Can modifications to how medical imaging findings are reported improve quality of care? A systematic review.

AIM: To synthesise the available evidence about the effects of modifications to diagnostic imaging reports that aim to optimise patient care. MATERIALS AND METHODS: Cochrane methods were used and CENTRAL, MEDLINE, EMBASE, and clinical trials registers were searched from inception to 31 March 2021. Randomised controlled trials of modifications to imaging reports aimed at optimising patient care for any condition were included. Two authors selected studies independently for inclusion, extracted data, assessed risk of bias, and judged certainty of evidence using GRADE. The primary outcome was quality of care (e.g., increased guideline-adherent care, reduced/increased imaging as appropriate). RESULTS: Five trials met eligibility criteria. One tested provision of information about appropriate osteoporosis treatment in bone density reports; two tested provision of criteria and treatment for heart failure in echocardiogram reports; one tested provision of reminders for when routine imaging is not needed in lumbar spine and knee radiography reports; and one tested inclusion of epidemiological data in lumbar spine imaging reports. All trials were susceptible to bias, and four did not blind all participants. Low certainty evidence from two trials found adding information about appropriate care may increase care quality compared to a standard report (RR 1.20 (95% CI 0.96 to 1.50), two trials, 1,548 participants, I2 = 49). This was supported by outcomes of two additional trials that also provided specific clinical guidance. CONCLUSIONS: The present review suggests that providing specific guidance on appropriate clinical intervention in imaging reports may improve patient care. Further high-quality trials are needed to confirm these findings. Prospective PROSPERO registration CRD42020153961.

Parental Care, Destabilizing Selection, and the Evolution of Tetrapod Endothermy.

Parental care has evolved convergently an extraordinary number of times among tetrapods that reproduce terrestrially, suggesting strong positive selection for this behavior in the terrestrial environment. This review speculates that destabilizing selection on parental care, and especially embryo incubation, drove the convergent evolution of many tetrapod traits, including endothermy.

Anatomy, ontogeny, and evolution of the archosaurian respiratory system: A case study on Alligator mississippiensis and Struthio camelus.

The avian lung is highly specialized and is both functionally and morphologically distinct from that of their closest extant relatives, the crocodilians. It is highly partitioned, with a unidirectionally ventilated and immobilized gas-exchanging lung, and functionally decoupled, compliant, poorly vascularized ventilatory air-sacs. To understand the evolutionary history of the archosaurian respiratory system, it is essential to determine which anatomical characteristics are shared between birds and crocodilians and the role these shared traits play in their respective respiratory biology. To begin to address this larger question, we examined the anatomy of the lung and bronchial tree of 10 American alligators (Alligator mississippiensis) and 11 ostriches (Struthio camelus) across an ontogenetic series using traditional and micro-computed tomography (µCT), three-dimensional (3D) digital models, and morphometry. Intraspecific variation and left to right asymmetry were present in certain aspects of the bronchial tree of both taxa but was particularly evident in the cardiac (medial) region of the lungs of alligators and the caudal aspect of the bronchial tree in both species. The cross-sectional area of the primary bronchus at the level of the major secondary airways and cross-sectional area of ostia scaled either isometrically or negatively allometrically in alligators and isometrically or positively allometrically in ostriches with respect to body mass. Of 15 lung metrics, five were significantly different between the alligator and ostrich, suggesting that these aspects of the lung are more interspecifically plastic in archosaurs. One metric, the distances between the carina and each of the major secondary airways, had minimal intraspecific or ontogenetic variation in both alligators and ostriches, and thus may be a conserved trait in both taxa. In contrast to previous descriptions, the 3D digital models and CT scan data demonstrate that the pulmonary diverticula pneumatize the axial skeleton of the ostrich directly from the gas-exchanging pulmonary tissues instead of the air sacs. Global and specific comparisons between the bronchial topography of the alligator and ostrich reveal multiple possible homologies, suggesting that certain structural aspects of the bronchial tree are likely conserved across Archosauria, and may have been present in the ancestral archosaurian lung.

Linking structure and function in the vertebrate respiratory system: A tribute to August Krogh.

High rates of pulmonary gas exchange require three things: 1) that gases at the contact surface of the lung's capillaries are replenished rapidly from the environment; 2) that this surface is large and thin; 3) that the capillaries are effectively perfused with blood. In spite of this uniform requirement, lungs have evolved complex and highly diverse architectures, but we have a poor understanding of the drivers of this diversity. Here, I briefly discuss some of the diversity in gross anatomical features directing airflow in avian and non-avian reptiles. I also review new insights into the cellular anatomy of the blood-gas barrier, which in mammals is composed of specialized endothelial as well as epithelial cells.

