Ketolysis is required for the proper development and function of the somatosensory nervous system.

Ketogenic diets are emerging as protective interventions in preclinical and clinical models of somatosensory nervous system disorders. Additionally, dysregulation of succinyl-CoA 3-oxoacid CoA-transferase 1 (SCOT, encoded by Oxct1), the fate-committing enzyme in mitochondrial ketolysis, has recently been described in Friedreich's ataxia and amyotrophic lateral sclerosis. However, the contribution of ketone metabolism in the normal development and function of the somatosensory nervous system remains poorly characterized. We generated sensory neuron-specific, Advillin-Cre knockout of SCOT (Adv-KO-SCOT) mice and characterized the structure and function of their somatosensory system. We used histological techniques to assess sensory neuronal populations, myelination, and skin and spinal dorsal horn innervation. We also examined cutaneous and proprioceptive sensory behaviors with the von Frey test, radiant heat assay, rotarod, and grid-walk tests. Adv-KO-SCOT mice exhibited myelination deficits, altered morphology of putative Aδ soma from the dorsal root ganglion, reduced cutaneous innervation, and abnormal innervation of the spinal dorsal horn compared to wildtype mice. Synapsin 1-Cre-driven knockout of Oxct1 confirmed deficits in epidermal innervation following a loss of ketone oxidation. Loss of peripheral axonal ketolysis was further associated with proprioceptive deficits, yet Adv-KO-SCOT mice did not exhibit drastically altered cutaneous mechanical and thermal thresholds. Knockout of Oxct1 in peripheral sensory neurons resulted in histological abnormalities and severe proprioceptive deficits in mice. We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.

Managing United States-China university relations and risks.

US universities must proactively address potential concerns.

Ketolysis is Required for the Proper Development and Function of the Somatosensory Nervous System.

Ketogenic diets are emerging as protective interventions in preclinical and clinical models of somatosensory nervous system disorders. Additionally, dysregulation of succinyl-CoA 3-oxoacid CoA-transferase 1 (SCOT, encoded by Oxct1 ), the fate-committing enzyme in mitochondrial ketolysis, has recently been described in Friedreich's ataxia and amyotrophic lateral sclerosis. However, the contribution of ketone metabolism in the normal development and function of the somatosensory nervous system remains poorly characterized. We generated sensory neuron-specific, Advillin-Cre knockout of SCOT (Adv-KO-SCOT) mice and characterized the structure and function of their somatosensory system. We used histological techniques to assess sensory neuronal populations, myelination, and skin and spinal dorsal horn innervation. We also examined cutaneous and proprioceptive sensory behaviors with the von Frey test, radiant heat assay, rotarod, and grid-walk tests. Adv-KO-SCOT mice exhibited myelination deficits, altered morphology of putative Aδ soma from the dorsal root ganglion, reduced cutaneous innervation, and abnormal innervation of the spinal dorsal horn compared to wildtype mice. Synapsin 1-Cre-driven knockout of Oxct1 confirmed deficits in epidermal innervation following a loss of ketone oxidation. Loss of peripheral axonal ketolysis was further associated with proprioceptive deficits, yet Adv-KO-SCOT mice did not exhibit drastically altered cutaneous mechanical and thermal thresholds. Knockout of Oxct1 in peripheral sensory neurons resulted in histological abnormalities and severe proprioceptive deficits in mice. We conclude that ketone metabolism is essential for the development of the somatosensory nervous system. These findings also suggest that decreased ketone oxidation in the somatosensory nervous system may explain the neurological symptoms of Friedreich's ataxia.

A multi-pronged investigation of option generation using depression, PET and modafinil.

