A blinded, placebo-controlled study on the clinical effects of vitamin E supplementation in dogs with osteoarthritis.

BACKGROUND: Vitamin E has a positive effect in the management of osteoarthritis in humans, and in a previous study of dogs. It has been suggested to decrease C-reactive protein concentrations and liver enzyme activities in humans and animals. OBJECTIVE: To assess the effect of vitamin E supplementation on lameness, pain, pain medication requirement, clinical pathology variables, and quality of life in large-breed dogs with naturally occurring osteoarthritis. ANIMALS: Fifty-seven client-owned dogs with naturally occurring osteoarthritis. METHODS: Dogs received either vitamin E or placebo for 90 days in a randomized, placebo-controlled, double-blinded, prospective clinical trial. Clinical lameness scores, pain medication requirements, and owner questionnaires were used to assess response to treatment every 30 days. Blood samples were collected at enrollment and at the end of the study period. RESULTS: Vitamin E administration did not improve pain, lameness, or quality of life as assessed by owners and veterinarians. Vitamin E supplementation did not decrease the requirement for rescue pain relief. No changes in clinical pathology variables were observed after 90 days of vitamin E supplementation. Body weight was negatively associated with the lameness scores and requirement for rescue pain relief. CONCLUSION: Vitamin E supplementation did not have any observable positive effects in dogs with naturally occurring osteoarthritis.

Diabetes Mellitus and the Kidneys.

The pathomechanisms implicated in diabetic kidney disease in people are present in dogs and cats and, in theory, could lead to renal complications in companion animals with long-standing diabetes mellitus. However, these renal complications develop during a long period, and there is little to no clinical evidence that they could lead to chronic kidney disease in companion animals.

Canine urinary lactate and cortisol metabolites in hypercortisolism, nonadrenal disease, congestive heart failure, and health.

Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function. We aimed to differentiate between HC and NAD via a urinary cortisol metabolites and lactate panel. We prospectively recruited 7 healthy dogs and 18 dogs with HC, 15 with congestive heart failure (CHF), and 9 with NAD. We analyzed urine by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. We normalized urinary lactate and cortisol metabolites to urine creatinine concentration, and then compared groups using a linear-mixed model and principal component (PC) analysis. A machine-learning classification algorithm generated a decision tree (DT) model for predicting HC. The least-squares means of normalized urinary 6ß-hydroxycortisol and PC1 of the HC and CHF groups were higher than those of the healthy and NAD groups (p = 0.05). Creatinine-normalized urinary 6ß-hydroxycortisol had better sensitivity (Se, 0.78; 95% CI: 0.55-0.91), specificity (Sp, 0.89; 95% CI: 0.57-0.99), and a likelihood ratio (LR; 7), than the Se (0.72; 95% CI: 0.49-0.88), Sp (0.89; 95% CI: 0.57-0.99), and LR (6.5) of PC1 for distinguishing HC from NAD. Lactate and dihydrocortisone had the highest decreasing node-weighted impurity value and were considered the most important features in the DT model; dihydrocortisol had no role in determining whether a dog had HC.

Haematological and biochemical reference intervals for wild green turtles (Chelonia mydas): a Bayesian approach for small sample sizes.

Animal health is directly linked to population viability, which may be impacted by anthropogenic disturbances and diseases. Reference intervals (RIs) for haematology and blood biochemistry are essential tools for the assessment of animal health. However, establishing and interpreting robust RIs for threatened species is often challenged by small sample sizes. Bayesian predictive modelling is well suited to sample size limitations, accounting for individual variation and interactions between influencing variables. We aimed to derive baseline RIs for green turtles (Chelonia mydas) across two foraging aggregations in North Queensland, Australia, using Bayesian generalized linear mixed-effects models (n = 97). The predicted RIs were contained within previously published values and had narrower credible intervals. Most analytes did not vary significantly with foraging ground (76%, 22/29), body mass (86%, 25/29) or curved carapace length (83%, 24/29). Length and body mass effects were found for eosinophils, heterophil:lymphocyte ratio, alkaline phosphatase, aspartate transaminase and urea. Significant differences between foraging grounds were found for albumin, cholesterol, potassium, total protein, triglycerides, uric acid and calcium:phosphorus ratio. We provide derived RIs for foraging green turtles, which will be helpful in future population health assessments and conservation efforts. Future RI studies on threatened species would benefit from adapting established veterinary and biomedical standards.

