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Bovine respiratory disease (BRD) represents a significant challenge in cattle management due to its multifactorial nature and lack of a gold standard diagnostic method. Procalcitonin (PCT) has emerged as a potential biomarker for bacterial infections in various species, including cattle. This study aimed to investigate plasma PCT concentration variations in pre-weaned dairy calves categorized as BRD-positive using clinical scores (WRSC; BRD-positive ≥5), thoracic ultrasonography with two cut-off (TUS; BRD-positive ≥1 or ≥3), or a combination of both methods (WRSC/TUS1cm or WRSC/TUS3cm). Additionally, the accuracy of PCT in diagnosing BRD was evaluated. A cross-sectional study was conducted on a convenience sample of 226 pre-weaned Italian-Friesian female calves. Clinical scoring, TUS, and plasma PCT analysis were performed. Calves were categorized based on TUS findings, clinical scores, or a combination of both methods. Statistical analyses were conducted to assess the differences in PCT concentrations among different groups and to determine the diagnostic accuracy of PCT. Results showed a significant increase in PCT levels in calves with lung consolidation detected by TUS using a 1 cm cutoff. However, the diagnostic accuracy of PCT in discriminating BRD-positive cases was poor (area under the curve 0.62). The optimal cutoff value for PCT was determined to be 86.63 pg/mL, with sensitivity of 49.7%, specificity of 71.8%, positive predictive value of 79.4% and negative predictive value of 39.5%. In conclusion, while PCT showed potential as a biomarker for BRD, its diagnostic accuracy was limited in this study. Future research should focus on integrating PCT measurements with other diagnostic methods and conducting longitudinal cohort studies to better understand its role in BRD diagnosis and management.

Abstract Background Bronchopneumonia (BP) in calves potentially causes systemic changes. Objectives To describe metabolic, arterial blood gas, and acid‐base disorders in calves with BP diagnosed by thoracic ultrasound (TUS), Wisconsin score (WISC), and combinations of WISC and TUS. Animals Two hundred thirty‐one dairy preweaned dairy calves from 13 dairy farms. Methods Cross‐sectional study. Each calf sequentially underwent arterial blood gas evaluation, WISC score, venous sampling, and TUS. Calves were grouped based on a single diagnostic method and combination of WISC and 2 TUS cutoffs (≥1 cm; ≥3 cm) as healthy, upper respiratory tract infection, subclinical BP, and clinical BP. Results Oxygenation and acid‐base variables were unaffected. Glucose concentration in TUS‐affected calves was significantly lower (P

Low-frequency air–bone gap (ABG) associated with pulsatile tinnitus (PT) and normal impedance audiometry represents a common finding in patients with third window syndromes. Other inner disorders, including Meniere’s disease (MD), perilymphatic fistula and intralabyrinthine schwannoma, might sometimes result in a similar scenario. On the other hand, PT is frequently associated with dural arteriovenous fistula (DAVF), while conductive hearing loss (CHL) is extremely rare in this clinical setting. A 47-year-old patient was referred to our center with progressive left-sided PT alongside ipsilateral fullness and hearing loss. She also experienced headache and dizziness. Otoscopy and video-oculographic examination were unremarkable. Conversely, a detailed instrumental audio-vestibular assessment revealed low-frequency CHL with normal impedance audiometry, slight left-sided caloric weakness, slightly impaired vestibular-evoked myogenic potentials on the left and normal results on the video-head impulse test, consistent with an MD-like instrumental profile. Gadolinium-enhanced brain MRI revealed an early enhancement of the left transverse sinus, consistent with a left DAVF between the left occipital artery and the transverse sinus, which was then confirmed by angiography. A trans-arterial embolization with Onyx glue was performed, resulting in a complete recession of the symptoms. Post-operatively, the low-frequency ABG disappeared, supporting the possible role of venous intracranial hypertension and abnormal pressure of inner ear fluids in the onset of symptoms and offering new insights into the pathomechanism of inner ear CHL.

