The A1/A2 ß-casein genotype of cows, but not their horn status, influences peptide generation during simulated digestion of milk.

The effect of the horn status of cows on their milk composition and quality is a controversial research topic. In this study, 128 milk samples from 64 horned and 64 disbudded Brown Swiss and Original Braunvieh cows were collected from alpine farms where both horned and disbudded cows were grazing on mountain pastures. The samples were analyzed for their detailed composition and protein digestion in a simulated in vitro digestion (INFOGEST). To exclude probable influences on digestion, the ß-casein genotype with its variants A1 and A2 was also included in the study. The effects of horn status and ß-casein genotype were investigated in linear mixed models, which included additional influencing random factors such as Original Braunvieh blood proportion, stage of lactation, and farm. Horn status did not have any effect on milk composition or digestion. In contrast, milk from A1A1 cows showed a different protein digestion than milk of A1A2 and A2A2 cows in the gastric phase, including smaller amounts of ß-casomorphin(BCM)21-associated peptides and larger amounts of BCM11-associated peptides. Abundances of BCM7 did not differ between ß-casein genotypes. At the end of the intestinal phase, the digested milk of A1A1 and A2A2 b-casein genotypes did not differ.

Strategies for keeping dairy cows and calves together - a cross-sectional survey study.

Although it is still most common to rear dairy calves separately from adult cattle, the interest in prolonged contact between dairy calves and lactating cows during early life is increasing. Previous research has documented positive effects of cow-calf contact (CCC) on for example early calf growth and udder health of suckled cows, but also negative effects such as increased separation distress and reduced weight gains after weaning. The aim of this study was to use information from European farms with prolonged cow-calf contact to identify innovative solutions to common challenges for CCC farms. Commercial dairy farms that kept calves with adult lactating cows for seven days or more after birth were invited to participate, and interviews were performed with 104 farmers from six countries. During interviews, information about farm management, calf rearing, farmers' perception of animal health on their farm, and farmers' drivers and barriers for implementing CCC were collected. We found that CCC was practised in a large variety of housing and management systems, and that calves could be reared together with their dam, with foster cows, or using a combination of the two. The contact period varied considerably (7-305 days) between farms and about 25% of the farms manually milk fed the calves during parts of the milk feeding period. Daily contact time varied between farms, from 30 minutes per day to permanent contact except at milking. Behaviours indicative of separation distress, most commonly vocalisation in cows and calves, were reported by 87% of the farmers. Strategies to alleviate separation distress, for example simultaneous gradual weaning and separation, were used on some farms. Building constraints were most often mentioned as a barrier for implementing CCC. Our findings suggest that CCC is practised in a variety of commonly used husbandry systems. Reported challenges were primarily related to weaning and separation, and to building constraints; these aspects should be areas of future research.

Periangular transmasseteric infraparotid approach in the treatment of condylar-base and low condylar­neck fractures.

AIM: Mandibular condylar fractures account for 25 to 52 % of all mandibular fractures. Though current literature favors open reduction and internal fixation (ORIF) of condylar­base and low condylar­neck fractures, extraoral approaches are usually considered to be complicated by the risk of facial nerve injury and other possible complications. This study was undertaken to demonstrate that the periangular transmasseteric infraparotid surgical approach (TMIP) to condylar­base and low condylar­neck fractures provides excellent access to the bony fragments with minimal risk of complications such as facial nerve and parotid gland injury. PATIENTS: In the period from January 2010 to December 2018, 81patients (96 fractures) with condylar­base and low condylar­neck fractures underwent ORIF via periangular transmasseteric infraparotid surgical approach. RESULTS: The results of this retrospective study showed minimal postoperative complications. The periangular transmasseteric infraparotid surgical approach allowed precise anatomic repositioning and fixation of the bony fragments in almost all cases except for two juvenile cases with noticeable scars and one case with plate fracture. There were no transient or permanent facial nerve palsies, parotid gland or salivary fistulae complications during a 12­month follow­up period. CONCLUSION: The periangular infraparotid transmasseteric approach to ORIF of condylar­base and low condylar­neck fractures is an effective and safe approach allowing accurate anatomic reposition and fixation of the fragments with minimum surgical complications (Tab. 1, Fig. 12, Ref. 21).

Condylar position and mandibular function after bilateral sagittal split osteotomy.

