French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Genomes of Novel Myxococcota Reveal Severely Curtailed Machineries for Predation and Cellular Differentiation.

Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, nonsoil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring (Zodletone Spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of 13 distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g., FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine learning approaches based on a set of 634 genes informative of social lifestyle predicted a nonsocial behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities but carried genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 million years ago (Mya) in response to the rise of soil as a distinct habitat on Earth. IMPORTANCE The phylum Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcota are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota have been encountered in a wide range of nonsoil, predominantly anaerobic habitats, and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA, that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of 13 pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcota has occurred in response to soil formation as a distinct habitat on Earth.

[Trauma and anorexia nervosa: the association between trauma characteristics, PTSD and the duration of the eating disorder]. / Trauma en anorexia nervosa: samenhang tussen traumakenmerken, PTSS en de duur van de eetstoornis.

BACKGROUND: Research into the prevalence of various traumatic events in anorexia nervosa (AN) is sparse, with the findings from these studies varying. In addition, the number and age at which traumatic events occurred was not consistently included in previous studies.
AIM: To study the prevalence of different types of traumatic events, whether they occurred in early childhood or not, the number of different events and their associations with PTSD symptoms, and the duration of the eating disorder among clinically admitted patients with AN.
METHOD: In the admission department of an eating disorder clinic, 60 female patients with AN completed questionnaires about traumatic events and symptoms of PTSD during the first week of admission.
RESULTS: Although physical violence during early childhood and traumatic sexual events in later childhood and adulthood were the most commonly reported, there was a variety of types of traumatic events that were frequently reported. In addition, patients who had experienced traumatic events at a young age and / or multiple types of traumatic events had a longer-lasting eating disorder.
CONCLUSION: A thorough inventory of trauma in patients with eating disorders seems important, as this could play a role in maintaining an eating disorder.

Home-based alcohol prevention program for parents and children: A randomized controlled trial.

Objective To evaluate the effectiveness of a home-based alcohol prevention program to delay initiation of alcohol use in children. Methods In 2011, a total of 1349 sixth-grade children (M=12.15, SD=0.47) and their mothers who could read and write Dutch were recruited from primary schools in the northern part of the Netherlands. They participated in a cluster randomized controlled trial with two conditions; (1) intervention group (5 modules which families received by mail every 4weeks over 5months), (2) control group (a factsheet information brochure). An independent statistician allocated the schools to the conditions (allocation ratio (1:1)). Participants and data-analyst were blind to randomization. The primary outcome was alcohol initiation. Results Of the participants, 680 were randomized to the intervention and 669 to the control condition. In the intervention condition (N=540) 5.4% of the children drank alcohol compared to 7.1% in the control condition (N=601). The difference was not significant (OR=.99, 95% CI=.96-1.02, p=52). Conclusion The present study showed no effects of 'In control: No alcohol!' on alcohol initiation. A critical evaluation of program design and content, and future studies in different target groups, are suggested. The trial is registered at trialregister.nl, number NTR2474.

A simple borehole dilution technique in measuring horizontal ground water flow.

Borehole dilution techniques use repeated fluid column profiling after establishment of an initial uniform condition to monitor the rate at which ambient ground water moves into a borehole. Application of the dilution technique in a monitoring well makes it possible to estimate the horizontal Darcy flow velocity of ground water in the aquifer surrounding the borehole. Previous investigators have demonstrated the technique using either relatively concentrated saline solutions or deionized water to produce a fluid column with properties distinctly different from those of local ground water. We present a new dilution technique using the food color Brilliant Blue FCF (Euro code E-133) to mark the fluid column and using a specially constructed photometric sensor to characterize the dilution of this dye over time. The effective application of this technique is documented by two practical examples.

Controlled drug release from polymeric delivery devices. III: In vitro-in vivo correlation for intravaginal release of ethynodiol diacetate from silicone devices in rabbits.

Forty female rabbits were implanted with silicone vaginal devices containing ethynodiol diacetate for up to 8 weeks. As predicted from in vitro studies, a Q - t1/2 (matrix-controlled) release profile was observed in vivo. The in vivo drug release profile was compared with in vitro data measured at three hydrodynamic conditions, and the diffusional resistance across the vaginal wall was estimated. Drug released from silicone devices yielded a prolonged plasma level when compared with data following intravaginal or intravenous administration of a solution dose. The rate constant for elimination was unchanged. The plasma concentration of the drug was related to the intravaginal drug release profile both theoretically and experimentally and was above the concentration required to inhibit fertilization.

