Prothrombin and activated partial thromboplastin times, thromboelastography, hematocrit, and platelet count in a feline hemorrhage/over-resuscitation model using lactated Ringer's solution or 6% tetrastarch 130/0.4.

OBJECTIVE: To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over-resuscitation model. DESIGN: Randomized crossover study. SETTING: University teaching hospital. ANIMALS: Six cats. INTERVENTIONS: Anesthetized cats underwent 3 treatments at 2-month intervals. The treatments were as follows: NHR-no controlled hemorrhage and sham resuscitation; LRS-controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven-controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T - 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05). MEASUREMENTS AND MAIN RESULTS: Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha-angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001). CONCLUSIONS: Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss.

Social media as a tool to understand the distribution and ecology of elusive mammals.

Comparatively little is known about the distribution and ecology of Aardvark (Orycteropus afer) and Temminck's Ground Pangolin (Smutsia temminckii). Both are elusive species that are normally nocturnal, solitary, and fossorial. Formally collected records have been used to map the distribution of these species, and social media records provide a tool to gather information on their distribution and ecology. We obtained 680 photographs and videos of aardvarks and 790 of ground pangolins in southern Africa from publicly available posts on Facebook and Instagram (2010-2019). The images provide new insights into the distribution, activity, drinking, and predation-and confirm that aardvarks are more diurnally active when they are in poor body condition. Social media can provide useful supplementary information for understanding of elusive mammals. These "soft" data can be applied to other species.

The Sensation and Pain Rating Scale: easy to use, clear to interpret, and responsive to clinical change.

Background: The Sensation and Pain Rating Scale (SPARS) allows rating of non-painful as well as painful percepts. While it performs well in the experimental context, its clinical utility is untested. This prospective, repeated-measures study mixed qualitative and quantitative methods to examine the utility and performance of the SPARS in a clinical context, and to compare it with the widely used 11-point NRS for pain. Methods: People presenting for outpatient physiotherapy (n = 121) provided ratings on the SPARS and NRS at first consultation, before and after sham and active clinical interventions, and at follow-up consultation. Clinicians (n = 9) reported each scale's usability and interpretability using Likert-type scales and free text, and answered additional questions with free text. Each data type was initially analysed separately: quantitative data were visualised and the ES II metric was used to estimate SPARS internal responsiveness; qualitative data were analysed with a reflexive inductive thematic approach. Data types were then integrated for triangulation and complementarity. Results: The SPARS was well received and considered easy to use, after initial familiarisation. Clinicians favoured the SPARS over the NRS for clarity of interpretation and inter-rater reliability. SPARS sensitivity to change was good (ESII=0.9; 95%CI: 0.75-1.10). The greater perceptual range of the SPARS was deemed especially relevant in the later phases of recovery, when pain may recede into discomfort that still warrants clinical attention. Conclusion: The SPARS is a promising tool for assessing patient percept, with strong endorsement from clinicians for its clarity and superior perceptual scope.

Temminck pangolins relax the precision of body temperature regulation when resources are scarce in a semi-arid environment.

Climate change is impacting mammals both directly (for example, through increased heat) and indirectly (for example, through altered food resources). Understanding the physiological and behavioural responses of mammals in already hot and dry environments to fluctuations in the climate and food availability allows for a better understanding of how they will cope with a rapidly changing climate. We measured the body temperature of seven Temminck's pangolins (Smutsia temminckii) in the semi-arid Kalahari for periods of between 4 months and 2 years. Pangolins regulated body temperature within a narrow range (34-36°C) over the 24-h cycle when food (and hence water, obtained from their prey) was abundant. When food resources were scarce, body temperature was regulated less precisely, 24-h minimum body temperatures were lower and the pangolins became more diurnally active, particularly during winter when prey was least available. The shift toward diurnal activity exposed pangolins to higher environmental heat loads, resulting in higher 24-h maximum body temperatures. Biologging of body temperature to detect heterothermy, or estimating food abundance (using pitfall trapping to monitor ant and termite availability), therefore provide tools to assess the welfare of this elusive but threatened mammal. Although the physiological and behavioural responses of pangolins buffered them against food scarcity during our study, whether this flexibility will be sufficient to allow them to cope with further reductions in food availability likely with climate change is unknown.

