Farm-level risk factors and treatment protocols for lameness in New Zealand dairy cattle.

AIMS: To identify farm-level risk factors for dairy cow lameness, and to describe lameness treatment protocols used on New Zealand dairy farms. METHODS: One hundred and nineteen farms from eight veterinary clinics within the major dairying regions of New Zealand were randomly enrolled into a cross-sectional lameness prevalence study. Each farmer completed a questionnaire on lameness risk factors and lameness treatment and management. Trained observers lameness scored cattle on two occasions, between October-December (spring, coinciding with peak lactation for most farms) and between January-March (summer, late lactation for most farms). A four-point (0-3) scoring system was used to assess lameness, with animals with a lameness score (LS) ≥2 defined as lame. At each visit, all lactating animals were scored including animals that had previously been identified lame by the farmer. Associations between the farmer-reported risk factors and lameness were determined using mixed logistic regression models in a Bayesian framework, with farm and score event as random effects. RESULTS: A lameness prevalence of 3.5% (2,113/59,631) was reported at the first LS event, and 3.3% (1,861/55,929) at the second LS event. There was a median prevalence of 2.8% (min 0, max 17.0%) from the 119 farms. Most farmers (90/117; 77%) relied on informal identification by farm staff to identify lame animals. On 65% (75/116) of farms, there was no external provider of lame cow treatments, with the farmer carrying out all lame cow treatments. Most farmers had no formal training (69/112; 62%). Animals from farms that used concrete stand-off pads during periods of inclement weather had 1.45 times the odds of lameness compared to animals on farms that did not use concrete stand-off pads (95% equal-tailed credible interval 1.07-1.88). Animals from farms that reported peak lameness incidence from January to June or all year-round, had 0.64 times odds of lameness compared to animals from farms that reported peak lameness incidence from July to December (95% equal-tailed credible interval 0.47-0.88). CONCLUSIONS: Lameness prevalence was low amongst the enrolled farms. Use of concrete stand-off pads and timing of peak lameness incidence were associated with odds of lameness. CLINICAL RELEVANCE: Veterinarians should be encouraging farmers to have formal lameness identification protocols and lameness management plans in place. There is ample opportunity to provide training to farmers for lame cow treatment. Management of cows on stand-off pads should consider the likely impact on lameness.

Novel multivariate methods to track frequency shifts of neural oscillations in EEG/MEG recordings.

Instantaneous and peak frequency changes in neural oscillations have been linked to many perceptual, motor, and cognitive processes. Yet, the majority of such studies have been performed in sensor space and only occasionally in source space. Furthermore, both terms have been used interchangeably in the literature, although they do not reflect the same aspect of neural oscillations. In this paper, we discuss the relation between instantaneous frequency, peak frequency, and local frequency, the latter also known as spectral centroid. Furthermore, we propose and validate three different methods to extract source signals from multichannel data whose (instantaneous, local, or peak) frequency estimate is maximally correlated to an experimental variable of interest. Results show that the local frequency might be a better estimate of frequency variability than instantaneous frequency under conditions with low signal-to-noise ratio. Additionally, the source separation methods based on local and peak frequency estimates, called LFD and PFD respectively, provide more stable estimates than the decomposition based on instantaneous frequency. In particular, LFD and PFD are able to recover the sources of interest in simulations performed with a realistic head model, providing higher correlations with an experimental variable than multiple linear regression. Finally, we also tested all decomposition methods on real EEG data from a steady-state visual evoked potential paradigm and show that the recovered sources are located in areas similar to those previously reported in other studies, thus providing further validation of the proposed methods.

Evaluation of S201086/GLPG1972, an ADAMTS-5 inhibitor, for the treatment of knee osteoarthritis in ROCCELLA: a phase 2 randomized clinical trial.