Pregnancy rate among beef heifers from timed insemination following synchronization with a progestin treatment.

Five trials were conducted with 958 virgin beef heifers to evaluate the effects of various breeding management methods on pregnancy rate at synchronized estrus and during a 45-day artificial insemination (AI) season. Synchronization was achieved with the progestin treatment regimen Syncro-Mate-B (SMB). Pregnancy rate at first service and cumulative pregnancy rate were affected (P less than .01) by trial. Pregnancy rate at first service was 55% for all heifers on the SMB treatment regimen and 67% for nontreated control heifers (P less than .01). However, cumulative pregnancy rate during the 5-day synchronized period was higher (P less than .01) among treated heifers (54%) than among control heifers (21%). The pregnancy rate was 6% higher (P less than .06) after 27 days of breeding for treated heifers than for control heifers. Neither pregnancy rate at 21 days nor final pregnancy rate after a 45-day AI season was significantly affected by treatment. Pregnancy rate at first service among heifers undergoing the SMB treatment regimen and inseminated 12 hr after first detected in estrus was not significantly different from that among heifers inseminated once from 45 to 55 hr after implant removal or heifers inseminated twice at 48 and 60 hr after implant removal, regardless of occurrence of estrus.

[Potentially malignant character of oral lichen planus and lichenoid lesions]. / Caractère potentiellement malin du lichen plan buccal et des lésions lichénoïdes.

INTRODUCTION: Many authors have reported the possible malignant transformation of oral lichen. The incidence of this event remains controversial. Many authors make a distinction between the "true" oral lichen planus (OLP) and lichenoid lesions (LL) according to the WHO clinical and histological classification. For these authors an increased risk of development of oral cancer could occur only on LL. Our aim was to check this hypothesis on a cohort followed for 10 years. MATERIAL AND METHODS: We included patients who were referred to our team for the first time between 1995 and 1997, still followed in 2010, with a histological diagnosis of buccal lichen planus. We classified lesions as OLP or LL according to the WHO clinical and histological classification: the two clinical criteria for OLP were a reticulated aspect and bilateral and symmetric lesions. Three histological criteria were necessary for the diagnosis: dense inflammatory infiltrate in the upper lamina propria, liquefaction degeneration of basal keratinocytes, and no signs of dysplasia. The final diagnosis was OLP, when all clinical ad histological criteria were met otherwise it was LL. We studied the patient's outcome between their first consultations and May 2010. RESULTS: Thirty-two patients, whose data was available, met inclusion criteria. Eight were diagnosed with OLP and 24 with LL. The mean follow-up was 164 months [154-183]. No oral cancer was observed in the OLP group. Two patients in the LL group presented with oral cancer after 45 and 143 months of follow-up. DISCUSSION: Malignant transformations were observed only in the LL group. Our results correlate with those of Van Der Meij et al. published in 2006. The strict use of the WHO diagnostic criteria seems to allow identifying patients at risk of developing oral cancer (LL) and others with only a benign course of this chronic oral mucosal disease. These results need to be confirmed by prospective multicentric studies.

Myofibrillar protein turnover: the proteasome and the calpains.

