Observations of Rogue Seas in the Southern Ocean.

We report direct observations of surface waves from a stereo camera system along with concurrent measurements of wind speed during an expedition across the Southern Ocean in the austral winter aboard the South African icebreaker S.A. Agulhas II. Records include water surface elevation across a range of wave conditions spanning from early stages of wave growth to full development. We give experimental evidence of rogue seas, i.e., sea states characterized by heavy tails of the probability density function well beyond the expectation based on bound mode theory. These conditions emerge during wave growth, where strong wind forcing and high nonlinearity drive wave dynamics. Quasiresonance wave-wave interactions, which are known to sustain the generation of large amplitude rogue waves, capture this behavior. Wave statistics return to normality as the wind forcing ceases and waves switch to a full developed condition.

Association of peri-operative prescription of non-steroidal anti-inflammatory drugs with continued prescription of opioids after total knee arthroplasty: a retrospective claims-based cohort study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the mainstays of multimodal pain management. While effective for acute pain control, recent pre-clinical evidence has raised concerns regarding an association between NSAIDs and chronic pain and potential opioid use. Our objective was to explore the association between peri-operative use of prescription NSAIDs and the need for continued opioid prescriptions lasting 90-180 days in previously opioid-naïve patients undergoing total knee arthroplasty. A database of health claims in the USA was used to identify all opioid-naïve adult patients who underwent primary knee arthroplasty between January 2010 and October 2021. We evaluated the magnitude of association between peri-operative prescription NSAID claims and claims for opioids at 90 days postoperatively using multivariable logistic regression models. Secondary outcomes included: the magnitude of association between peri-operative NSAID prescription and claims for opioids at 180 days postoperatively; and identifying other potential factors associated with opioid claims at 90 days postoperatively. After risk adjustment using multivariable logistic regression models in the 789,736-patient cohort, the adjusted odds ratio (95%CI) for a continuous claim of opioids at 90 and 180 days postoperatively among patients with a peri-operative NSAID prescription within 30 days was 1.32 (1.30-1.35), p < 0.001; and 1.12 (1.10-1.15), p < 0.001, respectively. This estimate of effect remained robust at 90 days after accounting for known potential confounders, including pre-existing knee pain and acute postoperative pain severity. Similar analysis of other pain medications (e.g. paracetamol) did not detect such an association. This population-based cohort study suggests that peri-operative prescription NSAID use may be associated with continued opioid prescription claims at 90 and 180 days after knee arthroplasty, even after adjusting for other observed covariates for continuous opioid claims. These novel findings can inform clinical decision-making for post-surgical pain management, risk-benefit discussions with patients and future research.

Evaluation of a Hyperbaric Oxygen Therapy Intervention in Individuals with Fibromyalgia.

OBJECTIVE: To evaluate the feasibility and safety of hyperbaric oxygen therapy (HBOT) in patients with fibromyalgia (FM). DESIGN: A cohort study with a delayed treatment arm used as a comparator. SETTING: Hyperbaric Medicine Unit, Toronto General Hospital, Ontario, Canada. SUBJECTS: Eighteen patients diagnosed with FM according to the American College of Rheumatology and a score ≥60 on the Revised Fibromyalgia Impact Questionnaire. METHODS: Participants were randomized to receive immediate HBOT intervention (n = 9) or HBOT after a 12-week waiting period (n = 9). HBOT was delivered at 100% oxygen at 2.0 atmospheres per session, 5 days per week, for 8 weeks. Safety was evaluated by the frequency and severity of adverse effects reported by patients. Feasibility was assessed by recruitment, retention, and HBOT compliance rates. Both groups were assessed at baseline, after HBOT intervention, and at 3 months' follow-up. Validated assessment tools were used to evaluate pain, psychological variables, fatigue, and sleep quality. RESULTS: A total of 17 patients completed the study. One patient withdrew after randomization. HBOT-related adverse events included mild middle-ear barotrauma in three patients and new-onset myopia in four patients. The efficacy of HBOT was evident in most of the outcomes in both groups. This improvement was sustained at 3-month follow-up assessment. CONCLUSION: HBOT appears to be feasible and safe for individuals with FM. It is also associated with improved global functioning, reduced symptoms of anxiety and depression, and improved quality of sleep that was sustained at 3-month follow-up assessment.