OBJECTIVE: To evaluate the efficacy and safety of the anti-catabolic ADAMTS-5 inhibitor S201086/GLPG1972 for the treatment of symptomatic knee osteoarthritis. DESIGN: ROCCELLA (NCT03595618) was a randomized, double-blind, placebo-controlled, dose-ranging, phase 2 trial in adults (aged 40-75 years) with knee osteoarthritis. Participants had moderate-to-severe pain in the target knee, Kellgren-Lawrence grade 2 or 3 and Osteoarthritis Research Society International joint space narrowing (grade 1 or 2). Participants were randomized 1:1:1:1 to once-daily oral S201086/GLPG1972 75, 150 or 300 mg, or placebo for 52 weeks. The primary endpoint was change from baseline to week 52 in central medial femorotibial compartment (cMFTC) cartilage thickness assessed quantitatively by magnetic resonance imaging. Secondary endpoints included change from baseline to week 52 in radiographic joint space width, Western Ontario and McMaster Universities Osteoarthritis Index total and subscores, and pain (visual analogue scale). Treatment-emergent adverse events (TEAEs) were also recorded. RESULTS: Overall, 932 participants were enrolled. No significant differences in cMFTC cartilage loss were observed between placebo and S201086/GLPG1972 therapeutic groups: placebo vs 75 mg, P = 0.165; vs 150 mg, P = 0.939; vs 300 mg, P = 0.682. No significant differences in any of the secondary endpoints were observed between placebo and treatment groups. Similar proportions of participants across treatment groups experienced TEAEs. CONCLUSIONS: Despite enrolment of participants who experienced substantial cartilage loss over 52 weeks, during the same time period, S201086/GLPG1972 did not significantly reduce rates of cartilage loss or modify symptoms in adults with symptomatic knee osteoarthritis.

Persistence of orthopaedic hoof blocks for the treatment of lame cattle kept permanently at pasture.

AIMS: To compare the retention by New Zealand dairy cows kept at pasture in a lame cow group, of three hoof block products commonly used in the remediation of lameness. METHODS: Sixty-seven farmer-presented Friesian and Friesian x Jersey dairy cows from a single herd in the Manawatu region (New Zealand) suffering from unilateral hind limb lameness attributable to a claw horn lesion (CHL) were randomly allocated to one of three treatments: foam block (FB), plastic shoe (PS) and a standard wooden block (WB). Blocks were applied to the contralateral healthy claw and checked daily by the farm staff (present/not present) and date of loss was recorded. Blocks were reassessed on Day 14 and Day 28 and then removed unless further elevation was indicated. Daily walking distances were calculated using a farm map and measurement software. Statistical analyses included a linear marginal model for distance walked until block loss and a Cox regression model for the relative hazard of a block being lost. RESULTS: Random allocation meant that differences between products in proportion used on left or right hind foot or lateral or medial claw were small. Mean distance walked/cow/day on farm tracks whilst the block was present was 0.32 (min 0.12, max 0.45) km/day; no biologically important difference between products in the mean distance walked was identified. Compared to PS, cows in the WB group were five times more likely to lose the block (HR = 4.8 (95% CI = 1.8-12.4)), while cows in the FB group were 9.5 times more likely to lose the block (HR = 9.5 (95% CI = 3.6-24.4)). CONCLUSIONS: In this study, PS were retained for much longer than either FB or WB. As cows were managed in a lame cow group for the study duration, walking distances were low and did not impact on the risk of block loss. More data are needed to define ideal block retention time. CLINICAL RELEVANCE: In cows with CHL the choice of block could be based on the type of lesion present and the expected re-epithelisation times.

Investigating the effect of prophylactic claw trimming on the interval between calving and first observed elevated locomotion score in pasture-based dairy cows.