Metabolic turnover of myofibrillar proteins in skeletal muscle requires that, before being degraded to AA, myofibrillar proteins be removed from the myofibril without disrupting the ability of the myofibril to contract and develop tension. Skeletal muscle contains 4 proteolytic systems in amounts such that they could be involved in metabolic protein turnover: 1) the lysosomal system, 2) the caspase system, 3) the calpain system, and 4) the proteasome. The catheptic proteases in lysosomes are not active at the neutral pH of the cell cytoplasm, so myofibrillar proteins would have to be degraded inside lysosomes if the lysosomal system were involved. Lysosomes could not engulf a myofibril without destroying it, so the lysosomal system is not involved to a significant extent in metabolic turnover of myofibrillar proteins. The caspases are not activated until initiation of apoptosis, and, therefore, it is unlikely that the caspases are involved to a significant extent in myofibrillar protein turnover. The calpains do not degrade proteins to AA or even to small peptides and do not catalyze bulk degradation of the sarcoplasmic proteins, so they cannot be the only proteolytic system involved in myofibrillar protein turnover. Research during the past 20 yr has shown that the proteasome is responsible for 80 to 90% of total intracellular protein turnover, but the proteasome degrades peptide chains only after they have been unfolded, so that they can enter the catalytic chamber of the proteasome. Thus, although the proteasome can degrade sarcoplasmic proteins, it cannot degrade myofibrillar proteins until they have been removed from the myofibril. It remains unclear how this removal is done. The calpains degrade those proteins that are involved in keeping the myofibrillar proteins assembled in myofibrils, and it was proposed over 30 yr ago that the calpains initiated myofibrillar protein turnover by disassembling the outer layer of proteins from the myofibril and releasing them as myofilaments. Such myofilaments have been found in skeletal muscle. Other studies have indicated that individual myofibrillar proteins can exchange with their counterparts in the cytoplasm; it is unclear whether this can be done to an extent that is consistent with the rate of myofibrillar protein turnover in living muscle. It seems that both the calpains and the proteasome are responsible for myofibrillar protein turnover, but the mechanism is still unknown.

Effect of two dietary concentrate levels on tenderness, calpain and calpastatin activities, and carcass merit in Waguli and Brahman steers.

The objective of this study was to compare carcass characteristics of a newly introduced breed, the Waguli (Wagyu x Tuli), with the carcass characteristics of the Brahman breed. Brahman cattle are used extensively in the Southwest of the United States because of their tolerance to adverse environmental conditions. However, Brahman carcasses are discounted according to the height of their humps because of meat tenderness issues. The Waguli was developed in an attempt to obtain a breed that retained the heat tolerance of the Brahman but had meat quality attributes similar to the Wagyu. Twenty-four animals were used. Six steers from each breed were fed a 94% concentrate diet and 6 steers from each breed were fed an 86% concentrate diet. Eight steers, 2 from each group, were harvested after 128 d, after 142 d, and after 156 d on feed. Waguli steers had larger LM, greater backfat thickness, greater marbling scores, and greater quality grades than the Brahman steers (P < 0.05). The Japanese Wagyu breed is well known for its highly marbled and tender meat, and these traits are also present in the Waguli. The Waguli had significantly lower Warner-Bratzler shear force values than the Brahman steers after 7 and 10 d of postmortem aging (P < 0.05); this difference decreased after 14 d postmortem (P = 0.2), when tenderness of the slower aging Brahman had increased to acceptable levels. Toughness of the Brahman has been associated with high levels of calpastatin in Brahman muscle, and the Waguli LM had significantly less calpastatin activity (P = 0.02) at 0 h postmortem than the Brahman LM. At 0-h postmortem, the total LM calpain activity did not differ between the Brahman and Waguli (P = 0.57). Neither diet nor days on feed had any significant effect on the 0-h postmortem calpain or at 0-h postmortem calpastatin activity, nor an effect on Warner-Bratzler shear-force values. In conclusion, LM muscle from the Waguli steers had a high degree of marbling, lower shear force values, and low calpastatin activity, all of which are related to more tender meat.

Effect of postmortem storage on activity of mu- and m-calpain in five bovine muscles.

An in situ system involving incubation of 60- to 80-g pieces of muscle at 4 degrees C under different conditions was used to determine the effects of time of postmortem storage, of pH, and of temperature on activities of mu- and m-calpain activity in bovine skeletal muscle. Casein zymograms were used to allow measurement of calpain activity with a minimum of sample preparation and to ensure that the calpains were not exposed to ionic strengths of 100 or greater before assay of their activities. In 4 of the 5 muscles (longissimus dorsi, lumbar; longissimus dorsi, thoracic; psoas major; semimembranosus; and triceps brachii) studied, mu-calpain activity decreased nearly to zero within 48 h postmortem. Activity of m-calpain also decreased in the in situ system used but at a much slower rate. Activities of both mu- and m-calpain decreased more slowly in the triceps brachii muscle than in the other 4 muscles during postmortem storage. Although previous studies have indicated that mu-calpain but not m-calpain is proteolytically active at pH 5.8, these studies have used calpains obtained from muscle at death. Both mu- and m-calpain are proteolytically inactive if their activities are measured at pH 5.8 and after incubating the muscle pieces for 24 h at pH 5.8. Western analysis suggested that neither the large 80-kDa subunit nor the small 28-kDa subunit of m-calpain was autolyzed during postmortem storage of the muscle pieces. As has been reported previously, the 80-kDa subunit of mu-calpain was autolyzed to 78- and then to a 76-kDa polypeptide after 7 d postmortem, but the 28-kDa small subunit was not autolyzed; hence, the autolyzed mu-calpain molecule in postmortem muscle is a 76-/28-kDa molecule and not a 76-/18-kDa molecule as previously assumed. Because both subunits were present in the postmortem calpains, loss of mu-calpain activity during postmortem storage is not due to dissociation of the 2 subunits and inactivation. Although previous studies have shown that the 76-/18-kDa mu-calpain molecule is completely active proteolytically, it is possible that the 76-/28-kDa mu-calpain molecule in postmortem muscle is proteolytically inactive and that this accounts for the loss of mu-calpain activity during postmortem storage. Because neither mu- nor m-calpain is proteolytically active at pH 5.8 after being incubated at pH 5.8 for 24 h, other proteolytic systems such as the caspases may contribute to postmortem proteolysis in addition to the calpains.