A Systematic Review and Meta-analysis of Non-pharmacological Methods to Manipulate Experimentally Induced Secondary Hypersensitivity.

This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free humans. We investigated the magnitude (change/difference in follow-up ratings from pre-manipulation ratings) of secondary hypersensitivity (primary outcome), and surface area of secondary hypersensitivity (secondary outcome), in 27 studies representing 847 participants. Risk of bias assessment concluded most studies (23 of 27) had an unclear or high risk of performance and detection bias. Further, 2 (of 27) studies had a high risk of measurement bias. Datasets were pooled by the method of manipulation and outcome. The magnitude of secondary hypersensitivity was decreased by diverting attention, anodal transcranial direct current stimulation, or emotional disclosure; increased by directing attention toward the induction site, nicotine deprivation, or negative suggestion; and unaffected by cathodal transcranial direct current stimulation or thermal change. Area of secondary hypersensitivity was decreased by anodal transcranial direct current stimulation, emotional disclosure, cognitive behavioral therapy, hyperbaric oxygen therapy, placebo analgesia, or spinal manipulation; increased by directing attention to the induction site, nicotine deprivation, or sleep disruption (in males only); and unaffected by cathodal transcranial direct current stimulation, thermal change, acupuncture, or electroacupuncture. Meta-analytical pooling was only appropriate for studies that used transcranial direct current stimulation or hyperbaric oxygen therapy, given the high clinical heterogeneity among the studies and unavailability of data. The evidence base for this question remains small. We discuss opportunities to improve methodological rigor including manipulation checks, structured blinding strategies, control conditions or time points, and public sharing of raw data. PERSPECTIVE: We described the effects of several non-pharmacological manipulations on experimentally induced secondary hypersensitivity in humans. By shedding light on the potential for non-pharmacological therapies to influence secondary hypersensitivity, it provides a foundation for the development and testing of targeted therapies for secondary hypersensitivity.

Chronic pain is no more prevalent in people living with HIV than in their uninfected counterparts in South Africa.

BACKGROUND: There are few studies on chronic pain prevalence in people living with HIV, and there are no studies comparing chronic pain prevalence in an HIV-infected group (HIV+) to that found in an uninfected group (HIV-) in the same population. This study was undertaken to (1) estimate the chronic pain prevalence in HIV+ individuals and (2) compare chronic pain prevalence between HIV+ and HIV- groups in a population. METHODS: Individuals ≥15 years old were recruited using multi-stage probability sampling in the 2016 South African Demographic and Health Survey. In an interview, participants were asked whether they currently had pain or discomfort, and if so, whether that pain or discomfort had persisted for at least 3 months (operational definition of chronic pain). Blood samples were taken from a volunteering sub-sample for HIV testing. RESULTS: A total of 6584 of 12,717 eligible individuals answered the questionnaire and were tested for HIV. Mean age: 39.1 years (95% confidence interval [CI]: 38.3-39.9), per cent female: 55% (95% CI: 52-56) and tested HIV+: 19% (95% CI: 17-20). The prevalence of chronic pain was 19% (95% CI: 16-23) in the HIV+ group, which was similar to that found in the HIV- group (20% [95% CI: 18-22]; odds ratio [adjusted for age, sex, socio-economic status] = 0.93 [95% CI: 0.74-1.17], p-value = 0.549). CONCLUSION: The prevalence of chronic pain in South Africans living with HIV was approximately 20%, and having HIV was not associated with an increased risk of chronic pain. SIGNIFICANCE: Using data from a large, national, population-based study in South Africa, I show for the first time that the prevalence of chronic pain in that population did not differ materially between the part of the population that was living with HIV compared with their uninfected counterparts (both approximately 20%). These findings run counter to the dogma that there is a greater risk of having pain in people living with HIV.

Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.

HIV-associated sensory neuropathy (HIV-SN) affects 14-38% of HIV+ individuals stable on therapy with no neurotoxic drugs. Polymorphisms in CAMKK2, P2X7R and P2X4R associated with altered risk of HIV-SN in Indonesian and South African patients. The role of CaMKK2 in neuronal repair makes this an attractive candidate, but a direct role for any protein is predicated on expression in affected tissues. Here, we describe expression of CaMKK2, P2X7R and P2X4R proteins in skin biopsies from the lower legs of HIV+ Indonesians with and without HIV-SN, and healthy controls (HC). HIV-SN was diagnosed using the Brief Peripheral Neuropathy Screen. Biopsies were stained to detect protein gene product 9.5 on nerve fibres and CaMKK2, P2X7R or P2X4R, and were examined using 3-colour sequential scanning confocal microscopy. Intraepidermal nerve fibre densities (IENFD) were lower in HIV+ donors than HC and correlated directly with nadir CD4 T-cell counts (r = 0.69, p = 0.004). However, IENFD counts were similar in HIV-SN+ and HIV-SN- donors (p = 0.19) and so did not define neuropathy. CaMKK2+ cells were located close to dermal and epidermal nerve fibres and were rare in HC and HIV-SN- donors, consistent with a role for the protein in nerve damage and/or repair. P2X7R was expressed by cells in blood vessels of HIV-SN- donors, but rarely in HC or HIV-SN+ donors. P2X4R expression by cells in the epidermal basal layer appeared greatest in HIV-SN+ donors. Overall, the differential expression of CaMKK2, P2X7R and P2X4R supports the genetic evidence of a role for these proteins in HIV-SN.

Rescheduling gabapentinoids had negligible effects on prescribing behaviour by general practitioners in England.

PURPOSE: To determine whether the rescheduling of gabapentinoids in England as Schedule 3 Controlled Substances in April 2019, changed prescribing behaviour for gabapentinoids by general practitioners. METHODS: Data on the monthly number of prescription items and the monthly average dose per prescription item were analysed for the period April 2017 to April 2021 under three models: (i) a simple linear regression, (ii) a linear spline with a knot at April 2019, and (iii) a parallel slopes model with time before and after the rescheduling as a covariate. Best fit models were selected based on them having the lowest corrected Akaike's information criterion. Auto-regressive integrated moving average (ARIMA) models were also generated. RESULTS: For gabapentin, the best fit model for the number of prescription items was the simple linear model, and for the dose per prescription item it was the parallel slopes model. For pregabalin, the best fit model was the linear spline for the number of prescription items and the dose per prescription item. For all models, the interval estimates for the slopes were consistent with no change or no meaningful change in prescribing behaviour after April 2019. Forecasts from ARIMA models for gabapentin and pregabalin were consistent with no change in the number of prescription items per month. However, forecasts for the dose per prescription item for gabapentin or pregabalin did not fully capture the post-April 2019 trajectories. CONCLUSION: The reclassification of gabapentinoids did not materially change the prescribing behaviour of these drugs by general practitioners in England.

Slow and Steady But Not Related to HIV Stigma: Physical Activity in South Africans Living with HIV and Chronic Pain.

HIV stigma may influence physical activity in people living with HIV (PLWH) and chronic pain. We prospectively examined the relationship between stigma, activity and chronic pain in a convenience sample of PLWH initiating antiretroviral therapy in an inner-city clinic in Johannesburg, South Africa. Participants wore accelerometers to measure daily duration and intensity of activity for 2 weeks. Stigma was assessed with the Revised HIV Stigma Scale. Participants [n = 81, 89% female, age mean (SD) 42 (8)] were active for a median of 7 h daily (IQR 5.2, 9.2), but at very low intensity, equivalent to a slow walk [median (IQR): 0.39 m s-1 (0.33, 0.50)]. Duration and intensity of activity was not associated with stigma, even after controlling for age, self-assessed wealth, pain intensity and willingness to engage in physical activity (p-values > 0.05). As stigma did not associate with greater activity, drivers of sustained activity in South African PLWH remain unclear.

