Hypothermia and rewarming times during general anesthesia in Hispaniolan Amazon parrots (Amazona ventralis): A comparative study between isoflurane, sevoflurane and desflurane.

OBJECTIVE: To evaluate induced hypothermia and rewarming times in Hispaniolan Amazon parrots (HAP; Amazona ventralis) anesthetized using isoflurane, sevoflurane or desflurane, and to describe selected cardiovascular and respiratory effects. STUDY DESIGN: Randomized, balanced, crossover experimental study. ANIMALS: A group of 12 adult HAP. METHODS: Parrots were premedicated with intramuscular butorphanol (0.5 mg kg-1) and anesthetized with the three inhalants with a 7 day washout period between events. Anesthesia was induced using isoflurane at 4 vol%, sevoflurane at 6 vol% or desflurane 12 vol% carried in oxygen, delivered via face mask. After orotracheal intubation, anesthesia maintenance was with end-tidal concentrations of 1.4-2% (Fe'Iso), 2.4-3% (Fe'Sevo) and 8.5-9.2% (Fe'Des). Hypothermia was defined as an esophageal temperature (BT) below 37.8 °C. External heat support was provided when BT dropped to 37.5 °C. Time for temperature decrease from 38.9 °C to 37.5 °C (T1), time to first increase in BT above 37.5 °C (T2) and time from external heat support to achieving 38.9 °C (T3) were recorded and compared via Friedman tests with post hoc Dunn's test. Heart rate, respiratory rate and end-tidal carbon dioxide, amongst other variables, were evaluated. RESULTS: All inhalants caused hypothermia (T1): isoflurane, 12 (2-37) minutes [median (range)]; sevoflurane, 12 (4-18) minutes; desflurane, 11.5 (6-24) minutes, with no significant differences between treatments (p > 0.05). T2 was significantly (p = 0.042) longer for sevoflurane than for desflurane but not isoflurane. Transient apnea was observed with all inhalants, including 25% of birds anesthetized with sevoflurane. Second-degree atrioventricular block and ventricular escape beats occurred with all inhalants with hypothermia potentially exacerbating cardiac arrhythmias. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia rapidly developed in butorphanol-sedated HAP anesthetized using isoflurane, sevoflurane or desflurane. Sevoflurane prolonged warming time. Hypothermia may be associated with an increased likelihood of bradyarrhythmia in parrots anesthetized with inhalants.

Development and Testing of the Spinal Cord Injury Bladder and Bowel Control Questionnaire (SCI-BBC-Q).

INTRODUCTION: Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient-reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI-BBC-Q) was developed. METHODS: The SCI-BBC-Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI-BBC-Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. RESULTS: The final 6-item SCI-BBC-Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI-BBC-Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI-BBC-Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. CONCLUSION: The SCI-BBC-Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery.

Multi-Flap Microsurgical Autologous Breast Reconstruction.

Microsurgical autologous breast reconstruction (MABR) remains the gold standard technique of breast reconstruction, providing a durable, natural, and aesthetically pleasing result. However, some patients may not be candidates for a traditional deep inferior epigastric perforator (DIEP) flap, either due to abdominal tissue paucity, the need for higher-volume reconstruction, or prior surgical procedures. In these patients, alternative flaps must be considered to achieve the optimal result. Such configurations include the conjoined (or double pedicle) DIEP flap, and alternative flaps such as the lumbar artery perforator (LAP) and profunda artery perforator (PAP) flaps, which can be combined in a stacked fashion. By combining multiple flaps in a conjoined or stacked fashion, breast reconstruction can be optimized to fulfill the three critical components of breast reconstruction in restoring the skin envelope, breast footprint, and conus shape. When harvesting multiple flaps, the surgical sequence of events must be meticulously planned to ensure an efficient and successful operation. Preoperative imaging can aid the surgeon in identifying the ideal perforator, assess for side branches for possible intra-flap anastomoses, expedite the operative time, and decrease intraoperative complications. Reconstructive surgeons should be familiar with the variety of configurations with conjoined and/or stacked flaps to address patient-specific reconstructive needs.