AIMS: To evaluate, in a pasture-based dairy herd, the response to a three-time point hoof trimming regime on lameness incidence and time from calving to observation of an elevated locomotion score (LS). METHODS: This study was conducted on a 940-cow spring-calving herd in New Zealand's North Island between May 2018 and May 2019. Cows (n = 250) were randomly allocated to the hoof trimming group, with the remainder assigned to the non-trim cohort. One trained professional hoof trimmer used the five-step Dutch method to trim the hind feet of the trimming group. Throughout the subsequent production season, the whole herd was locomotion-scored fortnightly using the 4-point (0-3) Dairy NZ lameness score. Kaplan-Meier survival curves were used to assess the univariable effect of trimming on the interval between calving and first LS of ≥ 2 and first LS ≥ 1. A multivariable Cox proportional hazards regression was used to further evaluate the effect of trimming on time to elevated LS. RESULTS: Mean lameness (LS ≥ 2) prevalence was 2.6%, with 30% of cows having ≥ 4 observations during the study period when at least one LS was ≥ 2. For LS ≥ 1, mean prevalence was 40%, with 98.6% of cows having ≥ 4 observations during the study period when at least one LS was ≥ 1 during lactation. Hoof trimming had no apparent effect on the incidence of clinical lameness (LS ≥ 2) (trimmed vs. non-trimmed: 33.2% vs. 28.8%, respectively), but for LS ≥ 1, there was a small decrease in the incidence of LS ≥ 1 (trimmed vs. non-trimmed: 96.9% vs. 99.3%, respectively). The hazard of a cow having a first observed LS ≥ 2 in the control group was 0.87 (95% CI = 0.66-1.14) times that of the trimmed group; however, the hazard of a cow having a first LS ≥ 1 was 1.60 (95% CI = 1.37-1.88) times higher in the control than in the trimmed group. CONCLUSION AND CLINICAL RELEVANCE: On this farm, prophylactic hoof trimming had no clinically relevant impact on the incidence of clinical lameness and was not associated with clinically beneficial reductions in time to first observed LS ≥ 2. This may be because claw horn imbalance was not pronounced on this farm, with 53% of cows needing no trim on either hind limb on the first trimming occasion. Further research on the response to prophylactic trimming in pasture-based dairy cattle is required.

High-fidelity and large-scale reconfigurable photonic processor for NISQ applications.

Reconfigurable linear optical networks are a key component for the development of optical quantum information processing platforms in the NISQ era and beyond. We report the implementation of such a device based on an innovative design that uses the mode mixing of a multimode fiber in combination with the programmable wavefront shaping of a SLM. The capabilities of the platform are explored in the classical regime. For up to 8 inputs and a record number of 38 outputs, we achieve fidelities in excess of 93%, and losses below 6.5dB. The device was built inside a standard server rack to allow for real world use and shows consistent performance for 2x8 circuits over a period of 10 days without re-calibration.

Graduate Student Literature Review: A systematic review on the associations between nonsteroidal anti-inflammatory drug use at the time of diagnosis and treatment of claw horn lameness in dairy cattle and lameness scores, algometer readings, and lying times.