Option generation is a critical process in decision making, but previous studies have largely focused on choices between options given by a researcher. Consequently, how we self-generate options for behaviour remain poorly understood. Here, we investigated option generation in major depressive disorder and how dopamine might modulate this process, as well as the effects of modafinil (a putative cognitive enhancer) on option generation in healthy individuals. We first compared differences in self-generated options between healthy non-depressed adults [n = 44, age = 26.3 years (SD 5.9)] and patients with major depressive disorder [n = 54, age = 24.8 years (SD 7.4)]. In the second study, a subset of depressed individuals [n = 22, age = 25.6 years (SD 7.8)] underwent PET scans with 11C-raclopride to examine the relationships between dopamine D2/D3 receptor availability and individual differences in option generation. Finally, a randomized, double-blind, placebo-controlled, three-way crossover study of modafinil (100 mg and 200 mg), was conducted in an independent sample of healthy people [n = 19, age = 23.2 years (SD 4.8)] to compare option generation under different doses of this drug. The first study revealed that patients with major depressive disorder produced significantly fewer options [t(96) = 2.68, P = 0.009, Cohen's d = 0.54], albeit with greater uniqueness [t(96) = -2.54, P = 0.01, Cohen's d = 0.52], on the option generation task compared to healthy controls. In the second study, we found that 11C-raclopride binding potential in the putamen was negatively correlated with fluency (r = -0.69, P = 0.001) but positively associated with uniqueness (r = 0.59, P = 0.007). Hence, depressed individuals with higher densities of unoccupied putamen D2/D3 receptors in the putamen generated fewer but more unique options, whereas patients with lower D2/D3 receptor availability were likely to produce a larger number of similar options. Finally, healthy participants were less unique [F(2,36) = 3.32, P = 0.048, partial η2 = 0.16] and diverse [F(2,36) = 4.31, P = 0.021, partial η2 = 0.19] after taking 200 mg versus 100 mg and 0 mg of modafinil, while fluency increased linearly with dosage at a trend level [F(1,18) = 4.11, P = 0.058, partial η2 = 0.19]. Our results show, for the first time, that option generation is affected in clinical depression and that dopaminergic activity in the putamen of patients with major depressive disorder may play a key role in the self-generation of options. Modafinil was also found to influence option generation in healthy people by reducing the creativity of options produced.

Substituent effects on the UV-visible spectrum and excited electronic states of dithiocarboxylates.

The absorption spectra of a series of dithiocarboxylates were investigated in the ultraviolet-visible region. Two questions that this study aimed to address were as follows: (1) What transitions give rise to the features in the electronic spectra? And (2) what are the long- and short-range substituent effects on the absorption spectra? A series of 11 dithiocarboxylates were prepared as organic soluble salts. Time-dependent density functional theory (TDDFT) was used to calculate excited state energies and oscillator strengths of electronic transitions. TDDFT at the CAM-B3LYP/def2-TZVPD level of theory predicts two low-energy n → π* transitions and two π → π* transitions at higher energy, consistent with the experimental spectra. This state ordering and density is in contrast to the better studied thiocarbonyls for which only two transitions within the singlet manifold appear in the UV-visible region. For derivatives of dithiobenzoate, the energy of the three lowest energy states are insensitive to changes to substituents para to the dithiocarboxylate group. In contrast, the energy of the highest ππ* state varies by 0.78 eV. This work shows that the results of TDDFT calculations can be used to predict the electronic absorption spectra of dithiocarboxylates, providing a useful tool for designing dithiocarboxylate light absorbers.

Practices for monitoring and responding to incoming data on self-injurious thoughts and behaviors in intensive longitudinal studies: A systematic review.

Advancements in the understanding and prevention of self-injurious thoughts and behaviors (SITBs) are urgently needed. Intensive longitudinal data collection methods-such as ecological momentary assessment-capture fine-grained, "real-world" information about SITBs as they occur and thus have the potential to narrow this gap. However, collecting real-time data on SITBs presents complex ethical and practical considerations, including about whether and how to monitor and respond to incoming information about SITBs from suicidal or self-injuring individuals during the study. We conducted a systematic review of protocols for monitoring and responding to incoming data in previous and ongoing intensive longitudinal studies of SITBs. Across the 61 included unique studies/samples, there was no clear most common approach to managing these ethical and safety considerations. For example, studies were fairly evenly split between either using automated notifications triggered by specific survey responses (e.g., indicating current suicide risk) or monitoring and intervening upon (generally with a phone-based risk assessment) incoming responses (36%), using both automated notifications and monitoring/intervening (35%), or neither using automated notifications nor monitoring/intervening (29%). Certain study characteristics appeared to influence the safety practices used. Future research that systematically evaluates optimal, feasible strategies for managing risk in real-time monitoring research on SITBs is needed.

