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Objetivo: La dopamina es un importante mediador de los efectos reforzadores de la cocaína, y las alteraciones en la actividad de la dopamina podrían estar involucradas en la dependencia de la cocaína. Los objetivos del presente estudio fueron caracterizar la actividad presináptica y postsináptica de la dopamina en individuos dependientes de la cocaína recientemente desintoxicados. En concreto, se evaluó la respuesta de la dopamina a una provocación aguda con anfetamina en las subregiones estriatales en individuos dependientes de cocaína y participantes sanos de comparación utilizando la tomografía por emisión de positrones (PET). Además, se investigó la relación entre esta respuesta a la dopamina y la elección de autoadministrarse cocaína en un modelo de laboratorio para las recaídas. Método: Veinticuatro individuos con dependencia de cocaína y 24 individuos sanos apareados se sometieron a exploraciones con [11C]racloprida en una situación inicial y después de la administración intravenosa de anfetamina (0,3 mg/kg). Los participantes con dependencia de cocaína también llevaron a cabo sesiones de autoadministración de cocaína, en las que tras una dosis de cebado (priming) de cocaína podían escoger entre autoadministrarse dosis posteriores de cocaína o recibir una recompensa económica. Resultados: La dependencia de cocaína se asoció con una acusada reducción de la liberación de dopamina provocada por anfetamina en cada una de las subregiones funcionales del estriado (estriado límbico: - 1,2 % en participantes con dependencia de cocaína frente a - 12,4 % en individuos sanos; estriado asociativo: - 2,6 frente a - 6,7 %, respectivamente; estriado sensoriomotor: - 4,3 frente a - 14,1 %, respectivamente). La disminución de la transmisión de dopamina en el estriado ventral y en el caudado anterior pronosticó la elección de cocaína frente al dinero. Conclusiones: La dependencia de cocaína se asocia a un deterioro de la actividad de la dopamina, y este deterioro parece desempeñar un papel fundamental en las recaídas. [ABSTRACT FROM AUTHOR]

Striatal dopamine D2 receptors have been implicated in the neurobiology of cocaine addiction. Previous imaging studies showed reduced striatal D2 receptor availability in chronic cocaine abusers, and animal studies suggested that Iow D2 receptor availability promotes cocaine self-administration. Here, D2 receptor availability was assessed with positron emission tomography (PET) and [11C]raclopride in the limbic, associative, and sensori-motor subdivisions of the striatum in 17 recently detoxified chronic cocaine-dependent (CCD) subjects and 17 matched healthy control (HC) subjects. In addition, the relationship between regional D2 receptor availability and behavioral measures obtained in cocaine self-administration sessions was investigated in CCD subjects. [11C]Raclopride binding potential was significantly reduced by 15.2% in the limbic striatum, 15.0% in the associative striatum, and 17.1 % in the sensori-motor striatum in CCD subjects compared to HC subjects. In CCD subjects, no relationship was detected between D2 availability in striatal regions and either the positive effects of smoked cocaine or the choice of cocaine over an alternative reinforcer (money) following a priming dose of cocaine (a laboratory model of relapse). Thus, this study confirms previous reports of a modest decrease in D2 receptor availability in CCD subjects, and establishes that this decrease is generalized throughout the striatum. However, this study failed to demonstrate a relationship between D2 receptor availability and cocaine-induced cocaine-taking behavior. Additional research is warranted to unravel potential neurobiological traits that might confer vulnerability to relapse in detoxified CCD subjects. [ABSTRACT FROM AUTHOR]

