Experimental ischemia–reperfusion: biases and myths—the proximal vs. distal hypoxic tubular injury debate revisited

Although the understanding of processes associated with hypoxic tubular cell injury has remarkably improved, controversies remain regarding the appropriateness of various animal models to the human syndrome of acute kidney injury (AKI). We herein compare available experimental models of hypoxic acute kidney damage, which differ both conceptually and morphologically in the distribution of tubular cell injury. Tubular segment types differ in their capacity to mount hypoxia-adaptive responses, mediated by hypoxia-inducible factors (HIFs), and in cell type–specific molecules shed into the urine, which may serve as early biomarkers for renal damage. These differences may be of value in the perception of the human AKI, its detection, and prevention

Deterministic Identification Over Multiple-Access Channels

Deterministic identification over K-input multiple-access channels with average input cost constraints is considered. The capacity region for deterministic identification is determined for an average-error criterion, where arbitrarily large codes are achievable. For a maximal-error criterion, upper and lower bounds on the capacity region are derived. The bounds coincide if all average partial point-to-point channels are injective under the input constraint, i.e. all inputs at one terminal are mapped to distinct output distributions, if averaged over the inputs at all other terminals. The achievability is proved by treating the MAC as an arbitrarily varying channel with average state constraints. For injective average channels, the capacity region is a hyperrectangle. The modulo-2 and modulo-3 binary adder MAC are presented as examples of channels which are injective under suitable input constraints. The binary multiplier MAC is presented as an example of a non-injective channel, where the achievable identification rate region still includes the Shannon capacity region.Comment: ISIT 2023 versio

Why Is Diabetes Mellitus a Risk Factor for Contrast-Induced Nephropathy?

Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media. The pathophysiology of this vulnerability is complex and involves various mechanisms, including a priori enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. The regulation of vascular tone and peritubular blood flow may also be altered, particularly due to defective nitrovasodilation, enhanced endothelin production, and a particular hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro- and macrovascular diseases and chronic tubulointerstitial changes further compromise regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these susceptible patients

Responsiveness of domesticated goats towards various stressors following long-term cognitive test exposure.

Current evidence suggests that frequent exposure to situations in which captive animals can solve cognitive tasks may have positive effects on stress responsiveness and thus on welfare. However, confounding factors often hamper the interpretation of study results. In this study, we used human-presented object-choice tests (in form of visual discrimination and reversal learning tests and a cognitive test battery), to assess the effect of long-term cognitive stimulation (44 sessions over 4-5 months) on behavioural and cardiac responses of female domestic goats in subsequent stress tests. To disentangle whether cognitive stimulation per se or the reward associated with the human-animal interaction required for testing was affecting the stress responsiveness, we conditioned three treatment groups: goats that were isolated for participation in human-presented cognitive tests and rewarded with food ('Cognitive', COG treatment), goats that were isolated as for the test exposure and rewarded with food by the experimenter without being administered the object-choice tests ('Positive', POS treatment), and goats that were isolated in the same test room but neither received a reward nor were administered the tests ('Isolation', ISO treatment). All treatment groups were subsequently tested in four stress tests: a novel arena test, a novel object test, a novel human test, and a weighing test in which goats had to enter and exit a scale cage. All treatment groups weretested at the same two research sites, each using two selection lines, namely dwarf goats, not selected for production traits, and dairy goats, selected for high productivity. Analysing the data with principal component analysis and linear mixed-effects models, we did not find evidence that cognitive testing per se (COG-POS contrast) reduces stress responsiveness of goats in subsequent stress tests. However, for dwarf goats but not for dairy goats, we found support for an effect of reward-associated human-animal interactions (POS-ISO contrast) at least for some stress test measures. Our results highlight the need to consider ontogenetic and genetic variation when assessing stress responsiveness and when interacting with goats