The objectives of this systematic review were to investigate the association between nonsteroidal anti-inflammatory drug (NSAID) use during the treatment of claw horn lameness in dairy cattle and locomotion score (LS), nociceptive threshold, and lying times. A total of 229 studies were initially identified and had their title and abstract screened. From this, we screened the full text of 23 articles, identifying 6 articles for inclusion in the systematic review. Of these 6, 5 reported LS, 2 reported nociceptor thresholds, and 1 reported lying times. The quality of evidence was assessed using a Cochrane risk-of-bias tool and CONSORT items reported for each included study. Due to heterogeneity between the studies, data were reported following Cochrane's Synthesis without meta-analysis guidelines. Identified heterogeneity between the studies included differences in LS systems and statistical analyses, length of time from enrollment to outcome reported, the NSAID used, concomitant treatments administered, and severity and chronicity of lameness. Recommendations are made with respect to consistency of LS reporting and analysis, along with improvements that may be noted with compulsory reporting guidelines. There were at least some concerns over the risk of bias in 4 of the studies, with risks of bias present in missing outcome data between the study groups. Within the 5 studies included with LS outcomes, there were 22 different pairwise comparisons with either NSAID or NSAID + block as the intervention, with measures of association with presence or absence of lameness as the outcome available for 20 of these comparisons. Animals in the NSAID intervention groups had a lower point estimate lameness risk than animals in the comparison groups in 3 of 8 and 9 of 14 analyses for LS outcomes <10 and ≥10 d post-treatment, respectively. However, there was no difference identified between animals in the NSAID intervention groups compared with the animals in the control group in any of these pairwise comparisons with lameness as the outcome. Twelve pairwise comparisons were reported in the 2 studies with nociceptor threshold as an outcome. Animals in the NSAID intervention groups had a greater nociceptor threshold point estimate compared with animals in the comparison groups in 6 of 6 and 1 of 6 analyses for outcomes <10 and ≥10 d post-treatment, respectively. However, no differences were identified between animals in the NSAID intervention groups and those in the comparison groups. All 4 pairwise comparisons reported in the study with lying times as an outcome found no differences between animals in the NSAID groups and those in the comparison groups. Despite the widespread use of NSAID in the treatment of claw horn lameness, there is a lack of studies of NSAID association with LS, nociceptive thresholds, or lying times. The limited evidence is consistent with no association with NSAID use and those parameters, but comparability across studies was limited by heterogeneity.

Elevated markers of gut leakage and inflammasome activation in COVID-19 patients with cardiac involvement.

BACKGROUND: A high proportion of COVID-19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS-CoV-2 and the renin-angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID-19 patients. METHODS: Plasma levels of a gut leakage marker (LPS-binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL-1ß, IL-18 and their regulatory proteins) were measured at three time points (day 1, 3-5 and 7-10) in 39 hospitalized COVID-19 patients and related to cardiac involvement. RESULTS: Compared to controls, COVID-19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT-pro-BNP levels, whereas IL-18, IL-18BP and IL-1Ra were associated with higher troponin levels. CONCLUSION: Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut-heart axis in COVID-19.

Assessment of the sanitary quality of ready to eat sesame, a low moisture street food from Burkina Faso.

BACKGROUND: Microbial contamination of edible low moisture food poses a significant public health risk for human. In this study, the microbial quality of sweet dehulled sesame seed croquettes, salted dehulled sesame seed and the raw sesame seed, sold under ambient conditions were examined. The samples were collected in the cities of Burkina Faso. The first type is sweet dehulled sesame seed croquettes (n1 = 25); the second type is salted dehulled sesame seed (n2 = 25) and the third type is raw sesame seed (n3 = 25). Assessment of the microbial quality was based on the total aerobic mesophilic bacteria, the thermotolerant coliforms, the yeasts and moulds, the E. coli, and the Salmonella spp. using ISO methods. RESULTS: The results showed the presence of microorganisms varying from <1.0 to 1.72 × 105 CFU g- 1 for thermotolerant coliforms, from <1.0 to 6,12 × 106 CFU g- 1 for the total mesophilic aerobic flora and from <1.0 to 8.10 × 105 CFU g- 1 for yeasts and moulds. The higher contaminations rates were mostly observed in raw sesame seed samples. No E coli or Salmonella pathogens were detected. Based on international standards of dehydrated food, 50.67% of the ready to eat sesame are satisficing while 17.33% are acceptable and 32% are not satisficing. CONCLUSION: Attention should be emphasized on the processing practices, especially in crowded places where RTE sesames seeds are mostly sold. The high numbers of all microbial groups in these sesame seed samples suggested that the production of RTE sesame seed should be improved by better hygiene. This study highlights also that RTE sesame seed might harbor a wide range of microorganisms when processes are weak of hygiene.

The influence of the SARS-CoV-2 lockdown on patients with inflammatory rheumatic diseases on their adherence to immunomodulatory medication: a cross sectional study over 3 months in Germany.

