Search

Alarm signals have evolved to communicate imminent threats to conspecifics but animals may also perceive other species' alarm displays to obtain adaptive information. In birds, mixed‐species foraging flocks are often structured around a focal sentinel species, which produces reliable alarm calls that inform eavesdropping non‐sentinel heterospecifics about predation risk. Ongoing work has revealed that several species can recognize the alarm calls of certain sentinel species even without prior encounters, including when these are from distant biogeographic regions. Similar work has yet to examine whether naive subjects' responses to unfamiliar sentinel alarm calls differ from responses to non‐sentinel alarm calls. Here we played the alarm calls of three subtropical Asian bird species that participate in mixed species flocks, to temperate North American birds. Birds responded most to the alarm call of an allopatric core sentinel and a local sympatric sentinel control species, less so to an allopatric non‐core sentinel, and least so to an allopatric non‐sentinel and a negative control stimulus. These patterns provide evidence that broad phylogenetic and geographic recognition is a pertinent aspect of sentinel alarm calls in general.

For parents of color, publicized racial violence can heighten concerns about their children's safety. The goal of this study was to test whether this form of race-related stress exacerbates maternal posttraumatic stress disorder (PTSD) symptoms over a 4-month period in families of color. Participants included 262 U.S. mothers with a lifetime mental health diagnosis (67.6% non-Hispanic White, 15.6% African-American/Black, 16.8% other family of color). Mothers completed online surveys and open-ended questions, including appraisals of the meaning of the 2020 race-related events (i.e., George Floyd's death, subsequent protests) in relation to their children's future. Open-ended responses were quantified using LIWC15 text analysis for emotion word frequency and thematic coding for perceived implications. In ANCOVA, there were significant racial group differences in appraisals, ds = 0.09-0.57. The responses from mothers of Black children included fewer positive and more negative emotion words than mothers of White children; they also included more perceived negative implications than all other mothers but did not vary on perceived positive implications. In regression analyses, there were significant moderating effects of race/ethnicity in the association between appraisals and PTSD symptom course such that negative appraisals predicted a subsequent increase in PTSD symptoms only for mothers of Black children, βs = .26-.37. Variations in event appraisals were unrelated to PTSD symptom course for other mothers. These findings provide longitudinal support for the link between vicarious racism exposure and PTSD symptoms and highlight one potential form of racism-related stress for parents of Black children., (© 2022 The Authors. Journal of Traumatic Stress published by Wiley Periodicals LLC on behalf of International Society for Traumatic Stress Studies.)