Unidirectional pulmonary airflow patterns in the savannah monitor lizard.

The unidirectional airflow patterns in the lungs of birds have long been considered a unique and specialized trait associated with the oxygen demands of flying, their endothermic metabolism and unusual pulmonary architecture. However, the discovery of similar flow patterns in the lungs of crocodilians indicates that this character is probably ancestral for all archosaurs--the group that includes extant birds and crocodilians as well as their extinct relatives, such as pterosaurs and dinosaurs. Unidirectional flow in birds results from aerodynamic valves, rather than from sphincters or other physical mechanisms, and similar aerodynamic valves seem to be present in crocodilians. The anatomical and developmental similarities in the primary and secondary bronchi of birds and crocodilians suggest that these structures and airflow patterns may be homologous. The origin of this pattern is at least as old as the split between crocodilians and birds, which occurred in the Triassic period. Alternatively, this pattern of flow may be even older; this hypothesis can be tested by investigating patterns of airflow in members of the outgroup to birds and crocodilians, the Lepidosauromorpha (tuatara, lizards and snakes). Here we demonstrate region-specific unidirectional airflow in the lungs of the savannah monitor lizard (Varanus exanthematicus). The presence of unidirectional flow in the lungs of V. exanthematicus thus gives rise to two possible evolutionary scenarios: either unidirectional airflow evolved independently in archosaurs and monitor lizards, or these flow patterns are homologous in archosaurs and V. exanthematicus, having evolved only once in ancestral diapsids (the clade encompassing snakes, lizards, crocodilians and birds). If unidirectional airflow is plesiomorphic for Diapsida, this respiratory character can be reconstructed for extinct diapsids, and evolved in a small ectothermic tetrapod during the Palaeozoic era at least a hundred million years before the origin of birds.

Concordance of the Vineland Adaptive Behavior Scales, second and third editions.

BACKGROUND: Because of its centrality in the conceptualization of intellectual disability, reliable and valid measurement of adaptive behaviour is important to both research and clinical practice. The manual of the Vineland Adaptive Behavior Scales, recently released in its third edition, provides limited reliability information obtained from a sample composed primarily of typically developing individuals. The goal of this study was to evaluate the concordance of the Vineland-3 with the Vineland-II in a sample more similar in ability level to those in which the Vineland is commonly used. METHODS: Both editions of the Vineland Interviews were conducted with a convenience sample of 106 parents/caregivers of individuals with neurodevelopmental disability, participating at two neurodevelopmental disorder research clinics. Administrations were up to 7 days apart, but most (90%) were simultaneous. The concordance correlation coefficient (CCC) (95% confidence interval) and mean differences (95% confidence interval) were calculated for domain standard scores and subdomain v-scale scores. RESULTS: Domain-level CCC ranged from 0.78 [0.70, 0.84] (Communication) to 0.86 [0.76, 0.92] (Motor). Subdomain CCC ranged from 0.71 [0.62, 0.78] (Receptive Language) to 0.91 [0.85, 0.95] (Fine Motor). Vineland-3 scores were lower than Vineland-II scores; 77% of participants had lower Adaptive Behavior Composite scores on the Vineland-3 than on the Vineland-II. For the subdomains, the magnitude of this difference depended upon the level of adaptive behaviour. For Communication, the domain with the lowest CCC, the mean difference ranged from -13.70 [-8.03, -19.35] for a Vineland-II score or 85 to a difference of -19.18 [-12.28, -26.87] for a Vineland-II score of 40. DISCUSSION: Amongst individuals with intellectual and developmental disabilities, the Vineland-3 produces lower scores than the Vineland-II, and these clinically significant differences tend to be larger for individuals with lower levels of ability. Thus, care must be taken in interpreting scores from the Vineland-3 relative to those obtained from the previous edition.

Uptake and virological outcomes of single- versus multi-tablet antiretroviral regimens among treatment-naïve youth in the HIV Research Network.

OBJECTIVES: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV). METHODS: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year. RESULTS: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/µL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/µL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]. CONCLUSIONS: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.

Surgical techniques in the management of rectal cancer: a modified Delphi method by colorectal surgeons in Australia and New Zealand.

