Repeated subcutaneous racemic ketamine in treatment-resistant depression: case series.

Interest in the use of parenteral ketamine has been increasing over the last 2 decades for the management of treatment-resistant depression (TRD). While intravenous (IV) ketamine has been the most common parenteral route of administration, subcutaneous (SC) and intramuscular options have been described. We developed a clinical treatment protocol for the use of repeated SC racemic ketamine (maximum six treatments, twice per week) in an inpatient psychiatric care setting with inclusion/exclusion criteria, dosing schedule, and description of treatment, assessment, and monitoring procedures. Results from the first 10 consecutive patients demonstrated the effectiveness of SC racemic ketamine in relieving symptoms of TRD as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR 16 ). Response (≥50% reduction in scores from baseline to endpoint) was achieved in 8/10 cases on the MADRS and 6/10 on the QIDS-SR 16 . Remission was achieved in 8/10 (based on MADRS ≤10) and 5/10 (based on QIDS-SR 16 ≤6). Patients tolerated the treatments well with only transient blood pressure changes and dissociative side effects. Repeated SC ketamine treatments could be a safe, feasible, and effective alternative to IV ketamine infusions for patients with TRD.

Elliptical and linear relationships with rumen temperature support a homeorhetic trajectory for DMI during recovery of feedlot cattle exposed to moderate heat load.

Most feedlot animals in Australia experience 2 to 3 moderate heat waves during summer. This study aimed to gain understanding of the physiological drivers in response to and during recovery from such events with a view to designing strategies to ensure rapid and safe recovery. Two hypotheses were tested during thermal challenge and recovery in climate-controlled rooms (CCR): firstly, the feedlot steer on a grain-based diet mounts appropriate physiological responses during moderate heat load and in recovery so that its performance and physiology state after recovery is not different to the feed restricted thermoneutral (FRTN) steer. Secondly, commonly used indicators of increased heat load, e.g., respiration rate (RR), panting score (PS), body surface temperatures (ST), and water consumption (WC), reflect rumen temperature (RT) during thermal challenge and recovery at the level of daily means. In this study, 36 Angus steers (live weight (LW) 451.5 ± 22.6 kg) made up 3 cohorts of 12 animals that sequentially underwent the CCR phase. For this 18-d phase, the steers were allocated to either a moderate heat load treatment (thermally challenged, TC, n = 18) or a FRTN treatment (n = 18). The TC group underwent 3 periods, Pre-Challenge (4 d, temperature humidity index (THI) range of 68 to 71), Challenge (7 d, THI 73 to 84 with diurnal cycling), and Recovery (7 d, THI 68 to 71). The FRTN group were held at thermoneutral conditions in the CCR (THI 66.9 ± 0.3), and each animal was offered an amount of feed was based on the feed intake of its LW matched TC pair. Thus, as DMI fell in the TC group during Challenge, feed restriction was imposed on the FRTN group. The data were collected by trained observers were DMI, RT, RR, PS, body STs (forehead, shoulder, leg, rump), and WC. Challenge induced a heat stress response in the TC group with reduced DMI and LW, and elevated RT, RR, PS, body STs, and WC (P < 0.001). These measures were unchanged or reduced in the FRTN group (P < 0.001). At the end of Recovery, the TC and FRTN groups had converged on most measures including LW. Daily mean RT of both groups showed strong linear relationships with THI, RR, PS, head ST, and WC (P ≤ 0.0022) but opposing elliptical relationships with DMI; that is, as DMI fell with increasing RT for the TC group, DMI increased with rising RT for the FRTN group. In all, the feedlot steers in this study demonstrated sufficient homeorhetic capacity to adjust to moderate heat load and recover from it.

Over any summer, most feedlot steers in Australia will encounter 2 to 3 moderate heat waves lasting 5 to 6 d. The ability of these animals to adjust to the hot conditions and recovery from them is not well understood. The advent of obtaining near real-time body (rumen) temperature from feedlot steers has the potential to help feedlot managers, veterinarians and nutritionists make decisions on the handling of feedlots animals during and after heatwaves. Using climate-controlled rooms, this study demonstrated that feedlot steers are physiologically capable of dealing with moderate heatwave conditions. The co-ordinated increases in respiration rate, sweating rate, body surface temperature, and water consumption alongside reduction in feed intake as heat load increases limits the rise in body temperature. By the end of a 7-d recovery period in thermoneutral conditions, the heat stressed steers were not different physiologically and performance-wise from thermoneutral counterparts feeding on a similar amount of food. However, during the recovery period, all animals appeared to be metabolically and physiologically constrained, and did not return to their pre-heatwave feed intake, body temperature or respiration rate. These findings will assist the management of feedlot animals through recovery after a heat wave.