RESUMEN: El estigma del VIH puede influir en la actividad física de las personas que viven con el VIH (PVVS) y el dolor crónico. Se examinó prospectivamente la relación entre el estigma, la actividad y el dolor crónico en una muestra de conveniencia de PVVS que iniciaba la terapia antirretroviral en una clínica del centro de la ciudad en Johannesburgo, Sudáfrica. Los participantes usaron acelerómetros para medir la duración diaria y la intensidad de la actividad durante dos semanas. El estigma se evaluó con la escala revisada de estigma del VIH. Los participantes [n = 81, 89% mujeres, media de edad (SD) 42 (8)] tenían una actividad de intensidad muy baja, para una mediana de siete horas diarias (IQR 5.2, 9.2), pero, equivalente a una marcha lenta [mediana (IQR): 0.39 m s−1 (0.33, 0.50)]. La duración y la intensidad de la actividad no se asociaron con los niveles de estigma, incluso después de controlar la edad, la riqueza autoevaluada, la intensidad del dolor y la voluntad de participar en la actividad física (valores de p > 0.05). Como el estigma no se asoció con una mayor actividad, los impulsores de la actividad sostenida en las PVVS sudafricanas siguen sin estar claros.

South African men and women living with HIV have similar distributions of pain sites.

BACKGROUND: No studies have investigated sex differences in the location and number of pain sites in people living with human immunodeficiency virus (HIV) (PLWH), despite evidence that women, in general, bear a greater burden of pain than men. AIM: To determine sex differences in the location and number of pain sites, and whether there were demographic or disease-related differences in the number of pain sites. SETTING: South African tertiary hospital HIV clinics and a community healthcare centreMethods: We conducted a retrospective analysis of records from South African PLWH who had pain. RESULTS: Of the 596 participant records, 19% were male (115/596) and the median number of pain sites for both sexes was 2 (interquartile range [IQR]: 1 to 3). Pain was most frequently experienced in the head (men: 12%, women: 38%), feet and ankles (men: 42%, women: 28%), abdomen (men = 19%, women = 28%) and chest (men = 20%, women = 20%). After correcting for multiple comparisons, males were less likely to experience headache than females (Fisher's exact text, odds ratio [OR] = 0.23, 95% confidence interval [CI]: 0.12 - 0.42, p = 0.000). Pain at other body sites was experienced similarly between the sexes. There was no meaningful variation in the number of pain sites between the sexes (logistic regression, p = 0.157). CONCLUSION: A similar location and number of pain sites were experienced by male and female South African PLWH. The locations of pain sites were different from previous reports, however, suggesting that research into pain in PLWH cannot necessarily be generalised across cultures.

Describing acid-base balance using three different methods of analysis in a feline acute haemorrhage-resuscitation model.

OBJECTIVE: To describe acid-base status using the Henderson-Hasselbalch, Stewart and semi-quantitative methods of analysis in a feline haemorrhage-resuscitation model. STUDY DESIGN: Randomized crossover study. ANIMALS: A total of six domestic cats (mean age, 21 months; weight, 4.9 kg). METHODS: Venous blood samples were taken before haemorrhage, after haemorrhage at 30 minute intervals during fluid resuscitation and at 24 hours. The cats were anaesthetized and underwent following treatments: no purposeful haemorrhage and resuscitation (NoPHR), purposeful haemorrhage followed by either lactated Ringer's solution (LRS) or 6% tetrastarch 130/0.4 (Voluven) for resuscitation. LRS and Voluven were administered at 60 and 20 mL kg-1 hour-1, respectively, for 120 minutes. Variables used for the analysis methods were measured or calculated from the blood samples and then compared among treatments over time using a general linear mixed model (p < 0.05; data reported as mean and standard deviation). RESULTS: The total blood loss at 120 minutes was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg-1 for NoPHR, LRS and Voluven, respectively. Total volumes of LRS and Voluven administered were 120 and 40 mL kg-1, respectively. All cats became acidaemic during anaesthesia regardless of treatment. The Henderson-Hasselbalch method indicated that anaesthetized cats undergoing severe haemorrhage and resuscitation manifest a mixed acidosis. The Stewart method indicated two counter metabolic processes that contributed to the overall pH-decrease in apparent strong ion difference (acidosis) and decrease in total weak acids (alkalosis). The semi-quantitative method identified the free water and chloride effects as variables causing acidosis and the albumin effect causing alkalosis. CONCLUSIONS AND CLINICAL RELEVANCE: In an experimental haemorrhage and resuscitation model in cats, blood pH was similar among treatments over time regardless of severe haemorrhage and resuscitation with LRS or Voluven or mild haemorrhage and no resuscitation.