BACKGROUND: Technological developments have allowed advances in minimally invasive techniques for total mesorectal excision such as laparoscopy, robotics, and transanal surgery. There remains an ongoing debate about the safety, benefits, and appropriate clinical scenarios for which each technique is employed. The aim of this study was to provide a panel of expert opinion on the role of each surgical technique currently available in the management of rectal cancer using a modified Delphi method. METHODS: Surveys were designed to explore the key patient- and tumor-related factors including clinical scenarios for determining a surgeon's choice of surgical technique. RESULTS: Open surgery was favoured in obese patients with an extra-peritoneal tumor and a positive circumferential resection margin (CRM) or T4 tumor when a restorative resection was planned. Laparoscopy was favoured in non-obese males and females, in both intra- and extra-peritoneal tumors with a clear CRM. Robotic surgery was most commonly offered to obese patients when the CRM was clear and if an abdominoperineal resection was planned. Transanal total mesorectal excision (taTME) was preferred in male patients with a mid or low rectal cancer, particularly when obese. Transanal endoscopic microsurgery/transanal minimally invasive surgery local excision was only offered to frail patients with small, early stage tumors. CONCLUSIONS: All surgical techniques for rectal cancer dissection have a role and may be considered appropriate. Some techniques have advantages over others in certain clinical situations, and the best outcomes may be achieved by considering all options before applying an individualised approach to each clinical situation.

New insight into the evolution of the vertebrate respiratory system and the discovery of unidirectional airflow in iguana lungs.

The generally accepted framework for the evolution of a key feature of the avian respiratory system, unidirectional airflow, is that it is an adaptation for efficiency of gas exchange and expanded aerobic capacities, and therefore it has historically been viewed as important to the ability of birds to fly and to maintain an endothermic metabolism. This pattern of flow has been presumed to arise from specific features of the respiratory system, such as an enclosed intrapulmonary bronchus and parabronchi. Here we show unidirectional airflow in the green iguana, a lizard with a strikingly different natural history from that of birds and lacking these anatomical features. This discovery indicates a paradigm shift is needed. The selective drivers of the trait, its date of origin, and the fundamental aerodynamic mechanisms by which unidirectional flow arises must be reassessed to be congruent with the natural history of this lineage. Unidirectional flow may serve functions other than expanded aerobic capacity; it may have been present in the ancestral diapsid; and it can occur in structurally simple lungs.

The Evolution of Unidirectional Pulmonary Airflow.

Conventional wisdom holds that the avian respiratory system is unique because air flows in the same direction through most of the gas-exchange tubules during both phases of ventilation. However, recent studies showing that unidirectional airflow also exists in crocodilians and lizards raise questions about the true phylogenetic distribution of unidirectional airflow, the selective drivers of the trait, the date of origin, and the functional consequences of this phenomenon. These discoveries suggest unidirectional flow was present in the common diapsid ancestor and are inconsistent with the traditional paradigm that unidirectional flow is an adaptation for supporting high rates of gas exchange. Instead, these discoveries suggest it may serve functions such as decreasing the work of breathing, decreasing evaporative respiratory water loss, reducing rates of heat loss, and facilitating crypsis. The divergence in the design of the respiratory system between unidirectionally ventilated lungs and tidally ventilated lungs, such as those found in mammals, is very old, with a minimum date for the divergence in the Permian Period. From this foundation, the avian and mammalian lineages evolved very different respiratory systems. I suggest the difference in design is due to the same selective pressure, expanded aerobic capacity, acting under different environmental conditions. High levels of atmospheric oxygen of the Permian Period relaxed selection for a thin blood-gas barrier and may have resulted in the homogeneous, broncho-alveolar design, whereas the reduced oxygen of the Mesozoic selected for a heterogeneous lung with an extremely thin blood-gas barrier. These differences in lung design may explain the puzzling pattern of ecomorphological diversification of Mesozoic mammals: all were small animals that did not occupy niches requiring a great aerobic capacity. The broncho-alveolar lung and the hypoxia of the Mesozoic may have restricted these mammals from exploiting niches of large body size, where cursorial locomotion can be advantageous, as well as other niches requiring great aerobic capacities, such as those using flapping flight. Furthermore, hypoxia may have exerted positive selection for a parasagittal posture, the diaphragm, and reduced erythrocyte size, innovations that enabled increased rates of ventilation and more rapid rates of diffusion in the lung.

Acceptability of digital anal cancer screening examinations in HIV-positive homosexual men.