Less is more? Ultra-low carbohydrate diet and working dogs' performance.

New Zealand farm working dogs are supreme athletes that are crucial to agriculture in the region. The effects that low or high dietary carbohydrate (CHO) content might have on their interstitial glucose (IG) and activity during work are unknown. The goals of the study were to determine if the concentration of IG and delta-g (a measurement of activity) will be lower in dogs fed an ultra-low CHO high fat diet in comparison to dogs fed a high CHO low fat diet, and to determine if low concentrations of IG are followed by reduced physical activity. We hypothesized that feeding working farm dogs an ultra-low CHO diet would reduce their IG concentrations which in turn would reduce physical activity during work. We prospectively recruited 22 farm dogs from four farms. At each farm, dogs were randomized to one of two diets and had a month of dietary acclimation to their allocated diet. The macronutrient proportions as a percentage of metabolizable energy (%ME) for the high CHO low fat diet (Diet 1) were 23% protein, 25% fat, and 52% CHO, and for the ultra-low CHO high fat diet (Diet 2) 37% protein, 63% fat, and 1% CHO. Following the acclimation period, we continuously monitored IG concentrations with flash glucose monitoring devices, and delta-g using triaxial accelerometers for 96 h. Dogs fed Diet 2 had a lower area under the curve (±SE) for IG (AUC Diet 2 = 497 ± 4 mmol/L/96h, AUC Diet 1 = 590 ± 3 mmol/L/96h; P = 0.002) but a higher area under the curve (±SE) for delta-g (AUC Diet 2 = 104,122 ± 6,045 delta-g/96h, AUC Diet 1 = 80,904 ± 4,950 delta-g/96h; P< 0.001). Interstitial glucose concentrations increased as the activity level increased (P < 0.001) and were lower for Diet 2 within each activity level (P < 0.001). The overall incidence of low IG readings (< 3.5 mmol/L) was 119/3810 (3.12%), of which 110 (92.4%) readings occurred in the Diet 2 group (P = 0.001). In the Diet 2 group, 99/110 (90%) of the low IG events occurred during the resting period (19:00-06:00). We conclude that feeding Diet 2 (ultra-low CHO high fat diet) to working farm dogs was associated with increased delta-g despite decreased IG concentrations. Interstitial glucose concentrations were positively associated with dogs' activity levels independent of diet. Lastly, events of low IG occurred at a low incidence and were predominantly seen between 19:00-06:00 in dogs fed the ultra-low CHO high fat diet.

One dog's waste is another dog's wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome.

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities' abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera's abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

Videofluoroscopy, CT angiography, and ultrasonography of congenital esophageal stenosis in a Labrador retriever.

A 7-week-old Labrador retriever presented for further investigation into acute onset regurgitation, following weaning from liquid to solid food. A videofluoroscopic swallow study demonstrated a severe, focal esophageal dilation in the mid-cervical region, with marked luminal narrowing distally. Computed tomography with angiography revealed esophageal stenosis, extending from C4-T2, secondary to circumferential esophageal wall thickening. With the concern for development of secondary aspiration pneumonia, the owners elected to euthanize the dog and consented to postmortem examination. A diagnosis of segmental, cervical esophageal muscular hypertrophy was made on necropsy, consistent with the fibromuscular thickening type of congenital esophageal stenosis reported in humans.

An alternative combination therapy with metronidazole, clindamycin and doxycycline for Babesia gibsoni (Asian genotype) in dogs in Hong Kong.