AIM: The purpose of this retrospective study was to perform an evaluation of postoperative positional changes of the condyle and mandibular function after bilateral sagittal split osteotomy (BSSO) with manual proximal segment positioning. PATIENTS: 45 patients were divided into the 2 groups ‒ G1 (advancement ‒ 14 patients) and G2 (setback - 31 patients). Rigid internal fixation screws were utilized in all cases. Inclusion criteria were only BSSO, no TMJ symptoms preoperatively and age 18 or older. RESULTS: The differences between pre- and postoperative condyle position were evaluated using measurements taken from preoperative CT scans and compared to CT scans made a minimum of 6 months postoperatively. The positional changes in both the axial and sagittal planes were measured and compared. The recovery of mandibular function was evaluated by measuring maximal interincisal opening (MIO). The results revealed that condylar positional changes after BSSO in both groups were minimal and not significantly different for all three dimensions measured. The recovery of mandibular function was faster in the group G2 than in the group G1. Mandibular function reached almost preoperative level in 6-12 months postoperatively in both groups. CONCLUSION: The results demonstrated that following BSSO, only insignificant condylar displacement and functional changes occurred within 6 to 12 months postoperatively (Tab. 4, Fig. 2, Ref. 47).

Clinical approach to rhizomicry based on a case of dentine dysplasia type 1.

Differential diagnosis of generalised rhizomicry (root dwarfism) includes many diseases and syndromes. When the patient has normal stature with no evidence of ghost teeth, no systematic diseases and no history of irradiation or chemotherapy, the dental features are pathognomonic for the diagnosis of dentine dysplasia type 1 (DD-1). In this report, we presented an adult case with DD-1 that had been left undiagnosed and the patient underwent dental implant therapy and orthodontic treatment, despite recognition of early tooth loss. The diagnosis of DD-1 was first established before an orthognathic surgery to correct the facial skeletal deformity. We also reviewed the clinicopathological aspects of this disease and clinical dental implications for this patient group.

Comparison of performance and fitness traits in German Angler, Swedish Red and Swedish Polled with Holstein dairy cattle breeds under organic production.

Although the use of local breeds is recommended by organic regulations, breed comparisons performed under organic production conditions with similar production intensities are scarce. Therefore, we compared data of local and widely used Holstein dairy cattle breeds from 2011 to 2015 regarding production, fertility and health from German and Swedish organic farms with similar management intensities within country. In Germany, the energy-corrected total milk yield tended to be lower in the local breed Original Angler Cattle (AAZ, 5193 kg) compared to the modern German Holstein Friesian breed (HO, 5620 kg), but AAZ showed higher milk fat and protein contents (AAZ v. HO: 5.09% v. 4.18% and 3.61% v. 3.31%, respectively). In Sweden, the widely used modern Swedish Holstein (SH) breed had the highest milk yield (9209 kg, fat: 4.10%, protein: 3.31%), while the local Swedish Polled (SKB) showed highest milk fat and protein contents (6169 kg, 4.47%, 3.50%, respectively), followed by the local breed Swedish Red (SRB, 8283 kg, 4.33%, 3.46%, respectively). With regard to fertility characteristics, the German breeds showed no differences, but AAZ tended to have less days open compared to HO (-17 days). In Sweden, breeds did not differ with regard to calving interval, but both local breeds showed a lower number of days open (-10.4 in SRB and -24.1 in SKB compared to SH), and SKB needed fewer inseminations until conception (-0.5 inseminations) compared to SH. Proportion of test day records with a somatic cell count content of ≥100 000 cells per ml milk did not reveal breed differences in any of the two countries. German breeds did not differ regarding the proportion of cows with veterinary treatments. In Sweden, SRB showed the lowest proportion of cows with general veterinary treatment as well as specific treatment due to udder problems (22.8 ± 6.42 and 8.05 ± 2.18, respectively), but the local breed SKB did not differ from SH in either of the two traits. In Sweden, we found no breed differences regarding veterinary treatments due to fertility problems or diagnosis of claw or leg problems during claw trimming. Our results indicate a stronger expression of the antagonism between production and functional traits with increasing production intensity. Future breed comparisons, therefore, need to consider different production intensities within organic farming in order to derive practical recommendations as to how to implement European organic regulations with regard to a suitable choice of breeds.

Which characteristics can be expected from p16+-squamous cell carcinomas of the posterior oral cavity and oropharynx? - Distinctive results from Central Germany.