(-)-N-Propyl-norapomorphine (NPA) is a full dopamine (DA) D2 receptor agonist and [11C]NPA is a suitable radiotracer to image D2 receptors configured in a state of high affinity for agonists with positron emission tomography (PET). In this study the vulnerability of the in vivo binding of [11C]NPA to acute fluctuation in synaptic DA was assessed with PET in baboons and compared to that of the reference D2 receptor antagonist radiotracer [11C]raclopride. Three male baboons were studied with [11C]raclopride and [11C]NPA under baseline conditions and following administration of the potent DA releaser amphetamine (0.3, 0.5, and 1.0 mg kg-1 i.v.). Kinetic modeling with an arterial input function was used to derive the striatal specific-to-nonspecific equilibrium partition coefficient (V3″). [11C]Raclopride V3″ was reduced by 24 ± 10%, 32 ± 6%, and 44 ± 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg-1, respectively. [11C]NPA V3″ was reduced by 32 ± 2%, 45 ± 3%, and 53 ± 9% following amphetamine doses of 0.3, 0.5, and 1.0 mg kg-1, respectively. Thus, endogenous DA was more effective at competing with [11C]NPA binding compared to [11C]raclopride binding, a finding consistent with the pharmacology of these tracers (agonist vs. antagonist). These results also suggest that 71% of D2 receptors are configured in a state of high affinity for agonists in vivo. In conclusion, [11C]NPA might provide a superior radiotracer to probe presynaptic DA function with PET in health and disease. Synapse 52:188-208, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic has disrupted medical care, increased isolation, and exacerbated anxiety in breast cancer patients. Since March 2020, Breastcancer.org experienced a sustained surge in requested pandemic‐related information and support. To characterize the pandemic‐related experiences of breast cancer patients, we surveyed the Breastcancer.org Community early in the COVID‐19 era. Methods: Breastcancer.org Community members were invited to complete an online questionnaire regarding their experience during the pandemic. Self‐reported data on demographics, comorbidities, care disruptions, anxiety, coping ability, telemedicine use, and satisfaction with care were collected. Results were analyzed using Stata 16.0 (Stata Corp., Inc). Results: Included were 568 current and previous breast cancer patients, primarily with U.S. residence. Overall, 43.8% reported at least one comorbidity associated with severe COVID‐19 illness and 61.9% experienced care delays. Moderate to extreme anxiety about contracting COVID‐19 was reported by 36.5%, increasing with number of comorbidities (33.0% vs. 55.4%, p = 0.021), current breast cancer diagnosis (30.4% vs. 42.5%, p = 0.011), and poorer coping ability (15.5% vs. 53.9%, p < 0.0001). Moderate to extreme anxiety about cancer care disruptions was reported by 29.1%, increasing with current breast cancer diagnosis (19.1% vs. 38.9%, p < 0.0001), actual delayed care (18.9% vs. 35.3%, p < 0.0001), and poorer coping ability (13.1% vs. 57.7%, p < 0.0001). Most utilized telehealth and found it helpful, but also expressed increased anxiety and subjectively expressed that these were less preferable. Conclusion: Early in the COVID‐19 pandemic, anxiety was reported by a large proportion of breast cancer patients, with increased prevalence in those with risk factors. Attention to mental health is critical, as emotional distress not only harms quality of life but may also compromise outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The value of the human–animal bond to human health and well-being, especially in a post-pandemic world, merits further study and advocacy. Social isolation and loneliness are widespread and exact a heavy toll on human physical and mental health, a burden worsened by the social distancing and quarantine measures of COVID-19. Interaction between humans and animals, whether experienced in the home or through animal-assisted therapy, has been shown to ease loneliness and lessen social isolation. This article describes how an innovative multidisciplinary partnership of leaders in the area of human–animal interaction—from veterinary science to nonprofit organizations and the pet care community—came together to advance research and practice, as well as tackle barriers in this promising area. It describes the concrete results already achieved by the initiative and offers a roadmap for others seeking to bring together diverse stakeholders to address issues and unmet needs through a similar collaborative model (herein called a consortium). The mental and physical human costs of social isolation and loneliness—and their possible amelioration through human–animal interaction (HAI)—have both received intense attention since the onset of the COVID-19 pandemic, and its lockdowns, quarantines, and related mitigation measures. Concern about society's "loneliness epidemic", however, predates the pandemic, as does serious inquiry into HAI as a positive intervention. Recognizing the potential of companion animals to make a difference on an important public health issue, the Consortium on Social Isolation and Companion Animals—a novel partnership of the Human Animal Bond Research Institute (HABRI) and Mars Petcare—launched a joint initiative in 2019 to advance HAI research, address barriers to HAI, and support best practices in bringing together animals and people to ease loneliness. Beginning with a first-ever summit of multidisciplinary thought leaders, this collaboration has already yielded actionable insights and research projects. As a novel partnership initiative in the HAI field, it offers a promising model for future cross-disciplinary forward thinking to elevate HAI for the mutual benefit of companion animals and their welfare, as well as vulnerable human populations. [ABSTRACT FROM AUTHOR]

