replication abilities of the U.S. (A/Ann Arbor/6/60) and Russian (A/Leningrad/134/17/57) cold-adapted vaccine donor strains in NHBE cultures. Since live attenuated pandemic influenza vaccines may potentially express a hemagglutinin and neuraminidase from a non-human influenza virus, we assessed which of the three cell cultures could be used to optimally evaluate the infectivity and cellular tropism of viruses derived from different hosts. Among the three cell types tested, NHBE cultures most adequately reflected the infectivity and cellular tropism of influenza virus strains with different receptor specificities. NHBE cultures could be considered for use as a screening step for evaluating the restricted replication of influenza vaccine candidates.


Candidate Biomarkers for the Prediction and Monitoring of Partial Remission in Pediatric Type 1 Diabetes.
The partial remission (PR) phase, a period experienced by most patients with type 1 diabetes (T1D) soon after diagnosis, is characterized by low insulin requirements and improved glycemic control. Given the great potential of this phase as a therapeutic window for immunotherapies because of its association with immunoregulatory mechanisms and β-cell protection, our objective was to find peripheral immunological biomarkers for its better characterization, monitoring, and prediction. The longitudinal follow-up of 17 pediatric patients with new-onset T1D over one year revealed that, during the PR phase, remitter patients show increased percentages of effector memory (EM) T lymphocytes, terminally differentiated EM T lymphocytes, and neutrophils in comparison to non-remitter patients. On the contrary, remitter patients showed lower percentages of naïve T lymphocytes, regulatory T cells (TREG), and dendritic cells (DCs). After a year of follow-up, these patients also presented increased levels of regulatory B cells and transitional T1 B lymphocytes. On the other hand, although none of the analyzed cytokines (IL-2, IL-6, TGF-β1, IL-17A, and IL-10) could distinguish or predict remission, IL-17A was increased at T1D diagnosis in comparison to control subjects, and remitter patients tended to maintain lower levels of this cytokine than non-remitters. Therefore, these potential monitoring immunological biomarkers of PR support that this stage is governed by both metabolic and immunological factors and suggest immunoregulatory attempts during this phase. Furthermore, since the percentage of TREG, monocytes, and DCs, and the total daily insulin dose at diagnosis were found to be predictors of the PR phase, we next created an index-based predictive model comprising those immune cell percentages that could potentially predict remission at T1D onset. Although our preliminary study needs further validation, these candidate biomarkers could be useful for the immunological characterization of the PR phase, the stratification of patients with better disease prognosis, and a more personalized therapeutic management.


Interleukin-1 and tumor necrosis factor-α trigger restriction of hepatitis B virus infection via a cytidine deaminase activation-induced cytidine deaminase (AID).
Virus infection is restricted by intracellular immune responses in host cells, and this is typically modulated by stimulation of cytokines. The cytokines and host factors that determine the host cell restriction against hepatitis B virus (HBV) infection are not well understood. We screened 36 cytokines and chemokines to determine which were able to reduce the susceptibility of HepaRG cells to HBV infection. Here, we found that pretreatment with IL-1β and TNFα remarkably reduced the host cell susceptibility to HBV infection. This effect was mediated by activation of the NF-κB signaling pathway. A cytidine deaminase, activation-induced cytidine deaminase (AID), was up-regulated by both IL-1β and TNFα in a variety of hepatocyte cell lines and primary human hepatocytes. Another deaminase APOBEC3G was not induced by these proinflammatory cytokines. Knockdown of AID expression impaired the anti-HBV effect of IL-1β, and overexpression of AID antagonized HBV infection, suggesting that AID was one of the responsible factors for the anti-HBV activity of IL-1/TNFα. Although AID induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV activity. The antiviral effect of IL-1/TNFα was also observed on different HBV genotypes but not on hepatitis C virus. These results demonstrate that proinflammatory cytokines IL-1/TNFα trigger a novel antiviral mechanism involving AID to regulate host cell permissiveness to HBV infection.


Reliability and Validity of a New Toileting Assessment Form for Patients with Hemiparetic Stroke.
Acquiring toileting independence is an important target of stroke rehabilitation. In planning an intervention for acquiring toileting independence, developing an assessment for individual subtasks that comprise toileting would assist in identifying specific tasks that prevent independence in patients and would facilitate interventions to improve toileting independence. To examine the reliability and validity of a newly developed toileting assessment form, the Toileting Tasks Assessment Form (TTAF), for assessing toileting subtasks in hemiparetic stroke. Validation and test-retest study. Subacute rehabilitation wards in Japan. Eighty-two therapists verified the form's content validity; 30 stroke patients who were using a wheelchair participated in the validation and test-retest study. Not applicable. The content validity of the assessment form was initially assessed based on a questionnaire. Subsequently, four occupational therapists used the form to evaluate video-recorded toileting performances simulated by participants with hemiparetic stroke. Two assessors evaluated each video-recorded performance once and repeated the evaluation of the same performance at 2 weeks later. The interrater reliability, intrarater reliability, internal consistency, and concurrent validity of the form were examined. Fleiss' κ coefficient for interrater reliability for each form item was 0.61 or more. Cohen's κ coefficient for intrarater reliability for each item was 0.60 or more. Cronbach's coefficient alpha ranged from 0.94 to 0.95. Spearman's rank correlation coefficients for the mean score on the form and the Functional Independence Measure (FIM) score for "toileting" ranged from 0.88 to 0.93 (P < .001). Spearman's rank correlation coefficients for the mean score on the form and the FIM score for "toilet transfer" ranged from 0.91 to 0.93 (P < .001). The TTAF demonstrated good reliability and validity. Further multicenter studies involving patients at different stroke phases are required to verify the reliability and validity of TTAF and confirm the generalizability of these findings.