Correlates of Quality of Life in Anxiety Disorders: Review of Recent Research.

PURPOSE OF REVIEW: Anxiety disorders are highly prevalent conditions that have a detrimental impact on quality of life (QOL), particularly when left untreated. In the present review, we summarize recent literature, published within the last 3 years, on QOL in anxiety disorders, with a focus on factors that may play a role in the relationship between anxiety and QOL. RECENT FINDINGS: We organize our findings into four categories: (1) subjective distress, (2) behavioral responses, (3) functional impairment, and (4) clinical factors. Results indicate that greater anxiety symptom severity is linked with poorer QOL, and cognitive behavioral therapies for anxiety yield positive effects on QOL. Additional transdiagnostic mechanisms are highlighted, including anxiety sensitivity, distress tolerance, emotion regulation, and avoidant coping. We examine the role of functional impairment, and we discuss factors related to treatment, including comorbidity and longitudinal effects. We also consider early research from the COVID-19 pandemic. Understanding the underlying factors that contribute to QOL detriments provides important insight into the impact of anxiety disorders and identifies targets for enhancing QOL through treatment.

Selective sorting of ancestral introgression in maize and teosinte along an elevational cline.

While often deleterious, hybridization can also be a key source of genetic variation and pre-adapted haplotypes, enabling rapid evolution and niche expansion. Here we evaluate these opposing selection forces on introgressed ancestry between maize (Zea mays ssp. mays) and its wild teosinte relative, mexicana (Zea mays ssp. mexicana). Introgression from ecologically diverse teosinte may have facilitated maize's global range expansion, in particular to challenging high elevation regions (> 1500 m). We generated low-coverage genome sequencing data for 348 maize and mexicana individuals to evaluate patterns of introgression in 14 sympatric population pairs, spanning the elevational range of mexicana, a teosinte endemic to the mountains of Mexico. While recent hybrids are commonly observed in sympatric populations and mexicana demonstrates fine-scale local adaptation, we find that the majority of mexicana ancestry tracts introgressed into maize over 1000 generations ago. This mexicana ancestry seems to have maintained much of its diversity and likely came from a common ancestral source, rather than contemporary sympatric populations, resulting in relatively low FST between mexicana ancestry tracts sampled from geographically distant maize populations. Introgressed mexicana ancestry in maize is reduced in lower-recombination rate quintiles of the genome and around domestication genes, consistent with pervasive selection against introgression. However, we also find mexicana ancestry increases across the sampled elevational gradient and that high introgression peaks are most commonly shared among high-elevation maize populations, consistent with introgression from mexicana facilitating adaptation to the highland environment. In the other direction, we find patterns consistent with adaptive and clinal introgression of maize ancestry into sympatric mexicana at many loci across the genome, suggesting that maize also contributes to adaptation in mexicana, especially at the lower end of its elevational range. In sympatric maize, in addition to high introgression regions we find many genomic regions where selection for local adaptation maintains steep gradients in introgressed mexicana ancestry across elevation, including at least two inversions: the well-characterized 14 Mb Inv4m on chromosome 4 and a novel 3 Mb inversion Inv9f surrounding the macrohairless1 locus on chromosome 9. Most outlier loci with high mexicana introgression show no signals of sweeps or local sourcing from sympatric populations and so likely represent ancestral introgression sorted by selection, resulting in correlated but distinct outcomes of introgression in different contemporary maize populations.