Objective: Patients with diffuse cutaneous systemic sclerosis (dcSSc) display a complex clinical phenotype. Transcriptional profiling of whole blood or tissue from patients are affected by changes in cellular composition that drive gene expression and an inability to detect minority cell populations. We undertook this study to focus on the 2 main subtypes of circulating monocytes, classical monocytes (CMs) and nonclassical monocytes (NCMs) as a biomarker of SSc disease severity., Methods: SSc patients were recruited from the Prospective Registry for Early Systemic Sclerosis. Clinical data were collected, as well as peripheral blood for isolation of CMs and NCMs. Age-, sex-, and race-matched healthy volunteers were recruited as controls. Bulk macrophages were isolated from the skin in a separate cohort. All samples were assayed by RNA sequencing (RNA-seq)., Results: We used an unbiased approach to cluster patients into 3 groups (groups A-C) based on the transcriptional signatures of CMs relative to controls. Each group maintained their characteristic transcriptional signature in NCMs. Genes up-regulated in group C demonstrated the highest expression compared to the other groups in SSc skin macrophages, relative to controls. Patients from groups B and C exhibited worse lung function than group A, although there was no difference in SSc skin disease at baseline, relative to controls. We validated our approach by applying our group classifications to published bulk monocyte RNA-seq data from SSc patients, and we found that patients without skin disease were most likely to be classified as group A., Conclusion: We are the first to show that transcriptional signatures of CMs and NCMs can be used to unbiasedly stratify SSc patients and correlate with disease activity outcome measures., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Melatonin, a neurohormone that binds to two G protein-coupled receptors MT 1 and MT 2, is involved in pain regulation, but the distinct role of each receptor has yet to be defined. We characterized the nociceptive responses of mice with genetic inactivation of melatonin MT 1 (MT 1 -/- ), or MT 2 (MT 2 -/- ), or both MT 1 /MT 2 (MT 1 -/- /MT 2 -/- ) receptors in the hot plate test (HPT), and the formalin test (FT). In HPT and FT, MT 1 -/- display no differences compared to their wild-type littermates (CTL), whereas both MT 2 -/- and MT 1 -/- /MT 2 -/- mice showed a reduced thermal sensitivity and a decreased tonic nocifensive behavior during phase 2 of the FT in the light phase. The MT 2 partial agonist UCM924 induced an antinociceptive effect in MT 1 -/- but not in MT 2 -/- and MT 1 -/- /MT 2 -/- mice. Also, the competitive opioid antagonist naloxone had no effects in CTL, whereas it induced a decrease of nociceptive thresholds in MT 2 -/- mice. Our results show that the genetic inactivation of melatonin MT 2 , but not MT 1 receptors, produces a distinct effect on nociceptive threshold, suggesting that the melatonin MT 2 receptor subtype is selectively involved in the regulation of pain responses., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Small rectal neuroendocrine tumours are good candidates for endoscopic resection provided that complete pathological resection (R0) is obtained and their risk of metastatic progression is low. We conducted a large multicentre nationwide study to evaluate the outcomes of the management of non-metastatic rectal neuroendocrine tumours ≤2 cm diagnosed endoscopically., Patients and Methods: The medical records, the endoscopic and pathological findings of patients with non-metastatic rectal neuroendocrine tumours ≤2 cm managed from January 2000-June 2018 in 16 French hospitals, were retrospectively analysed. The primary objective was to describe the proportion of R0 endoscopic resections., Results: A total of 329 patients with 345 rectal neuroendocrine tumours were included, 330 (96%) tumours were managed by local treatments: 287 by endoscopy only and 43 by endoscopy followed by transanal endoscopic microsurgery. The final endoscopic R0 rate was 134/345 (39%), which improved from the first endoscopy (54/225, 24%), to the second (60/100, 60%) and the third endoscopy (20/26, 77%). R0 was associated with endoscopic technique (90% for advanced techniques, 40% for mucosectomy and 17% for polypectomy), but not with tumour or patient characteristics. Twenty patients had metastatic disease, which was associated with tumour size ≥10 mm (odds ratio: 9.1, 95% confidence interval (3.5-23.5)), tumour grade G2-G3 (odds ratio: 4.2, (1.5-11.7)), the presence of muscular (odds ratio: ∞, (11.9-∞)) and lymphovascular invasion (odds ratio: 57.2, (5.6-578.9))., Conclusions: The resection of small rectal neuroendocrine tumours often requires multiple procedures. Training of endoscopists is necessary in order to better recognise these tumours and to perform the appropriate resection technique., (© Author(s) 2019.)

Objectives: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis., Methods: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes., Results: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified., Conclusions: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis., (© 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Trypanosomatids such as Leishmania, Trypanosoma brucei and Trypanosoma cruzi belong to the order Kinetoplastida and are the source of many significant human and animal diseases. Current treatment is unsatisfactory and is compromised by the rising appearance of drug resistant parasites. Novel and more effective chemotherapeutics are urgently needed to treat and prevent these devastating diseases, which relies on the identification of essential, parasite specific targets that are absent in the host. Lipids constitute essential components of the cell and carry out multiple critical functions from building blocks of biological membranes to regulatory roles in signal transduction, organellar biogenesis, energy storage, and virulence. The recent technological advances of lipidomics has facilitated the broadening of our knowledge in the field of cellular lipid content, structure, functions, and metabolic pathways., Main Body: This review highlights the application of lipidomics (i) in the characterization of the lipidome of kinetoplastid parasites or of their subcellular structure(s), (ii) in the identification of unique lipid species or metabolic pathways that can be targeted for novel drug therapies, (iii) as an analytic tool to gain a deeper insight into the roles of specific enzymes in lipid metabolism using genetically modified microorganisms, and (iv) in deciphering the mechanism of action of anti-microbial drugs on lipid metabolism. Lastly, an outlook stating where the field is evolving is presented., Conclusion: Lipidomics has contributed to the expanding knowledge related to lipid metabolism, mechanism of drug action and resistance, and pathogen-host interaction of trypanosomatids, which provides a solid basis for the development of better anti-parasitic pharmaceuticals.