Cases of tuberculosis identified during 1992–1994 through an active tuberculosis surveillance network among six hospitals that serve New York City (the TBNetwork) were analyzed according to the occupational status of the patients. Clinical data were obtained by review of medical records, and restriction fragment length polymorphism (RFLP) typing of Mycobacterium tuberculosis isolates was performed. No known nosocomial outbreaks of tuberculosis occurred at these hospitals in the study period. Occupational status was known for 142 of 201 patients whose isolates were available for strain typing. Patients infected by organisms with a clustered strain typing pattern, as determined by RFLP analysis, were presumed to have recently acquired disease. RFLP typing revealed that isolates from 13 (65%) of 20 health care workers and 50 (41%) of 122 non-health care workers had a clustered RFLP pattern. The strains infecting eight (89%) of nine health care workers seropositive for human immunodeficiency virus (HIV) had a clustered RFLP pattern. Multivariate analysis of 75 patients with known HIV and occupational status revealed that HIV status (P = .03) and health care worker status (P = .02; RR = 2.77) were independent risk factors for a clustered RFLP strain. These findings suggest that many of the apparently sporadic cases of tuberculosis among health care workers may be due to unrecognized occupational transmission. [ABSTRACT FROM PUBLISHER]

Background Dengue fever, a major public health problem throughout tropical and subtropical regions, has often unpredictable clinical evolution and outcomes. Thrombocytopenia is a common laboratory finding in dengue fever and severe dengue during the dengue critical phase. To the best of our knowledge, there is no clinical data about patient and disease factors that could predict in a short time the platelet recovery. Mean platelet volume (MPV), a measurement of platelet size, has a strong inverse correlation with platelet count and could indirectly reflect bone marrow activity. The aim of this study was to describe the behavior of MPV during the platelet count nadir and recovery. Methods An observational prospective study was conducted. We included patients with confirmed dengue virus infection with SD BIOLINE Dengue Duo kit (Abbott, Santa Clara, USA; former Alere Inc. Waltham, USA) attended at Fundación Valle del Lili, Cali - Colombia. Blood count was analyzed by xn-3000 system impedance method (Sysmex, Kobe, Japan). Laboratory and clinical data were recollected from clinical charts and clinical laboratory database. Platelet count (PC) and MPV were measured repeatedly during clinical management. Time was measured from the first blood count. A non-parametric analysis with a cubic smoothing spline was performed for platelet count and MPV. Results A total of 54 patients were analyzed from April 2016 to January 2016. 50% of patients had at least three blood counts. The median of the lowest PC was 112,500/L (IQR = 67,000–148,500), and the median of the highest MPV was 11. 25 fL (IQR = 10. 42–12. 15). MPV increased from the first blood count until day six, while platelets presented slight fluctuations. On the sixth day after first blood count, MPV presented a high peak that suggests an inverse relationship with a platelets decrease (Figure 1). Conclusion MPV increased with thrombocytopenia during the critical period and its decline precedes platelet count recovery. MPV could be useful to predict the platelet count recovery. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Candidemia and invasive candidiasis are major causes of morbidity and mortality among critically ill patients and neonates. Every year more than 250,000 people develop invasive candidiasis, causing more than 50,000 deaths worldwide. Candida albicans is the most frequently isolated species worldwide. However, species distribution, epidemiology, and resistance have changed. C. parapsilosis complex (CPC), which has a global rate of fluconazole (FCZ) resistance range between 2 and 5% and has been related to echinocandins resistance, is the second most isolated species at