MELAS: Phenotype Classification into Classic-versus-Atypical Presentations.

BACKGROUND AND PURPOSE: An increased number of pathogenic variants have been described in mitochondrial encephalomyopathy lactic acidosis and strokelike episodes (MELAS). Different imaging presentations have emerged in parallel with a growing recognition of clinical and outcome variability, which pose a diagnostic challenge to neurologists and radiologists and may impact an individual patient's response to therapeutic interventions. By evaluating clinical, neuroimaging, laboratory, and genetic findings, we sought to improve our understanding of the sources of potential phenotype variability in patients with MELAS. MATERIALS AND METHODS: This retrospective single-center study included individuals who had confirmed mitochondrial DNA pathogenic variants and a diagnosis of MELAS and whose data were reviewed from January 2000 through November 2021. The approach included a review of clinical, neuroimaging, laboratory, and genetic data, followed by an unsupervised hierarchical cluster analysis looking for sources of phenotype variability in MELAS. Subsequently, experts identified "victory-variables" that best differentiated MELAS cohort clusters. RESULTS: Thirty-five patients with a diagnosis of mitochondrial DNA-based MELAS (median age, 12 years; interquartile range, 7-24 years; 24 female) were eligible for this study. Fifty-three discrete variables were evaluated by an unsupervised cluster analysis, which revealed that two distinct phenotypes exist among patients with MELAS. After experts reviewed the variables, they selected 8 victory-variables with the greatest impact in determining the MELAS subgroups: developmental delay, sensorineural hearing loss, vision loss in the first strokelike episode, Leigh syndrome overlap, age at the first strokelike episode, cortical lesion size, regional brain distribution of lesions, and genetic groups. Ultimately, 2-step differentiating criteria were defined to classify atypical MELAS. CONCLUSIONS: We identified 2 distinct patterns of MELAS: classic MELAS and atypical MELAS. Recognizing different patterns in MELAS presentations will enable clinical and research care teams to better understand the natural history and prognosis of MELAS and identify the best candidates for specific therapeutic interventions.

Immune related endonucleases and GTPases are not associated with tumor response in patients with advanced non-small cell lung cancer treated with checkpoint inhibitors.

Immune related endonucleases have recently been described as potential therapeutic targets and predictors of response to treatment with immune checkpoint inhibitors (ICI). The aim is to evaluate the association between the expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d and Cytohesin-3) in parallel with the more common ICI-predictive markers, PD-L1 expression and Tumor Mutation Burden (TMB) with response to ICI therapy in an advanced non-small cell lung cancer (NSCLC) cohort. METHODS: Patients with advanced NSCLC treated with ICI single agent were divided into responders and non-responders according to RECIST v1.1 and duration of response (DOR) criteria. Immunohistochemistry was performed on pretreatment tumor tissue samples for PD-L1, CD73, CD39, VISTA, Arl4d, and Cytohesin-3 expression. TMB was estimated with NEOplus v2 RUO (NEO New Oncology GmbH) hybrid capture next generation sequencing assay. Resistance mutations in STK11/KEAP1 and positive predictive mutations in ARID1A/POLE were also evaluated. RESULTS: Included were 56 patients who were treated with ICI single agent. The median progression-free and overall survival for the whole cohort was 3.0 (95% CI, 2.4-3.6) and 15 (95% CI, 9.7-20.2) months, respectively. The distribution of CD73 in tumor cells and CD39, VISTA, Arl4d and Cytohesin-3 expression in immune cells were not different between responders and non-responders. Also, PD-L1 and TMB were not predictive for response. The frequency of STK11, KEAP1 and ARID1A mutations was low and only observed in the non-responder group. CONCLUSION: Separate and combined expression of 5 biomarkers involved in the immune response (CD73, CD39, VISTA, Arl4d, and Cytohesin-3) was not associated with response in our cohort of advanced NSCLC patients receiving single agent ICI. To confirm our findings the analysis of independent larger cohorts is warranted.

Involvement of the Spinal Cord in Primary Mitochondrial Disorders: A Neuroimaging Mimicker of Inflammation and Ischemia in Children.