Effect of bovine feeding system (pasture or concentrate) on the oxidative and sensory shelf life of whole milk powder.

Correlating volatile compounds with the sensory attributes of whole milk powder (WMP) is fundamental for appreciating the effect of lipid oxidation (LO) on sensory perception. LO compounds can adversely affect the sensory perception of WMP by imparting rancid, metallic, and painty notes. Whole milk powders derived from milk produced by cows maintained on a pasture diet (grass and grass-clover mix) versus a nonpasture diet [total mixed ration (TMR); concentrates and silage] were stored at room temperature 21°C (ambient storage) and 37°C (accelerated storage) and analyzed for volatile compounds and sensory attributes every 2 mo for a total of 6 mo. Thirteen volatile compounds originating from LO were chosen to track the volatile profile of the WMP during storage. Color, composition, total fatty acid, and free fatty acid profiling were also carried out. Significant variations in the concentrations of 14 fatty acids were observed in WMP based on diet. Concentrations of free fatty acids increased in all sample types during storage. Similar trends in sensory attributes were observed with an increase in painty attributes, corresponding to an increase in hexanal. Buttery/toffee attributes were found to be more closely correlated with TMR WMP. Those WMP derived from pasture diets were found to be more susceptible to LO from a volatile perspective, particularly in relation to aldehyde development, which is likely due to increased concentrations of conjugated linoleic acid and α-linolenic acid found in these samples.

An Irish National Diabetes in Pregnancy Audit: aiming for best outcomes for women with diabetes.

AIMS: The purpose of this study was to identify the number of pregnancies affected by pre-gestational diabetes in the Republic of Ireland; to report on pregnancy outcomes and to identify areas for improvement in care delivery and clinical outcomes. METHODS: Healthcare professionals caring for women with pre-gestational diabetes during pregnancy were invited to participate in this retrospective study. Data pertaining to 185 pregnancies in women attending 15 antenatal centres nationally were collected and analysed. Included pregnancies had an estimated date of delivery between 1 January and 31 December 2015. RESULTS: The cohort consisted of 122 (65.9%) women with Type 1 diabetes and 56 (30.3%) women with Type 2 diabetes. The remaining 7 (3.8%) pregnancies were to women with maturity-onset diabetes of the young (MODY) (n = 6) and post-transplant diabetes (n = 1). Overall women were poorly prepared for pregnancy and lapses in specific areas of service delivery including pre-pregnancy care and retinal screening were identified. The majority of pregnancies 156 (84.3%) resulted in a live birth. A total of 103 (65.5%) women had a caesarean delivery and 58 (36.9%) infants were large for gestational age. CONCLUSIONS: This audit identifies clear areas for improvement in delivery of care for women with diabetes in the Republic of Ireland before and during pregnancy.

Ultrastructure and intercellular contact-mediated communication in cultured human early stage follicles exposed to mTORC1 inhibitor.

The reproductive lifespan of a woman is determined by the gradual recruitment of quiescent follicles into the growing pool. In humans, ovarian tissue removal from its in vivo environment induces spontaneous activation of resting follicles. Similarly, pharmacological activation of the PI3K/Akt pathway leads to accelerated follicle recruitment, but has been associated with follicular damage. Recent findings demonstrate that everolimus (EVE), an mTORC1 inhibitor, limits primordial follicle activation. However, its potential benefit regarding growing follicle integrity remains unexplored. Ovarian cortical fragments were exposed to ± EVE for 24 h and cultured for an additional 5 days. After 0, 1 and 6 days of culture, fragments were either processed for ultrastructural analysis or subjected to follicular isolation for gene expression and immunofluorescence assessments. Data from transmission electron microscopy showed that growing follicles displayed similar ultrastructural features irrespective of the conditions and maintained close contacts between germinal and stromal compartments. Establishment of intra-follicular communication was confirmed by detection of a gap junction component, Cx43, in both groups throughout culture, whereas transzonal projections, which physically link granulosa cells to oocyte, formed later in EVE-treated follicles. Importantly, levels of GJA1 mRNA, encoding for the Cx43 protein, significantly increased from Day 0 to Day 1 in the EVE group, but not in the control group. Given that EVE-treated follicles were smaller than controls, these findings suggest that EVE might facilitate the establishment of appropriate intercellular communications without impairing follicle ultrastructure. Therefore, mTORC1 inhibitors might represent an attractive tool to delay the culture-induced primordial follicle activation while maintaining follicles in a functionally integrated state.