Fundación Valle del Lili (FVL). We aim to describe the clinical and microbiological characteristics of fungal infections by C. parapsilosis , and determine FCZ resistance rates. Methods An observational prospective study was conducted. The study included patients with CPC isolations attended at FVL from 2016 to 2017. The strains were identified by mass spectrometry (MALDI TOF® Bruker, Biotyper 3.1). Minimal inhibitory concentrations (MIC) were determined by broth microdilution (M27 A3 CLSI). Statistical univariate analysis was performed; Differences between resistant cases and nonresistant cases were assessed through U Mann–Whitney test, Pearson chi-squared test or Fisher exact test. Results 55 patients had CPC isolations during the study period: 18 newborns, 13 children, and 24 adults. Most isolations were from blood cultures (n = 31) (14 of them newborns), bronchoalveolar lavage (n = 9), peritoneal fluid (n = 8), and catheter tips (n = 3). The resistance was 36%. 52 strains were C. parapsilosis ss, of them, 20 were FCZ resistant; 3 strains were C. orthopsilosis , all of them FCZ sensitive. The MIC50 = 1 µg/mL and MIC90 = 16 µ/mL. Patients with previous antifungal treatment had a higher risk of FCZ resistance (RR: 2.14, 95% IC 1.07–4.26). The mortality brute rate was 30%, patients with diabetes and renal failure death risk (RR: 3.1, 95% CI: 1.4 – 6.9) and (RR: 2.96, 95% CI: 1.4 – 6.4), respectively. Candidemia was present in 50% of deaths among children with parenteral nutrition. Conclusion Fluconazole resistance in CPC has increased in the last decade. Newborns receiving parenteral nutrition had a higher proportion of CPC fungemia; we also found higher mortality rates among this population. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Chronic intermittent hypoxia (CIH) is a model for obstructive sleep apnea. The paraventricular nucleus (PVN) of the hypothalamus has been suggested to contribute to CIH-induced exaggerated cardiorespiratory reflexes, sympathoexcitation and hypertension. This may occur, in part, via activation of the dense catecholaminergic projections to the PVN that originate in the brainstem. However, the contribution of norepinephrine (NE) and activation of its alpha-adrenergic receptors (α-ARs) in the PVN after CIH exposure is unknown. We hypothesized CIH would increase the contribution of catecholaminergic input. To test this notion, we determined the expression of α-AR subtypes, catecholamine terminal density, and synaptic properties of PVN parvocellular neurons in response to α-AR activation in male Sprague-Dawley normoxic (Norm) and CIH exposed rats. CIH decreased mRNA for α 1d and α 2b AR. Dopamine-β-hydroxylase (DβH) terminals in the PVN were similar between groups. NE and the α 1 -AR agonist phenylephrine (PE) increased sEPSC frequency after Norm but not CIH. Block of α 1 -ARs with prazosin alone did not alter sEPSCs after either Norm or CIH but did prevent agonist augmentation of sEPSC frequency following normoxia. These responses to NE were mimicked by PE during action potential block suggesting presynaptic terminal alterations in CIH. Altogether, these results demonstrate that α 1 -AR activation participates in neuronal responses in Norm, but are attenuated after CIH. These results may provide insight into the cardiovascular, respiratory and autonomic nervous systems alterations in obstructive sleep apnea. • CIH decreased mRNA transcript for alpha-1d and 2b adrenoreceptors but not dopamine beta-hydroxylase terminals in PVN • CIH ablated the alpha-1 adrenergic receptor increases in synaptic currents • The reduction in adrenergic modulation of synaptic currents occurs via presynaptic action potential-independent mechanisms [ABSTRACT FROM AUTHOR]

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10–50 kDa), medium (MMW, 50–100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment. [ABSTRACT FROM AUTHOR]

The 88000: an engine for multiprocessing The Motorola 88000 chip set provides a well-balanced foundation for multiprocessor applications. In developing the 88000, the designers targeted it to multiprocessing applications by […]