Babesia spp. are globally distributed hemoparasites that cause disease in many mammalian species. The species Babesia gibsoni (Asian genotype) is prevalent and endemic in many Asian countries but has also been reported in growing numbers in countries outside of Asia. Standard therapies for the treatment of B. gibsoni often fail to result in consistent and successful clearance of the organism. This study evaluated the use of a combination of three antibiotics: metronidazole, clindamycin and doxycycline after atovaquone and azithromycin failed to eliminate the infection on a polymerase chain reaction (PCR) test. The aim of this study was to determine whether the triple antibiotic combination was an appropriate alternative or additional treatment for the elimination of B. gibsoni. The medical records of 24 patients treated from December 2012 to July 2015 were retrospectively analyzed. The diagnosis of B. gibsoni was confirmed with a PCR test that was also used to assess treatment response. All patients were initially treated with the standard therapy, atovaquone and azithromycin with a 25% success rate clearing B. gibsoni. Dogs that remained positive on PCR using the standard therapy were then treated with the triple antibiotic protocol achieving an 87% success rate. The inclusion of an alternative and potentially effective protocol for the treatment of B. gibsoni would increase the options for the current therapeutic options, could aid in clearance of the organism and offer a more affordable option for clients.

Role of electrolyte abnormalities and unmeasured anions in the metabolic acid-base abnormalities in dogs with parvoviral enteritis.

BACKGROUND: The strong ion model (SIM) is an alternative paradigm in the characterization of acid-base disturbances particularly in complex disorders. HYPOTHESIS/OBJECTIVES: To compare the acid-base changes in dogs with parvoviral enteritis (PE) using the Henderson-Hasselbalch (HH) approach, with 2 strong ion approaches. ANIMALS: Forty-four dogs with PE, and 16 age-matched control dogs. METHODS: Prospective controlled observational study. Acid-base status was evaluated using the HH model, Fencl-Stewart (FS) approach and a validated strong ion model (VDM). The acid-base changes according to each model were classified and compared. Statistical correlations between pH, CO2 , and various SIM variables were performed, as well as between the sum of effects (SOE) of the SIM and the individual variables comprising the SOE. RESULTS: The HH model identified acid-base disorders in 31/44 cases of which 16/31 were mixed with metabolic acidosis and concurrent respiratory alkalosis the most common (10/31). Using the FS approach, metabolic changes were present 36/42 cases, with changes in free water (FW), chloride, and unmeasured anions (UA) being the most prevalent. Both FW and UA correlated well with pH; however, UA were most consistently abnormal in severe acidemia. Similarly to the HH, the VDM detected acid-base disturbances in 28/44 cases. Major contributors to the acid-base changes were hyponatremia, hypochloremia, and Atot acidosis because of elevated globulins and increased UA. CONCLUSIONS AND CLINICAL IMPORTANCE: Acid-base changes are common and complex in dogs with PE, and were easier to understand using a SIM paradigm. Increases in UA have not been documented in PE in dogs.

Cortisol urinary metabolites in dogs with hypercortisolism, congestive heart failure, and healthy dogs: pilot investigation.

Nonadrenal diseases (NAD), including congestive heart failure (CHF), can affect the conversion of cortisone to cortisol favoring the production of cortisol's urinary downstream metabolites 5α/5ß-tetrahydrocortisol (THF) relative to tetrahydrocortisone (THE). We hypothesized that healthy dogs would have lower urinary levels of cortisol, cortisone, THF, and THE than dogs with hypercortisolism (HC) or CHF, and the latter would have higher urinary levels of THF and lower THE than dogs with HC. Four, 9, and 8 dogs with HC, CHF, and normal health, respectively, were included in a pilot prospective cross-sectional study. A single morning voided urine sample was analyzed for urinary cortisol metabolites by liquid chromatography-mass spectrometry. The percentages of conjugated urinary metabolites were significantly higher in dogs with CHF than in healthy dogs (p = 0.001), and not different in HC dogs (p = 0.07). Log-transformed urine cortisol metabolites-to-creatinine ratios in healthy dogs were significantly lower than the 2 other groups (p < 0.001). The urinary free THE:THF ratio was significantly higher (p < 0.001) than the urinary total and conjugated THE:THF ratios. Health status did not affect the total, conjugated, and free THE:THF ratios (p = 0.61). Additional studies are needed to investigate differences in cortisol metabolites between dogs with HC and NAD to accurately discriminate between the groups.