PURPOSE: Human papillomaviruses (HPV) link to a subset of head and neck squamous cell carcinomas (HNSCC). Our aim was to identify clinicopathological characteristics (CPC) of squamous cell carcinomas of the posterior oral cavity and oropharynx (SCCPOCO) associated with HPV p16+. METHODS: Using a retrospective cohort study design, we enrolled a sample of SCCPOCO patients treated in a Central German hospital over a 3-year period. The predictor variables: CPCs, were grouped into demographic, social, anatomic and prognostic. The main outcome variable was p16+. Appropriate statistics were computed, and P≤0.05 was considered statistically significant. RESULTS: Of 199 HNSCC patients, 23 had SCCPOCO and entered the analysis (mean age, 67±12 years; 4 females; 16 in stage I; 4 p16+; 22 underwent primary surgery). We found 8 cervical lymph node metastases (34.8%), 3 distant metastases (13%), 9 recurrences (30.1%) and 3 overall deaths (13%). With the exception of recurrence (P=0.006) and overall death (P=0.02), p16+ was not associated with predictor variables: young age, male gender, smoking, alcohol consumption, tumor location, TNM stages, time to recurrence, metastases, death from disease and survival of smokers (P>0.05). Primary brachytherapy failed to improve survival of p16+-SCCPOCO patients (P=0.04). CONCLUSIONS: The results of this study suggest that p16+- and p16--SCCPOCOs in Central Germany share similar CPCs, except recurrence and overall death. Upfront surgery with/without radio(chemo)therapy is recommended for all operable SCCPOCOs, regardless of HPV-status. Patients with p16+-SCCPOCOs require close follow-up. Future research should investigate the cause of these distinctive CPCs.

Intraoperative injection of combined fibrin sealant and methylene blue dye for surgery of branchial cleft cysts: A case report.

Differential diagnosis of a lateral neck mass, especially in paediatric patients, should include branchial cleft cysts (BrCC). It is often difficult to identify and completely resect all cystic components, especially when the lesion becomes infected and/or gigantic. Incomplete excision increases the likelihood of recurrences. We reported a simple technique to facilitate the BrCC resection. Tisseel fibrin glue (FG: Baxter AG, Vienna, Austria) was mixed with methylene blue dye in inverse portion to the cyst size and/or the FG volume before injecting into the cystic lumen. After polymerisation of the dyed glue, the lesion was better visualised and extirpated in toto with the aid of the dye colour and gelatinisation by FG. An up-to-date diagnostic and therapeutic algorithm for BrCC was also presented.

Oral lichenoid lesion related to dental amalgam: A case report.

Dental amalgam remains one of standard direct restorative materials for posterior teeth. However, direct contact of oral mucosa with this material can cause oral lichenoid lesion (OLL), albeit rare. It has been proposed that hypersensitivity reaction to mercury is responsible to the pathogenesis of OLL. In addition to clinical features and histopathological examination, allergic patch test and removing the suspected causal material are pivotal to the diagnosis. We reported a case of OLL associated with dental amalgam. The lesion subsided clinically after replacement of amalgam with resin composite material with no need of biopsy or pharmacological treatment. A concise review of clinico-pathological aspects and current recommendations on management of this disease was also presented.

Utilization of outer-midplane collector probes with isotopically enriched tungsten tracer particles for impurity transport studies in the scrape-off layer of DIII-D (invited).

Triplet sets of replaceable graphite rod collector probes (CPs), each with collection surfaces on opposing faces and oriented normal to the magnetic field, were inserted at the outboard mid-plane of DIII-D to study divertor tungsten (W) transport in the Scrape-Off Layer (SOL). Each CP collects particles along field lines with different parallel sampling lengths (determined by the rod diameters and SOL transport) giving radial profiles from the main wall inward to R-R sep ∼ 6 cm. The CPs were deployed in a first-of-a-kind experiment using two toroidal rings of distinguishable isotopically enriched, W-coated divertor tiles installed at 2 poloidal locations in the divertor. Post-mortem Rutherford backscatter spectrometry of the surface of the CPs provided areal density profiles of elemental W coverage. Higher W content was measured on the probe side facing along the field lines toward the inner target indicating higher concentration of W in the plasma upstream of the CP, even though the W-coated rings were in the outer target region of the divertor. Inductively coupled plasma mass spectroscopy validates the isotopic tracer technique through analysis of CPs exposed during L-mode discharges with the outer strike point on the isotopically enriched W coated-tile ring. The contribution from each divertor ring of W to the deposition profiles found on the mid-plane collector probes was able to be de-convoluted using a stable isotope mixing model. The results provided quantitative information on the W source and transport from specific poloidal locations within the lower divertor region.