BACKGROUND AND PURPOSE: Little is known about imaging features of spinal cord lesions in mitochondrial disorders. The aim of this research was to assess the frequency, imaging features, and pathogenic variants causing primary mitochondrial disease in children with spinal cord lesions. MATERIALS AND METHODS: This retrospective analysis included patients seen at Children's Hospital of Philadelphia between 2000 and 2019 who had a confirmed diagnosis of a primary (genetic-based) mitochondrial disease and available MR imaging of the spine. The MR imaging included at least both sagittal and axial fast spin-echo T2-weighted images. Spine images were independently reviewed by 2 neuroradiologists. Location and imaging features of spinal cord lesions were correlated and tested using the Fisher exact test. RESULTS: Of 119 children with primary mitochondrial disease in whom MR imaging was available, only 33 of 119 (28%) had available spine imaging for reanalysis. Nineteen of these 33 individuals (58%) had evidence of spinal cord lesions. Two main patterns of spinal cord lesions were identified: group A (12/19; 63%) had white ± gray matter involvement, and group B (7/19; 37%) had isolated gray matter involvement. Group A spinal cord lesions were similar to those seen in patients with neuromyelitis optica spectrum disorder, multiple sclerosis, anti-myelin oligodendrocyte glycoprotein-IgG antibody disease, and leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Group B patients had spinal cord findings similar to those that occur with ischemia and viral infections. Significant associations were seen between the pattern of lesions (group A versus group B) and the location of lesions in cervical versus thoracolumbar segments, respectively (P < .01). CONCLUSIONS: Spinal cord lesions are frequently observed in children with primary mitochondrial disease and may mimic more common causes such as demyelination and ischemia.

The Perirolandic Sign: A Unique Imaging Finding Observed in Association with Polymerase γ-Related Disorders.

Pathogenic variants in the polymerase γ gene (POLG) cause a diverse group of pathologies known as POLG-related disorders. In this report, we describe brain MR imaging findings and electroencephalogram correlates of 13 children with POLG-related disorders at diagnosis and follow-up. At diagnosis, all patients had seizures and 12 had abnormal MR imaging findings. The most common imaging findings were unilateral or bilateral perirolandic (54%) and unilateral or bilateral thalamic signal changes (77%). Association of epilepsia partialis continua with perirolandic and thalamic signal changes was present in 86% and 70% of the patients, respectively. The occipital lobe was affected in 2 patients. On follow-up, 92% of the patients had disease progression or fatal outcome. Rapid volume loss was seen in 77% of the patients. The occipital lobe (61%) and thalamus (61%) were the most affected brain regions. Perirolandic signal changes and seizures may represent a brain imaging biomarker of early-onset pediatric POLG-related disorders.

Beneficial antioxidant status of piglets from sows fed selenomethionine compared with piglets from sows fed sodium selenite.

BACKGROUND: Studies in mammals proved dietary organic selenium (Se) being superior to inorganic Se regarding effects on growth performance, antioxidative status, immune response, and Se homeostasis. However, the picture of possible effects of different Se sources and - levels can be expanded. The present field study evaluated the effects on weight gain, hematological and selected biochemical variables as well as plasma concentrations of vitamin E (vitE), total Se and selenobiomolecules in piglets throughout the suckling period. METHODS: Piglets were monitored from birth to 38 days of age (d). The mother sows' diets were enriched with l-selenomethionine (SeMet-0.26 and -0.43 mg Se/kg feed) or sodium selenite (NaSe-0.40 and -0.60 mg Se/kg feed) from 1 month prior to farrowing until the end of lactation period. Piglets received pelleted feed supplemented with Se similarly to the sows' diets from one week of age. Selenite at 0.40 mg Se/kg (NaSe-0.40) represents a common Se source and -level in pig feed and served as control diet. RESULTS: From 24d, piglets in SeMet-groups had higher mean body weight (BW) compared with piglets from sows fed NaSe-0.40. Furthermore, from five-d and above, piglets from sows fed NaSe-0.60 had significantly higher BW than offspring from sows fed NaSe-0.40. Neonatal piglets in group SeMet-0.43 had significantly lower red blood cell counts (RBC), hemoglobin (Hgb) and hematocrit (Hct) concentrations compared with piglets from sows fed with NaSe-0.40. Neonatal and 5d-old piglets in group SeMet-0.26 showed higher gamma-glutamyl transferase activity than piglets in group NaSe-0.40. From five d and above, group NaSe-0.60 excelled with increased specific hematological variables culminating at age 38d with increased Hct, mean corpuscular volume (MCV), and MC hemoglobin (MCH) as well as increased activities of aspartate transaminase and lactate dehydrogenase compared with the other groups. Generally, offspring in the SeMet groups had higher total Se-concentrations in plasma than those from sows fed selenite, and showed a dose-response effect on plasma Se-concentrations. Furthermore, SeMet-fed piglets had higher plasma levels of the selenoproteins (Sel) glutathione peroxidase 3 (GPx3) and SelP as well as selenoalbumin. Plasma vitE levels were significantly negatively correlated with RBC throughout trial period. CONCLUSIONS: Maternal supplementation with SeMet during gestation influenced hematology and clinical biochemistry in neonatal piglets in a different way than in offspring from sows receiving selenite enriched diets. Growth performance was positively influenced by both dietary Se source and Se level. Higher plasma levels of GPx3 observed in piglets receiving SeMet probably improved the protection against birth or growth related oxidative stress. These might prime the piglets for demanding situations as indicated by higher weight gain in offspring from sows fed with SeMet-supplemented diets. Our results on some enzyme activities might indicate that piglets fed NaSe-0.60 had to cope with increased levels of oxidative stress compared with those originating from sows fed SeMet or lower dietary levels of selenite. We assume that combining inorganic and organic Se sources in complete feed for breeding sows might be beneficial fro reproduction and the offspring's performance.