OBJECTIVES: To evaluate the influence of the SARS-CoV-2 pandemic on the adherence of patients with inflammatory rheumatic diseases (IRD) to their immunomodulatory medication during the three-month lockdown in Germany. METHODS: From 16th March until 15th June 2020, IRD patients from private practices and rheumatology departments were asked to answer a questionnaire addressing their behaviour with respect to their immunomodulating therapy. Eight private practices and nine rheumatology departments that included rheumatology primary care centres and university hospitals participated. A total of 4252 questionnaires were collected and evaluated. RESULTS: The majority of patients (54%) were diagnosed with RA, followed by psoriatic arthritis (14%), ankylosing spondylitis (10%), connective tissue diseases (12%) and vasculitides (6%). Most of the patients (84%) reported to continue their immunomodulatory therapy. Termination of therapy was reported by only 3% of the patients. The results were independent from the type of IRD, the respective immunomodulatory therapy and by whom the patients were treated (private practices vs rheumatology departments). Younger patients (<60 years) reported just as often as older patients to discontinue their therapy. CONCLUSION: The data show that most of the patients continued their therapy in spite of the pandemic. A significant change in behaviour with regard to their immunomodulatory therapy was not observed during the three months of observation. The results support the idea that the immediate release of recommendations of the German Society of Rheumatology were well received, supporting the well-established physician-patient relationship in times of a crisis.

Prevalence of disorders in preweaned dairy calves from 731 dairies in Germany: A cross-sectional study.

The objective of this cross-sectional study was to determine the prevalence of disorders in preweaned calves in 3 regions in Germany, exemplary for structural diversity in dairy farming. A farm visit was performed on a single occasion on 731 dairy farms in the northern, eastern, and southern regions of Germany between December 2016 and July 2019. Farms differed in herd size, geographical location, and management. In the northern region, the farms had a median of 90 milking cows and were often run as full-time family businesses, partly with external workers. The eastern region tended to have larger farms (a median of 251 milking cows), which were often large-scale agricultural enterprises with employees. In the southern region, the farms had a median of 39 milking cows and were often traditional family businesses, some of these being part-time businesses. Clinical examinations were performed on 14,164 preweaned dairy calves (median 12 calves per farm) by trained veterinarians. A complete data set was available for 13,656 calves. Almost half (42.0%) of the evaluated calves were classified as being affected by at least 1 of the common calf disorders. Omphalitis (O, 20.9%; n = 2,876) and diarrhea (D, 18.5%; n = 2,670) were the most frequently recorded diagnoses, whereas respiratory diseases (RD) were observed to a lesser extent (8.7%; n = 1,100). A striking feature was the fact that 7.1% (n = 987) of the calves were affected by more than 1 disorder at the same time (multimorbidity, M). The following combinations of disorders were frequently observed: O and D (n = 596), O and RD (n = 164), and D and RD (n = 140). Disorders such as O and D, as well as M, were predominantly observed in calves aged 2 wk. A gradual increase in the frequency of RD was observed with age. For all disorders except RD, male calves were more often affected than females. Omphalitis was predominantly diagnosed in the summer months, whereas RD, D, and M were more common in the fall. We detected several statistically significant differences in the prevalence of clinical signs and disorders in preweaned dairy calves between the 3 exemplary regions. The prevalence of RD was higher in the south (10.8%) than in the north (8.2%) and east (7.4%). In the north (33.2%), O was observed more frequently than in the other regions (east: 18.9%; south: 10.5%), whereas D was found less frequently in the north (13.8%) than in the east (21.6%) and south (20.0%).