Repeat epidural steroid injections for radicular pain due to lumbar or cervical disc herniation: what happens after 'salvage treatment'?.

AIMS: The aim of this study was to determine the efficacy of repeat epidural steroid injections as a form of treatment for patients with insufficiently controlled or recurrent radicular pain due to a lumbar or cervical disc herniation. PATIENTS AND METHODS: A cohort of 102 patients was prospectively followed, after an epidural steroid injection for radicular symptoms due to lumbar disc herniation, in 57 patients, and cervical disc herniation, in 45 patients. Those patients with persistent pain who requested a second injection were prospectively followed for one year. Radicular and local pain were assessed on a visual analogue scale (VAS), functional outcome with the Oswestry Disability Index (ODI) or the Neck Pain and Disability Index (NPAD), as well as health-related quality of life (HRQoL) using the 12-Item Short-Form Health Survey questionnaire (SF-12). RESULTS: A second injection was performed in 17 patients (29.8%) with lumbar herniation and seven (15.6%) with cervical herniation at a mean of 65.3 days (sd 46.5) and 47 days (sd 37.2), respectively, after the initial injection. All but one patient, who underwent lumbar microdiscectomy, responded satisfactorily with a mean VAS for leg pain of 8.8 mm (sd 10.3) and a mean VAS for arm pain of 6.3 mm (sd 9) one year after the second injection, respectively. Similarly, functional outcome and HRQoL were improved significantly from the baseline scores: mean ODI, 12.3 (sd 12.4; p < 0.001); mean NPAD, 19.3 (sd 24.3; p = 0.041); mean SF-12 physical component summary (PCS) in lumbar herniation, 46.8 (sd 7.7; p < 0.001); mean SF-12 PCS in cervical herniation, 43 (sd 6.8; p = 0.103). CONCLUSION: Repeat steroid injections are a justifiable form of treatment in symptomatic patients with lumbar or cervical disc herniation whose symptoms are not satisfactorily relieved after the first injection. Cite this article: Bone Joint J 2018;100-B:1364-71.

Impact of pain and functional impairment in US adults with haemophilia: Patient-reported outcomes and musculoskeletal evaluation in the pain, functional impairment and quality of life (P-FiQ) study.

INTRODUCTION: Standardized and disease-specific patient-reported outcome (PRO) instruments assessing pain, functional impairment and health-related quality of life (HRQoL) in people with haemophilia (PWH) have been used in studies, but infrequently in comprehensive care settings for individual assessment or treatment planning. AIM: To assess the impact of pain and functional impairment on HRQoL in PWH. METHODS: P-FiQ enrolled 381 adult PWH with a history of joint pain/bleeding and included 5 PROs and a clinical joint evaluation (Hemophilia Joint Health Score v2.1 [HJHS]). RESULTS: Median age was 34 years; 49.9% reported a history of joint procedure or surgery. On EQ-5D-5L, most reported problems with mobility (61.4%), usual activities (53.2%) and pain/discomfort (76.1%). On Brief Pain Inventory v2 Short Form, median worst pain (range 0-10) was 6, least pain 1, average pain 3 and current pain 2. Ankles were most frequently reported as the most painful joints (37.4%), followed by knees (23.7%) and elbows (18.9%). On International Physical Activity Questionnaire, 51% reported no activity in the prior week. On SF-36v2 health survey, median subscores were worse for 4 physical health domains vs 4 mental health domains. Among Hemophilia Activities List domains (range 0 [worst]-100 [best]), functions of the legs (median, 66.7) and lying/sitting/kneeling/standing (median, 67.5) were most impacted and self-care least impacted (median, 100.0). On HJHS, ankle scores (median, 6.0; range, 0-40) were worse than elbow/knee scores (median, 4.0/4.0). Results were consistent across PROs/HJHS. CONCLUSION: Data demonstrate challenges of predominantly ankle/knee pain and lower extremity functional impairment in US adult PWH, affecting HRQoL across PROs/HJHS.

First report on the safety and efficacy of an extended half-life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A.