Children with epilepsy experience cognitive deficits and well-being issues that have detrimental effects on their development. Pharmacotherapy is the standard of care in epilepsy; however, few interventions exist to promote cognitive development and to mitigate disease burden. We aimed to examine the impact of two different modalities of neurofeedback (NFB) on cognitive functioning and quality-of-life (QOL) measurements in children and adolescents with controlled focal epilepsy. The study also explored the effects of NFB on clinical outcomes and electroencephalography (EEG) quantitative analysis. Participants (n = 44) with controlled focal epilepsy were randomized to one of three arms: sensorimotor rhythm (SMR) NFB (n = 15), slow cortical potentials (SCP) NFB (n = 16), or sham NFB (n = 13). All participants received 25 sessions of intervention. The attention switching task (AST), Liverpool Seizure Severity Scale (LSSS), seizure frequency (SF), EEG power spectrum, and coherence were measured at baseline, postintervention, and at 3-month follow-up. In children and adolescents with controlled focal epilepsy, SMR training significantly reduced reaction time in the AST (p = 0.006), and this was correlated with the difference of change for theta power on EEG (p = 0.03); only the SMR group showed a significant decrease in beta coherence (p = 0.03). All groups exhibited improvement in QOL (p = < 0.05). This study provides the first data on two NFB modalities (SMR and SCP) including cognitive, neurophysiological, and clinical outcomes in pediatric epilepsy. Sensorimotor rhythm NFB improved cognitive functioning, while all the interventions showed improvements in QOL, demonstrating a powerful placebo effect in the sham group. • Neurofeedback (NFB) can improve cognitive performance in pediatric participants with pharmacoresponsive focal epilepsy. • Sensorimotor rhythm (SMR) NFB modulates theta activity, and this is associated with improvements in reaction time. SMR NFB decreases beta hyperconnectivity over the sensorimotor cortex. • Treatment expectations and positive motivation generate strong placebo effects on subjective QOL measurements. [ABSTRACT FROM AUTHOR]

Substance use disorder is a leading causes of preventable disease and mortality. Drugs of abuse cause molecular and cellular changes in specific brain regions and these neuroplastic changes are thought to play a role in the transition to uncontrolled drug use. Neuroimaging has identified neural substrates associated with problematic substance use and may offer clues to reduce its burden on the patient and society. Here, we provide a narrative review of neuroimaging studies that have examined the structures and circuits associated with reward, cues and craving, learning, and cognitive control in substance use disorders. Most studies use advanced MRI or positron emission tomography (PET). Many studies have focused on the dopamine neurons of the ventral tegmental area, and the regions where these neurons terminate, such as the striatum and prefrontal cortex. Decreases in dopamine receptors and transmission have been found in chronic users of drugs, alcohol, and nicotine. Recent studies also show evidence of differences in structure and function in substance users relative to controls in brain regions involved in salience evaluation, such as the insula and anterior cingulate cortex. Balancing between reward-related bottom-up and cognitive-control-related top-down processes is discussed in the context of neuromodulation as a potential treatment. Finally, some of the challenges for understanding substance use disorder using neuroimaging methods are discussed. [ABSTRACT FROM AUTHOR]

Summary: A better understanding of social deficits in alcohol use disorder (AUD) has the potential to improve our understanding of the disorder. Clinical research shows that AUD is associated with interpersonal problems and the loss of a social network which impedes response to treatment. Translational research between animal models and clinical research may benefit from a discussion of the models and methods that currently guide research into social cognition in AUD. We propose that research in AUD should harness recent technological developments to improve ecological validity while maintaining experimental control. Novel methods allow us to parse naturalistic social cognition into tangible components, and to investigate previously neglected aspects of social cognition. Furthermore, to incorporate social cognition as a defining element of AUD, it is critical to clarify the timing of these social disturbances. Currently, there is limited evidence to distinguish factors that influence social cognition as a consequence of AUD, and those that precede the onset of the disorder. Both increasing the focus on operationalization of social cognition into objective components and adopting a perspective that spans the clinical spectrum will improve our understanding in humans, but also possibly increase methodological consistency and translational dialogue across species. This commentary underscores current challenges and perspectives in this area of research. [ABSTRACT FROM AUTHOR]