Predictors of Post-operative Pain and Opioid Consumption in Patients Undergoing Liver Surgery.

BACKGROUND: Post-operative pain management is a critical component of perioperative care. Patients at risk of poorly controlled post-operative pain may benefit from early measures to optimize pain management. We sought to identify risk factors for post-operative pain and opioid consumption in patients undergoing liver resection. METHODS: This is a multi-institutional prospective nested cohort study of patients undergoing open liver resection. Opioid consumption and pain scores were collected following surgery. To estimate the effects of patient factors on opioid consumption (oral morphine equivalents-OME) and on pain scores (NRS-11), we used generalized linear models and multivariable linear regression model, respectively. RESULTS: One hundred and fifty-three patients who underwent open liver resection between 2013 and 2016 were included in the study. The mean patient age was 62.2 years, and 43.3% were female. Younger patients were significantly more likely to use more opioids in the early post-operative period (16.7 OME/10 years, p < 0.001). Patient factors that were significantly associated with increased NRS-11 pain scores also included younger patient age (difference in pain score of 0.3/10 years with cough and 0.2/10 years at rest, p < 0.01 for both) as well as a history of analgesic use (difference in pain score of 0.9 with cough and 0.6 at rest, p < 0.01 and p = 0.07, respectively). CONCLUSION: Younger patients and those with a history of analgesic use are more likely to report higher post-operative pain and require higher doses of opioids. Early identification of these patients, and measures to better manage their pain, may contribute to optimal perioperative care.

Both in vivo FSH depletion and follicular exposure to Gonadotrophin-releasing hormone analogues in vitro are not effective to prevent follicular depletion during chemotherapy in mice.

STUDY QUESTION: Does fertility preservation using gonadotrophin-releasing hormone (GnRH) analogues during chemotherapy act through a direct effect on the ovary or through inhibition of FSH secretion? SUMMARY ANSWER: The absence of FSH in vivo and the direct exposition of ovarian follicles to GnRH analogues in vitro did not prevent chemotherapy-induced ovarian damage. WHAT IS KNOWN ALREADY: The potential mechanisms of action of GnRH analogues in protecting ovaries against chemotherapy damage remain poorly understood. We previously showed that GnRH analogues have a limited inhibitory effect on gonadotropin secretion and follicular growth in mice. STUDY DESIGN SIZE, DURATION: Mouse models were developed to independently evaluate (i) the indirect effect of FSH depletion on chemotherapy-induced ovarian damage using Fshb-deficient (-/-) mice to mimic the profound inhibition of FSH secretion during GnRH analogues treatment and (ii) the direct in vitro effect of GnRH agonist and antagonist in follicles exposed to chemotherapy using a follicular culture system. PARTICIPANTS/MATERIALS, SETTING, METHODS: To assess the indirect effect of GnRH analogues through FSH inhibition, Fshb-/- mice were treated with 1 IU pregnant mare serum gonadotropin (control group) or saline (study group) for 7 days and with cyclophosphamide (200 mg/kg) on Day 5. Ovaries were collected 48 h post-cyclophosphamide to evaluate ovarian reserve, cellular apoptosis and proliferation. To evaluate the direct effects of GnRH analogues on growing follicles, isolated preantral follicles from prepubertal mice were cultured in vitro for 13 days with 1 µM GnRH analogues and 20 µM of 4-hydroperoxycyclophosphamide or not at Day 4. Oocytes were matured by adding epidermal growth factor (EGF)/hCG on Day 12. Follicular development, follicular survival, oocyte maturation rates, cAMP production, and steroidogenesis were evaluated. To assess the direct GnRH analogues effects on follicular reserve, whole neonatal ovaries were cultured in vitro under the same conditions for 2 days. Ovaries were processed 24 h post-chemotherapy for ovarian reserve, cellular apoptosis and proliferation analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Cyclophosphamide induced a significant follicular loss of more than 50% in Fshb-/- mice regardless of previous treatment with gonadotropins and no difference was observed in cell proliferation or apoptosis. In vitro experiments on growing follicles showed that 4-hydroperoxycyclophosphamide significantly decreased preantral follicle survival and maturation rates (55% and 37%, respectively) and delayed follicular development, regardless of the presence of GnRH analogues. Chemotherapy reduced granulosa cell numbers in all groups, while no change in cAMP production/106 granulosa cells was observed. Similarly, 4-hydroperoxycyclophosphamide induced apoptosis and significant follicular loss in cultured neonatal ovaries irrespective of GnRH analogues exposure. LIMITATIONS REASONS FOR CAUTION: As ovarian GnRH receptors expression differs in humans and mice, further studies are needed to validate our results in human ovaries. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate that ovarian damage occurred even in the absence of FSH, suggesting that inhibition of the pituitary-gonadal axis is not involved in ovarian protection during GnRH analogues treatment. Using in vitro models, no evidence for direct protective effect of GnRH analogues against cyclophosphamide metabolite damage was observed. At present, clinical efficiency of GnRH analogues to prevent chemotherapy-induced ovarian damage remains highly debated and these experimental results reinforced the question as they did not bring evidence of direct or indirect mechanisms of protection. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by the Belgian FNRS, 'Le Fonds Emile DEFAY', and 'La Fondation Rose et Jean Hoguet'. Authors have no conflict of interest to declare.