Antibodies to glutamate receptor subtype 3 (GluR3) are found in some patients suffering from epilepsy as the main disease, but not in patients whose epilepsy accompanies antiphospholipid syndrome or Sneddon's syndrome.
Autoantibodies (Ab's) to the "B" peptide (amino acids 372-395) of glutamate/AMPA receptor subtype 3 (GluR3) are found in serum and cerebrospinal fluid of some patients with different types of epilepsy. Since such anti-GluR3B Ab's can activate and/or kill neurons in vitro and in vivo, they may contribute to epilepsy. To investigate whether anti-GluR3B Ab's may also be relevant to epilepsy when it accompanies some autoimmune-diseases, we tested for these Ab's in patients suffering from epilepsy that accompanies anti-phospholipid syndrome (APS) or Sneddon's syndrome (SNS), both being autoimmune-diseases with frequent neurological complications. We tested 77 pediatric patients whose epilepsy is their main disease; 31 adult patients whose epilepsy accompanies APS (primary or SLE-associated) or SNS; 45 epilepsy-free APS and SNS patients; and 90 healthy controls. Compared to the controls, significantly elevated anti-GluR3B Ab's were found in 22/77 (29%) patients whose epilepsy is their main disease, but in none of the patients whose seizures accompany APS or SNS. Yet, all the APS and SNS patients harbored the characteristic anti-phospholipid Ab's (aPL), directed against cardiolipin and beta2-glycoprotein I, and had lupus anti-coagulant. Thus, anti-GluR3B Ab's are not crossreactive with aPL, and not produced as a non-specific consequence of seizures on the one hand, or autoimmune-diseases on the other. Taken together with new findings accumulated recently in our lab, we suggest that anti-GluR3B Ab's are produced primarily in the periphery due to specific/non-specific "irritation" of the immune system, and that once they reach the brain via a leaky blood-brain barrier they may cause neuronal/glial damage and facilitate the outburst of epilepsy and additional neurological abnormalities. In contrast, the presence of anti-GluR3B Ab's does not seem to increase the probability of developing APS, SNS or the seizures that often accompany these autoimmune-diseases. These findings may have important diagnostic and therapeutic implications.


Phylogenetic analyses of Norwegian Tenacibaculum strains confirm high bacterial diversity and suggest circulation of ubiquitous virulent strains.
Tenacibaculosis is a bacterial ulcerative disease affecting marine fish and represents a major threat to aquaculture worldwide. Its aetiological agents, bacteria belonging to the genus Tenacibaculum, have been present in Norway since at least the late 1980's and lead to regular ulcerative outbreaks and high mortalities in production of farmed salmonids. Studies have shown the presence of several Tenacibaculum species in Norway and a lack of clonality in outbreak-related strains, thus preventing the development of an effective vaccine. Hence, a thorough examination of the bacterial diversity in farmed fish presenting ulcers and the geographical distribution of the pathogens should provide important insights needed to strengthen preventive actions. In this study, we investigated the diversity of Tenacibaculum strains isolated in 28 outbreaks that occurred in Norwegian fish farms in the period 2017-2020. We found that 95% of the 66 strains isolated and characterized, using an existing MultiLocus Sequence Typing system, have not previously been identified, confirming the high diversity of this genus of bacteria in Norway. Several of these Tenacibaculum species seem to be present within restricted areas (e.g., Tenacibaculum dicentrarchi in western Norway), but phylogenetic analysis reveals that several of the strains responsible of ulcerative outbreaks were isolated from different localities (e.g., ST- 172 isolated from northern to southern parts of Norway) and/or from different hosts. Understanding their reservoirs and transmission pathways could help to address major challenges in connection with prophylactic measures and development of vaccines.


Unusual lipids in the Caribbean sponges Amphimedon viridis and Desmapsamma anchorata.
The phospholipid fatty acid composition of the Caribbean sponge Amphimedon viridis was studied, revealing the presence of the previously unreported substances 5,13-nonadecadienoic acid, 4-nonadecenoic acid, and 15-heneicosenoic acid. In A. viridis the very long-chain 5,9,23-nonacosatrienoic acid and 5,9,23-tricosatrienoic acid predominated in the mixture. The fatty acid composition of the sponge Desmapsamma anchorata was revised and 62 phospholipid fatty acids were characterized. The rare 8,13-octadecadienoic acid and 18-tetracosenoic acid were also characterized in the mixture. The two possible stereochemical isomers of 7-methyl-6-hexadecenoic acid, i.e., 7-methyl-6(Z)-hexadecenoic acid and the 7-methyl-6(E)-hexadecenoic acid were identified in both sponges, but D. anchorata had larger amounts. This is the first time that both stereoisomers have been identified in a sponge. The previously reported 7-methyl-8-hexadecenoic acid was not found in D. anchorata. Unprecedented aldehydes, comprising 15-and 17-docosenal, were also identified in the sponges.


The changing natural history of metastatic prostate cancer.
Since 1941, the understanding of prostate cancer pathogenesis and therapy has undergone a significant transformation. Rigorous translational research has identified multiple mechanisms underlying castration resistance, the fatal clinical state of the disease. Therapeutic approaches targeting these mechanisms in metastatic castration-resistant prostate cancer have now been clinically validated in the clinic including high-potency androgen signaling inhibition, novel cytotoxic chemotherapy, and bone-targeted therapies. Despite these advances, cure remains an elusive goal. The natural history of metastatic prostate cancer has evolved particularly in the last 2 decades in step with improved management of age-associated comorbidities, improved imaging, and the expansion of novel therapies, thus providing new opportunities and challenges. It is also important to note that the advent of prostate-specific antigen testing caused a stage shift in the disease spectrum, thus leading to earlier interventions and potentially positively impacting survival. The optimal sequencing and combinations of available therapies, predictive biomarkers, and better understanding of mechanisms of resistance remain high priority. Further refinement of the clinical niche for novel therapies in hormone-sensitive and castration-resistant disease through rationally designed clinical trials incorporating molecular, clinical, and imaging biomarkers and quality-of-life correlatives is of paramount importance.