A new animal model for delayed osseous union secondary to osteitis

Background: The treatment of infection-related delayed bone unions is still very challenging for the orthopedic surgeon. The prevalence of such infection-related types of osteitis is high in complex fractures, particularly in open fractures with extensive soft-tissue damage. The aim of this study was to develop a new animal model for delayed union due to osteitis. Methods. After randomization to infected or non-infected groups 20 Sprague–Dawley rats underwent a transverse fracture of the midshaft tibia. After intramedullary inoculation with staphylococcus aureus (103 CFU) fracture stabilization was done by intramedullary titanium K-wires. After 5 weeks all rats were euthanized and underwent biomechanical testing to evaluate bone consolidation or delayed union, respectively. Micro-CT scans were additionally used to quantitatively evaluate the callus formation by the score of Lane and Sandhu. Blood samples were taken to analyze infectious disease markers (day 1, 14 and 35). Results: Biomechanical testing showed a significant higher maximum torque in the non-infected group 5 weeks postoperatively compared with the infected group (p < 0.001). According to the Lane and Sandhu score a significantly higher callus formation was found in the non-infected group (p < 0.001). Similarly, the leucocyte count in the infected group was significantly higher than in the non-infected group (p < 0.05). Conclusions: Here we have established a new animal model for delayed osseous union secondary to osteitis. The animal model appears to be appropriate for future experimental studies to test new therapeutic strategies in these difficult to treat bone healing complications

Microresonator solitons for massively parallel coherent optical communications

Optical solitons are waveforms that preserve their shape while propagating, relying on a balance of dispersion and nonlinearity. Soliton-based data transmission schemes were investigated in the 1980s, promising to overcome the limitations imposed by dispersion of optical fibers. These approaches, however, were eventually abandoned in favor of wavelength-division multiplexing (WDM) schemes that are easier to implement and offer improved scalability to higher data rates. Here, we show that solitons may experience a comeback in optical communications, this time not as a competitor, but as a key element of massively parallel WDM. Instead of encoding data on the soliton itself, we exploit continuously circulating dissipative Kerr solitons (DKS) in a microresonator. DKS are generated in an integrated silicon nitride microresonator by four-photon interactions mediated by Kerr nonlinearity, leading to low-noise, spectrally smooth and broadband optical frequency combs. In our experiments, we use two interleaved soliton Kerr combs to transmit a data stream of more than 50Tbit/s on a total of 179 individual optical carriers that span the entire telecommunication C and L bands. Equally important, we demonstrate coherent detection of a WDM data stream by using a pair of microresonator Kerr soliton combs - one as a multi-wavelength light source at the transmitter, and another one as a corresponding local oscillator (LO) at the receiver. This approach exploits the scalability advantages of microresonator soliton comb sources for massively parallel optical communications both at the transmitter and receiver side. Taken together, the results prove the significant potential of these sources to replace arrays of continuous-wave lasers in high-speed communications.Comment: 10 pages, 3 figure

The neuronal guidance protein netrin-1 reduces alveolar inflammation in a porcine model of acute lung injury

Introduction: Acute lung injury (ALI) is an inflammatory disorder of pulmonary or extrapulmonary origin. We have previously demonstrated that netrin-1 dampens murine ALI, and in an attempt to advance this finding into future clinical practice we evaluated whether netrin-1 would reduce alveolar inflammation during porcine ALI. Methods: This was a controlled in vivo experimental study in pigs. We induced ALI through lipoploysaccharide (LPS) infusion (50 micro g/kg) for 2 hours. Following this, we exposed animals to either vehicle, intravenous netrin-1 (netrin-1 i.v.) or inhaled netrin-1 (netrin-1 inh.). Serum samples and bronchoalveolar lavage (BAL) were obtained to determine levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, interleukin-6 and interleukin-8 at baseline and 6 hours following treatment. Myeloperoxidase activity (MPO) and protein levels were determined in the BAL, and tissue samples were obtained for histological evaluation. Finally, animals were scanned with spiral CT. Results: Following LPS infusion, animals developed acute pulmonary injury. Serum levels of TNF-alpha and IL-6 were significantly reduced in the netrin-1 i.v. group. BAL demonstrated significantly reduced cytokine levels 6 hours post-netrin-1 treatment (TNF-alpha: vehicle 633 ± 172 pg/ml, netrin-1 i.v. 84 ± 5 pg/ml, netrin-1 inh. 168 ± 74 pg/ml; both P < 0.05). MPO activity and protein content were significantly reduced in BAL samples from netrin-1-treated animals. Histological sections confirmed reduced inflammatory changes in the netrin-1-treated animals. Computed tomography corroborated reduced pulmonary damage in both netrin-1-treated groups. Conclusions: We conclude that treatment with the endogenous anti-inflammatory protein netrin-1 reduces pulmonary inflammation during the initial stages of ALI and should be pursued as a future therapeutic option