Impaired post-irradiation survival of cyclooxygenase-2-deficient mice.

We investigated and evaluated post-irradiation survival in cyclooxygenase-2-deficient (COX-2 KO) mice. Thirty-day survival following exposure of COX-2 KO mice to a lethal dose of 8.5 Gy of gamma-rays was observed to be statistically significantly lower in both males and females, as well as when the sexes were merged, in comparisons with their wild-type counterparts. These findings were related to the previous observations concerning the detrimental influence of the COX-2 genetic disruption on hematopoiesis in sublethally irradiated mice. Deteriorated post-irradiation survival of COX-2 KO mice confirmed the previously anticipated conclusion regarding negative influence of the antiinflammatory action of COX-2 deficiency under the conditions of exposure of the animals to ionizing radiation.

Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 2016.

OBJECTIVES: Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformité Européene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016. METHODS: From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested. RESULTS: In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13-100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%). CONCLUSIONS: Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.

Biomechanical stress in myocardial infarctions: can endothelin-1 and growth differentiation factor 15 serve as immunohistochemical markers?

Myocardial infarctions go along with biomechanical stress, i.e. stretching of muscle fibres, and the expression of certain marker molecules. We tested if two of those markers, endothelin-1 (ET-1) and growth differentiation factor 15 (GDF-15), can be used as immunohistochemical markers for myocardial ischaemia/infarctions. The study included experiments with an animal model, the isolated perfused Langendorff heart, as well as the investigation of human tissue samples drawn during autopsies. The overall picture of our results showed that GDF-15 is very sensitive and expressed very fast, not only as a consequence of ischaemia/infarctions, but also under other circumstances. Even an expression only caused by agony had to be discussed. ET-1, on the other hand, was less sensitive but only positive in those human cases with ischaemia/infarction that also showed typical alterations in conventional histology. Therefore, both markers did not proof to be a suitable diagnostic tool for myocardial infarctions. However, positive staining for ET-1 was also seen in rats' hearts that suffered from arrhythmias after electric shock and in the myocardium of the right ventricle in human control cases in which a right heart failure has to be discussed. Thus, especially ET-1 should be subject of further studies that focus on these pathologies.

An independent assessment of reliability of the Melbourne Cerebral Palsy Hip Classification System.

PURPOSE: Neuromuscular (NM) hip dysplasia is common in patients with cerebral palsy (CP). Traditionally, migration percentage (MP) has been used to measure the severity of NM hip dysplasia; however, the MP has some limitations. The purpose of this study is to determine the intra- and inter-reliability of the Melbourne Cerebral Palsy Hip Classification System in the typical paediatric population of patients with CP. METHODS: A total of 65 anteroposterior pelvis radiographs in patients (age range 12 years to 21 years) with CP spanning all grades (I to VI) of the classification system were identified and collected for analysis in this institutional review board approved study. Four paediatric orthopaedic surgeons and one orthopaedic surgical resident classified each radiograph according to the Melbourne system. Then, at least four weeks later, the raters repeated the process with a re-randomised order of radiographs. Statistical analysis was performed using the intraclass correlation coefficient (ICC) where < 0 denotes poor agreement and > 0.8 indicates almost perfect agreement. RESULTS: The interobserver reliability was found to be excellent with the ICC of 0.853 (0.813 to 0.887) and 0.839 (0.795 to 0.877). The intraobserver reliability was also found to be excellent with the ICC in the range of 0.838 to 0.933 among the raters. Subgroup analysis indicated no differences in the reliability of observers based on clinical experience. CONCLUSION: This study independently demonstrates that the Melbourne Cerebral Palsy Hip Classification System for NM hip dysplasia in patients with CP can be reliably used for communication among various healthcare providers and research and epidemiological purposes.