OBJECTIVES: Anal cancer is more common in HIV-positive homosexual men than in HIV-negative homosexual men and the general population. Earlier diagnosis leads to improved prognosis. We aimed to determine if regular anal inspection and digital examination of asymptomatic homosexual men attending for routine HIV care were acceptable and to record the rate of referral for diagnosis of potentially malignant anal lesions. METHODS: We offered anal examinations to consecutive homosexual men with HIV infection aged ≥ 35 years during their routine HIV clinic visits, aiming to complete three examinations over a 12-month period. Acceptability questionnaires were completed at baseline and after each examination and doctors recorded examination findings and all resulting interventions. Hospital referral outcomes were collected and interventions were costed using the Australian Medical Benefits Schedule. RESULTS: Of 142 men who were offered enrolment in the study, 102 [72%; 95% confidence interval (CI) 64-79%] participated. Following the initial anal examinations, four men were referred to surgeons. Cancer was excluded in three men (3%; 95% CI 1-8%) and one was diagnosed with anal squamous cell carcinoma (SCC). Three men had anoscopy performed at the time and two were referred for colonoscopy. Ninety-eight per cent (95% CI 93-100%) of respondents said that they would probably have the examination next time. The intervention was estimated to cost approximately Australian $16 per examination. CONCLUSIONS: Regular anal digital examinations are an acceptable and inexpensive addition to the routine care of homosexual men with HIV infection.

Oral administration of domperidone in the first or third week of lactation: Effects on prolactin concentrations and mammary gene expression in sows and piglet growth.

The scope of the present study is endocrine and metabolic control of sow lactation. This project aimed to determine the impact of increasing prolactin concentrations via oral administration of the dopamine receptor antagonist domperidone in the first or third week of lactation in sows. Effects on sow hormonal and metabolic status, lactational performance, and gene expression in mammary epithelial cells were determined. Primiparous sows were divided in 3 treatments: 1) 10 mL of vehicle (table syrup) per os twice daily during the first and third weeks of lactation (Control, CTL, n = 23), 2) 0.5 mg/kg of domperidone per os twice daily during the first week of lactation (LACT1, n = 23), or 3) 0.5 mg/kg of domperidone given per os twice daily during the third week of lactation (LACT3, n = 22). Treated sows also received 10 mL of the vehicle twice daily during the other treatment period. Litter size was standardized to 12 ± 1 and piglets were weighed at birth, 24 h, and on d 8, 15, 22 (weaning), 35, and 56. Sow feed intake was recorded daily. Representative milk samples were obtained on d 7 and 21 of lactation for compositional analyses, and milk fat globules were used to measure mRNA abundances of various genes. Jugular blood samples were obtained from sows on d 1, 7, 14, and 21 of lactation to measure concentrations of prolactin, IGF-1, insulin, urea, and FFA. Concentrations of prolactin were increased (P < 0.01) at the end of the 7-d treatment period with domperidone, whether imposed in the first (LACT1) or third (LACT 3) week of lactation. No other blood variables were affected by treatments and neither was milk composition (P > 0.10). Sow BW, backfat thickness, or feed intake were not altered by treatments (P > 0.10), but piglet BW tended to be greater in litters from LACT3 compared with CTL sows on d 22 and 35 (P ≤ 0.10). Gene expression of EGF in milk fat globules tended to be (LACT1, P < 0.10) or was increased (LACT3, P < 0.05) after treatment, and the effect in LACT1 sows was maintained until d 21 of lactation. The mRNA abundance of SPP1 was increased (P < 0.05) in LACT1 vs CTL sows on d 7, and that of 3 major milk proteins tended to be (CSN1S2 and WAP, P < 0.10) or was greater (LALBA, P < 0.05) in LACT3 vs CTL sows on d 21 of lactation. Oral administration of domperidone during the first or third week of lactation increased prolactin concentrations and altered mRNA abundances of selected genes in milk fat globules. Yet, only the LACT 3 treatment positively affected piglet performance.

Exogenous porcine somatotropin administered to late pregnant gilts alters liver and muscle functionalities in pig foetuses.

