Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials

Evaluating the potential of high pressure high temperature and thermal processing on volatile compounds, nutritional and structural properties of orange and yellow carrots

The present study compares the impact of thermal and high pressure high temperature(HPHT) processing on volatile profile (via a non-targeted headspace fingerprinting) and structural and nutritional quality parameter (via targeted approaches) of orange and yellow carrot purees. The effect of oil enrichment was also considered. Since oil enrichment affects compounds volatility, the effect of oil was not studied when comparing the volatile fraction. For the targeted part, as yellow carrot purees were shown to contain a very low amount of carotenoids, focus was given to orange carrot purees. The results of the non-targeted approach demonstrated HPHT processing exerts a distinct effect on the volatile fractions compared to thermal processing. In addition, different colored carrot varieties are characterized by distinct headspace fingerprints. From a structural point of view, limited or no difference could be observed between orange carrot purees treated with HPHT or HT processes, both for samples without and with oil. From nutritional point of view, only in samples with oil, significant isomerisation of all-trans-β-carotene occurred due to both processing. Overall, for this type of product and for the selected conditions, HPHT processing seems to have a different impact on the volatile profile but rather similar impact on the structural and nutritional attributes compared to thermal processing

Enzyme replacement therapy in mice lacking arylsulfatase B targets bone-remodeling cells, but not chondrocytes

Mucopolysaccharidosis type VI (MPS-VI), caused by mutational inactivation of the glycosaminoglycan-degrading enzyme arylsulfatase B (Arsb), is a lysosomal storage disorder primarily affecting the skeleton. We have previously reported that Arsb-deficient mice display high trabecular bone mass and impaired skeletal growth. In the present study, we treated them by weekly injection of recombinant human ARSB (rhARSB) to analyze the impact of enzyme replacement therapy (ERT) on skeletal growth and bone remodeling. We found that all bone-remodeling abnormalities of Arsb-deficient mice were prevented by ERT, whereas chondrocyte defects were not. Likewise, histologic analysis of the surgically removed femoral head from an ERT-treated MPS-VI patient revealed that only chondrocytes were pathologically affected. Remarkably, a side-by-side comparison with other cell types demonstrated that chondrocytes have substantially reduced capacity to endocytose rhARSB, together with low expression of the mannose receptor. We finally took advantage of Arsb-deficient mice to establish quantification of chondroitin sulfation for treatment monitoring. Our data demonstrate that bone-remodeling cell types are accessible to systemically delivered rhARSB, whereas the uptake into chondrocytes is inefficient

Defective complex I assembly due to C20orf7 mutations as a new cause of Leigh syndrome

Background: Leigh syndrome is an early onset, progressive, neurodegenerative disorder with developmental and motor skills regression. Characteristic magnetic resonance imaging abnormalities consist of focal bilateral lesions in the basal ganglia and/or the brainstem. The main cause is a deficiency in oxidative phosphorylation due to mutations in an mtDNA or nuclear oxidative phosphorylation gene. Methods and results: A consanguineous Moroccan family with Leigh syndrome comprise 11 children, three of which are affected. Marker analysis revealed a homozygous region of 11.5 Mb on chromosome 20, containing 111 genes. Eight possible mitochondrial candidate genes were sequenced. Patients were homozygous for an unclassified variant (p.P193L) in the cardiolipin synthase gene (CRLS1). As this variant was present in 20% of a Moroccan control population and enzyme activity was only reduced to 50%, this could not explain the rare clinical phenotype in our family. Patients were also homozygous for an amino acid substitution (p.L159F) in C20orf7, a new complex I assembly factor. Parents were heterozygous and unaffected sibs heterozygous or homozygous wild type. The mutation affects the predicted S-adenosylmethionine (SAM) dependent methyltransferase domain of C20orf7, possibly involved in methylation of NDUFB3 during the assembly process. Blue native gel electrophoresis showed an altered complex I assembly with only 30-40% of mature complex I present in patients and 70-90% in carriers. Conclusions: A new cause of Leigh syndrome can be a defect in early complex I assembly due to C20orf7 mutations