Abstract Background Although thoracic auscultation (AUSC) in calves is quick and easy to perform, the definition of lung sounds is highly variable and leads to poor to moderate accuracy in diagnosing bronchopneumonia (BP). Hypothesis/Objectives Evaluate the diagnostic accuracy of an AUSC scoring system based on a standard lung sound nomenclature at different cut‐off values, accounting for the absence of a gold standard test for BP diagnosis. Animals Three hundred thirty‐one calves. Methods We considered the following pathological lung sounds: increased breath sounds (score 1), wheezes and crackles (score 2), increased bronchial sounds (score 3), and pleural friction rubs (score 4). Thoracic auscultation was categorized as AUSC1 (positive calves for scores ≥1), AUSC2 (positive calves for scores ≥2), and AUSC3 (positive calves for scores ≥3). The accuracy of AUSC categorizations was determined using 3 imperfect diagnostic tests with a Bayesian latent class model and sensitivity analysis (informative vs weakly informative vs noninformative priors and with vs without covariance between ultrasound and clinical scoring). Results Based on the priors used, the sensitivity (95% Bayesian confidence interval [BCI]) of AUSC1 ranged from 0.89 (0.80‐0.97) to 0.95 (0.86‐0.99), with a specificity (95% BCI) of 0.54 (0.45‐0.71) to 0.60 (0.47‐0.94). Removing increased breath sounds from the categorizations resulted in increased specificity (ranging between 0.97 [0.93‐0.99] and 0.98 [0.94‐0.99] for AUSC3) at the cost of decreased sensitivity (0.66 [0.54‐0.78] to 0.81 [0.65‐0.97]). Conclusions and Clinical Importance A standardized definition of lung sounds improved AUSC accuracy for BP diagnosis in calves.

A systemic and collaborative approach is required to facilitate European Small and Medium-sized Enterprises’ ecological and digital transition, able to frame issues within the complexity of the relationships and interconnections that characterise them. In light of this, the paper aims to investigate how the approach and methods of Systemic Design support an ‘open innovation’ process in industrial and interdisciplinary environments. The DigiCirc European project represents the reference case study, offering a space to test the challenges found in the literature with data collected in the field, emphasising the contribution made by the researchers in Systemic Design of the Politecnico di Torino, both as project partners in the ‘open innovation’ process and through activities supporting the start-ups and SMEs involved. The article is mainly geared toward scholars and design practitioners concerned with ‘open innovation’, and ecological and digital transition within socio-technical systems and in industrial and interdisciplinary environments. Article info Received: 20/03/2023; Revised: 29/04/2023; Accepted: 08/05/2023

(1) Background: Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is characterized by late-onset cerebellar ataxia, bilateral vestibulopathy, and sensory neuronopathy mostly due to biallelic RFC1 expansion. (2) Objectives: The aim of this case series is to describe vestibular, gait, and speech alterations in CANVAS via a systematic approach. (3) Methods: All patients (n = 5) underwent a standardized clinical–instrumental examination, including the perceptual and acoustic analysis of speech, instrumental gait, and balance analysis (posturographic data were acquired using a force plate [Kistler, Winterthur, Switzerland] while 3D gait analysis, inclusive of surface electromyography, was acquired using a motion capture system [SMART DX, BTS Bioengineering, Milan, Italy], a wireless electromyograph [FreeEMG, BTS Bioengineering, Milan, Italy]), and vestibular assessment with video-oculography. (4) Results: Five patients were included in the analysis: three females (patients A, B, C) and two males (patients D and E) with a mean age at evaluation of 62 years (SD ± 15.16, range 36–74). The mean age of symptoms’ onset was 55.6 years (SD ± 15.04, range 30–68), and patients were clinically and instrumentally evaluated with a mean disease duration of 6.4 years (SD ± 0.54, range 6–7). Video-Frenzel examination documented spontaneous downbeat nystagmus enhanced on bilateral gaze in all patients, except for one presenting with slight downbeat nystagmus in the supine position. All patients exhibited different degrees of symmetrically reduced VOR gain for allsix semicircular canals on the video-head impulse test and an unexpectedly normal (“false negative”) VOR suppression, consistent with combined cerebellar dysfunction and bilateral vestibular loss. Posturographic indices were outside their age-matched normative ranges in all patients, while 3D gait analysis highlighted a reduction in ankle dorsiflexion (limited forward rotation of the tibia over the stance foot during the stance phase of gait and fatigue of the dorsiflexor muscles) and variable out-of-phase activity of plantar flexors during the swing phase. Finally, perceptual-acoustic evaluation of speech showed ataxic dysarthria in three patients. Dysdiadochokinesis, rhythm instability, and irregularity were observed in the oral diadochokinesis task. (5) Conclusions: CANVAS is a recently discovered syndrome that is gaining more and more relevance within late-onset ataxias. In this paper, we aimed to contribute to a detailed description of its phenotype.

Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

High concentrations of urinary calcium counteract vasopressin action via the activation of the Calcium‐Sensing Receptor (CaSR) expressed in the luminal membrane of the collecting duct cells, which impairs the trafficking of aquaporin‐2 (AQP2). In line with these findings, we provide evidence that, with respect to wild‐type mice, CaSR knock‐in (KI) mice mimicking autosomal dominant hypocalcaemia, display a significant decrease in the total content of AQP2 associated with significantly higher levels of AQP2 phosphorylation at Ser261, a phosphorylation site involved in AQP2 degradation. Interestingly, KI mice also had significantly higher levels of phosphorylated p38MAPK, a downstream effector of CaSR and known to phosphorylate AQP2 at Ser261. Moreover, ATF1 phosphorylated at Ser63, a transcription factor downstream of p38MAPK, was significantly higher in KI. In addition, KI mice had significantly higher levels of AQP2‐targeting miRNA137 consistent with a post‐transcriptional downregulation of AQP2. In vivo treatment of KI mice with the calcilytic JTT‐305, a CaSR antagonist, increased AQP2 expression and reduced AQP2‐targeting miRNA137 levels in KI mice. Together, these results provide direct evidence for a critical role of CaSR in impairing both short‐term vasopressin response by increasing AQP2‐pS261, as well as AQP2 abundance, via the p38MAPK‐ATF1‐miR137 pathway. Key points: Calcium‐Sensing Receptor (CaSR) activating mutations are the main cause of autosomal dominant hypocalcaemia (ADH) characterized by inappropriate renal calcium excretion leading to hypocalcaemia and hypercalciuria. Current treatments of ADH patients with parathyroid hormone, although improving hypocalcaemia, do not improve hypercalciuria or nephrocalcinosis.In vivo treatment with calcilytic JTT‐305/MK‐5442 ameliorates most of the ADH phenotypes of the CaSR knock‐in mice including hypercalciuria or nephrocalcinosis and reverses the downregulation of the vasopressin‐sensitive aquaporin‐2 (AQP2) expression, providing direct evidence for a critical role of CaSR in impairing vasopressin response.The beneficial effect of calcilytic in reducing the risk of renal calcification may occur in a parathyroid hormone‐independent action through vasopressin‐dependent inhibition of cAMP synthesis in the thick ascending limb and in the collecting duct.The amelioration of most of the abnormalities in calcium metabolism including hypercalciuria, renal calcification, and AQP2‐mediated osmotic water reabsorption makes calcilytic a good candidate as a novel therapeutic agent for ADH. [ABSTRACT FROM AUTHOR]

Exposure to actual or simulated microgravity results in alterations of renal function, fluid redistribution, and bone loss, which is coupled to a rise of urinary calcium excretion. We provided evidence that high calcium delivery to the collecting duct reduces local Aquaporin 2 (AQP2)-mediated water reabsorption under vasopressin action, thus limiting the maximal urinary concentration to reduce calcium saturation. To investigate early renal adaptation into simulated microgravity, we investigated the effects of 10 days of strict bedrest in 10 healthy volunteers. We report here that 10 days of inactivity are associated with a transient, significant decrease (day 5) in vasopressin (copeptin) paralleled by a decrease in AQP2 excretion, consistent with an increased central volume to the heart, resulting in reduced water reabsorption. Moreover, bedrest caused a significant increase in calciuria secondary to bone demineralization paralleled by a decrease in PTH. Urinary osteopontin, a glycoprotein exerting a protective effect on stone formation, was significantly reduced during bedrest. Moreover, a significant increase in adrenomedullin (day 5), a peptide with vasodepressor properties, was observed at day 5, which may contribute to the known reduced orthostatic capacity post-bedrest. We conclude that renal function is altered in simulated microgravity and is associated with an early increase in the risk of stone formation and reduced orthostatic capacity post-bedrest within a few days of inactivity.

Asthma is a chronic inflammatory disorder of the airways that manifests as wheezing, shortness of breath, chest tightness, and coughing. Among the evaluation tools there is a new method, namely Impulse Oscillometry or IOS. It is a simple and non-invasive technique, based on the measurement of sound waves reflected by the resistance of the airways. The IOS machine produces and transmits small pulses of pressure along the tracheobronchial tree and records changes in pressure and flow to the mouth. A prospective study was conducted on 55 asthmatic patients assessed by IOS at time 0 and 3 months after initiation of inhaled corticosteroid (ICS) or ICS/LABA therapy, which demonstrated the value of IOS as a method of evaluation of the clinical response of the treatment implemented in the asthmatic patient. [ABSTRACT FROM AUTHOR]