Catecholamines for inflammatory shock: a Jekyll-and-Hyde conundrum

Catecholamines are endogenous neurosignalling mediators and hormones. They are integral in maintaining homeostasis by promptly responding to any stressor. Their synthetic equivalents are the current mainstay of treatment in shock states to counteract myocardial depression and/or vasoplegia. These phenomena are related in large part to decreased adrenoreceptor sensitivity and altered adrenergic signalling, with resultant vascular and cardiomyocyte hyporeactivity. Catecholamines are predominantly used in supraphysiological doses to overcome these pathological consequences. However, these adrenergic agents cause direct organ damage and have multiple ‘off-target’ biological effects on immune, metabolic and coagulation pathways, most of which are not monitored or recognised at the bedside. Such detrimental consequences may contribute negatively to patient outcomes. This review explores the schizophrenic ‘Jekyll-and-Hyde’ characteristics of catecholamines in critical illness, as they are both necessary for survival yet detrimental in excess. This article covers catecholamine physiology, the pleiotropic effects of catecholamines on various body systems and pathways, and potential alternatives for haemodynamic support and adrenergic modulation in the critically ill

McKean–Vlasov limit for interacting systems with simultaneous jumps

Motivated by several applications, including neuronal models, we consider the McKean–Vlasov limit for a general class of mean-field systems of interacting diffusions characterized by an interaction via simultaneous jumps. We focus our interest on systems where the rate of the jumps is unbounded, which are rarely treated in the mean-field literature, and we prove well-posedness of the McKean–Vlasov limit together with propagation of chaos via a coupling technique. To highlight the role of simultaneous jumps, we introduce an intermediate process which is close to the original particle system but does not display simultaneous jumps. This shows in particular that the simultaneous jumps contribute to the overall rate of convergence of the N-particle empirical measures by a term of order 1/√N

Strong existence and uniqueness of the stationary distribution for a stochastic inviscid dyadic model

We consider an inviscid stochastically forced dyadic model, where the additive noise acts only on the first component. We prove that a strong solution for this problem exists and is unique by means of uniform energy estimates. Moreover, we exploit these results to establish strong existence and uniqueness of the stationary distribution

Planar bone scintigraphy and CT findings in dogs with forelimb lameness

Scintigraphy has been used for many years in veterinary medicine, due to its high sensitivity, for the localization of lameness of unknown origin in horses and for the assessment of thyroid/skeletal neoplasia in dogs. In the last few years bone scintigraphy (BS) has become increasingly used in dogs for the localization of occult lameness, when clinical examination and radiographic exam are inconclusive [1]. This study describes BS and computed tomographic (CT) findings in dogs referred for monolateral forelimb obscure lameness, for which a precise localization had not been found by clinical examination nor radiographic exam (no abnormalities at all, mild radiological abnormalities which could not be related to the grade of lameness or symmetrical bilateral alterations). Eight dogs matched inclusion criteria: 3 mixed breed, 1 Bernese mountain dog, 1 Amstaff, 1 Labrador retriever, 1 Australian shepherd and 1 Boxer. BS images showed intense IRU (Increased Radiopharmaceutical Uptake) of elbow joint in 6 cases; these findings coincided to CT alterations of proximal ulna in 5 dogs (mostly located in the medial coronoid process - MCP region: bone density alterations, evidence of fragmentation, new bone formation). In one of these cases, an intense IRU was observed in correspondence of the region of the flexors attachment, with no concurrent abnormalities on CT examination. These findings were suggestive of an obscure form of flexor enthesopathy. In one case we observed diffuse and intense IRU of the carpus joint; this coincided with arthrosis and the presence of a subchondral cyst. One dog showed only mild IRU of the elbow joint, not compatible with the degree of lameness. Because of lack of significant IRU, CT and MRI examination were performed and revealed the presence of an expansive lesion in correspondence of the brachial plexus roots compatible with PNST (Peripheral Nerve Sheath Tumor). BS' high sensitivity allowed the localization of the lameness thanks to the assessment of functional bone state, as already stated in literature [2]. However, its low specificity required additional imaging (CT, MRI), targeted on the region identified on scintigraphic examination. In our experience, the combined use of functional and morphologic diagnostic imaging techniques (bone scintigraphy and computed tomography- magnetic resonance) has been helpful to reach a definitive diagnosis. Further studies, with an increased sample size, are needed to evaluate whether there is a correlation between bone density changes and grade of IRU in limbs affected by different pathologies