Mapping threatened Thai bovids provides opportunities for improved conservation outcomes in Asia.

Wild bovids provide important ecosystem functions as seed dispersers and vegetation modifiers. Five wild bovids remain in Thailand: gaur (Bos gaurus), banteng (Bos javanicus), wild water buffalo (Bubalus arnee), mainland serow (Capricornis sumatraensis) and Chinese goral (Naemorhedus griseus). Their populations and habitats have declined substantially and become fragmented by land-use change. We use ecological niche models to quantify how much potential suitable habitat for these species remains within protected areas in Asia and then specifically Thailand. We combined species occurrence data from several sources (e.g. mainly camera traps and direct observation) with environmental variables and species-specific and single, large accessible areas in ensemble models to generate suitability maps, using out-of-sample predictions to validate model performance against new independent data. Gaur, banteng and buffalo models showed reasonable model accuracy throughout the entire distribution (greater than or equal to 62%) and in Thailand (greater than or equal to 80%), whereas serow and goral models performed poorly for the entire distribution and in Thailand, though 5 km movement buffers markedly improved the performance for serow. Large suitable areas were identified in Thailand and India for gaur, Cambodia and Thailand for banteng and India for buffalo. Over 50% of suitable habitat is located outside protected areas, highlighting the need for habitat management and conflict mitigation outside protected areas.

Diversity in stomatal and hydraulic responses to post-flowering drought in common (Phaseolus vulgaris) and tepary (P. acutifolius) beans.

Plants differ widely in how soil drying affects stomatal conductance (gs) and leaf water potential (ψleaf), and in the underlying physiological controls. Efforts to breed crops for drought resilience would benefit from a better understanding of these mechanisms and their diversity. We grew 12 diverse genotypes of common bean (Phaseolus vulgaris L.) and four of tepary bean (P. acutifolius; a highly drought resilient species) in the field under irrigation and post-flowering drought, and quantified responses of gs and ψleaf, and their controls (soil water potential [ψsoil], evaporative demand [Δw] and plant hydraulic conductance [K]). We hypothesised that (i) common beans would be more "isohydric" (i.e., exhibit strong stomatal closure in drought, minimising ψleaf decline) than tepary beans, and that genotypes with larger ψleaf decline (more "anisohydric") would exhibit (ii) smaller increases in Δw, due to less suppression of evaporative cooling by stomatal closure and hence less canopy warming, but (iii) larger K declines due to ψleaf decline. Contrary to our hypotheses, we found that half of the common bean genotypes were similarly anisohydric to most tepary beans; canopy temperature was cooler in isohydric genotypes leading to smaller increases in Δw in drought; and that stomatal closure and K decline were similar in isohydric and anisohydric genotypes. gs and ψleaf were virtually insensitive to drought in one tepary genotype (G40068). Our results highlight the potential importance of non-stomatal mechanisms for leaf cooling, and the variability in drought resilience traits among closely related crop legumes.

Retinal Input to Macaque Superior Colliculus Derives from Branching Axons Projecting to the Lateral Geniculate Nucleus.