Importance of testing the internal consistency and construct validity of the Pittsburgh Sleep Quality Index (PSQI) in study groups of day and night shift workers: Example of a sample of long-haul truck drivers in South Africa.

Irregular work times promote inconsistent completion of the Pittsburgh Sleep Quality Index (PSQI) among shift workers. We aimed to demonstrate the importance of testing the internal consistency and construct validity of the PSQI and of the Epworth Sleepiness Scale (ESS) by presenting the methodology in a sample of long-haul truckers in South Africa. Internal consistency of the questionnaires was assessed by Cronbach's alpha (defined as raw alpha≥0.70), and construct validity by factor analysis. 302 participants (49.3%) reported at least one night shift/week. Overall, the PSQI and ESS's alpha were 0.42 and 0.85, respectively. The factors explained 19.6% of 57.0% of the variance. The PSQI's alpha was 0.46 in night shift workers and 0.38 in non-night shift workers. In this occupational group, the PSQI must be used with caution. Testing the internal consistency and construct validity among the assessed population seems necessary. Sleep questionnaires adapted to shift workers should be preferred.

Greater baseline pain inclusion criteria in clinical trials increase regression to the mean effect: a modelling study.

ABSTRACT: We modelled the effects of pain intensity inclusion thresholds (3/10, 4/10, and 5/10 on a 0- to 10-point numerical pain rating scale) on the magnitude of the regression to the mean effect under conditions that were consistent with the sample mean and variance, and intermeasurement correlation observed in clinical trials for the management of chronic pain. All data were modelled on a hypothetical placebo control group. We found a progressive increase in the mean pain intensity as the pain inclusion threshold increased, but this increase was not uniform, having an increasing effect on baseline measurements compared with study endpoint measurements as the threshold was increased. That is, the regression to the mean effect was magnified by increasing inclusion thresholds. Furthermore, the effect increasing pain inclusion thresholds had on the regression to the mean effect was increased by decreasing sample mean values at baseline and intermeasurement correlations, and increasing sample variance. At its smallest, the regression to the mean effect was 0.13/10 (95% confidence interval: 0.03/10-0.24/10; threshold: 3/10, baseline mean pain: 6.5/10, SD: 1.6/10, and correlation: 0.44), and at its greatest, it was 0.78/10 (95% confidence interval: 0.63/10-0.94/10; threshold: 5/10, baseline mean pain: 6/10, SD: 1.8/10, and correlation: 0.19). We have shown that using pain inclusion thresholds in clinical trials drives progressively larger regression to the mean effects. We believe that a threshold of 3/10 offers the best compromise between maintaining assay sensitivity (the goal of thresholds) and the size of the regression to the mean effect.

Brief Report: Polymorphisms in CAMKK2 may Influence Domain-Specific Neurocognitive Function in HIV+ Indonesians Receiving ART.