A sparse representation-based method for parcellation of the resting brain and its application to treatment-resistant major depressive disorder.

BACKGROUND: Parcellating brain regions into functionally homogeneous subdivisions is critical for understanding normal and abnormal brain functions. NEW METHOD: In this study, we developed a new sparse representation-based parcellation method for functional magnetic resonance imaging (fMRI) data, and applied the new method to investigate functional insular subdivisions in treatment-resistant major depressive disorder (MDD). Realistic simulations were implemented to demonstrate the feasibility of the method. Subsequently, the method was used to parcellate the insula in a sample of fifty-six MDD patients and thirty-six healthy volunteers (HVs). The optimal number of clusters was determined by an independent test-retest dataset. Finally, differences of the functional connectivity profiles of each insular subdivision between patients and HVs were inspected. RESULTS: The results from both simulated and test-retest fMRI datasets demonstrated the feasibility of the proposed elastic net-based (EN) method. With the proposed method, the insula was parcellated into four subdivisions (dorsal anterior dAI; ventral anterior vAI; middle, MI and posterior, PI). Whereas patients showed hypo-connectivity between vAI and right medial temporal lobe, there were no functional volumetric differences in insular subdivisions between MDD patients and HVs. COMPARISON WITH EXISTING METHOD: Results from both simulated and real fMRI datasets showed that the proposed EN method achieved higher accuracy than least absolute shrinkage and selection operator-based (LASSO) method. CONCLUSIONS: These findings suggest that EN-based parcellation has the potential to be a useful addition to the parcellation techniques for fMRI data, and provide evidence of decreased functional connectivity without functional volumetric changes of the insula in treatment-resistant MDD.

Abnormal functional connectivity within resting-state networks is related to rTMS-based therapy effects of treatment resistant depression: A pilot study.

BACKGROUND: Treatment resistant depression (TRD) remains a clinical challenge, and finding biomarkers that predict treatment response are a long sought goal to precisely indicate treatments. This pilot study aims to characterize brain dysfunction in TRD patients who underwent rTMS to define neuroimaging biomarkers that discriminate non-responders (NR) from responders (R). METHODS: 20 TRD patients who underwent a course of rTMS to the left DLPFC were categorized into R and NR groups based on a >50% reduction in HRSD scores. Utilizing resting-state fMRI and ICA techniques, this study compared baseline RSNs of R vs. NR as well as TRD vs. healthy volunteer group. Regression analysis was conducted to link regions with clinical improvements. ROC analysis was further conducted to confirm the utility of the identified regions in classifying the patients. RESULTS: Prior to treatment, non-responders displayed hyper-connectivity in ACC/VMPFC, PCC/pC, dACC and insula within RSNs that have been associated with MDD pathology. Regression results showed that regions associated with clinical improvements overlapped largely with regions that showed aberrant connectivity. ACC/VMPFC, dACC and left insula, which are hub regions of DMN and SN, exhibited excellent performance (highest sensitivity=100% and highest specificity=82%) in discriminating the response status of the patients. LIMITATIONS: Relatively small sample size. CONCLUSIONS: Our findings provide insight into fMRI predictive measures of treatment response to rTMS treatment, and demonstrate the potential of RSNs-based biomarkers in predicting response to rTMS treatment. Future studies are needed to validate the application of these measures to inform individual treatment indications.

Early changes in Achilles tendon behaviour in vivo following downhill backwards walking.

Downhill backwards walking causes repeated, cyclical loading of the muscle-tendon unit. The effect this type of repeated loading has on the mechanical behaviour of the Achilles tendon is presently unknown. This study aimed to investigate the biomechanical response of the Achilles tendon aponeurosis complex following a downhill backwards walking protocol. Twenty active males (age: 22.3 ± 3.0 years; mass: 74.7 ± 5.6 kg; height: 1.8 ± 0.7 m) performed 60 min of downhill (8.5°), backwards walking on a treadmill at -0.67 m · s(-1). Data were collected before, immediately post, and 24-, 48- and 168-h post-downhill backwards walking. Achilles tendon aponeurosis elongation, strain and stiffness were measured using ultrasonography. Muscle force decreased immediately post-downhill backward walking (P = 0.019). There were increases in Achilles tendon aponeurosis stiffness at 24-h post-downhill backward walking (307 ± 179.6 N · mm(-1), P = 0.004), and decreases in Achilles tendon aponeurosis strain during maximum voluntary contraction at 24 (3.8 ± 1.7%, P = 0.008) and 48 h (3.9 ± 1.8%, P = 0.002) post. Repeated cyclical loading of downhill backwards walking affects the behaviour of the muscle-tendon unit, most likely by altering muscle compliance, and these changes result in tendon stiffness increases.