The superior colliculus receives a direct projection from retinal ganglion cells. In primates, it remains unknown if the same ganglion cells also supply the lateral geniculate nucleus. To address this issue, a double-label experiment was performed in 2 male macaques. The animals fixated a target while injection sites were scouted in the superior colliculus by recording and stimulating with a tetrode. Once suitable sites were identified, cholera toxin - subunit B Alexa Fluor 488 was injected via an adjacent micropipette. In a subsequent acute experiment, cholera toxin subunit B - Alexa Fluor 555 was injected into the lateral geniculate nucleus at matching retinotopic locations. After a brief survival period, ganglion cells were examined in retinal flatmounts. The percentage of double-labeled cells varied locally, depending on the relative efficiency of retrograde transport by each tracer and the precision of retinotopic overlap of injection sites in each target nucleus. In counting boxes with extensive overlap, 76-98% of ganglion cells projecting to the superior colliculus were double-labeled. Cells projecting to the superior colliculus constituted 4.0 - 6.7% of the labeled ganglion cell population. In one particularly large zone, there were 5,746 cells labeled only by CTB-AF555, 561cells double-labeled by CTB-AF555 and CTB-AF488, but no cell labeled only by CTB-AF488. These data indicate that retinal input to the macaque superior colliculus arises from a collateral axonal branch supplied by about 5% of the ganglion cells that project to the lateral geniculate nucleus. Surprisingly, there exist no ganglion cells that project exclusively to the SC.Significance statement The retina contains a multitude of ganglion cell classes, projecting in parallel to different brain targets. The superior colliculus receives retinal input, but its source remains controversial. In two macaques, a green tracer was injected into the superior colliculus and an orange tracer into the lateral geniculate nucleus. When retinotopic overlap was optimal, ganglion cells containing the green tracer were also labeled by the orange tracer. This finding indicates that retinal input to the superior colliculus arises from axon collaterals of ganglion cells that project to the lateral geniculate nucleus, even though these two retinal targets serve utterly different functions. The next challenge is to determine the purpose of this projection and why it is shared.

Identification of diagnostic candidates in Mendelian disorders using an RNA sequencing-centric approach.

BACKGROUND: RNA sequencing (RNA-seq) is increasingly being used as a complementary tool to DNA sequencing in diagnostics where DNA analysis has been uninformative. RNA-seq enables the identification of aberrant splicing and aberrant gene expression, improving the interpretation of variants of unknown significance (VUSs), and provides the opportunity to scan the transcriptome for aberrant splicing and expression in relevant genes that may be the cause of a patient's phenotype. This work aims to investigate the feasibility of generating new diagnostic candidates in patients without a previously reported VUS using an RNA-seq-centric approach. METHODS: We systematically assessed the transcriptomic profiles of 86 patients with suspected Mendelian disorders, 38 of whom had no candidate sequence variant, using RNA from blood samples. Each VUS was visually inspected to search for splicing abnormalities. Once aberrant splicing was identified in cases with VUS, multiple open-source alternative splicing tools were used to investigate if they would identify what was observed in IGV. Expression outliers were detected using OUTRIDER. Diagnoses in cases without a VUS were explored using two separate strategies. RESULTS: RNA-seq allowed us to assess 71% of VUSs, detecting aberrant splicing in 14/48 patients with a VUS. We identified four new diagnoses by detecting novel aberrant splicing events in patients with no candidate sequence variants from prior DNA testing (n = 32) or where the candidate VUS did not affect splicing (n = 23). An additional diagnosis was made through the detection of skewed X-inactivation. CONCLUSION: This work demonstrates the utility of an RNA-centric approach in identifying novel diagnoses in patients without candidate VUSs. It underscores the utility of blood-based RNA analysis in improving diagnostic yields and highlights optimal approaches for such analyses.

Response to retention hypothesis as a source of targets for arterial wall-directed therapies to prevent atherosclerosis: A critical review.

The subendothelial retention of circulating lipoproteins on extracellular matrix proteins and proteoglycans is one of the earliest events in the development of atherosclerosis. Multiple factors, including the size, type, composition, surrounding pH, and chemical modifications to lipoproteins, influence the electrostatic interactions between relevant moieties of the apolipoproteins on lipoproteins and the glycosaminoglycans of proteoglycans. The length and chemical composition of glycosaminoglycan chains attached to proteoglycan core proteins determine the extent of initial lipoprotein binding and retention in the artery wall. The phenomena of hyperelongation of glycosaminoglycan chains is associated with initial lipid retention and later atherosclerotic plaque formation. This review includes a summary of the current literature surrounding cellular mechanisms leading to GAG chain modification and lipid retention and discusses potential therapeutic strategies to target lipoprotein:proteoglycan interactions to prevent the development and progression of atherosclerosis.