Addressing a real-life problem: treatment with intravenous thrombolysis and mechanical thrombectomy in acute stroke patients with an extended time window beyond 4.5 h based on computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging-guided treatment decision-making in wake-up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. METHODS: We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow-up was assessed with the modified Rankin Scale (mRS). RESULTS: A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4-14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9-10) and CTP mismatch 90% (IQR, 80%-100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow-up, 49.3% had an mRS score of 0-2 and 22.4% had an mRS score of 0-1. CONCLUSIONS: In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision-making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed.

Factors determining microbial colonization of liquid nitrogen storage tanks used for archiving biological samples.

The availability of bioresources is a precondition for life science research, medical applications, and diagnostics, but requires a dedicated quality management to guarantee reliable and safe storage. Anecdotal reports of bacterial isolates and sample contamination indicate that organisms may persist in liquid nitrogen (LN) storage tanks. To evaluate the safety status of cryocollections, we systematically screened organisms in the LN phase and in ice layers covering inner surfaces of storage tanks maintained in different biobanking facilities. We applied a culture-independent approach combining cell detection by epifluorescence microscopy with the amplification of group-specific marker genes and high-throughput sequencing of bacterial ribosomal genes. In the LN phase, neither cells nor bacterial 16S rRNA gene copy numbers were detectable (detection limit, 102 cells per ml, 103 gene copies per ml). In several cases, small numbers of bacteria of up to 104 cells per ml and up to 106 gene copies per ml, as well as Mycoplasma, or fungi were detected in the ice phase formed underneath the lids or accumulated at the bottom. The bacteria most likely originated from the stored materials themselves (Elizabethingia, Janthibacterium), the technical environment (Pseudomonas, Acinetobacter, Methylobacterium), or the human microbiome (Bacteroides, Streptococcus, Staphylococcus). In single cases, bacteria, Mycoplasma, fungi, and human cells were detected in the debris at the bottom of the storage tanks. In conclusion, the limited microbial load of the ice phase and in the debris of storage tanks can be effectively avoided by minimizing ice formation and by employing hermetically sealed sample containers.

Cell survival after cryopreservation of dissociated testicular cells from feline species.

Testicular cell suspension (TCS) can be cryopreserved for male germ-line preservation and fertility restoration. We aimed to validate a cryopreservation protocol for TCS of domestic cat to be applied in endangered felids species. Testis tissue from adult domestic cats was enzymatically dissociated and spermatogenic cells were enriched. The resulting TCS was diluted in 7.5% or 15% Me2SO based medium. Slow and fast freezing methods were tested. We examined the effects of freezing approaches using two combinations of fluorescent dyes: Calcein-AM with Propidium iodide (C/PI) and SYBR14 with Propidium iodide (S/PI). Ploidy analysis of domestic cat fresh TCS revealed that the majority of testicular cells were haploid cells. Based on microscopic observation, two size populations (12.3 ± 2.3 µm and 20.5 ± 4 µm in diameter) were identified and presumed to be mainly spermatids and spermatocytes, respectively. Both evaluation methods proved higher viability of aggregated cells before and after cryopreservation compared with single cells, and superiority of low concentration of Me2SO (7.5%) in association with slow freezing to preserve viability of testicular cells. However, S/PI resulted in a more precise evaluation compared with the C/PI method. The combination of 7.5% Me2SO-based medium with slow freezing yielded post thaw viability of S/PI labeled aggregated (49.8 ± 20%) and single cells (31.5 ± 8.1%). Comparable results were achieved using testes of a Cheetah and an Asiatic golden cat. In conclusion, TCS from domestic cat can be successfully cryopreserved and has the potential to support fertility restoration of endangered felids species.

[Myofascial chronic pelvic pain in women : A retrospective evaluation of the effects of specific diagnostics and therapy]. / Myofaszial bedingte chronische Unterbauchschmerzen bei Frauen : Eine retrospektive Auswertung der Auswirkungen einer spezifischen Diagnostik und Therapie.