Protection of Pea Aphids Associated with Coinfecting Bacterial Symbionts Persists During Superparasitism by a Braconid Wasp.

Bacterial endosymbionts that associate facultatively with insect herbivores can influence insect fitness and trophic interactions. The pea aphid, Acyrthosiphon pisum, can be protected from parasitism by the braconid wasp Aphidius ervi when harbouring particular symbiotic bacteria, with specific endosymbiont coinfections providing almost complete protection. However, studies often quantify aphid mummification with no control over parasitoid oviposition per aphid; thus, if mummy production fails or is low, the causes are often unclear. Here, we show that the high level of protection associated with the coinfecting endosymbionts Hamiltonella defensa and X-type is maintained even when pea aphids are superparasitised. This contrasts strongly with the protection provided by H. defensa alone, which has been shown by others to be overcome by superparasitism. By dissecting aphids exposed to two parasitoid attacks, we reveal that A. ervi deposits eggs equally freely in endosymbiont-infected and uninfected nymphs, and lack of mummification in endosymbiont-protected nymphs arises from failure of the wasp eggs to hatch or emerging larvae to develop.

Orbitofrontal dopamine depletion upregulates caudate dopamine and alters behavior via changes in reinforcement sensitivity.

Schizophrenia is associated with upregulation of dopamine (DA) release in the caudate nucleus. The caudate has dense connections with the orbitofrontal cortex (OFC) via the frontostriatal loops, and both areas exhibit pathophysiological change in schizophrenia. Despite evidence that abnormalities in dopaminergic neurotransmission and prefrontal cortex function co-occur in schizophrenia, the influence of OFC DA on caudate DA and reinforcement processing is poorly understood. To test the hypothesis that OFC dopaminergic dysfunction disrupts caudate dopamine function, we selectively depleted dopamine from the OFC of marmoset monkeys and measured striatal extracellular dopamine levels (using microdialysis) and dopamine D2/D3 receptor binding (using positron emission tomography), while modeling reinforcement-related behavior in a discrimination learning paradigm. OFC dopamine depletion caused an increase in tonic dopamine levels in the caudate nucleus and a corresponding reduction in D2/D3 receptor binding. Computational modeling of behavior showed that the lesion increased response exploration, reducing the tendency to persist with a recently chosen response side. This effect is akin to increased response switching previously seen in schizophrenia and was correlated with striatal but not OFC D2/D3 receptor binding. These results demonstrate that OFC dopamine depletion is sufficient to induce striatal hyperdopaminergia and changes in reinforcement learning relevant to schizophrenia.

Pregabalin reduces postoperative opioid consumption and pain for 1 week after hospital discharge, but does not affect function at 6 weeks or 3 months after total hip arthroplasty.