Separable cell cycle arrest and immune response elicited through pharmacological CDK4/6 and MEK inhibition in RASmut disease models.

The combination of CDK4/6 and MEK inhibition as a therapeutic strategy has shown promise in various cancer models, particularly in those harboring RAS mutations. An initial high-throughput drug screen identified a high synergy between the CDK4/6 inhibitor palbociclib and the MEK inhibitor trametinib when used in combination in soft tissue sarcomas. In RAS mutant models, combination treatment with palbociclib and trametinib induced significant G1 cell cycle arrest, resulting in a marked reduction in cell proliferation and growth. CRISPR-mediated RB1 depletion resulted in a decreased response to CDK4/6 and MEK inhibition, which was validated in both cell culture and xenograft models. Beyond its cell cycle inhibitory effects, pathway enrichment analysis revealed the robust activation of interferon pathways upon CDK4/6 and MEK inhibition. This induction of gene expression was associated with the upregulation of retroviral elements. The TBK1(TANK-binding kinase 1) inhibitor GSK8612 selectively blocked the induction of interferon-related genes induced by palbociclib and trametinib treatment, and highlighted the separable epigenetic responses elicited by combined CDK4/6 and MEK inhibition. Together, these findings provide key mechanistic insights into the therapeutic potential of CDK4/6 and MEK inhibition in soft tissue sarcoma.

A Phase I trial of Non-invasive Ventilation and seizure prophylaxis with levetiracetam In Children with Cerebral Malaria Trial (NOVICE-M Trial).

Background: African children with cerebral malaria and seizures caused Plasmodium falciparum are at greater risk of poor outcomes including death and neurological sequelae. The agonal events are severe hypoventilation and respiratory arrest often triggered by seizures. We hypothesised that prophylactic anti-seizure medication (ASM) could avert 'spikes' of intracranial pressure during or following seizures and that adequate ventilation could be supported by biphasic Cuirass Ventilation (BCV) which requires no intubation. Methods: A Phase I trial conducted in Kilifi, Kenya designed to provide data on safety, feasibility and preliminary data on seizure control using prophylactic ASM (levetiracetam) and BCV as non-invasive ventilatory support in children with cerebral malaria. Children aged 3 months to 12-years hospitalised with P falciparum malaria (positive rapid diagnostic test or a malaria slide), a Blantyre Coma Score ≤2 and a history of acute seizures in this illness are eligible for the trial. In a phased evaluation we will study i) BCV alone for respiratory support (n=10); ii) prophylactic LVT: 40mg/kg loading dose then 30mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10) and; iii) prophylactic LVT: 60mg/kg loading dose then 45mg/kg every 12 hours given via nasogastric tube for 72 hours (or until fully conscious) plus BCV support (n=10). Primary outcome measure: cumulative time with a clinically detected seizures or number of observed seizures over 36 hours. Secondary outcomes will be assessed by feasibility or ability to implement BCV, and recovery from coma within 36 hours. Safety endpoints include: aspiration during admission; death at 28 days and 180 days; and de-novo neurological impairments at 180 days. Conclusions: This is a Phase I trial largely designed to test the feasibility, tolerability and safety of using non-invasive ventilatory support and LVT prophylaxis in cerebral malaria. Registration: ISRCTN76942974 (5.02.2019); PACTR202112749708968 (20.12.2021).