Antimicrobial susceptibility profile of clinically relevant Bacteroides, Phocaeicola, Parabacteroides and Prevotella species, isolated by eight laboratories in the Netherlands

Objectives: Recently, reports on antimicrobial-resistant Bacteroides and Prevotella isolates have increased in the Netherlands. This urged the need for a surveillance study on the antimicrobial susceptibility profile of Bacteroides, Phocaeicola, Parabacteroides and Prevotella isolates consecutively isolated from human clinical specimens at eight different Dutch laboratories. Methods: Each laboratory collected 20–25 Bacteroides (including Phocaeicola and Parabacteroides) and 10–15 Prevotella isolates for 3 months. At the national reference laboratory, the MICs of amoxicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem, metronidazole, clindamycin, tetracycline and moxifloxacin were determined using agar dilution. Isolates with a high MIC of metronidazole or a carbapenem, or harbouring cfiA, were subjected to WGS. Results: Bacteroides thetaiotaomicron/faecis isolates had the highest MIC 90 values, whereas Bacteroides fragilis had the lowest MIC 90 values for amoxicillin/clavulanic acid, piperacillin/tazobactam, meropenem, imipenem and moxifloxacin. The antimicrobial profiles of the different Prevotella species were similar, except for amoxicillin, for which the MIC 50 ranged from 0.125 to 16 mg/L for Prevotella bivia and Prevotella buccae, respectively. Three isolates with high metronidazole MICs were sequenced, of which one Bacteroides thetaiotaomicron isolate harboured a plasmid-located nimE gene and a Prevotella melaninogenica isolate harboured a nimA gene chromosomally. Five Bacteroides isolates harboured a cfiA gene and three had an IS element upstream, resulting in high MICs of carbapenems. The other two isolates harboured no IS element upstream of the cfiA gene and had low MICs of carbapenems. Conclusions: Variations in resistance between species were observed. To combat emerging resistance in anaerobes, monitoring resistance and conducting surveillance are essential.</p

Численный анализ распространения и усиления волн цунами на северо-западном шельфе Черного моря