BACKGROUND: This study examined whether a perioperative regimen of pregabalin added to celecoxib improved pain scores and functional outcomes postdischarge up to 3 months after total hip arthroplasty (primary outcome) and acute postoperative pain and adverse effects (secondary outcomes). METHODS: One hundred and eighty-four patients were enrolled in a randomized, double-blind, placebo-controlled study. Two hours before receiving a spinal anaesthetic and undergoing surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either pregabalin 150 mg p.o. or placebo p.o. After surgery, patients received pregabalin 75 mg or placebo twice daily in hospital and for 7 days after discharge. Patients also received celecoxib 200 mg every 12 h for 72 h and morphine i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, 6 weeks, and 3 months after surgery. RESULTS: There was no difference between groups in physical function or incidence and intensity of chronic pain 3 months after total hip arthroplasty. The pregabalin group used less morphine [mean (sd): 39.85 (28.1) mg] than the placebo group [54.01 (31.2) mg] in the first 24 h after surgery (P<0.01). Pain scores were significantly lower in the pregabalin group vs the placebo group on days 1-7 after hospital discharge, and the pregabalin group required less adjunctive opioid medication (Percocet) 1 week after hospital discharge (P<0.05). CONCLUSIONS: Perioperative administration of pregabalin did not improve pain or physical function at 6 weeks or 3 months after total hip arthroplasty. Perioperative administration of pregabalin decreased opioid consumption in hospital and reduced daily pain scores and adjunct opioid consumption for 1 week after discharge.

Continuous regional anaesthesia provides effective pain management and reduces opioid requirement following major lower limb amputation.

OBJECTIVES: Postoperative stump pain after major lower limb amputation is a significant impediment to the recovery of amputees. The vast majority of patients require opioid analgesics following surgery, which are associated with opioid-related side-effects. Here, we investigate whether intraoperative placement of a peripheral nerve stump catheter followed by continuous infusion of local anesthetic is as effective at pain control as current analgesic practices. If beneficial, this procedure could potentially reduce post-amputation opioid consumption and opioid-related adverse effects. METHODS: A retrospective chart review was conducted of 198 patients over a 4-year period who had undergone a major lower limb amputation for indications related to peripheral vascular disease. Postoperatively, 102 patients received a perineural catheter were compared to 96 patients who did not. The primary outcomes of this study were the amount of morphine equivalents used in the first 72 hours postoperatively and postoperative pain intensity in the first 24 hours. RESULTS: A total of 198 lower-limb amputations were selected for analyses. Multiple regression analyses indicated that perineural catheter use was associated with a lower cumulative postoperative opioid consumption over the first 72 hours but not postoperative pain scores at 24 hours. Perineural catheter use led to a 40% reduction in opioid use during the first 72 hours postoperatively. Mixed model repeated measures analysis demonstrated that this opioid reduction was consistent over time. Other variables related to total opioid use included age, pre-surgical chronic pain, pre-surgical opioid use, patient-controlled analgesia. CONCLUSIONS: Continuous perineural infusions of local anesthetic are a safe and effective method for reducing post-amputation opioid analgesic medications after major lower limp amputation.

Perioperative gabapentin reduces 24 h opioid consumption and improves in-hospital rehabilitation but not post-discharge outcomes after total knee arthroplasty with peripheral nerve block.

BACKGROUND: This study was designed to determine whether a 4 day perioperative regimen of gabapentin added to celecoxib improves in-hospital rehabilitation and physical function on postoperative day 4 and 6 weeks and 3 months after total knee arthroplasty (TKA). METHODS: After Research Ethics Board approval and informed consent, 212 patients were enrolled in a randomized, double-blinded, placebo-controlled study. Two hours before surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either gabapentin 600 mg or placebo p.o. Two hours later, patients received femoral, sciatic nerve blocks, and spinal anaesthesia. After operation, patients received gabapentin 200 mg or placebo three times per day (TID) for 4 days. All patients also received celecoxib 200 mg q12 h for 72 h and i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, during hospitalization, on postoperative day 4 (POD4), and 6 weeks and 3 months after surgery. RESULTS: The gabapentin group used less morphine in the first 24 h after surgery [G=38.3 (29.5 mg), P=48.2 (29.4 mg)] (P<0.0125) and had increased knee range of motion compared with the placebo group in-hospital (P<0.05). There were no differences between groups in favour of the gabapentin group for pain or physical function on POD 4 [95% confidence interval (CI): pain: -1.4, 0.5; function: -6.3, 2.0], 6 weeks (95% CI: pain: 0.1, 1.9; function: -0.2, 6.5) or 3 months (95% CI: pain: -0.2, 1.7; function: -2.2, 4.3) after TKA. CONCLUSIONS: In the context of celecoxib, spinal anaesthesia, femoral and sciatic nerve blocks, a dose of gabapentin 600 mg before operation followed by 4 days of gabapentin 200 mg TID decreased postoperative analgesic requirements and improved knee range of motion after TKA. Gabapentin provided no improvement in pain or physical function on POD4 and 6 weeks or 3 months after surgery.