BACKGROUND: The prevalence of chronic pelvic pain of 11.8% in the general population underlines the importance of this disease. However, the specific diagnostics and therapy of the muscles of this region are not yet part of the standard examination. The following study examines the effects of specific diagnostics and therapy on myofascial chronic pelvic pain. OBJECTIVES: The effectiveness of targeted diagnostics and multimodal therapy in the context of chronic pelvic pain and the need for a complementary drug adjustment. MATERIALS AND METHODS: This study retrospectively evaluated the data of 59 patients, who were referred to a pain center for treatment-resistant chronic pelvic pain in the period from January 2012 to April 2017. The pain needed to be clearly identified as myofascial. A previous minimum duration of pain as well as previous operations or other treatment procedures did not constitute exclusion criteria. Previous traumatization was a reason for exclusion. Therapy components included manual therapeutic treatment, training in self-stretching exercises, medication with the active ingredients flupirtine or methocarbamol, as well as relaxation procedures. Therapy was evaluated on the basis of the German Pain Questionnaire. RESULTS: After the treatment interval, the following statistically significant improvements were recorded: The average pain intensity decreased by 29.95 points (standard deviation [SD] = 20.61). General quality of life (Marburg questionnaire on habitual well-being, MFHW) increased by 1.1 points (SD = 0.73). The depression and anxiety assessment decreased by 2.56 (SD = 3.99) and 2.63 points (SD = 5.21) respectively. CONCLUSION: A multimodal therapy concept with a manual therapeutic treatment focus can lead to an improvement in pain symptoms and quality of life in patients with myofascial chronic pelvic pain after a treatment period of 120 days. Myofascial syndromes of urogenital muscles must be considered in the assessment of the cause of chronic pelvic pain.

[Mesothelial proliferation of the tunica vaginalis testis]. / Mesotheliale Proliferate der Tunica vaginalis testis.

Proliferative changes seen in reactive mesothelial hyperplasia of a hydrocele sac may mimic malignant mesothelioma. There is no immunohistochemical staining that reliably separates benign from malignant mesothelial proliferations. However, the combined analysis of BAP1 by immunohistochemistry and CDKN2A by FISH has been reported to yield both a high specificity and sensitivity in this differential diagnosis. In addition, the evaluation of risk factors such as asbestos exposure or prior traumata may be helpful for the correct diagnosis. Exclusion of stromal invasion, which is diagnostic for malign mesothelioma, is of utmost importance. Therefore, extended histological workup is essential.

[A cross sectional study on patients with inflammatory rheumatic diseases in terms of their compliance to their immunsuppressive medication during COVID-19 pandemic]. / Einstellung von Patienten mit entzündlich-rheumatischen Erkrankungen zur immunsuppressiven Therapie im Rahmen der COVID-19 Pandemie ­ eine Situationsanalyse.

The current COVID-19 pandemic inherits an unprecedented challenge for the treating rheumatologists. On the one hand, antirheumatic drugs can increase the risk of infection and potentially deteriorate the course of an infection. On the other hand, an active inflammatory rheumatic disease can also increase the risk for an infection. In the recommendations of the German Society for Rheumatology (www.dgrh.de), it is recommended that our patients continue the antirheumatic therapy to maintain remission or low state of activity despite the pandemic. In this study, patients with inflammatory rheumatic disease were asked in the first weeks of the pandemic on their opinion of their immunomodulating therapy. The result shows that over 90% of the patients followed the recommendation of the rheumatologist to continue the antirheumatic therapy, and only a small percentage of the patients terminated the therapy on their own. This result was independent of the individual anti-rheumatic therapy. Taken together, the results of this study illustrate not only the trustful patient-physician partnership in a threatening situation but also the high impact of state-of-the art recommendations by the respective scientific society.

Scoring of tumor-infiltrating lymphocytes: From visual estimation to machine learning.