Выполнен численный анализ распространения длинных волн в северо-западной части Черного моря. Рассмотрено 10 возможных зон сейсмической генерации цунами. Расчеты выполнены на сетке с шагом 500 м. Показано, что положение очага цунами существенно влияет на распределение высот волн вдоль побережья. Как правило, наиболее интенсивные волны формируются у ближайшего участка берега. Землетрясения в Южнобережной сейсмической зоне не могут привести к цунамиопасности в западной части моря. Только сильные землетрясения в северо-западной части способны вызывать заметные колебания уровня Черного моря. Период цунами в районе Одессы составляет около 1 ч и зависит от магнитуды землетрясения, в районе Севастополя он в 2 – 3 раза меньше. В большинстве пунктов побережья экстремальные подъемы и понижения уровня моря не превышают по абсолютной величине начального смещения поверхности моря в очаге цунами. Для отдельных участков побережья Румынии и западного побережья Крыма наблюдается некоторое усиление волн, излученных из зон генерации, расположенных в более глубоководной части исследуемого района. С ростом магнитуды землетрясения усиление волн у берега становится более значительным.Виконаний чисельний аналіз розповсюдження довгих хвиль у північно-західній частині Чорного моря. Розглянуто 10 можливих зон сейсмічної генерації цунамі. Розрахунки виконані на сітці з кроком 500 м. Показано, що положення осередку цунамі суттєво впливає на розподіл висот хвиль уздовж побережжя. Як правило, найінтенсивніші хвилі формуються близько найближчої ділянки берега. Землетруси в південнобережній сейсмічній зоні не можуть призвести до цунамонебезпеки в західній частині моря. Лише сильні землетруси в північнозахідній частині здатні викликати помітні коливання рівня Чорного моря. Період цунамі в районі Одеси складає близько 1 години і залежить від магнітуди землетрусу, в районі Севастополя він в 2 – 3 рази менший. У більшості пунктів побережжя екстремальні підйоми і пониження рівня моря не перевищують за абсолютною величиною початкового зсуву поверхні моря в осередку цунамі. Для окремих ділянок побережжя Румунії і західного побережжя Криму спостерігається деяке посилення хвиль, які випромінюють із зон генерації, розташованих в більш глибоководній частині досліджуваного району. Із зростанням магнітуди землетрусу посилення хвиль біля берега стає значнішим.Numerical analysis of long wave propagation in the Black Sea northwestern part is carried out. Ten possible zones of tsunami seismic generation are considered. The calculation are performed on the grid with a step 500 m. It is shown that location of tsunami source effects essentially the distribution of waves’ heights along the coast. As a rule, the most intensive waves are formed in the part closest to the coast. Earthquakes in the South coast seismic zone can not result in tsunami threat in the western part of the sea. Only strong earthquakes in the Black Sea northwestern part can generate noticeable sea level oscillations. Tsunami period near Odessa is about one hour and it depends on the earthquake magnitude. In the Sevastopol region it is 2 – 3 times lower. In the majority of coastal points extreme rises and falls of the sea level do not exceed the absolute value of the initial sea surface elevation in the tsunami source. Some intensification of the waves generated in deeper regions of the area under study is possible in certain parts of the Romanian coast and the Crimean western coast. The wave intensification near the coast grows with the increase of the earthquake magnitude

Piezo1 Inactivation in Chondrocytes Impairs Trabecular Bone Formation

The skeleton is a dynamic tissue continuously adapting to mechanical stimuli. Although matrix‐embedded osteocytes are considered as the key mechanoresponsive bone cells, all other skeletal cell types are principally exposed to macroenvironmental and microenvironmental mechanical influences that could potentially affect their activities. It was recently reported that Piezo1, one of the two mechanically activated ion channels of the Piezo family, functions as a mechanosensor in osteoblasts and osteocytes. Here we show that Piezo1 additionally plays a critical role in the process of endochondral bone formation. More specifically, by targeted deletion of Piezo1 or Piezo2 in either osteoblast (Runx2Cre) or osteoclast lineage cells (Lyz2Cre), we observed severe osteoporosis with numerous spontaneous fractures specifically in Piezo1Runx2Cre mice. This phenotype developed at an early postnatal stage and primarily affected the formation of the secondary spongiosa. The presumptive Piezo1Runx2Cre osteoblasts in this region displayed an unusual flattened appearance and were positive for type X collagen. Moreover, transcriptome analyses of primary osteoblasts identified an unexpected induction of chondrocyte‐related genes in Piezo1Runx2Cre cultures. Because Runx2 is not only expressed in osteoblast progenitor cells, but also in prehypertrophic chondrocytes, these data suggested that Piezo1 functions in growth plate chondrocytes to ensure trabecular bone formation in the process of endochondral ossification. To confirm this hypothesis, we generated mice with Piezo1 deletion in chondrocytes (Col2a1Cre). These mice essentially recapitulated the phenotype of Piezo1Runx2Cre animals, because they displayed early‐onset osteoporosis with multiple fractures, as well as impaired formation of the secondary spongiosa with abnormal osteoblast morphology. Our data identify a previously unrecognized key function of Piezo1 in endochondral ossification, which, together with its role in bone remodeling, suggests that Piezo1 represents an attractive target for the treatment of skeletal disorders. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Pleiotropic functions of the tumor- and metastasis-suppressing Matrix Metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice

Matrix metalloproteinase-8 (MMP-8; neutrophil collagenase) is an important regulator of innate immunity which has onco-suppressive actions in numerous tumor types