BACKGROUND: Despite effective antiretroviral therapy (ART), milder forms of HIV-associated neurocognitive disorders remain prevalent and are characterized by neuroinflammation, synaptic dysfunction, and neuronal loss. METHODS: We explore associations between neurocognitive impairment in HIV+ Indonesians and 17 polymorphisms in adjacent genes involved in inflammation and neuronal growth/repair pathways, P2X4R and CAMKK2. HIV+ Indonesians (n = 59) who had received ART for 12 months were assessed to derive Z-scores for the attention, fluency, memory, executive, and motor speed domains relative to local control subjects. These were used to determine total cognitive scores. RESULTS: No alleles of P2X4R displayed significant associations with neurocognition in bivariate or multivariable analyses. In CAMKK2, rs2686344 influenced total cognitive scores in bivariate analyses (P = 0.04). Multivariable linear regression modeling independently associated rs2686344 with higher executive function Z-scores (P = 0.05) after adjusting for CD4 T-cell counts (adjusted R2 = 0.103, model P = 0.034), whereas rs1653588 associated with lower and rs1718120 (P = 0.05) with higher fluency Z-scores (P = 0.05) after adjusting for education and log10 HIV RNA copies/mL (adjusted R2 = 0.268, model P = 0.001). CONCLUSIONS: Polymorphisms in CAMKK2 may influence neurocognitive outcomes in specific domains in HIV+ Indonesians receiving ART for 12 months.

Investigation of biomarkers for impending fluid overload in a feline acute haemorrhage-resuscitation model.

OBJECTIVE: To determine biomarkers for impending fluid overload during intravenous fluid administration in a feline haemorrhage-resuscitation model. STUDY DESIGN: Randomized crossover study. ANIMALS: A group of six domestic cats (mean age and weight: 21 months; 4.9 kg, respectively). METHODS: The cats underwent three treatments, 2 months apart. They were anaesthetized and instrumented to measure a range of physiological, blood gas, haematological and biochemical variables over time. Samples were taken during a health check, before haemorrhage, after haemorrhage and then at 30 minute intervals during fluid resuscitation and 24 hours later. The three treatments were: 1) control, sham haemorrhage and resuscitation; 2) lactated Ringer's solution (LRS); and 3) 6% tetrastarch 130/0.4 (Vol) where the cats underwent a controlled haemorrhage then resuscitation by administering LRS and Vol at 60 and 20 mL kg-1 hour-1, respectively, for 120 minutes. Fluid overload was identified by nasal discharge and radiographic evidence. Biomarkers were variables that exceeded the reference interval for cats during treatment. Potential biomarkers were analysed using receiver operating characteristic curves (p < 0.05). RESULTS: Mean ± standard deviation total blood loss was 10.2 ± 2.3, 29.3 ± 9.0 and 29.1 ± 6.3 mL kg-1 for control, LRS and Vol, respectively. The total volume of LRS and Vol administered was 120 and 40 mL kg-1, respectively. Haematocrit, albumin, magnesium, chloride-to-sodium ratio and sodium-chloride difference were identified as potential biomarkers. These variables exceeded the reference intervals from 30 minutes of resuscitation onwards. A chloride-to-sodium ratio > 0.84 was the most sensitive (90%) and specific (75%) of all potential biomarkers. CONCLUSIONS AND CLINICAL RELEVANCE: Changes in physiological variables, haematocrit and albumin were poor biomarkers of impending fluid overload compared with electrolytes. Finding the ideal biomarker to identify impending fluid overload of commonly used intravenous fluids should improve the safety of their administration in cats.

Neurocognitive outcomes in indonesians living with HIV are influenced by polymorphisms in the gene encoding purinergic P2X receptor 7.