The impact of dung beetles on the free-living stages of ruminant parasites in faeces and their role as biological control agents in grazing livestock.

Dung beetles provide a variety of ecosystem services in both natural and farmed landscapes. Amongst these services, reductions in the abundance of the free-living stages of pests and parasites that develop in faeces is considered to be of great importance. There is evidence from Australia that enhanced dung beetle populations can reduce populations of pest fly species, particularly the bush fly, however, there is little empirical evidence for reductions in the incidence and impact of nematode parasitism in grazing ruminants. There are two main pathways whereby beetles can disrupt worm life-cycles: predaceous species that feed on eggs or larvae can directly reduce populations in dung whereas coprophagous species can affect parasite development, survival and translocation by altering the location, microclimate and infrastructure of dung deposits. In addition, predaceous mites that are phoretic on dung beetles, can also prey on larval stages in the faeces. To date, reductions in both larval survival and the acquisition of gastrointestinal nematode burdens in ruminants on pasture has been reported only in association with the activity of large tunnelers that bury dung 15 cm or more below ground. The activity of dwellers, rollers and shallow tunnelers can either limit or enhance larval development and translocation, depending on the influence of other factors, notably rainfall. Currently, the scientific evidence for dung beetles playing a major role in the control of gastrointestinal nematodes in domestic ruminants is very limited and may have been overestimated in assessments of their ecosystem services.

The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma.

BACKGROUND: Mesothelioma is an incurable cancer originating from the mesothelial cells that line the pleural, peritoneal and pericardial cavities. These cells synthesise large quantities of surface glycoproteins, rendering them dependent upon efficient endoplasmic reticulum (ER) function. When faced with elevated levels of secretory protein load, cells are said to experience ER stress, which has been implicated in the pathogenesis of many human diseases including cancer. METHOD: We set out to measure markers of ER stress in malignant mesothelioma and to determine whether ER stress signalling correlates with clinical parameters. RESULTS: We observed that expression of the ER stress-responsive transcription factor C/EBP homologous protein (CHOP) correlated with patient survival and remained an independent prognostic variable in pairwise comparisons with all clinical variables tested. The most parsimonious multivariate model in our study comprised only performance status and CHOP staining. In contrast, expression of the ER stress-responsive phosphatase growth arrest and DNA damage 34 (GADD34) correlated with the degree of mesothelial differentiation, being lost progressively in biphasic and sarcomatoid mesotheliomas. CONCLUSION: Our findings suggest that staining for CHOP provides prognostic information that may be useful in the stratification of patients with mesothelioma. Staining for GADD34 may prove useful in classification of mesothelioma histopathology.

Phylogeny and biogeography of southern African spoon-winged lacewings (Neuroptera: Nemopteridae: Nemopterinae).

Nemopteridae are a charismatic family of lacewings characterised by uniquely extended hind wings. They are an ancient widespread group in the drier regions of the world. The family comprises two subfamilies, Crocinae (thread-wings) and Nemopterinae (spoon- and ribbon-wings). The present distribution of the family has been largely influenced by the vicariant events of plate tectonics, resulting in relict populations in some parts of the world and extensive evolutionary radiations in others, particularly southern Africa where the vast majority of the species are endemic to the Western and Northern Cape Provinces of South Africa. This study aimed to establish the validity of the 11 currently recognised genera and infer their biogeographic history using molecular sequence data from four gene regions. The hypothesis that the Cape nemopterines co-evolved with certain taxa in the Cape Floristic Region was also tested. Phylogenetic analysis supports seven of the 11 currently recognised genera. The crown age of the Nemopterinae is estimated to be at ca. 145.6 Mya, indicating that the group has been present since the late Jurassic. Most of the genera appear to have diversified during the middle Eocene and into the middle Miocene (ca. 44-11 Mya) with recent rapid radiation of several of the genera occurring during the late Miocene (ca. 6-4.5 Mya). While these data support an initial radiation with the Rushioideae (Aizoaceae) it is recommended that further study including observations and gut content be carried out.