Marine Algae as a Potential Source for Anti-diabetic Compounds - A Brief Review.
Diabetes Mellitus (DM) is a major chronic metabolic disorder characterized by hyperglycemia that leads to several complications such as retinopathy, atherosclerosis, nephropathy, etc. In 2019, it was estimated that about 463 million people had diabetes, and it may increase up to 700 million in 2045. Marine macroalgae are the rich source of bioactive compounds for the treatment of diabetes mellitus. This review summarizes the recent epidemiology and possible use of marine macroalgae-derived bioactive compounds for the protection against chronic metabolic disease, diabetes mellitus and marine macroalgae as a nutraceutical supplement. The present therapies available for diabetes treatment are oral medicines and insulin injections. But continuous use of synthetic medicines provides low therapeutic with many side effects. In continuing search of anti-diabetic drugs, marine macroalgae remain as a promising source with potent bioactivity. Among existing marine algae, red and brown algae are reported to show anti-diabetic activity. Hence, the present review focuses on the epidemiology, diabetes biomarkers and different secondary bioactive compounds present in marine macroalgae to treat diabetes mellitus.


Structural insight into catalytic mechanism of PET hydrolase.
PET hydrolase (PETase), which hydrolyzes polyethylene terephthalate (PET) into soluble building blocks, provides an attractive avenue for the bioconversion of plastics. Here we present the structures of a novel PETase from the PET-consuming microbe Ideonella sakaiensis in complex with substrate and product analogs. Through structural analyses, mutagenesis, and activity measurements, a substrate-binding mode is proposed, and several features critical for catalysis are elucidated.


[Specificity of suprathreshold computer perimetry].
The problems encountered in linear suprathreshold computer perimetry are discussed in the light of results with the Fieldmaster 200 automatic perimeter utilizing different test conditions. A linear supraluminosity of the test points, especially in the central visual field, results in poor specificity of the periphery of the tested area if no substantial loss of sensitivity is acceptable. Taking the three-dimensional distribution of retinal thresholds into account, the supraluminosity of the perimetric stimuli should be adapted to the eccentricity of testing.


Progression of alcoholic acute to chronic pancreatitis.
Alcoholic chronic pancreatitis usually progresses from acute attacks to chronic pancreatitis within one to 19 years. The factors responsible for the appreciable variability in progression are unclear. In this study the relation between progression and the incidence and severity of acute episodes in a large cohort of patients with alcoholic chronic pancreatitis was analysed. All patients with at least one documented episode of acute pancreatitis have been studied prospectively over the past 30 years according to our protocol. Patients were classified according to their long term course into (a) calcific (n = 185), (b) non-calcific (n = 30), and (c) non-progressive (n = 39) chronic pancreatitis groups. The yearly incidence of acute attacks of pancreatitis was significantly higher in groups (a) and (b) than in group (c). Furthermore, the progression rate to advanced chronic pancreatitis (groups (a) and (b)) correlated with the incidence of severe pancreatitis (associated with pseudocysts in more than 55%). Pseudocysts were located primarily in the cephalic pancreas in groups (a) and (b) (58-71%) and in the pancreatic tail in group (c) (61%). In conclusion, these data suggest that the progression of acute to chronic pancreatitis is closely related to the incidence and severity of acute attacks. This finding and the primary location of pseudocysts in the cephalic pancreas (groups (a) plus (b)) are compatible with the 'necrosis-fibrosis' pathogenetic hypothesis.


The heparan sulfate motif (GlcNS6S-IdoA2S)3, common in heparin, has a strict topography and is involved in cell behavior and disease.
Heparan sulfate (HS) is a structurally complex polysaccharide that interacts with a broad spectrum of extracellular effector ligands and thereby is thought to regulate a diverse array of biologic processes. The specificity of HS-ligand interactions is determined by the arrangement of sulfate groups on HS, which creates distinct binding motifs. Biologically important HS motifs are expected to exhibit regulated expression, yet there is a profound lack of tools to identify such motifs; consequently, little is known of their structures and functions. We have identified a novel phage display-derived antibody (NS4F5) that recognizes a highly regulated HS motif (HS(NS4F5)), which we have rigorously identified as (GlcNS6S-IdoA2S)(3). HS(NS4F5) exhibits a restricted expression in healthy adult tissues. Blocking HS(NS4F5) on cells in culture resulted in reduced proliferation and enhanced sensitivity to apoptosis. HS(NS4F5) is up-regulated in tumor endothelial cells, consistent with a role in endothelial cell activation. Indeed, TNF-α stimulated endothelial expression of HS(NS4F5), which contributed to leukocyte adhesion. In a mouse model of severe systemic amyloid protein A amyloidosis, HS(NS4F5) was expressed within amyloid deposits, which were successfully detected by microSPECT imaging using NS4F5 as a molecularly targeted probe. Combined, our results demonstrate that NS4F5 is a powerful tool for elucidating the biological function of HS(NS4F5) and can be exploited as a probe to detect novel polysaccharide biomarkers of disease processes.