Unfortunately, children with cerebral malaria continue to have very poor outcomes including severe hypoventilation and respiratory arrest (i.e. breathing is too slow or stops) during hospitalization which is often triggered by seizures. We will explore the potential benefits of a special type of ventilation that applies suction or negative pressure to the chest (meaning keeping children breathing by pushing air in and out of their lungs) in combination with anticonvulsants given before children have had any fits We will use a device called biphasic Cuirass Ventilation (BCV) that can be used by non-specialists to help children breath. BCV applies both negative and positive pressure to the chest, covering both inspiration (breathing in) and expiration (breathing out) phases of breathing, which is more appropriate for periods of when the breathing is too slow or stops for a period of time. We will also use an anticonvulsant drug, called levetiracetam to prevent seizures. It has been safely used in Malawian children and shown to improve outcomes. This will be given directly into the stomach via a nasogastric tube (tubes down the nose into the stomach) The study will be carried out at Kilifi County Hospital, Kenya and plans to enrol 30 children aged 3 months to 12 years with cerebral malaria and a positive malaria test The first ten children with have the BCV device only to assist respiration until they recover from their coma. The next twenty children in the trial will have the BCV device in addition with anticonvulsants given before children have had any fits as a preventive strategy to stop fits. All children will have regular monitoring during the period of coma/ventilation and will be followed up on days 28 and 180. The study aims to generate feasibility and safety data to support future trials.

Enhancing the Intrinsic Antiplasmodial Activity and Improving the Stability and Selectivity of a Tunable Peptide Scaffold Derived from Human Platelet Factor 4.

The control of malaria, a disease caused by Plasmodium parasites that kills over half a million people every year, is threatened by the continual emergence and spread of drug resistance. Therefore, new molecules with different mechanisms of action are needed in the antimalarial drug development pipeline. Peptides developed from host defense molecules are gaining traction as anti-infectives due to theood of inducing drug resistance. Human platelet factor 4 (PF4) has intrinsic activity against P. falciparum, and a macrocyclic helix-loop-helix peptide derived from its active domain recapitulates this activity. In this study, we used a stepwise approach to optimize first-generation PF4-derived internalization peptides (PDIPs) by producing analogues with substitutions to charged and hydrophobic amino acid residues or with modifications to terminal residues including backbone cyclization. We evaluated the in vitro activity of PDIP analogues against P. falciparum compared to their overall helical structure, resistance to breakdown by serum proteases, selective binding to negatively charged membranes, and hemolytic activity. Next, we combined antiplasmodial potency-enhancing substitutions that retained favorable membrane and cell-selective properties onto the most stable scaffold to produce a backbone cyclic PDIP analogue with four-fold improved activity against P. falciparum compared to first-generation peptides. These studies demonstrate the ability to modify PDIP to select for and combine desirable properties and further validate the suitability of this unique peptide scaffold for developing a new molecule class that is distinct from existing antimalarial drugs.

A Global Dataset of Potential Chloride Deposits on Mars as Identified by TGO CaSSIS.

Chloride deposits are markers for early Mars' aqueous past, with important implications for our understanding of the martian climate and habitability. The Colour and Stereo Surface Imaging System (CaSSIS) onboard ESA's Trace Gas Orbiter provides high-resolution color-infrared images, enabling a planet-wide search for (small) potentially chloride-bearing deposits. Here, we use a neural network to map potentially chloride-bearing deposits in CaSSIS images over a significant fraction of the planet. We identify 965 chloride deposit candidates with diameters ranging from <300 to >3000 m, including previously unknown deposits, 136 (~14%) of which are located in the highlands north of the equator, up to ~36°N. Northern chloride candidates tend to be smaller than in the south and are predominantly located in small-scale topographic depressions in low-albedo Noachian and Hesperian highland terranes. Our new dataset augments existing chloride deposit maps, informs current and future imaging campaigns, and enables future modelling work towards a better understanding of the distribution of near-surface water in Mars' distant past.

Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Fish scale-derived hydroxyapatite for alveolar ridge preservation.