Prognostic risk factors of first recurrence in patients with primary stages I-II cutaneous malignant melanoma - from the population-based Swedish melanoma register.

BACKGROUND: Prognostic factors in patients with localized primary cutaneous malignant melanoma (CMM) are well described. However, prognostic factors for recurrence are less documented. OBJECTIVES: The aim of this study was to identify prognostic risk factors for first recurrence in patients with localized stages I-II CMM using population-based data. METHODS: This study included 1437 CMM patients registered in one region of Sweden during 1999-2012 follow-up through 31 December 2012. To identify first recurrence of CMM disease, data from a care data warehouse, the pathology and radiology department registries were used. Patients were also followed through a census register and the national Cause of Death Register. RESULTS: The 5- and 10-year recurrence-free survival (RFS) were 85.7% and 81.2%, respectively. The most common site of first recurrence was regional lymph node metastasis closely followed by distant metastasis. After adjusting for all prognostic factors, women had 50% lower risk of recurrence than men (HR = 0.5, 95% CI 0.4-0.7) and patients ≥70 had higher risk compared to patients 55-69 years (HR = 1.7, 95% CI 1.2-2.5). Other significant prognostic factors for risk of recurrence were tumour thickness, presence of ulceration, Clark's level of invasion and histogenetic type. CONCLUSION: Tumour thickness was found to be the predominant risk factor for recurrence. The prognostic factors for recurrence coincided with prognostic factors for CMM death. The most common site of first recurrence in stages I-II CMM is regional lymph node (42.8%) closely followed by distant metastases (37.6%), a fact which has to be taken into consideration when choosing follow-up strategies.

Fundoplication for laryngopharyngeal reflux despite preoperative dysphagia.

INTRODUCTION Fundoplication for laryngopharyngeal disease with oesophageal dysmotility has led to mixed outcomes. In the presence of preoperative dysphagia and oesophageal dysmotility, this procedure has engendered concern in certain regards. METHODS This paper describes a consecutive series of laryngopharyngeal reflux (LPR) patients with a high frequency of dysmotility. Patients were selected for surgery with 24-hour dual channel pH monitoring, oesophageal manometry and standardised reflux scintigraphy. RESULTS Following careful patient selection, 33 patients underwent fundoplication by laparoscopy. Surgery had high efficacy in symptom control and there was no adverse dysphagia. CONCLUSIONS Evidence of proximal reflux can select a group of patients for good results of fundoplication for atypical symptoms.

Metabolic load in dairy cows kept in herbage-based feeding systems and suitability of potential markers for compromised well-being.

Herbage feeding with only little input of concentrates plays an important role in milk production in grassland dominated countries like Switzerland. The objective was to investigate the effects of a solely herbage-based diet and level of milk production on performance, and variables related to the metabolic, endocrine and inflammatory status to estimate the stress imposed on dairy cows. Twenty-five multiparous Holstein cows were divided into a control (C+, n = 13) and a treatment group (C-, n = 12), according to their previous lactation yield (4679-10 808 kg) from week 3 ante partum until week 8 post-partum (p.p.). While C+ received fresh herbage plus additional concentrate, no concentrate was fed to C- throughout the experiment. Within C+ and C-, the median of the preceding lactation yields (7752 kg) was used to split cows into a high (HYC+, HYC-)- and low-yielding (LYC+, LYC-) groups. Throughout the study, HYC+ had a higher milk yield (35.9 kg/d) compared to the other subgroups (27.2-31.7 kg/d, p < 0.05). Plasma glucose (3.51 vs. 3.72 mmol/l) and IGF-1 (66.0 vs. 78.9ng/mL) concentrations were lower in HYC-/LYC- compared to HYC+/LYC+ cows (p < 0.05). Plasma FFA and BHBA concentrations were dramatically elevated in HYC- (1.1 and 1.6 mmol/l) compared to all other subgroups (mean values: 0.5 and 0.6 mmol/l, p < 0.05). Saliva cortisol, plasma concentrations of serum amyloid A (SAA), haptoglobin (Hp), beta-endorphin (BE) and activity of alkaline phosphatase (AP) were not different between C+ and C-. In conclusion, herbage-fed high-yielding cows without supplementary concentrate experienced a high metabolic load resulting in a reduced performance compared to cows of similar potential fed accordingly. Low-yielding cows performed well without concentrate supplementation. Interestingly, the selected markers for inflammation and stress such as cortisol, Hp, SAA, BE and AP gave no indication for the metabolic load being translated into compromised well-being.