The type 2 deiodinase ORFa-Gly3Asp polymorphism (rs12885300) influences the set point of the hypothalamus-pituitary-thyroid axis in patients treated for differentiated thyroid carcinoma.
Iodothyronine deiodinases D1, D2, and D3 play an important role in synthesis and degradation of T(3). The relationship between serum TSH and free T(4) (FT(4)) levels is determined by an individual set point of the hypothalamus-pituitary-thyroid axis. Several polymorphisms have been described in D1 and D2 of which some are associated with serum TSH and iodothyronine levels. In this study we investigate whether polymorphisms of D1 and D2 influence the set point of the hypothalamus-pituitary-thyroid axis. We collected 1905 serum FT(4) and TSH measurements during 11.5 ± 8.8 yr of follow-up in patients treated for differentiated thyroid carcinoma (DTC). We determined these polymorphisms: D1-rs11206244, D1-rs12095080, D2-rs225014, and D2-rs12885300. Effects of these polymorphisms on the set points of the hypothalamus-pituitary-thyroid axis were analyzed with a linear mixed model. The study was conducted at Leiden University Medical Center, a tertiary referral center for DTC. One hundred fifty-one consecutive patients were treated and cured for DTC. Slopes and intercepts of regression equations representing the relationship between InTSH and FT(4) were measured for all polymorphisms. DTC patients homozygous for the D2-rs12885300 T allele have an altered set point of the hypothalamus-pituitary-thyroid axis. The slope of the regression line (corrected for age, body mass index, and gender) for wild-type patients was -0.32 ± 0.028 (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)]), the intercept, 4.95. For heterozygous patients, the slope was -0.30 ± 0.028 (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)]), the intercept, 4.23. The slope of the homozygous patients was -0.35 ± 0.026 (ln[TSH(mU/liter)]/[FT(4)(pmol/liter)]) and the intercept, 6.07 (P = 0.036 compared with wild-type and heterozygous patients). Our data suggest that the negative feedback of FT(4) on TSH is weaker in patients homozygous for the D2-rs12885300 T allele than in wild-type and heterozygous subjects.


Schizophrenia is associated with a pattern of spatial working memory deficits consistent with cortical disinhibition.
Schizophrenia is associated with severe cognitive deficits, including impaired working memory (WM). A neural mechanism that may contribute to WM impairment is the disruption in excitation-inhibition (E/I) balance in cortical microcircuits. It remains unknown, however, how these alterations map onto quantifiable behavioral deficits in patients. Based on predictions from a validated microcircuit model of spatial WM, we hypothesized two key behavioral consequences: i) increased variability of WM traces over time, reducing performance precision; and ii) decreased ability to filter out distractors that overlap with WM representations. To test model predictions, we studied N=27 schizophrenia patients and N=28 matched healthy comparison subjects (HCS) who performed a spatial WM task designed to test the computational model. Specifically, we manipulated delay duration and distractor distance presented during the delay. Subjects used a high-sensitivity joystick to indicate the remembered location, yielding a continuous response measure. Results largely followed model predictions, whereby patients exhibited increased variance and less WM precision as the delay period increased relative to HCS. Schizophrenia patients also exhibited increased WM distractibility, with reports biased toward distractors at specific spatial locations, as predicted by the model. Finally, the magnitude of the WM drift and distractibility were significantly correlated, indicating a possibly shared underlying mechanism. Effects are consistent with elevated E/I ratio in schizophrenia, establishing a framework for translating neural circuit computational model of cognition to human experiments, explicitly testing mechanistic behavioral hypotheses of cellular-level neural deficits in patients.


Effect of Probiotic Lactobacillus reuteri on Salivary Cariogenic Bacterial Counts among Groups of Preschool Children in Jeddah, Saudi Arabia: A Randomized Clinical Trial.
To evaluate the effect of probiotic Lactobacilli reuteri lozenges on caries-associated salivary bacterial counts (Mutans streptococci and Lactobacillus), dental plaque accumulation, and salivary buffer capacity in a group of preschool children. The study group consisted of 178 healthy children (aged 3-6 years). Children were randomly grouped: the experimental group (n = 90) received L. reuteri probiotic lozenges and the control group (n = 88) received placebo lozenges, twice daily, for 28 days. Salivary Mutans streptococci and Lactobacillus counts, and buffer capacity were assessed using chair-side caries-risk test (CRT®) kits. The Simplified Oral Hygiene index (OHI-S) was used to assess dental plaque accumulation at baseline and after 28 days. After 28 days, the experimental group had a statistically significant reduction in Mutans streptococci and lactobacilli (p = 0.000 and p = 0.020, respectively) and both groups had less plaque accumulation than at baseline. While the buffer capacity in the experimental group increased more than in the control group, it was not statistically significant (p = 0.577). Compliance was 90%, with no adverse events. Consumption of probiotic lozenges containing L. reuteri reduces caries-associated bacterial counts significantly. Probiotics consumption may have a beneficial caries-preventive effect.


DosOpt: A Tool for Personalized Bayesian Dose Adjustment of Vancomycin in Neonates.
Our main aim has been to design a framework to improve vancomycin dosing in neonates. This required the development and verification of a computerized dose adjustment application, DosOpt, to guide the selection. Model fitting in DosOpt uses Bayesian methods for deriving individual pharmacokinetic (PK) estimates from population priors and patient therapeutic drug monitoring measurements. These are used to simulate concentration-time curves and target-constrained dose optimization. DosOpt was verified by assessing bias and precision through several error metrics and normalized prediction distribution errors on samples simulated from the Anderson et al PK model. The performance of DosOpt was also evaluated using retrospective clinical data. Achieved probabilities of target concentration attainment were benchmarked against corresponding attainments in our clinical retrospective data set. Simulations showed no systemic forecast biases. Normalized prediction distribution error values of the base model were distributed by standardized Gaussian (P = 0.1), showing good model suitability. A retrospective test data set included 149 treatment episodes with 1-10 vancomycin concentration measurements per patient (median 2). Individual concentrations in PK estimation improved probability of target attainment and decreased the variance of the estimation. Including 3 individual concentrations in the kinetics estimation increased the probability of Ctrough attainment within 10-15 mg/L from 16% obtained with no individual data (95% confidence interval, 11%-24%) to 43% (21%-47%). DosOpt uses individual concentration data to estimate kinetics and find optimal doses that increase the probability of achieving desired trough concentrations. Its performance started to exceed target levels attained in retrospective clinical data sets with the inclusion of a single individual input concentration. This tool is freely available at http://www.biit.cs.ut.ee/DosOpt.