Isolation and characterization of mu-calpain, m-calpain, and calpastatin from postmortem muscle. I. Initial steps.

Evidence has indicated that mu-calpain, m-calpain, and calpastatin have important roles in the proteolytic degradation that results in postmortem tenderization. Simple assays of these 3 proteins at different times postmortem, however, has shown that calpastatin and mu-calpain both rapidly lose their activity during postmortem storage, so that proteolytic activity of mu-calpain is nearly zero after 3 d postmortem, even when assayed at pH 7.5 and 25 degrees C, and ability of calpastatin to inhibit the calpains is 30% or less of its ability when assayed at death. m-Calpain, however, retains much of its proteolytic activity during postmortem storage, but the Ca(2+) requirement of m-calpain is much higher than that reported to exist in postmortem muscle. Consequently, it is unclear how the calpain system functions in postmortem muscle. To clarify this issue, we have initiated attempts to purify the 2 calpains and calpastatin from bovine semitendinosus muscle after 11-13 d postmortem. The known properties of the calpains and calpastatin in postmortem muscle have important effects on approaches that can be used to purify them. A hexyl-TSK hydrophobic interaction column is a critical first step in separating calpastatin from the 2 calpains in postmortem muscle. Dot-blot assays were used to detect proteolytically inactive mu-calpain. After 2 column chromatographic steps, 5 fractions can be identified: 1) calpastatin I that does not bind to an anion-exchange matrix, that does not completely inhibit the calpains, and that consists of small polypeptides <60 kDa; 2) calpastatin II that binds weakly to an anion-exchange matrix and that contains polypeptides <60 kDa; all these polypeptides are smaller than the native 115- to 125-kDa skeletal muscle calpastatin; 3) proteolytically active mu-calpain even though very little mu-calpain activity can be detected in zymogram assays of muscle extracts from 11- to 13-d postmortem muscle; this mu-calpain has an autolyzed 76-kDa large subunit but the small subunit consists of 24-, 26- and a small amount of unautolyzed 28-kDa polypeptides; 4) proteolytically active m-calpain that is not autolyzed; and 5) proteolytically inactive mu-calpain whose large subunit is autolyzed to a 76-kDa polypeptide and whose small subunit contains polypeptides similar to the proteolytically active mu-calpain. Hence, loss of calpastatin activity in postmortem muscle is due to its degradation, but the cause of the loss of mu-calpain activity remains unknown.

[Impact of metabolic syndrome on CRP levels]. / Importancia de los componentes del síndrome metabólico en los valores de proteína C reactiva.