Virtual care and the impact of COVID-19 on nursing: A single centre evaluation

AimsThe overall aim of this evaluation was to look at the impact of the changes in working practices during the pandemic on nurses. This secondary analysis provided an evaluation of virtual care and being able/required to work from home. DesignThis was secondary analysis of an evaluation using semi-structured interviews. MethodsConducted at a single National Health Service (NHS) university hospital in the United Kingdom between May-July 2020. Forty-eight operational leads and nurses participated in semi-structured interviews which were digitally recorded, transcribed verbatim and analysed using a framework analysis. ResultsTwo overarching themes emerged relating to the patient experience and nursing experience. There were both positive and negative elements associated with virtual care and remote working related to these themes. However, the majority of nurses found virtual clinics were useful when proper resources were provided, and managerial strategies were put in place to support them. Participants felt virtual care could benefit many but not all patient groups moving forward, and that flexibility around working from home would be desirable in the future. ConclusionVirtual care and remote working were implemented to accommodate the restrictions imposed because of the pandemic. The benefits of these changes to nurses and patients support these being business as usual. However, clear policies are needed to ensure nurses feel supported when working remotely and there are robust assessments in place to ensure virtual care is provided to patients who have access to the necessary technology. ImpactThis was a study of the move to virtual care and remote working during the COVID-19 pandemic. Telemedicine and flexible working were not common in the NHS prior to the pandemic but the current evaluation supports the role out of these as standard care with policies in place to ensure nurses and patients are appropriately supported.

The impact of leadership on the nursing workforce during the COVID-19 pandemic

AimsTo determine how the learning about protective factors from previous pandemics were implemented and the impact of this on nurses experience. BackgroundThe COVID-19 pandemic led to systemic change within healthcare settings and demands placed on frontline nurses has been overwhelming. Lessons learned from previous pandemics indicate that clear communication and strong visible leadership can mitigate the impact stressful events may have on nurses. Conversely, a lack of clear leadership and regulatory protocols in times of crisis can lead to an increase in psychological distress for nurses. DesignSecondary analysis of semi-structured interview transcripts. MethodsSecondary data analysis was conducted on data collected during a hospital-wide evaluation of barriers and facilitators to changes implemented to support the surge of COVID-19 related admissions in wave one of the pandemic. Participants represented three-levels of leadership: whole trust (n=17), division (n=7), ward/department-level (n=8), and individual nurses (n=16). Data were collected through semi-structured video interviews between May and July 2020. Interviews were analysed using Framework analysis. ResultsKey changes that were implemented in wave one reported at whole trust level included: a new acute staffing level, redeploying nurses, increasing the visibility of nursing leadership, new staff wellbeing initiatives, new roles created to support families and various training initiatives. Two main themes emerged from the interviews at division, ward/department and individual nurse level: impact of leadership, and impact on the delivery of nursing care. ConclusionsLeadership through a crisis is essential for the protective effect of nurses emotional wellbeing. While nursing leadership was made more visible during wave one of the pandemic and processes were in place to increase communication, system-level challenges resulting in negative experiences existed. By identifying these challenges, it has been possible to overcome them during wave two by employing different leadership styles, to support nurse wellbeing

Evaluation of the Family Liaison Officer (FLO) role during the COVID-19 Pandemic

ObjectivesDuring the first wave of COVID-19 heavy restrictions were placed on hospital visitations in the United Kingdom. To support communication between families and patients a central London hospital introduced the role of the Family Liaison Officer. Communication within healthcare settings is often the subject of contention, particularly for patients families. During periods of crisis communication can become strained for patients and their families. We aimed to evaluate the rapid implementation of this role to provide guidance if it was required in the future and to explore the potential for this to become a standard role. DesignService evaluation SettingSingle National Health Service hospital in London. MethodsSemi-structured video interviews with a convenience sample of 12 participants. Data were analysed using Framework Analysis. ParticipantsFamily Liaison Officers (n=5) and colleagues who experienced working alongside them (n=7). ResultsKey themes were identified from the interviews pertaining to the role, the team, the impact and the future. Two versions of the role emerged though the process based on the Family Liaison Officers previous background: Clinical Family Liaison Officers (primarily nurses) and Pastoral Family Liaison Officers (primarily play specialists). Both the Family Liaison Officers and their colleagues agreed that the role had a very positive impact on the wards during this time. Negative aspects of the role, such as a lack of induction, boundaries or clear structure were also discussed. ConclusionThe Family Liaison Officer was a key role during the pandemic in facilitating communication between patient, clinical team and family. The challenges associated with the role reflect the speed in which it was implemented but it was evident to those in the role and clinicians who the role was supporting that it has potential to help improve hospital communication, and the work of healthcare staff outside of a pandemic. Strengths and limitations of this studyO_LIThis was an in-depth evaluation of the Family Liaison Officer role from the perspective of those in the role and the clinical team who they were providing support. C_LIO_LIThe sample included representation of the different disciplines who worked in the FLO role. C_LIO_LIThe evaluation only represents the professional perspective and not the experience of the family. C_LI