Objective: Polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased risk of developing rheumatoid arthritis (RA). This study was undertaken to determine the role of IRF5 in a mouse model of arthritis development., Methods: K/BxN serum-transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, Toll-like receptor 2 (TLR2), TLR3, TLR4, and TLR7 to determine the pathways through which IRF5 might promote arthritis. In vitro studies were performed to determine the role of IRF5 in interleukin-1 (IL-1) receptor and TLR signaling., Results: Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient, and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1β formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce proinflammatory cytokine production in disease-relevant cell types in an IRF5-dependent manner., Conclusion: Our findings indicate that IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating proinflammatory cytokine production downstream of TLR7 and TLR3. Since TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA, since RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are up-regulated in the joints of RA patients., (© 2015, American College of Rheumatology.)

The involvement of melatonin in mammalian brain pathophysiology has received growing interest, but information about the anatomical distribution of its two G-protein-coupled receptors, MT1 and MT2 , remains elusive. In this study, using specific antibodies, we examined the precise distribution of both melatonin receptors immunoreactivity across the adult rat brain using light, confocal, and electron microscopy. Our results demonstrate a selective MT1 and MT2 localization on neuronal cell bodies and dendrites in numerous regions of the rat telencephalon, diencephalon, and mesencephalon. Confocal and ultrastructural examination confirmed the somatodendritic nature of MT1 and MT2 receptors, both being localized on neuronal membranes. Overall, striking differences were observed in the anatomical distribution pattern of MT1 and MT2 proteins, and the labeling often appeared complementary in regions displaying both receptors. Somadendrites labeled for MT1 were observed for instance in the retrosplenial cortex, the dentate gyrus of the hippocampus, the islands of Calleja, the medial habenula, the suprachiasmatic nucleus, the superior colliculus, the substantia nigra pars compacta, the dorsal raphe nucleus, and the pars tuberalis of the pituitary gland. Somadendrites endowed with MT2 receptors were mostly observed in the CA3 field of the hippocampus, the reticular thalamic nucleus, the supraoptic nucleus, the inferior colliculus, the substantia nigra pars reticulata, and the ventrolateral periaqueductal gray. Together, these data provide the first detailed neurocytological mapping of melatonin receptors in the adult rat brain, an essential prerequisite for a better understanding of melatonin distinct receptor function and neurophysiology., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The reproductive and adaptative behavior of wild rodents is synchronized primarily by the photoperiod. The viscacha, a South American rodent of nocturnal habits and seasonal reproduction is photoperiod-dependent and its reproductive behavior is regulated by the retinohypothalamic-pituitary pineal axis. Adult males exhibit an annual reproductive cycle with periods of maximum gonadal activity (summer-early autumn) and gonadal regression (winter). The corpus and the cauda, the most sensitive segments of the epididymis to changes induced by the photoperiod, were analyzed using electron microscopy and enzymatic biochemistry. During gonadal regression, principal and clear cells showed signs of involution with respect to the activity period. These were characterized by more irregular nuclei, smaller cytoplasms, large vacuoles, altered mitochondria, and glycogen deposits. All cellular populations of the epididymal epithelium in regression presented abundant lysosome-like dense bodies during the active period. In addition, we measured the activity of four acid glycosidases in the cauda epididymis along the reproductive cycle. N-acetyl-beta-D-glucosaminidase (NAG), an enzyme that degrades endocytosed substances from the epididymal lumen, increased significantly during gonadal regression relative to the active period. These results demonstrate that the viscacha epididymis exhibits significant ultrastructural and biochemical changes during the reproductive cycle. We demonstrate that during regression, melatonin secretion in viscacha increases. This study shows that the epididymal epithelium is reduced. Thus, we postulate that the changes observed in the epididymis are modulated by pineal melatonin. Despite these changes, the epididymis might maintain a microenvironment suitable for the survival of stored spermatozoa., ((c) 2009 Wiley-Liss, Inc.)