Cervical cystic lymphangioma in a young dog: CT findings

Lymphangioma is a rare lymphatic disorder; in veterinary medicine it is still considered a benign tumour, while in human medicine has been recently classified as a Lymphatic Malformation (LM), in fact it probably origins from a failure in development of connections between lympatic and venous system. Reported localizations of canine lymphangioma include skin, subcutaneous and fascial tissue of axilla, limbs, inguinal and mammary regions; lymph nodes; retroperitoneal space; nasopharynx. In the present report we describe the computed tomographic (CT) features of a cervical cystic lymphangioma in a young dog. A 1-year-old intact male Italian Shepherd dog was referred to the primary care veterinarian with a 1-month history of left ventrolateral neck swelling. No other clinical signs were present. Ultrasonographic (US) examination revealed a mass with hyperechoic thick wall, hypoechoic content with hyperechoic fluctuating areas. Fine needle aspiration biopsy (FNAB) revealed a cloudy pinkish fluid, citologically referable to serous-hematic fluid with chronic inflamation. For better assessment of the morphology and of the margins of the lesion, the dog was referred for CT examination. Pre- and post-contrast CT scan of head, neck and thorax were made. A mass located between the muscles of the caudal neck and thoracic/axillary regions (from the level of C4 to the level of T2) was found, which partially occupied the left visceral space of the neck and bulged into the thoracic inlet. The mass was ellipsoid-shaped (40x45x140 mm), with well-defined margins and heterogeneous soft tissue attenuation. It was apparently capsulated, with fluid-like content and soft tissue attenuating septa and small areas within the fluid. Adjacent to the mass three areas of soft tissue mineralization, smoothly marginated, were found. It was responsible for mild mass effect, without significant compression on the surrounding structures. Mild left axillary and left medial retropharyngeal lymphadenomegaly was noted, with normal shape and attenuation of the limph nodes. Post-contrast images showed moderate enhancement of the mass wall and the soft-tissue-attenuating areas/septa within it; no enhancement of the fluid was noted. No other abnormalities were found. The mass was completely surgically excised and submitted for histopathologic analysis, with a definitive diagnosis of cystic lymphangioma. In human literature CT features of lymphangioma are widely described, while in veterinary literature there are no reports about its CT appearance; moreover, human lymphangioma is described as preferentially located in the neck and axillary regions, while, to our knowledge, cervical localization has never been reported before for canine lymphangioma

Large deviations for Markov jump processes with uniformly diminishing rates

We prove a large-deviation principle (LDP) for the sample paths of jump Markov processes in the small noise limit when, possibly, all the jump rates vanish uniformly, but slowly enough, in a region of the state space. We further discuss the optimality of our assumptions on the decay of the jump rates. As a direct application of this work we relax the assumptions needed for the application of LDPs to, e.g., Chemical Reaction Network dynamics, where vanishing reaction rates arise naturally particularly the context of mass action kinetics

Drug resistance in B and non-B subtypes amongst subjects recently diagnosed as primary/recent or chronic HIV-infected over the period 2013–2016: Impact on susceptibility to first-line strategies including integrase strand-transfer inhibitors