A "China in the World" Paradigm for Scholarship.

In this introduction to the special issue, we use the expression "China in the world" paradigm to define scholarship that purposefully migrates across the traditional borders of comparative politics and international relations in the study of China. We argue that such a paradigm represents a view that many issues of Chinese domestic politics are now issues of international politics; as a result, domestic politics in a globalized contemporary China often cannot be sufficiently understood without considering international consequences. More than this, the paradigm is about scholarly attentiveness to the fact that the politics in China that we study also shapes how the rest of the world views China. We describe the paradigm and its antecedents in the scholarly literature. We then illustrate, with reference to three momentous events that captured public attention around the world in 2020, the paradigm's usefulness as a perspective to scholars reaching out to engage intellectually on contemporary affairs in an environment in which global responses to China require nuanced knowledge as all parties seek to avoid dangerous pitfalls. We conclude by summarizing the five articles included in the special issue and the broader implications of the "China in the world" paradigm.

Estrogen Withdrawal Increases Postpartum Anxiety via Oxytocin Plasticity in the Paraventricular Hypothalamus and Dorsal Raphe Nucleus.

BACKGROUND: Estrogen increases dramatically during pregnancy but quickly drops below prepregnancy levels at birth and remains suppressed during the postpartum period. Clinical and rodent work suggests that this postpartum drop in estrogen results in an estrogen withdrawal state that is related to changes in affect, mood, and behavior. How estrogen withdrawal affects oxytocin (OT) neurocircuitry has not been examined. METHODS: We used a hormone-simulated pseudopregnancy followed by estrogen withdrawal in Syrian hamsters, a first for this species. Ovariectomized females were given daily injections to approximate hormone levels during gestation and then withdrawn from estrogen to simulate postpartum estrogen withdrawal. These hamsters were tested for behavioral assays of anxiety and anhedonia during estrogen withdrawal. Neuroplasticity in OT-producing neurons in the paraventricular nucleus of the hypothalamus and its efferent targets was measured. RESULTS: Estrogen-withdrawn females had increased anxiety-like behaviors in the elevated plus maze and open field tests but did not differ from control females in sucrose preference. Furthermore, estrogen-withdrawn females had more OT-immunoreactive cells and OT messenger RNA in the paraventricular nucleus of the hypothalamus and an increase in OT receptor density in the dorsal raphe nucleus. Finally, blocking OT receptors in the dorsal raphe nucleus during estrogen withdrawal prevented the high-anxiety behavioral phenotype in estrogen-withdrawn females. CONCLUSIONS: Estrogen withdrawal induces OT neuroplasticity in the paraventricular nucleus of the hypothalamus and dorsal raphe nucleus to increase anxiety-like behavior during the postpartum period. More broadly, these experiments suggest Syrian hamsters as a novel organism in which to model the effects of postpartum estrogen withdrawal on the brain and anxiety-like behavior.

Determinants of weekly raw milk use by at-home meal preparers in the USA: evidence from the 2014-2016 American Time Use Survey - Eating and Health Module.