Objectives: To determine interobserver agreement between radiologists for computed tomography (CT) angiography and venography. CT venography of the lower extremities combined with standard CT angiography of the chest may result in an increased overall diagnosis rate of venous thromboembolism (pulmonary embolism or deep venous thrombosis)., Methods: The study had a retrospective cohort design. The population consisted of emergency department patients who were evaluated for suspected pulmonary embolism. A random sample of 50 patients diagnosed and treated for venous thromboembolism and 50 age- and gender-matched patients whose CT angiograms and venograms were read as negative were enrolled. The original reading (R1) was compared with readings of two study radiologists: R2, a general radiologist, and R3, a radiologist with fellowship training in cross-sectional imaging. All readers were blinded to each other., Results: Both R2 and R3 found both CT angiogram and venogram components technically adequate in 95% (95% CI = 89% to 98%) and 86% (95% CI = 78% to 92%) of studies, respectively. The agreement was very good for CT angiography (lowest agreement = 92%; lowest kappa = 0.83) and was good for CT venography (85%, kappa = 0.65). In nine cases, R1 read the CT angiogram as negative but the venogram as positive for DVT, whereas both R2 and R3 read both components as negative in four of these nine, suggesting a false-positive isolated DVT rate of 44% (95% CI = 19% to 73%). In no case did R1 read both scan components as negative when R2 and R3 agreed on presence of pulmonary embolism or DVT., Conclusions: Diagnosis of pulmonary embolism on CT angiography is more reliable than diagnosis of isolated DVT on CT venography.

Objectives: To determine the prevalence of hip and pelvic fractures in emergency department (ED) patients with hip pain and negative standard initial radiographs., Methods: This was a retrospective, cohort study at an academic, community-based ED. ED patients presenting during a one-year period with hip pain for whom a plain-film radiograph was obtained were included. Eligible patients were identified by query of electronic records. Plain radiographs and magnetic resonance images (MRIs) were ordered at the discretion of the treating physician. Initial plain radiographs were read at the point of care by board-certified radiologists. MRI images were reviewed by radiologists with fellowship training in musculoskeletal imaging. Structured follow-up at more than one month postvisit was conducted to rule out a subsequent diagnosis of hip fracture. Ninety-five-percent confidence intervals (95% CIs) and kappa (kappa) were calculated as appropriate., Results: Seven hundred sixty-four of 895 patients (85.3%) had follow-up completed (study group). Within the study group, 219 patients (29%) had evidence of fracture on initial radiographs. Of the 545 patients with negative initial radiographs, 62 patients (11.4%) underwent hip MRI during the ED visit. MRI identified 24 additional patients with hip fractures. Interobserver agreement for the presence of fracture on MRI was very good (kappa = 0.847). For patients with negative initial plain radiographs who did not have a hip MRI, follow-up did not identify any of these patients as having a subsequent diagnosis of fracture. Thus, 24 of 545 (4.4%; 95% CI = 3.0% to 6.5%) patients with negative initial plain radiographs had a hip fracture., Conclusions: In this cohort of ED patients with symptoms suspicious for hip fracture who had negative standard radiographs, the authors found that 4.4% were subsequently diagnosed as having fracture. Further studies are warranted to identify characteristics of patients requiring advanced hip imaging studies.

Background: Hepatitis C virus (HCV) is usually transmitted via the parenteral route, but there are widely discrepant findings on its possible sexual transmission. Thus there are no recommendations concerning protected sex for couples in which only one partner is HCV-infected. Whether HIV or other sexually transmitted diseases could favour HCV transmission remains unclear, but recent data suggesting an increasing incidence of acute HCV in HIV-infected men underline the major public health implications of this issue., Case Reports: Between June 2002 and July 2003, five HIV-infected homosexually active men presented with primary (n=4) and secondary (n=1) syphilis and concomitant abnormal liver function tests revealing acute asymptomatic HCV seroconversion. Other causes of acute viral hepatitis were inquired into and excluded. Highly at-risk sexual behaviour, including unprotected anal intercourse and unsafe oral sex, with concomitant syphilis, was found to be the only identifiable important risk factor for transmission of HCV., Conclusions: Sexual transmission may be fuelling a significant increase in HCV seroconversions among HIV-infected men who have highly risky sexual behaviours. Given the recent data suggesting the spread of sexually transmitted infections among HIV-infected gay men, specific recommendations concerning safe sex are urgently needed.