Dityrosine as a marker of acute myocardial infarction? Experiments with the isolated Langendorff heart.

The isolated Langendorff heart was used to evaluate dityrosine as a marker of acute myocardial infarctions. The animal model allowed the generation of local infarctions with defined survival times, as well as infarctions with and without reperfusion. The results showed that dityrosine, at least under the conditions of the animal model, occurs very shortly after early ischemia and infarctions, since positive staining results were already obtained after a survival time of only 5 min. Furthermore, it could be proved that the occurrence of dityrosine does not depend on a reperfusion of the ischemic muscle area and that there are no differences in the staining patterns of infarctions with and without reperfusion. Positive staining results for dityrosine in control hearts without infarctions had to be considered when evaluating the tissue samples of the study hearts. In part, the positive staining results of the control hearts seemed to be an artefact of the Langendorff system, easily identifiable by a distinctive staining pattern. Positive staining results in tissue samples of hearts that suffered from arrhythmia on the other hand implied that the occurrence of dityrosine is not specific for myocardial infarctions. Taking into account the results of previous works on human tissue samples, however, these findings did not question the use of dityrosine as a diagnostic tool; they simply showed that myocardial damage due to oxidative stress might occur under various pathologic conditions.

Model-Based Design of Biochemical Microreactors.

Mathematical modeling of biochemical pathways is an important resource in Synthetic Biology, as the predictive power of simulating synthetic pathways represents an important step in the design of synthetic metabolons. In this paper, we are concerned with the mathematical modeling, simulation, and optimization of metabolic processes in biochemical microreactors able to carry out enzymatic reactions and to exchange metabolites with their surrounding medium. The results of the reported modeling approach are incorporated in the design of the first microreactor prototypes that are under construction. These microreactors consist of compartments separated by membranes carrying specific transporters for the input of substrates and export of products. Inside the compartments of the reactor multienzyme complexes assembled on nano-beads by peptide adapters are used to carry out metabolic reactions. The spatially resolved mathematical model describing the ongoing processes consists of a system of diffusion equations together with boundary and initial conditions. The boundary conditions model the exchange of metabolites with the neighboring compartments and the reactions at the surface of the nano-beads carrying the multienzyme complexes. Efficient and accurate approaches for numerical simulation of the mathematical model and for optimal design of the microreactor are developed. As a proof-of-concept scenario, a synthetic pathway for the conversion of sucrose to glucose-6-phosphate (G6P) was chosen. In this context, the mathematical model is employed to compute the spatio-temporal distributions of the metabolite concentrations, as well as application relevant quantities like the outflow rate of G6P. These computations are performed for different scenarios, where the number of beads as well as their loading capacity are varied. The computed metabolite distributions show spatial patterns, which differ for different experimental arrangements. Furthermore, the total output of G6P increases for scenarios where microcompartimentation of enzymes occurs. These results show that spatially resolved models are needed in the description of the conversion processes. Finally, the enzyme stoichiometry on the nano-beads is determined, which maximizes the production of glucose-6-phosphate.

Community-acquired pneumonia in primary care: clinical assessment and the usability of chest radiography.

OBJECTIVES: To investigate the diagnostic value of different clinical and laboratory findings in pneumonia and to explore the association between the doctor's degree of suspicion and chest X-ray (CXR) result and to evaluate whether or not CXR should be used routinely in primary care, when available. DESIGN: A three-year prospective study was conducted between September 2011 and December 2014. SETTING: Two primary care settings in Linköping, Sweden. SUBJECTS: A total of 103 adult patients with suspected pneumonia in primary care. MAIN OUTCOME MEASURES: The physicians recorded results of a standardized medical physical examination, including laboratory results, and rated their suspicion into three degrees. The outcome of the diagnostic variables and the degree of suspicion was compared with the result of CXR. RESULTS: Radiographic pneumonia was reported in 45% of patients. When the physicians were sure of the diagnosis radiographic pneumonia was found in 88% of cases (p < 0.001), when quite sure the frequency of positive CXR was 45%, and when not sure 28%. Elevated levels of C-reactive protein (CRP) ≥ 50mg/L were associated with the presence of radiographic pneumonia when the diagnosis was suspected (p < 0.001). CONCLUSION: This study indicates that CXR can be useful if the physician is not sure of the diagnosis, but when sure one can rely on one's judgement without ordering CXR. KEY POINTS: There are different guidelines but no consensus on how to manage community-acquired pneumonia in primary care. When the physician is sure of the diagnosis the judgement is reliable without chest X-ray and antibiotics can be safely prescribed. Chest X-ray can be useful in the assessment of pneumonia in primary care, when the physician is not sure of the diagnosis.