The advent of effective antiretroviral therapy (ART) has decreased the prevalence and severity of HIV-associated neurocognitive disorders (HAND), but milder forms of HAND remain despite optimal treatment. Neuronal injury and loss due to inflammation may mediate HAND. P2X7R encodes purinergic P2X receptor 7 which influences neuroinflammatory pathways and carries polymorphisms associated with sensory neuropathy in HIV patients. We assessed associations between P2X7R polymorphisms and neurocognitive outcomes in Indonesian patients (n â€‹= â€‹59) as they commenced ART and after 3, 6 and 12 months. Z-scores were calculated over 5 domains using local controls and evaluated as continuous variables. Optimal linear regression models identified polymorphisms influencing attention, memory, executive function, motor speed and total cognitive function at each time point. rs504677 was associated with lower executive and motor speed Z-scores at 0, 3, 6, and 12 months, and with memory at 0 and 12 months. Memory was positively influenced by carriage of the rs208296 minor allele at 0, 3 and 6 months and by carriage of the rs208307 minor allele at 0 and 12 months. Higher attention Z-scores associated with carriage of minor alleles of rs1653598 after 0 and 12 months. These also positively influenced executive function and motor speed after 0-6 months. This study identifies polymorphisms in P2X7R which influence domain-specific neurocognitive outcomes in HIV+ â€‹Indonesians prior to and shortly after commencing ART. This implicates purinergic P2X receptor 7 in the pathogenesis of HAND.

Why It Is Important to Consider the Effects of Analgesics on Sleep: A Critical Review.

We review the known physiological mechanisms underpinning all of pain processing, sleep regulation, and pharmacology of analgesics prescribed for chronic pain. In particular, we describe how commonly prescribed analgesics act in sleep-wake neural pathways, with potential unintended impact on sleep and/or wake function. Sleep disruption, whether pain- or drug-induced, negatively impacts quality of life, mental and physical health. In the context of chronic pain, poor sleep quality heightens pain sensitivity and may affect analgesic function, potentially resulting in further analgesic need. Clinicians already have to consider factors including efficacy, abuse potential, and likely side effects when making analgesic prescribing choices. We propose that analgesic-related sleep disruption should also be considered. The neurochemical mechanisms underlying the reciprocal relationship between pain and sleep are poorly understood, and studies investigating sleep in those with specific chronic pain conditions (including those with comorbidities) are lacking. We emphasize the importance of further work to clarify the effects (intended and unintended) of each analgesic class to inform personalized treatment decisions in patients with chronic pain. © 2021 American Physiological Society. Compr Physiol 11:1-31, 2021.

Use of blood colour for assessment of arterial oxygen saturation in immobilized impala (Aepyceros melampus).

OBJECTIVE: To determine the relationship between arterial blood colour [as defined by the International Commission on Illumination (CIE) L∗a∗b∗ colour space] and haemoglobin oxygen saturation [functional saturation (SaO2) and fractional saturation (FO2Hb)], and if arterial blood colour can be used to predict arterial haemoglobin oxygen saturation. STUDY DESIGN: Descriptive study as an adjunct to two prospective randomized crossover studies. ANIMALS: A group of 10 wild caught adult female impala (Aepyceros melampus) weighing 34.1 ± 5.2 kg (mean ± standard deviation). METHODS: Impala were immobilized with potent opioids (0.09 mg kg-1 of etorphine or thiafentanil). A total of 163 arterial blood samples were collected anaerobically into heparinized syringes from arterial cannulae and analysed immediately using spectrocolourimetry and co-oximetry. Data were analysed by modelling the relationship between predicted arterial blood colour CIE L∗a∗b∗ components and SaO2 and FO2Hb. The models were then used to predict values for L∗, a∗ and b∗ to produce a colour palette for the range of SaO2 and FO2Hb used. The modified version of the Farnsworth-Munsell hue test was used to assess the subjective ordering of the resulting colour palette by 20 observers. RESULTS: The second-order polynomial (quadratic) model produced the best fit for all three arterial blood colour CIE L∗a∗b∗ components for both SaO2 and FO2Hb. The regression models were used to generate predicted arterial blood colour CIE L∗a∗b∗ components for the midpoint of each decile over a range of SaO2 and FO2Hb percentages (15% to 95%). The resulting colour palettes were correctly ordered by all observers in the SaO2 range of 45-95% saturation. CONCLUSIONS AND CLINICAL RELEVANCE: An association between arterial blood colour (as defined by CIE L∗a∗b∗ components) and SaO2 and FO2Hb exists, and arterial blood colour can be used to give a clinically useful estimate of arterial haemoglobin oxygen saturation in impala.