BACKGROUND: N8-GP (turoctocog alfa pegol) is an extended half-life glycoPEGylated recombinant factor VIII (FVIII) product developed for the prevention and treatment of bleeds in haemophilia A patients. AIM: This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years. METHODS: Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none'). RESULTS: Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg-1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg-1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified. CONCLUSION: The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.

Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the Pain, Functional Impairment, and Quality of life (P-FiQ) study.

INTRODUCTION: Haemophilia is characterized by frequent haemarthrosis, leading to acute/chronic joint pain. AIM: To assess self-reported prevalence, description and management of pain in adult males with mild-to-severe haemophilia and history of joint pain/bleeding. METHODS: Participants completed a pain survey and five patient-reported outcome instruments assessing pain, functional impairment and health-related quality of life (HRQoL). RESULTS: Of 381 participants enrolled, median age was 34 years; 77% had haemophilia A, 71% had severe disease and 65% were overweight/obese. Many (56%) were not receiving routine infusions; 30% never received routine infusions. During the prior 6 months, 20% experienced acute pain, 34% chronic pain and 32% both acute/chronic pain. Subjects with both acute/chronic pain (vs. none, acute or chronic) were more likely to be depressed (30% vs. 0-15%), obese (35% vs. 20-29%) and have lower HRQoL (mean EQ-5D visual analog scale, 69 vs. 83-86) and function (median overall Hemophilia Activities List, 60 vs. 88-99). Most common analgesics used for acute/chronic pain during the prior 6 months were acetaminophen (62%/55%) and non-steroidal anti-inflammatory drugs (34%/49%); most common non-pharmacologic strategies were ice (65%/33%) and rest (51%/33%). Hydrocodone-acetaminophen was the most common opioid for both acute/chronic pain (30%); other long-acting opioids were infrequently used specifically for chronic but not acute pain (morphine, 7%; methadone, 6%; fentanyl patch, 2%). CONCLUSION: Patients with chronic pain, particularly those with both acute/chronic pain, frequently experience psychological issues, functional disability and reduced HRQoL. Treatment strategies for acute pain (e.g. routine infusions to prevent bleeding) and for chronic pain (e.g. long-acting opioids) may be underused.

Survey of the anti-factor IX immunoglobulin profiles in patients with hemophilia B using a fluorescence-based immunoassay.

Essentials Studies characterizing neutralizing antibodies (inhibitors) in hemophilia B (HB) are lacking. The current study describes anti-factor (F) IX antibody profiles in 37 patients who have HB. Anti-FIX IgG4 levels exhibited a strong positive correlation with Nijmegen-Bethesda results. These data will help to more clearly define, predict, and treat alloantibody formation in HB. SUMMARY: Background Hemophilia B (HB) is an inherited bleeding disorder caused by the absence or dysfunction of coagulation factor IX (FIX). A subset of patients who have HB develop neutralizing alloantibodies (inhibitors) against FIX after infusion therapy. HB prevalence and the proportion of patients who develop inhibitors are much lower than those for hemophilia A (HA), which makes studies of inhibitors in patients with HB challenging due to the limited availability of samples. As a result, there is a knowledge gap regarding HB inhibitors. Objective Evaluate the largest group of patients with inhibitor-positive HB studied to date to assess the relationship between anti-FIX antibody profiles and inhibitor formation. Methods A fluorescence immunoassay was used to detect anti-FIX antibodies in plasma samples from 37 patients with HB. Results Assessments of antibody profiles showed that anti-FIX IgG1-4 , IgA, and IgE were detected significantly more often in patients with a positive Nijmegen-Bethesda assay (NBA). All NBA-positive samples were positive for IgG4 . Anti-FIX IgG4 demonstrated a strong correlation with the NBA, while correlations were significant, yet more moderate, for anti-FIX IgG1-2 and IgA. Conclusions The anti-FIX antibody profile in HB patients who develop inhibitors is diverse and correlates well with the NBA across immunoglobulin (sub)class, and anti-FIX IgG4 is particularly relevant to functional inhibition. The anti-FIX fluorescence immunoassay may serve as a useful tool to confirm the presence of antibodies in patients who have low positive NBA results and to more clearly define, predict, and treat alloantibody formation against FIX.

Von Willebrand factor for menorrhagia: a survey and literature review.

BACKGROUND: von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. METHODS: We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. RESULTS: Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg(-1) on day 1-6 of menstrual cycle. CONCLUSIONS: This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.