[Non hereditary porokeratosis of Mibelli].
After a short review of the literature on the clinical and histopathological features of PM, 66 cases of the disease observed in the past 14 years at the IPO Dermatology Deparment are presented. They are compared with the previously mentioned case reports, particularly the ones published in the portuguese literature. The existance of two forms of the disease is suggested, and the differences between them specified. Treatment is considered, with special emphasis on the cases with a small number of lesions.


Optical Antenna-Based Fluorescence Correlation Spectroscopy to Probe the Nanoscale Dynamics of Biological Membranes.
The plasma membrane of living cells is compartmentalized at multiple spatial scales ranging from the nano- to the mesoscale. This nonrandom organization is crucial for a large number of cellular functions. At the nanoscale, cell membranes organize into dynamic nanoassemblies enriched by cholesterol, sphingolipids, and certain types of proteins. Investigating these nanoassemblies known as lipid rafts is of paramount interest in fundamental cell biology. However, this goal requires simultaneous nanometer spatial precision and microsecond temporal resolution, which is beyond the reach of common microscopes. Optical antennas based on metallic nanostructures efficiently enhance and confine light into nanometer dimensions, breaching the diffraction limit of light. In this Perspective, we discuss recent progress combining optical antennas with fluorescence correlation spectroscopy (FCS) to monitor microsecond dynamics at nanoscale spatial dimensions. These new developments offer numerous opportunities to investigate lipid and protein dynamics in both mimetic and native biological membranes.


Exploring loss to follow-up: abnormal Pap screening in Hispanic patients.
The loss of patients to follow-up for abnormal findings from Pap screenings is an important public health concern, particularly among poor and minority women. This study explores factors affecting incomplete follow-up among a group of Hispanic women with low incomes. A qualitative descriptive study was conducted of 11 Hispanic patients with incomplete Pap smear follow-up at a public clinic in a major city in south Texas. Patients were interviewed using a semistructured, open-ended schedule of questions, and their medical records were abstracted. The clinic's five staff members also were interviewed. Comparative chronologies were constructed for each case, contrasting patient and staff accounts of the same set of events. All data were coded by at least two investigators. All study patients had mildly abnormal Pap smear results and had not met the follow-up criteria, but all understood and were committed to Pap screening. Although viewed by staff as noncompliant, none of the patients viewed her behavior this way. This staff-patient discrepancy was attributable to poor communication, mixed messages, clinic errors, and, perhaps most importantly, to a conflict between program policies and the specific circumstances of individual cases. Two case examples are presented to illustrate key points. Strategies that may help to reduce loss to follow-up among similar patients include the following: allowing clinic staff more flexibility in follow-up procedures for women who have consistently normal follow-up tests, including Spanish translations of written messages; enlisting patients' agreement in setting appointments; and updating patient records to reflect follow-up care that had been received in other clinics.


In vivo degradation of polyethylene liners after gamma sterilization in air.
Ultra-high molecular weight polyethylene degrades during storage in air following gamma sterilization, but the extent of in vivo degradation remains unclear. The purpose of this study was to quantify the extent to which the mechanical properties and oxidation of conventional polyethylene acetabular liners treated with gamma sterilization in air change in vivo. Fourteen modular cementless acetabular liners were revised at an average of 10.3 years (range, 5.9 to 13.5 years) after implantation. All liners, which had been machined from GUR 415 resin, had been gamma-sterilized in air; the average shelf life was 0.3 year (range, 0.0 to 0.8 year). After removal, the components were expeditiously frozen to minimize ex vivo changes to the polyethylene prior to characterization. The average duration between freezing and testing was 0.6 year. Mechanical properties and oxidation were measured with use of the small-punch test and Fourier transform infrared spectroscopy, respectively, in the loaded and unloaded regions of the liners. There was substantial regional variation in the mechanical properties and oxidation of the retrieved liners. The ultimate load was observed to vary by >90% near the surface. On the average, the rim and the unloaded bearing showed evidence of severe oxidation near the surface after long-term in vivo aging, but these trends were not typically observed on the loaded bearing surface or near the backside of the liners. The mechanical properties of polyethylene that has been gamma-sterilized in air may decrease substantially in vivo, depending on the location in the liner. The most severe oxidation was observed at the rim, suggesting that the femoral head inhibits access of oxygen-containing body fluids to the bearing surface. This is perhaps why in vivo oxidation has not been associated with clinical performance to date.


Daily Life Benefits and Usage Characteristics of Dynamic Arm Supports in Subjects with Neuromuscular Disorders.
Neuromuscular disorders cause progressive muscular weakness, which limits upper extremity mobility and performance during activities of daily life. Dynamic arm supports can improve mobility and quality of life. However, their use is often discontinued over time for unclear reasons. This study aimed to evaluate whether users of dynamic arm supports demonstrate and perceive quantifiable mobility benefits over a period of two months. Nine users of dynamic arm supports were included in this observational study. They had different neuromuscular disorders and collectively used four different arm supports. They were observed for three consecutive weeks during which they were equipped with a multi-sensor network of accelerometers to assess the actual use of the arm support and they were asked to provide self-reports on the perceived benefits of the devices. Benefits were experienced mainly during anti-gravity activities and the measured use did not change over time. The self-reports provided contextual information in domains such as participation to social life, in addition to the sensor system. However self-reports overestimated the actual use by up to three-fold compared to the accelerometer measures. A combination of objective and subjective methods is recommended for meaningful and quantifiable mobility benefits during activities of daily life.