Alveolar ridge resorption following tooth extraction poses significant challenges for future dental restorations. This study investigated the efficacy of fish scale-derived hydroxyapatite (FSHA) as a socket preservation graft material to maintain alveolar bone volume and architecture. FSHA was extracted from *Labeo rohita* fish scales and characterized using Fourier transform infrared (FTIR) analysis. In vitro, biocompatibility and osteogenic potential were assessed using Saos-2 human osteosarcoma cells. Cell viability, migration, and proliferation were evaluated using MTT and scratch assays. In vivo performance was assessed in a rat model, and FSHA was compared to a commercial xenograft (Osseograft) and ungrafted controls. Histological analysis was performed at 8-week post-implantation to quantify new bone formation. FTIR confirmed the purity and homogeneity of FSHA. In vitro, FSHA enhanced Saos-2 viability, migration, and proliferation compared to controls. In vivo, FSHA demonstrated superior bone regeneration compared to Osseograft and ungrafted sites, with balanced graft resorption and new bone formation. Histological analysis revealed an active incorporation of FSHA into new bone, with minimal gaps and ongoing remodeling. Approximately 50%-60% of FSHA was resorbed by 8 weeks, closely matching the rate of new bone deposition. FSHA stimulated more bone formation in the apical socket region than in coronal areas. In conclusion, FSHA is a promising biomaterial for alveolar ridge preservation, exhibiting excellent biocompatibility, osteogenic potential, and balanced resorption. Its ability to promote robust bone regeneration highlights its potential as an effective alternative to currently used graft materials in socket preservation procedures.

Relation between the Dantu blood group variant and bacteraemia in Kenyan children: a population-based case control study.

BACKGROUND: The Dantu blood group variant protects against P. falciparum infections but its wider consequences have not been previously explored. Here, we investigate the impact of Dantu on susceptibility to bacteraemia. METHODS: We conducted a case-control study in children presenting with community-acquired bacteraemia to Kilifi County Hospital in Kenya between 1998 and 2010. We used logistic regression to test for associations between the Dantu marker SNP rs186873296 A>G and both all-cause and pathogen-specific bacteraemia under an additive model. We used date of admission as a proxy measure of malaria transmission intensity, given known differences in malaria prevalence over the course of the study. RESULTS: Dantu was associated with protection from all-cause bacteraemia (OR=0.81, p=0.014), the association being greatest in homozygotes (OR=0.30, p=0.013). This protection was shared across the major bacterial pathogens but, notably, was only significant during the era of high malaria-transmission pre-2003 (OR=0.79, p=0.023). CONCLUSIONS: Consistent with previous studies showing the indirect impact on bacteraemia risk of other malaria-associated red cell variants, our study also shows that Dantu is protective against bacteraemia via its effect on malaria risk. Dantu does not appear to be under balancing selection through an increased risk of bacterial infections.

Reference Interval Creation for Symmetric Dimethylarginine (SDMA) in Healthy Hispaniolan Amazon Parrots (Amazona ventralis) and Quaker Parrots (Myiopsitta monachus).

Renal disease is often identified as a cause of morbidity and mortality in avian patients. However, currently, early antemortem detection of renal disease in avian patients is difficult. Anatomical and physiological differences between mammals and birds mean the use of commonly employed diagnostic testing (ie, measurement of blood urea nitrogen [BUN] and serum creatinine, urinalysis, and ultrasonography) are either nondiagnostic or difficult to achieve. Symmetric dimethylarginine (SDMA) is considered a more sensitive marker for renal disease in humans, dogs, and cats. However, SDMA has not yet been assessed for diagnostic use in any psittacine species. In this study, we establish reference ranges for SDMA in both Hispaniolan Amazon parrots (Amazona ventralis, HAP) and Quaker parrots (Myiopsitta monachus, QP). Blood was collected from 23 Amazon parrots and 32 Quaker parrots maintained in research facilities. Measurement of SDMA through a commercially available immunoassay (IA-SDMA) as well as creatinine, BUN, uric acid, phosphorus, calcium, sodium, potassium, and chloride were determined through IDEXX Laboratories. Plasma SDMA concentrations ranged from 6 to 15 µg/dL and 3 to 15 µg/dL for the HAP and QP, respectively. Sex was a confounding factor for the QP population, but sex did not have a significant effect on SDMA for the HAP population. No significant correlations were identified between SDMA concentrations and other parameters in either psittacine species. Our results show proof of concept for the IA-SDMA and provide reference intervals for SDMA in HAP and QP. Further investigation is required to determine the validity of this assay and the predictive power of SDMA in the detection of renal impairment for parrots and other common companion birds.

Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

Porcine lungs perfused with three different flows using the 8-h open-atrium cellular ex vivo lung perfusion technique.

The number of lung transplantations is limited due to the shortage of donor lungs fulfilling the standard criteria. The ex vivo lung perfusion (EVLP) technique provides the ability of re-evaluating and potentially improving and treating marginal donor lungs. Accordingly, the technique has emerged as an essential tool to increase the much-needed donor lung pool. One of the major EVLP protocols, the Lund protocol, characterized by high pulmonary artery flow (100% of cardiac output [CO]), an open atrium, and a cellular perfusate, has demonstrated encouraging short-EVLP duration results. However, the potential of the longer EVLP duration of the protocol is yet to be investigated, a duration which is considered necessary to rescue more marginal donor lungs in future. This study aimed to achieve stable 8-h EVLP using an open-atrium cellular model with three different pulmonary artery flows in addition to determining the most optimal flow in terms of best lung performance, including lung electrolytes and least lung edema formation, perfusate and tissue inflammation, and histopathological changes, using the porcine model. EVLP was performed using a flow of either 40% (n = 6), 80% (n = 6), or 100% (n = 6) of CO. No flow rate demonstrated stable 8-h EVLP. Stable 2-h EVLP was observed in all three groups. Insignificant deterioration was observed in dynamic compliance, peak airway pressure, and oxygenation between the groups. Pulmonary vascular resistance increased significantly in the 40% group (p < .05). Electrolytes demonstrated an insignificant worsening trend with longer EVLP. Interleukin-8 (IL-8) in perfusate and tissue, wet-to-dry weight ratio, and histopathological changes after EVLP were insignificantly time dependent between the groups. This study demonstrated that stable 8-h EVLP was not feasible in an open-atrium cellular model regardless of the flow of 40%, 80%, or 100% of CO. No flow was superior in terms of lung performance, lung electrolytes changes, least lung edema formation, minimal IL-8 expression in perfusate and tissue, and histopathological changes.

Coping equally: Equity of dyadic coping and depressive symptoms among adolescent couples.

INTRODUCTION: Many adolescents are in their first romantic relationship; at the same time, depressive symptoms generally increase during this developmental stage. In adults, equity of support in romantic relationships is associated with less depressive symptoms-especially in female partners, who are generally on "the losing side" of support transactions with male partners. This study examines whether equity of dyadic coping is associated with depressive symptoms in adolescent mixed-gender couples. We disentangle equity of positive and negative dyadic coping, as differential effects might arise. METHODS: Self-report data on dyadic coping and depressive symptoms were gathered from 124 mixed-gender couples aged between 16 and 21 years living in Switzerland between 2011 and 2013. Equity of dyadic coping was quantified by calculating the difference between received dyadic coping and provided dyadic coping for each partner separately. These difference scores and the overall level of dyadic coping were used to predict depressive symptoms in both partners using an Actor-Partner-Interdependence Model. RESULTS: For female adolescents, we found the expected curvilinear association between equity of negative dyadic coping behaviors and depressive symptoms (actor effect). Additionally, the female perception of equity of positive dyadic coping was correlated with less depressive symptoms in male partners (partner effect). For male adolescents, receiving more positive dyadic coping than they provided was associated with more depressive symptoms (actor effect). DISCUSSION: In female partners, results resembled those in adult mixed-gender couples. In male partners, results changed depending on the direction of inequity-possibly due to gender role development.