Neonatal maturity depends on the maternal capacity to provide nutrients for foetal growth. This study aimed to investigate the effects of systemic administration of recombinant porcine somatotropin (pST), one of the main regulators of growth and metabolism, to pregnant gilts during late gestation on circulating nutrients and expression levels of genes in liver and skeletal muscle of their 110-day-old foetuses. Gilts received either daily injections of sterile water (control [CTL] group, n = 15) or of 5 mg of pST (pST group, n = 17) from days 90 to 109 of gestation. At day 110 postconceptus, pairs of foetuses (one of small and one of average size within a litter) were selected. Circulating fructose concentrations were greater, but circulating concentrations of urea were lower in pST than in CTL foetuses. Expression levels of genes involved in carbohydrate and lipid metabolism were more affected by pST treatment in liver than in muscle. Hepatic molecular changes suggest an inhibition of energy-consuming processes (glycogen and lipid biosynthesis) and the activation of energy-producing pathway (mitochondrial oxidation) in pST compared to CTL foetuses. Expression levels of some genes involved in intracellular degradation of proteins were greater in the liver of pST foetuses, and combined with lower uremia, this suggests a higher utilisation of protein sources in pST foetuses than in CTL foetuses. In muscle, molecular changes were mainly observed in the IGF-insulin axis. Altogether, pST-treated gilts seem to have a greater ability to support foetal liver development by the reorientation of energy and protein metabolism.

Spindle Chirp and other Sleep Oscillatory Features in Young Children with Autism.

Objectives: To determine whether spindle chirp and other sleep oscillatory features differ in young children with and without autism. Methods: Automated processing software was used to re-assess an extant set of polysomnograms representing 121 children (91 with autism [ASD], 30 typically-developing [TD]), with an age range of 1.35-8.23 years. Spindle metrics, including chirp, and slow oscillation (SO) characteristics were compared between groups. SO and fast and slow spindle (FS, SS) interactions were also investigated. Secondary analyses were performed assessing behavioural data associations, as well as exploratory cohort comparisons to children with non-autism developmental delay (DD). Results: Posterior FS and SS chirp was significantly more negative in ASD than TD. Both groups had comparable intra-spindle frequency range and variance. Frontal and central SO amplitude were decreased in ASD. In contrast to previous manual findings, no differences were detected in other spindle or SO metrics. The ASD group displayed a higher parietal coupling angle. No differences were observed in phase-frequency coupling. The DD group demonstrated lower FS chirp and higher coupling angle than TD. Parietal SS chirp was positively associated with full developmental quotient. Conclusions: For the first time spindle chirp was investigated in autism and was found to be significantly more negative than in TD in this large cohort of young children. This finding strengthens previous reports of spindle and SO abnormalities in ASD. Further investigation of spindle chirp in healthy and clinical populations across development will help elucidate the significance of this difference and better understand this novel metric.

Demystifying moderators and mediators in intellectual and developmental disabilities research: a primer and review of the literature.

BACKGROUND: Intellectual and developmental disability (IDD) researchers have been relatively slow to adopt the search for moderators and mediators, although these variables are key in understanding how and why relationships exist between variables. Although the traditional method of causal steps is useful for describing and understanding moderators and mediators, it is not sufficient for statistical analysis. METHODS: The theoretical and statistical processes of evaluating moderators and mediators are explained in terms familiar to IDD psychologists, using examples from IDD literature. Moderator and mediator analyses in five leading IDD journals are assessed for patterns of usage. RESULTS: Although the number of publications in the past decade exceeds previous years, the field is still behind others in both the quantity and quality of the use of moderators and mediators. CONCLUSION: The field as a whole will advance if the recent theoretical and technical advances outlined in this paper are employed.

Prolactin and the swine mammary gland.

Prolactin is a hormone that is most important for mammary development in swine. It is also essential for both the onset and the maintenance of lactation. In early studies, exogenous recombinant porcine prolactin was used to detect its biological effects on mammary tissue. In these studies, a stimulatory role of prolactin for mammary development of prepubertal gilts was demonstrated. However, when injected throughout lactation, prolactin did not increase sow milk yield likely because mammary receptors were saturated. The secretion of prolactin is largely under negative regulation via dopamine. Inhibition studies using the dopamine agonist bromocriptine showed that prolactin is required in the last third of gestation to sustain mammary development in gilts. When creating a hyperprolactinemic state during that same period, with the dopamine antagonist domperidone, differentiation of mammary epithelial cells was stimulated and milk yield in the subsequent lactation was increased. Domperidone given throughout lactation also led to greater milk yield. A study using domperidone in prepubertal gilts, however, did not reproduce the stimulatory effect of exogenous prolactin on mammary development and demonstrated that timing of the prolactin increase in relation to age of the animals is most important to elicit a response on mammary tissue. Attempts were made to use feed ingredients such as the plant extract from milk thistle, sylimarin, to stimulate prolactin secretion in sows. However, even though prolactin concentrations were increased, this augmentation was not important enough to have an impact on mammary development in late gestation or to increase milk yield. The current knowledge that hyperprolactinemia has beneficial effects for mammary development at various physiological stages and can enhance milk yield in swine leads to new avenues in elaborating strategies that could be used at the farm level to improve sow lactation performance.