Association between computed tomographic thoracic injury scores and blood gas and acid-base balance in dogs with blunt thoracic trauma.

OBJECTIVE: To determine the association between thoracic injuries evaluated by computed tomography (CT) and arterial blood gas and acid-base status in dogs with blunt thoracic trauma caused by motor vehicle accidents. DESIGN: Prospective observational clinical study. SETTING: University teaching hospital. ANIMALS: Thirty-one client owned traumatized dogs and 15 healthy dogs. PROCEDURES: All trauma group dogs underwent a CT scan and simultaneous arterial blood gas analysis within 24 hours, but not before 4 hours, after the traumatic incident within a 45-month enrollment period. MEASUREMENTS AND MAIN RESULTS: Thorax injuries were classified as pulmonary, pleural space, or rib cage and each of these components was scored for severity using a CT composite pulmonary, pleural, and rib score. The trauma group arterial blood gas and acid-base status were evaluated for statistical difference from the control group. The pulmonary-arterial oxygen pressure was significantly lower in the trauma group compared to the control group that was supported by significant differences in the calculated variables of arterial blood oxygenation as well. There was also a significant correlation between the composite lung score and pleural score and the variables of arterial oxygen status. The pulmonary-arterial carbon dioxide pressure was not significantly different to any of the thoracic injury variables indicating normal alveolar ventilation. Acid-base imbalances were generally mild, insignificant, and variable. CONCLUSIONS AND CLINICAL RELEVANCE: Blunt thoracic trauma causes significant pulmonary and pleural injury and the blood oxygen economy is significantly affected by this. The functional measures of arterial blood oxygenation were well correlated with thoracic CT pathology. Alveolar ventilation was mostly spared but a clinically significant ventilation perfusion mismatch was present.

The Site of Bone Marrow Acquisition Affects the Myeloid to Erythroid Ratio in Apparently Healthy Dogs.

Bone marrow (BM) cytology and histopathology are complementary tools used to investigate hematological diseases. The purpose of this study was to determine if there are site-dependent differences in the diagnostic quality, myeloid to erythroid ratio (MER), and discordant findings in samples from different sites in the same dog. Eighteen apparently healthy dogs were used in the study. The sequence of sample acquisition was randomized according to a Latin square, and samples for BM cytology and histology were collected from both humeri and both ilial crests immediately after death. Board-certified clinical and anatomical pathologists read the cytology and histology, respectively. The data were analyzed using a mixed-effect model. The site of BM acquisition did not affect BM sample quality. The rate of discordant clinical findings between sites was 0.05 (95% confidence interval, 0.01-0.13). In general, by cytology, the MERs were slightly but significantly greater in samples from the ilial crests than from the humeri ( P = .01). The measured MER for histology was nearly twice that for cytology for all sites ( P < .001). In conclusion, there was a low-rate, site-dependent discordance in diagnostic findings in BM samples and differences in MER between the ilial crest and the humerus. A similar study is justified in sick dogs with hematological disease to determine the effect of sampling site on discordant findings between sites.

Medical and surgical management of gallbladder sludge and mucocoele development in a Miniature Schnauzer.

The factors enhancing mucocoele development in dogs remain poorly understood. A 7-year-old female spayed Miniature Schnauzer was presented to the Massey University Veterinary Teaching Hospital for progressive lethargy, inappetance and abdominal discomfort. Initial physical examination findings revealed a moderate degree of cranial abdominal pain, with subsequent diagnostic tests confirming the patient as having diabetes mellitus, with a concurrent marked hypertriglyceridaemia. In an attempt to localise the source of pain, an ultrasound examination of the abdomen was performed, revealing a marked degree of gallbladder sludge. With appropriate medical management including ursodeoxycholic acid and insulin therapy, the patient stabilised and was discharged. With persistence of clinical signs three months later, progression of the gallbladder sludge towards mucocoele development was suspected. Exploratory laparotomy was instigated, and an emergency cholecystectomy was performed. This case report therefore entails a suspected gallbladder mucocoele that developed in a diabetic patient with previously diagnosed biliary sludge. A unique feature of this case report is the presence of diabetes mellitus, which has been suggested to be a causative factor in the development of gallbladder mucocoeles. It is also hypothesised that gallbladder sludge and mucocoeles are associated, however it is yet to be ascertained whether this association is causal or contributory. The authors examined the possible relationship between this endocrinopathy and biliary sludge, and their possible effects on mucocoele development. Specific associated factors to sludge formation are also examined. The medical and surgical management of gallbladder mucocoeles is discussed.