OBJECTIVE: C-reactive protein (CRP) is considered a marker of subclinical atherosclerosis. The aim of the study was to assess whether the metabolic syndrome (MS) and parameters involved in its diagnosis might influence serum CRP values. PATIENTS AND METHOD: Cross-sectional study in outpatients of a HTA and Vascular Risk clinic. MS was diagnosed according to National Cholesterol Educational Program ATP-III guidelines, and hs-CRP was analyzed by nephelometry. RESULTS: A total of 1,969 patients (47% male) were evaluated and distributed into four groups: 1) 1,220 non-diabetics without MS; 2) 384 non-diabetics with MS; 3) 153 diabetics without MS, and 4) 212 diabetics with MS. Patients with MS had higher CRP in both non-diabetic 3.0 (1.7-4.4) mg/l vs. 1.7 (0.9-3.4) mg/l; p=0.001 (MW), and diabetic patients: 2.8 (1.5-4.6) mg/l vs. 2.2 (0.9-4.3) mg/l; p=0.01 (MW). Diabetic patients without MS had CRP values not different to non-diabetic without MS. CRP values increased in relation to the number of parameters included in the MS from 1.7 (2.2) mg/l, in patients without any parameters, to 4.2 (2.8) mg/l in patients who fulfilled five parameters (p=0.001) (KW). In multiple regression analysis abdominal obesity (p=0.001), TG (p=0.001) and glucose (p=0.02) were associated with CRP levels after correcting for other factors. Abdominal obesity (OR: 1.9; 95% CI: 1.5-2.4; p=0.001) and TG (OR: 1.4; 95% CI: 1.1 -1.7; p=0.003), but not glucose were independent factors related to the presence of high levels of CRP (>3 mg/l) in a logistic regression analysis. CONCLUSIONS: Diabetic and non-diabetic patients with MS have high CRP levels. Of the five components of MS, the most closely related to CRP is abdominal obesity.

Hip, pelvic, and thigh injuries and disorders in the adolescent athlete.

The common injuries and disorders that affect the hip joint, pelvis, and thigh and its surrounding tissues are discussed in this chapter. The clinician's challenge is to determine the severity of the injury and select the correct treatment and rehabilitation. Careful observation, diagnostic tests, and a thorough medical history aids this selection. The characteristics of several sports injuries are highlighted with the essential components of effective treatment and physical rehabilitation.

11 beta-methyl-19-norsteroids: novel progestational hormones.

PIP: The synthesis and biological properties of 2 11beta-methyl-19-norsteroids (17alpha-ethynyl-17beta-hydroxy-11beta-methylestr-4en-3-one and 3beta, 17beta-diacetoxy-17alpha-ethynyl-11beta-methylestr-4-ene) are described. In experimental animals both compounds exhibited potent progestational activities, antiestrogenic activities, and estrogenic responses in the estrogen-deficient state. It is suggested that the latter compound may be similar to other progestational agents in failing to alter hepatic excretory function and may possess anovulatory properties without some of the side effects associated with steroid contraceptives presently employed.^ieng

The biological properties of aspartame. IV. Effects on reproduction and lactation.

Intragastric administration of approximately 300 mg/kg/day of aspartame (APM) to female rats for seven days and to female hamsters for five days after mating did not affect postcoital fertility as measured by the number of implantation sites and normal appearing fetuses. In additional studies, the effect of APM fed at 1 to 14% in the diet to lactating rats and their litters of suckling young was studied using a pair-feeding experimental design. Levels of APM up to 4% in the diet (about 7 g/kg/day) did not affect food consumption, body weights, serum prolactin, serum gonadotropins, the mammary gland histology of the dams or the growth and survival rates of their pups. However, higher levels of 7.5 and 14% APM (about 9 g/kg/day) caused reduced food consumption due to diet palatability and resulted in body weight loss in dams and retarded growth rates in the young.

Reproductive performance of dairy cows with cystic ovaries following administration of Procystin.

Eighty-five postpartum Holstein cows were randomly assigned to receive 0, 50, 100, or 250 micrograms of the gonadotropin-releasing hormone product, Procystin when follicular cysts were diagnosed by palpation per rectum. Accurate reproductive records were maintained, and milk samples were collected at the time of diagnoses for assay for progesterone. An additional 101 cows were injected with only the 100 micrograms dose of Procystin when cysts were identified. Data showed that days from treatment to first observed estrus decreased with increasing doses of Procystin with no advantage of 250 micrograms over 100 micrograms. Days open and conception rates were similar among the treatment groups. Cows with less than 1 ng/ml progesterone in their milk at the time of treatment returned to estrus sooner than cows with progesterone concentrations greater than 1 ng/ml. In addition, gonadotropin-releasing hormone administered to those cows with low progesterone at the time of treatment led to significantly increased progesterone concentrations by 7 and 14 d posttreatment. We conclude that although Procystin administration hastened estrus of cows with ovarian cysts, breeding practices on the farms did not lead to an improvement in reproductive efficiency of the cows that possessed cysts.