Review: Improving the performance of neonatal piglets.

Newborn piglets have a high incidence of preweaning mortality that is not only associated with low birth weights but also with the presence of intra-uterine growth-restricted (IUGR) piglets. Such IUGR piglets are commonly seen in litters from hyperprolific sows as a result of insufficient placental transfer of nutrients. Nutritional strategies can be used prior to and during gestation to enhance foetal development and can also be implemented in the transition period to reduce the duration of farrowing and increase colostrum yield. Recent findings showed that the energy status of sows at the onset of farrowing is crucial to diminish stillbirth rate. Newborn piglets often fail to consume enough colostrum to promote thermostability and subsequent growth, and this is particularly problematic in very large litters when there are fewer available teats than the number of suckling piglets. One injection of 75 IU of oxytocin approximately 14 h after farrowing can prolong the colostral phase, hence increasing the supply of immunoglobulins to piglets. Nevertheless, assistance must be provided to piglets after birth in order to increase their chance of survival. Various approaches can be used, such as: (1) optimising the farrowing environment, (2) supervising farrowing and assisting newborn piglets, (3) using cross-fostering techniques, (4) providing nurse sows, and 5) providing artificial milk. Although research advances have been made in developing feeding and management strategies for sows that increase performance of their newborn piglets, much work still remains to be done to ensure that maximal outcomes are achieved.

Estrogen-related receptor gamma regulates mitochondrial and synaptic genes and modulates vulnerability to synucleinopathy.

Many studies implicate mitochondrial dysfunction as a key contributor to cell loss in Parkinson disease (PD). Previous analyses of dopaminergic (DAergic) neurons from patients with Lewy-body pathology revealed a deficiency in nuclear-encoded genes for mitochondrial respiration, many of which are targets for the transcription factor estrogen-related receptor gamma (Esrrg/ERRγ). We demonstrate that deletion of ERRγ from DAergic neurons in adult mice was sufficient to cause a levodopa-responsive PD-like phenotype with reductions in mitochondrial gene expression and number, that partial deficiency of ERRγ hastens synuclein-mediated toxicity, and that ERRγ overexpression reduces inclusion load and delays synuclein-mediated cell loss. While ERRγ deletion did not fully recapitulate the transcriptional alterations observed in postmortem tissue, it caused reductions in genes involved in synaptic and mitochondrial function and autophagy. Altogether, these experiments suggest that ERRγ-deficient mice could provide a model for understanding the regulation of transcription in DAergic neurons and that amplifying ERRγ-mediated transcriptional programs should be considered as a strategy to promote DAergic maintenance in PD.

Subglottal pressure and fundamental frequency control in contact calls of juvenile Alligator mississippiensis.

Vocalization is rare among non-avian reptiles, with the exception of the crocodilians, the sister taxon of birds. Crocodilians have a complex vocal repertoire. Their vocal and respiratory system is not well understood but appears to consist of a combination of features that are also found in the extremely vocal avian and mammalian taxa. Anatomical studies suggest that the alligator larynx is able to abduct and adduct the vocal folds, but not to elongate or shorten them, and is therefore lacking a key regulator of frequency, yet alligators can modulate fundamental frequency remarkably well. We investigated the morphological and physiological features of sound production in alligators. Vocal fold length scales isometrically across a wide range of alligator body sizes. The relationship between fundamental frequency and subglottal pressure is significant in some individuals at some isolated points, such as call onset and position of maximum fundamental frequency. The relationship is not consistent over large segments of the call. Fundamental frequency can change faster than expected by pressure changes alone, suggesting an active motor pattern controls frequency and is intrinsic to the larynx. We utilized a two-mass vocal fold model to test whether abduction and adduction could generate this motor pattern. The fine-tuned interplay between subglottal pressure and glottal adduction can achieve frequency modulations much larger than those resulting from subglottal pressure variations alone and of similar magnitude, as observed in alligator calls. We conclude that the alligator larynx represents a sound source with only two control parameters (subglottal pressure and vocal fold adduction) in contrast to the mammalian larynx in which three parameters can be altered to modulate frequency (subglottal pressure, vocal fold adduction and length/tension).