OBJECTIVE: The number of states in the USA that allows sales of raw milk for human consumption has been trending upwards and reached thirty-eight in 2016. These legislative changes could encourage raw milk consumption. The current study examined the determinants of weekly raw milk use by at-home meal preparers in the USA. DESIGN: Using the 2014-2016 American Time Use Survey - Eating and Health Module, multivariate logit regressions and average marginal associations were estimated to examine how at-home meal preparer characteristics, time use and shopping choices, underlying health and the presence of at-risk individuals in households and raw milk legalisation status are associated with the probability an at-home meal preparer consumed or served raw milk during an average week. SETTING: USA. PARTICIPANTS: At-home meal preparers aged 18 years and above. RESULTS: Estimated average marginal associations suggested younger at-home meal preparers, male at-home meal preparers, larger sized households and households located in non-metropolitan areas were more likely to use raw milk during an average week. Married households and households with a person aged 62 years or above were less likely to use raw milk. Variables indicating health characteristics of at-home meal preparers or the presence of an at-risk individual in the household were not statistically significant. CONCLUSIONS: There are many government-sponsored information resources about the risks of raw milk currently available. Additional education may be needed to prevent illnesses from raw milk.

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome.

The diagnosis of COVID-19 is normally based on the qualitative detection of viral nucleic acid sequences. Properties of the host response are not measured but are key in determining outcome. Although metabolic profiles are well suited to capture host state, most metabolomics studies are either underpowered, measure only a restricted subset of metabolites, compare infected individuals against uninfected control cohorts that are not suitably matched, or do not provide a compact predictive model. Here we provide a well-powered, untargeted metabolomics assessment of 120 COVID-19 patient samples acquired at hospital admission. The study aims to predict the patients infection severity (i.e., mild or severe) and potential outcome (i.e., discharged or deceased). High resolution untargeted LC-MS/MS analysis was performed on patient serum using both positive and negative ionization modes. A subset of 20 intermediary metabolites predictive of severity or outcome were selected based on univariate statistical significance and a multiple predictor Bayesian logistic regression model was created. The predictors were selected for their relevant biological function and include cytosine and ureidopropionate (indirectly reflecting viral load), kynurenine (reflecting host inflammatory response), and multiple short chain acylcarnitines (energy metabolism) among others. Currently, this approach predicts outcome and severity with a Monte Carlo cross validated area under the ROC curve of 0.792 (SD 0.09) and 0.793 (SD 0.08), respectively. A blind validation study on an additional 90 patients predicted outcome and severity at ROC AUC of 0.83 (CI 0.74 - 0.91) and 0.76 (CI 0.67 - 0.86). Prognostic tests based on the markers discussed in this paper could allow improvement in the planning of COVID-19 patient treatment.

Impact of COVID-19 lockdown on psychosocial factors, health, and lifestyle in Scottish octogenarians: the Lothian Birth Cohort 1936 Study

BackgroundLittle is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. MethodsLothian Birth Cohort 1936 members, mean age 84 years (SD=0.3), responded to an online questionnaire in May 2020 (n=190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. ResultsFour respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR=0.71, 95%CI 0.51- 0.98) and poorer self-rated general health (OR=0.62, 95%CI 0.42-0.92). Increased internet use associated with female sex (OR=2.32, 95%CI 1.12-4.86) and higher general cognitive ability (OR=1.53, 95%CI 1.03-2.33). Loneliness associated with living alone (OR=0.15, 95%CI 0.07-0.31) and greater anxiety symptoms (OR=1.76, 95%CI 0.45-1.24). COVID-19 related stress associated with lower emotional stability scores (OR=0.40, 95%CI 0.24-0.62). Decreased physical activity associated with less professional occupational class (OR=1.43, 95%CI 1.04-1.96), and lower general cognitive ability (OR=0.679, 95%CI 0.491-0.931). ConclusionsCharacteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes.

An approach for the extract generation and toxicological assessment of tobacco-free 'modern' oral nicotine pouches.