The central role of chloride in the metabolic acid-base changes in canine parvoviral enteritis.

The acid-base disturbances in canine parvoviral (CPV) enteritis are not well described. In addition, the mechanisms causing these perturbations have not been fully elucidated. The purpose of the present study was to assess acid-base changes in puppies suffering from CPV enteritis, using a modified strong ion model (SIM). The hypothesis of the study was that severe acid-base disturbances would be present and that the SIM would provide insights into pathological mechanisms, which have not been fully appreciated by the Henderson-Hasselbalch model. The study analysed retrospective data, obtained from 42 puppies with confirmed CPV enteritis and 10 healthy control dogs. The CPV-enteritis group had been allocated a clinical score, to allow classification of the data according to clinical severity. The effects of changes in free water, chloride, l-lactate, albumin and phosphate were calculated, using a modification of the base excess algorithm. When the data were summated for each patient, and correlated to each individual component, the most important contributor to the metabolic acid-base changes, according to the SIM, was chloride (P<0.001). Severely-affected animals tended to demonstrate hypochloraemic alkalosis, whereas mildly-affected puppies had a hyperchloraemic acidosis (P=0.007). In conclusion, the acid-base disturbances in CPV enteritis are multifactorial and complex, with the SIM providing information in terms of the origin of these changes.

Advances in the understanding of the pathogenesis, progression and diagnosis of myxomatous mitral valve disease in dogs.

A number of key questions remain unanswered in the pathogenesis of myxomatous mitral valve disease (MMVD). As MMVD typically afflicts small-breed dogs, a genetic basis has been implied. In addition, the fact that not all dogs within a risk group develop MMVDis still unexplained. Research into the pathogenesis of MMVD typically falls under three categorical divisions, namely genetic factors, mechanical factors of the valve and systemic factors. Genetic studies have implicated certain loci in the pathogenesis of MMVD. Of particular interest is the insulin-like growth factor (IGF)-1 locus, as IGF-1 is also associated with growth. The mechanical structure and function of the mitral valve have also received much attention in recent years. What has emerged is the notion of a highly complex dynamic structure, which has an uneven distribution of stress and strain according to the flow of blood. Research efforts have also identified a number of systemic factors such as cytokines and signalling pathways that may contribute to the failure of the valve. Serotonin remains an area of interest in this field. Taken together, the amalgamation of research efforts in these three areas will go a long way towards resolving the understanding of this disease.Another area of focus in MMVD has been the development of clinical tests to diagnose the onset of congestive heart failure. To this end, echocardiographic indices and biochemical markers have been investigated. Echocardiographic indices such as left atrial to aortic ratio and the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) have been identified as specific risk factors to predict progression. Advanced imaging studies such as cardiac magnetic resonance imaging have enabled investigators to determine the earliest remodelling changes that occur in MMVD.

Haemangiosarcoma of the os penis in a dog: The most common neoplasm of the canine penis.