The extent of tumor-infiltrating lymphocytes (TILs), along with immunomodulatory ligands, tumor-mutational burden and other biomarkers, has been demonstrated to be a marker of response to immune-checkpoint therapy in several cancers. Pathologists have therefore started to devise standardized visual approaches to quantify TILs for therapy prediction. However, despite successful standardization efforts visual TIL estimation is slow, with limited precision and lacks the ability to evaluate more complex properties such as TIL distribution patterns. Therefore, computational image analysis approaches are needed to provide standardized and efficient TIL quantification. Here, we discuss different automated TIL scoring approaches ranging from classical image segmentation, where cell boundaries are identified and the resulting objects classified according to shape properties, to machine learning-based approaches that directly classify cells without segmentation but rely on large amounts of training data. In contrast to conventional machine learning (ML) approaches that are often criticized for their "black-box" characteristics, we also discuss explainable machine learning. Such approaches render ML results interpretable and explain the computational decision-making process through high-resolution heatmaps that highlight TILs and cancer cells and therefore allow for quantification and plausibility checks in biomedical research and diagnostics.

Enhancing sensorimotor BCI performance with assistive afferent activity: An online evaluation.

An important goal in Brain-Computer Interfacing (BCI) is to find and enhance procedural strategies for users for whom BCI control is not sufficiently accurate. To address this challenge, we conducted offline analyses and online experiments to test whether the classification of different types of motor imagery could be improved when the training of the classifier was performed on the data obtained with the assistive muscular stimulation below the motor threshold. 10 healthy participants underwent three different types of experimental conditions: a) Motor imagery (MI) of hands and feet b) sensory threshold neuromuscular electrical stimulation (STM) of hands and feet while resting and c) sensory threshold neuromuscular electrical stimulation during performance of motor imagery (BOTH). Also, another group of 10 participants underwent conditions a) and c). Then, online experiments with 15 users were performed. These subjects received neurofeedback during MI using classifiers calibrated either on MI or BOTH data recorded in the same experiment. Offline analyses showed that decoding MI alone using a classifier based on BOTH resulted in a better BCI accuracy compared to using a classifier based on MI alone. Online experiments confirmed accuracy improvement of MI alone being decoded with the classifier trained on BOTH data. In addition, we observed that the performance in MI condition could be predicted on the basis of a more pronounced connectivity within sensorimotor areas in the frequency bands providing the best performance in BOTH. These finding might offer a new avenue for training SMR-based BCI systems particularly for users having difficulties to achieve efficient BCI control. It might also be an alternative strategy for users who cannot perform real movements but still have remaining afferent pathways (e.g., ALS and stroke patients).

Canonical maximization of coherence: A novel tool for investigation of neuronal interactions between two datasets.

Synchronization between oscillatory signals is considered to be one of the main mechanisms through which neuronal populations interact with each other. It is conventionally studied with mass-bivariate measures utilizing either sensor-to-sensor or voxel-to-voxel signals. However, none of these approaches aims at maximizing synchronization, especially when two multichannel datasets are present. Examples include cortico-muscular coherence (CMC), cortico-subcortical interactions or hyperscanning (where electroencephalographic EEG/magnetoencephalographic MEG activity is recorded simultaneously from two or more subjects). For all of these cases, a method which could find two spatial projections maximizing the strength of synchronization would be desirable. Here we present such method for the maximization of coherence between two sets of EEG/MEG/EMG (electromyographic)/LFP (local field potential) recordings. We refer to it as canonical Coherence (caCOH). caCOH maximizes the absolute value of the coherence between the two multivariate spaces in the frequency domain. This allows very fast optimization for many frequency bins. Apart from presenting details of the caCOH algorithm, we test its efficacy with simulations using realistic head modelling and focus on the application of caCOH to the detection of cortico-muscular coherence. For this, we used diverse multichannel EEG and EMG recordings and demonstrate the ability of caCOH to extract complex patterns of CMC distributed across spatial and frequency domains. Finally, we indicate other scenarios where caCOH can be used for the extraction of neuronal interactions.