Tobacco-free 'modern' oral nicotine pouches (MOPs), are similar in appearance and use to Swedish-style snus, but without tobacco. There are few identified methods to create test samples for toxicologically assessment of MOPs in vitro. In this study we present a simple method for the extraction of pouch material in cell culture media, providing consistent nicotine concentration and easy in vitro assessment. A series of contemporary in vitro screening assays (viability, cell health markers, oxidative stress and genotoxicity) using human oral fibroblasts (HGF) and human lung epithelial cells (H292) were employed. Extracts were generated from LYFT and compared to snus (CRP1.1) and cigarette (1R6F) reference products. MOP and CRP1.1 extracts were generated by incubating one pouch in 20 ml of cell culture media, while 1R6F AqE was prepared by smoking 1 cigarette into 20 ml of cell culture media. 1R6F demonstrated toxicological responses in most assays; CRP1.1 had minimal to moderate effects while MOP demonstrated little or no response in all assays. This study demonstrated the generation of MOPs extracts and their toxicological evaluation using in vitro screening approaches. Future product usage, pharmacokinetics and clinical studies will further substantiate the reduced risk potential of MOPs.

Targeting fear of positive evaluation in patients with social anxiety disorder via a brief cognitive behavioural therapy protocol: a proof-of-principle study.

BACKGROUND: Our aim was to develop a brief cognitive behavioural therapy (CBT) protocol to augment treatment for social anxiety disorder (SAD). This protocol focused specifically upon fear of positive evaluation (FPE). To our knowledge, this is the first protocol that has been designed to systematically target FPE. AIMS: To test the feasibility of a brief (two-session) CBT protocol for FPE and report proof-of-principle data in the form of effect sizes. METHOD: Seven patients with a principal diagnosis of SAD were recruited to participate. Following a pre-treatment assessment, patients were randomized to either (a) an immediate CBT condition (n = 3), or (b) a comparable wait-list (WL) period (2 weeks; n = 4). Two WL patients also completed the CBT protocol following the WL period (delayed CBT condition). Patients completed follow-up assessments 1 week after completing the protocol. RESULTS: A total of five patients completed the brief, FPE-specific CBT protocol (two of the seven patients were wait-listed only and did not complete delayed CBT). All five patients completed the protocol and provided 1-week follow-up data. CBT patients demonstrated large reductions in FPE-related concerns as well as overall social anxiety symptoms, whereas WL patients demonstrated an increase in FPE-related concerns. CONCLUSIONS: Our brief FPE-specific CBT protocol is feasible to use and was associated with large FPE-specific and social anxiety symptom reductions. To our knowledge, this is the first treatment report that has focused on systematic treatment of FPE in patients with SAD. Our protocol warrants further controlled evaluation.

Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.

Evaluating the combination of a Brief Motivational Intervention plus Cognitive Behavioral Therapy for Depression and heavy episodic drinking in college students.

[Correction Notice: An Erratum for this article was reported in Vol 34(2) of Psychology of Addictive Behaviors (see record 2020-16883-001). In the original article the order of authorship was incorrect. The correct second and third authors should appear instead as Brian Borsari and Jennifer E. Merrill.] Heavy episodic drinking (HED) and depressive symptoms often co-occur among college students and are associated with significant impairment. However, evidence-based treatments for these common co-occurring conditions are not available for college students. The current study compared the effectiveness of a treatment combining Cognitive-Behavioral Therapy for Depression and Brief Motivational Interviewing (CBT-D + BMI) versus Cognitive-Behavioral Therapy for Depression (CBT-D) alone among 94 college students with HED and depressive symptoms. Both treatment programs were associated with significant reductions of similar magnitude in HED, alcohol-related problems (ARP), and depressive symptoms at the end of treatment and at the 1-month follow-up assessment. Moderation analyses indicated that, among college students with fewer depressive symptoms at baseline, CBT-D was associated with greater sustained reduction in heavy drinking relative to CBT-D + BMI at the 1-month follow-up. Although the study did not include a no-treatment condition, the magnitude of improvement during treatment in both groups was greater than what is expected with passage of time. Although clinicians in college counseling centers may lack specialty training for co-occurring conditions, CBT-D is widely implemented in college settings. Our findings suggest that CBT-D may reduce both depressive symptoms and HED in college students and may be used to address a significant public health problem. (PsycINFO Database Record (c) 2020 APA, all rights reserved).