A castrated 9-year-old intact male boerboel cross-breed dog was presented with a month-long history of stranguria. On physical examination, a mass was noted at the caudal extremity of the os penis. Haematology, serum chemistry and urinalysis were all unremarkable. Abdominal and urethral ultrasound demonstrated an enlarged bladder and a dilated urethra, which was followed to the caudal extremity of the os penis. A hyperechoic, roughly spherical,vascularised mass was noted at the caudal os penis, which resulted in obstruction of the penile urethra. Radiographs demonstrated a soft tissue mass with osteolysis of the os penis. Cytology suggested an osteosarcoma. Treatment included amputation of the penis and adjuvant doxorubicin with carboplatin. Histopathology of the penis confirmed a haemangiosarcoma. The patient survived for 20 months. This is only the second published case report describing a penile haemangiosarcoma, and the first published report demonstrating the treatment and outcome of a case of haemangiosarcoma of the os penis. Based on published and unpublished reports, haemangiosarcoma appears to be the most common neoplasm of the canine penis.

Advances in the understanding of the pathogenesis, progression and diagnosis of myxomatous mitral valve disease in dogs.

A number of key questions remain unanswered in the pathogenesis of myxomatous mitralvalve disease (MMVD). As MMVD typically afflicts small-breed dogs, a genetic basis hasbeen implied. In addition, the fact that not all dogs within a risk group develop MMVDis still unexplained. Research into the pathogenesis of MMVD typically falls under threecategorical divisions, namely genetic factors, mechanical factors of the valve and systemicfactors. Genetic studies have implicated certain loci in the pathogenesis of MMVD. Ofparticular interest is the insulin-like growth factor (IGF)-1 locus, as IGF-1 is also associatedwith growth. The mechanical structure and function of the mitral valve have also receivedmuch attention in recent years. What has emerged is the notion of a highly complex dynamicstructure, which has an uneven distribution of stress and strain according to the flow ofblood. Research efforts have also identified a number of systemic factors such as cytokinesand signalling pathways that may contribute to the failure of the valve. Serotonin remainsan area of interest in this field. Taken together, the amalgamation of research efforts inthese three areas will go a long way towards resolving the understanding of this disease.Another area of focus in MMVD has been the development of clinical tests to diagnose theonset of congestive heart failure. To this end, echocardiographic indices and biochemicalmarkers have been investigated. Echocardiographic indices such as left atrial to aortic ratioand the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) have beenidentified as specific risk factors to predict progression. Advanced imaging studies such ascardiac magnetic resonance imaging have enabled investigators to determine the earliestremodelling changes that occur in MMVD.

Medical management of myxomatous mitral valve disease: An evidence-based veterinary medicine approach.

Myxomatous mitral valve disease (MMVD) is the most common heart disease of dogs. The current management of MMVD in dogs is mostly pharmacological, and the recommendations for treatment are based on a number of veterinary studies. Notwithstanding the current consensus regarding the medical management of MMVD, there remains active debate as to which drugs are the most effective. In order to understand how recommendations are constructed in the pharmacological management of diseases, the veterinarian needs to understand the concept of evidence-based veterinary medicine, and how the findings of these studies can be applied in their own practices. This review summarises the current veterinary literature and explains how the consensus regarding the management of MMVD has been reached. This review highlights the limitations of veterinary studies in order to provide veterinary practitioners with a sense of the difficulty there is in establishing the benefit of one treatment over the other. Veterinarians should therefore apply treatment recommendations based on the best evidence, integrated with a pathomechanistic understanding of the disease process and clinical experience.

Insights into metal borohydride and aluminohydride bonding: X-ray and neutron diffraction structures and a DFT and charge density study of [Na(15-crown-5)][EH(4)] (E = B, Al).

The neutron and X-ray structures of [Na(15-crown-5)][BH(4)] and [Na(15-crown-5)][AlH(4)], respectively, are reported, along with a topological analysis of their DFT-computed charge densities that explores the bonding between the anionic complex hydride [EH(4)](-) (E = B, Al) and the counterion [Na(15-crown-5)](+). In each case, the interaction is weak and mainly electrostatic in nature; however, notable differences are observed in the manner in which [BH(4)](-) and [AlH(4)](-) bind to the metal, which explains their different coordination modes. A range of unconventional E-H···H-C contacts is revealed to play an important role in the overall bonding and crystal packing of both complexes. These interactions can be classified as weak dihydrogen bonds based on the atoms in molecules approach.