Dibutyryl cAMP, aminophylline, and beta-adrenergic agonists protect against pulmonary edema caused by phosgene.
Phosgene is a toxic oxidant gas that causes the adult respiratory distress syndrome in exposed workers. Phosgene exposure markedly increased lung weight gain in buffer-perfused isolated rabbit lungs (31 +/- 5 g over 60 min after phosgene vs. 7.7 +/- 1.2 in control lungs, P less than 0.01) and markedly increased the lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.02 +/- 0.01 in control lungs, P less than 0.01). Pretreatment with dibutyryl adenosine 3',5' -cyclic monophosphate (DBcAMP), aminophylline, or terbutaline plus isoproterenol prevented the increase in lung weight caused by phosgene (31 +/- 5 g phosgene, 11.7 +/- 2.8 DBcAMP, 7.5 +/- 2.5 aminophylline, 6.1 +/- 1 terbutaline and isoproterenol, 6.1 +/- 1.2 control + aminophylline, and 7.7 +/- 1.2 control; all treatments were P less than 0.01 vs. the untreated phosgene group and not significantly different from control lungs). Pretreatment with aminophylline prevented the increase in lung leak index for 125I-albumin (0.28 +/- 0.03 after phosgene vs. 0.06 +/- 0.02 in aminophylline-treated lungs, P less than 0.01). Posttreatment with aminophylline and terbutaline also prevented the increase in lung weight caused by phosgene. These results indicate that phosgene dramatically increases the movement of fluid and protein across the pulmonary vasculature and that treatment with DBcAMP, aminophylline, terbutaline, or isoproterenol markedly reduces the pulmonary edema caused by phosgene.


Iterative data-driven forecasting of the transmission and management of SARS-CoV-2/COVID-19 using social interventions at the county-level.
The control of the initial outbreak and spread of SARS-CoV-2/COVID-19 via the application of population-wide non-pharmaceutical mitigation measures have led to remarkable successes in dampening the pandemic globally. However, with countries beginning to ease or lift these measures fully to restart activities, concern is growing regarding the impacts that such reopening of societies could have on the subsequent transmission of the virus. While mathematical models of COVID-19 transmission have played important roles in evaluating the impacts of these measures for curbing virus transmission, a key need is for models that are able to effectively capture the effects of the spatial and social heterogeneities that drive the epidemic dynamics observed at the local community level. Iterative forecasting that uses new incoming epidemiological and social behavioral data to sequentially update locally-applicable transmission models can overcome this gap, potentially resulting in better predictions and policy actions. Here, we present the development of one such data-driven iterative modelling tool based on publicly available data and an extended SEIR model for forecasting SARS-CoV-2 at the county level in the United States. Using data from the state of Florida, we demonstrate the utility of such a system for exploring the outcomes of the social measures proposed by policy makers for containing the course of the pandemic. We provide comprehensive results showing how the locally identified models could be employed for accessing the impacts and societal tradeoffs of using specific social protective strategies. We conclude that it could have been possible to lift the more disruptive social interventions related to movement restriction/social distancing measures earlier if these were accompanied by widespread testing and contact tracing. These intensified social interventions could have potentially also brought about the control of the epidemic in low- and some medium-incidence county settings first, supporting the development and deployment of a geographically-phased approach to reopening the economy of Florida. We have made our data-driven forecasting system publicly available for policymakers and health officials to use in their own locales, so that a more efficient coordinated strategy for controlling SARS-CoV-2 region-wide can be developed and successfully implemented.


Case Report of Untreated Pediatric Femoral Neck Fracture with Osteopenia.
Pediatric hip fractures are rare. This type of injury often requires surgery within 24 hours to prevent complications such as avascular necrosis, bone non-union, and premature physeal closure. Moreover, chronic disuse from untreated fracture causes severe osteopenia. Untreated pediatric hip fracture is uncommon in the developing world due to access to surgical care. Here, we report a pediatric patient who traveled from Honduras with untreated right femoral neck fracture. The delay in her initial surgical intervention left her with chronic non-union of her right hip joint and significant osteopenia of her right leg secondary to chronic disuse. This patient required a total right hip arthroplasty rather than the conventional internal fixation. It is crucial for emergency physicians to identify the causes of pediatric hip pain. Early detection of these pathologies allows for early orthopedics involvement and surgical intervention to avoid long-term complications. Pediatric orthopedic, femoral neck fracture, osteopenia.