Technical note: A comparison of reticular and ruminal pH monitored continuously with 2 measurement systems at different weeks of early lactation.

Subacute ruminal acidosis is one of the most important digestive disorders in high-yielding dairy cows fed highly fermentable diets. Monitoring of forestomach pH has been suggested as a potentially valuable tool for diagnosing subacute ruminal acidosis. The objective of the present study was to compare continuously recorded measurements of an indwelling telemetric pH sensor inserted orally in the reticulum with those obtained from a measurement system placed in the ventral sac of the rumen through a cannula. The experiment was conducted with 6 ruminally cannulated Holstein cows kept in a freestall barn. Equal numbers of cows were assigned to 2 treatment groups based on their previous lactation milk yield. Cows in treatment CON- were offered a diet consisting of only fresh herbage cut once daily, and cows in treatment CON+ got fresh herbage plus a concentrate supplement according to the individual milk yield of each cow to meet their predicted nutrient requirements. The experiment lasted from 2 wk before the predicted calving date until wk 8 of lactation. During the whole experiment, a pH value was recorded every 10 min in the reticulum using a wireless telemetry bolus including a pH sensor (eBolus, eCow Ltd., Exeter, Devon, UK), which had been applied orally using a balling gun. Simultaneously, in wk 2, before the estimated calving date and in wk 2, 4, 6, and 8 of lactation, the ruminal pH was measured every 30 s for 48 h with the LRCpH measurement system (Dascor Inc., Escondido, CA) placed in the ventral sac of the rumen through the cannula. The readings of the LRCpH measurement system were summarized as an average over 10 min for statistical analysis. The recorded pH values were on average 0.24 pH units higher in the reticulum than in the rumen. The reticular pH also showed less fluctuation (overall SD 0.19 pH units) than pH profiles recorded in the rumen (overall SD 0.51 pH units). Regardless of measurement system, pH was not influenced by treatment, but varied across week of lactation and decreased with advancing lactation. The difference between ruminal and reticular pH varied across week of lactation. Due to this variation, no fixed conversion factor can be provided to make pH measurements in the reticulum comparable with those in the rumen.

Validation of sun exposure and protection index (SEPI) for estimation of sun habits.

BACKGROUND: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individual's sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). METHOD: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. RESULTS: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearman's Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbach's alpha estimation showed values marginally lower than the desired >0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. CONCLUSIONS: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection.

Near infrared and skin impedance spectroscopy - a possible support in the diagnostic process of skin tumours in primary health care.

BACKGROUND/PURPOSE: The global incidence of skin cancer has increased drastically in recent decades, especially in Australia and Northern Europe. Early detection is crucial for good prognosis and high survival rates. In general, primary care physicians have considerably lower sensitivity and specificity rates for detection of skin cancer, compared to dermatologists. A probable main reason for this is that current diagnostic tools are subjective in nature, and therefore diagnostic skills highly depend on experience. Illustratively, in Sweden, approximately 155 500 benign skin lesions are excised unnecessarily every year. An objective instrument, added to the clinical examination, might improve the diagnostic accuracy, and thus promote earlier detection of malignant skin tumours, as well as reduce medical costs associated with unnecessary biopsies and excisions. The general aim of this study was to investigate the usefulness of the combination of near infrared (NIR) and skin impedance spectroscopy as a supportive tool in the diagnosis and evaluation of skin tumours in primary health care. METHODS: Near infrared and skin impedance data were collected by performing measurements on suspect malignant, premalignant and benign tumours in the skin of patients seeking primary health care for skin tumour evaluation. The obtained data were analysed using multivariate analysis and compared with the diagnosis received by the conventional diagnostic process. RESULTS: The observed sensitivity and specificity rates were both 100%, when discriminating malignant and premalignant skin tumours from benign skin tumours, and the observed sensitivity and specificity for separating malignant skin tumours from premalignant and benign skin tumours were also 100%, respectively. CONCLUSION: The results of this study indicate that the NIR and skin impedance spectroscopy may be a useful supportive tool for the general practitioner in the diagnosis and evaluation of skin tumours in primary health care, as a complement to the visual assessment.