Morphology and terminology of dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) male genitalia.

The external and internal male genitalia of 327 species of 11 tribes of the subfamily Scarabaeinae, including species of Deltochilini, Scarabaeini, Gymnopleurini, Ateuchini, and Coprini, among others, were examined. Descriptions of the variations in the genital segment, the aedeagus, the internal sac, and its sclerites and raspules are presented. An exhaustive comparison of structures, names, and terminology used in literature for Scarabaeinae male genitalia are discussed. The internal sac of the aedeagus is divided in areas for an easer comparison of its internal structures; basal, submedial, medial, and apical areas are described in detail and compared. The variation of apical and medial sclerites, as well as the raspules of the submedial area, are described and compared in detail among all the taxa studied.

The evolving culture of medical cannabis in Canada for the management of chronic pain.

Although used therapeutically for millennia, cannabis has been a prohibited substance worldwide for most of the 20th Century. With revision of prohibitive regulations in many jurisdictions during the past 2 decades, cannabis is increasingly available to patients as a potential treatment option for various symptoms. Pain relief, sleep promotion and alleviation of distress, depression and anxiety are the most common reasons for cannabis use. Canada has been at the forefront of medical cannabis (MC) legislation revisions to enable and facilitate access for therapeutic use. Although initially viewed with caution and stigma, attitudes to cannabis in general have changed. Medical cannabis is identified as the herbal plant product sourced from a grower/producer and is not at present a regulated pharmaceutical product. Medical cannabis use is currently prevalent in Canada but has bypassed the rigorous study required for usual drug approval. Although uptake has been enthusiastic by patients, the medical community has voiced cautions and concerns. Access to medical cannabis is fairly easy once an approval document is obtained from a healthcare professional, but without obligation for medical or pharmacy oversight. The greatest concern is a dearth of sound clinical evidence for effects and harms. Emerging concerns include prevalent patient self-management with information based on personal research, an abundance of on-line information which may not always be accurate, the emergence of designated "cannabis clinics," potential risks to society due to accidents, and high cost of the legal medical product leading to access via the recreational market. With cannabis now entrenched in Canadian healthcare, physicians must be sufficiently knowledgeable to provide guidance that is evidence-based and will ensure personal and societal harm reduction. Examination of the changing culture of medical cannabis in Canada will provide insight for countries that may be anticipating similar revisions of cannabis regulations to allow cannabis access for their patient population and learn from the issues created by recreational legalization.

Cdk12 maintains the integrity of adult axons by suppressing actin remodeling.

The role of cyclin-dependent kinases (CDKs) that are ubiquitously expressed in the adult nervous system remains unclear. Cdk12 is enriched in terminally differentiated neurons where its conical role in the cell cycle progression is redundant. We find that in adult neurons Cdk12 acts a negative regulator of actin formation, mitochondrial dynamics and neuronal physiology. Cdk12 maintains the size of the axon at sites proximal to the cell body through the transcription of homeostatic enzymes in the 1-carbon by folate pathway which utilize the amino acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in turn leads to uncontrolled F-actin formation and axonal swelling. Actin remodeling further induces Drp1-dependent fission of mitochondria and the breakdown of axon-soma filtration barrier allowing soma restricted cargos to enter the axon. We demonstrate that Cdk12 is also an essential gene for long-term neuronal survival and loss of this gene causes age-dependent neurodegeneration. Hyperhomocysteinemia, actin changes, and mitochondrial fragmentation are associated with several neurodegenerative conditions such as Alzheimer's disease and we provide a candidate molecular pathway to link together such pathological events.

Dung removal increases under higher dung beetle functional diversity regardless of grazing intensification.

Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.