Patterns of care and locoregional treatment outcomes in older esophageal cancer patients: The SEER-Medicare Cohort.
Optimal management of elderly patients with nonmetastatic esophageal cancer is unclear. Outcomes data after locoregional treatment are lacking for this group. We assessed outcomes associated with standard locoregional treatments in 2,626 patients (age > 65 years) from the Surveillance Epidemiology and End Results (SEER)-Medicare cohort diagnosed with nonmetastatic esophageal cancer from 1992 to 2002. In patients treated with radiotherapy alone (RT), surgery alone (S), chemoradiotherapy (CRT), or preoperative chemotherapy followed by surgery (CRT + S), overall and disease-free survival were compared using proportional hazards regression. Postoperative complications were compared using logistic regression. Mean age was 76 +/- 6 years. Seven percent underwent CRT + S, 39% CRT, 30% S, and 24% RT. One-year survival was 68% (CRT + S), 52% (CRT), 53% (S), and 16% (RT), respectively (p < 0.001). Patients who underwent CRT + S demonstrated improved overall survival compared with S alone (hazard ratio [HR] = 0.81; 95% confidence interval [CI], 0.66-0.98; p = 0.03) and RT (HR = 0.44; 95% CI, 0.35-0.55; p < 0.0001); and comparable survival to CRT (HR = 0.82; 95% CI, 0.67-1.01; p = 0.06). Patients who underwent CRT + S also had comparable postoperative mortality (HR = 0.96; 95% CI, 0.87-1.07; p = 0.45) and complications (OR = 0.89; 95% CI, 0.70-1.14; p = 0.36) compared with S alone. Preoperative chemoradiotherapy may be an acceptable treatment option in appropriately selected older esophageal cancer patients. This treatment modality did not appear to increase surgical complications and offered potential therapeutic benefit, particularly compared with surgery alone.


[Health targets and health reporting--significance of a basis for health reporting to achieve health targets].
This report demonstrates the benefits for future health policy performance related to a close connection between health monitoring activities and the implementation of health objectives. Health reports are basically useful for setting up and quantifying health targets, for the construction of target-related measures and evaluation procedures. On the other hand health objectives can be regarded as landmarks for the allocation of health monitoring resources. Deriving appropriate results for health policy makers from data collecting activities, health statistics, and related health reports could be more effective if these activities were connected with an elaborate health target programme. An interactive unit or working group of health target workers and health monitoring professionals is to guarantee optimum interaction between future health practice, research and policy.


A Muscle Biosignature Differentiating Between Limb-Girdle Muscular Dystrophy and Idiopathic Inflammatory Myopathy on Magnetic Resonance Imaging.
Background: The overlapping clinical presentations of limb-girdle muscular dystrophy (LGMD) and idiopathic inflammatory myopathy (IIM) make clinical diagnosis challenging. This study provides a comprehensive evaluation of the distributions and characteristics of muscle fat substitution and edema and aims to differentiate those two diseases. Methods: This retrospective study reviewed magnetic resonance imaging (MRI) of seventeen patients with pathologically proved diagnosis, comprising 11 with LGMD and 6 with IIM. The fat-only and water-only images from a Dixon sequence were used to evaluate muscle fat substitution and edema, respectively. The degrees of muscle fat substitution and edema were graded and compared using the appropriate statistical methods. Results: In LGMD, more than 50% of patients had high-grade fat substitution in the majority of muscle groups in the thigh and calf. However, <50% of IIM patients had high-grade fat substitution in all muscle groups. Moreover, LGMD patients had significantly higher grade fat substitution than IIM patients in all large muscle groups (p < 0.05). However, there was no significant difference in edema in the majority of muscle groups, except the adductor magnus (p = 0.012) and soleus (p = 0.009) with higher grade edema in IIM. Additionally, all the adductor magnus muscles in LGMD (100%) showed high-grade fat substitution, but none of them showed high-grade edema. Conclusions: MRI could be a valuable tool to differentiate LGMD from IIM based on the discrepancy in muscle fat substitution, and the adductor magnus muscle could provide a biosignature to categorizing LGMD.


Prevalence of, and risk factors for, angiographically determined coronary artery disease in type I-diabetic patients with nephropathy.
BACKGROUND--Thirty-five percent of type I-diabetic patients are dead of coronary artery disease by age 55 years, and the risk of death is increased eightfold to 15-fold in patients with nephropathy. However, the prevalence of coronary artery disease with respect to age is unknown and few risk factors have been identified. METHODS--One hundred ten insulin-dependent diabetic patients underwent routine pretransplant coronary angiography and cardiac risk factor assessment. Angiograms were evaluated by two angiographers for presence or absence of coronary artery disease (CAD, defined as one or more coronary artery stenoses of 50% or greater in diameter, and no CAD, defined as no stenosis of 25% or greater in diameter, respectively). Prevalence of CAD by age was determined, and associated risk factors were defined. RESULTS--Fifty-two of 110 patients had CAD. Coronary artery disease prevalence increased significantly with age; 13 of 16 patients older than 45 years of age had CAD. For patients 35 years of age or younger, associated risk factors included a family history of premature myocardial infarction, higher hemoglobin A1c level, hypertension for more than 5 years, lower high-density lipoprotein level, and smoking for more than 5 pack-years. For patients between 35 and 45 years of age, associated risk factors included number of years of diabetes, higher hemoglobin A1c levels, and smoking more than 5 pack-years. CONCLUSIONS--In type I-diabetic patients with nephropathy, CAD prevalence increased significantly with age and was found in the majority of patients older than 45 years of age. Coronary artery disease risk factors operative in the general population were significantly associated with CAD in this high-risk group. In addition, a role for hyperglycemia in accelerated atherogenesis was supported by the association of both higher hemoglobin A1c levels and number of years of diabetes with CAD.


Evidence for the ancestral origin of group I introns in the SSUrDNA of Naegleria spp.
The sequence variation within the group I intron in five Naegleria spp. was studied and compared with the sequence variation within the flanking small subunit ribosomal DNA. Considerable sequence divergence was observed in the introns as well as in the rDNA. In the intron deletions and insertions are only detected in the sequence contributing to the secondary structure, not in the open reading frame. Most of the sequence variation is detected in the unpaired loops. In the case of nucleotide substitution in helices, compensating base pair changes were observed. The sequence variation does not induce variation in the secondary structure model. The phylogenetic tree based on the intron sequences is similar to the tree based on the flanking rDNA sequences. This observation indicates that the intron might have been acquired at an early stage in evolution, and lost in the majority of Naegleria spp.