Objectives To characterize the prevalence of transmitted drug resistance mutations (TDRMs) by plasma analysis of 750 patients at the time of HIV diagnosis from January 1, 2013 to November 16, 2016 in the Veneto region (Italy), where all drugs included in the recommended first line therapies were prescribed, included integrase strand transfer inhibitors (InNSTI). Methods TDRMs were defined according to the Stanford HIV database algorithm. Results Subtype B was the most prevalent HIV clade (67.3%). A total of 92 patients (12.3%) were expected to be resistant to one drug at least, most with a single class mutation (60/68–88.2% in subtype B infected subjectsand 23/24–95.8% in non-B subjects) and affecting mainly NNRTIs. No significant differences were observed between the prevalence rates of TDRMs involving one or more drugs, except for the presence of E138A quite only in patients with B subtype and other NNRTI in subjects with non-B infection. The diagnosis of primary/recent infection was made in 73 patients (9.7%): they had almost only TDRMs involving a single class. Resistance to InSTI was studied in 484 subjects (53 with primary-recent infection), one patient had 143C in 2016, a total of thirteen 157Q mutations were detected (only one in primary/recent infection). Conclusions Only one major InSTI-TDRM was identified but monitoring of TDRMs should continue in the light of continuing presence of NNRTI-related mutation amongst newly diagnosed subjects, sometime impacting also to modern NNRTI drugs recommended in first-line therapy

Pollen morphology of alpine butterworts (Pinguicula L., Lentibulariaceae)

The pollen morphology of Pinguicula alpina, P. arvetii, P. grandiflora subsp. grandiflora, P. grandiflora subsp. rosea, P. hirtiflora, P. leptoceras, P. poldinii, P. reichenbachiana, and P. vulgaris, belonging to the Alpine flora, was studied. The pollen grains, coming from different populations, were investigated using light microscopy and scanning electron microscopy. The pollen size, the shape (P/E ratio), the number of colpori and the exine ornamentation are, for Pinguicula, important diagnostic characters. Pinguicula pollen grains are medium sized ( 30 \u3bcm), trinucleate, isopolar, radially symmetric. The shape of the grains is variable from oblate spheroidal to prolate spheroidal and they are (4)\u20135\u20139\u2013(10)-zonocolporate. The prevalent ornamentation is rugulate\u2013microreticulate, P. alpina has a rugulate\u2013reticulate ornamentation and only P. hirtiflora has a perforate ornamentation. A pollen key, based on micromorphological data, is presented

Evaluation of Androgen Receptor in Relation to Estrogen Receptor (AR/ER) and Progesterone Receptor (AR/PgR): A New Must in Breast Cancer?

Steroid nuclear receptors are known to be involved in the regulation of epithelial-mesenchymal transition process with important roles in invasion and metastasis initiation. Androgen receptor (AR) has been extensively studied, but its role in relation to breast cancer patient prognosis remains to be clarified. AR/ER ratio has been reported to be an unfavorable prognostic marker in early primary breast cancer, but its role in the patients with advanced disease has to be cleared. We retrospectively analyzed ER, PgR, and AR expression on a case series of 159 specimens of primary BC samples by using immunohistochemistry and 89 patients of these had luminal tumors for which AR and ER expression and survival data were available. For twenty-four patients both primary and metastatic tumors were available. A significantly shorter overall survival was observed in primary tumors with AR/PgR ratio 65 1.54 (HR = 2.27; 95% CI 1.30-3.97; p = 0.004). Similarly OS was significantly shorter when ER/PgR ratio 652 in primary tumors (HR = 1.89; 95% CI 1.10-3.24; p = 0.021). The analysis of the 24 patients who had biomarker determinations both in primary tumors and metastasis showed a better OS when AR/ER ratio in the metastasis was 65 0.90 (p = 0.022). Patients with a high AR/ER ratio in primary tumor that remained high in the metastasis had better prognosis in terms of OS (p = 0.011). Despite we suggested that the ratios AR/ER and AR/PgR could be used to identify patients with different prognosis, their real value needs to be better clarified in different BC settings through prospective studies