The application of risk analysis to international trade in animals and animal products.
In an era when arduous land and sea journeys separated exporting and recipient nations, the duration and stress of transport dictated localised sourcing of stock and provided an implicit quarantine. Clinically latent infection, which remained undetected prior to embarkation, often surfaced and was eliminated before reaching the importing country. Many nations which would not accept the risk of importation, on clinical grounds, could effectively isolate themselves by prohibiting entry. Passive acceptance characterised much of the response of industry to the perceived wisdom behind such decisions. Advances in transportation technology now permit the accumulation of an export consignment from across an entire country. The assembled shipment is a sentinel for the infection experience of the national herd. The journey to the final destination is measured in hours, rather than weeks. Parallel diagnostic and epidemiological advances face the challenge of compensating for the risks attendant in such widespread and rapid sourcing of stock. Nations which judge the risks as unacceptable face a concerted legal challenge on a series of levels, both domestic and international. Refusal of legal importation can be circumvented easily through the smuggling of germ plasm. National Veterinary Services must respond to the economic, social and political realities of this new international trading environment. The means of facing this challenge through quantitative risk analysis are described. The theory of risk analysis, as well as the qualitative and quantitative evolution of the import applications of this analysis, is explained. Current challenges and potential solutions are discussed.


Effects of rapid weight loss on mood and performance among amateur boxers.
To examine the effects of rapid weight loss on mood and performance among amateur boxers. Participants were 16 experienced amateur boxers. In stage 1, structured interviews were used to assess the type of strategies that boxers used to reduce weight and the value of performing at their desired weight in terms of performance. In stage 2, boxers completed a 4 x 2 minute (1 minute recovery) circuit training session. Boxers completed the circuit training session on three different occasions with a week between each. The first test was used to familiarise the boxers with the circuit training task; the second and third tasks were at their training weight and championship weight, respectively. Participants were given one week to reduce their body weight to their championship weight using their preferred weight making strategies; boxers reduced their body weight by an average of 5.16% of body weight. Boxers typically lost weight by restricting fluid and food intake in the week leading to competition. Repeated measures multivariate analysis of variance results indicated that rapid weight loss among boxers was associated with poor performance, increased anger, fatigue, and tension, and reduced vigour. Strategies used to make weight by boxers are associated with poor performance and a negative mood profile.


Impact of Consensus Definitions on Identification of Glomerular Lesions by Light and Electron Microscopy.
In 2020, a working group of 13 renal pathologists published consensus definitions for 47 individual glomerular lesions found on light microscopy (LM) and 47 glomerular lesions and 9 normal structures found on electron microscopy (EM). To test the impact of these definitions on identification of these lesions and structures, 2 surveys were circulated to all members of the Renal Pathology Society (RPS), each having 32 images (19 LM, 13 EM) and accompanying questions with 5 multiple-choice answers, one being the consensus choice of the working group. The first survey (survey 1 [S1]), answered by 297 RPS members, was sent in September 2020, before publication of the consensus definitions. The second (survey 2 [S2]), with images of the same lesions and structures (but not the same images) and the same questions and multiple choices in different order, was sent in April 2020, 5 months after the publication of the definitions. S2 was taken by 181 RPS members; 64% also took S1 and 61% reported having read the definitions paper (def. paper). Mean agreement with the consensus answers increased modestly between the 2 surveys (65.2% vs. 72.0%, P = 0.097); the increase was greater and significant when only respondents to S2 who read the def. paper were considered (65.2% vs. 74.8%, P = 0.026). Furthermore, in S2 agreement with consensus answers was greater among respondents who read this paper versus those who did not (66.9% vs. 74.8%, P < 0.0001). Publication of the consensus definitions modestly improved interobserver agreement in identification of glomerular lesions.


A method for selective section of vagal afferent or efferent axons in the rat.
Although normally a mixed nerve, intracranially the vagus separates into dorsal rootlets that contain afferent axons and ventral rootlets that contain efferents. Surgical procedures are described for exposing the ventral surface of the occipital bone at the level where the vagus passes through the posterior lacerated foramen. When the foramen is expanded medially and the dura lanced, the intracranial course of the vagus can be observed by use of an operating microscope. Under these conditions, either the efferent or the afferent rootlets can be severed selectively. When the dorsal rootlets are divided and the contralateral trunk is cut below the diaphragm, a selective bilateral subdiaphragmatic afferent vagotomy is produced with unilateral sparing of the efferents. Cutting the efferents intracranially has the converse effect.


Phosphatidylcholine profile-mediated group recognition in catfish.
Animal groups are integrated by emission of discrete signals from members, so-called social signals, which have evolved for each species. Among communication signals, chemical signals play an important role for recognition of group membership. The catfish Plotosus lineatus forms a dense school immediately after hatching, and school recognition is under the control of chemical signals emitted by the school members. The key substance(s) governing this recognition are deduced to be a mixture of phosphatidylcholines (PC). To substantiate this hypothesis that a mixture of PC molecular species functions as recognition of school-specific odor, we examined the ability of P. lineatus to discriminate between familiar and unfamiliar PCs. P. lineatus responded only to PCs from a familiar school, and not to those from unfamiliar schools. PC molecular species were then analyzed by quantitative high performance liquid chromatography, which resulted in not only a complex mixture of PC molecular species, but also school-specific PC profiles. Furthermore, multivariate analysis of the quantified PC peaks revealed the presence of various PC profiles. Finally, we showed that the modification of PC profiles disrupts the recognition of school odor in P. lineatus. Therefore, we conclude that the recognition of school odor in P. lineatus is governed by school-specific PC profiles.